Vitamin C megadosage is a term describing the consumption or injection of vitamin C (ascorbic acid) in doses well beyond the current United States Recommended Dietary Allowance of 90 milligrams per day, and often well beyond the tolerable upper intake level of 2,000 milligrams per day. There is no strong scientific evidence that vitamin C megadosage helps to cure or prevent cancer, the common cold, or some other medical conditions. Historical advocates of vitamin C megadosage include Linus Pauling, who won the Nobel Prize in Chemistry in 1954. Pauling argued that because humans and other primates lack a functional form of L-gulonolactone oxidase, an enzyme required to make vitamin C that is functional in almost all other mammals, plants, insects, and other life forms, humans have developed a number of adaptations to cope with the relative deficiency. These adaptations, he argued, ultimately shortened lifespan but could be reversed or mitigated by supplementing humans with the hypothetical amount of vitamin C that would have been produced in the body if the enzyme were working. Vitamin C megadoses are claimed by alternative medicine advocates including Matthias Rath and Patrick Holford to have preventive and curative effects on diseases such as cancer and AIDS, but scientific evidence does not support these claims. Some trials show some effect in combination with other therapies, but this does not imply vitamin C megadoses in themselves have any therapeutic effect.
Background Vitamin C is an essential nutrient used in the production of collagen and other biomolecules, and for the prevention of scurvy. It is also an antioxidant, which has led to its endorsement by some researchers as a complementary therapy for improving quality of life. Certain animal species, including the haplorhine primates (which include humans), members of the Caviidae family of rodents (including guinea pigs and capybaras), most species of bats, many passerine birds, and about 96% of fish (the teleosts), cannot synthesize vitamin C internally and must therefore rely on external sources, typically obtained from food. For humans, the World Health Organization recommends a daily intake of 45 mg/d of vitamin C for healthy adults, and 25–30 mg/d in infants. Since its discovery, vitamin C has been considered almost a panacea by some, although this led to suspicions of it being overhyped by others. Vitamin C has long been promoted in alternative medicine as a treatment for the common cold, cancer, polio, and various other illnesses. The evidence for these claims is mixed. Since the 1930s, when it first became available in pure form, some physicians have experimented with higher-than-recommended vitamin C consumption or injection. Orthomolecular-based megadose recommendations for vitamin C are based mainly on theoretical speculation and observational studies, such as those published by Fred R. Klenner from the 1940s through the 1970s. There is a strong advocacy movement for very high doses of vitamin C, yet there is an absence of large-scale, formal trials in the 10 to 200+ grams per day range. The single repeatable side effect of oral megadose vitamin C is a mild laxative effect if the practitioner attempts to consume too much too quickly. In the United States and Canada, a tolerable upper intake level (UL) was set at 2,000 mg/day, citing this mild laxative effect as the reason for establishing the UL. However, the European Food Safety Authority (EFSA) reviewed the safety question in 2006 and reached the conclusion that there was not sufficient evidence to set a UL for vitamin C. The Japan National Institute of Health and Nutrition reviewed the same question in 2010 and also reached the conclusion that there was not sufficient evidence to set a UL. About 70–90% of vitamin C is absorbed by the body when taken orally at normal levels (30–180 mg daily). Only about 50% is absorbed from daily doses of 1 gram (1,000 mg). Even oral administration of megadoses of 3g every four hours cannot raise blood concentration above 220 micromol/L.
Adverse effects Although sometimes considered free of toxicity, there are known side effects from vitamin C intake, and it has been suggested that intravenous injections should require "a medical environment and trained professionals." For example, a genetic condition that results in inadequate levels of the enzyme glucose-6-phosphate dehydrogenase (G6PD) can cause affected people to develop hemolytic anemia after using intravenous vitamin C treatment. The G6PD deficiency test is a common laboratory test. Because oxalic acid is produced during metabolism of vitamin C, hyperoxaluria can be caused by intravenous administration of ascorbic acid. Vitamin C administration may also acidify the urine and could promote the precipitation of kidney stones or drugs in the urine. Although vitamin C can be well tolerated at doses well above what government organizations recommend, adverse effects can occur at doses above 3 grams per day. The common "threshold" side effect of megadoses is diarrhea caused by oral consumption of vitamin C in such doses. Other possible adverse effects regardless of the mode of administration include increased oxalate excretion and kidney stones, increased uric acid excretion, systemic conditioning ("rebound scurvy"), preoxidant effects, iron overload, reduced absorption of vitamin B12 and copper, increased oxygen demand, and acid erosion of the teeth when chewing vitamin C tablets. In addition, one woman received a kidney transplant followed by high-dose vitamin C and died soon afterward as a result of calcium oxalate deposits that destroyed her new kidney. Her doctors concluded that high-dose vitamin C therapy should be avoided in patients with kidney failure.
Overdose Vitamin C generally exhibits low toxicity. The LD50 (the dose that will kill 50% of a population) is generally accepted to be 11,900 milligrams (11.9 grams) per kilogram in rat populations. The American Association of Poison Control Centers has reported zero deaths from vitamin C toxicity in 2018.
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