Supplementation with nitrate and nitrite salts in exercise: a word of caution

Journal Title (Medline/Pubmed accepted abbreviation): J. Appl. Phyiol.
Year: 2011
Volume: 111
Page: 616-617
doi: 10.1152/japplphysiol.00521.2011

Letter to the editor


A number of recent papers have found performance enhancing effects for nitrate supplementation, either in the form of sodium nitrate supplementation or consumption of naturally occurring nitrate in beetroot juice.  In the body, nitrate is converted to nitrite (NO2-), and then further reduced to nitric oxide (NO).  NO is likely responsible for ergogenic effects related to lower oxygen cost per unit of ATP produced.  The authors did raise a note of caution, however, because of potential linkages of nitrite to methemoglobinemia, which can greatly decrease the oxygen carrying capacity of the blood and create a life threatening situation in some cases.  The authors there did not recommend supplementation of nitrite salts.  The authors expressed less concern regarding supplementation of nitrates, though, because of the low conversion rate to nitrites in vivo.  This is especially true for nitrate-rich vegetables like beets and spinach, which have long been recognized as a key part of a healthy diet. 
                Additional EAS Academy note: The potential health risks of nitrate supplementation are still very much a matter of debate.  First, some case reports do describe cases of methemoglobinemia (“blue baby syndrome”) in infants exposed to well water.  The methemoglobinemia was originally attributed to a high nitrate content in the well water.  As pointed out in a review article by Hord et al. (Am J Clin Nutr 2009;90:1-10), though, it appears that nitrate exposure alone is not sufficient to produce methemoglobinemia.  The presence of a concomitant gastrointestinal infection or contamination of well water with bacteria that convert nitrate to nitrite seems to be necessary to act in conjunction with high nitrate exposure to produce methemoglobinemia.
                Second, nitrates and nitrites have been used for many years as preservatives for foods such as processed meats.  It has been proposed that nitrate/nitrite consumption can lead to the formation of carcinogenic N-nitroso compounds when they react with secondary amines or n-alkylamides in the intestine.  However, in the article by Hord et al. it is noted that while there might be evidence for carcinogenicity of some N-nitroso compounds in animals, not all of these compounds are direct mutagens (some requiring metabolic activation by P450 enzymes) and there is scant evidence of carcinogenicity in humans.  Further, the use of antioxidants such as vitamin C or sodium erythorbate typically accompanies the use of nitrates/nitrates in food and would reduce nitrosation potential.  This calls into question how representative animal and in vitro studies are of the in vivo situation in humans.  It will be interesting to see how the risk:benefit ratio of nitrate supplementation develops as new research becomes available.

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