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NMN or NR – Which one is better?

A photo showing a woman trying to choose between supplements to boost NAD+

NMN b-Nicotinamide Mononucleotide and NR (Nicotinamide Riboside) have been studied together, however, there has been little, if any, direct published comparison of the two compounds.

There have been a number of human clinical trials employing NR that have been published in the last several years, whilst those involving NMN have lagged, leading some to conclude that NR is the “safer” alternative. However, despite the fact that more than 11 human clinical studies, including NR, have been published thus far, virtually all of them have failed to demonstrate any benefit in people. The only apparent exception is this research from 2021, which shows a drop in the inflammatory marker IL-6 in the blood.

However, Dr. David Sinclair has said that he uses NMN instead of NR based on a study he conducted that discovered NR had no effect on the endurance of older mice, whereas NMN boosted their endurance to the point where they could run twice as long as those on placebo.

The following researches proved that the usage of NMN appears to be more advantageous for humans than NR;

1. NMN Enhances Aerobic Capacity in Amateur Runners

Researchers find in this six-week human study in 2021, that supplementation with Nicotinamide Mononucleotide (NMN) significantly increased the ventilatory threshold (VT) in amateur runners. The benefit was dose-dependent and was associated with muscle, not heart-related. The increased aerobic capacity is most likely the result of increased skeletal muscle O2 use. Larger doses of NMN have better results.

2. NMN Increased Muscle Insulin Activity

It was assessed in this study how fast and efficiently glucose is absorbed from the circulation in response to insulin. A faster insulin-stimulated glucose elimination rate indicates more insulin sensitivity, which is physiologically healthier. After 10 weeks of NMN supplementation, the individuals’ insulin-stimulated glucose disposal rate increased by 27%. This finding implies that NMN treatment improves insulin sensitivity and, perhaps, metabolic health via boosting NAD+ turnover rather than by altering muscle NAD+ concentration.

In contrast to NMN’s insulin-sensitizing effects, multiple randomized controlled studies in middle-aged and older men demonstrated that administration with NR had no effect on whole-body or muscle insulin sensitivity. Even though this experiment utilized 250 mg NMN, these NR studies employed a larger dosage of NR for a comparable period of time: For twelve weeks, 2000 mg, 1000 mg for 3 and 6 weeks. 1,2. Weight, blood pressure, lipid profile, fasting glucose, and insulin did not change in all the mentioned researches proving no effect of Nr for insulin sensitivity.

3. NMN Is More Bioavailable than NR

The bioavailability of medicine is the proportion of a given dosage that reaches the systemic circulation unmodified. By the result of different researches 1, 23, it is proven that NMN is more bioavailable than NR. It’s more stable in blood, it is more readily found in blood (10 times more than NR) for the tissues in the body. Whereas NR is not readily available and degrades in 1 hour, It usually degrades to NRM before reaching tissues and even supplementation won’t be effective.

4. NR Might Favors Reduction in Inflammation

Unlike NMN, NR had no effect on whole-body or muscle insulin sensitivity in middle-aged and older adults, but the same study discovered a significant decrease in the inflammatory marker IL-6. This result of research indicates that oral NR is accessible to human skeletal muscles and has anti-inflammatory properties, which may be beneficial in the aging, muscular, or inflammatory disease populations.

5. NASA Prefers NMN, Not NR

NASA is investigating NMN to determine if it can preserve astronauts’ muscles from atrophy and if it can safeguard their DNA from cosmic radiation. 

Scientist Harvard Professor Dr. Sinclair Prefers NMN Over NR 

Professor David Sinclair of Harvard University is one of the world’s foremost longevity researchers, having spent decades investigating the effects of NR, NMN, and NAD+ on human lifespan. He daily ingests NMN, not NR.

Dr. Sinclair has said in a recent interview that he takes 1,000 mg of NMN daily in addition to 1,000 mg of resveratrol without seeing any harmful effects for over a decade.

When being inquired about NR, Dr. Sinclair expressed that NR requires phosphate to work while NMN has everything it needs to be converted into NAD+. If to supplement with NR, the body would need to draw the resources it needs from other sources in the body such as phosphate in order to convert to NAD+. This can create a risk of deficiency or a need to supplement on phosphate when taking NR for example.

Faster Utilization of NMN as that or NR: The first human research of NMN was published. This Japanese research gave 10 males aged 40-60 a single dosage of 100 mg, 250 mg, or 500 mg NMN capsules. There were no side effects found. A single oral dose of NMN had no major side effects in healthy men. Oral administration of NMN was found to be safe and effective in reducing aging-related diseases in humans. The response of dosage was also measured. The 500 mg dosage showed a 2x response compared to the 250 mg dose. The rapid absorption suggests that NMN can skip the GI tract and liver making it a better choice.

Studies on NR That Anyone Should Be Aware Of

  • Published research indicates that NR may have detrimental effects on the mitochondria of heart cells. Treatment with the NAD+ precursor NR does not result in the expected effect of reestablishing NAD+-dependent protein activity.
  • The effect of DNA damage on NAD+ levels and the efficiency of Nicotinamide Riboside (NR) supplementation to restore NAD+ were studied in mice. They discovered that enhanced PARP enzyme activity necessary to repair DNA damage reduced NAD+ levels. NR did not raise NAD+ levels or improve cardiac function. The researchers doubled the NR dosage to see if it was more beneficial. The larger dosage was found to be harmful to the heart, presumably due to an excess of Nicotinamide (NAM), which suppresses Sirtuins.
  • NR supplementation (1000 mg/day) for one week did not modify human whole-body metabolism before, during, or after a one-hour aerobic activity, according to the UK and Australian researchers. Acute NR supplementation had no effect on human skeletal muscle signaling involved in metabolic adaptation to endurance exercise (using a cycling ergometer or stationary bike) or mitochondrial function and levels.

Thus far, published evidence indicates that individuals with NMN benefit more than those with NR. Of course, this is very early in the study process, and much more work is needed to determine whether NAD+ boosting substances are helpful in certain tissues or situations.

In addition, exercise is another way to restore diminishing NAD+ levels; for example, a recent study found that weight training doubles muscle NAD+ levels in middle age. To get to know details of this, please refer to our article here. This is a cost-effective measure that we may all use to reduce the loss of NAD+ and hence slow the rate of aging considerably.

 

Dr. David Sinclair’s comparison between NR and NMN (extract of his own Lifespan Podcast published in 2022).

Lifespan podcast screen cap showing David Sinclair's comment on NR vs NMN 1

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