Evaluation of Woolworths “contain no nitrites” Bacon

by Eben van Tonder
23 November 2022


I updated my review of curing systems by adding a section on the mechanism behind salt-only curing. It just so happens that the South African retailer, Woolworths launched their range of bacon with the claim “contain no nitrites.” In discussing salt-only-curing, I used them as an example and evaluated their claim. Here is the extract from Bacon Curing – a Historical Review.

The Mechanism of Salt-Curing

For years I never seriously looked at salt-only-curing. Yes, its mechanism is well known, or so I thought! The salt reduced the water in the meat which retards the micro activity and meat breakdown (enzymatic) while L-Arginine slowly oxidises to L-citrulline and nitric oxide and nitric oxide cures the meat.

The booklet that Edward De Bruin, my South African friend living in New Zealand sent me (Methods of Meat Curing, 1951, US Dep of Agriculture) reported that in a survey done in the early 1950s, it was found that 37 percent of the farmers used dry curing. The curing agent they used was salt only. The author describes it as follows, “a fine grade of sack salt or table salt applied to hams, shoulders, and bacons. All the salt was applied at one time by about one-half of the farmers, 10 pounds (4.5kg) of dry salt per 100 pounds (45kg) of meat being used. The liquid extracted from the meat during cure was not permitted to accumulate. Curing temperatures ranged from 20° to 50° F. (-6°C to 10°C), the average being about 40°F (4°C). Most hams weighed 20lb (20kg), 25lb (11kg), or 30lb (13.6kg) : shoulders and bacons weighed 20lb (20kg) pounds. The hams were cured for 1½ days per pound : shoulders and bacons, 1¾ days. About 50 percent of the farmers smoked their meat. Prior to smoking 3 to 1 days in hickory smoke, the meat was washed. The meat was stored in a dry, cool room with some air circulation. Consumption began immediately after the meat was cured and smoked, although some meat was stored for 9 months.”

The method was simple and effective. It took around 30 days to cure the meat and this was the problem. All subsequent curing methods from time immemorial, which is the subject of this work, were done to reduce this time. With the 20:20 hindsight we have peering back over aeons of time, we realise that what they were looking for was other ways to speed up the production of Nitric Oxide which is the curing molecule with its reddening effect on the meat and its broad spectrum antimicrobial activity.

The earliest progression from salt-only curing was the addition of nitrate directly through saltpetre and the oxidation of ammonium. This article sets out this progression. Following World War 1, nitrite was added directly and right from the start this was controversial. The motivation for the change from nitrate to nitrite was the availability of nitrate in a war situation and secondly, the speed of curing with nitrite curing being much faster than nitrate curing. Since that time, and especially from the 60s and 70s, the curing industry tried to find a system that does not rely on nitrate or nitrite. I believe this was done based on an inadequate understanding of the role of nitrate and nitrite in human health but it’s a discussion for another time. (The Truth About Meat Curing: What the popular media do NOT want you to know!)

When the industry found this to be impossible (curing without nitrate or nitrite), a trend began where some denied its inclusion in meat or at least tried to hide it. They did this by using an ancient method of curing where plants and fruits are used, naturally high in nitrate and nitrite but label declaration legislation does not necessitate you to declare all the chemical species naturally found in the plant matter. So, it is still nitrate and nitrite added to the meat which produces the nitric oxide which cures the meat, but using this strategy, producers did not have to include nitrate or nitrite on their labels.

Using this method of curing results in a healthier product due to the inclusion of minerals, vitamins, antioxidants and other beneficial plant constituents but to claim no-nitrite/ nitrate curing is false. A contemporary example of this may be the recent launch of Woolworths in South Africa.

Woolworths in South Africa launched a range of bacon recently which they claim to be cured without nitrite. They state on their packaging that their bacon is cured “using a combination of fruit and spice extracts without compromising on flavour, texture or colour, and it contains no nitrites.” The question is what “contains no nitrites?” Is it the bacon that contains no nitrites or the curing brine?

Maybe they added these indirectly through plant matter which, in the end, is exactly the same thing as adding it directly with a major difference being that adding it through plant matter makes the process uncontrolled – meaning they can’t control how much they add as opposed to the method of adding nitrate and nitrite directly which enables you to reduce the amount of ingoing nitrate and nitrite to the smallest possible ratio which is the “safest” way of doing it if you believe that nitrates and nitrites are bad for your health (an assumption that I do not subscribe to, see The Truth About Meat Curing: What the popular media do NOT want you to know!)  Whatever the consequence of adding it through plant matter, claiming “no nitrites” will be a blatantly false statement and I don’t believe this is what they are doing for one moment.

Of course, the “contain no nitrites” may mean that they took care to remove all residual nitrites from the bacon after it was cured. Residual nitrites are what is left in the bacon after curing. I will argue that nitrates and nitrates is not a big deal (The Truth About Meat Curing: What the popular media do NOT want you to know!) but I understand many consumers still have a negative perception of nitrites and if the products are not formulated right, it poses a problem. Residual nitrites can be reduced dramatically by employing a range of processing techniques and through bacteria. Staphylococcus xylosus and Staphylococcus carnosus have, for example, been shown to be also able to reduce the residual amounts of nitrates and nitrites (Neubauer and Götz, 1996; Gøtterup et al., 2007; Mah and Hwang, 2009; Bosse et al., 2016). Woolworths is a quality-driven company their statement, “contain no nitrites” means that they used nitrates and nitrites but removed any traces of it before its made available for sale, I applaud them for their work! There is a small technical matter related to the chemical generation of nitrate from nitric oxide in a meat system and the fact that nitrite will soon be generated through bacterial action which calls into question if one can call any cured meat system 100% free from nitrites, but that is a question for another forum and it is possible with the right approach.

All this is an example of how the industry is grappling with the fact that nitrates/ nitrites are used. Before any of this became an issue in the world, there was curing with salt only. It would seem to me that at the heart of the entire move away from salt-only-curing was the fact that we fundamentally missed the role of microorganisms with the ability to react with protein and to create nitric oxide which then cures the meat. Well, we “missed” it because it was so hard to see nor did we have the technology to identify and isolate certain bacteria with this ability, nor did we understand what bacteria need to be effective by way of nutrition.

We had glimpses of this from the world of salt-only curing! The mechanisms underpinning salt-only curing are only emerging now as a powerful method to cure meat without the use of nitrate or nitrite, directly or indirectly. Let me say it like this. Now that we are working out the mechanism of salt-only curing, we discover ways to do it as quickly as is done with nitrite curing. Despite many years of intense research into meat curing, it is remarkable that we are only now starting to understand how the oldest form of curing works.

Proteins and lipids or fats in meat tissues are degraded mainly by enzymes which are also present in the meat during the ripening of the hams/ bacon but the breakdown of proteins and fat cells is also achieved through bacteria (Flores and Toldrá, 2011) and they play a direct role in curing in salt-only systems. Morita et al. found that Nitric Oxide formed in salt-only curing systems is achieved from L-arginine due to nitric oxide synthase (NOS) in either Staphylococci or Lactobacilli. (Morita et al., 1998 and quoted by Gasasira, et al, 2013) Another study on the production of cured meat colour in nitrite-free sausages by Lactobacillus fermentum showed that nitrosylmyoglobin (a form of the meat protein, myoglobin, formed during curing) could be generated when the bacteria, Lactobacillus fermentum AS1.1880 was inoculated into the meat batter, and the formation of a characteristic pink colour with an intensity comparable to that in nitrite-cured sausage can be achieved using 108 CFU/g of the culture. In other words, bacteria, in a salt-only curing system can directly achieve what nitrite curing would later accomplish.

Despite the fact that even in the 1950s salt-only-curing was the biggest single way that bacon was produced on farms in the USA, I am going to look at two important salt-only-cured hams that have been the subject of research which elucidated the mechanisms underpinning salt-only-curing and to illustrate that the key, understanding the mechanism behind salt-only-curing, is bacteria. Microorganisms drive the process!

Parma ham is traditionally produced using only sodium chloride without the addition of nitrate or nitrite and develops a deep red colour, which is stable also on exposure to air. It has been shown that bacteria are responsible for the creation of nitric oxide without nitrate or nitrite which then cures the hams. Fascinatingly, despite the fact that we know that bacteria are responsible for the creation of nitric oxide which leads to nitrosylated heme pigments, the identity of the pigment of Parma ham has not been established. In one study, the stability of the pigment isolated from two different types of dry-cured ham (made with or without nitrite) was compared to that of the NO derivative of myoglobin formed by bacterial activity. Heme pigment from Parma ham made without nitrite was more stable against oxidation than the pigment from dry-cured ham with added nitrite.” (Møller and Skibsted, 2001) This is a most fascinating discovery! Further, heme pigments extracted from Parma ham and a bacterial (Staphylococcus xylosus) formed NO-heme derivative and have similar spectral characteristics (UV/ vis spectra and ESR).”  (Møller and Skibsted, 2001)

In China, Nuodeng ham is a dry-cured ham, traditionally made by Bai ethnic people in the Nuodeng village, Dali, Yunnan Province. As part of the production process, they use mineral-rich local salt reserves, and distilled corn liquor and rely on the favourable climate. From these hams, Kocuria rhizophila was isolated (Shi, 2021) and is probably responsible for the formation of the cured colour.

I can give many more examples. Dry-cured, long-cured or salt-only systems are in part enabled by bacterial action where the meat itself is fermented, nitric oxide is generated and the meat is cured. I return to this subject in the very last section of this article under the heading Bacterial Fermentation Curing. Woolworths in South Africa may very well rely on this mechanism of curing their bacon which is the only system where they can make the claim that nitrite is not present. If one would test their cure or their bacon at any time immediately following curing and in the time that it spends on the retail shelf or in the consumer’s refrigerator and nitrite is found, it will make their claim that no nitrites are present, false.

Besides the option of using plant matter that contains nitrate or nitrite, they could of course create the cured colour with proteins outside the meat environment and infuse these into the meat, which I doubt is what they are doing. They could use nitrite to cure the meat directly or indirectly and add bacteria that eliminates all nitrites post curing which is possible, but I would think improbable. The last option is that they could use nitrites at a level below 10 parts per million which will still cure the meat but is undetected in certain methods of testing for nitrites. The challenge will be that at those low levels the nitrite offers little protection against dangerous microorganisms but I notice that they add rosemary extract which could bolster this protecting mechanism. If this is what they are doing, it would unfortunately again make their claim of “contain no nitrites“, false. If, and I am by no means suggesting they are doing this, a clue would be if they are very sensitive to environmental exposure to nitrites during production as this could push the levels of nitrite in the bacon into the levels which are “detectable”.

The last option would be “underhanded” and with a company like Woolworths, there is no chance that they employ such a strategy. Friends of mine work in their meat department both in the compliance as well as operational departments and they would never be a party to anything not completely truthful. Well done to Woolworths then on your product which can only be using some form of fermentation.

Bacterial fermentation of meat is probably the closest one will ever get to a no-nitrite system which is a spectacular return to salt-only curing. Working out how to do it is, as the saying goes, the million-dollar question and if Woolworths found the way, I salute you! As far as our consideration of curing systems goes, our first consideration of curing, namely salt-only, will also be our final consideration under Bacterial Fermentation Curing. In between these two is the most fascinating story never told!

As far as Woolworths’ “contain no nitrites-bacon” is concerned, maybe they can be more specific about which one of the options they refer to when they make that claim.


Extract from Bacon Curing – a Historical Review.

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Starter Cultures in Processed Meat


The use of starter culture in meat processing seems to be as established as fermentation itself. How many know that this art which seems to have been with us forever was really only commercialised in the 1950s by the work of Dr Fritz Niinivaara? He is the father of the meat fermentation industry and the use of starter cultures we have today.

Dr Acton asked him to give a lecture about his life’s research in the area of meat preservation by fermentation and dehydration, and about the importance of bacteria in this process. At the time of delivering the lecture, Dr Fritz Niinivaara had spent half his life doing research on starter cultures and was Professor Emeritus, Department of Meat Technology, University of Helsinki, Finland.

I present the lecture in its entirety. The importance of this lecture goes beyond the starter culture industry. Dr Niinivaara’s recollections go back to the foundation of meat science as we know it today and are therefore of extreme importance, not just to the fermentation industry, but to meat science overall. It harkens back to a time when researchers were proud of their field of study and when much work was done to correct misconceptions about meat.

We strangely find ourselves in similar times which makes the lecture not just foundational to our trade, but also relevant for today. I will use this as the index page on all subsequent notes on meat fermentation which has become a field of intense interest to me personally. The index to this work will be after the references given by Dr Niinivaara to his lecture.

From Richard Bosman Quality Cured Meats

The History of Food Fermentation

Niinivaara writes that “the preservation of food by fermentation is as old a custom as is the history of man. It was, surely, learned by chance. The purpose of fermentation is not only to preserve the food but also to improve its flavour, consistency, texture, and nutritive value. So, fermentation creates new and unique products from a given raw material: wine from grapes; cheese from milk; beer from malt; and salami or dried ham from meat. Dried, fermented meat products have a shelf-life of months and a delicious flavour, quite different than the flavour of meat.”

Fermentations were carried out during centuries without any scientific knowledge about the nature of the processes involved. Up until recently, sausage-makers would transfer old curing brine to the newly-prepared one. Thus new brine would become inoculated with beneficial microorganisms, causing the desired changes in the cured meat during ripening. This traditional method was based on empirical observations, with almost no knowledge of bacteriology. Therefore, the results were not always satisfactory. Failure was not uncommon.

In the 19th century, Pasteur showed that fermentations are caused by specific types of organisms. The first defined bacterial starters, intended for the fermentation of milk, were introduced about 100 years ago. It was not until the 195O’s, however, that a pure starter culture became available for the fermentation of meat (Liicke et al., 1989). Shortly thereafter, pure cultures were mixed for even better results. The scientific basis of the use of starter cultures in the meat industry was for the first time presented in my doctoral dissertation in 1955. This study will be described later.

People often ask me: How did I become interested in the use of bacteria for the production of dried fermented sausage?

As a student and later as an assistant of Finnish Nobel Laureate (Biochemistry, 1945) Professor Artturi I. Virtanen, I became quite well acquainted with the importance of the bacterial cultures used in the processing of dairy products: cheese, butter, sour milk products (yoghurt), among others. Professor Virtanen had spent a great part of his life in the field of Dairy Science, having made many important discoveries. The results of his research significantly improved the quality of dairy products by ensuring the success of the delicate biological processes utilized then.

In 1947, Professor Virtanen asked me to initiate and to organize a new field of endeavour: meat research in Finland. Consequently, I left my work in biochemistry and started a brand new career without having the slightest idea about this new discipline, unaware of the nature of the problems to be solved.

I found my experience in Dairy Science to be quite useful. The fermentative changes in cheese were quite well known at that time, thanks to Professor Virtanen’s previous research work. The formation of the typical flavor, aroma and consistency depended on the activity of the appropriate microbial flora in the cheese. Cultured microbes were used in these processes.

The ripening of dry sausage, I supposed, might have been by a similar process, but the information on the kind or kinds of bacteria which played a role therein was non-existent. Some microbes could have been useful and desirable but also harmful if found to cause discoloration, unpleasant odor or putrefaction within the system,

Therefore, I concluded that it might be an interesting and economically important task to clarify the relationship between different microbes, the changes produced during the process and the quality of the final product.

Decisive for my future work was the discussions with Dr Niven and Dr Deibel in Chicago in 1953. Both of these scientists were interested in the role of microbes in meat fermentation, e.g., in the ripening of dry sausage. This was my first study trip to the U.S.A..

The First Successful Achievement with Pure Cultures for Meat Processing

In spite of the many unsuccessful experiments in the U.S.A., I decided to start the research in order to isolate bacteria and test the influence of these organisms in the manufacture of dry sausage. The main purpose of the studies was to isolate bacteria from good quality dry sausage and to determine their influence on the ripening process. The ultimate purpose of the study was to inoculate sausage batter with cultures of the isolated bacteria in order to improve the process by shortening the fermentation time, improving color and flavor and eliminating the risk of spoilage and discoloration inherent in the traditional process.

In addition to the organoleptic evaluation, microbiological, chemical and physical determinations were carried out. Variations in moisture content, drying loss, fat content, pH value, redox potential, photometric color determinations, and the content of glucose, lactic acid, nitrate, nitrite ammonia and hydroxylamine in the sausage, were carried out.

Microbiological analyses included differences in total bacterial count, aerobic and anaerobic microorganisms and micrococci were determined. The technological trials were carried out in the pilot plant of the Research Institute for the Meat Industry, in Hämeenlinna, Finland.

In the preliminary tests, the best results were achieved with a bacterial strain which we called “M-53.” In accordance with Bergey’s Manual, this organism was classified to be closest to Micrococcus aurantiacus. The “M-53” organism was then used as the starter organism in the original and subsequent research work. The results of this research work became the author’s Doctoral Dissertation in 1955 (Niinivaara, 1955).

In my dissertation, the following important observations were made and published. Using starter cultures:

  • Color formation was speeded up.
  • The pH value of the system was lowered more rapidly.
  • The desired consistency was achieved more rapidly.
  • Total processing time could be shortened considerably, a great economical advantage.
  • The process became fail-safe in view of the antagonistic nature of the starter culture which inhibited many spoilage or pathogenic organisms.

“It is a Long Way From Idea to Success.’’

There were many factors which led-through many difficulties to the success of utilizing starter cultures industrially. The first of these, a very important one, was the industrial propagation of suitable strains. Fortunately, I was able to start a good cooperation with an enthusiastic person from Germany, Herr Rudolf Müller, who agreed to develop the cultivation of microbes, i.e., “starter cultures”, on an industrial scale. At that time, there was no model to follow for this kind of product and, therefore, we had to overcome numerous difficulties. The greatest one of these was the preconceived opinion of many people in industry as well as in research institutes.

The bacterial culture methodology I had used at pilot plant scale was not directly applicable at industrial scale. A new method had to be developed. Lyophilizing technology was still in quite a primitive stage: it was not cost-effective, and it significantly decreased the activity of the microorganisms. If that were not enough, later on we had problems with bacteriophage, which destroyed the cultures towards the final stages of cultivation. Therefore, we were forced to isolate new phage-resistant strains exhibiting the characteristics we had determined to be desirable in starter cultures for sausage: nitrate reduction capacity, acid production capacity and an antagonistic effect towards harmful/ undesirable bacteria.

Finally, when after much toil lyophilized starter cultures became available, we met the skeptical attitude and preconceived opinion of the meat industry.

Fortunately, at that time I was working in the Research Institute for the Meat Industry in Hämeenlinna and therefore had the opportunity to organize experiments in order to demonstrate the advantageous influence of the starter cultures. Through Herr Müller, the positive, encouraging results obtained by the Finnish meat industry were transmitted to the German meat industry, where initially the attitude was very skeptical, as well. In fact, many leading European Meat Research Institutes would stubbornly not accept this innovative methodology and, therefore, discouraged further research on the subject.

Thus, Finnish meat industry was the first test laboratory in the development of the starter cultures for industrial use. The Finns (filled with “Suomalainen Sisu,” a mixture of courage, determination, inspiration and stubbornness), went from pilot-plant scale to the industrial level of applications. But slowly, through continued experimental work in Finnish industrial plants, and later on in the German meat industry, the beneficial influence of starter cultures on the production, quality and economics of dry fermented sausage was finally recognized. The use of starter cultures was accepted and became a reality. This was a key accomplishment!

