Vitamin C megadosage
Encyclopedia
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
(ascorbate) in doses comparable to the amounts produced by the livers of most other mammals and well beyond the current Dietary Reference Intake
Dietary Reference Intake
The Dietary Reference Intake is a system of nutrition recommendations from the Institute of Medicine of the U.S. National Academy of Sciences. The DRI system is used by both the United States and Canada and is intended for the general public and health professionals...
. 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.
Background
The World Health OrganizationWorld Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
recommends a daily intake of 45 mg/day of vitamin C for healthy adults. Vitamin C is necessary for production
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
of collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
and other biomolecules, and for the prevention of scurvy
Scurvy
Scurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
. Vitamin C is an antioxidant
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
, which has led to its endorsement by some researchers as a complementary therapy for improving quality of life
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...
. Since the 1930s, when it first became available in pure form, some physicians have experimented with higher than recommended vitamin C consumption or injection.
Primates, including humans, and guinea pigs do not synthesize vitamin C internally. 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
Irwin Stone
Irwin Stone was an American biochemist, chemical engineer, and author. He was the first to use ascorbic acid in the food processing industry as a preservative, and originated and published the hypothesis that humans require much larger amounts of Vitamin C for optimal health than is necessary to...
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.
Vitamin C has been promoted in alternative medicine
Alternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....
as a treatment for the common cold
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
, cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, polio and various other illnesses. The evidence for these claims is mixed. Orthomolecular
Orthomolecular medicine
Orthomolecular medicine is a form of complementary and alternative medicine that seeks to maintain health and prevent or treat diseases by optimizing nutritional intake and/or prescribing supplements...
-based megadose recommendations for vitamin C are based mainly on theoretical speculation and observational studies, such as those published by Fred R. Klenner
Fred R. Klenner
Frederick Robert Klenner, 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 wide range of illnesses, most notably polio. He authored 28 research papers during...
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
Side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequences of the use of a drug.Occasionally, drugs are...
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.
Common cold
The results of three meta-analysesMeta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
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
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
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.
A 2010 Cochrane Review
Cochrane Collaboration
The Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...
concluded:
Heart disease
Clinical trials investigating the use of vitamin C in the prevention of coronary diseaseCoronary disease
Coronary disease refers to the failure of coronary circulation to supply adequate circulation to cardiac muscle and surrounding tissue. It is already the most common form of disease affecting the heart and an important cause of premature death in Europe, the Baltic states, Russia, North and South...
or stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
s 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.
Cancer
In 1976 Linus PaulingLinus Pauling
Linus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...
and Ewan Cameron published a trial of 100 cancer patients which suggested that treatment with intravenous vitamin C significantly increased lifespans. Three large, placebo-controlled trials of only oral (not intravenous absorbic acid, as with Paulings' study) vitamin C in 1979, 1983 and 1985 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. 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
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
to cancer patients, it is not useful as a treatment for cancer in humans when doses do not exceed 1.5 grams ascorbic acid/kg body weight. In vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
tests on cell lines indicate that dehydroascorbic acid
Dehydroascorbic acid
Dehydroascorbic acid is an oxidized form of ascorbic acid. It is actively imported into the endoplasmic reticulum of cells via glucose transporters. It is trapped therein by reduction back to ascorbate by glutathione and other thiols. Therefore, L-dehydroascorbic acid is a vitamin C compound much...
(DHA), an oxidized form of ascorbic acid may interfere with the effectiveness of chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
. A systematic review of the use of vitamin C and other antioxidants as part of a chemotherapeutic regimen found no significant difference between groups. 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."
Treatment of phencyclidine psychosis
Large dosages of vitamin C can be used to augment an antipsychoticAntipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
in the treatment of acute phencyclidine
Phencyclidine
Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...
(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
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
or risperidone
Risperidone
Risperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism...
. The antagonist 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 (diet or supplements) reduces serum uric acidUric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
levels and is associated with lower incidence of gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
. The relative risk
Relative risk
In statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....
of gout was 45% lower for intakes of over 1500 mg/d.
Burns
Due to the unique metabolicMetabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
conditions after severe burn
Burn
A burn is an injury to flesh caused by heat, electricity, chemicals, light, radiation, or friction.Burn may also refer to:*Combustion*Burn , type of watercourses so named in Scotland and north-eastern England...
s, short term intravenous administration of vitamin C has been suggested as an adjuvant
Adjuvant
An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...
