Vitamin C (ascorbic acid)

Vitamin C, also known as ascorbic acid, is a water-soluble vitamin, which is essential for normal functioning of the body.

VITAMIN C

Vitamin C, also known as ascorbic acid, is a water-soluble vitamin, which is essential for normal functioning of the body. Unlike most mammals, humans do not have the ability to make their own vitamin C. We must therefore obtain vitamin C through our diet.

FUNCTION

Vitamin C is required for the synthesis of collagen, an important structural component of blood vessels, tendons, ligaments, and bone. Vitamin C also plays an important role in the synthesis of the neurotransmitter, norepinephrine. Neurotransmitters are critical to brain function and are known to affect mood. In addition, vitamin C is required for the synthesis of carnitine, a small molecule that is essential for the transport of fat to cellular organelles calledmitochondria, for conversion to energy (1).  Recent research also suggests that vitamin C is involved in the metabolism of cholesterol to bile acids, which may have implications for blood cholesterol levels and the incidence of gallstones(2).

Vitamin C is also a highly effective antioxidant. Even in small amounts vitamin C can protect indispensable molecules in the body, such as proteins, lipids (fats), carbohydrates, and nucleic acids (DNA and RNA) from damage by free radicals and reactive oxygen species that can be generated during normal metabolism as well as through exposure to toxins and pollutants (e.g. smoking). Vitamin C may also be able to regenerate other antioxidants such as vitamin E(1).

DEFICIENCY

Scurvy: Severe vitamin C deficiency has been known for many centuries as the potentially fatal disease, scurvy. By the late 1700’s the British navy was aware that scurvy could be cured by eating oranges or lemons, even though vitamin C would not be isolated until the early 1930’s. Symptoms of scurvy include bleeding and bruising easily, hair and tooth loss, joint pain and swelling. Such symptoms appear to be related to the weakening of blood vessels, connective tissue, and bone, which contain collagen. Early symptoms of scurvy such as fatigue may result from diminished levels of carnitine, needed to derive energy from fat, or decreased synthesis of the neurotransmitter norepinephrine (seeFunction). Scurvy is rare in developed countries because it can be prevented by as little as 10 mg of vitamin C daily (2). However, recent cases have occurred in children and the elderly on very restricted diets (4,5).

The RDA: In the U.S., the recommended dietary allowance (RDA) for vitamin C was recently revised upward from 60 mg daily for men and women. The RDA continues to be based primarily on the prevention of deficiency, rather than the prevention of chronic disease and the promotion of optimum health. The recommended intake for smokers is 35 mg/day higher than for nonsmokers, because smokers are under increased oxidative stress from the toxins in cigarette smoke and generally have lower blood levels of vitamin C (6).

Recommended Dietary Allowance (RDA) for Vitamin C
Life Stage Age Males (mg/day) Females (mg/day)
Infants 0-6 months 40 (AI) 40 (AI)
Infants 7-12 months 50 (AI) 50 (AI)
Children 1-3 years 15 15
Children 4-8 years 25 25
Children 9-13 years 45 45
Adolescents 14-18 years 75 65
Adults 19 years and older 90 75
Smokers 19 years and older 125 110
Pregnancy 18 years and younger 80
Pregnancy 19-years and older 85
Breastfeeding 18 years and younger 115
Breastfeeding 19 years and older 120

DISEASE PREVENTION

The amount of vitamin C required to prevent chronic disease appears to be more than that required simply for prevention of scurvy. Much of the information regarding vitamin C and the prevention of chronic disease is based on prospective studies, where vitamin C intake is assessed in large numbers of people who are followed over time to determine whether they develop specific chronic diseases.