In 1972, at my initiative, the International Starter Culture Symposium was organized in Helsinki. This event strongly influenced the opinion and effectively removed the prejudice from many meat scientists. Afterwards, cooperation with many countries developed and collaborative studies were carried out and published (Proceedings, Starter Culture Symposium, Helsinki, 1972).

Mixed Starter Cultures

After having gathered a great deal of information about the importance and role of the micrococci in the ripening process of dry sausage, we started to clarify the role of lactobacilli in the process. These investigations led to Esko Nurmi’s Doctoral Dissertation in 1966. As a result we were the first to develop the combined inoculation with mixed starters containing a pure culture of Micrococci and a pure culture of Lactobacillus plantarurn. The Micrococcus ensured color formation whilst the Lactobacilli was responsible for the decrease in pH-value and for the formation of the desired texture and consistency. This was another key accomplishment!

Before Nurrni’s findings, it was commonly believed that Lactobacilli were the main spoilage organism in European dry sausage (Coretti, 1958). These studies showed that lactobacilli are also useful and, in many cases, necessary organisms in the ripening process.

Some Aspects of the Properties of the Starter Cultures

Antagonistic Properties

Research carried out during recent years has proved that the antagonistic properties of starter cultures is a very important conservation factor. In addition to their role in fermentations, the suppression of spoilage and pathogenic bacteria offers new application for the use of starter cultures in food manufacturing. Just in the last years, the use of microorganisms as protective flora has expanded, for example, in the packages of cooked sausages

In my first publication on starter cultures (Niinivaara, 1955), the inhibitory effect of starter cultures was already mentioned. This was shown in laboratory trials, but also in technological experiments at pilot plant scale. We were able to show that the microbial formation of hydroxylamine is possible only when nitrate was present in the growth milieu. Hydroxylamine had an inhibitory effect on the growth of spoilage bacteria.

In the work by Pohja (a dear, inspiring co-worker of mine) and Niinivaara (1 957), we showed how the starter organisms inhibited the growth of many undesired organisms. Later, the antagonistic influence of starter cultures on the growth of Salmonella senftenberg in the dry sausage (Niinivaara et al., 1977) was shown. Pohja’s doctoral dissertation pointed out the first selection system of useful Micrococci. Later on, his work has been used as the model for other microbes. Thus, the starter cultures improve the hygienic conditions during processing and minimize the potential health risk caused by the pathogenic organisms.

The Gram-Negative Bacteria in the Fermentation

There are many indications that gram-negative bacteria play an advantageous role in the fermentation process. For instance, the proteolytic activity of the bacteria in this group can degrade proteins to form the desired aroma. On the other hand, we usually try to avoid the growth of gramnegative bacteria because many pathogenic organisms belong in this group.

Esko Petäjä (1977) started an investigation to clarify the role of gram-negative bacteria in sausage ripening. He isolated a Vibrio strain (Vibrio costicolus) that he used in the drying and fermentation of dried ham with limited success. Although it had a positive influence on the flavor of ham, Vibrio costicolus was found to be very sensitive, difficult to cultivate and apt to lose its fermentative capacity after freezing. Therefore, it never came into commercial use.

Petäjä also isolated several strains of Aeromonas. Two strains of his collection, Aeromonas X and Aeromonas 19, had the most favorable effect on the quality of sausage. The best results he achieved when Aeromonas was inoculated together with Lactobacilli.

These strains are not available commercially despite the fact that 12 years ago we achieved very interesting results in production trials carried out under the direction of Dr. Abraham Saloma in Argal S.A., a commercial operation in the city of Lumbier (Navarra), in Spain. This factory has for several years successfully used these starter cultures in the commercial production of Spanish dry sausages, Salchichon and Chorizo.

Starter Cultures and the Nitrite Problem

During the last decades, investigations have been carried out on the fate of nitrate/nitrite in cured meat products. Evidence exists that under certain circumstances the formation of carcinogenic nitrosamine is possible. This is one reason why many laboratories are trying to find out how to minimize the concentration of nitrite in meat products to a level where bacterial spoilage could be avoided without jeopardizing color formation.

My co-worker Eero Puolanne has worked on this problem. In 1977, he published his Doctoral Dissertation “The effect of lowered addition of nitrite and nitrate on the properties of dry sausage.” He was able to show that by using starter cultures it is possible to lower the nitrite and nitrate addition by one third from the normal level.

Investigation by Niven

By an astonishing coincidence, at the same time my work on the use of Micrococci was published, Charles Niven published his study on the use of Pediococcus cerevisiae (P acidilactici) as starter culture in the American type of dry sausage known as “summer sausage” (Niven 8, Wilson, 1955). We had worked independently of each other. After the discussion in Chicago in 1953, we did not have any contact with each other, but our studies were published exactly at the same time (April 1955). Niven’s Pediococci also became commercially available and was sold under the name ACCEL (E. Merck, Rahway, N.J.).

Future Research

The future opens many new perspectives to create new starter cultures and utilization of microorganisms in new fields.

Leistner, et al. (1 990) have mentioned the genetic possibilities of improving certain properties of bacteria. In the future we could, through gene technology, improve the production and activity of microbial protease, lipase, catalase, nitrate reductase, to name a few. In that way we could give new properties, or strengthen the desirable ones already existing in the microbe.

It seems also possible to transfer new genes into a given microorganism so that it may produce aroma components, vitamins, specific desirable metabolites, and so on. In addition to the research oriented towards the solution of old, traditional problems of meat fermentation, there are new elegant methods to create better cultures with stronger activity in those desirable reactions that favor a good fermentation process.

Much research has been carried out in the field of meat fermentations. Yet, we are far away from understanding the complete interrelations between the microbiology, the technology and external factors influencing the fermentation and ripening process (Buckenhuskes, 1990).

Financial Aid

A very significant step in starter culture research was the financial aid received from the United States Department of Agriculture. Two grants of considerable magnitude became available for this research in the years 1959-1 963 and 1964-1969. This financial support made it possible to continue the research work on starter cultures in Finland. Thirty-eight scholarly papers were published on this subject, thanks to the generosity of the USDA.

International Cooperation

The year after my studies on starter cultures were published, we started the international cooperation with Germany. The objective was to create starter culture technology and a distribution organization to deliver the cultures to the meat processors. This cooperation continued for about 20 years.

Many other international contacts came into being later on, which proved to be very beneficial for the research and development work. In that fashion, we were able to exchange thoughts and ideas, bacterial strains and even research work personnel between countries. Mutual cooperation was carried out with Yugoslavia, Hungary, Bulgaria and later with Spain. In all these countries, fermented sausages have for centuries constituted a very important gastronomical tradition. In addition, they play a significant role in the meat industry.

I would especially like to allude again to a very interesting and sympathetic cooperation with a meat processing firm in Spain. This cooperation started in 1976 by the initiative of Dr Abraham Saloma, who was then the technology director of this company, Argal, S.A., then a subsidiary of the Antonio Porta Labata Group. Under Dr Saloma’s direction, important improvements were achieved in the production of fermented salchichon and chorizo at commercial scale.

One significant accomplishment at Argal was the establishment of one of the most complete starter culture programs anywhere in the meat industry. More than 12 different strains of microbes (bacteria, yeasts and fungi) were daily propagated and incorporated into fermented products. Each particular sausage was inoculated with a tailored mixed starter culture that ensured distinctive characteristics and high quality in the final product. I would like to thank Dr Saloma for these pleasant years of fruitful cooperation, friendship and international understanding

The year 1955 was the birth year not only of starter cultures for meat, but also the birth year of the international cooperation called the European Meeting of Meat Research Workers (EMMRW), renamed the International Congress of Meat Science and Technology (ICoMST) in 1987. The birthplace of this Congress was the same small Finnish town, Hameenlinna, where much of the starter culture work originated and was carried out.

This Congress has gathered annually, without interruption, during 35 years, having become an international forum for lectures concerning not only starter culture research but meat science and technology across many international borders. More than 30 countries participate each year in this congress. It has been a wonderful feeling that the idea of scientific collaboration, originally expressed in a small circle amongst good friends and colleagues, was the seed for a great intercontinental cooperation

Some Remarks About My Life’s Other Activities

As I mentioned at the beginning of this lecture, I started meat research in Finland in 1947. There was no model in Europe to learn what meat science was all about and which problems had to be solved. Even in countries where meat research had been started, like in Germany, everything was destroyed by the war. Meat science laid in primitive stages in ruined Europe. The only way was to identify the problems and to produce solutions alone, and through research build the knowledge, to improve the quality of the products, to improve the economy of the production, to improve the utilization of the byproducts. We started our independent research work from zero in meat science and technology.

The most important question in the production of cooked sausages was the water-binding capacity of meat. This was the theme with which we worked during the first years, since 1952 in co-operation with German meat scientists Grau and Hamm.

The next step was to concentrate on the problems of the fermented meat products. As I described at the beginning of this lecture, the role of the beneficial microbes should be cleared up. The final goal was to find and cultivate microbes, add them as the pure cultures in the meat mass and by that way speed and ensure safety in the processing. Both things mean better economy in the production. Of decisive importance for this work was the encouraging discussion in the American Meat Institute Foundation with Dr. Niven (in 1953) and later the financial aid by USDA in the form of two grants of considerable amount. In many scholarly papers. New information about the basic problems in meat science was published in the international scientific journals and congresses. This research activity created a new field of food science. This made it possible to establish a professorship at the University of Helsinki for Meat Science and Technology. Through this research work, meat technology gained “saloon competence,” as people say in Europe. It became working knowledge.

Through financial aids by the meat producers, the chair and professorship of Meat Technology were founded. My duty was to start this academic activity in 1961 again from zero, like the industrial meat research 14 years earlier.

Besides the scientific research-partly continuing the old themes-the education of new generations of young students for leading technical positions in the meat industry was my duty with high challenge.

This professorship in Meat Technology was the first one in Europe. No models existed for the content of the instruction. No academic text books existed. The lectures, the exercise works had to be created from zero, again.

Now, more than 100 meat technologists are in leading positions in the Finnish meat industry. Eero Puolanne, one of my students, is continuing my academic career as professor of Meat Technology and Director of “my” Meat Research Institute.

Just before retiring and leaving my duties as university professor, I started a new activity in the field of meat.

It was generally known that consumers had lots of wrong information about the nutritive value of meat. Housewives, who in most homes are responsible for the preparation of meals, were confused when buying meat: which meat or which part of the carcass for which purpose. The strong propagation from the side of Die Grunen, the “greens,” vegetarians and raw food eaters, made the housewives still more confused. They often ask: “Is meat healthy for my family or is it not?” To improve the knowledge of the consumers about the quality and nutritive value of meat, to facilitate the choice of meat, to give new ideas in food preparation, we
founded a society that we called “Meat Information Center,” of which I was the first chairman and charter member

During the last years, we have been able to build a useful cooperation with many corresponding organizations abroad. The international cooperation helps us to get new ideas and to evaluate experiences about different activities

Last, but not least, I should like to mention the constructive cooperation with students in Finland: The Society of Food Science (“Lipidi”). I have made numerous studying excursions with my excellent students in many countries in the world, sharing ideas, promoting knowledge of food science, creating strong bonds with fellow professionals and fostering goodwill amongst many people internationally. This Society has selected a few honorary members, one of them being Abraham Saloma (since 1978). Other (“Lipidi”) honorary members are Professor Robert s. Harris (U.S.A.), Doctor Peter Zeuthen (Denmark), Professor Lothar Leistner (Germany), Professor Ferenc Lorincz (Hungary), Professor Torsten Storgards (Sweden), Professor Rainer Hamm (Germany), Professor Velimir Oluski (Yugoslavia), Doctor Sandor Balogh (Hungary), and Professor Ralston Lawrie (U.K.).

During the 22 years I was active in the University of Helsinki, I performed the duties of the chairman of this Society for 20 years. Like my job as University Professor, my position in this society was inherited by my successor in the office, my dear student, Professor Eero Puolanne.

In Conclusion

I am very happy to be able to review today, before this wonderful audience, many of the magnificent developments which have taken place during the past 35 years. Time has quickly flown from the first experiments when we inoculated sausages experimentally to the present, when starter cultures are indeed an integral, indispensable part of fermented meat and other food products. The reason why I was invited to participate in this very interesting meeting is that I was there when this beautiful story began.


Buckenhuskes. 1990. Lecture at the FIA-Conference 1990 at Singapore.

Coretti. 1958. Die Bakterienflora Frankfurter Rohwurste. Arch. Lebensmittelhygiene. 9: 32-35.

Krol, 6. 1984. Progress and problems of fermented sausages. Trends in Modern Meat Technology-1. pp. 55-57. Pudoc

Kunz, 6. 1989. Aspects in the use of starter cultures in meat products.

Kuusela, K.; Puolanne, E.; Petaja, E.; Niinivaara. F.P. 1978. A rapid method to estimate the activity of lactobacilli used as starter cultures. 24th European Meeting of Meat Research Workers, Kulrnbach.

Leistner, L. 1987. Perspectives of fermented meats. International Congress of Meat Science and Technology. Helsinki. pp. 323-

Leistner, L. and Sclinunsefridze als Starterkulturen beider Rohwurstherst ellemg. Starterkultur Symposium, Helsinki, 1972.

Lucke et al. 1989. Starter culture development. Proc of the COST 91 bis sub-programme “Food Technology of the EEC.” Goteborg.October 3-5.

Niinivaara, F.P 1955. About influence of bacterial pure cultures on the ripening and color formation of the dry sausage (in German). Acta Agralia Fennica. 85.

Niinivaara, F.P.; 1964. Bacterial pure cultures in the manufacture of fermented sausages. Food Technology 18, 2:25-31.

Niinivaara, F.P.; Sederholm, H. 1963. Uber die knotinuerliche Zuchtung von Mikroorganismen. 9th European Meeting Meat
Research Workers.

Niinivaara, F.P.; Sirvio, P.; Nurmi, E.; Puolanne, E. 1977. Der Einfluss von Starterkulturen und verschiedenen Zusatzstoffen auf das Wachstum von Salmonelle senftenberg in Rohwurst.

Fleischwirtschaft 57, 5: 1007-1 008, 101 1, 101 2.

Niven, C.F.; Deibel, R.H.; Wilson, G.D. 1955. The use of pure culture starters in the manufacture of summer sausage. Am. Meeting Amer. Meat Inst. 5 p.

Nurmi, E. 1966. Effect of bacterial inoculations on characteristics and microbial flora of dry sausage. Acta Agralia Fennica. Nr. 108. p. 7-73.

Petaja, E. 1977. The effect of gram-negative bacteria on the ripening and quality of dry sausage. Dissertation. J. Scientific Society of Finland. 49: 107-166.

Pohja, M.S.; Niinivaara, F.P. 1957. Uber die antagonistische Wirkung eines Mikrokokken-Stammes gegen die in Rohwurst
vorkommenden Bakterienstamrne. Zeitschrift fur Lebensmittel-Untersuchung und-forschung 106, 4: 298-301.

Pohja, M. 1960. Micrococci in fermented meat products. Dissertation. Acta Agralia Fennica, 96.

Puolanne, E. 1977, The effect of lowered addition of nitrite and nitrate on the properties of dry sausage (in German). Dissertation.

J. Scientific Agricultural Society of Finland. 49:1, 1-106.

Roca, M.; Incze, K. 1989. Antagonistic effect of some starter cultures on Enterobacteriaceae (E. coli). Meat Science 25, 123-131.

The Lecture Published

E F. Niinivaara, Reciprocal Meat Conference Proceedings, Volume 44, 1991, American Meat Science Association.

About Meat Curing (Nitrite, Nitrate and Nitric Oxide)


The use of nitrites and nitrates in meat curing has been one of the most researched matters in food science for many years. Over the years I have dedicated an enormous amount of time to understand not just its chemistry, but also the history of its use. Here I want to list all the work I have done on the subject The one document where I try and pull everything together is Bacon Curing – a Historical Review. I deal with its chemistry in an elementary manner in Bacon & the Art of Living, my book on the history of meat curing in Chapter two, The Curing Molecule.

The quest has been for years to try and find a way to cure meat without using nitrites and nitrates directly. It has recently been discovered that nitrate and nitrite are of huge physiological importance to humans. As such, the value of a quest to eliminate it from food must be reconsidered. This leads me to as the question:

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

Unfortunately, much of what follows is still subject to NDAs and therefore restricted access. In The Truth About Meat Curing: What the popular media do NOT want you to know! I start dealing with the health benefits of nitrates and nitrites.

It has been discovered in recent years that bacterial fermentation of meat yields nitric oxide which cures meat. A fundamental question follows namely if it is possible to have cured meat without any nitrites and nitrite present. I am not talking about using nitrite and nitrite but the newly developed meat fermentation systems. It is possible to effect curing without the use of nitrates and nitrites directly or indirectly. However, from a consideration of the various reactive nitrogen species, the question comes up if nitrite and nitrate will not eventually form in meat where nitric oxide is present.

Regarding Nitrite Free Curing Systems and RNS

Still, understanding the curing reaction should be the starting point for the serious meat curer. This led me to investigate the various reactions relevant to our trade.

Mechanisms of Meat Curing

Not just are the reactions beautiful and fascinating, but the history of its use and the development of the art of curing meat is without a question one of the most exciting stories never told!

Nitrate and Nitrite – their history and functionality

In the history of our art, one man stands tall as one of the most influential in the development of nitrite curing. I dedicate an entire section to the history of this remarkable man.

The Master Butcher from Prague, Ladislav NACHMÜLLNER

Nitrite curing was commercialized in 1918 and the impetus for its global spread following WW2 was the work of the Griffith Laboratories on the back of the work of Nachtmüllner. The German and American affinity for the direct use of sodium nitrite was however not shared internationally and in England in particular they have accessed nitrite for a very long time using bacterial fermentation of the brine itself. In the next section, I explore the development of curing systems pre-1918. In the next section, I review the major curing systems that have been used around the world since before nitrite curing became commonplace.

Bacon Curing Systems: From Antiquity till now.

In many of my earlier works, I still reflected on the quest for nitrite-free curing. Not all the considerations are irrelevant.

The Present and Future of Food Processing

In the following section, I reflect on some of the monumental developments in curing before the world wars.

The History of Bacon, Ingredients, and related technologies

I delve into the very early invention of the art.

The Salt Bridge

My Complete Work on Nitrites


Dapo’s Rusk Recipe

My adventure in Lagos, Nigeria takes me back to the foundation of the meat industry. It is fair to say that there are generally three meat products sold in the country being mince, stewing meat without bones, and stewing meat with bones. The challenge is to migrate from this to properly defined primal cuts.

As far as the production of sausages is concerned, due to the infancy of the meat industry, meat fillers that became commonplace in other developed markets are not available in Nigeria. What I love about this is that it forces me to think about the origins of the industry. As far as sausage fillers are concerned, such a filler is rusk.

The question then comes up as to the comparison between the use of rusk and meat extenders such as TVP (Texturised Vegetable Protein) or texturized soy protein to be specific. Without getting too technical about the difference, it made me ask for the most basic recipe for rusk. One can get amazingly creative with this basic recipe. One can add emulsifiers, and protein from various sources, and use them as a carrier of spices and other functional ingredients.

Oladapo Adenekan, the previous production manager of the old UTC who dominated the food trade in Nigeria for many years shared this recipe with me after our discussion about making our own rusk. In the bakery department, Samy is working with us to create our own rusk for use in our meat recipes.

