Research from the University of Illinois by Bosland et al.1 provides important insight about the effects of soy protein on hormone levels in men. This study is especially notable because of its size and duration. The results show that soy protein affects neither circulating levels of free testosterone (biologically active form) or insulin-like growth factor-1 (IGF-1). The former finding is consistent with a meta-analysis that was published earlier this year.2 The latter finding helps address a question that has been discussed for nearly two decades.
Bosland et al.1 conducted a 2-year parallel trial involving older males at risk of recurrence of prostate cancer after radical prostatectomy. Men were randomly allocated to receive daily a beverage powder containing either 19.2g of soy protein (n=81) provided as soy protein isolate or 19.8g of casein (n=78). The soy protein powder contained 41mg isoflavones expressed as aglycone equivalent weight. The effect of the intervention on the primary outcome – biochemical recurrence of prostate cancer – was reported in 2013.3
The effect of soy on testosterone levels has been a contentious issue for many years, despite a 2010 meta-analysis of clinical studies that showed neither soy protein nor isoflavones affect circulating levels of testosterone, sex hormone binding globulin, free testosterone or the free androgen index.4 Because questions about the effect of soy on testosterone levels continued to be raised in social media, several authors of the 2010 analysis published an updated analysis. This updated analysis, which included over 40 clinical studies, again found that neither soy nor isoflavones affect total or free testosterone levels.2 There was also no effect on estrogen levels (older men make more estrogen than older women).
IGF is a natural growth hormone and plays a crucial role in normal growth and development. The IGF system, which includes several forms of IGF and IGF binding proteins such as insulin-like growth factor binding protein-3 (IGFBP3), is of interest because it is thought to play a role in the etiology cancer.5 Several older studies found that soy protein increased IGF-1 levels, which raised concern that soy protein could increase cancer risk.6,7 A 2018 review concluded that “there is some evidence that large amounts of soy protein (>25 g/day) modestly increase IGF-1 levels above levels observed with the control protein.”8
In the study by Bosland et al.,1 at the final timepoint (18 months), IGF-1 levels in the soy group were 2.8% higher than baseline, whereas levels increased 22% in response to casein.1 Neither change, nor the difference between groups, was statistically significant. The IGF-1/IGFBP-3 ratio was 5.1% and 14.3% higher in the soy and casein groups, respectively. This ratio reflects the levels of bioavailable IGF-1.
For those concerned that soy protein might increase cancer risk by raising IGF-1 levels, the results from Bosland et al.1 are reassuring. It needs highlighting however that, as noted above, the 2018 review suggested that large amounts of soy protein might modestly increase IGF-1. The study by Bosland et al.1 intervened with about 19g of soy protein. While that amount might not be considered large by some standards, it is about twice the amount of soy protein typically consumed by older native Japanese adults.9 And it is close to the 25g/day established by the U.S. Food and Drug Administration as the threshold intake required for cholesterol reduction.10
In conclusion, new results combined with the existing literature show that dietary levels of soy protein, regardless of the form in which the protein is consumed, do not raise IGF-1 levels or lower testosterone levels in men.
- Bosland MC, Huang J, Schlicht MJ, et al. Impact of 18-month soy protein supplementation on steroid hormones and serum biomarkers of angiogenesis, apoptosis, and the growth hormone/IGF-1 axis: Results of a randomized, placebo-controlled trial in males following prostatectomy. Nutr Cancer. 2021:1-12.
- Reed KE, Camargo J, Hamilton-Reeves J, et al. Neither soy nor isoflavone intake affects male reproductive hormones: An expanded and updated meta-analysis of clinical studies. Reprod Toxicol. 2021;100:60-7.
- Bosland MC, Kato I, Zeleniuch-Jacquotte A, et al. Effect of soy protein isolate supplementation on biochemical recurrence of prostate cancer after radical prostatectomy: a randomized trial. JAMA. 2013;310:170-8.
- Hamilton-Reeves JM, Vazquez G, Duval SJ, et al. Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis. Fertil Steril. 2010;94:997-1007.
- Brahmkhatri VP, Prasanna C, Atreya HS. Insulin-like growth factor system in cancer: novel targeted therapies. BioMed research international. 2015;2015:538019.
- Khalil DA, Lucas EA, Juma S, et al. Soy protein supplementation increases serum insulin-like growth factor-I in young and old men but does not affect markers of bone metabolism. J Nutr. 2002;132:2605-8.
- Arjmandi BH, Khalil DA, Lucas EA, et al. Soy protein may alleviate osteoarthritis symptoms. Phytomedicine. 2004;11:567-75.
- Messina M, Magee P. Does soy protein affect circulating levels of unbound IGF-1? Eur J Nutr. 2018;57:423-32.
- Messina M, Nagata C, Wu AH. Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer. 2006;55:1-12.
- Food labeling: health claims; soy protein and coronary heart disease. Food and Drug Administration, HHS. Final rule. Fed Regist. 1999;64:57700-33.