Vitamin C megadosage

Vitamin C megadosage
Chemical structure of vitamin C
Chemical structure of vitamin C

Vitamin C megadosage is the consumption (or injection) of vitamin C (ascorbate) in doses comparable to the amounts produced by the livers of most other mammals and well beyond the current Dietary Reference Intake. A practitioner of vitamin C megadosage might consume several grams or commonly up to 20 grams or more per day under the assumption it leads to optimal health or healing of some condition. The dosage is usually divided and consumed in portions over the day. Injections of hundreds of grams per day are advocated by some physicians for therapy of certain conditions, poisonings, and recovery from trauma. People who practice vitamin C megadosage may consume many vitamin C pills throughout each day or dissolve pure vitamin C crystals in water or juice and drink it throughout the day.

Contents

Background

The World Health Organization recommends a daily intake of 45 mg/day of vitamin C for healthy adults.[1] Vitamin C is necessary for production of collagen and other biomolecules, and for the prevention of scurvy.[2] Vitamin C is an antioxidant, which has led to its endorsement by some researchers as a complementary therapy for improving quality of life.[3] Since the 1930s, when it first became available in pure form, some physicians have experimented with higher than recommended vitamin C consumption or injection.[4]

Primates, including humans, and guinea pigs do not synthesize vitamin C internally.[5] Nearly all other animals synthesize vitamin C internally, maintaining cellular vitamin C concentrations that are considerably higher than those achieved with the Reference Daily Intake set for humans. Irwin Stone coined the term hypoascorbia to describe the low level of vitamin C maintained in humans through their diet compared to the level other animals maintain through their internal production. He proposed that hypoascorbia is caused by a genetic defect in humans and most primates. Animals that produce ascorbate internally produce considerably higher amounts when they are stressed.[6]

Vitamin C has 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. 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 such doses of vitamin C, and 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. A tolerable upper limit (UL) of vitamin C was set at 2 grams for the first time in the year 2000, referencing this mild laxative effect as the reason for establishing the UL. This 2 g UL restricts the acceptance of formal vitamin C megadose trials by Institutional review boards.[citation needed]

Conditions

Common cold

The results of three meta-analyses show vitamin C in doses ranging from 200 mg to 2 grams per day used as prophylaxis (that is, before incidence of the cold) reduces the duration, but not the incidence, of the common cold by 8% for adults and 14% for children. Incidence appears to be reduced by 50% in stressed adults, such as soldiers or athletes, in extreme cold environments. Used at onset of symptoms no reduction in duration is observed. The clinical significance of these effects is uncertain, but the biological effect appears genuine.[7][8]

A 2010 Cochrane Review concluded:[9]

The failure of vitamin C supplementation to reduce the incidence of colds in the general population indicates that routine prophylaxis is not justified. Vitamin C could be useful for people exposed to brief periods of severe physical exercise. While the prophylaxis trials have consistently shown that vitamin C reduces the duration and alleviates the symptoms of colds, this was not replicated in the few therapeutic trials that have been carried out. Further therapeutic RCTs are warranted.

Heart disease

Clinical trials investigating the use of vitamin C in the prevention of coronary disease or strokes have produced equivocal results, with positive, negative and neutral outcomes. Issues with methodology, patient selection and study design make the results of the studies difficult to interpret.[10]