I share the recipe that Dapo gave me. This simple recipe set about an amazing journey of discovery leading right into the heart of the meat industry!

Rusk Formulation for Meat Filling

Wholesale Wheat Flour100.00
Cold Water5.00

Weight loss of 16%16.84



Spread over a tray

Set oven to 115o C and roast for 50 minutes.

The History of Rusk

Bisma Tirmizi does an excellent job chronikling the history of rusk. Her delightful story begins as she explains when she stumbled upon this information when her “six-year-old son came home from school saying that he wanted to have, ‘cake rusk and chai’.”

She writes, “I looked at him quizzically, to which he said, ‘If we don’t have them, can we make them?’ So I called up a friend of mine, who is a baker of sorts, and asked her if it was possible to make cake rusks at home. She laughed and said, ‘Of course, how do you think biscotti and cake rusk came to be, do you want my Italian nana’s recipe for biscotti or my Pakistani dad’s recipe for cake rusk?’

What do you think my answer was?

My research tells me that eating stale bread was a norm in ancient Europe. Ancient Roman soldiers are said to have carried a hard bread known as biscoctus, literally meaning ‘twice cooked’.

The sub-continental cake rusk may very well be a descendant of the ancient biscoctus. Food historians mention that recipes for foods named rusk began showing up during the reign of Elizabeth I.

The Oxford English Dictionary mentions that the word ‘rusk’ dates back to the year 1595 when referring to a twice-baked bread.

Alan Davidson says in The Oxford Companion to Food:

Rusk is a kind of bread dough incorporating sugar, eggs, and butter. It is shaped into a loaf or cylinder, baked, cooled, sliced, and then dried in low heat until hard. Rusks have a very low water content and keep well for extended periods. Sharing a common origin with the modern biscuit, medieval rusks were known as panis biscoctus, meaning twice-cooked bread, and were used as provision for armies and ships at sea.

In many countries there are breads that may resemble rusks, in that they are essentially oven-dried bread, whether plain like the Italian bruschetta or of a sweet kind [like the cake rusks of pre-Partition India]; but they may incorporate other ingredients such as spices [cardamom, cinnamon, nutmeg] or nuts.

It is said that the earliest modern cookie cakes are from 7th century Persia, since it was one of the first few regions to cultivate sugar, second to the region we know as the sub-continent, our very own home.

Sugar spread to Persia and then to the Eastern Mediterranean and Arabia, and with the Muslim invasion of Spain, and the Crusades we saw the advent of the developing spice trade. The cooking techniques and ingredients of India, Arabia and Persia spread into Northern Europe. So we can safely assume that the modern day cakes traveled to Europe from Asia, and then back to Asia, as if it was an import from Europe.

In the article titled How Sweet It Was: Cane Sugar from the Ancient World to the Elizabethan Period, Brandy and Courtney Powers say:

In 510 BC, hungry soldiers of the Emperor Darius were near the river Indus, when they discovered some ‘reeds which produce honey without bees’. Evidently, this early contact with the Asian sources of sugar cane made no great impression, so it was left to be rediscovered in 327 BC by Alexander the Great, who spread it’s culture through Persia and introduced it in the Mediterranean. This was the beginning of one of the first documented sugar and [cake] products of the Middle Ages.

However, cake rusks are a legacy of Elizabethan naval provisions. These were smallish lumps of bread twice baked so as to be indestructible enough to last out a long voyage at sea. The earliest known reference to them comes in an account of Drake’s voyages, written in 1595: ‘The provision…was seven or eight cakes of biscuits or rusks for a man.’

The modern, more refined cake rusk is sliced cake; re-baked, crisped and dried, and it dates to the mid-18th century. These hardened delightful cakes were enjoyed at tea times and were perfect for dunking in evening time tea or milk. These were re-introduced (in their modern form) to the sub-continent from England, where they were popularly served as shipboard fare; dried, tinned or stored for long periods of time.

Some historians suggest that the creation of rusks was just a basic need for home-cooks to get away from everyday kneading and to make the bread last longer. It is said that the first rusk was made by a byzantine baker.

When the time arrived to make cake rusks, I turned to my Italian Pakistani friend. Needless to say, they turned out delicious, perfect for an evening, of cake rusk and chai. Here it is, from my kitchen to yours.”

Bisma’s recipe, of course, goes well beyond the reason for Oladapo’s recipe which is for the meat curing establishment, but her story is engaging, and her recipe is worth sharing.


2 cups flour
6 eggs
225 grams butter
2 tsp. vanilla essence
3 tsp. baking powder (level)
½ tsp. salt
1 ¼ cup powder sugar
Orange food colouring


Preheat oven 350 degrees Fahrenheit (176o C). Cream butter and eggs in a cake mixer, add sugar and vanilla and mix, adding all dry ingredients and food colouring and mix. Once cake batter is ready, pour it into a greased 8 x 8 inch pan and bake for 55 minutes.

Once cake is ready let cool and slice, re-bake directly on the oven rack in a 300-degree Fahrenheit oven for 20 minutes. Let cool and harden completely and enjoy with a cup of tea, milk, or coffee. Store in an airtight cookie jar.

English Origins

The story then took on an unexpected twist. Suddenly, posting a short article motivated by Dapo’s rusk recipe lead me right into the heart of the meat industry. I discovered that like every meat ingredient, rusk had an evangelist who changed the ingredient to a legendary institution.

Robert Goodrick, the English Master Curer sent me the following clipping about a patented Rusk brand from the UK registered in the name of TB Finney & Co.

The listing in the 1914 Who’s Who in Business reads, “FINNEY, T. B., & CO., Ltd., Pepper, Seed, Spice and Rice Millers and Butchers’ Outfitters, Cornbrook Spice Mills, Trentham Street, Cornbrook, and Cornbrook Bakery, Rusholme Road, C.-on-M., Manchester. Hours of Business: 9 a.m. to 6 p.m. Established in 1894 by T. B. Finney. Incorporated as a Limited Company in 1911. Directors: T. B. Finney (Chairman), R. Finney, T. Bardsley, G. E. Cooper, C. Howard, and J. Pedder. Premises: Consist of five-storey Mill and outbuildings. Staff: Fifty. Specialities: “PAB ” for Sausage and Polony Making (Inventors and Sole Makers), Pepper, Seed, Spice and Rice, Peppers and Spices, warranted absolutely pure. Patents: PAB, Bergice Reekie, &c. Connection: United Kingdom, Foreign, Colonial. Telephone: No. 6632 City, Manchester. Telegraphic Address: ” Preservaline, Manchester.” Bankers: London City and Midland Bank, Ltd. (Chester Road).” (www.gracesguide.co.uk)

The very early use of rusk in the production of Polony is fascinating as its modern equivalent in TVP is used extensively in the production of Polony in South Africa. (The Origins of Polony) What is even more interesting is that the wide-scale use of rusk in England can be traced back to a single man or company. I am not suggesting that TB Finney was the only man who should receive the honours of establishing the status of rusk in the English world (and worldwide) as a filler, but certainly, he can be credited as one of them.

Robert included a photo of TB Finney and the title page of his publication, Handy Guide.

Courtesy of Robert Goodrick.

Courtesy of Robert Goodrick.

Recipes with Rusk

There are two recipes from Finney that immediately catch my eyes

Hog’s Puddings

14 lbs (6.3 kg) Lean Pork (55%)
4lbs (1.8 kg)Fat Pork (16%)
3lbs (1.3 kg) PAB (Rusk) (11.5%)
2 quarts (1.89L)water (16%)

Total: 11.29kg

8lbs Salt
4lbs White pepper
1oz Ground Cayenne
1/2oz Ground Mace
1/2oz Ground Nutmeg
1oz Ground Thyme
Use at 1/2oz per pound (14g’s per 453mL water) of pudding mixture.

Mix well and chop fine, fill into wide hog or narrow bullock casings. Boil 1/2 hour and place into cold water ’till cold.


10 lbs Lean Pork
4lbs Fat Pork
2lbs PAB (Rusk)
2 quarts water

41/2lbs Salt
2lbs White pepper
1/2oz Rubbed Parsley
1oz Rubbed Thyme
ľoz Ground Mace
ľoz Ground Nutmeg
Use at 1/2oz per pound of pudding mixture.

Mix well and chop fine, fill into wide hog or narrow bullock casings. Boil 1/2 hour and place into cold water ’till cold.

These recipes have a striking resemblance to how we make Russians, Viennas, or Lunch Loaves in South Africa. With the dominating influence of the English in the history of South Africa, I am convinced that the meat curing traditions are as much English as they are German and Dutch! The original history of these recipes may be Russian Jewish immigrants, Germans, especially from German West Africa (present-day Namibia), and even Polish/ Hungarian in terms of its distant heritage, but what we produce today are equally, if not greater in its reliance on the English tradition. Of all the nations on earth, the English remain most closely associated with the use of rusk in their sausages which has been replaced by texturized soy in places like South Africa.


The baking of rusk brought me back again to the foundations of the meat industry. I am deeply thankful for the opportunity to be involved in the Nigerian project as it allows me a unique vantage point as an amateur food historian to witness the birth of our industry firsthand. Thank you to people like Oladapo Adenekan who freely share his memories and experiences and who allow people like me and Samy a glimpse into his world. Enormous gratitude to Robert Goodrick for sharing these images and background with me. It is people like Robert, Dapo, and Samy that bring history to life, even on a subject seemingly as mundane as rusk. It makes one realise that there are no accidents and legends are created through dedication, skill, and focus which means that they walk in the footsteps of people like Thomas Finney! In the meat industry, there is no such thing as a mundane ingredient or concept!

(c) eben van tonder




Featured Image

Chapter 02: The Curing Molecule

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 PNO3. 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 NO3component 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.

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“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. stateSpecies
+5 NO3Nitrate ion, oxidizing agent in acidic solution.
+4NO2Nitrogen dioxide is a brown gas usually produced by the reaction of concentrated nitric acid with many metals. It dimerizes to form N2O4.
+3NO2An oxidizing agent usually produces NO(g) or a reducing agent to form the nitrate ion.
+2NONitrogen 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.
+1N2ODinitrogen oxide is also called nitrous oxide or laughing gas.
0N2Commonly found in air and very unreactive because of the very strong triple bond.
-1NH2OHNH2OH Hydroxylamine, a weak base, can act as either an oxidizing agent or a reducing agent.
-2N2H4Hydrazine, a colourless liquid, is a weak base. Used as rocket fuel. It is disproportionate to N2 and NH3.
-3NH3In 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.

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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!


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.


(c) eben van tonder

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Chapter 01: Bacon, my Teacher!

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.

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!


(c) eben van tonder

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The Life and Times of George Samworth Sen. – Foundation of Greatness!

The Life and Times of George Samworth Sen. - Foundation of Greatness!
Eben van Tonder 
3 September 2021


One of the iconic food producers in England is without question, the legendary Samworth Brothers. As an amateur food historian, my interest in the company is obvious. They owe their existence to the visionary work of several generations, beginning with George Samworth Sen, father of George Samworth born in 1868 who was the father of the Samworth Brothers George and Frank. Much has been written about George Samworth (born in 1868), but what do we know about his dad who was himself a pig buyer in Birmingham? As will be seen in this article, the legacy of this extraordinary family started with whom I will refer to for sake of clarity as George Samworth (I) and his son, born in 1868, George Samworth (II).

In 1896, his son George (II) would set up his own business as a pig dealer in Birmingham. Their existence spanned a time in England when the English pig breeds were established, the industrialisation of the meat processing trade took place and when the English producers had to weather the storm of the intense onslaught of foreign firms trying to wrestle slices of the lucrative English meat market from their hands. In the immortal words of Charles Dickens, “it was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity, it was the season of light, it was the season of darkness,” and in the life of George Samworth Senor and Junior, it was in a real sense their spring of hope.

Despite the lack of information on the life of George (I), I pressed on to glean insight into the times he lived and the man he was.

First I ask the question if it is possible to know what the discussions would have been around the dinner table of a pig trader in Birmingham towards the last half of the 1800s.

A. Dinner Table Conversations with George Samworth (I)

History provides ample information to know with a great degree of certainty the discussions they would have had around the dinner table in their Birmingham home.

Birmingham Above Knockcroghery

Birmingham, at this time, was and remained a key hub for the hog trade, linking the central and northern counties with the all-important southern counties well into the 1900s. The south with its dairy industries took the lead in hog production but this does not mean that the north and centre of England were not important and the key hub in this epic drama was Birmingham!

An example of its importance in the first half of the 1900s can be seen in a comparison that was made between Birmingham and the Irish village of Knockcroghery in the county of Roscommon almost right in the centre of Ireland. In a 1939 publication (Díosbóireachtaí Párlaiminte) the author mentions that if pork producers from this Irish town would bring their pigs to the Birmingham market, they would leave with £2000 more in their pocket than if they sold it in their home town the next day.

Joseph Harris, writing his epic work on pork husbandry in 1885 writes about the Birmingham pig market and says “Birmingham has long been one of the greatest pig markets in the kingdom, and the pig breeding of the district has been not a little affected and improved by the winter fat-stock show which has for some years been held here at Bingley Hall, with great success.” This places George Samworth Senior in a city, as important to the hog trade as Calne and Gillingham.

Getting into the Mind of a Hog-Man in the late 1800s

Besides confirmation of the importance of Birmingham, Harris’s writing gives us a glimpse into the mind of a hog man in the late 1800s and by extension, into the mind of George Samworth. This was his world and these are the times when he was growing up and when he started his career. In the dinner conversation with George and his family, these are exactly the kind of things that would be discussed.

The development of pig breeds through the incorporation of Chinese hogs into the English pig herds, the migration from lard pigs to the development of bacon pigs and re-organising the way pig husbandry was being done were all central issues at this time. See a series of articles I did on the subject The Old and the New Pig Breeds and The English Pig, the Kolbroek and the Kune Kune in Bacon & the Art of Living.

Hot topics at this time were the development of the Berkshire and Tamworth breeds and here Birmingham played a key role. Harris writes, “The town of Birmingham unites Staffordshire and Warwickshire. The old Warwickshire breed was a white or partly-coloured animal of the old-fashioned farm-yard type and has never been improved into a special breed. The Staffordshire breed was the “Tam worth.” At present, the Tamworth is rapidly going out of favor with farmers, from the want of aptitude to fatten, and are being replaced by useful pigs, the result of miscellaneous crosses of no special character. The best is the middle-sized white pigs, a cross of the Cumberland-York with local white breeds, often called the Cheshire. The northern cross improves the constitution, and gives hair of the right quality, hard, but not too much or too coarse.” (Harris, 1885)

At Bingley Hall, the class of Berkshire breeding-pigs under six months old generally brings from twenty to twenty-five pens. At present, however, the Berkshires in the Birmingham district are chiefly in the hands of amateur farmers, tenant farmers not having taken very kindly to them.” (Harris, 1885)

But the breed must be spreading rapidly if the ready sale of the young pigs at the Birmingham show be taken as evidence.” (Harris, 1885)

Mr Joseph Smith, of Henley-in-Arden, one of the most successful exhibitors of Berkshires, keeps three or four sows, and sells all their young; and others find the demand for young pigs constant throughout the year.” (Harris, 1885)

Mr Thomas Wright, of Quirry House, Great Barr, (who did so much toward founding the Bingley Hall show) considers the cross of the Berkshire with the Tam worth produces the most profitable bacon pigs in the kingdom, the Berkshire blood giving an extraordinary tendency to feed, and securing the early maturity in which alone the Tamworth breed is deficient. The cross of the Berkshire boar with large white sows has been found to produce most satisfactory results to plain farmers. My own notion with regard to all agricultural stock is, that we should abandon crosses and stick to our pure breeds, adapting them to our particular wants by careful selection.” (Harris, 1885)

The Tamworth breed is a red, or red-and-black pig, hardy, prolific, and the best specimens well-shaped, but slow in maturing. It seems a near relation to the old Berkshire; but modern Berks breeders carefully exclude all red-marked pigs from their breeding-sheds. Reddish hairs at the tips of the ears of Essex would be permitted and admired. Mr Alderman Baldwin, of Birmingham, is a noted breeder of this hardy, useful pig, which, however, does not seem to have any success as a prize winner. At the Royal Agricultural Show at Warwick, 1859, the Yorkshire and Berkshire breeds divided all the honors.” (Harris, 1885)

Improving the breeds was the talk of the town and George Samworth found himself in the middle of these developments.

Improved Oxfordshire

Birmingham, with its close proximity to Oxfordshire, would have been up to date with developments from this productive part of the country. The information is fascinating as it gives us the mechanism of introducing foreign genetics into the English hog gene pool.

An Essex Boar (Harris, 1885)

Harris writes about the Improved Oxfordshire the following: “These black pigs,” says Mr Sidney, “although they are scarcely numerous enough to enable them to claim the title of a breed, are interesting, because representing a successful attempt to unite the best qualities of the Berkshire and improved Essex. The old Oxfordshire breed was very like the old Berkshire. The first great improvement is traced to two Neapolitan boars imported by the late Duke of Marlborough when Marquis of Blandford, and presented by him to Mr Druce, senior, of Eynsham, and the late Mr Smallbones, in 1837. These Neapolitans were used with Berkshire sows, some of which were the result of Chinese crosses. Two families of jet black pigs were formed by Mr Smallbones and Mr Druce. On the death of Mr Smallbones, Mr Samuel Druce, jun., purchased the best of his stock, and had from his father, and also from Mr Fisher Hobbs, improved Essex boars. The produce was a decided “bit,” and very successful at local, Royal, and Smithfield Club shows. The improved Oxfords are of fair size, and all black, with a fair quantity of hair, very prolific, and good mothers and sucklers.” (Harris, 1885)

Mr Samuel Druce writes me: ‘I have recently raised one of Mr Crisp’s black Suffolk boars. In fact, wherever opportunity offers, I obtain good fresh blood of a suitable black breed, with the view of obtaining more lean meat than the Essex, better feeding qualities than the pure Berkshires, and plenty of constitution. I have never been troubled with any diseases among my pigs. Without change of boars of a different tribe, if of the same breed, constitution cannot be preserved. Where breeding in and – in from a limited stock is persisted in, constitution is lost, the produce of each sow becomes small in size and few in number. ‘The Oxford dairy farms have a first-rate market for pork in the University. Porkers at thirteen to sixteen weeks are wanted to weigh 60 lbs. to 90 lbs.; bacon pigs at nine to ten months, 220 lbs. to 280 lbs., but at that age, the improved Oxfords are easily brought to 400 lbs.” (Harris, 1885)

Essex Sow (Harris, 1885)

These were some of the things important to hog-men in Birmingham when George Samworth (I) was cutting his teeth in pig dealings. It is clear that there were a lot of technical developments taking place at this time. It is strange to think that pig breeding was at one point the “Silicon Valley-style” cutting-edge technology that grabbed the attention of young people but such were the times when George Samworth started his career. He certainly had the mind to understand it and the skill to put his knowledge to use.

The Pig Buyer

It is true that companies and people who excel in bacon and ham production have an intimate knowledge of pork farming and nutrition. The different disciplines go hand in hand. Over the years I have become familiar with most positions held related to the pork trade by, at some point, doing every conceivable job in the processing plant. I spend many days on pork farms as we integrated the requirements from the processing plant with what is delivered to the abattoir by the farmer. The one position which I never gave a second thought to and that suddenly became the focus of my interest after started doing work on the life of George Samworth is the role and life of the pig buyer.