Cardiovascular diseases (heart disease and stroke): Seven out of 12 prospective studies, which examined large numbers of people (700 to 87,000) over a number of years (3 to 20), found a significant relationship between higher levels of vitamin C intake and a lower risk of heart disease and stroke (1). The remaining studies, which did not find a relationship between vitamin C intake and cardiovascular diseases, compared individuals who were already consuming close to 100 mg daily with those consuming higher amounts. A careful experimental study at the NIH demonstrated that some human tissues (leukocytes) tend to become saturated with vitamin C at a dose of 100 mg/day(7). Thus, it is possible that once tissue saturation has been achieved, additional protective effects of vitamin C against cardiovascular diseases are small and therefore difficult to detect in prospective studies. Consistent with this possibility, at least 6 prospective studies have found low blood levels of vitamin C at baseline to be associated with a subsequent increase in the risk of heart disease or stroke (1,8). In a prospective study that followed more than 2,000 residents of a rural Japanese community for 20 years, the risk of stroke in those whose blood levels of vitamin C were in the highest quartile (1/4) was only 59% of those whose blood levels were in the lowest quartile (9). Additionally, the risk of stroke in those who consumed vegetables 6 to 7 days of the week was only 58 % of the risk in those who consumed vegetables 0 to 2 days of the week. The participants’ blood levels of vitamin C were highly correlated with their fruit and vegetable intake. Therefore, as in many studies of vitamin C intake and cardiovascular disease risk, it is difficult to separate the effects of vitamin C on stroke risk from the effects of other components of fruits and vegetables, emphasizing the benefits of a diet rich in fruits and vegetables.

Cancer: A large number of studies have shown that increased consumption of fresh fruits and vegetables is associated with a reduced risk for most types ofcancer (10). Such studies are the basis for dietary guidelines endorsed by the U.S. Department of Agriculture and the National Cancer Institute, which recommend at least 5 servings of fruits and vegetables per day. A number of case-control studies have investigated the role of vitamin C in cancer prevention.  Most have shown that higher intakes of vitamin C are associated with decreased incidence of cancers of the mouth, throat and vocal chords,esophagus, stomach, colon-rectum, and lung. Because the possibility of bias is greater in case control studies, prospective studies are generally given more weight in the evaluation of the effect of nutrient intake on disease.  In general, prospective studies in which the lowest intake group consumed more than 86 mg of vitamin C daily have not found differences in cancer risk, while studies finding significant cancer risk reductions found them in people consuming at least 80 to 110 mg of vitamin C daily (1).

A prospective study of 870 men over a period of 25 years found that those who consumed more than 83 mg of vitamin C daily had a striking 64% reduction in lung cancer compared with those who consumed less than 63 mg per day (11). Although most large prospective studies found no association between breast cancer and vitamin C intake, two recent studies found dietary vitamin C intake to be inversely associated with breast cancer risk in certain subgroups. In the Nurses’ Health Study, premenopausal women with a family history of breast cancer who consumed an average of 205 mg/day of vitamin C from foods had a 63% lower risk of breast cancer than those who consumed an average of 70 mg/day (12). In the Swedish Mammography Cohort, women who were overweight and consumed an average of 110 mg/day of vitamin C had a 39% lower risk of breast cancer compared to overweight women who consumed an average of 31 mg/day (13). A number of observational studies have found increased dietary vitamin C intake to be associated with decreased risk of stomach cancer, and laboratory experiments indicate that vitamin C inhibits the formation of carcinogenic compounds in the stomach. Infection with the bacteria, helicobacter pylori (H. pylori) is known to increase the risk of stomach cancer and also appears to lower the vitamin C content of stomach secretions. Although two intervention studies did not find a decrease in the occurrence of stomach cancer with vitamin C supplementation (6), more recent research suggests that vitamin C supplementation may be a useful addition to standard H. pylori eradication therapy in reducing the risk of gastric cancer (14).