Cancer

In 1976 Linus Pauling and Ewan Cameron published a trial of 100 cancer patients which suggested that treatment with intravenous vitamin C significantly increased lifespans.[11] Three large, placebo-controlled trials of only oral (not intravenous absorbic acid, as with Paulings' study) vitamin C in 1979, 1983 and 1985[12][13][14] did not find a positive effect of vitamin C in cancer patients and a re-analysis of Pauling and Cameron's initial data found that the comparison groups were not adequately controlled or randomized, with the vitamin C group being less sick than controls when entering the study.[15][16] More recent Phase I clinical trial studies, which were limited in scope to a "dose-finding phase," have confirmed that while vitamin C is not necessarily toxic to cancer patients,[17] it is not useful as a treatment for cancer in humans when doses do not exceed 1.5 grams ascorbic acid/kg body weight.[18] In vitro tests on cell lines indicate that dehydroascorbic acid (DHA), an oxidized form of ascorbic acid may interfere with the effectiveness of chemotherapy.[19] A systematic review of the use of vitamin C and other antioxidants as part of a chemotherapeutic regimen found no significant difference between groups.[20] A 2010 review of 33 years of research on vitamin C to treat cancer stated "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."[21]

Treatment of phencyclidine psychosis

Large dosages of vitamin C can be used to augment an antipsychotic in the treatment of acute phencyclidine (PCP) psychosis. Usually, 1000–2000 mg. of vitamin C are given intravenously over the course of 5–10 minutes. It is given in combination with a DA-2 antagonist such as haloperidol or risperidone. The antagonist is given intramuscularly and not combined with vitamin C. The vitamin acts synergistically with phencyclidine or its metabolites.[22]

Gout

In 2008, researchers established that higher vitamin C intake (diet or supplements) reduces serum uric acid levels and is associated with lower incidence of gout. The relative risk of gout was 45% lower for intakes of over 1500 mg/d.[23]

Burns

Due to the unique metabolic conditions after severe burns, short term intravenous administration of vitamin C has been suggested as an adjuvant treatment. One study used high intravenous doses of vitamin C (66 mg/kg/hour over 24 hours, for a total dose of around 110 grams) after severe burn injury,[24] but despite being described as promising, it has not been replicated by independent institutions and thus is not a widely accepted treatment.[25] Based on that study, the American Burn Association (ABA) considers high dose ascorbic acid an "option" to be considered for adjuvant therapy in addition to the more accepted standard treatments.[26] Guidelines released by the ABA noted there is likely no benefit beyond decreased intravenous fluid volume needs and there needs to be larger multicenter trials to replicate this study result before vitamin C is accepted as a standard treatment.[26] However, one medical review article noted vitamin C at the doses studied can be toxic, and recommended further validation by future studies before this therapy is clinically used,[24] and another noted that this therapy is not a mainstream treatment although the study results can be meaningful to physicians experienced in treating severe burns.[27]

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 for iron deficiency, iron overload may become an issue to people with rare iron-overload conditions, such as Beta (β) thalassemias and hemochromatosis.[citation needed]
  • 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 (favism), such as very large dosages of vitamin C. Common, inexpensive tests exist to determine G6PD deficiency.[citation needed]
  • There is a longstanding belief among the mainstream medical community that vitamin C causes kidney stones, which seems based little on science.[28] Although some individual recent studies have found a relationship,[29] there is no clear relationship between excess ascorbic acid intake and kidney stone formation.[30]

Side effects

Blood levels of vitamin C remain steady at approximately 200 mg per day. Although vitamin C can be well tolerated at doses well above the RDA recommendations, adverse effects can occur at doses above 3 grams per day though overload is unlikely. The common 'threshold' side effect of megadoses is diarrhea. Other possible adverse effects 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.[31] In addition, one case has been noted of a woman who had received a kidney transplant followed by high-dose vitamin C and died soon afterwards 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 renal failure.[32]

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 [11.9 grams] per kilogram in rat populations.[33] This is equivalent to a 70 kilogram human ingesting 850 grams of vitamin C.

