NMN, NR, and NADH Supplements: What the Evidence Actually Shows

NMN, NR, and NADH Supplements: What the Evidence Actually Shows

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Nicotinamide adenine dinucleotide (NAD) is a coenzyme essential for energy production in mitochondria throughout the body. It exists in two interconvertible forms: NAD+ (the oxidized form, carrying a positive charge) and NADH (the reduced form, with a hydrogen atom attached, making it electrically neutral) [1][2]. NAD+ participates in hundreds of metabolic reactions, including cellular respiration, DNA repair, sirtuin-mediated deacetylation, and regulation of circadian rhythm [2][3]. Every living cell depends on NAD+ to convert nutrients into usable energy via the electron transport chain.

The body synthesizes NAD+ from dietary precursors — primarily niacin (vitamin B3) and its derivatives, including nicotinamide (niacinamide), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN) [1][4]. Some NAD+ is stored in red blood cells, while excess is broken down in the liver and excreted in urine [1]. The predominant route for NAD+ replenishment in mammalian cells is the salvage pathway, which recycles nicotinamide generated from NAD+-consuming enzymes such as sirtuins, PARPs (poly ADP-ribose polymerases), and CD38 [3][5]. This pathway accounts for over 85% of NAD+ production in most tissues [5].

Interest in NAD-boosting supplements was sparked by preliminary laboratory research suggesting that NAD+ levels decline with age. A 2012 study found that NAD+ decreased in human skin tissue with advancing age (Massudi et al., PLoS One, 2012) [6], and a 2013 study in mice showed that raising NAD+ levels could reverse aspects of mitochondrial dysfunction (Gomes et al., Cell, 2013) [7]. These findings raised the hope that boosting NAD+ could provide benefits for aging. However, a subsequent study in humans found no significant difference in NAD+ levels between older and younger people (Elhassan et al., bioRxiv, 2019 — preprint), casting doubt on the assumption that age-related NAD+ decline is universal or that supplementation would necessarily provide a measurable effect [1][8].

If you already consume adequate vitamin B3 (14–16 mg daily for adults) from your diet — which is not difficult, as B3 is present in many foods — and/or supplements, it is unclear whether any of the NAD-boosting supplements discussed in this article provide meaningful additional benefit [1].

The three main categories of NAD-boosting supplements are:

  • NAD+/NADH — Direct supplementation with the coenzyme itself, usually in the reduced NADH form. NADH is 99.85% NAD by weight [1].
  • Nicotinamide riboside (NR) — A precursor to NAD+ that is converted to NMN by nicotinamide riboside kinases (NRK1/NRK2), then to NAD+ by NMNATs [5][9]. Sold as Niagen (nicotinamide riboside chloride), nicotinamide riboside hydrogen malate, and crystalline nicotinamide riboside (as in Elysium Health's Basis product) [1].
  • Nicotinamide mononucleotide (NMN) — A nucleotide that sits one enzymatic step closer to NAD+ than NR in the salvage pathway. NMN is converted directly to NAD+ by nicotinamide mononucleotide adenylyltransferases (NMNATs) [3][5]. Typically marketed as NMN or beta-NMN (identical compounds) [1].

This article reviews the human clinical evidence, forms, dosing, safety, and practical considerations for each of these NAD-boosting compounds.

Table of Contents

Overview

Nicotinamide adenine dinucleotide (NAD) is a coenzyme essential for energy production in mitochondria throughout the body. It exists in two interconvertible forms: NAD+ (the oxidized form, carrying a positive charge) and NADH (the reduced form, with a hydrogen atom attached, making it electrically neutral) [1][2]. NAD+ participates in hundreds of metabolic reactions, including cellular respiration, DNA repair, sirtuin-mediated deacetylation, and regulation of circadian rhythm [2][3]. Every living cell depends on NAD+ to convert nutrients into usable energy via the electron transport chain.

The body synthesizes NAD+ from dietary precursors — primarily niacin (vitamin B3) and its derivatives, including nicotinamide (niacinamide), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN) [1][4]. Some NAD+ is stored in red blood cells, while excess is broken down in the liver and excreted in urine [1]. The predominant route for NAD+ replenishment in mammalian cells is the salvage pathway, which recycles nicotinamide generated from NAD+-consuming enzymes such as sirtuins, PARPs (poly ADP-ribose polymerases), and CD38 [3][5]. This pathway accounts for over 85% of NAD+ production in most tissues [5].

Interest in NAD-boosting supplements was sparked by preliminary laboratory research suggesting that NAD+ levels decline with age. A 2012 study found that NAD+ decreased in human skin tissue with advancing age (Massudi et al., PLoS One, 2012) [6], and a 2013 study in mice showed that raising NAD+ levels could reverse aspects of mitochondrial dysfunction (Gomes et al., Cell, 2013) [7]. These findings raised the hope that boosting NAD+ could provide benefits for aging. However, a subsequent study in humans found no significant difference in NAD+ levels between older and younger people (Elhassan et al., bioRxiv, 2019 — preprint), casting doubt on the assumption that age-related NAD+ decline is universal or that supplementation would necessarily provide a measurable effect [1][8].

If you already consume adequate vitamin B3 (14–16 mg daily for adults) from your diet — which is not difficult, as B3 is present in many foods — and/or supplements, it is unclear whether any of the NAD-boosting supplements discussed in this article provide meaningful additional benefit [1].

