Inositol is a fascinating substance with a wide spectrum of action. Currently, it is widely discussed in the context of women’s health, but its key property is the ability to regulate carbohydrate metabolism. How does this happen, what do studies say about these reports, and is inositol safe to use with other glucose-regulating medications? We invite you to read on.
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How does inositol affect glucose-insulin metabolism?
Myo-inositol, one of the inositol isomers, plays a crucial role in cells as a precursor to important signaling molecules, including phosphatidylinositols and inositol phosphates, which participate in the transduction (transmission) of insulin signals. In muscle and fat cells, myo-inositol can support glucose transport by modulating the activity of the GLUT4 transporter, facilitating its translocation from the cell’s interior to the cell membrane. Additionally, inositol affects redox balance and mitochondrial function, which indirectly supports glucose metabolism and the efficiency of cellular responses to insulin – consequently reducing the need for its production.
At the level of insulin signaling pathways, myo-inositol acts as a “molecular bridge” in transmitting signals from the insulin receptor to intracellular effectors. Upon insulin binding to the tyrosine kinase receptor, phosphorylation of IRS (insulin receptor substrate) occurs, which activates phosphatidylinositol-3-kinase (PI3K). PI3K converts phosphatidylinositol-4,5-bisphosphate (PIP2) into PIP3, which in turn activates AKT kinase. AKT activation leads to the translocation of the GLUT4 transporter to the cell surface and the uptake of glucose from the bloodstream. Myo-inositol, as a precursor to PIP2 and other inositol derivatives, supports this signaling pathway, which translates into improved insulin sensitivity and more efficient glucose utilization by cells.
Efficacy of inositol in individuals with insulin resistance
The evaluation of the effectiveness of inositol supplementation in individuals diagnosed with insulin resistance – both in the so-called prediabetic state and that already associated with existing type 2 diabetes – is already being carried out in clinical studies. To determine the substance’s efficacy, markers reflecting both glycemic levels and tissue sensitivity to insulin are used. The most frequently analyzed parameters include fasting glucose and insulin concentrations, as well as the HOMA-IR index (Homeostatic Model Assessment of Insulin Resistance), which allows for estimating the degree of insulin resistance based on these two values. Some studies also include glycemic and insulin responses in the oral glucose tolerance test (OGTT), which enables the assessment of the body’s reaction to carbohydrate load.
Results of available review studies indicate that myo-inositol supplementation leads to a reduction in fasting insulin levels, accompanied by a decrease in HOMA-IR values1, which suggests an improvement in tissue sensitivity to insulin. Another study demonstrated the effectiveness of myo-inositol therapy as a prophylactic against glycemic metabolism disorders during pregnancy2 – interestingly, studies also pointed to an improvement in fetal health, indicating a decrease in preterm births in groups consuming the supplement3. There are also studies where improved insulin sensitivity was noted in healthy individuals, i.e., those without a diagnosis of insulin resistance or type 2 diabetes or at risk of gestational diabetes, although this is a study on a relatively small number of patients4.
Significantly, the observed changes do not result from directly “forcing” insulin secretion, but rather from improved insulin signaling and more efficient glucose utilization by cells. Such conclusions support the hypothesis that inositol may play a role in improving disturbed glucose-insulin metabolism through mechanisms related to insulin sensitivity regulation, rather than merely short-term lowering of blood glucose levels.
Synergy of inositol with other components
Using inositol in combination with other substances can further support the regulation of glucose-insulin metabolism in individuals with insulin resistance. An example is the combination of myo-inositol with berberine, a natural alkaloid found in common barberry. Berberine has the ability to lower blood glucose levels by activating AMPK, a key enzyme in the regulation of energy metabolism, which can increase glucose uptake by cells and improve insulin sensitivity. Such a combination typically exhibits synergistic action: inositol supports intracellular insulin signaling, increasing its effectiveness and consequently reducing the need for its overproduction, while berberine additionally aids glucose and lipid metabolism already within cells, which ultimately translates into an improved metabolic profile for patients.
Another example is the combination of inositol with folic acid. Folic acid participates in methylation reactions and homocysteine metabolism, and its dietary supplementation can support cardiovascular health and cell function. In the context of insulin resistance, folic acid does not directly affect insulin signaling to the same extent as inositol, but studies suggest that its presence can support carbohydrate metabolism and reduce oxidative stress, which is often one of the factors impairing insulin sensitivity. Consequently, the combination of inositol with folic acid can support patients both in terms of improving metabolic functions and overall cell health.
Sources:
- K.Pajtel, M.Pelczyńska, The use of inositol in light of the latest scientific research, Forum of Metabolic Disorders, no. 13/2022, vol.1.
- Miñambres I, Cuixart G, Gonçalves A et al., Effects of inositol on glucose homeostasis: Systematic review and meta-analysis of randomized controlled trials. Clinical Nutrition, no. 38/2019, vol. 3.
- R. D’Anna, A. Scilipoti, D. Giordano et al., myo-Inositol supplementation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: a prospective, randomized, placebo-controlled study. Diabetes Care. no. 36/2013, vol.4.
- Bañuls C, Rovira-Llopis S, Falcón R, et al., Chronic consumption of an inositol-enriched carob extract improves postprandial glycaemia and insulin sensitivity in healthy subjects: A randomized controlled trial. Clinical Nutrition no. 35/2016, vol. 3.
- L. Li, JD. Fang, Myo-inositol supplementation for the prevention of gestational diabetes: A meta-analysis of randomized controlled trials, European journal of obstetrics, gynecology, and reproductive biology, no. 273//2022.