Inositol’s history is fascinating and somewhat complicated too. It is also an old narrative since inositol has existed since the beginning of life. Inositol is a very stable molecule that performs critical tasks at the biological level, so much so that it is regarded as a prebiotic molecule.
Unfortunately, most people don’t about know inositol or the purpose it serves. Moreover, many do not know the difference between myo-inositol and d-chiro-inositol. In this post, we shall recount the main steps of scientists and researchers investigating the functions, differences, and therapeutic uses of inositols since their discovery. Thus, let us begin in 1850 when Joseph Scherer extracted inositol from muscular tissue.
What Exactly is Inositol?
Inositol is a naturally occurring molecule in the phospholipids of cell membranes, plasma lipoproteins, and the cell nucleus in the form of phosphate. When it comes to inositol, we are referring to a set of nine distinct stereoisomers, and hence the plural “Inositols” is more accurate. Generally, however, the name inositol refers to the most bioavailable form of myo-inositol.
Following Scherer’s discovery, other researchers devoted years to studying myo-inositol in organs. Eisenberg and Bolden observed in 1964 that the testes and the seminal fluid were abundant in free myo-inositol, with a concentration almost triple that of plasma.
What is the Difference Between Myo-inositol and D-chiro inositol?
Myo-inositol, which has a molecular structure with glucose, plays a role in cell signalling. It can promote glucose absorption, hence facilitating blood sugar reduction.
D-chiro inositol, the myo stereoisomer, is likewise implicated in insulin signalling. They are secondary insulin messengers as inositolophosphoglycans. Although their biological activities are not clear to many, it is essential to note that they serve distinct tasks.
As inositolofosfoglicans, D-chiro-inositol are both secondary insulin messengers but have different functions.
In 1988, Larner deduced that myo-inositol and d-chiro inositol were components of two distinct insulin chemical mediators. Although the two isomers are remarkably similar, their functions are somewhat distinct. Indeed, myo is involved in activating and using glucose transporters, while d-chiro is involved in glycogen production and storage.
The distinctions between the two molecules were thoroughly investigated to identify a treatment response for a condition known as PCOS or polycystic ovarian syndrome.
PCOS about Myo and D-Chiro
Larner proposed in the late 1980s that myo-inositol and d-chiro-inositol were components of two distinct insulin chemical mediators. In the same years, experts associated PCOS (polycystic ovarian syndrome) with insulin resistance and hyperinsulinemia in the gynaecological area. It was evident that the ovary has insulin receptors and that their development is essential for androgen synthesis. Myo d-chiro inositol has distinct functions in the ovary:
- Myo-inositol aids in glucose absorption and FSH signalling. FSH stands for follicular stimulating hormone.
- D-chiro-inositol enhances glucose storage and is linked to the insulin-dependent production of androgens.
In a healthy woman’s ovaries, 99% of the intracellular inositol pool comprises Myo-inositol, while the remainder comprises D-chiro-inositol. Another significant distinction between myo and d-chiro is their tissue distribution and existence. Indeed, each tissue controls the creation of the two inositols, myo and d-chiro, to maintain a constant ratio.
Remember that the distribution of Myo and D-chiro inositol in the tissues varies.
In women with PCOS, we notice a myo deficit at the ovarian level, which impairs the FSH signal. Additionally, research has shown the synthesis of d-chiro from myo-inositol. In other words, a small quantity of myo-inositol changes to d-chiro inositol due to the enzyme epimerase. Insulin activates this enzyme.
Myo-therapeutic inositol’s applications
Professor Chiu, a researcher at the University of Hong Kong, was one of the first to show the effectiveness of myo-inositol therapy in women seeking conception in 1992, establishing a link between myo-inositol and fertility. Today, myo-inositol is a safe and efficient treatment option for a variety of diseases and pathologies:
The myo-inositol treatment led to symptom remission and decreased male hormone output in PCOS. However, it also resulted in managing cholesterol levels, a more efficient breakdown of lipids, and a resultant drop in hunger and weight.
