Effects of dietary nitrate supplementation on the oxygen cost of exercise and walking performance in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled crossover trial

Abstract

Dietary nitrate supplementation has been shown to reduce the oxygen (O2) cost of exercise and enhance exercise tolerance in healthy individuals. This study assessed whether similar effects could be observed in individuals with type 2 diabetes (T2DM). In a randomized, double-blind, placebo-controlled crossover study, 48 participants with T2DM supplemented their diet for 4 days with either nitrate-rich beetroot juice (70ml/day, 6.43mmol nitrate/day) or nitrate-depleted beetroot juice as placebo (70ml/day, 0.07mmol nitrate/day). After each intervention period, resting plasma nitrate and nitrite concentrations were measured subsequent to participants completing moderate-paced walking. Pulmonary gas exchange was measured to assess the O2 cost of walking. After a rest period, participants performed the 6-min walk test (6MWT). Relative to placebo, beetroot juice resulted in a significant increase in plasma nitrate (placebo, 57±66 vs beetroot, 319±110µM; P< 0.001) and plasma nitrite concentration (placebo, 680±256 vs beetroot, 1065±607nM; P < 0.001). There were no differences between placebo juice and beetroot juice for the O2 cost of walking (946±221 vs 939±223ml/min, respectively; P = 0.59) and distance covered in the 6MWT (550±83 vs 554±90m, respectively; P = 0.17). Nitrate supplementation did not affect the O2 cost of moderate-paced walking or improve performance in the 6MWT. These findings indicate that dietary nitrate supplementation does not modulate the response to exercise in individuals with T2DM.

It is rocket science – why dietary nitrate is hard to ‘beet’! Part II: further mechanisms and therapeutic potential of the nitrate‐nitrite‐NO pathway

“…In a further crossover study in 48 patients with type 2 diabetes mellitus, not included in this analysis, Shepherd et al . found that 4 days' supplementation with nitrate‐rich beetroot juice did not reduce the O 2 cost of walking or the distance covered in a 6MWT compared to placebo . There were also no effects seen with blood pressure.…”

Cardiac effects of 6 months' dietary nitrate and spironolactone in patients with hypertension and with/at risk of type 2 diabetes, in the factorial design, double‐blind, randomized controlled VaSera trial

“…This ʻnitrate–nitrite–NO pathwayʼ appears to lack these tolerance issues , and to suppress ROS and reverse endothelial dysfunction , and has been extensively investigated clinically in studies up to 4–6 weeks, particularly for BP lowering . By contrast, patients with T2DM appear to lack any effect of dietary nitrate on BP .…”

“…This ʻnitrate-nitrite-NO pathwayʼ appears to lack these tolerance issues [14], and to suppress ROS [15] and reverse endothelial dysfunction [16], and has been extensively investigated clinically in studies up to 4-6 weeks, particularly for BP lowering [14,[16][17][18][19]. By contrast, patients with T2DM appear to lack any effect of dietary nitrate on BP [19][20][21]. However, we recently reported (with the main haemodynamic findings of the current study) that dietary nitrate lowered central aortic systolic BP {SBP; mean À2.6 [95% confidence interval (CI) À4.5, À0.75] mm Hg; p = 0.007}, despite no effect on brachial BP [22].…”

Inorganic Nitrate: Marker or Mediator of Mortality?

“…This appears to provide an alternative source of NO when endogenous synthesis through the oxygen‐dependent l ‐arginine NO synthase pathway is impaired. Trials of supplementation have suggested that adding nitrate to the diet can lower blood pressure, reduce the oxygen cost of exercise, and protect against ischemia–reperfusion injury, although not all studies report such changes …”

“…Trials of supplementation have suggested that adding nitrate to the diet can lower blood pressure, reduce the oxygen cost of exercise, and protect against ischemiareperfusion injury, 4 although not all studies report such changes. 5 The potential benefits of nitrate from the diet have led to calls from some quarters to raise the recommended daily intake. There do, however, remain a number of significant unanswered questions in the field.…”