Nicotinamide Mononucleotide (NMN)

Nicotinamide Mononucleotide (NMN and β-NMN) is a compound found naturally in the cells of our bodies and is integral to several cellular processes. NMN is a direct precursor to NAD+, a vital coenzyme essential for a myriad of cellular functions. The levels of NAD+ are known to decline as we age, and this decline is associated with aging and various age-related diseases. The has been shown in several clinical trials 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.

Legal

European Union (EU)

In the European Union, the classification and regulation of substances are often determined by their intended use and the claims made by the manufacturer or distributor. As of the latest update, Nicotinamide Mononucleotide (NMN) is classified as a chemical in the EU and has not been approved for human consumption. This classification is due to the EU's stringent regulations surrounding novel foods and substances, emphasizing consumer safety.

While NMN is not approved for human consumption in the EU, consumers may come across NMN products online that appear to be marketed for human use. However, these are officially sold either as chemicals for research and laboratory purposes or as supplements for animals, including dogs and cats. It is important for consumers to recognize the legal status and potential risks of such unapproved substances.

United States (US)

In November 2022, the US Food and Drug Administration (FDA) issued a statement saying that NMN may not be sold as a supplement, citing its status as being under investigation as a drug. This development is a reversal of the FDA's previous decision to allow its sale as a new dietary supplement (NDI). The reason for the reversal is unknown, but in December 2021, Metro International Biotech, a startup pharmaceutical company that has developed the NMN formulation MIB-626, wrote to the FDA: "As a company that has instituted publicly available clinical trials on ß-NMN, we request that FDA take the preclusion provision … seriously to protect the rights of companies that have spent significant time and research to develop drug products from competition from dietary supplements". According to Insider, the FDA confirmed that it had considered Metro's request.

Different Forms of NMN

Nicotinamide Mononucleotide (NMN) exists in two stereoisomeric forms, α-NMN and β-NMN, which have the same molecular formula but differ in the spatial arrangement of atoms. Recent advancements in NMN supplementation have led to the development of various formulations aimed at enhancing the compound's bioavailability and efficacy.

β-NMN

β-NMN is the biologically active form of NMN, predominantly utilized in scientific studies and supplements. It is integral in the biosynthesis of Nicotinamide Adenine Dinucleotide (NAD+), a vital coenzyme involved in numerous cellular processes, including energy metabolism, DNA repair, and cellular aging. When references are made to NMN in the context of supplementation or scientific research, it typically pertains to β-NMN due to its biological significance and activity.

α-NMN

α-NMN, on the other hand, does not participate in NAD+ biosynthesis and lacks the biological activity and associated health benefits of β-NMN. It is not the focus of NMN-related research or supplementation.

Liposomal NMN

Liposomal NMN is a form of NMN that is encapsulated within liposomes to enhance stability and bioavailability. This dietary supplement is available on the market and is being explored for its potential to increase the effectiveness of NMN supplementation. However, as of the latest updates, there are no published clinical studies specifically validating the benefits and efficacy of liposomal NMN, which means that while the theoretical advantages are promising, they have not yet been confirmed by scientific research.

MIB-626

MIB-626 doses of 1,000 mg taken once daily over 14 days doubles NAD+ levels (middle graph). When taken twice daily, MIB-626 triples NAD+ levels (right graph). The placebo capsules had no effect on NAD+ levels (left graph).

MIB-626, developed by Metro International Biotech, is a microcrystalline form of NMN. This formulation may offer enhanced stability, solubility, or bioavailability compared to the regular crystalline form of NMN, potentially optimizing the efficacy of NMN supplementation. MetroBiotech plans to bring MIB-626 on the market as drug, not as dietary supplement. For that reason, several clinical trials are ongoing evaluating the effects and safety of MIB-626 on humans.

Early results have indicated that a dosage of 1000 mg over 14 days can raise NAD+ levels (AUClast) about factor 1.7, and 2000 mg can increase by factor 3.7 above baseline in overweight or obese adults.

