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Vitamin C megadosage is the consumption of vitamin C (ascorbate) in doses thoroughly beyond the current Dietary Reference Intake. Proponents state that this administer is similar to the intake of other primates which, like humans, cannot synthesize vitamin C. Most animals synthesize vitamin C, reaching much higher cellular concentrations than humans. Vitamin C is a recognized antioxidant, which has led to its counter-signature by some researchers as a complementary therapy for improving quality of life. Vitamin C has been promoted in variant medicine as a treatment for the common cold, cancer, polio, and various other illnesses. The demonstrate for these claims is mixed, although vitamin C is generally regarded as a beneficial antioxidant. There is a basic advocacy movement for such doses of vitamin C, despite a prolonged lack of conclusive medical demonstrate or large scale, formal trials in the 10 to 200+ grams per day range. Advocates pan mainstream scientific studies for using doses which are too low, and mainly using vocalized vitamin C when intravenous vitamin C is preferred.

Background

Vitamin C is needed in the reduce to prevent scurvy; however, from the time it became available in pure manner in the 1930s, some physicians have experimented with vitamin C as a treatment for diseases other than shabby. Orthomolecular-based megadose recommendations for vitamin C are based mainly on theoretical conjecture and observational studies. The speculation arises from the fact that most animals synthesize vitamin C, and fulfil much higher cellular concentrations than humans. Irwin Stone coined the expression hypoascorbia to describe what he thought was a genetic defect in humans leading to a demean level of vitamin C than other primates. Observational studies began with calling by McCormick and Klenner, who used intravenous vitamin C to treat a wide range of illnesses. The highest administer treatments, published clinical results of specific orthomolecular therapy regimes pioneered by Drs. Klenner (repeated IV treatments, 400–700+ (mg/kg)/day) and Cathcart (pronounced use until the onset of diarrhea, up to ~150 grams ascorbate per day for flu), have remained experimentally unaddressed by standard medical authorities for decades.

A comprehensive systematic review of vitamin C and the cold initiate a minor effect (8% in adults, 14% in children) in preventing the cold, but not treating it, and a stout effect (50%) in preventing the cold in extreme environments. Its effect on cancer has been provocative, beginning with a heavily criticized 1976 study which found significantly increased survival amidst cancer patients treated with intravenous and oral vitamin C. Two subsequent studies using only pronounced ascorbate failed to replicate these findings, and vitamin C's use as a cancer treatment was dismissed by mainstream drug. Recently, it has been revived by several Canadian researchers, who have focused on intravenous vitamin C. Their Period I trial of intravenous vitamin C on cancer patients found no objective response to cancer, although no toxicity was discovered, either. Come what may, Phase I trials are designed to assess the safety of a possible treatment, not its efficacy .

Advocates denounce mainstream scientific studies for using doses which are too low, and mainly using word-of-mouth vitamin C when intravenous vitamin C is preferred.

Dosage

Oral megadose vitamin C as a debarment element is prescribed as part of a comprehensive individualized vitamin regimen. The typical specific's pharmacokinetics of oral solubilized vitamin C requires 5 or more administrations of immediately dissolvable vitamin C for 24 hour coverage as modulated by blood levels. Effective time release formulations of vitamin C may allow 24 hour coverage with on the other hand 3 oral administrations. Typical daily orthomolecular doses of oral vitamin C for preventative purposes register 5 - 25 grams of ascorbate per day in healthy adults. Less than 2 grams per day is not considered a just amount for orthomolecular "megadose" use in healthy people. Linus Pauling's retrospective analyses of diverse earlier vitamin C studies identified certain subgroups, which involved fleshly or cold stress, as statistically benefiting from even one gram per day against commonplace respiratory illnesses, but this amount is not considered optimal or even a megadosed always usage by advocates.

