Health Benefits and Possible Hazards of Soy Food

by Ben Best

1. INTRODUCTORY REMARKS
2. SOY VERSUS MILK PROTEIN
3. SOY FOOD AND CANCER
4. PHYTOESTROGEN EFFECTS
5. CARDIOVASCULAR DISEASE AND OBESITY

I. INTRODUCTORY REMARKS

Soybean products are often used as substitutes for meat and milk by American vegetarians. Soybeans are typically 36-46% protein, about 30% carbohydrate, and 17% lipid. The lipids are about 15% saturated fat, 24% monosaturated fat, and 61% polyunsaturated fat. About half the carbohydrate is insoluble (dietary fiber), and about half the carbohydrate is soluble (sucrose, raffinose, and stachyose) [MOLECULAR AND CELLULAR ENDOCRINOLOGY; Cederroth,CR; 304(1-2):30-42 (2009)].

Asians typically consume whole soybeans or fermented soybean products. Microorganisms fement soy to miso (which is added to soups and stews in Japan), tempeh (an Indonesian dish with meat-like texture), or soy sauce. Soy milk, which is more commonly used in North America, is formed by extracting proteins and lipids from soybeans with boiling water. Soy milk can be curdled to prepare tofu.

Soybeans contain isoflavones, which are compounds having antioxidant and estrogenic properties. Unless separated with alcohols, the isoflavones tend to adhere most strongly to the protein component of soybeans. When soy sauce is produced by acid hydrolysis rather than fermentation, the isoflavones are removed. In soy foods that do not remove isoflavones by processing, each gram of soy protein is associated with about 3.5 milligrams of aglycone isoflavone (i.e., isoflavone without an attached sugar molecule).

17β−ESTRADIOL	EQUOL

The primary isoflavones in soybeans are genistein and daidzein, both of which are very weak (phyto)estrogens compared to the natural mammalian estrogen 17β−estradiol. Daidzein, but not genistein, can be converted to the more estrogenic isoflavone equol by an intestinal microbe. Although all rodents metabolize daidzein to equol, only about 30% of North Americans have microbes that do so [JOURNAL OF NUTRITION; Setchell,KDR; 133(4):1027-1035 (2003)]. Insofar as equol exerts a considerable amount of the estrogenic effect from isoflavones, variability of effects between rodents and humans, as well as between humans, may be the result of equol production or non-production.

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II. SOY VERSUS MILK PROTEIN

Although soy protein is one of the most complete proteins (having all essential amino acids) for a plant protein, milk protein is traditionally regarded as being a more complete protein than soy protein. Milk protein from cows is about 80% casein and 20% whey, in contrast to human milk, which is about 40% casein and 60% whey [JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION; Luhovyy,BC; 26(6):707S-712S (2007)]. Whey protein is high in branch-chained amino acids (leucine, isoleucine and valine), which are all essential amino acids. Casein (curds) is separated from whey in the making of cheese. Casein is a self-adhesive clot-like protein that sits in the digestive tract and releases protein slowly. Compared to casein, soy has low methionine/glycine and lysine/argenine ratios [INTERNATIONAL JOURNAL OF MEDICAL SCIENCES; Velasquez,MT; 4(2):72-82 (2007)]. Milk protein is 2.6% methionine, in contrast to soy protein, which is 1.6% methionin [AMERICAN JOURNAL OF CLINICAL NUTRITION; Wilkinson,SB; 85(4):1031-1040 (2007)]. Casein has twice the amount of methionine per gram as does soy protein [Ibid.]. Methionine supplementation is recommended for infant soy formulas, and efforts are being made to develop soybean plants that have more methionine-rich protein [JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY; Friedman,M; 49(3):1069-1086 (2001)]. But less methionine in protein may actually be more healthy for adults than what the traditional ideal implies (egg protein has been used as the standard for being the most complete protein). (See Life Extension Benefits of Methionine Restriction and The Methionine Cycle for more detailed explanation.)

When consumed after resistance exercise, milk-based protein promoted muscle protein accretion nearly one-third more during a three hour recovery period than an equivalent amount of soy-based protein [AMERICAN JOURNAL OF CLINICAL NUTRITION; Wilkinson,SB; 85(4):1031-1040 (2007)], which may be due to slower release of milk protein into the bloodstream [Ibid. and JOURNAL OF NUTRITION; Bos,C; 133(5):1308-1315 (2003)].