Reduced NMN (NMNH)

Reduced Nicotinamide Mononucleotide (NMNH) is a novel, potentially more effective NAD+ precursor.

NMN-HAP

NMN-HAP is a hydroxyapatite-based nano-drug delivery system for nicotinamide mononucleotide that showed significantly enhancing NMN bioavailability and replenishing NAD+ levels in mice. NMN-HAP is currently not available as supplement.

Metabolism of NMN

Bioavailability

Levels of NAD+ and NAMN in blood were increased by oral administration of 250mg NMN. NAD metabolome in blood was measured every 4 weeks. Three asterisks mean statistical significance: p-value < 0.001.

Bioavailability is a crucial factor in the effectiveness of any dietary supplement, including Nicotinamide Mononucleotide (NMN). It refers to the proportion of a substance that enters the circulation when introduced into the body and is thus able to have an active effect. In the case of NMN, bioavailability determines how much of the compound reaches the bloodstream and subsequently contributes to NAD+ biosynthesis. One of the main challenges with NMN bioavailability is its absorption and transportation within the body. When taken orally, NMN needs to be absorbed through the gastrointestinal tract, which can present barriers to its effective uptake.

• Molecular Size: NMN's relatively large molecular size compared to other NAD+ precursors (like NR, or nicotinamide riboside) poses a challenge for its absorption in the gut.
• Enzymatic Degradation: NMN can be subject to degradation by enzymes in the digestive tract, potentially reducing the amount that actually enters the bloodstream.

To address these challenges, various strategies and formulations have been developed:

• Liposomal Encapsulation: Liposomal NMN involves wrapping NMN molecules in a lipid layer, which can help protect them from degradation in the digestive system and enhance absorption.
• Sublingual Administration: Taking NMN sublingually (under the tongue) is proposed to increase its bioavailability by allowing direct absorption into the bloodstream, bypassing the digestive system.
• Microcrystalline Formulation: MIB-626, a microcrystalline form of NMN developed by MetroBiotech, is believed to offer enhanced stability and bioavailability.

While various methods to enhance NMN’s bioavailability are being explored, conclusive evidence on the most effective form or administration method is still emerging. Current research is focused on understanding how different formulations affect NMN's absorption and utilization in the body. Future studies are expected to provide more insights and possibly lead to more effective NMN supplementation strategies.

Effect

• Taking 800 mg NMN per day increase blood cell NAD+ levels by ~43% in mild hypertension patients display significantly lower blood cell NAD+ levels.
• Taking 300 mg NMN per day increase serum NAD+ levels by ~38%.
• It is assumed that the NAD+ level increases continuously through the NMN intake until it reaches its maximum after 1-2 weeks.^{[Citation needed]}

	After	NMN Group		Placebo Group		NMN group
		NAD+ concentrate		NAD+ concentrate		NAMN
		Baseline	After	Baseline	After	After
Whole blood, 250 mg/day	12 weeks	0.176±0.063	1.07±0.16	0.194±0.081	0.53±0.12	3.51±1.86
250 mg/day	12 weeks					1.15 (mean)

Clearance

It is currently assumed that NAD+ levels go back to baseline after 1-2 weeks of stopping NMN administration.^{[Citation needed]} In clinical trials, the NAD+ levels were only measured 4 weeks after stopping administration

Controversy about NMN as Direct Precursor

NMN administration of NMN–HAP and free NMN increases plasma NAD+ and NR in mice

NMN is often advertised, for example by NMN suppliers, as a direct precursor to NAD+, purportedly making it more effective compared to other precursors like Nicotinamide Riboside (NR). However, NMN's role as a direct precursor is only effective when it is inside the cell. This raises questions about how NMN, when ingested or administered externally, enters the cell to contribute to NAD+ synthesis. The central controversy surrounding NMN as a precursor to NAD+ lies in its mechanism of cellular entry. While NMN is a direct precursor of NAD+ within the cell, the debate focuses on whether NMN can be directly absorbed by cells or if it must first be converted to NR. In that case, NR might have an advantage over NMN, as NMN would require one additional conversion step compared to NR.

