Vitamin C megadosage
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Vitamin C megadosage is the consumption of Vitamin C in doses which are well beyond the current Dietary Reference Intake. Proponents advocate that this dose is similar to the intake of other primates that cannot synthesize vitamin C, and is required to attain concentrations reached by most other animals, who synthesize vitamin C.Stone, Irwin. Homo sapiens ascorbicus, a biochemically corrected robust human mutant. Med. Hypotheses 5: 711-722, 1979. Cited in HYPOASCORBEMIA-240400. Online Mendeleian Inheritance in Man. High doses have been used in an attempt to obtain specific therapeutic effects"Although there is still controversy regarding anticancer effects of vitamin C, the use of vitamin C is considered a safe and effective therapy to improve the quality of life of terminal cancer patients". There is a strong advocacy movement for such doses of vitamin C, despite a prolonged lack of conclusive medical evidence or large scale, formal trials in the 10 to 200+ grams per day range.
Advocacy positions
Orthomolecular based megadose recommendations for vitamin C use, based on pharmacological principles and clinical observations, are several fold. Orthomolecularly recognized physicians have long considered intravenous medical use of buffered vitamin C in the range of 30 - 200+ grams per day, along with concurrent oral use, as fastest and most reliable in substantially ameliorating or even curing serious disease of varying type and severity. Lesser amounts of sodium ascorbate IV/IM have been used for toxins and toxic exposures. Megadose, orally administered vitamin C protocols have been recommended by orthomolecular advocates, both for prevention of illness, and separately, in greater frequency and dosages for treatment of frank illness against viral and bacterial infections, various oxidative and biological toxins, and a mechanism in reversing the development of atherosclerosis. Total vitamin C usage advocated with infectious diseases have typically ranged from about 40 to 300 grams per day in adults depending on severity, administration route(s), and tolerances. Vitamin C is sometimes recommended by advocates concurrently with conventional antibiotics for bacterial diseases.Oral megadose vitamin C as a prevention element, in a comprehensive individualized vitamin regimen, is considered to require both a minimum frequency and a minimum quantity for effectiveness. The typical individual's pharmacokinetics of oral solubilized vitamin C requires 5 or more administrations of immediately dissolvable vitamin C for 24 hour coverage as measured by blood levels. Effective time release formulations of vitamin C may allow 24 hour coverage with only 3 oral administrations. Typical daily orthomolecular doses of oral vitamin C for preventative purposes range 5 - 25 grams of ascorbate per day in healthy adults. Less than 2 grams per day is not considered a principled amount for orthomolecular "megadose" use in healthy people. Linus Pauling's retrospective analyses of several earlier vitamin C studies identified certain subgroups, which involved physical or cold stress, as statistically benefiting from even one gram per day against common respiratory illnesses, but this amount is not considered optimal or even a megadosed daily usage by advocates.Oral megadose vitamin C as an oral treatment element for infections and toxic exposures, with a comprehensive individualized or naturopathic regimen, is considered to require both a higher frequency and much greater quantity for effectiveness. Typical oral treatment frequencies with vitamin C range 15 minutes to 2 hours, the more frequent dosing considered more effective and tighter, more easy to optimize, especially during the first few hours of administration. Less frequent administrations during illness, every hour or two, reflect convenience of administration. Time release oral formulations are used for longer periods between doses such as during sleep. Pauling's recommendation of 1-2 grams of ascorbate per hour at the first sign or tickle of a cold is considered a minimal principled effort by advocates. Cathcart's "bowel tolerance" regimen, front loaded for higher frequency and amounts during the first several hours, is considered by advocates the most effective and the maximum practical oral use of vitamin C. Advocacy arguments
The advocates argue that the NIH does not take into account individual differences such as age, weight, etc. For example, heavier individuals generally need more vitamin C. They point out the figures represent the amount needed to prevent the acute form of deficiency disease, while subclinical levels of the disease are not even acknowledged. That the amount needed to prevent other diseases is not considered. Most mammals can synthesize their own vitamin C in their liver or kidney, and when they become sick they synthesize much larger amounts -- amounts similar to the "megadoses" suggested by vitamin C advocates for sick humans. The advocates believe that the established RDA is one that will prevent the onset of scurvy and is not necessarily the most optimal dosage, this belief contradicts statements made by the United States Department of Agriculture as to the purpose of the RDA. The advocates believe that the recommendations in the RDA is considerably less than the body-weight equivalent of what other mammals synthesize for themselves even when in good health. Claimed therapeutic applications of high doses
