Chapter 02: The Curing Molecule

10/09/2022 eben van tonder Bacon & the Art of Living Bacon Curing, Bacon History, bacon processing, nitrate, nitrite curing, sodium nitrite

Introduction to Bacon & the Art of Living

The story of bacon is set in the late 1800s and early 1900s when most of the important developments in bacon took place. The plotline takes place in the 2000s with each character referring to a real person and actual events. The theme is a kind of “steampunk” where modern mannerisms, speech, clothes and practices are superimposed on a historical setting. Modern people interact with old historical figures with all the historical and cultural bias that goes with this.

The Curing Molecule

Before we get into storytelling, it will be of great value to have a technical discussion about meat curing. The story will be more enjoyable if you understand how curing works. This chapter is designed to give you enough background to understand the fundamentals of curing and some of its complexities. This is not intended to be a science textbook and so I take the liberty to present matters in a somewhat simplified manner. I don’t for example always indicate when I am talking about an ionic compound when I write a simple notation for nitrite as NOO. I also added, “Want to know more?” sections for those who have a chemical background or those who want to gain a deeper understanding. Get through Chapter 2 and a story awaits which will blow your mind!

What is Meat Curing?

The most important question in a work on the history of meat curing is to understand what meat curing is! Meat curing is the process whereby meat is changed into a form that lasts outside a refrigerator. We can say that it imparts longevity to meat. In the curing process, there are two changes that we can identify with our senses. A delicious taste develops and the colour change to a characteristic pinkish/ reddish colour. A slightly less obvious characteristic is cured meat is safe from microorganisms which make us sick. These characteristics are observed through observation but what happens as far as chemical reactions are concerned?

The large molecule which is the building block for muscle or meat is called a protein. An important class of proteins in our body is called hemeproteins (also spelt haem protein or hemoprotein). These are proteins which have something attached to them that biochemists refer to as a heme prosthetic group. A prosthesis helps a person who lost a limb to still accomplish a certain task like a handshake. The prosthesis in the case of proteins is non-protein additions to the protein which accomplish specific tasks. The heme prosthetic group allows proteins to carry oxygen, facilitate electron transfer and participate in oxygen reduction among other processes. Curing is the reaction between protein and the small gaseous molecule called nitric oxide (NO).

In curing nitric oxide is bound onto this heme component. It is this binding of nitric oxide to the protein which we observe as a pinkish/ reddish colour. Nitric oxide is responsible for key characteristics of cured meat. The colour, the longevity and the fact that the product is free from microorganisms, likely to make us sick. Another characteristic of cured meat we observed with our senses is the cured taste. Exactly how the taste is altered through curing is something which we have not completely worked out yet.

Want to know more?

Nitric oxide is the most important molecule related to the cured colour of meat. This does not say that other chemical species also derived from nitrogen do not play a role in changing the colour. This is true related to colour formation as well as anti-microbial ability. An example is nitrogen dioxide (NO₂). The researcher Cornforth (1998) showed that pink rings that form in beef roasts cooked in gas ovens and turkey rolls are produced by nitrogen dioxide (NO₂). Similarly, we know that both nitrite and nitric oxide plays a very important role in the antimicrobial working of the curing process. The researcher, Scairer (2012), reported on the antimicrobial value of nitric oxide.

How is Nitric Oxide formed?

Let’s begin by looking at how nitric oxide is formed. For our discussion, what is essential to know is that it is formed both inside the body or by the body itself and outside the body. Almost every cell in our bodies can produce it. There are also two basic types of reactions that produce it.

i. Meat proteins contain an amino acid called L-Arginine. The body has the ability to access its nitrogen and combines it with an oxygen atom to create nitric oxide. Beginning in the 1990s scientists started to understand that certain bacteria also have the ability to convert L-arginine into L-citrulline and nitric oxide which cures meat. The exact mechanism is still under investigation but this remarkable discovery accomplishes what has become like the search for the holy grail namely the curing of meat without the use of nitrate or nitrite.

ii. The second major way that nitric oxide is created is the conversion of nitrate to nitrite and the nitrite to nitric oxide. The source of nitrate can be salts such as sodium or potassium nitrate or it occurs in large volumes in certain plants which we regularly consume. Bacteria break the nitrate down to nitrite and nitrite is changed into nitric oxide through mainly chemical reactions. In conventional curing operations, either nitrate or nitrite salts are used to create nitric oxide which cures meat.

This means that bacteria are involved in the reactions involving nitrate and L-Arginine. Interestingly enough, this seems to be the reason why this remarkable discovery remained unidentified for so many years. The conversion of L-Arginine only takes place when no nitrate is present. If nitrate is present the bacteria use the nitrogen found in nitrate and not L-arginine. That L-Arginine plays a role in salt-only, long-term curing processes has been suspected for many years and in the 1990s it was identified that the reaction was mediated through bacteria. What seemed to have happened was that the scientific community continued to relegate this to the realm of long-term cured hams and bacon. It is only in recent years that commercial quick-curing factories using bacterial fermentation became a reality in large high throughput commercial curing plants using bacterial fermentation and no nitrates or nitrites. In fact, so successful have these developments in meat fermentation been that meat curing is achieved in approximately the same time as is done with sodium nitrite.

That sets the first part of the stage for our discussion about meat curing. My own life is a good example of how only knowing the facts as I presented above about meat curing does not mean that you can use the techniques. The reality is that these methods can only be effectively applied within the framework of a complete curing system and developing such a system is far more complex than one imagines. I have, for example, known that bacteria are able to use L-Arginine to create nitric oxide for a full five years before I started to unravel the context and requirements of what it will take to use this to cure meat in a commercial curing operation. Colour stability and a safe microenvironment must be created. The formation of biofilm must be managed. The speed of the reaction must be increased. So I can go on and on and the point is simply this, it is a wonderfully complex endeavour.

Let’s return to the consideration of the two curing paths that we just looked at. In the course of this chapter, I will make repeated references to these two reactions. The story of bacon is, in a nutshell, the story of ways to produce nitric oxide in the fastest possible time to cure meat.

It has been an obsession of many curers and scientists to find another way to cure meat. In other words, not to use the nitrate-nitrite-nitric oxide path to curing due to questions that emerged about the safety of nitrate and nitrite. The use of bacteria to cure the meat achieves this! However, right at the outset, I want to caution that nitrate, nitrite and nitric oxide are like the Father, the Son and the Holy Spirit in that where you find one, you find them all due to the high reactivity of these nitrogen species (Reactive Nitrogen Species) as we refer to them. Creating nitric oxide with bacteria from L-Arginine may seem like solving the problematic use of nitrate and nitrites in meat curing but if the two cousins of nitric oxide (nitrate and nitrite) will in any event both appear in meat cured with bacteria only, is it really addressing the problem?

A far more fundamental question exists namely if the hysteria against nitrate and nitrite is warranted! Is the use of nitrite or nitrate really problematic? Are these really entities of concern when we consider human health? In recent years evidence started to emerge that the exact opposite is true namely that if we do not ingest sufficient nitrate and nitrite, this has far more detrimental health effects on humans than having them in our food.

Want to know more?

A closer look at the nitrate-nitrite-nitric oxide sequence in our bodies:

The researcher, Weitzberg (2010) reportes that “several lines of research . . . indicate that the nitrate-nitrite-nitric oxide pathway is involved in regulation of blood flow, cell metabolism, and signaling, as well as in tissue protection during hypoxia (meaning, a lower-than-normal concentration of oxygen in arterial blood).” This is the exact curing reaction when we begin with slatpetre (NO₃^–) or with nitrite NO₂^– as is the predominant current system of curing in high throughput curing operations. When we use sodium nitrite to cure the meat, the process still results in the formation of nitric oxide (NO). The curing reaction is therefore a “natural reaction” which takes place in our bodies and is essential to life.

Can we remove nitrogen (nitrate or nitrite) from our diets?

We are all aware of the importance of oxygen to our everyday lives. Without it, life as we know it is not possible. A second element as important to life as oxygen is nitrogen. Where does nitrogen come from and why is it important to life? Let’s take a step back and consider nitrogen for a moment before we return to nitrate and nitrite in food and the chemistry of curing.

The Importance of Nitrogen

I have written extensively about how reactive nitrogen species are formed from atmospheric nitrogen and I will leave the subject to be discussed later.

Sufficient to point out that nitrogen is one of the most essential plant foods and is taken up in the structure of plants. From the plants, they provide sustenance to animals when they eat the grass. The ability of animals to absorb nitrogen is a key element in what makes food nutritious. From very early it has been shown by various scientists that animals fed with food containing no nitrogen get sick and even die whereas animals fed with food high in nitrogen thrive. This is important since, in evaluating the use of nitrogen in meat curing (through nitric oxide), the first thing we must realise is that without nitrogen, there is no nutrition. We need nitrogen like we need water or oxygen to live.

Want to know more?

The role of nitrogen in plants:

Nitrogen is part of the green pigment of plants, responsible for photosynthesis, called chlorophyll. It further is responsible for a plant’s rapid growth, increasing seed and fruit production, and improving the quality of leaf and forage crops. (Plant Nutrients and Lilies) This is important as we will later see how nitrate, nitrite and nitric oxide not only cures meat and ensures the overall health of our bodies, but how the same reaction is key to the nutrition of plants. The curing reaction is by no ways something foreign. It is vitally important to all aspects of animal and plant life and humans form part of this group of animals.

Nitrogen as plant food:

Potassium (K) and nitrogen (N) together with phosphorous (P) are considered the primary nutrients of plants. These are normally lacking in the soil because plants use them for growth and thus deplete it. As we will see, nature replenishes nitrogen, but modern farming created the demand to add extra nitrogen to the soil. Potassium (K), nitrogen (N) and phosphorous (P) are all part of the macronutrients. The secondary nutrients are calcium (Ca), magnesium (MG), and sulphur (S). These nutrients are normally abundant in the soil. When lime is applied to acidic soil, large amounts of calcium and magnesium are added. Decomposing organic matter normally yields enough sulphur. Potassium (K) is absorbed in bigger volumes than any other mineral element except nitrogen and in some cases, calcium. It assists in the building of proteins, photosynthesis, and fruit quality and it reduces diseases. (Plant Nutrients and Lilies) The abundance of potassium in plants can be seen from where we first identified it namely from potash or plant ashes soaked in water in a pot. Potassium is derived from this practice predating the industrial revolution.

All proteins, the building blocks of muscles contain nitrogen. Our bodies use nitric oxide to stay healthy in many different ways. To such an extent that without nitric oxide in our bodies, life will not be possible. The question is now if the body produces enough nitric oxide on its own and the answer is no. We need to supplement what the body can produce through our diet. Some of the foods where we get nitrate or nitrite in our diets are:

-> Vegetables

By far the biggest source of nitrates is leafy green vegetables. The way that the nitrates end up as nitric oxide in our bodies is the nitrate-nitrite-nitric oxide sequence. These vegetables also contain nitrites and these turn into nitric oxide through the steps of nitrite-> various-chemical-reactions ->nitric oxide.

-> Water

Borehole water often has nitrate and nitrite from animal and human waste and fertilisers in surrounding areas. The sequence of reactions that change the nitrates in water into nitric oxide is the same as above namely nitrate-> nitrite-> nitric oxide.

-> Cured Meat

Nitrate salts are found naturally around the world. Potassium nitrate for example we know as saltpetre. Nitrite salts are manufactured salts containing sodium and nitrite. Saltpetre (potassium or sodium nitrate) is used in meat curing to this day. If we consume cured meat we ingest nitrates or nitrites and it ends up changing into nitric oxide in our bodies either through the reaction nitrate-nitrite-nitric oxide or nitrite-nitric oxide. Cured meat is, however by far the smallest and most insignificant source of nitrates and nitrites.

What is important to focus on here is the path from nitrate to nitric oxide. Let me illustrate it in greater detail using saltpetre as an example. Saltpetre can be represented as one nitrogen atom and three oxygen atoms and to make it easy, I will write it as NOOO to focus on the number of oxygen atoms. The astute observer will see that I leave the metal part of saltpetre out and I represent only the nitrate part. Nitrate joins forces with metals like sodium, calcium, or potassium to form sodium nitrate, potassium nitrate (which is known as saltpetre) or calcium nitrate. In terms of curing meat, only sodium plays a further role and we will look at that later, but for now, it’s helpful to ignore the first part of the pair and focus only on the nitrate part.

When nitrate connects to one of the metals it forms a very stable salt which does not easily lose an oxygen atom. We said we represent nitrate in this chapter as NOOO, but you remember that the actual representation is NO₃^–. The stable molecule now loses an oxygen atom through bacteria that use the extra oxygen atom in its metabolism. So, NOOO loses an oxygen atom through the action of bacteria and nitrite is formed which we represent as NOO (actually, NO₂^–). In contrast to nitrate, nitrite is an unstable molecule and is easily changed to one of the other Reactive Nitrogen Species (RNS) such as nitric oxide. If NOO loses an oxygen atom, NO or nitric oxide is formed. This reaction happens chemically and not through bacteria and it involves nitrate first changing into other forms before it ends up as nitric oxide.

Ancient curing methods start with nitrate, which is changed to nitrite and eventually to nitric oxide. This is the way that it was done before sodium nitrite became available around the world after World War I and many artisan curers still prefer to start with nitrate when they cure meat. The reason for this is that the bacteria also contribute to the development of flavours in the meat which one loses if one starts directly with nitrite in the form of sodium nitrite which does not require bacteria to change into nitric oxide to cure the meat. It became the norm following World War II to skip the step of changing nitrate to nitrite which is time-consuming and may result in inconsistent curing by beginning the reaction sequence by using sodium nitrite and not nitrate.

Whether you talk about the reaction nitrate-nitrite-nitric oxide or nitrite-nitric oxide, these scenario has at their heart the loss of one oxygen atom in every step. The opposite is also possible mainly that oxygen atoms can be added. At times, nitric oxide can gain an atom to form NOO or nitrite and NOO to form NOOO or nitrate. Remember that we said that where you find one, you are likely to find the others. So, where you have either nitrate, nitrite or nitric oxide, you are likely to find the others also.

Want to know more:

Ionic compounds:

It is easy to see that the 3 following the O which represents oxygen indicates that one nitrogen atom binds to three oxygen atoms in the nitrate molecule, but what does the minus sign indicate? The nitrogen and three oxygen atoms form a unit or a package. The nett charge of this package is, however, negative, which is what the minus sign indicates. We call this not a molecule, but a very special molecule called an ion (where there is only one atom) or an ionic compound as in the case of nitrate with nitrogen and oxygen atoms in the molecule. A compound is supply two or more elements grouped together. An ion is what we call a unit like this (which can be an atom or a molecule) but it has a net electrical charge which is either + (positive) or – (negative). Ionic compounds are held together by these ionic bonds or electrostatic forces, as we refer to them. The ion by itself has a charge as either + or – but when it connects with another ion of opposite charge, the molecule is neutral overall. It has a component which is positively charged (called an anion – a positively charged ion) and a negatively charged component (called a cation – a negatively charged ion). An example of an ionic compound from everyday life is table salt with one positively charged sodium ion (Na+) and one negatively charged chloride ion (Cl⁻) called sodium chloride or table salt. We call it a salt because one component is alkali and the other is acidic.

The combination of nitrogen and oxygen yields several salts of importance for example saltpetre. Like table salt is the colloquial term for sodium chloride, so the colloquial term for potassium nitrate is saltpetre. The nitrate component or ion, NO₃^– reacts with metal ions such as sodium, magnesium, potassium, or calcium. The metal components occur in solution (mixed into water) as a strong acid in the form of (HNO₃) with a strong base (KOH) which reacts to form a crystal [P⁺].[NO₃^–] or PNO_3. Traditionally, saltpetre refers to potassium nitrate.

Another metal it often combines with is sodium to form sodium nitrate. Sodium or natrum (German) is represented by the letters “Na” for sodium and again, the nitrate component which is NO₃^– combines to give sodium nitrate written as [Na⁺].[NO₃^–] to form NaNO₃.

The final example is the metal calcium, abbreviated Ca which represents calcium, but calcium combines with two sets of nitrates (NO₃^–) x 2 written as (NO₃)₂ and the complete name is therefore Ca(NO₃)_2.In our discussions here we ignore the metal part of the molecule being in our examples above potassium (K), sodium (Na) and Calcium (Ca). For easy of reference, when we talk about nitrate, we only refer to the NO₃^–component but often, there would be either K or Na or Ca attached to the nitrate but because it plays no role in the rest of the chemical reaction, we will conveniently ignore these metal components.

Summarise different metals that combine with nitrate:

NOOO (nitrate) + K (potassium) = KNO₃ (Potassium Nitrate)

NOOO (nitrate) +Na (sodium) = NaNO₃ (Sodium Nitrate)

NOOO (nitrate) + Ca (Calcium) = Ca(NO₃)₂ (Calcium Nitrate)

You not only learned three different metals that can attach to nitrate. The same three can also lose an oxygen atom to form a nitrite salt.

NOO (nitrite) + K (potassium) = KNO₂ (Potassium Nitrite)

NOO (nitrite) +Na (sodium) = NaNO₂ (Sodium Nitrite)

NOO (nitrite) + Ca (Calcium) = Ca(NO₂)₂ (Calcium Nitrite)

This is another equally likely reaction which involved the gaining of oxygen atoms and not losing it (reduction). An example of an oxidation reaction is the reaction with L-Arginine which we looked at briefly and the oxidation of ammonia (NO₃)/ ammonium (NH₄⁺), both of which creates nitric oxide and are mediated through bacteria. We will tell the story of the formation of nitric oxide from ammonia in a subsequent chapter.

We summarise the two reactions as follows:

-> Reduction (losing oxygen atoms)

One way to create nitric oxide is by removing oxygen atoms. We remove one of the three oxygen atoms from nitrate (NOOO), and we get nitrite (NOO). In the name, the “a” is replaced with an “i” and, nitrite has one less oxygen atom than nitrate. If we remove one more oxygen atom from nitrite (NOO) we get nitric oxide (NO) which is the primary curing molecule.

So, let’s review the simple but important chemistry. Don’t worry about trying to remember these. We will refer to them so many times that you will easily remember them when we are done.

NOOO or (NO₃^–) = Nitrate or Saltpetre

NOO or (NO₂^–) = Nitrite

NO = Nitric Oxide

When nitrate loses one oxygen atom, it changes to nitrite and nitrite that loses one oxygen atom changes to nitric oxide.

NOOO (nitrate) – O = NOO (nitrite)

NOO (Nitrite) – O = NO (nitric oxide)

We have seen that to form nitric oxide from nitrate salts, you lose two oxygen atoms. Chemists say that the number of oxygen atoms is reduced. The word “reduced” will be important as we will say that the nitrate or nitrite is reduced, we mean that it lost an oxygen atom.

The same salts that nitrate forms with metal are formed by the more reactive nitrite.

NOO (nitrite) + K (potassium) = KNO₂ (potassium nitrite)

NOO (nitrite) +Na (sodium) = NaNO₂ (Sodium Nitrite)

NOO (nitrite) + Ca (Calcium) = Ca(NO₂)₂ (Calcium Nitrite)

-> Oxidation (Gaining Oxygen Atoms)

Earlier, we have seen that nitric oxide is created by our bodies through certain processes in our cells. Instead of taking an oxygen atom away, it created nitric oxide by starting with a nitrogen atom and then it adds an oxygen atom to the nitrogen atom, and it forms nitric oxide. This process is called oxidation (adding an oxygen atom).

Ammonia is oxidized through bacteria which adds an oxygen atom to nitrogen and creates nitric oxide. More about this later when we drill down into sal ammoniac. Another way this happens is when ammonia is burned in the presence of oxygen. In this case, it is also oxidized to either nitrogen gas (N2) or nitric oxide (NO). It must be noted that the oxidation of ammonium salts usually produces nitrogen gas.

The Ever-Presence of Nitrogen

Let’s return to considering how gas, nitrogen, enters our world and becomes part of the nutrition of plants and animals. Otto et al (2010) estimate that with 1.4 billion lightning flashes each year, an estimated 8.6 billion tonnes of chemicals of one form or other are generated from the general formulation of NOx. Don’t get scared with the introduction of the x. It tells us we have a variable from which the exact number differs. You are already familiar with three of the forms this can take. Look at Nitric Oxide (NO), nitrite (NO2-), and nitrate (NO₃^–) and see if you can spot the function of the x which in this case is either an implied 1, an overtly stated 2 or 3. Can you tell me why the 1 is implied and for what form of nitrogen and oxide?

This estimate by Otto et al (2010) is staggering. It dwarfs what the curing industry can produce. It comprehensively obliterates the notion that nitrogen or nitric oxide or even nitrite for that matter are evil chemical species, which is produced by humans, and added to meat which will, so it is reported, do harm to the human body.

Otto, et al (010) and many others show conclusively that the presence of nitrate and nitric oxide is pervasive on planet earth. Nitrite is far less prevalent than nitrate. Nitrite is highly reactive and does not stay in this state very long (similar to nitric oxide). It forms a salt such as sodium nitrate which is more stable and is naturally found in some vegetables and meat, but still, nitrites often occur in vegetables. Most current sodium nitrites in dietary sources are made by humans. Nitric Oxide is also “fleeting” being a gas which quickly reacts to become another species.

Want to know more:

“Nitrogen is an essential element for all forms of life and is the structural component of amino acids from which animal and human tissues, enzymes, and many hormones are made. For plant growth, available (fixed) nitrogen is usually the limiting nutrient in natural systems. Nitrogen chemistry and overall cycling in the global environment are quite complex due to the number of oxidation states. Nitrogen itself has five valence electrons and can be found at oxidation states between −3 and +5. Thus, numerous species can form from chemical, biochemical, geochemical, and biogeochemical processes.” (Hanrahan, 2005) Below I list the oxidation state of different nitrogen species (and important chemical data).

Global nitrogen species and selected chemical data by: Hanrahan, 2005.

If you’re interested to learn more, google oxidation states. For those with a lively interest in this, I give the oxidation state of key nitrogen species.

The special Oxidation States of Nitrogen

Ox. state	Species
+5	NO₃	Nitrate ion, oxidizing agent in acidic solution.
+4	NO₂	Nitrogen dioxide is a brown gas usually produced by the reaction of concentrated nitric acid with many metals. It dimerizes to form N₂O₄.
+3	NO₂	An oxidizing agent usually produces NO(g) or a reducing agent to form the nitrate ion.
+2	NO	Nitrogen oxide is also called nitric oxide. A colourless gas is produced by the reaction of metals with dilute nitric acid which then reacts with O₂ in the air to form the brown NO₂ gas.
+1	N₂O	Dinitrogen oxide is also called nitrous oxide or laughing gas.
0	N₂	Commonly found in air and very unreactive because of the very strong triple bond.
-1	NH₂OH	NH2OH Hydroxylamine, a weak base, can act as either an oxidizing agent or a reducing agent.
-2	N₂H₄	Hydrazine, a colourless liquid, is a weak base. Used as rocket fuel. It is disproportionate to N₂ and NH₃.
-3	NH₃	In basic solutions and as NH₄ agent in aqueous solutions. When ammonia is burned in the presence of oxygen it is oxidized to either N₂ or NO. The oxidation of ammonium produces nitrogen gas. salts usually.

Demonstrating Oxidation and Reduction

Let’s illustrate this with a helpful diagram which illustrates both oxidation and reduction of nitrate found in beetroot.

Nitrate–nitrite–nitric oxide pathway. Adapted from Niayakiru et al., 2020 by Milton-Laskibar (2021).

In the illustration above, beetroot contains nitrate (NOOO). Nitrate loses an oxygen atom and nitrite (NOO) is created. This is done through bacteria. It loses another oxygen atom and nitric oxide (NO) is created. These are examples of reduction reactions or losing-an-oxygen-atom reactions. In our current survey, nitric oxide (NO) can now react with a heam protein to cure the meat.

Nitric oxide (NO) can gain an oxygen atom to create nitrite (NOO) and nitrite can gain an oxygen atom to create nitrate (NOOO). There is another mechanism whereby nitric oxide (NO) gains two oxygen atoms at once and nitrate (NOOO) is created directly, skipping the formation of nitrite (NOO) completely. These are all examples of oxidation reactions or gaining-an-oxygen-atom reactions.

I add another graph to explain the various ways that oxidation and reduction take place of nitrate, nitrite and nitric oxide.

Changing Perceptions

Meat curing is no longer the only industry to recognise the importance of nitric oxide. It turns out the molecule vilified for hundreds of years as purportedly being bad for us, possesses some remarkable qualities which recently became the intense subject of scientific investigation. Without it, life is not possible and the reason why few people know about it is that it has only been discovered as late as the 1980s and 1990s.

Want to know more:

Nitric oxide turns out to be an extremely important molecule.

The Biologically Essential Molecule, Nitric Oxide; Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS)

Years ago, before the importance of nitric oxide was appreciated, consumers looked upon the fact that nitrite (which is very reactive and much more poisonous than nitrate) is used in food with great scepticism. They failed to understand that in nature N (nitrogen) easily and often becomes NO (nitric oxide), NOO (nitrite) or NOOO (nitrate or saltpetre). Also, NOOO (nitrate or saltpetre) often and easily becomes NOO (nitrite) and NO (nitric oxide). Where you find NO, chances are that you will also find NOO and NOOO. Likewise, where you find NOO, you will find NO and NOOO. This is a normal part of the functioning of the human body.

The fact that nitrite is poisonous must be qualified by the statement that nitrite is poisonous under certain conditions. What exactly those conditions are will become a major focus of our study, but simply to say that because something is poisonous under specific conditions, that it is dangerous to include it in food is itself a false assertion.

During this work, I will introduce a very important comparison namely between Oxygen and Nitrogen. Oxygen is like nitrogen in that under certain conditions it is toxic and can lead to death. In fact, it can be stated that ANY cell with a nucleus, as a normal process of the metabolism of the cell, generates both reactive species of oxygen and nitrogen. (Griendling, 2016)

We understand that even oxygen has unintended negative consequences such as ageing us and causing the ultimate demise of the body despite the fact that we recognise it as foundational to life on earth. The same two-edged sword experience is what we encounter in the discipline of curing and it is extremely important to understand it and responsibly ensure that no negative environment exists that may cause the nitrogen species to be harmful to humans in any shape or form.

The facts so far are crystal clear. Nitric Oxide (NO), the curing molecule, as its cousins of nitrate or saltpetre (NOOO) and nitrite (NOO) are essential to human and animal life and the functioning of our bodies. Nitrogen is probably no more or less dangerous than oxygen.

It’s Present in our Bodies!

Green et al, (1982) gave us these interesting results of nitrate and nitrite found in our urine, saliva, plasma, gastric juices and milk which points to the fact that these compounds are ever-present in the body. It is part and parcel of human physiology!

When discussing nitric oxide which we have seen as an essential part of our biology, or whether we are talking about nitrate or even nitrite, the first thing to grasp is that these molecules are naturally part of the human body and, as you can see from the table above, they are found in our saliva and our gastric juices. There are other places they are also found on the human body, but we will get to that later. A blanket statement such as that nitrite is bad for us we can unequivocally call an incorrect statement!

Conclusion

The curing molecule is Nitric Oxide. There are different ways to produce nitric oxide. One is to start with the more stable nitrogen salt, saltpetre or nitrate (NOOO). Bacteria use nitrate or saltpetre in respiration in the absence of air and nitrite is created (NOO). Nitrite comes into contact with chemical elements which facilitates the loss of another oxygen atom which brings nitric oxide about which reacts with the protein. It is this reaction that presents itself to us as creating a pinkish/ reddish colour. Nitric Oxide, an extremely important and versatile molecule is created in the human body through a chemical reaction with the amino acid, L-Arginine. This same reaction is also mediated through bacteria added directly to the meat and fermentation becomes a very productive method to cure meat without the use of sodium nitrate or nitrate. So, nitric oxide comes to us through that which our bodies produce naturally or through our diet when we ingest either nitric oxide, nitrates or nitrites.

Stay in touch

Chapter 01: Bacon, my Teacher!

10/04/2022 eben van tonder Bacon & the Art of Living Bacon & the Art of Living, Bacon History, nitrite curing

Introduction to Bacon & the Art of Living

Bacon is more than a culinary delight! The universe chose this humble dish to be my teacher. It took many years to prepare me so that I could receive its lessons. First I had to be disillusioned. From my earliest consciousness, I was totally engrossed in my experience of life. I was taught the human mental pictures of language, religion, family, nationalism, geography, sport, school, music, history, mathematics, poetry, woodwork, war and love. At first, I believed everything. Love was unconditional, deceit was foreign, and life was simple. I must have been six or seven when I started noticing cracks in aspects of my belief system. That the worldview I was being taught was at times at odds with real life.

I wanted to figure it out and started testing using simple experiments. The first step was always to understand the system. Initially, I completely immersed myself in it. I studied the systems from within and not as an objective onlooker. I then design experiments based on the internal logic of the system. If a and b, naturally should follow c. I would change a or b or sometimes both while observing for changes in c.

The Most Elemental

In my 20s as I discovered the work of Michael E Porter and under his influence I sharpened my investigative strategy. I sought to identify the most fundamental elements which determine the essential characteristic of anything whether it is physical or abstract. The next question was this – are the fundamental elements fixed? Do they exist objectively and independently and if not, what are the things that influence their particular set of characteristics? Almost always I found such characteristics to be conditional.

This testing of anything and everything of great value and interest to me became my single-minded quest to the exclusion of any other pursuit in life. I started to appreciate the unfathomable value of old traditions. The benefit of others, infinitely more able to analyse than myself with often years of experience which I did not have. Their voices came with clarity, filtered by the sands of time into a purity that I enjoyed in my current existence that is very noisy and distracted by everything that the modern world offers.

Mental constructs which were discredited through experimentation reappeared in different perspectives as I changed my angle of looking at them. For example, I started to value the formative influence that the Christian tradition had in my life by instilling the value of disciplines like archaeology and the interpretation of ancient texts. Within the Christian framework, I wrested with the distance between us and the ancients who wrote the bible. Using the same techniques I was able to very carefully discover a body of ancient knowledge that holds the key to much of the puzzle of meat curing. I am indebted to my Christian teachers for schooling me in these. On a side note, spirituality and my connection with the mysterious “unknown” grew and I later embraced it as a valuable part of my human experience and a rich way to connect to others.

The Fog of Antiquity

The time before writing existed has a fog that obscures it from us. I discovered that the fog of millions of years contains small particles of light and reflections and just as we can know the make-up of distant stars by analysing its light, so we can decipher the knowledge of the ancients by studying the particles of the fog of antiquity. I learned that knowledge is not only acquired by sight, smell, hearing and touch but by our entire being. An example of this is my quest to know the food traditions of ancient civilisations. In Africa, I want to know the food people ate. The transmission of recipes from mother to daughter is like reciting poems or songs and carries clues about ancient times not written down anywhere. Even where I have no ancient writing to fall back on or recipes handed down I discovered that by visiting the old settlements, now uninhabited, with only ruins remaining, sitting amongst these or walking through them – the ancients would speak to me till I can see the flames of the fires where woman are preparing supper and I smell the aroma of the ancient dishes.