1. Direct Transport Mechanism: One hypothesis suggests that NMN can directly enter cells through specific transporters. The Slc12a8 transporter in the aged mouse ileum has been suggested to facilitate NMN's direct absorption. However, this idea has faced challenges due to conflicting research findings, and the functionality of Slc12a8 in humans has yet to be conclusively determined.
2. Dephosphorylation to NR: An alternative and currently more widely accepted theory proposes that NMN is not directly utilized by cells. Instead, it is first converted to Nicotinamide Riboside (NR) through dephosphorylation before cellular absorption. This conversion is mediated by enzymes like CD73. Once inside the cell as NR, it is then phosphorylated into NMN.

While direct transportation into the cell and dephosphorylation to NR can coexists, studies in mice indicate that orally ingested NMN is predominantly converted to NR in the intestinal tissue before absorption, challenging the view of NMN as a direct precursor to NAD+.

Potential Longevity Benefits

NMN supplementation has been associated with several potential benefits, primarily due to its role as a precursor to NAD+, a crucial coenzyme involved in various cellular processes. Here are some potential benefits based on preliminary research:

Prospects of increasing NAD+ by NMN

Potential health benefits in mouse models		Results of published human clinical trials
	Brain: improved brain function, protected from neurodegeneration, enhanced new myelin generation Lung: prevented pulmonary fibrosis, improved respiratory system function Liver: improved liver function, reduced hepatic steatosis, increased capacity to regenerate Heart: protected cardiomyocytes from injury caused by tachycardia Eye: exerted neuroprotective effects on photoreceptors Muscle: reduced atrophy, enhanced mitochondrial function and increased physical activity Vasculature: protected vasculature, increased capillary density, neovascularization, blood flow Inflammageing: improved immune cell function, reduced inflammation Skin: protected the skin from photodamage caused by UVB irradiation Reproduction: improved oocytes quality, restores fertility, increased the number of sperm		Safety: basically safe under the existing intervention dose and time Sleep quality: no significant improvement Muscle: prevented aging-related muscle dysfunctions and improving physical performance Ear: improved the right auditory ability of old men Cognition: no significant improvement Diabetes: increased muscle insulin sensitivity, insulin signaling, and remodeling in prediabetic women Telomere: increased telomere length Hypertension: significantly lowers blood pressure in mild hypertensive adults

In Humans

• Cellular Energy and Metabolism: By increasing NAD+ levels, NMN supplementation can potentially enhance cellular energy production and metabolism, leading to improved physiological functions and reduced age-related metabolic decline.
• Cognitive Function: Some research indicates that NMN may have neuroprotective effects, potentially improving cognitive function and reducing the risk of neurodegenerative diseases by maintaining neuronal health and resilience.
• Cardiovascular Health: NMN supplementation may offer cardiovascular benefits by improving blood flow and reducing the risk of age-related cardiovascular diseases, contributing to heart health and longevity.
• DNA Repair: Enhanced NAD+ levels through NMN supplementation can support DNA repair mechanisms, potentially reducing DNA damage and the risk of mutation, which are associated with aging and cancer.
• Insulin Sensitivity: NMN has been shown to improve insulin sensitivity, potentially reducing the risk of type 2 diabetes and metabolic syndrome, contributing to overall metabolic health.

Safety and Dosage

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.

Dosage

Human studies have tested a range of doses, with some trials using up to 1,200 mg over 6 weeks. The longest study was about 250 mg over 24 weeks. 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.

David Sinclair takes 1000 mg/day NMN in the morning.

