March 2016 Issue

Women's Health: Are Menopause Supplements Effective?
By Judith C. Thalheimer, RD, LDN
Today's Dietitian
Vol. 18 No. 3 P. 18

Today's Dietitian reviews what the research says and which brands are better than others.

Women who experience the various symptoms of menopause may turn to over-the-counter (OTC) supplements to ease their discomfort. Some natural compounds have been shown to be helpful, but are supplements on the market safe and effective? And do they provide anything that diet cannot?

Today's Dietitian provides an overview of the active compounds found in popular OTC menopause supplements and identifies those products containing amounts shown to be effective in clinical studies based on test results from ConsumerLab.com (CL), an independent evaluator of health and nutrition products.

What Works, and Why?
Symptoms of menopause such as hot flashes, flushing, vaginal dryness, and reduced sex drive are caused by naturally decreasing estrogen levels.1 While research results vary, natural compounds that have an estrogenlike effect in the body may lessen these symptoms.

Isoflavones
The most-studied compounds in the underresearched world of menopausal symptom relief are isoflavones, such as those found in soy (Glycine max) and red clover (Trifolium pretense).2 Isoflavones are phytoestrogens (plant estrogens) that have a mild estrogenic effect in the body.2 While a 2013 article in The Cochrane Database of Systematic Reviews found no conclusive evidence that phytoestrogens effectively reduce the frequency or severity of hot flashes, the authors wrote that the meta-analysis was limited by a lack of high-quality studies. The review did recommend more study of the isoflavone genistein, since four trials found that high levels (>30 mg/day) of genistein consistently reduced the frequency of hot flashes.3 Another isoflavone, daidzein, shows promise as well. A 2008 study in the journal Menopause reported a 43% reduction in hot flashes after eight weeks of treatment with a fermented soy germ product high in daidzein. Taking the supplement longer produced even better results: After 12 weeks, there was a 52% reduction in hot flashes reported, compared with a 39% reduction in the placebo group.4

Most of the isoflavones studied are extracted from soy protein.2 A 2006 review in The Journal of the American Medical Association found no reduction in hot flashes using soy isoflavone extracts after four to six weeks, but a significant reduction at 12 to 16 weeks and six months.5 In addition to soy, other plants are known to contain phytoestrogens. Some research has been done on red clover isoflavones, but results are inconsistent.2 A recent literature review in the Avicenna Journal of Phytomedicine concluded that red clover does seem to alleviate hot flashes in menopausal women, although the authors cautioned that the implications of this finding are limited due to a lack of good data.6

It's possible that isoflavone supplements are more effective in some women than others. About 95% of isoflavones are glycosides, meaning they're naturally attached to sugar molecules. Gut bacteria must remove these sugars before the body can absorb the isoflavones. It's important to note that not all women have the gut bacteria necessary to change isoflavones in this way, so the effectiveness of isoflavone supplements may vary.2

Black Cohosh
Black cohosh supplements are made from the roots and rhizomes of Cimicifuga racemosa, a plant in the buttercup family.2 Black cohosh has been shown in limited studies to help reduce hot flashes, relieve vaginal dryness, and protect bones from osteoporosis, possibly due to its estrogenlike effects.2 The scientific community still knows very little about this herb. How it may work and what the active components may be are still unknown.2 Compounds called triterpene glycosides often are listed on labels, but it's unknown whether these glycosides are responsible for any relief of menopausal symptoms. In fact, the most studied black cohosh product, Remifemin, which has shown promise for symptom relief, contains no triterpene glycosides.2 A 2014 study of Remifemin in menopausal women with uterine fibroids found a significant improvement in menopausal symptoms and a modest reduction in the size of fibroids after taking 40 mg a day for three months.7

The Best Supplements
An effective supplement should provide a dosage supported by the latest scientific information and be free of contaminants. Unfortunately, it can be difficult to tell exactly what a supplement has to offer just by looking at the label. Consumers should be aware that there's little independent oversight of supplement labels, so ingredients and amounts listed aren't necessarily accurate. CL ran tests on menopause supplements to determine exactly what each contained. The company looked for the amounts of active ingredients and the presence of contaminants like lead, cadmium, and arsenic.