It was not until my 38th birthday that powers greater than me determined that the crystal that would refrac the light of the reality of everything to me would be bacon. The new world of discovery started to open up, leading me into lands I could not imagine existed. All this through my pursuit of bacon which is so mundane that nobody has bothered to write the comprehensive story of its development. It became my teacher of the marvels of the natural world.

Meat Curing’s Ancient Origins

I love the unpretentious beginnings of meat curing which is the bedrock of bacon and ham. Its secrets were initially guarded by women before artisan guilds took over as custodians of its principles and practices. The curing of meat became intimately linked with the earliest desire of humans to explore far away from their habitation. When the horse was domesticated and long-distance travel became a thing as was already the case with long sea voyages, the curing of meat was essential to ensure nutrition thus enabling the fulfilment of a basic human desire for exploration and discovery. It made international trade possible as fleets and caravans of animals and people trading their commodities around the globe relied on its power to deliver nutrition. Other more unfortunate human characteristics were likewise enabled by meat curing – the desire to dominate. Cured meat would become the staple of armies for the building of empires.

It facilitated another basic human instinct of immortality, our final destination and our relationship with the departed. Here we get the first glimpse that bacon curing is not the application of an external preservative to food or colourant to meat. The curing of bacon and hams is not something done to the meat. It is unlocking secret powers inside the meat with the aid of salts or waters or what was naturally excreted from the human and animal bodies which would then facilitate the change in the essential nature of the meat. This change in the character of the meat made it last longer, taste delicious and caused the meat to “come to life again” by changing from a dull brown to a bright pinkish/ reddish colour. The ancients found that most of the excrements of the human and animal body namely sweat and urine were powerful agents to elicit this enigmatic change in meat.

Like the power of nature which allows huge and heavy ships, laden with many tonnes of produce, people and ammunition to stay afloat by natural forces that early humans did not fully understand; yet, they mastered its application – in the same way, the ancients could appreciate the fact that the curing of meat was something natural, intimately associated with the normal, healthy functioning of the human and animal body. In this sense, it was completely different from cooking a soup where different bits of ingredients are added or the baking of bread where heat cause the parts of the bread to clump together, rise and dry out to form a new, appetising whole.

The earliest cognitive and conscious humans recognised this. Since it could bring meat back to life, could this not prevent our deceased relatives and other loved ones from decaying? Bacon and hams, the curing of meat became the bedrock which allowed mummification to develop as stories from around the world were told by travellers of corpses in distant desert lands that do not undergo decay if they are exposed to particular salts, so powerful that thousands of years later we still have these naturally mummified bodies with us. They knew what salts caused this because women used the same salts in preserving meat. They started experimenting with the salts and applied them to the deceased with astonishing success, being able, not to bring the dead to life again, but to prevent decay!

The next progression naturally followed from the previous. If it could bring old meat back to life and safeguard the deceased from decay, surely this life-giving transformation must work for the living also. So, they incorporated it into the much-prized elixir of immortality. The quest to find a cocktail that would allow us to live forever and if we could not live forever, would have the ability to stay off the outwards ravages of old age at least for a time. They not only experimented with the salts responsible for curing. They applied the same bodily experiments of sweat, urine and saliva to the skin and bathed in it as is done to this day in India where cow urine is considered holy by some. They found that it kept the skin young and prevented acne in teens.

They observed that it indeed possessed life-giving power not just for the dead, but the living also. The same elements which stimulate meat curing can heal wounds and a host of other human ailments such as the relief of chest pain. Some were able to work out that by combining curing salts with saliva, for example, its potency is enhanced many times over.

Spices had the same effect on meat especially noticed by people living in the Mediterranean and the nations around the Black sea. To this day stories persist that these people can cure meat without the salts commonly associated with curing.

Meat Curing – A Life-Giving Principle?

The ancients knew that certain salts were not the only curing agents. The millions of years separating us from them means that this knowledge was lost except in a few isolated communities where certain aspects of the trade persist in salt-only long-term curing, spice curing in Italy and Spain and drying techniques in Turkey. These are however fragmented bits of knowledge viewed as oddities and nothing more. The wonder, the life-giving aspect revealed in meat curing has for the most part been lost.

Everything related to cured meat has, however not always been positive and some linked it with disease. Humans who do not understand that the answer to the fundamental question of the most basic realities of life is not fixed, started to make absolute pronouncements on matters which are relative, depending on multiple factors. Imminent scientists from the modern world report that people who consume cured meat tend to suffer from certain ailments. They made the fatal error of concluding that cured meat is unhealthy, causing cancer. In making this assertion, they chose to ignore the fundamental importance of the curing reaction to human and mammalian existence and the complex factors which make many foods turn against our bodies. They chose simple statements that obscure truth over the wonder of complexity.

In recent years through rigorous scientific investigation, the essential role of the curing reaction in meat has been elucidated. It was discovered that the curing reaction is essential to the functioning of the body of all animals, including humans. The body has the inherent ability to create the curing reaction in response to a host of diseases and invasive enemy microorganisms and viruses. More than a defence mechanism only, the curing reaction in the body generates chemical species involved in functions such as the signalling between different parts of the body.

Most recently we discovered that microorganisms, bacteria, in particular, can create the curing reaction in meat in a way that mimics the reactions created by what came to be known as curing salts, closely linked with how our bodies create the curing reaction without the aid of salts. In other words, certain bacteria, feeding on parts inherent in meat solicits the curing reaction in the same way as curing salts, plants, spices, waters and human bodily fluids such as urine, sweat and saliva do. The basic mechanism is the same as how the body creates these reactions “by itself!” This has been a remarkable discovery and ultimately answers the question if meat curing is possible without curing salts and for that matter, without spices or plant material or human or animal bodily fluids. The answer to this question is an overwhelming “yes!”

Can Something of Infinite Benefit be Harmful?

Let’s return to the question related to a possible link between cured meat and disease and ask the important question about the health effects of cured meat as follows. Is it possible that what has been known since antiquity as having great health benefits to humans, could have detrimental effects also? This of course relates to curing salts in particular. Can millions of years of human experience be wrong about cured meat? We already eluded to the answer. The resolution of the question is in the understanding of the interconnectedness of everything. That any classification of cured meat as cancer-causing is wrong in that it incorrectly presents the conclusion as an objective statement of truth which stands independent of any other fact while it is in reality at best only a conditionally true statement. Assigning cured meat with the designation of cancer-causing these scientists reveal a lack of understanding of the interconnectedness of life and a strawman position is presented about the modern curing industry. This is a very serious error as it portrays the false use of science.

Life taught me that even a false narrative is an opportunity to learn and grow and where I at first was annoyed by this wrong view I came to appreciate it. It intensified my own search for the conditions that make cured meat either good or bad. It forced me to look deeper than I would have done and to expose the fact that under certain conditions cured meat can be dangerous just as milk or water or oxygen can be harmful to the human body under certain conditions. More than anything, these false notions trusted me in the realm of nutrition. Bacon became the doorway that taught me about the relationship between humanity and our food.

My Teacher is Bacon!

Bacon became my teacher. Worlds opened up that have been lost to time, obscured in the fog of antiquity. Meat curing’s scope of influence is breathtaking. It aided almost every great human endeavour. The loss of this knowledge is tragic and I set out to tell its story from the perspective of my discovery of its secrets.

On my many travels around the globe, I wrote letters to my kids and colleagues recounting what I am learning. I present much of the work by publishing these letters, interspersed with chapters where I advance the storyline and explain essential detail. Like bacon, I also speak from a very specific environment that impacts the presentation of the facts. The southernmost tip of the great African continent became the backdrop of my discoveries and from here I set out on a global quest to learn how to make the best bacon on earth.

In the end, bacon not only taught me about health, nutrition and science but about my relationship with the entire human race and with my family. As Bacon taught me about life, the lessons reached into the most basic realities of my existence. Its story became my own story of love and life, tragedy and triumph, deceit and manipulation by others, respect and honour, great and enduring friendships and comradery.

What follows is the story of Bacon & the Art of Living!

Stay in touch

Therapeutic Uses of Inorganic Nitrite and Nitrate – From the Past to the Future

08/23/202208/24/2022 eben van tonder The Truth About Meat Curing: What the popular media do NOT want you to know! nitrate, nitrate curing, nitrite, nitrite curing, sodium nitrite

EarthwormExpress Introduction

I present a complete paper by Anthony R. Butler and Martin Feelisch where they trace the benefits and therapeutic uses of nitrate and nitrates. It forms part of a segment in EarthwormExpress, The Truth About Meat Curing: What the popular media do NOT want you to know! Having studied the matter of the potential detrimental addition of nitrites to curing brines from a human health perspective and having examined thousands of scientific articles on the subject I came to the conclusion that most of the negative press in the popular media on the subject is irrational and based on a partial evaluation of the salient points related to the issue.

Circulation

Volume 117, Issue 16, 22 April 2008; Pages 2151-2159

https://doi.org/10.1161/CIRCULATIONAHA.107.753814

Online published: Therapeutic Uses of Inorganic Nitrite and Nitrate

Abstract

Potential carcinogenic effects, blue baby syndrome, and occasional intoxications caused by nitrite, as well as the suspected health risks related to fertilizer overuse, contributed to the negative image that inorganic nitrite and nitrate have had for decades. Recent experimental studies related to the molecular interaction between nitrite and heme proteins in blood and tissues, the potential role of nitrite in hypoxic vasodilatation, and an unexpected protective action of nitrite against ischemia/reperfusion injury, however, paint a different picture and have led to a renewed interest in the physiological and pharmacological properties of nitrite and nitrate. The range of effects reported suggests that these simple oxyanions of nitrogen have a much richer profile of biological actions than hitherto assumed, and several efforts are currently underway to investigate possible beneficial effects in the clinical arena. We provide here a brief historical account of the medical uses of nitrite and nitrate over the centuries that may serve as a basis for a careful reassessment of the health implications of their exposure and intake and may inform investigations into their therapeutic potential in the future.

The presence of nitrite (NO₂⁻) and nitrate (NO₃⁻) in bodily fluids has been known for some time. Dietary studies carried out by Mitchell et al¹ at the beginning of the 20th century established that the amounts of nitrate excreted in the urine are higher than those ingested with the food, suggesting that the excess nitrate must be a product of endogenous biosynthesis. Later metabolic balance studies by Green et al^2,3 showed that this assumption was correct and provided unequivocal evidence for mammalian nitrate biosynthesis. Griess,⁴ using his eponymous chemical test, showed that human saliva contains small quantities of nitrite, and the detection of very high levels of nitrite in the urine of a volunteer, who happened to have contracted a fever, was the first indication that endogenous production of nitric oxide (NO) is part of the immune response. Nitrite is not normally present in urine, and it was Cruickshank and Moyes⁵ who realized that it originated from bacterial reduction of urinary nitrate, an observation that forms the basis of today’s dipstick tests for urinary tract infection. Shortly after the discovery by Palmer et al⁶ that vascular endothelial cells produce NO from l-arginine, Marletta et al⁷ reported that the same pathway accounts for the production of nitrite and nitrate by activated macrophages, and countless investigators have since used nitrite and nitrate to assess NO production in basic and translational research studies. More recently, the ease with which nitrate is reduced to nitrite and nitrite is converted into NO has occasioned interest in the role of plasma nitrite in vascular smooth muscle relaxation,⁸ the control of blood pressure and flow,⁸ and possible therapeutic uses of nitrite.^9,10 Subsequent animal experimental studies revealed that a number of organs are protected against ischemia/reperfusion-related tissue injury after systemic application of small amounts of nitrite,¹¹ suggesting further therapeutic uses. Strangely, this renewed interest in nitrite/nitrate, together with emerging data suggesting possible new roles for these anions in physiology, coincides with the conclusion by the International Agency for Research on Cancer that “ingested nitrate or nitrite under conditions that result in endogenous nitrosation is probably carcinogenic for humans.”¹² The purpose of this review is neither to consider the physiological role of naturally occurring nitrite and nitrate in organs and bodily fluids or their usefulness as biomarkers of NO activity nor to discuss their possible role as carcinogens; rather, it is to explore the uses of inorganic nitrite and nitrate in medicine, not only modern medicine but also medicine of the past. It transpires that medical interest in these oxyanions of nitrogen is not new.

Discovery and Chemical Properties

Nitrates, particularly potassium nitrate (known also as niter or nitre and saltpeter), have been known since prehistoric times, and in the Middle Ages, natural deposits were commercially exploited. The Chinese invented gunpowder around 800 CE, and with its appearance in Europe during the 13th century, potassium nitrate became strategically important. Demand increased further with the Agricultural Revolution of the 19th century and the use of nitrates as fertilizers. Natural sources were eventually supplemented by synthetically produced nitrate at the beginning of the last century.¹³

Nitrite is present at trace levels in soil, natural waters, and plant and animal tissues. In pure form, nitrite was first made by the prolific Swedish chemist Scheele¹⁴ working in the laboratory of his pharmacy in the market town of Köping. He heated potassium nitrate at red heat for half an hour and obtained what he recognized as a new “salt.” The 2 compounds (potassium nitrate and nitrite) were characterized by Péligot¹⁵ and the reaction established as 2KNO₃→2KNO₂+O₂.

The release of oxygen from a substance known to alchemists as “aerial niter” since the times of Paracelsus explains the role of nitrates in gunpowder, rocket propellants, and other explosives.¹⁶ Sodium nitrite rapidly gained importance in the development of organic chemistry during the 19th century, when it was discovered that nitrous acid (HNO₂) reacts with aromatic amines (ArNH₂) to produce diazonium ions,¹⁷ a highly important synthon for the dyestuffs industry and for synthetic organic chemistry generally: ArNH₂+HNO₂+H⁺→ArN=N⁺+2H₂0.

The mechanism of such diazotization reactions has been subject to extensive study.¹⁸ Diazotization may be responsible, in part, for the carcinogenic role of nitrite under certain conditions, particularly in the context of drug-nitrite interactions.¹⁹

Nitric acid (HNO₃) is a strong acid that is completely ionized at all biologically interesting pHs. Although nitrous acid (HNO₂) is a weak acid, with a pK_a of 3.15 (pK_a is the pH at which the acid is 50% dissociated), it is also, at physiological pHs, completely dissociated, except in the stomach, on the surface of airways, within select cellular compartments (eg, the mitochondrial intermembrane space, endosomes, secretory vesicles, lysosomes, and other acidic organelles), and on the skin.

Nitrite as a Vasodilator

The scope of this review is limited to inorganic nitrite and nitrate, but interest in a medical role for inorganic nitrite was first aroused because of the spectacular success of organic nitrites and related compounds in the treatment of angina pectoris. Butter,²⁰ writing about the treatment of angina in 1791, gave no drug treatment and had little more to offer than the recommendation of a tranquil lifestyle. However, while working at the Edinburgh Royal Infirmary in the 1860s, Brunton²¹ noted that the pain of angina could be lessened by venesection and wrongly concluded that the pain must be due to elevated blood pressure. As a treatment for angina, the reduction of circulating blood by venesection was inconvenient. Therefore, he decided to try the effect on a patient of inhaling amyl nitrite, a recently synthesized compound and one that his colleague had shown lowered blood pressure in animals (A. Gamgee, unpublished observation). The result was dramatic.²¹ Pain associated with an anginal attack disappeared rapidly, and the effect lasted for several minutes, generally long enough for the patient to recover by resting. For a time, amyl nitrite was the favored treatment for angina, but its volatility made it troublesome to administer, and it was soon replaced by chemically related compounds that had the same effect but were less volatile. The most popular replacement was glyceryl trinitrate (GTN), an organic nitrate better known as nitroglycerin.²² The fact that this compound is highly explosive and a component of dynamite appears not to have been a problem. In his 1894 textbook, Phillips²³ lists a number of chemically related compounds that can be used in the treatment of angina. The list includes not only amyl nitrite but also propyl, ethyl, and isobutyl nitrites, as well as GTN. A similar list is provided by White²⁴ in his 1899 textbook. GTN, a drug introduced into allopathic medicine thanks to extensive homoeopathic studies by Hahnemann,25 occasioned greatest favour among practising physicians, and by 1956, in a symposium on hypotensive drugs,26 it was the only drug of this type that was listed. GTN was first synthesized by Sobrero at the University of Torino in 1812, and considering the way in which he handled it, he was fortunate not to cause a fatal accident.27 He thought it too explosively violent to have any practical use. Nobel, the highly successful Swedish entrepreneur, was able to moderate its action by incorporating it into kieselguhr to form dynamite. It is largely from this invention that the Nobel family fortune is derived. Tragically, Nobel’s younger brother Emil was killed while working with GTN, a dark episode in Nobel’s life. Sobrero bitterly resented Nobel’s commercial success with what he saw as his invention, although Nobel always acknowledged his debt to Sobrero.28 It is a curious coincidence that by 1895 Nobel had developed angina and was prescribed GTN as treatment, but it is a happier coincidence that the 1998 Nobel Prize for Physiology or Medicine was awarded for the discovery of the role of NO as a signalling molecule in the cardiovascular system. Now that NO is known to be an important vasorelaxant, it is easy to see why drugs of this type act the way they do. Each is a substrate for ≥1 enzyme systems, possibly located in the vascular wall, that convert it into nitrite and subsequently to NO. One such enzyme, a mitochondrial aldehyde dehydrogenase, has been purified and partially characterized.²⁹ However, the contribution of this or other enzyme systems to the overall vasodilation by these drugs is difficult to assess because multiple metabolic pathways appear to act in concert.³⁰

In view of the range of organic nitrites and related compounds that act as vasodilators, it is not surprising that potassium and sodium nitrites were tested in this regard. In 1880, Reichert and Mitchell³¹ published a very full account of the biological action of potassium nitrite on humans and animals. At that time, the value of amyl nitrite in the treatment of angina was severely compromised by the short duration of its effect, so the search for an improved drug had begun. The effect of potassium nitrite on the nervous system, brain, spinal cord, pulse, arterial blood pressure, and respiration of healthy human volunteers was noted, as was the variability between individuals. The most significant observation was that even a small dose of <0.5 grains (≈30 mg) given by mouth caused, at first, an increase in arterial blood pressure, followed by a moderate decrease. With larger doses, pronounced hypotension ensued. They also noted that potassium nitrite, however administered, had a profound effect on the appearance and oxygen-carrying capacity of the blood. They compared the biological action of potassium nitrite with that of amyl and ethyl nitrites and concluded, rather interestingly, that the similarity of action depends on the conversion of organic nitrites to nitrous acid. Observations similar to those of Reichert and Mitchell were made by Atkinson³² and Densham.³³ Practicing physicians, including Hay³⁴ and Leech,³⁵ examined the therapeutic value of inorganic nitrites as hypotensive drugs and noted that, although of slower onset, their therapeutic effect lasts much longer, and they might be seen as superior drugs. They soon appeared in the Materia Medica of the time. In 1906, the drug supplier Squibb sold a 1-lb bottle of sodium nitrite (sodii nitris) for $1,³⁶ and by the mid-1920s, an injectable solution of sodium nitrite became available (Nitroskleran, E. Tosse & Co, Hamburg, Germany) for the treatment of hypertension and vasospasm.³⁷ Instructions for using sodium nitrite to treat angina are given in Martindale’s Additional Pharmacopoeia and in the US National Standard Dispensatory of 1905.³⁸ A textbook on Materia Medica for medical students in 1921 gives details of the appropriate dose,³⁹ but by the middle of the 20th century, its medicinal use had essentially ceased, largely because of adverse side effects. Blumgarten⁴⁰ noted that sodium and potassium nitrites often caused nausea, belching, stomachache, and diarrhoea. Although these side effects may have caused physicians to hesitate in prescribing sodium nitrite for angina, another event precipitated the fall of inorganic nitrite from favour (see below).

Interest in the vasodilator properties of nitrite enjoyed a renaissance with the notion that nitrite may be involved in the regulation of local blood flow after conversion to NO by nonenzymatic mechanisms^41,42 and an oxygen-sensitive nitrite-reductase⁴³ and S-nitrosothiol–synthase⁴⁴ function of haemoglobin. Like NO, inhaled nebulized nitrite has been shown to be an effective pulmonary vasodilator⁴⁵ and, along with organic nitrites,⁴⁶ suggested for potential use in neonatal pulmonary hypertension. Although there is no doubt that appropriate pharmacological doses of nitrite can normalize elevated blood pressure,⁴⁷ the question of whether physiological concentrations of nitrite are vasodilator active is still a matter of debate.^48,49

Conversion of Nitrite Into NO and NO-Related Products

In view of the close chemical connection between nitrite and NO, it is tempting to assume that nitrite acts as a source of NO when functioning as a vasodilator. However, such conversion requires either strongly acidic conditions or enzymatic catalysis. At low pH, nitrous acid can give rise to the spontaneous generation of NO: 2HNO₂→H₂O+N₂O₃ and N₂O₃→NO+NO₂.

Solutions of acidified nitrite have been used successfully to generate NO and to induce vasorelaxation in isolated blood vessel studies,⁵⁰ and the same reaction mechanism has been proposed to explain the biological action of nitrite.^51,52 However, pHs at which this occurs are generally not found within living systems,⁵³ with the exceptions mentioned above. On the other hand, the enzyme xanthine oxidoreductase converts nitrite into NO when oxygen levels are low, and this is a more likely course of action⁵⁴ in the vascular system, at least under ischemic conditions. In fact, recent data suggest that hypoxic NO formation from nitrite is carried out by multiple enzyme systems¹⁰ and occurs in virtually all tissues and organs (Feelisch et al, unpublished data, 2006). Independently of its reduction to NO, nitrite is converted into NO-related products, including S-nitrosothiols and NO-heme species, at normal physiological pH and oxygen levels.⁵⁵ Although it cannot be excluded that some of the biological effects of nitrite may be mediated by nitrite itself, it is fair to assume that most of the physiological and therapeutic actions of nitrite that require conversion into NO and NO-related products involve enzymatic catalysis.

Nitrite as an Antidote for Cyanide and Hydrogen Sulfide Poisoning

In popular literature, cyanide (CN⁻) is considered the acme of human poisons. In fact, it is by no means the most poisonous substance generally available, but it acts very rapidly, and it is on this rapid action that its reputation rests. Large doses cause instant death; even with low doses, the characteristic symptoms of cyanide poisoning (loss of consciousness, motionless eyes, dilated pupils, cold skin, and sluggish pulse and respiration) appear within seconds. Despite the catastrophic consequences of an overdose, potassium cyanide was used in medicine for many years as a treatment for chest complaints,⁵⁶ particularly a dry cough.⁵⁷ It was not removed from the British Pharmacopoeia until 1945.

By the end of the 19th century, it was established that the toxicity of cyanide was due to interference with the process of cellular respiration.⁵⁸ Keilin⁵⁹ showed that cyanide reacts with the ferric heme of the enzyme cytochrome c oxidase, a vital link between the tricarboxylic acid cycle and formation of metabolic water causing inhibition of mitochondrial respiration. Because cyanide also reacts with methemoglobin,⁶⁰ it should be possible to prevent the reaction of cyanide with cytochrome c oxidase by massively increasing the concentration of methemoglobin in the blood. Nitrite oxidizes the central iron atom of haemoglobin from the ferrous (Fe2+) to the ferric (Fe3+) state, producing methemoglobin, and is, therefore, a potential antidote for cyanide poisoning. The clinical use of nitrite in this setting was first proposed by Hug⁶¹ and is now universally used. Sodium thiosulfate also is included in the antidote to provide a source of sulfur to aid the conversion of cyanide into thiocyanate by rhodanese. The first cases of acute cyanide poisoning in humans to be treated with nitrite and thiosulfate were reported in 1934. One patient had ingested 5 g potassium cyanide but recovered after being given 1.5 g sodium nitrite and 18 g sodium thiosulfate.⁶² In many countries, nitrite is part of the cyanide antidote kit. Nowadays, patients are given an ampoule of amyl nitrite by inhalation or an intravenous injection of 3% sodium nitrite, followed by a slow injection of 50% sodium thiosulfate.⁶³

Although formation of methemoglobin is generally accepted as the explanation of the efficacy of nitrite as an antidote, evidence suggests that this is not the complete explanation.^64,65 There may be alternative or additional routes whereby nitrite detoxifies, but no details are available.⁶⁶ Compounds that promote NO release in vivo (like bradykinin) modify cyanide toxicity. Whether this is an alternative mode of action of nitrite in detoxification or just another source of nitrite from endogenous NO is, at this time, difficult to assess.

Nitrite also is an efficacious antidote to poisoning by hydrogen sulfide (H₂S), an occupational hazard with high lethality and long-term neurological sequelae in survivors. Like NO and CO, low concentrations of H₂S are produced endogenously and have vasodilator properties, but the physiological significance of its formation is currently unknown.⁶⁷ Supraphysiological concentrations of sulfide, as experienced after H₂S inhalation, lead to rapid inhibition of mitochondrial respiration by reversible binding to the central iron atom of cytochrome c oxidase in place of oxygen, explaining why H₂S poisoning shares many similarities with cyanide intoxication.⁶⁸ Nitrite administration, which is superior to that of oxygen alone⁶⁹ and often is combined with hyperbaric oxygen therapy, is most effective when given immediately after H₂S exposure.⁷⁰ It is thought to act via induction of methemoglobinemia and subsequent binding of hydrosulfide anions (HS⁻) to the oxidized blood pigment, leading to inhibition of cytochrome c oxidase and reinstitution of aerobic respiration in the tissues. Although this mode of action appears reasonable, the rather slow rate of methemoglobin formation by nitrite is inconsistent with the rapid recovery typically observed in the clinical setting, suggesting, as with the treatment of cyanide poisoning, the involvement of additional mechanisms. Although nitrite has been known for many years to have protective and antidotal effects against experimental sulfide poisoning in rodents,⁷¹ nitrite administration for H₂S intoxication was introduced into human therapy only in the mid-1970s.⁷² The recommended dosage regimen for nitrite in sulfide intoxication is identical to that established for the treatment of cyanide poisoning, ie, initiation with inhalations of amyl nitrite followed by intravenous injection of 10 mL of a 3% solution of sodium nitrite.⁷³

Other Medical Uses of Inorganic Nitrite

In view of the success of nitrite with angina, it was tried for the treatment of other medical conditions. Law⁷⁴ recommended the administration of very large doses (20 grains or 1.3 g) of sodium nitrite to treat epilepsy. Other physicians tried this dose and found that the side effects were far too serious to continue the treatment, with considerable consequences for the therapeutic use of inorganic nitrite. The toxic nature of such high doses was confirmed by Ringer and Murrell,⁷⁵ who concluded that Law had been using an impure sample of sodium nitrite that was largely sodium nitrate. They attempted to establish a safe dose, but the reputation of sodium nitrite had suffered, and because of the success of GTN, nitrite disappeared from widespread use. The final blow came when Magee and Barnes¹⁹ reported that certain nitrosamines, which could be formed in the stomach by reaction between nitrite and naturally occurring secondary amines in food, are strongly carcinogenic in rodents. Although these findings were quickly confirmed by others and have been extended to other animal species, a causal relationship between nitrite and nitrate exposure and human cancer has not been unequivocally demonstrated.⁷⁶ Nevertheless, further medical use of nitrite ceased for decades, except as an antidote in emergencies, and maximal contaminant levels of nitrite and nitrate levels in drinking water and foods soon became strictly regulated in most countries worldwide. In light of the negative image, nitrite has acquired over the years, it is somewhat surprising that the use of nitrite as an antibacterial agent in canned food has continued. More recently, the antimicrobial properties of nitrite that form the basis for its use in food preservation have been explored for potential benefit in lung and skin diseases.

Acidified Nitrite

Acidification is a prerequisite for nitrite to act as an antimicrobial agent, suggesting (albeit not proving) that the active principle is NO. It has been known for some time that the nitrite found in human saliva originates from nitrate that is actively secreted into the oral cavity and gets partially reduced there by the local commensal bacterial flora.⁷⁷ After swallowing, nitrite ends up in the acidic environment of the stomach, and the NO thus produced is thought to contribute to the antibacterial effects of gastric juice. Similarly, the nitrite produced from nitrate in sweat is believed to exert antimicrobial effects on the surface of the skin.⁷⁸ Thus, acidified nitrite may be a component of innate immunity at several locations on and within the body. Some attempts to capitalize on this insight point in potentially promising therapeutic directions, although few of these findings have made their way into the clinic.

The effectiveness of acidified nitrite in killing antibiotic-resistant Pseudomonas bacteria might offer a possibility to eradicate a major cause for chronic lung infections in cystic fibrosis patients,⁷⁹ provided a safe mode of administration can be found. The antimicrobial properties of NO can be exploited by dermal application of creams containing nitrite and an acidifying agent, eg, ascorbic acid, to treat a number of skin diseases.⁸⁰ The same concept has been demonstrated to increase microcirculatory blood flow in Raynaud patients^81,82 and to accelerate wound healing.⁸³ Although the effects of acidified nitrite are typically ascribed to the generation of NO, the possibility that part of the nitrite applied is absorbed and converted into NO-related products in the tissue cannot be excluded.

Use of Inorganic Nitrate in Medicine

Although modern manuals of Materia Medica and pharmacopeias state that potassium nitrate has no drug action other than as a diuretic (see below), historical records show that it has been used extensively in medicine over the years to treat a number of conditions. In view of the close chemical relationship between nitrite and nitrate, we suggest that the value of inorganic nitrate in medicine is due, at least in part, to its conversion into nitrite during administration or contamination with nitrite because of the manner in which it was manufactured.

Niter occurs in natural deposits in desert regions. Fairly large amounts are found in the northwestern provinces of China, and it was well known to early Chinese alchemists. They called it xiao shi (solve stone), and it was first recognized in the 4th century CE. It was a component of some of the elixirs of immortality concocted by Daoist savants as they searched for a means of realizing the Daoist ideal of life without death.⁸⁴ Entirely by chance, they mixed it with sulfur and charcoal and thus created gunpowder, which was used by the Chinese not only for fireworks but also for civil engineering and warfare. The first printed formula for gunpowder occurs in a Chinese manual of war that appeared in 1044 CE.

