What is the association between nitrite and nitrate exposure and type 2 diabetes?

By Pooja Toshniwal PahariaJan 19 2023Reviewed by Aimee Molineux

In a recent study published in PLoS Medicine, researchers evaluated the association between nitrate and nitrite exposure and T2D (type 2 diabetes) development risks.

Background

Nitrites and nitrates are naturally occurring substances present in soil and water and are ingested frequently from diet and drinking water sources. In addition, the compounds are utilized as food additive substances, primarily to increase storage duration and prevent bacterial contamination of processed meats.

Previous experimental studies reported the pros and cons of nitrate and nitrite exposure on the onset of T2D (type 2 diabetes). Debates have recently emerged in several nations concerning the ban on nitrates and nitrates as food additive substances.

However, clinical and epidemiological data on the association between nitrate/nitrite exposure and new-onset T2D are limited. A study conducted in Iran, comprising 2,193 individuals, reported an increased risk of T2D development among ascorbic acid-deficient individuals with greater dietary exposure to nitrite. However, the study did not distinguish between the origin of the nitrite/nitrate compounds and did not include data from all relevant commercial brands.

About the study

In the present study, researchers investigated whether exposure to dietary nitrates and nitrites increased T2D risks, differentiating between water- and food-originated nitrates and nitrites and those contained in food additive substances.

The study comprised 104,168 adult individuals who had participated in the NutriNet-Sante cohort study, conducted between 2009 and 2021 in France, with 79% women and an average participant age of 43. Exposure to nitrates and nitrites was assessed based on a series of three non-consecutive online 24-hour diet records, documented at baseline and semi-annually over 14 days (two weekdays and one weekend). All cases of T2D documented till 1 October 2021 were included in the study. Under-reporters were excluded from the analysis.

The dietary records were linked to the NutriNet-Sante database, including commercial brand/name details of >3,500 industrial substances, and the NutriNet-Sante database was linked to the SNIRAM (Système National d'Informations Inter-Régimes de l'Assurance Maladie) health insurance database of France. Additionally, fasting blood samples were obtained from 19,772 individuals. T2D risks were assessed by performing multivariable Cox proportional hazards modeling.

Data were adjusted for established risk factors, including lifestyle and socio-demographic (age, sex, body mass index, occupation, level of education), anthropometric (weight, height), medical history, nutritional intake (ascorbic acid, beta carotene, sodium, iron, artificial sweeteners, supplements), lifestyle factors (smoking habits, alcohol consumption, physical exercise), and hazard ratios (HR) were calculated. Information on the risk factors was obtained from five questionnaires filled out by the participants. Foods-originated nitrates and nitrites were determined based on the EEFSA (European food safety authority) concentration levels for natural dietary sources.

The SISE-Eaux governmental database comprising data on tap water quality across 34,955 municipalities of France was utilized for estimating nitrite intake from water sources. Food additive presence was investigated utilizing databases including OQALI (French observatory of food quality), INRAE (national research institute for agriculture, food, and the environment), Open Food Facts, and GNPD (global new products database). Food additive assessments were performed using ad hoc laboratory assays, EFSA-reported doses, and Codex FSFA (general standard for food additives).

Results

The median duration of follow-up was seven years, during which 969 new-onset cases of T2D were documented (with an average age of 59 years at the T2D onset). Foods-originated nitrites contributed to 95% of the total exposure to nitrites. Key foods contributing to foods-originated nitrite and nitrate exposure comprised vegetables and vegetable-based meals (41.0% and 60.0%, respectively), followed by processed meat for nitrite compounds (19.0%) and seasonings for nitrate compounds (23%).

Compared to the initial tertile, individuals in the highest tertile category of total nitrite exposure showed an increased likelihood of being older, having greater body mass index values, having positive familial T2D history, having a higher level of education, and were more physically active. In addition, the individuals consumed more saturated fatty acids, water, alcohol, sugar, beta-carotene, sodium, ascorbic acid, fruits, vegetables, and meats. Key food groups for additive-originated nitrites/ and nitrates were processed meat and its preparations. Nearly 74% and 32% of participants were exposed to sodium nitrite and potassium nitrate as food additive substances, respectively.

The total nitrite exposure and water- and food-originated nitrite exposure were correlated positively with greater T2D risks (HR_tertile 3.0 versus 1.0, equal to 1.3). Individuals with greater food additive-originated nitrite exposure (i.e., beyond the gender-specific median value) and especially those with greater sodium nitrite exposure (e250) showed greater T2D risks in comparison to individuals with no additive-originated nitrite exposure (HR value of 1.5 for higher consumers versus non-consumers).

However, no statistically significant evidence of an increase in T2D risks by exposure to total, water-originated, food-originated, or additive-originated nitrate compounds. (P_trend values for all were 0.70). Largely similar results were obtained in the sensitivity analyses after excluding the initial two follow-up years, dietary pattern adjustments, SSB (sugar-sweetened beverage) intake adjustments, comorbidity adjustments (cardiovascular diseases, hypertriglyceridemia, and hypertension), and excluding individuals <30 years, and those who did not have three documented 240-hour diet records).

Overall, the study findings showed no probable benefit for dietary intake of nitrates and indicated an increase in T2D risks by increased exposure to water-originated, food-originated, and additive-originated nitrite compounds among the NutriNet-Sante study participants. The study findings presented a novel finding concerning ongoing debates concerning updating rules and regulations for curbing the usage of nitrite compounds as food additive substances. However, further research using nitrite- and nitrate-specific biomarkers is required to validate the study findings.