text:
Vitamin C
|Systematic (IUPAC) name
(R)-3,4-dihydroxy-5-((S)- 1,2-dihydroxyethyl)furan-2(5H)-one
|Clinical data
|Multum Consumer Information
|Pregnancy cat.
|A (to RDA), C (above RDA)
|Legal status
|Unscheduled (AU) OTC (US) general public availability
|Pharmacokinetic data
|rapid & complete
|Protein binding
|varies according to plasma concentration
|CAS number
|ATC code
|NIAID ChemDB
|L-ascorbic acid
|Chemical data
|Mol. mass
|176.12 g/mole
|Physical data
|1.694 g/cm³
|Melt. point
|Boiling point
|(what is this?) (verify)
Vitamin C or L-ascorbic acid, or simply ascorbate (the anion of ascorbic acid), is an essential nutrient for humans and certain other animal species. Vitamin C refers to a number of vitamers that have vitamin C activity in animals, including ascorbic acid and its salts, and some oxidized forms of the molecule like dehydroascorbic acid. Ascorbate and ascorbic acid are both naturally present in the body when either of these is introduced into cells, since the forms interconvert according to pH.
Vitamin C is a cofactor in at least eight enzymatic reactions, including several collagen synthesis reactions that, when dysfunctional, cause the most severe symptoms of scurvy.[1] In animals, these reactions are especially important in wound-healing and in preventing bleeding from capillaries. Ascorbate may also act as an antioxidant against oxidative stress.[2] However, the fact that the enantiomer D-ascorbate (not found in nature) has identical antioxidant activity to L-ascorbate, yet far less vitamin activity,[3] underscores the fact that most of the function of L-ascorbate as a vitamin relies not on its antioxidant properties, but upon enzymic reactions that are stereospecific. "Ascorbate" without the letter for the enantiomeric form is always presumed to be the chemical L-ascorbate.
Ascorbate (the anion of ascorbic acid) is required for a range of essential metabolic reactions in all animals and plants. It is made internally by almost all organisms; the main exceptions are most bats, all guinea pigs, capybaras, and the Anthropoidea (i.e., Haplorrhini, one of the two major primate suborders, consisting of tarsiers, monkeys, and humans and other apes). Ascorbate is also not synthesized by some species of birds and fish. All species that do not synthesize ascorbate require it in the diet. Deficiency in this vitamin causes the disease scurvy in humans.[1][4][5]
Ascorbic acid is also widely used as a food additive, to prevent oxidation.
- 1 Vitamers
- 2 Biological significance
- 3 Role in mammals
- 4 Role in plants
- 5 Daily requirements
- 6 Therapeutic use
- 7 Testing for ascorbate levels in the body
- 8 Adverse effects
- 9 Dietary sources
- 10 Compendial status
- 11 History
- 12 Society and culture
- 13 See also
- 14 References
- 15 External links
The name 'vitamin C' always refers to the L-enantiomer of ascorbic acid and its oxidized forms. The opposite D-enantiomer called D-ascorbate has equal antioxidant power, but is not found in nature, and has no physiological significance. When D-ascorbate is synthesized and given to animals that require vitamin C in their diets, it has been found to have far less vitamin activity than the L-enantiomer.[3] Therefore, unless written otherwise, "ascorbate" and "ascorbic acid" refer in the nutritional literature to L-ascorbate and L-ascorbic acid, respectively. This notation will be followed in this article. Similarly, their oxidized derivatives (dehydroascorbate, etc., see below) are all L-enantiomers, and also need not be written with full sterochemical notation here.
Ascorbic acid is a weak sugar acid structurally related to glucose. In biological systems, ascorbic acid can be found only at low pH, but in neutral solutions above pH 5 is predominantly found in the ionized form, ascorbate. All of these molecules have vitamin C activity, therefore, and are used synonymously with vitamin C, unless otherwise specified.
Biological significance[edit]
The biological role of ascorbate is to act as a reducing agent, donating electrons to various enzymatic and a few non-enzymatic reactions. The one- and two-electron oxidized forms of vitamin C, semidehydroascorbic acid and dehydroascorbic acid, respectively, can be reduced in the body by glutathione and NADPH-dependent enzymatic mechanisms.[6][7] The presence of glutathione in cells and extracellular fluids helps maintain ascorbate in a reduced state.[8]
The vast majority of animals and plants are able to synthesize vitamin C, through a sequence of enzyme-driven steps, which convert monosaccharides to vitamin C. In plants, this is accomplished through the conversion of mannose or galactose to ascorbic acid.[9] In some animals, glucose needed to produce ascorbate in the liver (in mammals and perching birds) is extracted from glycogen; ascorbate synthesis is a glycogenolysis-dependent process.[10] In reptiles and birds the biosynthesis is carried out in the kidneys.
Among the animals that have lost the ability to synthesize vitamin C are simians and tarsiers, which together make up one of two major primate suborders, Haplorrhini. This group includes humans. The other more primitive primates (Strepsirrhini) have the ability to make vitamin C. Synthesis does not occur in a number of species (perhaps all species) in the small rodent family Caviidae that includes guinea pigs and capybaras, but occurs in other rodents (rats and mice do not need vitamin C in their diet, for example).
A number of species of passerine birds also do not synthesize, but not all of them, and those that do not are not clearly related; there is a theory that the ability was lost separately a number of times in birds.[11] In particular, the ability to synthesize vitamin C is presumed to have been lost and then later re-acquired in at least two cases.[12]
All tested families of bats, including major insect and fruit-eating bat families, cannot synthesize vitamin C. A trace of gulonolactone oxidase (GULO) was detected in only 1 of 34 bat species tested, across the range of 6 families of bats tested.[13] However, recent results show that there are at least two species of bats, frugivorous bat (Rousettus leschenaultii) and insectivorous bat (Hipposideros armiger), that retain their ability of vitamin C production.[14][15] The ability to synthesize vitamin C has also been lost in teleost fish.[11]
These animals all lack the L-gulonolactone oxidase (GULO) enzyme, which is required in the last step of vitamin C synthesis, because they have a differing non-synthesizing gene for the enzyme (Pseudogene ΨGULO).[16] A similar non-functional gene is present in the genome of the guinea pigs and in primates, including humans.[17][18] Some of these species (including humans) are able to make do with the lower levels available from their diets by recycling oxidised vitamin C.[19]
Most simians consume the vitamin in amounts 10 to 20 times higher than that recommended by governments for humans.[20] This discrepancy constitutes much of the basis of the controversy on current recommended dietary allowances. It is countered by arguments that humans are very good at conserving dietary vitamin C, and are able to maintain blood levels of vitamin C comparable with other simians, on a far smaller dietary intake.[citation needed]
Like plants and animals, some microorganisms such as the yeast Saccharomyces cerevisiae have been shown to be able to synthesize vitamin C from simple sugars.[21][22]
Ascorbic acid or vitamin C is a common enzymatic cofactor in mammals used in the synthesis of collagen. Ascorbate is a powerful reducing agent capable of rapidly scavenging a number of reactive oxygen species (ROS). Freshwater teleost fishes also require dietary vitamin C in their diet or they will get scurvy. The most widely recognized symptoms of vitamin C deficiency in fishes are scoliosis, lordosis and dark skin coloration. Freshwater salmonids also show impaired collagen formation, internal/fin hemorrhage, spinal curvature and increased mortality. If these fishes are housed in seawater with algae and phytoplankton, then vitamin supplementation seems to be less important, it is presumed because of the availability of other, more ancient, antioxidants in natural marine environment.[23]
Some scientists have suggested that loss of the vitamin C biosynthesis pathway may have played a role in rapid evolutionary changes, leading to hominids and the emergence of human beings.[24][25][26] However, another theory is that the loss of ability to make vitamin C in simians may have occurred much farther back in evolutionary history than the emergence of humans or even apes, since it evidently occurred soon after the appearance of the first primates, yet sometime after the split of early primates into the two major suborders Haplorrhini (which cannot make vitamin C) and its sister suborder of non-tarsier prosimians, the Strepsirrhini ("wet-nosed" primates), which retained the ability to make vitamin C.[27] According to molecular clock dating, these two suborder primate branches parted ways about 63 to 60 Mya.[28] Approximately three to five million years later (58 Mya), only a short time afterward from an evolutionary perspective, the infraorder Tarsiiformes, whose only remaining family is that of the tarsier (Tarsiidae), branched off from the other haplorrhines.[29][30] Since tarsiers also cannot make vitamin C, this implies the mutation had already occurred, and thus must have occurred between these two marker points (63 to 58 Mya).
It has been noted that the loss of the ability to synthesize ascorbate strikingly parallels the inability to break down uric acid, also a characteristic of primates. Uric acid and ascorbate are both strong reducing agents. This has led to the suggestion that, in higher primates, uric acid has taken over some of the functions of ascorbate.[31]
Absorption, transport, and excretion[edit]
Ascorbic acid is absorbed in the body by both active transport and simple diffusion. Sodium-Dependent Active Transport—Sodium-Ascorbate Co-Transporters (SVCTs) and Hexose transporters (GLUTs)—are the two transporters required for absorption. SVCT1 and SVCT2 import the reduced form of ascorbate across plasma membrane.[32] GLUT1 and GLUT3 are the two glucose transporters, and transfer only the dehydroascorbic acid form of Vitamin C.[33] Although dehydroascorbic acid is absorbed in higher rate than ascorbate, the amount of dehydroascorbic acid found in plasma and tissues under normal conditions is low, as cells rapidly reduce dehydroascorbic acid to ascorbate.[34][35] Thus, SVCTs appear to be the predominant system for vitamin C transport in the body.
SVCT2 is involved in vitamin C transport in almost every tissue,[32] the notable exception being red blood cells, which lose SVCT proteins during maturation.[36] "SVCT2 knockout" animals genetically engineered to lack this functional gene, die shortly after birth,[37] suggesting that SVCT2-mediated vitamin C transport is necessary for life.
With regular intake the absorption rate varies between 70 to 95%. However, the degree of absorption decreases as intake increases. At high intake (1.25 g), fractional human absorption of ascorbic acid may be as low as 33%; at low intake (<200 mg) the absorption rate can reach up to 98%.[38]
Ascorbate concentrations over renal re-absorption threshold pass freely into the urine and are excreted. At high dietary doses (corresponding to several hundred mg/day in humans) ascorbate is accumulated in the body until the plasma levels reach the renal resorption threshold, which is about 1.5 mg/dL in men and 1.3 mg/dL in women. Concentrations in the plasma larger than this value (thought to represent body saturation) are rapidly excreted in the urine with a half-life of about 30 minutes. Concentrations less than this threshold amount are actively retained by the kidneys, and the excretion half-life for the remainder of the vitamin C store in the body thus increases greatly, with the half-life lengthening as the body stores are depleted. This half-life rises until it is as long as 83 days by the onset of the first symptoms of scurvy.[39]
Although the body's maximal store of vitamin C is largely determined by the renal threshold for blood, there are many tissues that maintain vitamin C concentrations far higher than in blood. Biological tissues that accumulate over 100 times the level in blood plasma of vitamin C are the adrenal glands, pituitary, thymus, corpus luteum, and retina.[40] Those with 10 to 50 times the concentration present in blood plasma include the brain, spleen, lung, testicle, lymph nodes, liver, thyroid, small intestinal mucosa, leukocytes, pancreas, kidney, and salivary glands.
Ascorbic acid can be oxidized (broken down) in the human body by the enzyme L-ascorbate oxidase. Ascorbate that is not directly excreted in the urine as a result of body saturation or destroyed in other body metabolism is oxidized by this enzyme and removed.
Scurvy is an avitaminosis resulting from lack of vitamin C, since without this vitamin, the synthesized collagen is too unstable to perform its function. Scurvy leads to the formation of brown spots on the skin, spongy gums, and bleeding from all mucous membranes. The spots are most abundant on the thighs and legs, and a person with the ailment looks pale, feels depressed, and is partially immobilized. In advanced scurvy there are open, suppurating wounds and loss of teeth and, eventually, death. The human body can store only a certain amount of vitamin C,[41] and so the body stores are depleted if fresh supplies are not consumed. The time frame for onset of symptoms of scurvy in unstressed adults on a completely vitamin C free diet, however, may range from one month to more than six months, depending on previous loading of vitamin C (see below).