Vitamin C is needed in the diet to prevent scurvy, however, from the time it became available in pure form in the 1930s, some practitioners experimented with vitamin C as a monomolecular treatment for diseases other than scurvy. Modern clinical megadose Vitamin C use is with individualized, usually at higher than RDA amounts, of other vitamins and minerals as well as other nutrients. Common cold
A recent 55-study review found little positive effect of a vitamin C intake on the common cold at low, brief or single daily doses. At least 29 controlled clinical trials (many double-blind and placebo-controlled) involving a total of over 11,000 participants have been conducted into vitamin C and the common cold. In several of the largest studies, no effect on common cold incidence is observed, indicating to many scientists that vitamin C has no preventive effects in normally nourished subjects.[http://www.supplementwatch.com/suplib/supplement.asp?DocId=1278&templateId=100%20Supplementwatch.com] Supplement Watch However, other trials claim that vitamin C reduces the duration and severity of colds but not the frequency. Controlled trials and clinical experience demonstrate that vitamin C in single doses ranging from 100 mg to 2 grams per day have a relatively small effect in unstressed or nondeficient populations. The duration of colds was reduced by 7% for adults and 15% for children.Heart disease
Vitamin C is the main component of the three ingredients in Linus Pauling's patented but unvalidated preventive cure for lipoprotein(a)Rath MW, Pauling LC. Prevention and treatment of occlusive cardiovascular disease with ascorbate and substances that inhibit the binding of lipoprotein(A)]. USPTO. 11 Jan 1994. related heart disease, the other two being the amino acid lysine and niacin (a form of Vitamin B3). Lp(a) as an atherosclerotic, evolutionary substitute for ascorbate Rath M, Linus P. Hypothesis: Lipoprotein (a) is a surrogate for ascorbate. Proc Natl Acad Sci USA. Vol 87, 6204–6207, Aug 1990. is still discussed as a hypothesis by mainstream medical scienceKniffin CL, McKusick VA, Brennan P. APOLIPOPROTEIN(a); LPA. OMIMTM - Online Mendelian Inheritance in Man, Johns Hopkins University. 1986–2006 and the Rath-Pauling related protocols have not been rigorously tested, nor have they been evaluated by the FDA (because no one has submitted a drug approval application).Viral diseases, and poisons
Orthomolecular medicine and a minority of scientific opinion sees vitamin C as being a low cost and safe way to treat viral disease and to deal with a wide range of poisons.Vitamin C has a growing reputation for being useful in the treatment of colds and flu, owing to its recommendation by prominent biochemist Linus Pauling. In the years since Pauling's popular books about vitamin C, general agreement by medical authorities about larger than RDA amounts of vitamin C in health and medicine has remained elusive. Ascorbate usage in studies of up to several grams per day, however, have been associated with decreased cold duration and severity of symptoms, possibly as a result of an antihistamine effect. The highest dose treatments, published clinical results of specific orthomolecular therapy regimes pioneered by Drs. Klenner (repeated IV treatments, 400–700+ (mg/kg)/day) and Cathcart (oral use until the onset of diarrhea, up to ~150 grams ascorbate per day for flu), have remained experimentally unaddressed by conventional medical authorities for decades.The Vitamin C Foundation recommends an initial usage of up to 8 grams of vitamin C every 20–30 minutes in order to show an effect on the symptoms of a cold infection that is in progress. Most of the studies showing little or no effect employ doses of ascorbate such as 100 mg to 500 mg per day, considered "small" by vitamin C advocates. Equally importantly, the plasma half life of high dose ascorbate is approximately 30 minutes, which implies that most high dose studies have been methodologically defective and would be expected to show a minimum benefit. Clinical studies of divided dose supplementation, predicted on pharmacological grounds to be effective, have only rarely been reported in the literature. Essentially all the claims for high dose vitamin C remain to be scientifically refuted. The clinical effectiveness of large and frequent doses of vitamin C is an open scientific question.Cancer
