Nicotinamide Riboside (NR) as an Alternative to Nicotinamide Mononucleotide (NMN)

Nicotinamide mononucleotide (NMN) has been a popular dietary supplement due to its role in boosting NAD+ levels. Due to recent FDA approval as a novel drug, NMN is no longer available as a supplement in the United States. Can nicotinamide riboside (NR) serve as a good replacement?

Key takeaways:
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    Nicotinamide mononucleotide (NMN) is now banned as a supplement in the US due to FDA permission for research as a novel drug.
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    Nicotinamide riboside (NR) has various benefits ranging from healthy aging to boosting metabolic performance.
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    NR can go directly to cells, while NMN cannot.
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    NR is unstable and hard to absorb, so liposomal NR delivery is the most effective delivery strategy to raise NAD+ levels in the body.

Why are NMN supplements banned?

The FDA recently stated that NMN would no longer be considered a New Dietary Ingredient (NDI), which sparked several discussions within the pharmaceutical sector. As a cause for withdrawal, the FDA said NMN "has been permitted for research as a novel medication." Therefore, it is no longer legal to market it as a supplement. This decision has not yet gone into effect and products like Hello100 are still available for purchase but is important to be prepared.

What is nicotinamide riboside?

Nicotinamide riboside (NR) is an alternative form of vitamin B3. As a supplement, it does not require a prescription. The body changes NR into nicotinamide adenine dinucleotide (NAD+), which is a coenzyme or helper molecule. NAD+ is used to power the metabolic processes that turn food into energy, fix DNA damage, improve cellular defenses, and keep your body's internal clock, or circadian rhythm, in sync. However, the body's normal level of NAD+ declines with age.

Chronic diseases, including diabetes, heart disease, Alzheimer's disease, and eyesight loss, have all been linked to low NAD+ levels, as have aging and age-related health issues. It's interesting to know that increasing the amount of NAD+ in animals may help slow down the aging process and make it less likely that they will get chronic diseases.

Benefits of NR supplements

Lengthen lifespan

Some studies have shown that NR supplements improve lifespan in mice. In another study, they found that supplementation of 1 gram of NR for 21 days resulted in a decrease in inflammatory proteins and an increase in the NAD+ metabolome profile, which may increase lifespan.

Regular NR supplementation reduced the pace of weight gain in certain mouse trials, which is a common problem as humans get older. Researchers speculate that factors like a faster metabolism and more physical exercise may be the reason. NAD+ treatment, combined with a balanced eating plan, may assist in maintaining a healthy body weight by encouraging increased ATP generation. Higher ATP levels indicate efficient metabolism.

Boost insulin levels

Research findings indicate that NR administration improved insulin sensitivity in postmenopausal women who were overweight or obese.

Increase brain function

People think NR supplements may improve the connection between the brain and the blood vessels and increase blood flow to the brain. NR may improve mental clarity and reduce inflammation in the brain.

Enhance heart health

As observed in mice, NR ingestion over time improves heart function. In addition, boosting NAD+ via NR supplementation can rescue cardiac function in mouse models of cardiomyopathy. It can also reduce systemic inflammation and can increase the blood levels of NAD+ in heart failure patients.

Augment energy production

NAD+ treatment helps people have more energy by turning the chemical energy in their diet into fuel. They aid in boosting energy levels and lowering weariness and exhaustion due to their important function in ATP generation.

Dosage and side effects

NR can be bought as a pill or a capsule. The majority of NR supplement manufacturers advise consuming 250–300 mg (or 1-2 capsules) per day, depending on the brand. NR supplements can be taken on an empty stomach or with meals.

Studies have shown that NR is safe. A human study of NR found that it is safe for men and women who are overweight but otherwise healthy to take up to 1000 mg NR for a long time.

However, most human studies are short-lived and include a small number of people. More thorough human investigations are required to better understand its safety.

Some people have reported side effects ranging from mild to severe, such as indigestion, nausea, lethargy, headaches, diarrhea, and stomach pain, when it is taken in large doses. These side effects resolves after NR discontinuation.

Another study has also shown that 90 days of daily administration of 300 mg per kg of body weight in rats exhibited no negative effects. Also, unlike supplements with vitamin B3 (niacin), NR shouldn't make your face flush.