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% after 28 days of treatment, 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.[34] In another study, 40 mg/day of omeprazole lowered the fasting gastric vitamin C levels from 3.8 to 0.7 mcg/mL.[35]

Aspirin may also inhibit the absorption of vitamin C.[36][37][38]

Potential harmful effects

  • Some test-tube experiments have interpreted that vitamin C may have possible adverse effects on decomposition of lipid peroxides[39] in nonviable in vivo quantities and conditions,[40] and inhibit caspase-8 dependent apoptosis.[41] The effects were noted in test tube experiments and on only two of the 20 markers of free radical damage to DNA.[40] In April 1998 the journal Nature reported pro-oxidant effects of excessive doses of vitamin C / ascorbic acid in healthy human volunteers.[42]
  • 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."[43]
  • 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,[44] a known constituent of kidney stones. However, this oxalate issue is still controversial, with evidence being presented for[45] and against[46] 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.[citation needed]
  • Some writers[47] 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.[48] In another, ceruloplasmin levels were significantly reduced.[49]
  • Long term use of high-dose vitamin C supplements may be associated with increased incidence of age-related cataract in older women.[50]

Genetic deficiency and broad spectrum hypotheses

Linus Pauling's popular and influential book How to Live Longer and Feel Better, first published in 1986, advocated very high doses of vitamin C.

Since its discovery vitamin C has been considered almost a universal panacea[citation needed] by some, although this led to suspicions of it being overhyped by others.[51]

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. This mutation likely occurred 40 to 25 million years ago (in the 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.

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 much more when stressed.[6]

Matthias Rath is a controversial German physician who worked with Pauling and published in the Proceedings of the National Academy of Sciences.[52][53] 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).[54]

Genetic rationales for high doses

Four gene products are necessary to manufacture vitamin C from glucose. The loss of activity of the gene for the last step, Pseudogene ΨGULO (GLO), the terminal enzyme responsible for manufacture of vitamin C, has occurred separately in the history of several species. The loss of this enzyme activity is responsible for the inability of guinea pigs to synthesize vitamin C enzymatically, but this event happened independently of the loss in the haplorrhini suborder of primates, including humans. The remains of this non-functional gene with many mutations are, however, still present in the genome of the guinea pigs and in primates, including humans.[55][56] GLO activity has also been lost in all major families of bats, regardless of diet.[57] In addition, the function of GLO appears to have been lost several times, and possibly reacquired, in several lines of passerine birds, where ability to make vitamin C varies from species to species.[58]

Loss of GLO activity in the primate order supposedly occurred about 63 million years ago, at about the time it split into the suborders haplorrhini (which lost the enzyme activity) and the more primitive strepsirrhini (which retained it). The haplorrhini ("simple nosed") primates, which cannot make vitamin C enzymatically, include the tarsiers and the simians (apes, monkeys and humans). The suborder strepsirrhini (bent or wet-nosed prosimians), which are still able to make vitamin C enzymatically, include lorises, galagos, pottos, and to some extent, lemurs.[59]

Stone[60] and Pauling[61] calculated, based on the diet of primates[62] (similar to what our common ancestors are likely to have consumed when the gene mutated), that the optimum daily requirement of vitamin C is around 2,300 milligrams for a human requiring 2,500 kcal a day.

Pauling criticized the established US Recommended Daily Allowance, pointing out that it is based on the known quantities that will prevent acute scurvy but is not necessarily the dosage for optimal health.[63]

Regulation 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:

  • 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.[64]

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 that this belief is rejected by current science and medical research.[65]

There is some evidence regarding the applications and efficacy of vitamin C, but recommended governmental agency doses and frequency of intake 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. In 2004, they again argued 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.[66] According to these authors, the doses required to achieve blood, tissue and body "saturation" are much larger than previously believed.