One of the oldest accounts of the use of niter in Chinese medicine is as a treatment for what appears to be angina in an 8th century Chinese manuscript uncovered at the Buddhist grotto of Dunhuang.⁸⁵ The patient is instructed to take niter, hold it under the tongue for a time, and then swallow the saliva. The significance of the instructions is that under the tongue, even in a healthy mouth, nitrate-reducing bacteria convert some of the nitrate into nitrite.^77,86 So, if the patient follows the physician’s instructions fully, he or she will be taking in nitrite, known to be a treatment for the alleviation of anginal pain.

Arab physicians were among the most advanced of the medieval period, but there is no mention of niter in a book on cardiac drugs by Avicenna, born 980 CE. The first extant Arabic mention of niter occurs in a book by Kitab al-Jami’fi al-Adwiya al-Mufrada (Book of the Assembly of Medical Simples) finished by Abu-Muhammad al-Malaqi Ibn al-Baitar around CE 1240. Niter was called Thalji al-Sin (Chinese snow), indicating the contact between Chinese and Arab civilizations. It was about this time that Arabs started to use niter in gunpowder and as a component of prescriptions.

Niter does not occur naturally to any great extent in Europe, and the efficacious use of niter in early European medicine is easier to understand if one realizes how the niter was produced. When gunpowder became known in Europe (Roger Bacon mentions it in 1240 CE), there was enormous demand for niter, and much was shipped to Europe from India, where it occurs in natural deposits. But, the demand outstripped supply, and indigenous manufacture was started. It was made in plantations or “nitriaries,” particularly in France and Germany. Natural conditions were simulated by exposing heaps of decaying organic matter mixed with lime to atmospheric action.⁸⁷ Nitrates appeared as efflorescences and were converted into potassium salt by reaction with potassium carbonate (potash). Two groups of bacteria are responsible for this process: Nitrosomonas convert ammonia into nitrite, and Nitrobacter convert nitrite into nitrate.⁸⁸ It is quite possible that niter from nitriaries contained some nitrite, thus giving it medicinal value. This is unlikely in niter from natural deposits because they are old and aerial oxidation will, over time, convert all the nitrite into nitrate. So, the 8th century Chinese physician mentioned previously had to instruct the patient on how to generate nitrite, but European physicians of the 14th to 17th centuries, using niter from a different source, could prescribe it without further refinement because nitrite was there already.

However, such a prescription was rather hit-or-miss in that the amount of nitrite present was a matter of chance. In one of the most comprehensive accounts of the use of niter, methods of making it more effective are described. The book, by Challoner, was printed in London in 1584 and entitled A Short Discourse of the Most Rare and Excellent Vertue of Nitre.⁸⁹ The spelling of the English is idiosyncratic (rather like that of modern students) because spelling was not fully standardized until the publication of Johnson’s dictionary in 1775. Challoner’s book is concerned mainly with the value of niter in treating various dermatological conditions (“diseases of the skinne”), including “tawnie steynings, freckles, duskness and flegmatike evaporations.” It will, he claims, “restore the skinne and complexion to the native bewtie.” The key to understanding this claim lies in the first section of the book in which the author tells his readers how to make niter more effective (“yet more sharpe and subtile”). He describes 3 ways, all involving heating (called “calcination” by Challoner). Heat, of course, converts some of the niter into potassium nitrite, and so, without realizing it, Challoner anticipated the discovery of potassium nitrite by Scheele by nearly 200 years. As discussed above, nitrite has an antibacterial effect and accelerates wound healing, hence its effectiveness on infected skin blemishes (“skales, scrabbes, skurffe, dandruffe, pimples, tetters, bytes” and so on). Naturally occurring nitrite in saliva has the same effect and explains, in part, why most animals instinctively lick a wound.⁹⁰

Challoner does not stop with the application of niter to the skin. He claims that it can be used “for uncumbring and clensing of the lunges” and for the “remedie of hoarnesses, olde coughe and toughe coughe, weising in the windpipes,” and so on. For this use, he suggests making the niter into a pill and then “hold one of those pilles lounge under the tongue, to mixe thereof as much as may be with the moisture of the mouth … and lastlie swallow it,” a procedure curiously reminiscent of the Chinese prescription and anticipating some of the work of Lundberg et al.⁷⁷

Nitrate and the Treatment of Lung Diseases

For a time, amyl nitrite was used for relieving patients suffering an asthma attack. In an article⁹¹ in 1891, other nitrites, including sodium nitrite, were suggested for this purpose. The author remarks that the use of nitrites is not the treatment of choice but that it is said to be beneficial, probably by virtue of its smooth muscle–relaxing effects. However, relief could be delivered even better by a procedure using nitrate rather than nitrite. Blotting paper was soaked in a solution of niter and allowed to dry. Squares of the paper were burnt in a jar, and the patient inhaled the fumes. Apparently, this procedure was frequently successful in relaxing a bronchial spasm. It was first published as a patent in 1867,⁹² is described in detail in the Encyclopedia Britannica of 1911,⁹³ and occurred as recently as 1926 in the US Dispensatory.⁹⁴ The products of thermal decomposition of niter include NO, NO₂, and O₂.⁹⁵ Because NO is a poor bronchodilator and NO₂ is toxic, it is difficult to see how inhalation of this mixture brings relief. The combination possibly has an effect that is greater than the sum of its parts.

In addition to its use in asthma, sodium nitrate was given orally to treat chronic bronchitis.⁹⁶ It is unclear whether the apparent effectiveness of this treatment was secondary to its conversion to nitrite causing bronchial relaxation and antibacterial effects or due to an effect of nitrate itself.

Nitrates as Diuretics

Nitrates have been used as diuretics for centuries. One of the first descriptions of the medical use of potassium nitrate for the treatment of dropsy (edema) is found in Thomas Willis’ Pharmaceutice Rationalis of 1674.⁹⁷ Although it was long known that relatively large amounts (grams) were required to achieve effective diuresis, the dose-response relationship was first established in systematic “homeopathic provings” in 1825.⁹⁸ Clear differences in potency exist between various nitrate salts,⁹⁹ with ammonium nitrate being the most effective. Their mode of action was revealed by studies in dogs demonstrating an enhanced excretion of urinary chloride and sodium, resulting in a net loss of salt and water caused by increased glomerular filtration without an equivalent increase in tubular reabsorption.^100,101 Whether these effects are mediated by formation of nitrite or NO is unknown.

Extensive animal and human studies by Keith et al¹⁰² confirmed the superiority of the ammonium over the sodium salt of nitrate. They also demonstrated that nitrates can potentiate the effects of other diuretics and that toxic symptoms are remarkably rare, even when administered in doses of 10 to 15 g daily for several weeks. Thus, ammonium nitrate was introduced as a new, more effective diuretic in 1926 and was used with great success to treat various forms of edema in North America, particularly at the Mayo Clinic. After a time of exaggerated emphasis on possible toxic effects of nitrates during the preceding 2 decades, which led physicians to use lower, inadequate doses, it looked as though ammonium nitrate was here to stay as the diuretic of choice. What had triggered the fear of inducing severe cyanosis when potassium or sodium nitrate was used as a diuretic before was the toxicity associated with the use of massive amounts of bismuth subnitrate for diagnostic purposes,¹⁰³ which is somewhat surprising because the toxicity of large amounts of nitrate was well known for a long time.¹⁰⁴ Concerns about the safety of nitrates reached a new height with the appearance of case reports about transient methemoglobinemia after administration of ammonium nitrate.^105,106 The reasons for these rare complications (which disappeared on discontinuation of nitrate therapy in most cases) remain unclear but may have been due to contamination of the nitrate salt with nitrite, renal insufficiency causing elevated circulating levels of nitrate, or gastrointestinal disorders with enhanced reduction of nitrate to nitrite by the bacterial gut flora.¹⁰⁷ With alternative diuretics in the form of organic mercurials available, the therapeutic use of nitrates as diuretics was abandoned by the mid-1930s.

Nitrate in Other Medicinal Preparations

The fact that most nitrate salts are readily water soluble has been exploited to produce medicines that require quick dissolution or application in liquid form. Although the effects of most of these drugs (eg, cerium and silver nitrate) have little to do with the amounts of nitrate they contain, application of large enough quantities can cause methemoglobinemia.¹⁰⁸ Presumably, the same holds true for the excessive use of toothpastes aimed at treating dental hypersensitivity, some of which contain up to 10% potassium nitrate, although no intoxication from this source is documented in the literature.

Conclusions and Outlook

Despite the widespread use of sometimes astonishing amounts of nitrite and nitrate for different indications in medicine of the past, little use is made of them in contemporary medicine (except as antidote and solubility enhancer). This is a result of several factors, some of which we have described in this review. Apart from the replacement by more modern and effective medicines in some cases, the major driving force for this development appears to have been the fear fostered by discussions, in both the lay press and scientific literature, about the purported health risks of exposure to nitrite and nitrate. Reports about methemoglobinemia in infants caused by drinks or food prepared with nitrate-rich (and bacterially contaminated) well water and vegetables such as spinach, celery, and carrots (“blue baby syndrome”), intentional and occupational intoxications in adults, increasing nitrate levels in soil and lakes as a result of fertilizer overuse, and the formation of potentially carcinogenic N-nitrosamines all contributed to the negative image that nitrite and nitrate have held in recent years. As a result, major efforts have been made to remove as much nitrite and nitrate as possible from our drinking water, to advocate replacement of nitrite by other (often less effective) food preservatives, and to establish cultivation conditions that result in crops with reduced levels of nitrate. Although possible long-term consequences of a chronically reduced intake of nitrite and nitrate on human health are unknown, doubts have been raised about the general health risk of nitrite/nitrate intake.^76,109–112 Interestingly, the average dietary intake of nitrate roughly equals that produced by the endogenous production of NO.¹¹³ Thus, if nitrite truly were of concern to human health because of its propensity to form carcinogenic nitrosamines, then the human body would have a significant evolutionary design flaw because ≈5% of all ingested and endogenously produced nitrate eventually ends up as nitrite in the stomach, as pointed out by Archer¹⁰⁹ (so far about “intelligent design”). Despite the critical voices, the image of nitrite and nitrate remains stigmatized.

What appears to have the greatest potential to change our current perception of the risk and value of nitrite and nitrate is the most recent emergence of data on the physiological and pharmacological effects of relatively low concentrations/doses of nitrite. Previously considered a biologically inert oxidative decomposition product of NO, nitrite has been proposed to be a signalling molecule in its own right.55 Given its propensity for conversion into NO and related species, unequivocal evidence for this role may be difficult to provide unless nitrite-specific signalling pathways are identified. Although speculative, it is possible that the nitrite-based reaction channels of contemporary mammalian cells are a vestige of earlier bacterial pathways and that the evolutionarily more recent l-arginine/NO pathway uses signalling cascades originally evolved for nitrite, not the other way round. Regardless, surprisingly low amounts of nitrite have been demonstrated to exert potent cytoprotective effects against ischemia/reperfusion-related tissue damage in vivo,10,11 an action possibly mediated by modulation of mitochondrial function.113 Nitrate, which has been proposed to contribute to the health-promoting effects of the Mediterranean diet,114 has been demonstrated to inhibit platelet aggregation,115 to mildly lower blood pressure,116 to enhance gastric mucosal defence mechanisms,¹⁰⁷ and to reduce the oxygen cost of exercise.¹¹⁷ The last is perhaps one of the most surprising of the more recent findings across the spectrum of nitrate actions. This particular observation may explain why an enhanced production of NO, which not only elevates blood flow and thus oxygen transport to tissues but leads to increased levels of circulating nitrite and nitrate, is crucial for the adaptation of life to the chronic hypoxia experienced at high altitude.¹¹⁸ Taken together, these results have shifted the attention away from toxic and vasodilator properties to a focus on metabolic effects. Moreover, they make one wonder to what extent inorganic nitrate may contribute to the effectiveness of organic nitrates in the setting of heart failure, for example.

Although efforts are underway to assess the potential usefulness of inorganic nitrite in a number of clinical research studies at the US National Institutes of Health, none of these are likely to whet the appetite of the pharmaceutical industry to invest substantial amounts of money into drug development because not only are intellectual property claims related to simple inorganic compounds legally difficult to defend but the material itself is cheap and readily available. The situation may change if medicinal chemists come up with new prodrugs that allow targeted delivery of nitrite to specific tissues or organs or if nitrite/nitrate is intelligently used as an adjuvant to current therapeutics. Which of the many facets of nitrite and nitrate action is likely to form the basis for future pharmaceutical exploitation is difficult to predict at present. Although rational approaches to the pharmacological treatment of medical problems have a tendency to ridicule the wisdom of century-old folk medicine and to condemn the alchemist’s doing as quackery, there is much to learn from the past. In reviewing the therapeutic use of nitrite and nitrate over centuries, it appears that some of the potential that these simple compounds may hold for medical use has not been realized, often because the basis for some unwanted drug effects was not understood and thus could not be controlled at the time. But, even if the scare factor continues to dominate mainstream thinking, there is an obvious need for a careful reassessment of the health risks of nitrite and nitrate. If initiated soon, such activity may provide the necessary “activation energy” to overcome the fear and to stimulate the development of new therapeutic principles that use pathways regulated by nitrite and nitrate.

Sources of Funding

This work was supported by funds from the Guthrie Trust (a travel grant for visiting the Wellcome History of Medicine Library in London to Dr Butler) and the Medical Research Council (Strategic Appointment Scheme to Dr Feelisch).

Disclosures

None.

Footnotes

Correspondence to Anthony R. Butler, Bute Medical School, University of St. Andrews, St. Andrews, Fife, KY16 9ST, Scotland (e-mail arb3@st-andrews.ac.uk); or Martin Feelisch, Clinical Sciences Research Institute, Warwick Medical School, Gibbet Hill Rd, Coventry, CV4 7AL, England (e-mail mf@warwick.ac.uk).

References

1 Mitchell HH, Shonle HA, Grindley HS. The origin of nitrates in urine. J Biol Chem. 1916; 24: 461–490.Crossref Google Scholar
2 Green LC, Tannenbaum SR, Goldman P. Nitrate synthesis in the germfree and conventional rat. Science. 1981; 212: 56–58.Crossref Medline Google Scholar
3 Green LC, Ruiz de Luzuriaga K, Wagner DA, Rand W, Istfan N, Young VR, Tannenbaum SR. Nitrate biosynthesis in man. Proc Natl Acad Sci U S A. 1981; 78: 7764–7768.Crossref Medline Google Scholar
4 Griess P. Über Metadiamidobenzol als Regens auf Saltpetrige Säure. Chem Ber. 1878; 11: 624–627.Crossref Google Scholar
5 Cruickshank J, Moyes JM. The presence and significance of nitrites in urine. BMJ. 1914; 2: 712–713.Google Scholar
6 Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988; 333: 664–666.Crossref Medline Google Scholar
7 Marletta MA, Yoon PS, Iyengar R, Leaf CD, Wishnok JS. Macrophage oxidation of l-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988; 27: 8706–8711.Crossref Medline Google Scholar
8 Gladwin MT, Shelhammer JH, Schechter AN, Pease-Fye ME, Waciawiw MA, Panza JA, Ognibene FP, Cannon RO. Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans. Proc Natl Acad Sci U S A. 2000; 97: 11482–11487.Crossref Medline Google Scholar
9 Dejam A, Hunter CJ, Tremonti C, Pluta RM, Hon YY, Grimes G, Partovi K, Pelletier MM, Oldfield EH, Cannon RO, Schechter AN, Gladwin MT. Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formation. Circulation. 2007; 116: 1821–1831.Link Google Scholar
10 Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008; 7: 156–167.Crossref Medline Google Scholar
11 Dezfulian C, Raat N, Shiva S, Gladwin MT. Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics. Cardiovasc Res. 2007; 75: 327–338.Crossref Medline Google Scholar
12Ingested Nitrates and Nitrites. Lyon, France: International Agency for Research on Cancer; 2007. IARC Monographs volume 94. Available at: http://monographs.iarc.fr/ENG/Meetings/94-nitratenitrite.pdf. Accessed September 4, 2007.Google Scholar
13 Barnum DW. Some history of nitrates. J Chem Ed. 2003; 80: 1393–1396.Crossref Google Scholar
14 Scheele CW. Chemische Abhandlung von der Luft und dem Feuer. Upsala, Sweden: M. Swederus; 1777.Google Scholar
15 Péligot E. Sur l’acide hypoazotique et sur l’acide azoteux. Ann Chim Phys. 1841; 2: 58–68.Google Scholar
16 Debus AG. The Paracelsian aerial niter. Isis. 1964; 55: 43–61.Crossref Google Scholar
17 Williams DLH. Nitrosation Reactions and the Chemistry of Nitric Oxide. London, UK: Elsevier; 2004.Google Scholar
18 Ridd JH. Nitrosation, diazotisation and deamination. Quart Rev. 1961; 15: 418–436.Crossref Google Scholar
19 Magee PN, Barnes JM. The production of primary hepatic malignant tumours in the rat by feeding dimethylnitsoamine. Br J Cancer. 1956; 10: 114–122.Crossref Medline Google Scholar
20 Butter W. A Treatise on the Disease Commonly Called Angina Pectoris. London, UK: J. Johnson; 1791.Google Scholar
21 Brunton TL. On the use of nitrite of amyl in angina pectoris. Lancet. 1867; 2: 97–98.Crossref Google Scholar
22 Murrell W. Nitro-glycerine as a remedy for angina pectoris. Lancet. 1879; 1: 80–81, 113–115.Crossref Google Scholar
23 Phillips CDF. Materia Medica, Pharmacology and Therapeutics Inorganic Substances. 2nd ed. London, UK: J&A Churchill; 1894.Google Scholar
24 White WH. Materia Medica Pharmacy, Pharmacology and Therapeutics. London, UK: J&A Churchill; 1899.Google Scholar
25 Fye WB. Nitroglycerin: a homeopathic remedy. Circulation. 1986; 73: 21–29.Crossref Medline Google Scholar
26 Harrington M. Hypotensive Drugs. London, UK: Pergamon Press; 1956.Google Scholar
27 Bellamy A. The development of nitroglycerine as an explosive. Atti del convegno in celerazione del centenario della morte di Ascanio Sobrero. Turín, Italy: University of Turín; 1989.Google Scholar
28 Fant K. Alfred Nobel: En Biografi. Stockholm, Sweden: Norstedts Förlag; 1991: 302.Google Scholar
29 Chen Z, Zhang J, Stamler JS. Identification of the enzymatic mechanism of nitroglycerine bioactivation. Proc Natl Acad Sci U S A. 2002; 99: 8306–8311.Crossref Medline Google Scholar
30 Janero DR, Bryan NS, Saijo F, Dhawan V, Schwalb DJ, Warren MC, Feelisch M. Differential nitros(yl)ation of blood and tissue constituents during glyceryl trinitrate biotransformation in vivo. Proc Natl Acad Sci U S A. 2004; 101: 16958–16963.Crossref Medline Google Scholar
31 Reichert ET, Mitchell SW. On the physiological action of potassium nitrite. Am J Med Sci. 1880; 156: 158–180.Google Scholar
32 Atkinson GA. The physiology of the nitrites and nitro-glycerine. J Anat Physiol. 1888; 22: 225–239, 351–371.Medline Google Scholar
33 Densham B. The adjuvant action of the lactate ion on the vaso-dilator effect of sodium nitrite. J Physiol. 1927; 63: 175–179.Crossref Medline Google Scholar
34 Hay M. Nitrite of sodium in the treatment of angina pectoris. Practitioner. 1883; 30: 170–194.Google Scholar
35 Leech DJ. On the duration of the action of medicines. BMJ. 1885; 2: 1005–1011.Crossref Google Scholar
36 Squibb’s Materia Medica. New York, NY: E.R. Squibb & Sons; 1906.Google Scholar
37 Deusch G, Liepelt A. Die Hautkapillaren beim arteriellen Hochdruck und ihre Beeinflussung durch Nitrite. Deutsches Arch Klin Med. 1928; 160: 207–211.Google Scholar
38 Hare HA, Caspari C, Rusby HH. National Standard Dispensatory. Philadelphia, Pa: Lea Bros & Co; 1905.Google Scholar
39 Bennett RG. Materia Medica and Pharmacy for Medical Students. London, UK: HK Lewis; 1921.Google Scholar
40 Blumgarten AS. Textbook of Materia Medica and Therapeutics. New York, NY: MacMillan; 1934.Google Scholar
41 Modin A, Bjorne H, Herulf M, Alving K, Weitzberg E, Lundberg JO. Nitrite-derived nitric oxide: a possible mediator of “acidic-metabolic” vasodilation. Acta Physiol Scand. 2001; 171: 9–16.Medline Google Scholar
42 Zweier JL, Wang P, Samouilov A, Kuppusamy P. Enzyme-independent formation of nitric oxide in biological tissues. Nat Med. 1995; 1: 804–809.Crossref Medline Google Scholar
43 Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S, Yang BK, Waclawiw MA, Zalos G, Xu X, Huang KT, Shields H, Kim-Shapiro DB, Schechter AN, Cannon RO, Gladwin MT. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med. 2003; 9: 1498–1505.Crossref Medline Google Scholar
44 Angelo M, Singel DJ, Stamler JS. An S-nitrosothiol (SNO) synthase function of hemoglobin that utilizes nitrite as a substrate. Proc Natl Acad Sci U S A. 2006; 103: 8366–8371.Crossref Medline Google Scholar
45 Hunter CJ, Dejam A, Blood AB, Shields H, Kim-Shapiro DB, Machado RF, Tarekegn S, Mulla N, Hopper AO, Schechter AN, Power GG, Gladwin MT. Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator. Nat Med. 2004; 10: 1122–1127.Crossref Medline Google Scholar
46 Moya MP, Gow AJ, Califf RM, Goldberg RN, Stamler JS. Inhaled ethyl nitrite gas for persistent pulmonary hypertension of the newborn. Lancet. 2002; 360: 141–143.Crossref Medline Google Scholar
47 Beier S, Classen HG, Loeffler K, Schumacher E, Thöni H. Antihypertensive effect of oral nitrite uptake in the spontaneously hypertensive rat. Arzneimittelforschung. 1995; 45: 258–261.Medline Google Scholar
48 Lauer T, Preik M, Rassaf T, Strauer BE, Deussen A, Feelisch M, Kelm M. Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action. Proc Natl Acad Sci U S A. 2001; 98: 12814–12819.Crossref Medline Google Scholar
49 Dalsgaard T, Simonsen U, Fago A. Nitrite-dependent vasodilation is facilitated by hypoxia and is independent of known NO-generating nitrite reductase activities. Am J Physiol Heart Circ Physiol. 2007; 292: H3072–H3078.Crossref Medline Google Scholar
50 Furchgott RF, Bhadrakom. Reactions of strips of rabbit aorta to epinephrine, isopropylarterenol, sodium nitrite and other drugs. J Pharmacol Exp Ther. 1953; 108: 129–143.Medline Google Scholar
51 Farrari R, Cargoni A, Bernocchi P, Pasini E, Curello S, Ceconi C, Ruigrok TJC. Metabolic adaptation during a sequence of no-flow and low-flow ischemia. Circulation. 1996; 94: 2587–2596.Crossref Medline Google Scholar
52 Samlouilov A, Kuppusamy P, Zweier JI. Evaluation of the magnitude and rate of nitric oxide production from nitrite in biological systems. Arch Biochem Biophys. 1998; 357: 1–7.Crossref Medline Google Scholar
53 Butler AR, Ridd JH. Formation of nitric oxide from nitrous acid in ischemic tissue and skin. Nitric Oxide. 2004; 10: 20–24.Crossref Medline Google Scholar
54 Webb A, Bond R, McClean P, Uppal R, Benjamin N, Ahluwalia A. Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemic-reperfusion damage. Proc Natl Acad Sci U S A. 2004; 101: 13683–13688.Crossref Medline Google Scholar
55 Bryan NS, Fernandez BO, Bauer SM, Garcia-Saura MF, Milsom AB, Rassaf T, Maloney RE, Bharti A, Rodriguez J, Feelisch M. Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nat Chem Biol. 2005; 1: 290–297.Crossref Medline Google Scholar
56 Granville AB. Further Observations on the Internal Use of the Hydro-cyanic (Prussic) Acid. London, UK: Butgess & Hill; 1820.Google Scholar
57 Magendie F. Sur l’emploi de l’acide prussique dans le traitement de plusieurs maladies de poitrine, et particulièrement dans la phtisie pulmonaire. Ann Chim Phys. 1817; 6: 347–360.Google Scholar
58 Commoner B. Cyanide inhibition as a means of elucidating the mechanism of cellular respiration. Bio Rev (Cambridge Phil Soc). 1940; 15: 168–201.Crossref Google Scholar
59 Keilin D, Hartree EF. Cytochrome c and cytochrome oxidase. Proc Royal Soc London Series B. 1939; 127: 167–191.Crossref Google Scholar
60 Kobert R. Über Cyanmethämoglobin und den Nachweis der Blausäure. Stuttgart, Enke: Germany; 1891; Cited by: Keilin D. The History of Cell Respiration and Cytochrome. Cambridge, UK: CUP; 1966.Google Scholar
61 Hug E. Accion del nitrite de sodio del hiposulfate de sodio en el tratamiento de la intoxication provocada por el ciannuro de potassio en al conejo. Rev Soc Argent Biol. 1932; 3: 270–276.Google Scholar
62 Viana C, Cagnoli H, Cendan J. L’action du nitrite de sodium dans l’intoxication par les cyanures. C R Seances Soc Biol Fil. 1934; 115: 1649–1651.Google Scholar
63 Matthew H, Lawson AAH. Treatment of Common Acute Poisonings. 4th ed. Edinburgh, Scotland: Churchill Livingstone; 1979.Google Scholar
64 Cucinell SA, Groff WA, Vick JA, Weger N. Treatment of cyanide poisoning. Fed Proc. 1974; 33: 234. Abstract.Google Scholar
65 Isom GE, Way JL. Lethality of cyanide in the absence of inhibition of liver cytochrome oxidase. Biochem Pharmacol. 1976; 25: 605–608.Crossref Medline Google Scholar
66 Baskin SI, Froehlich HL, Groff WA. The dissociation of reversal of cyanide (CN) toxicity and methemoglobin formation by nitrite (N) in the isolated heart. Fed Proc. 1986; 45: 196. Abstract.Google Scholar
67 Ali MY, Ping CY, Mok YY, Ling L, Whiteman M, Bhatia M, Moore PK. Regulation of vascular nitric oxide in vitro and in vivo; a new role for endogenous hydrogen sulphide? Br J Pharmacol. 2006; 149: 625–634.Crossref Medline Google Scholar
68 Smith RP, Gosselin RE. Hydrogen sulfide poisoning. J Occup Med. 1979; 21: 93–97.Crossref Medline Google Scholar
69 Smith RP, Kruszyna R, Kruszyna H. Management of acute sulfide poisoning: effects of oxygen, thiosulfate, and nitrite. Arch Environ Health. 1976; 31: 166–169.Crossref Medline Google Scholar
70 Beck JF, Bradbury CM, Connors AJ, Donini JC. Nitrite as antidote for acute hydrogen sulfide intoxication? Am Ind Hyg Assoc J. 1981; 42: 805–809.Crossref Medline Google Scholar
71 Scheler W, Kabisch R. On the antagonistic alteration of acute H₂S poisoning in mice with methemoglobin forming agents. Acta Biol Med Ger. 1963; 11: 194–199.Medline Google Scholar
72 Stine RJ, Slosberg B, Beacham BE. Hydrogen sulfide intoxication: a case report and discussion of treatment. Ann Intern Med. 1976; 85: 756–758.Crossref Medline Google Scholar
73 Chen KK, Rose CL. Nitrite and thiosulfate therapy in cyanide poisoning. JAMA. 1952; 149: 113–119.Crossref Medline Google Scholar
74 Law WT. Sodium nitrite in the treatment of epilepsy. Practitioner. 1882; 28: 420–424.Google Scholar
75 Ringer S, Murrell W. Nitrite of sodium as a toxic agent. Lancet. 1883; 2: 766–767.Google Scholar
76 van Grinsven HJM, Ward MH, Benjamin N, de Kok TM. Does the evidence about health risks associated with nitrate ingestion warrant an increase of the nitrate standard for drinking water? Environ Health. 2006; 5: 26–30.Crossref Medline Google Scholar
77 Lundberg JO, Weitzberg E, Cole JA, Benjamin N. Nitrate, bacteria and human health. Nat Rev Microbiol. 2004; 2: 593–602.Crossref Medline Google Scholar
78 Weller R, Pattullo S, Smith L, Golden M, Ormerod A, Benjamin N. Nitric oxide is generated on the skin surface by reduction of sweat nitrate. J Invest Dermatol. 1996; 107: 327–331.Crossref Medline Google Scholar
79 Yoon SS, Coakley R, Lau GW, Lymar SV, Gaston B, Karabulut AC, Hennigan RF, Hwang SH, Buettner G, Schurr MJ, Mortensen JE, Burns JL, Speert D, Boucher RC, Hassett DJ. Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions. J Clin Invest. 2006; 116: 436–446.Crossref Medline Google Scholar
80 Weller R, Price RJ, Ormerod AD, Benjamin N, Leifert C. Antimicrobial effect of acidified nitrite on dermatophyte fungi, Candida and bacterial skin pathogens. J Appl Microbiol. 2001; 90: 648–652.Crossref Medline Google Scholar
81 Tucker AT, Pearson RM, Cooke ED, Benjamin N. Effect of nitric-oxide-generating system on microcirculatory blood flow in skin of patients with severe Raynaud’s syndrome: a randomised trial. Lancet. 1999; 354: 1670–1675.Crossref Medline Google Scholar
82 Khan F, Pearson RJ, Newton DJ, Belch JJF, Butler AR. Chemical synthesis and microvascular effects of new nitric oxide donors in humans. Clin Sci. 2003; 195: 577–584.Google Scholar
83 Weller R, Finnen MJ. The effects of topical treatment with acidified nitrite on wound healing in normal and diabetic mice. Nitric Oxide. 2006; 15: 395–399.Crossref Medline Google Scholar
84 Ts’ao TC, Ho PY, Needham J. An early mediaeval Chinese alchemical text on aqueous solutions. Ambix. 1959; 7: 122–155.Google Scholar
85 Butler AR, Moffett J. In: Lo EY, Cullen C, eds. Medieval Chinese Medicine: The Dunhuang Medical Manuscripts. London, UK: Routledge; 2004.Google Scholar
86 Duncan C, Dougall H, Johnson P, Green S, Brogan R, Leifert C, Smith L, Golden M, Benjamin N. Chemical generation of nitric oxide from the enterosalivary circulation of dietary nitrate. Nat Med. 1995; 1: 546–551.Crossref Medline Google Scholar
87 Pietsch G. Dissertation sur la Generation du Nitre. Berlin, Germany: Chez Haude et Spener; 1746.Google Scholar
88 Postgate J. Nitrogen Fixation. 3rd ed. Cambridge, UK: CUP; 1998.Google Scholar
89 Challoner T. A Short Discourse on the Most Rare and Excellent Vertue of Nitre. London, UK; G Dewes; 1584.Google Scholar
90 Benjamin N, Pattullo S, Weller R, Smith L, Omerod A. Wound licking and nitric oxide. Lancet. 1997; 349: 1776.Crossref Google Scholar
91 Pearse F. The treatment of paroxysmal nerve disorders. Practitioner. 1891; 46: 29–32.Google Scholar
92Cassan S. Relieving affections of the lungs or chest. UK Patent 2524; 1868.Google Scholar
93 Encyclopædia Britannica. Vol. XXIV, 11th ed. Cambridge, UK: CUP; 1911: 94.Google Scholar
94 Dispensatory of the United States of America. 21st ed. Philadelphia, Pa: JB Lippincott; 1926.Google Scholar
95 Oza TM. Thermal decomposition of sodium and potassium nitrites. J Indian Chem Soc. 1945; 22: 173–180.Google Scholar
96 Ziment I. History of the treatment of chronic bronchitis. Respiration. 1991; 58 (suppl 1): 37–42.Google Scholar
97 Willis T. Pharmaceutice Rationalis: Or an Exercitation of the Medicines in Humane Bodies. London, UK; T. Dring, C. Harper, and J. Leigh; 1697.Google Scholar
98 Jörg JCG. Materialien zu einer künftigen Heilmittellehre durch Versuche der Arzneyen an gesunden Menschen gewonnen u. gesammelt. Leipzig, Germany: Carl Cnobloch; 1825.Google Scholar
99 Hiatt EP. Comparison of the diuretic effects of nitrate salts with other diuretic agents. Am J Physiol. 1957; 189: 173–176.Crossref Medline Google Scholar
100 Cahn A. Die Magenverdauung im Chlorhunger. Ztschr F Physiol Chem. 1886; 10: 522–535.Google Scholar
101 Greene I, Hiatt EP. Renal excretion of nitrate and its effect on excretion of sodium and chloride. Am J Physiol. 1954; 180: 179–182.Crossref Google Scholar
102 Keith NM, Whelan M, Bannick EG. The action and excretion of nitrates. Arch Intern Med. 1930; 46: 797–832.Crossref Google Scholar
103 Beck EG. Toxic effects from bismuth subnitrate: with reports of cases to date. JAMA. 1909; 52: 14–18.Google Scholar
104 Alexander W. William Alexander’s Medizinische Versuche und Erfahrungen. Leipzig, Germany: A.d.E.; 1773.Google Scholar
105 Eustermann GB, Keith NM. Transient methemoglobinemia following administration of ammonium nitrate. Med Clin North Am. 1929; 12: 1489–1496.Google Scholar
106 Tarr L. Transient methemoglobinemia due to ammonium nitrate. Arch Intern Med. 1933; 51: 38–44.Crossref Google Scholar
107 Petersson J, Phillipson M, Jansson EA, Patzak A, Lundberg JO, Holm L. Dietary nitrate increases gastric mucosal blood flow and mucosal defense. Am J Physiol Gastrointest Liver Physiol. 2007; 292: G718–G724.Crossref Medline Google Scholar
108 Humphreys SD, Routledge PA. The toxicology of silver nitrate. Adverse Drug React Toxicol Rev. 1998; 17: 115–143.Medline Google Scholar
109 Archer DL. Evidence that ingested nitrate and nitrite are beneficial to health. J Food Prot. 2002; 65: 872–875.Crossref Medline Google Scholar
110 Addiscott TM, Benjamin N. Are you taking your nitrate? Food Sci Technol Today. 2000; 14: 59–61.Google Scholar
111 L’Hirondel JJ, L’Hirondel J-L. Nitrate and Man: Toxic, Harmless or Beneficial? Oxford, UK: CABI Publishing; 2002.Google Scholar
112 Suschek CV, Schewe T, Sies H, Kroncke KD. Nitrite, a naturally occurring precursor of nitric oxide that acts like a “prodrug.” Biol Chem. 2006; 387: 499–506.Medline Google Scholar
113 Shiva S, Sack MN, Greer JJ, Duranski M, Ringwood LA, Burwell L, Wang X, Macarthur PH, Shoja A, Raghavachari N, Calvert JW, Brookes PS, Lefer DJ, Gladwin MT. Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer. J Exp Med. 2007; 204: 2089–2102.Crossref Medline Google Scholar
114 Lundberg JO, Feelisch M, Bjorne H, Jansson EA, Weitzberg E. Cardioprotective effects of vegetables: is nitrate the answer? Nitric Oxide. 2006; 15: 359–362.Crossref Medline Google Scholar
115 Richardson G, Hicks SL, O’Byrne S, Frost MT, Moore K, Benjamin N, McKnight GM. The ingestion of inorganic nitrate increases gastric S-nitrosothiol levels and inhibits platelet function in humans. Nitric Oxide. 2002; 7: 24–29.Crossref Medline Google Scholar
116 Larsen FJ, Ekblom B, Sahlin K, Lundberg JO, Weitzberg E. Effects of dietary nitrate on blood pressure in healthy volunteers. N Engl J Med. 2006; 355: 2792–2793.Crossref Medline Google Scholar
117 Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol. 2007; 191: 59–66.Crossref Medline Google Scholar
118 Erzurum SC, Ghosh S, Janocha AJ, Xu W, Bauer S, Bryan NS, Tejero T, Hemann C, Hille R, Stuehr DJ, Feelisch M, Beall CM. Higher blood flow and circulating nitric oxide products offset high-altitude hypoxia among Tibetans. Proc Natl Acad U S A. 2007; 104: 17593–17598.Crossref Medline Google Scholar