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, but despite being described as promising, it has not been replicated by independent institutions and thus is not a widely accepted treatment. 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. Guidelines released by the ABA noted there is likely no benefit beyond decreased intravenous fluid volume needs and there needs to be larger multicenter trial
Multicenter trial
A multicenter research trial is a clinical trial conducted at more than one medical center or clinic. Most large clinical trials, particularly Phase III trials, are conducted at several clinical research centers...
s to replicate this study result before vitamin C is accepted as a standard treatment. However, one medical review article
Review article
Review articles are an attempt to summarize the current state of understanding on a topic. They analyze or discuss research previously published by others, rather than reporting new experimental results....
noted vitamin C at the doses studied can be toxic, and recommended further validation by future studies before this therapy is clinically used, 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.
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 contraindicationContraindication
In medicine, a contraindication is a condition or factor that serves as a reason to withhold a certain medical treatment.Some contraindications are absolute, meaning that there are no reasonable circumstances for undertaking a course of action...
s.
- 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.
- A genetic condition that results in inadequate levels of the enzyme glucose-6-phosphate dehydrogenaseGlucose-6-phosphate dehydrogenaseGlucose-6-phosphate dehydrogenase is a cytosolic enzyme in the pentose phosphate pathway , a metabolic pathway that supplies reducing energy to cells by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate...
(G6PD) can cause sufferers to develop hemolytic anemiaHemolytic anemiaHemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
after ingesting specific oxidizing substances (favism), such as very large dosages of vitamin C. Common, inexpensive tests exist to determine G6PD deficiency. - There is a longstanding belief among the mainstream medical community that vitamin C causes kidney stones, which seems based little on science. Although some individual recent studies have found a relationship, there is no clear relationship between excess ascorbic acidAscorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
intake and kidney stoneKidney stoneA kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...
formation.
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 effectAdverse effect
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
s can occur at doses above 3 grams per day though overload is unlikely. The common 'threshold' side effect of megadoses is diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
. Other possible adverse effects include increased oxalate
Oxalate
Oxalate , is the dianion with formula C2O42− also written 22−. Either name is often used for derivatives, such as disodium oxalate, 2C2O42−, or an ester of oxalic acid Oxalate (IUPAC: ethanedioate), is the dianion with formula C2O42− also written (COO)22−. Either...
excretion and kidney stone
Kidney stone
A kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...
s, increased uric acid excretion, systemic conditioning ("rebound scurvy
Scurvy
Scurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
"), preoxidant effects, iron overload, reduced absorption of vitamin B12
Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
and copper, increased oxygen demand and acid erosion of the teeth. 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
Calcium oxalate
Calcium oxalate is a chemical compound that forms needle-shaped crystals, known in plants as raphides. A major constituent of human kidney stones, the chemical is also found in beerstone, a scale that forms on containers used in breweries...
deposits that destroyed her new kidney. Her doctors concluded that high-dose vitamin C therapy should be avoided in patients with renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
.
Chance of overdose
As discussed previously, vitamin C generally exhibits low toxicity. The (the dose that will kill 50% of a population) is generally accepted to be 11900 milligrams [11.9 grams] per kilogram in rat populations. 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 inhibitorProton pump inhibitor
Proton-pump inhibitors are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar...
s (PPIs), are among the most widely-sold drugs in the world. One PPI, omeprazole
Omeprazole
Omeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease , laryngopharyngeal reflux and Zollinger–Ellison syndrome...
(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. In another study, 40 mg/day of omeprazole lowered the fasting gastric vitamin C levels from 3.8 to 0.7 mcg/mL.
Aspirin may also inhibit the absorption of vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
.
