Vitamin C

The term vitamin C applies to substances that possess antiscorbutic activity and includes two compounds and their salts: L-ascorbic acid, commonly called ascorbic acid, and L-dehydroascorbic acid.

Vitamin C is is an essential nutrient for humans, and for few animals. Most other animals, all higher plant species and probably all algal classes can synthesize vitamin C from glucose or other sugars. All vitamin C requiring animals lack the enzyme L-gulano-gamma-lactone oxidase, the final step in the synthesis of ascorbic acid from glucose.

Absorption of vitamin C from the lumen of the small intestine depends on the amount of dietary intake. At a dietary intake of 30 milligrams daily, the vitamin is nearly completely absorbed from the lumen of the small intestine into the enterocytes. At an intake of 30 to 180 milligrams daily, about 70% to 90% is absorbed. About 50% of a single dose of 1 to 1.5 grams is absorbed.
Once it is metabolized by small intestine, ascorbic acid are distrubuited to tissues. Higher levels of ascorbic acid are found in the pituitary gland, the adrenal glands, the various white blood cells and the brain.

In the diet fruits and vegetables supply the 90% of vitamin C. It's contained in green-leaf vegetables such as peppers, citrus friuts, brussels sprouts, cauliflower, cabbage, kale, kiwi, collards, mustard greens, broccoli, spinach and strawberries. Nuts and grains contain very little vitamin C. Cooking destroys vitamin C activity (it can destroy up to 75% of vitamin C conteined in foods).

The major deficiency syndrome of vitamin C is scurvy. This disease affects collagen and intercellular bound-cementing substance production. This leads to impaired blood vassels status resulting in hemorrhages, lowered speed of wound healing, swollen and bleeding gums, osteoporosis.
Generally, symptoms of scurvy include inflamed and bleeding gums, petechiae, ecchymosis, follicular hyperkeratosis, coiled hairs, perifollicular hemorrhages, impaired wound healing, dry eyes and mouth (Sjögren's syndrome), arthralgia, joint effusions, muscle weakness, myalgia, fatigue, depression, frequent infections, anemia, anorexia, diarrhea, and pulmonary and kidney problems that can lead to coma and death. All systems of the body are affected by scurvy.

Many of the symptoms of scurvy, particularly those having to do with connective tissue, can be explained by the known biochemical roles of vitamin C, particularly its role as a cofactor for prolyl and lysyl hydroxylase, enzymes important in the formation of collagen. Collagen synthetized in the absence of ascorbic acid—as occurs in scurvy—cannot properly form fibers, resulting in blood-vessel fragility, among other defects. In the prolyl and lysyl hydroxylase reactions, as well as in most of the biochemical reactions ascorbic acid participates of, it acts as a reducing agent. In these reactions  vitamin C reduces ferric and cupric ions to their ferrous and cuprous states forms which are required for the reactions to proceed.

Ascorbic acid is also involved in the biosynthesis of other connective tissue components, including elastin, fibronectin, proteoglycans, bone matrix and elastin-associated fibrillin. It also appears to play a role in collagen gene expression and cellular procollagen secretion.

The fatigue and weakness of scurvy may be due to L-carnitine deficiency. Ascorbic acid is a cofactor for crucial reactions in the carnitine biosynthetic pathway.

Ascorbic acid is involved in modulating iron absorption, transport and storage. It aids intestinal absorption of iron by reducing ferric iron to ferrous iron and may stimulate ferritin synthesis to promote iron storage in cells. It is involved in biosynthesis of corticosteroids, aldosterone, in turning cholesterol into bile acids, and plays as a reducing agent for mixed-function oxidases.

Vitamin C has an antioxidant activity. It may also have anti-atherogenic, anticarcinogenic, antihypertensive, antiviral, antihistaminic, immunomodulatory, opthalmoprotective and airway-protective actions. Vitamin C may aid the detoxification of some heavy metals, such as lead and other toxic chemicals.

Vitamin C is arguably the most important water-soluble biological antioxidant. It can scavenge both reactive oxygen species and reactive nitrogen species. Ascorbic acid or, more specifically, ascorbate is an excellent reducing agent, and it acts as a cofactor in various biochemical reactions to reduce the transition metals, iron and copper.

Ascorbate can be oxidized by most reactive oxygen and nitrogen species thought to play roles in tissue injury associated with various diseases.

