Soy food and isoflavone intake in relation to semen quality parameters among men from an infertility clinic, in Human Reproduction by Jorge Chavarro et al. of Harvard University, published online 07-23-08 |
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Copyright © 2008 Soy-n-Joy® Soy food and isoflavone intake in relation to semen quality parameters among men from an infertility clinic, in Human Reproduction by Jorge Chavarro et al. of Harvard University, published online 07-23-08 Chavarro, J.E., Toth, T.L., Sadio, S.M., and Hauser, R. of Harvard University published a paper on "Soy Food and Isoflavone Intake in Relation to Semen Quality Parameters among Men from an Infertility Clinic" in Human Reproduction with advance access online on July 23, 20081. They concluded that their data suggest that higher intake of soy foods and soy isoflavones is associated with lower sperm concentration. The association was particularly marked in men who were overweight or obese. All other sperm quality parameters were not affected. What do these really mean? Chavarro et al.'s comparison was made between subfertile men with zero and high soy intakes. Those with high sperm concentration in sperms per milliliter (note: this is not the same as total sperm count, which equals the sperm concentration multiplied by the semen volume. This total sperm count was not found to be negatively affected in the study by Chacarro et.al.) were still subfertile, meaning that their subfertility had not benefited from a zero soy or isoflavone intake, because soy was assumed to be the sole isoflavone source in the diet. Furthermore, the lower sperm concentration in the high-soy subfertile group was still on average more than double the minimum sperm concentration generally believed to be the baseline requirement for fertility. The subfertility of that group of men must be attributed to factors other than a high soy intake, or a lowered sperm concentration. Infertility expert Dr. Hossein Sadeghi-Nejad, an associate professor of urology at UMDNJ New Jersey Medical School and Hackensack University Medical Center, also noted2 that, in that study, although sperm counts decreased most among men who have the highest counts, that should not affect fertility, since sperm counts were still in the normal range. Further confounding complication comes from the fact that not all soy sources are created equal. Isolated soy protein, so frequently used in the preparation of soy-containing foods (including items such as veggie soy or tofu burger, ground meat substitute (TVP), soy or tofu chicken or turkey, liquid nutrition drinks with soy or soy protein, soy protein powders, high energy bars or diet bars, as quoted in the paper by Chavarro et al.) comes in low-isoflavone variety (from alcohol-washed soy) and high-isoflavone variety (from water-washed soy). The intakes of isoflavone so estimated, based on one set of reference standards (U.S. Department of Agriculture average numbers), could be miles apart from reality. Moreover, there is so much variation in composition between brands and varieties of the commodity, even for something as standard as soymilk (differing in soy solids) or tofu (differing much in soy solids from soft to medium to firm to extra firm), that the variation in isoflavone contents can render the data of isoflavone intakes invalid. Besides, the estimates of particular nutrient intake by recalling food intake frequencies and portions are notoriously inaccurate and unreliable. Together, these would undermine the overall validity and reliability of the experimental results, even though the estimates of sperm parameters could both be very valid and reliable. Even if the sample of human subjects is randomized to factor out the subfertile men bias in future studies, as suggested by Chavarro et al., the inherent deficiencies of a food intake recall approach to estimating isoflavone intake are still not remedied. Valid and reliable estimation of isoflavone intake can only happen with actual feeding trials, using known and controlled sources and dosages of dietary isoflavones, like what Mitchell et al. did in their UK human study3. In their paper, Chavarro et al. mentioned that "Only two studies have previously examined the relation between soy food or isoflavone intake and semen quality parameters in humans. Mitchell et al. (2001) evaluated the reproductive effects of daily supplementation with 40 mg of isoflavones for 2 months among 14 young men. There were no appreciable changes in semen quality parameters or reproductive hormone levels compared with pre-supplementation levels (Mitchell et al., 2001). However, the lack of a control group and the small size of the study make difficult the interpretation of their findings. In a study with a design similar to ours, Song et al. investigated the relationship between isoflavone intake and semen quality in a group of 48 men with abnormal semen parameters and 10 men with normal semen parameters. In contrast with our results, they found that isoflavone intake was positively related to sperm count