Short-Term Supplementation With Fermented Red Clover Extract Reduces Vascular Inflammation in Early Post-menopausal Women.

Kate A. Wickham,Line B. Nørregaard,Mette Hansen,Ylva Hellsten,Lasse Gliemann,Stephen S. Cheung,Mikkel Oxfeldt

doi:10.3389/fcvm.2022.826959

Kate A. Wickham, Line B. Nørregaard + Show 5 more

Open Access

https://doi.org/10.3389/fcvm.2022.826959

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Abstract

The decline in estrogen at menopause poses a critical challenge to cardiovascular and metabolic health. Recently, a growing interest in the role of phytoestrogens, with a particular focus on isoflavones, has emerged as they can bind to estrogen receptors and may mimic the roles of endogenous estrogen. Fermented red clover extract (RC) contains isoflavones with superior bioavailability compared to non-fermented isoflavones, however little is known regarding the impact of isoflavones on cardiovascular and metabolic health. We assessed markers of vascular health in plasma and skeletal muscle samples obtained from healthy but sedentary early post-menopausal women (n = 10; 54 ± 4 years) following 2 weeks of twice daily treatment with placebo (PLA) or RC (60 mg isoflavones per day). The two interventions were administered using a randomized, double-blind, crossover design with a two-week washout period. Plasma samples were utilized for assessment of markers of vascular inflammation. There was a statistically significant reduction (~5.4%) in vascular cell adhesion molecule 1 (VCAM-1) following 2 weeks of RC supplementation compared to PLA (p = 0.03). In contrast, there was no effect of RC supplementation compared to PLA on skeletal muscle estrogen receptor content and enzymes related to vascular function, and angiogenesis. Supplementation with RC reduces vascular inflammation in early post-menopausal women and future studies should address the long-term impact of daily supplementation with RC after menopause.

Highlights

Existing evidence clearly highlights that the loss of estrogen associated with menopause poses a critical challenge to cardiovascular and metabolic health [1, 2]
Plasma levels of vascular cell adhesion molecule 1 (VCAM-1) were significantly reduced by ∼5.4% following red clover extract (RC) compared to PLA (503.2 ± 84.4 vs. 534.8 ± 96.8 ng mL−1; p = 0.0321; d = 0.7; Figure 2A)
There was no statistically significant effect of RC supplementation compared to PLA on intracellular adhesion molecule 1 (ICAM-1) (628.2 ± 84.2 vs. 641.8 ± 93.2 ng mL−1; p = 0.1310; d = 0.4; Figure 2B), serum amyloid A (SAA) (3,732.4 ± 1,927.6 vs. 3,894.2 ± 2,021.3 ng mL−1; p = 0.5877; d = −0.1; Figure 2C), or C-reactive protein (CRP) (1,656.4 ± 1,354.4 vs. 1,620.5 ± 1,311.9 ng mL−1; p = 0.2536; d = 0.2; Figure 2D)

Summary

Introduction

Existing evidence clearly highlights that the loss of estrogen associated with menopause poses a critical challenge to cardiovascular and metabolic health [1, 2]. In pre-menopausal women, estrogen plays a cardioprotective role through the activation of several signaling cascades, which lead to the promotion of vasodilation and angiogenesis as well as the reduction in oxidative stress and fibrosis [7]. The withdrawal of estrogen production associated with menopause has been shown to increase oxidative stress and subsequently induce negative effects on cardiovascular health including increased sympathetic tone, endothelial dysfunction, vascular inflammation, and increased blood pressure [9, 10]. Endothelial dysfunction and subsequent alterations in vascular tone and blood flow have significant implications for peripheral tissue metabolism, whereby skeletal muscle angiogenesis can become impaired [11, 12]

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