Effect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetes

Abstract

Diets rich in green, leafy vegetables have been shown to lower BP and reduce the risk of cardiovascular disease. Green, leafy vegetables and beetroots are particularly rich in inorganic nitrate. Dietary nitrate supplementation, via sequential reduction to nitrite and NO, has previously been shown to lower BP and improve endothelial function in healthy humans.We sought to determine if supplementing dietary nitrate with beetroot juice, a rich source of nitrate, will lower BP, improve endothelial function and insulin sensitivity in individuals with type 2 diabetes (T2DM). Twenty-seven patients, age 67.2 +/-4.9 years, (18 male) were recruited for a double blind, randomised, placebo-controlled crossover trial. Participants were randomised to begin in either order a 2 week period of supplementation with 250 ml beetroot juice daily (active) or 250 ml nitratedepleted beetroot juice (placebo). At the conclusion of each intervention period 24 hour ambulatory blood pressure monitoring, tests of macro and microvascular endothelial function and a hyperinsulinaemic isoglycaemic clamp were performed. After two weeks administration of beetroot juice mean ambulatory systolic BP was unchanged: 134.6 ± 8.4 mmHg versus 135.1 ± 7.8 mmHg (mean ± SD) placebo vs. active -mean difference of -0.5 mmHg (placebo-active), p=0.737 (95% CI -3.9 to 2.8). There were no changes in macrovascular or microvascular endothelial function or insulin sensitivity. Supplementation of the diet with 7.5 mmoles of nitrate per day for 2 weeks caused an increase in plasma nitrite and nitrate concentration, but did not lower BP, improve endothelial function or insulin sensitivity in individuals with T2DM.3

A single dose of sodium nitrate does not improve oral glucose tolerance in patients with type 2 diabetes mellitus

“…In accordance, both other markers of insulin sensitivity (ISI-M and HOMA-IR), whose equations put less emphasis on basal blood glucose concentrations, did not show any improvements in whole-body insulin sensitivity. The apparent lack of improvement in whole-body insulin sensitivity after ingestion of a single bolus of sodium nitrate tends to be in line with two recent studies that assessed the impact of nitrate supplementation on insulin sensitivity by the application of a hyperinsulinemic euglycemic clamp [24,27]. In those studies, respectively 3 days and 14 days of dietary nitrate supplementation appeared to be ineffective in improving insulin sensitivity in healthy volunteers [24] and patients with type 2 diabetes [27].…”

Inorganic Nitrate Mimics Exercise-Stimulated Muscular Fiber-Type Switching and Myokine and γ-Aminobutyric Acid Release

“…However, a small number of human trials assessing the anti-diabetic effects of short-term nitrate supplementation have thus far proved disappointing (40); it remains to be seen whether larger, longerterm studies in diabetic or pre-diabetic populations (in which disease is less advanced) will demonstrate the beneficial effects observed in rodent models.…”

Medium-term effects of dietary nitrate supplementation on systolic and diastolic blood pressure in adults

“…Blood pressure (BP) control is a global public health priority as hypertension contributes to 24 the burden of heart disease, stroke and kidney failure and premature death and disability [1]. 25 The burden of hypertension is particularly important in developing countries where the 26 limited access to adequate treatments and health care and the concomitant occurrence of 27 communicable diseases and nutritional deficiencies increase the risk for disability and 28 cardiovascular fatal events [2].…”

“…Eight studies had a cross-over study design [7,16, 26]and the remaining five studies adopted a parallel study design [17][18][19]27,28]. Ten studies 129 used a double-blind placebo controlled design [7,16,18,[22][23][24][25][26][27][28]. The trials were conducted characteristics of the studies included in the analysis are presented in Table S1 of the online 133 supplementary material.…”

“…two studies recruited patients with high BP [16,18], and three studies recruited patients with 137 type 2 diabetes [24], hypercholesterolemia [28] and heart failure [22]. In addition, there was a slight over-representation of men (54%) and the mean BMI of the subjects ranged between 22…”