The key function is fairly obvious – they bought pigs as intermediaries between the farmer and the factory. We get a glimpse of the role of the pig buyers from Ruth Guiry (2016). She is writing about life in another key hog town, Limerick in Ireland, but the function and role of the pig buyer could not have been much different in Birmingham. She writes that “the number of pigs produced by ‘small man’s industry’ in the city’s lanes could not meet the constant demands of the bacon factories, so a constant supply of good quality pigs from elsewhere was necessary to ensure the continual working and profitability of the bacon factories. The pig buyers … therefore played a central role in the success of the bacon industry, linking the farmers who produced the pigs with the factories that processed them. While many buyers were independent, others were employed directly by the bacon factories to source pigs at fairs..” (Guiry, 2016)

The pig trader was a skilled person. Guiry gives the following insight on the skill of the pig buyer which dovetails beautifully with the preceding section where we tried to glean insight into the dinner conversations in the Samworth household. She writes that “these pig buyers were known to be skilled, knowledgeable men who were able to quickly and accurately estimate the value of an animal …. They ensured a high quality of animal for the bacon factories, checking that a pig wasn’t too fat or too lean, that its limbs were of the right proportion and the health of the animal adequate.” (Guiry, 2016)

She mentions that the pig buyer often had to travel through the country in the course of their work. The “pig buying” happened at the station, at shows and also in the country. She describes the comradery among the pig buyers. Again, her focus is on the pig buyers in Limerick, but it is easy to see how it could be transferred to the buyers in Birmingham. She writes, “The Gores, they were from Waterford, now I know some of the Cork people, in rugby, and there’s one of them there, but Noel Murphy people were in Cork Rugby, they were pig buyers as well from Cork…well involved, they would all book into the same place …. these nights away … before the fairs, were sort of rousing affairs, you get all the pig buyers from … in the one boarding house … the crack was good like.” (Guiry, 2016)

The pig buyers often had their own lorries to transport the pigs to the abattoirs. Pig buying was a lucrative business with many pig buyers owning large properties so that they could keep some of the pigs in their back yard or somewhere else on their property. One of their other duties became the calibration of the scales. Falconer (1916) reports that it became customary for the pig buyers in Birmingham to calibrate the scales every morning. They would place half a cwt* or cwt* on the platform and then they adjusted the index till it showed a cwt* or half a cwt*.

The legendary Phil Armour from Chicago generated the funds required to start his packing plant through retail stores he started after selling equipment at the Californian gold rush. Sir David de Villiers Graaf of South Africa secured the funding for his meat enterprise through clever legal footwork after the Cape government forced him out of his shop to build the Cape Town Railway station. George Samworth (I), I suspect, did this through pig buying! Far from being a peripheral function, I now understand that the role of the pig buyer was key to the success of the meat processing trade and there was a lot of money in this line of work.

The story is usually taken up with the life of George Samworth (II), born in 1868. (1) Having looked at what certainly would have occupied the thinking of George Samworth (I), we delve into the annals of history to see if there are any tangible footprints left about him. Beaver & Lawrence (2005) begins the account of the life of his son, George Samworth (II) in riveting style. They write that he left school at age eleven and, “after trying a number of jobs in agriculture, found employment with a consortium of Birmingham pig dealers.” This means that he finally got employment with the same group that George (I), his father was associated with. I set out to see if I could find any information on his dad. A tantalising bit of information comes to us courtesy of the Birmingham Daily Post, 3 December 1892.

B. In the Shoes of George Samworth (I)

A Great Heritage from George Samworth (I)

The newspaper article reports that George Samworth, Sen. pig dealer, New Canal Street was summoned for selling ten pigs at the cattle siding at the London and North-Western Railway in Fazeley Street in violation of the markets clauses of the Consolidation Act.

It is here that we find a unique insight into the character of this remarkable man! Mr Bell (from the Town Clerk’s office) prosecuted and Mr O’Connor defended. Mr Bell said that inspector Wiltshire went to the Fazeley street siding on the 27th of October, and from what he heard went to the defendant and asked him if he had sold any pigs there. He said he did not, but the inspector subsequently saw a man named Laxton, of Coventry, who would be called, and who would state that the defendant sold him the two pigs remarking that he was fairly caught. Mr Bell then read the 90th of the Consolidation Act of 1883, under which the summons was taken out, however, because it was a fact that dealers carried on business in the cattle siding, which was an improper place, whilst the Corporation had provided a pig market at an expense of some £34 000.

“Mr Brame: Is this part of the new pig market that the pig dealers themselves have provided?”

– “Mr Bell: Oh, no.”

– “Arthur Wiltshire, an inspector, gave evidence bearing out Mr Bell’s opening statement and said that defendant remarked “They tell me you have fairly caught me, but I will not let you do it any more. I am not going to sell any more pigs on the sidings.” The new market was open at the time“.

– “Mr Carter: It is not customary to allow pigs to be sold in the sidings?

“Witness: No.”

– “Mr Laxton also gave evidence“.

– “O’Connor: Was the old market crowned?

“Witness: No.”

– “What was it moved for? Because they wanted it for vegetables.”

– “Mr O’Connor said that there was no intention on the part of the defendant to commit an offence, and he would ask the Bench to bear in mind that the new pig market had only been opened on the day on which the offence was committed, and the Act required, and the Act required that the market should be opened before the offence could be committed.”

– “The Bench fined defendant 10s and cost.”

(Birmingham Daily Post, 1892)

In the 1891 England & Wales Census, George is listed as a pig dealer, 41 at the time. His oldest son George was 22. We know that George (II) was born in 1868 which would have made him 22 at the time of the census, thus confirming we are dealing with the right family. The census report that his wife was Mary Samworth and that they had 10 children and one servant. The kids were George (22), Charles (19), Ernest (14), Louisa (12), Sara (10), Helen (8), Emily (7), Edith (5), William (3) and Sydney (8 months).

From this, we have a few important clues besides the fact that we are talking about the right person, the father of the man who would become the father of the Samworth Brothers, George and Frank. The fact that he had a servant is the first clue that he was successful in his trade and a man of means. The 1891 senses list the occupation of George Samworth, son of George Samworth also as a pig dealer which all confirm that we are on the right track.

The Back Story – Courtesy of Kieron McMahon**

Let’s leave the details of the court case aside for a moment and reflect on the fact that George Samworth was a pig dealer, had a servant and lived in a comfortable dwelling in Birmingham. More information came to light which confirms this and gives us remarkable insight into the man, his character and abilities and the environment where George Samworth, his son and father of the Samworth Brothers grew up in. It comes to us in the form of the back story to the events described in the newspaper article above, courtesy of Kieron McMahon, a world-class blogger from England and his site, Midlands Pubs, Birmingham.

Old Pig Market, Bordesley St & Allison St, courtesy of Google Earth.

Stone in Bordesley Street, laid by Joseph Horton, Esq. on 16 February 1892.

On the corner of Bordesley Street and Allison Street, Birmingham is a three-gabled brick building that was erected in 1891/2. It is the old pig market. Joseph Horton Esq. was the man responsible for identifying a suitable pig market. Two sites were identified, one on Montague Street and the other on Albert Street. The pig dealers preferred the latter. Due to problems obtaining the properties, the Bordesley & Allison site was seen as a good compromise by the pig dealers. The Corporation did not see it their way and so started what became known as the Pig Market Dispute.

Pig buying in Birmingham was monopolised at this time in the hands of a few men who were known as the Birmingham Pig Salesmen’s Association. One of them was George Samworth who was one of the men spearheading the development of the Bordesley & Allison site. It was a private enterprise. The other men who took the lead in the construction with George Samworth were Daniel John Foster, Joseph Doolan, Patrick Long, Joseph Gosling and John Jones. The design of the building was done by Owen & Ward.

The Corporation preferred the Montague Street site which the pig traders never liked. They nevertheless pressed on with their development and the two sites were effectively constructed at the same time. The Bordesley & Allison site was completed first in what was a race to see who would finish their construction first and was opened in 1892.

The Corporation responded with legal action against George Samworth, Daniel John Foster, Joseph Doolan, Patrick Long, Joseph Gosling and John Jones to stop pig trading at the site, claiming that it “infringed the manorial rights and statutory rights of the Corporation who collected tolls on the sales of livestock.“( McMahon) The Pig Market Dispute went on for some time. Essentially, there could not be two pig markets in Birmingham and sales at this site ceased in the late 1890s.

Fazley street where George sold the pigs which landed him in a spot of trouble is 0.3 miles away from the Bordesley & Allison site from where they were already selling pigs.

From the trial of George Samworth (I), one sentence in particular with the accompanied exchange between Mr Bell, appearing for the Corporation and Mr Brame now takes on new meaning! Let’s look at it again. It reads that “it was a fact that dealers carried on business in the cattle siding, which was an improper place, whilst the Corporation had provided a pig market at an expense of some £34 000.” Mr Brame then asked, “Is this part of the new pig market that the pig dealers themselves have provided?” to which Mr Bell replied, “Oh, no.

Here we have a clear reference to the two pig markets which existed and it seems as if the one which the Corporation provided was in operation by October 1892. George clearly did not see himself confined to either of the two locations to ply his trade.

World-Class Schooling for Young George Samworth

The technical requirement to be a good pig buyer gives us insight into the mental aptitude and alertness of George Samworth (I), grandfather of George and Frank Samworth. It was simply a requirement of the job to be very sharp with uncanny attention to detail! Their dad, George Samworth (II) grew up in this environment.

His dad, George Samworth (I) was a formidable man and a leader in his trade. Reflecting on the incident of the sale of the ten pigs on 27 October 1892 and the leadership he took in the creation of the pig market in Bordesley Street which was completed in the same year, sometime before October, shows clearly him to be an exceptional leader and driven for success which he, no doubt, passed on to his son who worked with him. George Samworth (I) undoubtedly saw in this event, the arrest over selling 10 pigs at the wrong location, his dad’s drive for success. He was willing to trade from a different site than the two recognised sites which existed in Birmingham for pig trading at the time. It gives us a glimpse into the Samworth household and answers the question as to the topics that would have been discussed around the dinner table, especially in the middle 1890s. His son George may have left school at age 11 but what an education he received!


Four things stand out that George Samworth (I) no doubt passed on to his son along with the art of pig buying. These are skill, business acumen, a fierce drive to succeed and leadership! Do I hear the words of David Samworth of People, Quality, Profits?” There is, however, another remarkable observation to be made. George Samworth (II), the son of George Samworth (I), father of the Samworth Brothers did not sit back and enjoy the spoils handed to him by his dad. He took everything his dad taught him and he used these to excel even further when he started his own Pig Buying company in 1896.

This trait would become characteristic of the Samworth Brothers and that of future generations. From the first time I started learning about this family, it is something very peculiar that struck me. The ability that each son had to carve out his own unique success, built upon the success of his dad. As if there is a built-in drive to do better than the previous generation! It is remarkable and something we see right here from the founder of the company himself! His ability to transcend the achievements of his dad.

George Samworth (II) was perfectly prepared for greatness! Both nature and nurture played an indispensable part in preparing the young pig trader to take everything his dad gave him and set future generations of Samworth brothers and children up to create a legend! An utterly unique feature of the story that continues to run through the veins of his children, grandchildren and great-grandchildren is the absolute focus to build upon what has been handed down to them and do better than what previous generations achieved.

From the time of the birth of George Samworth in 1868, he was being prepared for greatness through hard work, dedication, sacrifice and a legendary father who led and taught by example!

(c) Eben van Tonder

* CWT Definition

CWT refers to a centum or cental weight, meaning hundredweight.

A hundredweight (CWT) is a unit of measurement used to define the quantities of certain commodities being bought and sold. It is used in some commodities trading contracts. Pricing by hundredweight also is a standard option for shipping packages that take up less than an entire truckload. Usage of hundredweight more generally has declined in favor of contract specifications in pounds or kilograms.

The value of a hundredweight differs in its American and British usages. In the United States, a hundredweight is a unit of mass equal to 100 pounds. In the United Kingdom, a hundredweight is a unit of mass equal to 112 pounds.” (investopedia)

** Kieron McMahon

I mention Kieron in particular because the information that he unearthed is not readily available. People deem it somehow “less important” when in actual fact, I came to appreciate the fact that such information is of the greatest importance. The entire sage of the “Pig Market Dispute” in Birmingham is relegated to dark, obscure archives and inscriptions on cornerstones scattered around the city and if someone does not take the time and make the effort to dig these stories up, they will be lost to us forever.

In my research on bacon and meat curing, I deal with this all the time. I want to state it clearly: there is no information available about the pig buyers association in Birmingham, about the Pig Market Dispute or the location of the pig trading site from any of the major English newspapers of the time that I have access to or any of the usual repositories of archive information I regularly consult. I have spent today going through countless old, out of print English journals related to agriculture, trade and industry, many of them from Birmingham and could find no reference to George Samworth, pig buyers or anything that could fill out the information required to change George Samworth into a flesh and blood person. At least, nothing remotely comparable to what Kieron unearthed! His site was relegated to pages 5 or 6 in one of my google searches.

Pubs and pork buying is not something that will be top of the list of school-leavers career choices these days. What we must appreciate is that these were the cutting edge technologies of the time and as far as pubs are concerned, key centres for the exchange of information. Was Lloyd of London, the start of the worldwide insurance industry not formed in just such a pub or coffee shop in London?! Meat curing and preservation was exactly the “global warming” issue of the 1800s. There was a real possibility that the world would run out of food. It was not possible for countries like England to have achieved the enormous advances in feeding their population nutritious food if men like George Samworth and others did not achieve the small victories they did. Nor would that have gone far if there were no reading rooms and pubs around where information could be disseminated and shared. It is the exact premise of my work at the Earthworm Express where I seek to tell small stories of enormous importance to understand our world. In my book on the history of meat curing, Bacon & the Art of Living, I devoted a chapter to celebrating the pub culture of the British and after what I’ve seen from Kieron and his team, I will be doing a major review of not just this chapter but I now want to weave it more deliberately into my entire work!

Today we have other challenges, but one thing I know for certain is that it will likewise take young dynamic visionaries who are able to exploit the latest technology and innovation who will save our planet from catastrophe. Men like George Samworth and the thousands of others I feature in my blog.

We live in a universe where we are in an endless quest for partnerships. In life, business – on every level. Molecules want to connect. That is what they are there for! All of life wants relationships to create and be more effective. Life affirms relationships! The British pubs, coffee shops and reading rooms was the catalyst where these relationships were formed. Like water to chemical reactions, they were the ether that drove these processes of the past! These thoughts elevate the work of Kiron to another universe!

I, therefore, want to give kudos to Kieron McMahon. He is not some pub-mad nutcase who simply write a blog about what he is passionate about – he is a key historian who, against the tide of academia, is able to pick up on what is really important and write about it. Kieron is absolutely spot on in his focus on pubs! Without people like him, these stories will be lost forever and I salute him for this! In years to come people will understand it, value it and talk about it. Why? Because he took the time to research it and to write his work down!

Further Reading

The Irish Pig Buyers seems to have been a breed of people in their own class. Why Ireland excelled in Pig Buyers is something for further investigation. Here is a delightful article from the Limerick Leader, 26 April 1986, entitled, Rise and Fall of Parish Pig Buyers.


Beaver, P. & Lawrence, A.. 2005. A Taste of Tradition. Tudor Rose.

Birmingham Daily Post, 3 December 1892.

Díosbóireachtaí Párlaiminte: Tuairisc Oifigiúil, Volume 78 By Ireland. Oireachtas. Dáil – Ireland

Falconer, J. 1916. The Irish Law Times and Solicitors’ Journal, Volume 50

Guiry, R.. 2016. Pigtown, A History of Limerick’s bacon Industry. Limerick City and County Council

Harris, J.. 1885. Harris on the Pig. Breeding, Rearing, Management and Improvement, Orange Judd Company, New York.


McMahon, Kieron. Midlands Pubs

www.myheritage.com – George Samworth Senior

www.myheritage.com – George Samworth Junior


1. “George Samworth was born in Birmingham in 1868, the eldest of a family of thirteen children. At the age of eleven, he left school and, after trying a number of jobs in agriculture, found employment with a consortium of Birmingham pig dealers. They were engaged in buying pigs from farmers in the surrounding countryside and re-selling them, still alive to pork butchers’ shops in the Birmingham area. His working week amounted to some 65 hours and his starting wage about ten shillings (50p) a week. George did well in his and gained a thorough knowledge in the trade of pig dealing.” (Beaver & Lawrence, 2005)

“Beaver and Lawrence do an excellent job of describing the life of the young George in such brilliant terms that I will do it a disservice to not quote them verbatim. They write, “For an intelligent young man, entry into the pig dealing trade was easy: no special premises or equipment were required and, as all business was done on a ready cash basis, very little capital was involved. On buying expeditions, he travelled in the guard’s van with this bicycle and on arrival at his destination area, cycled from farm to farm examining, bargaining for and buying pigs from individual farmers. these were sold to local pork butchers in the Birmingham area, of which there were then over 100 trading in the city alone.” (Beaver & Lawrence, 2005)

He had two sons, George and Frank and four daughters, Evelyn, Mable, Doris and Hilda. George Senior started his own firm in 1896 and his two sons, Geoge and Frank both joined his firm, Frank doing so at age 14. Four years before he started his own firm, in 1892, an article appeared about a pig dealer from New Canal Street, Birmingham, who was summoned for selling ten pigs at the cattle siding of the London and North-Western Railway in Fazeley Street in violation of the markets clauses of the Consolidations Act.

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Part 6: More Health Benefits of Nitrite

By Eben van Tonder
4 September 2022

Part 6 in our series, The Truth About Meat Curing: What the popular media do NOT want you to know!


The importance of nitrite in our diet can hardly be overstated. These dietary sources include cured meats even though it is by no means the largest source. The challenge is to understand the factors which prevent cured meats from being seen as a superfood and address these. The presence of nitrites does not seem to be one of these!

In Part 5. Nitrite – the Misunderstood Compound we looked at the protective effects of dietary Nitrate/Nitrite on lifestyle-related diseases mainly from the work of Kobayashi (2015). We also looked at work done which shows the adverse effect of the lack of nitrites on the body. Here I list more health benefits, this time mainly from the work of Rassaf (2014).


By way of overview, let’s briefly list again the sources of nitrite for the human body.

– Three Sources of Nitrite

1. NO -> produced endogenously from L-arginine by NO-synthases (NOSs)

In the body, nitric oxide (NO) is oxidised to nitrite. (Rassaf, 2014)

NO rapidly reacts with oxyhaemoglobin to form methemoglobin and nitrate. (Rassaf, 2014)

On the other hand, several pathways exist in the body that provides the reduction of nitrite to NO, with haemoglobin, myoglobin, neuroglobin, cytoglobin, xanthine oxidoreductase, eNOS and mitochondrial enzymes being involved (for reviews see: van Faassen et al2009; Lundberg et al., 2009). The extent of contribution of the different pathways depends on the tissue, the pH, oxygen tension and redox status (Feelisch et al., 2008).