Soy protein increases insulin sensitivity and reduces liver lipotoxicity, in contrast to casein which has the opposite effect [BIOCHEMICA ET BIOPHYSICA ACTA Tovar,AR; 1801(3):367-371 (2010)]. Elderly Fischer 344 rats normally have a high prevalence of fatal nephropathy (kidney disease), but substituting soy protein for casein in the diet reduces the nephropathy considerably [JOURNAL OF GERONTOLOGY; Shimokawa,I; 48(1):B27-B32 (1993))]. Literature reviews reinforce the conclusion that casein can be damaging to a sensitive kidney, whereas soy protein has no such effect [CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION; Lentine,K; 13(3):333-336 (2004) and TOXICOLOGIC PATHOLOGY; Rao,GN; 30(6):651-656 (2002)]. Casein proteins from milk, however, can reduce blood pressure [JOURNAL OF NUTRITION; Fitzgerald,RJ; 134(4):980S-988S (2004)].

Vegetarian diets are commonly deficient in calcium and Vitamin B₁₂, which is expected when substituting soy for milk products and meat. Nutritional supplements are especially of benefit for vegetarians.

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III. SOY FOOD AND CANCER

Epidemiological studies suggest that a diet high in soy foods reduces cancer risk. A Western woman has more than triple the risk of getting breast cancer as an Asian woman [JOURNAL OF THE NATIONAL CANCER INSTITUTE)]. Asian women consuming more than 20 milligrams daily of phytoestrogens from soy food (isoflavones) are one-third less likely to contract breast cancer as those consuming less than 4 milligrams daily [JOURNAL OF EPIDEMIOLOGY; Nagata,C; 20(2):83-89 (2010)]. Japanese and Caucasian women living in Hawaii have more than triple the incidence of breast cancer compared to Japanese women living in Japan (who consume more soy foods) [Ibid.]. A similar pattern is seen for prostate cancer in men [Ibid.]. But factors other than soy food consumption may be responsible for some of these differences, such as greater consumption of seafoods, less consumption of saturated fat, greater consumption of green tea, and lower rates of obesity in Japan.

The soy flavonoids genistein and daidzein are most often credited with the anticarcinogenic effect associated with soy foods. Genistein can induce cell cycle arrest and apoptosis (although at much higher concentrations normally seen in blood), increase cell adhesion (reducing metastasis potential), and decrease metalloproteinase expression (metalloproteinases degrade extracellular matrix proteins, which facilitates cancer cell migration and invasion) [CANCER METASTASIS REVIEWS; Pavese,JM; 29(3):465-482 (2010)]. Isoflavone phosphorylation of various kinases, including tyrosine kinase, are believed to underly some isoflavone effects on cancer. Some of these effects are independent of estrogenic action [JOURNAL OF NUTRITION; Brownson,DM; 132(11 Suppl):3482S-3489S (2002) and BREAST CANCER RESEARCH; Limer,JL; 6(3):119 (2004)].

Rats fed soy protein isolate with depleted isoflavones only had 30% reduction in breast cancer when subjected to the cancer-inducing agent 7,12-Dimethylbenz(a)anthracene [JOURNAL OF NUTRITION; Hawrylewicz,EJ; 125(3 suppl):698S-708S (1995)]. And rats fed soybean protein supplemented with methionine had 40% more mammory tumors [Ibid.]. These results suggest that less methionine in soy may contribute as least as much as isoflavones to the anti-cancer effect of soy foods.

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IV. PHYTOESTROGEN EFFECTS

17β−ESTRADIOL	GENISTEIN	DAIDZEIN

Phytoestrogens are chemicals from plants ("phyto" means "plant") that affect mammalian estrogen receptors. No phytoestrogen stimulates estrogen receptors as effectively as the mammalian estrogen hormone 17β−estradiol. As mentioned above, the primary phytoestrogens in soy foods are the isoflavones genistein and daidzein.

Genistein and daidzein are similar to the estrogen estradiol (17β−estradiol). By binding to estrogen receptors, isoflavones can potentially have estrogen agonist or estrogen antagonist activity. Only agonist effects have been observed [ENDOCRINOLOGY; Kuiper,GGJM; 139(10):4252-4263 (1998)]. The potential for estrogenic effects from soy foods has been a source of enthusiasm, worry, and controversy in connection with the consumption isoflavones. Although the estrogenic effect of isoflavones is only one hundredth to one thousandth that of 17β−estradiol, consuming soy foods can cause isoflavone concentrations in the bloodstream to be 10,000 times greater than that of 17β−estradiol [FOOD CHEMISTRY AND TOXICOLOGY; Rimbach,G; 46(4):1308-1319 (2008)].