The three main categories of NAD-boosting supplements are:

  • NAD+/NADH — Direct supplementation with the coenzyme itself, usually in the reduced NADH form. NADH is 99.85% NAD by weight [1].
  • Nicotinamide riboside (NR) — A precursor to NAD+ that is converted to NMN by nicotinamide riboside kinases (NRK1/NRK2), then to NAD+ by NMNATs [5][9]. Sold as Niagen (nicotinamide riboside chloride), nicotinamide riboside hydrogen malate, and crystalline nicotinamide riboside (as in Elysium Health's Basis product) [1].
  • Nicotinamide mononucleotide (NMN) — A nucleotide that sits one enzymatic step closer to NAD+ than NR in the salvage pathway. NMN is converted directly to NAD+ by NMNATs [3][5]. Typically marketed as NMN or beta-NMN (identical compounds) [1].

Forms and Bioavailability

NAD+ and NADH

NADH is the form used in clinical studies, as direct NAD+ exhibits poor cellular uptake when taken orally [3][10]. Stabilized NADH (such as the branded product ENADA) has been used at doses of 5–20 mg in clinical trials [1]. Oral NADH is absorbed in the small intestine, though bioavailability data in humans is limited. The primary advantage of NADH supplementation is that it provides the coenzyme directly without requiring conversion. However, because NADH is chemically unstable and sensitive to light, moisture, and stomach acid, stabilized or enteric-coated formulations are necessary for oral delivery [1][11].

Nicotinamide Riboside (NR)

NR is available in several commercial forms:

  • Nicotinamide riboside chloride (Niagen) — The most extensively studied form in clinical trials. Manufactured by ChromaDex (now Niagen Bioscience). Found in the product Tru Niagen [1].
  • Nicotinamide riboside hydrogen malate — An alternative salt form [1].
  • Crystalline nicotinamide riboside — Used in Elysium Health's Basis product, combined with pterostilbene. ChromaDex has claimed that the nicotinamide riboside in Basis is not identical to Niagen, though both raise NAD+ levels [1][12].

NR is orally bioavailable with high and consistent absorption, entering cells directly via equilibrative nucleoside transporters without significant gut degradation [3][10]. Once inside cells, NR is phosphorylated by nicotinamide riboside kinases (NRK1 and NRK2) to form NMN, which is then adenylated by NMNATs to form NAD+ [5][9]. A pharmacokinetic study among 11 healthy adults showed that single doses of 100 mg, 300 mg, or 1,000 mg of Niagen increased NAD+ levels in a dose-dependent fashion (Trammell et al., Nat Commun, 2016) [13]. In a longer trial, daily doses of 100 mg, 300 mg, and 1,000 mg of Niagen for 8 weeks increased whole blood NAD+ levels by 22%, 51%, and 142%, respectively, within two weeks, and these increases were maintained throughout the study (Conze et al., Sci Rep, 2019) [14]. Most commercially available NR supplements provide approximately 250 mg per daily dose [1].

Nicotinamide Mononucleotide (NMN)

NMN is a ribonucleotide consisting of a nicotinamide base linked to a ribose sugar with a phosphate group at the 5' position (molecular formula: C11H15N2O8P, molecular mass: 334.22 Da) [3]. It is water-soluble and functions as the immediate biosynthetic precursor to NAD+ in the salvage pathway [5].

NMN administered orally is rapidly absorbed from the small intestine, with peak plasma concentrations observed within 15–60 minutes of ingestion [3][15]. Human pharmacokinetic studies show that single doses of 100–900 mg elevate plasma NMN levels in a dose-dependent manner, alongside increases in NAD+ and its metabolites [3][15]. The bioavailability of oral NMN is characterized by rapid absorption followed by quick metabolism and clearance, with a half-life of approximately 1–2 hours. However, chronic supplementation at 250–900 mg daily for 4–12 weeks sustains elevated NAD+ levels in blood and tissues without accumulation of NMN itself [3][15][16].

The mechanism of NMN absorption remains debated. Evidence supports both direct cellular uptake via a specific transporter (Slc12a8) and extracellular dephosphorylation to NR by the enzyme CD73 before re-entry into cells [3][5][17]. Detection of intact NMN in plasma after oral dosing supports at least partial direct absorption [3][15].

Alternative delivery forms include sublingual (powders, lozenges) and liposomal encapsulation. Sublingual forms claim to bypass gastrointestinal and first-pass hepatic metabolism. Liposomal NMN has shown promise in small studies — one double-blind trial reported an 84% increase in blood NAD+ levels after four weeks with liposomal NMN, compared to lower elevations with standard capsules [3][18]. However, no peer-reviewed human studies have directly compared sublingual to oral administration, and claims of 2–3 times higher bioavailability remain unsubstantiated [3][19].

NR vs. NMN: Head-to-Head

Standard oral NR has historically shown higher effective bioavailability of the intact molecule compared to standard oral NMN, because NMN's phosphate group may require extracellular conversion to NR before cellular uptake [3][10]. However, NMN appears more stable in the bloodstream once absorbed, and both precursors are equally effective at elevating NAD+ levels in blood [3][10]. Head-to-head comparisons in 2026 trials demonstrated that NMN approximately doubles baseline NAD+ concentrations after 14 days of daily supplementation, comparable to the increases seen with NR [3]. The practical difference between the two precursors may be minimal for most users.