Safety

When it comes to NMN (Nicotinamide Mononucleotide) supplementation, safety is a primary concern, especially given the relatively early stage of human studies in this area. The current body of research, mostly comprising animal studies and limited human trials, suggests that NMN is generally well-tolerated at various dosages. However, there are several important safety considerations to keep in mind:

• Human Study Limitations: Most research on NMN has been conducted in animal models, primarily mice. While these studies are promising, human biology can respond differently, and the long-term effects of NMN in humans are still not fully understood.
• Dosage and Tolerance: The tolerability of NMN appears to be dose-dependent. Human studies have tested a range of doses, with some trials using up to 1,250 mg per day or 2,000 mg per day of the specialized NMN formulation MIB-626. These studies have generally reported good tolerability, but individual responses can vary.
• Interactions with Medications: The potential interactions between NMN and various medications are not yet fully understood. Individuals taking prescription medications, particularly those for chronic conditions, should consult with a healthcare provider before starting NMN supplementation.
• Long-term Safety: The long-term safety of NMN supplementation is an area that requires further research. While short-term studies have shown promising results, the effects of prolonged NMN use over years or decades are not yet known.
• Purity and Quality of Supplements: The market for NMN supplements varies widely in terms of product purity and quality. It is crucial to source NMN from reputable suppliers who provide third-party testing and quality assurance to ensure the product is free from contaminants and accurately labeled in terms of dosage.
• Population-Specific Effects: Different populations, such as the elderly, those with chronic illnesses, or those with specific genetic backgrounds, may respond differently to NMN supplementation. Tailored studies are needed to understand these variable responses better.

In summary, while NMN supplementation is an exciting area of research with potential health benefits, especially related to aging and metabolic health, it is essential to approach it with caution. Ongoing research and clinical trials will continue to inform safer usage guidelines and help identify the full spectrum of NMN's effects in humans.

Side Effects

Overall, there have been no serious side effects in humans clinical trials that have been due to the use of NMN. When taken at higher doses than intended, you could be facing side effects such as nausea, diarrhea, indigestion, and stomach discomfort. However, these are common side effects of supplements when taken in amounts that are too high.

Some individuals reported in NMN forums low energy and tiredness potentially caused by methyl donor deficiency (see next section). The side effects can occur from the beginning or after a longer period of use.

It is important to monitor for any adverse reactions, especially when starting supplementation or changing dosages.

Methyl Donor Deficiency

There is a theoretical concern that consuming NMN could deplete methyl groups in the body and might lead to a Methyl Donor Deficiency associated with symptoms such as low energy and tiredness. NMN is converted to NAD+ in the body, which can then be broken down into nicotinamide. Nicotinamide is then methylated by the liver to form N1-methylnicotinamide, which is excreted in the urine. This methylation process consumes a methyl group from S-adenosylmethionine (SAMe), the primary methyl donor in the body.

For this reason, some individuals who take NMN also supplement with methyl donors such as Trimethylglycine (TMG) or Vitamin B Complex to ensure that they are not depleting their body's supply of methyl groups. Some individuals take methyl donors as a precautionary measure, while others may begin supplementation after experiencing sleepiness attributed to NMN.

However, there is no clear evidence yet as clinical trials are lacking. While the biochemical pathway is known, the actual impact of NMN supplementation on the global status of methyl groups is not well-established in humans. It would likely require substantial NMN consumption coupled with an insufficient intake of dietary methyl donors to significantly affect these groups. There could be also a compensatory mechanisms in place slowing down the conversion of NMN to NAD+ or the methylation of nicotinamide if methyl groups were being depleted.

Types of NMN Administration

Nicotinamide Mononucleotide (NMN) can be administered in various forms, each with its unique considerations. Below is a breakdown of the common types of NMN administration:

