Redefining the Narrative on Dietary Nitrites: Unveiling the Balance Between Risks and Benefits in Processed Meats

7 February 2024
Eben van Tonder

Table of Contents

Introduction

Over the last week, I looked at the issue of nitrites from several perspectives. In Navigating Nitrites: Understanding Their Role in Diet and Health, I go into details of what amines are and unpack the meaning of N-nitrosamines which are cancer-causing and are alleged to be one of the primary dangers in bacon. I also point out the dietary value of nitrites in humans. I summarised some of my work in EarthwormExpress in The Role of Ascorbate in the Nitrate-Nitrite-Nitric Oxide Pathway: Integrating Insights from Earthworm Express. In Savouring the Safety: The Evolutionary Journey of Nitrosamine Risk Mitigation in Bacon, I looked at the evolution of humans and how our diets changed around 13000 years ago with the agricultural revolution. Where amines come from which is essential for nitrosamine formation in a reaction with nitrites. I investigate why this reaction was unlikely before the agricultural revolution, why it is equally unlikely in bacon and how regular exercise removes the risk from bacon completely by eliminating the dangers of consuming bacon’s fat and salt. I addressed the concern that bacon could form nitrosamines at frying temperatures in The Low Risk of Nitrosamine and Amine Formation in Bacon: Temperature Evaluation.

I expanded on these articles in YouTube posts:

Further questions come up which I address here.

How is Nitrites Healthy?

The risk of nitrites is to a large extent dose dose-dependent and in the well-regulated meat industry, minuscule amounts are used as an effective way to protect us from potentially deadly bacteria. In the dosages that it’s used in meat curing, nitrites are healthy! To understand why, we begin by looking at the mucosa and gastric mucosa in particular.

Gastric Mucosal and Its Health

“Mucosal” refers to anything pertaining to the mucosa, which is a type of membrane that lines various cavities in the body and covers the surface of internal organs. These membranes produce mucus, a thick protective fluid. The mucosa is found in several parts of the body, including the digestive tract (from the mouth to the anus), the respiratory tract, the urogenital tract, and the eyes (in the form of conjunctiva).

Gastric mucosal integrity refers to the health, structure, and function of the stomach lining, which plays a critical role in protecting the stomach’s inner layers from the harsh acidic environment. Humans have high acidity levels in their stomachs, similar to vultures to deal with harmful bacteria that scavengers typically consume. This is a clue to our past when humans existed as scavengers. The stomach lining, or gastric mucosa, is composed of a thick layer of mucus, bicarbonate, epithelial cells, and tight junctions between these cells, all of which contribute to its integrity and function. This protective barrier is essential for several reasons:

Protection Against Acid: The stomach produces hydrochloric acid (HCl) to aid in digestion. Gastric mucosal integrity ensures that this potent acid does not damage the stomach’s own tissues.
Enzyme Activity: The gastric mucosa contains cells that produce digestive enzymes, such as pepsinogen, which is activated into pepsin by stomach acid. A healthy mucosa allows for the proper functioning of these enzymes in digesting proteins.
Mucus Production: Mucus-secreting cells in the gastric mucosa produce a thick, bicarbonate-rich mucus that coats the stomach lining, providing a physical barrier against acid and digestive enzymes and preventing damage to the lining.
Tissue Repair and Renewal: The gastric mucosa has a high turnover rate, with cells being rapidly replaced to repair any damage from the acidic environment. Maintaining the integrity of the mucosa is crucial for this continual process of renewal and repair.
Prevention of Ulcers and Erosions: By protecting the stomach lining from acid-induced damage, a healthy gastric mucosal barrier prevents the development of ulcers (deep sores) and erosions (shallow breaks).
Defensive Mechanisms: Beyond physical and chemical barriers, the gastric mucosa also plays a role in immune defence, hosting immune cells that help prevent infection by pathogens that may enter the stomach with ingested food.

Thus, maintaining the integrity of the gastric mucosa is vital for digestive health and overall well-being.