Featured Image Credit: https://www.savoryonline.com/recipes/candy-bacon-hearts/

The Truth About Meat Curing: What the popular media do NOT want you to know!

08/15/202208/23/2022 eben van tonder The Truth About Meat Curing: What the popular media do NOT want you to know! Bacon & the Art of Living, Bacon Curing, bacon processing, nitrate curing, nitrite curing, nitrites and cancer, truth about curing, truth about nitrates, truth about nitrites

So much miss information and reporting for the sake of sensation-seeking on this matter that I had to do this short series. One can keep silent for only so long!

The series is in response to the following documentary, “The Meat Lobby: How the Meat Industry Hides the Truth | ENDEVR Documentary” on YouTube https://youtu.be/nX1KUPZC3Ck

There are many similar ones on the web and every so often a newspaper decides to run articles on the matter.

Part 1: Setting the stage

Part 2: The Curing Molecule

In this instalment, I refer to Fathers of Meat Curing and my article on the work of Dr Polenske, Saltpeter: A Concise History and the Discovery of Dr Ed Polenske.

Part 3: Steps to secure the safety of cured meat

I discuss steps taken by the meat industry, academia and government right from the inception of nitrite curing to ensure it is completely safe. The article I did which I discuss is Regulations of Nitrate and Nitrite post-1920’s: the problem of residual nitrite.

Part 4: The Benefit of Nitrites

Therapeutic Uses of Inorganic Nitrite and Nitrate – From the Past to the Future.

Please mail me at ebenvt@gmail.com or Whatsapp on +27715453029 for any comments, questions or feedback or post your question/ comment below.

Cover Photo

Cover photo is courtesy of Robert Goodrick.

Chat on WhatsApp

Nitrite Cured Meat: It’s Fantastic but is it also Bad?

12/28/2021 eben van tonder Curing, a review, Nitrite Curing, nitrite free curing health, nitrite curing, nitrite free curing

Nitrite Cured Meat: It’s Fantastic but is it also Bad?
By Eben van Tonder
15 February 2021

Introduction

I started my career in meat curing in 2008 when I founded the South African bacon brand Woody’s and the company Woody’s Consumer Brands with Oscar and Anton. I never imagined that the most exciting journey on earth would follow which I chronicled in Bacon & the Art of Living. I wanted to know as much as possible about the world of curing and the chemical, biological and bacterial reactions that fascinated me. One of the first books I consumed was Ronald Pegg and Fereidoon Shahidi’s work, Nitrite Curing of Meat: The N-Nitrosamine Problem and Nitrite Alternatives.

I delved into the matter with great interest. I discovered that nitrates are present in many vegetables, but they first need to change to nitrites through bacterial action before they change chemically into nitric oxide which then cures the meat. Nitrates are not very toxic, but once they change into nitrite and is fried, their reaction in the stomach is of particular concern.

As I learned more I discovered the importance of cured products in a world before refrigeration. They are extremely effective to protect us against pathogens, including the mother of all pathogens, Clostridium Botulinum. Its protective action extends into the age of refrigeration! Far from a villain chemical, it turns out that nitrite is an amazing compound that naturally occurs all around us and is, amongst others, formed in our mouths when we consume a wide variety of food including fruits and vegetables.

The question is now obvious. We know that adding nitrites to meat is doing a world of good in giving us safe food that lasts long without refrigeration and just happens to also taste delicious but are we causing more harm than good? Should we stop using it if we ingest far more nitrites from some vegetables than from cured meat? How do we evaluate a matter when scientists continually conclude any discussion on the matter with the words “more research on the topic is required?”

When did we realise that nitrite is not only beneficial but under certain conditions may be problematic? What exactly is the concern with its use? How did we end up using this? What physiological role does it play in humans? What benefits do we derive from ingesting it?

I will provide a brief overview. More than this, I use this as a landing page for material on the subject. Some of my consultancy work relates to exactly this topic and proprietary information is therefore restricted with password protection. Why “password” protected? Because the obvious next question is this: “Is there anything we can do to change it?” To manage the negative elements so that it is removed, and the product is wholly healthy! The answer is a resounding YES! But that is proprietary information! 🙂

A. How did we Realise there is a Problem?

What is the actual issue then and how did humans realise that there is a problem?

The Realization of Danger of Nitrites in Cured Meat and The Responses Since 1926

Nitrate was used as a curing agent for many thousands of years. The basic value initially related to the preventing of spoilage and in a world before refrigeration bacon soon became the staple meat source for the masses in a large part of the world. Curing with saltpetre, the common name for nitrate salts, takes about a month and apart from retarding spoilage, it imparts into meat a characteristic pinkish/ reddish colour and a very agreeable cured meat taste. In the 1800s a new method of curing was invented which reduced the time to cure meat considerably. It was called tank curing on account of the tanks that were used to cure the meat in or mild curing due to a reduced need for salt. It was invented in Ireland. When our understanding of chemistry and bacteriology matured, we realised the reason why tank curing sped meat curing up. For curing to take place nitrate (saltpetre) must first be converted to nitrite through bacterial action before it can be changed into nitric oxide which, we discovered, is the real curing molecule. So, nitrate (saltpetre) to nitrite curtesy of microorganisms (bacteria) and nitrite to nitric oxide through is a chemical reaction.

What was achieved through tank curing was that the step of bacteria changing nitrate into nitrite is cut out. Still, we do not add the nitrite directly. It is “added” through fermentation. The old brine is re-used and in doing so, the liquid is replete with nitrite that was already converted from nitrate. This, naturally, speeds the process up by cutting a step out. Before the late 1800’s curers did not have a clue what caused curing apart from saltpetre. They arrived at the process of tank curing through experimentation and observation without any inkling to microorganisms changing nitrate to nitrite.

The curing reaction was being unravelled by scientists late in the 1800s and early in the 1900s. As we learned that going from nitrite to nitric oxide is much quicker than going from nitrate first to nitrite and then to nitric oxide. We also realized that nitrite forms a salt with sodium to create sodium nitrite. Late in the 1800s and early in the 1900s sodium nitrite was being used in the dye industry and chemists stocked it because it became an important medication to treat some blood disorders. Butchers used it as the source of nitrite. It is easier and “cleaner” than the indirect creation of nitrite through fermentation (tank curing or mild curing). Sodium nitrite can be dissolved directly in a brine and will immediately start penetrating the meat and change to nitric oxide.

Tank curing soon lost its place as the quickest way to cure meat in favour of the direct addition of nitrites to curing brines. There was an issue with nitrites though in that most people at this time knew that nitrite was a potent toxin. Understandably, from very early, humans who did not “see” the conversion of nitrate to nitrites and did not understand that nitrites were in any event present in cured meat grappled with the concept of a toxic substance being introduced in food preparations.

During the First World War, curing brines came onto the market which included nitrites. The days of tank curing were numbered, and a controversy was born about how healthy this is. Several investigations were made into the matter. No sooner was the matter of the toxicity of nitrites settled through scientific investigation when another, far more dangerous issue came onto the scene in the 1970s of n-nitrosamines. Let’s run through the chronology of some of the key studies and some of the important ways that governments around the world responded to it.

We picked the investigations into this matter up in 1926 which looked at the matter of nitrite as a toxin. If it was simply a matter of concentration, it would be easily settled because we regularly use substances if food which, in too high dosages can harm or even kill us. Alcohol is a very good example. The way to mitigate the risk is to determine the “safe” levels and to ensure that producers use the appropriate dosages.

1926

A 1926 study by Kerr and co-workers was based on the general knowledge of nitrite’s toxicity and the publics very negative perceptions about it. In the report, they state that public health was the primary motivation behind the study. (Kerr, et al, 1926: 543) I quote from their report. “The first experiment involving the direct use of nitrite was formally authorized January 19, 1923, as a result of an application by one of the large establishments operating under Federal meat inspection. Before that time other requests for permission to experiment with nitrite had been received but had not been granted. The authorization for the first experiment specified that the whole process was to be conducted under the supervision of bureau inspectors and that after the curing had been completed the meat was to be held subject to laboratory examination and final judgment and would be destroyed if found to contain an excessive quantity of nitrites or if in any way it was unwholesome or unfit for food. This principle was rigidly adhered to throughout the experimental period, no meat being passed for food until its freedom from excessive nitrites had been assured, either by laboratory examination or through definite knowledge from previous examinations, that the amount of nitrite used in the process would not lead to the presence of an excessive quantity of nitrites in the meat. By “excessive” is meant a quantity of nitrite materially in excess of that which may be expected to be present in similar meats cured by the usual process.” (Kerr, et al, 1926: 543)

“The maximum nitrite content of any part of any nitrite-cured ham [was found to be] 200 parts per million. The hams cured with nitrate in the parallel experiment showed a maximum nitrite content of 45 parts per million.” (Kerr, et al, 1926: 543) The conclusion was that “hams and bacon could be successfully cured with sodium nitrite, and that nitrite curing need not involve the presence of as large quantities of nitrite in the product as sometimes are found in nitrate- cured meats.” (Kerr, et al, 1926: 545)

Related to the health concerns, the report concluded the following:

“The presence of nitrites in cured meats, was already sanctioned by the authoritative interpretation of the meat inspection and pure food and drugs acts sanctioning the use of saltpeter; as shown previously, meats cured with saltpeter and sodium nitrate regularly contain nitrites. (Wiley, H, et al, 1907) (Kerr, et al, 1926 : 550)
The residual nitrites found in the nitrite-cured meats were less than are commonly present in nitrate-cured meats. The maximum quantity of nitrite found in nitrite-cured meats, in particular, was much smaller than the maximum resulting from the use of nitrate. (Kerr, et al, 1926 : 550)
The nitrite-cured meats were also free from the residual nitrate which is commonly present in nitrate-cured meats. (Kerr, et al, 1926 : 550)
On the contrary, the more accurate control of the amount of “nitrite and the elimination of the residual or unconverted nitrate are definite advantages attained by the substitution. (Kerr, et al, 1926 : 550)

Following further studies, the Bureau set the legal limit for nitrites in finished products at 200 parts per million. (Bryan, N. S. et al, 2017: 86 – 90) Conventional wisdom that surfaced in the 1920s suggested that nitrate and nitrate should continue to be used in combination in curing brines (Davidson, M. P. et al; 2005: 171) as was the case with the Irish curing method or the tank curing concept of the previous century. Nitrite gives the immediate quick cure and nitrate acts as a reservoir for future nitrite and therefore prolongs the supply of nitrite and ensures a longer curing action. This concept remained with the curing industry until the matter of N-nitrosamines came up in the 1960s and ’70s, but remarkably enough, it persists in places like South Africa where to this day, using the two in combination is allowed for bacon. More about this later.

1931

The USDA progressed the ruling on nitrate and nitrites further in 1931 by stating that where both nitrites and nitrates are used, the limit for nitrite is 156 ppm nitrite and 1716 nitrate per 100lb of pumped, cured meat. (Bryan, N. S. et al, 2017: 86 – 90)

1960’s – N-Nitrosamine

Up to the 1960’s the limit on the ingoing level of nitrites was based on its toxicity. In the late 1950s an incident occurred in Norway involving fish meal that would become a health scare rivalled by few in the past. 1960’s researchers noticed that domestic animals fed on a fodder containing fish meal prepared from nitrite preserved herring were dying from liver failure. Researchers identified a group of compounds called nitrosamines which formed by a chemical reaction between the naturally occurring amines in the fish and sodium nitrite. Nitrosamines are potent cancer-causing agents and their potential presence in human foods became an immediate worry. An examination of a wide variety of foods treated with nitrites revealed that nitrosamines could indeed form under certain conditions. Fried bacon, especially when “done to a crisp,” consistently showed the presence of these compounds. (Schwarcz, J) In bacon, the issue is not nitrates, but the nitrites which form N-nitrosamines.

This fundamentally sharpened the focus of the work of Kerr and co-workers of the 1920s in response to the general toxicity of nitrites to the specific issue of N-nitrosamine formation. Reviews from 1986 and 1991 reported that “90% of the more than 300 N-nitroso compounds that have been tested in animal species including higher primates causes cancer, but no known case of human cancer has ever been shown to result from exposure to N-nitroso compounds.” However, despite this, there is an overwhelming body of indirect evidence that shows that a link exists and “the presence of N-nitroso compounds in food is regarded as an etiological risk factor. It has been suggested that 35% of all cancers in humans are dietary related and this fact should not surprise us. (Pegg and Shahidi, 2000)

Studies have been done showing that children who eat more than 12 nitrite-cured hot dogs per month have an increased risk of developing childhood leukaemia. The scientists responsible for the findings themselves cautioned that their findings are preliminary and that much more studies must be done. It may nevertheless be a good approach for parents to reduce their own intake of such products along with that of their children in cases where intake is high. (Pegg and Shahidi, 2000)

These studies must be balanced by the fact that an overwhelming amount of data has been emerging since the 1980s that indicate that N-nitroso compounds are formed in the human body. What is important is that we keep on doing further research on N-nitrosamines and the possible link to cancer in humans. Not enough evidence exists to draw final conclusions.

1970 – The response to the N-Nitrosamine scare.

Back in the 1970s, so grave was the concern of the US Government about the issue that in the early 1970’s they seriously considered a total ban on the use of nitrites in foods. (Pegg and Sahidi, 2000) The response to the N-nitrosamine issue was to go back to the approach that was implemented following the work of Kerr and co-workers in 1926.

The first response was to eliminate nitrate from almost all curing applications. The reason for this is to ensure greater control over the curing. Meat processors continued to use nitrate in their curing brines from 1920 until the 1970s. One survey from 1930 reported that 54% of curers in the US still used nitrate in their curing operations. 17% used sodium nitrite and 30% used a combination of nitrate and nitrite. By 1970, 50% of meat processors still used nitrate in canned, shelf stable. In 1974 all processors surveyed discontinued the use of nitrates in these products including in bacon, hams, canned sterile meats, and frankfurters. One of the reasons given for this change is the concern that nitrate is a precursor for N-nitrosamine formation during processing and after consumption. (Bryan, N. S. et al, 2017: 86 – 90)

The reason for the omission in bacon, in particular, is exactly the fact that the nitrates will, over time continue to be converted to nitrites which will result in continued higher levels of residual nitrites in the bacon compared to if only nitrite is used. The N-nitrosamine formation from nitrites is a reaction that can happen in the bacon during frying or in the stomach after it has been ingested. It will not happen from the more stable nitrates.

It has been discovered that nitrate continues to be present in cured meats. Just as the view that if nitrate was added, no nitrite is present in the brine as was the thinking in the time before the early and mid-1800s, in exactly the same way it is wrong to think that by adding nitrite only to meat, that no nitrate is present. “Moller (1971) found that approximately 20% of the nitrite added to a beef product was converted to nitrate within 2 hours of processing. Nitrate formation was noted during incubation before thermal processing, whereas after cooking only slight nitrate formation was detected. Upon storage, the conversion of nitrite to nitrate continued. Herring (1973) found a conspicuous level of nitrate in bacon formulated only from nitrite. As greater concentrations of nitrite were added to the belly, a higher content of nitrate was detected in the finished product. They reported that 30% of the nitrite added to bacon was converted to nitrate in less than one week and the level of nitrate continued to increase to approximately 40% of the added nitrite until about 10 weeks of storage. Moller (1974) suggested that when nitrite is added to meat, simultaneous oxidation of nitrite to nitrate and the ferrous ion of to the ferric ion of metMb occurs.” Adding ascorbate or erythorbate plays a key role in this conversion. (Pegg and Shahidi, 2000) The issue is not the nitrate itself, but the uncontrolled curing that results from nitrate and the higher residual nitrites.

Secondly, the levels of ingoing nitrite were reduced, especially for bacon. The efficacy of these measures stems from the fact that the rate of N-nitrosamine formation depends on the square of the concentration of residual nitrites in meats and by reducing the ingoing nitrite, the residual nitrite is automatically reduced and therefore the amount of N-nitrosamines. (Pegg and Sahidi, 2000) Legal limits were updated in 1970 in response to the nitrosamine paranoia. A problem with this approach is however that no matter by how much the ingoing nitrite is reduced, the precursors of N-Nitrosamine still remain in the meat being nitrites, amines, and amino acids.

An N-nitrosamine blocking agent was introduced in the form of sodium ascorbate or erythorbate. “There are several scavengers of nitrite which aid in suppressing N-nitrosation; ascorbic acid, sodium ascorbate, and erythorbate have been the preferred compound to date. Ascorbic acid inhibits N-Nitrosamine formation by reducing to give dehydroascorbic acid and NO. Because ascorbic acid competes with amines for , N-Nitrosamine formation is reduced. Ascorbate reacts with nitrite 240 times more rapidly than ascorbic acid and is, therefore, the preferred candidate of the two. (Pegg and Sahidi, 2000)

More detailed studies identified the following factors to influence the level of N-nitrosamine formation in cured meats. Residual and ingoing nitrite levels, preprocessing procedure and conditions, smoking, method of cooking, temperature and time, lean-to-adipose tissue ratio, and the presence of catalyst and/ or inhibitors. It must be noted that in general, levels of N-nitrosamines formation have been minuscule small, in the billions of parts per million, and sporadic. The one recurring problem item remained fried bacon. In its raw state bacon is generally free from N-nitrosamines “but after high-heat frying, N-nitrosamines are found almost invariably.” One report found that “all fried bacon samples and cooked-out bacon fats analyzed” were positive for N-nitrosamines although at reduced levels from earlier studies. (Pegg and Sahidi, 2000)

Regulatory efforts since 1920 have shown a marked decrease in the level of N-nitrosamines in cured meats, even though it is still not possible to eliminate it completely. “Cassens (1995) reported a marked decrease (approx 80%) in residual nitrite levels in of US prepared cured meat products from those determined 20 years earlier; levels in current retail products were 7 mg/kg from bacon.” This and similar results have been attributed to lower nitrite addition levels and the increased use of ascorbate or erythorbate. (Pegg and Sahidi, 2000)

Despite the actions of governments and the curing industry, consumer demand has grown over the years to eliminate nitrites in food. Evidence has started to emerge that links the prevalence of colon cancer, for example, not just to the use of nitrites but to the use of saltpetre or the far less toxic cousin of nitrite called nitrate. Much of the evidence is either anecdotal or indirect but it is sufficient to fuel public suspicion and legitimate industry concerns.

B. Can’t we just Remove the Nitrites?

What is clear from our survey above is that it is a technical and complex field. Can we not just remove the nitrites and sell nitrite-free bacon? When we talk about nitrite-free bacon, it is important to know exactly what we are talking about. The term can imply several things.

– Is the Problem Synthetic Nitrites Only (I.e. Sodium Nitrite Added Into the Brine)?

Is it that no synthesized nitrite must be used in the curing of the meat? Tank curing or fermented nitrate containing plant juices would then be an appropriate curing procedure. Celery and other plants are filled with nitrates which are part of plant nutrition, absorbed from the soil through the roots. Certain spice companies started using these plant extracts and then through a process of fermentation, allowed microorganisms to reduce the nitrite to nitrate like what was done in tank curing using old brine and they sold the plant extracts to be added to the meat as an ingredient. They called it a “natural curing agent” but in my opinion, they were actually deceiving the public. After the bacterial fermentation, the plant juices were now filled with nitrates. They cleverly circumvented the requirement to declare the use of nitrites in the curing process and in reality, nitrites were still present, now in usually much larger quantities as was the case using sodium nitrite.

– Is the Problem All Nitrites in the Brine and Meat, Including Either Sodium Nitrite or Nitrite that Formed Through Bacterial Action, Either through Reduction or Oxidation or Chemically and Irrespective of the Source?

Nitrite-free bacon can mean that no nitrites should be used in the curing process added directly or generated indirectly. Indirectly it can be generated through fermentation but there are other sources of nitrite which forms as a result of the decomposition of meat. In long-term curing, for example, the same colour, even a better taste and longer shelf life is achieved by the use of salt only. I mention this because it introduces a very important issue. For curing to take place, you don’t actually need nitrate or nitrite. You need nitrogen. The nitrogen must then react with oxygen to create nitric oxide (NO) which is a gas! Nitrate and nitrite are only the nitrogen source! Once Nitric Oxide is created, it must react with the meat proteins, myoglobin.

As the proteins of a dead animal or other constituents of meat are being broken down, nitrogen is made available and in long term curing, certain processes are involved and one of them is the combination of the nitrogen molecule, made available through decomposition, with an oxygen molecule and curing takes place if the overall destruction of the meat is managed through the removal of water which retards (even stops) the action of microorganisms and favours the effect of enzymes.

So, this can be done completely without any outside source of nitrogen but the process is very slow and there is no way that the world demand for cured meat will be satisfied through this. It will also be extremely expensive due to the weight loss involved in removing the moisture. No matter how you look at it, nitrogen must be accessed somehow, or it is not curing.

It is extremely important to know that curing is something that happens to the meat itself and it mimics a natural, biological process of nitric oxide being formed in our bodies. The meat protein in either its oxygenated state or with a nitric oxide molecule presents red. This is an extremely important concept to understand. Curing is a characteristic of meat itself and is a natural process. It is NOT the imposition upon the meat of a colouring agent. The fact that nitrogen is used in curing is completely consistent with natural biological processes. Even the reduction and interaction of nitrate and nitrite, including the chemical reduction to nitric oxide, is a biological process, essential to life!

I give one example from a review article by Shiva (2013). I anticipate that very soon consumers may demand food with high nitrate (NO3-) in a swing in perceptions of these molecules which will in all likelihood be driven by people who regularly work out. Shiva summarizes this work as follows. “Nitrite dependent inhibition of ccox also potentially regulates responses to physiological hypoxia (the absence of enough oxygen in the muscles), such as that present in the muscle during exercise. Larsen and colleagues recently demonstrated that ingestion of NO3- (nitrate) decreased whole-body oxygen consumption during exercise without changing maximal attainable work rate in human subjects.” Directly as a result of this work, several booster supplements are currently on the market and sold in gyms and health shops around the world containing nitrates.

Shiva continues, “This increase in exercise efficiency, which was associated with augmented plasma NO2- levels, has now been corroborated by a number of studies in various exercise models. While the underlying mechanism of this beneficial effect is not completely elucidated, a decrease in the rate of oxygen consumption due to proton leak and state 4 respiration in the skeletal muscle of subjects receiving NO3- was reported.” (Shiva, 2013)

Right there, the entire matter is resolved and in a few short years, the public will demand more nitrates in meat (and by implication, nitrite also)! 🙂 🙂

Furthermore, not only is the reaction of nitrite to nitric oxide not foreign in our physiology, the reaction of nitric oxide with myoglobin is an extremely important physiological reaction that is mimicked in curing. Jens Moller and Leif Skibsted write that “Nitrosylmyoglobin (MbFe^IINO), the NO complex of iron (II) myoglobin, as formed in meat products, has now also been observed in vivo in rats. MbFe^IINO thus seems important in controlling radical processes associated with oxidation”. (Møller and Skibsted, 2002)

The issue is that our best available source of nitrogen is through nitrite and nitrite itself but is both beneficial and problematic at the same time.

The fact that the reaction of oxygen (O2) and Nitric Oxide are both matters that all butchers work with daily is important. None of these reactions is “unnatural!” This is seen in the colour of fresh meat and cured meat. I dedicated a chapter to it in Bacon & the Art of Living, called Fresh Meat Colour vs Cooked Cured Colour.

I plan to do much more work about the physiological reason why nitric oxide fits onto the colouring site of a protein apart from the short quotes above, but I will deal with this separately and update this section with a link reference.

– If the Meat itself Does Not Change Colour (Curing), is the use of External Colourant Permitted/ Desirable?

There is another way of achieving a red colour in meat which we alluded to and that is through an artificial process that involves the use of an external colourant. Legally there are colourants that are allowed in meat, but how will consumer groups respond to this? This is not something natural and inherently part of meat itself. It is an external colourant that is brought to bear upon the meat matrix. This is even more objectionable to some than nitrite and the extreme objection against it goes back to the start of the meat trade where butchers used to disguise old and sometimes putrid meat as fresh by colouring it with an external colourant.

– Is the Real Issue Actually Residual Nitrite That We Must Eliminate? (I.e., Not Ingoing Nitrite but Nitrite Left in Meat After Curing)

Another possible meaning of nitrite-free bacon refers not to the fact that nitrite was somewhere involved in the supply of the nitrogen source to form nitric oxide, but the real meaning may refer to the question of whether any nitrite is left in the product when the consumer fries it in the pan. It is after all not the initial source of the nitrogen atom, which is the real issue, but how much nitrite is left after the meat has been cured. This is what is referred to as residue nitrite. The other question which goes hand in hand with this is to what degree can the consumer be guaranteed that no appreciable amount of nitrite is left in the product he buys?

– Is The Objective to Eliminate All Manipulation of Colour (Natural or Artificial) and Resign Ourselves to Selling Brown Bacon and Hams (uncured, salted only)?