Quality Concerns

A 2021 analysis by ChromaDex of 22 top-selling NMN products on Amazon found that only 14% met or exceeded label claims, 23% were slightly below (88–99% of claimed NMN), and 64% contained less than 1% of claimed NMN, with 14% having none detectable [3]. This extreme variability underscores the importance of third-party testing when selecting NMN supplements.

Evidence for Benefits

Chronic Fatigue Syndrome (CFS) — NADH

Chronic fatigue syndrome has been associated with increased activity of enzymes that deplete ATP, the primary energy currency of cells. Since NADH is directly involved in ATP generation, there has been interest in using it to increase energy and reduce fatigue in CFS patients [1].

Crossover trial (n=26): A study among 26 people with CFS who received 10 mg of stabilized NADH (ENADA) or placebo daily for 4 weeks showed that 31% of NADH recipients experienced a clinically meaningful improvement in symptoms (defined as improvement of at least 10%), compared to only 8% on placebo. However, no formal between-group statistical comparison was performed. One participant reported feeling overly stimulated while taking NADH (Forsyth et al., Ann Allergy Asthma Immunol, 1999) [20].

Controlled trial with active comparator (n=20): A study of 20 CFS patients — 12 receiving 5 mg NADH daily (increased to 10 mg if symptoms did not improve) and 8 receiving nutritional supplements plus psychological therapy for up to 24 months — showed that both groups improved during the first 3 months compared to baseline, but there was no significant between-group difference, and neither group improved beyond 3 months (Santaella et al., P R Health Sci, 2004) [21].

NADH + CoQ10 combination (n=73, positive): A study among 73 CFS patients found that taking 20 mg NADH with 200 mg CoQ10 daily for 8 weeks modestly improved overall Fatigue Impact Scale (FIS-40) scores by approximately 7.5 points (out of 160) compared to baseline, and this improvement was statistically significant compared to placebo (Castro-Marrero et al., Antioxid Redox Signal, 2015) [22].

NADH + CoQ10 combination (n=144, negative): A larger study among 144 CFS patients found the same combination of 20 mg NADH and 200 mg CoQ10 daily for 8 weeks did NOT improve physical functioning, psychosocial symptoms, overall FIS-40 scores, or sleep quality compared to placebo. Although the NADH/CoQ10 group showed modest improvement in perception of cognitive fatigue (approximately 1.1 points out of 40) compared to baseline, this was not significant versus placebo (Castro-Marrero et al., Nutrients, 2021) [23].

Expert opinion: Based on the limited evidence, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has stated that NADH may be tried by people with CFS to relieve fatigue or cognitive dysfunction (Nacul et al., Medicina (Kaunas), 2021) [24].

Alzheimer's Disease and Cognitive Function — NADH

Dementia (n=19, uncontrolled): An uncontrolled study among 19 people with mild to moderate dementia (Alzheimer's, vascular, and fronto-temporal types) found that 10 mg of NADH (ENADA) daily for 3 months did not improve measures of cognition compared to baseline (Rainer et al., J Neural Transm (Vienna), 2000) [25].

Alzheimer's disease (n=24, controlled): A study among 24 people with probable Alzheimer's disease showed that those who took 10 mg of NADH (ENADA) daily for 6 months experienced no cognitive decline and had higher scores on the Mattis Dementia Rating Scale compared to placebo. However, there was no between-group difference in attention, memory, or clinician-rated dementia severity (Demarin et al., Drugs Exp Clin Res, 2004) [26].

Parkinson's Disease — NADH

NADH is a coenzyme involved in the synthesis of L-DOPA, a precursor of dopamine — the neurotransmitter deficient in Parkinson's disease [1].

Open-label study (n=885): An open-label study among 885 Parkinson's patients already receiving conventional medication found that 5 mg enteric-coated NADH by mouth or 12.5 mg NADH by 30-minute infusions every other day for 2 weeks improved disability scores on the Birkmayer-Neumayr scale by similar amounts (19.8% vs 20.6%, respectively) (Birkmayer et al., Acta Neurol Scand Suppl, 1993) [27].

Open-label study with levodopa (n not specified): An open-label study showed that 10 mg NADH by 30-minute infusion for 7 days along with 100 mg levodopa improved UPDRS scores by 9.3 points (out of 199) and slightly increased blood levels of levodopa compared to baseline (Kuhn et al., J Neural Transmission, 1996) [28].

Placebo-controlled trial (negative): A placebo-controlled study showed that infusions of 25 mg NADH for 4 days, then intramuscular injections of 25 mg NADH on days 20 and 35, did NOT improve UPDRS scores compared to placebo. Both groups improved compared to baseline (7.6 and 5.3 points, respectively) (Dizdar et al., Acta Neurol Scand, 1994) [29].

Depression — NADH

Open-label study (n=188): One open-label study among 188 people with depression found that 5 mg NADH by mouth or 12.5 mg NADH by injection daily for up to approximately 10 months improved symptoms in 93% of participants, with 32% showing marked improvement (improvement greater than half the original disability). However, the lack of a control group prevents conclusions about causality (Birkmayer et al., New Trends Clin Neuropharmacol, 1991) [30].