Secretion of Gastric Juices: It contains glands that produce gastric juices, which include hydrochloric acid (HCl) to lower the stomach’s pH, enzymes like pepsin to initiate the digestion of proteins, and intrinsic factors essential for the absorption of vitamin B12.
Production of Mucus: The gastric mucosa secretes a thick layer of mucus that coats the stomach lining. This mucus is rich in bicarbonate ions, creating a neutralizing layer that protects the mucosa from the acidic gastric juice, preventing self-digestion.
Barrier Function: The integrity of the gastric mucosa acts as a barrier against mechanical, chemical, and bacterial insults. This is crucial for preventing damage from the highly acidic gastric environment.
Absorption: While the stomach is primarily a site of digestion, the gastric mucosa also absorbs certain substances, such as water, electrolytes, and some drugs like aspirin and alcohol.
Immune Function: The gastric mucosa contains immune cells that are part of the gut-associated lymphoid tissue (GALT). These cells help to defend against pathogens ingested with food.

Factors that can compromise gastric mucosal integrity include chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), excessive alcohol consumption, Helicobacter pylori infection, chronic stress, and certain diseases. A compromised gastric mucosa can lead to gastritis (inflammation of the stomach lining), peptic ulcers, and an increased risk of gastric cancer.

Endogenous and Dietary Sources of Nitric Oxide

This leads us to the discussion of the benefits of nitrites because nitrites lead directly to the formation of nitric oxide especially in an environment of high acidity as found in the human stomach. Nitric oxide directly impacts the health of the stomach lining. The source of Nitric Oxide is twofold. On the one hand, it is produced endogenously by gastric mucosa cells through nitric oxide synthase (NOS) enzymes and on the other hand, it comes from dietary nitrates and nitrites. NO generally plays a vital role in maintaining gastric mucosal integrity and modulating blood flow, underlining the importance of NO in gastric health.

Let’s look at the two ways that nitric oxide is produced more closely.

-> Endogenous Production

The body produces nitric oxide through two primary pathways: the enzymatic conversion of L-arginine into NO by nitric oxide synthase (NOS) enzymes, and the non-enzymatic reduction of dietary nitrates and nitrites. In the stomach, NO can be produced endogenously by the cells of the gastric mucosa, including endothelial cells and certain types of gastric epithelial cells, through the action of NOS enzymes. This endogenous NO plays a direct role in maintaining gastric mucosal integrity, modulating blood flow, and other protective functions.

-> Dietary Sources

Additionally, dietary nitrates and nitrites, found in certain vegetables and processed meats, can be converted into NO within the stomach. This conversion process is facilitated by the acidic environment of the stomach, where nitrates and nitrites can be reduced to nitric oxide. This NO can then exert local effects, including the modulation of mucosal blood flow and protective actions against mucosal damage.

-> Systemic vs. Local Effects

While NO produced systemically (i.e., in the bloodstream and tissues outside the stomach) has widespread effects on blood vessel dilation and cardiovascular health, the NO produced locally in the stomach primarily affects the gastric lining. This local production of NO is crucial for the specific benefits mentioned, such as protecting the mucosal integrity, regulating blood flow to the mucosa, and influencing gastric motility.

Therefore, the benefits of nitric oxide to the lining of the stomach can be attributed to both endogenously produced NO by the stomach’s own cells and NO generated from dietary nitrates and nitrites within the stomach’s environment. These mechanisms highlight the significance of nitric oxide in maintaining gastric health and preventing disorders such as gastritis and peptic ulcers.

Nitric oxide (NO) has several beneficial effects on the gastrointestinal tract, including the lining of the stomach, due to its roles in various physiological processes. Here are some key benefits:

I give the benefits of NO but I categorise the effects as stemming from local production within the stomach which is derived from dietary sources such as cured meats or systemic effects throughout the body, and noting which benefits are derived from both:

— Regulation of Blood Flow (Local and Systemic)

Local: Nitric oxide locally produced in the stomach’s mucosal cells induces vasodilation, enhancing blood flow to the gastric lining. This local effect is critical for the repair and maintenance of the gastric mucosa and for the efficient transport of nutrients and oxygen.
Systemic: Systemically produced NO also plays a role in overall vascular health, promoting blood flow throughout the body, including the gastrointestinal tract. This systemic action supports the local effects of maintaining gastric health.

