Google the words "soy" and "bone mineral density," and the search engine will return more than 45,000 hits. Scrolling through the list is a bit like watching a tennis match: Soy improves BMD. Soy proteins fail to increase BMD. Soy protein maintains some BMD indices. Soy has no effect on BMD content. So on and so forth.
Both anecdotally and scientifically, the consumption of soy products among East Asian populations (particularly in Japan and China) has been linked with decreased rates of osteoporosis and related fractures, as well as other conditions prevalent in the West, including cardiovascular diseases and certain cancers.
In 1995, data from the First International Symposium on the Role of Soy in Preventing and Treating Chronic Disease strongly indicated that soy protein consumption could significantly reduce serum cholesterol levels. Four years later, the FDA approved a health claim for labels for foods that contained at least 6.25 grams of soy protein per serving (American Journal of Clinical Nutrition, September 2000, Vol. 72:3, pp. 679-680).
At the time, the other health benefits of soy were unclear, but that didn't stop consumer products companies from jumping on the bean-derivative bandwagon -- soy began cropping up in such "women-friendly" products as supplements, nutrition bars, and face creams.
Since then, women's health specialists have learned more, most notably that soy isoflavones act like estrogen substances such as 17 ß-estradiol. While consuming products with soy may not do any harm, does it actually have benefits for slowing down osteoporosis and general bone deterioration? A number of recent studies have taken a closer look at a possible link between soy intake and bone health. On the whole, the researchers found that soy has a significant influence on the bones, but it may not be the ultimate organic answer.
Asian advantage?
Given the degree to which soy products are a staple in the East Asian diet, it only makes sense that research has focused on those populations.
"The Japanese consume a diet that is very rich in the isoflavones genistein and daidzein, which are found in soybeans and soy products," wrote Dr. Chisato Nagata and colleagues from Gifu University School of Medicine and Matsunami General Hospital, both in Gifu, Japan. "Some researchers assume that the lower incidence of osteoporosis in Japanese women is attributable to a high consumption of soy foods" (Osteoporosis International, March 2002, Vol. 13:3, pp. 200-204).
Testing that assumption, Nagata's group performed a cross-section study of 87 postmenopausal Japanese women. On a questionnaire, the women were asked to indicate the average frequency with which they had consumed soy products during the past year (miso soup, tofu, soy milk, bean curd) and in what quantities.
Bone mineral density was measured at the calcaneus and expressed in g/cm2 (OsteoAnalyzer, CooperSurgical, Lake Forest, CA). A radioimmunoassay was used to measure serum estradiol (E2) -- a precursor of estrogen that maintains BMD levels -- and sex hormone-binding globulin (SHBG), which is used to transport sex steroids.
According to the results, there was no significant correlation between soy and isoflavone intake and BMD. However, there was a significant correlation between the ratio of serum E2 to SHBG and BMD (p = 0.0003).
The authors attributed the lack of positive results for soy to the fact that the majority of the subjects consumed less than 90 mg of isoflavones per day. "Their intake of isoflavones and, probably, serum isoflavonoid levels may have been too low to exhibit an estrogenic effect on bone," they stated.
The authors pointed out that BMD at the heel may not respond as well to soy intake as other parts of the skeleton. Also, soy consumption did have a favorable effect on BMD and E2/SHBG levels, both of which play a role in estrogen deficiency and subsequent bone loss.
In a second study, Chinese investigators found a more promising connection between soy isoflavones and BMD. This one-year study, led by Dr. Yu-Ming Chen from the Chinese University of Hong Kong, investigated the effects of different dosages of concentrated soy-derived isoflavones on bone mass.
The patient population consisted of 175 postmenopausal Hong Kong women of Chinese origin. They were randomly assigned to three groups to take daily either a mid-dose intake of 40 mg of soy isoflavones, a high-dose intake of 80 mg of soy, or a corn starch placebo. Bone mineral content (BMC) and BMD were measured at the lumbar spine (L1-L4) and at the left hip (QDR 4500, Hologic, Bedford, MA).
Chen's group found "significantly higher positive rates of change in BMC at the total hip and trochanter in subjects in the high-dose group compared with those in the placebo and mid-dose groups." But there was no change in BMD in all three groups, they reported (Journal of Clinical Endocrinology & Metabolism, October 2003, Vol. 88:10, pp. 4740-4747).
Focusing on BMC, they noted that soy was particularly effective in women who had started out with lower initial BMC values, showing higher rates of change at the total hip and trochanter.
"An increase of 10 mg isoflavones (supplementation per day) was associated with yearly increases of 0.18, 0.30, and 0.20% of BMC," at the total hip, trochanter, and intertrochanter, respectively, they added.
Why soy intake had no sway over BMD was unclear, the group stated, but suggested that a soy-induced increase in osteoblastic activities may exert a greater influence on BMC.
Replacing HRT?
Of course, estrogen replacement therapy (ERT) and hormone replacement therapy (HRT) are au courant for treating osteoporosis. But the adverse side effects range from relatively mild (uterine bleeding, breast pain) to serious (increase risks for ovarian cancer and heart attack).
These side effects "cause women to search for alternatives to traditional therapy," Dr. D. Lee Alekel and co-authors wrote in the American Journal of Clinical Nutrition. "Isoflavone-containing soy may be a potential alternative.... Isoflavones may combine with the estrogen receptor ... and stimulate estrogen activity, thus having an estrogenic effect on bone and blood vessels (September 2000, Vol. 72:3, pp. 844-852).
Researchers from Alekel's group are from Iowa State University in Ames and Fujicco, a soy product manufacturer in Kobe, Japan. Their 24-week study examined the effect of isoflavone-rich soy protein, isoflavone-poor soy protein, and whey protein on the attenuation of bone loss in perimenopausal women.
