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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 (41).
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 (42).
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 (42). 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 (43). 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 (44). 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 Forms of 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
*Source of intake should be from foods or formula only.
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 (45, 46), 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 (47). 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 (45). To find out why the Linus Pauling Institute considers the study's conclusions unwarranted, see Vitamin 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 (48).
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 (49).
Antioxidant Supplements and HMG-CoA Reductase Inhibitors (Statins)
A 3-year randomized controlled trial in 160 patients with documented coronary heart disease (CHD) and low HDL levels found that a combination of simvastatin (Zocor) and niacin increased HDL2 levels, inhibited the progression of coronary artery stenosis (narrowing), and decreased the frequency of cardiovascular events, such as myocardial infarction (heart attack) and stroke (50). Surprisingly, when an antioxidant combination (1,000 mg vitamin C, 800 IU alpha-tocopherol, 100 mcg selenium, and 25 mg beta-carotene daily) was taken with the simvastatin-niacin combination, the protective effects were diminished. Since the antioxidants were taken together in this trial, the individual contribution of vitamin C cannot be determined. In contrast, a much larger randomized controlled trial of simvastatin and an antioxidant combination (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) in more than 20,000 men and women with coronary artery disease or diabetes found that the antioxidant combination did not diminish the cardioprotective effects of simvastatin therapy over a 5-year period (51). These contradictory findings indicate that further research is needed on potential interactions between antioxidant supplements and cholesterol-lowering agents, such as HMG-CoA reductase inhibitors (statins).
Linus Pauling Institute Recommendations
The Linus Pauling Institute recommends a vitamin C intake of at least 400 mg daily—the amount that has been found to fully saturate plasma and circulating cells with vitamin C in young, healthy nonsmokers (13). Consuming at least five servings (2½ cups) of fruits and vegetables daily may provide about 200 mg of vitamin C. Most multivitamin supplements provide 60 mg of vitamin C.
Older adults (65 years and older)
Although it is not yet known with certainty whether older adults have higher requirements 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. A vitamin C intake of at least 400 mg daily may be particularly important for older adults who are at higher risk for chronic diseases.
For more information on the difference between Dr Linus Pauling's recommendation and the Linus Pauling Institute's recommendation for vitamin C intake, select the highlighted text. |
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