2. Nitrite reduced from nitrate

Sources for nitric oxide (NO) formation in mammals. NO is formed by the endothelial NOS (eNOS) using L-arginine as a substrate in an oxygen-dependent manner. Dietary nitrate is reduced to nitrite via commensal bacteria in the oral cavity. Nitrite can be reduced to NO in eNOS independently via deoxygenated myoglobin (Mb), haemoglobin (Hb), neuroglobin (Ng), xynthin oxidoreductase, protons, aldehyde oxidase and enzymes of the respiratory chain to bioactive NO. (figure and description by Rassaf, 2014)

3. Dietary sources

Cured meat, baked goods, beets, corn, spinach etc. are major sources of nitrite. (Rassaf, 2014)

Reference list below for nitrite dietary contributions.

Sindelar (2012), as quoted by (Kobayashi, 2015)
Hord (2009) as quoted by (Kobayashi, 2015)

Benefits of Nitrate

As I said, I now list more health benefits of nitrite.

In Part 5. Nitrite – the Misunderstood Compound from the work of Rassaf (2014)

-> Contribute to protection against UV-induced cell damage.

The presence of nitrite, but not nitrate, reduced the extent of apoptosis, or the death of cells which occurs as a normal and controlled part of an organism’s growth or development, in cultured endothelial cells during UVA-irradiation in a concentration-dependent manner by inhibiting lipid peroxidation. (Rassaf, 2014) Endothelial cells form the inner lining of a blood vessel and provide an anticoagulant barrier between the vessel wall and blood.

The protective effect described above was abolished by simultaneous administration of a NO scavenger (Suschek et al., 2003) suggesting that nitrite-derived NO may contribute to protection against UV-induced cell damage (Suschek et al., 2006). (Rassaf, 2014)

-> Protection of gastric mucosa from hazardous stress.

We look at this when we considered the work of Kobayashi (2015) but due to the importance, I mention the point again. Nitrite, generated from nitrate by oral bacteria ‘the so called enterosalivary cycle’, and then converted to NO (Benjamin et al., 1994; Lundberg et al., 1994200920062008; Kapil et al., 2010a) in the stomach was also suggested to play an important role in the protection of gastric mucosa from hazardous stress (Miyoshi et al., 2003). (Rassaf, 2014)

-> Cardiovascular Benefits

Since the rate of NO generation from nitrite depends on the reduction in oxygen and pH, nitrite could be reduced to NO in ischaemic tissue or tissue lacking oxygen and exert protective effects (for review, see van Faassen et al., 2009). Nitrite-mediated protection was independent of endothelial nitric oxide synthase (Webb et al., 2004; Duranski et al., 2005).

-> The Brain

Depending on the timing of application nitrite might not only reduce irreversible brain injury following ischaemia/reperfusion but also vasospasm following cerebral haemorrhage. (Rassaf, 2014) Ischaemia/ reperfusion refers to the paradoxical exacerbation of cellular dysfunction and death, following restoration of blood flow to previously ischaemic tissues which refers to the demand of tissue for energy, for example from oxygen, and this demand is not matched by supply moslty due to to a lack of blood flow.

-> Protection of the Liver

Nitrite exerted profound dose-dependent protective effects on cellular necrosis which refers to the loss of cell membrane integrity as a result of exposure to a noxious stimulus and apoptosis which refers to a form of programmed cell death that occurs in multicellular organisms. Nitrite has a highly significant protective effect observed at near-physiological nitrite concentrations. (Rassaf, 2014)

-> Protection of the Lungs

In a mouse model of pulmonary arterial hypertension, inhaled nebulized nitrite has been demonstrated to be a potent pulmonary vasodilator that can effectively prevent or reverse pulmonary arterial hypertension. (Rassaf, 2014)

-> Protection of the kidneys

In rats subjected to 60 min of bilateral renal ischaemia and 6 h of reperfusion sodium nitrite administered topically 1 min before reperfusion significantly attenuated renal dysfunction and injury. (Rassaf, 2014)

Renal ischemia associated with renal artery stenosis (RAS) which is the narrowing of one or more arteries that carry blood to your kidneys is the most frequent condition occurring with renin-dependent hypertension. Renovascular hypertension (RVH) results from occlusion (the blockage or closing of a blood vessel or hollow organ) of blood flow to either kidney, which stimulates renin release. Increased renin leads to a series of actions that rapidly leads to increased systemic blood pressure or hypertension or abnormally high blood pressure. (Rassaf, 2014)

Similarly, in mice subjected to bilateral renal ischaemia for 30 min and 24 h reperfusion, renal dysfunction, damage and inflammation were increased; these effects were all reduced following nitrite treatment 1 min prior to reperfusion. (Rassaf, 2014)

-> Crush syndrome and shock

Limb muscle compression and subsequent reperfusion are the causative factors in developing a crush syndrome. In rats subjected to bilateral hind limb compression for 5 h followed by reperfusion for 0 to 6 h, nitrite administration reduced the extent of rhabdomyolysis markers such as potassium, lactate dehydrogenase and creatine phosphokinase. Nitrite treatment also reduced the inflammatory activities in muscle and lung tissues, finally resulting in a dose-dependent improvement of survival rate. (Rassaf, 2014)

Similarly, in a mouse shock model induced by a lethal tumour necrosis factor challenge, nitrite treatment significantly attenuated hypothermia, mitochondrial damage, oxidative stress and dysfunction, tissue infarction and mortality. (Rassaf, 2014)

Nitrite could also provide protection against toxicity induced by Gram-negative lipopolysaccharide. (Rassaf, 2014)


Rassaf (2014) concluded that “taken together, the nitrate-nitrite-NO pathway appears to play a crucial role in protecting the heart, vessel, brain, kidney and lung against ischaemia/reperfusion injury. Nitrite treatment may be advantageous in well-known NO deficient states such as, for example, hyperlipidaemia. Timing and dose of nitrite application as well as the potential to convert nitrite to NO in the tissue are important to obtain a reduction in injury.

That nitrite is not a compound to be avoided at all costs is clear. It is essential to our health and dealing with the stress and strain of living life and mediating the effects of the many injuries we incur. The mass hysteria against the use of nitrites in cured meat is unfounded. The discussion about adapting our formulations to include the latest science related to diet and nutrition needs to take place as it is true for every food group in existence but lumping the meat industry into the same group as producers of cigarettes, for example, is unjustified and dangerous. A far more balanced and responsible discussion is called for and I hope that this series contributes to the discussion.

The full list of contributions to this series is available at The Truth About Meat Curing: What the popular media do NOT want you to know!


Hord, N.G.; Tang, Y.; Bryan, N.S. Food sources of nitrates and nitrites: The physiologic context for potential health benefits. Am. J. Clin. Nutr. 2009, 90, 1–10.

Kobayashi, J. (2015) NO-Rich Diet for Lifestyle-Related Diseases, Article in Nutrients, June 2015, DOI: 10.3390/nu7064911

Rassaf T, Ferdinandy P, Schulz R. Nitrite in organ protection. Br J Pharmacol. 2014 Jan;171(1):1-11. doi: 10.1111/bph.12291. PMID: 23826831; PMCID: PMC3874691.

Part 5. Nitrite – the Misunderstood Compound

by Eben van Tonder
1 September 2022

Part 5 in our series, The Truth About Meat Curing: What the popular media do NOT want you to know!


The accusation is widespread in the media, sensation-seeking documentaries and celebrity chefs alike that nitrite, derived from ammonia, nitrate (Salpeter) or added in the form of sodium nitrite in meat curing is tantamount to poisoning consumers and inviting cancer into your lives. I am a meat curing professional. My interest in the truth about nitrites is in the first place to be certain that I am not engaged in an action where harmful products are produced. To state this slightly differently, what steps can I take to ensure the safest possible product is made available?

The issue of nitrites is complex and to develop even a rudimentary understanding of all the issues requires that we work through a lot of technical information. Despite this, the basic evaluation is simple and well within the grasp of the general public. Here I desire to share with you what I discovered about this remarkable compound!

It is part of a short series I’ve put together on the matter entitled, The Truth About Meat Curing: What the popular media do NOT want you to know! After preliminary discussions, we now place the spotlight squarely on nitrite. We discover that instead of poison, even though this is true in large dosages and under certain conditions, it is a vitally important compound for the normal functioning of our bodies. That the sources are mostly from vegetables and not cured meat, and that any possible harmful effect is removed through the simultaneous consumption of vitamins A, C, E, etc.

What I discovered is that an entirely different (and positive) world exists related to nitrites generally and dietary nitrites in particular. The evidence is clear, overwhelming and available to anybody with an honest interest in the matter that nitrites are beneficial to human health and essential for the optimal functioning of our bodies. We will discover that there is a seemingly unresolved issue in that while nitrites, in balanced concentrations, have overwhelmingly beneficial results in the human body (may I even call it essential?!), there is seemingly contradictory information which shows that nitrites are involved, under certain conditions in the generation of N-Nitrosamines which can be cancer-causing. Parallel to this is the indication of many studies that there seems to be a relationship between the consumption of cured meats and cancer and even though the exact reason has not been elucidated, it begs the question as to possible reasons for this. How do we deal with this seemingly contradictory information, that n-nitrosamines which are the obvious culprit for any possible link between cured meat and cancer on the one hand come from nitrites and on the other hand, nitrites play an vital part in our general health and the resolution of many common diseases and ailments? Can it be that nitrosamines are not the culprit of what seems to be a link between cancer and cured meat? Can it be that lifestyle or general nutritional habits alter the nature of an important chemical in our bodies from beneficial to harmful and if this is the case, what are those factors? Is it fair to label bacon as possibly cancer-causing? When it comes to the full array of reactive nitrogen species of which nitrite is a part, is it possible to have the one without the other, especially in light of the fact that the curing molecule is nitric oxide, also one of the reactive nitrogen species? Is the statement that curing was done with no nitrite even a sensical one in light of the oxidation of nitric oxide to nitrite and nitrite to nitrate in the curing environment? It begs the question if no nitrite curing which has been the goal of meat scientists for so many years even valid question to ask or is this something that will sell products without any real benefit to the consumer as far as the removal of the real risk of n-nitrosamine formation. This is an extremely timely question as we stand at the dawn of a time when no-nitrite curing will become a reality across the world. The emphasis is about to squarely shift to nitric oxide and in light of this future trend we have to ask, can nitric oxide contribute to nitrosamine formation as is the case with nitrites which would mean that removing nitrites from the curing system has no real benefit as far as nitrosamine formation is concerned.

We have to continue the questioning. If ingesting dietary nitrite has overwhelmingly positive effects on human physiology, should nitrite curing not rather be encouraged and embraced and should ham and bacon not be seen as a superfood instead of something to be avoided? I ask another question which is the focus of my own work and that of a small band of like-minded food professionals and scientists – how do we turn ham, bacon and the cured meats we love into superfoods in such a decisive manner that there can be no argument from any quarter about this status!? These are all valid questions and despite the mammoth task ahead, I will do my best to interact with all these questions in this document. Where I fail, please point it out to me so that I can improve on the document and evolve in my thinking, but please, do it from a position of constructive interaction and partnering with me in seeking the truth!

I will try and deal as honestly as a layman can with these complex questions, believing that I have a sacred responsibility to the consumer to do exactly this and if the evidence points away from what I would like it to say, that I should have the integrity follow the lead of the evidence. My ultimate goal is therefore the TRUTH and not to generate “likes” on social media posts. Anybody with a meaningful contribution or who wants to correct me on any point can contact me at ebenvt@gmail.com or WhatsApp me at +27 71 545 3029.

History of Nitric Oxide and the Close Link between Nitrate, Nitrite and Nitric Oxide.

Nitric oxide (NO) was discovered in 1772. Nitroglycerine (NG), a vasodilator acting via NO production, was synthesized in 1847. The effect of nitroglycerine was studied on healthy volunteers by Constantin Hering in 1849 and it was proven to cause headaches. Later in 1878, nitroglycerine was used by William Murrell for the first time to treat angina. Towards the end of the 19th century, nitroglycerine was established as a remedy for relief of anginal pain.” (Ghasemi, 2011) Angina is a type of chest pain caused by reduced blood flow to the heart. In 1916, Mitchell et al. suggested that body tissues can also produce nitrate and Richard Bodo in 1928 showed a dose-dependent increase of coronary flow in response to sodium nitrite administration. In the 1970s, it was shown that nitrite-containing compounds stimulate guanylate cyclase,” which is an enzyme that converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) and pyrophosphate. An increase of cyclic guanosine monophosphate (cGMP), also caused by the intake of nitrite containing compounds cause vascular relaxation and it is presumed that cGMP activation may occur via the formation of NO. (Ghasemi, 2011)

In 1980, Furchgott and Zawadzki showed that endothelial cells are required for acetylcholine-induced relaxation of the vascular bed which refers to the vascular system or a part thereof, through the endothelium-derived relaxing factor. Even though they could not initially pinpoint what caused the relaxation of the endothelium, scientists knew that such a relaxing factor existed and the race was on to identify it. The endothelium is the thin membrane that lines the inside of the heart and blood vessels. The breakthrough came in 1987 when it was shown that endothelium-derived relaxing factor and NO are the same or almost the same thing. Nitric oxide was the agent responsible for relaxing the endothelium. (Ghasemi, 2011)

In 1992, NO was proclaimed as the molecule of the year and in 1999, Furchgott, Ignarro, and Murad were awarded the Nobel Prize in Physiology or Medicine for studies in the NO field. Due to the proven roles played by NO physiologically and pathologically, research on NO was increased rapidly and at the end of the 20th century, the rate of NO publications was approximately 6,000 papers per year, with currently more than 100,000 references invoking NO listed in PubMed.” (Ghasemi, 2011)

In our earlier discussion of nitric oxide as the curing molecule in bacon, we referred to S. J. Haldane who was the first person to demonstrate that the addition of nitrite to haemoglobin (blood protein) produces a nitric oxide (NO)-heme bond, called iron-nitrosyl-hemoglobin (HbFeIINO). He showed that nitrite is further reduced to nitric oxide (NO) in the presence of muscle myoglobin (muscle protein key in supplying oxygen to the muscle) and forms iron-nitrosyl-myoglobin. It is nitrosylated myoglobin that gives cured meat, including bacon and hot dogs, their distinctive red colour and protects the meat from oxidation and spoiling. Discovering that Nitric Oxide (NO) is a key molecule in human physiology should not have been a surprise to meat scientists. There was, an understanding in meat science since the time of Haldane that the nitrate-nitrite-NO pathway was the curing reactions in meat from saltpetre to nitric oxide. It was later decided to use nitrite directly for reasons elucidated in a previous part of this series, Part 2: The Curing Molecule

When we say that the reduction of nitrite to nitric oxide occurs chemically, we refer to the non-enzymatic reduction of nitrite to nitric oxide. Ghasemi (211) gives us the technical details of this. “NO was found to be synthesized from L-arginine by the enzymes known as NO synthase (NOS) (EC in two separate mono-oxygenation steps; first, L-arginine is converted to N-hydroxyarginine in a reaction requiring one O2 and one NADPH and the presence of tetrahydrobiopterin (BH4) and in the second step, by oxidation of N-hydroxyarginine citrulline and NO are formed. At least three NOS enzyme isoforms including neuronal, inducible, and endothelial (eNOS) have been identified and encoded by different genes.”

This non-enzymatic production of Nitric Oxide was suggested in 1997 by Ghafourifar and Richter. They postulated the “existence of mitochondrial NOS and in 1994, Lundberg and colleagues and Benjamin and colleagues demonstrated NOS-independent NO formation. Non-enzymatic NO production by one-electron reduction of nitrite, a blood and tissue NO reservoir, seems to be found everywhere and greatly accelerated under hypoxic conditions or conditions of low oxygen levels in your body tissues. This finding changes the general belief that nitrate and nitrite are waste products of NO.” (Ghasemi, 2011)

I want to refer as an important sidenote at this point to the work of Vanek (2022) which we will look at in much greater detail in a following discussion since they beautifully elucidates the reason for the importance of Nitric Oxide and how it binds to the meat protein we rely on in meat curing, forming the reddish/ pinkish colour of cured meat and giving muscles its characteristic red colour. The important point is that just as nitric oxide is produced through enzymes and non-enzymatic ways to react with myoglobin, in the same way and hugely important to meat curing is that myoglobin has also been shown to have enzymatic functions and is responsible for the decomposition of bioactive nitric oxide to nitrate. The importance of this point can hardly be over-stated! If we are able to convert L-arginine into Nitric Oxide in other ways besides indigenously through NO synthase (the enzymes responsible for oxidising nitrogen in L-Arginine to nitric oxide), and so cure meat, and should we find that this can be done through bacteria, then we still do not strictly speaking have meat curing with no nitrite present as the nitrate will be converted through bacteria in the meat to nitrite and albeit this being present at very low dosages, there will still be nitrite in the meat that we cured.

Allow me to state it again. If we are able to access L-arginine either through bacteria or enzymes directly (as we do in salt-only-long-term-cured-hams) and as a result of this do not start our curing process with nitrite (as is the case with long-term salt-only cured hams) and we are able to claim that we cure meat with no nitrite salts as we are indeed able to do at the present time, then we can not say that we eliminated nitrite from meat curing because there is the likelihood that some of the NO will be converted to nitrate which will be reduced to nitrite again and we are back at the beginning of the quest for nitrite-free curing. Stated a different way, it would seem that curing without nitrite is not possible. This is the heart of the conundrum of people propagating that meat has been cured with no nitrites in that we are dealing with REACTIVE nitrogen species and where you find the one, you are likely to find the others. Our nitrogen species of interest, when we refer to “we will find the one where we find the others” are nitrate, nitrite and nitric oxide, but as we will see further on, these are by no means the only nitrogen species we will encounter in the human muscle and in meat curing alike.

The extent to which what I suggest above is true, we will have to verify through experimentation. The rest of this document is dedicated to answering the following question: why would we want to eliminate a physiologically important species of nitrogen from our diet in any event!? So, on the one hand, is nitrite free curing a realistic goal and secondly, why would we want to do it? Are there other ways to overcome the health concerns associated with cured meats?

Effects of Nitrite in Human physiology.

– Sources of nitrogen for Human Physiology and the Value of Nitrite

The great discovery of the past few decades is that nitrate and nitrite have a fundamentally important role in our physiology and nitrite in particular, namely to act as a reservoir for nitric oxide (NO) which is a physiologically important molecule. Apart from nitric oxide being generated from the amino acid, L-Arginine, nitric oxide is generated through what is referred to as the nitrate-nitrite-Nitric Oxide pathway which is, as we have said before, exactly the same pathway of bacon curing. So, in order for this mechanism to work, we need a direct source of nitrates or nitrites and nature provided this for us in what we eat. The biggest source is vegetables which account for 60%–80% of the daily nitrate intake in a Western diet. As you will see from the table below, they not only supply us with nitrates but with nitrites directly as well. It has been shown that elevations in the blood plasma nitrite levels can occur by increasing the dietary nitrate intake. (Kobayashi, 2015)

Nitrate, nitrite and nitric oxide are closely linked as the difference between them is one oxygen atom. NO3 (nitrate), NO2 (nitrite) and NO (nitric oxide). Nitrate is reduced to nitrite through bacteria and nitrite to nitric oxide through chemical means (enzyme and non-enzyme driven). NO can be oxidized back to nitrite again and nitrite to nitric oxide. Nitric oxide, in the presence of myoglobin, can be converted directly back to nitrate. As a result of this, where one finds nitrate and bacteria such as in the mouth or digestive tract, you will always find nitrite and nitric oxide and where you have nitric oxide, one can find nitrite and nitrate. This is true in meat curing and true in the human body. “In humans and other mammals, about one-quarter of all circulating inorganic nitrate (NO3), derived from diet or oxidation of endogenous (within the body) nitric oxide (NO), is actively taken up by the salivary glands and excreted in saliva. As a result, salivary nitrate levels are 10–20 times higher than those levels found in our blood. The mechanism behind this massive nitrate accumulation in saliva has remained elusive. The work by Qin et al. reports that the protein sialin can function as an effective nitrate transporter.” (Lundberg, 2012)

With these brief remarks, we are then thrust into the domain of the nitrate-nitrite-NO cycle in the human body. Nitrite is no longer viewed as something to be avoided at all cost, but as a chemical essential for human life and cured meat becomes by far, not the biggest contributor of nitrate and nitrite to our system, but the possibility exists for it to become an important one as we can use the same basic principles that gave us cured meat, reduce the fat and salt and find ways to introduce essential goodness of plant matter and we are confronted with the amazing opportunity to change processed food into a superfood! In this one statement, I seek to address the unfounded negative perception of nitrite, give a clue as to the possible real reason behind the health concerns related to processed meat (fat, salt, phosphates, etc) and give a roadmap for future work by imaginative food scientists in the incorporation of healthy plant matter into the sought after food group, allowing for all the conveniences that make processed-meats a well-loved and very convenient food for our era!