A final solution for some is to simply omit accessing nitrogen in any shape or form altogether and not be concerned about the brownish colour that develops. I have over a few years followed the work of a New Zealand company, interestingly enough also called Woody’s who follow this approach and I am amazed at the success they have had with their brand positioning. Good old strict hygiene is used to sort shelf-life issues out and they educate their customers that the browner bacon is actually healthier bacon. The brown bacon they sell becomes a source of comfort for their clients. If this is advisable as a universal approach to bacon or ham is debatable in a world where not everybody shares the strict attention to detail of this company, but I applaud them for their honesty and the practical way in which they have dealt with this thorny issue (see Woody’s Free Range Farm) In the end, I feel much of the problems are self-inflicted in a world where bacon flitches are no longer wrapped in cloth, palletized and shipped any longer.

By William James Topley – This image is available from Library and Archives Canada under the reproduction reference number PA-026092 and under the MIKAN ID number 3424485

How to Explain it?

As you can see from this short overview, the matter is not simple but the fact that there is an issue to address is clear. For myself, I am satisfied that in the minuscule levels that nitrite is used and remains present in bacon and hams, these products are completely safe to eat. The consumer is, however, also not wrong to be concerned about the matter. The problem is that the explanation above is already so technical – who can follow this? Let alone a dissertation by Dr Sebranek or Dr Møller, two of the world authorities on the subject. If anybody must understand what they are saying before one can decide which bacon is healthy and not and which brine to use or not, only a handful of people will ever make a meaningful determination on the matter. This business of reduction and oxidation, bacterial, enzymatic reactions are all very confusing for people without an advanced degree in chemistry, like me. The only way that I could make any sense of it was to follow the story right from the beginning. As it unfolded. And what a story it turned out to be!

C. Review: How did we get here?

I will tell the story, at least the parts that are pertinent to the discussion about nitrite, from a series of articles I did on the subject over a few years and from extracts of a book I wrote about the history of bacon called Bacon & the Art of Living. One article where I deal with the full sweep of its history is Bacon Curing – a Historical Review.

Before we jump into the detail, let’s establish a timeline. Broadly speaking the development of bacon curing to where we are with the direct addition of nitrite to curing brine can be divided into the following timeline.

The Prehistory of Bacon Curing experimenting with various salts (sodium chloride, sal ammoniac, nitrate also called saltpetre) From antiquity to the end of the 1500s.
Saltpetre gained popularity as it becomes widely available as a vitalizer, an ingredient in gunpowder and as medication. 1600 to 1800.
William Oake invented Tank Curing/ Mild Curing around 1832 (aged 25) – an Indirect Addition of Nitrite to Curing Brines.
Dr. Ed Polenski’s Article on Nitrite in saltpetre brines, 1891.
The academic work of German and English researchers identifying Nitrate and Nitric Oxide as the curing agents. Notwang (1892), Lehmann (1899), Kiskalt (1899), Haldane (1901).
The work of Ladislav Nachmullner and the first curing brine containing sodium nitrite (1915).
The Impact of the First and Second World War in changing the indirect use of Nitrites to the direct addition of nitrites to curing brines.
The Griffith Laboratories as evangelists of the direct addition of nitrites to curing brines. Prague Salt (1925).
“Houston, we have a problem!” The n-nitrosamine problem and the response of the curing industry and world governments, late 1950s.
Must we Remove Nitrite from Food or Manage it?

D. Why do we use it at all?

Its anti-microbial ability now becomes important, especially as it relates to C Botulinum. Nitrite as a key hurdle in botulinum prevention remains relevant. I looked at the most important microorganism in a 2015 article, Clostridium Botulinum – the priority organism

The Anti-Microbial Efficacy of Nitrite

In 2015 I had the privilege to interact with Dr R. Bruce Tompkin on the issue of the antimicrobial efficacy of nitrate and nitrite. Dr Tompkin was one of the founders of the HACCP system. We had some correspondence about the possibility of replacing nitrite as a hurdle and his insights are still helpful to this day. For this, I will be eternally grateful. It was written before I discovered that tank curing came from Ireland and there are other sections where my understanding evolved. I nevertheless share it with you as I wrote five years ago. I am thankful for experts from around the world who continue taking the time to give input not just on the matter of nitrite replaces, but on a wide array of meat and processing-related subjects. I can honestly say that if you do not know in our trade you do not want to know! (or you have been so busy that there was no time to find out!) Which I fully understand!!

I looked at this issue in 2015 in an article, Concerning Nitrate and Nitrite’s antimicrobial efficacy – chronology of scientific inquiry.

E. Further Work on Nitrite Free Bacon and its role in Human Physiology

Conclusion

I have no doubt that this matter can be resolved scientifically. In terms of marketing, this can be done in a way that the consumer will be fully in-step, all the way and is taken along, not left behind or feel that half-baked ideas are thrust down his/her throat. This work is important, not just for the uncompromising drive to better and healthier food, but for the overall quest to be better in every way! To offer safe and delicious food should be the desire of every food producer on earth. Anything less both in terms of taste, quality, and safety is a crime! In this work, I can end with a quote from no finer man than Nelson Mandela who said that “what counts in life is not the mere fact that we lived. It is what difference we have made to the lives of others that will determine the significance of the life we lead!”

References

Jens K. S. Møller and Leif H. Skibsted. 2002. Nitric Oxide and Myoglobins. Chemical Reviews 2002102 (4), 1167-1178DOI: 10.1021/cr000078y

Shiva, S. 2013. Nitrite – A physiological store of nitric oxide and modulator of mitochondrial function. Redox Biology. Volume 1, Issue 1, 2013, Pages 40-44. Download

Chapter 12.05: The Preserving Power of Nitrite

06/27/2021 eben van tonder Bacon and the art of living, Bacon History, Best Bacon, best bacon on earth antimicrobial properties of nitrite, nitrite curing

Introduction to Bacon & the Art of Living

The Preserving Power of Nitrite

October 1959

Dear Lauren,

Star_Tribune_Tue__Dec_29__1959_ — From Star Tribune, Minneapolis, Minnesota, 25 December 1959.

It is almost Christmas and I am looking forward to your visit! There is a possibility that Tristan will be here also. You can imagine my great excitement!

I am sure you read the news of the international opposition to the policies of the South African government. I am very happy about this for the policies of the National Party are diabolical and nothing but a perpetuation of the suppression of the black man since the day Europeans set foot on this great continent. I include a newspaper clipping from a newspaper from Minnesota. The government is set on creating independence from Brittain where the opposition to the Apartheid policies is gaining momentum. I am sure they will succeed because the National Party is very determined.

The white people live under the wrong assumption that they need laws to secure their future. They desire to preserve their heritage of this land by oppressing others. This can never to the basis for the survival of a nation. I am glad that Oscar and I decided years ago to seek independence through economic means and not political. I often wondered if we would have been able to start our bacon company if we were black.

My goal is not to judge every small part of history but to report the story as it unfolded. I wrote to Tristan about how it happened that the direct addition of sodium nitrite in curing brines replaced tank curing as the most advanced way of curing bacon. The question revolved around the fact that nitrite, in too high dosages is toxic. Thinking very simplistically about it, the fact that it is toxic is not only something to be very conscious of but also contributes to its usefulness in bacon curing. It means that we place a substance, toxic to microorganisms in the very small dosages we add in brine, inside the meat and we coat the bacon from the outside with smoke, another toxin for microorganisms that protects the meat from the outside. The important point is the small dosages we use, it is not harmful to humans.

Preservation Through the Right Brine Composition

Conventional wisdom that surfaced in the 1920s suggested that nitrate and nitrate should continue to be used in combination in curing brines (Davidson, M. P. et al; 2005: 171) as was the case with the Danish curing method and the mother brine concept of the previous century. Nitrite gives the immediate quick cure and nitrate acts as a reservoir for future nitrite and therefore prolongs the supply of nitrite and ensures a longer curing action. The question comes up if there are any other reasons why one should continue to use nitrate? Is there, for example, any preservative role of nitrate and while we are considering this question, what exactly is the preservative value of nitrite?

Clostridium Botulinum – the Key Organism

The first thing to remember when considering the effectiveness of a preservative is that not all preservatives are equally effective against all microorganisms. A second point is that different microorganisms are generally associated with different kinds of food. When we look at bacon in particular, what are some of the microorganisms associated with it? Some of these are Lactobacillus, Pseudomonas, Clostridium, yeasts like Dabaryomyces and moulds like Aspergillus and Penicillium. (Jay, J. M. et al.; 2005: 102) We then want to look at antimicrobials that are particularly effective against these and other organisms associated with bacon.

Before we look at this list more carefully and how these organisms are managed, one organism is the starting point when considering the antimicrobial efficacy of any chemical. The first and most important microorganism, to begin with, associated with bacon and other foods is clostridium botulinum. (see Concerning Clostridium Botulinum – the priority organism)

Montclair Tribune; 20 April 1972: 28

The reason for its priority in food safety is that certain types of toxins count as some of the most lethal substances on earth. A headline appeared in a newspaper in California in 1972, reporting that nitrate has been found effective against botulism. (Montclair Tribune; 20 April 1972: 28) The headline incorrectly read “Nitrate useful against botulism.” The study is reporting on deals with nitrite.

The discovery was newsworthy. Botulism is a serious and potentially fatal disease that caused considerable alarm since it was identified in the early 1800s by Justinus Kerner. (Emmeluth, D.; 2010: 16) It is caused by a toxin called botulin, a neurotoxic protein produced by the bacteria clostridium botulinum. It is so poisonous that one-millionth of a gram can kill an adult human. 500mL is enough to kill every person on earth. (Sterba, J. P.; 28 April 1982)

Preventing it remained a focus for the food industry throughout the 1900s and into the present day and any consideration of the anti-microbial effect of nitrate and nitrite must include its effectiveness in preventing it. It affects humans and animals and one of the ways we contract it is through food.

Clostridium botulinum was isolated as the microorganism causing botulism in 1895 by Emile Emergem, professor of bacteriology at the University of Ghent, in Belgium. (Emmeluth, D.; 2010: 19) The following year an article appeared in The Centralia Enterprise and Tribune in Centralia, Wisconsin, reporting on a warning issued by the Connecticut State Department of Health, issued in its weekly bulletin, in response to two cases of botulism that occurred in New Haven, the week prior. The warning identified home canned foods as the usual source of botulism. Especially “improperly processed, non-acid fruits and vegetables which are served cold.” The incidents of the previous week were traced back to improperly processed home-canned figs. (The Centralia Enterprise and Tribune; 25 January 1896: 5)

Such was the public’s concern over botulism that in 1896 when in the US new Food and Drug Administration rules came into effect allowing low-level radiation of food, concern was raised by some consumer groups that this would destroy “more common and more vulnerable spoilage bacteria” while deadly botulism bacteria would grow undetected. The argument was that the more common spoilage bacteria would alert the consumer that the food has gone bad before the deadly botulism toxins could be produced. The FDA responded to this concern by pointing out that at higher radiation levels it would share the concern, but that the levels were to low to completely destroy the spoilage bacteria. (The Laredo Times; 1 December 1896: 14)

It is interesting that this same principle is still a recognised hurdle against botulism where spoilage bacteria is allowed to be present in certain food in order to cause spoilage before clostridium botulinum toxin formation takes place. The Montclair Tribune article of 20 April 1972 reported on work done by Dr. Richard A. Greenberg, director of research for Swift & Company, on behalf of the American Meat Institute. After studying canned ham he suggested that the unblemished botulism safety record of the curing industry in the USA may be due to the use of nitrites. So, clostridium botulinum will feature prominently in our considerations of the efficacy of nitrate and nitrite as antimicrobial agents, but other bacteria will also be considered.

The historical perspective

There are many reviews of the antimicrobial efficacy of nitrate and nitrite. I rely exclusively on a review article written by Dr R. Bruce Tompkin (1), the former Vice President for Food Safety, ConAgra Refrigerated Prepared Foods, published as part of Davidson, M. P. et al’s, 2005 publication, “Antimicrobial in Food, Third edition.” Dr Tomkin is an exceptionally qualified man to write such a review. He is a “microbiologist with more than 45 years in the food processing industry and one of the developers of HACCP.” (Maple Leaf Press release) He arranges the material chronologically which provided insight into why the research was conducted and why certain important points were missed early on.

It is in line with our approach of first understanding the historical background to any technology associated with the bacon industry.

10262188_10152414306796650_3469446068461831418_n

Observations

We remain with the story of nitrite and nitrate as science started to unlock the fascinating secret of its full effect in cured meats since the 1930s. Most of the research focuses on canned and cured meat and we incorporate some of these important findings and see what can be applied to bacon. The focus on research of nitrite and its effectiveness in canned cured meat makes sense since botulin formation occurs mostly from canned food and due to its deadly nature, it is the priority organism in food safety. All consideration of preservatives must, therefore, start with the question if its effective against clostridium botulism, its spores and toxins.

“Unlike most other antimicrobial agents, there has been a long, controversial history over whether nitrate and nitrite have antimicrobial properties.” (Davidson, M. P. et al.; 2005: 172) An avalanche of investigations followed, elucidating the efficacy of these chemicals as antimicrobials.

Tanner and Evans (1933) said that sodium chloride (normal table salt), is the most effective component in curing mixtures and that sodium nitrite present, apparently produced no effect on organisms. They then cited MacNeal and Kerr who said that potassium nitrate (saltpetre), in acid solutions had marked inhibitory efficacy. They said that this effect was “incompatibly greater than that of salt.” They believed that the claim of meatpackers that small amounts of nitrate in the pickle produced better preservation of the meat was born out by their results. It seemed that nitrate was especially valuable in preventing a high degree of acidity of souring of meat. (Davidson, M. P. et al.; 2005: 172)

Brooks et al (1940) looked at bacon curing in the United Kingdom and concluded that bacon can be produced with nitrite only. “They said that the characteristic cured flavour of bacon is primarily the result of the action of nitrite. The conversion of nitrate to nitrite in commercial bacon curing brines is mainly the result of the growth of micrococci. The presence of nitrate or microbial action during the curing process is not essential for bacon flavour.” Rapid chilling, as was practised in the United States, was also not detrimental, as some speculated. (Davidson, M. P. et al.; 2005: 172)

Tarr and Sutherland (1940) showed that nitrite delayed spoilage in fish. Tarr (1941) revealed the importance of pH to the efficacy of nitrite. At pH 7.01 there was little or no inhibition, but at p”H 5.7 and 6.0, complete or strong microbial inhibition occurred.” (Davidson, M. P. et al.; 2005: 173)

Jensen and Hess (1941) insisted that nitrite’s role was purely colour development and said that nitrate “exerts a definite inhibitory effect upon bacteria.” They reported that nitrite reacts with protein during the heating process and is destroyed, “thus leaving the meat in much the same state as freshly cooked uncured meat.” Scott (1955) agreed. Jensen and Hess said that a combination of heat, nitrate, nitrite, and salt caused the destruction of anaerobic spores at much lower temperatures. (Davidson, M. P. et al.; 2005: 173)

Yesair and Cameron (1942) took up this concept and reached the conclusion that curing salts do not assist in thermal destruction but inhibit outgrowth. Stumbo et al. (1945) reported that nitrite delayed germination, although salt was the stronger inhibitor. Nitrate alone or in combination with other ingredients did not “appreciably influence spoilage.” (Davidson, M. P. et al.; 2005: 173)

Jensen et al. (1949) looked at the combination of heat and curing salts. The magical temperature range where increased inhibition occurs in tubes of pork was between 50 deg C and 65 deg C, for 30 minutes. Raising the temperature and heating it for longer times did not increase the effect. However, looking at the effect of canned ham, increasing salt and nitrite increased inhibition. Studying these effects of C. sporogenes 369 showed that increasing nitrate did not increase the inhibition. (Davidson, M. P. et al.; 2005: 173)

Steinke and Foster 1951 found salt to be major factor retarding botulinal outgrowth in temperature-abused products. Having a moderately high brine of 5.05% to 5.37% and a pH range of 6.1 to 6.5. A combination of sodium nitrate, nitrate, and nitrite was the most inhibitory. (Steinke and Foster 1951) (Davidson, M. P. et al.; 2005: 174) Bulman and Ayres (1952) found that a mixed cure of salt, nitrate, and nitrite yielded the maximum inhibition. (Davidson, M. P. et al.; 2005: 174)

“Henry et al. (1954) found that at pH 7.5 or above, nitrite enhanced bacterial growth in curing brine. A pH of 5.6 to 5.8 was optimal for antibacterial efficacy. At pH 5.3 or below, nitrite rapidly disappeared and was ineffective. Nitrite was more inhibitory in the presence of ascorbate.” (Davidson, M. P. et al.; 2005: 175)

Castellani and Niven (1955) said that nitrite was not known to have any practical preservative value against those organisms not inhibited by high salt in cured meat. They also found that if a broth medium (pH 6.55) was autoclaved with glucose, a very small amount added nitrite prevented staphylococcal growth when incubated anaerobically. (Davidson, M. P. et al.; 2005: 175)

Lechowich (1956) showed that S. aureus growth can occur in any combination of salt, nitrite, and nitrate that is palatable and permissible. (Davidson, M. P. et al.; 2005: 175) Scott (1955) said that because nitrate exhibited relatively poor antimicrobial inhibition and nitrite, although effective, has been shown to be unstable, the control of salt concentration and resultant water activity is the most reliable bacteriostatic system for cured meats. (Davidson, M. P. et al.; 2005: 175) As late as in 1957, Eddy was very cautious when expressing an opinion about the antimicrobial ability of nitrite. He wrote: “Taken in their totality, these observations leave no doubt inhibition by nitrite is at least a possibility”. (Davidson, M. P. et al.; 2005: 176)

Tomkin summarizes the findings from 1950 to 1960 and state that it was found that salt, per se, had no antimicrobial effect, other than its possible influence on water activity. (Davidson, M. P. et al.; 2005: 176) He further states that by the end of the 1960s nitrite was recognized as an effective antimicrobial agent, but its value as a preservative in perishable meat was still in doubt. The majority of studies focused on and proved its effectiveness in shelf-stable canned meat. (Davidson, M. P. et al.; 2005: 176) Brine content was shown to be an important factor in botulinal outgrowth and toxin formation. (Davidson, M. P. et al.; 2005: 177)

Following 1960, the focus shifted towards the role of nitrite in the total inhibitory system in cured meat. (Davidson, M. P. et al.; 2005: 177) In 1962, Eddy and Ingram investigated “the survival of S. aureus in vacuum-packed, sliced bacon. They found that staphylococci grew among the natural microflora of the bacon but growth was better when the number of saprophytic microorganisms was low and the storage temperature was high. (Doyle, M. 1989. : 476)

Gould (1964) showed that the toxicity of nitrite was 3 to 5 times greater at pH 6 than at pH 7. (Davidson, M. P. et al.; 2005: 177) Brownlie (1966) indicated that at pH 7.0, the presence of nitrite caused very little or no inhibition. At pH 6.0 and below, increasing the amount of nitrite from 25 to 200 μg/g caused progressively greater inhibition. (Davidson, M. P. et al.; 2005: 178) Brownlie (1966) has shown that nitrite was more inhibitory at 0°C than at the other temperatures tested (10°C and 25°C) Several studies showed that salt becomes more inhibitory as storage temperatures are decreased in perishable vacuum-packed cured meat. (Davidson, M. P. et al.; 2005: 177)

Brownlie (1966) showed the inhibitory effect of sodium nitrite concentration, pH and temperature. Brine content was shown to be an important factor in botulinal outgrowth and toxin formation. (Davidson, M. P. et al.; 2005: 177) According to studies by Riemann Anon (1968), C. botulinum type A, the most toxic form, seemed to be completely inhibited by 4.5% brine at pH 5.3, 5.5% brine at pH 6.1, and 8.6% brine at pH 6.5. (Davidson, M. P. et al.; 2005: 180)

Studies by Baird-Parker and Baillie (1974) indicated that when adding sodium nitrite and L-ascorbic acid as filter-sterilized solutions, the number of strains showing growth in broth was found to decrease with increasing nitrite (50, 100, 150, 200 μg/g), decreasing temperature (25°C, 20°C, 15°C), decreasing pH (7.0, 6.5. 6.0, 5.5), increasing salt (1.5%, 3.0%, 4.5%, 6.0% w/v), and decreasing inoculum level (106, 103, 101). Adding L-ascorbic acid (1.0%) markedly increased the effectiveness of nitrite. (Davidson, M. P. et al.; 2005: 180)

Adding haemoglobin resulted in a lower level of residual nitrite after processing, decreasing botulinal inhibition. (Davidson, M. P. et al.; 2005: 181) Tompkin et al. concluded that Isoascorbate, ascorbate, cysteine, and ethylenediaminetetraacetic acid (EDTA) share a common function in meat, which later was demonstrated to be the sequestering of iron. (Davidson, M. P. et al.; 2005: 180)

Grever (1974) indicated that Bacillus species are less sensitive to nitrite than clostridia. (Davidson, M. P. et al.; 2005: 187) Tompkin et al (1979) also showed that although isoascorbate enhances the antibotulinal effect of nitrite in freshly prepared perishable cured meat that is temperature abused, isoascorbate also reduces the efficacy of nitrite by causing more rapid depletion of residual nitrite. (Davidson, M. P. et al.; 2005: 187) According to Crowther et al. (1976), studying mixtures of nitrite, nitrate, ascorbate and brine levels and their effect on botulinal toxins in vacuum packed back bacon, a higher percentage of samples analysed were toxic with the addition of 200 μg/g of nitrite than with 100 μg/g of nitrite. The addition of ascorbate enhanced the antibotulinal effect of 100 μg/g but not 200 μg/g of nitrite. These values raise a question concerning the conclusions that (1) protection was greater if the level of nitrite was increased to 200 μg/g and (2) sodium ascorbate at a level up to 2000 μg/g did not reduce the protection afforded by nitrite against C. botulinum. (Davidson, M. P. et al.; 2005: 187)

Crowther et al. (1976) also reported that S. aureus grew well in the medium-salted bacon, regardless of the level of nitrite or ascorbate. (Davidson, M. P. et al.; 2005: 189)

Shaw and Harding (1978) studied the effect of nitrate and nitrite on the microbial flora of Wiltshire bacon. The predominant flora of the bacon after curing consisted of micrococci, Moraxella species, and Moraxella-like bacteria. Omitting nitrate led to higher numbers of Moraxella species in the cured bacon. However, bacon that was sliced and vacuum packaged developed a flora mainly of micrococci and lactics. Including nitrate in the bacon enhanced the growth of micrococci. (Davidson, M. P. et al.; 2005: 189)

Shaw and Harding (1978) showed that because higher numbers of lactics were present in bacon with the lowest initial nitrite concentration, it was suggested that nitrite could be important in delaying the sour spoilage caused by the growth of lactics. (Davidson, M. P. et al.; 2005: 189) Various botulinal studies were conducted in the USA in the 1970s. It showed that vacuum-packaged bacon prepared with 0.7% sugar (sucrose) or more provides sufficient fermentable carbohydrate that naturally occurring lactics cause a decline in pH to inhibitory levels. (Davidson, M. P. et al.; 2005: 190)

The botulinal studies in the ’70s also showed that brine levels below 4.0% are not inhibitory to botulinal outgrowth. As the brine level exceeds 4.0%, outgrowth is increasingly delayed. If a lactic fermentation develops in the interim, the combination of relatively higher brine and decreasing pH can prevent botulinal outgrowth. (Davidson, M. P. et al.; 2005: 190)

These same studies showed that the level of residual nitrite at the time the bacon is abused influences the extent of the delay in botulinal outgrowth. The level of nitrite added to the product is not important, aside from the fact that the amount of added nitrite partially determines the level of residual nitrite. (Davidson, M. P. et al.; 2005: 190)

It also showed that the addition of ascorbate or isoascorbate can act in concert with residual nitrite to retard botulinal outgrowth in freshly produced bacon. However, ascorbate and isoascorbate can also have a negative effect by causing more rapid loss of residual nitrite during processing and storage. (Davidson, M. P. et al.; 2005: 190)

Nurmi and Turunen (1970) studied the effect of adding nitrite to a previously autoclaved broth medium (pH 6.0). Lactobacilli (78 strains), micrococci and staphylococci (24 strains), and Pediococcus cerevisiae (1 strain) were examined for their tolerance to nitrite in the presence and absence of 4.01% salt. At 200 μg/g growth was delayed or slower. At 40 μg/g growth was comparable to that in the control without nitrite, results were subsequently reported that showed the production of enterotoxin A to decrease as pH decreased, salt increased, and nitrite increased (Tompkin et al., 1973).

Morse and Mah (1973) studied the effect of glucose on enterotoxin B synthesis in a broth medium buffered to an alkaline pH (7.7). Adding glucose caused decreased toxin production. Glucose repression of enterotoxin B production was also reported to occur at pH 6.0 but to a lesser degree than at pH 7.7 (Morse and Baldwin, 1973).

Bean and Roberts (1974, 1975) The inhibitory effect of nitrite in the recovery medium increased with increasing salt content, decreasing incubation temperature, and decreasing pH. (Davidson, M. P. et al.; 2005: 190)

Zeuthen (1980) conducted studies on the effect of pH on the rate of microbial growth in sliced ham. They found that the lower pH meat resulted in ham with a pH of 6.0 with residual nitrite after processing and the higher pH meat resulted in a ham with a pH of 6.35 with a higher residual nitrite level. The brine level of both products was equal. During 7 – 8 weeks of storage at 5 deg C, the rate of microbial growth was considerably slower in the sliced ham prepared with the lower pH meat. (Davidson, M. P. et al.; 2005: 203)

In the 1980s, the USDA adopted a regulation for bacon that requires a maximum of 120 μg/g sodium nitrite and the addition of 550 μg/g sodium ascorbate or isoascorbate. (Davidson, M. P. et al.; 2005: 203)

It was also shown during this period that the mechanism of nitrite inhibition differs in different bacterial species. (Davidson, M. P. et al.; 2005: 203)

In 1988, the USDA initiated a series of increasingly restrictive policies on the rate of chilling for perishable cured meat manufactured under USDA inspection. Dr. Tompkin continues that this is a case where the epidemiologic data indicate a negligible public health concern for cured meats but the evidence from challenge studies and predictive modeling suggests otherwise. He notes that the situation is a reminder of Morris Ingram’s frustration with the increase in research on nitrite’s role in botulinal inhibition in the 1970s. At the time he stated, ” What we need at the present time, in my opinion, is not more inoculated pack experiments but a rationale for interpreting them” (Ingram, 1974).” Since 1990 there has been an increased interest of L. monocytogenes in ready-to-eat foods.

McClure et al (1991) found the efficacy of sodium nitrite to be temperature and pH-dependent. At a pH value of 6.0 sodium nitrite had little effect in delaying the time to detect visible growth except at the highest level tested (200 ppm) and a temperature of 15 deg C or below. At pH 6.0 and 5 deg C, no growth was observed with any of the levels of sodium nitrite evaluated (50, 100, 200, 400 μg/g). Buchanan and Golden, 1995; Buchanan et al., 1997) conducted an extensive series of experiments that led to the conclusion that nonthermal inactivation of L. monocytogenes by sodium nitrite is pH-dependent and related to the concentration of undissociated nitrous acid. (Davidson, M. P. et al.; 2005: 203)

Duffy et al. (1994) inoculated a variety of vacuum-packaged cooked sliced meat with L. monocytogenes and found the lag time increased and the rate of growth decreased at 0 deg C and 5 deg C with the addition of sodium nitrite (0 to 315 μg/g). The effectiveness of sodium nitrite was significantly increased with the addition of sodium ascorbate. (Davidson, M. P. et al.; 2005: 203)

Points of Application

Here are a few practical applications that flow from the consideration of nitrite and nitrate in bacon.

– An important economic and food safety consideration is shelf life. In order to extend shelf life, good manufacturing practices, a thorough food safety program and using the correct heat, freezing and pH during processing are as important as antimicrobial chemicals. Some argue that these may have the ability to replace most antimicrobial’s in food. An example of this is the contention that much of the improved shelf life in the US on bacon and poultry products is “attributed to improvements in sanitation between cooking and packaging as a requirement to control Listeria contamination”. (private communication with Dr Tompkin)

– It is possible, in manufacturing certain products, to reduce the pH. We suggest manipulating the pH of the meat to levels of between 5.6 and 5.8. Not below 5.3 since reducing the pH will increase the rate of nitrite depletion (private communication with Dr. Tompkin) and 5.3 has been shown to be a threshold.

– Use nitrite and salt in combination with a low temperature, targeting an internal core temp of between 50 and 65 deg C for at least 30 minutes.

– The goal of keeping the meat temperature below 5 deg C from receiving meat till before smoking/ cooking and then rapid chilling and freezing and keeping the finished product below 5 deg C is an excellent way of increasing the lag time and the reduce the rate of growth of L. monocytogenes. As a general policy, meat must be kept below this during processing.

– Related to the greening of bacon. “Greening is due to the growth of certain other lactobacilli which also occur on cured meats and is a very old problem. It is a major problem at times if cooked product is held in storage allowing for the lactobacilli to multiply and then the product is used as rework into a new product. Over time the repetitive addition of aged rework leads to a high population of lactobacilli that are exceptionally heat resistant. They are microaerophilic meaning they can not tolerate much oxygen and grow well under the perimeter of sausages or in vacuum packaged meats. Upon opening the packages the product turns green.” (private communication with Dr. Tompkin)

Another reason often cited for a green discolouration in cured meat is nitrite burn. It is caused by a combination of excessive levels of nitrite and reduced pH (Deibel and Evans, 1957). The levels that nitrite is used in cured meat is so low that greening in bacon is unlikely to occur as a result of nitrite and reduced pH. (private communication with Dr. Tompkin)

10170683_10152501991376650_4986278986190926576_n

Nitrite’s role in cured meat is far more than only colour and taste. It is a key component of a very complex environment with definite antimicrobial efficacy. It is an effective hurdle against clostridium botulinum. Its antimicrobial efficacy extends to other organisms, the level of which differs from organism to organism. It is definitely an important general antimicrobial hurdle.

Regarding nitrate, enough early research has been done that show efficacy if it’s used in conjunction with nitrite and salt to warrants its inclusion in brine curing mixes. The efficacy of nitrate and nitrite is strongly tied to brine composition, pH, heat treatment and adding complementary chemicals. The story of saltpetre (potassium nitrate) and sodium nitrite is epic in the true sense of the word.

It is a huge responsibility to not only produce the best bacon on earth, but also the safest bacon on earth! This is a consideration that never featured high on my agenda in the early years, but as time went by, I started becoming obsessed with it. I know you will have many questions and you can contribute with the most recent research on the subject. Please continue to update this letter in particular when you eventually combine them all into a book.

I wish it was December already that I could see you again. We count the days!

Lots of love from Cape Town,

Dad and Minette.

Notes

(1) Dr. Tompkin is retired and currently associated with the School of Applied Technology as part of the Illinois Institute of Technology. For his background, see https://appliedtech.iit.edu/people/bruce-tompkin.