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. The effects were noted in test tube experiments and on only two of the 20 markers of free radical damage to DNA. In April 1998 the journal Nature reported pro-oxidantPro-oxidantPro-oxidants are chemicals that induce oxidative stress, through either creating reactive oxygen species or inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues...
effects of excessive doses of vitamin C / ascorbic acid in healthy human volunteers. - In June 2004, Duke UniversityDuke UniversityDuke University is a private research university located in Durham, North Carolina, United States. Founded by Methodists and Quakers in the present day town of Trinity in 1838, the school moved to Durham in 1892. In 1924, tobacco industrialist James B...
researchers reported an increased susceptibility to osteoarthritisOsteoarthritisOsteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
in guinea pigs fed a diet high in vitamin C. However, a 2003 study at Umeå UniversityUmeå UniversityUmeå University is a university in Umeå in the mid-northern region of Sweden. The university was founded in 1965 and is the fifth oldest within Sweden's present borders....
in Sweden, found that "the plasma levels of vitamin C, retinolRetinolRetinol is one of the animal forms of vitamin A. It is a diterpenoid and an alcohol. It is convertible to other forms of vitamin A, and the retinyl ester derivative of the alcohol serves as the storage form of the vitamin in animals....
and uric acid were inversely correlated to variables related to rheumatoid arthritisRheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
disease activity." - A speculated increased risk of kidney stoneKidney stoneA kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...
s 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 metabolismMetabolismMetabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
of vitamin C to dehydroascorbic acidDehydroascorbic acidDehydroascorbic acid is an oxidized form of ascorbic acid. It is actively imported into the endoplasmic reticulum of cells via glucose transporters. It is trapped therein by reduction back to ascorbate by glutathione and other thiols. Therefore, L-dehydroascorbic acid is a vitamin C compound much...
, which is then metabolized to oxalic acidOxalic acidOxalic acid is an organic compound with the formula H2C2O4. This colourless solid is a dicarboxylic acid. In terms of acid strength, it is about 3,000 times stronger than acetic acid. Oxalic acid is a reducing agent and its conjugate base, known as oxalate , is a chelating agent for metal cations...
, 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 copperCopperCopper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
absorption from high doses of vitamin C. CeruloplasminCeruloplasminCeruloplasmin is a ferroxidase enzyme that in humans is encoded by the CP gene.Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 1948...
levels seem specifically lowered by high vitamin C intake. In one study, 600 milligrams of vitamin C daily led to lower ceruloplasminCeruloplasminCeruloplasmin is a ferroxidase enzyme that in humans is encoded by the CP gene.Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 1948...
levels similar to those caused by copper deficiency. In another, ceruloplasmin levels were significantly reduced. - Long term use of high-dose vitamin C supplements may be associated with increased incidence of age-related cataractCataractA cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light...
in older women.
Genetic deficiency and broad spectrum hypotheses
Panacea (medicine)
The panacea , named after the Greek goddess of healing, Panacea, also known as panchrest, was supposed to be a remedy that would cure all diseases and prolong life indefinitely...
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
L-gulonolactone oxidase
L-gulonolactone oxidase is an enzyme that catalyzes the reaction of D-glucuronolactone with oxygen to L-xylo-hex-3-gulonolactone and hydrogen peroxide. It uses FAD as a cofactor...
, 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
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...
-winning chemist Linus Pauling
Linus Pauling
Linus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...
, after contact with Irwin Stone
Irwin Stone
Irwin Stone was an American biochemist, chemical engineer, and author. He was the first to use ascorbic acid in the food processing industry as a preservative, and originated and published the hypothesis that humans require much larger amounts of Vitamin C for optimal health than is necessary to...
, 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 grams per day orally, thus approaching the amounts released by the liver directly into the circulation in other mammals: an adult goat
Goat
The domestic goat is a subspecies of goat domesticated from the wild goat of southwest Asia and Eastern Europe. The goat is a member of the Bovidae family and is closely related to the sheep as both are in the goat-antelope subfamily Caprinae. There are over three hundred distinct breeds of...
, 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.
Matthias Rath
Matthias Rath
Matthias Rath is a doctor, businessman, and vitamin entrepreneur. He earned his MD degree in Germany. Rath claims that a program of nutritional supplements , including formulations that he sells, can treat or cure diabetes, cardiovascular disease, cancer, and HIV/AIDS...
is a controversial German physician who worked with Pauling and published in the Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
The Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States 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
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
provided by lipoprotein(a), a lipoprotein found in vitamin C-deficient species (higher primates and guinea pigs).
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 ΨGULOL-gulonolactone oxidase
L-gulonolactone oxidase is an enzyme that catalyzes the reaction of D-glucuronolactone with oxygen to L-xylo-hex-3-gulonolactone and hydrogen peroxide. It uses FAD as a cofactor...