Oral megadose vitamin C as an oral treatment element for infections and toxic exposures, with a full individualized or naturopathic regimen, is considered to require both a higher frequency and much greater volume for effectiveness. Typical oral treatment frequencies with vitamin C range 15 minutes to 2 hours, the more numerous dosing considered more effective and tighter, more easy to optimize, principally during the first few hours of administration. Less frequent administrations during complaint, every hour or two, reflect convenience of administration. Time release oral formulations are acclimatized for longer periods between doses such as during sleep. Pauling's counsel of 1-2 grams of ascorbate per hour at the first sign or tickle of a cold is considered a token principled effort by advocates. Cathcart's "bowel tolerance" regimen, front filled up for higher frequency and amounts during the first several hours, is considered by advocates the most clobber and the maximum practical oral use of vitamin C.

The Vitamin C Foundation recommends an initial convention of up to 8 grams of vitamin C every 20–30 minutes in order to show an effect on the symptoms of a old infection that is in progress. Equally importantly, the plasma half life of tall dose ascorbate is approximately 30 minutes, which implies that most high-frequency dose studies have been methodologically defective and would be expected to display a minimum benefit. Clinical studies of divided dose supplementation, predicted on pharmacological grounds to be junk, have only rarely been reported in the literature. Essentially all the claims for lavish dose vitamin C remain to be scientifically refuted.

Conditions

Common cold

See also: Vitamin C and the usual cold

The results of three meta-analyses show that vitamin C in doses ranging from 200 mg to 2 grams per day decrease duration, but not incidence, of the common cold by 8% for adults and 14% for children. Degree appears to be reduced by 50% in stressed adults such as soldiers or athletes in stern, cold environments. The clinical significance of these effects is uncertain, but the biological take place appears genuine.

Major inaccuracies have been discovered in influential reviews of vitamin C and the unfeeling.

Heart disease

Vitamin C is the main component of the three ingredients in Linus Pauling's patented but unvalidated antidote cure for lipoprotein(a), which related heart disease, the other two being the amino acid lysine and niacin (a frame of Vitamin B3). Lp(a) as an atherosclerotic, evolutionary substitute for ascorbate is still discussed as a proposition by mainstream medical science and the Rath-Pauling related protocols have not been rigorously tested, nor receive they been evaluated by the FDA (because no one has submitted a drug approval application).

Cancer

In 1976 Linus Pauling and Ewan Cameron published a woe of 100 patients treated with intravenous vitamin C for which showed significantly increased lifespans. Two unselfish, placebo-controlled trials of only oral vitamin C in 1979 and 1985 did not finger a positive effect of vitamin C in cancer patients. A recent in vitro study develop that low levels of vitamin C inhibited tumor growth, but high levels increased tumor vegetation.

In 2005 in vitro (test tube) research funded by the National Institutes of Condition indicated that vitamin C administered in pharmacological concentrations (i.e. intravenous) was preferentially toxic to certain strains of cancer cells. The authors noted: "These findings give plausibility to intravenous ascorbic acid in cancer treatment, and prepare unexpected implications for treatment of infections where H ₂ O ₂ may be beneficial." In 2006 the Canadian Medical Link Journal published a case study of three individuals that demonstrated that intravenous vitamin C capability subdue advanced-stage cancer, though the authors concede that impromptu remissions have been known to occur.

In 2007, a Phase I trial of intravenous vitamin C on cancer patients was announced. The recently published nuisance of intravenous vitamin C on cancer patients found no objective response to cancer, although no toxicity was discovered, either. The coach purpose of this study was to evaluate the safety and tolerability of vitamin C (ascorbic acid) addicted by injection into the vein. (A Phase I trial assesses only the safety and tolerability of a treatment, not its efficacy.)

In September 2007 a read funded by the NIH at Johns Hopkins University found that Vitamin C prevents the rise of cancer cells in an animal model, supposedly by the elimination of the HIF-1 (hypoxia-induced agent) protein, which is necessary for cancer growth in oxygen starved environments. The authors, in any way, noted that this study was very preliminary and people "should not high-priority out and buy bulk supplies of antioxidants as a means of cancer prevention."

