Effects of Inulin-type Fructans With Different Degrees of Polymerization on Inflammation, Oxidative Stress and Endothelial Dysfunction in Women With Polycystic Ovary Syndrome

A Randomized, Double-Blind, Placebo-Controlled Trial

Rahele Ziaei; Zahra Shahshahan; Hatav Ghasemi-Tehrani; Zahra Heidari; Reza Ghiasvand

Disclosures

Clin Endocrinol. 2022;97(3):319-330. 

In This Article

Abstract and Introduction

Abstract

Objective: Polycystic ovary syndrome (PCOS) is associated with several cardiovascular risk factors. Prebiotics were proposed to beneficially affect risk factors associated with metabolic disorders. The aim of this study was to investigate and compare the effects of inulin-type fructans (ITFs), as well-studied prebiotics, with different degrees of polymerization, on markers of inflammation, oxidative stress and endothelial dysfunction in PCOS patients.

Design: A randomized, double-blind, placebo-controlled trial. Patients: Seventy-five PCOS women were randomly assigned to receive 10 g/day of either high-performance inulin (HPI) or oligofructose-enriched inulin (OEI) or placebo for 12 weeks.

Measurements: Biochemical indices and blood pressure levelswere assessed before and after the intervention.

Results: In the intent-to-treat analysis, high-sensitive C-reactive protein (hs-CRP) decreased in HPI and OEI groups, over the 12 weeks, and the changes were significant in the HPI group, compared to placebo (changes from baseline in the HPI group: −0.11 vs. placebo group: 0.004 mg/L [conversion factor to SI units (nmol/L): 9/5238]; p = .007). Serum levels of nitric oxide (NO) increased, and endothelin-1 and total oxidant status decreased in HPI and OEI groups, at the end of the trial; however, these changes were not significantly compared to placebo (p = .07, .36 and .22, respectively). No differences in systolic and diastolic blood pressure were found. Per-protocol analysis (n = 68) yielded consistent results for all endpoints, with the exception that the significant effect of ITFs on serum hs-CRP levels in the unadjusted ITT analysis became nonsignificant in the per-protocol analysis (p = .06).

Conclusion: A 12-week supplementation with long-chain ITFs had favourable effects on inflammatory status among PCOS patients.

Introduction

Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries.[1] The worldwide prevalence of PCOS varies between 4% and 21% depending on diagnostic criteria used and ethnic group assessed.[2]

In addition to hyperandrogenic concerns and reproductive abnormalities, PCOS is associated with several cardiovascular risk factors including insulin resistance (IR), obesity, dyslipidaemia, hypertension and endothelial dysfunction, affecting multiple aspects of a woman's overall health.[3]

PCOS is a heterogeneous polygenic disorder with strong epigenetic and environmental influencing factors, including diet and other lifestyle factors.[4] The exact pathogenesis of PCOS is not entirely understood; however, low-grade inflammation and oxidative stress (OS) were proposed to be involved. Women with PCOS exhibit higher circulating levels of C-reactive protein (CRP) and other inflammatory markers, as well as OS biomarkers, independent of obesity.[5] IR and hyperandrogenism (HA), as key players in the clinical and metabolic manifestations of the disease, are proposed to be derived from inflammation.[6] Strong evidence exists on the correlation between altered gut microbiota and the development of PCOS.[7] Following gut dysbiosis, lipopolysaccharides (LPS) penetrate the systemic circulation, defined as metabolic endotoxaemia. The resulting LPS-induced inflammation might interfere with insulin receptors function and induce hyperinsulinaemia, leading to increased androgen production and disrupted normal follicular growth.[7]

Endothelial dysfunction, as an early and possibly reversible feature of atherosclerosis, is frequently seen in women with PCOS, even in young and normal-weight women, which is mainly attributed to low-grade inflammation, HA and IR.[8] Because of early endothelial dysfunction, women with PCOS are at increased risk for future cardiovascular diseases. Evidence exists on the role of the gut microbiome in regulating endothelial function.[9] Decreased levels of nitric oxide (NO), as the main endothelial-derived relaxing factor, elevated levels of endothelin-1 (ET-1), as one of the best makers of vascular dysfunction and reduced vasodilatory responses to ET-1, were all reported in these women.[10]

Inulin-type fructans (ITFs) are well-studied prebiotics, and their modulating effects on the gut microbiome were documented in several studies.[11] Prebiotic effects of ITFs differ based on their degree of polymerization (DP).[12] However, studies aiming to compare biological functions of long-chain and short-chain inulin, have reported contradictory results.[12,13] Literature suggests the beneficial effects of ITFs on inflammation and inflammation-related metabolic defects.[14] Also, ITFs improved endothelial dysfunction in an animal model of cardiovascular disease, via modulation of the NO synthesis pathway.[15]

Since PCOS is a proinflammatory state and the underlying low-grade inflammation was proposed to be originated from gut dysbiosis, we hypothesize that targeting inflammatory responses and OS by ITFs might be a novel and safe approach in the management of the disease. Also, the beneficial impact of HPI, as a long-chain ITF, on these outcomes might be more pronounced than OEI. To examine this hypothesis, a randomized, double-blind, placebo-controlled clinical trial was designed to investigate and compare the effects of ITFs with different DP on systolic and diastolic blood pressure, serum levels of high-sensitive CRP (hs-CRP), total oxidant status (TOS) and endothelial dysfunction.

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