Have a look at the table below which gives the main dietary sources for nitrate and nitrites. Pay close attention to where hot dogs and bacon feature on the list!

Sindelar (2012), as quoted by (Kobayashi, 2015)

Hord (2009) as quoted by (Kobayashi, 2015)

When we ingest nitrates from leafy green vegetables or cured meat, it is absorbed in the upper gastrointestinal tract which comprises the mouth, salivary glands, oesophagus, stomach, and small intestine. The levels in the blood reach the highest level around 30–60 min after the nitrates have been swallowed. Approximately 25% of nitrate absorbed by the body reappears in our mouth through our salivary glands which pump it back into our mouths. Here it is reduced by the bacteria on our tongue from nitrate to nitrite. As it reaches our stomach, a part of the nitrites which we swallow is what we call protonated (adding hydrogen to the nitrite) and nitrous acid is formed which is the form that nitrite takes on when diluted into water (NO2− + H+ → HNO2). This reaction is similar to what happens to nitrite when we dilute it into the curing brine and inject it into meat which is also a more acidic environment like the stomach. Similar to meat curing, the nitrite we ingested now decomposes to form a variety of nitrogen oxides such as Nitric Oxide, the curing molecule, nitrogen dioxides (NO2), and dinitrogen trioxide (N2O3) (2 HNO2 → N2O3 + H2O, N2O3 → NO + NO2). These nitrogen oxides form additional bioactive adducts, such as S-nitrosothiols and N-nitrosamines. S-nitrosothiols sound very intimidating but are not. They are proteins discovered in the 90s and have since been shown to be key in many biochemical processes in our body. Specifically, S-nitrosothiols play a key role in the total system encompassing our heart and blood vessels, for example, the widening of blood vessels as a result of the relaxation of the blood vessel’s muscular walls and preventing thrombosis. N-nitrosamines are known to us by now as formed by the reaction of nitrite with secondary amines which can be cancer-causing.” (Kobayashi, 2015)

The next point requires us to know what gastric mucosa refers to. It is the mucous membrane layer of the stomach, which contains the glands and the gastric pits. Blood flow plays an important role in the protection of normal gastric mucosa and in the protection and healing of damaged mucosa. “Nitric Oxide production in the stomach is greatly enhanced in the presence of micronutrients that naturally occur in plants called dietary polyphenols and vitamin C or ascorbic acid, whereas because of its lower stability and shorter half-life relative to S-nitrosothiols, the released Nitric Oxide in the stomach is thought to locally contribute to increasing the gastric mucosal blood flow and mucous thickness to ensure the normal gastric physiology, and serves as the first-line host defence against harmful bacteria which we swallowed with our food. However, not all the nitrite reacts with H+(escapes the protonation) in the acidic milieu of the stomach and enters the systemic circulation, and then reaches the peripheral organs, including skeletal muscles, where it acts in an endocrine manner (like hormones) to exert NO-like activity. An interesting side note is that because the levels of nitrite in the blood are depends to a large degree on the amount of nitrate in the saliva and its reduction to nitrite, the use of antibacterial mouthwash and frequent spitting of saliva consequently decrease the plasma levels of nitrite.” (Kobayashi, 2015) We just said that Nitric Oxide production in the stomach is greatly enhanced in the presence of micronutrients that naturally occur in plants called dietary polyphenols and vitamin C or ascorbic acid. As we will see later, these substances and in particular vitamin A, C and E plays an important role as “blocking” agents by reacting with the partially digested amino acids called amines, and with secondary amines in particular called N-Nitrosamones denoting a reaction between the amine and nitroso component in nitrite, binding nitrogen and nitrogen (therefore the name, N-Nosotros-amines), blocking the formation of n-nitrosamines. Let me state it again. If we ingest nitrite with vitamins a, c, e, etc., these vitamins react with the secondary amines before nitrite can react with it, therefore blocking nitrosamine formation. This is something to look at on its own and we will not spend much more time on this important point. Here, my goal is to show that nitrite is NOT the harmful cancer-causing entity we believed it was, but turns out to be indispensable for healthy living! We can, therefore, for the moment, suspend the concerns about N-nitrosamine formation but rest assured that we will return to this in great detail! For now, let us continue with our focus on nitrites and the diagram below shows the main way we get nitrates and nitrites into our body.

(Kobayashi, 2015)

“The plasma nitrite which reaches peripheral tissues is stored in various organs. Although there have been few reports dealing with the tissue levels of nitrate/nitrite following dietary nitrate supplementation in humans, animal studies show that dietary nitrate certainly increases the tissue levels of nitrate/nitrite following an increase in the plasma levels of nitrate/nitrite, which accordingly exerts therapeutic efficacy for animal models of various disease conditions. Interestingly, while acute dietary nitrate intake increases the plasma levels of nitrite in rodents and humans, chronic dietary nitrate intake does not always increase the plasma and tissue levels of nitrite but increases the tissue levels of nitrate and S-nitrosylated products. Although the mechanism underlying this finding is yet to be clarified, there might be some redox equilibrium of nitrate-nitrite-NO after chronic dietary nitrate intake, resulting in oxidation or reduction of the tissue nitrite to form nitrate or S-nitrosylated species, respectively. On the other hand, animal models chronically fed a diet deficient in nitrate/nitrite exhibit significantly diminished plasma and tissue levels of nitrate/nitrite, resulting in increased ischemia-reperfusion injuries in the heart and liver compared with the animal models fed a normal diet. Ischaemia-Reperfusion injury (IRI) is defined as the paradoxical exacerbation of cellular dysfunction and death, following the restoration of blood flow to previously ischaemic tissues. Ischemia or ischaemia is a restriction in blood supply to any tissues, muscle group, or organ of the body, causing a shortage of oxygen. These results suggest that dietary nitrate intake is important in the maintenance of steady-state tissue levels of nitrate/nitrite for NO-mediated cytoprotection. Cytoprotection is a process by which chemical compounds provide protection to cells against harmful agents. (Kobayashi, 2015) The key point is the importance of nitrate and nitrate in our diets and the possible harmful effect of nutrition deficiency in these compounds.

“Historically, the fact that nitrate and nitrite are present in human saliva has received little attention, because no one could attribute any kind of function to these anions. However, this lack of interest ceased in the 1970s, when researchers formulated a pathophysiological model for gastric cancer based on the accumulation of nitrate in saliva. Commensal bacteria in the mouth reduce parts of the salivary-derived nitrate to nitrite (NO2), and when swallowed into the acidic stomach, this nitrite yields reactive intermediates that can react with dietary compounds to promote the formation of N-nitrosamines (a versatile class of carcinogens in rodents). With the emergence of this theory, nitrate immediately fell into deep disgrace, and ever since that time, authorities worldwide have put strict regulations on allowable levels of nitrate in our food and drinking water.” (Lundberg, 2012)

In the 1990s, research on nitrate took an unexpected turn when two research groups independently showed that salivary nitrate was a substrate for the formation of NO, and we looked at the development of our understanding of the importance of this molecule in our lives earlier on. It was revealed that NO plays “a key role in virtually every aspect of human physiology, including regulation of cardiovascular function, cellular energetics, immune function, neurotransmission, and more. The newly described alternative means of NO generation from nitrate was fundamentally different from the NO synthase pathway; it did not use arginine as a substrate, and it was independent of NO synthases. After the discovery that nitrate could be a substrate for the formation of a potentially beneficial biological messenger, the interest in nitrate shifted away from only being focused on carcinogenesis, and instead, researchers started to study potential NO-like physiological effects of this anion. From intense research performed during the past 15 y, it is now clear that administration nitrate or nitrite has robust NO-like effects in humans and other mammals. These effects include vasodilation, reduction in blood pressure, protection against experimental ischemia-reperfusion injury, reduction in cellular oxygen consumption, reversal of metabolic syndrome, reduction in oxidative stress, stimulation of mucosal blood flow and mucus formation in the gastrointestinal tract, and more.” We will spend time further on many of these in particular looking at lifestyle diseases.

“Intriguingly, most of these nitrate effects occur at dietary doses easily achievable through a normal diet rich in vegetables. Bioactivation of nitrate requires initial reduction to the more reactive nitrite anion, and this reaction is mainly carried out by commensal bacteria in the oral cavity and to a lesser degree, the tissues by mammalian enzymes. Salivary-derived nitrite is partly reduced to NO in the acidic stomach as described above, but much nitrite also survives gastric passage and enters the systemic circulation, which is evident from the marked nitrite increase in plasma seen after ingestion of nitrate. In blood and tissues, nitrite can undergo additional metabolism to form NO and other bioactive nitrogen oxides, including S-nitrosothiols. A number of enzymes and proteins have been shown to act as nitrite reductases, including deoxygenated haemoglobin, myoglobin, xanthine oxidase, mitochondrial respiratory chain enzymes, and more.” (Lundberg, 2012)

This matter of nitrate-nitrite-Nitric Oxide as the reaction sequence from nitrate in saliva becomes very interesting to us in the meat curing industry for one specific reason. When we surveyed the approach taken by the industry and the US government in particular, we noted in Part 3: Steps to secure the safety of cured meat, of our series that the direct application of nitrite was seen as a way to bypass the first bacteria mediated reduction step of nitrate to nitrite. The reasons given by industry and scientists alike was that it would yield better control in the curing process amongst others, as it relates to the lowest possible dosage of nitrite to effect curing since the dose dependency of the toxicity of nitrites was recognised from very early.

Lundberg (2012) surveyed the work of Qin in identifying sialin as the nitrate transporter to the saliva. This is relevant to curing. Lundberg describes a disorder which leads to ineffective transport of nitrate as follows, “Mutations in the sialin gene cause Salla disease and infantile sialic acid storage disorder, which are serious autosomal recessive lysosomal storage disorders characterized by early physical impairment and mental impairment.”

A fibroblast is a type of cell that contributes to the formation of connective tissue. It secretes collagen proteins that help maintain the structural framework of tissues. “Fibroblasts from patients with infantile sialic acid storage disorder show a lower nitrate transport activity compared with healthy controls. The work by Qin et al. also tested the importance of sialin for nitrate transport in the pig in vivo. Interestingly, adenovirus-dependent expression of a sialin mutant vector (sialinH183R) in the salivary gland decreases NO3 secretion in saliva after ingestion of a nitrate-rich diet compared with control animals.” (Lundberg, 2012)

“Sialin is expressed not only in the salivary glands but also in the brain, heart, lung, kidney, and liver, although seemingly at lower levels. The functional importance of nitrate transport into cells in these tissues would be of interest to study. In this context, it is interesting to note that nitrate metabolism does, indeed, occur in mammalian cells, although to a much lesser degree than in bacteria. The work by Jansson et al. reported on a functional mammalian nitrate reductase in numerous tissues, including liver, kidney, and intestines. Xanthine oxido reductase was identified as the major mammalian nitrate reductase, but the study indicated the presence of other unidentified nitrate reductases as well.” (Lundberg, 2012) The observation that nitrate metabolism occurs in mammalian cells, although to a much lesser degree than in bacteria should not escape our notice. I discussed the matter with a collaborator on key projects, Richard Bosman and we speculated that the reason for the curing in long-term salt-only-dry-cured hams probably has more to do with the relaxing of the muscles as a result of early cell breakdown and the accompanying invasion of bacteria able to oxidize L-arginine than with the endogenous oxidants in the meat. This fact possibly further points to a symbiotic evolution of humans with oral cavity bacteria positioned to fulfil this vital role of reducing nitrate to the more reactive nitrite.

“The work by Qin et al. proposes that sialin functions as the major NO3 uptake system in salivary gland cells; however, a remaining question is how this nitrate is further transported to saliva through the apical portion of the cells. Sialin seems to be a versatile anion transporter that also mediates H+-dependent transport of NO2, aspartate, and glutamate. Previously, antagonism between nitrate, perchlorate, iodine, and thiocyanate for secretion in human saliva was shown, but in the work by Qin et al., these anions are not studied. It will be of interest to study if sialin also transports these anions. Definitive evidence for a functional role of sialin in nitrate transport and systemic nitrite/NO homeostasis in humans is lacking, but with the identification of this protein as an important nitrate transporter, it now seems possible to study this area. One approach could be to study the nitrate–nitrite–NO pathway in genetically engineered mice or perhaps, patients with Salla disease. Are salivary and plasma levels of nitrate/nitrite different in these patients? Do these animals or the patients exhibit any signs of systemic NO deficiency, including increased blood pressure, altered blood flow responses, different cellular energetics, or others? In the case that NO homeostasis is disturbed in Salla disease, would the patients benefit from substitution with nitrite?” (Lundberg, 2012)

This is the relevant question. Look at the possible suggestions. Is it possible to bypass nitrate and the bacterial reduction to nitrite and instead, would a solution be to administer nitrite directly as happens when we ingest nitrate which is transported to the saliva glands and in the mouth, are converted to nitrite, which, in the mouth and in the reducing environment in the stomach is changed to the physiologically vital nitric oxide? Lundberg (2012) puts his finger on the issue when he asks, “By giving nitrite instead of nitrate, one could bypass the initial nitrate transport step that might be disturbed in these patients, and NO and other bioactive nitrogen oxides would form directly from nitrite in blood and tissues.” He points to the fact that this therapeutic approach “was recently successfully tested in another genetic disorder involving a disturbed NO homeostasis.” Homeostasis refers to a self-regulating process by which biological systems maintain stability while adjusting to changing external conditions. “Another approach could be to study the proposed negative consequences of nitrate transport. If salivary nitrate transport promotes nitrosamine formation, which has been believed for a long time, are nitrosamine levels and occurrence of gastric malignancies lower in subjects lacking the transporter?” (Lundberg, 2012)

Huizing reports by 2021 that “plasma-membrane nitrate transport in salivary gland acinar cells, remains enigmatic.” (Huizing, 2021) Our hiatus into this question has, however, not been without reward.

  • We have seen the widespread distribution of nitrate to physiologically vital sites in the body;
  • We glimpsed at the key role of nitrite in the blood plasma, mainly derived from ingested nitrate and nitrates.
  • We see how other scientists in other fields of study came to the same conclusion as food scientists in the early 1900 namely that a direct application of nitrite, bypassing the time and bacteria dependant reduction step of nitrate has beneficial consequences.

In the discussion about possible negative effects of nitrite, one very important point to remember is that our overall natural design favours an adequate intake of nitrites. This can be seen by its presence in our blood. Here, nitrite is reduced to nitric oxide.

Gladwin (2008) that “recently, multiple physiologic studies have surprisingly revealed that nitrite represents a biologic reservoir of NO that can regulate hypoxic vasodilation, cellular respiration, and signalling.” They summarise that “studies suggest a vital role for deoxyhemoglobin- and deoxymyoglobin-dependent nitrite reduction. Biophysical and chemical analysis of the nitrite-deoxyhemoglobin reaction has revealed unexpected chemistries between nitrite and deoxyhemoglobin that may contribute to and facilitate hypoxic NO generation and signalling. The first is that haemoglobin is an allosterically regulated nitrite reductase, such that oxygen binding increases the rate of nitrite conversion to NO, a process termed R-state catalysis. The second chemical property is oxidative denitrosylation, a process by which the NO formed in the deoxyhemoglobin-nitrite reaction that binds to other deoxyhemes can be released due to heme oxidation, releasing free NO. Third, the reaction undergoes a nitrite reductase/anhydrase redox cycle that catalyzes the anaerobic conversion of 2 molecules of nitrite into dinitrogen trioxide (N2O3), an uncharged molecule that may be exported from the erythrocyte. We will review these reactions in the biologic framework of hypoxic signalling in blood and the heart.”

It is interesting that nitric oxide produced in the endothelium is oxidised to nitrite. In this instance, one could say that it “bypasses” the intestinal section where it could react with amino acids to form n-nitrosamines which some of them can cause cancer. Rassaf (2014) states that Nitric Oxide is produced in the body from the amino-acid L-arginine by the NO-synthases (NOSs). Three different NOSs exist: the endothelial NOS (eNOS, NOS III), the inducible NOS (iNOS, NOS II) and the neuronal NOS (nNOS, NOS I). This may be one way that the body uses to “manage” the possible harmful effects of nitrite but there are others as we have already eluded to and will look at in greater detail further on, namely ways to “block” nitrite through ingested vitamins. Still, there is another important mechanism which we will discuss in the future when we focus on n-nitrosamines and ways to mediate its possible harmful effect. Note that making it mandatory to include vitamin C in cured meats has been a strategy employed by the industry and regulated by governments from very early on. I will say a bit more about this at the end of this article.

Let’s return to the endothelial. The endothelial is the largest organ system in the body. I repeat the definition as I realise that these concepts may be new to many of the readers and repetition aids learning! It refers to a single layer of cells, called endothelial cells which lines the inside of all blood vessels (arteries, veins and capillaries). Inductable NOS is expressed after cell activation only and then produces NO for comparatively long periods of time (hours to days) in response to autoimmune and chronically inflammatory diseases in humans and neurodegenerative diseases and heart infarction, during tumour development, after transplantation, during prostheses failure and myositis. (Kröncke, 1998) Neuronal or nNOS relates to the brain. “Brain nNOS exists in particulate and soluble forms and the differential subcellular localization of nNOS may contribute to its diverse functions and has been implicated in modulating physiological functions such as learning, memory, and neurogenesis, as well as being involved in a number of human diseases.” (Zhou, 2009)

Let’s return to Gladwin (2008) who now describes a fascinating cycle of Nitric Oxide in the blood which relies on its conversion to nitrite. As we have seen above, Nitric Oxide is produced in endothelium and then diffuses to adjacent smooth muscle to activate soluble guanylyl cyclase that produces cGMP, and ultimately produces smooth muscle relaxation. Nitric oxide is subject to rapid inactivation reactions with haemoglobin that greatly limit its lifetime in blood, however recent studies suggest that NO formed from endothelial NO synthases is also oxidized by oxygen or plasma ceruloplasmin to form nitrite.  Nitrite transport in blood provides an endocrine (from glands) form of NO that is shuttled from the lungs to the periphery while limiting the exposure of authentic NO to the scavenging red cell environment. Then during the rapid haemoglobin deoxygenation from artery to vein, the nitrite is reduced back to NO. Such a cycle conserves NO in the one-electron oxidation state. In this model, the nitrite pool represents the “live payload,” only one electron away from NO.”

