Inositol is the cyclitol (cyclohexanehexanol) that is the critical component of the phosphoinositide second messenger system — the system that converts the extracellular signals (hormones, neurotransmitters, growth factors) into the intracellular responses (enzyme activation, gene expression, cell proliferation) through the generation of the inositol phosphate second messengers. The phosphoinositide system is one of the most important and most evolutionarily conserved signalling systems in nature — it is present in all eukaryotes (from the yeast to the humans), and it is responsible for the regulation of virtually every aspect of the cellular function, including the metabolism, the growth, the differentiation, the survival, and the synaptic transmission. The inositol is the backbone of the phosphoinositides (the phosphatidylinositol, the PIP, the PIP2, the PIP3), and it is the precursor of the inositol phosphates (the IP1, the IP2, the IP3, the IP4, the IP5, the IP6, the PPIns) — which are the second messengers that mediate the intracellular responses to the extracellular signals. The inositol is obtained from the diet (from the fruits, the grains, the nuts, the seeds) and from the endogenous synthesis (from the glucose-6-phosphate through the enzyme inositol synthase). The typical dietary inositol intake is 1-2g daily from the normal diet, and the therapeutic doses for the insulin signalling and for the neurological function are 2-18g of the inositol supplement daily — making the inositol one of the most evidence-based interventions for the insulin resistance, the polycystic ovary syndrome (PCOS), and the mood disorders.
Inositol and the Insulin Signalling
Inositol is a critical component of the insulin signalling pathway — the PIP2 is the precursor of the PIP3, which is the product of the PI3K (phosphoinositide 3-kinase) and the essential activator of the Akt kinase (which is the central mediator of the insulin’s effects on the glucose uptake, the glycogen synthesis, and the protein synthesis). The inositol deficiency therefore impairs the insulin signalling and contributes to the insulin resistance — which is one of the most common and most serious metabolic abnormalities in the developed world and which is the primary driver of the type 2 diabetes, the metabolic syndrome, and the cardiovascular disease. The myo-inositol is the most abundant and most biologically active form of the inositol in the human body, and it is the specific form that is involved in the insulin signalling and in the other phosphoinositide-dependent cellular processes. The myo-inositol is transported into the cells by the sodium-dependent myo-inositol transporter (SMIT), and its intracellular concentration is tightly regulated by the inositol synthesis and by the inositol degradation (through the inositol polyphosphate phosphatase). Without adequate inositol and phosphoinositide signalling, the insulin signalling is impaired, the glucose uptake is reduced, and the insulin resistance develops — the hallmark of the inositol deficiency and of the metabolic dysfunction.
The clinical importance of the inositol for the insulin sensitivity is underscored by the observation that the inositol supplementation improves the insulin sensitivity and reduces the blood glucose in people with the insulin resistance, the PCOS, and the type 2 diabetes. A meta-analysis of 10 RCTs in over 500 participants with the PCOS found that the myo-inositol supplementation at 2-4g daily significantly improved the insulin sensitivity (by 15-25%, as measured by the HOMA-IR), reduced the fasting blood glucose (by 8-12%), reduced the fasting insulin (by 15-20%), reduced the testosterone (by 15-25%), and improved the ovulation rate and the fertility — making the inositol one of the most effective interventions for the PCOS and for the metabolic dysfunction in women.
Practical Application
For general inositol supplementation for the insulin signalling and for the mood support, the evidence-based approach is to supplement with 2-18g of myo-inositol daily (as the pure myo-inositol powder, which is the most affordable and the most bioavailable form). The inositol should be taken in the divided doses (2-6g per dose, 2-3 times per day) to minimise the gastrointestinal symptoms (which are common at doses above 10g daily). The inositol is generally well-tolerated with no significant adverse effects at doses up to 30g daily, though it may cause the nausea, the diarrhoea, and the flatulence at the high doses. For comprehensive insulin signalling and mood support, inositol pairs well with the chromium (which is an insulin-sensitising mineral that works through a complementary mechanism involving the chromodulin), with the magnesium (which is a cofactor for many of the enzymes of the glucose metabolism and which has complementary effects on the insulin sensitivity), with the alpha-lipoic acid (which has antioxidant and insulin-sensitising effects), and with the berberine (which activates the AMPK and reduces the intestinal glucose absorption).
Leave a Reply