References

Davidson, P. M. et al. 2005. Antimicrobials in Food, Third Edition. CRC Press.

Doyle, M. 1989. Bacterial Pathogens. Marcel Dekker, Inc.

Emmeluth, D. 2010. Botulism. Infobase Publishing.

Jay. M. J. et al. 2005. Modern Food Microbiology. Springer Science + Business Media.

The Centralia Enterprise and Tribune. Centralia, Wisconsin. 25 January 1896.

The Laredo Times. Laredo, Texas. 1 December 1896.

Maple Leaf Press release: http://investor.mapleleaf.com/phoenix.zhtml?c=88490&p=irol-newsArticle&ID=1363993&highlight=

McCarthy, M. Chairman of the Committee of nitrite and alternative curing agents in food. Et al. 1981. The Health Effects of Nitrate, Nitrite, and N- Nitroso Compounds. National Academy Press.

Montclair Tribune. Montclair, California. 20 April 1972.

Sterba, J. P.. 28 April 1982. The History of Botulism. The New York Times.

http://medical-dictionary.thefreedictionary.com/Clostridium+putrificum

Images

Image 1: Clipping from newspaper article: Montclair Tribune (Montclair, California), 20 April 1972.

Chapter 12.04: The Direct Addition of Nitrites to Curing Brines – The Spoils of War

06/26/202106/27/2021 eben van tonder Bacon and the art of living, Bacon History, Best Bacon direct addition of nitrite, nitrite curing, sodium nitrite

Introduction to Bacon & the Art of Living

The Direct Addition of Nitrites to Curing Brines – the Spoils of War

September 1959

Dear Tristan,

I thought I would write your sister this time around but then realised that I have to finish my tale of how sodium nitrite became the most popular way to add nitrite to curing brines. It one of the most epic developments in the curing world.

From a scientific standpoint, using sodium nitrite as the source of nitrite is an important progression of the technology of bacon curing but there was a problem. The general public saw sodium nitrite as a poison and the cost was exorbitant. It would require more than just an energetic and brilliant Master Butcher from Prague to convince the world that it is an improvement in curing technology.

Early Public Perception about Nitrite

Between the mid-1800s and early 1900s, industry and informed members of the public knew nitrite as an ingredient in medication ^[8] (Vaughn E, et al.;2010; Jul–Aug; 18(4): 190–197) and sodium nitrite as an intermediary in the chemicals dye industry. (Concerning Chemical Synthesis and Food Additives) Most people, however, knew nitrite as a toxic chemical that kills livestock and people if the drinking water has even small traces of it. Such was the concern that nitrite levels in drinking water were reported in local newspapers every week to alert the public to possible contamination. It is, therefore, no wonder that the public and authorities were very skeptical about its use in food.

At the beginning of the 1900s, scientists developed a detailed understanding of the chemistry of curing which showed the priority of nitrites. In contrast to this, the general public and their elected officials were against the direct use of nitrites in food. As is many times the case, the scientific understanding was not general knowledge.

Three parts of the world now become the focus of our attention namely Prague, Germany and in the USA, Chicago. Events, dates, and places will start to overlap and two processes will become very important, the electric arc method of extracting nitrogen from the atmosphere and the Haber process.

As we do so, it is important to understand one more point in chemistry namely the close proximity of nitric oxide (), nitrous acid (), nitric acid (), nitrite (), nitrate () and ammonia (). All have a nitrogen atom as part of either the molecule or the ion. The Haber process yields ammonia () and the electric arc process, either nitrous acid () or nitric acid (). From any of these, nitrite () can be formed. (Webb, H. W.; 1923)

Germany 1910 – 1920 – the Race to Access Atmospheric Nitrogen

Austerity for the middle class in Germany during the Great War.

By the end of the war, the largest stockpiles of nitrite in the history of humanity were in Germany. It was created by the most productive chemicals industry in the world. How this happened is fascinating!

By the late 1800s, it was apparent that the world’s growing populations will not be fed unless atmospheric nitrogen can be harvested. Solving the problem of how to achieve this became one of the biggest priorities of science. After an intense search and various processes tested on an industrial scale, including the electric arc method, the German chemist, Fritz Harber finally solved the problem with the help of Robert Le Rossignol who developed and build the required high-pressure device to create ammonia from atmospheric nitrogen.

The process was first demonstrated in 1909. The German dyes manufacturer, BASF acquired the technology and under the leadership of Carl Bosch, the first Haber-process factory went into operation in Oppau, Germany in 1913. (Concerning the direct addition of nitrite to curing brine) As a direct consequence of this development, Germany was no longer reliant on saltpetre from Chili (sodium nitrate) as fertilizer to feed its massive agriculture industry. Another consequence of the Haber process is that it made World War One possible on an industrial scale. Nitrogen is key in ammunition production. Germany and its allies could escalate the war to a never before seen level.

When ammonia is made from atmospheric nitrogen, it was possible to produce nitrates and nitrites. The concept of using nitrites as a preservative in food was not something new. There are good examples of Germans toying with the use of nitrite in food, even before the war. The German scientist, Glage (1909) wrote a pamphlet where he outlined the practical methods for obtaining the best results from the use of saltpetre in the curing of meats and in the manufacture of sausages. (Hoagland, Ralph, 1914: 212, 213)

Glage gives for the partial reduction of the saltpetre to nitrites by heating the dry salt in a kettle before it is used. It is stated that this partially reduced saltpetre is much more efficient in the production of colour in the manufacture of sausage than is the untreated saltpetre (Hoagland, Ralph, 1914: 212, 213), pointing to the fact that nitrite was being considered as a preservative and for its effect of meat colour, from the earliest times. This means that by the 1910s, German scientists tried to solve the problem by still using saltpetre as a starting point to the reaction but getting to a reduced state faster. The line of thinking of using nitrate as the starting point was finally perfected by the Irish, Danes, and British who allowed the reduction to take place at the normal pace through bacterial means. In developing tank curing, there is no indication that they had any inkling of why it worked. They merely joined different known methods which resulted in faster curing in one cohesive system.

The main obstacle to using nitrite directly was still its cost. When BASF’s new Haber process came into operation, sodium nitrite became generally and cheaply available which meant for curing of meat that it could be added directly without allowing a bacterial reduction of nitrate to nitrite first. Solving the problem by using sodium nitrite was now a serious possibility. The Great War provided the environment to “motivate” the entire meat-curing industry to change from saltpetre to sodium nitrite when saltpetre was suddenly not available for curing and survival was linked to the speed of curing which all resulted in the fact that public perceptions were put aside.

It was a document from the University of Vienna which was the first breakthrough in my research which unlocked the mechanism of how sodium nitrite became the curing chemical of choice. According to it, saltpetre was reserved for the war effort and was consequently no longer available as curing agent for meat during World War One. (University of Vienna). It was reserved for the manufacturing of explosives, and for example, the important industry of manufacturing nitrocellulose, used as a base for the production of photographic film, to be employed in war photography. (Vaupel, E., 2014: 462) It gets even better. The prohibition on the use of saltpetre gives us the background of why people started using sodium nitrite as curing salt instead of saltpetre in Germany.

In August 1914, the War Raw Materials Department (Kriegsrohstoffabteilung or KRA) was set up under the leadership of Walther Rathenau. It was Rathenau who was directly responsible for the prohibition on the use of saltpetre. (11) He, therefore, is the person in large part responsible for creating the motivation for the meat industry in Germany to change from saltpetre to sodium nitrite as a curing medium of choice. It was the vision and leadership of Walther Rathenau, the man responsible for restricting the use of saltpetre, which drove Germany to produce synthesized Chilean Saltpeter. He saw this as one of the most important tasks of his KRA. He said: “I initiated the construction of large saltpetre factories, which will be built by private industries with the help of government subsidies and will take advantage of recent technological developments to make the import of saltpetre entirely unnecessary in just a few months“. (Lesch, J. E., 2000: 1)

Fritz Harber was one of the experts appointed by Rathenau to evaluate a study on the local production of nitric acid. During World War One production was shifted from fertilizer to explosives, particularly through the conversion of ammonia into a synthetic form of Chile saltpetre, which could then be changed into other substances for the production of gunpowder and high explosives (the Allies had access to large amounts of saltpetre from natural nitrate deposits in Chile that belonged almost totally to British industries; Germany had to produce its own). It has been suggested that without this process, Germany would not have fought in the war, or would have had to surrender years earlier.” (www.princeton.edu)

So it happened that Germany became the leader in the world in synthesised sodium nitrate production and it effectively replaced its reliance on saltpetre from Chile with synthesised sodium nitrate, produced by BASF and other factories. As a result of the First World War, sodium nitrite was produced at levels not seen previously in the world and in large factories that were built, using the latest processing techniques and technology. Sodium nitrite, like sodium nitrate, was later used in the production of explosives. Nitroglycerin is an example of an explosive used extensively by Germany in World War One that uses sodium nitrite in its production.

Ball-and-stick model of Amyl nitrite used in the production of nitroglycerin. Amyl nitrite is produced from sodium nitrite. The diagram shows the amyl group attached to the nitrite functional group.

Sodium nitrite and the coal-tar dye industry

The importance of the manufacturing cost of nitrite and the matter surrounding availability can be seen in the fact that sodium nitrite has been around since well before the war. Despite the fact that it was known that nitrite is the curing agent and not nitrate, and despite the fact that sodium nitrite has been tested in meat curing agents, probably well before a clandestine 1905 test in the USA, it did not replace saltpetre as the curing agent of choice. This was due to cost restrictions as much as public opinion.

The technology that ultimately is responsible for synthesising Chilean Saltpeter and made low-cost sodium nitrite possible was incubated in the coal-tar dye and textile industry and in the medical field. The lucrative textiles and dye industry was the primary reason for German institutions of education, both in science and engineering to link with industry, resulting in strong, well-organised skills driven German economy. For example, “Bayer had close ties with the University of Göttingen, AGFA was linked to Hofmann at Berlin, and Hoechst and BASF worked with Adolph Baeyer who taught chemists in Berlin, Strasbourg, and Munich.” (Baptista, R. J.. 2012: 6)

“In the late 1870s, this knowledge allowed the firms to develop the azo class of dyes, discovered by German chemist Peter Griess, working at an English brewery, in 1858. Aromatic amines react with nitrous acid to form a diazo compound, which can react, or couple, with other aromatic compounds.” (Baptista, R. J.. 2012: 6) Nitrous acid (HONO) is to nitrite (NO2-) what nitric acid (NO3) is to nitrate (NO3-). According to K. H. Saunders, a chemist at Imperial Chemical Industries, Ltd., Martius was the chemist to whom the introduction of sodium nitrite as the source of nitrous acid was due. (Saunders, K. H., 1936: 26)

The Economic Imperative

The simple fact is that ammonia can be synthesized through the direct synthesized ammonia method at prices below what can be offered through Chilean Saltpeter. (Ernst, FA. 1928: 92 and 100) Sodium Nitrite can be supplied at prices below Chilean saltpetre and this made sodium nitrite the most effective curing agent at the lowest price since World War One.

As an example of the cost differences, the price of Nitric Acid (HNO3) from direct synthesis in 1928 was $23.60 per ton HNO3 plus the cost of 606 lb. of NH3 by-product and from Chilean Nitrate at $32.00 per ton of HNO3, plus the cost of 2840 N NO3 by-product. (Ernst, FA. 1928: 112)

The Advantage of Scale and Technology

By 1927, Germany was still by far the world’s largest direct syntheses ammonia producer. Production figures for the year 1926/ 1927 exceeded Chilean saltpetre exports even if compared with the highest levels of exports that Chilean saltpetre ever had in 1917. A total of 593 000 tons of nitrogen was fixed around the world in 1926/27. Of this figure, Germany produced 440 000 tons or 74%. The closest competitor was England through the Synthetic Ammonia and Nitrates Ltd. with a total capacity of 53 000 tons of nitrogen per year. (Ernst, FA. 1928: 119, 120) In the USA, seven direct synthesis plants were in operation with a combined capacity of 28 500 tons of nitrogen per year. (Ernst, FA. 1928: 120)

Supporting Evidence from the USA

The thesis that before the war, the production of sodium nitrite was not advanced enough for its application in the meat industry (resulting in high prices and low availability) is confirmed when we consider the situation in the USA. The first US plant for the fixation of atmospheric nitrogen was build in 1917 by the American Nitrogen Products Company at Le Grande, Washington. It could produce about one ton of nitrogen per day. In 1927 it was destroyed by a fire and was never rebuild. (Ernst, FA, 1928: 14)

An article in the Cincinnati Enquirer of 27 September 1923 reports that as a result of cheap German imports of sodium nitrite following the war, the American Nitrogen Products Company was forced to close its doors four years before the factory burned down. The imports referred to, was as a result of Germany selling their enormous stockpiles of sodium nitrite at “below market prices” and not directly linked to a lower production price in Germany, even though this was probably the case in any event. (The Cincinnati Enquirer ( Cincinnati, Ohio), 27 September 1923. Page 14.)

The meat curers initially used sodium nitrite directly (i.e. not mixed with sodium chloride). It looks similar to regular table salt. Several cases of poisoning were reported including the mass poisoning of 34 people including a child who died in Leipzig. The Government promptly banned its use (Hans Marquardt , et al, 1999:21), but in the prevailing war conditions, and with the Government’s inability to stamp out the massive black market in foods, there can be no doubt that this practice persisted throughout the war.

The practice of colouring curing salt containing sodium nitrite pink, probably stems from this indecent or incidents like this, in order to prevent people from confusing sodium nitrite with table salt. The practice became law in most countries in subsequent years and the remains to this day. The Vienna University document indicates that the fast curing of sodium nitrite was recognised and after the war, the ban was lifted. Walter Rathenau’s actions may have motivated the change, but it was the developments in synthesizing ammonia, sodium nitrate and sodium nitrite which provided the price point for the compound to remain the curing agent of choice, even after the war and after the prohibition on the use of saltpetre was lifted.

By 1909, the world production of inorganic nitrogen by the electric arc method and some miscellaneous processes were standing at a combined 3000 metric tons. The Haber process was not invented yet. One year after Ladic started working as a meat curer, by 1913, the arc and miscellaneous processes yielded 18 000 metric tons and the Haber process, 7000 metric tons.

By 1917, the arc and miscellaneous processes delivered 30 000 metric tons and the Haber process, 100 000 metric tons. This was 5 years after Ladic learned the art of curing and possibly started using sodium nitrite in meat curing. Over these five years, he has seen a dramatic increase in the availability of nitrite and therefore a reduction in nitrite prices. In 1920, the Haber process delivered a staggering 308 000 metric ton of nitrogen, compared to the 33 600 metric tons of the arc and miscellaneous processes. (Scott, E. Kilburn. 1923; : 859–76)

World War One broke out on 28 July 1914 and lasted until 11 November 1918. When the war ended, Germany had huge stockpiles of sodium nitrite (along with many other war chemicals). They had to pay a massive war debt and raise the German economy from the dead. These were desperate times and Germany threw its full energy and industriousness behind this effort. The effort focused on the lucrative market of the USA.

The USA – 1910’s – Nitrite on Trial

The drama of the sale of German nitrites played itself out in the USA and particularly in Chicago. This directly led to the creation of a legendary curing salt, Prague Salt, which later became Prague Powder. We used Prague Powder during all the years that I was with Woodys. These events played out in America.

We begin our US story by looking at public and government views on nitrite. During the 1910s, the USA wrestled with the question of whether nitrites in food constitute adulteration and its consideration created its own epic drama. Vastly opposing views were held in relation to preservatives and colourants generally. Prof. Julius Hortvet, a chemist at the Minnesota Dairy and Food Commission said in an address delivered on 16 July 1907, at the Eleventh Annual Convention of the Association of State and National Food and Dairy Departments, in Jamestown, “Some state laws go so far as to inflict fine and imprisonment for making an article appear better than it really is.” He presented the opposing view when he said that he believes that “if we must have legislation in regards to this, it would be wiser to reserve it and punish the man who did not make his food product as attractive as possible.” (American Food Journal; 1907)

In his speech, he made the following prophetic comment about saltpetre which in years to come would become one of the dominant arguments for the use of nitrite in foods. He said that “we know . . that certain substances, as salt and saltpetre, have caused death from the effects of large doses.” He then draws a brilliant comparison between these products and alcohol when he said that “alcohol is classed as a poison.” His point was that what is good for alcohol, which is a poison if consumed in high concentrations and large volumes, should be good for saltpetre (i.e. limit the amount of nitrate and nitrite in foods instead of banning it altogether, as is the case with alcohol). “In short,” he said, “the whole question sometimes is relative.” (American Food Journal; 1907)

He was “not contending that certain articles commonly used in . . . . food may or may not under certain circumstances act as a poison.” He was “simply defending . . . against two possible evils: first, the addition to . . . food of any substances that will tend to augment the possibilities of harm arising from our daily diet.” His second point sounds like one directed to the use of nitrite and its medicinal use when he said that “he is secondly defending against,” the addition to . . . foods of substances having therapeutic or even toxic properties by persons unqualified to prescribe such substances.” (American Food Journal; 1907) He is possibly tripped up by a lack of scientific understanding about nitrites at the time, but both cautionary notes are commended and points that I have for years lived by.

In the 1910s, the US Department of Agriculture had the right to promulgate “standards of purity for food products and to determine what is regarded as adulteration therein.” (American Food Journal; 1907 vol 2 no 2, 15 Feb 1907, p43) Whether these standards would become law was an open question at this stage. If there was a dispute about a substance, it was heard by a special organ of the US Department of Agriculture, the Referee Board of Consulting Scientific Experts, created in 1908. The battleground about the use of nitrites itself was not the meat industry. It seems that the meat industry considered and possibly used it in secret. The battle played out in its use as a bleaching agent in flour. The controversy came to a head in a landmark court case in 1910 related to flour.

The millers were infuriated because the attorney general opted for a jury trial instead of referring the matter to the Referee Board of Consulting Scientific Experts. (Chicago Daily Tribune; 7 July 1910; Page 15) I can only suspect that the attorney general was himself against the use of nitrites in food and probably did not want scientists to decide.

A court case was brought by the US Federal Government against the Mill and Elevator Company of Lexington, Nebraska. The charge was that they adulterated and misbranded flour and sold it to a grocer in Castle, Missouri. The government seized as evidence 625 sacks of flour from the grocer. The court case lasted five weeks. The case was brought by the government under the pure food and drug act of 1906. (Chicago Daily Tribune; 7 July 1910; Page 15) This is an act “for preventing the manufacture, sale, or transportation of adulterated or misbranded or poisonous or deleterious foods, drugs, medicines, and liquors, and for regulating traffic therein, and for other purposes.” (www.fda.gov)

The government contended that “poisonous nitrites are produced in the flour by bleaching.” They did not share the view of Prof. Julius Hortvet that we looked at earlier who said that these matters are relative to the amount of the substance used since alcohol is also a poison if used in the right quantity. The Federal Government said that “any amount of poison introduced into food is an adulteration.” (Chicago Daily Tribune; 7 July 1910; Page 15)

The issue was that as much as 80% of the flour produced in the USA during that time was bleached with a nitrogen peroxide process. Flour naturally has a creamy tint. The cheaper the grade, the more creamy it is. In ages past, flour was bleached simply by age. The chemical bleaching process with nitrogen peroxide instantly changes the yellowest flour whiter than the highest grade. The process results in residue traces of nitrous and nitric acid being left in the flour which produce nitrites and nitrates. (Chicago Daily Tribune; 7 July 1910; Page 15)

The defence argued that “nitrates (and nitrites) were present in such small quantities that no man could eat enough bread at one time to be poisoned by them.” (Chicago Daily Tribune; 7 Jul 1910; Page 15) The government contended that “if this view were upheld by the courts all foodstuffs manufactured could introduce quantities of poison into their products, infinitely small in each case, but devastating in their cumulative effect.” (Chicago Daily Tribune, 7 Jul 1910, Thu, Page 15) (I will look at the arguments and provide an overview of how the international food industry answered it in the years following 1910 in a separate letter)

This was a case of huge importance to the industry as can be seen from the list of people called upon by the defence. Pierce Butler of St Paul acted as a special attorney for the defence. (Chicago Daily Tribune; 7 Jul 1910; Page 15) Whether he still had the position in 1910 when the case was heard must be verified, but he was a lawyer of such stature that in 1908, Butler was elected President of the Minnesota State Bar Association. From 1923 to 1939 he served as Associate Justice of the Supreme Court of the United States. (saintpaulhistorical.com)

Apart from Butler, “a large staff of distinguished lawyers fought for the company whose flour was seized, and for the millers of Nebraska, the millers of Kansas, and the company who makes the bleaching machines. Among the experts who testified were all the toxicologists who testified in a previous landmark case (the Swope case), professors of chemistry and medicine from twenty universities, doctors, bakers, millers, and housewives.” (Chicago Daily Tribune; 7 Jul 1910; Thu, Page 15) After seven hours of deliberation, the jury returned a verdict in favour of the government upholding the charge that the bleached flour was both adulterated and misbranded. (Chicago Daily Tribune; 7 Jul 1910; Thu, Page 15) It is fair to conclude that by 1910, nothing was more sensitive in food production than the presence of nitrites and the use of sodium nitrite in food was highly controversial.

Sodium Nitrite Tested in Meat Curing in Chicago

In the early 1900s, in Chicago, the powerful meatpacking companies set up by Phil Armour, Gustav Swift, and Edward Morris were all looking for ways to reduce steers to beef and hogs to pork in the quickest, most economical and the most serviceable manner.” (The Indiana Gazette. 28 March 1924). The earliest reference to a test of meat curing with sodium nitrite in the USA places a secret experiment conducted where sodium nitrite was used to cure meat in 1905. ^[11] This was probably done in Chicago. When the “Pure Food and Drug Act and Meat Inspection Act” of 1906 was promulgated, it made the use of sodium nitrite in food illegal. It was not specifically forbidden, but the act was applied, for example in the 1910 court case we just looked at, in such a way that it was seen as making its use in food illegal.

During the 1910s a very interesting article appeared in Chicago that places a company with the technology to produce sodium nitrite in the same city. It appeared in the American Food Journal of 15 February 1907 entitled “Cheap Nitrogen.” It said that a Chicago-based company was producing nitric acid by the electric arc method invented by Prof. Mościcki of the University of Freiburg, Switzerland, that we looked at before. The method, in reality, was able to produce both nitric and nitrous acid (US patent US1097870) and dates back to 1901. (cesa-project.eu) The article states that the process made its production “cheap enough to be commercially applicable.” (American Food Journal. Vol 2. No 2. 15 Feb 1907, p29) The entrepreneur behind this company was William M. Thomas, who set an experimental plant up in Marshfield Avenue, Chicago. His main goal was probably to produce fertilizer. (Chicago Sunday Tribune, Nov 10, 1907)

We have already referred to the electric arc method several times. Mościcki, the inventor of the process was the former assistant to Józef Wierusz-Kowalski (1896), professor of physics, and rector (provost) at Albert-Ludwigs University in Freiburg, Switzerland. Prof Mościcki was an interesting person. After a very successful academic career and a career as an inventor, he became the 3rd president of the second Polish Republic. He was in office from 4 June 1926 to 30 September 1939. Another interesting fact relates directly to his invention is that in Bern, Switzerland, his patent application was handled by none other than Albert Einstein.

“In 1905 Einstein evaluated Prof Mościcki’s special arc furnace which employed a rotating electric arc and was used for the production of nitric (and nitrous) acid…” ”The field generated by an electromagnet was used to rotate the arc. The 26-year-old physicist (Einstein) and the still young (38) but already renowned inventor and scholar (Prof Mościcki’s) met and discussed the patented idea. Einstein was curious to know why an electric arc changed its orientation in a magnetic field.” Prof Mościcki’s became a successful businessman in Switzerland. (Zofia Gołąb-Meyer Marian. 2006) ^[12]

When we looked at the career of Ladic Nachtmullner, we have seen that the first production of nitrous acid in Switzerland was in 1910, during World War One based on the invention of Prof Mościcki. This happened “immediately after his procedure was patented.” “A factory was opened in Chippis in Wallis canton, Switzerland.” “In the subsequent years, this procedure was substantially perfected and nitrous acid could be supplied not only to Switzerland but also to neighbouring countries.” (cesa-project.eu)

What is interesting in relation to Chicago is that the American Food Journal article says that the Chicago company was already in production by 1907 manufacturing nitric acid “in a small way” from free nitrogen, using the technology invented by Mościcki’s. (American Food Journal. Vol 2. No 2. 15 Feb 1907, p29) In the USA the fixation of atmospheric nitrogen was a priority and they knew they lagged behind Germany. The first US plant for the fixation of atmospheric nitrogen was built in 1917 by the American Nitrogen Products Company at Le Grande, Washington. It could produce about one ton of nitrogen per day. In 1927 it was destroyed by a fire and was never rebuild. (Ernst, FA, 1928: 14)

We can conclude then with great certainty that there was at least one company in Chicago by 1907 that could produce sodium nitrite. Was this venture funded by the meatpacking companies? It is a question for further discovery. A much larger project got underway in 1917, but by 1923, the USA was not in a position to supply material quantities of sodium nitrite.

Nitrite Curing Known in the USA Pre-1925

A document, published in the USA in 1925 shows that sodium nitrite as a curing agent has been known well before 1925. The document was prepared by the Chicago based organisation, The Institute American Meat Packers and published in December 1925. The Institute started as an alignment of the meatpacking companies set up by Phil Armour, Gustavus Swift, Nelson Morris, Michael Cudahy, Jacob Dold and others with the University of Chicago.

A newspaper article about the Institute sets its goal, apart from educating meat industry professionals and new recruits, “to find out how to reduce steers to beef and hogs to pork in the quickest, most economical and the most serviceable manner.” (The Indiana Gazette. 28 March 1924). The document is entitled, “Use of Sodium Nitrite in Curing Meats“, and it is clear that the direct use of nitrites in curing brines has been practised from earlier than 1925. (Industrial and Engineering Chemistry, December 1925: 1243) The article begins “The authorization of the use of sodium nitrite in curing meat by the Bureau of Animal Industry on October 19, 1925, through Amendment 4 to B. A. I. Order 211 (revised), gives increased interest to past and current work on the subject.” Sodium Nitrite curing brines would therefore have arrived in the USA, well before 1925.

It continues in the opening paragraph, “It is now generally accepted that the saltpetre added in curing meat must first be reduced to nitrite, probably by bacteria, before becoming available as an agent in producing the desirable red colour in the cured product. This reduction is the first step in the ultimate formation of nitrosohemoglobin, the colour principle. The change of nitrate to nitrite is by no means complete and varies within considerable limits under operating conditions. Accordingly, the elimination of this step by the direct addition of smaller amounts of nitrite means the use of less agent and a more exact control.”

Aftermath of the Great War

At the end of World War One, England had its own stockpiles of nitrite to dispose of Sodium nitrite in the UK appeared for sale in an advertisement in the Times of London on 1 May 1919, 6 months after the armistice. (The Times, London)

The stockpile of the English was dwarfed by what was available from Germany. The German Government did not wait long before they started selling their war stockpile. An article appeared in The Watchman and Southron on 19 Feb 1921 and shows that German goods, especially chemicals have been making its way to the USA in such quantities that it was seen as a threat to the local industry.

Restrictions on German Sodium Nitrite in the USA

Our three worlds of Germany, Prague, and the USA now merge. The Detroit Free Press (Detroit, Michigan) reported on 14 Jan 1921 that “large stocks of imported sodium nitrite are offered at extremely low prices by agents of German manufacturers.”

Some of the tactics used by Germany to get goods into the USA, including goods subjected to presidential restrictions, were to import goods through the “concealment of the origin of shipment.” German chemicals, subject to such restrictions have been making their way into the USA “appearing as having been shipped from Switzerland, Italy and elsewhere. “Also, there has been extensive smuggling.” The article states that the German plans to sell their products in the USA and economic domination have been made as early as May 1919. (The Watchman and Southron, 19 Feb 1921, page 3)

Great emphasis is placed on sodium nitrite. The author of an article that appeared in The Watchman and Southron, 19 Feb 1921, misread its importance when it was reported that “sodium nitrite would seem to be of minor importance.” “Since the first of the year (Jan 1921), the Germans have glutted the American sodium nitrite market, threatening to destroy the hitherto prosperous American industry, and no relief has yet been obtained through the war trade board.” (The Watchman and Southron, 19 Feb 1921, page 3)

In April 1921, the call made in February for greater control over the import of sodium nitrite was answered when the war trade board in the USA placed an embargo on the importation of sodium nitrite. In the future, it could only be imported under license.

An article that appeared in the Detroit Free Press, 22 April 1921, reported that the goal of the embargo was to “check the heavy imports from Germany and Norway which have swamped the market in the country and reduced prices to a level below the cost of manufacture in the United States. (Detroit Free Press, 22 Apr 1921, Page 18) On 7 May 1924, The Indianapolis News, reports that the tariff for importing sodium nitrite was increased by a massive 50% from 3 cents a pound to 4.5 cents per pound. This was the maximum duty permitted under the Fordney-McCumber tariff act. The additional duty was levied in response to a petition filed by the American Nitrogen Products Company of Seattle, Washington. (Detroit Free Press, 22 Apr 1921, Page 18) In June it is reported that the measures were effective and that sodium nitrite prices were increasing. (Detroit Free Press, Detroit, Michigan, 11 June 1921, p4)

German Sodium Nitrite Appears as Curing Agent in the USA – Ingredients for Deceit.

Union Stock Yard, Chicago, 1910

Then arrived 1925 and everything seems to change as sodium nitrite became available through the Griffith Laboratories in a curing mix for the meat industry. They described Prague Salt and how they came upon the concept in official company documents as follows, “The mid-twenties were significant to Griffith as it had been studying closely a German technique of quick-curing meats. Short on manpower and time, German meat processors began curing meats using Nitrite with salt instead of slow-acting saltpetre, potassium nitrate. This popular curing compound was known as “Prague Salt.” (Griffith Laboratories Worldwide, Inc.)

In Canada, Prague Salt was classified as food adulteration. A progress report from the Canadian department of agriculture in 1925 lists the fact that “one sample of Prague salt” was tested and it was found to contain “5.87 % of potassium nitrite.” It calls it an adulteration. (Progress Report for the Years Canada. Dept. of Agriculture. Division of Chemistry, 1912)

In 1925 in the USA however, the fortunes of nitrite seem to change overnight. If the courts continue to find against the use of an ingredient in food that is seen as a food adulteration, the easiest way to solve the problem is to change the law. In Oct 1925 the American Bureau of Animal Industries legalised the use of sodium nitrite as a curing agent for meat. In December of the same year (1925) the Institute of American Meat Packers document appeared which we already referenced, “created by the large packing plants in Chicago,” entitled “The use of sodium Nitrite in Curing Meats.”