Raising NAD+ Levels — Nicotinamide Riboside

Multiple studies confirm that NR reliably raises blood NAD+ levels, though translating this biochemical change into clinical benefit has proven difficult [1][13][14].

Dose-response in healthy adults (n=11): Single doses of Niagen at 100 mg, 300 mg, or 1,000 mg increased NAD+ levels without serious adverse events. Two people reported flushing at 300 mg and two others reported "feeling hot" at 1,000 mg (Trammell et al., Nat Commun, 2016) [13].

Eight-week dose-response (n=overweight adults): Daily doses of 100 mg, 300 mg, and 1,000 mg of Niagen for 8 weeks increased whole blood NAD+ by 22%, 51%, and 142%, respectively, within two weeks. These increases were maintained for the study duration. There were no reports of flushing, no significant differences in adverse events between NR and placebo groups, and no elevation of LDL cholesterol (Conze et al., Sci Rep, 2019) [14].

Older adults (n=24): Healthy adults aged 55–79 taking 500 mg Niagen twice daily for six weeks had a 60% increase in average blood NAD+ levels compared to placebo. Flushing was reported in one NR participant and two placebo participants. Nausea, leg cramps, and increased bruising were each reported in one NR participant (Martens et al., Nat Commun, 2018) [31].

NR + pterostilbene (n=120): A study of Basis (Elysium Health) — 250 mg NR plus 50 mg pterostilbene per capsule — among 120 older adults found that one capsule or two capsules daily for two months increased blood NAD+ by 40% and 55%, respectively. There was a slight but significant increase in LDL ("bad") cholesterol with two capsules and among overweight people taking one capsule. There were no significant changes in total cholesterol, triglycerides, or blood pressure. Six of 80 people taking Basis reported nausea, mild fatigue, or moderate abdominal discomfort (Dellinger et al., NPJ Aging Mech Dis, 2017) [12].

Energy and Physical Performance — Nicotinamide Riboside

Due to NAD's role in cellular energy production, it was hoped that NR would improve functional energy levels. However, this has not been demonstrated in clinical studies [1].

The maker of Niagen (ChromaDex, now Niagen Bioscience) previously claimed that Niagen increased energy but removed that claim in 2021 following a challenge by the National Advertising Division (NAD) of the Better Business Bureau. The claim was apparently based only on laboratory research showing increased cellular energy, not functional improvements [1]. In March 2026, the NAD recommended that Niagen Bioscience discontinue claims that Tru Niagen is "clinically proven to significantly increase NAD+ levels, and help maintain them with daily use," along with broader health benefit claims. Niagen Bioscience agreed to discontinue certain claims but stated it would appeal [1].

Physical performance review: A review of clinical studies evaluating NR for physical performance in older adults found small, short-term studies with mixed results (Cusodero et al., Exp Gerontol, 2020) [32].

Peripheral Artery Disease — Nicotinamide Riboside

Walking distance (n=89): A study among 89 adults (average age 71) with lower extremity peripheral artery disease (PAD) found that 500 mg NR (from ChromaDex) twice daily for 6 months increased 6-minute walking distance by an average of 7 meters, while walking distance decreased by 10.6 meters in the placebo group. This between-group difference was statistically significant — although largely driven by the decline in the placebo group rather than improvement with NR. NR did NOT improve maximum treadmill walking time, degree of difficulty when walking, or overall physical activity compared to placebo (McDermott et al., Nat Commun, 2024) [33].

Cognitive function in PAD (n=8): A small study among 8 older adults (average age 67) with PAD found that 1,000 mg NR daily for 4 weeks did NOT significantly improve executive function, attention, language, processing speed, or episodic memory compared to baseline (Szarvas et al., J Pharmacol Exp Ther, 2025) [34].

Alzheimer's Disease — Nicotinamide Riboside

Animal studies: NR has been shown in mice to reduce amyloid plaque components and improve cognitive function (Gong et al., Neurobiol Aging, 2013) [35], and to improve stem cell function (Zhang et al., Science, 2016) [36].

Biomarker analysis (n=22): Analysis of blood from 22 healthy middle-aged and older adults who took 500 mg Niagen twice daily for 6 weeks suggested NR raised NAD+ levels in the brain and reduced biomarkers associated with Alzheimer's. However, this was based on measurements of peripheral blood compounds believed to originate from the brain — it does not prove NR can treat or prevent Alzheimer's disease (Vreones et al., Aging Cell, 2023) [37].

Mild cognitive impairment (n=20): A study among 20 older adults (average age 76) with mild cognitive impairment found that NR did NOT significantly improve short-term memory, executive function, attention, concentration, working memory, language, or orientation compared to placebo. Those in the placebo group actually showed greater improvements in physical function, lower extremity strength, and gait speed. NR was given as a titrated dose: 250 mg for week 1, 500 mg for week 2, 750 mg for week 3, then 1,000 mg daily. One person experienced severe nausea, which resolved when the dose was temporarily reduced (Orr et al., Geroscience, 2024) [38].