According to the American Cancer Society, there have been no studies that have demonstrated a benefit from supplemental forms of Vitamin C in decreasing cancer risk in humans.[http://www.cancer.org/docroot/PED/content/PED_3_2X_Common_Questions_About_Diet_and_Cancer.asp]Common Questions About Diet and Cancer Two large, placebo-controlled trials in 1979 and 1985 Creagan ET, Moertel CG, O'Fallon JR, et al. Failure of high-dose vitamin C therapy to benefit patients with advanced cancer. A controlled trial. N Engl J Med 1979;301:687–90Moertel CG, Fleming TR, Creagan ET, et al. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N Engl J Med 1985;312:137–41 could not show any positive effect of vitamin C in cancer patients. Some in vitro studies have suggested that large doses of Vitamin C may actually encourage growth and proliferation of certain tumor lines.[http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17602832&ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum] Reciprocal effects of ascorbate on cancer cell growth and the expression of matrix metalloproteinases and transforming growth factor-betaIn 2005 in vitro (test tube) research by the National Institutes of Health indicated that vitamin C administered in pharmacological concentrations (i.e. intravenous) was preferentially toxic to several strains of cancer cells. The authors noted: "These findings give plausibility to intravenous ascorbic acid in cancer treatment, and have unexpected implications for treatment of infections where H2O2 may be beneficial." Qi Chen et al. "Pharmacologic ascorbic acid concentrations selectively kill cancer cells." Proceedings of the National Academy of Sciences of the United States of America (PNAS) 102(38) 13604–13609. PMID 16157892 In 2006 the Canadian Medical Association Journal published a case study of three individuals that demonstrated that intravenous vitamin C might subdue advanced-stage cancer, though the authors concede that spontaneous remissions have been known to occur. Sebastian J. Padayatty and others. Vitamin C documented to quell advanced-stage cancer in three cases involving bladder, lung, kidney and lymphoma tumors. Canadian Medical Assn Journal 174: 937–42, 2006The study underwent rigorous case reporting standards as outlined by the U.S. National Cancer Institute.In January 2007 the US Food and Drug Administration approved a Phase I clinical trial to investigate what doses of intravenous vitamin C are safe as possible cancer treatments. (A Phase I trial assesses only the safety and tolerability of a treatment, not its efficacy.)September 2007 - A study funded by the NIH at John Hopkins University found that Vitamin C prevents the growth of cancer cells in an animal model, supposedly by the elimination of the HIF-1 (hypoxia-induced factor) protein, which is necessary for cancer growth in oxygen starved environments.[http://www.jhu.edu/~gazette/2007/17sep07/17bigc.html]September 2007 - study funded by the NIH at John Hopkins University on the cancer stopping mechanism of Vitamin C The authors, however, noted that this study was very preliminary and people "should not rush out and buy bulk supplies of antioxidants as a means of cancer prevention."
Lifespan
A 10-year study from UCLA showed that in a population of more than 11,000 US adults aged 25-74, men who took 800 mg of vitamin C daily lived about six years longer than men who took only 60 mg of vitamin C daily. [http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=1591317&dopt=Books 'Vitamin C intake and mortality among a sample of the United States population.' Epidemiology. 1992 May;3(3):194-202.] Published 1992. Accessed January 4, 2008. Possible adverse effects
While being harmless in most typical quantities, as with all substances to which the human body is exposed, vitamin C can still cause harm under certain conditions. In the medical community, these are known as contraindications.Side-effects
Although vitamin C can be well tolerated at doses well above the RDA recommendations, megadosing may cause side effects such as stomach upset and laxative effects such as diarrhea. The dose at which these effects may occur varies with the individual and health condition.Chance of overdose
As discussed previously, vitamin C generally exhibits low toxicity. The LD50 (the dose that will kill 50% of a population) is generally accepted to be 11900 milligrams per kilogram in rat populations. Vitamin C proponent Dr. Robert Cathcart M.D. reports that he has used intravenous doses of 60 grams, with simultaneous oral doses of unspecified amount, with no adverse effects.Conflicts with prescription drugs
Pharmaceuticals designed to reduce stomach acid, such as the proton pump inhibitors (PPIs), are among the most widely-sold drugs in the world. One PPI, omeprazole (Prilosec), has been found to lower the bioavailability of vitamin C by 12%, independent of dietary intake. The probable mechanism of vitamin C reduction, intragastric pH elevated into alkalinity, would apply to all other PPI drugs, though not necessarily to doses of PPIs low enough to keep the stomach slightly acidic.Potential harmful effects
