NUTRITION AND EPIDEMIOLOGY

GUEST EDITOR:

P&&ion Vol. 13, No. 9, 1997

SUSHMA PALMER, DSC

Central European Center for Health and the Environment (CECHE), Washington, DC

Vitamin C: What Do We Know and How Much Do We Need?

NADINE R. SAHYOUN, PHD, RD

From the National Center for Health Statistics, Ofice of Analysis, Epidemiology and Health Promotion, Hyattsville, Maryland, USA

Vitamin C has long been known as an essential nutrient that prevents the defi- ciency disease scurvy. However, the grow- ing importance of vitamin C lies in its potential protection against chronic dis- eases of old age. Cardiovascular disease and cancer, the two leading causes of death among the adult population in the United States,’ and other age-related degenerative conditions such as cataracts and cognitive dysfunction are believed to be in part caused by oxidant damage to DNA, pro- tein, and other macromolecules.2~3 Mainte- nance of tissue integrity is dependent on the balance between the production and neutralization of toxic oxidants. The pro- tective effect of vitamin C is attributed to its antioxidant properties and to its role as a reducing agent and free radical quencher, although the exact mechanism has not been fully elucidated. Vitamin C is located in the water-soluble component of the body and is believed to be the first line of defense.4s5 It neutralizes superoxide, sin- glet oxygen, hydroxyl radical, and hypo- chlorous acid.6

Based on our current knowledge of the function of vitamin C as an antioxidant and based on the emerging evidence of the protective effect of vitamin C against chronic diseases, the question that is being asked is whether the amount of vitamin C needed to prevent scurvy the same as the amount needed to provide optimal health. A vast number of epidemiologic studies have examined the association between cancer, heart disease, and dietary intake of vitamin C, foods containing vitamin C, or

Nutrition 13:835-836, 1997 OElsevier Science Inc. 1997 Printed in the USA. All rights reserved.

plasma vitamin C values. These observa- tional studies can suggest, but not estab- lish, causal relations. Moreover, the ability to compare and replicate epidemiologic studies is complicated by differences in study design that may include variability in underlying nutrient status of study pop- ulations, nutrient assessment methods, and handling and analyses of biological sam- ples. Yet, despite these limitations and dif- ficulties, the overall evidence supports an inverse relationship between antioxidants and a number of age-related chronic con- ditions.

Sauberlich’ conducted a comprehen- sive review of epidemiologic studies that investigated the association between vita- min C and cancer. Even though the studies reported varied results, the review indi- cated evidence of an inverse association between vitamin C intake and certain can- cers, especially cancer of the stomach. In a review paper, Block* examined 75 epide- miologic studies and reported that, overall, the results suggested an inverse relation- ship between vitamin C and cancer, espe- cially for oral, esophageal, and gastric can- cer. Thirty-three out of 46 studies that examined a vitamin C index or plasma ascorbate values in 11 non-hormone-de- pendent cancer sites found statistically sig- nificant protective effects. And, 21 out of 29 studies that examined the effect of fruit consumption, found significant protection associated with frequent consumption or high risk associated with low consump- tion. There appears to be more positive than negative studies linking high levels of

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vitamin C to lower risk of some forms of cancer. The possible anticarcinogenic ef- fect of vitamin C is believed to involve its ability to detoxify carcinogens or block carcinogenic processes through its action as antioxidant or as a free-radical scaven- ger.p

Although the results are not consistent, there is emerging evidence linking high intake of vitamin C and/or high plasma levels of the vitamin with reduced mortal- ity from heart disease.iO-12 Gey et al.‘0 observed from a cross-sectional survey of population groups throughout Europe an inverse correlation between plasma levels of vitamin C and ischemic heart disease. Enstrom and coworkersii analyzed data from the First National Health and Nutri- tion Examination Survey Epidemiologic Follow-up Study cohort and reported strong inverse trends between high dietary plus supplemental intake of vitamin C, mortality from all causes, and mortality from cardiovascular diseases for both sexes. This was also observed in a study of elderly people in the Boston area, in which serum vitamin C and dietary plus supple- mental intake of vitamin C were inversely associated with overall mortality and mor- tality from heart disease.‘* It has been shown that oxidation of low-density li- poprotein (LDL) and lipid membranes play a crucial role in atherosclerosis.i3 Al- though the mechanism is still unclear, it has been suggested that vitamin C can protect circulating and membrane lipids by directly intercepting free radicals gener- ated in the aqueous phase thus preventing

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836 VITAMIN C: WHAT DO WE KNOW AND HOW MUCH DO WE NEED?

their attack on the lipid phase. Vitamin C is also believed to protect lipids indirectly by sparing or reconstituting the active forms of vitamin E.i4 Vitamin C was shown to be more effective at preventing lipid peroxidation than any other endoge- nous antioxidant in plasma and LDL in- cluding vitamin E.15 In addition to cancer and heart disease, higher vitamin C intake and status are associated with lower risk of other age-related disorders such as degen- erative eye disorders,i6*i7 which are be- lieved to result in part from oxidative de- struction.

