Soy Part 2—Research
by Jack Norris, RD • Last updated March 2011
There is a great deal of controversy surrounding soy foods, mostly due to their isoflavones which can bind to estrogen receptors and affect thyroid hormone.
There is significant evidence that eating moderate amounts (one to two servings per day) of traditional soy foods, whether fermented or not, can reduce the risk of prostate cancer and can lower LDL cholesterol.
People have been concerned that moderate amounts of soy could increase the risk of breast cancer or be harmful to women with breast cancer, especially if their cancer is estrogen receptor positive. However, the research to date has been quite reassuring, showing mostly benefits for breast cancer prevention.
Everyone who eats soy should make sure they are getting enough iodine. People with hypothyroidism might need their synthetic thyroid hormone dosage adjusted if they start eating more soy due to the possibility that soy might interfere with it. There is some concern that eating soy could push some people with subclinical hypothyroidism into overt hypothyroidism, so limiting soy for such people might be a good idea.
Soy infant formula has been shown to be safe except possibly for infants with congenital hypothyroidism, whose thyroid function should be monitored. Soy formula is not intended for pre-term infants.
While one observational study found that tempeh was linked to better cognition in older people, tofu has been associated with worse cognition. This is most likely due to confounding variables, including tofu being processed with formaldehyde in Indonesia. Many clinical studies have found that soy increases cognition. Unless you are in Indonesia, you do not need to worry about tofu harming cognition.
Some soy meats or foods containing isolated soy protein are processed with hexane and there may be small amounts of hexane residues in the final product. It is not known if this is harmful, but it might be a good idea to use soy foods from companies who do not use hexane in their processing methods (linked to below).
The phytates in soy can lower the absorption of calcium, zinc, iron, and magnesium. However, you do absorb these minerals from soy foods and eating moderate amounts of soy should not cause deficiencies.
At moderate amounts, soy does not cause feminine characteristics in men. At high amounts, as in twelve servings a day or more, a small percentage of men who are particularly sensitive to soy might develop tender, enlarged breast tissue.
Introduction—Why the Fuss?
By far, soy is the most controversial of plant foods, with gluten taking a distant second place.
Much of the controversy is due to some fairly unique components of soy, isoflavones. Isoflavones are also called phytoestrogens or “plant estrogens”, because they can attach to estrogen receptors in cells. The estrogenicity of soy has raised questions of potential benefits, such as for bone health of post-menopausal women, as well as concerns such as for women with estrogen receptor positive breast cancer.
In addition to the isoflavones, soy also contains phytates that can bind minerals and lower their absorption from foods.
Between 1990 and 2010, there were over 10,000 peer-reviewed journal articles on soy (122). A large percentage of these were conducted in animals which can make the results irrelevant to humans because species differ in how they metabolize soy isoflavones and because the amount of isoflavones given to the animals is often much greater than any human would eat. This much research makes soy one of the most researched foods and also increases the chances of finding results that are outliers – studies that by random chance, or the inability to control variables, could show soy to be harmful (or helpful) when it actually is not. The large number of studies allow people who want to make a case against soy to simply highlight a handful when the bulk of research provides a different view. Of course, someone could make a case in favor of soy in the same way. It is, therefore, important to perform a comprehensive review of the research on any given topic, which I do below for the most important controversies surrounding the potential harm of soy foods.
Because some studies look at individual isoflavones, I will give a little background on them. Table 1 shows the breakdown of the typical isoflavone components of soy foods.
|Table 1. Typical Isoflavone Content of Soy 122|
|Isoflavone||If Fermented||% of Total|
|Food||Range or Average g/100 g|
|Wheat||0.52 – 1.05|
|Corn||0.62 – 1.17|
|Barley||0.85 – 1.18|
|Oats||0.90 – 1.42|
|Peas||0.72 – 1.23|
|Soybean||1.20 – 1.75|
|Lupine bean||0.76 – 1.63|
Soybeans contain phytic acid, also known as phytate, which can inhibit the absorption of calcium, zinc, iron, and possibly magnesium. Many whole plant foods contain phytate, but soy has more than most. Hidvegi and Lasztity estimated the phytate content per 100 grams of food (97) in Table 2.
While phytic acid has a bad reputation, it has some benefits. In their 2002 review, Minerals and Phytic Acid Interactions: Is It a Real Problem for Human Nutrition?, Lopez et al point out that phytates can prevent lipid peroxidation, iron oxidation of colorectal tissue, and calcium-based kidney stones (98).
Three studies on adults (99, 100, 101) have shown calcium to be absorbed from soy at rates comparable to that of cow’s milk. One study on Chinese boys found calcium from soy milk to be absorbed at 43% while calcium from cow’s milk was absorbed at 64% (109, see Table 3).
A study from Victoria University (2010) found calcium absorption to be the same from fortified soymilk as from cow’s milk in post-menopausal women (101).
A study from Purdue University (2005) found that the calcium in soymilk fortified with calcium carbonate was absorbed at the same rate (21%) as the calcium in cow’s milk (100). The calcium in soymilk fortified with tricalcium phosphate was absorbed at a lower rate of 18%.