If the body then generates enough Nitric Oxide, is there a requirement for additional dietary intake of nitrate or nitrite? “It has been suggested that the nitrate-nitrite-NO pathway serves as a backup system to ensure sufficient NO generation under hypoxic conditions when NOS may be malfunctioning.” (Ghasemi, 2011)

“It has been shown that 3-day dietary supplementation with sodium nitrate (0.1 mmol/kg/day) could reduce significantly diastolic blood pressure in non-smoking healthy volunteers. Recently, a large cohort study of 52,693 patients from 14 countries with acute coronary syndrome, of whom 20% were on chronic nitrate, demonstrated that chronic nitrate therapy (medication routinely taken at home and started at least 7 days prior to index event) was associated with reduced severity of myocardial injury in response to acute coronary events. The result showed that the proportion of these subjects with ST-segment elevation myocardial infarction was 41% in nitrate-naïve patients compared to only 18% in nitrate users and conversely a higher percent of nitrate users (82%) presented with non-ST-segment elevation acute coronary syndrome compared to 59% in nitrate-naïve patients.” (Ghasemi, 2011)

“Increasing nitrate or nitrate dietary intake provides significant cardioprotection against ischemia-reperfusion (I/R) injury in mice and it has been proposed that nitrite-/nitrate-rich foods may provide protection against cardiovascular conditions characterized by ischemia. It has been suggested that the nitrate-nitrite-NO pathway serves as a backup system to ensure sufficient NO generation under hypoxic conditions when NOS may be malfunctioning.” (Ghasemi, 2011)

“Abundant consumption of fruits and vegetables, especially green leafy vegetables, is associated with lower risk of cardiovascular disease. It has been proposed that inorganic nitrate, which is found in vegetables with a high concentrations, i.e. >2000-3000 mg/nitrate/kg, is the major factor in contributing to the positive health effects of vegetables via bioconversion to nitrite, NO, and nitroso-compounds, NOx intake now being considered as a dietary parameter for assessing cardiovascular risk.” (Ghasemi, 2011)

“Any intervention that increases blood and tissue concentration of nitrite may provide cardioprotection against I/R injury because it serves as a NOS-independent source of NO and reacts with thiols to form S-nitrosothiols. Nitrate-nitrite-NO pathway can be boosted by exogenous administration of nitrate or nitrite and this may have important therapeutic as well as nutritional implications. However, additional studies are required to clarify the protective roles of nitrate, considering the medical status of subjects, concomitant use of inhibitors of endogenous nitrosation (e.g. vitamin C and E), or foods containing high levels of nitrosatable precursors (e.g. fish). Some individuals, including those with high blood pressure and atherosclerosis, may benefit from increased nitrate while those with oesophagal dysplasia should avoid foods with high concentration of nitrate.” (Ghasemi, 2011)

The value of nitrite in the human body, however, goes far beyond only a reservoir of Nitric Oxide. We have eluded time and time again to many of the benefits and we now drill down on some of the different benefits or tahre, its role in resolving some of the negative lifestyle diseases prevalent in our modern era. “Nitrite-induced transnitrosylation in organs might be an alternative in vivo nitrite signalling for the mammalian biology including protection of protein thiols from irreversible oxidation, transcriptional modulation, and posttranslational regulation of most classes of proteins present in all cells, and also that changes in plasma nitrite levels even within the physiological ranges (e.g., postprandial and fasting) can affect tissue levels of S-nitrosothiol and subsequent cellular biology.” (Kobayashi, 2015)

-> Protective Effects of Dietary Nitrate/Nitrite on Lifestyle-Related Diseases

Kobayashi (2015) reviewed nitrites’ protective effect on lifestyle-related diseases. They write: “Lifestyle-related disease is a chronic disease characterized by oxidative and proinflammatory state with reduced NO bioavailability. The cellular redox balance in these patients shifts toward a more oxidizing state which affects a number of protein functions at the transcriptional and posttranslational levels, consequently disrupting the cellular homeostasis. However, increased NO bioavailability can improve the intracellular redox environment by S-nitrosylation-mediated modulation of most classes of proteins present in all cells. Recently, accumulating evidence has suggested that dietary nitrate/nitrite improves the features of lifestyle-related diseases by enhancing NO availability, and thus provides potential options for prevention and therapy for these patients. Based on the recent evidence, the beneficial effects of a diet rich in these components are discussed below, focusing on insulin resistance, hypertension, cardiac ischemia/reperfusion injury, chronic obstructive pulmonary disease (COPD), cancer, and osteoporosis.”

Insulin Resistance

“The insulin receptor shares a signalling pathway with the activation of endothelial NOS (eNOS) to regulate the postprandial blood flow and efficient nutrient disposition to peripheral tissues. Therefore, insulin resistance is always associated with impaired NO availability, suggesting that a reciprocal relationship exists between insulin activation and endothelial function. Insulin resistance is improved by NO at various levels including insulin secretion, mitochondrial function, modulation of inflammation, insulin signalling and glucose uptake. For example, insulin-stimulated NO production has physiological consequences resulting in capillary recruitment and increased blood flow in skeletal muscle, leading to efficient glucose disposal.” (Kobayashi, 2015)

However, the most important mechanism to improve insulin resistance might be at the post-receptor level of insulin signalling. In diabetic states, increased adiposity releases free fatty acids and produces excessive reactive oxygen species (ROS) through a toll-like receptor 4 (TLR4)-mediated mechanism, which activates a number of kinases and phosphatases, and then disrupts the balance of protein phosphorylation/dephosphorylation associated with insulin signalling. The mechanisms underlying the NO-mediated beneficial effects on insulin resistance are as follows: First, NO suppresses the TLR4-mediated inflammation and ROS production by inactivating IkB kinase-β/nuclear factor-κB (IκκB/NF-κβ), the main trigger for the induction of a number of proinflammatory cytokines. Second, Wang et al., indicated that NO mediates the S-nitrosylation of protein-tyrosine phosphatase 1B (PTPB1) and enhances the effects of insulin. Because PTPB1 dephosphorylates the insulin receptor and its substrates, attenuating the insulin effect, its phosphatase activity tends to be suppressed by eNOS-mediated S-nitrosylation. In contrast, when the vascular eNOS activity is impaired, PTPB1 suppresses the downstream signalling to PI3K/Akt, leading to insulin resistance. Therefore, NO might act as a key regulatory mediator for the downstream signalling linking glucose transporter 4 (GLUT4) translocation and glucose uptake. Third, Jiang recently reported that NO-dependent nitrosylation of GLUT4 facilitates GLUT4 translocation to the membrane for glucose uptake, and improves insulin resistance. Fourth, excess nutrients also overproduce superoxide in the mitochondrial respiratory chain, leading to the subsequent formation of ROS. NO can inhibit mitochondrial ROS production through the S-nitrosylation of mitochondrial respiratory chain complex 1 enzyme and by improving the efficiency of oxidative phosphorylation in the mitochondria.” (Kobayashi, 2015)

“Indeed, the therapeutic potential of dietary nitrate/nitrite has been supported by recent studies demonstrating the improvements of insulin resistance in humans and animals as a result of its enhancing the NO availability in plasma and tissues. As mentioned above, insulin resistance always accompanies metabolic and endothelial dysfunction, which leads to hypertension and atherosclerosis. Enhancement of the availability of NO might therefore be a promising strategy for the prevention and treatment of patients with not only insulin resistance but also endothelial dysfunction.” (Kobayashi, 2015)

-> Cardiac Ischemia/Reperfusion Injury

“During heart ischemia, ATP is progressively depleted in cardiac muscle cells, which impairs ion pumps, leads to the accumulation of calcium ions, and consequently damages the cell membrane stability. On reperfusion, the cardiac muscle cells are further injured, because in the mitochondria, ROS are produced in large quantities due to massive electron leaks and the formation of superoxide with the resupplied oxygen, which denatures cytosolic enzymes and destroys cell membranes by lipid peroxidation. ROS-mediated dysfunction of the sarcoplasmic reticulum also induces massive intracellular calcium overload, leading to the opening of the mitochondrial permeability transition pore and causing cell apoptosis or necrosis, depending on the intracellular ATP levels. The availability of vascular NO would thus be expected to be impaired due to the reduced NOS activity in ischemia and subsequent consumption by superoxide during reperfusion, resulting in severe ischemia/reperfusion injury.” (Kobayashi, 2015)

“Nitrite, nitrate, and NO-related compounds (e.g., S-nitrosothiols) are constitutively present in blood and tissues. The nitrite level in cardiac tissue is a couple of times higher than that in plasma due to an unknown form of active transport from blood to tissues or due to the oxidation of endogenously generated-NO to nitrite by ceruloplasmin, and serves as a significant extravascular pool for NO during tissue hypoxia. Carlström et al., showed that dietary nitrate increased the tissue levels of nitrite and S-nitrosothiols in the heart, and attenuated oxidative stress and prevented cardiac injury in Sprague-Dawley rats subjected to unilateral nephrectomy and a high-salt diet. Shiva et al., recently showed that the nitrite stored in the heart and liver via systemic and oral routes augmented the tolerance to ischemia/reperfusion injury in the mouse heart and liver.” (Kobayashi, 2015)

“Although the genetic overexpression of eNOS in mice attenuates myocardial infarction, in general, the protective effects of NO on cardiac ischemia/reperfusion injury depend on the local stock of nitrite and its subsequent reduction to NO at the critical moment when NOS activity is lacking under hypoxic conditions. Indeed, the tissue levels of S-nitrosothiols (NO-mediated signalling molecules) are enhanced through the nitrite reduction due to NOS inhibition, hypoxia, and acidosis, suggesting that the tissue nitrite stores can be regarded as a backup and on-demand NO donor. There are a number of factors that have been demonstrated to reduce nitrite in the tissues, including deoxyhemoglobin, deoxymyoglobin, xanthine oxidoreductase, heme-based enzymes in the mitochondria and acidosis during ischemia. In patients with coronary heart disease, the different consequences of myocardial infarction may depend on the patient’s daily intake of nitrate/nitrite. Indeed, Bryan et al., showed that dietary nitrite (50 mg/L) or nitrate (1 g/L) supplementation in drinking water for seven days maintained higher steady-state levels of nitrite and nitroso compounds, as well as nitrosyl-heme, in mouse cardiac muscle, and these mice exhibited a smaller cardiac infarct size after ischemia/reperfusion injury compared with control mice fed a diet deficient in nitrate/nitrite for seven days. These findings suggest that this protective nitrate/nitrite may be derived at least in part from dietary sources.” (Kobayashi, 2015)

“Shiva et al., demonstrated that the cytoprotective effects of nitrite on ischemia/reperfusion injury are mediated by post-translational S-nitrosylation of complex 1 in the mitochondrial respiratory chain, which consequently inhibits the overall mitochondrial ROS formation and apoptotic events. Another possible cytoprotective effect of nitrite may be mediated by the effects of S-nitrosylation on the intracellular Ca2+ handling, which decreases Ca2+ entry by inhibiting L-type Ca2+ channels and increasing the sarcoendoplasmic reticulum (SR) Ca2+ uptake by activating SR Ca2+ transport ATPase (SERCA2a) [102]. These effects will lead to an attenuation of the increase in cytosolic Ca2+ during ischemia and Ca2+ overload during reperfusion.” (Kobayashi, 2015)

“Intriguingly, recent large-scale epidemiological studies reported the preventive effects of antioxidant supplementations including vitamins E, C, and beta carotene rich in fruits and vegetables on cardiovascular disease, whereas no beneficial effects were shown in other studies, and in some cases, a decrease in cardiovascular protection with these supplementations was observed. On the other hand, a number of epidemiological studies have shown the preventive effects of fruits and vegetables on coronary heart disease. It should be noted that the consumption of an appropriate amount of fruits and vegetables, which might contain balanced doses of nitrate/nitrite and vitamins, might be more effective with regard to health maintenance and improvement than antioxidant supplementation alone.” (Kobayashi, 2015) It is this finding in particular that gives direction to my work with two collaborators Richard Bosman and Dr Jess Goble. Whether we will succeed in our quest, time will tell but we have some impressive early breakthoughs and with solid support of scientists, industry professionals and inventors of new technology which has the potential to unluck the application of these fruits and vegetables to meat, we are hopeful and extremely motivated!

-> Chronic Obstructive Pulmonary Disease (COPD)

“COPD is considered to be a lifestyle-related disease because long-term tobacco smoking and subsequent chronic bronchitis are causally associated with this disease. Varraso et al., recently reported the importance of a healthy diet in multi-interventional programs to prevent COPD. They showed that high intake of whole grains, polyunsaturated fatty acids, nuts, and long chain omega-3 fats, and low intake of red/processed meats, refined grains and sugar-sweetened drinks, were associated with a lower risk of COPD in both women and men.” (Kobayashi, 2015)

“Because cured meats such as bacon, sausage and ham contain high doses of nitrite for preservation, antimicrobial and colour fixation, epidemiological studies have demonstrated that the consumption of cured meats is positively linked to the risk of newly diagnosed COPD. Nitrite generates reactive nitrogen species, which may cause nitrosative damage to the lungs, eventually leading to structural changes like emphysema. This is supported by an animal study in which rats chronically exposed to 2000 and 3000 mg/L of sodium nitrite in their drinking water for two years showed distinct lung emphysema. However, the dose of nitrite used in that study was 250–350 mg/kg/day, which was too high to compare with those achieved in standard human diets.

In fact, cured meats have been reported to generally comprise only 4.8% of the daily nitrite intake, and 93% of the total ingestion of nitrite is derived from saliva, suggesting that cured meats provide minimal contributions to the human intake of nitrite, even if they are frequently consumed. In addition, the recent nitrite levels in processed meats have been approximately 80% lower than those in the mid-1970s in the US. Therefore, discussions encompassing all ingested sources of nitrite should consider whether or not the nitrite derived only from the consumption of cured meats might be responsible for the development of COPD.” (Kobayashi, 2015)

“On the other hand, a number of epidemiological studies have shown the beneficial effects of n-3 fatty acids, vitamins, fruits and vegetables on lung functions and the risk of COPD. Although it may be difficult to isolate the specific effects of these dietary nutrients, as discussed above, the nitrate and nitrite derived from vegetables and fruits are reduced to NO, which is followed by the formation of S-nitrosothiols, rather than the formation of nitrosamines especially in the presence of reducing agents such as vitamin C and E in the stomach. It has been shown that high dietary nitrate intake does not cause the expected elevation of the gastric nitrite concentrations or appreciable changes in the serum nitrite concentrations.” (Kobayashi, 2015) As I stated previously, these findings do not cause the industry to sit back and proclaim, “you see, consumption of cured meat is safe” even though the validation is encouraging – in the case of me and my collaborators it energises us to do even better and work to turn cured meat into a superfood.

“As mentioned above, different from the effects of the direct elevation of nitrite concentration in the plasma, the entero-salivary route of dietary nitrate/nitrite might enhance the availability of NO through the formation of S-nitrosothiols and its transnitrosylation to the other thiol residues of proteins, suggesting that, depending on the tissues and organs, separate metabolic pathways might exist for NO availability in this entero-salivary route. Consistent with this idea, Larsen et al., recently demonstrated that acute intravenous infusion of nitrite enhanced the plasma levels of nitrite, whereas it did not affect the oxygen consumption (VO2) or the resting metabolic rate (RMR) in humans. Instead, dietary nitrate significantly reduced the VO2 and RMR by improving the mitochondrial respiratory chain function and enhancing efficient O2 consumption, suggesting that rather than direct nitrite infusion to enhance the plasma nitrite levels, biologically active nitrogen oxide (including the S-nitrosothiols produced in the stomach) might be an important molecule for the transfer of biological NO activity for cardiopulmonary function [126]. Because COPD is a state of protein-energy malnutrition due to an increased resting metabolic rate and VO2, the effects of dietary nitrate on the reduction of the RMR and VO2 might be advantageous for patients with COPD.” (Kobayashi, 2015)

“Whether the role of NO in COPD is protective or pathogenic depends on the origin and concentration range of NO. NO activity derived from dietary nitrate and constitutive NOS might be protective against COPD largely through the S-nitrosothiol-mediated mechanism including inhibition of the noncholinergic nonadrenergic nerve activity, bronchial smooth muscle relaxation, reduction of airway hyperresponsiveness, downregulation of the proinflammatory activity of T lymphocytes, and antimicrobial defence. However, the deleterious effects of NO on the development of COPD might be derived from iNOS-mediated pro-inflammatory signalling, which is consequently (not causally) reflected by the huge amount of NO in the exhaled air of patients with COPD.” (Kobayashi, 2015)

“Recent human studies have demonstrated that dietary nitrate (beetroot juice containing approximately 200–400 mg of nitrate) improved the exercise performance and reduced blood pressure in COPD patients. However, large-scale epidemiological evidence of the impact of nitrate is still lacking.” (Kobayashi, 2015)

-> Lowering Blood Pressure

An obvious benefit of nitrite is its role as a reservoir of Nitric Oxide which is a key molecule which blood pressure. The blood pressure-lowering and performance-enhancing effects of nitrites have been known for many years. (Keller, 2017) This is due to the fact that the nitrite anion (NO–2) acts as an endogenous nitric oxide source. (Keszler, 2008) Nitrite is reduced to nitric oxide (NO). “One major mechanism of nitrite reduction is the direct reaction between this anion and the ferrous heme group of deoxygenated haemoglobin.” The oxidation reaction of nitrite with oxyhemoglobin (oxyHb) which is formed by the combination of haemoglobin with oxygen, is also well established and generates nitrate and methemoglobin (metHb). (Keszler, 2008)

“Increased consumption of fruits and vegetables is associated with a reduction of the risk of cardiovascular disease. The DASH studies recommended the consumption of diets rich in vegetables and low-fat dairy products to lower blood pressure, and these effects are thought to be attributable to the high calcium, potassium, polyphenols and fiber and low sodium content in these food items. However, vegetable diets containing high nitrate levels increase the plasma levels of nitrate and nitrite, which are the physiological substrates for NO production. Accumulating evidence has recently indicated that the nitrate/nitrite content of the fruits and vegetables could contribute to their cardiovascular health benefits in animals and humans.” (Kobayashi, 2015)

“A number of publications have demonstrated that dietary nitrate reduces blood pressure in humans. Larsen et al., reported that the diastolic blood pressure in healthy volunteers was reduced by dietary sodium nitrate (at a dose of 0.1 mmol/kg body weight per day) corresponding to the amount normally found in 150 to 250 g of a nitrate-rich vegetable, such as spinach, beetroot, or lettuce. Webb et al., studied the blood pressure and flow-mediated dilation of healthy volunteers, and showed that the vasoprotective effects of dietary nitrate (a single dose of 500 mL of beetroot juice containing 45.0 ± 2.6 mmol/L nitrate), were attributable to the activity of nitrite converted from the ingested nitrate [86]. Kapil et al., also showed a similar finding that consuming 250 mL of beetroot juice (5.5 mmol nitrate) enhanced the plasma levels of nitrite and cGMP with a consequent decrease in blood pressure in healthy volunteers, indicating that there was soluble guanylate cyclase-cGMP-mediated vasodilation following a conversion of the nitrite to bioactive NO. They later presented the effects of dietary nitrate on hypertension, and showed the first evidence that daily dietary nitrate supplementation (250 mL of beetroot juice daily) for four weeks reduced the blood pressure, with improvements in the endothelial function and arterial stiffness in patients with hypertension. Because arterial vascular remodelling is the major histological finding associated with ageing, these vascular structural changes represent vascular wall fibrosis with increased collagen deposits and reduced elastin fibers, which result in arterial stiffening and subsequent hypertension in elderly patients. Sindler et al., recently demonstrated that dietary nitrite (50 mg/L in drinking water) was effective in the treatment of vascular ageing in mice, which was evidenced by a reduction of aortic pulse wave velocity and normalization of NO-mediated endothelium-dependent dilation. They showed that these improvements were mediated by reduction of oxidative stress and inflammation, which were linked to mitochondrial biogenesis and health as a result of increased dietary nitrite. These beneficial effects were also evident with dietary nitrate in their study, suggesting that dietary nitrate/nitrite may be useful for the prevention and treatment of chronic age-associated hypertension.” (Kobayashi, 2015)

