Soy Protein Does Not Improve Cognition, BMD, or Plasma Lipids in Postmenopausal Women

Yael Waknine

July 06, 2004

July 6, 2004 — A soy protein supplement containing isoflavones does not improve cognitive function, bone mineral density (BMD), or plasma lipid levels in healthy postmenopausal women aged 60 years and older, according to the results of a one-year, double-blind, placebo-controlled, randomized trial published in the July 7 issue of JAMA.

"Postmenopausal estrogen therapy has been posited to have some beneficial effects on aging processes, but its use has risks," write Sanne Kreijkamp-Kaspers, MD, PhD, and colleagues of the Julius Center for Health Sciences and Primary Care at the University of Utrecht in the Netherlands. The investigators postulated that isoflavones (estrogen-like compounds that occur naturally in plant foods) might confer positive effects on cognitive function, BMD, and low-density lipoprotein (LDL) and total cholesterol, with fewer adverse effects.

The researchers enrolled 202 healthy women aged 60 to 75 years with no contraindications to estrogen therapy. Women were randomly assigned to receive 25.6 g of soy protein containing 99 mg isoflavones (52 mg genistein, 41 mg daidzein, 6 mg glycetein) or total milk powder placebo daily for one year.

Adherence was good among the 175 women included in the final analysis. Median blood levels of genistein were significantly higher in the soy group compared with the placebo group (615.1 nmol/L vs.17.2 nmol/L; P < .001).

At one year, memory scores in the soy group were slightly higher than those in the placebo group but not significantly so. Scores on tests for verbal skills and tasks requiring concentration and visual attention were similar between the two groups.

Both groups showed similar decreases in BMD in the hip and lumbar regions of the spine. However, the soy group showed a mean BMD increase in the intertrochanter region of the hip compared with a decrease in the placebo group (+0.004 g/cm2 vs. -0.009 g/cm2; BMD change, 1.31%; P = .02).

"[A]lthough the BMD of the intertrochanter region of the hip was significantly higher in the soy group, it was only 1 comparison among 13 BMD measurements and may well be a chance finding," the authors write.

In the soy group, LDL and total cholesterol remained constant compared with a small and insignificant decrease in the placebo group.

Years since menopause, body mass index, smoking status, history of estrogen use, equol production, and baseline cholesterol level did not affect the results.

"A possible reason for the striking discrepancy between the promising findings in animal research and subsequent lack of confirmation in human trials, especially for BMD and cognitive function, may be found in species differences in the metabolism of isoflavones," the authors write. "One of the main metabolites of the isoflavone daidzein in rodents is equol...research shows that only about one third of people will produce equol when exposed to high amounts of daidzein."

Timing may also be a factor. "In our trial women were on average 18 years menopausal.... [T]he most pronounced effects of estrogen on cognitive function have been reported in perimenopausal women and not in late postmenopausal women. With respect to bone, it has been suggested that it is easier to prevent changes or losses after menopause than reverse them after they have already taken place," the authors note. "The influence of the timing of the supplementation needs to be elucidated in further research."

This study was supported by grants from the Netherlands Organization for Scientific Research and the Netherlands Organization for Health Research and Development.

JAMA. 2004;292:65-74

Reviewed by Gary D. Vogin, MD

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