• Oral Powder (Dissolved in Water): NMN powder can be dissolved in water and consumed as a drink. The benefit of this method, compared to capsules, is that the dosage can be easily adjusted, for example, reduced if side effects appear. In animal studies, particularly with mice, NMN is often mixed into the animals' drinking water.
• Oral Powder (Mixed with Food): NMN powder can also be mixed with food items such as yogurt. This method is considered oral ingestion, similar to dissolving it in water, and subjects the NMN to the digestive process. Mixing NMN with food can be convenient for those who prefer not to take it sublingually or in capsule form and may help mask any unpleasant taste of the NMN powder when dissolved in water. However, the effectiveness and bioavailability of NMN when mixed with food have not been extensively studied, and the presence of other food components and the acidic environment might potentially influence the stability and absorption of NMN.
• Capsule Form: NMN is encapsulated for easy consumption, offering a convenient and taste-neutral method. Like oral powder, capsules subject NMN to the digestive process. Capsule form is often used in clinical trials as it allows for precise dosing and is generally well-accepted by participants. It also enables the blinding of participants in placebo-controlled trials, maintaining the integrity of the study, as it is easier to make placebo capsules or tablets that are indistinguishable from the active ones.
• Sublingual Powder: This form of NMN is taken by placing the powder directly under the tongue, allowing it to dissolve and be absorbed through the mucous membranes in the mouth. The general guideline is to hold the substance under the tongue for approximately 1 to 5 minutes to allow for adequate absorption through the sublingual gland. Some individuals believe sublingual administration offers better bioavailability due to direct absorption into the bloodstream, bypassing the digestive system. However, while this method is promoted in many YouTube videos, there is no evidence of any positive or negative effects and there is currently no clinical study utilizing sublingual administration. Furthermore, this method is relatively inconvenient, especially for those who might find the taste of sublingual powder too strong.

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. 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.

Dr. David Sinclair suggests 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.

A recent RCT clinical trial investigated the effects of the time-dependent intake of NMN (250 mg/day) on older adults (≥ 65 years) over 12 weeks. Aging-induced insufficient physical activity and deterioration of physical function result in fatigue. This symptom frequently occurs among the elderly and has been complained by 27–50% of community-dwelling older adults in their daily life. Overall, NMN intake in the afternoon (in contrast to the morning) effectively improved lower limb function and reduced drowsiness in older adults. These findings suggest the potential of NMN in preventing loss of physical performance and improving fatigue in older adults.

Additionally, it's noteworthy that two MIB-626 trials utilized a twice per day administration regimen. This dosing schedule is significant because it could potentially offer more consistent NAD+ level support throughout the day, although the specific implications of this frequency in relation to circadian rhythms and overall efficacy remain an area for further research.

Stability and Storage

NMN powders are thought to degrade into NAD+ when left at room temperature. However, this may be true for pure NMN supplements, some supplements use NMN in a stabilized form. This form has been shown to be more stable thus resulting in less breakdown at room temperature.

Humidity or water can have negative effects on NMN and result in the degradation of NMN into NAD+. This fact is not disputed and thus NMN powder should be stored in a dry place in a resealable container.

In addition, scientists have tested NMN powders and found that these do not need to be kept in the refrigerator or freezer. The purity at 1 year when stored in a plastic bottle at room temperature was found to be 99.8%. Also a NMN manufacturer published NMN stability results when putting NMN into double pharmaceutical polyethylene bags. After 6 month under condition of 40℃ and 75% relative humidity the samples had > 99% purity.

However, it is advised if storing for the long-term (> 3 months), NMN supplements should be kept in the refrigerator to ensure its stability.

Overall, NMN powders are stable when stored at room temperature, especially when provided in a stabilized form. However, they need to be kept away from high-humidity environments as water can speed up the degradation of NMN. So if you plan to consume the powder immediately (< 1–2 months) you do not need to store it in the refrigerator but if stored for> 3 months it is best to store it in the refrigerator.

Always consult the manufacturer of you specific NMN supplements to obtain proper storage instructions for your product. If concerned, storing the NMN in the refrigerator does not have negative effects on the NMN and thus can be done.

NMN appears to be stable in water; in one study 93%–99% of NMN was maintained intact in drinking water at room temperature for 7–10 days.

