Saturday, 31 May 2014

The Science of Soy - The Eastern Viewpoints; Part A2: Soy and Risk of Breast cancer in Japanese Population

By Kyle J. Norton

Soy foods, including tofu have been in traditional Chinese diet over thousands of year, according to Chinese literature. The reduced risk of chronic disease in Asian population, including metabolic syndrome such as cardiovascular diseases, obesity and diabetes and lesser menopause symptoms in advanced age, may be aided by eating a lot of soy food accompanied with large portion of vegetables and fruits. Indeed, according to the study, only 10% of women in the East are experience symptoms of menopause in advanced age compared to over 70% of their Western counterparts.
According to Dr. Mark Messina, Ph.D., Soy foods contributed from 6.5%8  to 12.8%7  of total protein intake in older adult in Japan.(b)

The approval of cardiovascular benefit of soy by FDA in 1999 accompanied with the discovery of health benefits in clinical studies over past decade, prompted the promotion and advertisement of soy's health benefits in every aspect in Western society. Evidences could be seen by walking through the supermarkets and drug  stores.  Soy supplements and products such as tofu, soy milk, soy-based infant formula, and meatless “texturized vegetable protein” burgers were widely available. According to the United Soybean Board’s 2004–2005, 25% of Americans consumed soy foods or beverages at least once per week, and 74% viewed soy products as healthy.

Today, the promotion of soy is no longer existed, it may be results of discovery of adverse effects in single ingredient and animal studies, as intake of soy is associated to induce risk of certain mammary cancers and infertility. The publication of the result have drawn many criticisms. According to Thomas Badger, director and senior investigator at the Arkansas Children’s Nutrition Center in Little Rock, these effects are seen only under certain experimental conditions that are not likely to occur in humans—and therein lies the crux of the debate(a). Equol (4',7-isoflavandiol), an isoflavandiol metabolized from daidzein may be the causes, as 90% of Eastern population are equol producers but only 30% in the West.
The explanation of the positive effect of soy isoflavones in reduced risk of mammary cancers by  University of Goettingen may be interesting, as researchers said" Most importantly, there is dispute as to whether isoflavones derived from soy or red clover have negative, positive or any effect at all on the mammary gland or endometrium. It is beyond any doubt that soy products may have cancer preventing properties in a variety of organs including the mammary gland. However, these properties may only be exerted if the developing organ was under the influence of isoflavones during childhood and puberty".

Soybean is  a genus Glycine, belonging to the family Fabaceae, one of the legumes that contains twice as much protein per acre as any other major vegetable or grain crop, native to Southeast Asia. Now, it is grown worldwide with suitable climate for commercial profits.

1. Carbohydrates
2. Dietary fiber
3. Fat
4. Protein
5. Essential amino acid
6. Vitamin A
7. Vitamin B6
8. Vitamin B12
9. Vitamin C
10. Vitamin K
11. Calcium
12. Iron
13. Magnesium
14. Phosphorus
15. Potassium
16. Sodium
17. Zinc
18. Etc.

1. Isoflavones
2. Genistein
3. Saponins
4. Beta-sitosterol
5. Daidzein

I. Soy in Eastern population
A. The Japanese population
Japan, an island nation in the Pacific Ocean, lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south(c). According to Moriyama, Japanese women and men live longer and healthier than everyone else on Earth, it may be result of  healthier Japanese diet and lifestyle. According to the World Health Organization, the Japanese have an average of 75 years healthy living with disability-free, it may be due to average soy intake 10 to 70 times higher than in Western people(d)(e).
A.2. Soy and Risk of Breast cancer in Japanese Population
Breast cancer (malignant breast neoplasm) is a cancer started in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. There is also rare cases that breast cancer started in other areas of the breast. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.
The searching of keyword in PubMed with keywords, soy and breast cancer in Japanese women, found 15 related studies.
Epidemiologic evidence suggesting high intake of soy in Japanese population is associated to reduce risk of breast cancer(1) and regular consumption of probiotic beverage and isoflavones since adolescence was inversely associated with the incidence of breast cancer in Japanese women(2)(2a).

The study in the testing of oral administration of  IF-rich tablet (20 and 40 mg/day) on climacteric women,  showed  the product not only reduced risk of breast cancer but also improved of bone density, hypertension and climacteric symptoms, cardiovascular diseases, gynecological problems and possible immune potentiation(3)

Japanese women have lower incidence of and mortality from breast cancer, compared to Caucasians, it may be result of large amount intake soy protein and isoflavones, as high dietary intake of phytoestrogens, mainly in the form of soy products, can produce circulating levels of phytoestrogens that are known experimentally to have oestrogenic effects(4).

According to the Loma Linda University, Asian population consumes as much as 25 g of soy protein or 100 mg of isoflavones per day(5).
Epidemiological Western studies have linked levels of Genistein and daidzein in stimulating breast tumor growth and antagonize the effects of tamoxifen have been inclusive. Some researchers  suggested that women with current or past breast cancer should be aware of the risks of potential tumor growth when taking soy products(6).

