The Science of Soy - The Eastern Viewpoints; Part A1: Soy and the risk of cerebral infarction (CI) and myocardial infarction (MI) in Japan population

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 genus Glycine, 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.
Nutrients
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.
Phytochemicals
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(1). 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(1a)(1b)
A.1. Soy and the risk of cerebral infarction (CI) and myocardial infarction (MI) in Japan population

The searching of the Keywords in PubMed, soy and heart diseases  and stroke in Japan found 3 studies, all showed the positive effect of soy in reduced risk heart disease and stroke.

Cerebral infarction (CI) is defined as a type of ischemic stroke due to blockage in the blood vessels supplying blood to the brain.
Myocardial infarction (MI) is also known as heart attack. It is defined as a condition of blood stop flowing properly to part of the heart as a result of not receiving enough oxygen.

According to National Cardiovascular Center, Japan, the studied 40,462 Japanese (40 to 59 years old, without cardiovascular disease or cancer at baseline), yields interest results.
People who consume more soy are less likely to be current smokers but more likely to be hypertensive, with men are more likely to have diabetes mellitus. The frequency of soy intake was positively related to daily intake of rice, vegetables, fruits, fish, potassium, calcium, carbohydrate, polyunsaturated fatty acid, saturated fatty acid, fiber, and isoflavones for both sexes.

The study started in the 1990 with food-frequency questionnaire included 44 foods with 3 questions to assess soy, bean, and miso consumption. The 1995 follow-up questionnaire covered 147 foods with 8 questions on soy products.

The result is astonishing, during a follow-up period that averaged 12.5 years, 1230 strokes were documented, of which 1137 were confirmed through imaging or autopsy. eventhrough high isoflavone intake was associated with reduced risk of CI and MI in middle-aged Japanese subjects, but not in men and dietary isoflavones and may be beneficial to postmenopausal women for the prevention of ischemic CVD(2). Intake of miso soup showed to reduce risk of hypertension but did not contributed to ischemic CVD mortality in neither men or women.

Strong evidences of epidemiological studies from the East and West have shown that hyperlipidemia is a major risk factor in contribution to heart diseases, notably on intermediate end points(3)(4). Soy foods intake has been known to contain lowering cholesterol and blood pressure effects. According to the Veterans Affairs Medical Center, daily soy protein showed a significantly decreased serum concentrations of total cholesterol, LDL cholesterol, and triglycerides without significantly affecting serum HDL cholesterol concentrations.(4). But the study suggested that  the mechanism of reduced risk of cerebral infarction (CI) and myocardial infarction (MI) for postmenopausal Japanese women may  not be through reduction of lipid profile but through exposure to a large quantity of isoflavones, which act as estrogen agonist because estrogen receptors are not occupied with plasma estradiol in postmenopausal women.

In case of hypertension in the subject of study, although the disease have been shown to contribute to the early risk factor for the progression heat disease and stroke(6)(7)(8)(9). Consumption of soy has no effect in reduce risk of the development of cerebral infarction (CI) and myocardial infarction for people with  histories of hypertension and diabetes mellitus and medication use for hypercholesterolemia, even soy has shown effectively in reduced high blood pressure(12)

In support to the above, the dietary intervention study targeting female students by using cake containing soybean protein and isoflavone at the Mukogawa Women's University, 4 weeks dietary intake of soy protein found to reduce CHD risk among Japanese female students with a high plasma cholesterol level(10) and Dr. Nagata C. at the Gifu University School of Medicine, Gifu, Japan, in the study of association between soy product intake and mortality from cancer and heart disease in Japan, suggested that soy foods intake showed a preventive role in against stomach cancer and heart disease death(11).

Dr. Yoshihiro Kokubo and the research team also acknowledged the limitation of the study such as ethic group, measurement errors with nutrient intake or  due to it self report, but insisted that nationwide annual health screenings may ease the self report concern.
 They also clarified that the result of the study of dietary intake of isoflavones, are not relevant to the association of isoflavone supplement use with ischemic CVD.

In deed, the effectiveness of soy isoflavone in reduced risk of  cerebral infarction (CI) and myocardial infarction in this case, yields some questions due to it ethnicity.
a. If soy is found to be effective in reduce risk of hypertension and hyperlipidemia, why it does not contribute to the reduce risk of cerebral infarction (CI) and myocardial infarction in men with histories of hypertension and diabetes mellitus and medication use for hypercholesterolemia.
Would the medication be the cause?  As epidemiological study insisted the lowering effect of blood pressure and cholesterol are associated to reduce risk heart disease and stroke.

b. Although soy isoflavone showed an effectiveness in reduce risk of cerebral infarction (CI) and myocardial infarction and mortality, would dietary with high in fruit and vegetable also best known for the reduce risk of heart disease and stroke be also taken into account?

c. The effectiveness of the study may only be true for equol producers population as 90% of subjects' study are equol producers?

d. Would the "Japanese Phenomenon" interfere with the study, as administration of isoflavone "inexperienced" women at the time of menopause, the phytoestrogens appear to share the same effects as estrogen used in classical preparations for hormone replacement therapy?


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References
(a) The Science of Soy: What Do We Really Know? by Julia R. Barrett
(b) Guideline for healthy soy intake(the Unite Soybean board)
(1) Japan, Wikipedia
(1a)  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)
(1b) 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)
(5) Soy intake and breast cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population by Nagata C¹, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, Wakai K, Inoue M, Tsugane S, Sasazuki S; Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan.(PubMed)
(6) 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)
(7) Associations of intakes of fat, dietary fiber, soy isoflavones, and alcohol with levels of sex hormones and prolactin in premenopausal Japanese women by Tsuji M¹, Tamai Y, Wada K, Nakamura K, Hayashi M, Takeda N, Yasuda K, Nagata C.(PubMed)
(8) Plasma isoflavone level and subsequent risk of breast cancer among Japanese women: a nested case-control study from the Japan Public Health Center-based prospective study group by Iwasaki M¹, Inoue M, Otani T, Sasazuki S, Kurahashi N, Miura T, Yamamoto S, Tsugane S; Japan Public Health Center-based prospective study group.(PubMed)
(9) Isoflavones--safe food additives or dangerous drugs? by Wuttke W¹, Jarry H, Seidlová-Wuttke D.(PubMed)
(10) Effect of a soybean product on serum lipid levels in female university students by Takahashi K¹, Kamada Y, Hiraoka-Yamamoto J, Mori M, Nagata R, Hashimoto K, Aizawa T, Matsuda K, Kometani T, Ikeda K, Yamori Y.(PubMed)
(11) Ecological study of the association between soy product intake and mortality from cancer and heart disease in Japan by Nagata C.(PubMed)
(12) Association of blood pressure with intake of soy products and other food groups in Japanese men and women by Nagata C¹, Shimizu H, Takami R, Hayashi M, Takeda N, Yasuda K.(PubMed)
(13) Effects of dietary intake of soy protein and isoflavones on cardiovascular disease risk factors in high risk, middle-aged men in Scotland by Sagara M¹, Kanda T, NJelekera M, Teramoto T, Armitage L, Birt N, Birt C, Yamori Y.(PubMed)