See also

References

  1. ^ "Vitamin and mineral requirements in human nutrition, 2nd edition" (PDF). World Health Organization. 2004. http://whqlibdoc.who.int/publications/2004/9241546123_chap7.pdf. Retrieved 2007-02-20. 
  2. ^ Gropper SS, Smith JL, Grodd JL (2004). Advanced Nutrition and Human Metabolism (4th ed.). Belmont, CA. USA: Thomson Wadsworth. pp. 260–275. 
  3. ^ Yeom CH, Jung GC, Song KJ (2007). "Changes of terminal cancer patients' health-related quality of life after high dose vitamin C administration". J. Korean Med. Sci. 22 (1): 7–11. doi:10.3346/jkms.2007.22.1.7. PMC 2693571. PMID 17297243. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2693571. Retrieved 2007-08-03. 
  4. ^ "Vitamin C (Ascorbic Acid)". University of Maryland Medical Center. April 2002. http://www.umm.edu/altmed/ConsSupplements/VitaminCAscorbicAcidcs.html. Retrieved 2007-02-19. 
  5. ^ Pauling L (1970). "Evolution and the need for ascorbic acid". Proc. Natl. Acad. Sci. U.S.A. 67 (4): 1643–1648. doi:10.1073/pnas.67.4.1643. PMC 283405. PMID 5275366. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=283405. Retrieved 2007-07-27. 
  6. ^ a b Stone, I. (1979). "Homo sapiens ascorbicus, a biochemically corrected robust human mutant". Medical hypotheses 5 (6): 711–721. doi:10.1016/0306-9877(79)90093-8. PMID 491997.  edit
  7. ^ Douglas RM, Hemilä H (2005). "Vitamin C for Preventing and Treating the Common Cold". PLoS Medicine 2 (6): e168. doi:10.1371/journal.pmed.0020168. PMC 1160577. PMID 15971944. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1160577. 
  8. ^ Gorton, HC,; Jarvis K. (1999 Oct;22). "The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections.". Journal of Manipulative and Physiological Therapeutics (PubMed) 8: 530–533. http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&orig_db=PubMed&term=The%20effectiveness%20of%20vitamin%20C%20in%20preventing%20and%20relieving%20the%20symptoms%20of%20virus-induced%20respiratory%20infection&cmd=search&cmd_current=. 
  9. ^ Hemilä, H; Chalker E, Douglas B (2000). "Vitamin C for preventing and treating the common cold". Cochrane Database of Systematic Reviews 3 (2): CD000980. doi:10.1002/14651858.CD000980. ISSN 1464-780X. PMID 10796569. 
  10. ^ Houston, M. C. (2010). "The role of cellular micronutrient analysis, nutraceuticals, vitamins, antioxidants and minerals in the prevention and treatment of hypertension and cardiovascular disease". Therapeutic Advances in Cardiovascular Disease 4 (3): 165. doi:10.1177/1753944710368205. PMID 20400494.  edit
  11. ^ Cameron E, Pauling L (October 1976). "Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer". PNAS 73 (10): 3685–3689. Bibcode 1976PNAS...73.3685C. doi:10.1073/pnas.73.10.3685. PMC 431183. PMID 1068480. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=431183. 
  12. ^ Creagan ET, Moertel CG, O'Fallon JR, et al. (September 1979). "Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial". NEJM 301 (13): 687–690. doi:10.1056/NEJM197909273011303. PMID 384241. 
  13. ^ Moertel CG, Fleming TR, Creagan ET, Rubin J, O'Connell MJ, Ames MM (January 1985). "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". NEJM 312 (3): 137–141. doi:10.1056/NEJM198501173120301. PMID 3880867. 
  14. ^ Tschetter, L; et al. (1983). "A community-based study of vitamin C (ascorbic acid) in patients with advanced cancer". Proceedings of the American Society of Clinical Oncology 2: 92. 
  15. ^ DeWys, WD (1982). "How to evaluate a new treatment for cancer". Your Patient and Cancer 2 (5): 31–36. 
