What is inositol?

In recent years, inositol has emerged as a subject of intense scientific interest, particularly for its potential role in managing conditions like diabetes, gestational diabetes, and polycystic ovary syndrome (PCOS). But what exactly is this compound, and why is it generating such excitement in the medical community?

Inositol is a naturally occurring cyclohexane-1,2,3,4,5,6-hexol compound, once classified as a member of the B-vitamin family but now considered a pseudovitamin. It exists in nature in nine stereoisomeric forms, with myo-inositol (MI) being the most abundant, accounting for about 99% of the inositol in the human body. Another important isomer is D-chiro-inositol (DCI), which has also shown significant therapeutic potential.

Found in a variety of foods including fruits, vegetables, beans, grains, and nuts, inositol plays crucial roles in numerous biological functions. It’s a key component of cell membranes and is involved in cell signaling, insulin action, neurotransmitter function, and calcium concentration regulation within cells. Inositol and its derivatives act as second messengers in various cellular processes, particularly in the insulin signaling cascade.

The relationship between inositol and glucose metabolism is of particular interest to researchers. Inositol appears to enhance insulin sensitivity, potentially improving the body’s ability to regulate blood sugar. It may also enhance glucose uptake in cells and affect the activity of enzymes involved in glucose metabolism. These properties make it a promising candidate for managing conditions characterized by insulin resistance, such as type 2 diabetes, gestational diabetes, and PCOS.

In PCOS, inositol supplementation has shown potential in improving ovulatory function, reducing androgen levels, and addressing metabolic disturbances. For gestational diabetes, studies suggest that inositol might help prevent its onset in at-risk pregnant women and improve outcomes when used as a treatment.

Beyond its effects on glucose metabolism and reproductive health, inositol has also been studied for its potential benefits in other areas. Some research suggests it may have positive effects on blood pressure, lipid profiles, and even liver health in the context of non-alcoholic fatty liver disease (NAFLD).

While the research is promising, it’s important to note that many studies are still in early stages, and more large-scale clinical trials are needed to fully establish inositol’s efficacy and safety profile for various health condition

Prevention of Gestational Diabetes (GDM):

Most studies show a significant reduction in GDM incidence with inositol supplementation. Risk reduction ranges from OR 0.29 to 0.53 across studies.

Treatment of Gestational Diabetes:

Some evidence for improved insulin resistance and reduced need for insulin treatment. Potential reduction in risk of neonatal hypoglycemia.

Glucose Metabolism:

Consistent reductions in fasting glucose and post-OGTT glucose levels (Oral Glucose Tolerance Test).

Improvements in insulin sensitivity (reduced HOMA-IR).

Maternal Outcomes:

Potential reduction in hypertensive disorders of pregnancy.

Mixed results on the need for insulin treatment.

Fetal/Neonatal Outcomes:

Some evidence for reduced risk of neonatal hypoglycemia.

Inconsistent findings on birth weight and macrosomia.

Type 2 Diabetes:

Limited evidence suggests improvements in fasting blood glucose and HbA1c.

Dosage identified in studies:

Most effective dosage appears to be 2000-4000 mg myo-inositol daily for GDM prevention. Often combined with 400 μg folic acid.

Strength of Evidence:

Multiple meta-analyses and Cochrane reviews support the potential benefits of inositol. However, many studies note the need for larger, more diverse trials to confirm findings. Overall evidence quality is often rated as low to moderate due to study limitations and heterogeneity.

Practical Implications:

Inositol supplementation shows promise for preventing GDM, particularly in high-risk populations. The optimal dosage appears to be 2000-4000 mg of myo-inositol daily, often split into two doses. Potential benefits for type 2 diabetes management, but more research is needed.

More research is needed to establish long-term safety and effectiveness across diverse populations. Patients should consult healthcare providers before starting any supplement regimen during pregnancy or for diabetes management. 

