Beneficial Effects of Inorganic Nitrate/Nitrite in Type 2 Diabetes and its Complications

Zahra Bahadoran; Asghar Ghasemi; Parvin Mirmiran; Fereidoun Azizi; Farzad Hadaegh


Nutr Metab. 2015;12(16) 

In This Article

Abstract and Introduction


Background and aim: The ability of inorganic nitrate and nitrite to convert to nitric oxide (NO), and some of its properties e.g. regulation of glucose metabolism, vascular homeostasis, and insulin signaling pathway, have recently raised the hypothesis that inorganic nitrate and nitrite could be potential therapeutic agents in type 2 diabetes. In this review, we reviewed experimental and clinical studies investigating the effect of nitrate/nitrite administration on various aspects of type 2 diabetes.

Findings: Studies showed that an altered metabolism of nitrate/nitrite and impaired NO pathway occurs in diabetes which could contribute to its complications. Some important beneficial properties, including regulation of glucose homeostasis and insulin signaling pathway, improvement of insulin resistance and vascular function, hypotensive, hypolipidemic as well as anti-inflammatory and anti-oxidative effects have been observed following administration of inorganic nitrate/nitrite.

Conclusion: It seems that dietary nitrate/nitrite could be a compensatory fuel for a disrupted nitrate/nitrite/NO pathway and related disorders in diabetes. Although some beneficial properties of nitrate/nitrite have been reported by experimental investigations, long-term clinical studies with various doses of inorganic nitrate/nitrite supplementation, are recommended to confirm these effects.


Inorganic nitrate and nitrite are both naturally occurring as well as food additive compounds in the human diet. Vegetables and other plant based foods are the most common sources of dietary intake of nitrate and contribute up to 85 % total dietary nitrate intake; green leafy vegetables including lettuce and spinach, cabbage, rocket, red beetroot, and radish have higher concentrations of nitrate.[1] Drinking water could also provide considerable amounts of nitrate; main sources of dietary nitrite are processed meat and animal food products.[1] Because of the long-term concerns regarding adverse effects of dietary nitrate and nitrite such as acute toxicity, e.g. methemoglobinemia, production of N-nitroso compounds, carcinogenic properties and potential anti-thyroid effect, strict regulations and limitations have been legislated for nitrate/nitrite levels of drinking water and the use of nitrate fertilizer and food additives.[2]

Over the past two decades, data on a possible association between high nitrate/nitrite exposure and the risk of childhood type 1 diabetes is controversial; Virtanen et al. in 1994 showed that dietary intake of nitrite, but not nitrate, was positively related to the risk of type 1 diabetes in Finnish children.[3] Similar associations have also been reported by others;[4–6] some studies however showed no significant association.[7] In contrast, recent investigations have highlighted the beneficial therapeutic effects of nitrate/nitrite against type 2 diabetes, properties attributed to the potential effects of nitrate/nitrite on their ability to convert to nitric oxide.[8,9] Current evidence reveals that dietary nitrate/nitrite could restore NO homeostasis and maintain the steady-state NO levels in pathological conditions related to a disrupted NO pathway.[10] Some evidence also indicates that nitrate/nitrite-rich foods such as green leafy vegetables play a protective role against type 2 diabetes and cardiovascular disease.[11] It has also been suggested that high-nitrate content in the diet has a beneficial role in prevention of type 2 diabetes and insulin resistance,[12] to the best of our knowledge, so far there is no epidemiological study or clinical investigation to confirm or reject this hypothesis.

In this review we discuss the possible link between type 2 diabetes and nitrate/nitrite metabolism and also the potential effects of these compounds on improvement of glycemic control and prevention of type 2 diabetes complications.