Preliminary clinical trials offer hope and suggest that omega-3s beat soy and herbs; more clinical study needed
by Craig Weatherby
The most common and effective—but far from infallible—treatment for hot flashes has been prescription hormone replacement therapy (HRT).
But the jury remains out when it comes to judging HRT’s relative health risks and flash-reducing rewards.
Women’s reluctance to take HRT just for hot flashes rose in 2004 when the large Women’s Health Initiative (WHI) trial indicated that taking HRT for more than four years raises their risks for breast cancer, heart attack, and stroke.
Those fears were eased somewhat by reexaminations of the WHI's results, but most doctors say that taking HRT solely for menopause symptoms makes sense only if they're pretty severe. The Australian Medical Association presents a good summary of the current consensus on HRT risks and benefits, here.
Aside from HRT, the prescription remedies with the best evidence of efficacy are certain anti-depressants—not including Prozac (fluouxetine)—micronized progesterone, and synthetic progestins.
Non-prescription remedies fall short
While several non-prescription treatments—isoflavones, black cohosh, etc.—have shown promise in preliminary investigations, none possess conclusive evidence of efficacy (Low Dog T 2005; Carrol DG 2006; Albertazzi P 2006; Cheema D et al. 2007).
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.
But when combined with prior findings, the results of a new clinical trial put marine omega-3s in the post position, leading other non-prescription contenders for the hot-flash-fighting crown.
Early last month, we reported on research concerning the mood effects of omega-3s (See “Omega-3s Affirmed as Mood Lighteners”).
And the women participating in one of the clinical trials, conducted in Canada, also reported about one-third fewer hot flashes.
Canadian trial finds omega-3s may fight hot flashes
Dr. Michel Lucas and his colleagues at Quebec’s Université Laval recruited 120 women age 40 to 55 and divided them into two groups.
When the study started, the average number of daily hot flashes experienced by all of the women was 2.8.
Women in the first group took fish oil capsules standardized to provide one gram of EPA—one of the two key omega-3s in fish oil—every day for eight weeks.
Women in a second, “control” group took capsules containing sunflower oil free of EPA.
The women taking omega-3 EPA reported 1.58 fewer daily flashes, compared with only 0.5 fewer flashes in the control (sunflower oil) group.
As the researchers wrote, “The odds of being a responder among those taking EPA were about three times greater than among those taking placebo.”
(By “responder”, they meant someone who experienced positive results.)
Of course, as the Canadians noted, “These results need to be confirmed by a clinical trial specifically designed to evaluate hot flashes in more symptomatic women.”
But the Laval team made this key point in a press release, “The change that can be attributed to the use of omega-3s, i.e. a decrease of 1.1 hot flashes per day, is equivalent to results obtained with hormone therapy and antidepressants.”
Italian trials found omega-3s more effective than soy
Four years ago, researchers from Torino, Italy’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 (Campagnoli C et al. 2004).
Isoflavones from soy and red clover, which have been promoted to alleviate hot flashes and other menopausal symptoms, are closely related to the antioxidant polyphenolic compounds in tea, berries, and chocolate.
The participants were 57 postmenopausal women who’d reported suffering more than five troublesome hot flashes per day.
The researchers divided the investigation into two parts, called Study A and Study B, with 29 women participating in Study A and 28 participating in Study B.
Both of the 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 take either two 60 mg of supplemental 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.
But the women enrolled in part B also took an omega-3-rich fat supplement every day of the entire six-month period.
Each fat capsule contained 200 mg of omega-3s—a full 75 percent of its potentially active ingredients, by weight—plus 20 mg of omega-6 GLA, 15 mg of Vitamin E, and a mixture of policosanols (from wheat germ) and lipoic acid (25 mg).
It’s unlikely that any of the ancillary ingredients in the fat supplement were present in amounts large enough to have any likely effect other than to protect the omega-3s from oxidation.
Omega-3s fought 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 (omega-3s plus soy) group enjoyed a “progressive and highly significant reduction” in the number of hot flashes: a decline about 44 percent greater than the one experienced by the women who got soy only, without omega-3s.
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 wrote, “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.” (Campagnoli C et al. 2004).
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.” (Campagnoli C et al. 2004).
(The “serotoninergic system” is the metabolic process that produces serotonin, which is a key mood-modulating neurotransmitter in the brain.)
Like the new Canadian findings, the results of the Torino team's small but well-controlled pilot investigation from 2005 do not prove that omega-3s can reduce hot flashes reliably.
However, the combined success of the three trials should encourage other researchers to test the hypothesis in larger studies.
In the meantime, it can’t hurt women with hot flashes to try cooling their hormonal flames with fatty fish and fish oil, since they have no serious adverse side effects.
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- 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.