Non-Olympian trials in Torino put soy and omega-3s to the test
by Craig Weatherby
The history of menopausal women and their attempts to alleviate the misery of hot flashes has been fraught with the failure of remedies both natural and pharmaceutical.
But the Italian city of Torino, host of the 2006 Winter Olympics, may have brought us more than a transitory sports spectacle: researchers in the mountain-ringed metropolis may have found a new role for omega-3s in women’s health.
Hormones for hot flashes: heart fears dampen demand
- Hormone replacement therapy (HRT) has been the only reliably effective treatment, but it may pose unacceptable risks.
- Previous alternatives to HRT have not proven better than placebo.
- The results of a new two-part study indicate that supplemental marine omega-3s may provide a reduction in hot flashes about 44 percent greater than the reduction produced by soy isoflavone or placebo pills.
The most common and effective—albeit far from infallible—treatment for hot flashes has been a doctor’s prescription for hormone replacement therapy (HRT), which provides supplemental estrogen or a combination of estrogen and progestin. (Aside from HRT, the prescription remedies with the best evidence of efficacy are micronized progesterone and synthetic progestins.)
To quote from a review article published earlier this year by a leading researcher in the field (Albertazzi P 2006), “Hot
flashes are known to respond readily to placebo, which alone decreases their frequency by 20-40%. … estrogen therapy reduces hot flashes by about 70-80%; this is twice as effective as placebo. However, estrogen is unable to be universally used, either because of contraindications or because of an unwillingness of women to take it. Furthermore, hot flashes may persist in spite of adequate estrogen replacement.”
Women’s reluctance to take HRT just for hot flashes—as unpleasant and disruptive as they can be—was increased in 2004. That year witnessed the early cessation of a trial in the large Women’s Health Initiative trial, which it seemed to show that HRT produces higher risks of breast cancer, heart attack and stroke.
However, the prematurely truncated WHI trial did not isolate the health effects, good or bad, of HRT in women aged 50-54 years experiencing menopausal symptoms: the subgroup most likely to experience cardiovascular benefits. Out of 16,608 women in the trial, only 574 fit both criteria. At the time, many expert observers noted that the rewards of HRT among these women may well outweigh the risks, but the trial authors failed to explore the balance in this highly relevant subgroup.
Thus, the jury remains out on the relative health risks and hot-flash-reducing rewards of HRT among women who need it most.
Common HRT alternatives: most come up shortWhat about non-prescription treatments? While several have shown promise in preliminary investigations, none enjoy conclusive evidence of efficacy, because we lack sufficient data from repeated, rigorously controlled clinical trials.Women's health advocate Christiane Northrup, M.D. notes that soy foods, soy isoflavones, and topical progesterone cream have been shown to decrease hot flashes in some women. For a detailed discussion of the controversial issue of hot-flash treatment, we recommend her excellent bestseller, The Wisdom of Menopause.As we noted, one challenge facing any alternative to HRT is that hot flashes respond to placebo (inactive) treatments more strongly than most medical conditions. Accordingly, any proposed treatment for hot flashes has to be highly effective to improve on the very strong placebo effect seen in most clinical trials. (As we will see, marine omega-3s may fit the bill.)In a literature review published last year—which echoes the authors of other recent reviews—noted medical herbalistTieraona Low Dog, M.D. found little evidence to support use of the most commonly touted natural alternatives to HRT, with the exception of black cohosh:
The class of anti-depressants known as serotonin reuptake inhibitors (e.g., Prozac) have also been promoted as beneficial for reducing hot flashes, but, as the author of the review cited above (Albertazzi P 2006) noted, “These are, at best, approximately half as effective as estrogen for the relief of menopausal symptoms, and are only marginally better than placebo.”
- “The majority of studies indicate that extract of black cohosh (Actaea racemosa L.) improves menopause-related symptoms; however, methodologic shortcomings in the trials were identified… ongoing studies funded by the National Institutes of Health (NIH) will provide more definitive safety and efficacy data.”
- “Single clinical trials do not support the use of dong quai (Angelica sinensis L.), ginseng (Panax ginseng C.A. Mey), or evening primrose seed oil (Oenothera biennis L.) for improving menopausal symptoms.”
- “Soy isoflavone extracts appear to have minimal to no effect, although definitive conclusions are difficult given the wide variation in product composition and dose.… Semipurified isoflavone red clover leaf extracts have minimal to no effect in reducing menopausal symptoms.”
However, the encouraging results of two new controlled clinical trials suggest that omega-3 fatty acids deserve more study as possible aids to reducing hot flashes.
Twin Torino trials test omega-3s and soy
Researchers in the hormonal gynecology unit of Torino’s Azienda Hospital conducted two small, overlapping clinical trials designed to test the ability of soy isoflavones and marine omega-3s to reduce hot flashes.
