h. How is this vitamin absorbed in the body? If it is stored in the body, identify the storage location (organs, tissues, etc.).
Vitamin C is stored throughout body tissues and blood. Ascorbic acid content of blood components, fluid, and tissue varies widely on an individual basis.
Absorption and BioavailabilityTransport of vitamin C is a saturable and dose dependent process that occurs by active transport. At the intestine and cells AA is oxidized to DHAA, which is more quickly transported across the cell membrane. Once inside the tissue or intestinal epithelium the vitamin is reduced back to AA. | The degree of intestinal absorption decreases as intake of AA increases. Intakes of 1 to 1.5 grams results in 50% absorption, but at intakes over 12 grams only 16% of the vitamin is absorbed. In contrast, an intake of less than 20 mg, has a 98% absorption rate (13). Absorption of vitamin C is greater when several individual doses of vitamin C, in quantities less than one gram, are taken throughout the day rather than one megadose (17). Eighty to ninety-five percent of the vitamin C found in foods is absorbed (13). Furthermore, the bioavailability of synthetic and "natural" forms of the vitamin differ very little despite the claims made by manufacturers (13,17). Vitamin C absorption can be impaired by a number of factors. A single large dose saturates the enzyme kinetics for vitamin C, leading to excess AA in the intestinal lumen, which causes numerous gastrointestinal problems. Pectin and zinc also inhibit AA absorption, but this mechanism is not well understood. A high iron concentration in the gastrointestinal tract may cause oxidative destruction and in turn impair uptake (13).
TransportActive transport is the main mechanism of vitamin C distribution within the body. Simple diffusion may occur in the mouth and stomach but accounts for only a very small percentage of uptake (13). Sodium-independent transport systems shuttle vitamin C across the basolateral membrane of the intestinal cells. In the plasma absorbed ascorbic and dehydroascorbate (DHAA) can either be transported freely or be bound to albumin. Ascorbate can also move into body cells and tissues (13). As previously mentioned DHAA is the primary form of vitamin C that crosses cellular membranes. The adrenal and pituitary glands, red blood cells, lymphocytes, and neutrophils all receive vitamin C in the form of DHAA (13,17).
StorageVitamin C is stored throughout body tissues and blood. Ascorbic acid content of blood components, fluid, and tissue varies widely on an individual basis. Tissue concentrations exceed those found in the plasma by three to ten times. Energy-driven transport pumps are responsible for the higher tissue concentrations of vitamin C versus the plasma. Both tissue and plasma levels of vitamin C are correlated to intake up to 90 mg / day (13). The total body pool of vitamin C has been estimated, using radiolabeled isotopes, to a maximum of 20 mg/kg body weight. This corresponds to a plasma AA concentration of 57 umol/L. Alternate techniques of measurement have estimated maximum total body AA stores to be 22 mg/kg (17). The pituitary glands, adrenal glands, and lens of the eye contain the highest vitamin C content (at least140umol/ 100 g wet weight) within the body (13,17). In contrast the saliva and plasma have the lowest AA content (17). Vitamin C content of cardiac tissue is between 28 and 85 ml/100g wet weight, while that in skeletal muscle is approximately 17 ml/100g wet weight (16). Other tissues with intermediate levels of vitamin C include the kidneys, brain, liver, lungs, and thyroid. The water-soluble properties of vitamin C prevent it from being stored in the adipose tissue of the body.
ExcretionThe average half-life of AA is believed to be between 16 and 20 days (17). Its half-life is inversely related to intake. The water-soluble properties of vitamin C lead to urinary excretion of the vitamin. Metabolites of vitamin C including dehydroascorbate (DHAA), oxalic acid, 2-O-methyl ascorbate, and 2-ketoascorbitol are also excreted from the body via the urinary system (13,17). The kidneys play a major role in vitamin C excretion and retention. DHAA and AA can be reabsorbed by the kidney tubules as long as body pool levels are equal to or less than 1500 mg. Levels within the body that are 1500 mg or less will result in no urinary excretion of vitamin C (13). As levels increase above 1500 mg the reabsorption efficiency of the kidneys decreases. Thus, body pool levels from 1500 to 3000 mg relate to tissue saturation of the vitamin (13). Plasma ascorbate levels between 0.8 and 1.4 mg/dl are considered the renal threshold. Above these levels, vitamin C will be excreted rather than reabsorbed by the kidneys (13).
