Soy and hot flashes: Should the 2012 meta analysis be updated?

Transcription

1 Soy and hot flashes: Should the 2012 meta analysis be updated? Mark Messina, PhD, MS Soy Nutrition Institute Nutrition Matters, Inc. Loma Linda University August 23, 2018

2 The Hot Flash Hypothesis Isoflavones can mitigate the drop in estrogen levels Herman Adlercreutz, MD, PhD University of Helsinki, Finland % of women with hot flashes Japan Canada USA China Exp Gerontol 29: 307, 1994; Maturitas 2006 Lancet 339 (8803), 1233

3 Soy isoflavone supplements are significantly more effective than placebo in reducing the frequency and severity of hot flashes. Menopause 19: , 2012

4 Only trials intervening with extracts derived from soybeans were eligible* *1 trial used synthetic genistein

5 Decrease in Hot Flash Frequency & Severity in Response to Isoflavones Symptom Frequency 13 studies 1196 women Severity 9 studies 988 women Group Placebo Isoflavones Net Placebo Isoflavones Net Percent Decrease 1 P < P = 0.001

6 Decrease in Hot Flash Frequency & Severity in Response to Isoflavones Symptom Frequency 13 studies 1196 women Severity 9 studies 988 women Percent Group Decrease Placebo 29.6 Isoflavones Net Placebo 21.4 Isoflavones Net 1 P < P = 0.001

7 Decrease in Hot Flash Frequency & Severity in Response to Isoflavones Symptom Frequency 13 studies 1196 women Severity 9 studies 988 women Group Percent Decrease Placebo 29.6 Isoflavones 50.2 Net Placebo 21.4 Isoflavones Net P < P = 0.001

8 Additional findings: 1. Effects are not transient 2. Efficacy unrelated to baseline frequency 3. Efficacy affected by the isoflavone profile of the supplement

9 Additional findings: 1. Effects are not transient 2. Efficacy unrelated to baseline frequency 3. Efficacy affected by the isoflavone profile of the supplement

10 the reduction in hot flashes was related to genistein dose, not total isoflavone content of the treatments.

11 Isoflavone Profile of Two Commonly Used Soy Supplements Soybeans Supplements Whole soy Soygerm Genistein Daidzein Glycitein

12 mg/day 1 High Genistein Supplements Reduce Hot Flash Frequency More than Low Genistein Supplements Number of trials (n) Net % decrease > Median, 18.8 mg 2 P = 0.03 between groups (random effects model)

13 Isoflavones and the Alleviation of Menopausal Hot Flashes Expected 50-65% ( 50 mg total isoflavones) ( 19 mg genistein) Approximately two servings of traditional soyfoods

14 Womens Health 10: 549, 2014 it is surprising that genistein-rich isoflavone supplements have not been embraced as a treatment for hot flashes to a greater extent than they have, especially in light of the FDA s approval of Brisdelle

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16 it seems unlikely that soy isoflavones have enough estrogenic activity to have an important impact on vasomotor symptoms of estrogen deficiency in perimenopausal women.

17 Arch Intern Med 171: 1369, 2011 A meta-analysis of 19 randomized, placebo controlled trials concluded that there was a statistically significant improvement in hot flashes with soy treatment, but the mean reduction was 0.39 hot flashes per day (less than one-half hot flash per day) compared with placebo. This difference is so small as to be clinically unimportant

18 The overall result showed a standardized mean difference of (95% CI, to -0.25) in favor of soy

19 J Clinical Oncol 2018 Soy is not recommended for hot flashes in patients with breast cancer due to lack of effect. (Grade D).

20 At the end of the study, 48.4% of women in the soy isoflavone group and 31.7% in the placebo group reported having hot flashes (P= 0.02).

21 Cochrane Database Syst Rev. 2013, CD No conclusive evidence shows that phytoestrogen supplements effectively reduce the frequency or severity of hot flushes and night sweat in perimenopausal or postmenopausal women, although benefits derived from concentrates of genistein should be further investigated.

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23 Evid Based Med.19: 178, 2014 Among 12 trials that assessed soy isoflavone extracts (tablets, capsules) evidence that extracts reduced VMS frequency or severity was not conclusive. The authors summary suggests that extracts with a minimum of 30 mg genistein are the sole products producing sufficient evidence to recommend their use.

24 Therapeutic efficacy of soy supplementation may vary based on the relative amounts of genistein and daidzein. (meta-analysis not cited)

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26 Intestinal Metabolism OH A O C Daidzein Asians: 50-60% Non-Asians: 25-30% O OH B OH OH 80-90% of population CH 3 OH O Equol OH O OH O-desmethylangolensin (ODMA)

27 J Womens Health (Larchmt) 21: , 2012

28 Examples of subsequently published hot flash trials

29 Effects of Genistein (54 mg/d) on Hot Flashes in 99 Postmenopausal Women with Metabolic Syndrome Number per day Placebo Genistein Months Difference between groups, p<0.001 Endocrine 55: 899, 2017

30 Effect of Isoflavones (90 mg/d) 1 on Hot Flash Frequency 2 in Chinese Postmenopausal Women 3 Number/day % Placebo (n=33) % 0 months 6 months Isoflavones (n=37) % genistein, 47.8% daidzein 2 0, none; 1, <3x/d; 2, 3-9x/d; 4, 10x/d 3 Women mostly abstained from eating soy 3 p<0.05. J Clin Biochem Nutr 53: 102, 2013