The possible anti-atherogenic activity of vitamin C may be explained in a few ways. Oxidation of low-density lipoprotein (LDL) is thought to be a key early step in atherogenesis. Vitamin C protects against LDL peroxidation by scavenging peroxyl radicals in the aqueous phase. Vitamin C may enhance endothelial function by promoting the synthesis of nitric oxide (also known as NO and EDRF for endothelium-derived relaxing factor) or by preventing its inactivation by scavenging superoxide radicals. Superoxide reacts with nitric oxide to form peroxynitrite. High concentrations of vitamin C are required to prevent the interaction of superoxide with nitric oxide, extracellularly. Although such high plasma concentrations are feasible if vitamin C is given parenterally, they are likely not to occur with oral administration of vitamin C.

Increased oxidative stress to the gastric mucosa has been reported in Helicobacter pylori-associated gastritis, a condition that predisposes to gastric cancer. There is evidence that preliminary supplemental vitamin C can inhibit the growth of Helicobacter pylori in both in vitro and animal studies. Thus it might have the potential to reduce the incidence of H. pylori-induced ulcers and subsequent gastric carcinoma. In vitro high concentrations of vitamin C inhibited up to 90% of H. pylori growth. There was also significant inhibition of growth in animal experiments using oral administration of vitamin C.

Vitamin C possible anticarcinogenic effects may be accounted for its ability to detoxify carcinogens, as well as its ability to block carcinogenic processes through its antioxidant activity.
Evidence appears to suggest that vitamin C may have cancer-preventive activity, at least for certain types of cancer. However, the role of vitamin C, if any, in the treatment of cancer remains very unclear. A recent cell-culture study of human breast carcinoma lines showed vitamin C to improve the antineoplastic activity of doxorubicin, cisplatin and paclitaxel. The mechanism of the effect may be pro-oxidant, not antioxidant, activity of the vitamin in potentiating the effects of these chemotherapeutic agents. Another study suggests that the pro-oxidant form of vitamin C may upregulate some of the enzymes involved in DNA repair. This possible activity may play some anticarcinogenic role.
There are numerous epidemiological and case-control studies showing a consistent relationship between higher dietary intakes of vitamin C and lower incidence of cancer, particularly colon-rectal, stomach, lung, breast, esophageal, oral cavity and larynx-pharynx cancers. In one review of 75 epidemiologic studies, 54 found significant evidence of reduced cancer risk in those with higher dietary vitamin C intake.

There is some evidence that vitamin C inhibits the replication of human immunodeficiency virus 1 (HIV-1) in vitro. One study showed upregulation of the expression of glucose transporter 1 (Glut1) in HIV-infected cells Glut1 is one of the transport proteins for ascorbic acid. Increased cellular concentrations of ascorbate may be toxic to HIV-infected cells due to degradation of the viral nucleic acid by the action of the pro-oxidant form of vitamin C. The mechanism of the anti-HIV effect of the vitamin in vitro, however, is unclear, as is the relevance of this finding to HIV-positive individuals.

Because supplemental vitamin C was not shown, in several studies, to reduce the incidence of the common cold, many concluded that it was of no use whatever in colds. But in three trials with subjects under acute physical stress, vitamin C supplementation resulted in a 50% reduction in common cold incidence. And in four British trials, there was an average 30% reduction in incidence among those receiving vitamin C.

Vitamin C has also been found to be of benefit in patients with pneumonia and bronchitis.
The possible immunomodulatory activity of vitamin C may also be due, in part, to an antihistaminic effect.

It has also shown benefit in some with asthma.
Vitamin C may protect against asthma and other obstructive pulmonary diseases, as well as it may protect the airways against the effects of allergens, viral infections and irritants in some. Allergens, viruses and irritants, including ozone, nitrogen oxides and sulfur oxides, subject the airways to increased oxidative stress which can lead to bronchoconstriction. The possible protective action of vitamin C appears clearly due to its antioxidant properties.

Some studies suggest a protective effect of vitamin C supplementation against cataracts. Age-related lens opacities are thought to be due to oxidative stress. Ocular tissue concentrates vitamin C, and the antioxidant action of the vitamin could account for its possible effect in protection against cataracts.


The antioxidant properties of vitamin C can also account for its role in protecting against the tissue-damaging effect of some toxic chemicals and heavy metals.

On the other hand, vitamin C's antioxidant activity is marked and appears to play an important role in its possible cardioprotective activity. Several studies have shown that vitamin C, either alone, or in combination with other nutrients significantly inhibits LDL-cholesterol oxidation.
Vitamin C supplementation has also been shown, in some studies, to significantly reduce total serum cholesterol. Some others have not shown this benefit. And there have been several observational reports associating high plasma vitamin C concentrations with higher levels of HDL-cholesterol.

