Vitamin C

Vitamin C (ascorbate) promotes TETs to catalyze the hydroxylation of 5mC to 5hmC as a cofactor of TETs.

From: Nutritional Epigenomics , 2019

Vitamin C

Larry R. Engelking , in Textbook of Veterinary Physiological Chemistry (Third Edition), 2015

Abstract:

Vitamin C is a powerful reducing agent that participates in several important hydroxylation reactions. Na+-coupled transporters help to facilitate entry of vitamin C into cells. Glial cells in the brain regenerate vitamin C from DHA. Vitamin C is needed for collagen, carnitine, catecholamine, and bile acid biosynthesis. Oxalate is a natural degradation product of vitamin C. Vitamin C uses Fe++ and Cu++ as cofactors, and it enhances intestinal Fe++ absorption. Vitamin C deficiency can result in "scurvy." Although most mammals can synthesize vitamin C from glucose, it cannot be formed in primates, fish, flying mammals, songbirds, or the guinea pig. Vitamin C is a natural preservative added to pet food products

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Vitamin C

Robert B. Rucker , Francene Steinberg , in Encyclopedia of Biological Chemistry, 2004

Defining Ascorbic Acid Status

The requirements for vitamin C in humans (given as the range for female–male and expressed as the recommended dietary allowance, RDA or adequate uptake, AI) are as follows: infants, 40 mg per day (AI based on what is present in human milk); children (3–13 years), 15–45 mg per day (extrapolated from the RDA for adults); adolescence, 45–65 mg per day; adults (>19 years), 75–90 mg per day; lactating mothers, 115–120 mg per day. In keeping with these estimates, more recent clinical investigations have noted vitamin C deficiency in 2–6% of individuals surveyed (often defined as individuals meeting less than two-thirds of the RDA). With regard to marginal vitamin C status based on plasma ascorbic acid values, e.g., <20 μg/dL, the prevalence ranges from 17 to 24% US. In this regard, smokers are more likely to have marginal vitamin C status compared to nonsmoking adults. Several studies suggest that smokers require over 200 mg vitamin C daily to maintain plasma vitamin C concentrations at a level equivalent to that of nonsmokers.

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Vitamin C

Martin Kohlmeier , in Nutrient Metabolism, 2003

Nutritional summary

Function: Vitamin C is essential for gums, arteries, other soft tissues, and bone (collagen synthesis), for brain and nerve function (neurotransmitter and hormone synthesis), for nutrient metabolism (especially iron, protein, and fat), and for antioxidant defense (directly and by reactivating vitamin E) against free radicals (free radicals increase the risk of cancer and cardiovascular disease).

Food sources: Many fruits and vegetables provide at least 20% of the recommended daily intake per serving; citrus fruits, berries, and tomatoes are especially rich sources. Prolonged storage, extensive processing, and overcooking greatly diminish vitamin C content of foods.

Requirements: Adult women should get at least 75 mg/day, men at least 90 mg/day (Food and Nutrition Board Institute of Medicine, 2000). Age over 50, smoking, strenuous exercise, heat, infections, and injuries each may increase needs.

Deficiency: Scurvy (symptoms include painful swelling and bleeding into gums, joints, and extremities, poor wound healing, fatigue, and confusion) has become rare in most countries; 10 mg/day prevent it. Lower than optimal intake may diminish immune function and wound healing, and increase the risk of heart disease and cancer, especially in susceptible individuals. If intakes are low, stores last only a few weeks.

Excessive intake: Daily doses of 2000 mg or more may irritate stomach and bowels, cause kidney stones, and interfere with copper status.

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Vitamin C

F.M. Steinberg , R.B. Rucker , in Encyclopedia of Biological Chemistry (Second Edition), 2013

Abstract

Ascorbic acid (vitamin C) is an important redox cofactor in plant and animal systems. Most animals make sufficient ascorbic acid; however, for those that lack the enzyme necessary for synthesis, ascorbic acid is a true vitamin. A deficiency causes the disease scurvy in humans, characterized by impairments in growth, extracellular matrix, and hormonal regulation. Ascorbic acid carries out mono- and dioxygenase reactions by free-radical-dependent mechanisms. Ascorbate metabolism is linked to that of glutathione. Data suggest that optimal intakes of ascorbic acid should be 75–90  mg d−1 for adult humans, and possibly higher in some circumstances.