Cataracts: Cataracts are a leading cause of blindness in the U.S. Cataracts occur more frequently and become more severe as people age. Decreased vitamin C levels in the lens of the eye have been associated with increased severity of cataracts in humans. Some, but not all, studies have observed increased dietary vitamin C intake (15) and increased blood levels of vitamin C(16) to be associated with decreased risk of cataracts. Those studies that have found a relationship suggest that vitamin C intake may have to be higher than 300 mg/day for a number of years before a protective effect can be detected (1). Recently, a 7-year controlled intervention trial of a daily antioxidant supplement containing 500 mg of vitamin C, 400 IU of vitamin E, and 15 mg of b-carotene in 4,629 men and women found no difference between the antioxidant combination and a placebo on the development and progression of age-related cataracts (17). Therefore, the relationship between vitamin C intake and the development of cataracts requires further clarification before specific recommendations can be made.

Lead toxicity: Although the use of lead paint and leaded gasoline has been discontinued in the U.S., lead toxicity continues to be a significant health problem, especially in children living in urban areas. Abnormal growth and development has been observed in infants of women exposed to lead during pregnancy, while children who are chronically exposed to lead are more likely to develop learning disabilities, behavioral problems, and to have low IQs. In adults, lead toxicity may result in kidney damage and high blood pressure. In a study of 747 older men, blood lead levels were significantly higher in those who reported total dietary vitamin C intakes averaging less than 109 mg/day compared to men who reported higher vitamin C intakes (18). A much larger study of 19,578 people, including 4,214 children from 6 to 16 years of age, found higher serum vitamin C levels to be associated with significantly lower blood lead level (19). An intervention trial that examined the effects of vitamin C supplementation on blood lead levels in 75 adult male smokers found that 1,000 mg/day of vitamin C resulted in significantly lower blood lead levels over a 4-week treatment period compared to placeb (20). A lower dose of 200 mg/day did not significantly affect blood lead levels, despite the finding that serum vitamin C levels were not different than those of the group that took 1,000 mg/day. The mechanism for the relationship between vitamin C intake and blood lead levels is not known, although it has been postulated that vitamin C may inhibit intestinal absorption or enhance urinary excretion of lead.

DISEASE TREATMENT

Cardiovascular diseases:

Vasodilation: The ability of blood vessels to relax or dilate is compromised in individuals with atherosclerosis.  The damage to the heart muscle caused by a heart attack and damage to the brain caused by a stroke is related, in part, to the inability of blood vessels to dilate enough to allow blood flow to the affected areas.  The pain of angina pectoris is also related to insufficient dilation of the coronary arteries.  Treatment with vitamin C has consistently resulted in improved dilation of blood vessels in individuals with atherosclerosis as well as those with angina pectoris, congestive heart failure, high cholesterol, and high blood pressure.  Improved blood vessel dilation has been demonstrated at a dose of 500 mg of vitamin C daily (21).

Hypertension (high blood pressure): Individuals with high blood pressure are at increased risk of developing cardiovascular diseases.  Several studies have demonstrated a blood pressure lowering effect of vitamin C supplementation. One recent study of individuals with high blood pressure found that a daily supplement of 500 mg of vitamin C resulted in an average drop in systolic blood pressure of 9% after 4 weeks (22). It should be noted that those participants who were taking anti-hypertensive medication continued taking it throughout the 4-week study. Because the findings regarding vitamin C and high blood pressure have not yet been replicated in larger studies it is important for individuals with significantly high blood pressure to continue current therapy (medication, lifestyle changes, etc.) in consultation with their health care provider.

Cancer: Studies in the 1970’s and 1980’s conducted by Linus Pauling and colleagues suggested that very large doses of vitamin C (10 grams/day intravenously for 10 days followed by at least 10 grams/day orally indefinitely) were helpful in increasing the survival time and improving the quality of life of terminal cancer patients (23). However, two randomized placebo-controlled studies conducted at the Mayo clinic found no differences in outcome between terminal cancer patients receiving 10 grams of vitamin C/day orally or placebo(24) There were significant methodological differences between the Mayo Clinic and Pauling’s studies, and recently, two researchers from the NIHsuggested that the route of administration (intravenous versus oral) may have been the key to the discrepant results (25). Intravenous (IV) administration can result in much higher blood levels of vitamin C than oral administration, and levels that are toxic to certain types of cancer cells in culture can be achieved with intravenous but not oral administration of vitamin C. Thus, it appears reasonable to reevaluate the use of high-dose vitamin C as cancer therapy.