(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 pig
Guinea pig
The guinea pig , also called the cavy, is a species of rodent belonging to the family Caviidae and the genus Cavia. Despite their common name, these animals are not in the pig family, nor are they from Guinea...
s to synthesize vitamin C enzymatically, but this event happened independently of the loss in the haplorrhini
Haplorrhini
The haplorhines, the "dry-nosed" primates , are members of the Haplorhini clade: the prosimian tarsiers and the anthropoids...
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. GLO activity has also been lost in all major families of bats, regardless of diet. In addition, the function of GLO appears to have been lost several times, and possibly reacquired, in several lines of passerine
Passerine
A passerine is a bird of the order Passeriformes, which includes more than half of all bird species. Sometimes known as perching birds or, less accurately, as songbirds, the passerines form one of the most diverse terrestrial vertebrate orders: with over 5,000 identified species, it has roughly...
birds, where ability to make vitamin C varies from species to species.
Loss of GLO activity in the primate
Primate
A primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...
order supposedly occurred about 63 million years ago, at about the time it split into the suborders haplorrhini
Haplorrhini
The haplorhines, the "dry-nosed" primates , are members of the Haplorhini clade: the prosimian tarsiers and the anthropoids...
(which lost the enzyme activity) and the more primitive strepsirrhini
Strepsirrhini
The clade Strepsirrhini is one of the two suborders of primates. Madagascar's only non-human primates are strepsirrhines, and others can be found in southeast Asia and Africa...
(which retained it). The haplorrhini ("simple nosed") primates, which cannot make vitamin C enzymatically, include the tarsier
Tarsier
Tarsiers are haplorrhine primates of the genus Tarsius, a genus in the family Tarsiidae, which is itself the lone extant family within the infraorder Tarsiiformes...
s 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 loris
Loris
Loris is the common name for the strepsirrhine primates of the subfamily Lorisinae in family Lorisidae. Loris is one genus in this subfamily and includes the slender lorises, while Nycticebus is the genus for the slow lorises....
es, galago
Galago
Galagos , also known as bushbabies, bush babies or nagapies , are small, nocturnal primates native to continental Africa, and make up the family Galagidae...
s, potto
Potto
The potto is a strepsirrhine primate from the Lorisidae family. It is the only species in genus Perodicticus...
s, and to some extent, lemur
Lemur
Lemurs are a clade of strepsirrhine primates endemic to the island of Madagascar. They are named after the lemures of Roman mythology due to the ghostly vocalizations, reflective eyes, and the nocturnal habits of some species...
s.
Stone and Pauling calculated, based on the diet of primates (similar to what our common ancestors
Common descent
In evolutionary biology, a group of organisms share common descent if they have a common ancestor. There is strong quantitative support for the theory that all living organisms on Earth are descended from a common ancestor....
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
Calorie
The calorie is a pre-SI metric unit of energy. It was first defined by Nicolas Clément in 1824 as a unit of heat, entering French and English dictionaries between 1841 and 1867. In most fields its use is archaic, having been replaced by the SI unit of energy, the joule...
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
Scurvy
Scurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
but is not necessarily the dosage for optimal health.
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 AdministrationFood and Drug AdministrationThe Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
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 that this belief is rejected by current science and medical research.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
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
(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.
See also
- Ascorbic acidAscorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
- MicronutrientMicronutrientMicronutrients are nutrients required by humans and other living things throughout life in small quantities to orchestrate a whole range of physiological functions, but which the organism itself cannot produce. For people, they include dietary trace minerals in amounts generally less than 100...
- Macronutrient
- Megavitamin therapyMegavitamin therapyMegavitamin therapy is the use of large doses of vitamins, often many times greater than the recommended dietary allowance in the attempt to prevent or treat diseases...
- Orthomolecular medicineOrthomolecular medicineOrthomolecular medicine is a form of complementary and alternative medicine that seeks to maintain health and prevent or treat diseases by optimizing nutritional intake and/or prescribing supplements...
- Uric acidUric acidUric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
- VitaminVitaminA vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
External links
- The Vitamin C Foundation principal organisition promoting megadosage. Accessed July 2007
- Quackwatch article critical of megadosing Charles W. Marshall, Ph.D. Accessed July 2007