Self-reported cognitive decline (n=37): A study among 37 adults (average age 67) with self-reported cognitive decline or mild cognitive impairment found that 1 g of NR (TruNiagen by ChromaDex) daily for 8 weeks did NOT improve overall cognitive function or scores for immediate memory, language, attention, delayed memory, or visuospatial index compared to placebo. Although the NR group showed a small reduction in phosphorylated tau 217 (a blood biomarker for Alzheimer's) while the placebo group showed a 17% increase (a statistically significant difference), there were no significant between-group differences in other Alzheimer's biomarkers, including neurofilament light chain and glial fibrillary acidic protein. One person taking NR experienced worsening of an underlying gait disorder (Wu et al., Alzheimers Dement (N Y), 2025) [39].

Cholesterol — Nicotinamide Riboside

NR has been promoted for lowering cholesterol levels in the liver, although this has only been shown in laboratory and animal studies (Lee et al., J Med Food, 2015) [40] and not in clinical trials [1].

Blood Sugar and Insulin Resistance — Nicotinamide Riboside

Overweight men with insulin resistance (n=40): A study in Denmark among 40 overweight men with insulin resistance (HOMA-IR >= 2.5) found that 1,000 mg NR (Niagen) twice daily for three months did NOT decrease fasting blood sugar levels or HbA1c, or improve insulin sensitivity compared to placebo. There were no improvements in body composition (body fat, lean mass, or total body mass). Side effects included itching, excessive sweating, bloating, and changes in stool (Dollerup et al., Am J Clin Nutr, 2018) [41].

Long COVID — Nicotinamide Riboside

Brain fog and fatigue (n=32): A 24-week study among 32 adults (average age 47) with long COVID (particularly "brain fog" and at least two other symptoms) found that 1,000 mg NR twice daily significantly increased NAD+ levels 2- to 3-fold, but there were NO significant improvements in cognitive function, fatigue severity, sleep quality, anxiety symptoms, or depression compared to placebo. Side effects possibly related to NR included muscle and leg cramps, nausea, bruising, worsening of headaches, flushing, rash, and vertigo. This study was funded by Niagen Bioscience (Wu et al., eClinicalMedicine, 2025) [42].

Note: The FDA sent a warning letter to ChromaDex in November 2020 for promoting Niagen as preventing or treating COVID-19, including claims that low NAD+ levels can worsen COVID-19 [1].

Raising NAD+ Levels — NMN

Like NR, NMN reliably raises blood NAD+ levels. Human clinical trials have consistently used daily oral doses ranging from 250 to 1,200 mg per day over periods of several weeks to months [3][43].

Postmenopausal women with prediabetes (n=25): Taking 250 mg NMN daily for 10 weeks increased NAD+ content in peripheral blood mononuclear cells (immune cells) by approximately 43% compared to placebo. However, skeletal muscle NAD+ content was not increased (Yoshino et al., Science, 2021) [44].

Multicenter trial (n=80): A randomized, double-blind, placebo-controlled trial among 80 healthy middle-aged adults (aged 40–65) administered 300 mg, 600 mg, or 900 mg NMN daily for 60 days. Blood NAD+ levels increased significantly in all NMN groups compared to placebo (p <= 0.001), with peak elevations at 600 mg and 900 mg. No significant changes occurred in blood glucose, insulin sensitivity, lipids, or blood pressure. Six-minute walk distance improved (p < 0.01), and blood biological age did not rise as it did in the placebo group (p < 0.05) [3][45].

Healthy Japanese adults (n=30): A 12-week study using 250 mg/day NMN significantly raised whole-blood NAD+ at weeks 4, 8, and 12 (returning to baseline by week 16), with no adverse effects beyond minor gastrointestinal issues. No significant impacts on body composition, glucose metabolism, lipid profiles, or amino acid levels were observed [3][46].

Insulin Sensitivity — NMN

Postmenopausal women with prediabetes (n=25): Taking 250 mg NMN daily for 10 weeks increased muscle insulin sensitivity by 25% compared to baseline, with upregulated insulin signaling (pAKT, pmTOR) and muscle remodeling genes. There was no improvement in muscle insulin sensitivity in the placebo group, and neither group showed improvement in liver insulin sensitivity (Yoshino et al., Science, 2021) [44]. However, this study has been criticized because at baseline, the placebo group had 2.35 times more liver fat than the treatment group, and liver fat is known to reduce muscle insulin sensitivity. It is therefore unclear if the difference was due to NMN or baseline differences in liver fat (Brenner, Science, 2021) [47].

Exercise Performance — NMN

Recreational runners (n=48): A study among 48 recreational runners (average age 36) taking 300 mg or 600 mg NMN twice daily for 6 weeks while training 5–6 times weekly found dose-dependent improvements in the time until breathing begins to increase during exercise (VT1) and power output at the anaerobic threshold (VT2) compared to placebo. However, neither dose increased maximum oxygen consumption or improved the ratio of oxygen consumption to heart rate. A lower dose (150 mg twice daily) did not improve any outcome. No adverse effects were reported. The researchers speculated that NMN may improve skeletal muscle oxygen utilization but noted it does not appear to provide a cardiac benefit (Liao et al., J Int Soc Sports Nutr, 2021) [48].

Systematic review of 10 RCTs: A 2024 systematic review found non-significant overall improvements in physical strength and aerobic performance with NMN across diverse adult populations, with dose-dependent trends favoring aerobic capacity but no alterations in skeletal muscle index. NMN was well-tolerated, with only 8.2% of 437 participants experiencing minor, unrelated adverse events [3][49].

