Human clinical trial supports bioavailability, safety of nicotinamide riboside

A single dose of nicotinamide riboside (NR) may significantly increases levels of NAD+, which is key to cellular energy metabolism and mitochondrial function, says data from studies with mice and humans using ChromaDex’s Niagen NR.

Data from the study, performed in the laboratory of Dr Charles Brenner at the University of Iowa and published in Nature Communications, also supported the safety profile of the ingredient, which is a no-flush version of niacin (vitamin B3).

Along with collaborators at Queens University Belfast and ChromaDex, the Iowa-based researchers demonstrated that NR is not only effective at safely increasing NAD+ metabolism in people but also showed that NR produces a greater increase in liver NAD+ as well as in longevity-promoting sirtuin activities than the other B3 vitamins in mice.

“We obtained convincing evidence that oral supplementation of NR boosts NAD+ and enhances the body’s utilization of NAD+ to a greater degree than the familiar forms of vitamin B3. NR is the most efficient NAD+ precursor,” said Dr Brenner in a release.

Nicotinamide riboside

NR is found naturally in trace amounts in milk and other foods, and is a more potent, no-flush version of niacin (vitamin B3). Published research has shown that NR is a potent precursor to NAD+ in the mitochondria of animals. NAD+ is an important cellular co-factor for improvement of mitochondrial performance and energy metabolism.

As organisms age, NAD+ levels drop, which leads to a decrease in mitochondrial health; this in turn leads to age-related health issues.  Low NAD+ levels limit activity of a group of enzymes called sirtuins, which are believed to play a key role in longevity. NAD+ levels also can be depleted by lifestyle choices such as overeating and lack of exercise. By boosting NAD+, NR may increase mitochondrial health and induce the creation of new mitochondria.

Irvine, CA-based Chromadex has been accumulating the IP surrounding NR for a couple of years, having licensed patents from Cornell University, Dartmouth College, and Washington University in St Louis.

As the science develops, more and more companies are launching products containing the ingredient.

Commenting on the new results, Frank Jaksch, founder and CEO of ChromaDex, said: “These results are highly significant because the degree of NAD+ boosting with reported health benefits in mice has been translated in people with an orally supplemented NR. This validates NR as the most efficient NAD+ precursor, and one that does not cause flushing or inhibit the activity of sirtuins.”

Study details

Dr Brenner and his co-workers recruited 12 healthy men and women aged between 30 and 55, and with BMIs of 18.5 to 29.9 kg/m2, to participate in their randomized, double-blind, three-arm crossover pharmacokinetic study. Participants were randomly assigned to consume a single dose of NR chloride at doses of 100, 300 and 1,000 mg.

Results showed that blood NAD+ metabolism increased in every NR group in a dose-dependent manner.

The researchers also reported that NR significantly increased levels of a metabolite called nicotinic acid adenine dinucleotide (NAAD), which was not previously thought to be involved in the conversion of NR to NAD+.

“NAAD is a reliable biomarker of increased NAD+ metabolism,” explained Dr Brenner. “The more NAD+ produced, the more we see the NAAD biomarker.”

The largest increases in NAD+ metabolism were observed for the high doses of NR, but the lower doses also showed efficacy, said ChromaDex in a release. Commercially-available dietary supplements are formulated with NR doses ranging from 75 mg (Doctor's Best Energy Featuring Niagen 75 mg) to 250 mg (Basis by Elysium  and N(r) – Niagen by High Performance Nutrition, Inc).

“Maintaining a more youthful metabolism could mean higher resting metabolic rate, resistance to weight gain, and the ability to maintain muscle mass and resist tissue damage over time,” said Dr Brenner.

Source: Nature Communications

7, Article number: 12948 (2016), doi:10.1038/ncomms12948

“Nicotinamide riboside is uniquely and orally bioavailable in mice and humans”

Authors: S.A.J. Trammell, et al.