Nicotinamide Riboside (NR): What Is It?
Nicotinamide riboside (NR) is essentially a form of vitamin B3 but is structurally and biochemically different from niacin (NA) and nicotinamide (NAM), the other vitamin B3 alternatives.
Vitamin B3 is an essential micronutrient that is required to maintain your levels of NAD+ (nicotinamide adenine dinucleotide).
What is NAD?
NAD+ is a coenzyme, working as an essential partner in cellular energy production. As a coenzyme, NAD+ works alongside several enzymes in the mitochondrial membrane, hence the prefix “-co” in its name.
They are your enzyme’s best friend, helping fuel the “cellular machine” that creates the energy needed by every major function in your body on a cellular level.
Why is NAD+ important?
Due to its critical role in cellular energy production, the absence of NAD+ in your body would render most bodily functions useless. Without NAD, your lungs wouldn’t be able to draw in oxygen, your heart wouldn’t be able to pump blood, and your brain synapses wouldn’t be able to fire.
NAD+ also helps facilitate DNA repair and regulate cellular activity by working with sirtuins and poly (ADP-ribose) polymerases (PARPs), key enzymes involved in regulating cells’ response to damage from things like overeating, drinking, sleep disruption, and sedentary patterns.
NAD+ and Aging
Research in 2012 from a team at the Department of Pharmacology at the University of New South Wales showed age-associated changes in NAD metabolism. The study revealed NAD+ levels decline by up to 50% in human skin tissue between the ages of 40-60 and that NAD+ depletion may play an important role in the aging process.
In the paper, the researchers stated, “A strong negative correlation was observed between NAD+ levels and age in both males and females.”
In addition, NAD’s involvement in cellular respiration, particularly in the mitochondria, contributes to overall mitochondrial health. And the scientific community holds a keen interest in NAD’s involvement in mitochondrial dysfunction, one of the hallmarks of aging.
In recent years, research has focused on understanding NAD's role in addressing these age-associated functional declines.
Nicotinamide riboside increases NAD+ levels.
NR is a precursor to NAD, meaning that it serves as a “building block” to make the NAD+ molecule. Its discovery as a vitamin precursor of NAD+ in 2004 makes it one of the latest breakthroughs in NAD+ research.
NR is a naturally occurring vitamin as a novel form of vitamin B3, but its applications as a supplement have gained headwinds as a “healthy aging” vitamin. It’s highly efficient at elevating NAD, making it one of the most exciting interventions in healthy aging solutions.
Niagen®, a nature-identical patented form of NR, effectively elevates NAD+ levels. A clinical trial published in Scientific Reports shows that Niagen® increases NAD+ up to 50% after two weeks.
NAD+ is not a great standalone supplement.
Although supplementation with NR is clinically proven to increase NAD+ levels, supplementing with NAD+ as a standalone ingredient is not so effective.
NAD+ is a very large molecule that is unable to enter the cell directly. Instead, your body must first break it down into smaller pieces before passing through the cell membrane. The pieces are reassembled on the inside of the cell.
Compared to standalone NAD, NR can enter the cell directly without requiring a breakdown.
Also, in capsule form, NAD+ as a straight ingredient quickly degrades when exposed to light and heat. An FDA briefing document denotes the molecule’s inability to survive in a capsule form under ordinary storage conditions.
Where do we get nicotinamide riboside in nature?
NR is naturally found in minute quantities in dairy milk and yeast. However, you would have to consume a lot of milk to achieve any noticeable difference in NR in your diet.
For example, the amount of NR in a 250mg supplement is more than 1,000 times the amount in an 8-ounce glass of milk.
Unfortunately, there is no current data on the amount of NR measured in brewer’s yeast, but the quantities would likely still be insignificant compared to a 250mg supplement of NR.
Currently, the best way to take NR is in supplement form. The recommended serving size for Niagen® nicotinamide riboside is 300mg per day in order to see the best effects of elevated NAD+ levels.
How safe is nicotinamide riboside?
There are several supplements on the market that have NR as an active ingredient. However, Niagen® is the only form that has been successfully notified to the Food and Drug Administration (FDA).
Niagen® is the subject of three FDA safety notifications, successfully reviewed twice under the FDA’s New Dietary Ingredient Notification (NDIN) program.
Achieving FDA acceptance of an NDIN is a major accomplishment as it is a highly rigorous safety review process. Very few companies that do submit an NDIN to the FDA received a no-objection.
Niagen® is also the only form of NR to be successfully notified to the FDA as Generally Recognized As Safe (GRAS). An FDA no-objection to a GRAS notification is also a recognition of the quality of the science and the safety of the ingredient.
In addition to the US, Niagen® has achieved regulatory acceptance in Canada, the European Union, and Australia.
Tru Niagen® is NSF Certified for Sport®.
As for products on the shelf, Tru Niagen®, ChromaDex’s consumer product of NR, bears the NSF Certified for Sport® seal.
The Certified for Sport® certification includes current Good Manufacturing Practice (cGMP) certification of the Tru Niagen® manufacturing facility and testing to confirm the absence of over 270 athletic banned substances and harmful contaminants like lead and arsenic.
cGMP regulations require manufacturers to take proactive steps to guarantee the identity, strength, quality, and purity of their products.
Nicotinamide riboside vs. other vitamin B3s
NR is a novel form of vitamin B3. So how does it stack up to the other vitamin B3s like niacin (NA) or nicotinamide (NAM)?
Niacin and nicotinamide have been around for many years and appear in many different products, such as multivitamins and breakfast cereals. As such, the FDA considers these vitamin B3 forms to be safe and has “grandfathered” their use.
However, NR bypasses several steps that niacin and nicotinamide have to go through to create NAD.
NR is more efficient due to its simplicity in building NAD. Studies suggest that your body may more readily use it under some conditions of high stress compared to other NAD+ precursors.
Also, in terms of side effects, niacin and nicotinamide are not ideal. Niacin can cause symptoms of skin flushing, burning sensations, and itching.
Although nicotinamide has no visibly noticeable side effects, studies suggest nicotinamide can inhibit sirtuin activity, negatively impacting mitochondrial health and cellular repair.
Niagen® nicotinamide riboside reports no attributable adverse effects during published clinical trials.
Nicotinamide riboside vs. NMN
NMN (nicotinamide mononucleotide) is often pitted against NR. However, NMN only has two published clinical studies, one of which did not measure its effect on NAD+ levels.
Niagen® nicotinamide riboside, on the other hand, has 12 published human clinical studies to date, 9 of which show that Niagen® effectively and safely increases NAD+ levels.
Also, a variety of studies, including a recent preclinical study on NMN’s metabolism in mammalian cells, indicates that NMN cannot enter cells directly and must convert into NR before it enters.
More alarmingly, NMN has not been subjected to any regulatory review for safety by any authoritative government body anywhere. Therefore, the safety of NMN as an NAD+ precursor supplement is not clear at this time.
The future of nicotinamide riboside.
General interest in NAD+ and aging has garnered more interest in NAD+ research in recent years, and NR’s unique property of efficiently elevating NAD+ levels makes it an exciting prospect in aging research.
Currently, many studies are underway surrounding the positive effects of NR on other health issues, examining the impact of NR on brain health, muscle function, and heart health.
It’s only a matter of time before NR starts to raise possibilities as a more holistic approach to wellness.