Vitamin C

Most people don't need to supplement vitamin C, and megadoses are physiologically wasted. Absorption plateaus around 200-400mg/day, and above 1,000mg less than half is absorbed, the rest is excreted. The Cochrane review of 29 trials (11,306 participants) found regular supplementation does not prevent colds in the general population, though it does cut cold incidence by 52% in people under heavy physical stress like marathon runners and soldiers. It's one of the most thoroughly studied supplements; the research is less flattering than most supplement sites present.

The pharmacokinetics are the key to understanding vitamin C supplementation. Your body's SVCT1 transporters are saturable - plasma levels plateau at 200-400mg/day oral intake, with absorption above 80-90% below this threshold. At 1,000mg, less than half is absorbed. Beyond that, excess is excreted via the kidneys. This means megadosing (1,000mg+) in well-nourished adults is largely physiologically redundant.

At the cellular level, vitamin C concentrates in leukocytes (neutrophils, macrophages) at 50-100 times plasma levels. It enhances neutrophil chemotaxis, phagocytosis, and the oxidative burst that kills pathogens, while simultaneously protecting host tissue from oxidative damage. Vitamin C also supports T-lymphocyte and B-lymphocyte differentiation and proliferation, extending its role across both innate and adaptive immune responses. During infection, plasma and leukocyte vitamin C levels plummet rapidly, which is why baseline adequacy matters for immune readiness (Carr & Maggini 2017, PMID: 29099763).

The definitive Cochrane review (29 trials, 11,306 participants) found that regular supplementation does not prevent colds in the general population (pooled RR 0.97, 95% CI 0.94-1.00), but reduces cold duration by about 8% in adults and 14% in children. The standout finding: in people under heavy physical stress - marathon runners, soldiers, skiers - vitamin C cut cold incidence by 52%. Therapeutic dosing (started after symptom onset) showed no consistent, significant, or reproducible effect on either duration or severity.

What vitamin C will not do: prevent heart disease or cancer. The Physicians' Health Study II (14,641 men, 8 years, 500mg/day) found zero cardiovascular benefit (HR 0.99, 95% CI 0.89-1.10, for major events - all secondary endpoints null including MI, stroke, and CV mortality) and zero cancer benefit (HR 1.02, 95% CI 0.94-1.10 for total cancer; HR 1.03, 95% CI 0.93-1.15 for prostate cancer, across 1,943 total cancers). A meta-analysis of 7 RCTs confirmed the null (RR 1.00, 95% CI 0.95-1.05 for cancer incidence), and a Mendelian randomization study found zero causal association between genetically elevated plasma vitamin C and cancer. These were well-nourished men already at plasma saturation from diet - supplementation was redundant.

Vitamin C has strong evidence for boosting absorption of plant-based iron. Taking as little as 50-100mg with a meal significantly improves non-heme iron uptake.

A safety note for men: doses above 1,000mg/day increase kidney stone risk. The mechanism is straightforward - ascorbic acid is metabolized to dehydroascorbic acid, then to 2,3-diketogulonic acid, which cleaves into oxalate. Calcium oxalate constitutes roughly 80% of all human kidney stones, and urinary oxalate excretion increases steeply above 1,000mg/day. The HPFS/NHS cohorts (40,500 men and 156,000 women tracked for over a decade) found men taking 1,000mg+ had a 19% increased risk (HR 1.19, 95% CI 1.01-1.40), and a meta-analysis confirmed 62% higher odds (OR 1.62). Women do not appear to share this risk, likely due to estrogen's protective effect on renal calcium excretion, differential GI calcium absorption binding free oxalate in the gut, and possible variations in hepatic oxalate synthesis. Those with chronic kidney disease should avoid supplemental vitamin C entirely due to impaired oxalate clearance. The optimal daily dose for most adults is 200-400mg - enough to saturate plasma without the diminishing returns and risks of megadosing.