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A study published in PLOS Medicine looks at dietary exposure to nitrites and nitrates and type 2 diabetes risk.
Prof Tom Sanders, Professor emeritus of Nutrition and Dietetics, King’s College London, said:
“About 1 in 12 adults in the UK has type 2 diabetes and of these 90% are overweight or obese. Previous studies have shown high intakes of red and especially processed meat are associated with a greater risk of type 2 diabetes, and it has generally been assumed that this because these foods are associated with unhealthy weight gain. Current healthy eating advice discourages the consumption of meat products especially those high in fat, salt or preserved with nitrate/nitrites. In the UK, potassium and sodium salts of nitrates/nitrites are permitted food additives to preserve meat products (mainly those of pork e.g. bacon, ham, pate, sausages, salami). Nitrate itself has no preservative properties until it is converted to nitrite by bacteria during pickling. Nitrite reacts with myoglobin and prevents the growth of the deadly toxin Clostridium botulinum. However, nitrite can also react with amino acids to form nitrosamines (known carcinogens) that can also damage the beta-cells in the pancreas that produce insulin. So it is reasonable to suspect that foods preserved with nitrate/nitrite might increase the risk of type 2 diabetes.
“This French observational study reports a 27% increase in risk of developing type 2 diabetes in those with highest total dietary nitrite intake. No relationship of total nitrate intake or nitrate additives to risk of type 2 diabetes was found. Food and water provided most of the estimated nitrite intake. Food additives only accounted 0.3 mg out of the total intake of 5.7 mg nitrite in the whole cohort. The tertile with the highest intake of nitrite additives (0.51 mg) also had far higher intake total nitrite intake 8.0 mg vs 3.3 mg than in the lowest tertile nitrite additive intake (0.14 mg); they also consumed more red meat and processed meat products (an additional 20 and 9g/d respectively) so they differed in other ways. The authors then report that risk of type 2 diabetes was 53% higher in those with the highest intake sodium nitrite. This focus is surprising because nitrite/ nitrate containing additives are normally used in tandem and both would be expected to contribute to the generation of nitrosamines in the foods to which they are added. In my opinion, there was no justification singling out sodium nitrite especially as comparison, which are not prespecified, can throw up spuriously findings.
“The fundamental weakness of this study is how the food additive intake was assessed. Other limitations are the relatively young age of the cohort and the relatively low incidence of new cases of type 2 diabetes (about 1% of the study population over 7 years). Estimates of intake were based on recalls of dietary intake on two separate occasions at the beginning of the study with no further estimates in the follow up period of over 7 years. Diet recalls are inferior to the more widely used food frequency questionnaires that measure diet intake over a longer period. A 24 h diet recalls only give a broad-brush picture of dietary intake and lack the granularity of detail required to estimate food additive intake (such as product names). The researchers had to guess which foods contain the various nitrite and nitrate additives, the levels used in the products and the amounts of the food consumed. The levels of nitrite provided as food additives in this study on average was 0.51 mg/d and as most participants were female and an average body weight of 60 kg can be assumed which gives an intake of 0.009 mg/kg/body weight per day which is much lower than the ADI (acceptable daily intake) of 0.07 mg/kg body weight/d and is almost 7 times lower than the minimum exposure assessment made by European Food Safety Authority (EFSA) which was 0.06 mg/kg body weight/day and 69 lower than the 95th centile exposure estimate of 0.55 mg/kg body weight/day. These large differences raise serious concerns about the accuracy and veracity of the data reported in this paper.
“The researchers made estimates of nitrite/nitrate content based on international guidelines provided by the Codex Alimentarius Commission for use of nitrite/nitrate additives in food from Codex Alimentarius and not the European Regulations that control the use of the additives and specify levels and types of foods in which they are permitted in EU countries including France. This seems strange as the EFSA had comprehensively reviewed both nitrite/nitrite additives and the authors could have used a much more accurate and appropriate source of data to make their calculations.
“In my opinion, for reasons given above, the data reported in this paper are unreliable. If other researchers are able replicate this association of risk of type 2 diabetes with nitrite intake with appropriate adjustment for differences in body weight, it would provide ammunition for further controls on the use of nitrite/nitrate containing additives especially as there are alternatives methods of preservation.
“EFSA Panel on EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) Re-evaluation of potassium nitrite (E 249) and sodium nitrite (E 250) as food additives. EFSA Journal 2017, e04786, https://doi.org/10.2903/j.efsa.2017.4786″
Prof Gunter Kuhnle, Professor of Nutrition and Food Science, University of Reading, said:
“Nitrites and nitrates are fascinating compounds that are a great example of the big problem in nutrition research: some people believe that they are healthy and improve heart health – and nitrate-rich foods such as beetroot are promoted for that – and some people believe that they increase the risk of cancer and many other diseases. Both is supported by evidence, and it is very difficult for scientists and the consumer to navigate the facts. This is exacerbated by political and commercial interests to ban nitrite and nitrate and promote nitrate free alternatives. But this study does not support that additives are responsible for an increased risk for type 2 diabetes.
