Vitamin C

What is Vitamin C?

Vitamin C or L-ascorbic acid is an essential nutrient for humans, in which it functions as a vitamin. Ascorbate (an ion 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; notable mammalian exceptions are most or all of the order chiroptera (bats), and the entire suborder Anthropoidea (Haplorrhini) (tarsiers, monkeys and apes). It is also needed by guinea pigs and some species of birds and fish. Deficiency in this vitamin causes the disease scurvy in humans. It is also widely used as a food additive.

The pharmacophore of vitamin C is the ascorbate ion. In living organisms, ascorbate is an anti-oxidant, since it protects the body against oxidative stress, and is a cofactor in several vital enzymatic reactions. Ascorbic acid was finally isolated in 1933 and synthesized in 1934.

The uses and recommended daily intake of vitamin C are matters of on-going debate, with RDI ranging from 45 to 95 mg/day. Proponents of megadosage propose from 200 to upwards of 2000 mg/day. A recent meta-analysis of 68 reliable antioxidant supplementation experiments, involving a total of 232,606 individuals, concluded that consuming additional ascorbate from supplements may not be as beneficial as thought.

Vitamin C is purely the L-enantiomer of ascorbate; the opposite D-enantiomer has no physiological significance. Both forms are mirror images of the same molecular structure. When L-ascorbate, which is a strong reducing agent, carries out its reducing function, it is converted to its oxidized form, L-dehydroascorbate. L-dehydroascorbate can then be reduced back to the active L-ascorbate form in the body by enzymes and glutathione. During this process semidehydroascorbic acid radical is formed. Ascorbate free radical reacts poorly with oxygen, and thus, will not create a superoxide. Instead two semidehydroascorbate radicals will react and form one ascorbate and one dehydroascorbate. With the help of glutathione, dehydroxyascorbate is converted back to ascorbate. The presence of glutathione is crucial since it spares ascorbate and improves antioxidant capacity of blood. Without it dehydroxyascorbate could not convert back to ascorbate.

L-ascorbate is a weak sugar acid structurally related to glucose which naturally occurs either attached to a hydrogen ion, forming ascorbic acid, or to a metal ion, forming a mineral ascorbate.

Biosynthesis

The vast majority of animals and plants are able to synthesize their own vitamin C, through a sequence of four enzyme-driven steps, which convert glucose to vitamin C. In reptiles and birds the biosynthesis is carried out in the kidneys.

Among the animals that have lost the ability to synthesise vitamin C are simians (specifically the suborder haplorrhini, which includes humans), guinea pigs, a number of species of passerine birds (but not all of them—there is some suggestion that the ability was lost separately a number of times in birds), and many (probably all) major families of bats, including major insect and fruit-eating bat families. 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 defective form of the gene for the enzyme (Pseudogene ΨGULO).

Some of these species (including humans) are able to make do with the lower levels available from their diets by recycling oxidised vitamin C.

Most simians consume the vitamin in amounts 10 to 20 times higher than that recommended by governments for humans. 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.

An adult goat, a typical example of a vitamin C-producing animal, will manufacture more than 13 g of vitamin C per day in normal health and the biosynthesis will increase "many fold under stress". Trauma or injury has also been demonstrated to use up large quantities of vitamin C in humans.

Some microorganisms such as the yeast ''Saccharomyces cerevisiae'' have been shown to be able to synthesize vitamin C from simple sugars.

Vitamin C in evolution

Venturi and Venturi suggested that the antioxidant action of ascorbic acid developed firstly in plant kingdom when, about 500 Mya, plants began to adapt to mineral deficient fresh-waters of estuary of rivers. Some biologists suggested that many vertebrates had developed their metabolic adaptive strategies in estuary environment. In this theory, some 400-300 million years ago when living plants and animals first began the move from the sea to rivers and land, environmental iodine deficiency was a challenge to the evolution of terrestrial life. In plants, animals and fishes, the terrestrial diet became deficient in many essential marine micronutrients, including iodine, selenium, zinc, copper, manganese, iron, etc. Freshwater algae and terrestrial plants, in replacement of marine antioxidants, slowly optimized the production of other endogenous antioxidants such as ascorbic acid, polyphenols, carotenoids, flavonoids, tocopherols etc., some of which became essential “vitamins” in the diet of terrestrial animals (vitamins C, A, E, etc.).

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 (Hardie et al.,1991). 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 haemorrhage, spinal curvature and increased mortality.

If these fishes are housed in seawater with algae and phytoplankton, then vitamin supplementation seems to be less important, presumably because of the availability of other, more ancient, antioxidants in natural marine environment.