and motility and inversely related to sperm DNA damage (Song et al., 2006)." Chavarro et al. did not account for why their results contradicted the findings by Mitchell et al., other than a criticism of Mitchell et al.'s "lack of a control group and the small size of the study make difficult the interpretation of their findings." But Chavarros' criticism of Mitchell's design is not necessarily valid. According to Mitchell et al., "the study design was an open, within-subject assessment of the effects of a food supplement containing phytoestrogens on the reproductive system in adult males. A sample size of 12 was calculated to give 95% power to detect a 20% change in parameters at a level of 5% significance." To detect the level of change in sperm concentration found in Chavarro's study, Mitchell's sample size is adequate for the purpose. Of course, the incorporation of a control group with double-blind placebo use will strengthen the study, but in Mitchell's approach, the test subjects themselves also serve as a control group. Even if Chavarro's criticism of Mitchell's experimental design is valid, yet in a presumptive study, based on Mitchell's cause-and-effect approach, the results simply cannot be ignored and should form the directional basis for a larger-scale confirmation study. Besides, the dosage of isoflavones used by Mitchell et al. was 40 mg per man per day for two months, an intake equivalent to one serving of soy food a day, as typical in Eastern countries, or double the amount cautioned by Dr. Chavarro as worrisome. And yet the null hypothesis prevailed. Dr. Chavarro was quoted2 as saying that research in animals has shown that isoflavones and estrogen can have a potentially negative affect on reproduction, including decreased fertility. However, there is very little evidence of how these findings apply to humans, he said. The new research, he added, lends support to how results of animal studies apply to humans. But as far as negative effects of isoflavones in animal studies are concerned, Mitchell et al. pointed out that "doses administered to experimental animals may be up to 10-fold higher than the equivalent average human consumption," whereas in their human study, "a daily food supplement containing 40 mg of genistein and daidzein over a 2 month period had no effect on gonadotrophin or sex hormone concentrations or on semen quality." Dr. Chavarro made no reference to the potential flaw of possibly 10-fold dosage of isoflavones in animal studies, as Mitchell et al. did. A 10-fold dosage is very likely to have exceeded the normal physiological range, and overstepped into the pharmacological zone or even the toxic zone. The results can be very misleading. The scientific researcher is obliged to bring both sides of the argument to light, which Mitchell professionally did. In addition, Chavarro et al. did not explain why their results, implying a negative effect of soy isoflavones on sperm parameters, were contradictory to the 2006 findings of Song et al. of Rochester Medical Center, Rochester, NY4. Song et al. reported on the beneficial effects of dietary intake of plant phytoestrogens on semen parameters and sperm DNA integrity in infertile men. For the benefit of readers, I shall recapitulate Song et al.'s abstract as follows: "The authors recruited 48 men with abnormal semen parameters whose partners had been trying to conceive for at least one year. Controls consisted of 10 men with normal semen analyses who had fathered a pregnancy within the previous year. DNA integrity was measured using sperm chromatin structure assay (SCSA) and total antioxidant capacity (TAC) of seminal plasma was assessed using colorimetric TAC assay. Block food frequency questionnaires (NutritionQuest) were used to estimate the dietary intake of isoflavones (genistein and daidzein) of each patient. Higher mean levels of genistein and daidzein were observed in fertile control men compared to infertile men (genistein, 527 ± 183 ug/day in infertile men vs. 1722 ± 714 ug/day in fertile controls; daidzein, 241 ± 84 ug/day vs. 788 ± 327 ug/day, p<0.05). Of note, the levels of daidzein and genistein were higher in men with better sperm DNA integrity (DNA fragmentation index, DFI < 30%) compared to men with poor sperm DNA integrity (DFI 30%, p=0.08). Interestingly, the authors performed regression analysis which revealed significant correlation (P<0.05) between dietary intake of genistein and semen parameters including sperm count (r=0.448), motility (r=0.311), progressive motility (r=0.424) and sperm DNA fragmentation index (r= - 0.325). Furthermore, similar correlations were found between daidzein and semen parameters. The investigators did not observe the correlation between dietary intake of isoflavones and seminal total antioxidant capacity (r=0.138 with genistein, r= 0.141 with daidzein, p>0.05). In conclusion, the authors noted that they observed an association between dietary phytoestrogens and semen parameters including sperm DNA integrity. They suggested that a larger population study and basic research should