Research Update

Latest Soy and Bone Studies Disappointing

Given the estrogen-like effects of soybean isoflavones it is understandable that there has been considerable interest in the possible skeletal benefits of soyfoods.

The first human study to evaluate the effects of isoflavone-containing soy products on bone mineral density (BMD) was published in 1998.1  That 6-month study found the consumption of 40 g/d isolated soy protein that provided 90 mg isoflavones inhibited bone loss in postmenopausal women in comparison to the consumption of a similar amount of a mixture of casein and nonfat dry milk.  Since that first trial more than 25 others have evaluated the effects of soyfoods, soy protein or isoflavone supplements on BMD.  The results of this research have been mixed, however.  

Unquestionably, the most impressive clinical findings come from Italian researchers who reported that over a three year period, postmenopausal osteopenic women in the placebo group lost nearly 12% of their spinal BMD whereas those women given 54 mg genistein (equivalent to about 100 mg total isoflavones or 4 servings of traditional soyfoods) gained about 9%.2  Consistent with these findings are the results of the two Asian epidemiologic studies that evaluated the relationship between soyfood intake and fracture; in each, higher soy intake was associated with an approximate one-third reduction in risk.3,4  However, research published within the past year hasn’t supported the hypothesis that isoflavones exert skeletal benefits.  

Most recently, Weaver et al.5 conducted a blinded, randomized, crossover intervention trial to compare the effects of isoflavone supplements with oral hormone replacement therapy or with an oral bisphosphonate on net bone resorption and calcium absorption in postmenopausal women.  Subjects were given 41Ca by intravenous injection and baseline measures of urinary 41Ca were collected over the subsequent 100 days.  Twenty-four hour urine samples were collected approximately every 10 days during all pre- (50 d) and intervention (50 d) periods for the measurement of 41Ca by Accelerator Mass Spectrometry.  41Ca enters the bone and once soft-tissue clearance is complete its appearance in the urine represents a stable marker of bone resorption that can be monitored for a lifetime.  

There were no effects of any treatment on calcium absorption but as expected, hormone therapy and bisphosphonate treatment inhibited bone resorption by 24.4 and 21.7%, respectively.  Soybean isoflavones inhibited net bone resorption by 9%, a little more than one-third the effect of estrogen.  However, although statistically significant, that inhibition was in response to the consumption of an intake of more than 200 mg total isoflavones.  This amount is roughly five fold higher than typical Japanese intake and realistically not possible to obtain via the consumption of soyfoods.6  It would be interesting to determine if smaller amounts of isoflavones still had at least some effect on net bone resorption using this methodology.

Another recent study of interest evaluated the effects of isoflavone supplements and soy protein on BMD in 131 healthy older postmenopausal women although only 97 completed the trial.7

Subjects were randomly assigned into one of four intervention groups:

• soy protein (18 g) plus isoflavone tablets (105 mg isoflavone aglycone equivalents)
• soy protein plus placebo tablets
• control protein plus isoflavone tablets
• control protein plus placebo tablets

No significant differences in BMD were observed among groups from baseline to one year after the intervention.  The one year duration of this study is a bit of a limitation as is the small subject number, but there was not even a suggestion of a beneficial effect.  

Overall, the results of these two studies are quite disappointing.  Still, it is intriguing that as noted previously, two Asian epidemiologic studies reported soy intake to be protective against fracture.3,4  Whether this is because traditional soyfoods differ from isolated soy protein and isoflavone supplements, protection requires lifelong intake, or soy intake is merely reflective of a bone-protective lifestyle remains to be determined.

REFERENCES:

1. Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF, Erdman JW, Jr. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr. 1998;68:1375S-9S.
2. Marini H, Bitto A, Altavilla D, Burnett BP, Polito F, Di Stefano V, Minutoli L, Atteritano M, Levy RM, et al. Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study. J Clin Endocrinol Metab. 2008 Dec;93:4787-96.
3. Zhang X, Shu XO, Li H, Yang G, Li Q, Gao YT, Zheng W. Prospective cohort study of soy food consumption and risk of bone fracture among postmenopausal women. Arch Intern Med. 2005 Sep 12;165:1890-5.
4. Messina M, Watanabe S, Setchell KD. Report on the 8th International Symposium on the Role of Soy in Health Promotion and Chronic Disease Prevention and Treatment. J Nutr. 2009 Apr;139:796S-802S.
5. Weaver CM, Martin BR, Jackson GS, McCabe GP, Nolan JR, McCabe LD, Barnes S, Reinwald S, Boris ME, Peacock M. Antiresorptive Effects of Phytoestrogen Supplements Compared to Estradiol or Risedronate in Postmenopausal Women Using 41Ca Methodology. J Clin Endocrinol Metab. 2009 Jul 7.
6. Messina M, Nagata C, Wu AH. Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer. 2006;55:1-12.
7. Kenny AM, Mangano KM, Abourizk RH, Bruno RS, Anamani DE, Kleppinger A, Walsh SJ, Prestwood KM, Kerstetter JE. Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial. Am J Clin Nutr. 2009 Jul;90:234-42.