Media Bias, Conflicts of Interest Distort Study Findings on SupplementsJune 2006
By Lyle MacWilliam, MSc, FP
Reducing Fat and Colorectal Cancer Risk
Similar to the previous studies, the Women’s Health Initiative colorectal cancer study28 was designed to evaluate whether a diet low in total fat, with abundant intake of fresh fruits and vegetables, helps prevent colorectal cancer. The findings reveal that dietary intervention did not reduce the incidence of this cancer in postmenopausal women. As in its companion studies, the power of this study was heavily compromised because participants in the intervention group were simply incapable of reaching the targeted fat-reduction levels. At a power of 40%, the study had less probability of detecting a reduction in colorectal cancer risk than the flip of a coin. Consequently, the negative findings are not surprising.
The slight elevation of risk reported in the findings, while far from significant, is also not surprising. In this context, the authors acknowledge that the intervention was accompanied by a statistically significant decrease in total vitamin E and gamma tocopherol intakes, an outcome that does not appear to have been anticipated or controlled for. The study was designed in 1991, when the authors would not have been aware of the negative influence that a concomitant reduction of vitamin E, particularly gamma tocopherol, would have on cancer risk.30
An across-the-board reduction in all fats, as mandated in the study, would inadvertently reduce blood levels of the fat-soluble tocopherols—precisely what was observed. Because of the important role played by gamma tocopherol in reducing the risk of colorectal cancer,31-35 its concomitant reduction within the intervention group may have had the antagonistic effect of enhancing colorectal cancer risk.
The three studies that were spun out of the Women’s Health Initiative fat-reduction trial had crippling design flaws that call their findings into question. Hobbled with statistical powers ranging from 40% to 60%, the authors would have been better off tossing a coin. At least that way they would not have squandered tens of millions of taxpayer dollars on studies that were simply incapable of doing the job.
Saw Palmetto: Another Study Designed to Fail?
At first blush, the results of a San Francisco study of saw palmetto’s effects on enlargement of the prostate, published in the February 9 issue of the New England Journal of Medicine,36 are puzzling. The negative finding that the plant extract was not effective in alleviating problems associated with an enlarged prostate is inconsistent with a large body of evidence that shows otherwise, including more than 20 studies demonstrating saw palmetto’s ability to alleviate commonly associated symptoms.37 One such study, a meta-analysis of 21 clinical trials involving over 3,000 men, concluded that saw palmetto showed a benefit versus placebo and showed benefits comparable to the drug finasteride (Proscar®), with significantly fewer side effects than the drug.37
The San Francisco study was a well-designed, double-blind, placebo-controlled trial with clear inclusion and exclusion criteria. It adhered closely to the standard protocols for clinical trials and all participants were screened to have a 75% adherence rate to the daily supplementation regimen (the final adherence rate was 92%). The primary outcome was to determine whether the use of saw palmetto, at a dose of 160 mg twice daily, would reduce symptoms of benign prostatic hyperplasia (BPH).
So why were the findings at odds with other similar studies?
First, the study examined men with moderate-to-severe BPH.37 The exclusion of patients with only mild disease may have limited the study’s ability to detect benefits.
Second, by design, the study investigated the effect of a single herbal ingredient, saw palmetto, even though many physicians find that moderate-to-severe BPH requires aggressive, multimodal treatment to achieve effective relief. From a scientific perspective, this approach cannot be faulted; however, from a clinical perspective, it is an example of where science’s compulsion to isolate a single variable often misses the larger picture. Nutritional researchers have long known that when it comes to prevention, there is no single “magic bullet”—a fundamental truth that the drug industry has been loath to accept.
In this context, the study overlooked the established value of ancillary herbal remedies such as nettle root and pygeum, which may work synergistically with saw palmetto. Because nettle root and pygeum may be particularly effective in more aggressive cases of prostate enlargement, their inclusion in the San Francisco trial would have made perfect sense.38-41
What can we conclude about the San Francisco study? Despite the trial’s solid fundamentals, the investigators’ decision to focus on only the more aggressive cases of benign prostatic hyperplasia, their use of a single moderate dose of saw palmetto (rather than a dosage range), and their disregard for the synergistic role of other herbal antagonists give it the appearance of failure by design.