Authors	Key findings summarized	Quality of evidence
Ayçil Özturan et al. (2019)	– Improved fasting blood glucose and HbA1c in diabetic patients – Reduced incidence of GDM in at-risk pregnant women – Improved insulin sensitivity and reduced insulin resistance	NA
Brown et al. (2016)	– May reduce maternal fasting blood glucose – May reduce maternal 1-hour postprandial blood glucose – May reduce the risk of neonatal hypoglycemia	Overall quality of evidence was judged to be low due to imprecision from small sample sizes
Chen et al. (2024)	– Reduced treatment requirement with insulin  – Decreased HOMA-IR	All included studies were judged to have high quality (Jadad scores ≥ 3)
Li & Fang (2022)	– Reduced incidence of GDMReduced 2-h glucose OGTT – Increased gestational age at birth – Decreased incidence of preterm delivery	All included studies were judged to have high quality (Jadad scores ≥ 3)
Li & Shi (2024)	Prevention of GDM:  – Reduced incidence of GDM – Improved fasting glucose – Reduced risk of pregnancy-induced hypertension  Treatment of GDM: – Improved insulin resistance – Reduced risk of neonatal hypoglycemia	Overall quality of evidence was rated as very low using GRADE methodology
Liu & Liu (2022)	– Reduced incidence of GDM  – Reduced 2-h glucose OGTT  – Reduced HOMA-IR	All included studies were judged to have high quality (Jadad scores ≥ 3)
Miñambres et al. (2019)	– Reduced fasting plasma glucose – Reduced 2h plasma glucose after OGTT – Reduced risk of abnormal glucose tolerance – Reduced HOMA-IR	NA
Motuhifonua et al. (2023)	– May reduce incidence of GDM – May reduce hypertensive disorders of pregnancy – May reduce preterm birth	Overall risk of bias was judged to be low, but certainty of evidence was low to very low for most outcomes
Vitagliano et al. (2018)	– Lower rate of GDM – Lower fasting glucose levels at OGTT – Lower preterm delivery rate	The overall quality of evidence was rated as very low (GRADE score 1) due to methodological flaws in the included studies
Zhang et al. (2019)	– Reduced incidence of GDM – Reduced preterm delivery	The overall quality of the included studies was high, with Jadad scores ranging from 3 to 5
Zheng et al. (2015)	– Reduced incidence of GDM – Reduced birth weight – Reduced fasting, 1-hour, and 2-hour glucose OGTT	NA

Metabolic Parameters

• Improved insulin sensitivity
• Reduced fasting insulin levels
• Decreased HOMA index (measure of insulin resistance)
• Reduced fasting plasma glucose
• Potential improvements in lipid profiles

Hormonal Balance

• Reduction in total and free testosterone levels
• Increased sex hormone-binding globulin (SHBG) levels
• Decreased androstenedione levels
• Potential reduction in LH/FSH ratio (luteinizing hormone/follicle stimulating hormone ratio)

Menstrual Regularity and Ovulation

• Increased likelihood of regular menstrual cycles
• Improved ovulation rates
• Potential benefits for oocyte quality and maturation

Comparison with Metformin

• Similar efficacy to metformin in improving metabolic and hormonal parameters
• Potentially better tolerability with fewer side effects
• Non-inferiority in most outcomes related to PCOS management

Body Composition

• Potential for greater reduction in BMI compared to placebo
• May assist in weight management for PCOS patients

Fertility and Assisted Reproductive Technology (ART)

• Improved oocyte quality in women undergoing ART procedures
• Potential benefits for overall fertility in PCOS patients

Different Forms and Combinations of Inositol

• Myo-inositol (MI) as the most studied form
• Potential benefits of D-chiro-inositol (DCI) at lower doses
• Promising results from combined MI and DCI therapy (often in a 40:1 ratio)

Dosage identified in studies:

• Myo-inositol (MI) dosages typically ranged from 1000 mg to 4000 mg daily
• Common MI dosage: 2000 mg twice daily (4000 mg total)
• D-chiro-inositol (DCI) dosages ranged from 600 mg to 1200 mg daily
• Combined therapy often used a 40:1 ratio of MI to DCI
• Example of combined therapy: 1100 mg MI + 27.6 mg DCI daily
• Some studies combined inositol (usually MI) with 400 μg folic acid
• Treatment durations in studies varied, often ranging from 12 to 24 weeks
• Some effects (e.g., changes in SHBG levels) may require longer treatment durations (≥24 weeks) to become significant

