Inositol — the quiet vitamin for nerves, hormones, and fertility?

Aim of the study: Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Inositol may have insulin-sensitizing effects; however, its effectiveness in managing PCOS remains uncertain. To inform the 2023 international evidence-based guidelines on PCOS, this systematic review and meta-analysis evaluated the effectiveness of inositol, alone or combined with other therapies, in managing PCOS.

Results: The evidence supporting the use of inositol in managing PCOS is limited and inconclusive. When making shared decisions about using inositol for PCOS, clinicians and their patients should consider the uncertainty of the evidence along with individual values and preferences.

Aim of the study: Several oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been shown to be safe and effective in improving the endocrine, metabolic, and reproductive abnormalities seen in polycystic ovary syndrome (PCOS), giving healthcare providers and patients more options. These oral insulin sensitizers are more convenient, practical, and economical than injectable agents.

Results: Twenty-two trials involving 1079 patients with PCOS were included in this study. Compared with metformin, treatment with myo-inositol + D-chiro-inositol was associated with a greater improvement in menstrual frequency (odds ratio 14.70 [95% confidence interval (CI) 2.31-93.58]). Combination therapies of myo-inositol + D-chiro-inositol and metformin + thiazolidinediones were more effective than the respective single-drug therapies in reducing total testosterone levels. Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + D-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) than metformin alone (mean differences: - 0.72 [95% CI (- 1.11)-(- 0.34)] to - 0.89 [95% CI (- 1.460)-(- 0.32)]).

Aim of the study: Insulin resistance (IR) plays a key role in PCOS. Insulin-sensitizing agents such as metformin and inositols have been shown to improve the endocrine and metabolic aspects of PCOS.

Results: Insulin sensitivity improved in both treatment groups. BMI decreased significantly, and the menstrual cycle was normalized in about 50% of the women. No significant changes in acne or hirsutism were observed. Both insulin sensitizers, metformin and myo-inositol, appear useful for women with PCOS in lowering BMI, improving insulin sensitivity, and improving the menstrual cycle, with no significant differences between the two treatments.

Aim of the study: This study evaluates the frequency of metabolic abnormalities in patients with PCOS and the effects of myo-inositol (MI) and D-chiro-inositol (DCI), in a 40:1 ratio, on hormonal and metabolic parameters.

Results: Of the patients enrolled, 55.9% were overweight or obese, 50% had IR, 17.6% had a history of gestational diabetes mellitus, and 61.8% had a family history of diabetes mellitus. At the end of the study, BMI (p = 0.0029) and HOMA-IR (p < 0.001) had significantly decreased, as had the number of patients with elevated insulin levels. Supplementation led to decreases in total testosterone (p < 0.001), free testosterone (p < 0.001), FAI (p < 0.001), and LH (p < 0.001), and increases in SHBG (p < 0.001) and estradiol (p < 0.001). Supplementation improved the metabolic and hormonal profile of patients with PCOS phenotype A (EMS type I). This builds on previous work showing that combined inositol treatment may be effective in PCOS. The study presented here used a lower concentration than in earlier research; however, significant changes in hormonal and metabolic parameters were still observed.

Aim of the study: Myo-inositol (cis-1,2,3,5-trans-4,6-cyclohexanehexol; MI) is the most prominent of nine inositol stereoisomers. MI, its phosphate derivatives, and associated lipids are widely found in vegetables and animal tissues and are known to take part in many biological processes. This review analyzes the presence, functions, and impact of MI on male fertility.

Results: Published information was identified and compiled on MI, including its identification, natural dietary sources and absorption, biosynthesis, and concentrations, as well as the roles of MI and its derivatives (PI, PIP, GPI, IPG) in several human tissues and body fluids in health and disease. One section focused on the presence, biosynthesis, and functions of MI in the mammalian male reproductive tract and sperm, and summarized reports describing the impact of MI supplementation in vivo and in vitro on human semen quality and fertility. Studies reported a modest improvement in sperm motility in fresh and frozen-thawed semen, as well as better sperm performance in natural and assisted fertility. MI was reported to be an effective supplement for sperm quality. However, several study designs lacked appropriate controls or data analysis to confirm the significance of the findings.

Aim of the study: Polyendocrine metabolic ovarian syndrome (PMOS) is a common hormonal disorder that disrupts ovulation and fertility in women of reproductive age. It is often associated with insulin resistance and hormonal imbalances, which can make successful conception more difficult, particularly through assisted reproductive technologies (ART).

Results: A total of 39 studies were included in this meta-analysis. Metformin significantly improved LBR (RR: 1.24, 95% CI: 1.06-1.38; p = 0.006) and reduced the risk of ovarian hyperstimulation syndrome (OHSS) (RR: 0.68, 95% CI: 0.48-0.97; p = 0.03). CPR showed a non-significant improvement (RR: 1.10, 95% CI: 0.99-1.23; p = 0.09). Myo-inositol significantly reduced irregular menstrual periods (RR: 0.78, 95% CI: 0.68-0.89; p = 0.0004), but had no significant effect on CPR. In conclusion, this study highlights the potential roles of metformin and myo-inositol in managing PMOS, particularly in assisted reproduction. Myo-inositol may improve menstrual regularity, while metformin may be associated with better conception-related outcomes and a lower risk of ovarian hyperstimulation syndrome (OHSS). However, these findings should be interpreted cautiously because of substantial differences between studies and confidence intervals that approach the null effect for some outcomes.

Aim of the study: Gestational diabetes mellitus (GDM) is a common metabolic disorder affecting approximately 14% of pregnancies worldwide, with incidence increasing alongside rising obesity rates among women of reproductive age. GDM significantly affects placental structure and function, leading to adverse outcomes for mothers and fetuses.

Results: We discuss the potential mechanisms by which myo-Ins might affect glucose balance, oxidative stress, inflammation, and lipid metabolism in the placenta, highlighting possible protective effects against placental dysfunction caused by GDM. Some clinical evidence suggests that myo-Ins supplementation may reduce the risk of GDM, improve insulin sensitivity, and lessen adverse pregnancy outcomes. However, the timing, dosage, and specific effects on the placenta require further study to optimize its therapeutic effectiveness. This review highlights the potential of myo-Ins as an additional therapy for GDM and emphasizes the need for further research to clarify its mechanisms of action and long-term benefits for maternal and fetal health.