Nicotinamide Riboside Protects Against Diabetes and Neuropathy: Preclinical Findings

Synopsis

Male C57BL/6J mice fed a high-fat diet (HFD) develop prediabetes with insulin resistance and sensory neuropathy. When given low doses of streptozotocin, these mice model type 2 diabetes (T2D), showing high blood sugar, severe insulin resistance, and diabetic neuropathy affecting sensory and motor neurons. Because boosting NAD+ metabolism may improve blood sugar control and protect nerves, nicotinamide riboside (NR) was added to the HFD. In prediabetic mice, NR improved glucose tolerance, reduced weight gain, liver damage, and fat buildup in the liver, while protecting against sensory nerve damage. In T2D mice, NR significantly lowered blood glucose levels, weight gain, and liver fat, also protecting against neuropathy. The nerve protection from NR was not solely due to better blood sugar control. Corneal confocal microscopy, a sensitive method for detecting nerve damage, showed NR's protective effect on small nerves in living mice. Metabolomic analysis revealed that liver NADP+ and NADPH levels were reduced in prediabetes and T2D but largely preserved with NR supplementation. These findings support testing NR in humans with obesity, T2D, and related nerve complications.

Journal

Scientific Reports