Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults

Abstract

Nicotinamide adenine dinucleotide (NAD⁺) has emerged as a critical co-substrate for enzymes involved in the beneficial effects of regular calorie restriction on healthspan. As such, the use of NAD⁺ precursors to augment NAD⁺ bioavailability has been proposed as a strategy for improving cardiovascular and other physiological functions with aging in humans. Here we provide the evidence in a 2 × 6-week randomized, double-blind, placebo-controlled, crossover clinical trial that chronic supplementation with the NAD⁺ precursor vitamin, nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD⁺ metabolism in healthy middle-aged and older adults. Our results also provide initial insight into the effects of chronic NR supplementation on physiological function in humans, and suggest that, in particular, future clinical trials should further assess the potential benefits of NR for reducing blood pressure and arterial stiffness in this group.

Fig. 1

Study flow diagram

Fig. 2

NAD⁺ metabolome. NAD⁺and related metabolite concentrations in peripheral blood mononuclear cells increased after oral placebo vs. NR supplementation normalized to total protein content. Data are mean ± SD. * indicates unadjusted P < 0.05 by one-tailed paired t-test. N = 21 (Group A = 11; Group B = 10)

Fig. 3

Blood pressure. Effect of 6 weeks of oral placebo vs. NR supplementation on a systolic (SBP) and b diastolic (DBP) blood pressure, and c pulse pressure (PP) in healthy middle-aged and older adults as a whole N = 24 (Group A = 12; Group B = 12), and overall change from placebo in blood pressure parameters (d−f) in subjects with normal (N = 11) vs. above normal (N = 13) baseline BP. Data are mean ± SD. P-values reported in individual bars based on a one-tailed paired t-test (panels a−c only) and an adjusted alpha level set at 0.006

Fig. 4

Arterial function. Effect of 6 weeks of oral placebo vs. NR supplementation on a aortic pulse wave velocity (PWV) as a whole (N = 24; 12 per group), b subgroups of individuals with normal (N = 11) vs. above-normal (N = 13) baseline BP); c carotid artery compliance (CC) and d brachial artery flow-mediated dilation (FMD) in the overall groups (N = 24; 12 per group). Data are mean ± SD. P-values reported in individual bars based on one-tailed paired t-test (panels a, c, and d only) and an adjusted alpha level set at 0.006