The potential for soy protein or soy isoflavones to alter bone metabolism and bone loss is currently contradictory and inconclusive. Our two best measurements are bone density testing with DXA (an xray test) measures or bone metabolism markers. The lack of agreement in the literature is thought to be related to variations in study design using different soy products, (ie soy protein isolate, whole soy foods, or extracted soy isoflavones), different populations with sometimes perimenopausal women, other times early or even late postmenopause, and then of course different durations and dosage and bone marker assessments. All these different approaches make it very difficult to determine the effectiveness of soy, and therefore difficult to make clinical judgments.
Soybeans contain a class of compounds called phytoestrogens, comprising mostly genistein, daidzein and glycitein, all of which have a biochemical structure similar to 17 beta estradiol. The binding of isoflavones to estrogen receptors is preferential for the estrogen receptor beta and thus indicates that soy isoflavones act as selective estrogen modulators. Daidzein is similar in shape to a drug called Ipriflavone which is used in Europe to treat osteoporosis. In the U.S., Ipriflavone is available as a nutritional supplement.
Bone mineral density (BMD) is the gold standard for determining fracture risk due to nontraumatic events. Bone turnover is an independent predictor of fracture risk.
While the effects of soy on bone metabolism has been inconsistent, many positive studies do exist that suggest a role for soy in slowing bone turnover and bone density in women. Soy appears to have a pro estrogen effect on bone in some experimental evaluations. The bone density of ovariectomized rats was evaluated in which soy replaced casein in the diet, compared to another group that received estrogen. The addition of soy inhibited bone loss, although not to the same extent as was achieved with the estrogen treatment. Another study of ovariectomized rats also reported a positive effect of the soy phytoestrogen genistein in maintaining bone. These authors also reported that genistein suppresses the bone losing cells (osteoclasts), both in the test tube and in vivo. Arjmandi also did a double-blind, randomized, controlled trial using 40g of soy protein containing isoflavones over 3 months in postmenopausal women. Bone resorption was decreased, when compared to milk protein.
Several human studies have provided further insight and comfort in the possible role of soy in our bone health. A study conducted at the University of Illinois found that menopausal women had an increase in mineral levels and density in their lumbar spines after taking 55-90 mg of isoflavones for six months. The placebo group showed the lowest bone density and the greatest bone loss, while the estrogen group showed the highest bone density and the slowest bone loss. What was surprising was that the soybean diet was effective in preventing bone loss in the fourth lumbar vertebra and, although less so, in the right hip as well. Soybean seems to have more of an effect on trabecular bone (more predominant in the spine) than on cortical bone (more predominant in the hip). The soy did not show as great an ability in preventing bone loss as the estrogen group, but the positive effect it showed is encouraging.
A study of the relation of soy isoflavone intake and bone mineral density was conducted within the Study of Womenâ€™s Health Across the Nation, a US cohort study of women aged 42-52 years. For African-American and Caucasian women, average intakes of genistein was too low to pursue analyses. For Chinese women, no association between genistein and bone mineral density was found. Pre-menopausal, but not peri-menopausal, Japanese women whose intakes were greater had a higher bone density of the spine and femoral neck. Mean spinal bone density of those women in the highest group was 7.7% greater than that of women in the lowest group. Bone density of the femoral neck was 12% greater in the highest intake group versus the lowest.
Other positive studies on soy and bone density also give some credence to the role of soy and bone health. In a study estimating the daily intakes of soy isoflavones in the diets of 478 postmenopausal Japanese women who reported soy consumption, high consumption of soy products was associated with increased bone mass.
A very recent analysis of nine studies further increases our optimism about using soy to inhibit bone resorption. Nine studies with a total of 432 menopausal women were evaluated for meta-analysis. Amount of soy intake varied amongst the nine studies from 37 mg of isoflavones per day to 118 mg of isoflavones per day. Testing for urinary peptides (deoxypyridinoline) of bone turnover demonstrated that when all nine study results are combined, those who consumed isoflavones had a decrease in these biomarkers of -2.08 nmol/mmol when compared to those who did not consume isoflavones. In five of the studies, isolated soy protein was used, as a group, there was no significant effect on urinary deoxypyridinoline. In the current analysis, significant reduction in urinary deoxypyridinoline did not occur in those studies with isoflavones of less than 90 mg/day. In a review of the research in 2003, the author concluded that 90mg of isoflavones per day is required to achieve benefits on bone health.
In contrast to the positive studies, several clinical trials using a variety of soy protein isolate formulations found no clinically important effects of soy on bone metabolism and bone turnover markers. Further inconsistent research can be seen with several clinical trials using soy protein or isoflavones demonstrating a positive effect on BMD, while others have not had positive findings.
I mentioned variations in dosing, duration, soy formulations used, and different study populations as possible reasons for inconsistent results on the effects of soy isoflavones on bone turnover and bone density. But, another significant consideration may be due to how the isoflavones are metabolized in the gut. In the recent study mentioned about analyzing nine studies 10 the significant effects on urinary peptides occurred in Asian women but not Caucasian women. This may be due to the conversion of isoflavones into its active metabolite equol in intestinal flora, and that only one-third of Caucasian women can metabolize isoflavones into equol, whereas more than half of Asian women possess this ability.
Soy isoflavones may also have more of an effect in post-menopausal women than in pre or perimenopausal women. In one study, 53.3 mg of isoflavones per day was associated with an increase in bone density in postmenopausal women, but not pre-menopausal women.
An area of soy foods that may be overlooked, is the amount of calcium in some soy foods. A diet that includes greater amounts of soy products can account for a meaningful amount of calcium, and some soy foods can offer as much or more calcium than a serving of dairy products.
With the inconsistent research, it is difficult to draw confident conclusions about the role of soy in bone health. My clinical advice is to increase soy foods as part of a regular diet in prevention strategies for all pre, peri and postmenopausal women. For all women who have significant risk factors for osteoporosis, I would in addition, recommend soy supplementation so that their total daily soy isoflavone intake would deliver approximately 90 mg of soy isoflavones per day. For treatment of peri and postmenopausal women who already have osteoporosis, I would not consider soy an adequate treatment alone. In addition to the 90 mg per day of soy isoflavones and typical supplementation including calcium, vitamin D and other potential nutrients (K, boron, magnesium, manganese, and more), dietary and exercise advice, for these women who already have osteoporosis, I am in favor of proven conventional therapies to reduce fracture risk.
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