dietary nitrates, nitrites and nitrosamines, processed meats and some vegetables

see also:

• foods that may be toxic or bad for you

• N-nitrosamines are carcinogenic and in the GIT appear to be a significant contributory cause of stomach cancer, oesophageal cancer and perhaps colorectal cancer (bowel cancer)
• nitrosamines in the gut may form from dietary nitrites which may already be in the food or may form from dietary nitrates, and the risk seems highest when processed meats with nitrites are fried (eg. bacon)

• nitrites can combine with amino acids from proteins to form N-nitrosamines (N-NAs)
  • this is particularly likely when nitrites and protein are heated during cooking but can also occur in the gut perhaps due to microbiome enzymic activities
  • this can be reduced by presence of anti-oxidants such as ascorbic acid
    • hence risk of this from dietary nitrates in vegetables is lower if there are concomitant anti-oxidants (eg. citrus fruits, capsicum, broccoli, kale, spinach, tomatoes)
  • this can be enhanced by oxidants such as presence of heme
    • heme is a porphyrin ring with a single iron atom that forms the core of haemoglobin and myoglobin and hence is present in red meats in particular but also in white meats
    • frying meats causes minimal breakdown of heme (~10-15%) whereas prolonged cooking, stewing, braising, boiling, baking or microwaving have much higher heme breakdown rates
    • thus fried bacon in particular, provides the heat, the nitrites, the protein and the heme to facilitate formation of nitrosamines
• from cured meats:
  • 15 different N-NAs have been identified in meat derivatives such as sausages, salami, and bacon, the specific types and concentrations of N-NAs in food are influenced by multiple factors, including meat type, the presence of amino and carbonyl precursors, storage duration, and processing conditions such as temperature, pH, smoking intensity, and fermentation processes²⁾
  • in the European study, among adults, nitrite intake was primarily attributable to animal sources and 12 to 19% of individuals exceeded the acceptable daily intake (ADI)³⁾
• from dietary nitrates
  • it is estimated that up to 97% of total human exposure to N-NAs results from endogenous nitrosation, a process in which dietary nitrate is reduced to nitrite — primarily by oral and gut microbiota — which subsequently reacts with amines to form N-NAs⁴⁾

• nitrites are needed in cured meats to prevent botulism and currently there has not been found a suitable alternative
• just adding pure salt to meat does little to prevent botulism, but it will delay the meat going off from other bacteria
• a bit of history:
  • nitrates had been used in curing meats for centuries
    • initially as incidentally contaminated with salt
    • later in the 16thC, it was intentionally added by adding saltpetre (potassium nitrate or in Chile, Chilean saltpetre which is sodium nitrate) which was also a critical ingredient of gunpowder
  • when it was found that the nitrate was being converted to nitrite by bacteria in the meat and it was the nitrite that was the actual active ingredient, in the 1920's nitrite was added instead of nitrate which allowed more precise and lower amounts to be added with confidence) as they solve several problems:
    • nitrite prevents Clostridium botulinum spores from germinating and producing botulinum toxin
    • nitrite via nitric oxide formation binds myoglobin to keep it pink instead of going grey (discovered by Haldane in 1901)
    • nitrite reduces the rate the fat goes rancid
  • a short history of botulism from cured meats:
    • Kerner, a German doctor documented over 200 cases of sausage poison between 1817-1822 which he supposed was from a toxin in food - and it was called Kerner's disease or, later botulism (from the Latin for sausage) - the bacterium was found 70 yrs later after another outbreak from ham and the toxin was given its name