In Japanese population, serum of isoflavones and insulin levels were not associated with breast cancer risk, in a case-control study of 63 histologically confirmed breast cancer patients and 76 controls, of serum isoflavone, insulin and adiponectin levels with breast cancer risk(7).

The review of Soy for breast cancer survivors, also rejected the above claim of adult consumption of soy affecting the risk of developing breast cancer or that soy consumption affects the survival of breast cancer patients(8). In deed, in Japanese study in testing the serum concentrations of genistein and daidzein, showed urinary excretion in 10 women and 9 men who consumed a typical low-fat diet with much rice and soy products, fish, and vegetables, in a rural village south of Kyoto, Japan, indicated a co-related to isoflavonoids  intake and serum concentrations of genistein and daidzein and suggested that these may be a result of low mortality in breast and prostate cancer of Japanese women and men, respectively(9). In fact, tofu is found to be associated with the serum concentrations of genistein and daidzein  but fermented product, such as miso showed a slight association with serum concentrations of these phytoestrogens with serum concentrations of equol showed associated with dietary intake of tofu and miso soup(10).

Soymilk, a flavor drink on breakfast in Asian diet, when combined with combination with probiotic Lactobacillus casei Shirota (LcS) also showed to prevent the development of mammary tumors through suppression of tumor growth and might be a beneficial dietary style for breast cancer prevention(11). Intake of soy combined with seaweed in equol producers, showed seaweed favorably alters estrogen and phytoestrogen metabolism and these changes likely include modulation of colonic bacteria, in healthy postmenopausal women(12). In premenopausal Japanese women study with randomly assigned to receive either a soymilk-supplemented diet (n = 31) or a normal (control) diet (n = 29), involved three consecutive menstrual cycles showed the  estrone and estradiol levels were decreased by 23% and 27%, respectively, in the soymilk-supplemented group but insisted that larger studies will be required to confirm the ability of soy products to reduce serum estrogen levels(12a). Other study in 50 healthy premenopausal Japanese women, also showed a similar result as blood samples drawn from each subject on Days 11 and 22 of her menstrual cycle, suggested that  the consumption of soy products lowers the risk of developing breast cancer risk in modifying estrogen metabolism(12b).

In postmenopausal Japanese women, according to the study from the Takayama, with participants members aged 35 years or older in 1992 with follow-up was conducted from the time of the baseline study (September 1, 1992) to the end of March 2008, concluded that soy and isoflavone intakes may have a protective effect on postmenopausal breast cancer. Risks of breast cancer were  decreased  among women with a moderate intake of soy and isoflavone(13).

In a total of 678 breast cancer cases and 3,390 age- and menopausal status-matched noncancer controls, soy showed a protective effect against breast cancer risk differs by receptor status, including with  ER-positive (ER+) and HER2-negative (HER2-)(14). Genistein a major component of soybean isoflavone, has been found to induce breast cancer in some Western study, also exerted its anti breast cancer preventive effect in a breast cancer cell overexpressing HER-2,  as genistein enhances necrotic-like cell death of the breast cancer cells through the inactivation of HER-2 receptor and Akt which plays a key role in multiple cellular processes in combined with chemotherapeutic agent (15).

 Unfortunately, report on a Japan Collaborative Cohort (JACC) Study. From 1988 to 1990, 30,454 women aged 40-79 years, completed a questionnaire on diet and other lifestyle features, suggested  that consumption of soy food has no protective effects against breast cancer, but insisted that further large-scale investigations eliciting genetic factors may clarify different roles of various soybean-ingredient foods on the risk of breast cancer(16).

According to DR. Nagata C. the protective risk against breast cancer only found in in Asian but not Western populations with intake of soy, may be due to consume levels of soy typical in Asian diets. Researchers should also take account of amount of soy isoflavones consumed, the form and food source of isoflavones, timing of isoflavone exposure, estrogen receptor status of tumors, and equol-producer status and hormonal profile of individuals. These factors might explain the heterogeneity of results from studies(17).

 Dr, Rice S.  Dr. Whitehead SA., in the differentiation of phytoestrogens and breast cancer--promoters or protectors? said "a paradox concerning the epidemiology of breast cancer and the dietary intake of phytoestrogens that bind weakly to oestrogen receptors and initiate oestrogen-dependent transcription. In Eastern countries, such as Japan, the incidence of breast cancer is approximately one-third that of Western countries whilst their high dietary intake of phytoestrogens, mainly in the form of soy products, can produce circulating levels of phytoestrogens that are known experimentally to have oestrogenic effects. The actions of phytoestrogens on oestrogen receptors and key enzymes that convert androgens to oestrogens in relation to the growth of breast cancer cells. In addition, it compares the experimental and epidemiological evidence pertinent to the potential beneficial or harmful effects of phytoestrogens in relation to the incidence/progression of breast cancer and their efficacy as natural alternatives to conventional HRT"(18).