Universal panacea hypothesis
Since its discovery vitamin C has been considered a universal panacea by some, although this led to suspicions of it being overhyped by others.Humans and higher primates, as well as guinea pigs and small number of other animal species, carry a mutated and ineffective form of the enzyme L-gulonolactone oxidase, the fourth and last step in the ascorbate-producing machinery. Cosmic rays or a retrovirus could have caused this mutation, about 40 to 25 million years ago (in the case of anthropoids lineage). The three surviving enzymes continue to produce the precursors to vitamin C but the process is incomplete and the body then disassembles them.It is agreed by most researchers, proponents and critics altogether, that the amounts of vitamin C consumed by our common anthropoid ancestor in its normal habitat (African rainforests) was amply sufficient to prevent death from scurvy and did not limit its ability to reproduce: i.e., it was an evolutionarily feasible change. BourneBourne G. H. (1949). Vitamin C and immunity. Brit. J. Nutrit., 2: 341-346. (quoted in Stone), Pauling and, recently, Milton, showed that these amounts were likely 10 to 20 times higher than what modern humans consume when eating cultivated species, as opposed to the less palatable vitamin-C-rich plant species growing in rainforests. In the 1960s, the Nobel-Prize-winning chemist Linus Pauling, after contact with Irwin Stone, began actively promoting vitamin C as a means to greatly improve human health and resistance to disease. His book How to Live Longer and Feel Better was a bestseller and advocated taking more than 10,000 milligrams per day orally, thus approaching the amounts released by the liver directly into the circulation in other mammals: an adult goat, a typical example of a vitamin-C-producing animal, will manufacture more than 13,000 mg of vitamin C per day in normal health and as much as 100,000 mg daily when faced with life-threatening disease, trauma, or stress. Pauling's book sold widely and many advocates today see its influence as the reason there was a marked downward trend in US heart disease from the early 1980s onwards.Stone's work also informed the practise of Dr. Robert Cathcart, in the 1970s and 1980s. Cathcart developed the concept of bowel tolerance, the use until the onset of diarrhea, followed by tapering of dose. He found that seriously ill people could often tolerate levels of tens of grams per day before their bowel tolerance limit is reached.Matthias Rath is a controversial German physician who once worked with Pauling and published in the National Academy of Sciences. He is an active proponent and publicist for high dose vitamin C. Pauling's and Rath's extended theory Rath, M., Pauling, L. (1992) A unified theory of human cardiovascular disease leading the way to the abolition of this disease as a cause for human mortality. Journal of Orthomolecular Medicine 7: 5-15.7. states that deaths from scurvy in humans during the ice age, when vitamin C was scarce, selected for individuals who could repair arteries with a layer of cholesterol, provided by lipoprotein(a), a lipoprotein found in vitamin C-deficient species (higher primates and guinea pigs). Pauling and Rath theorised that, although eventually harmful, lipoprotein deposition on artery walls was beneficial to the Human species and a "surrogate for ascorbate" in that it kept individuals alive until access to vitamin C allowed arterial damage to be repaired. Atherosclerosis is thus a vitamin-C-deficiency disease. Based on another study by Pauling and colleagues published in the National Academy of Sciencesand other studies, Rath argued publicly that high doses of vitamin C can be effectively used against viral epidemics such as HIV, SARS and bird flu.It has been suggested by some advocates that vitamin C is really a food group in its own right, like carbohydrates or protein, and should not be seen as a pharmaceutical or vitamin at all. {Irwin Stone: "The Healing Factor"} Politics of vitamin C
Regulation
There are regulations in most countries which limit the claims on the treatment of disease that can be placed on food, drug, and nutrient product labels. Regulations include:Advocacy arguments
Vitamin C advocates argue that there is a large body of scientific evidence that the vitamin has a wide range of health and therapeutic benefits but which they claim have been ignored. They claim the following factors affect the marketing and distribution of vitamin C, and the dissemination of information concerning the nutrient The Politics of Therapeutic Evaluation: The Vitamin C and Cancer Controversy Evelleen Richards, Social Studies of Science, Vol. 18, No. 4 (Nov., 1988), pp. 653-701:Next Page
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