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!

Introduction

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).

Nitrite

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)

Conclusion

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!

References

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.