By Phyllis D. Light, LMT, AHG, BS, and Carolynn J. Thomas, BSN, MSPH, RN
The controversy over the primary and secondary disease prevention properties attributable to vitamin C, or ascorbic acid, continues unabated. Proponents hail vitamin C as an inexpensive and effective life insurance supplement. But long-range prevention studies focused on vitamin supplementation notoriously are inexact and obscured by the difficulty of accurately accounting for measurement of dietary intake and other confounders such as genetics, lifestyle, concomitant supplements and medications, and health behaviors. Still, a recently published, vigorous study affirming the cardioprotective nature of vitamin C supplementation in women has revived the traditional disagreements.1
History and Function of the Supplement
Among the earliest controlled research studies, A Treatise of the Scurvy, published in 1754, began the journey of vitamin C research. James Lind studied 12 men aboard the H.M.S. Salisbury who suffered from scurvy, a condition common among sailors at sea for about a month. Scurvy symptoms include swollen and bleeding gums, open skin sores, dry skin, fatigue, bone lesions, and impaired wound healing. Lind concluded that a beneficial substance in citrus cured scurvy. Previous to this, lime juice was believed to possess beneficial properties and effects against scurvy, and Lind’s study quantitatively supported these beliefs. But, despite this study’s published results, the British Navy waited 40 years before officially requiring lime or lemon juice as a food staple on ships. Once this official action was taken, scurvy virtually disappeared, and hospital admissions of sick sailors dropped by 50%.2,3
Vitamin C first was isolated in 1928 by the Hungarian biochemist and Nobel Prize winner Albert Szent-Györgyi, PhD.4 The body requires this water-soluble vitamin for the synthesis of collagen, the main structural component of blood vessels, bone, organs, tendons, ligaments, skin, and hair. (See Table 1 for other functions.) With the exception of humans, primates, bats, and guinea pigs, most mammals manufacture vitamin C. Humans require dietary vitamin C for healthy physiologic functioning.5
As an antioxidant, vitamin C protects low-density lipoprotein (LDL) cholesterol from oxidative damage; when LDL is damaged, oxidized cholesterol leads to heart disease.6 In addition, lipoprotein-a, a major component of arterial plaque, is reduced in the presence of vitamin C. In this way, vitamin C is believed to help maintain cardiovascular health by inhibiting the formation of lesions along blood vessel walls.6
Women and Heart Disease
Heart disease is the leading cause of death among American women, killing six times as many women as breast cancer.7 More than 250,000 women die each year from heart attacks, while another 32,000 women die of congestive heart failure. On average, women who smoke experience heart attacks 19 years earlier in life than non-smokers. Moreover, women with diabetes are two to three times more likely to experience heart attacks. Women have a significantly higher mortality rate from heart attacks than men, but receive only 33% of the performed angioplasties, stent procedures, and bypass surgeries.7 For additional information on statistics and current research on women’s heart disease, see www.americanheart.org.
Nurse’s Health Study and Other Research on Vitamin C
In 1976, the largest cohort study of women, the Nurse’s Health Study, began when approximately 121,700 female registered nurses between ages 30 and 55, living in 11 large U.S. states, completed a mailed questionnaire of lifestyle and medical history. Follow-up questionnaires were sent every two years to collect information on potential risk factors and identify newly diagnosed cases of coronary heart disease (CHD). Included in the questionnaires was a semi-quantitative food-frequency questionnaire to assess the intake of micronutrients and other dietary components. The final sample, after controlling for non-response and missing or extraneous data, was a cohort of 85,118 women who were followed for 16 years for the occurrence of CHD. This study had as its primary endpoint, incident CHD including any non-fatal myocardial infarction, or fatal coronary event diagnosed after the 1980 questionnaire but before June 1, 1996.1
An intensive review of medical records was performed on incident cases to confirm diagnosis. After adjusting for age, smoking history, and several other coronary risk factors, the final analysis of the study revealed a CHD risk reduction of approximately 28% with vitamin C supplementation. This percentage also included adjusting for the intake of phytonutrients and other dietary antioxidants.1
