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.

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Finally – Finally – The Human Nitrogen Cycle – Basis for its Physiological Value

December 1990
By Eben van Tonder
(Latest review: 25 December 2022)

Introduction

The most monumental changes imaginable took place related to our understanding of the essential role of nitrate, nitrite and nitric oxide in human physiology over the last few decades. We look at how our understanding changed and how the discoveries came about.

The four final chapters form a unit:

• Chapter 16.05: Finally – Nitrosamines
• Chapter 16.06: Finally – Nitrite is Physiologically Vital
• Chapter 16.07: Finally – The Human Nitrogen Cycle – Basis for Nitrite’s Physiological Value
• Chapter 16.08: Finally – Bacon, the Superfood

Sources of Nitrogen for Human Physiology and the Value of Nitrite

The great discovery of the past few decades is that nitrate and nitrite, in particular, have a fundamentally important role in our physiology, namely to act as a reservoir for nitric oxide (NO), a physiologically important molecule. It is important to remember that this is not its only role, as we have seen in the previous chapter, as nitrite itself, on its own, plays an important role in several health benefits which accrue to us from itself not and not merely from it being a reservoir of nitric oxide. Having said this, it is still true that one of its greatest values is exactly in its role as such a reservoir.

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. The latter was the curing reaction for the last few decades and it is only now that we are returning to the development of a new set of curing techniques exploiting its generation bacterially from L-Arganine, as it was principally done when dry curing was the major way of curing meat.

In order for the nitrate-nitrite-Nitric Oxide pathway to work in our bodies, we need a direct source of nitrates or nitrites and nature provides 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 blood plasma nitrite levels can occur by increasing the dietary nitrate intake. (Kobayashi, 2015)

Non-Bacterial Reduction of NO₃^–  to NO₂^–

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 calls into question the wisdom to try and find a meat-curing system which will result in absolutely no nitrites ever being present in the cured meat. (Communication Record: Leif Horsfelt Skibsted)

An example of enzymatic (non-bacterial reduction) of nitrate to nitrite is Xanthine Oxidase. “Xanthine Oxidase is an enzyme naturally produced by cows. Some of this enzyme ends up in their milk and therefore cheese. This enzyme is an important part of a cow’s normal metabolic processes and is crucial for its health. this enzyme when combined with sodium nitrate can help inhibit Clostridia species of microbes. Sodium nitrate, when added to milk, will react with xanthine oxidase and transform into sodium nitrite. Nitrites can inhibit Clostridia, thereby alleviating one source of late blowing.” (cheesescience.org)

Plant-based reductase activity has been found in hawthorn berry, Schisandra, green tea, beet root, pine bark, holy basil, gymnema sylvestre, L9H, ashwagandha root, salvia, St. John wort, broccoli, stevia, spinach, ginkgo, kelp, tribulus, eleuthero, epimedium, eucommia, rhodiola, green tea, codonopsys, panax ginseng, astragalus, dodder seed, cordyceps, berries, tea, beer, grapes, wine, olive oil, chocolate, cocoa, coffee, walnuts, peanuts, Corojo, pomegranates, popcorn, yerba mate, and mixtures thereof.

In humans and other mammals, about one-quarter of all circulating inorganic nitrate (NO₃⁻), derived from diet or oxidation of nitric oxide (NO) from within the body itself, 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)

Plant-Based Reduction of NO₂^– to NO

Hawthorn berry, Schisandra, green tea, beetroot, pine bark and mixtures of these. Hawthorn berry refers to any portion of a plant of the genus Crataegus (for example, Crataegus oxyacantha) including the berry, leaf, or flower, especially the berry.

Nitrate-nitrite-NO cycle in Humans

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 costs but as a chemical essential for human life. Cured meat may still not be the biggest source of nitrates in our system. Still, the possibility exists for it to become an important one, and in terms of nitrites, it is one of the key dietary sources. We can use the same basic principles that gave us cured meat being the nitrate-nitrite-NO cycle, reduce the fat and salt and find ways to introduce essential goodness of plant matter. 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 real possible reason behind the health concerns related to processed meat (fat, salt, phosphates, etc) and give a roadmap for the 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!

Look at the table below, which gives the primary dietary sources for nitrate and nitrites. Pay close attention to where hot dogs and bacon feature on the list!

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 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. 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) and we developed extremely effective ways to block these products from forming in meat curing as we dealt with in the chapter in nitrosamines. (Finally – Nitrosamines)

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 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 stomach’s acidic milieu, 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 depend 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 already developed in the chapter on nitrosamines, these substances and in particular vitamins A, C and E, play 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.

“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 regular diet. Ischaemia-Reperfusion injury (IRI) is 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 maintaining steady-state tissue levels of nitrate/nitrite for NO-mediated cytoprotection. Cytoprotection is a process by which chemical compounds protect 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.

