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Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin that is naturally present in some foods, added to others, and available as a dietary supplement. Humans, unlike most animals, are unable to synthesize vitamin C endogenously, so it is an essential dietary component [1].
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Vitamin C is required for the biosynthesis of collagen, L-carnitine, and certain neurotransmitters; vitamin C is also involved in protein metabolism [1,2]. Collagen is an essential component of connective tissue, which plays a vital role in wound healing. Vitamin C is also an important physiological antioxidant [3] and has been shown to regenerate other antioxidants within the body, including alpha-tocopherol (vitamin E) [4]. Ongoing research is examining whether vitamin C, by limiting the damaging effects of free radicals through its antioxidant activity, might help prevent or delay the development of certain cancers, cardiovascular disease, and other diseases in which oxidative stress plays a causal role. In addition to its biosynthetic and antioxidant functions, vitamin C plays an important role in immune function [4] and improves the absorption of nonheme iron [5], the form of iron present in plant-based foods. Insufficient vitamin C intake causes scurvy, which is characterized by fatigue or lassitude, widespread connective tissue weakness, and capillary fragility [1,2,4,6-9].
The intestinal absorption of vitamin C is regulated by at least one specific dose-dependent, active transporter [4]. Cells accumulate vitamin C via a second specific transport protein. In vitro studies have found that oxidized vitamin C, or dehydroascorbic acid, enters cells via some facilitated glucose transporters and is then reduced internally to ascorbic acid. The physiologic importance of dehydroascorbic acid uptake and its contribution to overall vitamin C economy is unknown.
The total body content of vitamin C ranges from 300 mg (at near scurvy) to about 2 g [4]. High levels of vitamin C (millimolar concentrations) are maintained in cells and tissues, and are highest in leukocytes (white blood cells), eyes, adrenal glands, pituitary gland, and brain. Relatively low levels of vitamin C (micromolar concentrations) are found in extracellular fluids, such as plasma, red blood cells, and saliva [4].
Intake recommendations for vitamin C and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine (IOM) of the National Academies (formerly National Academy of Sciences) [8]. DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and gender [8], include:
Table 1 lists the current RDAs for vitamin C [8]. The RDAs for vitamin C are based on its known physiological and antioxidant functions in white blood cells and are much higher than the amount required for protection from deficiency [4,8,11]. For infants from birth to 12 months, the FNB established an AI for vitamin C that is equivalent to the mean intake of vitamin C in healthy, breastfed infants.
Fruits and vegetables are the best sources of vitamin C (see Table 2) [12]. Citrus fruits, tomatoes and tomato juice, and potatoes are major contributors of vitamin C to the American diet [8]. Other good food sources include red and green peppers, kiwifruit, broccoli, strawberries, Brussels sprouts, and cantaloupe (see Table 2) [8,12]. Although vitamin C is not naturally present in grains, it is added to some fortified breakfast cereals. The vitamin C content of food may be reduced by prolonged storage and by cooking because ascorbic acid is water soluble and is destroyed by heat [6,8]. Steaming or microwaving may lessen cooking losses. Fortunately, many of the best food sources of vitamin C, such as fruits and vegetables, are usually consumed raw. Consuming five varied servings of fruits and vegetables a day can provide more than 200 mg of vitamin C.
The U.S. Department of Agriculture's (USDA's) FoodData Central lists the nutrient content of many foods and provides a comprehensive list of foods containing vitamin C arranged by nutrient content and by food name.
Supplements typically contain vitamin C in the form of ascorbic acid, which has equivalent bioavailability to that of naturally occurring ascorbic acid in foods, such as orange juice and broccoli [14-16]. Other forms of vitamin C supplements include sodium ascorbate; calcium ascorbate; other mineral ascorbates; ascorbic acid with bioflavonoids; and combination products, such as Ester-C, which contains calcium ascorbate, dehydroascorbate, calcium threonate, xylonate and lyxonate [17].
A few studies in humans have examined whether bioavailability differs among the various forms of vitamin C. In one study, Ester-C and ascorbic acid produced the same vitamin C plasma concentrations, but Ester-C produced significantly higher vitamin C concentrations in leukocytes 24 hours after ingestion [18]. Another study found no differences in plasma vitamin C levels or urinary excretion of vitamin C among three different vitamin C sources: ascorbic acid, Ester-C, and ascorbic acid with bioflavonoids [17]. These findings, coupled with the relatively low cost of ascorbic acid, led the authors to conclude that simple ascorbic acid is the preferred source of supplemental vitamin C [17].
