Subcutaneous NAD for Male Fertility: Not Recommended
There is no evidence supporting the use of subcutaneous NAD (Nicotinamide Adenine Dinucleotide) therapy to improve male fertility, and current guidelines explicitly state that supplements for male infertility are of questionable clinical utility with inadequate data to recommend specific agents. 1
Guideline Position on Supplements for Male Fertility
The most recent AUA/ASRM guidelines (2021) provide clear direction on this issue:
Clinicians should counsel patients that the benefits of supplements (including antioxidants and vitamins) are of questionable clinical utility in treating male infertility, with inadequate data to provide recommendations for specific agents (Conditional Recommendation; Evidence Level: Grade B). 1
This recommendation applies broadly to all supplements, including novel agents like NAD, which lack any published evidence in the male fertility literature. 1
Why NAD Is Not Recommended
NAD supplementation is not mentioned in any major fertility guidelines because:
No clinical trials have evaluated subcutaneous NAD for male fertility outcomes (pregnancy rates, live birth rates, or sperm parameter improvements). 1
The 2024 AUA/ASRM guideline update specifically notes that future therapeutic options remain understudied, and translation of newer advances will be slow before moving from laboratory to clinical practice. 1
Even established antioxidant supplements with more research backing have been deemed of questionable benefit. 1
Evidence-Based Alternatives That Actually Work
Instead of unproven supplements like NAD, guidelines recommend interventions with demonstrated efficacy:
For Hormonal Abnormalities
Aromatase inhibitors, hCG, or SERMs may be used for infertile men with low serum testosterone (Conditional Recommendation; Evidence Level: Grade C), though benefits remain limited compared to ART. 1
FSH analogues may improve sperm concentration, pregnancy rate, and live birth rate in idiopathic infertility (Conditional Recommendation; Evidence Level: Grade B). 1
For Structural Issues
Varicocelectomy should be considered in men with clinical varicocele and abnormal semen parameters, as it improves both semen quality and fertility rates. 1
Microsurgical testicular sperm extraction (micro-TESE) achieves 40-60% sperm retrieval rates in non-obstructive azoospermia, far exceeding any supplement's potential. 1
For Optimal Outcomes
- Assisted reproductive technology (IVF/ICSI) offers superior pregnancy rates compared to empiric medical therapy and should be discussed early, particularly when female partner age is a consideration. 1
Critical Pitfalls to Avoid
Never prescribe testosterone or anabolic steroids to men desiring fertility—these completely suppress spermatogenesis through negative feedback on the hypothalamus and pituitary, causing azoospermia that can take months to years to recover. 1
Avoid delaying effective treatment with unproven supplements, as female partner age is the most critical factor determining conception success, and time lost on ineffective therapies reduces overall pregnancy chances. 1
What Actually Helps: Lifestyle Modifications
The evidence supports these modifiable factors over supplements:
Smoking cessation, maintaining healthy body weight (BMI <25), and minimizing heat exposure to the testes have documented benefits for spermatogenesis. 2
Weight loss and metabolic optimization can normalize gonadotropins and improve testosterone levels in men with obesity and metabolic syndrome. 1
Avoiding gonadotoxic exposures (certain medications, environmental toxins, excessive heat) protects fertility better than any supplement. 1
The Bottom Line
Subcutaneous NAD has zero evidence for male fertility improvement and should not be recommended. 1 Men seeking fertility optimization should focus on evidence-based interventions: treating underlying hormonal abnormalities, correcting structural problems like varicocele, optimizing lifestyle factors, and proceeding to ART when indicated rather than pursuing unproven supplements that delay effective treatment. 1