A pilot study of intravenous vitamin C on cancer patients was conducted in 2005.

In 2008 researchers at the Nationalist Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, gave vitamin C intravenously to mice with considerate derived cancers and found that it slowed tumor growth by up to 53%. By injecting into the bloodstream it is on to get much larger amounts of the vitamin to a tumor than is possible with vocalized supplements. The Cancer Treatment Centers of America (CTCA) in Zion, Illinois, is currently (2008) testing the protection of intravenous vitamin C in late-stage cancer patients for whom there is no other treatment chance.

Vitamin C supplementation may interfere with effective cancer chemotherapy. A 2008 investigation from Memorial Sloan-Kettering Cancer Center found that vitamin C was enchanted up by cancer cells and protected the cells from chemotherapy drugs, raising the chance that vitamin C might impair the effectiveness of chemotherapy.

Treatment of phencyclidine psychosis

Brawny dosages of vitamin C can be used in the acute treatment of phencyclidine (PCP) psychosis, It operates as a non-essential rather than primary treatment. Usually, 1000-2000 mg. of vitamin C are given intravenously during the course of 5–10 minutes. It is given in combination with a DA-2 antagonist such as haloperidol or risperidone. The competition is given intramuscularly and not combined with vitamin C. The vitamin acts synergistically with phencyclidine or its metabolites.

Gout

In 2008 researchers established that higher vitamin C intake reduces serum uric acid levels, and is associated with humble incidence of gout. The effect is more pronounced as intake increases into the megavitamin row

Lifespan

A 10-year study from UCLA showed that in a denizens of more than 11,000 US adults aged 25–74, men who took 800 mg of vitamin C common lived about six years longer than men who took only 60 mg of vitamin C common. Nevertheless, this study has been challenged on the basis that the age structure of the assortment taking vitamin C was different from that of the men who did not, thus creating a misleading denouement. The authors of this second, seemingly contradictory, study, taking into account details such as all-inclusive food consumption, found no evidence of such a protective effect.

Possible adverse effects

While being innocuous in most typical quantities, as with all substances to which the human body is exposed, vitamin C can quiescent cause harm under certain conditions. In the medical community, these are known as contraindications.

• As vitamin C enhances iron absorption for iron deficiency, iron strain may become an issue to people with rare iron-overload conditions, such as Beta (β) thalassemias.

• A genetic stipulation that results in inadequate levels of the enzyme glucose-6-phosphate dehydrogenase (G6PD), can genesis sufferers to develop hemolytic anemia after ingesting specific oxidizing substances (favism), such as Dialect right large dosages of vitamin C. There are common, inexpensive tests for G6PD deficiency.

• There is a longstanding assent among the mainstream medical community that vitamin C causes kidney stones, which seems based particle on science. Although some individual recent studies have found a relationship there is no cleanly relationship between excess ascorbic acid intake and kidney stone organization.

Side-effects

Although vitamin C can be well tolerated at doses well atop the RDA recommendations, megadosing may cause side effects such as stomach upset and laxative effects such as diarrhea. The quantity at which these effects may occur varies with the individual and health stipulation.

• Relatively large doses of vitamin C may cause indigestion, particularly when bewitched on an empty stomach. This generally occurs at doses larger than 10,000 mg / day, but may chance at much higher doses if the patient is ill.
• When taken in large doses, vitamin C causes diarrhea. The minutest dose that brings about this laxation effect varies on the party. This has been called the "bowel tolerance limit". It ranges from 5 to 25 grams per day in vigorous individuals to 300 grams per day in severely ill patients, such as those with AIDS or cancer.
• It has been suggested that Brobdingnagian doses of acidic vitamin C solution (ascorbic acid) swished around the door, rather than swallowed directly without a neutral rinse, may erode dentition.
• A 31-year-old Australian maid who had received a kidney transplant died soon afterward as a result of calcium oxalate deposits that destroyed her new kidney aim. Doctors concluded that high-dose vitamin C therapy should be avoided in patients with kidney dereliction. However, oxalate-induced kidney failure has been reported in people with no ostensible kidney problem.
• High dosage vitamin C ingestion may cause early sally of puberty in females. The source of the vitamin appears independent of the effect.

