Inositol and ALA show synergistic promise in PCOS

The authors from Milan, Italy, note ALA’s multifaceted actions, including anti-inflammatory, antioxidant, and insulin-sensitising properties. 

The review concludes that the synergistic effect of the inositol MYO (myoinositol) plus ALA may be particularly beneficial in obese or overweight patients with a family history of type 2 diabetes mellitus, while also showing promise in regulating menstrual cycles and ovulation patterns. 

The authors state: “With further exploration, this innovative combination therapy could revolutionise the treatment landscape for PCOS, offering new hope for affected women worldwide.” 

PCOS​

Polycystic Ovary Syndrome (PCOS) poses a significant health challenge for women, affecting 4–25% of those in their reproductive age​. 

This endocrinopathy increases the risk of metabolic syndrome, type 2 diabetes mellitus, cardiovascular diseases, and endometrial cancer.

It has been suggested​ that insulin resistance, chronic inflammation, and consequentially, oxidative stress may play an essential role in the pathogenesis of PCOS. 

It has previously been hypothesised​ that an anomaly in the intracellular signalling responsible for the production and release of DCI-IGP mediator could be another trigger mechanism at the basis of insulin resistance in PCOS patients. 

Metformin is recommended​ by the 2018 international evidence-based guidelines for the assessment and treatment of PCOS for the management of weight, hormonal, and metabolic outcomes in PCOS adult patients, where lifestyle modifications are not sufficient. 

Metformin has however encountered challenges​ due to its side effects, leading to treatment discontinuation in some patients. 

Another class of insulin sensitisers that are more recently used in PCOS treatment​ are inositols. Nine stereoisomers of inositols are available, but the most biologically important and widely distributed is MYO.

However, the authors suggest that hope lies in the potential of a combination of inositols and ALA, as it exhibits insulin-mimetic properties and has been found to reduce postprandial blood glucose through distinct pathways. 

ALA, known for its anti-inflammatory and antioxidant effects​, plays a vital role in improving insulin's metabolic pathway.

The combination of inositols and ALA has emerged as a potential therapeutic strategy for managing PCOS, aiming to tackle insulin resistance, lower androgen levels, and enhance reproductive outcomes in affected patients.

The review ​

The authors of the review carried out literature searches on PubMed, published in English up to September 2022, including clinical trials in published systematic review articles or in published meta-analyses. In total, 14 studies conducted between 2010 and 2022 were included. 

One study​ investigated the effects of a treatment based on ALA alone in PCOS patients, in which ALA was administered to six non-obese, non-diabetic patients with PCOS for a cycle of 16 weeks, showing a significant amelioration in insulin sensitivity and a notable decrease in triglyceride levels, demonstrating that ALA also exerts an anti-atherogenic effect. 

However, the authors note that in another study​ including a group of non-obese patients, the administration of MYO alone was not sufficient to ameliorate compensatory hyperinsulinemia, potentially due to an abnormal epimerase activity, which, in turn, results in a reduced DCI-IPG synthesis and release, and not to a nutritional deficiency of inositol. 

The authors note that it is the combination of MYO plus ALA shown to create a synergistic effect that improves insulin resistance in PCOS patients, especially in obese/overweight patients with type 2 diabetes.

One study​ demonstrated how the treatment with a combination of ALA (400 mg) plus MYO (1 g) for 12 weeks had an effect on improving insulin sensitivity in PCOS obese patients.

The authors of the review conclude: “ALA is a valid therapeutic strategy applicable in the treatment of PCOS patients. Its multiple actions, including anti-inflammatory, antioxidant, and insulin-sensitising, may be of utmost importance in the treatment of a very complex syndrome.”

However, the authors state: “Of course, not all PCOS women show signs of IR and, to date, accordingly to the last diagnostic criteria, insulin resistance is not included among the distinctive diagnostic features of PCOS.

“Therefore, this therapeutic effect may be restricted to those PCOS patients with a prevalent metabolic signature.” 

Journal: Nutrients

https://www.mdpi.com/2072-6643/15/14/3209​

“Alpha Lipoic Acid Efficacy in PCOS Treatment: What Is the Truth?”

Authors: Alice Guarano, Anna Capozzi, Martina Cristodoro, Nicoletta Di Simone, and Stefano Lello.