Currently, there is no clinical evidence suggesting that vitamin C would adversely affect the survival of cancer patients. However, vitamin C should not be used in place of  therapy that has been demonstrated effective in the treatment of a particular type of cancer, for example, chemotherapy or radiation therapy.  If an individual with cancer chooses to take vitamin supplements, it is important that the clinician coordinating his or her treatment is aware of the type and dose of each supplement. While research is underway to determine whether combinations of antioxidant vitamins might be beneficial as an adjunct to conventional cancer therapy, definitive conclusions are not yet possible (26).

In a presentation at a meeting of the American Cancer Society, a scientist suggested that supplemental vitamin C might enhance the growth of cancer cells or protect them from cell-killing free radicals produced by radiation and some forms of chemotherapy.  An article published in the Spring/Summer 2000 issue of the Linus Pauling Institute newsletter, Is vitamin C harmful for cancer patients?, provides additional insight on this topic.

Diabetes mellitus: Numerous observational studies have found that people withdiabetes have lower plasma levels of vitamin C (approximately 30% lower) than do people without diabetes.  However, a number of methodological flaws have been attributed to such studies, and it is not clear whether diabetes is the cause of lower plasma levels of vitamin C.  Recently a large population-based study found no difference in blood levels of vitamin C between over 200 individuals with newly diagnosed diabetes and 1,800 individuals without diabetes once dietary intake of vitamin C and cigarette smoking were taken into consideration (27).  Though few studies have demonstrated improved bloodglucose levels upon supplementation of diabetic individuals with vitamin C, doses of between 100 and 600 mg of vitamin C daily have been found to normalize cellular sorbitol levels, which may have implications for decreasing some of the long-term complications of diabetes (28).  Cardiovascular diseases are the leading cause of death in individuals with diabetes (See Disease Prevention: Cardiovascular Diseases). Vitamin C has also been found to improve blood vessel dilation, which is often impaired in diabetic individuals (See Disease Treatment: Cardiovascular Diseases). The link between cardiovascular diseases and diabetes may be related to increased oxidative stress, giving credibility to the idea that the antioxidant properties of vitamin C may benefit individuals with diabetes.  While the role of vitamin C in the management of diabetes is by no means clear, maintaining an adequate intake of vitamin C may help prevent some of the complications of diabetes.

Common cold: The work of Linus Pauling stimulated public interest in the use of large doses (greater than 1 gram/day) of vitamin C to prevent infection with the viruses responsible for the common cold.  Reviews of the research conducted on this issue over the past 20 years conclude that, in general, large doses of vitamin C do not have a significant effect on the incidence of the common cold (29).  However, a few studies have indicated that certain susceptible groups (e.g., individuals with low dietary intake and marathoners) may be less susceptible to the common cold when taking supplemental vitamin C.  Additionally, large doses of vitamin C have been found to decrease the duration and severity of colds, an effect that may be related to the antihistamineeffects found to occur with large doses (2 grams) of vitamin C (30).

SOURCES

Food sources: As shown in the table below different fruits and vegetables vary in their vitamin C content, but 5 servings should average out to at least 200 mg of vitamin C. One fruit serving should be considered to be one medium piece of fruit, 1/2 cup of canned or cooked fruit, or 3/4 cup of fruit juice. One vegetable serving should be considered to be one cup of raw leafy vegetables, 1/2 cup of other vegetables cooked or raw, or 3/4 cup of vegetable juice.  If you wish to check foods you eat frequently for their nutrient content, search the USDA food composition database.

Food Serving Vitamin C (mg)
Orange juice 3/4 cup (6 ounces) 75
Grapefruit juice 3/4 cup (6 ounces) 60
Orange 1 medium 70
Grapefruit 1/2 medium 44
Strawberries 1 cup, whole 82
Tomato 1 medium 23
Sweet red pepper 1/2 cup, raw chopped 141
Broccoli 1/2 cup, cooked 58
Potato 1 medium, baked 26

 

Supplements:Vitamin C (L-ascorbic acid) is available in many forms, but there is little scientific evidence that any one form is better absorbed or more effective than another.

