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The Truth About Nitrates and Nitrites

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Most of the concern about the safety of nitrates has arisen from epidemiological data on their potential to form N-Nitrosamines; these are thought to be cancer causing and also responsible for causing “blue-baby” syndrome. However, one must be careful in evaluating the data and when drawing any conclusions.

Let us review the data for both these concerns.

i) Blue-baby syndrome (methemoglobinemia)

One case back in the 1950’s caused considerable sensation when a baby’s hemoglobin was thought to be compromised by supposedly excessive nitrates in well water and converting the hemoglobin to a form that was not able to transport oxygen easily. However, the infant was living in a rural area and the well water had higher burden of bacterial load that was likely the culprit and not the nitrates per se.

Additionally, there have been few if any cases of methemoglobinemia. When nitrates and/or nitrites are injected (through i.v.) there is little or no change in the hemoglobin status. In other words, there is little or no conversion of hemoglobin into methemoglobin. So nitrates causing blue-baby syndrome seems highly unlikely as a health concern.

ii) N-Nitrosamine formation associated with consumption of “cured” meats (meat treated with cured meatnitrates/nitrites for preservation), again one must review the data carefully.

In any scientific debate, it is important to understand the strengths and limitations of epidemiological research (the study of disease in populations).

  • Foods are heterogenous (made of different substances) and complex in terms of their composition and contribution to the overall diet; ascribing an individual component of food as ‘‘good” or ‘‘bad” is fraught with difficulty due to many confounders.
  • There are other components (or confounders) that are likely to be present in the consumption of meat that unfortunately and erroneously implicate nitrates as posing a health risk including:

A)      Saturated fats

B)      Pesticides

C)      Hormones

D)     Biological e.g. high bacterial loads

E)      Other harmful chemicals

F)      Toxins

G)     Cooking practices e.g. charring of food which produces known carcinogens.

Interpretation of epidemiological studies demands careful criteria to assess their validity:

1. Strength of association – The magnitude of the effect demonstrated

2. Exposure to a potential cause must precede the disease

3. Consistency – Are there similar findings in many studies without contradictory results?

4. Theoretical plausibility – Does biological/physiological/metabolic knowledge support the findings

5. Coherence – Are there no alternate hypotheses?

6. Specificity – No confounding factors are found

7. Dose-response – Is there a higher risk with higher exposure?

8. Experimental – Animal and in-vitro studies show the effect.

Some misconceptions about interpreting such studies include:

1.       Statistical significance should not be mistaken for evidence of a substantial association.

2.       Association does not prove causation (other evidence must also be considered).

3.       Uncertainty about whether there is a causal relationship (or even an association) is not sufficient to suggest action should not be taken.

In the last 20 years there is accumulating evidence that nitrates are beneficial for health. This includes:

  • Mediterranean, Japanese and DASH diets – ALL of which are very high in nitrate content. In some cases up to 20 times! All these diets are supported in the literature for their health benefits. In fact most physicians recommend such diets to their patients.
  • Many TCM formulas for heart health are extremely high in nitrate content. In fact their high nitrate content explains their benefit. These formulas have been used for over thousands of years as proof for their safety and efficacy.
  • Mother’s milk is very rich in nitrate content by several folds which reduces as the infant ages. If nitrates were an issue for methemoglobinemia then why does nature ensure such high concentrations?
  • People living at high altitudes (i.e. Tibet) have very high levels of nitrate levels. These levels are physiologically important to allow adapting to the poor oxygen concentrations at these high altitudes.
  • Recent data from the UK, Sweden and the US supports that certain vegetables rich in nitrates like kale, spinach, bok-choy, celery and beet root have extremely high nitrate content and are beneficial when consumed. (For example a typical plate of salad contains around 1200mg of nitrate which is 3-4 folds higher than that allowed by WHO or Health Canada. Yet, how often has eating salads been associated with disease or health risk?)

Other studies also call into question whether nitrates pose any health risk:

  1. Occupational exposure to very high levels of nitrate occurs in fertilizer workers, who have elevated body burdens of nitrate and elevated salivary nitrate and nitrite levels, yet they show no increased incidence of gastric cancers.
  2. Studies in Canada, Italy, Sweden and Germany involving thousands of study subjects have failed to show any association of risk rather have demonstrated an inverse association between estimated nitrate intake and gastric cancer.
  3. In a review of 14 epidemiological studies, 13 of which were case-control studies, Blot et al. could not conclude any relationship between cured meat consumption during pregnancy and brain or any other cancers. It may be that in the limited number of epidemiological studies linking nitrate, nitrite or cured meats to a specific cancer site, other as yet uncharacterized dietary or environmental factors may be involved instead.