Some scientists have suggested that the loss of human ability to make vitamin C may have caused a rapid simian evolution into modern man. However, the loss of ability to make vitamin C in simians must have occurred much further back in evolutionary history than the emergence of humans or even apes, since it evidently occurred sometime after the split in the Haplorrhini (which cannot make vitamin C) and its sister clade which retained the ability, the Strepsirrhini ("wet-nosed" primates). These two branches parted ways about 63 million years ago (Mya). Approximately 5 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. 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 evolutionary loss of the ability to break down uric acid. 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.

Absorption, transport, and disposal

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 imported the reduced form of ascorbate across plasma membrane. GLUT1 and GLUT3 are the two glucose transporters and only transfer dehydroascorbic acid form of Vitamin C. 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. 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, Knockout animals for SVCT2 die shortly after birth, 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 (12g), fractional human absorption of ascorbic acid may be as low as 16%; at low intake (<20 mg) the absorption rate can reach up to 98%. 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 half-life for the remainder of the vitamin C store in the body increases greatly, with the half-life lengthening as the body stores are depleted.

Although the body's maximal store of vitamin C is largely determined by the renal threshold for blood, there are many tissues which 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.

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 which 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.

Deficiency

Scurvy is an avitaminosis resulting from lack of vitamin C, since without this vitamin, the synthesised collagen is too unstable to perform its function. Scurvy leads to the formation of liver 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,

Nobel prize winner Linus Pauling and Dr. G. C. Willis have asserted that chronic long term low blood levels of vitamin C (chronic scurvy) is a cause of atherosclerosis.

Western societies generally consume 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, which is higher than the RDA recommendation. In human dietary studies, all obvious symptoms of scurvy previously induced by extremely low vitamin C intake, can be reversed by vitamin C supplementation as small as 10 mg a day. However, needed vitamin C intake for dealing with infection or large amounts of tissue repair (such as in burns) is much higher than the minimal dose needed to reverse scurvy.

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Vitamin C Physiological Function

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;

Collagen, carnitine, and tyrosine synthesis, and microsomal metabolism

Ascorbic acid performs numerous physiological functions in human body. These functions include the synthesis of collagen, carnitine and neurotransmitters, the synthesis and catabolism of tyrosine and the metabolism of microsome. Ascorbate acts as a reducing agent (i.e. electron donor, anti-oxidant) in the above-described syntheses, maintaining iron and copper atoms in their reduced states.

Vitamin C acts as an electron donor for eight different enzymes: 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 making vitamin C essential to the development and maintenance of scar tissue, blood vessels, and cartilage.

  • 2 are necessary for synthesis of carnitine. Carnitine is essential for the transport of fatty acids into mitochondria for ATP generation.
  • The remaining three have the following functions in common but do not always do this:
    • dopamine beta hydroxylase participates in the biosynthesis of norepinephrine from dopamine.
    • another enzyme adds amide groups to peptide hormones, greatly increasing their stability.
    • one modulates tyrosine metabolism.

Antioxidant

Ascorbic acid is well known for its antioxidant activity. Ascorbate acts as a reducing agent to reverse oxidation in aqueous solution. When there are more free radicals (Reactive oxygen species) in the body versus antioxidant, a human is under the condition called Oxidative stress. Oxidative stress induced diseases encompass cardiovascular diseases, hypertension, chronic inflammatory diseases and diabetes The plasma ascorbate concentration in oxidative stress patient (less than 45 µmol/L) measured is lower than healthy individual (61.4-80 µmol/L) According to McGregor and Biesalski (2006). This reaction can generate superoxide and other ROS. However, in the body, free transition elements are unlikely to be present while iron and copper is bound to diverse proteins. thus, ascorbate as a pro-oxidant is unlikely to convert metals to create ROS in vivo.

Immune system

Some advertisements claim that Vitamin C "supports" or is "important" for immune system function. These claims are partially supported by the scientific evidence (see Chandra RK, 1997, "Nutrition and the immune system: an introduction". The American Journal of Clinical Nutrition 66 (2): 460S–463S. PMID 9250133.)

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Vitamin C Daily Requirements

The North American Dietary Reference Intake recommends 90 milligrams per day and no more than 2 grams per day (2000 milligrams per day). Other related species sharing the same inability to produce vitamin C and requiring exogenous vitamin C consume 20 to 80 times this reference intake.

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. It is generally agreed that a balanced diet without supplementation 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.

United States vitamin C recommendations

  • 60 mg/day: Health Canada 2007
  • 60–95 milligrams per day: United States' National Academy of Sciences.
  • 500 milligrams per 12 hours: Professor Roc Ordman, from research into biological free radicals.
  • 3,000 milligrams per day ''(or up to 30,000 mg during illness)'': the Vitamin C Foundation.
  • 6,000–12,000 milligrams per day: Thomas E. Levy, Colorado Integrative Medical Centre.
  • 6,000–18,000 milligrams per day: Linus Pauling's personal use.

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Vitamin C" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.