Incidentally, none of the negative news articles reporting on the results of the study chose to mention that the researchers conducting the investigation have received consulting fees and financial support from major players in the drug industry. These include Merck, which manufactures the prostate drug Proscar®; GlaxoSmithKline, which makes Avodart®; and TAP Pharmaceutical Products. Inc., makers of Lupron®.
Consequently, when considering the study’s negative findings on an herbal supplement that cannot be patented, one should not disregard the considerable financial interests of the study’s authors.
It is no wonder that health-conscious readers are becoming frustrated and alarmed at the mixed messages promulgated by the mainstream news media. It seems one day we are told that something is good for us and the next day we are told that it is not. We could certainly be excused for wondering why scientists cannot get it straight for once.
If there is any consolation, it helps to understand that science never progresses smoothly—there will always be new findings that appear to refute long-held beliefs. Controversy is the crucible for change, and paves the road that science must travel to arrive at a final truth. Unfortunately, it does not help when media bias and conflicts of interest keep throwing up detours along the way.
In this respect, researchers and peer-reviewed journals bear a heavy responsibility and a fiduciary duty to report the results of clinical trials in a fair and unbiased manner. To their credit, the vast majority of investigators take great pains to ensure proper study design and unbiased reporting of their findings. As always, however, there are exceptions to the rule. Simply put, headline-grabbing pronouncements by the news media and by researchers elbowing for their 15 minutes of fame are not conducive to the advancement of science.
So, too, the national and local media has a public duty to ensure that their reporting of important scientific findings is balanced, accurate, and complete. Sensational headlines, disregard for study limitations, and—by design or otherwise—fundamental misrepresentation of the facts serves no good purpose, other than to bolster author Norman Mailer’s claim that “once a newspaper touches a story, the facts are lost forever.”
1. Available at: www.holisticprimarycare.net. Accessed March 1, 2006.
2. Available at: www.facsnet.org/tools/ ref_tutor/epidem/data.php3. Accessed March 1, 2006.
3. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006 Feb 23;354(8):795-808.
4. Rizzo R, Grandolfo M, Godeas C, Jones KW, Vittur F. Calcium, sulfur, and zinc distribution in normal and arthritic articular equine cartilage: a synchrotron radiation-induced X-ray emission (SRIXE) study. J Exp Zool. 1995 Sep 1;273(1):82-6.
5. Murav’ev I, Venikova MS, Pleskovskaia GN, Riazantseva TA, Sigidin I. Effect of dimethyl sulfoxide and dimethyl sulfone on a destructive process in the joints of mice with spontaneous arthritis. Patol Fiziol Eksp Ter. 1991 Mar;(2):37-9.
6. Lawrence RM. Methylksulfonylmethane (MSM): a double-blind study of its use in degenerative arthritis. Int J Anti-Aging Med. 1998;1:50.
7. Usha PR, Naidu MU. Randomized, double-blind, parallel, placebo-controlled study of oral glucosamine, methylsulfonylmethane and their combination in osteoarthritis. Clin Drug Invest. 2004 Jun;24(6):353-63.
8. Hochberg MC. Nutritional supplements for knee osteoarthritis—still no resolution. N Engl J Med. 2006 Feb 23;354(8):858-60.
9. Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006 Feb 16;354(7):669-83.
10. Dreosti IE. Magnesium status and health. Nutr Rev. 1995 Sep;53(9 Pt 2):S23-7.
11. Dimai HP, Porta S, Wirnsberger G, et al. Daily oral magnesium supplementation suppresses bone turnover in young adult males. J Clin Endocrinol Metab. 1998 Aug; 83(8):2742-8.
12. Segala M, ed. Osteoporosis. In: Disease Prevention and Treatment. Life Extension Media; 2000:501-6.
13. Gallai V, Sarchielli P, Morucci P, Abbritti G. Magnesium content of mononuclear blood cells in migraine patients. Headache. 1994 Mar;34(3):160-5.
14. Cohen L, Kitzes R. Infrared spectroscopy and magnesium content of bone mineral in osteoporotic women. Isr J Med Sci. 1981 Dec;17(12):1123-5.