Inositol can enhance male infertility symptoms such as motility and sperm count. It improves oocyte and embryonic quality in women.
Again, myo-inositol increases the sensitivity of the serotonin receptor, popularly known as the happy hormone, which is beneficial for anxiety disorders.
Additionally, inositol’s advantages have been explored in diabetes and the prevention of metabolic syndrome.
Researchers have used D-chiro-inositol alone to treat PCOS women since the late 1990s. Nestler pioneered the use of d-chiro-inositol for treating PCOS in a well-known trial. He demonstrated that administering 1.200 mg of D-chiro-inositol for eight weeks could increase insulin sensitivity and ovarian function, decrease androgen and triglyceride levels, and restore menstruation in obese PCOS patients. Regrettably, researchers have not seen these startling findings in their recent trials. A critical variation from the first clinical studies was the increased dose of D-chiro inositol to 2.400 mg. These findings necessitated a halt to the studies.
Since the confirmation of the initial positive results on D-chiro inositol in subsequent studies was not possible, researchers decided to call off the exercise. But why?
As expected, Myo partly converts d-chiro-inositol through epimerase. This is an insulin-sensitive type of enzyme. Myo-inositol, on the other hand, is the most plentiful. However, the scenario changes when a person’s health is at risk, as with PCOS. Indeed, in PCOS women, the epimerase enzyme activity increases, resulting in a significant decrease in the Myo: D-chiro ratio at the intraovarian level. This occurs due to the accelerated conversion of myo to d-chiro caused by elevated circulating insulin levels.
This phenomenon, dubbed the ovarian paradox, originated as an intuition later validated experimentally. Because the ovary is never insulin resistant, the activity of epimerase (mediated by insulin) was more understood in women with PCOS. This leads to a myo-inositol deficiency and, thus, reduces oocyte quality.
Clinical evidence supports the intuition on ovarian paradox on the success of Myo-Inositol-based PCOS and fertility treatments. This answers the contradictory results of high doses of D-chiro-inositol for a long period. The significance of d-chiro in lowering insulin levels, on the other hand, remains unquestionable.
Myo and D-chiro 40:1: A Balancing Issue
Using intuition about the ovarian paradox and the distinct roles of myo and d-chiro inositol, a group of Italian scientists focused on the importance of proper myo and D-chiro inositol supplementation. They also did consider the need to restore the impairment by restoring the proper myo/d-chiro ratio at the ovarian level.
However, the issue is: what is the best dose to maximise d-chiro-inositol activity without impairing ovarian function?
To address this concern, we attempt to highlight many essential assumptions that got reinforced in a review published in one of the world’s distinguished endocrinology publications, Cell Press:
- The ratio of myo/d-chiro-inositol is tissue-specific.
- In healthy women, the standard ratio of myo and d-chiro inositol in the follicular fluid is 100:1. This indicates an excess of myo-inositol and minimal traces of d-chiro inositol.
- In women with PCOS, the ratio changes are to the disadvantage of myo-inositol. At the same time, an excess of d-chiro inositol exists due to the increasing epimerase activity and hyperinsulinemia.
- In women with PCOS, myo insufficiency at the ovarian level impairs the FSH signal, the critical hormone for follicle development. This decreases oocyte quality, anovulation, and infertility. As a result, myo-inositol is essential for FSH signalling, oocyte maturation, and embryonic development.
- Unlike myo-inositol, the function of d-chiro-inositol at the ovarian level remains unclear. High doses of d-chiro inositol over extended durations result in a decrease in oocyte quality and ovarian response.
Considering the unique Myo and D-chiro-inositol ratios (remember the 100:1 ratio in the ovary) and the distinct physiological functions of the two inositols, combined oral therapy of Myo and D-chiro-inositol in the 40:1 ratio (the physiological plasma ratio) is the effective alternative treatment for PCOS women.
Evan is the founder of Fertility2Family and is passionate about fertility education & providing affordable products to help people in their fertility journey. Evan is a qualified enrolled nurse and has expertise in guiding & managing patients through their fertility journeys.