Clinical Trials

Starting in 2020, with the assessment of the safety of a single dose administration of NMN, there have been around 10 randomized controlled trials (RCTs) exploring the compound's effects in various contexts. The trials have varied in duration, with the longest running for 12 weeks. In terms of dosage, they have explored a range of quantities, with the highest being 1,250 mg of NMN per day and 2,000 mg (2 g) of MIB-626, a specific formulation of NMN, per day. The following table provides a comprehensive overview of these trials, detailing their design, participant demographics, dosages, and key findings:

Clinical Trials of NMN

Clinical Trial	Design (dosage is per day, 2x means twice per day)	Participants	Outcome
2020, Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men	singe admission up to 500 mg	10 healthy men age 40-60	admission was safe and well-tolerated
2021, Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women	RCT, 10 weeks placebo (n=12) 250 mg (n=13)	25 postmenopausal women with prediabetes overweight or obese (BMI 25.3 - 39.1) age 56-66	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
2021, Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study	RCT, 6 weeks placebo (n=12) 300 mg (n=12) 600 mg (n=12) 1200 mg (n=12)	48 young and middle-aged recreationally trained runners age 35 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.
2021, The Impacts of Short-Term NMN Supplementation on Serum Metabolism, Fecal Microbiota, and Telomere Length in Pre-Aging Phase NMN.com article	90 days 300 mg in warm water	8 healthy men age 45–60	* NMN doubles the telomere length of humans over a 90-day period of time.
2022, Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women	RCT, 4 weeks placebo (n=15) 1250 mg (n=16)	31 healthy adult men and women age 20–65	Oral administration of 1250 mg of NMN, when administered once daily for up to 4 weeks, was safe and well-tolerated in healthy adult men and women. Oral administration of NMN in humans has a low adverse effect on renal function. Results indicate that NMN can be administered orally to humans at doses 1250 mg once daily for up to 4 weeks without causing hepatotoxicity and vasodilative flushing, and is believed to have a higher upper tolerable limit compared to NAM and NA.
2022, Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study	RCT, 12 weeks placebo, before 12 pm placebo, after 6 pm 250 mg, before 12 pm 250 mg, after 6 pm	108 older adults age ≥ 65	NMN intake in the afternoon is more effective in improving lower limb function and reducing drowsiness in older adults.
2022, Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men	RCT, 12 weeks placebo (n=10) 250 mg (n=10)	20 healthy male age ≥ 65 BMI 22–28 nonsmokers	250 mg of NMN per day for 12 weeks significantly increased NAD+ blood levels in healthy males older than 65. The supplementation regimen improves walking speed and grip strength in the aged men. These findings suggest NMN supplementation may be used to ameliorate age-related muscle deterioration.
2022, A Multicentre, Randomised, Double Blind, Parallel Design, Placebo Controlled Study to Evaluate the Efficacy and Safety of Uthever (NMN Supplement), an Orally Administered Supplementation in Middle Aged and Older Adults	RCT, 60 days placebo (n=31) 300 mg (n=31)	66 healthy subjects age 40-65	NAD+ levels increase by 11.3% after 30 days, 38% after 60 days
2022, Nicotinamide Mononucleotide Is Safely Metabolized and Significantly Reduces Blood Triglyceride Levels in Healthy Individuals	single intravenous administration 300 mg	10 healthy adults age 20-70	300 mg intravenous NMN administration is tolerated by humans significantly increased blood NAD+ levels
2023, 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)	healthy males and females age 40-65 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
2023, MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of β-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults	RCT, 2 weeks 1000 mg MIB-626 2x1000 mg MIB-626 placebo	32 overweight or obese adults age 55-80	MIB-626 was well tolerated Blood NMN concentrations significantly higher in treated groups compared to placebo Substantial dose-related increases in blood NAD levels and its metabolome Changes in NMN or NAD levels not related to sex, BMI, or age Very little unmodified NMN excreted in urine Facilitates design of efficacy trials in disease conditions
2023, Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study	RCT, 4 weeks 2x500 mg/day MIB-626 placebo	30 overweight or obese adults age ≥ 45	MIB-626 treatment increased circulating NAD and metabolites No significant change in muscle strength, muscle fatigability, aerobic capacity, and stair-climbing power Significant reduction in body weight, diastolic blood pressure, total LDL, and non-HDL cholesterol Insulin sensitivity and hepatic and intra-abdominal fat unchanged Adverse events similar between groups Provides rationale for larger trials on NAD augmentation for cardiometabolic outcomes in older adults
2023, Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial	RCT, 12 weeks, capsules placebo (n=17) 2x125 mg (n=17)	34 healthy male and female age 40-59	250 mg of NMN for 12 weeks does not significantly reduce artery stiffness — a risk factor for cardiovascular disease, dementia, and death — in healthy middle-aged adults. However, NMN reduces artery stiffness in individuals with high blood-glucose and body mass index (weight/height). Blood vessel biological aging is reversed by 2 years with NMN treatment.
2023, Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study	RCT, 24-week placebo 250 mg	male patients with diabetes reduced grip strength (<26 kg) or walking speed (<1.0 m/s) age ≥ 65	NMN was tolerable without any severe adverse events NMN did not improve grip strength and walking speed Improved prevalence of frailty in the NMN group (P = 0.066) Different changes in central retinal thickness between the two groups (P = 0.051)
2023, NAD+ exhaustion by CD38 upregulation contributes to blood pressure elevation and vascular damage in hypertension NMN.com article	6 weeks, lifestyle modifications no NMN (n=10) 800 mg (n=9)	19 mild hypertensive adults age 18-80	Supplementing hypertension patients with 800 mg of oral NMN per day for six weeks significantly lowers their blood pressure. Hypertension patients display significantly lower blood cell NAD+ levels, and taking NMN increases their blood cell NAD+ levels by ~43%. Adults with hypertension have cells lining blood vessels — endothelial cells — with elevated concentrations of the NAD+ consuming enzyme CD38, which partially explains their lower NAD+ levels.
2022, Oral Administration of Nicotinamide Mononucleotide Is Safe and Efficiently Increases Blood Nicotinamide Adenine Dinucleotide Levels in Healthy Subjects
2023, Nicotinamide mononucleotide (NMN) intake increases plasma NMN and insulin levels in healthy subjects