  16. ^ Barrett, S (2008-10-23). "High Doses of Vitamin C Are Not Effective as a Cancer Treatment". Quackwatch. http://www.quackwatch.org/01QuackeryRelatedTopics/Cancer/c.html. Retrieved 2010-05-06. 
  17. ^ Riordan HD, Casciari JJ, González MJ, et al. (December 2005). "A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients". P R Health Sci J 24 (4): 269–276. PMID 16570523. 
  18. ^ Hoffer LJ, Levine M, Assouline S, et al. (June 2008). "Phase I clinical trial of i.v. ascorbic acid in advanced malignancy". Ann. Oncol. 19 (11): 1969. doi:10.1093/annonc/mdn377. PMID 18544557. 
  19. ^ Heaney ML, Gardner JR, Karasavvas N, et al. (October 2008). "Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs". Cancer Res. 68 (19): 8031–8038. doi:10.1158/0008-5472.CAN-08-1490. PMID 18829561. 
  20. ^ Block, K; Koch, A; Mead, M; Tothy, P; Newman, R; Gyllenhaal, C (2007). "Impact of antioxidant supplementation on chemotherapeutic efficacy: A systematic review of the evidence from randomized controlled trials" (pdf). Cancer Treatment Reviews 33 (5): 407–418. doi:10.1016/j.ctrv.2007.01.005. PMID 17367938. http://odspracticum.od.nih.gov/2010/bios/Dwyer-Impact.pdf.  edit
  21. ^ Cabanillas, F (2010). "Vitamin C and cancer: what can we conclude--1,609 patients and 33 years later?". Puerto Rico health sciences journal 29 (3): 215–7. PMID 20799507.  edit
  22. ^ Giannini AJ, Loiselle RH, DiMarzio LR, Giannini MC (September 1987). "Augmentation of haloperidol by ascorbic acid in phencyclidine intoxication". The American journal of psychiatry 144 (9): 1207–1209. PMID 3631319. 
  23. ^ Choi, MD, DrPH, Hyon K.; Xiang Gao, MD, PhD; Gary Curhan, MD, ScD (March 9, 2009). "Vitamin C Intake and the Risk of Gout in Men". Archives of Internal Medicine. 169 (5): 502–507. doi:10.1001/archinternmed.2008.606. PMC 2767211. PMID 19273781. http://archinte.ama-assn.org/cgi/content/abstract/169/5/502. 
  24. ^ a b Berger MM (October 2006). "Antioxidant micronutrients in major trauma and burns: evidence and practice". Nutr Clin Pract 21 (5): 438–49. PMID 16998143. 
  25. ^ Greenhalgh DG (2007). "Burn resuscitation". J Burn Care Res 28 (4): 555–65. PMID 17665515. 
  26. ^ a b Pham TN, Cancio LC, Gibran NS (2008). "American Burn Association practice guidelines burn shock resuscitation". J Burn Care Res 29 (1): 257–66. doi:10.1097/BCR.0b013e31815f3876. PMID 18182930. 
  27. ^ Smith DC (March 1990). "'Cured' myasthenia". Anaesthesia 45 (3): 252. PMID 1970713. 
  28. ^ Goodwin JS, Tangum MR (November 1998). "Battling quackery: attitudes about micronutrient supplements in American academic medicine". Arch. Intern. Med. 158 (20): 2187–2191. doi:10.1001/archinte.158.20.2187. PMID 9818798. http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=9818798. 
  29. ^ Massey LK, Liebman M, Kynast-Gales SA (2005). "Ascorbate increases human oxaluria and kidney stone risk" (PDF). J. Nutr. 135 (7): 1673–1677. PMID 15987848. http://jn.nutrition.org/cgi/reprint/135/7/1673.pdf. 
  30. ^ Naidu KA (2003). "Vitamin C in human health and disease is still a mystery? An overview." (PDF). J. Nutr. 2 (7): 7. doi:10.1186/1475-2891-2-7. PMC 201008. PMID 14498993. http://www.nutritionj.com/content/pdf/1475-2891-2-7.pdf. 
  31. ^ Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids: a report of the Panel on Dietary Antioxidants and Related Compounds, Subcommittees on Upper Reference Levels of Nutrients and of Interpretation and Use of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Washington, D.C: National Academy Press. 2000. pp. 156–161. ISBN 0-309-06949-1. 
  32. ^ Nankivell, BJ; Murali KM (2008). "Renal failure from vitamin C after transplantation". NEJM 358 (4): e4. doi:10.1056/NEJMicm070984. PMID 18216350. http://content.nejm.org/cgi/reprint/358/4/e4.pdf. 
