Daily 400 mcg folic acid is recommended preconception to reduce neural tube defect risk.

The MRC Vitamin Study found a 72% protective effect of folic acid (4 mg/day) against recurrence of neural tube defects in a landmark double-blind multinational RCT of 1,195 completed pregnancies.

Inositol (myo-inositol or D-chiro-inositol) shows evidence of benefit for some metabolic measures & potential benefit for ovulation induction in PCOS; evidence for IVF-related outcomes (oocyte quality, fertilization, clinical pregnancy) is promising but rated as limited & inconclusive by guideline authors.

Myo-inositol supplementation improved insulin sensitivity, reduced fasting insulin, & improved androgen profiles vs placebo in women with PCOS; fewer gastrointestinal adverse events than metformin.

No statistically significant overall effect of inositol on depressive, anxiety, or OCD symptoms vs placebo; a non-significant trend toward benefit in PMDD subgroup (p=0.07). Evidence base is small & heterogeneous.

CoQ10 supplementation significantly improved statin-associated muscle pain (WMD −1.60), weakness (WMD −2.28), cramps (WMD −1.78), & tiredness (WMD −1.75) across 12 RCTs (n=575), though plasma creatine kinase was not significantly reduced.

CoQ10 100 mg three times daily over 2 years reduced major adverse cardiovascular events (15% vs 26% placebo) & all-cause mortality (10% vs 18% placebo; RR 0.58, 95% CI 0.35–0.95) in addition to standard therapy.

Meta-analysis of 3 high-quality double-blind RCTs (n=520) meeting CONSORT criteria found women taking Vitex agnus-castus were 2.57 times more likely to experience PMS symptom remission vs placebo (OR 2.57, 95% CI 1.52–4.35). Majority of trials are excluded due to incomplete reporting.

Placebo-controlled RCT reported improved PMS symptom scores with Vitex preparations; extract standardization matters.

Vitamin D at 700–800 IU/day reduced hip fracture risk by 26% (RR 0.74) & any nonvertebral fracture by 23% (RR 0.77); no significant benefit was observed at 400 IU/day.

Vitamin D insufficiency is prevalent among athletes, particularly indoor athletes & those in northern latitudes in winter. Insufficiency is associated with reduced muscle strength, power, & endurance; supplementation of 2,000–6,000 IU/day recommended to maintain 25(OH)D >40 ng/mL.

Vitamin D supplementation reduced risk of acute respiratory tract infection (adjusted OR 0.88, 95% CI 0.81–0.96); greatest benefit in those with baseline deficiency (<25 nmol/L) & those receiving daily or weekly dosing rather than bolus doses.