It has been shown that smokers who have diets poor in vitamin C are at a higher risk of lung-borne diseases than those smokers who have higher concentrations of vitamin C in the blood.[42]
Nobel prize winner Linus Pauling and Canadian researcher G. C. Willis have asserted that chronic long term low blood levels of vitamin C ("chronic scurvy") is a cause of atherosclerosis.[43]
Western societies generally consume far more than sufficient Vitamin C to prevent scurvy. In 2004, a Canadian Community health survey reported that Canadians of 19 years and above have intakes of vitamin C from food of 133 mg/d for males and 120 mg/d for females;[44] these are higher than the RDA recommendations.
Notable human dietary studies of experimentally induced scurvy have been conducted on conscientious objectors during WW II in Britain, and on Iowa state prisoners in the late 1960s. These studies both found that all obvious symptoms of scurvy previously induced by an experimental scorbutic diet with extremely low vitamin C content could be completely reversed by additional vitamin C supplementation of only 10 mg a day. In these experiments, there was no clinical difference noted between men given 70 mg vitamin C per day (which produced blood level of vitamin C of about 0.55 mg/dl, about 1/3 of tissue saturation levels), and those given 10 mg per day. Men in the prison study developed the first signs of scurvy about 4 weeks after starting the vitamin C free diet, whereas in the British study, six to eight months were required, possibly due to the pre-loading of this group with a 70 mg/day supplement for six weeks before the scorbutic diet was fed.[45]
Men in both studies on a diet devoid, or nearly devoid, of vitamin C had blood levels of vitamin C too low to be accurately measured when they developed signs of scurvy, and in the Iowa study, at this time were estimated (by labeled vitamin C dilution) to have a body pool of less than 300 mg, with daily turnover of only 2.5 mg/day, implying an instantaneous half-life of 83 days by this time (elimination constant of 4 months).[46]
Moderately higher blood levels of vitamin C measured in healthy persons have been found to be prospectively correlated with decreased risk of cardiovascular disease and ischaemic heart disease, and an increase life expectancy. The same study found an inverse relationship between blood vitamin C levels and cancer risk in men, but not in women. An increase in blood level of 20 micromol/L of vitamin C (about 0.35 mg/dL, and representing a theoretical additional 50 grams of fruit and vegetables per day) was found epidemiologically to reduce the all-cause risk of mortality, four years after measuring it, by about 20%.[47] However, because this was not an intervention study, causation could not be proven, and vitamin C blood levels acting as a proxy marker for other differences between the groups could not be ruled out. However, the four-year long and prospective nature of the study did rule out proxy effect from any vitamin C lowering effects of immediately terminal illness, or near-end-of-life poor health.
Studies with much higher doses of vitamin C, usually between 200 and 6000 mg/day, for the treatment of infections and wounds have shown inconsistent results.[48] Combinations of antioxidants seem to improve wound healing.[49]
Role in mammals[edit]
In humans, vitamin C is essential to a healthy diet as well as being a highly effective antioxidant, acting to lessen oxidative stress; a substrate for ascorbate peroxidase in plants (APX is plant specific enzyme);[5] and an enzyme cofactor for the biosynthesis of many important biochemicals. Vitamin C acts as an electron donor for important enzymes:[50]
Enzymatic cofactor[edit]
Ascorbic acid performs numerous physiological functions in the human body. These functions include the synthesis of collagen, carnitine, and neurotransmitters; the synthesis and catabolism of tyrosine; and the metabolism of microsome.[8] During biosynthesis ascorbate acts as a reducing agent, donating electrons and preventing oxidation to keep iron and copper atoms in their reduced states.
Vitamin C acts as an electron donor for eight different enzymes:[50]
- Three enzymes (prolyl-3-hydroxylase, prolyl-4-hydroxylase, and lysyl hydroxylase) that are required for the hydroxylation of proline and lysine in the synthesis of collagen.[51][52][53] These reactions add hydroxyl groups to the amino acids proline or lysine in the collagen molecule via prolyl hydroxylase and lysyl hydroxylase, both requiring vitamin C as a cofactor. Hydroxylation allows the collagen molecule to assume its triple helix structure, and thus vitamin C is essential to the development and maintenance of scar tissue, blood vessels, and cartilage.[41]
- Two enzymes (ε-N-trimethyl-L-lysine hydroxylase and γ-butyrobetaine hydroxylase) that are necessary for synthesis of carnitine.[54][55] Carnitine is essential for the transport of fatty acids into mitochondria for ATP generation.
- The remaining three enzymes have the following functions in common, but have other functions as well:
- dopamine beta hydroxylase participates in the biosynthesis of norepinephrine from dopamine.[56][57]
- Peptidylglycine alpha-amidating monooxygenase amidates peptide hormones by removing the glyoxylate residue from their c-terminal glycine residues. This increases peptide hormone stability and activity.[58][59]
- 4-hydroxyphenylpyruvate dioxygenase modulates tyrosine metabolism.[60][61]
Ascorbic acid is well known for its antioxidant activity, acting as a reducing agent to reverse oxidation in liquids. When there are more free radicals (reactive oxygen species, ROS) in the human body than antioxidants, the condition is called oxidative stress,[62] and has an impact on cardiovascular disease, hypertension, chronic inflammatory diseases, diabetes[63][64][65][66] as well as on critically ill patients and individuals with severe burns.[62] Individuals experiencing oxidative stress have ascorbate blood levels lower than 45 µmol/L, compared to healthy individual who range between 61-80 µmol/L.[67]
It is not yet certain whether vitamin C and antioxidants in general prevent oxidative stress-related diseases and promote health. Clinical studies regarding the effects of vitamin C supplementation on lipoproteins and cholesterol have found that vitamin C supplementation does not improve certain disease markers in the blood.[68][69] Vitamin C may contribute to decreased risk of cardiovascular disease and strokes through a small reduction in systolic blood pressure,[69] as well as reduce levels of resistin serum,[70] another likely determinant of oxidative stress and cardiovascular risk. However, so far there is no consensus that vitamin C intake has an impact on cardiovascular risks in general, and an array of studies found negative results.[71] Meta-analysis of a large number of studies on antioxidants, including vitamin C supplementation, found no relationship between vitamin C and mortality.[72]
Ascorbic acid behaves not only as an antioxidant but also as a pro-oxidant.[62] Ascorbic acid has been shown to reduce transition metals, such as cupric ions (Cu2+), to cuprous (Cu1+), and ferric ions (Fe3+) to ferrous (Fe2+) during conversion from ascorbate to dehydroascorbate in vitro.[73] This reaction can generate superoxide and other ROS. However, in the body, free transition elements are unlikely to be present while iron and copper are bound to diverse proteins[62] and the intravenous use of vitamin C does not appear to increase pro-oxidant activity.[74] Thus, ascorbate as a pro-oxidant is unlikely to convert metals to create ROS in vivo. However, vitamin C supplementation has been associated with increased DNA damage in the lymphocytes of healthy volunteers in one study,[75] which has been criticized on methodological grounds.[76]
Immune system[edit]
Vitamin C is found in high concentrations in immune cells, and is consumed quickly during infections. It is not certain how vitamin C interacts with the immune system; it has been hypothesized to modulate the activities of phagocytes, the production of cytokines and lymphocytes, and the number of cell adhesion molecules in monocytes.[77]
Vitamin C is a natural antihistamine. It both prevents histamine release and increases the detoxification of histamine. A 1992 study found that taking 2 grams vitamin C daily lowered blood histamine levels 38 percent in healthy adults in just one week.[78] It has also been noted that low concentrations of serum vitamin C has been correlated with increased serum histamine levels.[79][80]
In 2013, researchers discovered that Vitamin C alone can kill drug-resistant Mycobacterium tuberculosis by producing oxidative radicals that damage DNA.[81]
Role in plants[edit]
Ascorbic acid is associated with chloroplasts and apparently plays a role in ameliorating the oxidative stress of photosynthesis. In addition, it has a number of other roles in cell division and protein modification. Plants appear to be able to make ascorbate by at least one other biochemical route that is different from the major route in animals, although precise details remain unknown.[82]
Daily requirements[edit]
The North American Dietary Reference Intake recommends 90 milligrams per day and no more than 2 grams (2,000 milligrams) per day.[83] Other related species sharing the same inability to produce vitamin C require exogenous vitamin C consumption 20 to 80 times this reference intake.[84] There is continuing debate within the scientific community over the best dose schedule (the amount and frequency of intake) of vitamin C for maintaining optimal health in humans.[85] A balanced diet without supplementation usually contains enough vitamin C to prevent scurvy in an average healthy adult, while those who are pregnant, smoke tobacco, or are under stress require slightly more.[83] However, the amount of vitamin C necessary to prevent scurvy is less than the amount required for optimal health, as there are a number of other chronic diseases whose risks are increased by a low vitamin C intake, including cancer, heart disease, and cataracts. A 1999 review suggested a dose of 90–100 mg Vitamin C daily is required to optimally protect against these diseases, in contrast to the lower 45 mg daily required to prevent scurvy.[86]
High doses (thousands of milligrams) may result in diarrhea in healthy adults, as a result of the osmotic water-retaining effect of the unabsorbed portion in the gastrointestinal tract (similar to cathartic osmotic laxatives). Proponents of orthomolecular medicine[87] claim the onset of diarrhea to be an indication of where the body's true vitamin C requirement lies, though this has not been clinically verified.
|United States vitamin C recommendations[83]
|Recommended Dietary Allowance (adult male)
|90 mg per day
|Recommended Dietary Allowance (adult female)
|75 mg per day
|Tolerable Upper Intake Level (adult male)
|2,000 mg per day
|Tolerable Upper Intake Level (adult female)
|2,000 mg per day
Government recommended intake[edit]
Recommendations for vitamin C intake have been set by various national agencies:
- 40 milligrams per day or 280 milligrams per week taken all at once: the United Kingdom's Food Standards Agency[1]
- 45 milligrams per day 300 milligrams per week: the World Health Organization[88]
- 80 milligrams per day: the European Commission's Council on nutrition labeling[89]
- 90 mg/day (males) and 75 mg/day (females): Health Canada 2007[90]
- 60–95 milligrams per day: United States' National Academy of Sciences.[83] The United States defined Tolerable Upper Intake Level for a 25-year-old male is 2,000 milligrams per day.
- 100 milligrams per day: Japan's National Institute of Health and Nutrition.[91] The NIHN did not set a Tolerable Upper Intake Level.
Therapeutic use[edit]
Vitamin C functions as an antioxidant and is necessary for the treatment and prevention of scurvy, though in nearly all cases dietary intake is adequate to prevent deficiency and supplementation is not necessary.[92][93][94][95][96][97] Though vitamin C has been promoted as useful in the treatment of a variety of conditions, most of these uses are poorly supported by the evidence and sometimes contraindicated.[98][99][100][101] Vitamin C may be useful in lowering serum uric acid levels, resulting in a correspondingly lower incidence of gout,[102] although a more recent study revealed that Vitamin C given in doses of 500 mg/day does not reduce uric acid (urate) levels to a clinically significant degree in patients with established gout.[103] Neither prophylactic nor therapeutic use is supported in the prevention or treatment of pneumonia.[104] People with the highest levels of ascorbic acid in their blood stream seem to be at a significantly reduced risk of having a stroke and low ascorbic acid has been suggested as a way of identifying those at high risk of stroke.[105] A meta-analysis of 44 clinical trials has shown a significant positive effect of vitamin C on endothelial function when taken at doses greater than 500 mg per day. The researchers noted that the effect of vitamin C supplementation appeared to be dependent on health status, with stronger effects in those at higher cardiovascular disease risk.[106]
Vitamin C's effect on the common cold has been extensively researched. It has not been shown effective in prevention or treatment of the common cold, except in limited circumstances (specifically, individuals exercising vigorously in cold environments).[107][108] Routine vitamin C supplementation does not reduce the incidence or severity of the common cold in the general population, though it may reduce the duration of illness.[107][109][110][111] Vitamin C supplementation above the RDA has been used in trials to study a potential effect on preventing and slowing the progression of age-related cataract, however no significant effects were found from the research.[112]
Generally, properly run mainstream studies have found no support for significant benefit for heart disease or cancer, and only some benefits to isolated specific conditions.[113] Several individuals and organizations advocate large doses of vitamin C in excess of 10–100 times RDI in the form of oral or intravenous therapy.[not in citation given][114] Megadoses of vitamin C are employed not as a nutritional supplement but as a therapeutic agent, and have been used to treat a number of health conditions.[citation needed] Clinical trials of vitamin C megadoses have provided contradictory results, dismissing or confirming (International Journal of Oncology, No. 1/2013) these claims.
