Inositol, often referred to as vitamin B8, is a sugar alcohol that plays a crucial role in cell signaling pathways and contributes to improved glycemic responses. While the body naturally produces inositol and it can be found in various foods, research suggests that inositol supplementation, particularly with myo-inositol (MI) and D-chiro-inositol (DCI), may offer several health benefits, including potential support for weight loss and metabolic health.
Understanding Inositol and Its Forms
Inositol exists in nine stereoisomeric forms, with myo-inositol (MI) and D-chiro-inositol (DCI) being the most studied. These two forms work differently and likely through different signal pathways, leading to different effects when supplemented. Every tissue in the body has its own ratio of MI to DCI. MI is the most abundant form of inositol in humans and can be converted into various derivatives through epimerization, phosphorylation, or methylation. The NAD/NADH epimerase, an insulin-dependent enzyme, converts MI into DCI based on the specific needs of the tissue for these two molecules.
The Link Between Inositol and Insulin Sensitivity
One of the primary ways inositol may promote weight loss is through its role in insulin regulation. Inositol enhances the body's insulin sensitivity, helping manage blood sugar levels. MI-derived phosphoinositol-3-phosphate (PIP3) enhances glucose transport inside the cells through the stimulation of GLUT4 translocation to the cell membrane. Its derivative inositolphosphoglycan (MI-IPG) plays a pivotal role in downregulating the release of free fatty acids (FFA) from adipose tissues, hindering the enzyme adenylate cyclase. Indeed, FFA are known to reduce glucose disposal, causing IR and increased triglyceride synthesis. DCI upregulates pyruvate dehydrogenase leading to the production of ATP by the Krebs’ cycle. MI and DCI promote glycogen synthase, inducing glucose conversion to glycogen stored inside cells. MI modulates the activation of glucose transporters and glucose utilization, and glycogen synthesis takes place under the control of DCI.
Conditions like PCOS are often associated with insulin resistance, which can hinder weight management efforts. Inositol's ability to improve insulin sensitivity may help overcome this obstacle, potentially leading to weight loss.
Inositol and Polycystic Ovary Syndrome (PCOS)
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, affecting 6 to 18% of this group. PCOS encompasses a broad spectrum of biochemical/clinical signs and symptoms such as irregular menstrual cycles, polycystic ovaries, acne, overweight, androgen excess with consequent hirsutism and as aforementioned IR. It is also associated with several long-term health consequences, including obesity, infertility, obstetric complications, type 2 diabetes, cardiovascular disease, psychological distress and ostensibly mood disorders. Independently of body habitus, women with PCOS manifest a 50-70% incidence of IR, resulting in a compensatory hyperinsulinemia, which derives many of the phenotypic features of this disease.
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New research has shown that a combination of MI and DCI is an effective approach to treat PCOS and is better than MI or DCI given alone. Ovacure® is a dietary supplement with MI (1000 mg/ capsule), DCI (25 mg/ capsule) and folic acid (200 mcg/capsule), reproducing the plasma physiological ratio of MI to DCI of 40:1. DCI and MI combination, have been shown to improve insulin sensitivity and promote ovulation.
Several studies suggest that inositol supplementation, particularly the combination of MI and DCI, can improve various aspects of PCOS, including:
- Improved Insulin Sensitivity: Both MI and DCI have been shown to improve insulin sensitivity in women with PCOS.
- Hormonal Balance: Inositol supplementation may help regulate menstrual cycles, promote ovulation, and improve egg quality.
- Metabolic Outcomes: Studies have demonstrated that inositol can positively impact metabolic outcomes in PCOS, such as reducing insulin resistance, improving lipid profiles, and supporting weight management.
Research on Myo-Inositol and D-Chiro-Inositol in PCOS
A prospective study of 150 subjects diagnosed with PCOS according to the Rotterdam criteria explored the relationship between the combination of MI and DCI in a 40:1 ratio and its effects on the PCOS metabolic outcomes (insulin resistance, diabetes, dyslipidemia, weight and BMI) as well as the effect of adding metformin to this combination. All 99 patients were treated with 2 tablets of Ovacure® per day over a period of six months. In addition, 82 patients out of the 99 were given metformin. Following therapy with Ovacure®, paired sample t-test, showed a very significant decrease among the 99 participants of the mean fasting glucose by an average of 4 mg/dL (p<0.001), the mean HOMA-IR decreased by 1.2, and HbA1c levels decreased by 0.21%. The lipid panel displayed a positive effect as the total cholesterol decreased by 14.63 mg/dL (p<0.001), LDL decreased by 7.74 mg/dL on the average (p<0.001), TG decreased by 14.15 mg/dL (p<0.05).
After 6 months of treatment, glucose fasting, HOMA-IR and HbA1c decreased significantly when the patients were treated with Ovacure®. When comparing the metabolic outcomes according to the treatment strategy (Ovacure® alone versus Ovacure® and metformin), the combination didn’t offer any advantage on the insulin levels compared to the treatment with Ovacure® alone.
A meta-analysis of nine randomized controlled trials (RCTs) involving 247 cases and 249 controls revealed significant decreases in fasting insulin and homeostasis model assessment (HOMA) index after MI supplementation. The trial sequential analysis of insulin meta-analysis illustrates that the cumulative z-curve crossed the monitoring boundary, providing firm evidence of the intervention effect.
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Myo-Inositol and D-Chiro-Inositol Ratio
Ovacure® is a dietary supplement with MI (1000 mg/ capsule), DCI (25 mg/ capsule) and folic acid (200 mcg/capsule), reproducing the plasma physiological ratio of MI to DCI of 40:1.
Based on these and other data, many authors recommend the use of MI and DCI in a ratio of 40:1 as a first line approach in PCOS. Furthermore, we recommend the addition of metformin for those who need additional weight loss and sugar control.
Inositol and BMI Reduction: A Meta-Analysis
A meta-analysis of 15 controlled clinical trials investigated the effect of inositol on adult's BMI. The results of pooled analysis showed that inositol supplementation significantly decreased BMI scores (WMD = −0.41 kg/m2; 95% CI: −0.78, −0.04; p = 0.028). Subgroup analysis was performed by dose, duration, age, type of inositol. The effect of intervention was more clinically significant in participants with polycystic ovary syndrome (PCOS) and overweight/obesity. The meta‐analysis suggests that oral inositol supplementation has positive effect on BMI reduction. Inositol supplementation could be considered as an adjunct treatment to improve body mass index.
In the meta‐analysis of 15 controlled clinical trials, inositol supplementation was associated with reductions in BMI. Subgroup analysis showed that intervention for less than 12 weeks and at a dosage <1000 mg had more clinically significant effect. Supplementation is more effective in people over 40 years of age than in other age groups. Their results showed that inositol supplementation was more effective in people with PCOS and overweight/obesity than in other populations.
Dosage and Safety Considerations
The dosage range of inositol supplementation was 600-4450 mg/day administered for 6-48 weeks. It is important to note that in terms of safety and possible side effects, only the highest dose of MI (12 g/day) causes mild gastrointestinal side effects such as nausea, bloating, and diarrhea. In addition, the intensity of harmful events stays also the similar at 30 g/day. Healthcare providers generally consider inositol safe when taken in low doses for up to 10 weeks.
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