A key player suddenly emerges onto the scene in the Griffith Laboratories, based in Chicago and very closely associated with the powerful meatpacking industry. In that same year (1925) Hall was appointed as chief chemist by the Griffith Laboratories and Griffith started to import a mechanically mixed salt from Germany consisting of sodium nitrate, sodium nitrite and sodium chloride, which they called “Prague Salt.”

Probably the biggest of the powerful meat packers was the company created by Phil Armour. You will recall that Phil was the mentor who set David de Villiers Graaff on his course to build refrigerated railway cars to transport meat which became the backbone of his Anglo Boer War supply to the English forces. More than any other company at that time, Armour’s reach was global. It was said that Phil had an eye on developments in every part of the globe. (The Saint Paul Daily Globe, 10 May 1896, p2) He passed away in 1901 (The Weekly Gazette, 9 Jan 1901), but the business empire and network that he created endured long enough to have been aware of developments in Prague in the 1910s and early ’20s.

Could one of the offers of employment that Ladislav received before 1926 have been from Armour or one of the other meatpackers in Chicago? Griffith Laboratories is formed in the year following the armistice in 1919. This is the same year when the United Kingdom starts selling its sodium nitrite stockpile. Two years later, even cheaper German and Norwegian sodium nitrite start arriving in the USA. In response to this, import duties are levied against German sodium nitrite.

By April 1921, the import duties have been bolstered by a blanket embargo on importing sodium nitrite, except where a special permit is granted. In 1924, the tariffs on sodium nitrite are increased by 50% to the maximum allowed level permitted under the law. By this time, the use of sodium nitrite in curing brines were in all likelihood the norm in Chicago and the 50% increase would have impacted the bottom line of these companies.

Is it possible that by calling it the curing mix from Germany, Prague Salt (as opposed to German Salt or German Nitrites), did Griffith sidestep the import tariff and the required permit for importing sodium nitrite completely? My thesis is that it is entirely possible, even probable. It probably misrepresented the content in Prague Powder (mislabeling) as well as misrepresenting the country of origin.

Just as a side note, I have over the years seen the same trend returning to the meat industry. More and more companies pack their products without declaring the ingredients and apart from protecting the exact composition, I have seen many illegal ingredients going into meat curing in this way.

When Phil Armour passed away, his personal fortune was estimated at $50 000 000. This is almost $1,500,000,000 in 2016. So powerful were the packing companies that US anti-trust legislation was created to break these companies up. The point is that big money was at stake and a big influence on parts of the American government.

Prague Salt

Is it possible that Prague Salt is no more than a clever name given to a curing brine? Taking the full weight of the historical context of events in Prague, Germany, and the USA into account in the 1910s and 1920s; particularly the severe measures to keep German sodium nitrite out of the USA, with the last blow being dealt, in 1924; understanding the extreme pressure on the packing houses to deliver huge volumes of bacon faster, I seriously doubt it. The name was probably deliberate in referring to the salt invented by Ladic in Prague but instead of giving him credit for the invention, it was in all likelihood a ruse to distract the attention from the real issue that German sodium nitrite was still coming into the USA despite a ban.

It seems that the name, Prague Salt was crafted to misrepresent the country of origin and possibly its real composition. Importing salt was no problem. There is a possibility, of course, based on the popularity of salt from Bohemia, and the fact that we know it was widely exported, including to Germany, that the original mix was done in Germany, could even have contained salt from Prague, mixed with German sodium nitrites. Whether this was so or not, the name had enough of a basis in reality in Ladislav Nachtmullner, Praganda and the famous salts from Prague to get it past the customs officers at the American harbours and into the meatpacking plants of Chicago and later, around the world. The fact that it was tested in Canada and found to contain nitrite shows that this was not declared at borders, at least in one of the events of the import into Canada and even though this does not prove that it was done in the US also, it builds the case for the theory that it was imported into the US without disclosure of its nitrite content at the borders.

Prof. Julius Hortvet, in his address in Pittsburgh, had these prophetic concluding remarks about the future of science in the food industry. He said that “…it is imperative that the use of colouring matter should be kept under intelligent control. Regulations of the food industries will in future depend more than ever before on the results of scientific investigations, and the laboratory will become the dominant factor in the shaping of food standards and food laws.” (American Food Journal; 1907)

The legal status of nitrites as food additive was clarified in 1925 through proper legislation, based on Prof. Hortvet’s principle of “intelligent control” when science decided the matter and it was taken out of the hands of “the court of popular opinion.” However, the involvement of the packing plants and Griffith in everything that happened in 1925 raises suspicion of collusion with the US government.

The real hero in the story is the master butcher from Prague who through practical application and the exact scientific inquiry that Prof Hortvet spoke about, developed the first commercially successful curing mix, Praganda. Unknowingly, he became the central figure in the saga about the naming of Prague Powder and the worldwide phenomena of the direct addition of nitrites to curing brines. Finally, there is Griffith Laboratories. The way in which Prague Salt came into the USA was probably not above board. They did, however, became pivotal around the world in making the direct addition of sodium nitrite through Prague Salt and later, Prague Powder a worldwide phenomenon. If Ladislav was the messiah to the bacon industry with his nitrite containing curing mix, Griffith was his St. Paul, the evangelist to the gentiles!

They preached the gospel of a new curing brine that swept the world. So much so that today, it is universally used as the curing brine of choice and only a handful of artisan curing operations still use the tank curing method. Several British processors, including Direct Table Foods from Bury St Edmunds, United Kingdom, retain Tank Curing as one of the methods used to cure bacob.

This was one of the most significant developments in the world of bacon curing. As I have said many times before, understanding the limitations and the mechanics of the system is very important to the modern-day curing plant manager. The tale of nitrite and how sodium nitrite became the curing salt of choice is riveting and involves some of the most important names in scientific history.

Well, my son, there you have it. A story of suspense, intrigue, and risk-taking! Remarkable! I am excited to see you soon during your upcoming vacation. There is a chance that Lauren may come home over the same time. What a blessing that will be to Minette and me. Liam is finishing school this year as Luan is going to Grade 1. We can all go up in Kirstenbosch with Skeleton Gorge one morning and spend the day in the Botanical Gardens in Cape Town. I can not wait to see you!

Lots of love from Cape Town,

Dad and Minette.

Notes

1. The colour changes in meat.

The meat colour generally “changes” (either red, purple or brown), based on how many electrons are spinning around the iron atom which is part of myoglobin. Nitric oxide stabilizes or fixes the myoglobin colour through a reversible chemical bond. It does not colours the meat. (Pegg, B. R. and Shahidi, F.; 2000: 23 – 45) This is an important point to remember because, in the consideration of the use of nitrite in meat, nitrite can not be viewed as a meat colourant.

2. Rate of reaction.

The reaction of nitrite in meat is slow, in part due to the very small quantity used in the curing brine. The rate of reaction, as always, depends on the concentration of the reactants, the pH and temperature.

3. Nitrosating species from nitrous acid.
“The first step in the reaction sequence beginning with nitrous acid is the generation of either a nitrosating species or the neutral radical nitric oxide (NO).” (Sebranek, J. and Fox, J. B. Jn.. 1985)

The following list gives the relative reactivities of various nitrosating species, species 1 being the strongest and species 5 being the weakest.

Species 1:

Source: “From smoke which has many other phenolic compounds”

Species 2:

Source: From curing salt

Species 3:

Source: Found in the air.

Species 4:

Source: Nitrous acid anhydride

Species 5:

Nitrose derivatives of citrate, acetate, sulphate, phosphate.

Sources: Cure ingredients, weakly reactive under certain conditions.

I excluded those found under very acidic conditions. (Comparison by Sebranek, J. and Fox, J. B. Jn.. 1985)

4. The term “nitrite”

“The term nitrite is used generically to denote both the anion, , and the neutral nitrous acid , but it is the latter which forms nitrosating compounds.” (Comparison by Sebranek, J. and Fox, J. B. Jn.. 1985)

5. Reducing agents in the meat system.

One such mechanism for the conversion of “nitrite to nitric oxide in meat is by oxidation of myoglobin to metmyoglobin (brown coloured meat; Fe3+). This oxidation-reduction coupling produces both nitric oxide and metmyoglobin. It has been suggested by Kim et al. (2006) that metmyoglobin can be converted back to deoxymyoglobin through metmyoglobin reducing activity (MRA), a reaction facilitated by lactate. It is the enzyme activity of LDH that helps convert lactate to pyruvate and produce more NADH. Hendgen-Cotta et al. (2008) suggested that deoxymyoglobin can convert nitrite to nitric oxide and the generation of more deoxymyoglobin is likely to result in more nitric oxide (NO) from nitrite and less residual nitrite.” (Mcclure, B. N.; 2009: 28)

Several specific biochemical reducing systems have been the subject of intense investigation as far as their importance in the development of cured meat colour is concerned.

“Endogenous compounds such as cysteine, reduced nicotinamide adenine dinucleotide, cytochromes, and quinones are capable of acting as reductants for NOMb formation (Fox 1987). These reductants form nitroso-reductant intermediates with NO and then release the NO to Mb, forming a NOmetMb complex that is then reduced to NOMb. In model systems, the rate-limiting step in the production of NOMb was the release of NO from the reductant-NO complex (Fox and Ackerman 1968). Several researchers have investigated the effects of endogenous muscle metabolites including peptides, amino acids, and carbohydrates on the formation of NOMb. Tinbergen (1974) concluded that low-molecular-weight peptides such as glutathione and amino acids with free sulfhydryl groups were responsible for the reduction of nitrite to NO, which is subsequently complexed with Mb to produce NOMb. Similar work by Ando (1974) also suggested that glutathione and glutamate are involved in cured-meat colour formation. Depletion of these compounds in meat via oxidation occurs with time, but reductants such as sodium ascorbate or erythorbate are added to nitrite-cured meats before processing to ensure good colour development (Alley et al. 1992) The role of reductants in heme-pigment chemistry is somewhat ambiguous, but they can promote oxidation and even ring rupture under certain conditions. Thus to form cured meat pigment, two reduction steps are necessary. The first reduction of nitrite to NO and the second is conversion of NOmetMB to NOMb.” (Pegg, B. R., and Shahidi, F.; 2000: 44, 45)

6. Sugar as reducing agent.

“Sugars itself does not reduce dinitrogen trioxide in the way that ascorbate or erythorbate does, but it contributes to “maintaining acid and reducing conditions favorable” for the formation of nitric oxide.” (Kraybill, H. R.. 2009)”Under certain conditions reducing sugars are more effective than nonreducing sugars, but this difference is not due to the reducing sugar itself. The exact mechanism of the action of the sugars is not known. It may be dependent upon their utilization by microorganisms or the enzymatic systems of the meat tissues.” (Kraybill, H. R.. 2009)

7. Ascorbate or erythorbate supplements sugar.

An excellent reducing agent was discovered in the 1920s when ascorbate was isolated. As early as 1927, two German chemists, J. Tillmans and P. Hirsch (1927) observed that there is a correlation between the reducing capacity of animal tissue and their vitamin C content. (Concerning the Discovery of Ascorbate) . It reacts so aggressively (effectively) with nitrite, that a less effective, but more manageable cousin (an isomer of ascorbate), erythorbate turned out to be the most practical to use in curing brines along with nitrite and salt.

Ascorbate (vitamin C) reacts so aggressively (effectively) with nitrite, that a less effective, but more manageable cousin (an isomer of ascorbate), erythorbate turned out to be the most practical to use in curing brines along with nitrite and salt.

The old curing brines of the 1800s consisting of saltpeter (nitrate), sugar (create reducing conditions) (6) and salt are, therefore, equivalent to the current curing brines of nitrite (being added directly), erythorbate (reducing agent) and salt. The same general functionality at vastly reduced curing time.

Today, nitrate is still being added to many curing brines as a reservoir for future nitrite as bacteria continue to change nitrate into nitrite. This bolsters the residual nitrite levels in cured meat which is important since it was found that nitrite has a unique anti-microbial function in cured meat, in addition to its function of fixing the cured colour and contributing to the cured taste. It is unique in the sense that it is the most effective chemical control against a highly lethal pathogen, clostridium botulinum. (Concerning Nitrate and Nitrite’s antimicrobial efficacy – chronology of scientific inquiry)

Table salt remains the most important curing agent, but salt alone will not give the cured colour or taste and will not, on its own, be effective against clostridium botulinum. Sugar is still being used in many brines today, mostly to enrich the taste profile and to create browning during frying, especially in bacon. Its contribution to reducing conditions is now secondary and since the addition of ascorbate or erythorbate. Saltpeter has been replaced by sodium nitrite.

8. Nitrite as medicine.

“The organic nitrite, amyl of nitrite, was initially used as a therapeutic agent in the treatment of angina pectoris in 1867, but was replaced over a decade later by the organic nitrate, nitroglycerin (NTG), due to the ease of administration and longer duration of action.” BACK TO POST

9. Azo dye and textile colouring in 1895.

“Dyeing with Diazotised Dyestuffs

All the diazotised dyestuffs belong to the substantive group, and therefore, all that has been said with regard to these dyestuffs and their manner of application applies to the former also. In the majority of instances, however, the dyeings obtained directly are not sufficiently fast to be usable in that condition. Nevertheless, they can be converted into fast dyeings — provided the dyestuff contains free amino groups — by diazotising, followed by developing or coupling. The chemical reactions and method of procedure are just the sam.e as in the case of cotton.

In practice, the diazotising is effected in the following manner : —

The dyed and rinsed silk is entered at once into the cold diazotising bath and is worked about constantly for fifteen to thirty minutes. For every 100 parts of silk, the bath contains 3 parts of sodium nitrite dissolved in 1500-2000 parts of cold water, 8-10 parts of crude hydrochloric acid (20° Be.) being added. The operation must be conducted in wooden vats, metal vessels or fittings (lead excepted) being unsuitable. At one time, ice was used for cooling during the process, but this has been given up in favour of water at ordinary temperature, and in some cases, e. g. diazo indigo blue, the bath may be allowed to rise to 20-30° C. As a rule, the diazotisation will be complete in fifteen minutes, though some dyestuffs take longer and have to be left in the nitrite bath for half an hour. The goods are centrifuged or squeezed, contact with metal being avoided. A lead-lined hydro-extractor may be used, or else the goods must be wrapped in packing-cloth.

The intermediate diazo compound formed on the fiber is very unstable and sensitive to light, especially direct sunlight. The operation must therefore be carried on in a shady room, and care be taken to prevent any part of the diazotised goods from getting dry, or streaks and spots will be formed in the coupling stage. The diazotised material is rinsed and then immediately entered into the developing bath. The nitrite baths will keep for a considerable time and can be freshened up for use by the addition of one-third the original amounts of nitrite and acid. During the whole process the bath should smell strongly of nitrous acid. In the case of light shades, the bath may be weaker in nitrite and acid.” (Ganswindt, A; 1895: 98, 99) BACK TO POST

10. The Professional Career of Ladic

After his apprenticeship, he worked in several factories in Praha (Kracik, Beranek, Ugge-Sitanc and Miskovsky) as an assistant. His first work as a specialist in his field was with A. Chmel, Fr. Hlousek in Paha, Fr. Strnad in Lazne Luhacovice, and later in Germany, at the factories of Josef Sereda, Fr. Seidl, Zemka and Leopold Fisher in Berlin.

He worked as a “cellar man” at Josef Cifka, Vaclav Miskovsky in Praha, Kat. Rabus & Son in Zagreb, Jugoslavia,

Later he worked as a Foreman (Workman Leader) for the companies, Fr. Maly, Vacl. Havrda, A. Kadlec in Praha and Alexander Brero, Hard a/Bodensee Vorarlbersko and, in the end, he worked as a “Quick Production Specialist” for the export of hams for Carl Jorn A.-., Hamburg, Germany, Herrmann Spier, Elberfeld, Westfalsko, Karl Frank, Urach b/Stuttgart, Wurttemberg, A. Brero & Co, St. Margrethen, Switzerland.

11. The first War Raw Materials Department (KRA) in Germany was created (KRA) in mid-August 1914, as suggested by Walther Rathenau. (Vaupel, E. 2014: 462) Walter was the son of the founder of AEG and “one of the few German industrialists who realized that governmental direction of the nation’s economic resources would be necessary for victory, Rathenau convinced the government of the need for a War Raw Materials Department in the War Ministry. As its head from August 1914 to the spring of 1915, he ensured the conservation and distribution of raw materials essential to the war effort. He thus played a crucial part in Germany’s efforts to maintain its economic production in the face of the tightening British naval blockade.”

References:

Ladislav Nachmüllner vulgo Praganda. Nachmüllnerová, Eva, Editor, 2000, Translated by Monica Volcko

1907. American Food Journal. Volume 2.Chicago Daily Tribune, 7 Jul 1910, Thu. P15Chicago Sunday Tribune, Nov 10, 1907, The Cincinnati Enquirer ( Cincinnati, Ohio), 27 September 1923. Page 14

The Detroit Free Press (Detroit, Michigan) reported, 14 Jan 1921, p 16Detroit Free Press, Detroit, Michigan, 11 June 1921, p4

Detroit Free Press, 22 Apr 1921, Fri, Page 18Ernst, FA. 1928. Fixation of Atmospheric Nitrogen. D van Nostrand, Inc.http://www.fda.gov/RegulatoryInformation/Legislation/ucm148690.htm

Gamgee, A. 1867 – 1868. Researches on the Blood. On the Action of Nitrites on the Blood. Proceedings of the Royal Society of London. Vol. 16 (1867 – 1868), pp. 339-342. Published by: Royal Society.

Ganswindt, A. 1895. Dyeing. Silk, Mixed silk fabrics and artificial silks. Translated from German by Charles Salter. Scott, Greenwood & Son.Griffith Laboratories Worldwide, Inc. official company documents.

Hoagland, Ralph. 1914. Coloring matter of raw and cooked salted meats. United States Department of Agriculture. National Agricultural Library. Digital Collections.

Hiemstra-Kuperus, E. 2010. The Ashgate Companion to the History of Textile Workers, 1650–2000. Ashgate Publishing, Ltd.

The Indiana Gazette, 28 March 1924The Indianapolis News, 7 May 1924, Wed, Page 1

Jones, G. 1920. Nitrogen: Its Fixation, Its Uses in Peace and War. The Quarterly Journal of Economics. Vol. 34, No. 3 (May, 1920), pp. 391-431. Oxford University Press.

Kim-Shapiro, D. B., Schechter, A. N., Gladwin, M. T. 2006. Unraveling the Reactions of Nitric Oxide, Nitrite, and Hemoglobin in Physiology and Therapeutics. Arteriosclerosis, Thrombosis, and Vascular Biology. Published online before print January 19, 2006.

Kraybill, H. R.. 2009. Sugar and Other Carbohydrates in Meat Processing. American Meat Institute Foundation, and Department of Biochemistry, The University of Chicago, Chicago, Ill. USE OF SUGARS AND OTHER CARBOHYDRATES IN THE FOOD INDUSTRY. Chapter 11, pp 83–88. Advances in Chemistry, Vol. 12. Publication Date (Print): July 22, 2009 . 1955

Ladislav Nachmüllner vulgo Praganda Nachmüllnerová, Eva. OSSIS,2000Mcclure, B. N.; 2009.

The effect of lactate on nitrite in a cured meat system. Iowa State University.Packer, L. 1996. Nitric Oxide, Part 1. Academic Press.

Pegg, B. R. and Shahidi, F. 2000. Nitrite Curing of Meat. Food & Nutrition Press, Inc.

Polenske. E.. 1891 Works from the Imperial Health office, Volume 7, Springer, Berlin, S. 471-474Progress Report for the Years Canada. Dept. of Agriculture. Division of Chemistry.

Sebranek, J. and Fox, J. B. Jn.. 1985. A review of nitrite and chloride chemistry: Interactions and implications for cured meats. J. Sci. Food. Agric. 1985, 36, 1169 – 1182.

The Saint Paul Daily Globe, 10 May 1896,

http://saintpaulhistorical.com/items/show/183

http://www.stm-ke.sk/index.php/en/detached-expositions/solivar-near-presov

Scott, E. Kilburn. 1923. “NITRATES AND AMMONIA FROM ATMOSPHERIC NITROGEN. Lecture I”.

Journal of the Royal Society of Arts 71 (3702). Royal Society for the Encouragement of Arts, Manufactures and Commerce: 859–76.

http://www.jstor.org/stable/41356346.

Sullivan, G. A., 2011. “Naturally cured meats: Quality, safety, and chemistry”. Graduate Theses and Dissertations. Paper 12208.Sydney Morning Herald on 1 Mar 1870 (p4)

The Times, London, Greater London, England, 1 May 1919, Page 18Toldr, F.. 2010.

Handbook of Meat Processing. John Wiley & Sons Inc.Turmock, D.. 1989.

Eastern Europe: A Historical Geography 1815-1945.

RoutledgeVaughn E. Nossaman, Bobby D. Nossaman, Philip J. Kadowitz; Cardiol Rev. Author manuscript; available in PMC 2011 July 1; Published in final edited form as: Cardiol Rev. 2010 Jul–Aug; 18(4): 190–197. 10.1097/CRD.0b013e3181c8e14a

The Watchman and Southron, 19 Feb 1921, Sat, First Edition, page 3

The Weekly Gazette, 9 Jan 1901, Wed, Page 3

Webb, H. W.. 1923. Absorption of Nitrous Gasses. Edward Arnolds & Co, London.

Zofia Gołąb-Meyer Marian. 2006. Albert Einstein and Ignacy Mościcki’s, Patent Application. Smoluchowski Institute of Physics, Jagellonian University, Cracow, PolandImages

Image

1: Old Prague: Old Prague Logansport Pharos-Tribune Sat Oct 19, 1895Image

2: Ladislav Nachmüllner from Ladislav Nachmüllner vulgo Praganda Nachmüllnerová, Eva. OSSIS, 2000.Image

3: Ladislav Nachmüllner from Ladislav Nachmüllner vulgo Praganda Nachmüllnerová, Eva. OSSIS, 2000.Image

4: Sodium nitrite, photos by Prof Duchon.Image

5: Germany. http://theintersectionist.com/wp-content/uploads/2012/05/austerity-for-middle-class-meat-market.jpg

Image 6 and 7: Notice of sale by UK government: The Times, 1 May 1919, Thu, Page 18Image 8: Union Stock Yard, Chicago. The Modern Packing House. 1905, 1921. Nickerson & Collins.

The Quest for Nitrite Free Curing

01/18/202110/06/2021 eben van tonder Nitrite, nitrite free curing, Sodium Nitrite nitrite, nitrite curing, nitrite free curing

The Quest for Nitrite Free Curing

18 January 2020

Introduction

I have been involved in the curing industry for almost 15 years now and during this time I fell in love with one of the most enigmatic salts from antiquity called nitrites. Over the years I have written extensively on the development of meat curing (Bacon Curing – a Historical Review). I tracked its development from millennia ago in Salt – 7000 years of meat-curing and Nitrate salt’s epic journey: From Turfan in China, through Nepal to North India. Ancient developments came together for me in the article And then the mummies spoke!.

Despite the fact that I am convinced that current processing methods of hams and bacon do not pose any health rish for consumers, the demand for nitrite free bacon is not going away. Bacon and ham have always been a product for the people and whatever our personal views on the matter, the clear and growing consumer demand must be catered for.

Over the years I have seen spice companies acting with great dishonesty. They develop curing mixes that they claim accomplish meat curing without nitrites. The way they did this was by using plant extracts which are naturally replete with nitrate. Through bacterial reduction, they achieved the conversion of nitrates to nitrites which was then sold as a “natural” curing agent due to the fact that no synthetic ntirite was added. They circumvented food labeling legislation by not adding synthetic nitrite. In reality they still add nitrites to curing brines.

I have friends from around the world who build their brands on the claim that it is nitrite free and having investigated those claims, I can confidently say that they definitely add nitrites to curing of meat. It is an embarrassment just waiting to be exposed!

The Spanish Case

A Spanish producer launched a new curing system in the early part of the 2010s. They claim great results and that only plant and fruit extracts are being used. Despite this being a step in the right direction, several aspects of the development did not sit well with me, in particular the fanatical secrecy surrounding the product.

We were preparing for sausage trails today and the interview with the CEO milled through my mind. I do not understand the secrecy! Certainly there is a place for protecting proprietary information, but when the way it is being done goes against the food legislation governing all of us, it does not sit well with me. If the entire commercial viability of the approach is based upon complete secrecy, how do they expect to win the hearts and minds of the very consumers they are trying to rich out to by its nitrite-free curing brine. How will “trust me, I’m a doctor” in terms of this product be different from “trust me when I say that nitrites is not really bad for you?”

In the absence of information, people speculate and since the company is creating an enviroemt where people will speculate, let me also “speculate”. I asked the question how I would have done it if I had to copy what they did. For starters, remember that my approach is predicated on science. I have extensively looked at the curing reaction in Reaction Sequence: From nitrite (NO2-) to nitric oxide (NO) and the cooked cured colour and the colour of fresh meat in Difference between Fresh Cured and Cooked Cured Colour of Meat. There is a fundamental reason why the world works the way it works and understanding nitrite curing is intimae associated with our most fundamental understanding of the universe. In Fathers of Meat Curing I review some of the key developments.

– What they get right.

The company claims that they address Listeria spp (broad spectrum), Listeria
monocytogenes, E Coli H157, and Clostridium spp (broad spectrum). The organism responsible for the existence of the meat curing industry is Clostridium Botulinum. (Clostridium Botulinum – the priority organism) and the fact they address it in their research is significant. The curing brine is effective against Clostridium Botulinum is very important. Personally I would like to know how effective it is against damaging the spore and preventing its viability. I am not sure if the study looked at that. If not, I would ask for that detail.

– Questions about antimicrobial efficacy

Challenge tests were performed where the brines efficacy was tested against sodium nitrite and compounds such as sodium nitrite plus sodium erythorbate, and a control with no antimicrobial. They claim to have demonstrated that their product performs equally well against listeria mono and Clostridium botulinum. Still, my reservations will stand.

In reviewing references to the brine, I found a claim that it its anti-microbial activity is especially effective if used with dehydrated lactic acid. Dehydrated lactic acid will itself be effective against amongst other, Listeria Monosytogenes. The one that worries me is still the efficacy against Clostridium. The claim is that its efficacy is due to traditionally processed Mediterranean fruit and spice extracts. What bothers me is that through the ages of meat processing, the producer claim that extracts were used which until now has been hidden from science. There is a lack of understanding of the experimental character of the meat curer who would, over thousands of years, if not millennia, certainly have stumbled upon these miracle substances and have incorporated it into his or her processing techniques long ago.

A further claim is made that these extracts are high in naturally occurring compounds with antimicrobial and antioxidative capacities. There are indeed a number of extracts who claim exactly this. However, what is the role of these antioxidative agents in meat curing. The context of the claims seems to point to pathogen eradication when in actual fact its role is in the prevention of fat rancidity and the development of off flavours.

– Questions about colour

The claim is made that it is these extracts are responsible for the meat flavor as well as its typical reddish color and pathogen protection, without the risk of nitrosamine formation. It is the claims about antimicrobial efficacy of the compound that is the most worrying and second to this, is the claim about the fact that it imparts a cured colour to the meat.

The most fundamental question will be this – is it causing the meat to change colour or is it imparting a colour to the meat. Is it an external colour which is imposed upon the meat or is the meat itself changing colour as it does in the case of nitrite curing?

Identifying which one it is is very simple. Let me walk you through it. For the meat to change colour, it is a reversible reaction. During curing, meat often turns brown due to oxidation, just to turn the regular pinkish/ redish colour of cured meat. It the meat is able to go from brown to pinkish/ redish, back to brown and again back to pinkish redish, you are dealing with the meat changing colour.

Secondly, look at the fat. If the fat inside the meat change colour (to pink for example), it is an external colourant applied to the meat and whether this is a plant extract or not, it must be approved as a meat colourant by the relative legislative body.

Look for an accumulation of brine. Especially in pork belly (streaky bacon) this will be noticeable where the injected brines are often trapped between the horizontal layers of fat and connective collagen. If an external colour is used, the brine pockets will display a brighter colour than in the meat surrounding it. It is one of the many reasons why it is not advisable to use a colourant in ham or bacon injection.

No plant extract without nitrogen will cause the meat itself to change colour. This is one of the laws of nature. There are colours imparted to long term cured meats which forms a purplish colour, but as far as my knowledge goes, the exact mechanism is not well understood and despite a considerable effort, scientists have not been able to replicate this effect in short cured hams and bacon.

The molecule responsible for the cured colour of meat is Nitric Oxide. Without Nitric Oxide being produced somehow by the magical concoction of spice extracts, the meat itself will not change colour and a colourant will be used. The fact that this may be a natural colourant is then a matter for consumers to decide whether they are satisfied with this, but that the meat is not “cured” in the traditional sense of the word is a fact. At best you can call it fresh and coloured meat.

– Questions about flavour

If the plant extracts impart flavour to the meat and it is not natural, does this mean that meat prepared in this way is “flavoured meat?”

How Would I have Done it?

I did not speak to anybody about the production of this product, but as an interesting question, while I was working today on sausages, I wondered how I would have done it. For background to this, read my article, Regulations of Nitrate and Nitrite post-1920’s: the problem of residual nitrite.

For starters it would have been very easy if one used nitrates. I see no mention of it in their literature. If I had to guess how the cure is made, I would say they possibly could be using reduced amount of nitrates but my guess would be that if this is used, residue nitrites are disposed of during the curing process. How to convert the nitrate quickly to nitrite would have been the challenge. I would have used techniques developed through the celery and beetroot juice developments where nitrates in plant extracts were converted to nitrite. In salami manufacturing, the use of starter cultures have become so commonplace that it will be easy to impregnate the brine with bacterial cultures who can achieve the conversion quickly. I would have elevated the levels of ascorbic acid, to ensure that nitrites are rapidly converted to nitric oxide which achieves the cure. I would add plant extracts to bolster the reduction to NO, to add flavour, to assist in the colour and to confuse the issue. Paprika, red chili’s, red pepper, etc are good colour enhancers especially for a darker, reddish colour. In terms of micro I would rely on nitrite, nitrate and the anti microbial action of the plant extracts which I would add. I would set out a tight schedule in terms of how long the product must be cured before the important test is done for nitrites.

From correspondence with the company, I learned that they say that the meat itself does not change colour which means that they are not using nitrate, but in the absence of full disclosure, how do we know? Who says that the statement is not purposefully vague? However, lets take them at their word. Lets assume that nitrates are not used. Like them, I would reply on plant extracts.

Supporting Correspondence

Remember that I have no knowledge if this is actually how the curing brine is being made. I discovered one bit of information that I can use to get some idea if I am on the right track or not.

