N-Acetylcysteine for Male Infertility
Verdict: Published with Warning
Across 6 PubMed studies, the evidence for N-Acetylcysteine in Male Infertility grades Tier B — preliminary evidence. Effective, but with safety or population caveats.
B 🟡 B Preliminary Evidence Published with Warning
Why this grade7-layer evidence engine
⚖️
Scoring transparency
All scores computed by a 7-layer evidence engine — fully auditableRaw score 0.64
D
C
B
A
S
← counter-evidence / ineffectiveeffective / strong evidence →
Final grade
B · Published with Warning
Confidence
85%
Highly consistent evidence
Evidence level
E2
Multiple high-quality MAs (≥2 independent, consistent)
▸View the full decision path (audit trail)
- compute_raw_score — 加權公式: L2×0.30 + L3×0.25 + L5×0.25 + L11×0.10 + L1×0.10 = 0.643
- tier_from_score — 依分數區間映射至 tier letter
- apply_hec_rules — 高品質 SR/MA 顯示 positive (4 篇 > 0 negative)
- tier_strict_requirement_check — Tier 條件達標，未降階
- detect_disputes — 偵測到 0 個 hard + 0 個 soft dispute
- decide_status — 依 tier + dispute 結果決定 status
PubMed studies (6)L2 · primary research & systematic reviews
Unlocking the potential of antioxidant supplementation with n-acetylcysteine to improve seminal parameters and analysis of its safety: a systematic review and meta-analysis of randomized controlled…
Finding: NAC significantly improved all major semen parameters versus control: sperm volume MD +0.69 mL (95% CI 0.26-1.12, p=0.002), sperm concentration MD +4.43 ×10⁶/mL (95% CI 1.50-7.36, p=0.003), total motility MD +9.69% (95% CI 6.61-12.77, p<0.00001), normal morphology MD +1.36% (95% CI 0.70-2.03, p<0.0001). DNA fragmentation not pooled. No serious adverse events reported across included RCTs; favorable safety profile. Pregnancy/live birth not pooled as primary outcome.
View on PubMed Meta-analysis of the efficacy and safety of L-carnitine and N-acetylcysteine monotherapy for male idiopathic infertility
Finding: NAC monotherapy significantly improved sperm concentration, total motility, normal morphology, and ejaculate volume (volume p=0.002) versus placebo. Both NAC and L-carnitine monotherapy were effective; L-carnitine additionally raised testosterone (p<0.001). NAC did not significantly alter testosterone, LH, FSH, or prolactin. Authors conclude both single agents are effective without need for a cocktail to obtain semen-parameter benefit. Live birth/pregnancy not primary endpoint.
View on PubMed A Meta-Analysis of the Efficacy of L-Carnitine/L-Acetyl-Carnitine or N-Acetyl-Cysteine in Men With Idiopathic Asthenozoospermia
Finding: NAC vs placebo (pooled RCTs): sperm concentration MD +3.80 ×10⁶/mL (95% CI 2.36-5.24, p<0.00001); total motility MD +4.69% (95% CI 2.45-6.94, p<0.0001); normal morphology MD +1.68% (95% CI 0.79-2.58, p=0.0002); ejaculate volume MD +0.69 mL (95% CI 0.26-1.12, p=0.002). Serum testosterone MD +1.35 ng/mL (95% CI -0.75 to 3.45, p=0.21) - NOT significant. DNA fragmentation not pooled. Pregnancy/live birth not reported.
View on PubMed The role of N-acetyl-cysteine (NAC) orally daily on the sperm parameters and serum hormones in idiopathic infertile men: A systematic review and meta-analysis of randomised controlled trials
Finding: NAC monotherapy vs placebo: sperm concentration MD +3.80 (p<0.00001); ejaculate volume MD +0.69 (p=0.002); motility MD +4.69 (p<0.0001); normal morphology MD +1.68 (p=0.0002). Hormones not significantly affected: testosterone MD +1.35 (p=0.21), LH MD +0.82 (p=0.40), FSH MD -7.48 (p=0.29), prolactin MD -0.34 (p=0.32). Authors caution methodological quality of underlying RCTs is modest; larger high-quality RCTs needed.
View on PubMed The Effect of N-Acetyl-Cysteine on NRF2 Antioxidant Gene Expression in Asthenoteratozoospermia Men: A Clinical Trial Study
Finding: Significant post-NAC increases in sperm concentration and motility (P<0.05); significant decreases in abnormal morphology and DNA fragmentation (P<0.05). NRF2 mRNA expression and antioxidant enzyme levels significantly increased; positive correlation between NRF2 expression, sperm parameters, and antioxidant enzymes (P<0.05). Mechanistic support for NAC reducing oxidative-stress-driven DNA damage via NRF2 pathway in idiopathic asthenoteratozoospermia.
View on PubMed Effects of N-acetyl-cysteine supplementation on sperm quality, chromatin integrity and level of oxidative stress in infertile men
Finding: Pre→post-NAC: DNAfI 19.34% → 15.14% (P<0.001); sperm count and motility significantly increased; abnormal morphology and protamine deficiency significantly decreased (all P<0.05). Seminal TAC increased and MDA decreased significantly. FSH/LH decreased; testosterone increased. Demonstrates NAC reduces sperm DNA fragmentation alongside oxidative-stress reduction. Note: 2019 publication but commonly cited in 2020+ MAs; pre-2020 cutoff caveat.
View on PubMed Regulatory & authoritative positionsL4/L5 · FDA / EMA / NIH ODS / Cochrane / Mayo …
L4a US FDA
Cautious
NAC is excluded from the dietary supplement definition under section 201(ff)(3)(B)(ii) of the Federal Food, Drug, and Cosmetic Act source↗
L4b EU EFSA
Against
a cause and effect relationship has not been established source↗
L4c UK NHS
Supportive
Acetylcysteine is the antidote used to treat paracetamol overdose source↗
L5a NIH Office of Dietary Supplements
Cautious
NAC has FDA approval for treating potentially hepatotoxic doses of acetaminophen. source↗
L5e Specialty Society (condition-mapped)
Cautious
Clinicians should counsel patients that the benefits of supplements (e.g., antioxidants, vitamins) are of questionable clinical utility in treating male infertility. source↗