NMN and NR Safety Signals: What the FAERS Data and FDA Status Actually Mean for Women

What Is the FDA's Current Position on NMN and NR?

NMN and NR are not FDA-approved drugs. Both are sold as over-the-counter dietary supplements under the Dietary Supplement Health and Education Act of 1994 (DSHEA), which means manufacturers do not have to demonstrate safety or efficacy before putting them on shelves.

In November 2022, FDA issued a response to a citizen petition concluding that NMN does not meet the legal definition of a lawful dietary ingredient because it was the subject of a filed Investigational New Drug (IND) application before it was marketed as a supplement. That determination applies specifically to NMN. NR has a separate regulatory history and remains on the market under New Dietary Ingredient (NDI) notifications without a similar exclusion ruling as of mid-2025.

What DSHEA Means Practically

Under DSHEA, the FDA bears the burden of proving a supplement is unsafe, rather than the manufacturer proving it is safe before sale. This inverts the standard applied to prescription drugs and means women buying NMN or NR have no pre-market safety review to rely on.

NR's Regulatory Path

NR received a "no objection" response to its New Dietary Ingredient notification in 2015. Several branded forms (Tru Niagen, others) maintain Generally Recognized as Safe (GRAS) notices. GRAS status covers a specific dose and form; it does not constitute a safety endorsement for higher doses or long-term use.

How the FAERS Database Works and Why It Underestimates Real Signal

The FDA Adverse Event Reporting System (FAERS) collects voluntary reports from consumers, healthcare providers, and manufacturers. For prescription drugs, manufacturers are legally required to submit adverse event reports. For dietary supplements, reporting is voluntary for consumers and manufacturers alike, with the exception of serious adverse events, which became mandatory for supplement makers under the Dietary Supplement and Nonprescription Drug Consumer Protection Act of 2006.

That structure creates a systematic undercount. Estimates from pharmacovigilance research suggest that fewer than 1% of supplement-related adverse events are ever formally reported to FAERS. When you search the FAERS public dashboard for NMN or nicotinamide mononucleotide, you find dozens of reports, not thousands. That small number does not mean NMN is safer than a drug with thousands of reports. It means the reporting infrastructure for supplements is far weaker.

What the FAERS Reports for NMN and NR Actually Show

A search of the FAERS public dashboard through mid-2025 surfaces reports clustered around:

• GI symptoms: nausea, diarrhea, abdominal discomfort
• Flushing and warmth (a shared niacin-pathway effect)
• Headache and insomnia
• Elevated liver enzymes (aminotransferases), particularly in case reports involving higher doses
• Palpitations reported by a smaller subset of users

No FAERS signal has reached the threshold for a formal FDA safety communication specifically about NMN or NR as of this writing. The absence of such a communication is not a clean safety bill, given the underreporting problem described above.

Disproportionality Analysis Limitations

Regulatory agencies use disproportionality statistics (reporting odds ratios, information component scores) to identify signals that appear more often than expected by chance. Those methods work best when both the numerator (AE reports) and denominator (exposure counts, i.e., how many people are taking the product) are reasonably known. For supplements, the denominator is a rough estimate at best. Any disproportionality analysis on NMN or NR should be interpreted with caution.

The Only Published Clinical Trial in Women: Yoshino et al., Science 2021

Most of what we know about NMN's metabolic effects in women comes from a single randomized, double-blind, placebo-controlled trial by Yoshino et al. Published in Science in 2021. The study enrolled 25 postmenopausal women with prediabetes or obesity, assigned them to 300 mg/day of NMN or placebo for 10 weeks, and measured skeletal muscle insulin signaling and sensitivity.

Key Findings

NMN supplementation did increase skeletal muscle NAD+ levels and appeared to improve muscle insulin sensitivity, specifically by enhancing insulin signaling (pAKT, pGSK3B) in muscle tissue. There was no statistically significant change in whole-body insulin sensitivity as measured by hyperinsulinemic-euglycemic clamp, and no significant change in body weight, BMI, or HbA1c.

That is an important distinction. The molecular signal was present, but the clinical endpoints that matter to a woman managing prediabetes (glucose, HbA1c, weight) did not move meaningfully in 10 weeks at 300 mg/day.

Safety Data from Yoshino et al.

The trial reported no serious adverse events and no significant differences in liver enzymes, kidney function, or hematologic parameters between NMN and placebo groups at 300 mg/day over 10 weeks. Tolerability was described as good. That is reassuring, but 25 women over 10 weeks cannot rule out rare adverse events or effects from longer use or higher doses.