A discussion of past population-based research in vitamin C supplementation is presented in the literature.1,3,6,8 One study has shown that deficiencies in vitamin C intake are associated with increased CHD risk; however, several other studies have not proven a CHD reduction benefit associated with higher vitamin C intakes.7 The First National Health and Nutrition Examination Study (NHANES I) Epidemiologic Follow-up Study showed a 45% reduced risk of CHD in men and a 25% reduced risk of CHD in women corresponding to a higher (300 mg/d) intake of vitamin C.9 A large prospective epidemiologic study in Finnish men and women suggested a vitamin C-associated risk reduction of CHD in women but not in men.6 Singh et al studied 595 elderly subjects in urban India and found a vitamin C-associated CHD risk reduction.10 Studies such as these used varying doses of vitamin C, some quite low, and other antioxidant vitamins, including vitamin E. A recent meta-analysis on the role of vitamin C and antioxidant vitamins showed no evidence of CHD prevention.6
A long-term prospective study to draw definitive conclusions on the benefit of vitamin C for primary prevention of CHD would be impractical and cost-prohibitive, especially in the context of the inherent limitations of study design and the complexity of making statistical adjustments for confounders such as other underlying conditions, dietary intake, varieties of supplementation including concomitant vitamin E and antioxidants, and measuring tissue saturation.11
Dosing, Food Sources, and Supplements
Since the average half-life of ascorbic acid in human adults is 10-20 days, vitamin C has to be supplied regularly through diet or tablets to maintain an adequate pool in the body. Taking 100 mg/d adequately saturates the body pools, and the recommended daily allowance (RDA) for adults (> 19 yr) has gradually increased to 100-120 mg/d as new research elucidates advantages of this nutrient. In his editorial comment on the Nurse’s Health Study, Balz Frei, PhD, director and endowed chair of the Linus Pauling Institute at Oregon State University, concludes that increasing the current RDA to 500 mg/d is warranted.11 A scientific advisory panel to the U.S. government-sponsored Alliance for Aging Research recently recommended that all healthy adults increase their vitamin C intake to 250-1,000 mg/d, which may be adequate for preventive purposes.12 Others contend that larger quantities may be beneficial to reverse processes in cancer, asthma, and heart disease.13
Certain conditions and activities—including smoking, diabetes, burns, infections, stress, wound healing, hormone therapy, and pregnancy—diminish the body’s pool of vitamin C. Increased supplementation in those conditions is warranted to maintain a body pool sufficient to counteract ongoing losses.6
Rich dietary sources of vitamin C include citrus fruits, strawberries, cantaloupe, tomatoes, cabbage, broccoli, and dark-green leafy vegetables. As illustrated in Table 2, different fruits and vegetables vary in their vitamin C content. Over-the-counter vitamin C (L-ascorbic acid) is available in many forms, but research has shown that time-released formulations are absorbed better than regular vitamin C.14
Safety and Drug Interactions
Research demonstrates that vitamin C supplementation is safe and non-toxic. Excess vitamin C is eliminated via the kidneys. Doses of 6-10 g/d cause gastrointestinal problems and diarrhea in some people.
A number of drugs are known to lower vitamin C levels, thus requiring an increase in intake. Estrogen-containing medications, e.g., birth control pills and hormone replacement therapies, lower plasma and white blood cell levels of vitamin C. Frequent aspirin use can lower vitamin C levels.
Large doses of vitamin C can reduce the effectiveness of anticoagulant medications such as warfarin, requiring more intensive monitoring of blood levels and increased dosages to maintain therapeutic effectiveness and prevent blood clots. Persons on anticoagulants should limit their vitamin C intake to no more than 1,000 mg/d. Higher doses of vitamin C can interfere with the interpretation of certain laboratory tests (e.g., serum bilirubin, serum creatinine, and the assay for occult blood via guaiac testing of stool samples).5
Vitamin B12 absorption can be reduced when taken simultaneously with vitamin C. This can be a concern when vitamin B12 is taken for a medical reason such as anemia or as part of a protocol to reduce homocysteine levels. Elevated homocysteine levels have been identified as a risk factor of cardiovascular disease. Another major concern for heart patients is the concomitant use of antioxidants (1,000 mg/d of vitamin C, 800 IU/d of vitamin E, 100 mcg/d of selenium, and 25 mg/d of beta-carotene) could diminish the protective effects of statins.15
Although scurvy rarely occurs today, many researchers believe that a significant number of people suffer from chronic shortages of vitamin C. Poor nutrition, aging, lifestyle issues, environmental influences, and continuous stress contribute to this chronic shortage. The protective and curative effects of this compound are not adequately appreciated, despite a number of studies. Therefore, no clear consensus on dose recommendations for primary prevention is lauded in conventional circles. However, in terms of CHD risk reduction in women, vitamin C experts support increased intake of ascorbic acid to doses between 250 mg/d and 1,000 mg/d.