Natural vs. synthetic vitamin C: Natural and synthetic L-ascorbic acid are chemically identical and there are no known differences in their biological activities or bioavailability (31).

Mineral ascorbates: Mineral salts of ascorbic acid are buffered and therefore, less acidic than ascorbic acid. Some people find them less irritating to the gastrointestinal tract than ascorbic acid. Sodium ascorbate and calcium ascorbate are the most common forms, although a number of other mineral ascorbates are available. Sodium ascorbate generally provides 131 mg of sodium per 1,000 mg of ascorbic acid, and pure calcium ascorbate provides 114 mg of calcium per 1,000 mg of ascorbic acid.

Vitamin C with bioflavonoids: Bioflavonoids are a class of water-soluble plant pigments that are often found in vitamin C-rich fruits and vegetables, especially citrus fruits. Although many bioflavonoids are thought to function as antioxidants, there is little evidence that the bioflavonoids in most commercial preparations increase the bioavailability or efficacy of vitamin C (32).

Ascorbate and vitamin C metabolites: One such supplement (Ester-C®) contains mainly calcium ascorbate, but also contains small amounts of the vitamin C metabolites dehydroascorbate (oxidized ascorbic acid), calcium threonate, and trace levels of xylonate and lyxonate. Although the metabolites are supposed to increase the bioavailability of vitamin C, the only published study in humans found no difference between Ester-C® and commercially available ascorbic acid tablets with respect to the absorption and urinary excretion of vitamin C (32). Ester-C® should not be confused with ascorbyl palmitate, which is also marketed as “vitamin C ester” (see below).

Ascorbyl palmitate: Ascorbyl palmitate is actually a vitamin C ester (vitamin C that has been esterified to a fatty acid). In this case, vitamin C is esterified to the saturated fatty acid, palmitic acid, resulting in a fat-soluble form of vitamin C. Ascorbyl palmitate has been added to a number of skin creams due to interest in its antioxidant properties as well as the important role of vitamin C in collagen synthesis (33). Although ascorbyl palmitate is also available as an oral supplement, it is likely that most of it is hydrolyzed (broken apart) to ascorbic acid and palmitic acid in the digestive tract before it is absorbed (34). Ascorbyl palmitate is also marketed as, “vitamin C ester,” which should not be confused with Ester-C® (see above).

For a more detailed review of scientific research on the bioavailability of different forms of vitamin C, see The Bioavailability of Different Preparations of Supplemental Vitamin C.

SAFETY

Toxicity: A number of possible problems with very large doses of vitamin C have been suggested, mainly based on in vitro experiments or isolated case reports, including: genetic mutations, birth defects, cancer, atherosclerosis,kidney stones, “rebound scurvy“, increased oxidative stress, excess iron absorption, vitamin B-12 deficiency, and erosion of dental enamel. However, none of these adverse health effects have been confirmed, and there is no reliable scientific evidence that large amounts of vitamin C (up to 10 grams/day in adults) are toxic or detrimental to health. With the latest RDA published in 2000, a tolerable upper intake level (UL) for vitamin C was set for the first time. A UL of 2 grams (2,000 milligrams) daily was recommended in order to prevent most adults from experiencing diarrhea and gastrointestinal disturbances (6). Such symptoms are not generally serious, especially if they resolve with temporary discontinuation or reduction of high-dose vitamin C supplementation. For a more thorough discussion of the Linus Pauling Institute’s response to the UL for vitamin C, see the article, The New Recommendations for Dietary Antioxidants: A Response and Position Statement by the Linus Pauling Institute, in the Spring/Summer 2000 newsletter. A more detailed discussion of vitamin C and the risk of kidney stones can be found in the article,What About Vitamin C and Kidney Stones?, in the Fall/Winter 1999 newsletter.