“Nitrate is found in most vegetables, but the content is very variable depending on growing condition. There is a very good database [1] that content varies up to 10,000 fold for some foods. It is also found in drinking water and it is used as food additive. Nitrite is also found in vegetables and drinking water – and used as food additive. To make this more complicated, nitrate can be converted into nitrite by bacteria – for example in fermented meat products (such as salami) but also the oral microbiome. Nitrite can form nitric oxide in the body and lower blood pressure – something that is used extensively when marketing certain foods. However, nitrite can form carcinogenic nitrosamines in the intestinal tract and is a likely explanation for the link between red and processed meat intake and colorectal cancer. For this reason, there has been considerable research into nitrite replacement – but also political and commercial campaigns calling for a ban on nitrite.
“Investigating the impact of nitrite and nitrate on health is difficult outside of controlled intervention studies, as the food content is very variable. A portion of salad could contain anything from 1 mg to 10g of nitrate and it is impossible to know the actual content without measuring a sample. The study by Srour and colleagues uses average values and therefore do not have a very reliable measure of intake – which raises a lot of questions about the results. Even though they divide intake into categories, this is often not sufficient to address this variability.
“Following on from that, it is very difficult to attribute the results to nitrate and nitrite, but rather a specific dietary pattern. The authors show that those in the highest category of nitrite intake consume a diet commonly seen as “healthy” with less added sugar, less “ultra-processed food” and more fruits and vegetables than those in the lowest category – but also more sugar, saturated fat, processed meat and alcohol. The authors find that these people have a higher risk of developing type 2 diabetes, but the data do not really allow to attribute this to nitrate and nitrite intake, but rather to their dietary pattern. A high intake of sugar and meat has been associated with an increased risk of type 2 diabetes, and it is not obvious why this should not explain at least some of the observations seen.
“Notably, the study does not support the claim in the press release and paper that food additives are responsible for the increased risk: nitrite from additives contributes only about 4-6% of total nitrite intake in the population and it is not clear why this should have a stronger impact on risk than nitrite from other sources. There is also no mechanistic explanation to explain such an effect and it is more likely that nitrite intake is a surrogate marker for other behavioural factors.”
[1] https://onlinelibrary.wiley.com/doi/10.1002/mnfr.201600982
Dr Duane Mellor, Registered Dietitian and Senior Lecturer, Aston Medical School, Aston University, said:
“This is another analysis of the Nutrient-Sante cohort, which this time looks at the associated risk of nitrite and nitrate consumption on risk of developing type 2 diabetes in a French population. This study finds no link between nitrate intake and risk of developing type 2 diabetes, but did find a link between type 2 diabetes and nitrite intake. This could be influenced by where people live, in that those consuming the most nitrite overall, tended to live in areas where more nitrite was in the water. This could reflect confounding, in that nitrite intake could reflect a range of other factors which could not be controlled for. Having said this, the researchers did control of many factors associated with risk of developing type 2 diabetes, including weight, smoking, age, physical activity and sugar intake. It is of interest that the dose response relationship appears to use grams, when intake was measured in mg for nitrites, so this needs to be considered when looking at the data. The researchers also tried to look at how the body converts nitrate which is found in many foods from vegetables to meat into nitrite, which can be reduced by mouthwash. However, they found that even then nitrate intake was not linked to risk of type 2 diabetes. It could be questioned how accurate estimating intakes of individual additives like sodium nitrite which was less than 1mg per day from a record of just 2 days food intake per year, as it assumes people ate the same the other 363 days of the year.
“When considering the meaning of this data, it is perhaps worth noting that the use of nitrites as an additive is often as sodium nitrite which is used to cure meats like bacon, which if someone is seeking to reduce their risk of type 2 diabetes would be something people would be encouraged to eat less of. The best way to reduce your risk of developing type 2 diabetes is to be physically active, maintain a healthy weight for you and eat a varied diet based on vegetables, pulses, nuts, seeds and fruit along with wholegrain and moderate intakes of dairy foods and meat (especially processed meats).”
‘Dietary exposure to nitrites and nitrates in association with type 2 diabetes risk: Results from the NutriNet-Santé population-based cohort study’ by Bernard Srour et al. was published in PLOS Medicine at 19:00 UK time Tuesday 17 January 2023.
DOI: 10.1371/journal.pmed.1004149
Declared interests
Prof Gunter Kuhnle: “I have conducted research into the effect of nitrite and nitrate on colorectal cancer risk and have worked on projects to reduce the nitrite content in meat products.”
Prof Tom Sanders: “I have no conflicts of interest to declare other than advice to charities such as HEART UK and the BRITISH NUTRITION FOUNDATION which are all pro bono.”
For all other experts, no reply to our request for DOIs was received.