be performed to confirm these findings and to clarify the mechanism of the effects of isoflavones on sperm physiology." In other words, Song et al. found a much higher isoflavone intake (by average more than three times) in normal, fertile men, than infertile men in their sample. And although they did not report on sperm concentration in sperms per milliliter of semen, they did report that sperm count, motility, progressive motility, and sperm DNA integrity, all important parameters contributing to men fertility, were better in their sample of normal, fertile men, even though their soy intake was on average higher by more than three times that of the infertile men in their sample. So at least that higher soy intake did not appear to harm fertility in the sample of normal, fertile men, because they were successful in making pregnancy happen, whereas a low soy intake did not appear to offer protection against infertility. Of course, whether a high soy intake will benefit, and a low soy intake will harm human fertility, will need to be enlightened by research based on cause-and-effect.. The only conclusion Chavarro et al. could possibly draw from their study was that among subfertile men, based on a sample of 99 subfertile men by convenience, there were some with assumed higher soy intake by diet recall and gross calculation, and those, by association, not cause-and-effect, exhibited reduced sperm concentration compared with a sample of other subfertile men, similarly recruited by convenience, who did not eat soy. Any conclusion extrapolating beyond that is unsubstantiated, speculative hyperbole. A better approach taking care of both cause-and-effect relationship and the experimental requirements of validity and reliability is to recruit a sufficient number of normal, fertile men who do not consume any soy and measure their sperm parameters. Then split them into two groups, ask one group to continue staying away from soy foods, and the other group to regularly consume (say on a daily basis, at a pre-determined time, like in the morning for breakfast, continuously for a period of 6 months, or longer) a pre-determined normal quantity of a pre-selected soy food of known isoflavone concentration (say a given soymilk), and periodically take measurements of the sperm parameters of all individuals in both groups. The comparative results before, during, and at the conclusion of the trial period, and within and between groups, after controlling for all confounding parameters, will be statistically very revealing. Then we can repeat the same trial in other countries, and try to establish some basis of a universal scientific truth, to see whether soy isoflavones help, do not affect, or hurt sperm parameters in normally fertile men. Why go by convenience for a non-affirmative association that does not reveal cause-and-effect relationship and that lacks experimental validity and reliability by using a biased sample of subfertile men and generate nothing but sensational journalism? Generally, from the viewpoint of the media, things that are normal or meet expectation do not feature a news angle and are therefore not newsworthy or worth emphasized coverage. For example, if a dog bites a man, it is something that could happen anytime anywhere and is therefore not very worth reporting on, whereas, if a man bites a dog, because the event is rare and not expected, then it is something newsworthy. The same applies to coverage on soy. Because of its long history of safe human use, thousands of scientific research reports, and U.S. FDA's endorsement of soy protein's heart-health benefits, most people perceive and believe soy to be healthy. One more research paper reinforcing the healthiness of soy, like the paper written by Song et al., or another paper on the safety of soy, like the paper written by Mitchell et al., will not draw much public attention. This is also expected from the law of diminishing marginal utility, a fundamental law of economics, like after eating four oranges in a row, the fifth orange will not appeal to you too much. But if someone happens to report on soy negatively (and one can expect that everything on earth comes with positivity, negativity, and neutrality, in terms of helping, hurting, or not affecting mankind in specific ways, and only the ratio of the three kinds of impacts differs), then it is newsworthy. The fact, firstly, that Dr. Chavarro did not try to explain the reasons for the differences of his findings with those of the two prior human studies by other researchers that reflected positively or neutrally on the roles played by soy isoflavones in sperm quality; secondly, that he did not mention in his paper that half-a-serving a day or one serving soy food every other day is sufficient to cause an alarm until press release5 time (Dr Chavarro found that men in the highest intake category had, on average, 41 million sperm/ml less, or one-third to one-half less, than men who did not eat soy foods. "Men in the highest intake group had a mean soy food intake of half a serving per day: in terms