Vitamin C megadosage is a time period describing the consumption or injection of vitamin C (ascorbic acid) in doses nicely past the present Really helpful Dietary Allowance of 90 milligrams per day, and sometimes nicely past the tolerable higher consumption stage of two,000 milligrams per day.[1] There isn’t any scientific proof that vitamin C megadosage helps to treatment or forestall most cancers, the widespread chilly, or a wide range of different medical circumstances.[2][3]
Historic advocates of vitamin C megadosage embody Linus Pauling, who received the Nobel Prize in Chemistry in 1954. Pauling argued that as a result of people lack a useful type of L-gulonolactone oxidase, an enzyme required to make vitamin C that’s useful in most different mammals, crops, bugs, and different life types, people have developed quite a few diversifications to deal with the relative deficiency. These diversifications, he argued, finally shortened lifespan however might be reversed or mitigated by supplementing people with the hypothetical quantity of vitamin C that may have been produced within the physique if the enzyme have been working.
Vitamin C megadoses are claimed by different medication advocates together with Matthias Rath and Patrick Holford to have preventive and healing results on illnesses corresponding to most cancers and AIDS,[4][5] however the accessible scientific proof doesn’t assist these claims.[3] Some trials present some impact together with different therapies, however this doesn’t suggest vitamin C megadoses in themselves have any therapeutic impact.[6]
Contents
Background[edit]
Vitamin C is an important nutrient used within the manufacturing of collagen and different biomolecules, and for the prevention of scurvy.[7] It is usually an antioxidant, which has led to its endorsement by some researchers as a complementary remedy for enhancing high quality of life.[8] Sure animal species, together with the haplorhine primates (which embody people),[9][10] members of the Caviidae household of rodents (together with guinea pigs and capybaras),[11] most species of bats,[12] many passerine birds,[13] and about 96% of fish (the teleosts),[13] can’t synthesize vitamin C internally and should due to this fact depend on exterior sources, sometimes obtained from meals.
For people, the World Well being Group recommends a day by day consumption of 45 mg/day of vitamin C for wholesome adults, and 25–30 mg/day in infants.[14] The vitamin C article supplies examples of suggestions from particular person international locations. None exceed 110 mg/day.
Since its discovery, vitamin C has been thought of virtually a panacea by some,[15] though this led to suspicions of it being overhyped by others.[16] Vitamin C has lengthy been promoted in different medication as a therapy for the widespread chilly, most cancers, polio, and varied different diseases. The proof for these claims is blended. Because the Nineteen Thirties, when it first grew to become accessible in pure kind, some physicians have experimented with higher-than-recommended vitamin C consumption or injection.[17] Orthomolecular-based megadose suggestions for vitamin C are primarily based primarily on theoretical hypothesis and observational research, corresponding to these printed by Fred R. Klenner from the Nineteen Forties by way of the Seventies. There’s a sturdy advocacy motion for very excessive doses of vitamin C, but there may be an absence of large-scale, formal trials within the 10 to 200+ grams per day vary.
The only repeatable facet impact of oral megadose vitamin C is a gentle laxative impact if the practitioner makes an attempt to devour an excessive amount of too shortly. In america and Canada, a tolerable higher consumption stage (UL) was set at 2,000 mg/day, citing this delicate laxative impact as the rationale for establishing the UL.[1] Nonetheless, the European Meals Security Authority (EFSA) reviewed the protection query in 2006 and reached the conclusion that there was not enough proof to set a UL for vitamin C.[18] The Japan Nationwide Institute of Well being and Vitamin reviewed the identical query in 2010 and likewise reached the conclusion that there was not enough proof to set a UL.[19]
About 70–90% of vitamin C is absorbed by the physique when taken orally at regular ranges (30–180 mg day by day). Solely about 50% is absorbed from day by day doses of 1 gram (1,000 mg). Oral administration, even of megadoses, can’t increase blood focus above 0.22 mM.[20]
Relative deficiency speculation[edit]
People and different species that can’t synthesize their very own vitamin C carry a mutated and ineffective type of the enzyme L-gulonolactone oxidase, the fourth and final step within the ascorbate-producing equipment. Within the anthropoids lineage, this mutation seemingly occurred 40 to 25 million years in the past.[citation needed] The three surviving enzymes proceed to supply the precursors to vitamin C, however the absence of the fourth enzyme means the method isn’t accomplished, and the physique finally disassembles the precursors.
