Strongest evidence (moderate strength)
- Reduced Pain (8 studies): 6 of 8 studies showed benefit, with small-to-moderate effects. The strongest support comes from postoperative settings (dental surgery, hip/knee arthroplasty); doses varied, and effects may require 60 days of supplementation.
- Reduced Interleukin-6 (7 studies): 4 of 7 studies reported reduced inflammation, with small-to-moderate effects. Doses of 250–1000 mg/day were used, primarily in clinical populations (cardiac surgery, sepsis, hemodialysis).
- Reduced Systolic Blood Pressure (4 studies): all 4 studies found benefit, with moderate effects. Only one study reported a specific dose (130 mg/day); populations included diabetes, general adults, and heat-exposed workers.
- Reduced Oxidative Stress (4 studies): 3 of 4 studies showed benefit, with mixed effect sizes. Doses of 1000 mg/day (often combined with vitamin E) for 12 weeks were reported in clinical groups.
Mixed or weaker evidence (low strength)
- Mortality (7 studies): 5 neutral, 1 beneficial (meta-analysis in COVID-19), 1 harmful. High-dose vitamin C in sepsis/COVID-19 raised safety concerns; no data for healthy populations.
- Tumor Necrosis Factor Alpha (5 studies): 2 beneficial (moderate effect) and 3 neutral; benefits seen in acute/septic settings but not in chronic disease.
- Lung Function (4 studies): 2 beneficial (one in children of smokers), 2 neutral (COPD/asthma meta-analyses). Uncertain generalizability.
- Diastolic Blood Pressure, Cognitive Function, Uric Acid, Hospital Stay, Gingival Index: each outcome had 2–3 small studies with neutral or inconsistent results, often not reaching statistical significance.
Effective dose patterns
The most consistent dose ranges across multiple outcomes were 250–1000 mg/day. For interleukin-6 and TNF-alpha, 1 g/day was commonly used in acute settings. For systolic blood pressure, only one study reported a dose (130 mg/day), limiting conclusions. Many studies did not report doses or durations.
Population insights
The strongest evidence comes from clinical populations—surgery patients, those with sepsis or cardiac disease, and older adults with sarcopenia. For general healthy adults, data are sparse or neutral. The studies on blood pressure included general adults but with very low dosing details.
Notable caveats
- Publication bias is a concern for several outcomes (pain, blood pressure): null studies may be underreported.
- Many evidence bases are small (3–4 studies), making conclusions preliminary.
- Safety signals emerged: high-dose vitamin C in sepsis and COVID-19 two large RCTs showed potential harm.
- Effects are often context-dependent—apparent in acute clinical settings but not in chronic or healthy populations.