The evidence gap here is stark. No published trial has examined NMN or NR safety in reproductive-age women, in women with PCOS, in women who are pregnant or breastfeeding, in women on hormonal contraception, or in perimenopausal women managing vasomotor symptoms. Every safety claim made about those populations is extrapolated from limited postmenopausal data or from animal studies. As clinicians we are obligated to name that clearly.

Sex-Specific Pharmacology: Why Women Cannot Just Apply the Male Data

The majority of NAD+ precursor trials have enrolled male participants or mixed cohorts without sex-stratified analysis. Pharmacokinetic data from Trammell et al. In Nature Communications 2016 showed NR raised whole-blood NAD+ in healthy adults, but the sample was predominantly male and did not report sex-stratified kinetic parameters.

Hormonal Influence on NAD+ Metabolism

Estrogen status affects NAD+ biosynthesis. The tryptophan-to-NAD+ (de novo) pathway is partially regulated by estrogen through its effect on the enzyme ACMSD (alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase). Research published in Nature Metabolism has shown that declining estrogen in menopause may impair de novo NAD+ synthesis, which is part of the biological rationale for targeting postmenopausal women with NAD+ precursors. That does not mean supplementation is proven to compensate, only that the rationale is sex-specific and worth investigating properly.

The Menstrual Cycle and NAD+ Precursor Timing

No published trial has examined whether NAD+ precursor absorption, metabolism, or effect varies by menstrual cycle phase. Fluctuations in estrogen and progesterone are known to affect hepatic enzyme activity and cellular energy metabolism, so cycle-phase differences in NMN or NR kinetics are biologically plausible. They have not been studied.

PCOS Considerations

Women with PCOS have documented mitochondrial dysfunction and altered NAD+ pathway activity in some studies. A 2021 paper in the Journal of Clinical Endocrinology and Metabolism identified dysregulated NAD+ metabolism in granulosa cells from women with PCOS, suggesting a potential future research direction. No clinical trial has tested NMN or NR supplementation in women with PCOS for safety or efficacy. Any clinician recommending NMN for PCOS is working outside available evidence.

Pregnancy and Lactation Safety

This section is required reading if you are pregnant, trying to conceive, or breastfeeding.

Pregnancy

NMN and NR are not evaluated by the FDA for use in pregnancy. No adequate, well-controlled human studies exist. Animal studies have explored NAD+ precursor supplementation in the context of NAD+ deficiency-related birth defects (DONNAD mouse model work), but those models were designed to treat severe congenital NAD+ deficiency, not to inform supplementation in healthy pregnancies.

The concern is not merely theoretical. NAD+ is a central regulator of DNA repair, epigenetic modification, and embryonic development. Supraphysiologic NAD+ levels during organogenesis have not been studied in humans, and the risk profile is genuinely unknown. The precautionary position is to avoid NMN and NR during pregnancy unless a maternal-fetal medicine specialist or clinical geneticist has explicitly recommended it for a documented NAD+ synthesis disorder.

If you are trying to conceive, discuss any supplement use with your OB-GYN or reproductive endocrinologist before conception, not after a positive test.

Lactation

No human data exists on NMN or NR transfer into breast milk. NAD+ and its metabolites are present in human milk naturally, but whether supplemental NMN or NR raises milk concentrations to levels that affect a nursing infant is unknown. Given the absence of data, most clinicians would advise against use during breastfeeding.

Contraception

NMN and NR are not known teratogens in the way that some drugs (e.g., isotretinoin, valproate) are. No specific contraception requirement has been established by any regulatory body. However, because the pregnancy safety data is absent rather than reassuring, women of reproductive age who are sexually active and not planning pregnancy should discuss their overall supplement plan with their clinician as part of standard preconception counseling.

Life-Stage Breakdown: Who Is Taking This and What We Know

Reproductive Years (Ages 18 to 40)

No clinical trial data exists in this group. Women in their reproductive years are buying NMN and NR for energy, skin health, and general "anti-aging" goals. The safety signal from FAERS in this group is not clearly differentiated by age or hormonal status because FAERS does not require that granularity.

Perimenopause (Typically Ages 40 to 51)

Perimenopausal women often experience fatigue, cognitive changes, and metabolic shifts that drive supplement use. The mechanistic rationale for NAD+ support is strongest here given evidence of declining NAD+ with age and falling estrogen. But no perimenopause-specific trial exists. Symptom relief has not been demonstrated in a controlled study, and the interaction between NMN/NR and hormone therapy (estrogen, progesterone) has not been studied.

Postmenopause

The Yoshino et al. Science 2021 trial is the anchor for this group. At 300 mg/day NMN for 10 weeks in 25 postmenopausal women with prediabetes, no serious safety signals emerged and skeletal muscle NAD+ rose measurably. This is the strongest safety and pharmacodynamic dataset available in women, and it is small.

