Long-Term Multivitamin Use May Cut Colon Cancer Risk
January 1, 1999
Long-Term Multivitamin Use May Cut Colon Cancer Risk
By Barbara A. Biedrzycki, RN, MSN, AOCN, CRNP
Summary—The importance of folate as a necessary component for DNA synthesis, the production of red blood cells, regulation of embryonic function, and fetal nerve cell development has been well established. Studies show folate plays a positive role in preventing heart disease. Now another benefit has been demonstrated through a large prospective study of more than 100,000 nurses participating in the Nurses’ Health Study. Congruent with the hypothesis that folate intake is the major nutritional factor associated with a decreased risk of colon cancer, researchers conclude that using multivitamins for 15 years or more may decrease the risk of colon cancer by 75%.1
In 1976, 121,700 female registered nurses between ages 52 and 77 responded to a call for volunteers to participate in a longitudinal Nurses’ Health Study. Information is updated every two years with follow-up surveys. Of the initial respondents, 88,756 met the criteria to become part of this study to explore multivitamin use, folate intake, and colon cancer in women. The following exclusion criteria were used:
• cancer diagnosis except nonmelanoma skin cancer, ulcerative colitis, or familial polyposis syndrome;
• submission of incomplete information on aspirin and multivitamin use;
• not answering 10 or more food-frequency questions on the survey;
• and implausibly high or low energy scores for total energy intake.
In 1980, the participants completed a semiquantitative food frequency survey to establish a dietary cohort. They received comparable but expanded surveys in 1984, 1986, and 1990. Requested information included age, weight, height, smoking history, physical activity, aspirin use, history of colonoscopy or sigmoidoscopy, and parental history of colon cancer. The analytic cohort group received biennial questionnaires from the Nurses’ Health Study. From this, data regarding multivitamin use from 1980 to 1992 were extracted.
Cases of colon cancer were identified by the research participants themselves or by next of kin for decedents, and permission was sought to explore hospital records and pathology reports. A study physician conducted a blind review of the data and confirmed 655 new cases of colorectal adenocarcinoma, excluding cancer in situ, with 442 in the colon, 143 in the rectum, and 70 at undetermined sites.
The researchers explored the relationship of total, supplementary, and dietary intake of folate to colon cancer. Other variables possibly related to colon cancer were analyzed, including cigarette smoking before age 30, family history of colon cancer, physical activity level, body mass index, aspirin use, ingestion of red meat as a main dish, alcohol, and fiber.
Four categories to quantify folate intake were used:
• < 200 mcg/d;
• 201-300 mcg/d;
• 301-400 mcg/d;
• and > 400 mcg/d
The first three categories represented mostly dietary intake, but intake > 400 mcg/d folate usually indicated supplement usage. Eighty-six percent of women in the > 400 mcg/d category verified multivitamin supplement use. While the daily supplemental dose of folate varies, 97% used 100 mcg or more, 87% used 200 mcg or more, and 69% used 400 mcg or more. Testing for a trend based on folate as the continuous variable in the multivariate model, the significant value of p < 0.01 indicates a strong positive trend in a reduction of the relative risk for colon cancer and higher total intake of folate.
Although a positive trend toward colon cancer risk reduction began to emerge after five years of multivitamin use, researchers found women who took multivitamins did not have a statistically significant risk reduction in colon cancer until 15 years of use. The lower risk of colon cancer after 15 years of multivitamin use applied only to proximal and distal colon cancer. Long-term multivitamin intake did not affect risk of rectal cancer. Researchers concluded from data collected in the Nurses’ Health Study that 68 new cases of colon cancer occur in 10,000 women between 55 and 69 years of age over a 10-year period, while only 15 cases occur when multivitamins are used for at least 15 years. That is an amazing decreased risk of about 75%.
There are many nutrients in multivitamins besides folate, so vitamins A, C, D, and E and calcium were examined for their possible relationship to colon cancer risk. None of those nutrients demonstrated a significant relationship to colon cancer risk after adjustments were made for folate. The insignificant relationships were:
• p = 0.15 for vitamin A;
• p > 0.2 for vitamin C;
• p > 0.2 for vitamin D;
• p > 0.2 for vitamin E;
• and p > 0.2 for calcium.
An analysis of subjects with only dietary folate intake, excluding multivitamin users, did not demonstrate a significant risk reduction in colon cancer.
One might speculate that women who take daily multivitamins may engage in other health-promoting behaviors that may reduce their cancer risk. "Health-seeking behaviors" — identified by the researchers as low body mass index, lower prevalence of smoking, lower intake of saturated fat, and higher intakes of fiber and aspirin — correlated closely with high dietary folate intake, derived mainly from fruits and vegetables. Such behaviors did not correlate with a reduced colon cancer risk.
The study provides strong evidence that using multivitamins for 15 years or more may decrease a woman’s risk for colon cancer. Researchers acknowledge that causality cannot be concluded. Although prospective studies like this are valuable, the Nurses’ Health Study is observational rather than randomized. A double-blind, randomized clinical trial is needed to provide scientific evidence of a relationship between multivitamin use, including folate, and reduction in colon cancer.
Implications for Practice
Folate, also known as folic acid, is required for DNA synthesis in that it is necessary for regenerating methionine, which is the methyl donor for DNA methylation. Folate also is needed for production of essential purines and pyrimidines. If there is insufficient folate, errors in DNA methylation and subsequent DNA synthesis or repair may affect colon carcinogenesis.1
Folate is naturally available in barley, beans, dates, chicken, whole grains, pork, root vegetables, spinach, wheat germ, salmon, tuna, milk, and oranges.2 In 1973, when the U.S. Food and Drug Administration authorized an increase in folate, about one-fourth of all Americans began to ingest additional 400 mcg of folate from vitamin supplements and fortified cereals.
The unexplained and dramatic drop in the incidence of colon cancer among Caucasians in the late 1980s is of great interest. Prior to this study, health care professionals believed the colon cancer reduction was due to increased use of screening with fecal occult blood tests and sigmoidoscopies. This new information leads one to speculate that the increase in folate through dietary supplements and cereal enrichment led to the colon cancer reduction almost two decades ago.1
In other research, data from the Nurses’ Health Study showed a relationship between folate and multivitamin use and lower risk of coronary heart disease. Researchers concluded that folic acid reduces the production of homocysteine, a blood vessel irritant, and may offer protection from heart disease.3 (See "Homocysteine and Cereal: Help the Heart by Eating Right" in RN Advanced Practice Alert, September 1998, p. 20.)
References
1. Giovannucci E, Stampfer MJ, Colditz GA, et al. Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study. Ann Int Med 1998;129:517-524.
2. Judelson, DR , Dell, DL. The American Medical Women’s Association: The Women’s Complete Wellness Book. New York City: Golden Books; 1998:152.
3. Malinow MR, Duell PB, Hess DL, et al. Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. NEJM 1998;338:1009-1015.
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