Nicotinamide Mononucleotide (NMN)

Nicotinamid mononukleotid (NMN) is a naturally occurring compound found in the cells of our bodies and is closely related to NAD+ (Nicotinamide Adenine Dinucleotide), a coenzyme essential for various cellular processes, including energy metabolism, DNA repair, and cellular signaling. The decline of NAD+ levels has been associated with aging and various age-related diseases.

Key points about NMN include:

1. Precursor to NAD+: NMN is a direct precursor to NAD+, meaning it plays a critical role in producing this essential coenzyme. By supplementing with NMN, researchers hypothesize that we can boost NAD+ levels in the body.
2. Potential Anti-Aging Properties: Preliminary studies, primarily in mice, suggest that NMN supplementation can confer various health benefits, such as improved energy metabolism, enhanced DNA repair, and potentially slowed aging processes.
3. Safety and Dosage: While NMN shows promise, comprehensive studies on its long-term safety, effective dosage, and potential side effects in humans are ongoing.
4. Natural Sources: NMN is found in several food sources, including broccoli, cabbage, cucumber, avocados, and edamame, albeit in small quantities.
5. Research Frontier: NMN and its impact on longevity is an active area of research, with new findings and insights emerging regularly.

Taking NMN

When to Take

Our body has a natural rhythm where NAD levels fluctuate throughout the day rather than remaining constant, closely tied to our circadian rhythms. A study by Shin Imai and his team highlighted that NAD plays a crucial role in regulating our body's internal clock. The Sirt-1 gene, which is influenced by NAD, signals our body when it's time to eat or sleep.

For those considering NMN supplementation, it's recommended to take NMN in the morning when the natural rise in NAD and Sirt-1 activity should happen. Taking NMN e.g. at night might disrupt the NAD cycle and potentially affecting the sleep or hunger. This can be especially beneficial for frequent travelers trying to adjust to a new time zone, as a morning dose of NMN can help reset the body's internal clock and reduce jet lag.

Combining NMN with Methyl Donors

There's a theoretical concern regarding the consumption of NMN (nicotinamide mononucleotide) and its potential to use up methyl groups in the body. The reasoning is as follows:

1. NMN is converted into NAD+ in the body.
2. NAD+ can be broken down into nicotinamide.
3. Nicotinamide is then methylated by the liver to form N1-methylnicotinamide, which can be excreted in the urine. This methylation process consumes a methyl group from SAMe (S-adenosylmethionine), the primary methyl donor in the body.

The potential concern is that excessive NMN supplementation might lead to a decrease in the body's available methyl groups, which play crucial roles in various biological processes including DNA methylation and neurotransmitter synthesis.

For that reason, some individuals who take NMN also supplement with Trimethylglycine (TMG), a methyl donor, to ensure that they are not depleting their body's methyl groups. However, this is a precautionary measure and not necessarily based on concrete evidence.

However, there are a few important points to consider:

1. No clear evidence yet: While the pathway is known, the actual significance of NMN supplementation on global methyl group status is not well-established in humans. It's a theoretical concern, and it would require substantial NMN consumption to have a significant impact.
2. Compensatory mechanisms: The human body has various feedback mechanisms. If methyl groups were being depleted at a concerning rate, the body would likely slow down the conversion of NMN to NAD+ or the methylation of nicotinamide.
3. Methyl donors in diet: Many people consume methyl donors like choline, betaine, and folate in their diets. These can help replenish methyl groups.

Effects

• Human studies have shown that show that taking 1000 mg over 10 days raises your NAD levels about two-fold. But you can go as high as 2000 mg and triple the amount.

NMN in food

NMN is present in various types of natural food.

Food Type	Name	mg/100g-Food
vegetable	edamame	0.47–1.88
vegetable	broccoli	0.25–1.12
vegetable	cucumber seed	0.56
	cucumber peel	0.65
vegetable	cabbage	0.0–0.90
fruit	avocado	0.36–1.60
fruit	tomato	0.26–0.30
other	mushroom	0.0–1.01
meat	beef (raw)	0.06–0.42
seafood	shrimp	0.22

Studies

Study	Design	Participants	Outcome
Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men	singe admission of up to 500 mg oral admission at 9 AM	10 healthy men 40-60 years	admission was safe and well-tolerated
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women	RCT, 10 weeks placebo (n=12) 250 mg/day (n=13)	25 postmenopausal women with prediabetes overweight or obese (BMI 25.3 - 39.1) 56 - 66 years	increase in skeletal muscle insulin signaling, insulin sensitivity, and muscle remodeling improvement in muscle insulin sensitivity is clinically relevant and is similar to the improvement observed after ~10% weight loss
Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study	RCT, 6 weeks placebo (n=12) 300 mg/day (n=12) 600 mg/day (n=12) 1200 mg/day (n=12)	48 young and middle-aged recreationally trained runners 35 years in average	The combination of NMN supplementation and exercise further improves ventilatory threshold even among healthy young and middle-aged people. The improvement of aerobic capacity is in a dosage-dependent, large dosage of NMN with exercise has better effects. The improvement is muscle, not cardiac, related.
The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial	RCT, 8.5 weeks (60 days) placebo (n=20) 300 mg (n=20) 600 mg (n=20) 900 mg (n=20)	both males and females 40-65 (49.3 in average) years and healthy BMI between 18.5 and 35	Oral administration of NMN up to 900 mg/day for 60 days was safe and well tolerated blood NAD concentration was significantly and dose-dependently increased significant improvement of six-minute walking test, blood biological age, and SF-36 scores 900 mg/day oral dose did not give significantly better efficacy than 600 mg/day dose

See also

• Wikipedia article about NMN