I looked at mail communication that was made public related to the product under the access to information law. In this communication, regulators are asking questions which I echo.

The company has to make known the materials used (more detail than edible spice and fruit extracts) and if they claim that the meat colour is changed itself, show how by which mechanism this is achieved. Failing which, it is an external colourant and must comply with colouring legislation. Failing such disclosure is against the letter and spirit of our food laws. (Refer to my article Concerning Chemical Synthesis and Food Additives)

The question is asked as to “what kind of processes are being used e.g. physical, chemical or microbiological for the extracts? How many steps are there in the extraction process?”

Another good question that came up was for a “simple flowchart”. The company claimed, I assume, that “simple ethanol water extraction, using traditional methods of extraction and no selective physical or chemical extraction of constituents” are used. The legislature ask for “further detail, for example, is the extract a standardized product? How do you prevent variation?” These questions would be asked from us who use the product in processing and the company has to comply.

The all important question is then asked related to the “active component or components that are being used as a substitute for nitrite/nitrate preservatives to prevent the growth of harmful microorganisms and/or increase shelf-life? If this is considered commercially sensitive information can you describe how it kills or prevents the growth of microorganisms? These are the same questions I have raised above. Meat science is not an isolated discipline being pursued in dark corners any longer. It is done at almost every university and high profile meat institutes and if another product was available for curing meat apart from nitric oxide, television programs would have been made about the discovery and every scientist on earth would have known about it.

Related to the colour of the meat, it seems as if the company stated that the meat does not actually change colour. The legislator asks, “Does any component impart a colour change in the pork meat?” The statement is then made that the company has said that “no component used imparts a colour change in the pork meat.” This being the case, the follow up question is then “Does any component prevent colour change?”

In terms of flavour, using the plant extracts will certainly qualify the products as flavoured bacon? How does the plant extracts not impart their flavour to the meat and how is the flavouring natural?

A Better Way

I am of the opinion that the use of pant extracts is warranted. I am working on a completely new direction that may or may not include plant extracts. Even if I opt for plant extracts, I have an ongoing problem with current extraction processes and prefer the products to be used in the form in which it is found in nature. The discussion from the legislator with the Spanish company bears this preference up. Resent equipment developments make a better raw material possible. Another key lesson to learn from the Spanish example is the importance of taking the consumer and industry along in the process. A man walking too far ahead of the people he is trying to lead is a man out for a walk and not a leader. He will achieve nothing! Bacon and ham and health – they all belong to all of us!

A list of my complete work on Nitrite

Mechanisms of Meat Curing – From Hoagland in 1914 to Pegg and Shahidi in 2000

08/14/201608/16/2016 eben van tonder Nitrite, recent history, Sodium Nitrite history food science, Hoagland, Meat curing, Mechanisms of meat curing, nitrite curing, sodium nitrite

Mechanisms of Meat Curing – From Hoagland in 1914 to Pegg and Shahidi in 2000.
By: Eben van Tonder
14 August 2016

BACKGROUND AND OVERVIEW

Managing a meat curing operation in Cape Town at Woodys Consumer Brands (Pty) Ltd., the need exist to have a thorough understanding of meat curing mechanisms to ensure that conditions exist to optimise cured colour development, limit bacterial growth and deliver good product flavour and taste.

In the next three articles we look at colour development. This first article sets the historical context by reviewing the 1914 landmark article by Hoagland; we briefly outline the current understanding of cured colour development from the work of Pegg and Shahidi and we overview one mechanism that has recently been described. Overall, we focus on the importance of nitric oxide (NO) in cured colour development for both fresh and cooked cured meat.

INTRODUCTION

The formation of cured meat colour takes place “by the reaction of nitrite with the natural meat pigment myoglobin to form dinitrosyl ferrochrome (DNFH). The pigment, which gives meat its characteristic cured-meat colour, is formed from the meat pigment myoglobin, which consists of an iron porphyrin complex, the heme group, attached to the protein globin. In the presence of nitrite, the bright red nitrosomyoglobin is formed, in which the H2O in the axial position on the heme iron is replaced by nitric oxide (NO). The NO is formed from nitrite by the natural reducing activity of the muscle tissue, which is accelerated by the addition of reductants such as ascorbic acid. In heatprocessed cured meat, the globin has been split off to a heat-stable pink pigment, nitrosyl hemochromogen.” (Soltanizadeh, N., Kadivar, M.. 2012)

This understanding of curing developed over many years with input from a variety of scientists. (The Fathers of Modern Meat Curing) One of these influential minds was Ralph Hoagland. His brilliance is seen in his academic work that helped to shape the meat curing industry. He had wide appeal in academic and industry circles as well as the popular press. He contributed immensely to the developing sciences of nutrition and meat processing with a special interest in pork processing and pork nutrition.

He was the Senior Biochemist, Biochemie Division, Bureau of Animal Industry, United States Department of Agriculture in Chicago who was, at this time, one of the curing centers of the world along with Denmark and Calne, in the United Kingdom where the Harris operation started.

He served as the department head of the Minnesota College of Agriculture (part of the University of Minnesota), appointed in 1909. The College of Agriculture later became the College of Biological Sciences. (http://cbs.umn.edu/ and The Bismarck Tribune; 1912)

In 1908 he published results obtained upon studying the action of saltpeter upon the colour of meat and “found that the value of this agent in the curing of meats depends upon its reduction to nitrites and nitric oxid, with the consequent production of NO-hemoglobin, to which compound the red color of salted meats is due.” He found that “saltpeter, as such, [had] no value as a flesh-color preservative.” (Hoagland, R. 1914)

In 1914 he published, Colouring Matter of Raw and Cooked Salted Meat. Reviewing this article has two important objectives.

1. It shows what was understood by 1914 about meat curing and colour formation in particular. This has important implication for determining an accurate chronology of developments around the direct addition of nitrite to curing brines, such as the invention of Praganda in Prague in 1915 and later, the introduction of Prague Salt in Chicago (The Naming of Prague Salt) where Hoagland worked for a time.

2. It is a novel way for an introduction into meat curing mechanisms and shows the progression in our understanding.

I interject the thoughts of Hoagland from 1914 with quotes on our current understanding by two of the leading scientists on the subject namely Ronald B. Pegg and Fereidoon Shahidi with quotes from their 2000 publication, Nitrite Curing of Meat.

Ronald Pegg is currently a professor at the Department of Food Science & Technology, University of Georgia. A great piece appeared about him in FST News (from the University of Georgia Department of Food Science and Technology). “He is a researcher who feels equally at home in the classroom and the laboratory. In addition to inspiring students with the chemistry of chocolate and coffee, he’s become one of the nation’s most sought-after experts on the nutrient content of food and the bioactive compounds that make blueberries, peanuts and other nutritionally dense superfoods so “super.” Pegg joined the faculty of UGA in 2006. He immediately saw the need for a more hands-on, practical approach to teaching food chemistry. His work with students has earned him Food Science and Technology Outstanding Undergraduate and Graduate Professor awards five times. Pegg has received a major teaching honor from his department, the college or the university every year since 2007.” “In addition to his time in the classroom, Pegg has received accolades from producer groups for his research into bioactive chemistry and the health benefits of pecans, peanuts, peaches and other crops.” (http://www.foodscience.caes.uga.edu/)

His research and publishing partner in Nitrite Curing of Meat is Fereidoon Shahidi. He is a university research professor at the Department of Biochemistry, Memorial University of Newfoundland St. John’s, Canada. This monumental food scientist “has received numerous awards, including the 2005 Stephen Chang Award from the Institute of Food Technologists, for his outstanding contributions to science and technology. Between 1996 and 2006, Shahidi was the most published and most frequently cited scientist in the area of food, nutrition, and agricultural science as listed by the ISI.” (wikipedia.org/wiki/Fereidoon_Shahidi)

THE COLOUR OF FRESH MEAT

Hoagland starts with the colour pigment of fresh meat, oxyhemoglobin. The word itself tells us what it is. Oxy is oxygen, connected to hem which is hamatin or the colouring group and globin, the protein. In Oxyhemoglobin, ogygen is connected to “hemoglobin, which is the protein molecule in red blood cells that carries oxygen from the lungs to the body’s tissues and returns carbon dioxide from the tissues back to the lungs.” (medicinenet)

Hoagland states that oxyhemoglobin, is “part of which is one of the constituents of the blood remaining in the tissues, while the remainder is a normal constituent of the muscles,” and “responsible for the red color of fresh lean meat, such as beef, pork, and mutton.” (Hoagland, R. 1914) Today we know that the colour of fresh lean meat is due to myoglobin, “the pigment in muscle that carries oxygen” (medicinenet), as opposed to protein in the blood.

The reason for using hemoglobin, instead, may have been “a matter of convenience” and “a matter of necessity since myoglobin was not isolated and purified until 1932,” (Theorell, 1932) a full 18 years after Hoagland published. “In spite of the differences between hemoglobin and myoglobin, Urbain and Jensen (1940) considered the properties of hemoglobin and its derivatives sufficiently like those of myoglobin to allow the use of hemoglobin in studies of meat pigments.” (Cole, Morton Sylvan, 1961: 2)

Despite the fact that it is oxymyoglobin that is responsible for the bright red colour of fresh meat, we follow his arguments using oxyhemoglobin since the same mechanisms of colour development applies in both proteins. Pegg and Shahidi uses myoglobin.

Our current understanding: Oxymyoglobin (Mb, bright red, – ferrous state)

Oxymyoglobin is the result of myoglobin’s affinity for and it results in a bright red bloom within minutes of fresh meat’s exposed to air. The reaction is rapid and reversible. The continued red bloom depends on a “continuing supply of .” (Pegg, R. B and Shahidi, F; 2000: 31) This is “because the enzymes involved in oxidative metabolism rapidly use the available .” (Pegg, R. B and Shahidi, F; 2000: 31)

“With time, the small layer of oxymyoglobin present on the surface of the meat propagates downward, but the depth to which diffuses depends on several factors, such as the activity of oxygen-utilizing enzymes (i.e., consumption rate of the meat), temperature, pH, and external pressure. In other words, as air diffuses inward, an and a color gradient are established throughout the meat. Muscles differ in their rates of enzyme activity which, in turn, regulate the amount of available in the outermost layers of tissue. As the pH and temperature of the tissue increase, enzymes become more active and the content is reduced. Consequently, maintaining the temperature of the meat near freezing point minimizes the rate of enzyme activity and the utilization and helps maintain a bright red color for the maximum possible time.” (Pegg, R. B and Shahidi, F; 2000: 31)

THE COLOUR OF CURED MEAT

Generally, Hoagland saw the cured colour of meat as “the same color as the fresh meat.” (Hoagland, R. 1914) There is a difference between the cured colour of fresh meat and the cured colour of cured-cooked meat. He recognised this difference and said that “the red color is not destroyed on cooking, but rather it is intensified.” (Hoagland, R. 1914)

The nature of these two different kinds of colour is the subject of his article, “undertaken for the purpose of obtaining more complete information concerning the color of raw and cooked salted meats.” (Hoagland, R. 1914)

HISTORICAL BACKGROUND

In his historical summary, he lists the following developments that lead up to his own work.

-> Weiler and Riegel

“Weiler and Riegel (1897), in the examination of a number of samples of American sausages, obtained a red coloring matter on extracting the samples with alcohol and other solvents, which color they concluded to be in some manner due to the action of the salts used in curing upon the natural color of the meat. On account of similarity of spectra, this color was considered to be methemoglobin.” (Hoagland, R. 1914)

Our current understanding: metmyoglobin (metMb, brown, ferric state)

Methemoglobin and metmyoglobin actually is the brown colour of meat which develops after meat has been standing for some time. Myoglobin exists within the interior of meat and has a purple-red colour. “This is the colour of Myoglobin” (Pegg, R. B and Shahidi, F; 2000: 31) Reductants generated within a cell by enzyme activity prevents the meat from turning brown, until this is no longer available. The heme iron (in the ferrous state – ) is oxidized to the ferric state () . (Pegg, R. B and Shahidi, F; 2000: 31)

It is generated as follows. The superoxide anion () is removed from the hematin. A water molecule is added. This gives a high-spin ferric hematin. “The ferric ion, unlike its ferrous counterpart, has a high nuclear charge and does not engage in strong bonding. Therefore, metmyoglobin is unable to form an oxygen adduct. (Pegg, R. B and Shahidi, F; 2000: 31)

-> Lehmann and Kisskalt

Lehmann (1899) identified nitrite as responsible for the red colour of meat and not nitrate. Kisskalt (1899) confirmed this and noted that “if the meat was first allowed to stand several days in contact with saltpeter and then boiled, the red color appeared” (Hoagland, R. 1914)

-> John Scott Haldane

John Scott Haldane (1901) made several important observations after an extensive study of the colour of cooked salted meat.

He attributed the colour of cooked salted meat “to the presence of the nitric oxide hemochromogen” (reduced hematin; Fe in reduced ferrous state, ; obtained by boiling oxymyoglobin/ oxyhemoglobin with a reducing agent). (Hoagland, R. 1914) He correctly concluded that nitric oxide hemochromogen is “resulting from the reduction of the coloring matter of the uncooked meat, nitric-oxid hemoglobin (NO-hemoglobin).” Hemochrome can be any of a number of complexes with the iron-porphyrin complex with one or two basic ligands (normally amines).

The terms nitric oxide hemochromogen, nytrosomyochrome, nitrosyl hemochrome, nitric oxide hemochrome, nitric oxide denatured globin hemochromogen, denatured globin nitric oxide ferrohemochrome, pigment of cured, heated meat, all as synonyms to refer to the same thing. (ICMSF; 1980: 140) Chromogen is a substance which can be easily converted into dye or other coloured compound for example through oxidation. Since the 1940’s, the term “hemochrome” (hem and chrome) has been used instead of “hemochromogen” and “parahematin.” “The term “hemochromogen” is associated historically with an erroneous conception of one of these substances as the colored component of hemoglobin. These compounds are in any case not “chromogens” in the chemical sense, i.e., ieuco compounds. The new term has the additional advantage of greater brevity.” (Lemberg, R. and Legge, J. W.; 1949: 165)

Linossier was the first to describe it and produced it by passing nitric oxide through hematin. (Haldane, J. S.. 1901) After careful study and observation, Haldene drew the following brilliant conclusions.

1. “The red colour of cooked salt meat is due to the presence of NO-haemochromogen.” (Haldane, J. S.. 1901)

2. “The NO-haemochromogen is produced by the decomposition by heat of NO-haemoglobin, to which the red colour of unsalted meat is due.” (Haldane, J. S.. 1901)

3. “The NO-haemoglobin is formed by the action of nitrite on haemoglobin in the absence of oxygen, and in presence of reducing agents.” (Haldane, J. S.. 1901)

4. “The nitrite is formed by reduction within the raw meat of the nitre used in salting.” (Haldane, J. S.. 1901)

5. “The nitrite is destroyed by prolonged cooking.” (Haldane, J. S.. 1901)

Our current understanding: nitric oxide hemochrome (Cooked Cured Meats – one nitric oxide molecule per heme).

When heated, NO-myoglobin (nitrosyl myoglobin) is transformed to nitrosyl myocromogen, which is denatured NO-myochromogen. This happens upon thermal processing. The globin unfolds (denatures); the iron atom comes loose from the globin; the unfolded globin folds itself around the heme functional part (moiety) which is the iron-porphyrin complex. This brings about the characteristic reddish-pinkish colour of cooked cured meat. (Pegg, R. B and Shahidi, F; 2000: 42)

By way of application, note that “there is a direct relationship between the concentration of NO-myoglobin in the muscle and the intensity of the cured colour” and NOT the nitrite level. “When muscle tissue are cured with equivalent amounts of nitrite, a more intense cured meat colour is produced in,” for example, corned beef as opposed to ham. “The addition of excess nitrite to that required to fix the pigment does not increase the intensity of the cured meat colour.” (Pegg, R. B and Shahidi, F; 2000: 42) This being the case, it is also true that if the concentration of nitrite and therefore nitric oxide formation is to low, that it will impact colour development.

He mentions Orlow (1903) who stated that “the red color of sausages is due to the action upon the color of the fresh meat of the nitrites resulting from the reduction of the saltpeter used in the process of manufacture.” (Hoagland, R. 1914)

“Humphrey Davy in 1812 (cited by Hermann, 1865) and Hoppe-Seyler (1864) noted the action of nitric oxid upon hemoglobin, but it appears that Hermann (1865) was the first to furnish us with much information as to the properties of this derivative of hemoglobin. He prepared NO-hemoglobin by first passing hydrogen through dog’s blood until spectroscopic examination showed that all of the oxyhemoglobin had been reduced to hemoglobin, then saturating the blood with pure nitric oxid prepared from copper and nitric acid, and finally again passing hydrogen through the blood to remove all traces of free nitric oxid.” (Hoagland, R. 1914)

By the time of publishing this article in 1914, he notes that NO-hemoglobin was mentioned very briefly in most of the texts on physiological or organic chemistry as being a hemoglobin derivative of “but little practical importance.” “Abderhalden (1911) and Cohnheim (1911), however, describe this compound quite fully.” (Hoagland, R. 1914)

Hoagland conducted several further experiments with NO-hemoglobin and outlined it in his 1914 paper.

COLOUR OF FRESH, CURED MEAT

He first deals with the Colour of Uncooked Salted Meats. “To a sample of finely ground fresh beef was added 0.2 per cent of potassium nitrate, and the material was placed in a refrigerated room at a temperature of 34 deg F (1 deg C) for seven days. At the end of that period the meat had a bright-red color, but gave evidences of incipient putrefaction.” (Hoagland, R. 1914) He did the same by curing the meat with nitrite. He correctly concluded that the colour of fresh meat, cured with nitrite, is due to NO-hemoglobin. (Hoagland, R. 1914)

Our current understanding: nitric oxide myoglobin (NOMb, red, ).

“When nitrite is added to comminuted meat, the meat turns brown because nitrite acts as a strong heme oxidant. The oxidizing capacity of nitrite increases as the pH of meat decreases, but nitrite itself may also partly be oxidized to nitrate during curing and storage. Myoglobin and are oxidized to metMb by nitrite. The ion itself can be reduced to . These products can combine with one another to form an intermediate pigment, nitrosylmetmyogloboin ().” (Pegg, R. B and Shahidi, F; 2000: 40)

“Nitrosylmetmyoglobin is unstable. It auto-reduces with time and in the presence of endogenous and exogenous reductants in the postmortem muscle tissue to the corresponding relatively stable Fe(II) form, nitrosylmyoglobin (NOMb).” (Pegg, R. B and Shahidi, F; 2000: 40)

A new suggestion was proposed as a mechanism for the meat curing process by Killday et al. (1988)

FullSizeRender

“They suggested that is more adequately described as an imidazole-centered protein radical. This radical undergoes autoreduction yielding NOMb, and lacking exogenous reductants, reducing groups within the protein can donate electrons to the imidazole radical.” (Pegg, R. B and Shahidi, F; 2000: 40)

An interesting study by Corforth et al. (1998) strengthened the mechanism posed by Killday et al. (1988). “Cornforth and co-workers examined the relative contribution of CO and towards pink ring formation in gas oven cooked beef roast and turkey rolls. Data showed that pinking was not evident with up to 149 ppm of CO or 5 ppm of NO present in the burning gases; however, as little as 0.4 and 2.5ppm of was sufficient to cause pinking of the turkey and beef products, respectively. Cornforth et al. (1998) proposed that pinking previously attributed to CO and NO gas in ovens is instead due to which has much greater reactivity than NO with moisture at the surface of meats. Their argument was predicated on the fact that NO has a low water solubility unlike that of . Therefore on the basis of this consideration, NO would be an unlikely candidate to cause pink ring, since at the low levels typical of gas ovens or smokehouses, NO would be unable to enter the aqueous meat system in sufficient quantity to cause pink ring at depths up to 1 cm from the surface. On the other hand, reacts readily with water to produce nitrous and nitric acid.” (Pegg, R. B and Shahidi, F; 2000: 40, 42)

“Nitrous acid produced at meat surfaces would be free to diffuse inwards, where endogenous or exogenous meat reductants, including Mb itself may regenerate NO. Nitric oxide binds to MetMb followed by rapid autoreduction to NOMb as suggested by Killday et al. (1988).” (Pegg, R. B and Shahidi, F; 2000: 42)

NOMb is therefore responsible for the characteristic red colour of fresh cured meat before thermal processing. The NOMb pigment can be produced by the direct action of NO on a deoxygenated solution of Mb, but in conventional curing, it arises from the action of nitrite, as stated above. (Pegg, R. B and Shahidi, F; 2000: 42)

Hoagland’s conclusion in his 1914 article is, however, limited to NO formation and its role in cured colour formation. He states that “the evidence is ample to show that the action of saltpeter in the curing of meats is primarily to cause the formation of NO-hemoglobin ; but it is very possible that under certain conditions of manufacture or processing to which salted meats are subject, the NO-hemoglobin may undergo changes.”

COLOUR OF COOKED, CURED MEAT

“Haldane has shown that the red color of cooked salted meats is due to the presence of NO-hemochromogen, a reduction product of NO-hemoglobin to which the color of uncooked salted meats is due.”… “While Haldane’s work seems to show clearly that the color of cooked salted meats is due to NO-hemochromogen, it has seemed desirable to study the subject further and to determine especially if the NO-hemoglobin of uncooked meats be reduced to NO-hemochromogen under other conditions than by cooking. The fact that in the examination of certain uncooked salted meats a coloring matter had been obtained similar to NO-hemoglobin yet not possessing all of the properties of that compound, as has already been noted, led the writer to believe that the coloring matter of some uncooked salted meats might be due, in part at least, to NO-hemochromogen. NO-hemochromogen is but briefly mentioned in the literature. The compound is described by Linossier (1887), Haldane (1901), and by Abderhalden (1911).” (Hoagland, R. 1914)

“The structural relation between NO-hemoglobin and NO-hemochromogen is simple. NO-hemoglobin is a molecular combination of nitric oxid and hemoglobin—the latter compound consisting of the proteid group, globin, on one hand, and the coloring group, hemochromogen, on the other. NO-hemoglobin and NO-hemochromogen differ from each other simply in that one contains the proteid group, globin, while the other does not. Apparently, then, a method of treatment which would split off the globin group from NO-hemoglobin should result in the production of NO-hemochromogen, provided, of course, that the procedure did not in turn change or destroy the NO-hemochromogen produced. As has already been noted by Haldane, it was found that when a solution of NO-hemoglobin was heated to boiling, a brick-red precipitate formed, in contrast to the dark-brown precipitate which formed on heating a solution of oxyhemoglobin or of blood. The brick-red precipitate was filtered off and was then extracted with alcohol, which gave a lightred colored extract showing a spectrum with a fairly heavy band just at the right of the D line. This spectrum corresponds with that of NO-hemochromogen. On standing, the color of the extract faded rapidly.” (Hoagland, R. 1914)

“The evidence seems to show very clearly that the color of cooked salted meats is due to the NO-hemochromogen resulting from the reduction of the NO-hemoglobin of the raw salted meats on boiling.” (Hoagland, R. 1914)

“It is very probable that in the case of meats which have been cured with saltpeter or of meat food products in which saltpeter has been used in the process of manufacture, the reduction of NO-hemoglobin to NO-hemochromogen takes place to a greater or lesser degree, depending upon conditions of manufacture and storage. The two compounds are so closely allied that their differentiation in one and the same product is not a matter of great importance.” (Hoagland, R. 1914)

Our current understanding: Nitrosylmyochromogen or nitrosylprotoheme.

Upon thermal processing, globin denatures and detaches itself from the iron atom and surrounds the hem moiety. Nitrosylmyochromogen or nitrosylprotoheme is the pigment formed upon cooking , and it confers the characteristic pink colour to cooked cured meats.” (Pegg, R. B and Shahidi, F; 2000: 44)

“Although the Cooked Cured Meat Pigment (CCMP) is a heat-stable NO hemochrome as evident by the fact that it doesnt undergo further colour change upon additional thermal processing, it is susceptible to photodissociation. Furthermolre in the presence of oxygen, CCMP’s stability is limited by the rate of loss of NO.

This effect is important if cured meats are displayed under strong fluorescent lighting while they are also exposed to air. Under these conditions, the surface colour of cured meat will fade in a few hours, whereas under identical conditions, fresh meat will hold its colour for a few days.” “A brownish-gray colour develops on the exposed meat surface during colour fading; this pigment, sometimes called hemichrome, has its heme group in the ferric state. The most effective way of preventing light fading is to exclude contact with the cured meat surfaces. It is routinely accomplished by vacuum packaging the meat in impermiable films. If is absent from the package, NO cleaved from the heme moieties by light cannot be oxidized and can recombine with the heme.” (Pegg, R. B and Shahidi, F; 2000: 44)

CONCLUSION

Hoagland and other researchers from that period laid the foundation to much of our current understanding of meat curing by drawing a distinction between fresh cured meat colour and cooked cured colour. The first detailed mechanism in the development of cured meat colour that started to emerge was through the action of nitric oxide. Pegg and Shahidi stated in 2000 that “to form cured meat pigment, two reduction steps are necessary. The first reduction of nitrite to NO and the second is conversion of NOmetMB to NOMb.” (Pegg, B. R. and Shahidi, F.; 2000: 44, 45)

An interesting side note. Hoagland wondered if it is possible to produce the cooked cured colour of meat in another way than curing with nitrite and heat treatment. Pegg and Shahidi has dedicated much work along similar lines – to identify a curing system that will replace nitrite curing. In meat curing, this has always been the holy grail which on the one hand will in all likelihood remain an unattainable concept and on the other hand, as our understanding of nitrite grows, will be deemed unnecessary.

The chemical reaction sequence from nitrite to NO, leading to the formation of NOMb will be described in the next article.

References:

The Bismarck Tribune (Bismarck, North Dakota); 10 July 1912; page 2.

Cole, Morton Sylvan, “Relation of sulfhydryl groups to the fading of cured meat ” (1961). Retrospective Theses and Dissertations. Paper 2402

Haldane, J. S.. 1901. The Red Colour of Salted Meat. Journal of Hygiene 1: 115 – 122

Hoagland, R. 1914. Cloring matter of raw and cooked salted meats. Laboratory Inspector, Biochemie Division, Bureau of Animal Industry. Journal of Agricultural Research, Vol. Ill, No. 3 Dept. of Agriculture, Washington, D. C. Dec. 15, 1914.

Lemberg, R. and Legge, J. W.. 1949. Hematin Compounds and Bile Pigments. Interscience Publishers, Inc.

Soltanizadeh, N., Kadivar, M.. 2012. A new, simple method for the production of meat-curing pigment under optimised conditions using response surface methodology. Meat Science 92 (2012) 538–547 Elsevier Ltd.

http://cbs.umn.edu/academics/departments/bmbb/about/history/timeline

http://www.foodscience.caes.uga.edu/documents/Newsletter2016June16colorforweb.pdfhttps://en.wikipedia.org/wiki/Fereidoon_Shahidi

http://www.medicinenet.com

Images:

Image 1: Ralph Hoagland. Oakland Tribune, 5 July 1927

	eben van tonder on Saltpeter, Horse Sweat and Bil…
	eben van tonder on Saltpeter, Horse Sweat and Bil…
	William Ramwell on Saltpeter, Horse Sweat and Bil…
	eben van tonder on Rusk
	Des Basterfield on Rusk
	Kjell on Bacterial Migration Into Meat
	eben van tonder on Carcass Sanatising
	Klaas on Carcass Sanatising
	Tabitha Levine on Joshua Penny and Khoikhoi Ferm…
	eben van tonder on The Origins of Polony

Introduction to Bacon & the Art of Living

The Curing Molecule

What is Meat Curing?

How is Nitric Oxide formed?

Can we remove nitrogen (nitrate or nitrite) from our diets?

The Importance of Nitrogen

-> Reduction (losing oxygen atoms)

-> Oxidation (Gaining Oxygen Atoms)

The Ever-Presence of Nitrogen

Demonstrating Oxidation and Reduction

Changing Perceptions

It’s Present in our Bodies!

Conclusion

Share this: EarthwormExpress Article

Like this:

Introduction to Bacon & the Art of Living

The Most Elemental

The Fog of Antiquity

Meat Curing’s Ancient Origins

Meat Curing – A Life-Giving Principle?

Can Something of Infinite Benefit be Harmful?

My Teacher is Bacon!

Share this: EarthwormExpress Article

Like this:

EarthwormExpress Introduction

Circulation

Abstract

Discovery and Chemical Properties

Nitrite as a Vasodilator

Conversion of Nitrite Into NO and NO-Related Products

Nitrite as an Antidote for Cyanide and Hydrogen Sulfide Poisoning

Other Medical Uses of Inorganic Nitrite

Acidified Nitrite

Use of Inorganic Nitrate in Medicine

Nitrate and the Treatment of Lung Diseases

Nitrates as Diuretics

Nitrate in Other Medicinal Preparations

Conclusions and Outlook

Footnotes

References

Share this: EarthwormExpress Article

Like this:

Part 1: Setting the stage

Part 2: The Curing Molecule

Part 3: Steps to secure the safety of cured meat

Part 4: The Benefit of Nitrites

Cover Photo

Share this: EarthwormExpress Article

Like this:

Introduction

A. How did we Realise there is a Problem?

The Realization of Danger of Nitrites in Cured Meat and The Responses Since 1926

1926

1931

1960’s – N-Nitrosamine

1970 – The response to the N-Nitrosamine scare.

B. Can’t we just Remove the Nitrites?

– Is the Problem Synthetic Nitrites Only (I.e. Sodium Nitrite Added Into the Brine)?

– Is the Problem All Nitrites in the Brine and Meat, Including Either Sodium Nitrite or Nitrite that Formed Through Bacterial Action, Either through Reduction or Oxidation or Chemically and Irrespective of the Source?

– If the Meat itself Does Not Change Colour (Curing), is the use of External Colourant Permitted/ Desirable?

– Is the Real Issue Actually Residual Nitrite That We Must Eliminate? (I.e., Not Ingoing Nitrite but Nitrite Left in Meat After Curing)

– Is The Objective to Eliminate All Manipulation of Colour (Natural or Artificial) and Resign Ourselves to Selling Brown Bacon and Hams (uncured, salted only)?

How to Explain it?

C. Review: How did we get here?

D. Why do we use it at all?

The Anti-Microbial Efficacy of Nitrite

E. Further Work on Nitrite Free Bacon and its role in Human Physiology

Conclusion

References

Share this: EarthwormExpress Article

Like this:

Introduction to Bacon & the Art of Living

The Preserving Power of Nitrite

Preservation Through the Right Brine Composition

Clostridium Botulinum – the Key Organism

The historical perspective

Observations

Points of Application

Further Reading

Notes