Testing for ascorbate levels in the body[edit]
Simple tests use dichlorophenolindophenol, a redox indicator, to measure the levels of vitamin C in the urine and in serum or blood plasma. However these reflect recent dietary intake rather than the level of vitamin C in body stores.[1] Reverse phase high performance liquid chromatography is used for determining the storage levels of vitamin C within lymphocytes and tissue. It has been observed that while serum or blood plasma levels follow the circadian rhythm or short term dietary changes, those within tissues themselves are more stable and give a better view of the availability of ascorbate within the organism. However, very few hospital laboratories are adequately equipped and trained to carry out such detailed analyses, and require samples to be analyzed in specialized laboratories.[115][116]
Adverse effects[edit]
Common side-effects[edit]
Relatively large doses of ascorbic acid may cause indigestion, particularly when taken on an empty stomach. However, taking vitamin C in the form of sodium ascorbate and calcium ascorbate may minimize this effect.[117] When taken in large doses, ascorbic acid causes diarrhea in healthy subjects. In one trial in 1936, doses of up to 6 grams of ascorbic acid were given to 29 infants, 93 children of preschool and school age, and 20 adults for more than 1400 days. With the higher doses, toxic manifestations were observed in five adults and four infants. The signs and symptoms in adults were nausea, vomiting, diarrhea, flushing of the face, headache, fatigue and disturbed sleep. The main toxic reactions in the infants were skin rashes.[118]
Possible side-effects[edit]
As vitamin C enhances iron absorption,[119] iron poisoning can become an issue to people with rare iron overload disorders, such as haemochromatosis. A genetic condition that results in inadequate levels of the enzyme glucose-6-phosphate dehydrogenase (G6PD) can cause sufferers to develop hemolytic anemia after ingesting specific oxidizing substances, such as very large dosages of vitamin C.[120]
There is a longstanding belief among the mainstream medical community that vitamin C causes kidney stones, which is based on little science.[121] Although recent studies have found a relationship,[122][123] a clear link between excess ascorbic acid intake and kidney stone formation has not been generally established.[124] Some case reports exist for a link between patients with oxalate deposits and a history of high-dose vitamin C usage.[125]
In a study conducted on rats, during the first month of pregnancy, high doses of vitamin C may suppress the production of progesterone from the corpus luteum.[126] Progesterone, necessary for the maintenance of a pregnancy, is produced by the corpus luteum for the first few weeks, until the placenta is developed enough to produce its own source. By blocking this function of the corpus luteum, high doses of vitamin C (1000+ mg) are theorized to induce an early miscarriage. In a group of spontaneously aborting women at the end of the first trimester, the mean values of vitamin C were significantly higher in the aborting group. However, the authors do state: 'This could not be interpreted as an evidence of causal association.'[127] However, in a previous study of 79 women with threatened, previous spontaneous, or habitual abortion, Javert and Stander (1943) had 91% success with 33 patients who received vitamin C together with bioflavonoids and vitamin K (only three abortions), whereas all of the 46 patients who did not receive the vitamins aborted.[128]
A study in rats and humans suggested that adding Vitamin C supplements to an exercise training program lowered the expected effect of training on VO2 Max. Although the results in humans were not statistically significant, this study is often cited as evidence that high doses of Vitamin C have an adverse effect on exercise performance. In rats, it was shown that the additional Vitamin C resulted in lowered mitochondria production.[129] Since rats are able to produce all of their needed Vitamin C, however, it is questionable whether they offer a relevant model of human physiological processes in this regard.
A cancer-causing mechanism of hexavalent chromium may be triggered by vitamin C.[130]
Vitamin C is water soluble, with dietary excesses not absorbed, and excesses in the blood rapidly excreted in the urine. It exhibits remarkably low toxicity. The LD50 (the dose that will kill 50% of a population) in rats is generally accepted to be 11.9 grams per kilogram of body weight when given by forced gavage (orally). The mechanism of death from such doses (1.2% of body weight, or 0.84 kg for a 70 kg human) is unknown, but may be more mechanical than chemical.[131] The LD50 in humans remains unknown, given lack of any accidental or intentional poisoning death data. However, as with all substances tested in this way, the rat LD50 is taken as a guide to its toxicity in humans.
Dietary sources[edit]
The richest natural sources are fruits and vegetables, and of those, the Kakadu plum and the camu camu fruit contain the highest concentration of the vitamin. It is also present in some cuts of meat, especially liver. Vitamin C is the most widely taken nutritional supplement and is available in a variety of forms, including tablets, drink mixes, crystals in capsules or naked crystals.
Vitamin C is absorbed by the intestines using a sodium-ion dependent channel. It is transported through the intestine via both glucose-sensitive and glucose-insensitive mechanisms. The presence of large quantities of sugar either in the intestines or in the blood can slow absorption.[132]
Plant sources[edit]
While plants are generally a good source of vitamin C, the amount in foods of plant origin depends on the precise variety of the plant, soil condition, climate where it grew, length of time since it was picked, storage conditions, and method of preparation.[133]
The following table is approximate and shows the relative abundance in different raw plant sources.[134][135] As some plants were analyzed fresh while others were dried (thus, artifactually increasing concentration of individual constituents like vitamin C), the data are subject to potential variation and difficulties for comparison. The amount is given in milligrams per 100 grams of fruit or vegetable and is a rounded average from multiple authoritative sources:
|Plant source
(mg / 100g)
|Kakadu plum
|Camu Camu
|Indian gooseberry
|Rose hip
|Chili pepper (green)
|Guava (common, raw)
|Red pepper
|Chili pepper (red)
|Brussels sprouts
|Wolfberry (Goji)
|73 †
|Persimmon (native, raw)
† average of 3 sources; dried
|Plant source
(mg / 100g)
|Melon, cantaloupe
|Mandarin orange
|Passion fruit
|Cabbage raw green
|Melon, honeydew
|Tomato, red
|Plant source
(mg / 100g)
|Horned melon
Animal sources[edit]
The overwhelming majority of species of animals (but not humans or guinea pigs) and plants synthesize their own vitamin C.[151] Therefore, some animal products can be used as sources of dietary vitamin C.
Vitamin C is most present in the liver and least present in the muscle. Since muscle provides the majority of meat consumed in the western human diet, animal products are not a reliable source of the vitamin. Vitamin C is present in human breast milk, but only in limited quantity in raw cow's milk.[152] All excess vitamin C is disposed of through the urinary system.
The following table shows the relative abundance of vitamin C in various foods of animal origin, given in milligrams of vitamin C per 100 grams of food:
|Animal Source
(mg / 100g)
|Calf liver (raw)
|Beef liver (raw)
|Oysters (raw)
|Cod roe (fried)
|Pork liver (raw)
|Lamb brain (boiled)
|Chicken liver (fried)
|Animal Source
(mg / 100g)
|Lamb liver (fried)
|Calf adrenals (raw)
|Lamb heart (roast)
|Lamb tongue (stewed)
|Camel milk (fresh)
|Human milk (fresh)
|Goat milk (fresh)
|Cow milk (fresh)
Food preparation[edit]
Vitamin C chemically decomposes under certain conditions, many of which may occur during the cooking of food. Vitamin C concentrations in various food substances decrease with time in proportion to the temperature they are stored at[155] and cooking can reduce the Vitamin C content of vegetables by around 60% possibly partly due to increased enzymatic destruction as it may be more significant at sub-boiling temperatures.[156] Longer cooking times also add to this effect, as will copper food vessels, which catalyse the decomposition.[131]
Another cause of vitamin C being lost from food is leaching, where the water-soluble vitamin dissolves into the cooking water, which is later poured away and not consumed. However, vitamin C does not leach in all vegetables at the same rate; research shows broccoli seems to retain more than any other.[157] Research has also shown that fresh-cut fruits do not lose significant nutrients when stored in the refrigerator for a few days.[158]
Vitamin C is available in caplets, tablets, capsules, drink mix packets, in multi-vitamin formulations, in multiple antioxidant formulations, and as crystalline powder. Timed release versions are available, as are formulations containing bioflavonoids such as quercetin, hesperidin, and rutin. Tablet and capsule sizes range from 25 mg to 1500 mg. Vitamin C (as ascorbic acid) crystals are typically available in bottles containing 300 g to 1 kg of powder (a 5 ml teaspoon of vitamin C crystals equals 5,000 mg). The bottles are usually airtight and brown or opaque in order to prevent oxidation, in which case the vitamin C would become useless, if not damaging.
Industrial synthesis[edit]
Vitamin C is produced from glucose by two main routes. The Reichstein process, developed in the 1930s, uses a single pre-fermentation followed by a purely chemical route. The modern two-step fermentation process, originally developed in China in the 1960s, uses additional fermentation to replace part of the later chemical stages. Both processes yield approximately 60% vitamin C from the glucose feed.[159]
Research is underway at the Scottish Crop Research Institute in the interest of creating a strain of yeast that can synthesize vitamin C in a single fermentation step from galactose, a technology expected to reduce manufacturing costs considerably.[21]
World production of synthesized vitamin C is currently estimated at approximately 110,000 tonnes annually. The main producers have been BASF/Takeda, DSM, Merck and the China Pharmaceutical Group Ltd. of the People's Republic of China. By 2008 only the DSM plant in Scotland remained operational outside the strong price competition from China.[160] The world price of vitamin C rose sharply in 2008 partly as a result of rises in basic food prices but also in anticipation of a stoppage of the two Chinese plants, situated at Shijiazhuang near Beijing, as part of a general shutdown of polluting industry in China over the period of the Olympic games.[161] Five Chinese manufacturers met in 2010, among them Northeast Pharmaceutical Group and North China Pharmaceutical Group, and agreed to temporarily stop production in order to maintain prices.[162] In 2011 an American suit was filed against four Chinese companies that allegedly colluded to limit production and fix prices of vitamin C in the United States. According to the plaintiffs, after the agreement was made spot prices for vitamin C shot to as high as $7 per kilogram in December 2002 from $2.50 per kilogram in December 2001. The companies did not deny the accusation but say in their defense that the Chinese government compelled them to act in this way.[163] In January 2012 a US judge ruled that the Chinese companies can be sued in the U.S. by buyers acting as a group.[164]
Food fortification[edit]
In 2005, Health Canada evaluated the effect of fortification of foods with ascorbate in the guidance document, Addition of Vitamins and Minerals to Food.[165] Ascorbate was categorized as a 'Risk Category A nutrients', meaning it is a nutrient for which an upper limit for intake is set but allows a wide margin of intake that has a narrow margin of safety but non-serious critical adverse effects.[165]
Compendial status[edit]
The need to include fresh plant food or raw animal flesh in the diet to prevent disease was known from ancient times. Native people living in marginal areas incorporated this into their medicinal lore. For example, spruce needles were used in temperate zones in infusions, or the leaves from species of drought-resistant trees in desert areas. In 1536, the French explorers Jacques Cartier and Daniel Knezevic, exploring the St. Lawrence River, used the local natives' knowledge to save his men who were dying of scurvy. He boiled the needles of the arbor vitae tree to make a tea that was later shown to contain 50 mg of vitamin C per 100 grams.[168][169]
Authorities have occasionally recommended the benefit of plant food to promote health and prevent scurvy during long sea voyages. John Woodall, the first appointed surgeon to the British East India Company, recommended the preventive and curative use of lemon juice in his book, The Surgeon's Mate, in 1617.[170] The Dutch writer, Johann Bachstrom, in 1734, gave the firm opinion that "scurvy is solely owing to a total abstinence from fresh vegetable food, and greens, which is alone the primary cause of the disease."[171][172]
Scurvy had long been a principal killer of sailors during the long sea voyages.[173] According to Jonathan Lamb, "In 1499, Vasco da Gama lost 116 of his crew of 170; In 1520, Magellan lost 208 out of 230;...all mainly to scurvy."[174]
While the earliest documented case of scurvy was described by Hippocrates around 400 BC, the first attempt to give scientific basis for the cause of this disease was by a ship's surgeon in the British Royal Navy, James Lind. Scurvy was common among those with poor access to fresh fruit and vegetables, such as remote, isolated sailors and soldiers. While at sea in May 1747, Lind provided some crew members with two oranges and one lemon per day, in addition to normal rations, while others continued on cider, vinegar, sulfuric acid or seawater, along with their normal rations. In the history of science, this is considered to be the first occurrence of a controlled experiment. The results conclusively showed that citrus fruits prevented the disease. Lind published his work in 1753 in his Treatise on the Scurvy.[175]
Lind's work was slow to be noticed, partly because his Treatise was not published until six years after his study, and also because he recommended a lemon juice extract known as rob.[176] Fresh fruit was very expensive to keep on board, whereas boiling it down to juice allowed easy storage but destroyed the vitamin (especially if boiled in copper kettles).[131] Ship captains concluded wrongly that Lind's other suggestions were ineffective because those juices failed to prevent or cure scurvy.