“In addition, hypertension is also a major cause of ischemic heart and cardiac muscle remodelling, which lead to congestive heart failure. Bhushan et al., reported that dietary nitrite supplementation in drinking water (50 mg/L sodium nitrite, for nine weeks) increased the cardiac nitrite, nitrosothiol, and cGMP levels, which improved the left ventricular function during heart failure in mice with hypertension produced by transverse aortic constriction. They also showed that dietary nitrite improved the cardiac fibrosis associated with pressure-overloaded left ventricular hypertrophy through NO-mediated cytoprotective signalling. Although a number of studies on the acute effects of dietary nitrate have been conducted using animal models and healthy humans, more evidence in patients with hypertension, as well as additional studies on the long-term effects of dietary nitrate, will be needed in the future.” (Kobayashi, 2015)

-> Cancer

“In the stomach, swallowed nitrite is decomposed to form a variety of nitrogen compounds, including N-nitrosoamines. In the 1950s, Magree et al., first reported that N-nitrosodimethylamine caused malignant primary hepatic tumours in rats. After this report, a number of studies followed in relation to the carcinogenic effects of N-nitroso compounds in animal models. In particular, the dietary intake of red and cured meats was found to be associated with an increased risk of certain types of cancer due to the relatively large amounts of nitrite added. However, the methodological aspects have been challenged concerning the high dose of nitrosatable amines, and the physiological difference between animals and humans.” (Kobayashi, 2015)

“In the stomach, the nitrosonium ion (NO+) derived from nitrite can bind to thiol compounds (R-SH) and amines (especially secondary amines: R1-NH-R2), forming S-nitrosothiol and N-nitrosamine, respectively. However, while N-nitrosamine formation occurs even at neutral or basic pH, S-nitrosothiol formation tends to occur only under acidic conditions. In addition, this reaction kinetically occurs much more easily than N-nitrosamine formation, particularly in the presence of vitamins C and E and polyphenols, which are highly present in fruits and vegetables, which also eliminate potent nitrosating agents such as the N2O3 formed from nitrite by decomposing them to NO. This might partly explain why patients with achlorhydria and non-vegetarians eating large amounts of cured meats are at risk of developing gastric cancer.” (Kobayashi, 2015)

“However, this idea appears to be inconsistent with the belief that dietary nitrite is a major cause of cancer. This is because, according to the average nitrate/nitrite intake of adults in the US, most of the daily nitrate intake (around 90%) comes from vegetables, and the nitrite intake is primarily derived from recycled nitrate in the saliva (5.2–8.6 mg/day nitrite), with very little coming from cured meats (0.05–0.6 mg/day nitrite in 50g/day cured meats) and other dietary sources (0–0.7 mg/day nitrite) [136], suggesting that the entero-salivary route may be the more important source of nitrosamine exposure than exogenous intake including cured meats, that is, spitting out saliva all day long might prevent cancer development more effectively than cutting cured meats. However, recent experimental and epidemiological studies could not demonstrate a positive relationship between nitrate consumption and the risk of cancer, and the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives concluded in 2008 that there was no evidence that nitrate was carcinogenic in humans. Consistent with this, recent studies have found no link between dietary nitrate and cancer.” (Kobayashi, 2015)

“Bradbury et al., reported a large-scale study (>500,000 participants) of the associations between fruit, vegetable, or fiber consumption and the risk of cancer at 14 different sites. They showed that there was an inverse association between fruit intake and the risk of upper gastrointestinal tract and lung cancer, as well as an inverse association between fiber intake and liver cancer. The dietary intake of vegetables, as well as fruits and fiber, was inversely associated with the risk of colorectal cancer, suggesting that there is little evidence that vegetable intake is associated with the risk of any of the individual cancer sites reviewed.” (Kobayashi, 2015)

“However, chronic inflammation, including inflammatory bowel disease and Helicobacter pylori-induced gastritis induce inducible NOS (iNOS) and generate large quantities of NO, forming nitrosating and oxidant species such as N2O3 and peroxynitrite, which might cause mutagenesis through deamination, nitration of DNA, or inhibition of the DNA repair system. Depending on the sites and amounts of NO generation, NO might represent a double-edged sword in the sense that it confers both protective and deleterious effects on cancer development.” (Kobayashi, 2015)

“Meta-analyses of primary and secondary cancer prevention trials of dietary antioxidant supplements, such as beta carotene, vitamins A, C, and E, showed a lack of efficacy, and on the contrary, an increased risk of mortality. Although the general role of NO in carcinogenesis is complicated, and many unknown mechanisms remain to be resolved, the dietary nitrate/nitrite (at least that obtained from plant-based foods such as fruits and vegetables) has obvious inhibitory effects on cancer risk by playing some synergistic role with other nutrients in these foods.” (Kobayashi, 2015) It is again findings like these that give direction to our product developments.

-> Osteoporosis

“Lifestyle habits, such as smoking, alcohol intake, little or no exercise, and an inadequate amount of calcium intake all influence the calcium-vitamin D metabolism and bone mineral density, in some cases leading to osteoporosis, particularly in postmenopausal women. The implications of NOS-mediated NO in the regulation of bone cell function have been well described in a number of publications. For example, iNOS-induced NO production following stimulation with proinflammatory cytokines, such as interleukin 1 (IL-1) and tumor necrosis factor-α (TNF-α), inhibits bone resorption and formation, resulting in osteoporosis in patients with inflammatory diseases such as rheumatoid arthritis. On the other hand, eNOS, a constitutive NO synthase, plays an important role in regulating osteoblast activity and bone formation, because eNOS knockout mice exhibit osteoporosis due to defective bone formation, and eNOS gene polymorphisms were reported to be causally linked to osteoporosis in postmenopausal women.” (Kobayashi, 2015)

“In addition, Wimalawansa et al., showed that some of the beneficial effects of estrogen on bone metabolism are mediated through a NO-cGMP-mediated pathway, suggesting that NO donor therapy might provide a promising alternative to estrogen therapy. In this context, it has been shown that organic nitrate NO donors, such as glycerol trinitrate, isosorbide dinitrate and mononitrate all have beneficial effects on experimental and clinical osteoporosis, and a number of epidemiological studies also indicated that a high fruit and vegetable intake appears to have a protective effect against osteoporosis in men and pre- and postmenopausal women. However, few studies have been conducted to evaluate the detailed mechanism by which inorganic nitrate/nitrite prevents osteoporosis at the molecular level, and thus further basic research will be needed for this purpose.” (Kobayashi, 2015)

-> Methemoglobinemia (MetHb)

A negative effect of nitrite in the body relates to its link with methemoglobinemia. It is historically this link which contributed to cast nitrite in a negative light and day plays a dominant role in establishing what the WHO regards as safe levels of ingested nitrites.

“Methemoglobinemia (MetHb) is a blood disorder which the US National Institute of Health defines as occurring when “an abnormal amount of methemoglobin is produced.” They explain that “hemoglobin is the protein in red blood cells (RBCs) that carries and distributes oxygen to the body. Methemoglobin is a form of hemoglobin. Inherited (congenital) methemoglobin occurs when the disorder “is passed down through families.” Our interest is in what is referred to as acquired MetHb which is “more common than inherited forms and occurs in some people after they are exposed to certain chemicals and medicines.” One such chemical is nitrites. (National Libary of medecine) “Elevated levels of nitrite in the blood can trigger the oxidation of hemoglobin, leading to methemoglobinemia.” Keszler (2008) suggests a simplified model of the kinetics involved where the end products of the reaction are methemoglobin (metHb) and nitrate.

The “World Health Organization (WHO) used data based on the risk of methemoglobinemia to set an accept­able daily intake (ADI) for nitrate of 3.7 mg/kg body weight per day, equivalent to 222 mg nitrate per day for a 60-kg adult, and nitrite of 0.07 mg/kg body weight per day, equi­valent to 4.2 mg nitrite per day for a 60-kg adult. (Keller, 2017)

The upper limit represented by the WHO ADI corresponds to the concentration of dietary nitrate that lowers blood pressure in normotensive and hypertensive adults. (Keller, 2017)

Very high concentrations of nitrate in drinking water may cause methemoglobinemia, particularly in infants (blue baby syndrome). “In the 1940s, Comly first reported cases of cyanotic infants who received formula prepared with well water containing a high nitrate content. Based on the subsequent analyses of the infantile cases of methemoglobinemia, the US Environmental Protection Agency (EPA) set a Maximum Contaminant Level (MCL) for nitrate of 44 mg/L (equal to 10 mg/L nitrogen in nitrate). However, it is now thought that methemoglobinemia per se was not caused by nitrate itself, but by faecal bacteria that infected infants and produced NO in their gut. A recent report by Avery has argued that it is unlikely that nitrate causes methemoglobinemia without bacterial contamination, and also that the 40–50 mg/L limit on nitrate in drinking water is not necessary.” (Kobayashi, 2015)

However, there are now legal limits to the concentrations of nitrate and nitrite in both food and drinking water. The WHO showed that the Acceptable Daily Intake for humans (ADI) for nitrate and nitrite were 3.7 and 0.07 mg/kg body weight/day, respectively, which were based on the calculations from the doses of <500 mg of sodium nitrate/kg body weight that were harmless to rats and dogs. The international estimates of nitrate intake from food are 31–185 mg/day in Europe and 40–100 mg/day in the United States. However, the Ministry of Health, Labour and Welfare of Japan reported that the average intake of nitrate in the Japanese population is around 200–300 mg/day, which is one and a half times to two times the ADI. Furthermore, according to a report by Hord, in which the daily nitrate and nitrite intakes were calculated based on the variations using the vegetable and fruit components of the DASH (Dietary Approaches to Stop Hypertension) dietary pattern, the level easily exceeds 1,200 mg/day nitrate. This is more than five-fold higher than the WHO’s ADI of 3.7 mg nitrate/kg body weight/day, and more than two-fold the US Environmental Protection Agency’s level of 7.0 mg nitrate/kg body weight/day for a 60 kg individual. Furthermore, as indicated in Figure 2, approximately 25% of the ingested nitrate is secreted in saliva, and 20% of the secreted nitrate in the saliva is converted to nitrite by commensal bacteria on the tongue, indicating that about 5% of the originally ingested nitrate is swallowed into the stomach. Therefore, for a DASH diet containing 1200 mg nitrate, an individual would be expected to swallow approximately 45 mg of nitrite a day, which easily exceeds the ADI of nitrite. Therefore, a comprehensive reevaluation of the health effects of dietary sources of nitrate/nitrite might be required in the near future.” (Kobayashi, 2015)

– Other International Views on Nitrite/ Nitrate from Dietary Sources besides from the USA and Europe

The Food Standards Australia New Zealand and the European Food Safety Authority concluded that the major sources of estimated nitrate and nitrite exposure, across different population groups, were vegetables and fruits (including juices). Processed meats only accounted for 10% of total dietary exposure to nitrite in the European survey. Consumption and exposure to dietary nitrate and nitrite is not considered an ‘‘appreciable health and safety risk’’, according to the Australian agency. (Keller, 2017)

Given the established vasoprotective, performance-enhancing, blood pressure lowering effects of dietary nitrates in humans, specific recommendations to encourage plant-based, nitrate-rich foods may produce significant public health benefits. (Keller, 2017)

Is vitamin C and E the crucial link that saves bacon’s bacon?

Three important nitrosamines, namely N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), and N-nitrosomorpholine (NMOR), are classified as probably carcinogenic to humans (Group 2B) by the International Agency for Research on Cancer (IARC) (IARC 2000). (Erkekoglu, 2010)

Intrinsic antioxidant systems, such as protective enzymatic antioxidants as well as antioxidants available in the human diet, provide an extensive array of protection that counteract potentially injurious oxidizing agents. (Erkekoglu, 2010)

It was found that antioxidants protected the cells against nitrite and nitrosamines. (Erkekoglu, 2010) Dietary antioxidants can be a saviour when exposure to dietary genotoxic/carcinogenic compounds is the case. (Erkekoglu, 2010)

Erkekoglu, 2010 confirmed the DNA damaging effect of nitrosamines as shown in other studies (Robichová et al. 2004b; Arranz et al. 2006; 2007; Garcia et al. 2008a; b). Additionally, they used sodium nitrite to show the genotoxic effects of nitrite alone. They showed that antioxidants supplementation was capable of reducing both tail intensity and tail moment in all of the nitrosamine treatments, particularly in NDMA. They proposed that this may be related to antioxidants’ reduction of CYP2E1 and CYP2A6. They write, “CYP2E1 is responsible for α-hydroxylation of N-alkylnitrosamines with short alkyl chain, whereas cyclic nitrosamines like NPYR, NPIP, and NMOR may be activated by CYP2A6 and by CYP2E1 to a lesser extent (Kamataki et al. 2002). Furthermore, inhibition of CYP450 enzymes may not be the only mechanism underlying the protection of antioxidants. Alternative mechanisms by antioxidants may be as follows: ROS scavenging capacity, the conversion of reactive compounds to less toxic and easily excreted compounds, alteration of cell proliferation, stimulation of DNA-repair induced by nitrosamines, induction of Phase II enzymes, and NAD(P): quinine oxidoreductase activity (Roomi et al. 1998; Chaudière and Ferrari-Iliou 1999; Gamet-Payrastre et al. 2000; Surh et al. 2001; Surh 2002).” (Erkekoglu, 2010)


It is obvious that the overwhelming weight of evidence is that nitrite is not the destructive chemical that it was made out to be and that the negative media frenzy is completely misguided, to put it mildly. The health benefits of nitrate, nitrite and nitric oxide are clear. An obvious path for improving the geneneral healt and nutritional status associated with cured meats is the incorporation of vegetable and plant matter into its formulation. The fact that nitrire-free curing may possibly never be achieved has been raised and warrants further investigation. The next two segments will focus on N-nitrosamines and why the protein myaglobin evolved in such a way that it wants to react with oxygen and nitric oxide.

Want to Know More?

Gladwin, M. T., Kim-Sharipo, D. B.. (2008) The functional nitrite reductase activity of the heme-globins. Review in Translation Hematology, October 1, 2008. Blood (2008) 112 (7): 2636–2647. https://doi.org/10.1182/blood-2008-01-115261

Moncada, Salvador and Higgs, Annie. 1993. The L-Arginine-Nitric Oxide Pathway. New England Journal of Medicine doi: 10.1056/NEJM199312303292706 DO – 10.1056/NEJM199312303292706. Massachusetts Medical Society, https://doi.org/10.1056/NEJM199312303292706


Erkekoglu P, Baydar T. Evaluation of the protective effect of ascorbic acid on nitrite- and nitrosamine-induced cytotoxicity and genotoxicity in human hepatoma line. Toxicol Mech Methods. 2010 Feb;20(2):45-52. doi: 10.3109/15376510903583711. PMID: 20100056.

Ghasemi A, Zahediasl S. Is nitric oxide a hormone? Iran Biomed J. 2011;15(3):59-65. PMID: 21987110; PMCID: PMC3639748.

Gladwin, M. T. and Kim-Shapiro, D. B.. (2008) The functional nitrite reductase activity of the heme-globins. ASH Publication, Blood. Review in Translational Hematology. Blood (2008) 112 (7): 2636–2647. https://doi.org/10.1182/blood-2008-01-115261

Hlinský, Tomáš, Michal Kumstát, and Petr Vajda. 2020. “Effects of Dietary Nitrates on Time Trial Performance in Athletes with Different Training Status: Systematic Review” Nutrients 12, no. 9: 2734. https://doi.org/10.3390/nu12092734

Hord, N.G.; Tang, Y.; Bryan, N.S. Food sources of nitrates and nitrites: The physiologic context for potential health benefits. Am. J. Clin. Nutr. 2009, 90, 1–10.

Huizing M, Hackbarth ME, Adams DR, Wasserstein M, Patterson MC, Walkley SU, Gahl WA; FSASD Consortium. Free sialic acid storage disorder: Progress and promise. Neurosci Lett. 2021 Jun 11;755:135896. doi: 10.1016/j.neulet.2021.135896. Epub 2021 Apr 20. PMID: 33862140; PMCID: PMC8175077.

Keller, Rosa M. BS; Beaver, Laura PhD, MS; Prater, M. Catherine; Hord, Norman G. PhD, MPH, RD. Dietary Nitrate and Nitrite Concentrations in Food Patterns and Dietary Supplements. Nutrition Today: 9/10 2020 – Volume 55 – Issue 5 – p 218-226, doi: 10.1097/NT.0000000000000253

Keszler A, Piknova B, Schechter AN, Hogg N. The reaction between nitrite and oxyhemoglobin: a mechanistic study. J Biol Chem. 2008 Apr 11;283(15):9615-22. doi: 10.1074/jbc.M705630200. Epub 2008 Jan 17. PMID: 18203719; PMCID: PMC2442280.

Kobayashi, J. (2015) NO-Rich Diet for Lifestyle-Related Diseases, Article in Nutrients, June 2015, DOI: 10.3390/nu7064911

Kröncke KD, Fehsel K, Kolb-Bachofen V. Inducible nitric oxide synthase in human diseases. Clin Exp Immunol. 1998 Aug;113(2):147-56. doi: 10.1046/j.1365-2249.1998.00648.x. PMID: 9717962; PMCID: PMC1905037.

Lundberg JO. Nitrate transport in salivary glands with implications for NO homeostasis. Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):13144-5. doi: 10.1073/pnas.1210412109. Epub 2012 Jul 31. PMID: 22851765; PMCID: PMC3421160.

Rassaf T, Ferdinandy P, Schulz R. Nitrite in organ protection. Br J Pharmacol. 2014 Jan;171(1):1-11. doi: 10.1111/bph.12291. PMID: 23826831; PMCID: PMC3874691.

Sindelar, J.J.; Milkowski, A.L. Human safety controversies surrounding nitrate and nitrite in the diet. Nitric Oxide 2012, 26, 259–266.

Vanek T, Kohli A. Biochemistry, Myoglobin. [Updated 2022 Jul 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544256/

Zhou L, Zhu DY. Neuronal nitric oxide synthase: structure, subcellular localization, regulation, and clinical implications. Nitric Oxide. 2009 Jun;20(4):223-30. doi: 10.1016/j.niox.2009.03.001. Epub 2009 Mar 17. PMID: 19298861.

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

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.


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


Online published: Therapeutic Uses of Inorganic Nitrite and Nitrate


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 al2,3 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 pKa of 3.15 (pKa 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 mechanisms41,42 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 patients81,82 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).




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).


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