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Vitamin C

I.W. Jennings M.R.C.V.S. , in Vitamins in Endocrine Metabolism, 1970

Pituitary

The amount of vitamin C in the pituitary is relatively high, but its function there is not known. Experimentally, the content of vitamin C can be depleted by injections of hypothalamic extracts in the rat. In this animal, there is a sex difference in tissue ascorbate content, and hypophysectomy in the male rat reduces tissue levels to those characteristic of the female. It is assumed that this sex variation is dependent on differences in liver biosynthetic enzyme activities, themselves under the control of pituitary-stimulated testicular androgens.

Thyroid

Experimental hyperthyroidism reduces tissue concentrations and increases requirements for ascorbic acid. In experimental deficiency in guineapigs there is haemorrhagic infiltration of the gland (or bleeding from capillaries in the gland), particularly in acute scurvy. In chronic scurvy the gland becomes hyperplastic and hypersecretory. All three changes are reversible by restoration of dietary ascorbate to an adequate level.

The Adrenal Cortex

The adrenal cortex is rich in vitamin C where its presence can be demonstrated by chemical, histochemical or biological methods. In the rat the ascorbate level may reach 400–450 mg/100 gms as compared with 1.5 mg in plasma, 35 mg in the lung, or 60 mg in the spleen. The adrenal ascorbate content is greater in animals able to synthesise it, than in those animals which require exogenous supplies of preformed vitamin. It is present chiefly in the zona fasciculata and the zona reticularis, in association with the mitochondria, mainly as ascorbic acid—there is very little detectable dehydroascorbic acid present.

In spite of the great amount of work being done on corticosteroids there is as yet no definite knowledge of the role of vitamin C in the adrenal cortex, and at the moment one can only assume that the two forms of the acid are involved in oxidation and reduction reactions as hydrogen acceptors and donors.

Stimulation of the adrenal cortex by ACTH or by adrenalin leads to depletion of both ascorbic acid and cholesterol. Depletion of the former has been used in countless experiments as an index of the effect of various stressful stimuli, such as infectious diseases, physical trauma, and reaction to shock of various kinds. The autonomic nervous system does not appear to play any direct rôle in depleting the hormonal or ascorbate content of the cortex.

ACTH exerts its secretory effect on the two inner zones of the cortex, the outer zone, or zona glomerulosa being largely independent of hypophyseal control. With the electron microscope, cells can be seen to respond to ACTH stimulation by increase in the number and size of mitochondria and by a decrease in the number and size of lipid vacuoles in which it is assumed that formed cortical hormones are discharged from the cell. A sustained increase in the level of ACTH stimulation induces a sustained increase in the rate of hormonal production and a rise in the level of the pyridine nucleotides which have a coenzymatic rôle in the hydroxylation of steroid molecules. There is a simultaneous rise in the content of enzymes and co-enzymes required for the energy-yielding systems of the cells. However, if the stressful stimulus is unduly prolonged or excessive, a state of adrenal exhaustion supervenes, with complete depletion of ascorbate. Mitochondria become reduced in size and number. This is associated, in prolonged depletion, with haemorrhage into the gland due to capillary fragility, when the supporting framework of the adrenal blood vessels is no longer able to contain the pressure of the circulating blood. This is assumed to be due to inability to synthesize collagen to maintain the structural integrity of the capillaries. Although the turnover of new collagen is relatively low in the adult, it is an important and continuing process in infants. In the aged too, there is a requirement in blood vessels for new collagen to reinforce walls weakened by the depolymerization of old collagen, which is an inevitable aging process.

In old age there is decreased cortical response to the ACTH stimulus.

This can be restored to a certain extent by administration of ascorbic acid, which causes a rise in blood 17-hydroxysteroids and in excreted urinary 17-ketosteroids. The connection between ascorbic acid and steroid hormone synthesis is therefore marked, but not as yet understood.

Adrenal Medulla

A high concentration of vitamin C is found in the medulla of mammals. It is present in the form of dehydroascorbic acid, and is one of the cofactors required in the enzymatic catalysis of dihydroxyphenylethylamine to noradrenalin, thus:

3,4 dihydroxyphenylethylamine + ascorbate + O2 → noradrenalin + dehydroascorbate + H2O

The enzyme concerned, Dopamine hydroxylase (1.14.2.1) has been isolated from bovine adrenal glands, and has been shown to be a copper containing protein. During the reaction part of the protein-bound copper undergoes cyclic reduction and oxidation. The enzyme (E) is first reduced by ascorbate.

