Therapeutics Metabolic and Endocrine Agents

Inositol Treatment for PCOS Should Be Science-Based and Not Arbitrary

Roseff S, Montenegro M

International journal of endocrinology, 2020, 6461254, 2020
DOI 10.1155/2020/6461254 PMID 32308679 PMC PMC7140126

RRM Academy Synopsis

Reviewers back one inositol ratio for PCOS ovulation over others

A 2020 review of studies in women with PCOS argues that the 40 : 1 inositol ratio is the best supported for restoring ovulation. The authors call most other mixes and added ingredients poorly supported.

About 9 in 10 obese women with PCOS taking D-chiro-inositol ovulated in a 1999 trial
About 9 in 10 obese women with PCOS taking D-chiro-inositol ovulated in a 1999 trial. Source: Roseff S et al., 2020, PMID 32308679.
Study at a glance, narrative review: Reviewers back the 40 : 1 inositol ratio for restoring ovulation in PCOS
Study at a glance, narrative review: Reviewers back the 40 : 1 inositol ratio for restoring ovulation in PCOS. Source: Roseff S et al., 2020, PMID 32308679.

Key Findings

  • A meta-analysis of nine randomized trials (247 cases, 249 controls) of myo-inositol, alone or with D-chiro-inositol, found lower fasting insulin (standardized mean difference −1.021, 95% CI −1.791 to −0.251, P=0.009).
  • The pooled analysis also found a lower HOMA index, a marker of insulin resistance (standardized mean difference −0.585, 95% CI −1.145 to −0.025, P=0.041).
  • A 2019 trial gave 56 patients, 8 per group, one of seven inositol ratios for 3 months. The authors report the 40 : 1 ratio was best for restoring ovulation.
  • In the first controlled trial (1999, 44 obese women with PCOS), 19 of 22 (86%) women taking D-chiro-inositol ovulated, against 6 of 22 (27%) on placebo.
  • In 18 healthy volunteers given single doses, myo-inositol total absorption (AUC) was 19.1% lower with D-chiro-inositol and 31.8% lower with phlorizin plus other compounds.

Interpretation

This narrative review compared trials behind the many inositol ratios sold for PCOS. The authors point to the 40 : 1 ratio as the best supported. Women on this ratio ovulated more often in a placebo-controlled trial and in a dose-finding trial. A meta-analysis also found lower insulin resistance markers with this ratio. Most other ratios, and the extra ingredients sold with them, have little trial support behind them. The findings support larger, controlled trials of the 40 : 1 ratio to confirm the best dose for restoring ovulation in PCOS.

RRM Context

RRM clinicians treat PCOS, now named PMOS (Polyendocrine Metabolic Ovarian Syndrome), as an ovulation problem with a root cause. Evaluation comes first, before any product. Inositol is a supplement. Its trial record should set how much weight it gets, apart from how it is marketed. Ovulation is the goal here, and that fits the restorative aim of getting ovulatory cycles back.

Abstract

The aim of this paper is to critically analyze the composition of many inositol-based products currently used to treat Polycystic Ovary Syndrome (PCOS). Several different combinations of myo-inositol and D-chiro-inositol, with and without additional compounds such as micro- and macroelements, vitamins, and alpha-lipoic acid, have been formulated over the years. Such therapeutic proposals do not take various features of inositol stereoisomers into consideration. As an example, it is important to know that D-chiro-inositol treatment may be beneficial when administered in low doses, yet the progressive increase of its dosage results in the loss of its advantageous effects on the reproductive performance of women and a deterioration in the quality of blastocysts created via in vitro fertilization (IVF). In addition, we have to consider that the intestinal absorption of myo-inositol is reduced by the simultaneous administration of D-chiro-inositol since the two stereoisomers compete with each other for the same transporter that has similar affinity for each of them. A decrease in myo-inositol absorption is also found when it is coadministered with inhibitors of sugar intestinal absorption and/or types of sugars such as sorbitol, maltodextrin, and sucralose. The combination of these may require higher amounts of myo-inositol in order to reach a therapeutic dosage compared to inositol administration alone, a particularly important fact when physicians strive to obtain a specific plasma level of the stereoisomer. Finally, we must point out that D-chiro-inositol was found to be an aromatase inhibitor which increases androgens and may have harmful consequences for women. Therefore, the inositol supplements used in PCOS treatment must be carefully defined. Clinical evidence has demonstrated that the 40 : 1 ratio between myo-inositol and D-chiro-inositol is the optimal combination to restore ovulation in PCOS women. Therefore, it is quite surprising to find that inositol-based treatments for PCOS seem to be randomly chosen and are often combined with useless or even counterproductive molecules, all of which can weaken myo-inositol's efficacy. Such treatments clearly lack therapeutic rationale.

Topics

Related research

Therapeutics › Metabolic and Endocrine Agents › Insulin Sensitizing Agents
Scott Roseff, Marta Montenegro
S Roseff, M Montenegro
PMID 32308679 32308679 DOI 10.1155/2020/6461254 10.1155/2020/6461254 Roseff et al. 2020, Roseff 2020