Animal data does not support the contention that nitrates are toxic or carcinogenic! For example:

In 2000, the results of a comprehensive battery of rodent carcinogenicity and mutagenicity studies by the U.S. National Toxicology Program (NTP), including a standard, 2-year chronic cancer bioassay of sodium nitrite in rats and mice, were presented to the NTP Technical Reports Review Subcommittee for evaluation. Remember this is nitrite and not nitrates. The final NTP Technical Reportindicated that the only adverse finding in both rats and mice was an ‘‘equivocal evidence” finding that sodium nitrite weakly increased the number of forestomach tumors in female mice but not in male mice or male or female rats. All other organ sites in both rats and mice showed no evidence of carcinogenicity. In short, any suspicion of sodium nitrite’s carcinogenicity in rodents was not supported by this state-of-the-art cancer bioassay study. Shortly thereafter, in 2000, nitrite was also reviewed and evaluated for potential listing as a developmental and reproductive toxicant under the Proposition 65 Statute in California. A review of 99 studies on sodium nitrite led the state’s Developmental and Reproductive Toxicant Identification Committee of eight independent scientists to conclude that sodium nitrite should not be listed as a developmental toxicant or as a male or female reproductive toxicant under California’s Proposition 65 law.

Nitrate/nitrite is a reservoir for NO, an important signalling molecule with a myriad of health benefits including:

  • Immunity and increasing resistance to pathogens
  • Reduction of blood pressure
  • Improvement of the functioning of endothelial cells, possibly the hall-mark in cardiovascular health.
  • Improvement of cardiovascular functioning in conditions of poor circulation
  • Counteracts the effects of ischemic heart disease like angina
  • Improves exercise physiology of muscles i.e. has an oxygen sparing effect.
  • Effective in disease conditions where there is poor oxygen status i.e. asthma, COPD (chronic obstructive pulmonary disease), angina, chronic kidney disease and high altitude or mountain-sickness.
  • Gastric protection against H pylori and healing of inflamed mucous membranes.

In summary nitrates have been incorrectly projected as villains yet in reality they have key health promoting health effects.

Let me know your thoughts on nitrates and nitrites in the comments below.

You may also be interested in:

“The NOx Pathway: There’s NOthing Like It!”
“Nitric Oxide’s Role in Modern Medicine”

Image by © 2013 Milles Studio via DollarPhotoClub

References:

W.J. Blot, B.E. Henderson, J.D. Boice Jr., Childhood cancer in relation to cured meat intake: review of the epidemiological evidence, Nutr. Cancer 34 (1999) 111–118.

H. Moller, Adverse health effects of nitrate and its metabolites: epidemiological studies in humans, in: P.o.t.I. Workshop, (Ed.), Health Aspects of Nitrates and its Metabolites (Particularly Nitrite), Council of Europe Press, Strasbourg Cedex, France, 1995, pp. 255–268.

National Toxicology Program, NTP Technical Report on the toxicology and carcinogenesis studies of sodium nitrite (CAS NO. 7632-00-0)IN F344/N rats and B6C3F1 mice(drinking water studies), NIH Publication No. 01-3954, 2001, pp. 7–273.

D.L. Archer, Evidence that ingested nitrate and nitrite are beneficial to health, J. Food Prot. 65 (2002) 872–875.

C. Duncan, H. Li, R. Dykhuizen, R. Frazer, P. Johnston, G. MacKnight, L. Smith, K. Lamza, H. McKenzie, L. Batt, D. Kelly, M. Golden, N. Benjamin, C. Leifert, Protection against oral and gastrointestinal diseases: importance of dietary nitrate intake, oral nitrate reduction and enterosalivary nitrate circulation, Comp. Biochem. Physiol. A Physiol. 118 (1997) 939–948.

R.S. Dykhuizen, R. Frazer, C. Duncan, C.C. Smith, M. Golden, N. Benjamin, C. Leifert, Antimicrobial effect of acidified nitrite on gut pathogens: importance of dietary nitrate in host defense, Antimicrob. Agents Chemother. 40 (1996) 1422–1425.

R.S. Dykhuizen, A. Fraser, H. McKenzie, M. Golden, C. Leifert, N. Benjamin, Helicobacter pylori is killed by nitrite under acidic conditions, Gut 42 (1998) 334–337.

M. Eichholzer, F. Gutzwiller, Dietary nitrates, nitrites, and N-nitroso compounds and cancer risk: a review of the epidemiologic evidence, Nutr. Rev. 56 (1998) 95–105.

N.S. Bryan, J.W. Calvert, J.W. Elrod, S. Gundewar, S.Y. Ji, D.J. Lefer, Dietary nitrite supplementation protects against myocardial ischemia–reperfusion injury, Proc. Natl. Acad. Sci. USA 104 (2007) 19144–19149.

Y. Tang, H. Garg, Y.J. Geng, N.S. Bryan, Nitric oxide bioactivity of traditional Chinese medicines used for cardiovascular indications, Free Radic. Biol. Med. 47 (2009) 835–840.

J.O. Lundberg, E. Weitzberg, NO generation from nitrite and its role in vascular control, Arterioscler. Thromb. Vasc. Biol. 25 (2005) 915–922.

J.O. Lundberg, E. Weitzberg, J.A. Cole, N. Benjamin, Nitrate, bacteria and human health, Nat. Rev. Microbiol. 2 (2004) 593–602.

C. Dezfulian, N. Raat, S. Shiva, M.T. Gladwin, Role of the anion nitrite in ischemia–reperfusion cytoprotection and therapeutics, Cardiovasc. Res. 75(2007) 327–338.

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