Inositol

Pronunciation

Inositol (in-o-sĭ-tol)

Summary

Essential for the growth of tissues, inositol is found in nine different forms (isomers), including myo-, d-chiro-, scyllo-, muco-, epi-, neo-, allo-, l-chiro-, and the synthetic cis-inositol (89). Myo-inositol (MI) and D-chiro-inositol (DCI) are the two main forms in our bodies (6) and most commonly used as supplements (87). Previously considered an essential B vitamin (vitamin B8), it is now known that the human body can synthesize four grams of inositol per day, whereas approximately one gram per day can be obtained from the diet (24). For this reason, inositol is now mainly referred to as an essential pseudovitamin (47). Inositol is a constituent of phospholipids in cellular membranes, a precursor of secondary messengers in metabolic pathways, and a component of reproductive fluids (62). It may play an important role in conditions related to insulin resistance, such as polycystic ovarian syndrome, metabolic syndrome, gestational diabetes, and other diabetic complications (20). Additionally, since MI can cross the blood-brain barrier, it may be beneficial in treating symptoms of affective disorders (67). Dietary sources of inositol are primarily found in fruits, beans, grains, and nuts (16).

Main Medical Uses

Polycystic ovarian syndrome (PCOS) may be treated with supplements containing inositol (3, 78), including MI (15, 19, 25, 28, 30, 33, 34, 35, 36, 50, 52, 72, 76, 79, 88, 90, 91, 94, 95, 98), DCI (30, 49, 69, 75), or their combination (4, 17, 51). Supplementation with MI is effective in reducing gonadotropin doses and the length of ovarian hyperstimulation in women with PCOS undergoing in vitro fertilization (55). It can similarly reduce gonadotropin doses in non-PCOS women (10) leading to a trend of increased implantation frequency (57). MI may lower birth weight (97) and reduce the risk of gestational diabetes (18, 21, 40, 61, 92, 96, 97). It may also reduce the risk of preterm delivery (40, 92, 96) and neonatal/infant death, retinopathy, and hemorrhage in respiratory distress syndrome (42, 43, 45). MI can also improve outcomes related to male fertility (9, 39). Inositol may be effective in treating panic disorder (5, 71). Metabolic syndrome can also be treated with inositol (63) or MI (37, 59, 83). There is some evidence to suggest that inositol supplementation may be effective in OCD (31), though it may not provide further benefits beyond those of serotonin reuptake inhibitors (32).

Dosing and Administration

For an explanation of the classes of evidence, please see the Rating Scales for Evidence-Based Decision Support.

Adverse Effects

At doses greater than 12g per day, gastrointestinal effects, such as nausea, flatulence, and diarrhea, may occur. However, the incidence of these events are considered mild and do not increase in severity as the dose increases (11). The use of MI in treating PCOS is associated with fewer adverse effects than metformin (28). Intravenous administration up to 80mg/kg/day of MI in infants did not increase the incidence of adverse events compared with placebo (74). Increasing doses (300-2400mg) of DCI has been shown to negatively impact oocyte quality in patients with PCOS (48).

Forms

Initially, the name “inositol” was given to the most abundant isomer found naturally. However, to distinguish it from the other eight forms, it was re-labelled as “myo-inositol”. The term “inositol” now encompasses all nine isomers, but MI remains the form that is often assumed when referring to inositol (29).

Isoforms of inositol take on differential physiological roles. Both MI and DCI are involved in insulin signaling; DCI is more involved in glycogenesis, while MI decreases intestinal absorption of glucose (14) and increases glucose uptake through glucose transporter activation and utilization (27). Each isomer has differences in tissue distribution and treatments combining MI and DCI have been based on an observed plasma ratio of 40:1 (26).

Associated Interactions and Depletions

Pharmacokinetics

Absorption

Softgel capsules of MI (0.6g) are equally as bioavailable as powdered MI (2g) in healthy subjects (12). Intestinal transportation of MI across the apical membrane is accomplished by the sodium/inositol symporter 2 (SMIT2) (2). SMIT1/SMIT2 and the H+ myo-inositol transporter are responsible for inositol uptake throughout the body and brain (24). MI can pass the blood-brain barrier (85, 86).

Metabolism

MI oxygenase metabolizes MI to D-glucuronic acid in the renal cortical tubules. D-glucuronic acid is then converted by aldehyde reductase to L-gluconate. Metabolism of L-gluconate results in xylulose and ribulose, which both can be degraded through glycolysis (24).

Excretion

If not reabsorbed by the SMT2 transporters on the apical membrane of the proximal convoluted tubules (56), both MI and DCI inositol are excreted in the urine (24).

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