Chance of overdose

As discussed once upon a time, vitamin C generally exhibits low toxicity. The LD ₅₀ (the dose that will kill 50% of a inhabitants) is generally accepted to be 11900 milligrams per kilogram in rat populations. Vitamin C proponent Dr. Robert Cathcart M.D. reports that he has familiar intravenous doses of 60 grams, with simultaneous oral doses of unspecified amount, with no adverse effects.

Conflicts with preparation drugs

Pharmaceuticals designed to reduce stomach acid, such as the proton blow up inhibitors (PPIs), are among the most widely-sold drugs in the world. One PPI, omeprazole (Prilosec), has been start to lower the bioavailability of vitamin C by 12%, independent of dietary intake. The probable identity theory of vitamin C reduction, intragastric pH elevated into alkalinity, would apply to all other PPI drugs, but not necessarily to doses of PPIs low enough to keep the stomach slightly acidic.

Quiescent harmful effects

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

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

• In June 2004, Duke University researchers reported an increased susceptibility to osteoarthritis in guinea pigs fed a reduce 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 coordinated to rheumatoid arthritis disease activity."

• A speculated increased risk of kidney stones may be a side significance of taking vitamin C in larger than normal amounts (more than 1 gram). The developing 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. How on earth, this oxalate issue is still controversial, with evidence being presented for and against the conceivability of this side effect.

• "Rebound scurvy" is a theoretical, never observed, outfit that could occur when daily intake of vitamin C is rapidly reduced from a hugely large amount to a relatively low amount. Advocates suggest this is an exaggeration of the spring back effect which occurs because ascorbate-dependent enzyme reactions proceed with for 24–48 hours after intake is lowered, and use up vitamin C which is not being replenished.

• Some writers set up identified a risk of poor copper absorption from high doses of vitamin C. Ceruloplasmin levels feel specifically lowered by high vitamin C intake. In one study, 600 milligrams of vitamin C every day led to lower ceruloplasmin levels similar to those caused by copper deficiency. In another, ceruloplasmin levels were significantly reduced.

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

Genetic deficiency and chick spectrum hypotheses

Since its discovery vitamin C has been considered almost a widespread panacea by some, although this led to suspicions of it being overhyped by others.

Humans and higher primates, as immeasurably as guinea pigs and small number of other animal species, carry a mutated and incompetent form of the enzyme L-gulonolactone oxidase, the fourth and last step in the ascorbate-producing machinery. Cosmic rays or a retrovirus could give birth to caused this mutation, about 40 to 25 million years ago (in the the truth of anthropoids lineage). The three surviving enzymes continue to produce the precursors to vitamin C but the make is incomplete and the body then disassembles them.

It is agreed by most researchers, proponents and critics perfectly, that the amounts of vitamin C consumed by our common anthropoid ancestor in its normal element (African rainforests) was amply sufficient to prevent death from scurvy and did not limit its faculties 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 new-fashioned humans consume when eating cultivated species, as opposed to the less palatable vitamin-C-priceless plant species growing in rainforests.

In the 1960s, the Nobel-Prize-winning chemist Linus Pauling, after ring up with Irwin Stone, began actively promoting vitamin C as a means to greatly recover human health and resistance to disease. His book How to Live Longer and Feel Improved was a bestseller and advocated taking more than 10,000 milligrams per day orally, hence approaching the amounts released by the liver directly into the circulation in other mammals: an adult goat, a ordinary example of a vitamin-C-producing animal, will manufacture more than 13,000 mg of vitamin C per day in conventional health and as much as 100,000 mg daily when faced with life-menacing disease, trauma, or stress. Pauling's book sold widely and many advocates today see its control as the reason there was a marked downward trend in US heart disease from the primitive 1980s onwards.