It was 1795 before the British navy adopted lemons or lime as standard issue at sea. Limes were more popular, as they could be found in British West Indian Colonies, unlike lemons, which were not found in British Dominions, and were therefore more expensive. This practice led to the American use of the nickname "limey" to refer to the British. Captain James Cook had previously demonstrated and proven the principle of the advantages of carrying "Sour krout" on board, by taking his crews to the Hawaiian Islands and beyond without losing any of his men to scurvy.[177] For this otherwise unheard of feat, the British Admiralty awarded him a medal.
The name antiscorbutic was used in the eighteenth and nineteenth centuries as general term for those foods known to prevent scurvy, even though there was no understanding of the reason for this. These foods included but were not limited to: lemons, limes, and oranges; sauerkraut, cabbage, malt, and portable soup.[178]
Even before the antiscorbutic substance was identified, there were indications that it was present in amounts sufficient to prevent scurvy, in nearly all fresh (uncooked and uncured) foods, including raw animal-derived foods. In 1928, the Arctic anthropologist Vilhjalmur Stefansson attempted to prove his theory of how the Inuit are able to avoid scurvy with almost no plant food in their diet, despite the disease's striking European Arctic explorers living on similar high cooked-meat diets. Stefansson theorised that the natives get their vitamin C from fresh meat that is minimally cooked. Starting in February 1928, for one year he and a colleague lived on an exclusively minimally cooked meat diet while under medical supervision; they remained healthy. Later studies done after vitamin C could be quantified in mostly raw traditional food diets of the Yukon First Nations, Dene, Inuit, and Métis of the Northern Canada, showed that their daily intake of vitamin C averaged between 52 and 62 mg/day, an amount approximately the dietary reference intake (DRI), even at times of the year when little plant-based food was eaten.[179]
In 1907, the needed biological-assay model to isolate and identify the antiscorbutic factor was discovered. Axel Holst and Theodor Frølich, two Norwegian physicians studying shipboard beriberi in the Norwegian fishing fleet, wanted a small test mammal to substitute for the pigeons then used in beriberi research. They fed guinea pigs their test diet of grains and flour, which had earlier produced beriberi in their pigeons, and were surprised when classic scurvy resulted instead. This was a serendipitous choice of model. Until that time, scurvy had not been observed in any organism apart from humans, and had been considered an exclusively human disease. (Pigeons, as seed-eating birds, were also later found to make their own vitamin C.) Holst and Frølich found they could cure the disease in guinea pigs with the addition of various fresh foods and extracts. This discovery of a clean animal experimental model for scurvy, made even before the essential idea of vitamins in foods had even been put forward, has been called the single most important piece of vitamin C research.[181]
In 1912, the Polish American biochemist Casimir Funk, while researching beriberi in pigeons, developed the concept of vitamins to refer to the non-mineral micronutrients that are essential to health. The name is a blend of "vital", due to the vital biochemical role they play, and "amines" because Funk thought that all these materials were chemical amines. Although the "e" was dropped after skepticism that all these compounds were amines, the word vitamin remained as a generic name for them. One of the vitamins was thought to be the anti-scorbutic factor in foods discovered by Holst and Frølich. In 1928, this vitamin was referred to as "water-soluble C," although its chemical structure had still not been determined.[182]
From 1928 to 1932, the Hungarian research team of Albert Szent-Györgyi and Joseph L. Svirbely, as well as the American team led by Charles Glen King in Pittsburgh, first identified the anti-scorbutic factor. Szent-Györgyi had isolated the chemical hexuronic acid (actually, L-hexuronic acid) from animal adrenal glands at the Mayo clinic, and suspected it to be the antiscorbutic factor but could not prove it without a biological assay. At the same time, for five years King's laboratory at the University of Pittsburgh had been trying to isolate the antiscorbutic factor in lemon juice using the original 1907 model of scorbutic guinea pigs which developed scurvy when not fed fresh foods but were cured by lemon juice. They had also considered hexuronic acid, but had been put off the trail when a coworker made the explicit (and mistaken) experimental claim that this substance was not the antiscorbutic substance.[183]
Finally, in late 1931, Szent-Györgyi gave Svirbely, formerly of King's lab, the last of his hexuronic acid with the suggestion that it might be the anti-scorbutic factor. By the spring of 1932, King's laboratory had proven this but published the result without giving Szent-Györgyi credit for it, leading to a bitter dispute over priority claims (in reality it had taken a team effort by both groups, since Szent-Györgyi was unwilling to do the difficult and messy animal studies).[183]
Meanwhile, by 1932, Szent-Györgyi had moved to Hungary and his group had discovered that paprika peppers, a common spice in the Hungarian diet, was a rich source of hexuronic acid, the antiscorbutic factor. With a new and plentiful source of the vitamin, Szent-Györgyi sent a sample to noted British sugar chemist Walter Norman Haworth, who chemically identified it and proved the identification by synthesis in 1933.[184][185][186] Haworth and Szent-Györgyi now proposed that the substance L-hexuronic acid be called a-scorbic acid, and chemically L-ascorbic acid, in honor of its activity against scurvy.[187] Ascorbic acid turned out not to be an amine, nor even to contain any nitrogen.
In part, in recognition of his accomplishment with vitamin C, Szent-Györgyi was awarded the unshared 1937 Nobel Prize in Medicine.[188] Haworth also shared that year's Nobel Prize in Chemistry, in part for his vitamin C synthetic work.[180]
Between 1933 and 1934 not only Haworth and fellow British chemist (later Sir) Edmund Hirst had synthesized vitamin C, but also, independently, the Polish chemist Tadeus Reichstein, succeeded in synthesizing the vitamin in bulk, making it the first vitamin to be artificially produced.[189] The latter process made possible the cheap mass-production of semi-synthetic vitamin C, which was quickly marketed. Only Haworth was awarded the 1937 Nobel Prize in Chemistry in part for this work, but the Reichstein process, a combined chemical and bacterial fermentation sequence still used today to produce vitamin C, retained Reichstein's name.[190][191] In 1934 Hoffmann–La Roche, which bought the Reichstein process patent, became the first pharmaceutical company to mass-produce and market synthetic vitamin C, under the brand name of Redoxon.[192]
In 1957, the American J.J. Burns showed that the reason some mammals are susceptible to scurvy is the inability of their liver to produce the active enzyme L-gulonolactone oxidase, which is the last of the chain of four enzymes that synthesize vitamin C.[193][194] American biochemist Irwin Stone was the first to exploit vitamin C for its food preservative properties. He later developed the theory that humans possess a mutated form of the L-gulonolactone oxidase coding gene.[195]
In 2008, researchers at the University of Montpellier discovered that in humans and other primates the red blood cells have evolved a mechanism to more efficiently utilize the vitamin C present in the body by recycling oxidized L-dehydroascorbic acid (DHA) back into ascorbic acid which can be reused by the body. The mechanism was not found to be present in mammals that synthesize their own vitamin C.[19]
Society and culture[edit]
- In February 2011 Swiss Post issued a postage stamp bearing a depiction of a model of a molecule of vitamin C to mark the International Year of Chemistry. Swiss chemist Tadeus Reichstein synthesized the vitamin for the first time in 1933.[196]
See also[edit]
- ^ a b c d "Vitamin C". Food Standards Agency (UK). Retrieved 2007-02-19.
- ^ Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, Chen S, Corpe C, Dutta A, Dutta SK, Levine M (February 2003). "Vitamin C as an antioxidant: evaluation of its role in disease prevention". J Am Coll Nutr 22 (1): 18–35. doi:10.1080/07315724.2003.10719272. PMID 12569111.
- ^ a b Aboul-Enein HY, Al-Duraibi IA, Stefan RI, Radoi C, Avramescu A (1999). "Analysis of L- and D-ascorbic acid in fruits and fruit drinks by HPLC". Seminars in Food Analysis 4 (1): 31–37. Archived from the original on December 15, 2013.
- ^ "Vitamin C". University of Maryland Medical Center. January 2007. Retrieved 2008-03-31.
- ^ a b Higdon J (2006-01-31). "Vitamin C". Oregon State University, Micronutrient Information Center. Retrieved 2007-03-07.
- ^ Meister A (April 1994). "Glutathione-ascorbic acid antioxidant system in animals". J. Biol. Chem. 269 (13): 9397–400. PMID 8144521.
- ^ Michels A, Frei B (2012). "Vitamin C". In Caudill MA, Rogers M. Biochemical, Physiological, and Molecular Aspects of Human Nutrition (3 ed.). Philadelphia: Saunders. pp. 627–654. ISBN 1-4377-0959-1.
- ^ a b Gropper SS, Smith JL, Grodd JL (2005). Advanced nutrition and human metabolism. Belmont, CA: Thomson Wadsworth. pp. 260–275. ISBN 0-534-55986-7.
- ^ Wheeler GL, Jones MA, Smirnoff N (May 1998). "The biosynthetic pathway of vitamin C in higher plants". Nature 393 (6683): 365–9. Bibcode:1998Natur.393..365W. doi:10.1038/30728. PMID 9620799.
- ^ Bánhegyi G, Mándl J (2001). "The hepatic glycogenoreticular system". Pathol. Oncol. Res. 7 (2): 107–10. doi:10.1007/BF03032575. PMID 11458272.
- ^ a b Martinez del Rio C (July 1997). "Can passerines synthesize vitamin C?". The Auk 114 (3): 513–16. doi:10.2307/4089257. JSTOR 4089257. Retrieved 2 May 2011.
- ^ Drouin G, Godin JR, Pagé B (2011). "The genetics of vitamin C loss in vertebrates". Curr. Genomics 12 (5): 371–8. doi:10.2174/138920211796429736. PMC 3145266. PMID 22294879.
- ^ Jenness R, Birney E, Ayaz K (1980). "Variation of l-gulonolactone oxidase activity in placental mammals". Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology 67 (2): 195–204. doi:10.1016/0305-0491(80)90131-5.
- ^ Cui J, Pan YH, Zhang Y, Jones G, Zhang S (Feb 2011). "Progressive pseudogenization: vitamin C synthesis and its loss in bats". Mol. Biol. Evol. 28 (2): 1025–31. doi:10.1093/molbev/msq286. PMID 21037206.
- ^ Cui J, Yuan X, Wang L, Jones G, Zhang S (Nov 2011). "Recent loss of vitamin C biosynthesis ability in bats". PLoS ONE 6 (11): e27114. doi:10.1371/journal.pone.0027114. PMID 22069493.
- ^ Harris JW (1996). Ascorbic acid: biochemistry and biomedical cell biology. New York: Plenum Press. p. 35. ISBN 0-306-45148-4.
- ^ Nishikimi M, Kawai T, Yagi K (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): 21967–72. PMID 1400507.
- ^ 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): 408–11. doi:10.1016/S0304-4165(99)00123-3. PMID 10572964.
- ^ a b Montel-Hagen A, Kinet S, Manel N, Mongellaz C, Prohaska R, Battini JL, Delaunay J, Sitbon M, Taylor N (March 2008). "Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C". Cell 132 (6): 1039–48. doi:10.1016/j.cell.2008.01.042. PMID 18358815. Lay summary – Science Daily (March 21, 2008).
- ^ Milton K (June 1999). "Nutritional characteristics of wild primate foods: do the diets of our closest living relatives have lessons for us?". Nutrition 15 (6): 488–98. doi:10.1016/S0899-9007(99)00078-7. PMID 10378206.
- ^ a b Hancock RD, Viola R. "Ascorbic acid biosynthesis in higher plants and microorganisms" (PDF). Scottish Crop Research Institute. Retrieved 2007-02-20.
- ^ Hancock RD, Galpin JR, Viola R (May 2000). "Biosynthesis of L-ascorbic acid (vitamin C) by Saccharomyces cerevisiae". FEMS Microbiol. Lett. 186 (2): 245–50. doi:10.1111/j.1574-6968.2000.tb09112.x. PMID 10802179.
- ^ Hardie LJ, Fletcher TC, Secombes CJ (1991). "The effect of dietary vitamin C on the immune response of the Atlantic salmon (Salmo salar L.)". Aquaculture 95 (3–4): 201–14. doi:10.1016/0044-8486(91)90087-N.
- ^ Challem JJ, Taylor EW (July 1998). "Retroviruses, ascorbate, and mutations, in the evolution of Homo sapiens". Free Radic. Biol. Med. 25 (1): 130–2. doi:10.1016/S0891-5849(98)00034-3. PMID 9655531.
- ^ Bánhegyi G, Braun L, Csala M, Puskás F, Mandl J (1997). "Ascorbate metabolism and its regulation in animals". Free Radic. Biol. Med. 23 (5): 793–803. doi:10.1016/S0891-5849(97)00062-2. PMID 9296457.
- ^ Stone I (June 1979). "Homo sapiens ascorbicus, a biochemically corrected robust human mutant". Med. Hypotheses 5 (6): 711–21. doi:10.1016/0306-9877(79)90093-8. PMID 491997.
- ^ 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.
- ^ Poux C, Douzery EJ (May 2004). "Primate phylogeny, evolutionary rate variations, and divergence times: a contribution from the nuclear gene IRBP". Am. J. Phys. Anthropol. 124 (1): 1–16. doi:10.1002/ajpa.10322. PMID 15085543.
- ^ Goodman M, Porter CA, Czelusniak J, Page SL, Schneider H, Shoshani J, Gunnell G, Groves CP (June 1998). "Toward a phylogenetic classification of Primates based on DNA evidence complemented by fossil evidence". Mol. Phylogenet. Evol. 9 (3): 585–98. doi:10.1006/mpev.1998.0495. PMID 9668008.
- ^ Porter CA, Page SL, Czelusniak J, Schneider H, Schneider MPC, Sampaio I, Goodman M (January 1997). "Phylogeny and Evolution of Selected Primates as Determined by Sequences of the ε-Globin Locus and 5′ Flanking Regions". International Journal of Primatology 18 (2): 261–295. doi:10.1023/A:1026328804319.
- ^ Proctor P (November 1970). "Similar functions of uric acid and ascorbate in man?". Nature 228 (5274): 868. Bibcode:1970Natur.228..868P. doi:10.1038/228868a0. PMID 5477017.
- ^ a b Savini I, Rossi A, Pierro C, Avigliano L, Catani MV (April 2008). "SVCT1 and SVCT2: key proteins for vitamin C uptake". Amino Acids 34 (3): 347–55. doi:10.1007/s00726-007-0555-7. PMID 17541511.
- ^ Rumsey SC, Kwon O, Xu GW, Burant CF, Simpson I, Levine M (July 1997). "Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid". J. Biol. Chem. 272 (30): 18982–9. doi:10.1074/jbc.272.30.18982. PMID 9228080.
- ^ May JM, Qu ZC, Neel DR, Li X (May 2003). "Recycling of vitamin C from its oxidized forms by human endothelial cells". Biochim. Biophys. Acta 1640 (2–3): 153–61. doi:10.1016/S0167-4889(03)00043-0. PMID 12729925.
- ^ Packer L (1997). "Vitamin C and redox cycling antioxidants". In Fuchs J, Packer L. Vitamin C in health and disease. New York: M. Dekker. ISBN 0-8247-9313-7.[page needed]
- ^ May JM, Qu ZC, Qiao H, Koury MJ (August 2007). "Maturational loss of the vitamin C transporter in erythrocytes". Biochem. Biophys. Res. Commun. 360 (1): 295–8. doi:10.1016/j.bbrc.2007.06.072. PMC 1964531. PMID 17586466.
- ^ Sotiriou S, Gispert S, Cheng J, Wang Y, Chen A, Hoogstraten-Miller S, Miller GF, Kwon O, Levine M, Guttentag SH, Nussbaum RL (May 2002). "Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival". Nat. Med. 8 (5): 514–7. doi:10.1038/nm0502-514. PMID 11984597.
- ^ Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J, Cantilena LR (April 1996). "Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance". Proc. Natl. Acad. Sci. U.S.A. 93 (8): 3704–9. Bibcode:1996PNAS...93.3704L. doi:10.1073/pnas.93.8.3704. PMC 39676. PMID 8623000.
- ^ Oreopoulos DG, Lindeman RD, VanderJagt DJ, Tzamaloukas AH, Bhagavan HN, Garry PJ (October 1993). "Renal excretion of ascorbic acid: effect of age and sex". J Am Coll Nutr 12 (5): 537–42. doi:10.1080/07315724.1993.10718349. PMID 8263270.
- ^ Hediger MA (May 2002). "New view at C". Nat. Med. 8 (5): 445–6. doi:10.1038/nm0502-445. PMID 11984580.
- ^ a b MedlinePlus Encyclopedia Ascorbic acid
- ^ "The influence of smoking on Vitamin C status in adults". BBC news and Cambridge University. 2000-09-31. Retrieved 2007-12-12.
- ^ Rath M, Pauling L (December 1990). "Immunological evidence for the accumulation of lipoprotein(a) in the atherosclerotic lesion of the hypoascorbemic guinea pig". Proc. Natl. Acad. Sci. U.S.A. 87 (23): 9388–90. Bibcode:1990PNAS...87.9388R. doi:10.1073/pnas.87.23.9388. PMC 55170. PMID 2147514.
- ^ Statistics Canada, Canadian Community Health Survey, Cycle 2.2, Nutrition (2004)[dead link]
- ^ Pemberton J (June 2006). "Medical experiments carried out in Sheffield on conscientious objectors to military service during the 1939-45 war". Int J Epidemiol 35 (3): 556–8. doi:10.1093/ije/dyl020. PMID 16510534.
- ^ Hodges RE, Baker EM, Hood J, Sauberlich HE, March SC (May 1969). "Experimental scurvy in man". Am. J. Clin. Nutr. 22 (5): 535–48. PMID 4977512.
- ^ Khaw KT, Bingham S, Welch A, Luben R, Wareham N, Oakes S, Day N (March 2001). "Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition". Lancet 357 (9257): 657–63. doi:10.1016/S0140-6736(00)04128-3. PMID 11247548.
- ^ Hemilä H (October 2007). "The role of vitamin C in the treatment of the common cold". Am Fam Physician 76 (8): 1111, 1115. PMID 17992770.
- ^ Barbosa E, Faintuch J, Machado Moreira EA, Gonçalves da Silva VR, Lopes Pereima MJ, Martins Fagundes RL, Filho DW (2009). "Supplementation of vitamin E, vitamin C, and zinc attenuates oxidative stress in burned children: a randomized, double-blind, placebo-controlled pilot study". J Burn Care Res 30 (5): 859–66. doi:10.1097/BCR.0b013e3181b487a8. PMID 19692922.
- ^ a b Levine M, Rumsey SC, Wang Y, Park JB, Daruwala R (2000). "Vitamin C". In Stipanuk MH. Biochemical and physiological aspects of human nutrition. Philadelphia: W.B. Saunders. pp. 541–67. ISBN 0-7216-4452-X.
- ^ Prockop DJ, Kivirikko KI (1995). "Collagens: molecular biology, diseases, and potentials for therapy". Annu. Rev. Biochem. 64: 403–34. doi:10.1146/annurev.bi.64.070195.002155. PMID 7574488.
- ^ Peterkofsky B (December 1991). "Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy". Am. J. Clin. Nutr. 54 (6 Suppl): 1135S–1140S. PMID 1720597.
- ^ Kivirikko KI, Myllylä R (1985). "Post-translational processing of procollagens". Annals of the New York Academy of Sciences 460: 187–201. Bibcode:1985NYASA.460..187K. doi:10.1111/j.1749-6632.1985.tb51167.x. PMID 3008623.
- ^ Rebouche CJ (December 1991). "Ascorbic acid and carnitine biosynthesis". Am. J. Clin. Nutr. 54 (6 Suppl): 1147S–1152S. PMID 1962562.
- ^ Dunn WA, Rettura G, Seifter E, Englard S (September 1984). "Carnitine biosynthesis from gamma-butyrobetaine and from exogenous protein-bound 6-N-trimethyl-L-lysine by the perfused guinea pig liver. Effect of ascorbate deficiency on the in situ activity of gamma-butyrobetaine hydroxylase". J. Biol. Chem. 259 (17): 10764–70. PMID 6432788.
- ^ Levine M, Dhariwal KR, Washko P, Welch R, Wang YH, Cantilena CC, Yu R (1992). "Ascorbic acid and reaction kinetics in situ: a new approach to vitamin requirements". J. Nutr. Sci. Vitaminol. Spec No: 169–72. doi:10.3177/jnsv.38.Special_169. PMID 1297733.
- ^ Kaufman S (1974). "Dopamine-beta-hydroxylase". J Psychiatr Res 11: 303–16. doi:10.1016/0022-3956(74)90112-5. PMID 4461800.
- ^ Eipper BA, Milgram SL, Husten EJ, Yun HY, Mains RE (April 1993). "Peptidylglycine alpha-amidating monooxygenase: a multifunctional protein with catalytic, processing, and routing domains". Protein Sci. 2 (4): 489–97. doi:10.1002/pro.5560020401. PMC 2142366. PMID 8518727.
- ^ Eipper BA, Stoffers DA, Mains RE (1992). "The biosynthesis of neuropeptides: peptide alpha-amidation". Annu. Rev. Neurosci. 15: 57–85. doi:10.1146/annurev.ne.15.030192.000421. PMID 1575450.
- ^ Englard S, Seifter S (1986). "The biochemical functions of ascorbic acid". Annu. Rev. Nutr. 6: 365–406. doi:10.1146/annurev.nu.06.070186.002053. PMID 3015170.
- ^ Lindblad B, Lindstedt G, Lindstedt S (December 1970). "The mechanism of enzymic formation of homogentisate from p-hydroxyphenylpyruvate". J. Am. Chem. Soc. 92 (25): 7446–9. doi:10.1021/ja00728a032. PMID 5487549.
- ^ a b c d McGregor GP, Biesalski HK (November 2006). "Rationale and impact of vitamin C in clinical nutrition". Current Opinion in Clinical Nutrition and Metabolic Care 9 (6): 697–703. doi:10.1097/01.mco.0000247478.79779.8f. PMID 17053422.
- ^ Kelly FJ (March 1998). "Use of antioxidants in the prevention and treatment of disease". J Int Fed Clin Chem 10 (1): 21–3. PMID 10181011.
- ^ Mayne ST (March 2003). "Antioxidant nutrients and chronic disease: use of biomarkers of exposure and oxidative stress status in epidemiologic research". J. Nutr. 133 Suppl 3: 933S–940S. PMID 12612179.
- ^ Tak PP, Zvaifler NJ, Green DR, Firestein GS (February 2000). "Rheumatoid arthritis and p53: how oxidative stress might alter the course of inflammatory diseases". Immunol. Today 21 (2): 78–82. doi:10.1016/S0167-5699(99)01552-2. PMID 10652465.
- ^ Goodyear-Bruch C, Pierce JD (November 2002). "Oxidative stress in critically ill patients". Am. J. Crit. Care 11 (6): 543–51; quiz 552–3. PMID 12425405.
- ^ Schorah CJ, Downing C, Piripitsi A, Gallivan L, Al-Hazaa AH, Sanderson MJ, Bodenham A (May 1996). "Total vitamin C, ascorbic acid, and dehydroascorbic acid concentrations in plasma of critically ill patients". Am. J. Clin. Nutr. 63 (5): 760–5. PMID 8615361.
- ^ Jacques PF, Sulsky SI, Perrone GE, Jenner J, Schaefer EJ (January 1995). "Effect of vitamin C supplementation on lipoprotein cholesterol, apolipoprotein, and triglyceride concentrations". Annals of Epidemiology 5 (1): 52–9. doi:10.1016/1047-2797(94)00041-Q. PMID 7728285.
- ^ a b Fotherby MD, Williams JC, Forster LA, Craner P, Ferns GA (April 2000). "Effect of vitamin C on ambulatory blood pressure and plasma lipids in older persons". J. Hypertens. 18 (4): 411–5. doi:10.1097/00004872-200018040-00009. PMID 10779091.
- ^ Bo S, Ciccone G, Durazzo M, Gambino R, Massarenti P, Baldi I, Lezo A, Tiozzo E, Pauletto D, Cassader M, Pagano G (2007). "Efficacy of antioxidant treatment in reducing resistin serum levels: a randomized study". PLoS Clin Trials 2 (5): e17. doi:10.1371/journal.pctr.0020017. PMC 1865087. PMID 17479165.
- ^ Mayer-Davis EJ, Monaco JH, Marshall JA, Rushing J (1997). "Vitamin C intake and cardiovascular disease risk factors in persons with non-insulin-dependent diabetes mellitus. From the Insulin Resistance Atherosclerosis Study and the San Luis Valley Diabetes Study". Prev Med 26 (3): 277–83. doi:10.1006/pmed.1997.0145. PMID 9144749.
- ^ Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (February 2007). "Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis". JAMA 297 (8): 842–57. doi:10.1001/jama.297.8.842. PMID 17327526.
- ^ Satoh K, Sakagami H (1997). "Effect of metal ions on radical intensity and cytotoxic activity of ascorbate". Anticancer Res. 17 (2A): 1125–9. PMID 9137459.
- ^ Mühlhöfer A, Mrosek S, Schlegel B, Trommer W, Rozario F, Böhles H, Schremmer D, Zoller WG, Biesalski HK (August 2004). "High-dose intravenous vitamin C is not associated with an increase of pro-oxidative biomarkers". Eur J Clin Nutr 58 (8): 1151–8. doi:10.1038/sj.ejcn.1601943. PMID 15054428.
- ^ Podmore ID, Griffiths HR, Herbert KE, Mistry N, Mistry P, Lunec J (April 1998). "Vitamin C exhibits pro-oxidant properties". Nature 392 (6676): 559. Bibcode:1998Natur.392..559P. doi:10.1038/33308. PMID 9560150.
- ^ Carr A, Frei B (June 1999). "Does vitamin C act as a pro-oxidant under physiological conditions?". FASEB J. 13 (9): 1007–24. PMID 10336883.
- ^ Preedy VR, Watson RR, Sherma Z (2010). Dietary Components and Immune Function (Nutrition and Health). Totowa, NJ: Humana Press. pp. 36; 52. ISBN 1-60761-060-4.
- ^ Johnston CS, Martin LJ, Cai X (April 1992). "Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis". J Am Coll Nutr 11 (2): 172–6. PMID 1578094.
- ^ Johnston CS, Solomon RE, Corte C (December 1996). "Vitamin C depletion is associated with alterations in blood histamine and plasma free carnitine in adults". J Am Coll Nutr 15 (6): 586–91. doi:10.1080/07315724.1996.10718634. PMID 8951736.
- ^ Clemetson CA (April 1980). "Histamine and ascorbic acid in human blood". J. Nutr. 110 (4): 662–8. PMID 7365537.
- ^ Catherine Vilchèze, Travis Hartman, Brian Weinrick & William R. Jacobs Jr. "Vitamin C Slays TB Bacteria", The Scientist, 21 May 2013. Retrieved on 27 October 2005.
- ^ Smirnoff N (1996). "BOTANICAL BRIEFING: The Function and Metabolism of Ascorbic Acid in Plants". Annals of Botany 78 (6): 661–9. doi:10.1006/anbo.1996.0175.
- ^ a b c d Food and Nutrition Board, Institute of Medicine. "Dietary Reference Intakes (DRIs): Estimated Average Requirements)" (PDF). United States National Academy of Sciences. Retrieved 2013-01-12.
- ^ Milton K (September 2003). "Micronutrient intakes of wild primates: are humans different?". Comp. Biochem. Physiol., Part a Mol. Integr. Physiol. 136 (1): 47–59. doi:10.1016/S1095-6433(03)00084-9. PMID 14527629.
- ^ "Linus Pauling Vindicated; Researchers Claim RDA For vitamin C is Flawed" (Press release). Knowledge of Health. July 6, 2004. Retrieved March 17, 2014.
- ^ Carr AC, Frei B (June 1999). "Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans". Am. J. Clin. Nutr. 69 (6): 1086–107. PMID 10357726.
- ^ Cathcart RF (November 1981). "Vitamin C, titrating to bowel tolerance, anascorbemia, and acute induced scurvy". Med. Hypotheses 7 (11): 1359–76. doi:10.1016/0306-9877(81)90126-2. PMID 7321921.
- ^ World Health Organization (2004). "Chapter 7: Vitamin C". Vitamin and Mineral Requirements in Human Nutrition, Second Edition. Geneva: World Health Organization. ISBN 92-4-154612-3. Retrieved 2007-02-20.
- ^ "Commission Directive 2008/100/EC of 28 October 2008 amending Council Directive 90/496/EEC on nutrition labelling for foodstuffs as regards recommended daily allowances, energy conversion factors and definitions". The Commission of the European Communities.
- ^ "Vitamin C". Natural Health Product Monograph. Health Canada.
- ^ Shibata K, Fukuwatari T, Imai E, Hayakawa T, Watanabe F, Takimoto H, Watanabe T, Umegaki K (January 2012). "Dietary Reference Intakes for Japanese 2010: Water-Soluble Vitamins". Journal of Nutritional Science and Vitaminology 59 (Supplement): S67–S82. doi:10.3177/jnsv.59.S67.
- ^ WHO (2001-06-04). "Area of work: nutrition. Progress report 2000" (PDF). Archived from the original on 2007-07-03.
- ^ Olmedo JM, Yiannias JA, Windgassen EB, Gornet MK (August 2006). "Scurvy: a disease almost forgotten". Int. J. Dermatol. 45 (8): 909–13. doi:10.1111/j.1365-4632.2006.02844.x. PMID 16911372.
- ^ Shenkin A (2006). "The key role of micronutrients". Clin Nutr 25 (1): 1–13. doi:10.1016/j.clnu.2005.11.006. PMID 16376462.
- ^ Woodside JV, McCall D, McGartland C, Young IS (2005). "Micronutrients: dietary intake v. supplement use". Proc Nutr Soc 64 (4): 543–53. doi:10.1079/PNS2005464. PMID 16313697.
- ^ Stanner SA, Hughes J, Kelly CN, Buttriss J (2004). "A review of the epidemiological evidence for the 'antioxidant hypothesis'". Public Health Nutr 7 (3): 407–22. doi:10.1079/PHN2003543. PMID 15153272.
- ^ Rivers JM (1987). "Safety of high-level vitamin C ingestion". Annals of the New York Academy of Sciences 498: 445–54. Bibcode:1987NYASA.498..445R. doi:10.1111/j.1749-6632.1987.tb23780.x. PMID 3304071.
- ^ "Vitamin C (Ascorbic acid)". MedLine Plus. National Institute of Health. 2006-08-01. Retrieved 2007-08-03.
- ^ Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2008). "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases". In Bjelakovic, Goran. Cochrane Database Syst Rev (2): CD007176. doi:10.1002/14651858.CD007176. PMID 18425980.
- ^ Huang HY, Caballero B, Chang S, Alberg A, Semba R, Schneyer C, Wilson RF, Cheng TY, Prokopowicz G, Barnes GJ, Vassy J, Bass EB (May 2006). "Multivitamin/mineral supplements and prevention of chronic disease". Evid Rep Technol Assess (Full Rep) (139): 1–117. PMID 17764205.
- ^ Brzozowska A, Kaluza J, Knoops KT, de Groot LC (April 2008). "Supplement use and mortality: the SENECA study". Eur J Nutr 47 (3): 131–7. doi:10.1007/s00394-008-0706-y. PMID 18414768.
- ^ Choi HK, Gao X, Curhan G (March 2009). "Vitamin C intake and the risk of gout in men: a prospective study". Arch. Intern. Med. 169 (5): 502–7. doi:10.1001/archinternmed.2008.606. PMC 2767211. PMID 19273781.
- ^ Stamp LK, O'Donnell JL, Frampton C, Drake JM, Zhang M, Chapman PT (2013). "Clinically insignificant effect of supplemental vitamin C on serum urate in patients with gout; a pilot randomised controlled trial.". Arthritis & Rheumatism 65 (6): 1636–42. doi:10.1002/art.37925. PMID 23681955.
- ^ Hemilä H, Louhiala P (2007). "Vitamin C for preventing and treating pneumonia". In Hemilä, Harri. Cochrane Database Syst Rev (1): CD005532. doi:10.1002/14651858.CD005532.pub2. PMID 17253561.
- ^ Myint PK, Luben RN, Welch AA, Bingham SA, Wareham NJ, Khaw KT (January 2008). "Plasma vitamin C concentrations predict risk of incident stroke over 10 y in 20 649 participants of the European Prospective Investigation into Cancer Norfolk prospective population study". Am. J. Clin. Nutr. 87 (1): 64–9. PMID 18175738. "...persons in the top quartiles of baseline plasma vitamin C concentrations had a 42% lower risk (relative risk: 0.58; 95% CI: 0.43, 0.78) than did those in the bottom quartile, independently of age, sex, smoking, body mass index, systolic blood pressure, cholesterol, physical activity, prevalent diabetes and myocardial infarction, social class, alcohol consumption, and any supplement use."
- ^ Effect of vitamin C on endothelial function in health and disease: A systematic review and meta-analysis of randomised controlled trials Atherosclerosis Volume 235, Issue 1, Pages 9–20, July 2014. Published April 16, 2014. Accessed June 25, 2014.
- ^ a b Douglas RM, Hemilä H, Chalker E, Treacy B (2007). "Vitamin C for preventing and treating the common cold". In Hemilä, Harri. Cochrane Database Syst Rev (3): CD000980. doi:10.1002/14651858.CD000980.pub3. PMID 17636648.
- ^ Heimer KA, Hart AM, Martin LG, Rubio-Wallace S (May 2009). "Examining the evidence for the use of vitamin C in the prophylaxis and treatment of the common cold". J Am Acad Nurse Pract 21 (5): 295–300. doi:10.1111/j.1745-7599.2009.00409.x. PMID 19432914.
- ^ Audera C, Patulny RV, Sander BH, Douglas RM (October 2001). "Mega-dose vitamin C in treatment of the common cold: a randomised controlled trial". Med. J. Aust. 175 (7): 359–62. PMID 11700812.
- ^ Sasazuki S, Sasaki S, Tsubono Y, Okubo S, Hayashi M, Tsugane S (January 2006). "Effect of vitamin C on common cold: randomized controlled trial". Eur J Clin Nutr 60 (1): 9–17. doi:10.1038/sj.ejcn.1602261. PMID 16118650.
- ^ Hemilä H, Chalker E (January 2013). "Vitamin C for preventing and treating the common cold". Cochrane Database of Systematic Reviews.
- ^ Mathew MC, Ervin AM, Tao J, Davis RM (2012). "Routine Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract". Cochrane Database Syst Rev 6: CD004567. doi:10.1002/14651858.CD004567.pub2. PMID 22696344.
- ^ "Antioxidants: Beyond the Hype" (in quote=little support ... mostly negative ... no effect on overall rates of cardiovascular disease ... same effect as a placebo ... combination of vitamin C, vitamin E, beta-carotene, and zinc offered some protection against the development of advanced age-related macular degeneration). Harvard School of Public Health. Retrieved 27 October 2013.
- ^ Douglas RM, Hemilä H (June 2005). "Vitamin C for preventing and treating the common cold". PLOS Medicine 2 (6): e168; quiz e217. doi:10.1371/journal.pmed.0020168. PMC 1160577. PMID 15971944.
- ^ Emadi-Konjin P, Verjee Z, Levin AV, Adeli K (2005). "Measurement of intracellular vitamin C levels in human lymphocytes by reverse phase high performance liquid chromatography (HPLC)" (PDF). Clinical Biochemistry 38 (5): 450–6. doi:10.1016/j.clinbiochem.2005.01.018. PMID 15820776.[dead link]
- ^ Yamada H, Yamada K, Waki M, Umegaki K (2004). "Lymphocyte and Plasma Vitamin C Levels in Type 2 Diabetic Patients With and Without Diabetes Complications" (PDF). Diabetes Care 27 (10): 2491–2. doi:10.2337/diacare.27.10.2491. PMID 15451922.
- ^ Pauling, Linus. (1976). Vitamin C, the Common Cold, and the Flu. San Francisco, CA: W.H. Freeman and Company.
- ^ "Toxicological evaluation of some food additives including anticaking agents, antimicrobials, antioxidants, emulsifiers and thickening agents". World Health Organization. 4 July 1973. Retrieved 2007-04-13.
- ^ Fleming DJ, Tucker KL, Jacques PF, Dallal GE, Wilson PW, Wood RJ (December 2002). "Dietary factors associated with the risk of high iron stores in the elderly Framingham Heart Study cohort". The American Journal of Clinical Nutrition 76 (6): 1375–84. PMID 12450906.
- ^ Cook JD, Reddy MB (January 2001). "Effect of ascorbic acid intake on nonheme-iron absorption from a complete diet". The American Journal of Clinical Nutrition 73 (1): 93–8. PMID 11124756.
- ^ Goodwin JS, Tangum MR (November 1998). "Battling quackery: attitudes about micronutrient supplements in American academic medicine". Archives of Internal Medicine 158 (20): 2187–91. doi:10.1001/archinte.158.20.2187. PMID 9818798.
- ^ Massey LK, Liebman M, Kynast-Gales SA (July 2005). "Ascorbate increases human oxaluria and kidney stone risk". The Journal of Nutrition 135 (7): 1673–7. PMID 15987848.
- ^ Thomas LD, Elinder CG, Tiselius HG, Wolk A, Akesson A (2013). "Ascorbic Acid Supplements and Kidney Stone Incidence Among Men: A Prospective Study". JAMA Intern Med. 173 (5): 1–2. doi:10.1001/jamainternmed.2013.2296. PMID 23381591.
- ^ 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.
- ^ Mashour S, Turner JF, Merrell R (August 2000). "Acute renal failure, oxalosis, and vitamin C supplementation: a case report and review of the literature". Chest 118 (2): 561–3. doi:10.1378/chest.118.2.561. PMID 10936161.
- ^ Ovcharov R, Todorov S (1974). "[The effect of vitamin C on the estrus cycle and embryogenesis of rats]". Akusherstvo I Ginekologii͡a (in Bulgarian) 13 (3): 191–5. PMID 4467736.
- ^ Vobecky JS, Vobecky J, Shapcott D, Cloutier D, Lafond R, Blanchard R (1976). "Vitamins C and E in spontaneous abortion". International Journal for Vitamin and Nutrition Research 46 (3): 291–6. PMID 988001.
- ^ Javert CT, Stander HJ (1943). "Plasma Vitamin C and Prothrombin Concentration in Pregnancy and in Threatened, Spontaneous, and Habitual Abortion". Surgery, Gynecology, and Obstetrics 76: 115–122.
- ^ Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, Sastre J, Viña J (January 2008). "Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance". The American Journal of Clinical Nutrition 87 (1): 142–9. PMID 18175748.
- ^ "Cancer-Causing Compound Can Be Triggered By Vitamin C". 2007-03-13. Retrieved 2009-12-26.
- ^ a b c "Safety (MSDS) data for ascorbic acid". Oxford University. 2005-10-09. Retrieved 2007-02-21.
- ^ Wilson JX (2005). "Regulation of vitamin C transport". Annu. Rev. Nutr. 25: 105–25. doi:10.1146/annurev.nutr.25.050304.092647. PMID 16011461.
- ^ "The vitamin and mineral content is stable". Danish Veterinary and Food Administration. Retrieved 2010-02-26.[dead link]
- ^ "National Nutrient Database". Nutrient Data Laboratory of the US Agricultural Research Service. Retrieved 2007-03-07.[dead link]
- ^ a b "Natural food-Fruit Vitamin C Content". The Natural Food Hub. Retrieved 2007-03-07.
- ^ "Using local foods".
- ^ Prior LD, Eamus D, Duff GA (1997). "Seasonal Trends in Carbon Assimilation, Stomatal Conductance, Pre-dawn Leaf Water Potential and Growth in Terminalia ferdinandiana, a Deciduous Tree of Northern Australian Savannas". Australian Journal of Botany 45 (1): 53–69. doi:10.1071/BT96065.
- ^ Brand JC, Rae C, McDonnell J, Lee A, Cherikoff V, Truswell AS (1987). "The nutritional composition of Australian aboriginal bushfoods. I". Food Technology in Australia 35 (6): 293–296.
- ^ Justi KC, Visentainer JV, Evelázio de Souza N, Matsushita M (December 2000). "Nutritional composition and vitamin C stability in stored camu-camu (Myrciaria dubia) pulp". Arch Latinoam Nutr 50 (4): 405–8. PMID 11464674.
- ^ Vendramini AL, Trugo LC (2000). "Chemical composition of acerola fruit (Malpighia punicifolia L.) at three stages of maturity". Food Chemistry 71 (2): 195–198. doi:10.1016/S0308-8146(00)00152-7.
- ^ Poole KE, Loveridge N, Barker PJ, Halsall DJ, Rose C, Reeve J, Warburton EA (January 2006). "Reduced vitamin D in acute stroke". Stroke 37 (1): 243–5. doi:10.1161/01.STR.0000195184.24297.c1. PMID 16322500.
- ^ "Nutrient data: Guavas, common, raw". National Nutrient Database for Standard Reference Release 25. United States Department of Agriculture.
- ^ "Nutrient data: Persimmons, native, raw". National Nutrient Database for Standard Reference Release 25. United States Department of Agriculture.
- ^ "Nutrient data: 'Tomatoes, red, ripe, raw, year round average". National Nutrient Database for Standard Reference Release 25. United States Department of Agriculture.
- ^ "09038, Avocados, raw, California". National Nutrient Database for Standard Reference, Release 26. United States Department of Agriculture, Agricultural Research Service. Retrieved 14 August 2014.
- ^ "Nutrient data: Onion". National Nutrient Database for Standard Reference Release 25. United States Department of Agriculture.
- ^ "Nutrient data: Horned melon (Kiwano)". National Nutrient Database for Standard Reference Release 25. United States Department of Agriculture.
- ^ Nutrient Data Laboratory (2010). USDA National Nutrient Database for Standard Reference, Release 23. United States Department of Agriculture Research Service. Retrieved 2011.
- ^ Chatterjee, IB (1973). "Evolution and the Biosynthesis of Ascorbic Acid". Science 182 (4118): 1271–1272. Bibcode:1973Sci...182.1271C. doi:10.1126/science.182.4118.1271. PMID 4752221.
- ^ Stone I (September 1979). "Eight decades of scurvy". Australas Nurses J 8 (11): 28–30. PMID 118729.[dead link]
- ^ Elwood, McCluskey. "Which Vertebrates Make Vitamin C?".
- ^ Clark S (8 January 2007). "Comparing Milk: Human, Cow, Goat & Commercial Infant Formula". Washington State University. Archived from the original on 2007-01-29. Retrieved 2007-02-28.
- ^ Toutain PL, Béchu D, Hidiroglou M (November 1997). "Ascorbic acid disposition kinetics in the plasma and tissues of calves". Am. J. Physiol. 273 (5 Pt 2): R1585–97. PMID 9374798.
- ^ Mal G (2000). Indian Veterinary Journal 77: 695–6.
- ^ Roig MG, Rivera ZS, Kennedy JF (May 1995). "A model study on rate of degradation of L-ascorbic acid during processing using home-produced juice concentrates". Int J Food Sci Nutr 46 (2): 107–15. doi:10.3109/09637489509012538. PMID 7621082.
- ^ Allen MA, Burgess SG (1950). "The losses of ascorbic acid during the large-scale cooking of green vegetables by different methods". Br. J. Nutr. 4 (2–3): 95–100. doi:10.1079/BJN19500024. PMID 14801407.
- ^ Combs GF (2001). The Vitamins, Fundamental Aspects in Nutrition and Health (2nd ed.). San Diego, CA: Academic Press. pp. 245–272. ISBN 978-0-12-183492-0.
- ^ Miranda H (2 June 2006). "Fresh-Cut Fruit May Keep Its Vitamins". WebMD. Retrieved 2007-02-25.
- ^ "The production of vitamin C" (PDF). Competition Commission. 2001. Retrieved 2007-02-20.
- ^ Starling S (2008-06-26). "DSM vitamin plant gains green thumbs-up". Decision News Media SAS. Retrieved 2010-02-25.
- ^ "Vitamin C: Distruptions to Production in China to Maintain Firm Market". Flexnews. 2008-06-30. Retrieved 2010-02-25.
- ^ "Bizbites October 11". Global Times. October 11, 2010. Retrieved 15 October 2010.
- ^ U.S. courts confront China's involvement in price fixing Andrew Longstreth , Reuters, Mar 11, 2011. Accessed March 2011
- ^ Vitamin C Makers Can Be Sued by Buyers Acting as Group January 27, 2012, Bloomberg , Business Week. Accessed January 2012
- ^ a b "Addition of Vitamins and Minerals to Food, 2005". Health Canada. Retrieved 2010-02-25.
- ^ British Pharmacopoeia Commission Secretariat (2009). "Index, BP 2009". Retrieved 4 February 2010.
- ^ "Japanese Pharmacopoeia, Fifteenth Edition". 2006. Retrieved 4 February 2010.
- ^ "Jacques Cartier's Second Voyage - 1535 - Winter & Scurvy". Retrieved 2007-02-25.
- ^ Martini E (June 2002). "Jacques Cartier witnesses a treatment for scurvy". Vesalius 8 (1): 2–6. PMID 12422875.
- ^ John Woodall, The Surgions Mate … (London, England : Edward Griffin, 1617), p. 89. From page 89: "Succus Limonum, or juice of Lemons … [is] the most precious help that ever was discovered against the Scurvy[;] to be drunk at all times; … "
- ^ Armstrong A (1858). "Observation on Naval Hygiene and Scurvy, more particularly as the later appeared during the Polar Voyage". British and foreign medico-chirurgical review: or, Quarterly journal of practical medicine and surgery 22: 295–305.
- ^ Johann Friedrich Bachstrom, Observationes circa scorbutum [Observations on scurvy] (Leiden ("Lugdunum Batavorum"), Netherlands: Conrad Wishof, 1734) p. 16. From page 16: " … sed ex nostra causa optime explicatur, quae est absentia, carentia & abstinentia a vegetabilibus recentibus, … " ( … but [this misfortune] is explained very well by our [supposed] cause, which is the absence of, lack of, and abstinence from fresh vegetables, … )
- ^ Lamb J (2011-02-17). "Captain Cook and the Scourge of Scurvy". British History in depth. BBC.
- ^ Lamb J (2001). Preserving the self in the south seas, 1680–1840. University of Chicago Press. p. 117. ISBN 0-226-46849-6.
- ^ Lind J (1753). A Treatise of the Scurvy. London: A. Millar. In the 1757 edition of his work, Lind discusses his experiment starting on page 149.
- ^ Singh S; Edzard Ernst (2008). Trick of Treatment: The Undeniable Facts about Alternative Medicine. WW Norton & Company. pp. 15–18. ISBN 978-0-393-06661-6.
- ^ Beaglehole JH, Cook JD, Edwards PR (1999). The journals of Captain Cook. Harmondsworth [Eng.]: Penguin. ISBN 0-14-043647-2.
- ^ Reeve J, Stevens DA (2006). "Cook's Voyages 1768–1780". Navy and the Nation: The Influence of the Navy on Modern Australia. Allen & Unwin Academic. p. 74. ISBN 1-74114-200-8.
- ^ Kuhnlein HV, Receveur O, Soueida R, Egeland GM (June 2004). "Arctic indigenous peoples experience the nutrition transition with changing dietary patterns and obesity". J. Nutr. 134 (6): 1447–53. PMID 15173410.
- ^ a b Zetterström R (May 2009). "Nobel Prize 1937 to Albert von Szent-Györgyi: identification of vitamin C as the anti-scorbutic factor". Acta Paediatr. 98 (5): 915–9. doi:10.1111/j.1651-2227.2009.01239.x. PMID 19239412.
- ^ Norum KR, Grav HJ (June 2002). "[Axel Holst and Theodor Frolich--pioneers in the combat of scurvy]". Tidsskr. Nor. Laegeforen. (in Norwegian) 122 (17): 1686–7. PMID 12555613.
- ^ Rosenfeld L (April 1997). "Vitamine--vitamin. The early years of discovery". Clin. Chem. 43 (4): 680–5. PMID 9105273.
- ^ a b Svirbely JL, Szent-Györgyi A; Waugh (1932). "The chemical nature of vitamin C". Biochem. J. 26 (3): 865–70. Bibcode:1932Sci....75..357K. doi:10.1126/science.75.1944.357-a. PMC 1260981. PMID 16744896.
- ^ Juhász-Nagy S (March 2002). "[Albert Szent-Györgyi--biography of a free genius]". Orv Hetil (in Hungarian) 143 (12): 611–4. PMID 11963399.
- ^ Kenéz J (December 1973). "[Eventful life of a scientist. 80th birthday of Nobel prize winner Albert Szent-Györgyi]". Munch Med Wochenschr (in German) 115 (51): 2324–6. PMID 4589872.
- ^ Szállási A (December 1974). "[2 interesting early articles by Albert Szent-Györgyi]". Orv Hetil (in Hungarian) 115 (52): 3118–9. PMID 4612454.
- ^ "The Albert Szent-Gyorgyi Papers: Szeged, 1931-1947: Vitamin C, Muscles, and WWII". Profiles in Science. United States National Library of Medicine.
- ^ "Pitt History - 1932: Charles Glen King". University of Pittsburgh. Retrieved 2007-02-21. "In recognition of this medical breakthrough, some scientists believe that King also deserved Nobel Prize recognition."[dead link]
- ^ Stacey M, Manners DJ (1978). "Edmund Langley Hirst. 1898-1975". Adv Carbohydr Chem Biochem. Advances in Carbohydrate Chemistry and Biochemistry 35: 1–29. doi:10.1016/S0065-2318(08)60217-6. ISBN 9780120072354. PMID 356548.
- ^ Boudrant J (May 1990). "Microbial processes for ascorbic acid biosynthesis: a review". Enzyme and Microbial Technology 12 (5): 322–9. doi:10.1016/0141-0229(90)90159-N. PMID 1366548.
- ^ Bremus C, Herrmann U, Bringer-Meyer S, Sahm H (June 2006). "The use of microorganisms in L-ascorbic acid production". J. Biotechnol. 124 (1): 196–205. doi:10.1016/j.jbiotec.2006.01.010. PMID 16516325.
- ^ Bächi B (2008). "[Natural or synthetic vitamin C? A new substance's precarious status behind the scenes of World War II]". NTM (in German) 16 (4): 445–70. doi:10.1007/s00048-008-0309-y. PMID 19579835.
- ^ Burns JJ, Evans C (December 1956). "The synthesis of L-ascorbic acid in the rat from D-glucuronolactone and L-gulonolactone". J. Biol. Chem. 223 (2): 897–905. PMID 13385237.
- ^ Burns JJ, Moltz A, Peyser P (December 1956). "Missing step in guinea pigs required for the biosynthesis of L-ascorbic acid". Science 124 (3232): 1148–9. Bibcode:1956Sci...124.1148B. doi:10.1126/science.124.3232.1148-a. PMID 13380431.
- ^ Henson DE, Block G, Levine M (April 1991). "Ascorbic acid: biologic functions and relation to cancer". J. Natl. Cancer Inst. 83 (8): 547–50. doi:10.1093/jnci/83.8.547. PMID 1672383.
- ^ Stephens T (2011-02-17). "Let the chemical games begin!". Swiss Info. Swiss Broadcasting Corporation. Retrieved 2011-02-23.
External links[edit]
- Vitamin C Fact Sheet from the U.S. National Institutes of Health
- Vitamin C bound to proteins in the PDB
- National Nutrient Database at USDA Website


text:
Marks and Spencer electrocution victim named
A contractor who died at the Marks and Spencer shop in Tunbridge Wells on Saturday has been named as 62-year-old Philip Dodd.
Mr Dodd was a widower who lived in Horley in Surrey. His family have been informed.
Follow the story on ITV News Meridian.

subset: commoncrawl


text:
Moving light technical specialist Scot Townsend has joined Clay Paky America as Technical Services Manager, replacing Giovanni Zucchinali who has returned to Clay Paky in Italy.
"Scot is a great addition to the team," says CEO of Clay Paky America PJ Turpin. "We are very pleased that Scott has decided to join us. He is a great guy who knows the industry and knows moving lights." Townsend joins Clay Paky America after working for a major lighting rental company in the Los Angeles area.
"I wanted to get in with a good company on the ground floor," says Townsend of his new job. "Clay Paky makes some fantastic lights, and I was looking for a change of pace from the rental and production world."
Hailing from Fort Worth, TX, Townsend studied history at Texas Christian University (TCU). Not wanting to become a teacher, Townsend initially worked in the automotive industry upon leaving TCU. "It just was not for me," says Townsend of his initial career choice. "As a kid, I had never wanted to be the rock star but always the guy who traveled with the band and made it all happen. It was just something I had always wanted to do, so I decided to give it a try."
In 1999, Townsend moved to Los Angeles to further his new career and worked on some of the largest productions of the past six years. "I did not travel the traditional routes into the industry," notes Townsend. "History was my thing at university rather than theatre or electrical engineering."
Although in recent years Townsend has had little free time, he still embraces his first passion–history, as well as gaining a new passion more related to his chosen profession–music.


text:
Topic: Family Law with Bellinger Law Office
Air Date: 12/19/2012, 7:30 p.m. WPTA -
Various questions and answers regarding family law with Robert Bellinger and Lierin Rossman
What are your thoughts CLICK HERE to leave us a "Your2Cents" comment.
TextCaster alerts from Indiana's NewsCenter are your defining source for instant information delivered right to your cell phone and email. It's free, easy and instant. Sign-Up Now!
Powered by Summit City Chevrolet
© Copyright 2014, A Granite Broadcasting Station. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


text:
This week's adoptable cat is Cookie, a Tuxedo cat.
Cookie, a one-and-a-half-year-old spayed female, is laid back but curious. She loves to play with string and cat toys. She has been with Manatee County Animal Services since Aug 17.
You can visit Cookie (A052683) at the Manatee County Animal Services downtown adoption center this week. The downtown center is open from 11 a.m. to 6 p.m. Tuesday through Friday and 10 a.m. to 4 p.m. on Saturdays.
Adoptions at Manatee County Animal Services, which include spay/neuter, vaccinations, health check and microchip, are $80 for dogs, plus a $10 license fee for those in Manatee County and $60 for cats, plus the license fee. Some animals who have been at the shelter too long are available for the $10 license fee. The downtown adoption center is open from 10 a.m. to 4 p.m. Tuesday through Saturday.
For more information, visit www.mymanatee.org/pets or call 941-742-5824. The animal services webpage features updated photos and descriptions of the pets available for adoption. Pet owners can also use the site to locate missing pets.
Pets are also available for adoption locally at:
- Animal Network Inc. at Petsmart, 4425 14th St. W.
- Humane Society of Manatee County, 2515 Tamiami Trail
- Bishop Animal Shelter SPCA, 5718 21st Ave. W.
- Gulf Shore Animal League at Pet Supermarket, 6908 Manatee Ave W.
- Nates Place Dog and Cat Adoption Center, 8435 Cooper Creek Blvd.


text: Kevin Gausman, RHP, Louisiana State University: Gausman was an unsigned sixth-round pick of the Dodgers in the 2010 draft. He's had an excellent season, going 11-1 in 16 starts for LSU, posting a 2.72 ERA with a 128 strikeouts and only 27 walks in 115 innings, with 100 hits allowed. Gausman fires mid-90s heat from a 6-5, 190 frame, mixing it with an excellent change-up. His breaking ball is still a work in progress but has strong moments, and his upside is as high as anyone's. He projects as a number-one starter, and would make a terrific one-two punch with phenom Dylan Bundy, already in the farm system. Gausman is a draft-eligible sophomore and should be signable this early in the draft. He was a sixth-round pick back in 2010 from a Colorado high school. He still has some remaining physical projection, unusual for a college pitcher with his sort of experience.


text:
The purpose of form 212-234-000 -Out of state applications- is to provide a means for an employer to formally request to receive the out-of-state supplemental report for a specific year and state. The form will also allow the department to convey out-of-state reporting requirements and to obtain information needed by the department to set a business up for supplemental reporting.
End of main content, page footer follows.
© Washington State Dept. of Labor & Industries. Use of this site is subject to the laws of the state of Washington.
Do you plan to access the Labor and Industries website from a mobile device? (such as a phone or tablet)


text:
The Waterwheel
A publication of the Student Development Office for Students in the College of Arts and Sciences and the residents students at the St. Davids Campus.
The Waterwheel is published each Monday of the academic year. If you have an announcement that you would like to advertise in The Waterwheel, please email the body of your ad to Michael Schmersahl by Noon on the Friday prior to the upcoming week's publication (firstname.lastname@example.com). Please keep ads to 100 words or less.
Students in the College of Arts and Sceinces are responsible for reading The Waterwheel every week, and for the information printed. If you would like to request a hard copy of The Waterwheel, email email@example.com or pick up a copy in the Student Development Office (Walton 200).


text:
Miami's NEO A&M has signed a new agreement with Pittsburg State allowing more options for transfer students.
This new arrangement applies to NEO students who transfer to PSU.
Now those students can apply their Pitt State credit hours toward a NEO Associate's Degree.
PSU already has this arrangement with some community colleges in Kansas, but this is the first such agreement with a community college in another state.


text:
"The SC AgriBiz & Farm Expo had a great second year. The event put agribusiness in the spotlight, reminding everyone that our industry is vital to South Carolina. I want to thank all the sponsors and exhibitors for helping make this year such a success. Here's to a great 2014, and may next year's expo be even better." - Hugh Weathers, SC Commissioner of Agriculture
"Thanks to everyone who exhibited, attended, sponsored and help with all aspects of the 2014 SC AgriBiz & Farm Expo. This is a great event because of the outstanding team work from everyone. I am blessed to work with each of you! Please share any inputs as we move forward!" - Jody A. Martin, Expo Show Manager
"Many thanks to all who took part in the 2014 SC AgriBiz & Farm Expo. Because of everyone's great love and passion for agriculture, 2014 was a success! With everyone's support and outreach, we look forward to greater things in 2015." – Cullen Bryant, Farmer, Expo Management Team
"What a tremendous 2nd year for the SC AgriBiz and Farm Expo! Thank you to the sponsors, exhibitors, speakers, attendees and volunteers that made this event possible! I can't wait to work with all of you as we begin moving forward with the 2015 expo!" – Brandie Hayes, Sales Coordinator, Expo Management Team
"I had a great time being a part of the 2014 AgriBiz & Farm Expo and I'm looking forward to seeing everyone again next year. Thanks to all who sponsored, exhibited and attended this great event." - Amanda Williamson, Expo Management Team
Request More Information
Jody Martin
Show Manager
Brandie Hayes
Sales Coordinator
Amanda Williamson
Administrative Assistant


text:
These lenses offer no optical zoom. Look for autofocus instead of fixed focus, as well as selectable macro and landscape focus modes.
Best for: snapshooter, budget buyer
Allows compact or ultracompact camera designs.
Easy and quick camera operation.
Lenses usually offer relatively wide angle of view,
which is good for landscapes and group shots.
Can't zoom in close to faraway subjects.
Lens doesn't usually accept converters for different
focal lengths or filters.
Usually lowest optical quality available.