Combined inorganic nitrate/nitrite supplementation improves oxygen consumption capacity in Type 2 diabetic patients: potential roles of circulating nitrite and adaptations in skeletal muscle

Deficiencies in oxygen consumption capacity (VO₂max) are early, common, whole-body impairments in patients with type 2 diabetes mellitus (T2DM). This poses a challenge to exercise prescription, a cost-effective intervention for T2DM. More importantly, decreases of 1 ml/(kg*min) in VO₂max have been associated with a 9% increased risk of all-cause mortality; therefore, maintaining or increasing VO₂max over time is beneficial. Interestingly, increased circulating nitric oxide (NO) can improve exercise performance when supplemented through precursors, nitrate and nitrite (abundant in beetroot).

We hypothesized that increased circulating nitrate and nitrite levels would increase VO₂max and skeletal muscle respiratory capacity of T2DM patients in a randomized, double-blind, placebo-controlled, 8-week intervention with beetroot juice. Decreased VO₂max and impairments in several indices of skeletal muscle respiratory capacity were observed in T2DM before supplementation. VO₂max was positively correlated with circulating nitrite, and not nitrate, before and after nitrate/nitrite supplementation. There, were also trends for improvement in multiple aspects of skeletal muscle respiratory capacity after nitrate/nitrite supplementation. However, none were significantly improved, perhaps due to decreased statistical power.

These findings suggest circulating nitrite levels might be associated with improvements in VO₂max of T2DM patients after nitrate/nitrite supplementation. Nevertheless, future studies with a larger number of muscle biopsies from T2DM patients undergoing nitrate supplementation are still necessary to identify plausible functional and molecular events happening in skeletal muscle that might contribute to the already evident improvements in VO₂max.