Nicotinamide Mononucleotide (NMN)

Nicotinamide Mononucleotide (NMN) is a compound found naturally in the cells of our bodies and is integral to several cellular processes. It is closely related to NAD+, a vital coenzyme essential for a myriad of cellular functions, including energy metabolism, DNA repair, and cellular signaling. The levels of NAD+ are known to decline as we age, and this decline is associated with aging and various age-related diseases.

NMN is a direct precursor to NAD+, meaning it is crucial in the synthesis of this indispensable coenzyme. The hypothesis is that by supplementing with NMN, we can boost the levels of NAD+ in the body, potentially counteracting age-related cellular decline and improving overall health. Preliminary studies, mainly in mice, suggest that NMN supplementation could offer a range of health benefits, such as enhanced energy metabolism and improved DNA repair, indicating its potential role in slowing the aging processes.

However, while NMN shows significant promise, comprehensive studies determining its long-term safety, effective dosage, and potential side effects in humans are still in progress. NMN is also present in several food sources, including broccoli, cabbage, cucumber, avocados, and edamame, but only in small quantities.

NMN and its impact on longevity are at the cutting edge of anti-aging research, with new discoveries and insights emerging regularly, deepening our understanding of the aging process and potential interventions to extend health and lifespan.

Sources of NMN in Food

NMN is naturally present in a variety of foods, albeit in relatively small quantities. Here is a list of some foods known to contain NMN, along with their respective NMN content.

Food Type	Name	NMN Content (mg/100g-Food)
Vegetable	Edamame	0.47–1.88
Vegetable	Broccoli	0.25–1.12
Vegetable	Cucumber Seed	0.56
Vegetable	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

While these foods can contribute to NAD+ levels through the provision of NMN, the quantities present are relatively small, and it is currently unclear whether dietary intake alone can significantly impact NAD+ levels in the body. Therefore, research into NMN supplementation is ongoing to explore its potential in maintaining or elevating NAD+ levels and mitigating age-related decline.

Considerations for NMN Supplementation

When considering NMN supplementation, it is crucial to understand the potential interactions and impacts of NMN. Here are some considerations based on current knowledge and research.

Optimal Timing for Supplementation

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 suggested 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 S-adenosylmethionine (SAMe), 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. NOVOS use B vitamins and phosphatidylcholine as methyl donors in their product to avoid the side effects of TMG and because they think that TMG is already too deep into the methylation pathways, not allowing the body to choose the amount of methylation for itself.

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.

Dosage and Effects

Human studies have indicated that a dosage of 1000 mg over 10 days can raise NAD levels about two-fold, and dosages as high as 2000 mg can triple the amount. However, the long-term safety, efficacy, and optimal dosage of NMN are still under investigation, and more comprehensive studies are needed to establish concrete guidelines for NMN supplementation.

Clinical Trials

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