See also

• Nicotinamide Adenine Dinucleotide (NAD+)
• NAD+ Boosters
• NAD+ Precursor
• NMN Manufacturer
• Wikipedia - Nicotinamide mononucleotide

Todo

• 2023, Potential Synergistic Supplementation of NAD+ Promoting Compounds as a Strategy for Increasing Healthspan
  • 2022, Improvement of tissue-specific distribution and biotransformation potential of nicotinamide mononucleotide in combination with ginsenosides or resveratrol
• 2018, Sirtuin 3-dependent mitochondrial redox homeostasis protects against AGEs-induced intervertebral disc degeneration
• https://www.nmn.com/news/nmn-tablet-blood-nad-levels-humans
• https://link.springer.com/article/10.1007/s13668-023-00475-y
• https://www.lifespan.io/topic/nmn-nicotinamide-mononucleotide-benefits-side-effects/
• https://novoslabs.com/frequently-asked-questions/nmn-nicotinamide-mononucleotide/can-you-take-nmn-if-you-have-a-mthfr-mutation-or-suffer-from-reduced-methylation/
• https://ajtm.journals.publicknowledgeproject.org/index.php/ajtm/article/view/2535
• https://www.nature.com/articles/s41598-018-30792-0
• https://www.nmn.com/news/new-study-shows-nmn-rejuvenates-stem-cells-and-mitochondria-by-activating-longevity-protein

2022, Nicotinamide Mononucleotide Supplementation Improves Mitochondrial Dysfunction and Rescues Cellular Senescence by NAD⁺/Sirt3 Pathway in Mesenchymal Stem Cells

• Slc12a8
  • 2021, NAD⁺ metabolism and its roles in cellular processes during ageing
  • 2022, Slc12a8 in the lateral hypothalamus maintains energy metabolism and skeletal muscle functions during aging
  • https://patents.google.com/patent/US11564936B2/