the vitamin or during periods of stress.i8 Yet, this pool may not be sufficient for optimal human health considering the vitamin’s other metabolic functions in the body. In fact, it has been shown that the body pool can be increased to 3000 mg with intakes of 200 mg/d.i8 Although vitamin C content varies widely by type of body tissue, Levine et all9 showed that at least in plasma, no meaningful increase in concentration was produced with intakes of vitamin C above 200 mg, and neutrophils, monocytes, and lym- phocytes became saturated at intakes of 100 mg. Based on available data, the Food and Nutrition Board in its ex- panded framework will develop various nutrient-based reference levels and in the process will review new scientific evi- dence including the roles of nutrients in preventing or delaying the onset of chronic disease.20 However, the fact that many of the antioxidant reactions in the body are linked in cascades or interre- lated processes indicate that any single antioxidant may be less effective alone than in combination with complementary agents.21~22 Few studies have examined such interactions.iO,i* In the prospective Base1 study, Gey et al.10 found that an age-standardized cumulative index of antioxidant vitamins (vitamins C, E, and p-carotene) was more significantly and inversely associated with all cause mor-

tality and mortality from cancer than the values of the single antioxidants. Sahyoun et al.12 did not find any inter- actions among the nutrients, however, the outcome of interest may have been too few in numbers to test such interac- tions.

Despite all the information available on vitamin C, we still do not know what the optimal dietary level should be for human beings. The U.S. Recommended Dietary Allowance (RDA) for vitamin C prepared by the Food and Nutrition

I Board has been based on the amount necessary to prevent scurvy while allow- ing for adequate reserves of vitamin C. It is also based on the amount of vitamin C metabolized daily, but does not take into account functions of vitamin C not linked to scurvy such as its antioxi- dant property whose protection against chronic diseases may take a long time to manifest itself. The selected adequate to- tal-body pool of 1500 mg of ascorbic acid prevents scurvy and includes a re- serve that should provide adequate vita- min C for over a month on a diet low in

Future research may need to concen- trate on the complex interrelations be- tween antioxidants, and dietary recom- mendations may need to be based on a combination of nutrients. However, until more information is available, supple- mentation, especially of megadoses of vitamin C, is not necessary but a dietary increase to levels beyond the 1989 RDAi8 of 60 mg is warranted. Most of the vitamin C is obtained from fruits and vegetables and an intake of 200-300 mg is not difficult to incorporate into one’s diet. In fact, the dietary guidelines pro- duced by the United States Department of Agriculture and the National Cancer Institute suggest an intake of five or more servings of fruits and vegetables per day. Menus that follow these guide- lines provide an average of 217-225 mg/d of vitamin C.*3 Consuming this amount of vitamin C through diet in- cludes the added benefits of ingesting other antioxidants such as carotenoids and possibly other protective substances that have yet to be identified but that are believed to be present in this food group.

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Healthy people 2000: national health pro- motion and disease prevention objectives. Washington, DC: United States Department of Health and Human Services, Public Health Service, 1990. DHHS Pub No. (PHS) 91-50212 Halliwell B. Oxidants and human disease: some new concepts. FASEB .I 1987;1:358 Block G. The data support a role for anti- oxidants in reducing cancer risk. Nutr Rev 1992;50:207 Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Nat1 Acad Sci 1989;86:6377 Esterbauer H, Gebicki J, Puhl H, et al. The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Rad Biol Med 1992;13:341 Anderson R, Theron AJ. Physiological potential of ascorbate, p-carotene and cu-tocopherol individually and in combi- nation in the prevention of tissue damage, carcinogenesis and immune dysfunction mediated by phagocyte-derived reactive oxidants. In: Bourne GH, ed. Aspects of some vitamins, minerals and enzymes in health and disease. World Rev Nutr Diet 1990;62:27 Sauberlich HE. Evaluation of publicly available scientific evidence regarding cer- tain nutrient-disease relationships: SB. Vi- tamin C and cancer. Life Sciences Re-

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Taylor A, Jacques PF, Epstein EM. Rela- tions among aging, antioxidant status, and cataract. Am J Clin Nutr 1995;62(suppl): 1439s Snodderly DM. Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins. Am J Clin Nutr 1995;62(suppl):1448S Committee on Dietary Allowances, Food and Nutrition Board, National Research Council. Recommended Dietary Allow- ances, 10th ed. Washington, DC: National Academy of Sciences, 1989 Levine M, Comy-Cantilena C, Wang Y, et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Nat1 Acad Sci 1996;93:3704 Revisiting dietary allowances and require- ments. Nutr Rev 1996;54:246 Block G, Met&es M. Ascorbic acid in can- cer prevention. In: Moon TE, Micozzi MS, eds. Nutrition and cancerprevention, inves- tigating the role of micronutrients. New York Marcel Dekker, Inc. 1989:341 Jacques PF, Halpem AD, Blumberg JB. Influence of combined intakes on their plasma concentrations in an elderly popu- lation. Am J Clin Nutr 1995;62:1228 Lachance P, Langseth L. The RDA con- cept: time for a change? Nutr Rev 1994;52: 266