15. Murray M. Calcium. Encyclopedia of Nutritional Supplements. Rocklin, CA: Prima Health; 2006:149-58.
16. Ullom-Minnich P. Prevention of osteoporosis and fractures. Am Fam Physician. 1999 Jul;60(1):194-202.
17. Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM. Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial. Ann Intern Med. 1996 Feb 15;124(4):400-6.
18. Meyer HE, Smedshaug GB, Kvaavik E, et al. Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. J Bone Miner Res. 2002 Apr;17(4):709-15.
19. Bischoff-Ferrari HA, Zhang Y, Kiel DP, Felson DT. Positive association between serum 25-hydroxyvitamin D level and bone density in osteoarthritis. Arthritis Rheum. 2005 Dec 15;53(6):821-6.
20. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med. 1992 Dec 3;327(23):1637-42.
21. Chapuy MC, Pamphile R, Paris E, et al. Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study. Osteoporos Int. 2002 Mar;13(3):257-64.
22. Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003 Mar 1;326(7387):469.
23. Vieth R. Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):575-9.
24. Grossman MI, Kirsner JB, Gillespie IE. Basal and histalog-stimulated gastric secretion in control subjects and in patients with peptic ulcer or gastric cancer. Gastroenterology. 1963 Jul;45:14-26.
25. Recker RR. Calcium absorption and achlorhydria. N Engl J Med. 1985 Jul 11;313(2):70-3.
26. Howard BV, Van HL, Hsia J, et al. Low-fat dietary pattern and risk of cardiovascular disease: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006 Feb 8;295(6):655-66.
27. Prentice RL, Caan B, Chlebowski RT, et al. Low-fat dietary pattern and risk of invasive breast cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006 Feb 8;295(6):629-42.
28. Beresford SA, Johnson KC, Ritenbaugh C, et al. Low-fat dietary pattern and risk of colorectal cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006 Feb 8;295(6):643-54.
29. Howell A, Cuzick J, Baum M, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet. 2005 Jan 1;365(9453):60-2.
30. MacWilliam LD. What makes gamma tocopherol superior to alpha tocopherol. Life Extension. April, 2006:25-31.
31. Available at: www.medscape.com. Accessed March 1, 2006.
32. Campbell S, Stone W, Whaley S, Krishnan K. Development of gamma (gamma)-tocopherol as a colorectal cancer chemopreventive agent. Crit Rev Oncol Hematol. 2003 Sep;47(3):249-59.
33. Campbell SE, Stone WL, Whaley SG, Qui M, Krishnan K. Gamma (gamma) tocopherol upregulates peroxisome proliferator activated receptor (PPAR) gamma (gamma) expression in SW 480 human colon cancer cell lines. BMC Cancer. 2003 Oct 1;3:25.
34. Christen S, Hagen TM, Shigenama EK, Ames BN. Chronic inflammation, mutation, and cancer. In: Parsonnet J, ed. Microbes and Malignancy: Infection as a Cause of Human Cancers. New York: Oxford University Press; 1999:35-88.
35. Stone WL, Papas AM. Tocopherols and the etiology of colon cancer. J Natl Cancer Inst. 1997 Jul 16;89(14):1006-14.
36. Bent S, Kane C, Shinohara K, et al. Saw palmetto for benign prostatic hyperplasia. N Engl J Med. 2006 Feb 9;354(6):557-66.
37. Available at: www.crn.org. Accessed March 1, 2006.
38. Maar K. Regression of the symptoms of prostatic adenomas. Results of 6 months’ conservative treatment using ERU capsules. Fortschr Med. 1987 Jan 10;105(1):18-20.
39. Lopatkin N, Sivkov A, Walther C, et al. Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms—a placebo-controlled, double-blind, multicenter trial. World J Urol. 2005 Jun;23(2):139-46.
40. Hartmann RW, Mark M, Soldati F. Inhibition of 5-alpha-reductase and aromatase by PHL-0081, a combination of PY102 (Pygeum africanum) and UR102 (Urtica dioica) extracts. Phytomedicine. 1996;3(2):121-8.
41. Choo MS, Bellamy F, Constantinou CE. Functional evaluation of Tadenan on micturition and experimental prostate growth induced with exogenous dihydrotestosterone. Urology. 2000 Feb;55(2):292-8.
42. Ioannidis JP. Why most published research findings are false. PLoS Med. 2005 Aug;2(8):e124. Epub 2005 Aug 30.