Muscle Strength and Physical Function in Older Adults — NMN

Healthy older men (n=20): A study among 20 healthy older men (average age 72) found that 250 mg NMN daily for 12 weeks increased blood NAD+ levels but did NOT produce statistically significant increases in skeletal muscle mass, walking speed, leg strength, or grip strength, nor reductions in abdominal or liver fat mass, nor improvements in cognitive function compared to placebo. Note: The abstract of this study has been described as misleading in its conclusion that NMN can be "efficient for preventing aging-related muscle dysfunctions" (Igarashi et al., NPJ Aging, 2022) [50].

Older men with grip strength (n=20, different trial): A 12-week trial of 250 mg daily NMN showed significant gains in left-hand grip strength (p=0.019), gait speed (p=0.033), and performance on the 30-second chair-stand test at 6 weeks (p=0.031), with no changes in skeletal muscle mass [3][16].

Older men with impairments (n=14): A 24-week study among 14 older men (mean age 81.1) with diabetes and baseline impairments (grip strength <26 kg or walking speed <1.0 m/s) found NO significant differences in grip strength or walking speed after 250 mg daily NMN versus placebo [3][51].

Sleep — NMN

Older Japanese adults (n=108): A study among 108 older adults (average age 72) found that 250 mg NMN daily for 12 weeks did NOT improve sleep quality or duration compared to placebo, regardless of whether it was taken in the morning or evening. Those who took NMN in the afternoon had a modest decrease in daytime drowsiness compared to placebo (but morning dosing did not have this effect). Afternoon dosing also led to slightly greater improvement on one test of physical performance (repeated sit-to-stand) compared to morning NMN or placebo, although all three groups improved modestly on this test (Kim et al., Nutrients, 2022) [52].

Additional sleep evidence: Other trials have reported that NMN maintained or improved PSQI sleep quality scores and reduced daytime dysfunction after 12 weeks of 250 mg/day supplementation (Morifuji et al., Geroscience, 2024). A further trial showed NMN reduced sleep latency and increased deep and REM sleep, as measured by wearable devices (Zhao et al., 2022). These findings suggest NMN may support sleep in certain populations, potentially through NAD+ restoration aiding circadian rhythm regulation, though evidence remains inconsistent [3].

Anti-Aging Claims — NMN

The central claim driving NMN's popularity is that it counters age-related decline by restoring NAD+ levels, which decline by up to 50% by middle age in some tissues [3]. Proponents point to rodent studies showing NMN extended healthspan, improved vascular function, and mitigated frailty markers [3][5][53].

However, the translation to humans has been disappointing:

  • Human trials consistently show NAD+ elevation but inconsistent and small effects on clinical outcomes [3][43][49].
  • No randomized controlled trials have extended beyond several months to evaluate long-term efficacy against aging-related endpoints such as disease incidence or mortality [3][54].
  • Rigorous mouse studies, including the Interventions Testing Program (ITP) evaluating NR (a similar NAD+ precursor), found NO significant lifespan extension across multiple strains and sexes [3][55].
  • A 2024 preprint reported an 8.5% lifespan increase in naturally aging female mice with lifelong NMN treatment, but peer-reviewed confirmation remains pending [3].
  • Independent reviews highlight the paucity of large-scale, placebo-controlled trials tracking hard outcomes, with most human studies being industry-funded and small (n<100) [3][54].

The scientific consensus as of 2026 is that while NAD+ precursors reliably increase NAD+ levels, there is no strong evidence for benefits in longevity or age-related diseases [3][43][55].

Preclinical Evidence — NMN (Animal Studies)

While human evidence remains limited, preclinical research in animal models has been more promising, which is partly why NMN has attracted so much interest. Key preclinical findings include:

Aging and metabolism in mice: Long-term oral NMN supplementation (up to 300 mg/kg/day for 12 months) in wild-type aging mice suppressed weight gain, improved energy metabolism, enhanced insulin sensitivity, eye function, and physical activity, while mitigating age-associated physiological deterioration without toxicity (Mills et al., Cell Metab, 2016) [53].

Vascular function: NMN reversed vascular endothelial dysfunction and oxidative stress in aged mice, restoring nitric oxide bioavailability and arterial elasticity to youthful levels (de Picciotto et al., 2016) [3].

Cardiovascular disease models: In pressure overload-induced heart failure models, NMN improved systolic function and reduced hypertrophy in a SIRT3-dependent manner by enhancing fatty acid oxidation and energy production [3].

Neurodegenerative disease models: In Alzheimer's mouse models, NMN enhanced autophagy, promoted phosphorylated tau clearance, and reduced oxidative stress and amyloid pathology. In ALS models, NMN increased neurite complexity and supported mitochondrial integrity [3].

Fertility: NMN restored oocyte NAD+ levels and quality in aged female mice, and ameliorated muscle atrophy via boosted mitochondrial biogenesis [3].

Important caveat: These preclinical results have not translated convincingly to human outcomes. Species-specific differences in NAD+ metabolism and bioavailability, plus the much higher relative doses used in animal studies, limit direct extrapolation [3][54].

NADH

Clinical studies have used 5–20 mg daily of stabilized NADH [1]:

  • Chronic fatigue syndrome: 10–20 mg daily, alone or combined with 200 mg CoQ10 [20][22][23]
  • Cognitive support (Alzheimer's/dementia): 10 mg daily [25][26]
  • Parkinson's disease: 5 mg orally (enteric-coated) or 12.5–25 mg by infusion/injection [27][28][29]

NADH supplements should be taken on an empty stomach for optimal absorption, as food can interfere with the enteric coating [1].

