Vitamin C megadosage



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 not producing vitamin C, and is required to attain concentrations reached by most other animals, who produce vitamin C. High doses have been used in an attempt to obtain specific therapeutic effects There is a strong advocacy movement for such doses of vitamin C, despite a prolonged lack of conclusive medical evidence or testing in the 10 to 200 grams per day range. 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.

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. 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) 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 is still discussed as a hypothesis by mainstream medical science 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. Two large, placebo-controlled trials in 1979 and 1985 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.

In 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." 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.

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. 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."

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.


 * As vitamin C enhances iron absorption, iron poisoning can become an issue to people with rare iron-overload conditions, such as haemochromatosis


 * A genetic condition that results in inadequate levels of the enzyme glucose-6-phosphate dehydrogenase (G6PD), can cause sufferers to develop hemolytic anemia after ingesting specific oxidizing substances, such as very large dosages of vitamin C.

Side-effects

 * Relatively large doses of vitamin C may cause indigestion, particularly when taken on an empty stomach. This generally occurs at doses larger than 10,000 mg / day, but may not occur if the patient is ill.
 * When taken in large doses, vitamin C causes diarrhea. The minimum dose that brings about this effect varies on the individual. This has been called the "bowel tolerance limit". It ranges from 5 to 25 grams per day in healthy individuals to 300 grams per day in severely ill patients, such as those with AIDS or cancer.
 * It has been suggested that large doses of vitamin C as an acid may increase the incidence of mouth ulcers and erode dentition.

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 Robert Cathcart reports that he has used intravenous doses of 60 grams, with simultaneous oral doses of unspecified amount, with no adverse effects. The United States Council for Responsible Nutrition has set an Upper Level of 2 grams, based on transient diarrhoea. Their publication on vitamin C safety notes that Very large doses of vitamin C have been taken daily over the course of many years, and only minor undesirable effects have been attributed with any certainty to the vitamin’s use... Clearly, vitamin C has a low order of toxicity.

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, 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

 * Some test-tube experiments have interpreted that Vitamin C may have possible adverse effects on decomposition of lipid peroxides in nonviable in vivo quantities and conditions and inhibit caspase-8 dependent apoptosis. In April 1998 the journal Nature reported pro-oxidant effects of excessive doses of vitamin C / ascorbic acid. The effects were noted in test tube experiments and on only two of the 20 markers of free radical damage to DNA. They have not been supported by further evidence from living organisms.


 * In April 2000, University of Southern California researchers reported a thickening of the arteries of the neck in persons taking high vitamin C doses. The scientists found that participants who consumed the most vitamin C from supplements had the greatest increase in atherosclerosis, particularly among smokers.


 * In June 2004, Duke University researchers reported an increased susceptibility to osteoarthritis in guinea pigs fed a diet high in vitamin C. However, a 2003 study at Umeå University in Sweden, found that "the plasma levels of vitamin C, retinol and uric acid were inversely correlated to variables related to rheumatoid arthritis disease activity."


 * A speculated increased risk of kidney stones may be a side effect of taking vitamin C in larger than normal amounts (more than 1 gram). The potential mechanism of action is through the metabolism of vitamin C to dehydroascorbic acid, which is then metabolized to oxalic acid, a known constituent of kidney stones. However, this oxalate issue is still controversial, with evidence being presented for and against the possibility of this side effect.
 * "Rebound scurvy" is a theoretical, never observed, condition that could occur when daily intake of vitamin C is rapidly reduced from a very large amount to a relatively low amount. Advocates suggest this is an exaggeration of the rebound effect which occurs because ascorbate-dependent enzyme reactions continue for 24–48 hours after intake is lowered, and use up vitamin C which is not being replenished.


 * Some writers have identified a risk of poor copper absorption from high doses of vitamin C. Ceruloplasmin levels seem specifically lowered by high vitamin C intake. In one study, 600 milligrams of vitamin C daily led to lower ceruloplasmin levels similar to those caused by copper deficiency. In another, ceruloplasmin levels were significantly reduced.


 * Some alternative medecine proponents suggest that doses of around 6-10 grams per day of vitamin C can induce an abortion in women under 4 weeks of pregnancy. This is based on evidence that high-dose vitamin C increases estrogen levels that may contribute to abortion in early-stage pregnancy, and that these properties have been demonstrated in laboratory animals. . This theory however is in direct opposition to Dr. Klenner's claim that there were no miscarries in over 300 consecutive pregnant patients who received 3g to 6g per day of Vitamin C, whereby Dr. Klenner concluded that failure to use this agent in sufficient amounts in pregnancy borders on malpractice.

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. Bourne (quoted in Stone ), Pauling and, recently, Milton, showed that these amounts were likely 10 to 20 times higher than what Modern Man consumes when eating cultivated species, as opposed to the less palatable vitamin C-rich plant species growing in rainforests.



In the 1960s 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 in 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 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 Sciences and 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"}

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:
 * Claims of therapeutic effect with respect to the treatment of any medical condition or disease are prohibited by the Food and Drug Administration (in the USA, and by the corresponding regulatory agencies in other countries) unless the substance has gone through a well established clinical trial with neutral oversight.
 * In the United States, the following notice is mandatory on food, drug, and nutrient product labels which make health claims: These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

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 :


 * There is some evidence of the applications and efficacy of vitamin C, but governmental agency dose and frequency of intake recommendations have remained relatively fixed. This has led some researchers to challenge the recommendations. In 2003 Steve Hickey and Hilary Roberts of the Manchester Metropolitan University published a fundamental criticism of the approach taken to fix the nutritional requirement of vitamin C. They again argued in 2004 that the RDA which is based on blood plasma and white blood cell saturation data from the National Institutes of Health (NIH) was based on flawed data. According to these authors, the doses required to achieve blood, tissue and body "saturation" are much larger than previously believed. They allege that the Institute of Medicine (IoM) and the NIH have failed to respond to an open letter from a number of scientists and medical researchers, notably Doctors Steve Hickey, Hilary Roberts, Ian Brighthope, Robert Cathcart, Abram Hoffer, Archie Kalokerinos, Tom Levy, Richard Passwater, Hugh Riordan, Andrew Saul and Patrick Holford, which called for revision of the RDI (Reference Daily Intake).