  33. ^ "Safety (MSDS) data for ascorbic acid". Oxford University. October 9, 2005. http://physchem.ox.ac.uk/MSDS/AS/ascorbic_acid.html. Retrieved 2007-02-21. 
  34. ^ E. B. Henry, A. Carswell, A. Wirz, V. Fyffe & K. E. L. Mccoll (September 2005). "Proton pump inhibitors reduce the bioavailability of dietary vitamin C". Alimentary Pharmacology & Therapeutics. http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2036.2005.02568.x?cookieSet=1&journalCode=apt. Retrieved 2007-02-21. 
  35. ^ C. Mowat, A. Carswell, A. Wirz, K.E. McColl (April 1999). "Omeprazole and dietary nitrate independently affect levels of vitamin C and nitrite in gastric juice.". Alimentary Pharmacology & Therapeutics. http://www.ncbi.nlm.nih.gov/pubmed/10092303. Retrieved 2011-02-14. 
  36. ^ Loh HS, Watters K & Wilson CW (1 November 1973). "The Effects of Aspirin on the Metabolic Availability of Ascorbic Acid in Human Beings". J Clin Pharmacol 13 (11): 480–486. PMID 4490672. http://jcp.sagepub.com/cgi/content/abstract/13/11/480. 
  37. ^ Basu TK (1982). "Vitamin C-aspirin interactions". Int J Vitam Nutr Res Suppl 23: 83–90. PMID 6811490. 
  38. ^ Ioannides C, Stone AN, Breacker PJ & Basu TK (1982). "Impairment of absorption of ascorbic acid following ingestion of aspirin in guinea pigs". Biochem Pharmacol 31 (24): 4035–4038. doi:10.1016/0006-2952(82)90652-9. PMID 6818974. 
  39. ^ [1] Vitamin C produces gene-damaging compounds Accessed July 2007
  40. ^ a b Balz Frei, Ph.D. (November, 2001). "Vitamin C Doesn't Cause Cancer!". Oregon State University. http://lpi.oregonstate.edu/f-w01/cancer.html. Retrieved 2007-02-21. 
  41. ^ Perez-Cruz I, Cárcamo JM, Golde DW (January 2007). "Caspase-8 dependent TRAIL-induced apoptosis in cancer cell lines is inhibited by vitamin C and catalase". Apoptosis 12 (1): 225–234. doi:10.1007/s10495-006-0475-0. PMID 17031493. 
  42. ^ Ian D. Podmore, Helen R. Griffiths, Karl E. Herbert, Nalini Mistry, Pratibha Mistry and Joseph Lunec (9 April 1998). "Vitamin C exhibits pro-oxidant properties". Nature 392 (6676): 559. Bibcode 1998Natur.392..559P. doi:10.1038/33308. PMID 9560150. 
  43. ^ Hagfors, L; Leanderson P, Skoldstam L (2003). "Antioxidant intake, plasma antioxidants an oxidative stress in a randomized, controlled, parallel, maditerranean dietary intervention study on patients with rheumatoid arthritis.". Nutr J: 30:2:5. 
  44. ^ Hokama S, Toma C, Jahana M, et al. (2000). "Ascorbate conversion to oxalate in alkaline milieu and Proteus mirabilis culture". Mol Urol 4 (4): 321–328. PMID 11156698. 
  45. ^ Massey LK, Liebman M, Kynast-Gales SA (July 2005). "Ascorbate increases human oxaluria and kidney stone risk". J Nutr 123 (7): 1673. PMID 15987848. 
  46. ^ Stephen Lawson (November 1999). "What About Vitamin C and Kidney Stones?". The Linus Pauling Institute. http://lpi.oregonstate.edu/f-w99/kidneystones.html. Retrieved 2007-02-21. 
  47. ^ acu-cell
  48. ^ Jacob RA, Skala JH, Omaye ST, Turnlund JR. (December 1987). "Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men.". J Nutr. 117 (12): 2109–2115. PMID 3694287. 
  49. ^ Finley EB, Cerklewski FL (April 1983). "Influence of ascorbic acid supplementation on copper status in young adult men". Am J Clin Nutr. 37 (4): 553–556. PMID 6837490. 
  50. ^ Rautiainen S, Lindblad BE, Morgenstern R, Wolk A (February 2010). "Vitamin C supplements and the risk of age-related cataract: a population-based prospective cohort study in women". The American Journal of Clinical Nutrition 91 (2): 487–493. doi:10.3945/ajcn.2009.28528. PMID 19923367. 
