NAD+ Supplementation and Fertility
Direct Answer
Current medical guidelines do not recommend NAD+ supplementation (nicotinamide riboside or nicotinamide mononucleotide) for improving fertility or pregnancy outcomes in either men or women, citing insufficient high-quality evidence and questionable clinical utility. 1, 2
Guideline Position on NAD+ and Fertility Supplements
Male Infertility
The WHO (2017) provides a strong recommendation against antioxidant supplementation, including NAD+ precursors, for men with abnormal semen parameters or male infertility due to insufficient evidence. 1
The AUA/ASRM (2021) states that supplements including antioxidants have questionable clinical utility for treating male infertility because data are inadequate to support any specific agent. 1
The European Association of Urology (2025) characterizes antioxidant therapy evidence as "conflicting" and of low quality, recommending against routine use. 2
A Cochrane systematic review of 61 studies (6,264 infertile men) showed that after removing high-risk-of-bias trials, antioxidant therapy did not increase live-birth rates. 2
Female Infertility
Guidelines provide no recommendation for NAD+ supplementation in women with PCOS or unexplained infertility because evidence is insufficient and study results are highly heterogeneous. 1
The European Association of Urology provides no guideline-level recommendation for alpha-lipoic acid (a related antioxidant) in female infertility, reflecting the absence of high-quality data. 3
Across 48 antioxidant trials reviewed by Cochrane, only 7 studies reported clinical pregnancy data and only 4 reported live-birth data, yielding low-quality evidence with inadequate safety information. 3
Critical Evidence Gap: Research vs. Guidelines
Promising Animal Research (Not Yet Guideline-Supported)
While guidelines uniformly recommend against NAD+ supplementation, recent animal studies show potential mechanisms:
Female fertility: NMN supplementation restored oocyte quality in aged mice by recovering NAD+ levels, improving ovulation, meiotic competency, and fertilization ability. 4, 5
PCOS model: Nicotinamide riboside (NR) prevented ovarian NAD+ decline, normalized estrous cycles, enhanced ovulation, and improved oocyte quality in DHEA-induced PCOS mice. 6
Aging ovaries: NR supplementation increased follicle numbers, ovulatory potential, and live birth rates in aging mice by improving mitochondrial function and reducing oxidative stress. 7
However, these are exclusively animal studies with no human clinical trial data demonstrating live-birth improvements, which is why guidelines cannot endorse this approach. 1, 2, 3
Evidence-Based Fertility Management Algorithm
Step 1: Baseline Evaluation (Both Sexes)
Male partner:
- Perform at least two semen analyses following WHO criteria. 2
- Obtain reproductive history including smoking status, BMI, heat exposure, medication use, and presence of varicocele. 2
- Conduct physical examination to identify correctable urological causes. 2
- Perform karyotype and Y-chromosome microdeletion testing if severe oligozoospermia (<5×10⁶/ml) or non-obstructive azoospermia. 8
Female partner:
- Assess ovulatory function, tubal patency, and uterine anatomy. 1
- Evaluate for PCOS, endometriosis, or other reproductive disorders. 1
Step 2: Prioritize Evidence-Based Interventions
Lifestyle modifications (strongest evidence):
- Weight optimization: Achieve BMI 18.5–25 kg/m² through diet and exercise; this improves sperm parameters in men and ovulatory function in women. 2, 3
- Complete smoking cessation: Provides established benefits for both male and female fertility. 2, 3
- Regular physical activity: Enhances sperm quality and overall reproductive health. 2
- Avoid heat exposure: Men should avoid hot tubs, saunas, and tight underwear. 2
First-line pharmacotherapy:
- Women with PCOS: Clomiphene citrate or letrozole; metformin for clomiphene-resistant cases. 1
- Men with low testosterone desiring fertility: Aromatase inhibitors, hCG, or SERMs—never testosterone monotherapy, which suppresses spermatogenesis. 1
Step 3: Timing Considerations
If female partner ≥35 years old or couple attempting conception >12 months: Refer to reproductive endocrinology immediately; do not delay proven treatments while trialing supplements. 2, 3
Implement lifestyle modifications for at least 3 months before considering any supplementation. 2
Step 4: Assisted Reproductive Technology
- When first-line medical therapies fail or in cases of severe male factor infertility, proceed to IVF/ICSI as definitive treatment. 1
Critical Pitfalls to Avoid
Do Not Delay Proven Treatments
The most important clinical error is postponing evidence-based fertility interventions (IVF, ovulation induction) while trialing NAD+ supplements, because age-related fertility decline—especially in women—continues unabated during the trial period. 2, 3
Do Not Use Supplements as Monotherapy
Antioxidants should never replace lifestyle modifications (weight loss, smoking cessation, exercise), which have stronger supporting evidence. 2
NAD+ supplementation has no proven benefit on live-birth rates in humans, which is the only definitive fertility outcome. 2, 3
Do Not Assume Male Data Applies to Females
- Evidence for antioxidants is insufficient in both sexes, but the mechanisms and outcomes differ; do not extrapolate male infertility data to female patients. 3
Testosterone Warning
- Never prescribe testosterone monotherapy to men desiring fertility; it suppresses FSH and LH, causing azoospermia that can take months to years to recover. 1
If Patient Explicitly Requests NAD+ Supplementation
Shared Decision-Making Approach
If a patient insists on trying NAD+ precursors after counseling about lack of evidence:
Counsel explicitly that current guidelines do not support this intervention and no human data demonstrate live-birth improvements. 1, 2
Ensure this does not delay referral to reproductive endocrinology or proven treatments. 2, 3
Consider off-label trial only after 3 months of lifestyle optimization and baseline fertility evaluation. 2
Reassess at 2–3 months; if no improvement in semen parameters or conception after 12 months total conservative management, escalate to ART. 2
Safety Profile
No adverse effects were reported in antioxidant trials at therapeutic doses, indicating a favorable safety profile. 2
However, the absence of consistent benefit, high heterogeneity across studies, and no data on live-birth rates mean clinicians should prioritize evidence-based interventions rather than NAD+ supplementation. 1