Stone's work also informed the practise of Dr. Robert Cathcart, in the 1970s and 1980s. Cathcart developed the concept of bowel immunity, the use until the onset of diarrhea, followed by tapering of dose. He found that really ill people could often tolerate levels of tens of grams per day before their bowel variation limit is reached.

Matthias Rath is a controversial German physician who once worked with Pauling and published in the Federal 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 ignoble in humans during the ice age, when vitamin C was scarce, selected for individuals who could put back in arteries with a layer of cholesterol, provided by lipoprotein(a), a lipoprotein found in vitamin C-flawed species (higher primates and guinea pigs). Pauling and Rath theorised that, although sooner harmful, lipoprotein deposition on artery walls was beneficial to the Human species and a "surrogate for ascorbate" in that it kept individuals humming until access to vitamin C allowed arterial damage to be repaired. Atherosclerosis is therefore a vitamin-C-deficiency disease.

Based on another study by Pauling and colleagues published in the Federal Academy of Sciencesand other studies, Rath argued publicly that squiffed 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 deep down 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 Deputy"}

Regulation of vitamin C

Regulation

There are regulations in most countries which limit the claims on the treatment of blight that can be placed on food, drug, and nutrient product labels. Regulations categorize:

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

Advocacy arguments

Vitamin C advocates argue that there is a generous body of scientific evidence that the vitamin has a wide range of health and corrective benefits but which they claim have been ignored. They demand the following factors affect the marketing and distribution of vitamin C, and the dissemination of information as to the nutrient :

• There is some evidence of the applications and efficacy of vitamin C, but governmental power dose and frequency of intake recommendations have remained relatively fixed. This has led some researchers to dare the recommendations. In 2003 Steve Hickey and Hilary Roberts of the Manchester Metropolitan University published a fundamental judgement 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 pasty blood cell saturation data from the National Institutes of Health (NIH) was based on faulty data. According to these authors, the doses required to achieve blood, combination and body "saturation" are much larger than previously believed. They aver that the Institute of Medicine (IoM) and the NIH have failed to respond to an open letter from a million 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 reworking of the RDI (Reference Daily Intake).

See also

• Ascorbic acid
• Micronutrient
• Macronutrient
• Megavitamin psychotherapy
• Orthomolecular medicine
• Uric acid
• Vitamin
• Vitamin C and the common cold

Back reading

• Pauling, Linus (1970). Vitamin C and the Common Cold . W. H. Freeman & Company. ISBN 071670160X.  
• Pauling, Linus (1976). Vitamin C, the Proverbial Cold, and the Flu'' . W H Freeman & Co. ISBN 0716703610.  
• Pauling, Linus (1986). How to Live Longer and Feel Best . Oregon State University press "20th Anniversary Edition". ISBN 0380702894.  
• Cameron, Ewan; Linus Pauling, (1979). Cancer and Vitamin C . Pauling Pioneer of Science and Medicine. ISBN 0393500004.  
• Levy, Thomas E. (2002). Vitamin C Infectious Diseases, & Toxins . Xlibris. ISBN 1401069630.  

References

1. ^ ^{a b} Pauling L (1970). "Maturation and the need for ascorbic acid". Proc. Natl. Acad. Sci. U.S.A. 67 (4): 1643–8. doi: 10.1073/pnas.67.4.1643 . PMID 5275366.  
2. ^ Stone, Irwin. Homo sapiens ascorbicus, a biochemically corrected flavourful human mutant. Med. Hypotheses 5: 711-722, 1979. Online Mendelian Inheritance in Man.
3. ^ Yeom CH, Jung GC, Performance KJ (2007). "Change
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