  51. ^ Harri Hemilä (January 2006). "Do vitamins C and E affect respiratory infections?" (PDF). University of Helsinki. http://ethesis.helsinki.fi/julkaisut/laa/kansa/vk/hemila/dovitami.pdf. Retrieved 2007-02-21. 
  52. ^ Rath M, Pauling L (1990). "Immunological evidence for the accumulation of lipoprotein(a) in the atherosclerotic lesion of the hypoascorbemic guinea pig". Proc Natl Acad Sci USA. 87 (23): 9388–9390. doi:10.1073/pnas.87.23.9388. PMC 55170. PMID 2147514. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=55170. 
  53. ^ Rath M, Pauling L (1990). "Hypothesis: lipoprotein(a) is a surrogate for ascorbate". Proc Natl Acad Sci USA 87 (16): 6204–6207. doi:10.1073/pnas.87.16.6204. PMC 54501. PMID 2143582. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=54501. 
  54. ^ 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 (1): 5–15. http://orthomolecular.org/library/jom/1992/pdf/1992-v07n01-p005.pdf. 
  55. ^ Nishikimi M, Kawai T, Yagi K (25 October 1992). "Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species". J Biol Chem 267 (30): 21967–21972. PMID 1400507. http://www.jbc.org/cgi/pmidlookup?view=long&pmid=1400507. 
  56. ^ Ohta Y, Nishikimi M (October 1999). "Random nucleotide substitutions in primate nonfunctional gene for L-gulono-gamma-lactone oxidase, the missing enzyme in L-ascorbic acid biosynthesis". Biochim Biophys Acta 1472 (1-2): 408–411. doi:10.1016/S0304-4165(99)00123-3. PMID 10572964. http://linkinghub.elsevier.com/retrieve/pii/S0304-4165(99)00123-3. 
  57. ^ A trace of GLO was detected in only 1 of 34 bat species tested, across the range of 6 families of bats tested: See Jenness R, Birney E, Ayaz K (1980). "Variation of L-gulonolactone oxidase activity in placental mammals". Comparative Biochemistry and Physiology 67B: 195–204.  Earlier reports of only fruit bats being deficient were based on smaller samples.
  58. ^ Carlos Martinez del Rio (July 1997). "Can passerines synthesize vitamin C?". The Auk. http://findarticles.com/p/articles/mi_qa3793/is_199707/ai_n8765385. 
  59. ^ Pollock JI, Mullin RJ (May 1987). "Vitamin C biosynthesis in prosimians: evidence for the anthropoid affinity of Tarsius". Am J Phys Anthropol 73 (1): 65–70. doi:10.1002/ajpa.1330730106. PMID 3113259. 
  60. ^ Stone, Irwin (1972). The Healing Factor: Vitamin C Against Disease. Grosset and Dunlap. ISBN 0-448-11693-6. OCLC 3967737. http://www.vitamincfoundation.org/stone/. 
  61. ^ Pauling, Linus (1970). "Evolution and the need for ascorbic acid". Proc Natl Acad Sci USA 67 (4): 1643–1648. doi:10.1073/pnas.67.4.1643. PMC 283405. PMID 5275366. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=283405. 
  62. ^ Milton K (2003). "Micronutrient intakes of wild primates: are humans different?" (PDF). Comp Biochem Physiol a Mol Integr Physiol 136 (1): 47–59. doi:10.1016/S1095-6433(03)00084-9. PMID 14527629. http://nature.berkeley.edu/miltonlab/pdfs/kmilton_micronutrient.pdf. 
  63. ^ Pauling, Linus (1986). How to Live Longer and Feel Better. W. H. Freeman and Company. ISBN 0-380-70289-4. OCLC 15690499 154663991 15690499. 
  64. ^ "Dietary Supplement Health and Education Act of 1994". http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/ucm148003.htm. 
  65. ^ Richards E (November 1988). "The Politics of Therapeutic Evaluation: The Vitamin C and Cancer Controversy". Social Studies of Science 18 (4): 653–701. doi:10.1177/030631288018004004. JSTOR 284966. 
  66. ^ Hickey S, Roberts H (September 2005). "Misleading information on the properties of vitamin C". PLoS Med. 2 (9): e307; author reply e309. doi:10.1371/journal.pmed.0020307. PMC 1236801. PMID 16173838. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1236801. 