31 1. Vahid Dastjerdi, M., Eslami, B., Alsadat Sharifi, M., Moini, A., Bayani, L., Mohammad Khani, H., and Alipour, S. Effect of soy isoflavone on hot flushes, endometrial thickness, and breast clinical as well as sonographic features. Iran J Public Health. 2018, 47, Imhof, M., Gocan, A., and Schmidt, M. Soy germ extract alleviates menopausal hot flushes: placebo-controlled double-blind trial. Eur J Clin Nutr Vitale, S.G., Caruso, S., Rapisarda, A.M.C., Cianci, S., and Cianci, A. Isoflavones, calcium, vita and inulin improve quality of life, sexual function, body composition and metabolic parameters in menopausal women: result from a prospective, randomized, placebo-controlled, parallel-group study. Prz Menopauzalny. 2018, 17, Costa, J.G., Giolo, J.S., Mariano, I.M., Batista, J.P., Ribeiro, A.L.A., Souza, T.C.F., de Oliveira, E.P., Resende, A.P.M., and Puga, G.M. Combined exercise training reduces climacteric symptoms without the additive effects of isoflavone supplementation: A clinical, controlled, randomised, double-blind study. Nutr Health. 2017, 23,

32 5. Tit, D.M., Pallag, A., Iovan, C., Furau, G., Furau, C., and Bungau, S. Somatic-vegetative symptoms evolution in postmenopausal women treated with phytoestrogens and hormone replacement therapy. Iran J Public Health. 2017, 46, Lee, H., Choue, R., and Lim, H. Effect of soy isoflavones supplement on climacteric symptoms, bone biomarkers, and quality of life in Korean postmenopausal women: a randomized clinical trial. Nutr Res Pract. 2017, 11, Fontvieille, A., Dionne, I.J., and Riesco, E. Long-term exercise training and soy isoflavones to improve quality of life and climacteric symptoms. Climacteric. 2017, 20, Bitto, A., Arcoraci, V., Alibrandi, A., D'Anna, R., Corrado, F., Atteritano, M., Minutoli, L., Altavilla, D., and Squadrito, F. Visfatin correlates with hot flashes in postmenopausal women with metabolic syndrome: effects of genistein. Endocrine. 2017, 55, Malik, S., Pannu, D., Prateek, S., Sinha, R., and Gaikwad, H. Comparison of the symptomatic response in Indian menopausal women with different estrogen preparations for the treatment of menopausal symptoms: a randomized controlled trial. Arch Gynecol Obstet. 2016, 293,

33 5. Tit, D.M., Pallag, A., Iovan, C., Furau, G., Furau, C., and Bungau, S. Somatic-vegetative symptoms evolution in postmenopausal women treated with phytoestrogens and hormone replacement therapy. Iran J Public Health. 2017, 46, Lee, H., Choue, R., and Lim, H. Effect of soy isoflavones supplement on climacteric symptoms, bone biomarkers, and quality of life in Korean postmenopausal women: a randomized clinical trial. Nutr Res Pract. 2017, 11, Fontvieille, A., Dionne, I.J., and Riesco, E. Long-term exercise training and soy isoflavones to improve quality of life and climacteric symptoms. Climacteric. 2017, 20, Bitto, A., Arcoraci, V., Alibrandi, A., D'Anna, R., Corrado, F., Atteritano, M., Minutoli, L., Altavilla, D., and Squadrito, F. Visfatin correlates with hot flashes in postmenopausal women with metabolic syndrome: effects of genistein. Endocrine. 2017, 55, Malik, S., Pannu, D., Prateek, S., Sinha, R., and Gaikwad, H. Comparison of the symptomatic response in Indian menopausal women with different estrogen preparations for the treatment of menopausal symptoms: a randomized controlled trial. Arch Gynecol Obstet. 2016, 293,

34 10. Chi, X.-X. and Zhang, T. The effects of soy isoflavone on bone density in north region of climacteric Chinese women. J Clin Biochem Nutr. 2013, 53, Cianci, A., Cicero, A.F., Colacurci, N., Matarazzo, M.G., and De Leo, V. Activity of isoflavones and berberine on vasomotor symptoms and lipid profile in menopausal women. Gynecol Endocrinol Amato, P., Young, R.L., Steinberg, F.M., Murray, M.J., Lewis, R.D., Cramer, M.A., Barnes, S., Ellis, K.J., Shypailo, R.J., Fraley, J.K., et al. Effect of soy isoflavone supplementation on menopausal quality of life. Menopause. 2013, 20, Ye, Y.B., Wang, Z.L., Zhuo, S.Y., Lu, W., Liao, H.F., Verbruggen, M.A., Fang, S., Mai, H.Y., Chen, Y.M., and Su, Y.X. Soy germ isoflavones improve menopausal symptoms but have no effect on blood lipids in early postmenopausal Chinese women: a randomized placebocontrolled trial. Menopause Palacios S, Lilue M, Mejia A et al. (2017) Omega-3 versus isoflavones in the control of vasomotor symptoms in postmenopausal women. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 33: 951, 2017

35 J Nutr 140: 2318S-2321S, 2010