Isoflavones from soy and red clover, which have been promoted for hot flashes and other menopausal symptoms, are closely related to the antioxidant polyphenolic compounds in tea, berries, and chocolate.
The researchers divided the investigation in two parts, called Study A and Study B.
The participants were 57 postmenopausal women (29 in Study A, 28 in Study B) who’d reported suffering more than five troublesome hot flashes per day.
Both of the overlapping studies were double-blind, randomized, placebo-controlled, cross-over trials—therefore meeting the highest standard of reliability—and each lasted for six months.
After a two-week observation period, all of the women in both groups (Study A and Study B) were randomized to receive two capsules per day providing either 60mg of soy isoflavones or a placebo (inactive substance) for three months (i.e., half the study period).
Thereafter, women who had taken isoflavones for the first three months were given placebo for the second three months, and vice-versa.
In addition to the soy isoflavone and placebo capsules that all of the women in both study groups (A and B) took during alternating three-month periods, the women enrolled in part B also took a "PUFA" (polyunsaturated fatty acid) supplement every day of the entire six-month period.
Each PUFA capsule contained 200mg of omega-3s—a full 75 percent of its potentially active ingredients, by weight—plus 20mg of omega-6 GLA, 15 mg of Vitamin E, and a mixture of policosanols and lipoic acid (25mg).
It's unclear why the research team did not just use 100 percent fish oil, since none of the ancillary ingredients in the supplements were present in amounts large enough to have any likely effect other than to protect the omega-3s from oxidation.
Results suggest omega-3s may fight hot flashes better than soy
During the three-month soy period of the trial, the women in Study A—the non-omega-3 group—did not experience reductions in hot flash frequency significantly greater than the declines reported during the three-month placebo pill period.
As the study authors said, “The reduction in hot flushes [flashes] during the 12 weeks of treatment with isoflavones was not statistically different from that observed during the 12 weeks of placebo.”
In contrast, women in the Study B group (omega-3s plus soy) enjoyed a “progressive and highly significant reduction” in the number of hot flashes: a decline about 44 percent greater than the one experienced by women in the study A (soy without omega-3s) group.
This outcome led the researchers to attribute the benefits seen in study group B to the marine omega-3s in the PUFA/omega-3 capsules. As they said, “In these two trials the isoflavone extract did not show greater efficacy on the hot flushes than the placebo. The reduction of hot flushes [flashes] observed in the Study B [group] might be due to the PUFA [omega-3] supplement.”
The Italian researchers also offered a plausible explanation as to why omega-3s might reduce hot flashes:
“PUFAs, particularly Omega-3 fatty acids, could reduce hot flushes through their influence on neuronal [brain cell] membranes and/or the modulation of the neurotransmitter function and the serotoninergic system. Studies specifically designed to document the action of [omega-3] PUFAs on hot flushes would be welcome.”
Note: the “serotoninergic system” is the metabolic process that produces serotonin, which is a key mood-modulating neurotransmitter in the brain.
The results of the Torino team's small but well-controlled pilot investigation do not prove that omega-3s can reduce hot flashes reliably. However, they should encourage other researchers to test the hypothesis in larger studies.
- Campagnoli C, Abba C, Ambroggio S, Peris C, Perona M, Sanseverino P. Polyunsaturated fatty acids (PUFAs) might reduce hot flushes: an indication from two controlled trials on soy isoflavones alone and with a PUFA supplement. Maturitas. 2005 Jun 16;51(2):127-34. Epub 2004 Dec 25.
- Low Dog T. Menopause: a review of botanical dietary supplements. Am J Med. 2005 Dec 19;118(12 Suppl 2):98-108. Review.
- Writing Group for the Women's Health Initiative Investigators. Risks and benefits of oestrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomised controlled trial. JAMA 2002;288:321-333.
- Naftolin F, Taylor HS, Karas R, Brinton E, Newman I, Clarkson TB, et al. The Women's Health Initiative could not have detected cardioprotective effects of starting hormone therapy during the menopausal transition. Fertility and Sterility 2004;81(6):1498-501.
- Albertazzi P. A review of non-hormonal options for the relief of menopausal symptoms. Treat Endocrinol. 2006;5(2):101-13.
- Carroll DG. Nonhormonal therapies for hot flashes in menopause. Am Fam Physician. 2006 Feb 1;73(3):457-64. Review.
- Slopien R, Meczekalski B, Warenik-Szymankiewicccz A. Relationship between climacteric symptoms and serum serotonin levels in postmenopausal women. Climacteric. 2003;6:53–57.
- Yehuda S, Carasso RL. Modulation of learning, pain thresholds and thermoregulation in the rat by preparations of free purified linolenic and linoleic acids: determination of the optimal O3 to O6 ratio. Proc Natl Acad Sci U S A. 1993;90:10345–10349.