Red Clover Isoflavone Reduces Loss of Lumbar Spine Bone Density

Mindy Hung

February 11, 2004

Feb. 11, 2004 — A phytoestrogen isoflavone derived from red clover reduced loss of lumbar spine bone density in women, but had no effect on the hip, according to results of a study published in the February issue of the American Journal of Clinical Nutrition.

Charlotte Atkinson, PhD, and colleagues from the Institute of Public Health at Cambridge University, U.K., enrolled women aged 49 to 65 years (N = 205) in a double-blind, randomized, placebo-controlled trial.

The investigators selected women from the breast-screening unit of a Cambridge hospital according to the extent of dense tissue seen on their most recent mammogram. The primary outcome measure was breast density. Women were not eligible if they had a personal history of breast cancer or major breast surgery or if they were currently taking hormone replacement therapy.

Subjects were randomly assigned to receive daily placebo or a red clover–derived isoflavone tablet (26 mg biochanin A, 16 mg formononetin, 1 mg genistein, and 0.5 mg daidzein) for one year.

At baseline and 12 months, investigators took fasting blood samples, performed dual energy x-ray absorptiometry, asked women to make a 24-hour urine collection, and to complete a food-frequency questionnaire in order to measure bone density, body composition, bone turnover markers, and diet. To check for compliance, investigators also asked women to make a urine collection at six months.

A total of 177 women completed the trial. After one year, women receiving the isoflavone supplement lost significantly less lumbar spine bone mineral content and bone mineral density than those receiving placebo ( P = .04 and P = .03 for content and density, respectively). Treatment did not affect hip bone mineral content or bone mineral density, markers of bone resorption, or body composition.

Bone formation markers in the treatment group were significantly increased ( P = .04 and P = .01 for bone-specific alkaline phosphatase and N-propeptide of collagen type I, respectively) compared with placebo in postmenopausal women. There were no significant changes in other outcomes in interactions between treatment group and menopausal status.

To date, this was one of the longest intervention studies with an isoflavone supplement, although the investigators acknowledge the study was relatively short term with respect to the outcome measures.

"Nevertheless," Dr. Atkinson and colleagues write, "our findings suggest that, through attenuation of bone loss, the isoflavone supplement has a potentially protective effect on the lumbar spine."

Am J Clin Nutr. 2004;79:326-333

Reviewed by Gary D. Vogin, MD


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