The first-in-humans, double-blind, placebo-controlled, randomized study assessed the safety and efficacy of taking repeat doses of Basis — a combination of nicotinamide riboside (NR) and pterostilbene — in a population of 120 healthy adults ages 60-80. The results? Regular doses of Basis increased NAD+ levels by an average of 40 percent.
Metabolism, Aging, and NAD+
A properly functioning metabolism is essential to health and longevity. In the scientific sense of the word, metabolism refers to the sum of every chemical reaction that happens inside the body, an enormous web of interactions on the molecular level that aim to keep the you in what biologists call homeostasis: a state of balance, best illustrated by our near constant body temperature, which persists even in a wide range of circumstances. This is all made possible by an elegant choreography between coenzymes (or, “helper molecules”) and specific proteins acting as metabolic sensors, attuned to, and responding to ambient conditions in the cell and the body as a whole. The coenzyme nicotinamide adenine dinucleotide (NAD+) and a family of proteins called sirtuins make up an important part of this choreography.
NAD+ in Energy Creation, Genome Integrity, and More
First discovered in 1906, NAD+ is a coenzyme found in all living cells, and it has two main categories of roles in the body. One is is turning nutrients into energy. In that process NAD+ transfers electrons in redox reactions to help synthesize ATP, the energy currency of the cell. Importantly, NAD+ isn’t “used up” or consumed in creating energy. In the other category of roles, NAD+ works with proteins to carry out essential biological processes like DNA damage repair, mitochondrial function, maintaining chromosomal integrity, gene expression, epigenetic and posttranslational modifications, and calcium signaling. Sirtuins are some of the proteins that regulate these processes, especially those that help keep the cell healthy during stressful conditions, including aging.
Several things are important to know about the relationship between NAD+ and sirtuins. Sirtuins require NAD+ to function, and NAD+ is used up in this process (and in all the other processes except energy creation). This means that the body needs to constantly synthesize it. Finally, NAD+ is known to decline in organisms, including humans, as they age. This led researchers to the notion that restoring NAD+ levels, on the one hand, and activating sirtuins, on the other, could have health benefits.
NAD+ Replenishment Improves Health in Animal Studies
And so far the preclinical research supports this idea. In fact, using NAD+ precursors, including one of the two primary ingredients in Basis, nicotinamide riboside, has shown significant value in maintaining robust health and preventing age-related health problems animal studies. For example, one study demonstrated that mitochondrial dysfunction, a hallmark of aging, was caused by declining NAD+ levels in old animals leading to a breakdown of communication between the nucleus and the mitochondria. Remarkably, one week of NMN (another NAD+ precursor) administration in old mice was shown to reverse the observed mitochondrial dysfunction in a manner requiring one of the sirtuins. In another study, NR was shown to reverse the decline in the number and function of adult stem cells in mice, and to increase the lifespan of these animals. Likewise, the polyphenol resveratrol has been demonstrated to be a potent sirtuin activator with poor bioavailability in humans; pterostilbene, the other ingredient in Basis, is a natural analog with better bioavailability.
The Trial: Basis Increases NAD+ in Humans
Basis combines the ingredients nicotinamide riboside and pterostilbene with the goal of synergistically supporting metabolic health by increasing NAD+ levels and activating sirtuins. Since human data on NAD+ supplementation is limited — one previous study on 12 participants showed that NR could increase NAD+ levels in the blood over a 24-hour period — this study by Elysium sought to determine whether NAD+ levels could be sustained over a longer time period: eight weeks, thereby extending the base of safety and efficacy data on the ingredients.
We did that in a placebo-controlled trial of 120 healthy adults between the ages of 60 and 80, the first repeat-dose trial for NR as well as the first test of the combination of NR and pterostilbene in humans. The results? Participants taking the recommended dose of Basis (250 mg of NR; 50 mg of pterostilbene) saw NAD+ levels increase by an average of 40 percent over baseline after 30 days, a number that was sustained at 60 days. Participants taking twice the recommended dose of Basis saw their NAD+ levels increase by 90 percent over baseline after 30 days and 55 percent at 60 days. And those taking the placebo had no NAD+ increase at all. There were no serious adverse events reported in the study.
Topics for Future Study: Liver Enzymes, Blood Pressure, Lipids
The science of NAD+ is thriving. The strength of this study is in the demonstration that NAD+ levels in whole blood can be significantly increased in humans in a safe and sustainable way by taking Basis. While secondary and exploratory endpoints of the trial suggested a possible role of Basis in liver health, blood pressure, and mobility (see complete study for details), the data isn’t sufficiently powered to draw definitive conclusions. This study represents an important first step that future clinical studies can build upon — and these trials are underway.
The clinical trial was conducted using the best practices with respect to ethics and trial design. It’s most similar to a phase one trial that pharmaceutical companies are required to conduct in the early stages of drug development. This study was a randomized (participants randomly assigned to groups), double-blinded (neither participants nor researchers know which group gets placebo, regular dose, double dose), placebo-controlled (one group gets an inactive substance) study carried out at testing sites in London, Ontario (Canada), Orlando, Florida, and Irvine, California.
Since the primary objective of the study was to evaluate safety and tolerability of Basis, participants had standard clinical check-ups including self-reported adverse events, complete blood count (CBC), electrolytes (Na, K, Cl), kidney function (creatinine), and liver function (AST, ALT, GGT and bilirubin).
The main secondary objective of the study was evaluating the potential benefits of Basis in increasing the concentration of NAD+ in the blood. The sample collection, preparation, and analysis of NAD+ in the blood required an original method that was created specifically for this trial.