Tolerable Upper Intake Level (UL) for Vitamin C
Age Group UL (mg/day)
Infants 0-12 months Not possible to establish*
Children 1-3 years 400
Children 4-8 years 650
Children 9-13 years 1,200
Adolescents 14-18 years 1,800
Adults 19 years and older 2,000

Does vitamin C promote oxidative damage under physiological conditions?Vitamin C is known to function as a highly effective antioxidant in living organisms. However, in test tube experiments, vitamin C can interact with some free metal ions to produce potentially damaging free radicals. Although free metal ions are not generally found under physiological conditions, the idea that high doses of vitamin C might be able to promote oxidative damage in vivo has received a great deal of attention. Widespread publicity has been given to a few studies suggesting a pro-oxidant effect of vitamin C (35,36), but these studies turned out to be either flawed or of no physiological relevance. A recent comprehensive review of the literature found no credible scientific evidence that supplemental vitamin C promotes oxidative damage under physiological conditions or in humans (37). Studies that report a pro-oxidant effect for vitamin C should be evaluated carefully to determine whether the study system was physiologically relevant, and to rule out the possibility of methodological and design flaws.

For example, a study in the June 15, 2001, issue of the journal Science shows that lipid hydroperoxides (rancid fat molecules) can react with vitamin C to form products that could potentially harm DNA, although the reaction of these products with DNA was not demonstrated in the study. To find out why the Linus Pauling Institute considers the study’s conclusions unwarranted, seeVitamin C doesn’t cause cancer! in the Linus Pauling Institute Newsletter.

Drug interactions: A number of drugs are known to lower vitamin C levels, requiring an increase in its intake. Estrogen-containing contraceptives (birth control pills) are known to lower vitamin C levels in plasma and white blood cells. Aspirin can lower vitamin C levels if taken frequently.  For example, two aspirin tablets taken every six hours for a week has been reported to lower white blood cell vitamin C by 50%, primarily by increasing urinary excretion of vitamin C.

There is some evidence, though controversial, that vitamin C interacts with anticoagulant medications (blood thinners) such as warfarin (Coumadin).  Large doses of vitamin C may block the action of warfarin, requiring an increase in dose to maintain its effectiveness. Individuals on anticoagulants should limit their vitamin C intake to 1 gram/day and have their prothrombin time monitored by the clinician following their anticoagulant therapy. Because high doses of vitamin C have also been found to interfere with the interpretation of certain laboratory tests (e.g., serum bilirubin, serum creatinine, and the guaiac assay for occult blood) it is important to inform one’s health care provider of any recent supplement use (38).

THE LINUS PAULING INSTITUTE RECOMMENDATION

The Linus Pauling Institute recommends that generally healthy adults of all ages consume at least 200 mg of vitamin C daily. Eating 5 servings/day of most fruits and vegetables will provide at least 200 mg of vitamin C. Although vitamin C from supplements is easily absorbed and utilized by the body, most of the epidemiologic evidence showing decreased chronic disease risk with increased vitamin C intake is based on vitamin C consumption from fruits and vegetables, not from supplements. The amounts of vitamin C required to maintain optimum body levels in special populations, such as children, pregnant women and older adults, have not been established. Similarly, the amounts of vitamin C required to derive therapeutic benefits in diseased individuals are not known, but are likely higher than 200 mg/day.

Older adults (65 years and older): While there is no conclusive evidence that generally healthy older adults have a higher requirement for vitamin C than younger people, some older populations have been found to have vitamin C intakes considerably below the RDA of 75 and 90 mg/day for women and men, respectively, as well as the 200 mg/day recommended by the Linus Pauling Institute. Because older adults are at higher risk for most of the chronic diseases that adequate vitamin C intake may protect against (see Disease Prevention), ensuring a daily vitamin C intake of at least 200 mg is especially important.

For more information on the difference between Dr Linus Pauling’s recommendation and the Linus Pauling Institute’s recommendation for vitamin C intake, click on the highlighted text.

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