— Protection of Mucosal Integrity (Local)

Local: NO’s role in protecting the gastric mucosa is primarily local. It defends against damage from acidic gastric juices and protects against ulcer formation by promoting mucus production. This action creates a protective barrier between the stomach lining and the acidic environment.

— Anti-inflammatory Effects (Local and Systemic)

Local: Locally produced NO within the stomach lining has anti-inflammatory properties that reduce inflammation, crucial for preventing and healing gastritis and ulcers.
Systemic: NO produced in other parts of the body contributes to a general anti-inflammatory response that can also benefit gastric health by reducing systemic inflammation that could otherwise affect the stomach.

— Modulation of Gastric Motility (Local)

Local: The modulation of gastric motility by NO is a local effect. NO acts as a neurotransmitter in the enteric nervous system, influencing the relaxation of smooth muscle in the gastrointestinal tract, thereby regulating gastric emptying and intestinal transit time.

— Antimicrobial Activity (Local)

Local: The antimicrobial properties of NO in the stomach are a local phenomenon. NO helps defend against pathogenic bacteria in the stomach, maintaining a healthy balance of gut flora and protecting the stomach lining from infections that could lead to gastritis or ulcers.

— Healing and Repair (Local and Systemic)

Local: In the stomach, NO directly contributes to the regeneration of the gastric mucosa following injury or irritation. This local effect is crucial for healing ulcers and preventing chronic gastric diseases.
Systemic: Systemic production of NO can support overall tissue repair and healing processes throughout the body, indirectly benefiting gastric health by promoting a conducive environment for healing.

By categorizing the effects of nitric oxide into local and systemic actions, it becomes clear how NO’s diverse roles are crucial for both the direct maintenance of gastric health and its contribution to overall physiological well-being. The value of cured meat is undeniable because of its nitrite content coupled with the ascorbate (vitamin C) which is always added wherever nitrite is used for curing.

The Chemistry of Amines, Nitrites, and Ascorbate

We have previously considered the fact that combining nitrite with ascorbate in cured meat formulations mimics the occurrence of nitrate in leafy green vegetables where it co-exists with vitamin C. It decisively mitigates the risk of nitrosamine formation in the cured meats and when ingested together when I summarised some of my work in EarthwormExpress in The Role of Ascorbate in the Nitrate-Nitrite-Nitric Oxide Pathway: Integrating Insights from Earthworm Express.

I deal with the history of the nitrosamine controversy as it impacted bacon production and the mandatory inclusion of vitamin C in curing brines in Chapter 15.06 of Bacon & the Art of Living, Regulations of Nitrate and Nitrite post-1920’s: The Problem of Residual Nitrite. The relevance of repeating the discussion within the context of the physiological value of nitrite in the human stomack is that this reaction, nitrites and Vitamin C, is what created nitric oxide from nitrite. Yes, it also prevents nitrosamine formation, but as I have explained in “The Low Risk of Nitrosamine and Amine Formation in Bacon: Temperature Evaluation” amines are unlikely to be formed from frying bacon and even if amines should be foemed in miniscule concentrations, vitamin C will prevemt the reaction with nitrosamines. In the reamining part of this article I will say a few more things about this reaction. The overwhelming different note to this particular article is the emphasis on the fact that nitrites is beneficial! Its beneficial nature stems from its marriage with Vitamin C in the cured meat brine, as it is in leafy green vegetables as well as the elevated acidity levels we have as humans with the birth of our evolutionary path, as scavangers.

A question comes up related to the reaction in the stomack between amines, vitamin C and nitrites which I want to adress briefly.

When ingested together, ascorbate prefers to react with nitrites, forming nitric oxide rather than allowing nitrites to interact with amines to create potentially harmful nitrosamines. This preference is due to ascorbate’s reducing properties, showcasing its protective role in the diet. The question comes up as to why the reaction of vitamin C is with nitrite and not also with the amines.