Alternative medicine usage among women of all ages, races, and socioeconomic backgrounds has increased significantly as women continue to seek support in finding ways to maintain a healthy lifestyle.12 National public health initiatives and advocacy groups have been much more active in educating and motivating women on the local level with programs such as "The Heart Truth for Women—Red Dress Program" supported by the U.S. Department of Health and Human Services (www.nhlbi.nih.gov/health/hearttruth/whatis/reddress.htm) and WomenHeart: The National Coalition for Women with Heart Disease (www.womenheart.org).
There is consensus that women can lower their heart disease risk with smoking cessation, blood pressure control, cholesterol reduction, weight maintenance, physical activity, and prevention and treatment of diabetes. The specific behavioral and medicinal methods of achieving such risk-factor reduction goals require the marrying of two approaches. Both conventional and alternative medicine must reach out to women and motivate change to effect a reduction in the numbers of women succumbing to heart disease. Although age and family history also influence risk, research shows that risk factor modifications can reduce heart disease risk by 82%.13
For women, the latest evidence supports the efficacy of supplementing their diets with 1,000 mg/d of time-released L-ascorbic acid to improve their heart health. This is one specific stepping stone toward reducing risk. Women must be more proactive in harnessing resources that can empower them toward risk factor reduction.
Ms. Light is Director of Herbal Studies, Clayton College of Natural Health. Ms. Thomas is a clinical research consultant in Birmingham, AL.
1. Osganian SK, et al. Vitamin C and risk of coronary heart disease in women. J Am Coll Cardiol 2003;42: 246-252.
2. Lind J. A Treatise on Scurvy. Edinburgh: Sands, Murray and Cochran for Kincaid A and Donaldson A; 1753.
3. Sauberlich HE. A history of scurvy and vitamin C. In: Packer L, Fuchs J, eds. Vitamin C in Health and Disease. New York: Marcel Decker Inc; 1997:1-24.
4. Svirbely JL, Szent-Györgyi A. The chemical nature of vitamin C. Biochem J 1932:26,865-26,870.
5. Frei B., Ed. Vitamin C: The Linus Pauling Institute—Micronutrient Information Center. Available at: http://lpi.oregonstate.edu/infocenter/vitamins/vitaminC. Accessed July 22, 2003.
6. Naidu KA. Vitamin C in human health and disease is study a mystery? An overview. Nutrition J 2003;2:7.
7. National Center on Health Statistics; National Heart, Lung and Blood Institute; and American Heart Association’s 2002 Heart and Statistics Update. Available at: www.americanheart.org/downloadable/heart/10590179711482003HDSStatsBookREV7-03.pdf. Accessed Nov. 5, 2003
8. Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr 1999;69: 1086-1107.
9. Enstrom JE et al. Vitamin C intake and mortality among a sample of the United States population. Epidemiology 1992;3:194-202.
10. Singh RB, et al. Dietary intake, plasma levels of antioxidant vitamins and oxidative stress in relation to coronary artery disease in elderly subjects. Am J Cardiol 1995;76:1233-1238.
11. Frei B. To C or not to C, that is the question. J Am Coll Cardiol 2003;42:253-255.
12. Voelker R. Recommendations for antioxidants: How much evidence is enough? JAMA 1994;271:1148-1149.
13. Larsen HR. Vitamin C: Your ultimate health insurance. Available at: www.yourhealthbase.com/vitamin_C.html. Accessed Oct. 10, 2003.
14. Cheraskin E. Are there merits in sustained-release preparations? J Orthomolecular Med 2001;16:49-50.
15. Brown BG, et al. Antioxidant vitamin and lipid therapy: End of a long romance? Arterioscler Thromb Vasc Biol 2002;22:1535-1546.
16. Gokce N, et al. Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 1999;99: 3234-3240.
17. Simon JA, Hudes ES. Serum ascorbic acid and gallbladder disease prevalence among U.S. adults: The Third National Health and Nutrition Examination Survey (NHANES III). Arch Intern Med 2000;160: 931-936.
18. Hallberg L. Bioavailability of dietary iron in man. Annu Rev Nutr 1981;1:123-127.