In a study from Creighton University (1991), soybeans, grown in different mediums to produce a different phytate content, were used to determine calcium absorption (99). They found that calcium from high-phytate soybeans was absorbed at 31%, while calcium from low-phytate soybeans was absorbed at 41%. Calcium from milk was absorbed at 38%.
|Table 3. Mineral Absorption Rates in Chinese Boys 109|
|Dephytinized soy milk||50.9||20.1||20.6|
Soy and Bones
Although a 2010 (3) and 2008 (4) meta-analysis each found that soy isoflavone supplements of 82 and 90 mg/day, respectively, increases bone mineral density in menopausal women, a more recent, clinical trial found little benefit from 80 or 120 mg of soy isoflavone supplements for three years (6).
There is a plethora of evidence that soy does not harm bones; including a cross-sectional study from the Chinese University of Hong Kong (2003) which found that women who ate the most soy (10 g/day of soy protein or more) had greater bone mineral density than those in the lower intake groups (104).
Studies have shown that the zinc in soy is absorbed at a rate of about 10–20%.
A 2004 study from Switzerland showed that removing the phytic acid from a wheat and soy flour increased zinc absorption from 22.8% to 33.6% in healthy adults (108). Copper absorption was unaffected.
Table 2 shows results from a 2003 absorption study on Chinese boys (109). Zinc absorption rates were lower from soymilk than cow’s milk.
A study from University of Gothenburg in Sweden (1987), found that adding milk to a meal with meat sauce reduced zinc absorption from 25.2% to 20.7% (110). Adding soy to a meal with meat sauce decreased zinc absorption to 18-20%. Meals of only soy had zinc absorption rates of 14-21%.
Iron from plant foods is generally not absorbed as well as iron from meat. But a type of iron in soy, ferritin iron, is absorbed at about 30% among people with low iron stores, and this is a high rate of absorption. Ferritin iron makes up a large percentage of the iron found in soybeans; up to 90% (127). Some soy foods have a decent amount of iron, including extra firm tofu (3.35 mg per 1/2 cup), edamame (1.75 mg per 1/2 cup), and soy nuts (1.7 mg per 1/4 cup). There is no reason to worry that moderate amounts of soy might cause iron deficiency.
Also note that adding vitamin C to a meal (in a dose of about 100 mg) has been shown to significantly increase absorption of the iron in plant foods in numerous studies. I found no studies on vitamin C’s effect on iron absorption from soy foods in adults, but two showed that it significantly increased iron absorption from soy formula in infants (114, 115).
I found no studies looking at the effect of soy on magnesium absorption. Phytates have been shown to bind magnesium, so it would be no surprise if the magnesium in soy is absorbed at a lower rate than from other foods. Leafy green vegetables, whole grains, nuts, and seeds are the best sources of magnesium and people eating such foods while adding a few servings of soy per day should not be in danger of magnesium deficiency.
In their 2007 review, Hotz and Gibson say that fermentation can reduce the amount of zinc and iron-binding phytates in soybeans and should, therefore, increase the amount of zinc and iron absorbed from fermented soy foods such as tempeh and miso (111).
The effects of fermenting soy foods on rates of zinc absorption have not been tested in humans, but one study from the University of the Witwatersrand, South Africa (1990) found that the iron in tempeh was absorbed better than from other soy foods, at a rate of 10 – 15%; the iron from tofu was absorbed at a range of about 3 to 8% (113). Again, absorption rates of plant iron vary greatly according to someone’s current iron status and the amount of iron in the food, which can account for a large range of absorption amounts.
It requires twelve servings of soy (and probably much more for most men) to have any sort of noticeable feminizing effects. While one epidemiological study raised concerns about soy and sperm quantity (14), two clinical studies have shown no effects of soy on sperm quality or quantity (15, 126).
In 2011, there was a case report of a 19-year old vegan male who was eating a great deal of soy foods – enough to provide 360 mg of isoflavones per day, the equivalent of about 14 servings (10). He also had type 1 diabetes. After eating this way for a year, he developed low free testosterone levels and erectile dysfunction. After ceasing the soy products (and the vegan diet), his symptoms normalized within a year. There was no reason why he needed to stop being vegan rather than just cutting way down on, or eliminating for a period, soy foods.
A 2008 case report described a 60 year old man who developed gynecomastia (the enlargement of the mammary glands in a male) after drinking 3 quarts of soymilk (the equivalent of 12 servings) a day (123). His breasts returned to normal after discontinuing the soymilk.
Gynecomastia – Male Breasts
In contrast to the case report above, in a 2004 study, 20 men with prostate cancer were given either 450 mg (amount found in about 18 servings of soy) or 900 mg (amount found in about 36 servings of soy) of isoflavones for 84 days (124). Two of the men, who had no gynecomastia at baseline, receiving the 900 mg developed mild cases of gynecomastia. One man was taking a drug that likely increased the gynecomastia. Two men had hot flashes probably related to the isoflavones. Given the very large amounts of isoflavones they were taking, this study should allay fears of feminization in men rather than cause any sort of alarm.