The reduced form then reacts with oxygen

and the substrate (RH)

to give the hydroxylated product; in this case, dihydroxyphenylethylamine (RH) is converted to noradrenalin. The protein-bound copper is also reoxidised to the Cu++ state during this reaction. The function of ascorbate therefore in catecholamine synthesis is to reduce the essential metal on the enzyme so that the reduced enzyme may mediate in the hydroxylation reaction (Friedman and Kaufman, 1966).

The Gonads

Vitamin C is present in high concentration in the interstitial cells of the testis and in the ovary.

There is a sex difference in the activities of the liver enzymes responsible for ascorbate synthesis in the rat, manifested as a much greater activity in the male, with concomitant higher level of ascorbate in the tissues. One of the enzymes, gulonolactone hydrolase, which is activated by growth hormone, is much reduced in activity in the hypophysectomized animal, with resulting decrease in tissue ascorbate levels in both sexes.

Hypophysectomy in the male rat decreases the activities of gulonolactone hydrolase, gulonate NADP reductase, and gulonolactone oxygen oxidoreductase to the levels characteristic of female rats. Castration of male rats leads to a reduction in activity of all three enzymes to the female level. It seems therefore that the higher tissue levels of ascorbic acid are dependent on the rate of hepatic biosynthesis, which in turn is kept at a high level in the male rat by the stimulatory effect of testicular androgens (Stubbs, McKernan and Haufrect, 1967).

Stimulation of the rabbit ovary by gonadotropin causes a rapid and marked decrease in ovarian interstitial cell ascorbate content, suggesting a correlation between ascorbate level and oestrogenic hormone production. The decrease is followed by a moderate compensatory increase in ascorbate content.

Gonadotropic stimulation of the corpus luteum of pregnancy likewise causes a rapid decrease in ascorbate content, followed by a pronounced rise. This also suggests an association between vitamin C and steroid production (Hökfelt, 1950).

However, increased production of hormone in non-steroid producing glands, such as the anterior lobe of the pituitary, is also associated with decreased ascorbate content, which may perhaps reflect increased activity of the gland. Much work remains to be done on this problem.

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AGING – NUTRITIONAL ASPECTS

N.P. Hays , S.B. Roberts , in Encyclopedia of Food Sciences and Nutrition (Second Edition), 2003

Vitamin C

Vitamin C has three main roles in human metabolism – enyzme cofactor, chemical reductant, and antioxidant. Although the 2000 DRI for vitamin C is increased compared with the previous RDA value, recent research has provided evidence that the currently recommended intake of vitamin C may still be too low for all age groups, including elderly persons. For the same vitamin C intake, elderly persons have lower circulating levels compared with young adults, perhaps because of either impaired absorption of vitamin C from the gut or impaired reabsorption from the kidney. Recent studies examining vitamin C bioavailability, urinary excretion, and steady-state plasma vitamin C concentration as a function of dose suggest that the recommended vitamin C intake should be increased from 90  mg (for men) and 75   mg (for women) to 120   mg per day. Although preliminary studies indicate that even higher doses of vitamin C may prevent low-density lipoprotein oxidation, may improve wound healing, and are inversely correlated with blood pressure in elderly persons, results are inconsistent and further research is needed.

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Potential Role of Vitamin C in the Prevention of Alzheimer's Disease

Kazuma Murakami PhD , ... Takahiko Shimizu PhD , in Diet and Nutrition in Dementia and Cognitive Decline, 2015

Summary Points

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VC, high in citrus fruits and vegetables, is effective as an antioxidant in biological fluids due to its water solubility, and it plays a well-known role in ameliorating cell damage by neutralizing ROS.

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VC supplementation can maintain memory function and reduce dementia and cognitive decline in AD patients.

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VC in combination with vitamin E is neuroprotective in minimizing the risk for AD.

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Low levels of VC and SOD were correlated with a dementia status, suggesting that SOD might be an indicator of vulnerability as an antioxidant enzyme in dementia, including AD.

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The ratio of VC in CSF to VC in plasma can predict the onset of cognitive decline in AD patients.

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VC mitigated the increased Aβ oligomer associated with behavioral abnormality in AD mice.

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VC recovered protein carbonylation and glutathione decline found in AD mice.

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VC rescued the downregulation of SOD1 in AD mice.

