Always Ask Who Are the Direct and Indirect Sponsors Behind Every Health Research!
By Chris D. Meletis, ND
3 April 2008
Chris D. Meletis, N.D. is Dean of Clinical Education, Chief Medical Officer and Medicinary Director at the National College of Naturopathic Medicine, in Portland, Oregon. In this administrative role, he oversees the operations of more than a dozen teaching clinics and the daytoday activities of several hundred student clinicians and physicians.
He is an experienced professor, private practice physician, and a formulate of nutriceutical products for the retail and professional markets.
Dr. Meletis is the author of numerous articles, publications and books, including: A Naturopathic Guide to Clinical Nutrition, The Practitioner's Guide to Orthopedic Testing, and Better Sex, Naturally.
Despite years of studies showing the benefits of multinutrient supplements and dietary nutrients, recently authors of a Harvard Men’s Health Watch article declared that individuals should stop taking multivitamins, claiming that they may be harmful to our health.1
The controversy that the Harvard authors stirred up revolves primarily around one nutrient found in multivitamins, specifically, folic acid. They based their claims primarily on one study published in JAMA that showed an increased incidence of precancerous colorectal polyps in 1,021 men and women given folic acid supplements.2 In the double-blind, placebo-controlled, randomized clinical trial conducted between July 1994 and October 2004, men and women with a recent history of colorectal adenomas were randomly assigned into two groups. One group of 516 subjects received 1 mg/day of folic acid while another group of 505 subjects received a placebo.
During the first 3 years, 987 participants underwent colonoscopy follow-up. In this first follow-up period, the incidence of at least 1 colorectal adenoma was 44.1 percent (221 subjects) in the folic acid group compared to 42.4 percent (206 subjects) for the placebo group. Incidence of at least 1 advanced lesion was 11.4 percent (57 subjects) in the folic acid group and 8.6 percent (42 subjects) for the placebo group. A total of 607 participants underwent a second follow-up, and the incidence of at least 1 colorectal adenoma was 41.9 percent (127 subjects) for the folic acid group and 37.2 percent (113 subjects) for the placebo group. In this second follow-up period, 35 subjects taking folic acid developed at least 1 advanced lesion while 21 subjects taking a placebo developed an advanced lesion. During the second follow-up period, folic acid was associated with higher risks of having 3 or more adenomas (11 participants in the placebo group compared to 27 participants in the folic acid group).
No significant association was found between folic acid and risks of death, colorectal cancer, myocardial infarction, coronary revascularization, or stroke. The researchers did, however, observe a higher rate of noncolorectal cancers among participants in the folic acid group (54 subjects) versus 32 in the placebo group. This difference was due to an excess of prostate cancer, with 24 cases in the folic acid group and 9 cases in the placebo group. According to the researchers, “Although a significant excess of prostate cancers was observed in the folate group, this might be spurious given the number of adverse events evaluated.”
The results were contradictory to a large number of epidemiological studies, animal studies and smaller human studies using folic acid supplements that show that low levels of folate are linked to decreased risks of colorectal cancer.3-8 The study was considered to be important since it was a randomized, placebo controlled trial.
A Closer Look
After reporting on the study above, the writers of the Harvard Men’s Health Watch article came to the conclusion that people should not take multivitamins until the safety of folic acid is confirmed.
However, let’s take a closer look at the JAMA study the Harvard article used as a basis for the warning about multivitamins. First, the study was done on people with a pre-existing history of colon polyps, which are more common in individuals with poor diets, constipation, low vitamin D, smoking, etc. Therefore, the study population was essentially unhealthy and may have had existing microscopic, non-detectable disease that was not identified prior to the study’s start. Furthermore, their folic acid levels could have been significantly compromised compared to normal controls (which were not used in the study) and with folic acid levels low prior to treatment for a protracted time they could have had a head start on the disease process. Individuals who do not consume enough folate-containing dark, leafy vegetables (as is likely the case in the subjects studied) also are low in other cancer-protective phytonutrients and minerals found in those vegetables.
The folic acid used in the study, which was consumed in tablet rather than capsule form, was provided by Wyeth, which makes Centrum®, and likely included the same binders and excipients used in Centrum that may lower bioavailability of folic acid. Additionally, the study authors neglected to take into account the fact that B vitamins do not occur alone in nature; they occur in synergy and they are more effective when combined. In fact, many biochemical functions of folate are dependent on the adequate availability of other B vitamins. A study in rodents indicated that a combined deficiency of folate, riboflavin, and vitamins B6 and B12 may increase the risk of DNA damage and colorectal cancers. In the ten-week study, 96 mice were fed diets with different combinations of B vitamin depletion. The researchers found that although folate depletion alone did not affect DNA, a mild depletion of all four B vitamins significantly increased the DNA damage.9
Vitamin B6 alone also has been shown to reduce the risk of colon disease in epidemiological studies by more than 20 percent, adding further merit to the fact that folic acid is only one piece of the puzzle.10
Other Flaws in The Study
The researchers who conducted the study that indicated folic acid may increase the risk of precancerous colon polyps did not control for a number of important factors. Vitamin D deficiency has been linked extensively to an increased risk of colon cancer and other cancers as well, yet the authors never tested the subjects’ vitamin D levels. They also never controlled for subjects who are taking acid blockers, which can lower folic acid levels and prevent nutrient absorption, nor did they report whether the subjects were asked to take the folic acid with or without food. They also did not evaluate the subjects’ fiber intake, an important factor given that fiber consumption is linked to a reduction in colon cancer risk.