Physiological RoleVitamin C has been studied for many years. It participates in numerous biochemical reactions, suggesting that vitamin C is important for every body process from bone formation to scar tissue repair (13). The only established role of the vitamin appears to be in curing or preventing scurvy. Vitamin C is the major water-soluble antioxidant within the body. The vitamin readily donates electrons to break the chain reaction of lipid peroxidation. The water-soluble properties of vitamin C allow for the quenching of free radicals before they reach the cellular membrane. Tocopherol and glutathione also rely on AA for regeneration back to their active isoforms. The relationship between AA and glutathione is unique. Vitamin C reduces glutathione back to the active form. Once reduced, glutathione will regenerate vitamin C from its DHAA or oxidized state. The prophylactic effects of vitamin C as an antioxidant during exercise, when free radical formation is high, will be discussed in future sections of this literature review. A well-known function of AA is the role it plays in hydroxylation reactions that are essential for the formation of collagen. Vitamin C is important in collagen formation as it allows for a tight cross-linking of the triple helix, thereby resulting in stabilization of the peptide. Evidence also suggests that AA may be involved in collagen gene expression. However, this mechanism is not well understood. Carnitine synthesis prefers to use vitamin C as the reducing agent (13). Carnitine facilitates the beta-oxidation of fat, through its role transporting long chain fatty acids from the cytoplasm into the mitochondrial matrix of cardiac and skeletal muscle. High concentrations of AA are found in adrenal and brain tissue where they are fairly resistant to AA depletion. Vitamin C is directly involved in the enzyme activity of two copper dependent mono-oxygenases, which are important in the formation of norepinephrine and serotonin (13,17). Furthermore, AA regulates the activity of some neurons within the brain. Some of these functions include neurotransmitter membrane receptor synthesis, and neurotransmitter dynamics. Indirectly, AA plays important regulatory roles throughout the entire body due to its involvement in the synthesis of hormones, hormone-releasing factors, and neurotransmitters (13). Animal models have also shown that AA is an important factor in development of the nervous system, specifically in the maturation of glial cells and myelin (17) Vitamin C is important to a host of numerous other functions within the body. The vitamin is an important aid in the absorption and conversion of iron to its storage form. Bile acid formation, and hence cholesterol degradation are highly dependent on AA. Some hypothesize that vitamin C may even have a hypocholesterolemic effect. This has been suggested because the enzyme needed for the first step in bile acid synthesis, cholesterol 7-alpha hydroxylase, is dependent upon the presence of vitamin C. Ascorbic acid may also has vasodilatory and anticlotting effects within the body by stimulating nitric oxide release. Physiological effects such as an antihistamine modified bronchial tone, and insulin responses have been linked to AA. The protection of neural and endothelial tissue, along with effects on cellular tone can also be attribute to vitamin C. Multiple other mechanisms of function for vitamin C have been proposed, but experimental results addressing these topics are variable. Possible other functions for vitamin C include regulation of cellular nucleotide concentrations, immune function, and the endocrine system. Vitamin C has been proposed by some to have pharmacological benefits in preventing cancer, infections, and the common cold. However, these benefits have yet to be reported in the scientific literature. The role of vitamin C in preventing cancer is controversial, but has been studied for cancers of the oral cavity, uterus, esophagus, bladder, and pancreas. The research is at best equivocal and more studies are needed to further address the role of vitamin C in preventing cancer.
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