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Antioxidants in HIV in Africa

Germaine S. Nkengfack Nembongwe , Heike Englert , in HIV/AIDS, 2018

Vitamin C

Vitamin C also known as ascorbic acid is a water soluble vitamin found mostly in fruits and vegetables. The rich sources of vitamin C in African food are mostly fresh fruits and vegetables (oranges, lime, lemon, tangerine, guava grapefruits, mango, kiwano, lettuce, amaranth, spinach, pepper varieties, cabbage, tomato, potatoes, etc.). However, due to its high sensitivity to heat and light, in addition to the long preparation methods in Africa—partly for hygienic purposes— most of the water soluble vitamins including vitamin C is lost before consumption. The most available sources of vitamin C in the African diet are in fresh fruits. Also, a variety of fruit and vegetable juices consumed in Africa are fortified with vitamin C and therefore constitutes a rich source of this nutrient. Vitamin C, like most other water soluble vitamins, is very sensitive to atmospheric conditions such as heat and light and already mentioned, thus caution should be taken when preparing vitamin C-rich food. For example, vegetables should be washed before slicing, and not overcooked to reduce vitamin C loss. Other factors affecting vitamin C content of food is duration and period of storage, duration of transport from farm to market and harvesting season The longer the storage and transport time, the more the loss in vitamin C. 44

Vitamin C is the first line of antioxidants defense in the plasma, capable of protecting the body against superoxide, hydrogen peroxide, and hydroxyl radicals. Vitamin C does this by capturing peroxide radical from the hydrophilic phase before starting the lipid peroxidation. In this way, vitamin C and vitamin E prevent the peroxidation of the biomembranes. Besides being capable of regenerating vitamin E, vitamin C also acts as an antioxidant.

Increased use of vitamin C coupled with low dietary intake can lead to vitamin C deficiency during an HIV infection. 34,45 Studies suggest that high doses of vitamin C in HIV can mildly improve clinical parameters such as CD4 cell count and viral load. Thus enhance immune function and protect blood cells from ROS. 9,45 Another study in Tanzania shows that a combination of vitamin C and vitamin E could protect red blood cells from ROS. 46

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Topical Skin Care and the Cosmetic Patient

Patricia K. Farris MD , in Master Techniques in Facial Rejuvenation (Second Edition), 2018

Vitamin C

Vitamin C, or L-ascorbic acid, is a water-soluble antioxidant that is a popular cosmeceutical ingredient [17]. Topical application of vitamin C prior to UV exposure confers photoprotection against sunburn and UV-induced immunosuppression [18]. In addition, vitamin C acts as a cofactor for lysyl and prolyl hydroxylase, the enzymes responsible for the synthesis of collagen. Clinical studies confirm that consistent use of topical vitamin C improves skin wrinkling and gives it a more youthful appearance [19]. Vitamin C inhibits tyrosinase and reduces melanin, making it an effective skin-lightening agent. Vitamin C is also an effective anti-inflammatory compound and has been evaluated in the postprocedure setting. Clinical studies have demonstrated that topical vitamin C significantly reduces postcarbon dioxide (CO2) laser resurfacing erythema [20].

Products containing vitamin C in combination with other antioxidants have been shown to provide added benefits when compared with vitamin C alone. Topical application of vitamin C plus vitamin E confers greater photoprotection than either ingredient alone, whereas a formulation containing vitamin C, E, and the botanical antioxidant ferulic acid provided eight times the photoprotection of vitamin C alone [21]. Combination antioxidants have also been looked at in the postprocedure setting. In a split-face, double-blind, vehicle-controlled study, patients were treated with vitamin C, E, and ferulic acid (CEferulic, SkinCeuticals, New York, USA) or vehicle immediately after fractionated CO2 resurfacing. The antioxidant combination resulted in less edema and erythema when compared with vehicle control (Fig. 5.1) [22].

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Inflammatory Bowel Disease

Alyssa M. Parian MD , ... Amy C. Brown PhD , in Integrative Medicine (Fourth Edition), 2018

Vitamin C

Vitamin C or ascorbic acid is an essential water-soluble vitamin that has been found to be low in IBD patients, at least partially due to inadequate intake. 50,52,56 More than 50% of Crohn's patients have been reported to be vitamin C deficient. 56 The wound-healing effects of vitamin C are particularly important. 88 Although excess vitamin C is not life threatening because it is water soluble, high levels may cause diarrhea, nausea, vomiting, abdominal pain, and oxalate kidney stones. Excessive repletion of vitamin C (i.e., intravenous infusions) has not been shown to have any proven health benefits and is not recommended.

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