of their isoflavone content that is comparable to having one cup of soy milk or one serving of tofu, tempeh or soy burgers every other day," he said5); and thirdly, that he did not point out that in Micthell et al.'s study, which lasted for 6 months (sufficient for two full 3-month cycles for sperm parameter recovery), each of the 14 men truly got the isoflavone equivalent of one full serving of soy food, or double the amount of Chavarro's alarm threshold a day, or equivalent to the typical daily intake in Eastern countries, and suffered no harm to his sperm quality parameters, pointed more toward the direction of sensational journalism. While informed science journalist Jess Halliday of AP-Foodtechnology.com6 rightly pointed out that the study methodology did not allow for a cause behind the observation to be established (unlike Mitchell et al.'s direct human feeding trials, epidemiological studies, like that of Chavarro's, only suggest co-happening association, never cause-and-effect), Chavarro still included his speculation in the report. He said it may be down to the estrogenic activity of the isoflavones interfering with hormone signals, and therefore affecting sperm production. This is certainly unsubstantiated, speculative hyperbole, and not grounded in reality-based, scientific truth. The way to look at soy or tofu, just like looking at any other thing on earth, is not to expect perfect benefits without caveats. The one fact we can rely on to give ourselves peace of mind is that soy has been consumed regularly in substantial quantities in Asia for ages, and yet Asian fertility has not suffered, at least in population numbers. Even if you are a soy lover, your intake of isoflavones is limited by the amount of soyfood that brings you natural satiety. That level of isoflavone, together with natural whole-soy components, can also help us reduce the risks of heart disease, breast cancer, prostate cancer, osteoporosis, and postmenopausal symptoms. But if you are taking isoflavone supplement pills, in amounts which overwhelm our bodies' natural response, then you may easily tip the physiological balance and elicit pharmacological or even toxic effects, as true for everything appearing beneficial at physiological level. For example, green tea has been branded a super-food because of its content of polyphenolic antioxidants. But you must think twice about taking green tea extract pills, each containing the equivalence of 60 cups of green tea. More is not necessarily better. For instance, drinking too much water can bring about water intoxication, and likewise taking in too much oxygen can elicit oxygen poisoning, even though we cannot live without either water or oxygen. Like people naturally developing overweight and obesity in the nowadays over-abundant and calorigenic food environment, according to the physical law of energy balance dictating that caloric input in excess of expenditure is accumulated, primarily as storage fat, to allow for human survival in lean times, our slow-to-adapt genes are dictating our bodies' response to external environmental changes, according to how they have evolved with environmental challenges over the millions of years of human existence on earth. It may be to our best advantage to stay within the physiological boundaries defined by our natural genetic response, so that we do not shoot ourselves in the foot. The conventional wisdom of doing things in moderation may sound a bit nagging, but it is still valid. References Cited: 1 Chavarro, J.E., Toth, T.L., Sadio, S.M., and Hauser, R. 2008. Soy Food and Isoflavone Intake in Relation to Semen Quality Parameters among Men from an Infertility Clinic. Human Reproduction. Advance Access published online on July 23, 2008. Human Reproduction, doi:10.1093/humrep/den243. Abstract published online at http://humrep.oxfordjournals.org/cgi/content/abstract/den243v1 2 Reinberg, S. 2008. Soy Linked to Low Sperm Count. HealthDay News, 07-23-2008. Web-link at http://health.msn.com/health-topics/sexual-health/mens-sexual-health/articlepage.aspx?cp-documentid=100211543>1=31028 3 Mitchell, J.H., Cawood, E., Kinniburgh, D., Provan, A., Collins, A.R., and Irvine, D.S. 2001. Effect of a Phytoestrogen Food Supplement on Reproductive Health in Normal Males. Clinical Science (London). 100(6): 613-618. 4 Song, G, Kochman, L., Andolina, E., Herko, R.C., Brewer, K.J., and Lewis, V. 2006. Beneficial Effects of Dietary Intake of Plant Phytoestrogens on Semen Parameters and Sperm DNA Integrity in Infertile Men. Fertility and Sterility. 86(3): S49. 5 Anon. 2008. Soy Foods are Associated with Lower Sperm Concentrations. European Society of Human Reproduction & Embryology, July 24, 2008 press release. Web-link at http://www.eshre.com/emc.asp?pageId=1135. 6 Halliday, J. 2008. Study links low sperm with high soy consumption. AP-Foodtechnology.com, 07-24-2008. Web-link at http://www.ap-foodtechnology.com/news/ng.asp?n=86696&c=gPTKXx15OjXcIoCz8xaCIA%3D%3D First posted 7-28-2008. If you have any questions or comments, please e-mail us at contactus@soynjoy.net. |