Falling levels of estrogen with the advent of menopause can result in sudden feelings of heat in the face, neck and chest (hot flashes), often accompanied by perspiration. When these feelings occur at night (night sweats), they can disrupt sleep and cause daytime fatigue. Health concerns over sex hormone replacement therapy (notably estrogen replacement therapy) to relieve menopausal symptoms have caused many women to turn to soy isoflavones. Although there is no evidence of harm, evidence of benefit remains debatable [COCHRANE DATABASE OF SYSTEMATIC REVIEWS; Lethaby,A; 4:CD001395 (2007)]. Women given tablets enriched with the α_S1−casein portion of milk protein showed reduced psychological stress [EUROPEAN JOURNAL OF CLINICAL NUTRITION; Kim,JH; 61(4):536-541 (2007)].

There has been worry about the estrogenic effects of isoflavones on men, but no effect of bioavailable testosterone in men has been seen [FERTILITY AND STERILITY; Hamilton-Reeves,JM; 94(3):997-1007 (2010)]. Nonethless, phytoestrogens have been shown to reduce fertility in both male and female rodents [WOMEN'S HEALTH; Bhupathy,P; 6(1):77-95 (2010)]. When used in combination, genistein and daidzein have a more pronounced effect in reducing the ability of human sperm to fertilize an ovum [Ibid.]. Male rats fed a diet containing 150 micrograms per gram total isoflavones (genistein plus daidzein) (not an unusually large amount for commercial rat diets) showed significantly greater psychological stess than male rats fed diets with no isoflavones [PSYCHOPHARMACOLOGY; Hartley,DE; 167(1):46-53 (2003)].

In North America, up to one-third of infants are fed with soy formula milk. Male marmoset monkeys fed soy formula milk have shown reduced testosterone as infants, but no adverse reproductive effects upon maturity [HUMAN REPRODUCTION; Tan,KAL; 21(4):896-904 (2006)]. Unlike monkeys, however, human infants do not produce equol from daidzein, and effects similar to those in monkeys have not been seen in humans [AMERICAN JOURNAL OF CLINICAL NUTRITION; Badger,TM; 89(suppl):1668S-1672S (2009)]. Nonetheless, many authorities still advocate caution in the use of soy infant formula [INTERNATIONAL JOURNAL OF ANDROLOGY; Cederroth,CR; 33(2):304-316 (2009) and FRONTIERS OF ENDOCRINOLOGY; Patisaul,HB; 31(4):400-419 (2010)].

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V. CARDIOVASCULAR DISEASE AND OBESITY

Estrogen inhibits processes associated with chronic inflammation that lead to atherosclerotic placques in blood vessels [JOURNAL OF CLINICAL INVESTIGATION; Caulin-Glaser,T; 98:36-42 (1996)]. Soy-based diets may counter the inflammatory processes leading to atherosclerosis [JOURNAL OF NUTRITIONAL BIOCHEMISTRY; Nagarajan,S; 21(4):255-260 (2010)].

Experimental consumption of isolated soy protein with isoflavones has been associated with an average LDL cholesterol reduction of about 3% [CIRCULATION; Sacks,FM; 113(7):1034-1044 (2006)]. Phytates associated with soy protein have also been shown to reduce cardiovascular risk factors [AMERICAN JOURNAL OF CLINICAL NUTRITION; Hanson,LN; 84(4):774-780 (2006)]. Diastolic blood pressure in Japanese men has been found to vary inversely with soy food intake [WOMEN'S HEALTH; Bhupathy,P; 6(1):77-95 (2010)]. Rats fed a soy protein rich diet have shown decreased oxidative stress, increased endothelial function, and reduced blood pressure  [THE FASEB JOURNAL; Mahn,K; 19(2):1755 (2005)].

Post-menopausal women typically develop an increased proportion of visceral fat, an effect that can be reversed by sex hormone replacement therapy [JOURNAL OF ENDOCRINOLOGY AND METABOLISM; Gambacciani,M; 82(2):414-417 (1997)]. Genistein has been shown to down-regulate transcription factors for fat cell (adipocyte) generators, such as PPARγ (although in much higher amounts than is normally seen in the blood stream) [EXPERIMENTAL BIOLOGY AND MEDICINE; Orgaard,A; 233(9):1066-1080 (2008)]. Soy-fed mice show reduced body fat and improved insulin sensitivity [DIABETES; Cederroth,CR; 57(5):1176-1185 (2008)]. Improved insulin sensitivity is seen in the offspring of soy-fed monkeys [AMERICAN JOURNAL OF PRIMATOLOGY; Wagner,JD; 71(9):802-811 (2009)].

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