When ingested together, ascorbate (vitamin C) reacts with nitrites before amines do due to its strong reducing properties. Ascorbate is a potent antioxidant, meaning it can readily donate electrons to other molecules. Nitrites, under acidic conditions (such as those in the stomach), can form nitrosating agents, which are capable of reacting with amines to form nitrosamines. Nitrosamines are concerning because some are carcinogenic. However, the presence of ascorbate inhibits the formation of nitrosamines by reducing nitrite to nitric oxide, thereby preventing the nitrites from reacting with amines to form nitrosamines.

The reaction between ascorbate and nitrite is favoured first due to the redox potential of ascorbate, which makes it a preferred electron donor in the presence of nitrite, reducing nitrite to nitric oxide and other non-harmful molecules before the nitrite has a chance to interact significantly with amines to form nitrosamines.

As for the reaction between amines and ascorbate, under normal dietary conditions, this interaction is minimal and not of significant concern. Amines and ascorbate do not readily react with each other in the body under normal conditions. Ascorbate, through its reduction of nitrites and its role as an antioxidant, primarily acts to prevent harmful reactions rather than engage in direct reactions with amines.

Conclusion

The exploration of nitrites, their role in the diet, and their impact on health as delineated in “Navigating Nitrites: Understanding Their Role in Diet and Health” and subsequent articles and YouTube posts, presents a nuanced view of this often misunderstood compound. By delving into the historical context, the biochemical pathways, and the balance between potential risks and benefits, this body of work highlights the complexity of dietary nitrites. It challenges prevailing perceptions, particularly concerning nitrosamines and their association with cancer risk, and illuminates the positive aspects of nitrite consumption within regulated limits. The discussion extends beyond the confines of nitrites alone, considering the broader implications for food safety, nutritional science, and public health. It underscores the importance of a balanced perspective that acknowledges both the protective measures inherent in our dietary practices and the evolutionary adaptations that have shaped human interaction with food. This comprehensive analysis not only contributes to the scholarly discourse on nitrites but also offers practical insights for consumers seeking to make informed dietary choices.

References

“EarthwormExpress.” Insight into the historical use and dietary significance of nitrites.
“The Role of Ascorbate in the Nitrate-Nitrite-Nitric Oxide Pathway: Integrating Insights from Earthworm Express.” Analysis of ascorbate’s role in mitigating nitrosamine formation.
“Savouring the Safety: The Evolutionary Journey of Nitrosamine Risk Mitigation in Bacon.” Evolutionary perspective on dietary changes and nitrosamine risks.
“Bacon is Safe: Evaluating Frying and Perspectives from Evolution.” Examination of cooking practices and their implications for nitrosamine formation.
“Amines, Nitrosamines, Nitrite, and Bacon as a Superfood.” Discussion on the nutritional benefits of bacon when considering nitrite content and potential health risks.
“Balancing Gut Acidity, Diet, and N-Nitrosamine Risks.” Exploration of dietary factors influencing gut health and nitrosamine risk.
Hord, N.G., Tang, Y., Bryan, N.S. “Food sources of nitrates and nitrites: the physiologic context for potential health benefits.” American Journal of Clinical Nutrition, 2009.
Lundberg, J.O., Weitzberg, E., Gladwin, M.T. “The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics.” Nature Reviews Drug Discovery, 2008.
Sindelar, J.J., Milkowski, A.L. “Human safety controversies surrounding nitrate and nitrite in the diet.” Nitric Oxide, 2012.
Tsoukalas, D., Fragoulakis, V., Sarandi, E., Docea, A.O., Papakonstantinou, E., Tsilimidos, G., Tsatsakis, A.M., Calina, D., Drakoulis, N. “Dietary Intake of Nitrate and Nitrite and Risk of Colorectal Cancer: A Systematic Review and Meta-Analysis of Prospective Studies.” Cancer Epidemiology, Biomarkers & Prevention, 2019.

This list includes a mix of primary research articles, reviews, and the author’s own publications to provide a comprehensive foundation for the conclusions drawn in the paper.