Soy Metabolite Tied to Dementia Risk Factor

Elderly Japanese people who produced equol — a metabolite of dietary soy created by certain gut bacteria — had lower levels of white matter lesions, researchers reported.

“White matter lesions are significant risk factors for cognitive decline, dementia, and all-cause mortality,” said lead author Akira Sekikawa, MD, PhD, of the University of Pittsburgh, on a press call. “We found 50% more white matter lesions in people who cannot produce equol compared to people who can produce it, which is a surprisingly huge effect.”

About 40-70% of Japanese people harbor gut bacteria that can convert soy isoflavones into equol, but only 20-30% of Americans do, Sekikawa noted. The prevalence difference may be due to variances in intestinal bacteria, forms of isoflavones consumed, or genetic factors.

The study assessed serum levels of equol collected from 2008 to 2012 from 91 cognitively normal elderly Japanese people; MRI and PET scans were taken 6 to 9 years later. About half (51%) of study participants were equol producers who were divided along the median into low and high producers.

Comparing non-producers, low producers, and high producers, white matter lesion percentage was inversely associated with equol-producing status: 1.19, 0.89, and 0.58, respectively (P<0.01 for trend), Sekikawa and co-authors reported in Alzheimer’s & Dementia: Translational Research & Clinical Interventions.

Equol production was not correlated with amyloid-beta status, they said. High levels of dietary isoflavones had no effect on white matter lesion levels when equol wasn’t produced.

Equol is a metabolite of the soy isoflavone daidzein transformed by gut bacteria. People who don’t eat food containing daidzein can’t produce equol. If daidzein is consumed, equol can’t be produced without specific gut bacteria present.

Preclinical studies have shown that equol is the most bioactive of all soy isoflavones and their metabolites, Sekikawa and colleagues said.

A recent cross-sectional analysis of elderly Japanese people found that equol producers had significantly higher cognitive scores and lower prevalence of mild cognitive impairment than non-producers. And earlier research from Sekikawa’s team linked equol production with less coronary artery calcification.

In the current study, mean age of participants was 82 and about half (52%) were women. Comorbidities included hypertension (55%), dyslipidemia (55%), and diabetes (13%). Median white matter lesion percentage was 1.10, and 24% of participants were amyloid-beta positive. Basic characteristics were similar across equol-producing status.

The significant inverse association between equol-producing status and white matter lesions remained after adjusting for hypertension, apolipoprotein E (APOE)4 status, and other covariates. The association was seen in both sexes.

The study had several limitations, the researchers noted. Blood levels reflect dietary levels over the previous few days, though data show a good correlation with 28-day dietary records. The study also did not look at potentially important variables like physical activity, inflammation, and sleep.

Equol is available as a dietary supplement, but Sekikawa cautioned against taking it to prevent dementia. “We cannot prove that equol protects against dementia until we get a randomized clinical trial with sufficient evidence,” he said. The findings warrant that a clinical trial of equol targeting white matter lesions should be undertaken, he added.