Nitrate supplements may lower risk of diabetes complications, mortality in hyperglycaemic adults

Increased levels of urinary nitrate appear to contribute to a reduction in the risk of congestive heart failure and diabetic retinopathy and may also lower the risk of death from all causes, cardiovascular disease (CVD), and diabetes in adults with hyperglycaemia, suggests a study.

“These findings indicate that inorganic nitrate supplementation can be considered as a supplementary treatment for people with hyperglycaemia,” the researchers said.

The study included 6,208 individuals with hyperglycaemia who participated in the National Health and Nutrition Examination Survey from 2005 to 2014. Diabetes complications included the following: angina, stroke, myocardial infarction, congestive heart failure, coronary heart disease, diabetic retinopathy, and nephropathy. Mortality data were taken from the National Death Index until 2015.

The research team measured urinary nitrate using ion chromatography along with electrospray tandem mass spectrometry, which was log-transformed and categorized into tertiles. They also generated logistic regression models and Cox proportional hazards models to explore the association of urinary nitrate with the risk of diabetes complications and disease-specific mortalities, respectively.

Participants in the highest tertile of urinary nitrate had lower risks of congestive heart failure (odds ratio [OR], 0.41, 95 percent confidence interval [CI], 0.27‒0.60) and diabetic nephropathy (OR, 0.50, 95 percent CI, 0.41‒0.62) than those in the lowest tertile after adjustment for potential confounders, such as urinary perchlorate and thiocyanate. [J Clin Endoc Metab 2023;108:1318-1329]

During a total follow-up period of 41,463 person-years, participants in the highest tertile of nitrate also had a reduced risk of mortality from all causes (hazard ratio [HR], 0.78, 95 percent CI, 0.62‒0.97), CVD (HR, 0.56, 95 percent CI, 0.37‒0.84), and diabetes (HR, 0.47, 95 percent CI, 0.24‒0.90), showing dose-dependent linear relationships (p>0.05 for nonlinearity).

On the other hand, no significant association was seen between nitrate and cancer mortality (HR, 1.13, 95 percent CI, 0.71‒1.80).

“This information is of importance in providing effective treatment plans for patients with hyperglycaemia using natural sources of nitrate for decreasing the risk of diabetes complications and improving long-term survival,” the researchers said.

“Besides, the results of the stratification analysis also indicated that the public health system may consider focusing on inorganic nitrate supplementation to the male and elder population with hyperglycaemia,” they added.

Mechanism

Earlier vivo and vitro studies that examined the health effects of nitrate in the models of hyperglycaemic conditions found that nitrate supplementation could improve pancreatic islet blood flow and insulin secretion by modulating reactive oxygen species (ROS) signaling with an improvement of glucose tolerance and lipid profile. [Free Radic Biol Med 2012;53:1017‐1023]

Likewise, nitrate supplements could help normalize the recovery of the heart following ischaemia-reperfusion injury, as well as restore ischaemic hind limb blood flow. [Diabetes 2014;63:270‐281]

Additionally, the addition of nitrate in diet could result in better kidney function and provide beneficial renovascular effects in aged rats with metabolic syndrome and reduced kidney function by reducing oxidative stress and restoring nitric-oxide homeostasis in the kidney. [Redox Biol 2021;48:102209; Nat Rev Nephrol 2021;17:575‐590]

“The hyperglycaemia condition disrupts metabolism of nitrate/nitrite and nitric oxide, and dietary nitrate intake can restore nitric oxide homeostasis,” the researchers said.