A 2008 epidemiological study found that men attending a fertility clinic had lower sperm concentrations if they ate more soy, but the amount of soy was very small (≥ .3 servings/day) and part of the difference could be explained by a higher ejaculate volume (14). Two more recent clinical trials using 62 mg/day of isoflavones for two months and 480 mg/day of isoflavones for three months found no difference in sperm count, concentration, or motility.
Messina sums up the rest of the literature on soy and feminizing characteristics in men in his 2010 review (122):
In contrast to the results of some rodent studies, findings from a recently published metaanalysis and subsequently published studies show that neither isoflavone supplements nor isoflavone-rich soy affect total or free testosterone (T) levels. Similarly, there is essentially no evidence from the nine identified clinical studies that isoflavone exposure affects circulating estrogen levels in men. Clinical evidence also indicates that isoflavones have no effect on sperm or semen parameters, although only three intervention studies were identified and none were longer than 3 months in duration. Finally, findings from animal studies suggesting that isoflavones increase the risk of erectile dysfunction are not applicable to men, because of differences in isoflavone metabolism between rodents and humans and the excessively high amount of isoflavones to which the animals were exposed. The intervention data indicate that isoflavones do not exert feminizing effects on men at intake levels equal to and even considerably higher than are typical for Asian males.
A 2009 meta-analysis of five retrospective and two prospective studies found that participants with a higher soy intake (roughly one serving per day) had a reduced risk for endometrial cancer and ovarian cancer, when compared with lower soy intakes. Two other studies of three years in duration found that soy isoflavones in the amounts of 70, 80, and 120 mg/day did not have a negative effect on the endometrium. However, one study using 90 mg of isoflavones for five years (equivalent to 3.5 servings of soy per day) did result in cell growth (though non-cancerous) of the endometrium among some subjects. Women at risk for endometrial cancer might use caution in eating more than one serving per day of soy.
A 2010 review by Wendy N. Jefferson of the Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, summarized the literature on soy and ovarian function (117):
For the most part, the studies conducted to date suggest that a diet containing lower levels of soy, e.g. 1–2 servings of soy/d, as part of a well-balanced diet should not pose harmful effects on the function of the ovary as it relates to ovulation. These levels are similar to that found in a traditional Asian diet (10–25 mg/day isoflavones) and even up to 50 mg/day isoflavones has little impact on serum circulating levels of hormones involved in reproduction. Although the levels of phytoestrogens typically found in soy foods pose minimal risk in the adult female, the female reproductive system is dependent on hormones for proper function and phytoestrogens at very high levels can interfere with this process.
Additionally, a 2009 meta-analysis of five retrospective and two prospective studies found that participants with a higher soy intake (roughly one serving per day) had a reduced risk for endometrial cancer and ovarian cancer, when compared with lower soy intakes (119).
A 2014 cross-sectional study from Adventist Health Study-2 found that a higher intake of isoflavones was associated with an increased rate of never becoming pregnant and of being childless (136). Among the highest soy intake category of > 50 mg/day (average of 79 mg/day or about three servings), compared to those in the lowest intake category (average of 3.7 mg/day), there was a 15% higher rate of being childless (1.15, 1.02-1.29). This finding was adjusted for age, educational level, and marital status.
The authors did not distinguish between involuntary and voluntary childlessness.
This issue warrants further attention, but given that it is a cross-sectional study and the findings were rather weak, it seems unlikely that isoflavones cause childlessness.
Isolated soy protein is rumored by some to have unusually large amounts of MSG (it doesn’t), and MSG, in turn, is rumored to be an excitotoxin (for practical purposes, it’s not) that will destroy brain cells. I cover this topic in some blog posts at JackNorrisRD.com (link).
Two studies have examined soy intake and risk of hypospadias. Neither found a statically significant risk with more soy intake. It appears that factors other than soy are the most likely the cause of hypospadias, although more studies are warranted.
Hypospadias is a male birth defect in which the opening of the urethra (the tube through which urine passes) is not located at the tip of the penis as it should be. The milder forms of hypospadias, which are by far the largest number of cases, are relatively easy to repair which usually results in a penis with normal or near-normal function and appearance, and no future problems (135).
A 2004 case-control study from the Netherlands (133) found no link between maternal soy intake and an increased risk of hypospadias. Women who had a soy protein intake of 20 g or more had the exact same risk as those eating no soy (1.0, 0.5-2.2).
A 2000 UK prospective study, of 7,928 boys born to mothers taking part in the Avon Longitudinal Study of Pregnancy and Childhood, found 51 cases of hypospadias (134). There was a trend of more soy meats and soy milk being associated with an increased risk for hypospadias, but the findings were not statistically significant, nor were the results adjusted for any confounding variables.
Two of three studies have found an increased risk of hypospadias if the mothers were vegetarian; more information can be found in Hypospadias and Vegetarian Diets.