Nicotinamide Riboside (NR)

Clinical studies have used doses ranging from 100 mg to 3,000 mg daily, often divided into two doses [1][13][14][31]:

  • General NAD+ boosting: 250–300 mg daily (typical commercial dose) [1]
  • Higher-dose protocols: 500–1,000 mg twice daily (used in PAD, long COVID, and cognitive trials) [33][38][42]
  • Onset of effect: NAD+ increases are detectable within 2 weeks and maintained with continued use [14]

Most commercial NR products provide approximately 250 mg per daily dose [1].

Nicotinamide Mononucleotide (NMN)

Clinical studies have used 250–1,200 mg daily [1][3]:

  • General NAD+ boosting: 250–500 mg daily [44][46][50]
  • Exercise performance: 600–1,200 mg daily, divided into two doses [48]
  • Onset of effect: Blood NAD+ increases within hours; sustained elevations observed within 14–30 days at 250–1,000 mg/day [3]

NMN should be taken in divided doses with meals to minimize stomach discomfort [3][10]. No peer-reviewed studies have compared daily supplementation to cycling (intermittent on/off periods), and daily administration remains the standard approach in research [3].

Methylation Considerations

High intake of NAD+ precursors (particularly NMN and niacinamide) can increase production of methylated metabolites like N1-methyl-nicotinamide, potentially straining methylation capacity over time [3]. This theoretical concern is more pronounced with chronic high doses and may be mitigated by methyl donors such as trimethylglycine (TMG) [3].

From the MicroVitamin range

MicroVitamin contains 500 mg of TMG (trimethylglycine/betaine anhydrous) alongside niacin (vitamin B3 at the RDA-aligned dose of 16 mg) — both nutrients that support methylation pathways, which may be relevant for those supplementing with higher-dose NAD+ precursors. MicroVitamin.

Safety and Side Effects

NADH

NADH is generally well tolerated at doses of 5–20 mg daily. Reported side effects are rare and mild [1]:

  • Feeling overly stimulated (reported in one CFS trial participant) [20]
  • No serious adverse events have been reported in clinical trials

Nicotinamide Riboside

NR is generally well tolerated at doses up to 1,000 mg twice daily. Commonly reported side effects include [1][14][31][41]:

  • Flushing: Reported at 300 mg (2 participants) and 1,000 mg (2 participants feeling "hot") in one study [13]. Generally less common than with niacin.
  • Gastrointestinal: Nausea, bloating, changes in stool, abdominal discomfort [12][41]
  • Musculoskeletal: Leg cramps, muscle cramps [31][42]
  • Other: Headache, itching, excessive sweating, increased bruising, rash, vertigo [31][41][42]
  • At high doses (1,500 mg twice daily): Increased risk of abdominal pain (Berven et al., Nat Commun, 2023) [56]
  • LDL cholesterol: A combination of NR and pterostilbene (Basis) caused a slight but significant increase in LDL cholesterol with two capsules daily and among overweight people taking one capsule [12]. Importantly, NR alone (Niagen) at comparable doses did not elevate LDL cholesterol [14].

Nicotinamide Mononucleotide (NMN)

NMN has been well tolerated in human trials at doses up to 1,250 mg daily for periods of 3 weeks to 12 weeks [3][10]:

  • Gastrointestinal: Minor GI issues (nausea, gas, diarrhea) are the most commonly reported side effects [3][46]
  • No serious adverse events have been reported in clinical trials, with no significant changes in vital signs, ECGs, or liver/kidney function tests [3][10]
  • Preclinical safety: In rats, subchronic administration at up to 1,500 mg/kg/day for 90 days showed no adverse effects. The no-observed-adverse-effect level (NOAEL) was established at 1,500 mg/kg/day, with no genotoxic or mutagenic potential [3][57]
  • Only 8.2% of 437 participants across a systematic review of 10 RCTs experienced minor, unrelated adverse events [3][49]

Vitamin B3 Upper Intake Level

All NAD boosters are sources of vitamin B3, which has an established Tolerable Upper Intake Level of 35 mg per day for adults in the United States. Nearly all NAD-boosting products exceed this limit [1]. However, this limit is based on skin flushing, which is primarily associated with nicotinic acid (niacin), not nicotinamide or its derivatives [1]. European agencies have set separate Tolerable Upper Intake Levels for nicotinamide (niacinamide) specifically: 500 mg in the UK and 900 mg in the European Union [1].

Toxicities at high intakes of nicotinamide include [1]:

  • Liver injury
  • Damage to the macula (part of the retina)
  • Gout
  • Declines in platelet counts
  • Impaired glucose control
  • Increased blood levels of anticonvulsant drugs

Cancer Concerns

There is a theoretical concern, based on animal research, that compounds that raise NAD+ levels — including NR, NADH, and possibly NMN — may increase the risk of cancer development, promote the growth of existing cancers, and increase the risk of metastasis [1][58][59].