Eighty women were randomized into three groups based on the three different kinds of protein, with the whey group acting as the control. The protein was consumed as a muffin and a powder; the women were instructed to avoid other food items with soy isoflavones.
Bone densitometry was performed on a QDR 2000+ (Hologic) with BMD and BMC assessments made at the lumbar spine (L1-L4) at baseline and post-treatment. Overall body composition was taken, and the percentage changes in lumbar spine BMD, BMC, and body weight were calculated for each group.
According to the results, the mean percentage changes in lumbar spine BMD and BMC did not decline in the two soy groups, although significant losses occurred in the whey group. Again, soy had significant treatment effect on BMC, but not on BMD. For the soy isoflavone-rich soy protein group, the percentage change losses in BMD and BMC were 5.6% and 10.1%, respectively. The other treatment plans had no effect, the authors said.
"Thus, initial bone mass, bone turnover, body mass or composition, and (isoflavone-rich soy protein) treatment were significant contributors to percentage changes in lumbar spine BMD and BMC," they wrote. "Our positive results ... suggest that dietary isoflavones may be effective in preventing vertebral bone loss due to ovarian hormone deficiency."
The authors stressed that additional research was needed, but that soy isoflavone consumption might serve as an alternative or adjunct therapy for women who refuse HRT. One limitation of the study was that the 24-week period was not enough to determine if the bone loss would be sustained over time. Bone remodeling cycles range from 30 to 80 weeks.
Another group, from the U.K., also studied the possibility of isoflavone as an option for women who choose not to use HRT. Their patient population was larger (205 women), and the participants were given a red clover-derived isoflavone tablet (Promensil, Novogen, Sydney, Australia).
They chose these tablets over soy protein because the former "contain ... relatively large portions of ... diadzein and genistein (which) may be more important than other isoflavones," they wrote in the American Journal of Clinical Nutrition (February 2004, Vol. 79:2, pp. 326-333).
Dr. Charlotte Atkinson and colleagues recruited women from the breast screening program at Addenbrooke's Hospital in Cambridge, where Atkinson is based.
"The primary outcome measure was breast density, and women were selected for the study according to the extent of dense tissue seen on their most recent mammogram," they explained. The women received either the isoflavone tablet or a placebo. BMD and body composition were assessed with DEXA at baseline and one year later (QDR 4500A, Hologic).
They also found that decreases in BMC and BMD of the hip were greater in the placebo group than in the isoflavone group. In addition, the loss of lumbar spine BMC and BMD was lower in the isoflavone group. Finally, in the intervention group, bone formation markers were significantly increased. The group called for more long-term studies to determine if this attenuation of bone loss with isoflavone could have a protective effect on the lumbar spine.
Old bones, new tricks?
The most recent research has focused on soy isoflavones and bone formation. First, Laura Harkness, Ph.D., and colleagues at Case Western Reserve University in Cleveland conducted a randomized trial with a crossover design to test the effect of soy on bone formation, resorption, BMD, and BMC over a one-year period.
Group 1 was enrolled in phase A (110 mg/day of soy isoflavone) for six months before crossing over to phase B (placebo) for another six months. Group 2 did the opposite.
"The study supplement dose was selected because the potential dose to affect bone turnover is estimated at 100 mg/day," they explained (Journal of Women's Health, November 2004, Vol. 13:9, pp. 1000-1007).
BMC and BMD of the lumbar spine and femoral neck were obtained with densitometry (QDR 4500C, Hologic) at baseline, at six months, and then at one year. Laboratory samples of bone turnover markers were also garnered.
There was no significant difference in total spine BMD in either group, but for those in group 1, there was a spike in BMD at the L3 spine after isoflavone treatment compared to pretreatment, Harkness reported. This same uptick in L3 BMD was seen in the treatment group versus the placebo group. Finally, they saw a significant increase during the placebo period in L4 spine BMD for group 1 compared to pretreatment and isoflavone treatment. There were no meaningful changes in group 2.
In terms of bone markers, the group reported a 37% decrease in bone resorption with isoflavone treatment. "This decrease in bone resorption represents a return to urinary (helical peptide) levels found in premenopausal women," they said. "There is a complex relationship between bone turnover and bone mass." Specifically, levels of serum osteocalcin, another marker of bone formation, returned to premenopausal levels, resulting in less bone turnover and less bone mass loss.
Unfortunately, researchers from Oklahoma State University in Stillwater did not have the same luck with soy and bone marker formation. In their study population, they still saw bone loss despite soy supplementation.
Dr. Bahram Arjmandi and colleagues enrolled 62 postmenopausal women in their yearlong study. The women were either randomized to receive 25 grams of soy protein daily or put in a control group. Whole-body, total hip, and lumbar spine BMD and BMC were assessed at the beginning and end of the treatment period with densitometry (QDR 4500C, Hologic).
According to their results, subjects in both groups lost 1.3% whole-body BMD, while the soy group lost 1.0% lumbar BMD (versus 0.9% in the control). There was no change observed in the total hip. An increase in bone formation was seen in both groups, but the soy offered no influence over bone resorption.
"Our findings do not support a bone-protective role for soy protein and its isoflavones at the level used in this study," they wrote (Nutrition Journal, February 23, 2005, Vol. 4:1).
However, the group acknowledged that the soy dose in this study may have been too low. The true power of soy isoflavones may lie in how much is consumed, rather than if it's consumed at all. Researchers across the board agreed that 80 grams may be the minimum amount necessary to truly bring about changes in the bone.
By Shalmali Pal
AuntMinnie.com staff writer
March 25, 2005
Related Reading
Soy use linked to thickening of uterus lining, July 15, 2004
Plant estrogens may fight menopausal bone loss, March 10, 2004
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