Authors	Key findings summarized
Fatima et al. (2023)	– No significant difference between myo-inositol (MI) and metformin (MET) for BMI, fasting insulin, fasting blood sugar, HOMA index, and LH/FSH ratio – Both MI and MET equally beneficial in improving metabolic and hormonal parameters in – PCOS MI may be better tolerated than MET due to fewer gastrointestinal side effects
Greff et al. (2023)	– Inositol increased likelihood of regular menstrual cycle – Greater reduction in BMI compared to placebo – Reduced total testosterone free testosterone and androstenedione levels  – Increased sex hormone-binding globulin levels – Reduced fasting plasma glucose and insulin levels – Non-inferior to metformin in most outcomes – Fewer side effects compared to metformin
Unfer et al. (2016)	– Myo-inositol (MI) improved insulin sensitivity, reduced insulin levels, and restored ovulation in many PCOS patients – MI reduced LH, FSH ratio, androgen levels, and improved lipid profiles – MI improved oocyte quality and maturation in women undergoing ART procedures D-chiro-inositol (DCI) showed benefits at lower doses, but high doses may negatively affect oocyte quality – Combined therapy of MI and DCI (40:1 ratio) showed promising results in improving metabolic and hormonal parameters
Unfer et al. (2017)	– Significant decrease in fasting insulin in MI-treated group – Significant decrease in HOMA index in MI-treated group  – Trend towards reduction in testosterone in MI-treated group  – Significant increase in SHBG in MI-treated group  – No significant difference in androstenedione levels

Inositol and Blood Pressure: A Natural Approach to Hypertension

High blood pressure is a common health concern, and inositol supplementation might offer a natural way to address it. A comprehensive meta-analysis by Hashemi Tari et al. (2021) found that inositol can significantly reduce both systolic and diastolic blood pressure. The average reductions were impressive: 5.69 mmHg for systolic and 7.12 mmHg for diastolic blood pressure.

What’s particularly interesting is that the effects were more pronounced in certain groups. People over 50 years old and those with metabolic syndrome seemed to benefit the most. The study also found that longer durations of supplementation tended to yield better results (Tari et al., 2021).

These findings suggest that inositol could be a valuable tool in managing hypertension, with effects comparable to some lifestyle interventions like the DASH diet. However, it’s important to note that more large-scale studies are needed to confirm these results.

Balancing Lipid Profiles with Inositol

When it comes to managing cholesterol and triglycerides, inositol shows promise as well. A meta-analysis by Tabrizi et al. (2018) revealed that inositol supplementation can significantly improve lipid profiles in people with metabolic diseases.

The study found that inositol reduced triglycerides, total cholesterol, and LDL-cholesterol levels. It’s worth noting that the benefits were more pronounced in certain groups. For instance, non-PCOS patients showed greater improvements in triglycerides and total cholesterol, while PCOS patients benefited more in terms of HDL-cholesterol levels (Tabrizi et al., 2018).

Inositol and Non-Alcoholic Fatty Liver Disease: A Promising Avenue

Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly common, and inositol might offer a new approach to managing this condition. While human studies are still limited, the available research is encouraging.

A systematic review by Pani et al. (2020) highlighted that inositol supplementation in animal models reduced hepatic triglycerides and cholesterol accumulation. It also helped maintain normal liver structure and reduced the activity of fatty acid synthesis enzymes.

In the one human randomized controlled trial included in the review, pinitol (a form of inositol) significantly reduced liver fat content and improved liver enzyme levels. It also showed antioxidant effects, increasing glutathione peroxidase activity (Pani et al., 2020).

These findings suggest that inositol could play a role in preventing or treating NAFLD by reducing liver fat accumulation and providing antioxidant protection. However, it’s crucial to note that more human studies are needed to confirm these effects and establish the optimal supplementation regimen.

While the research on inositol’s benefits for blood pressure, lipid profiles, and NAFLD is promising, it’s important to remember that these studies are still in their early stages. Always consult with a healthcare professional before starting any new supplement regimen, especially if you have existing health conditions or are taking medications.