Reproducibility crisis. Impact on uncontrolled release of nutraceutical preparations

In the last decade, natural integrative treatments of Polycystic Ovary Syndrome (PCOS) – a complex ovarian syndrome characterized by anovulation/androgenism/cystic ovaries – gained momentum, given that a plethora of nutraceuticals flooded into the market. Namely, two inositol isomers - myo-inositol (myo-Ins) and D-chiroinositol (D-Chiro-Ins) have been proven to be effective in PCOS treatment, by improving insulin resistance, serum androgen levels and many features of the metabolic syndrome. However, DCI alone, mostly when it is administered at high dosage, negatively affects oocyte quality. On the contrary, the association myo-Ins/DChiro-Ins in a combination reproducing the plasma physiological ratio (40:1) – as claimed by a Consensus Conference (Bevilacqua et al., 2015) and confirmed by a recent clinical pilot study (Nordio, 2019) - represents, up to now, the most promising alternative in achieving better clinical results, by counteracting PCOS at both systemic and ovary level. Honestly, we still lacking a compelling clinical vindication of that assumption, the outstanding experimental results performed in animals notwithstanding (Bevilacqua et al., 2019). However, data gathered suggest that the two inositol should be administered according to a physiological ratio, which would mirror the concentrations found in the blood (Bizzarri et al., 2016), or in the ovarian follicle (Chiu et al., 2002). However, only few, pivotal studies based on these correct physiological premises have been performed so far. It is staggering. As a result, a good opportunity – treatment of a complex syndrome through natural and safe compounds – risks to be wasted.