External links


Wikimedia Foundation. 2010.

Игры ⚽ Поможем написать реферат

Look at other dictionaries:

  • Vitamin C (disambiguation) — Vitamin C is an essential nutrient, chemically known as ascorbic acid.Vitamin C may also refer to:*Vitamin C megadosage, high doses used in an attempt to obtain specific therapeutic effects *Caffeine, as a slang term *Vitamin C (artist), Colleen… …   Wikipedia

  • Vitamin C — This article is about ascorbic acid as a nutrient; for its chemical properties, see the article ascorbic acid; for other uses, see the disambiguation page. Vitamin C …   Wikipedia

  • Vitamin — This article is about the set of organic compounds. For the nutritional supplement preparation, see multivitamin. For the manga, see Vitamin (manga) …   Wikipedia

  • Orthomolecular medicine — Intervention MeSH D009974 Biologically based alternative and comple …   Wikipedia

  • Nutrition — The Nutrition Facts table indicates the amounts of nutrients which experts recommend to limit or consume in adequate amounts. Nutrition (also called nourishment or aliment) is the provision, to cells and organisms, of the materials necessary (in… …   Wikipedia

  • Human nutrition — For aspects of nutrition science not specific to humans, see Nutrition. Human nutrition is the provision to humans to obtain the materials necessary to support life. In general, humans can survive for two to eight weeks without food, depending on …   Wikipedia

  • Megavitamin therapy — is the use of large doses of vitamins, often many times greater than the recommended dietary allowance (RDA) in the attempt to prevent or treat diseases. It is typically used in complementary and alternative medicine by practitioners who call… …   Wikipedia

  • Fred R. Klenner — Frederick Robert Klenner, (Oct 22, 1907 – May 20, 1984) was an American medical researcher and doctor in general practice in Reidsville, North Carolina. From the 1940s on he experimented with the use of vitamin C megadosage as a therapy for a… …   Wikipedia

  • Irwin Stone — Infobox Scientist name =Irwin Stone box width = image width = caption = birth date =1907 birth place = death date =1984 death place = residence = citizenship = nationality =USA ethnicity = field =biochemistry , chemical engineering work… …   Wikipedia

  • Thomas H. Jukes — Thomas Hughes Jukes (August 26, 1906 ndash; November 1, 1999) was a British American biologist known for his work in nutrition, molecular evolution, and for his public engagement with controversial scientific issues, including DDT, vitamin C and… …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”