Mouse study on breast cancer: A laboratory study in mice found that 70% of those consuming a nicotinamide riboside-enriched diet for 2 weeks prior to being implanted with triple-negative breast cancer (a highly aggressive type with high NR uptake) developed detectable tumors, compared to 55% of control mice. Metastases to the brain were also more common among mice given NR (82% vs. 25%) (Maric et al., Biosens Bioelectrol, 2022) [58]. It is unknown whether NR affects less aggressive cancers — some animal research suggests it may not (Hamity et al., Pain, 2020; Acklin et al., Neurooncol Adv, 2022) [60][61].

Proposed alternative approach: One group of researchers has suggested that reducing NAD+ levels — rather than raising them — may be a promising cancer treatment approach (Gujar et al., PNAS, 2016) [62].

Anecdotal PSA elevation: One consumer reported that after one year taking Elysium Basis (which provides NR), PSA levels rose sharply from 1.8 to 4.9, returning to 1.9 after stopping the supplement for one month. Elysium Health acknowledged that "a handful of people" had reached out about PSA changes but stated they have no data showing a correlation [1].

No link with other forms of B3: There does not appear to be any evidence linking other forms of vitamin B3 (niacin and niacinamide) with increased cancer risk. Higher intake of niacin has been associated with lower risk of cancer-related death, and niacinamide supplementation was shown in one study to reduce the risk of some types of skin cancer [1].

Practical recommendation: While no evidence currently demonstrates that NR, NMN, or NADH causes cancer in humans, it would be prudent to avoid NAD-boosting supplements if you have been diagnosed with cancer [1].

Kidney Concerns — NMN

There is some concern that NMN supplementation may cause or worsen kidney inflammation associated with aging, based on an animal study [1][63]:

Mouse study: Aged mice (equivalent to approximately 79-year-old humans) given water containing NMN for 8 weeks showed increased levels of an inflammatory protein (IL-1beta) in their kidneys, with the greatest increase in mice given NMN alone. Mice given NMN also experienced injury to part of the kidney and buildup of toxic NMN breakdown products in blood and organs due to less efficient kidney filtering (Saleh et al., bioRxiv, 2024 — preprint) [63].

Although this evidence is preliminary, it may be prudent for people with impaired kidney function, or at risk for kidney injury, to avoid NMN until more is known [1].

Drug Interactions

No clinical studies have specifically examined interactions between NAD-boosting supplements (NMN, NR, or NADH) and common medications such as blood pressure medications, statins, or antiplatelet drugs [3][10]. No such interactions have been reported in existing trials. However, due to the absence of dedicated research, any potential interactions remain unknown [3].

General precautions include:

  • Anticonvulsant drugs: High doses of nicotinamide (a metabolite of all NAD precursors) may increase blood levels of anticonvulsant drugs [1].
  • Glucose-lowering medications: High doses of nicotinamide may impair glucose control, which could interact with diabetes medications [1].
  • Blood thinners: Niacinamide has mild anticoagulant potential at high doses; caution is advised when combining NAD precursors with anticoagulant or antiplatelet medications [3].
  • Immunosuppressants and chemotherapy: Given the theoretical concern about NAD+ promoting cancer cell growth, individuals on cancer treatment should consult their oncologist before taking NAD-boosting supplements [1][58].
  • Levodopa (Parkinson's): NADH has been studied alongside levodopa and appeared to modestly increase levodopa blood levels in one study; coordination with a neurologist is advisable [28].

Consultation with a healthcare professional is recommended before starting NAD-boosting supplementation, especially for those with pre-existing health conditions, those taking medications (particularly blood pressure medications, statins, antiplatelet drugs, or immunosuppressants), pregnant or nursing women, and people with liver or kidney conditions [3][10].

Dietary Sources

NAD+ Precursors from Food

The primary dietary source of NAD+ is niacin (vitamin B3) and its derivatives. Most people obtain adequate B3 from food alone, as it is widely distributed in the diet [1]. The Recommended Dietary Allowance for niacin is 14 mg/day for women and 16 mg/day for men [1].

Top dietary sources of niacin (vitamin B3):

Food Serving Niacin (mg NE)
Chicken breast 3 oz (85g) 11.4
Tuna (light, canned) 3 oz (85g) 8.6
Turkey breast 3 oz (85g) 10.0
Salmon 3 oz (85g) 8.6
Beef (lean) 3 oz (85g) 6.2
Peanuts 1 oz (28g) 4.4
Mushrooms 1 cup 3.5
Brown rice 1 cup cooked 3.0
Fortified cereals 1 serving 20.0+
Lentils 1 cup cooked 2.1

NE = niacin equivalents (includes tryptophan conversion, where 60 mg tryptophan = 1 mg niacin).

NMN in Foods

NMN occurs naturally in trace amounts in certain foods, though quantities are far below supplemental doses [3][64]:

Food NMN Content (mg/100g)
Edamame 0.47–1.88
Avocado 0.36–1.60
Broccoli Variable, relatively high
Cabbage 0.0–0.90
Tomato 0.26–0.30
Raw meats/seafood 0.06–0.42

To obtain the equivalent of a 250 mg supplement dose from food alone, one would need to consume approximately 13–53 kg of edamame or 16–69 kg of avocado — making supplementation the only practical way to achieve trial-level doses [64].

Nicotinamide Riboside in Foods

NR is found naturally in cow's milk (approximately 3.9 micromol/L) and trace amounts in other foods, but like NMN, dietary amounts are too low to achieve the doses used in clinical trials [9].

References

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