Nitrites Unfortunate Fall into Disfavour and its Redemption

“Historically, the fact that nitrate and nitrite are present in human saliva has received little attention because no one could attribute any function to these anions. However, this lack of interest ceased in the 1970s when researchers formulated a pathophysiological model for gastric cancer based on nitrate accumulation in saliva. Bacteria in the mouth, existing in a long-term biological symbiosis, reduce parts of the salivary-derived nitrate to nitrite (NO2−). When swallowed into an 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 nitrate levels 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 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. Instead, researchers started to study the potential NO-like physiological effects of this anion. From intense research performed during the past 15 years, it is now clear that the administration of nitrate or nitrite has robust NO-like effects in humans and other mammals. (Lundberg, 2012) We discussed many of these effects in the previous chapter and it includes 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. (Finally – Nitrites is Physiologically Vital)

Sialin and the Direct Addition of Nitrite

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 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 were 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. (Chapter 15.06: Regulations of Nitrate and Nitrite post-1920’s: the problem of residual nitrite.)

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 (LSD’s), inherited metabolic 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. It is interesting to note that nitrate metabolism does, indeed, occur in mammalian cells, although to a much lesser degree than in bacteria. Jansson et al. reported on a functional mammalian nitrate reductase in numerous tissues, including the liver, kidney, and intestines. Xanthine oxidoreductase (XOR) was identified as the major mammalian nitrate reductase, but the study also indicated the presence of other unidentified nitrate reductases.” (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.

“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 (the region of a polarized cell that forms a tip). 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, is 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 is 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(2021) reports 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 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 the possible negative effects of nitrite, one 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.

Nitrite as Reserviour of Nitric Oxide

Gladwin (2008) writes 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 NO generation and signalling when there is low levels of oxygen in your body tissues. 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.”(Lundberg, 2012)

“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).” (Lundberg, 2012) 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. 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.

Endothelium

The endothelial is the largest organ system in the body. It refers to a single layer of cells, called endothelial cells, which lines the inside of all blood vessels (arteries, veins and capillaries). Nitric oxide synthases are a family of enzymes catalyzing the production of nitric oxide from L-arginine. “Inducible 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 or heart attack, during tumour development, after transplantation, during prostheses failure and myositis (i.e. inflammation of the muscles that you use to move your body). (Kröncke, 1998)

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. Guanosine 3′,5′-cyclic monophosphate (cyclic GMP or cGMP) is a second messenger molecule that modulates various downstream effects, including vasodilation, retinal phototransduction, calcium homeostasis, and neurotransmission. Endothelial NOS (eNOS), also known as nitric oxide synthase 3 (NOS3) or constitutive NOS (cNOS), is an enzyme that in humans is encoded by the NOS3 gene. 

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.” (Gladwin, 2008)

Different Types of NOS

There are three isoforms of nitric oxide synthase (NOS) named according to their activity or the tissue type in which they were first described. We have looked at eNOS. The one is neuronal or nNOS relates to the brain. “Brain Neuronal Nitric Oxide Synthase (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)

Two of the enzymes (nNOS and eNOS) are constitutively expressed in mammalian cells and synthesise NO in response to increases in intracellular calcium levels. In some cases, however, they are able to increase NO production independently of calcium levels in response to stimuli such as shear stress.

The other is inducible NOS (or iNOS). “iNOS activity is independent of the level of calcium in the cell, however, its activity – like all of the NOS isoforms – is dependent on the binding of calmodulin. Increases in cellular calcium lead to increases in levels of calmodulin and the increased binding of calmodulin to eNOS and nNOS leads to a transient increase in NO production by these enzymes. By contrast, iNOS is able to bind tightly to calmodulin even at very low cellular concentrations of calcium. Consequently, iNOS activity doesn’t respond to changes in calcium levels in the cell. As a result, the production of NO by iNOS lasts much longer than from the other isoforms of NOS, and tends to produce much higher concentrations of NO in the cell.” (reading.ac.uk)

“These enzymes are also sometimes referred to by number so that nNOS is known as NOS1, iNOS is known as NOS2 and eNOS is NOS3. Despite the names of these enzymes, all three isoforms can be found in a variety of tissues and cell types. The general mechanism of NO production from NOS is illustrated below.” (reading.ac.uk)

Is Dietary NO Necessary?

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, NO_x 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. “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) For a detailed discussion of the various physiological benefits to humans, please refer to Finally – Nitrites is Physiologically Vital.

Conclusion: Bacon, a Superfood

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 and the potential to convert nitrite to NO in the tissue are essential to obtain a reduction in injury.

That nitrite is not a compound to be avoided at all costs is evident. It is essential to our health, 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.

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(c) Eben van Tonder

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(c) eben van tonder

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References

https://www.cheesescience.org/xanthine_oxidase.html