Myo-Inositol (MI) belongs to a sugar family & is a stereoisomer of sugar alcohol. It is the precursor of inositol triphosphate which acts as a secondary messenger & regulates hormones such as thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH) and insulin (1).
MI has been studied for its insulin-sensitizing effect. Due to its beneficial effects, it has been used as a supplement for a number of metabolic disorders related to insulin resistance (IR), & metabolic syndromes like gestational diabetes mellitus and polycystic ovary syndrome (PCOS) (1).
MI is the most abundant form of inositol in humans. It goes under reactions such as epimerization, phosphorylation, or methylation of its hydroxyl groups to turn into different derivatives. Tissues have a different conversion rate of MI to D-chiro-Inositol (DCI). The NAD/NADH epimerase, an insulin-dependent enzyme, converts MI into DCI. This conversion depends on the specific needs of the tissue (1).
Clinical evidence shows that these two stereoisomers (MI & DCI) exert beneficial effects when combined at a physiological ratio of 40:1 in patients with PCOS (2).
The enzyme epimerase converts MI to DCI, maintaining a physiological ratio of 40:1, which varies from tissue to tissue. The conversion rate of MI to DCI ranges from 7% to about 9% in normal healthy females and is much lesser in women with PCOS due to insulin resistance in the systemic circulation. In the setting of epimerase deficiency, less MI can be converted to DCI, a state of relative DCI deficiency occurs, and insulin resistance is promoted. This, in turn, leads to the metabolic complications of hyperinsulinemia (3)
Insulin mediators
Myo-inositol (MI) and D-chiro-inositol (DCI) act as insulin mediators. They increase insulin sensitivity & improve metabolic and ovulatory functions.
MI exerts its beneficial effects in ovaries, it maintains insulin regulation & also shows beneficial effects in improving ovarian functions such as steroidogenesis. MI and DCI regulate glucose metabolism by a different mechanism of action. MI supports glucose uptake whereas DCI promotes glycogen synthesis. Therefore DCI is highly concentrated in glycogen storage tissues like liver, & muscles whereas MI is more abundantly present in brain, heart, or ovary where glucose requirement is higher (2).
Mechanism of action of DCI
DCI restores normal insulin sensitivity in the insulin target tissues. It reduces the circulating androgen and insulin which in turn increases the ovulation frequency. MI is highly concentrated in ovaries and it enhances insulin regulation and other ovarian functions (2).
Some studies have suggested that PCOS affected women with insulin resistance, have excessive androgen levels and this could be because of an imbalance in MI/DCI ratio in the ovaries, which results in DCI overproduction and MI deficiency. A study by, Facchinetti et al. concluded that the physiological MI/DCI ratio is 40 : 1 and, therefore supplementation with MI plus DCI in the ratio of 40 : 1 has shown improvement in the clinical outcomes in PCOS young overweight women (2).
Role of MI & DCI in ovaries
In the ovary, MI and DCI have specific roles. MI supports FSH signaling, whereas DCI is responsible for insulin-mediated testosterone synthesis. In the normal ovary, these activities proceed in balance, allowing the maintenance of normal hormonal levels and facilitating ovarian function. In the polycystic ovary, systemic insulin resistance (hyperinsulinemia) accentuates epimerase activity, thus creating a higher DCI-to-MI ratio. This promotes hyperandrogenism and reduces the efficiency of MI-mediated FSH signaling (3).
Role of Myo-Inositol
- Myo-inositol administration improves reproductive axis functioning in PCOS patients reducing the hyperinsulinemic state that affects LH secretion (4)
- Consistent significant changes were observed in Group A (under MYO+folic acid administration) since several hormonal parameters changed during the treatment interval. Indeed mean plasma LH, PRL, T, and insulin levels significantly decreased, as well as LH/FSH ratio, the index of insulin sensitivity glucose/insulin ratio, and the HOMA index (4).
- Insulin response, evaluated thirty minutes following oral glucose load, was significantly reduced in group A patients as well as the AUC of insulin with respect to baseline conditions (4).
- Another study with MI, DCI & folic acid supplementation reported the following observations,
- Reduces LH/FSH ratio (40.05%) (5).
- Reduces total testosterone (6.84%) levels (5).
- Reduces HOMA Index (5.54%) i.e. reduces insulin resistance (5).