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(a) The Science of Soy: What Do We Really Know? by Julia R. Barrett
(b) Guideline for healthy soy intake(the Unite Soybean board)
(c) Japan, Wikipedia
(d)  Erdman JW Jr. AHA Science Advisory: soy protein and cardiovascular disease: a statement for healthcare professionals from the Nutrition Committee of the AHA. Circulation. 2000; 102: 2555–2559
(Soy protein and cardiovascular disease)
(e) van der Schouw YT, Kreijkamp-Kaspers S, Peeters PH, Keinan-Boker L, Rimm EB, Grobbee DE. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women. Circulation. 2005; 111: 465–471(Cardiovascular diseases in women)
(1)  Soy intake and breast cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population(PubMed)
(2) Probiotic Beverage with Soy Isoflavone Consumption for Breast Cancer Prevention: A Case-control Study by Toi M1, Hirota S, Tomotaki A, Sato N, Hozumi Y, Anan K, Nagashima T, Tokuda Y, Masuda N, Ohsumi S, Ohno S, Takahashi M, Hayashi H, Yamamoto S, Ohashi Y.(PubMed)
(2a) Yamamoto S1, Sobue T, Kobayashi M, Sasaki S, Tsugane S; Japan Public Health Center-Based Prospective Study on Cancer Cardiovascular Diseases Group.(PubMed)
(3) Isoflavones for prevention of cancer, cardiovascular diseases, gynecological problems and possible immune potentiation by Watanabe S1, Uesugi S, Kikuchi Y.(PubMed)
(4) Phytoestrogens and breast cancer--promoters or protectors? by Rice S1, Whitehead SA.(PubMed)
(5) Estimated Asian adult soy protein and isoflavone intakes, by Messina M1, Nagata C, Wu AH.(PubMed).
(6) Effects of soy phytoestrogens genistein and daidzein on breast cancer growth by de Lemos ML.(PubMed)
(7) Minatoya M1, Kutomi G, Asakura S, Otokozawa S, Sugiyama Y, Ohnishi H, Akasaka H, Miura T, Mori M, Hirata K.(PubMed)
(8) Soy for breast cancer survivors: a critical review of the literature by Messina MJ1, Loprinzi CL.(PubMed)
(9) Association of serum phytoestrogen concentration and dietary habits in a sample set of the JACC Study by Ozasa K1, Nakao M, Watanabe Y, Hayashi K, Miki T, Mikami K, Mori M, Sakauchi F, Washio M, Ito Y, Suzuki K, Kubo T, Wakai K, Tamakoshi A; JACC Study Group.(PubMed)
(10) Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet by Adlercreutz H1, Honjo H, Higashi A, Fotsis T, Hämäläinen E, Hasegawa T, Okada H.(PubMed)
(11) Lactobacillus casei Shirota enhances the preventive efficacy of soymilk in chemically induced breast cancer by Kaga C1, Takagi A, Kano M, Kado S, Kato I, Sakai M, Miyazaki K, Nanno M, Ishikawa F, Ohashi Y, Toi M.(PubMed)
(12) Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women by Teas J1, Hurley TG, Hebert JR, Franke AA, Sepkovic DW, Kurzer MS.(PubMed)
(12a) Effect of soymilk consumption on serum estrogen concentrations in premenopausal Japanese women by Nagata C1, Takatsuka N, Inaba S, Kawakami N, Shimizu H.(PubMed)
(12b) Decreased serum estradiol concentration associated with high dietary intake of soy products in premenopausal Japanese women by Nagata C1, Kabuto M, Kurisu Y, Shimizu H.(PubMed)
(13) Soy isoflavone intake and breast cancer risk in Japan: from the Takayama study by Wada K1, Nakamura K, Tamai Y, Tsuji M, Kawachi T, Hori A, Takeyama N, Tanabashi S, Matsushita S, Tokimitsu N, Nagata C.(PubMed)
(14) Effect of soybean on breast cancer according to receptor status: a case-control study in Japan by Suzuki T1, Matsuo K, Tsunoda N, Hirose K, Hiraki A, Kawase T, Yamashita T, Iwata H, Tanaka H, Tajima K.(PubMed)
(15) Genistein, a soy isoflavone, enhances necrotic-like cell death in a breast cancer cell treated with a chemotherapeutic agent by Satoh H1, Nishikawa K, Suzuki K, Asano R, Virgona N, Ichikawa T, Hagiwara K, Yano T.(PubMed)
(16) Consumption of soy foods and the risk of breast cancer: findings from the Japan Collaborative Cohort (JACC) Study by Nishio K1, Niwa Y, Toyoshima H, Tamakoshi K, Kondo T, Yatsuya H, Yamamoto A, Suzuki S, Tokudome S, Lin Y, Wakai K, Hamajima N, Tamakoshi A(PubMed)
(17) Factors to consider in the association between soy isoflavone intake and breast cancer risk.
(18)  Phytoestrogens and breast cancer--promoters or protectors? by Rice S1, Whitehead SA.(PubMed)

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