Platelet aggregation has been reduced in two studies utilizing 2,000-3,000 milligrams of vitamin C daily for one to six weeks. No effect was noted on platelets in another study using 250 milligrams of vitamin C daily for eight weeks. Leukocyte adhesion to endothelium, an activity implicated in atherogenesis, was significantly inhibited in smokers receiving 2,000 milligrams of vitamin C daily for ten days.

Several studies have shown that vitamin C has positive effects on hypertension. Here, too, there have been some conflicting results, but the preponderance of evidence suggests a positive effect. Epidemiological studies also consistently show that lower vitamin C intake is associated with hypertension. In one recent randomized, double-blind, placebo-controlled study, hypertensive patients received placebo or 500 milligrams of vitamin C daily for 30 days. Vitamin C resulted in a 13 mm Hg reduction in systolic blood pressure. Placebo had no effects.

Several other studies have shown that both oral administration (1,000-2,000 milligrams) and intra-arterial infusion with vitamin C can exert significant, positive effects on vasodilation in coronary artery disease patients. Similar benefits have been found in several other test groups, including smokers and those with both type 1 and type 2 diabetes.

Recently, serum ascorbic acid levels were found to be inversely related to prevalence of gall bladder disease among women but not among men.

In another recent study, this one a double-blind, placebo-controlled trial of vitamin C in patients with conservatively treated wrist fractures, treatment with 500 milligrams of vitamin C daily for 50 days significantly reduced the incidence of reflex sympathetic dystrophy (RSD). Followup continued for one year. The researchers proposed that "this simple and cheap means of prevention could also be useful in the prophylaxis of RSD after other injuries, such as trauma of the foot or ankle, talar and calcaneal fractures, or crural fractures."

It may be of benefit in some burn victims and may be helpful, generally, in promoting wound healing and gum health.
It was the use of vitamin C as an antioxidant therapy in dermal burns that led the researchers to believe that an antioxidant therapy might also be of benefit in preventing post-traumatic dystrophy (after wrist fracture). Researchers have found that vitamin C helps protect endothelial cells and reduces capillary permeability by reducing lipid peroxidation after burns. Some of these same mechanisms apparently account for reported beneficial effects of vitamin C in a variety of wounds, in addition to burns. There is some evidence that supplemental vitamin C may decrease permeability of gum surface tissue and may, by that and other mechanisms, help protect against periodontal gum disease.

VITAMIN C

Main Actions:	antioxidant, anti-atherogenic, anticarcinogenic, antihypertensive, antiviral, antihistaminic, immunomodulatory, opthalmoprotective and airway-protective, detoxifying
Main Uses:	chronic diseases due to oxidant damage of body moleculed cardiovascular diseases and cancer colds, respiratory infections, asthma cataracts H. pyolri-induced ulcers and gastric carcinomas gallbladder disorders in women wounds, burns, healthy gums
Standard Dosage:	The minimum dosage to avoid scurvy is equivalent to 10 mg daily. Yet, the recommended minimum dosage is between 45 mg and 2 g daily; however: smokers should take twice as minimum daily dosage pregnant women should take 10 mg more than minimum daily dosage nursing mothers should take 30 mg more than minimum daily dosage
Contraindications:	Vitamin C is contraindicated in those with known hypersensitivity to the substance or to any ingredient in a vitamin C-containing product. Pregnant women and nursing mothers should avoid using supplemental doses of vitamin C higher than RDA amounts Those with preexisting kidney stone disease or a history of renal insufficiency, defined as serum creatine greater than 2 and/or creatinine clearance less than 30, should exercise caution in the use of higher than RDA amounts of vitamin C Those with hemochromatosis, thalassemia, sideroblastic anemia, sickle cell anemia and erythrocyte G6PD deficiency shouldn't exceed RDA amounts of vitamin C Large amounts of vitamin C (more than 10g) can lead to gastrointestinal disorders, such as nausea, abdominal cramps, diarrhea and flatulent distention.
Drug Interactions:	The intake of a large dosage of vitamin C used at the same time as aluminum-containing antacids has been reported to increase urinary aluminum excretion, suggesting increased aluminum absorption from these antacids Chronic use of high dose aspirin may lead to impaired vitamin C status Vitamin C may potentiate the antineoplastic activity of some chemotherapeutic agent

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