Within the Sixties, the Nobel-Prize-winning chemist Linus Pauling, after contact with Irwin Stone,[21] started actively selling vitamin C as a method to drastically enhance human well being and resistance to illness. His e book How you can Dwell Longer and Really feel Higher was a bestseller and advocated taking greater than 10 grams per day orally, thus approaching the quantities launched by the liver straight into the circulation in different mammals: an grownup goat, a typical instance of a vitamin C-producing animal, will manufacture greater than 13,000 mg of vitamin C per day in regular well being and way more when pressured.[citation needed]
Matthias Rath is a controversial German doctor who labored with and printed two articles discussing the attainable relationship between lipoprotein and vitamin C with Pauling.[22][23] He’s an lively proponent and publicist for high-dose vitamin C. Pauling’s and Rath’s prolonged principle states that deaths from scurvy in people throughout the Pleistocene, when vitamin C was scarce, chosen for people who may restore arteries with a layer of ldl cholesterol offered by lipoprotein(a), a lipoprotein present in vitamin C-deficient species.[24]
Stone[25] and Pauling[9] believed that the optimum day by day requirement of vitamin C is round 2,300 milligrams for a human requiring 2,500 kcal per day. For comparability, the FDA’s really useful day by day allowance of vitamin C is simply 90 milligrams.[1]
Adversarial results[edit]
Though generally thought of freed from toxicity, there are actually recognized uncomfortable side effects from vitamin C consumption, and it has been steered that intravenous injections ought to require “a medical environment and trained professionals.”[26]
For instance, a genetic situation that ends in insufficient ranges of the enzyme glucose-6-phosphate dehydrogenase (G6PD) may cause victims to develop hemolytic anemia after utilizing intravenous vitamin C therapy.[27] The G6PD deficiency check is a standard laboratory check.
As a result of oxalic acid is produced throughout metabolism of vitamin C, hyperoxaluria could be attributable to intravenous administration of ascorbic acid.[26] Vitamin C administration may additionally acidify the urine and will promote the precipitation of kidney stones or medicine within the urine.[26]
Though vitamin C could be nicely tolerated at doses nicely above what authorities organizations suggest, hostile results can happen at doses above 3 grams per day. The widespread “threshold” facet impact of megadoses is diarrhea. Different attainable hostile results embody elevated oxalate excretion and kidney stones, elevated uric acid excretion, systemic conditioning (“rebound scurvy”), preoxidant results, iron overload, diminished absorption of vitamin B12 and copper, elevated oxygen demand, and acid erosion of the tooth when chewing vitamin C tablets.[1] As well as, one case has been famous of a girl who acquired a kidney transplant adopted by high-dose vitamin C and died quickly afterwards on account of calcium oxalate deposits that destroyed her new kidney. Her docs concluded that high-dose vitamin C remedy ought to be averted in sufferers with kidney failure.[28]
Overdose[edit]
As mentioned beforehand, vitamin C typically reveals low toxicity. The LD50 (the dose that can kill 50% of a inhabitants) is mostly accepted to be 11,900 milligrams (11.9 grams) per kilogram in rat populations.[29] The American Affiliation of Poison Management Facilities has reported zero deaths from vitamin C toxicity.[30]
Interactions[edit] – “vitamin c megadose”
Prescribed drugs designed to cut back abdomen acid, such because the proton-pump inhibitors (PPIs), are among the many most generally offered medicine on the planet. One PPI, omeprazole (Prilosec), has been discovered to decrease the bioavailability of vitamin C by 12% after 28 days of therapy, unbiased of dietary consumption. The possible mechanism of vitamin C discount, intragastric pH elevated into alkalinity, would apply to all different PPI medicine, although not essentially to doses of PPIs low sufficient to maintain the abdomen barely acidic.[31] In one other examine, 40 mg/day of omeprazole lowered the fasting gastric vitamin C ranges from 3.8 to 0.7 µg/mL.[32] Aspirin may additionally inhibit the absorption of vitamin C.[33][34]
Regulation[edit]
There are rules in most international locations that restrict the claims relating to therapy of illness that may be positioned on meals and dietary complement product labels. For instance, claims of therapeutic impact with respect to the therapy of any medical situation or illness are prohibited by america Meals and Drug Administration even when the substance in query has gone by way of nicely carried out scientific trials with constructive outcomes. Claims are restricted to Construction:Perform phrasing (“Helps maintain a healthy immune system”) and the next discover is necessary on meals and dietary complement product labels that make all these well being claims: These statements haven’t been evaluated by the Meals and Drug Administration. This product isn’t supposed to diagnose, deal with, treatment, or forestall any illness.[35]
