Potent Red Clover isoflavone-probiotic mix combine to ease menopausal signs: Study


The fermented form of isoflavone and probiotic-rich red clover is effective in halting the accelerated bone loss and associated symptoms seen in menopausal women, according to a Danish study.

The team from Denmark’s Aarhus University publish findings that point towards the botanical’s ability to reduce vasomotor symptoms such as hot flush frequency and hormonal fluctuations that are characteristic of the menopause.

Key to the plant’s effectiveness is its preparation as study author Max Norman Tandrup Lambert reveals details of a method that unlocks the isoflavone’s bioavailability.

"It is the fermentation process of the Red Clover extract that makes the difference,” said Lambert, a researcher based at Aarhus University Hospital’s Department of Clinical Medicine.

“The lactic acid fermentation increases the bioavailability of the bioactive oestrogen-like isoflavones or phytoestrogens that Red Clover has in abundance.”

Current menopause treatments

The study gains extra significance as current approaches such as hormone therapy alleviate symptoms but are also linked to an increase in cancer and cardiovascular risk.

As with the majority of botanicals, the issue of bioavailability is raised in this research. Isoflavones are bound to sugar molecules in the plant making them difficult to digest and preventing absorption.

Hence, isoflavones consumed as a supplemental pill or capsule can pass through the intestine without entering circulation.

“This problem is bypassed when the Red Clover extract undergoes a fermentation process that separates the sugar molecules from the isoflavones increasing bioavailability," explains Lambert.

In addition, the use of probiotics have demonstrated an ability to increase the uptake of these compounds and may thereby improve efficacy of isoflavone treatments.

Up to 80% of women may experience symptoms during menopause and it is estimated that in 2030 the at risk groups of pre and post- menopausal women will reach 1.2 billion globally.

Core symptoms include hot flushes (HF) and night sweats (NS), collectively referred to as vasomotor symptoms (VMS); sleep disturbance and other secondary symptoms often also present.

Study details

In a parallel, double blind, randomised control trial, 62 pre-menopausal women aged 40–65 that reported more than 5 hot flushes per day and had a follicle stimulating hormone (FSH) level of over 35 International Units Per Litre (IU/L), which indicated the menopause "stage," were enrolled.

These women received either twice-daily treatment with bioavailable Red Clover extract (RCE), providing 34 milligrams per day (mg/d) of isoflavones and probiotics, or a placebo formulation for 12 weeks.

A heterogeneous culture of probiotic lactic acid bacteria (of which its exact make-up was not disclosed) was added to the RC extract to aid fermentation and improve bioavailability.

A significant decrease in 24hr hot flush frequency (HFF) and intensity (HFI) was found when comparing change from baseline to 12 months of the RCE (-4.3 HF/24hr) with placebo (0.79 HF/24hr,

Self-reported HFF (rHFF) was also significantly reduced in the RCE (-2.97 HFs/d) group compared to placebo (0.036 HFs/d). RCE remained well tolerated with an absence of significant side effects.

“After 12 weeks we tested again and were speechless about the data,” said Lambert. “There was a much greater effect than we had hoped for."

"The fact that the research we have contributed has direct practical application is a great positive," added co author Per Bendix Jeppesen.

Bioavailability standards

The issue of bioavailability has been highlighted within this study, which the research team say has often been neglected when conducting studies of this nature.

“Previous studies fail to account for inter-individual differences in GI microbiota of their participants or the molecular form of the isoflavones provided,” they commented.

“This has led to high variability in isoflavone bioavailability, bioactivity and efficacy in other clinical trials.”

Indeed, a study looking at commercial preparations found significantly lower determined concentrations compared to labelled isoflavone contents in nine of the 50 products tested.

Source: PLOS One
Published online ahead of print: doi.org/10.1371/journal.pone.0176590
“Combined Red Clover isoflavones and probiotics potently reduce menopausal vasomotor symptoms.”
Authors: Max Norman Tandrup Lambert, Anne Cathrine Thorup, Esben Søvsø Szoscka Hansen, Per Bendix Jeppesen

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