Difference between NR and NMN

The molecular structures of NMN and NR are very similar, but NMN has an extra phosphate group. Because of the extra phosphate groups, NMN is a bigger molecule than NR.

Experts have demonstrated that NMN must be converted to NR before entering cells, where NAD+ production occurs, since it is too big to pass through cellular membranes. Otherwise, an NMN-specific transporter would be required to deliver NMN into cells.

According to a 2007 study, NR significantly increases yeast NAD+ levels and extends lifespan even without caloric restriction. Additional research on the subject shows that NR raises NAD+ in mammalian cells by up to 270%. The two precursors, NMN and NR, are still up for discussion as to which is safer and more effective.

Since NMN must be changed into NR first in order to pass through the cell membrane and enter cell, the cell would convert the NR into back into NMN for NAD+ synthesis. If this is the case, the more effective molecule would be NR.

Is NR better than NMN for longevity?

Notably, the molecular structure of NAD+ is more similar to NMN than NR. Scientific findings also have pointed out that NMN has better anti-aging effects. But both molecules have human clinical studies on their effectiveness to boost NAD+ levels.

Similar to NMN, NR has also been shown to increase NAD+ in a safe and effective way in a number of human clinical studies so far.

A reason why NR could be better than NMN is that NAD+ production through NMN is not as efficient as NR because NMN must first be changed into NR before it can enter cells. Hence, NR can go directly to the cells to boost intracellular NAD+, whereas NMN cannot; NMN would first be converted to NR to promote NAD+ production.

How to optimize NR effects

Because NR isn't stable in the blood, it breaks down in plasma and leaves the blood 45 minutes after a 50 mg/kg injection. In humans, NR is never detected above trace levels in blood plasma.

Oral supplementation with 1,000 mg per day for three weeks had little to no effect on NR,. Since NR is unstable and hard to absorb, we need a more effective way to give it to people.

The same problem is faced by NMN: most NMN is also destroyed by the stomach acid. The best NMN supplements with highest bioavailability in the market are of liposomal formulation.

NR can also be formulated in liposomes for optimal delivery and absorption to give the most effective dose of NR and raise NAD+ levels in the body. When liposomes are used to deliver NR, about 90% of it gets into the bloodstream without being broken. Therefore, when buying an NR supplement in the market, choose a liposomal NR formulation.

If you are currently taking NMN, NR may be a good replacement that provides many of the same benefits.

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Comments

David Jordan David Jordan
prefix 1 month ago
NMN is NOT banned, at least not yet. You can test this by going to, oh, I don't know, maybe Amazon and using its internal search function. It's still available from other sources, too. The statement in the summary at the beginning of the article is incorrect.

What has happened so far is that one company researching a proprietary alternative, which they would control and sell, has requested a ban. What is reported to be happening already (and if it isn't happening as reported, will happen very soon) is the supplements industry is opposing the ban, communicating with the FDA, etc.

I get that writers on health issues are under pressure to continue publishing articles, so may publish the easiest article. A more informative article would be to investigate the issue and discuss the status and progress of a potential ban, and whether it really will occur.

Thanks, however, for pointing out the use of NR as an alternative. Another possibility, per at least one writer on longevity and anti-aging topics, is simple niacin.
Healthnews Team Healthnews Team
prefix 1 month ago
Thank you for sharing your concern. Healthnews received a response from the FDA. In case you missed it, here it is:
https://healthnews.com/longevity/longevity-supplements/are-nmn-supplements-still-on-sale-in-the-u-s/
Alex savtchenko Alex savtchenko
prefix 1 month ago
Hi do you also have a face cream with nmn or Nr or nad or something that works good thanks
Robert Clarke Robert Clarke
prefix 1 month ago
Why is no one reporting that the reason NMN was banned is because a pharmaceutical company is developing a prescription only version of the supplement. They can then monopolize the NMN market for themselves.
I learned of their lobbying efforts with the FDA quite some time ago. Pay to play Washington politics. Why is it that so many of these insider political stories are never mentioned in the US News
Bob Shafer Bob Shafer
prefix 1 month ago
Now I have seen statements that NR gets converted into NMN and statements that make the exact opposite argument. So how are we the consumer suppose to know the truth?