Vitamin C status is typically assessed by measuring plasma vitamin C levels [4,14]. Other measures, such as leukocyte vitamin C concentration, could be more accurate indicators of tissue vitamin C levels, but they are more difficult to assess and the results are not always reliable [4,9,14].
Acute vitamin C deficiency leads to scurvy [7,8,11]. The timeline for the development of scurvy varies, depending on vitamin C body stores, but signs can appear within 1 month of little or no vitamin C intake (below 10 mg/day) [6,7,22,23]. Initial symptoms can include fatigue (probably the result of impaired carnitine biosynthesis), malaise, and inflammation of the gums [4,11]. As vitamin C deficiency progresses, collagen synthesis becomes impaired and connective tissues become weakened, causing petechiae, ecchymoses, purpura, joint pain, poor wound healing, hyperkeratosis, and corkscrew hairs [1,2,4,6-8]. Additional signs of scurvy include depression as well as swollen, bleeding gums and loosening or loss of teeth due to tissue and capillary fragility [6,8,9]. Iron deficiency anemia can also occur due to increased bleeding and decreased nonheme iron absorption secondary to low vitamin C intake [6,11]. In children, bone disease can be present [6]. Left untreated, scurvy is fatal [6,9].
Until the end of the 18th century, many sailors who ventured on long ocean voyages, with little or no vitamin C intake, contracted or died from scurvy. During the mid-1700s, Sir James Lind, a British Navy surgeon, conducted experiments and determined that eating citrus fruits or juices could cure scurvy, although scientists did not prove that ascorbic acid was the active component until 1932 [24-26].
Today, vitamin C deficiency and scurvy are rare in developed countries [8]. Overt deficiency symptoms occur only if vitamin C intake falls below approximately 10 mg/day for many weeks [5-8,22,23]. Vitamin C deficiency is uncommon in developed countries but can still occur in people with limited food variety.
Vitamin C inadequacy can occur with intakes that fall below the RDA but are above the amount required to prevent overt deficiency (approximately 10 mg/day). The following groups are more likely than others to be at risk of obtaining insufficient amounts of vitamin C.
Studies consistently show that smokers have lower plasma and leukocyte vitamin C levels than nonsmokers, due in part to increased oxidative stress [8]. For this reason, the IOM concluded that smokers need 35 mg more vitamin C per day than nonsmokers [8]. Exposure to secondhand smoke also decreases vitamin C levels. Although the IOM was unable to establish a specific vitamin C requirement for nonsmokers who are regularly exposed to secondhand smoke, these individuals should ensure that they meet the RDA for vitamin C [4,8].
Most infants in developed countries are fed breastmilk and/or infant formula, both of which supply adequate amounts of vitamin C [8,14]. For many reasons, feeding infants evaporated or boiled cow's milk is not recommended. This practice can cause vitamin C deficiency because cow's milk naturally has very little vitamin C and heat can destroy vitamin C [6,12].
Some medical conditions can reduce the absorption of vitamin C and/or increase the amount needed by the body. People with severe intestinal malabsorption or cachexia and some cancer patients might be at increased risk of vitamin C inadequacy [27]. Low vitamin C concentrations can also occur in patients with end-stage renal disease on chronic hemodialysis [28].
Due to its function as an antioxidant and its role in immune function, vitamin C has been promoted as a means to help prevent and/or treat numerous health conditions. This section focuses on four diseases and disorders in which vitamin C might play a role: cancer (including prevention and treatment), cardiovascular disease, age-related macular degeneration (AMD) and cataracts, and the common cold.
Epidemiologic evidence suggests that higher consumption of fruits and vegetables is associated with lower risk of most types of cancer, perhaps, in part, due to their high vitamin C content [1,2]. Vitamin C can limit the formation of carcinogens, such as nitrosamines [2,29], in vivo; modulate immune response [2,4]; and, through its antioxidant function, possibly attenuate oxidative damage that can lead to cancer [1].
Most case-control studies have found an inverse association between dietary vitamin C intake and cancers of the lung, breast, colon or rectum, stomach, oral cavity, larynx or pharynx, and esophagus [2,4]. Plasma concentrations of vitamin C are also lower in people with cancer than controls [2]. 041b061a72