• in the early 1970's it was discovered that the nitrite when heated with proteins as in cooking bacon, resulted in the production of nitrosamines which were found to be carcinogenic hence in 1978 it was mandated that ascorbate or erythrobate was added to bacon to reduce the formation of nitrosamines
• in 1978, a rat study showed being fed nitrites resulted in twice the rate of lymphomas but 2 years later the study was reviewed and found to be erroneous and there was no evidence that lymphoma rates were increased.
• in 2015, the WHO International Agency for Research on Cancer concluded that processed meats were Group I carcinogens which indicates confidence in evidence that they can cause cancer but does not ascribe what that risk is which was given as being there is a 18% higher risk of colorectal cancer per 50g per day intake of processed meat
• a higher risk of colorectal cancer has been reported when higher intakes of nitrates were consumed with lower vitamin C (83.9 mg/d) or higher red meats (≥ 43.5 g/d)⁵⁾
• in 2023, the European Food Safety Authority (EFSA) published the findings on public health implications associated with the presence of N-nitrosamines (N-NAs) in the food supply
• in 2023-2025, Europe lowered the permissible amounts of nitrite to a level which still minimised the risk of botulism and thus bacon is much safer now
• a 2026 14 year prospective European “EPIC” study of 450,000 people showed a 30 g/day increase in processed meat consumption was associated with a 9% (95% CI: 2-17) increase in gastric cancer risk and a 13% (95% CI: 0-27) increase in oesophageal adenocarcinoma risk. The study also appeared to show an increased risk of gastric cancer in women consuming white meat but not in men - a result suggesting more research is needed to validate this. ⁶⁾

• total dietary exposure to nitrites is usually set at 0.07 mg nitrites/kg bw/day but most people would exceed this, especially infants eating processed meats⁷⁾
• nitrites may be present either via:
  • addition of nitrites to foods such as cured meats
  • conversion from nitrates in food via bacteria (see below under nitrates)
    • eg. “uncured meats”, certain vegetables
  • nitrites naturally occurring in foods
• a higher nitrite intake in men was linked to higher rates of colorectal cancer (bowel cancer)
• possible increased risk of thyroid cancer in women