Analysis[edit]
Most cancers[edit]
The usage of vitamin C in excessive doses as a therapy for most cancers was promoted by Linus Pauling, primarily based on a 1976 examine printed with Ewan Cameron which reported intravenous vitamin C considerably elevated lifespans of sufferers with superior most cancers.[36][2] This trial was criticized by the Nationwide Most cancers Institute for being designed poorly, and three subsequent trials carried out on the Mayo Clinic couldn’t replicate the outcomes.[2][37] Nonetheless, the trials on the Mayo Clinic have been carried out with oral doses of ascorbate, not intravenous ascorbate as was finished within the unique trial, and it has been steered that this distinction is a attainable cause for the failure of the Mayo Clinic trials to duplicate the unique trial outcomes.[38]
Preliminary scientific trials in people have proven that it’s unlikely to be a “miracle pill” for most cancers and extra analysis is critical earlier than any definitive conclusions about efficacy could be reached.[26] A 2010 assessment of 33 years of analysis on vitamin C to deal with most cancers acknowledged “we have to conclude that we still do not know whether Vitamin C has any clinically significant antitumor activity. Nor do we know which histological types of cancers, if any, are susceptible to this agent. Finally, we don’t know what the recommended dose of Vitamin C is, if there is indeed such a dose, that can produce an anti-tumor response.”[37]
The American Most cancers Society has acknowledged, “Although high doses of vitamin C have been suggested as a cancer treatment, the available evidence from clinical trials has not shown any benefit.”[2]
Burns[edit]
One scientific trial used excessive intravenous doses of vitamin C (66 mg/kg/hour for twenty-four hours, for a complete dose of round 110 grams) after extreme burn damage,[39] however regardless of being described as promising, it has not been replicated by unbiased establishments and thus isn’t a broadly accepted therapy.[40] Primarily based on that examine, the American Burn Affiliation (ABA) considers high-dose ascorbic acid an choice to be thought of for adjuvant remedy along with the extra accepted commonplace therapies.[41]
Cardiac results[edit]
Atrial fibrillation (AF) is a standard cardiac rhythm disturbance related to oxidative stress. 4 meta-analyses have concluded that there’s sturdy proof that consuming 1–2 g/day of vitamin C earlier than and after cardiac operations can lower the danger of post-operative AF.[42][43][44][45] Nonetheless, 5 randomized research didn’t discover any such profit in america, in order that the profit was restricted to much less rich international locations.[45][46]
Train-induced bronchoconstriction[edit]
Train-induced bronchoconstriction (EIB) signifies acute narrowing of the airways on account of vigorous train. EIB appears to be attributable to the lack of water attributable to elevated air flow, which can result in the discharge of mediators corresponding to histamine, prostaglandins, and leukotrienes, all of which trigger bronchoconstriction. Vitamin C participates within the metabolism of those mediators and would possibly thereby affect EIB.[47] A meta-analysis confirmed that 0.5 to 2 g/day of vitamin C earlier than train decreased EIB by half.[48]
Endothelial operate[edit]
A meta-analysis confirmed a big constructive impact of vitamin C on endothelial operate. Profit was discovered of vitamin C in doses starting from 0.5 to 4 g/day, whereas decrease doses from 0.09 to 0.5 g/day weren’t efficient.[49]
Frequent chilly[edit]
A often cited meta-analysis calculated that varied doses of vitamin C (day by day doses beneath 0.2 grams have been excluded) don’t forestall the widespread chilly within the basic neighborhood, though 0.25 to 1 g/day of vitamin C halved the incidence of colds in folks beneath heavy short-term bodily stress.[50] One other meta-analysis calculated that, in youngsters, 1–2 g/day vitamin C shortened the length of colds by 18%, and in adults 1–4 g/day vitamin C shortened the length of colds by 8%.[50] There’s proof of linear dose-dependency within the impact of vitamin C on widespread chilly length as much as 6–8 g/day.[51][jargon] As famous above, there may be an absence of large-scale, formal trials within the 10 to 200+ grams per day vary, so no data is accessible for these greater dosages. Moreover, the cited research of bigger day by day doses of vitamin C don’t have in mind the quick excretion charge of vitamin C at gram-level doses, which makes it mandatory to offer the overall day by day quantity in smaller, extra frequent doses to take care of greater plasma ranges.[52] As of 2014, a minimum of 16 research had discovered that vitamin C dietary supplements didn’t forestall the widespread chilly and had minimal impact at finest in shortening chilly lengths.[3]