PCOS and Inositol

Studies have shown that inositol may alleviate some of the symptoms associated with PCOS including insulin resistance, elevated androgen levels, menstrual irregularity and anovulation/oligo-ovulation.

Inositol has also been shown to improve outcomes in individuals with PCOS going through fertility treatment. Whilst the overall body of evidence is limited,[1] inositol is commonly accepted to be a low-risk supplement that offers benefits for those with PCOS and some other conditions.[2]

Inositol is a form of sugar that humans both make in our kidneys (at a rate of around 2 grams per kidney per day) and in our liver and brain at lower rates.[3] We also consume inositol through our diet (typically 0.5-1.0 grams per day) through whole grains, some nuts and legumes, cantaloupe and some citrus fruits.[4] Our consumption of inositol through our diet is typically much lower than our ancestors as we seldom consume animal liver and kidneys and consume less unprocessed food.[5]

There are nine distinct forms of inositol that are stereoisomers, i.e., they only differ in the spacing of the atoms within the molecule.[6],[7] Myo-inositol (MI) and D-Chiro-inositol (DCI) are the two forms of inositol which are most commonly found in supplements.[8] MI can be converted to DCI and the naturally occurring ratio of MI to DCI varies in different tissues in the body.[9],[10]

MI plays an important role in a variety of biological processes as it mediates signal transduction, i.e., affects the way in which cells respond to substances outside the cell such as hormones, neurotransmitters (or chemical messengers) and growth factors (proteins that stimulate cell growth, differentiation, survival, inflammation and tissue repair).[11],[12],[13] MI and its derivatives are implicated within a number of biological processes, including:[14]

Forms secondary messengers in response to insulin to assist with insulin signaling;
Acts as a second messenger of follicle stimulating hormone (FSH), a key hormone required to stimulate the growth of eggs in the ovaries;[15] and

Assists with osmoregulation, the process of maintaining salt and water balance across membranes in the body.[16]

DCI is similarly involved in a number of key biological processes, including:[17]

Increases sensitivity to insulin by promoting the conversion of glucose into glycogen for energy storage;[18] and
Acts as an aromatase inhibitor, blocking the hormone aromatase that converts androgens into estrogen in the ovaries.[19],[20],[21]

Inositol deficiency can contribute to a number of health complications, particularly for those who already have Type 1 or Type 2 diabetes:[22]

Increasing insulin resistance and elevated glucose and insulin levels;
Diabetic neuropathy, nerve damage which can cause pain and numbness in the legs, feet and hands and problems within the digestive system, urinary tract, blood vessels and heart;[23]
Diabetic nephropathy, or diabetic kidney disease, damage to the kidneys’ filtering system which can lead to kidney failure;[24] and
Diabetic retinopathy, loss of vision or blindness due to damage to blood vessels in the retina.[25]

Certain factors are believed to contribute to deficiency in inositol:[26]

Consumption of caffeine, sugar and other refined carbohydrates;
Sodium or magnesium deficiency;
Increasing age;
Use of certain medications including antibiotics, lithium and valproic acid;
Damage to the kidneys or intestines;
Insulin resistance and / or elevated glucose levels; and
Type 1 and 2 diabetes.

Inositol supplements are believed to support individuals with PCOS in a number of ways:[27],[28],[29],[30]

Increase insulin sensitivity and, alone or in combination with choline and metformin, lead to a reduction in body mass index (BMI);[31],[32],[33]
Reduce androgen levels and improve metabolic indicators such as blood pressure and cholesterol in individuals with “lean PCOS”;[34]
Promote ovulation and increase menstrual regularity;[35] and
Improve outcomes of fertility treatment, alone or in combination with metformin and clomiphene, improving the number of good quality mature eggs and successful pregnancies.[36],[37],[38]

One study showed that most individuals with PCOS appear to benefit from inositol supplements; however, the minority of individuals who exhibit ovarian dysfunction (OD) and polycystic ovaries (PCO) but not androgen excess (AE) do not appear to benefit.[39] Find out more about Types of PCOS (4 cluster model).

In addition to PCOS, inositol supplements may benefit individuals with other health conditions or risk factors:[40]

Metabolic syndrome, a group of risk factors that increase the risk for chronic disease, including diabetes, heart disease and stroke;
Gestational diabetes and preterm birth;
Pregnancy complications such as neural tube defects;[41]
Depression;
Panic disorder, a type of anxiety disorder associated with unexpected panic attacks;
Bipolar disorder, a mental health condition associated with intense shifts in mood, thinking patterns, energy levels and behavior;
Insomnia;
Post-traumatic stress disorder (PTSD), a mental health condition that is triggered by the experience of a traumatic event;[42]
Acute respiratory distress syndrome (ARDS), a lung condition that causes low blood oxygen;[43]
Type 2 diabetes;
Obsessive-compulsive disorder (OCD), a disorder associated with uncontrollable and recurring thoughts (obsessions), repetitive behaviors (compulsions) or both;[44] and
Attention-deficit hyperactivity disorder (ADHD), a disorder associated with symptoms of inattention, hyperactivity and/or impulsivity.[45]

Some studies have shown that inositol supplements can be most effective when administered in the ratio of 40:1 for MI and DCI, the ratio at which these are normally present in the blood.[46] The absorption of these compounds and their therapeutic benefit have been shown to be significantly improved when taken in conjunction with alpha-lactalbumin (α-La),[47] a protein naturally found in cow and human milk.[48]

Commercial supplement preparations vary widely in their overall dosing and ratio of MI to DCI and are therefore likely to offer highly variable benefits.[49] In particular, preparations with a high concentration of DCI should be treated with caution as this could increase the androgen levels in the ovarian theca cells and impair the action of MI.[50] In higher doses, inositol can cause mild side effects such as nausea, gas and diarrhea.[51]

Reviewed by Kayla Patterson CSM MSHI, expert on bridging the gap between clinical workflows and technology solutions

Sources

PCOS and Inositol