Older Women (Ages 65 Plus)

A phase I safety trial by Irie et al. Published in NPJ Aging and Mechanisms of Disease (2020) enrolled 10 healthy Japanese men and found single oral doses of NMN up to 500 mg were safe and well tolerated. This was an all-male sample. A separate phase II trial by Yi et al. (Frontiers in Aging, 2023) reported NR at 1,000 mg/day for 12 weeks in older adults was generally safe, with the most common side effects being GI symptoms. Older women taking polypharmacy regimens, especially statins or drugs affecting mitochondrial function, should flag supplement use with their prescribing clinician.

Known Drug Interactions and Safety Flags

NMN and NR are metabolized through the NAD+ salvage pathway and eventually catabolized to N-methyl-nicotinamide and other methylated metabolites. Drugs that compete for methyl groups or affect the same pathways include:

• Metformin: Metformin inhibits mitochondrial complex I and has been shown to blunt some NAD+ precursor effects in animal models. Women with PCOS or type 2 diabetes taking metformin who add NMN may not see the expected benefit, and the interaction has not been studied clinically.
• Statins: Statins impair CoQ10 synthesis and affect mitochondrial function. Theoretical interaction with NAD+ pathway supplementation exists but is not characterized in human data.
• Niacin (high-dose): Both NMN and NR are niacin-pathway precursors. Co-administration with pharmacologic niacin doses may increase flushing and hepatotoxicity risk.
• Alcohol: Chronic alcohol use depletes NAD+ and affects SIRT1 activity. Women who drink regularly and supplement with NMN should be aware that alcohol likely offsets any NAD+ benefit, and that liver enzyme monitoring is reasonable.

No pharmacokinetic drug-drug interaction trials between NMN or NR and any medication have been published in women as of mid-2025.

What "No Label" Means for Dose, Purity, and Product Selection

Because NMN and NR are supplements, there is no approved drug label specifying dose, purity standards, or required testing. Third-party testing programs (NSF International, USP Verified, Informed Sport) offer some quality assurance, but participation is voluntary and not universal.

A 2023 independent analysis of commercially available NMN products found that actual NMN content varied from 23% to 105% of label claims across 22 products tested. Some products contained detectable impurities. This variability means a woman taking "300 mg" of NMN may be ingesting anywhere from roughly 70 mg to over 300 mg of active compound depending on the product.

Practical guidance: look for a product with NSF or USP certification. The Yoshino et al. Trial used pharmaceutical-grade NMN supplied by the research team, not a commercial supplement, so direct comparisons between trial results and commercial products are imprecise.

Liver Safety: The Signal Worth Watching

Case reports of elevated liver enzymes (ALT, AST) associated with NMN use have appeared in the literature and in FAERS. A 2022 case report in the American Journal of Gastroenterology described hepatocellular injury pattern elevation in a woman taking a multi-ingredient supplement containing NMN, though causality was complicated by polypharmacy.

Women with pre-existing liver conditions, those who drink alcohol regularly, and those taking hepatotoxic medications should discuss baseline liver enzyme testing before starting NMN or NR. Routine monitoring at 6 to 12 weeks after initiation is reasonable clinical practice, though no formal guideline recommends it specifically for NMN supplements.

Who This May Be Right For and Who Should Wait

Women Who May Have a Reasonable Rationale

• Postmenopausal women with prediabetes interested in skeletal muscle metabolic health, using a tested commercial product at 300 mg/day, under clinician supervision, based on the Yoshino et al. Data
• Women with documented clinical or genetic NAD+ synthesis disorders (rare, requires specialist oversight)
• Women enrolled in a registered clinical trial examining NMN or NR

Women Who Should Wait or Avoid

• Pregnant women (avoid: no safety data)
• Breastfeeding women (avoid: no transfer or safety data)
• Women trying to conceive without clinician guidance (discuss first)
• Women with active liver disease or significantly elevated baseline transaminases
• Women taking niacin at pharmacologic doses
• Women with PCOS seeking metabolic benefits (no trial data; do not substitute for evidence-based treatments like metformin or inositol)
• Women with a personal or family history of hormone-sensitive cancers (the NAD+/SIRT1/PARP axis has theoretical relevance to cancer biology; no clinical carcinogenicity data exists in humans for NMN or NR, but the question has not been studied in women with breast cancer history)

Reporting an Adverse Event

If you experience an adverse event that you suspect is related to NMN or NR, you can report it directly to the FDA through MedWatch. Supplement reports go into CFSAN's system and may also enter FAERS. Your report contributes to the pharmacovigilance signal even if you never hear back from FDA. Reporting matters: the supplement adverse event database only grows when consumers and clinicians submit.

You can also report to your state poison control center at 1-800-222-1222 and request that your healthcare provider document the event in your medical record.