Myo-inositol versus D-chiro-inositol

Myo-inositol versus D-chiro-inositol

Posted on Oct 20th 2019 | By: Dr. Travis H Johnson, DO, MS

There has been a lot of buzz recently about myo-inositol and PCOS. Some of the articles circulating on sites like the Examiner read much less like a serious journalistic endeavor and much more like a paid advertisement for a particular brand of myo-inositol. I'm writing this piece to give a more balanced account of the primary literature on myo-inositol, D-chiro-inositol, PCOS and insulin resistance. Here you'll find evidence-based reasoning and hopefully decide which form of inositol is right for you to try. This is a very big topic, but along the way, I hope to inform anyone reading this of the similarities and differences between myo-inositol and D-chiro-inositol.

Let's start with some important biochemistry terminology. This will give us a common language, provide context for the discussion and illustrate the most fundamental difference between myo-inositol and D-chiro-inositol. In the terms of biochemistry, myo-inositol and D-chiro-inositol are what are known as chiral epimers of each other.

The easiest and most common analogy used to explain chiral epimers is the human hand. Take a look down at your hands right now. You've known your whole life that your left and right hand are mirror images of each other. Now, lay one hand on top of the other. You'll immediately notice that they are not superimposable meaning they don't neatly overlap. That is the essence of chiral epimers; chiral epimers are any two molecules which are non-superimposable mirror images of each other, like your left and right hands. This is a very important concept in biochemistry. And, it is the most fundamental difference between myo-inositol and D-chiro-inositol. They have the same exact molecular weight and are made of all of the same atoms attached in exactly the same ways, except that one is like your left hand and the other is like your right hand. This has some important biochemical consequences and leads to all of their functional differences.

Probably the most important similarity between myo-inositol and D-chiro-inositol is that they are both used during insulin signal transduction. They both serve as second messengers, with different but equally necessary and complementary roles. Both are crucial to good health, and a deficiency in either can lead to sub-optimal wellness. They are both used in different tissues of the body in a variety of roles. For example, D-chiro-inositol activates an enzyme called pyruvate dehydrogenase, which is a very important energy metabolism enzyme. Activating it is an important step in proper glucose disposal. Myo-inositol has several important roles too. And insulin signaling is a very active area of research, so our understanding is improving every year. In addition to insulin signaling, myo-inositol and D-chiro-inositol are used in a variety of other signaling pathways. But let's not get sidetracked with signaling pathways aside from insulin.

spilled white powder in glass jarThe insulin signaling pathway is particularly interesting in PCOS. This is because one of the most common features of PCOS is insulin resistance. In fact, even PCOS women who aren't insulin resistant at the time that they're diagnosed with PCOS are more likely to develop insulin resistance later in life than their peers without PCOS. And PCOS women with insulin resistance are more likely to develop type II diabetes and metabolic syndrome (aka syndrome X), which are themselves risk factors for a host of health problems. Based on this observation, lots of research has tried to identify genetic risk factors for PCOS by looking at genes related to insulin metabolism. To date, the results have been hazy, with no clear genetic causes for PCOS.

Studies have largely focused on genes that are known risk factors for type II diabetes. However, a large body of evidence points to errors in inositol metabolism as a possible cause for PCOS.

Identifying genetic factors in inositol metabolism is a focus of active research. The conversion of myo-inositol to D-chiro-inositol is particularly interesting because errors here have been strongly implicated in PCOS. The conversion is also interesting because Myo-inositol is abundant in a variety of foods and D-chiro-inositol isn't. In fact, urinary excretion of D-chiro-inositol has been shown to be greater than dietary intake in healthy adults. This means that the body must make D-chiro-inositol. Strong circumstantial evidence supports the theory that the body makes D-chiro-inositol from myo-inositol. And more evidence suggests that some people are less able to make this conversion than others. An inability to make this conversion would lead to an imbalance in the ratio of D-chiro-inositol to myo-inositol. And, since both are necessary for separate but complementary roles in insulin signaling, changes in either direction could have negative effects.

One model for the etiology of PCOS proposes that impaired conversion of myo-inositol (MYO) to D-chiro-inositol (DCI) leads to an elevated ratio of MYO/DCI. This in turn leads to overproduction of testosterone and all of the other symptoms of PCOS. Some people take this model and see it as black and white: either you make the conversion or you don't. This leads to a lot of bad hypotheses and incorrect conclusions. Considering the spectrum of human genetic diversity (take height for example), why should this trait be black/white, yes/no, or on/off?

With a little imagination, we can see this impaired conversion of myo-inositol to D-chiro-inositol as a spectrum. Some women make the conversion efficiently, and they have no symptoms of PCOS. Others may make the conversion with some degree of efficiency, but not quite enough to have an optimal MYO/DCI ratio. Their symptoms may be mild. At the other end of the spectrum, some people would be completely unable to make this conversion, and they would consequently present with the most severe symptoms. And, as part of the human tapestry, there would be everything in between as well.

Which brings us to the question of which inositol is right for me?

Along this spectrum, people who are completely unable to convert myo-inositol to D-chiro-inositol are only going to benefit from supplementation with D-chiro-inositol. Other people who make the conversion, but with less than optimal efficiency, may benefit from large doses of myo-inositol. And, folks in between, might see the best results from a blend of the two. Interestingly, clinical trials have shown that large doses of myo-inositol (4000 mg daily) benefit women with PCOS and smaller doses of D-chiro-inositol (1200 mg daily) benefit women with PCOS also. It might be tempting to think that there is a conflict here, that one set of studies must be false.

But, keep in mind the following; clinical data are always averages. If you take a group of women with PCOS all along the spectrum, some might see phenomenal results with myo-inositol and others might see phenomenal results with D-chiro-inositol. But, on average, both treatments will appear to be effective. And, if you review the literature on D-chiro-inositol, myo-inositol, and PCOS, you'll find that they all dovetail very nicely with the view of PCOS as s spectrum of impaired conversion of myo-inositol to D-chiro-inositol.

This is far from the whole story of PCOS, but it is a good introduction, I hope. And, hopefully, it will help readers decide whether to choose myo-inositol or D-chiro-inositol: that is, to choose what works for them. Inositol metabolism is by no means the whole story of PCOS; clearly environmental and lifestyle choices make a difference. And there are doubtless multiple genetic factors that contribute to the variation in both severity and type of symptoms that each individual has. But, the clinical successes (not to mention the anecdotal) of D-chiro-inositol are reconciled with the clinical successes of myo-inositol by thinking of PCOS as a spectrum. And, after all, as anyone who has ever been to a PCOS support group can tell you, PCOS comes in all shapes and sizes.

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_ Sun TH, Heimark DB, Nguygen T, Nadler JL, Larner J (2002). Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls. Biochem. Biophys. Res. Commun. 293 (3): 1092-8.

_ Nestler JE, Jakubowicz DJ, Iuorno MJ (2000). Role of inositolphosphoglycan mediators of insulin action in the polycystic ovary syndrome. J. Pediatr. Endocrinol. Metab. 13 Suppl 5: 1295-8.

_ Larner J (2002). D-chiro-inositol its functional role in insulin action and its deficit in insulin resistance. Int. J. Exp. Diabetes Res. 3 (1): 47-60.

_ Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G (1999). Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N. Engl. J. Med. 340 (17): 1314-20.

_ Luorno MJ, Jakubowicz DJ, Baillargeon JP, et al (2002). Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome. Endocrine practice 8 (6): 417-23.