Niagen® (nicotinamide riboside) and nicotinamide mononucleotide (NMN) are two well-known NAD+ precursors, but NMN falls short as a safe and effective method to elevate NAD+ (nicotinamide adenine dinucleotide).
Why does it matter? In recent years, NAD+ continues to be at the forefront of research in aging, health, and disease.
However, the popularity of NAD+ research also opened the door for misinformation about NAD+ and NAD+ precursors.
For example, labeling NMN as an NAD+ precursor is a misnomer. An NAD+ precursor is a “building block” for the cell to build NAD+. However, outside cells, NMN is a precursor to nicotinamide riboside, which, in turn, becomes NAD+.
Also, nicotinamide riboside carries a longer history than NMN. The leading global regulatory bodies accept Niagen® as safe. Currently, NMN may not be lawful for sale as a dietary supplement in the U.S. or any other international market. Yet, NMN is commercially available.
So, which one should you trust? The evidence overwhelmingly favors Niagen®, but here’s a breakdown to adequately assess these NAD+ precursors in detail.
According to Clinicaltrials.gov, a government-sponsored database of human clinical studies, as well as the World Health Organization (WHO) International Clinical Trials Registry, there are a total of 41 ongoing studies involving nicotinamide riboside vs. a mere eight for NMN, a 5:1 ratio. The world’s leading academic and medical researchers are conducting these studies, placing their trust and confidence in Niagen® over NMN to investigate the various health benefits of raising NAD+ levels in humans.
Niagen® has been the subject of eight human clinical studies. These studies provide a broader and far more convincing foundation of scientific evidence as the preferred cellular nutrient for elevating NAD+ levels.
In contrast, NMN has been the subject of only one published clinical study. The study, published in the Endocrine Journal in 2020 stands as the only human study that has evaluated NMN to date. However, the study failed to adequately assess the effect of NMN supplementation on NAD+ levels.
Overall, to date, a collection of human clinical studies comprehensively show that Niagen® effectively and safely increases NAD+ levels. The continued use of Niagen® in these trials further reflect the trust that the precursor holds in the scientific community. Overwhelmingly, the body of research favors Niagen® as the best choice for a NAD+ precursor.
Here is a summary of the Niagen® human clinical studies and their results:
A clinical trial published in Scientific Reports in 2019 concludes Niagen® both safely and effectively increases NAD levels in a dose-dependent manner in healthy overweight adults. The study used an 8-week randomized, double-blind, placebo-controlled trial to conduct its evaluation. After two weeks, the study results are as follows:
Similarly, an earlier study published in Nature Communications in 2018 shows Niagen® supplementation is well-tolerated and effectively elevates NAD+ in a group of healthy middle-aged and older adults. The subjects were 60 healthy men and women between the ages of 55-79. Supplementation was randomized, placebo-controlled, and implemented using a crossover design. The study administered a dosage of 500mg, twice per day for six weeks.
A different study published in Nature Communications in 2016 reports that a single dose of Niagen® can elevate human blood NAD+ levels 2.7-fold.
A study published in PLOS One in 2017 monitored Niagen® effects with a gradual increase in dosage. The study administered 250 mg of Niagen® to eight healthy volunteers on Days 1 and 2, then gradually administered higher doses each subsequent day after. Days 7 and 8, the study administered a peak dose of 1000mg twice daily. The study concluded on Day 9, showing oral administration of Niagen® to be well-tolerated in humans with no adverse effects.
A study published in Cell Reports in 2019 investigated Niagen®’s effects on skeletal muscle. The study supplemented 12 marginally-overweight older men with 1000mg of Niagen® daily for 21 days. Supplementation was randomized, double-blind, placebo-controlled and implemented using a crossover design. The study concluded, “oral nicotinamide riboside increased human skeletal muscle NAAD, a sensitive marker of increased NAD+ metabolism.”
A study published in the American Journal of Clinical Nutrition in 2018, concluded that 2000mg of daily Niagen® supplementation over a period of 12 weeks is safe. In addition, the subjects showed an increase in NAD+ metabolites in urine samples.