• acceptable daily intake (ADI) of nitrates in the European Union is 3.65 mg/kg of body weight
• nitrates are the main source of nitrogen for terrestrial plants
• mainly found in:
  • “uncured meat” products with “no added nitrates or nitrites”
    • this is actually misleading as they usually add nitrates via adding celery and a starter culture of the right bacteria to convert it to nitrite which is back to the imprecise Medieval method but it is required to be labeled uncured as it does not have synthetic additives but only biologic additives
  • 80% of dietary nitrates come from leafy vegetables, celery and beetroot
    • arugula, spinach, and lettuce have the highest nitrate content with beetroot and celery ranking in the next place⁸⁾
    • concentration largely depending on geographics, seasonality and the cultivation system
    • the highest accumulation of nitrates is observed in the stems, peduncles, and leaves of plants
  • other potential exposures⁹⁾
    • polluted wells and groundwater from fertilizer run off, treatment of water with chloramines, oxidation of ammonia from human and animal waste, etc
      • maximum permissible concentration of nitrates in drinking water is often set at 50 mg/L
      • this is a major problem in South-West Romania and other countries
      • in 1991, the Nitrates Directive (Journal of Laws UE.L.1991.375.1 of 1991.12.31)) was drawn up to reduce and monitor nitrate pollution of water supplies aimed at protecting human health and aquatic ecosystems.
    • PM atmospheric exposures and contamination of foods etc,
      • the use of nitrogen oxide-rich manure in agriculture is a major contributor to nitrogen-rich particulate matter emissions
    • anti-sensitivity tooth paste
    • breast milk
    • salivary concentration of nitrates
      • content of nitrates in saliva is about 10 times higher than nitrates in plasma
      • these nitrates are reduced to nitrites by commensal bacteria, and then to biologically active nitric oxides (NO and NO2) and potentially to nitrosamines
        • this may be increased if HCl acid secretion is disturbed
    • endogenous production via production of nitric oxide (NO)
      • L-arginine is metabolized to citrulline with the formation of NO in a pathway that is catalyzed by nitric oxide synthases
    • medications:
      • some antidiarrhoeals, diuretics, vasodilators, nitrosourea
• potential effects
  • production of nitrites and their issues (see above)
    • human cells cannot reduce nitrate to nitrite but bacteria can
    • uncured meats with bacterial culture conversion of nitrate to nitrite
    • GIT microbiome actions
      • anaerobic bacteria can convert 20% of nitrates into nitrites ¹⁰⁾
  • vasodilational effects via production of nitric oxide
    • potential benefits such as blood pressure regulation, improved vascular endothelial function, and enhanced tissue insulin sensitivity
    • potentially reduces cardiovascaulr risk in the DASH diet which is 550% of the daily allowable intake of nitrates for an adult
    • possible anti-inflammatory effects
    • potential for hypotension especially in those already on antihypertensive agents
    • potential headaches and migraines
      • it is well known that topical nitrates such as GTN cause headaches
        • nitrate-induced headaches typically manifest in one of two ways:
          • “immediate” headaches with mild to medium severity developing within an hour of medication ingestion
            • thought to be due to NO induced vasodilatation
          • “delayed” headaches occurring 3 to 6 h after nitrate intake that are much more severe, with migraine-like symptoms
            • these are more dose dependent and more likely in those with a FH of migraines
            • the mechanism is thought to be NO stimulation of CGRP release, glutamate, cyclic GMP (cGMP), or S-nitrosylation-mediated changes in ion channel function
      • migraine sufferers appear to have a significantly higher abundance of nitrate-reducing bacteria in their mouths and guts than non-sufferers¹¹⁾
  • nitrates increase risk of aberrant S-nitrosylation
    • this is a chemical process whereby a molecule related to nitric oxide (NO) binds to sulfur (S) atoms within proteins (producing “SNO”)
    • aberrant S-nitrosylation reactions contribute to some forms of cancer, autism, Alzheimer's disease, Parkinson's disease and other conditions
      • S-nitrosylation of protein CRTC1, impairs its ability to regulate genes that are critical for forming and maintaining connections between brain cells, an essential process for learning and long-term memory¹²⁾
  • may cause methaemoglobinaemia
    • usually only in infants with very high intakes (eg. contaminated well water or large intakes of nitrate vegetables)
  • adverse thyroid effects
    • nitrates can interfere with gastrointestinal iodine absorption by inhibiting Na+/K + ATP-ase
    • thyroid gland can concentrate monovalent anions, i.e. nitrates, leading to inhibition of iodine uptake
    • nitrates can also interfere with thyroid function by binding to the sodium iodide symporter, thereby interfering with iodide uptake by the thyroid gland
    • maternal exposure to nitrates has been shown to reduce iodine uptake and may result in increased TSH levels in newborns
    • combined exposure to perchlorates, nitrates, and thiocyanates may affect maternal thyroid function and TSH rise during pregnancy and there is a possibility that exposure to these compounds may impair growth in girls aged 6–8 years¹³⁾
    • a deficiency of selenium in combination with an increased amount of nitrates may have a negative impact on the iron and iodine status of postpartum women
    • the effect of nitrates on thyroid function can be strong in the presence of dietary iodine deficiency but when there is adequate dietary iodine, the effect is weak
    • genetic factors may be important in this relationship
  • may have benefits in exercise:¹⁴⁾
    • beet juice (BJ):
      • the International Olympic Committee classified beet juice alongside caffeine, β-alanine, creatine as a dietary supplement that can improve athletic performance when taken in the right dosage and in a specific type of exercise.
      • BJ is a source of dietary fiber, minerals such as calcium, iron, sodium and potassium as well as a number of antioxidant compounds, including betalain.
      • the effects of BJ on physical performance have been attributed to the high levels of inorganic nitrate found in this product (< 250 mg per 100 g of fresh BJ)
      • maximum serum NO2 concentrations are seen 2–3 h after nitrate supplementation
      • nitrate from BJ increases blood flow to type 2 fibers leading to improvements in resistance training, modulates contractile function by modulating Ca2 + handling, increase mitochondrial function reducing oxygen cost during muscle contraction