In recent studies about Inositols and PCOS, the predominant forms of inositol are Myo-Inositol (MI) and D-Chiro-Inositol (DCI). Within the ovaries, MI is the more highly expressed of the two and acts to regulate glucose uptake and FSH (follicle-stimulating hormone) signaling. DCI expressed at lower levels, modulates insulin-induced androgen synthesis.
Studies using DCI
Despite the lower expression of DCI, preliminary work to understand the connection between Polycystic Ovary Syndrome (PCOS) and inositols was performed using DCI.
Partly because of the specific link between androgen synthesis and DCI, but also because women with PCOS were found to have reduced serum levels and increased urinary loss of that isoform.
Initial results were encouraging; women with PCOS (diagnosed using the Rotterdam criteria), who were treated with DCI, had improved insulin sensitivity and 86% saw restoration in ovulation.
However, the sample size was only 22 so conclusions are speculative at best, and larger, more well-designed studies are imperative for further validation.
Subsequent studies, using higher doses of DCI, found that oocyte (egg) quality deteriorated with high concentrations of the compound.
Studies using MI
In contrast, women with PCOS symptoms who took a MI supplement had improved ovarian function and enhanced oocyte and embryo quality. This, in turn, led to studies looking at the effectiveness of just giving MI as a supplement, and, encouragingly,
Some women did see an improvement in their symptoms. However, it soon became apparent that an excess of MI could have a paradoxical effect, exacerbating the imbalance between MI and DCI.
Studies using MI and DCI
More recent studies have used a combination of MI and DCI for maximal benefit, although the optimal proportion of each remains controversial.
The rationale behind using a combination of the two comes from the suggestion that PCOS-induced insulin resistance is caused by an imbalance between MI and DCI and that the ratio of the two might be insulin-dependent.
The normal ratio of MI: DCI in the ovary is estimated to be 100:1, based on measurements taken from the follicular fluid.
However, the normal physiological ratio of MI: DCI in the plasma is 40:1 and this is the combination used in most commercially available inositol supplements.
Certainly, some studies show that this combination of MI and DCI can be effective at improving ovulation and increasing menstrual cycle regularity, but there is scant reliable evidence that it is the optimal dose.
The ovary is not metabolically active, thus what is happening in the plasma is unlikely to be indicative of what is happening in the ovary and there is no data on the ovarian uptake of free MI/DCI following exogenous delivery.
Meaning that dietary supplements, given in the proportions currently accepted as standard, may not even be reaching the target organ (the ovary) in the case of PCOS.
MI and DCI given in combination prior to in vitro fertilization (IVF) has been shown to improve pregnancy rates when compared to DCI given in isolation, but only in younger women. As this data came from a single study, further validation is necessary.