The researchers administered 1000mg of Niagen®, twice daily over a period of 12 weeks in a randomized, placebo-controlled, double-blind, parallel-group designed clinical trial. The subjects consisted of 40 healthy, obese men ranging in ages of 40-70.
Here is a summary of the one published NMN human clinical study and its result:
Published in the Endocrine Journal in 2020, researchers conducted a small, non-blinded, uncontrolled (no placebo) trial consisting of 10 healthy Japanese male subjects aged 40-60. The study administered NMN over the course of three visits, each spaced more than a week apart. Subjects received a single 100, 250, or 500mg dose of NMN.
The study concluded that NMN supplementation shows no serious adverse effects and tolerability in moderately high doses but it did not assess the effect on NAD+ levels or the safety of daily NMN supplementation over any significant period of time. Therefore, as a small, uncontrolled study, it only serves to open the door for potential further trials after showing its tolerability in human subjects. In other words, it is unclear if the daily, long-term supplementation of NMN is either safe or effective.
Nicotinamide riboside, once absorbed into the body, enters cells directly, whereas NMN cannot. A collection of compelling published studies conducted by some of the field’s leading researchers demonstrate that NMN cannot enter cells directly; rather, it must be converted to nicotinamide riboside first.
A study published in Nature Communications in 2016 on NMN’s metabolism in mammalian cells suggests NMN cannot directly enter the cell. Nicotinamide riboside and NMN are chemically identical with the exception of one phosphate group present on NMN. The study demonstrates that this additional phosphate group requires supplemental NMN to be first converted into nicotinamide riboside before it can enter the cell. This, in fact, is the same reason NAD+ supplementation provides no advantage over nicotinamide riboside. NAD+ is too large and contains multiple phosphate groups. NAD+ must be broken down into individual parts before entering the cell, then, it reforms back into NAD+.
A study published in Nature Metabolism in 2019 claimed to have identified a transport protein for NMN in the small intestine of mice. Mark S. Schmidt & Charles Brenner questioned the validity of this claim, stating there is an absence of evidence for this NMN transporter. A substance absorbed through the intestine does not necessarily mean that the same substance is available to cells of other tissues. Also, it is unknown whether this supposed transporter identified in mouse intestine is present in humans.
The available evidence demonstrates that once absorbed by the body, NMN cannot enter cells directly and instead must first be converted to nicotinamide riboside, bringing the efficacy of NMN supplementation into serious question.
Niagen® (nicotinamide riboside), has achieved virtually unprecedented regulatory acceptance in key markets around the world.
Niagen® has been successfully reviewed twice under the US Food and Drug Administration’s (FDA) New Dietary Ingredient Notification (NDIN) program.
Niagen® was successfully notified to the FDA as Generally Recognized As Safe (GRAS).
Niagen® received approval as a Natural Health Product by Health Canada.
Niagen® received approval as a Novel Food Ingredient by the European Commission.
Niagen® received approval as a permissible ingredient in Complimentary Medicines by the Therapeutic Goods Administration of Australia.
These approvals and acceptance by the world’s leading authoritative regulatory bodies is a clear, unequivocal recognition of the quality of the science, the safety of the ingredient, and the reproducibility of the production process.
In comparison, no NMN ingredient or product holds these qualifiers.
Tru Niagen®, ChromaDex’s consumer product of nicotinamide riboside, bears the NSF Certified for Sport® seal. The Certified for Sport® includes certification that Tru Niagen® is made to current Good Manufacturing Practice (cGMP) standards, testing to confirm the level of Niagen® in the product is consistent with the amount claimed on the label and testing to confirm the absence of over 270 athletic banned substances and harmful contaminants.
On the other hand, lack of regulatory status for NMN, precludes NMN products from bearing the NSF Certified for Sport® seal.
After reviewing the facts – the science, the safety, the regulatory acceptance – the choice is clear. No evidence shows NMN as a safe and effective method for elevating NAD+ levels in humans.
Nicotinamide riboside provides a sound basis for confidence. The studies behind it are overwhelmingly positive, and the regulatory approvals are ironclad.
In contrast, NMN’s lack of review and acceptance by regulatory bodies is a safety concern.
So, do you want to buy with self-assurance? Or take a gamble on an unproven product? Below is an overview to help you decide: