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The NuGOwiki Metabolite Database is a joint initiative of NuGO and HMDB
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All Metabolites | Biochemical | Nutritional | Functional | Metabolic Pathways | Diseases | Phenotypes | Physiological Processes | Protein |
| Vitamin C | |||||||
|---|---|---|---|---|---|---|---|
 | |||||||
| Chemical Name | (2S)-2-[(1R)-1,2-dihydroxyethyl]-4,5-dihydroxy-furan-3-one | ||||||
| Chemical Formula | C6H8O6 | ||||||
| CAS Number | 50-81-7 | ||||||
| Chemical Information | HMDB00044 | ||||||
| Biochemical Taxonomy |
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| Functional Taxonomy |
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| Nutritional Taxonomy | Not Available | ||||||
| Metabolic Pathways |
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| Biofluid Location |
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| Tissue Location |
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| Normal Biofluid Concentrations |
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| Normal Tissue Concentrations | Not Available | ||||||
| Diseases / Conditions Related to Nutrition |
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| Other (Monogenic Disorders) | Not Available | ||||||
| Abnormal Biofluid Concentrations |
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| Abnormal Tissue Concentrations | Not Available | ||||||
| Physiological Processes | Not Available | ||||||
| Authors: | |
| Affiliations: |
Introduction
guidelines
Ascorbic acid is an essential nutrient in human diets. Its biologically active form is vitamin C, a water-soluble vitamin. Unlike most mammals, primates (including humans) and a few other species in all divisions of the animal kingdom, notably the guinea pig, have lost the ability to synthesize ascorbic acid and must obtain it in their diet. It is necessary for the synthesis of collagen particularly to maintain connective tissue and bone. Ascorbic acid is an electron donor for enzymes involved in collagen hydroxylation, biosynthesis of carnitine and norepinephrine, tyrosine metabolism, and amidation of peptide hormones; its deficiency causes scurvy. The amount of vitamin C necessary to prevent scurvy may not be adequate to maintain optimal health. The ability of vitamin C to donate electrons also makes it a potent water-soluble antioxidant that readily scavenges free radicals such as molecular oxygen, superoxide, hydroxyl radical, and hypochlorous acid. In this setting, several mechanisms could account for a link between vitamin C and heart disease. One is the relation between LDL oxidation and vitamins C and E. Vitamin C in vitro can recycle vitamin E, which can donate electrons to prevent LDL oxidation in vitro. As the lipid-phase vitamin E is oxidized, it can be regenerated by aqueous vitamin C. Other possibilities are that vitamin C could decrease cholesterol by mechanisms not well characterized, or could improve vasodilatation and vascular reactivity, perhaps by decreasing the interactions of nitric oxide with oxidant.
Catabolism
guidelines
In guinea pigs, significant amounts of vitamin C are converted to CO2 via an oxidative pathway but this does not occur in man. The main catabolic products of vitamin C in man are dehydroascorbic acid (HMDB01264), diketoglucuronic acid and oxalic acid.
Diseases / Conditions Related to Nutrition
- Bacterial meningitis
- Hemodialysis (after a 4 hour dialysis session)
- Hemodialysis (before a 4 hour dialysis session)
- Patients with Canavan disease
- Pediatric traumatic brain injury
Vitamin C deficiency
Lack of ascorbic acid in the daily diet leads to a disease called scurvy, a form of avitaminosis that is characterized by:
- loose teeth
- superficial bleeding
- fragility of blood vessels
- poor healing
- compromised immunity
- mild anemia
It is eventually fatal, and was a common condition among sailors and during winter. Scurvy is now very rare in industrialized countries. It should not be confused with "subclinical scurvy" or "chronic scurvy", both high-dose advocate terms for the normal human condition of blood levels lower than those typical among mammals.
Diabetes
Diabetic patients have low levels of ascobric acid (Will and Byers, 1996, Kajanachumpol 1997). An overview is given by Chertow.
Coronary Heart Disease
Until recently, the results of most prospective studies indicated that low or deficient intakes of vitamin C were associated with an increased risk of cardiovascular diseases and that modest dietary intakes of about 100 mg/day were sufficient for maximum reduction of cardiovascular disease risk among nonsmoking men and women (Carr AC, 1999). In addition, several studies had failed to find significant reductions in the risk of coronary heart disease (CHD) among vitamin C supplement users in well-nourished populations (Losonczy KG, 1996)(Kushi LH, 1996). One notable exception was the First National Health and Nutrition Examination Study (NHANES I) Epidemiologic Follow-up Study (Enstrom JE, 1992). This study found that the risk of death from cardiovascular diseases was 42% lower in men and 25% lower in women who consumed more than 50 mg/day of dietary vitamin C and who regularly took vitamin C supplements, corresponding to a total vitamin C intake of about 300 mg/day (1). Results from the Nurses’ Health Study, based on the follow-up of more than 85,000 women over 16 years, also suggest that higher vitamin C intakes may be cardioprotective (Osganian SK,2003). In this study, vitamin C intakes of more than 359 mg/day from diet plus supplements or supplement use itself were associated with a 27-28% reduction in CHD risk. However, in those women who did not take vitamin C supplements, dietary vitamin C intake was not significantly associated with CHD risk. More recently, a pooled analysis of 9 prospective cohort studies, including more than 290,000 adults who were free of CHD at baseline and followed for an average of 10 years, found that those who took more than 700 mg/day of supplemental vitamin C had a 25% lower risk of CHD than those who did not take vitamin C supplements (Knekt P,2004). Data from the National Institutes of Health (NIH) indicate that plasma and circulating cells in healthy, young subjects became fully saturated with vitamin C at a dose of about 400 mg/day (Levine M, 2001). The results of the pooled analysis of prospective cohort studies suggest that maximum reduction of CHD risk may require vitamin C intakes high enough to saturate plasma and circulating cells, and thus the vitvitamin C body pool (2).
Cancer
A large number of studies have shown that increased consumption of fresh fruits and vegetables is associated with a reduced risk for most types of cancer (Steinmetz KA, 1996). Such studies are the basis for dietary guidelines endorsed by the U.S. Department of Agriculture and the National Cancer Institute, which recommend at least 5 servings of fruits and vegetables per day. A number of case-control studies have investigated the role of vitamin C in cancer prevention. Most have shown that higher intakes of vitamin C are associated with decreased incidence of cancers of the mouth, throat and vocal chords, esophagus, stomach, colon-rectum, and lung. Because the possibility of bias is greater in case-control studies, prospective studies are generally given more weight in the evaluation of the effect of nutrient intake on disease. In general, prospective studies in which the lowest intake group consumed more than 86 mg of vitamin C daily have not found differences in cancer risk, while studies finding significant cancer risk reductions found them in people consuming at least 80 to 110 mg of vitamin C daily(Carr AC, 1999).
A prospective study of 870 men over a period of 25 years found that those who consumed more than 83 mg of vitamin C daily had a striking 64% reduction in lung cancer compared with those who consumed less than 63 mg per day (3). Although most large prospective studies found no association between breast cancer and vitamin C intake, two recent studies found dietary vitamin C intake to be inversely associated with breast cancer risk in certain subgroups. In the Nurses' Health Study, premenopausal women with a family history of breast cancer who consumed an average of 205 mg/day of vitamin C from foods had a 63% lower risk of breast cancer than those who consumed an average of 70 mg/day (Zhang S,1999). In the Swedish Mammography Cohort, women who were overweight and consumed an average of 110 mg/day of vitamin C had a 39% lower risk of breast cancer compared to overweight women who consumed an average of 31 mg/day (Michels KB,2001). A number of observational studies have found increased dietary vitamin C intake to be associated with decreased risk of stomach cancer, and laboratory experiments indicate that vitamin C inhibits the formation of carcinogenic compounds in the stomach. Infection with the bacteria, helicobacter pylori (H. pylori) is known to increase the risk of stomach cancer and also appears to lower the vitamin C content of stomach secretions. Although two intervention studies did not find a decrease in the occurrence of stomach cancer with vitamin C supplementation (Food and Nutrition Board, 2000), more recent research suggests that vitamin C supplementation may be a useful addition to standard H. pylori eradication therapy in reducing the risk of gastric cancer (Feiz HR, 2002).
Associated decreased protein/metabolite profile
Associated increased protein/metabolite profile
Other (Monogenic) Disorders
guidelines
No genetic diseases have been described associated with vitamin C.
Nutritional Information
The recommended dietary allowance
In the U.S., the recommended dietary allowance (RDA) for vitamin C was recently revised upward from 60 mg daily for men and women. The RDA continues to be based primarily on the prevention of deficiency disease, rather than the prevention of chronic disease and the promotion of optimum health. The recommended intake for smokers is 35 mg/day higher than for nonsmokers, because smokers are under increased oxidative stress from the toxins in cigarette smoke and generally have lower blood levels of vitamin C.
Detailed tables with RDA are provided by the Linus Pauling vitamin database for detailed info.
Food sources
Different fruits and vegetables vary in their vitamin C content. Check the Linus Pauling vitamin database and Wikipedia vitamin C for detailed info.
Toxicity
A number of possible problems with very large doses of vitamin C have been suggested, mainly based on in vitro experiments or isolated case reports, including: genetic mutations, birth defects, cancer, atherosclerosis, kidney stones, "rebound scurvy", increased oxidative stress, excess iron absorption, vitamin B-12 deficiency, and erosion of dental enamel. However, none of these adverse health effects have been confirmed, and there is no reliable scientific evidence that large amounts of vitamin C (up to 10 grams/day in adults) are toxic or detrimental to health. With the latest RDA published in 2000, a tolerable upper intake level (UL) for vitamin C was set for the first time. A UL of 2 grams (2,000 milligrams) daily was recommended in order to prevent most adults from experiencing diarrhea and gastrointestinal disturbances (reference). Such symptoms are not generally serious, especially if they resolve with temporary discontinuation or reduction of high-dose vitamin C supplementation.
Drivers for biological variation
Vulnerable groups
Markers of homeostasis and / or health
| Category | Markers | sign yes/no/? | Inverse/D | S/I | ref | score | comments |
| inflammation, immune response | CRP / hsCRP | Yes | D | S & I | 12, 15 | 4 | |
| fibrinogen | |||||||
| Albumin | Yes | D | S | 5 | 3 | ||
| White blood cell count | No | D | I | 2 | 3 | ||
| TNF-alpha | Yes | D | I | 3 | 3 | ||
| Il-6 | No | D | I | 2 | 3 | ||
| Il1-beta | No | D | I | 2 | 3 | ||
| Il-10 | No | D | I | 2 | 3 | ||
| Prostaglandin F2alpha | |||||||
| Prostaglandin E1 (PGE1) | |||||||
| Prostaglandin E2 (PGE2) | Yes | D | I | 12 | 3 | ||
| Thromboxane B2 | |||||||
| Nitric Oxide (NO) | Yes | I | I | 4 | 3 | ||
| Serum Amyloid A (SAA) | |||||||
| NfkB | |||||||
| alpha1-antichymotrypsin | |||||||
| oxidative stress | 8(OH)-DG | ||||||
| F2-isoprostanes | Yes & No | D | I | 2, 6, 12 | 4 | ||
| 8-iso-prostaglandin F2alpha | Yes | D | S & I | 8, 9, 12 | 4 | ||
| oxidized LDL | Yes & No | D | I | 7 | 4 | ||
| SOD | |||||||
| TBARS | |||||||
| myeloperoxidase | |||||||
| nitrotyrosine | Yes | I | I | 23 | 3 | ||
| Metabolic stress | diastolic BP | Yes & No | ? | S & I | 11, 13, 14, 16-18 | 4 | |
| systolic BP | Yes & No | ? | S & I | 11, 13, 14, 16-18 | 4 | ||
| total cholesterol | Yes & No | D | I | 19-21 | 4 | ||
| LDL | Yes & No | D & I | S & I | 16-19 | 4 | ||
| HDL | Yes & No | D | S & I | 10, 16-19, 22 | 4 | ||
| HDL/TC | |||||||
| triglycerides | No | D | I | 17, 19 | 3 | ||
| homocysteine | |||||||
| tPA/PAI-1 | |||||||
| Fibrin fragment D-dimer | |||||||
| Factor VIIa | |||||||
| sICAM | No | D | I | 1, 7 | 4 | ||
| Monocyte chemoattractant protein 1 (MCP1) | Yes | D | I | 3 | 3 | MCP receptor transcript levels are increased by vitamine C treatment | |
| fasting glucose | |||||||
| fasting insulin | |||||||
| OGTT | |||||||
| insulin tolerance test | |||||||
| HbA1c | |||||||
| fructosamine |
Other resources
- Bendich A, Langseth L. The health effects of vitamin C supplementation: a review. J Am Coll Nutr. 1995 Apr;14(2):124-36.
- Block G, Jensen CD, Norkus EP, Hudes M, Crawford PB. Vitamin C in plasma is inversely related to blood pressure and change in blood pressure during the previous year in young Black and White women. Nutr J. 2008 Dec 17;7:35.
- Block G, Jensen CD, Dalvi TB, Norkus EP, Hudes M, Crawford PB, Holland N, Fung EB, Schumacher L, Harmatz P. Vitamin C treatment reduces elevated C-reactive protein.Free Radic Biol Med. 2009 Jan 1;46(1):70-7. Epub 2008 Oct 10.
- Bo S, Ciccone G, Durazzo M, Gambino R, Massarenti P, Baldi I, Lezo A, Tiozzo E, Pauletto D, Cassader M, Pagano G. Efficacy of antioxidant treatment in reducing resistin serum levels: a randomized study. PLoS Clin Trials. 2007 May 4;2(5):e17.
- Eskurza I, Monahan KD, Robinson JA, Seals DR Ascorbic acid does not affect large elastic artery compliance or central blood pressure in young and older men. Am J Physiol Heart Circ Physiol. 2004 Apr;286(4):H1528-34.
- Fotherby MD, Williams JC, Forster LA, Craner P, Ferns GA. Effect of vitamin C on ambulatory blood pressure and plasma lipids in older persons. J Hypertens. 2000 Apr;18(4):411-5.
- Fu Q, Liu BW. Oxidative Modification Reduces HDL-induced Cholesterol Efflux from Cultured Human Arterial Smooth Muscle Cells. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2000;32(3):248-252.
- Holowatz LA, Kenney WL. Local ascorbate administration augments NO- and non-NO-dependent reflex cutaneous vasodilation in hypertensive humans. Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H1090-6. Epub 2007 May 4.
- Huang HY, Appel LJ, Croft KD, Miller ER 3rd, Mori TA, Puddey IB. Effects of vitamin C and vitamin E on in vivo lipid peroxidation: results of a randomized controlled trial. Am J Clin Nutr. 2002 Sep;76(3):549-55.
- Jacques PF. Effects of vitamin C on high-density lipoprotein cholesterol and blood pressure. J Am Coll Nutr. 1992 Apr;11(2):139-44.
- Jacques PF, Sulsky SI, Perrone GE, Jenner J, Schaefer EJ. Effect of vitamin C supplementation on lipoprotein cholesterol, apolipoprotein, and triglyceride concentrations. Ann Epidemiol. 1995 Jan;5(1):52-9.
- Jaja SI, Aisuodionwe SI, Kehinde MO, Gbenebitse S. The effect of vitamin C and/or warmth on forearm blood flow and vascular resistance in sickle cell anaemia subjects. Niger Postgrad Med J. 2002 Jun;9(2):92-4.
- Kaikkonen J, Porkkala-Sarataho E, Morrow JD, Roberts LJ 2nd, Nyyssönen K, Salonen R, Tuomainen TP, Ristonmaa U, Poulsen HE, Salonen JT. Supplementation with vitamin E but not with vitamin C lowers lipid peroxidation in vivo in mildly hypercholesterolemic men. Free Radic Res. 2001 Dec;35(6):967-78.
- Majewicz J, Rimbach G, Proteggente AR, Lodge JK, Kraemer K, Minihane AM. Dietary vitamin C down-regulates inflammatory gene expression in apoE4 smokers. Biochem Biophys Res Commun. 2005 Dec 16;338(2):951-5. Epub 2005 Oct 17.
- Mayer-Davis EJ, Monaco JH, Marshall JA, Rushing J, Juhaeri. 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. 1997 May-Jun;26(3):277-83
- Nieman DC, Henson DA, McAnulty SR, McAnulty L, Swick NS, Utter AC, Vinci DM, Opiela SJ, Morrow JD. Influence of vitamin C supplementation on oxidative and immune changes after an ultramarathon. J Appl Physiol. 2002 May;92(5):1970-7.
- Paniz C, Bairros A, Valentini J, Charão M, Bulcão R, Moro A, Grune T, Garcia SC.The influence of the serum vitamin C levels on oxidative stress biomarkers in elderly women.Clin Biochem. 2007 Dec;40(18):1367-72. Epub 2007 Aug 29.
- Sánchez-Moreno C, Cano MP, de Ancos B, Plaza L, Olmedilla B, Granado F, Martín A. High-pressurized orange juice consumption affects plasma vitamin C, antioxidative status and inflammatory markers in healthy humans. J Nutr. 2003 Jul;133(7):2204-9.
- Sánchez-Moreno C, Cano MP, de Ancos B, Plaza L, Olmedilla B, Granado F, Elez- Martínez P, Martín-Belloso O, Martín A. Pulsed electric fields-processed orange juice consumption increases plasma vitamin C and decreases F2-isoprostanes in healthy humans. J Nutr Biochem. 2004 Oct;15(10):601-7.
- Scott DA, Poston RN, Wilson RF, Coward PY, Palmer RM. The influence of vitamin C on systemic markers of endothelial and inflammatory cell activation in smokers and non-smokers.Inflamm Res. 2005 Mar;54(3):138-44.
- Simon JA, Schreiber GB, Crawford PB, Frederick MM, Sabry ZI. Dietary vitamin C and serum lipids in black and white girls. Epidemiology. 1993 Nov;4(6):537-42.
- Tofler GH, Stec JJ, Stubbe I, Beadle J, Feng D, Lipinska I, Taylor A. The effect of vitamin C supplementation on coagulability and lipid levels in healthy male subjects. Thromb Res. 2000 Oct 1;100(1):35-41.
- Van Hoydonck PG, Schouten EG, Manuel-Y-Keenoy B, van Campenhout A, Hoppenbrouwers KP, Temme EH. Does vitamin C supplementation influence the levels of circulating oxidized LDL, sICAM-1, sVCAM-1 and vWF-antigen in healthy male smokers? Eur J Clin Nutr. 2004 Dec;58(12):1587-93.
Determinants of requirements
| Category | Determinants of status | sign yes/no/? help | independent of intake yes/no/? |
| general | gender | ||
| age (adults) | Yes | Yes | |
| age (children) | Yes | Yes | |
| ethnicity | |||
| physiological status | polymorphisms | ||
| pregnancy | Yes | Yes | |
| lactation | Yes | Yes | |
| menopause | Yes | Yes | |
| physical fitness | Yes | Yes | |
| gut flora | |||
| anthropometric variables | body weight | ||
| BMI | Yes | No | |
| waist circumference | Yes | No | |
| fat free mass | |||
| Lifestyle variables | smoking | Yes | Yes |
| physical activity | Yes | Yes | |
| alcohol use | |||
| medication use (incl. contraceptive pill) | |||
| stress |
Reference
- Lester Packer and Jürgen Fuchs,Vitamin C in Health and Disease, Marcel Dekker Inc. New York 1997
Other resources
- Enstrom JE. Counterpoint--vitamin C and mortality. Nutr Today. 1993;28:28-32.
- Frei B. To C or not to C, that is the question! J Am Coll Cardiol. 2003;42(2):253-255.
- Kromhout D. Essential micronutrients in relation to carcinogenesis. Am J Clin Nutr. 1987;45(5 Suppl):1361-1367.