Soy and Red Clover Isoflavones
All of the soy and red clover isoflavone products CL tested contained the number of milligrams of isoflavones listed on their labels. CL's testing also found clinically significant levels of one or more components (total isoflavones, genistein, and/or daidzein) in all but one product. Unfortunately, while the products accurately state total isoflavones, none of the labels tell the consumer how much of the specific isoflavones, like genistein and daidzein, they contain. Moreover, all of the labels give total isoflavones in their glycocidic form, which includes the weight of the naturally attached sugar. Consumers realistically will get only about one-half the listed milligrams of isoflavones once the sugar has been split off in their gut.2 None of the brands tested exceeded the contamination levels for lead, cadmium, or arsenic.2

According to the American Cancer Society, women with estrogen-receptor-positive breast cancer shouldn't take isoflavone supplements, although soyfoods are considered healthful and safe.8

Black Cohosh
Since the active components of black cohosh are still unknown, CL was unable to test supplements for clinical efficacy. The two supplements that listed triterpene glycoside content on their labels were accurate, and none of the tested products were contaminated with significant levels of unwanted plant species. Of the five black cohosh supplements tested, one, Nature's Way Black Cohosh Root, had lead levels slightly over the acceptable range. This product was the only supplement of any kind in the study not to earn an "approved" rating.

The biggest concern surrounding black cohosh supplements is that there have been several reports of severe liver injury. It's unknown whether these cases were caused by the herb itself, or by contaminants in the product used.2

Beyond Supplements
CL recommends women who want to get isoflavones directly from food focus on foods and beverages made from soy protein. Multiple studies show that consuming 20 g to 60 g per day of soy protein modestly decreases the frequency and severity of hot flashes.9 In addition to isoflavones, soy-based foods have many biologically active compounds that could potentially play a role in their health effects.2 Soy flour, soy beans, and soy protein provide clinically significant levels of aglycone isoflavones in a 100-g serving. Tempeh, miso, and tofu also are good sources. Soy oils and soy lecithin don't contain isoflavones, and soy sauce has very little.2

Isoflavones are found in legumes other than soy, as well as in foods like flaxseed, green tea, broccoli, and whole grains. In addition, other phytoestrogens, such as polyphenols, flavonoids, and isoflavonoids, can be found in a wide variety of foods, including grapes and wine, citrus fruits and juices, leafy greens, onions, tomatoes, chocolate, apples, berries, and capsicum peppers.10

While more work needs to be done to understand the role of isoflavone and black cohosh supplements in reducing menopausal symptoms, the majority of products on the market contain levels of compounds in line with the latest science and appear to be safe for most women. For women suffering from menopausal symptoms who don't want to use prescription treatments, these OTC remedies may be helpful. And for those who prefer to avoid the unknowns of the supplement market, a varied, healthful diet that regularly includes soy protein may just do the trick.

— Judith C. Thalheimer, RD, LDN, is a freelance nutrition writer, a community educator, and the principal of JTRD Nutrition Education Services.

References
1. Menopause: what is menopause? MedicineNet.com website. http://www.medicinenet.com/menopause/page2.htm. Updated September 25, 2015. Accessed January 5, 2016.

2. Product review: menopause supplements (soy and red clover isoflavones, black cohosh) and progesterone creams. ConsumerLab.com website. https://www.consumerlab.com/reviews/soy-isoflavones_red-clover_black-cohosh_supplements/phytoestrogens/. Updated September 16, 2015. Accessed December 6, 2015.

3. Lethaby A, Marjoribanks J, Kronenberg F, Roberts H, Eden J, Brown J. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database Syst Rev. 2013;12:CD001395.

4. Khaodhiar L, Ricciotti HA, Li L, et al. Daidzein-rich isoflavone aglycones are potentially effective in reducing hot flashes in menopausal women. Menopause. 2008;15(1):125-132.

5. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA. 2006;295(17):2057-2071.

6. Ghazanfarpour M, Sadeghi R, Latifnejad Roudsari R, et al. Effects of red clover on hot flash and circulating hormone concentrations in menopausal women: a systematic review and meta-analysis. Avicenna J Phytomed. 2015;5(6):498-511.

7. Xi S, Liske E, Wang S, et al. Effect of isopropanolic cimicifuga racemosa extract on uterine fibroids in comparison with tibolone among patients of a recent randomized, double blind, parallel-controlled study in Chinese women with menopausal symptoms. Evid Based Complement Alternat Med. 2014;2014:717686.

8. Simon S. How your diet may affect your risk of breast cancer. American Cancer Society website. http://www.cancer.org/cancer/news/features/how-your-diet-may-affect-your-risk-of-breast-cancer. Published May 21, 2015.

9. Natural medicines in the clinical management of menopausal symptoms. Natural Medicines Comprehensive Database website. http://naturaldatabase.therapeuticresearch.com/ce/ceCourse.aspx?s=
ND&cs=&pc=12%2D110&cec=1&pm=5

10. Patisaul HB, Jefferson W. The pros and cons of phytoestrogens. Front Neuroendocrinol. 2010;31(4):400-419.

ADVERTORIAL