Some of the study authors also have drug company affiliations. One of the researchers reported being a consultant to Merck and Bayer, another researcher reported receiving research support from Merck and also is a consultant to Merck, Bayer, GlaxoSmithKline, and Procter & Gamble.
Multivitamins Essential to Good Health
In a country where residents habitually eat less than the amount of fruits and vegetables necessary for optimal health is it really wise to ask people to give up multivitamins? In 1988–1994, an estimated 27 percent of adults met the USDA guidelines for fruit (equal to or more than two servings) and 35 percent met the guidelines for vegetables (equal to or more than three servings). In 1999–2002, 28 percent and 32 percent of adults met fruit and vegetable guidelines, respectively. There was a significant decrease in vegetable consumption over time and only 11 percent met USDA guidelines for both fruits and vegetables in 1988–1994 and 1999–2002, indicating no change in consumption.11
This further emphasizes the importance of consuming a high-quality multivitamin to make up for the nutrient deficiencies that occur due to poor diets. In fact, numerous studies have uncovered the benefits of taking multivitamins. A year ago, researchers reported in the American Journal of Clinical Nutrition that greater concentrations of selenium were associated with reduced prostate cancer risk in men who reported a high intake of vitamin E, in multivitamin users, and in smokers.12
Interestingly, the university that is now recommending that people don’t take multivitamins came to the conclusion 6 years ago that everyone should be taking multivitamins. In a June 2002 review published in JAMA, Harvard researchers reported that suboptimal intake of some vitamins, above levels causing classic vitamin deficiency, is a risk factor for chronic diseases and common in the general population, especially the elderly. “Most people do not consume an optimal amount of all vitamins by diet alone,” the Harvard researchers wrote.13
Folic acid, when used with other B vitamins in multivitamins has been shown to lower levels of homocysteine, an amino acid linked to heart disease. Furthermore, folic acid has been firmly established as a crucial nutrient for women of childbearing age in order to prevent birth defects.
The bottom line is that folic acid (in a reductionistic mind set) can be treated as though it is a drug and studied alone. Or, one can look at folic acid as a building block for health that must work with other nutrients (such as those found in the diet, in multivitamins and in a good green drink) to serve as the steel for a strong foundation of optimal health.
References
1. Multivitamins and Your Health: A Reappraisal. Harvard Men’s Health Watch. March 2008. 12(8):1-4.
2. Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, McKeown-Eyssen G, Summers RW, Rothstein RI, Burke CA, Snover DC, Church TR, Allen JI, Robertson DJ, Beck GJ, Bond JH, Byers T, Mandel JS, Mott LA, Pearson LH, Barry EL, Rees JR, Marcon N, Saibil F, Ueland PM, Greenberg ER. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007 Jun 6;297(21):2351-9.
3. Giovannucci E. Epidemiologic studies of folate and colorectal neoplasia: a review. J Nutr. 2002;132(suppl):2350S-2355S.
4. Benito E, Cabeza E, Moreno V, Obrador A, Bosch FX. Diet and colorectal adenomas: a case-control study in Majorca. Int J Cancer. 1993;55:213-219.
5. Tseng M, Murray SC, Kupper LL, Sandler RS. Micronutrients and the risk of colorectal adenomas. Am J Epidemiol. 1996;144:1005-1014.
6. Baron JA, Sandler RS, Haile RW, Mandel JS, Mott LA, Greenberg ER. Folate intake, alcohol consumption, cigarette smoking, and risk of colorectal adenomas. J Natl Cancer Inst. 1998;90:57-62.
7. Breuer-Katschinski B, Nemes K, Marr A, et al. Colorectal Adenoma Study Group. Colorectal adenomas and diet: a case-control study. Dig Dis Sci. 2001;46:86-95.
8. Khosraviani K, Weir HP, Hamilton P, Moorehead J, Williamson K. Effect of folate supplementation on mucosal cell proliferation in high risk patients for colon cancer. Gut. 2002 Aug;51(2):195-9.
9. Liu Z, Choi SW, Crott JW, Keyes MK, Jang H, Smith DE, Kim M, Laird PW, Bronson R, Mason JB. Mild depletion of dietary folate combined with other B vitamins alters multiple components of the Wnt pathway in mouse colon. J Nutr. 2007 Dec;137(12):2701-8.
10. Theodoratou E, Farrington SM, Tenesa A, McNeill G, Cetnarskyj R, Barnetson RA, Porteous ME, Dunlop MG, Campbell H. Dietary Vitamin B6 Intake and the Risk of Colorectal Cancer. Cancer Epidemiology Biomarkers & Prevention. January 1, 2008; 17:171-182.
11. Casagrande SS, Wang Y, Anderson C, Gary TL. Have Americans Increased Their Fruit and Vegetable Intake? The Trends Between 1988 and 2002. American Journal of Preventive Medicine. April 2007. 32(4); 257-263.
12. Peters U, Foster CB, Chatterjee N, Schatzkin A, Reding D, Andriole GL, Crawford ED, Sturup S, Chanock SJ, Hayes RB. Serum selenium and risk of prostate cancer-a nested case-control study. Am J Clin Nutr. 2007 Jan;85(1):209-17.
13. Fletcher RH, Fairfield KM. Vitamins for chronic disease prevention in adults: clinical applications. JAMA. 2002 Jun 19;287(23):3127-9.