Myo-inositol versus D-chiro-inositol

How are they similar? Different? Which one is right for me?

 

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 transduction³. 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.

 

The 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’t¹. 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 complimentary 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-inotiol (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.

 

 

¹R S Clements, Jr, and B Darnell. “Myo-inositol content of common foods: development of a high-myo-inositol diet”. Am J Clin Nutr 1980 33: 1954-67. PMID 7416064.

 

² 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. PMID 12051772.

 

³ 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. PMID 11117673.

 

⁴ 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. PMID 11900279.

 

⁵ 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. PMID 10219066.

 

⁶ 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. PMID 15251831.

Chiral Balance says:

Hi Anita,

It is important to mention that 380 (though it is the very high end) is a normal DHEA-S for a woman in her 20s (which I’m just guessing your daughters). And, while 480 is elevated, it may be transient and your doctor should be able to tell you whether is it clinically concerning. For example, as testosterone and estrogen comes down SHBG can decrease as well. As SHBG decreases, it can release DHEAS, but in principle those levels should come down over time. If it is concerning, you should have your daughters follow up with their physician and follow the DHEAS level to look for interval changes.

Ursula says:

Hi, is DCI available in powder form like myo anywhere? I have been diagnosed with PCOS and took DCI for 4 weeks, but I have issues taking pills and it was hard for me to continue to take daily. I would like to try it again, but I don’t know if I can keep up with the dosage long term. I have not tried myo so that is also an option, buying the powder form to mix in drinks. Is eight weeks a standard trial to tell if myo also works? -Thanks

Chiral Balance says:

Hi Ursula,

No, DCI is not available in powder form, but you can open the capsules and take the powder that way. You will find that it has a mild sweet flavor, which is the natural flavor of D-chiro-inositol. I can’t make firm suggestions about a protocol for trying myo-inositol. But, I think 8 weeks sounds like a reasonable trial.

Lindsay says:

I have PCOS and have read a bunch of research saying that a combination of MI (myo-inositol) and DCI (d-chiro-inositol) can improve the probability of ovulation. My question is, what should the dosage be? Can I take 4000mg of MI and 1200mg of DI? Or is there a specific ratio that helps (I have heard that the ratio is somewhere around 40:1, but that would mean that I would only take 100mg of DI, which seems low to me). What are your thoughts on dosages for the combination? Thanks in advance!

Peyton says:

Hi, my comment is probably in the wrong place but I just have to bring something up. I have PCOS & I also have under-developed breasts AKA insufficient glandular tissue and sometimes called “tuberous” breasts. I have always known in my heart that the under-development of my breasts was linked to my PCOS. My doctor says not a chance, but as I have recently been researching my condition I have found through blogs etc. that most women complaining of under-developed or tuberous breasts also have PCOS and make the same link that I have always made! Do you know of any research suggesting a link between the two or have any guess why the two might be related? I wonder if it is somehow possible for the breasts to finally finish developing through some sort of treatment. Thanks for your input!

Peyton says:

I also wanted to ask if you recommend myo or chiro inositol for me. I haven’t actually been given the PCOS diagnosis yet, but I know that I have it. Everything else has been ruled out, but my doctor is incompetent and illiterate when it comes to PCOS. My doctor says there are only three things that mean PCOS (hirsutism, acne, and cysts on ovaries) and you must have two of the three to get the diagnosis. I have hirsutism and I am waiting on my ultra sound. I bet I have cysts due to pain. I know there is much more to it than that. My hormone levels are normal, but they have taken all tests separate and at random times. How do they know my hormones spike for ovulation if they just take my blood on any given day? They don’t! I also have a period every month, but the cycle is always a different number. My doctor said she suspects I don’t ovulate, but gave no explanation. Also, I am about 20lbs over weight holding it all in my stomach and can’t lose it. I have Tuberous breasts. I also was having a bad time with pimples and oily skin, but after being on the pill that subsided. After stopping the pill I now have blackheads out of control. I also have pain in my belly button, ovaries, tailbone and sides during my period. I am sure that I have cysts, so I am sure that I will get the PCOS diagnosis even though there is more to it than my doctor knows. Which inositol do you recommend to me? Can it hurt me to take both even if I don’t need one? I feel safer taking both. I just want this nightmare over.
One more thing! Will either Myo or Chiro Inositol interact with Goat’s Rue?

Peyton says:

New question. What exactly is Vitex supposedly treating? I don’t know that I understand. Is it supposed to make receptors more sensitive? I am confused. Also, can Vitex, Goat’s Rue, Myo Inositol & DCI all be taken together? I apologize for so many questions and comments!

Chiral Balance says:

Hi Lindsay,

I’m aware of the 40:1 recommendation (and a few other ratios), though I can’t recall the source of the top of my head, the argument was that 40:1 was the “physiological ratio”. I wish I had the related study in front of me, because the line of reasoning has a couple of pretty basic flaws. For example, the ratio of myo to DCI differs from tissue to tissue, so touting one ratio as the ratio is an oversimplification. Perhaps more importantly, in a typical healthy individual, DCI and myo can be readily interconverted to satisfy the immediate needs of the cell. Without getting too technical, consider this: the equilibrium ratio of myo to DCI is about 2:1. For the ratio in some tissue in the body to be 40:1, that would actually imply that DCI was being used in greater quantity than myo, not the other way around. Saying that 40:1 is the right ratio is a little like taking a snapshot at the halfway point of a marathon and saying you can tell who the fastest runner is. It requires a number of faulty assumptions.
Ultimately, my recommendation is to try either myo or DCI, but not both, for at least a good 60 days. If the first one you try doesn’t work, you could try the other. If there is still no results, you could try both at once.

Chiral Balance says:

Hi Peyton,

Your doctor may be wrong or may be right about the link between PCOS and tuberous breasts. I don’t want to bore you with a bunch of statistical jargon, but the real way to answer this question, is to take detailed medical histories from large groups of women with and without PCOS. If it is observed that tuberous breasts are statistically significantly more common among women with PCOS than without, then a connection seems a logical conclusion. Since there are no good data on the incidence of tuberous breasts themselves, then a comparison of the incidence in two groups would be difficult. But, considering there is a suggested genetic element to tuberous breasts, it is at least plausible that it shares some common etiology with PCOS. Honestly, very little is known about the causes or incidence of tuberous breasts, so it might have been more appropriate for your doctor to acknowledge the lack of information than to flatly deny a relationship. On the other hand, since it is developmental, your doctor might simply want to focus on moving forward.

Chiral Balance says:

Hi Peyton,

In the absence of a firm diagnosis of PCOS, I can’t strongly recommend either myo or DCI. And, while I’m sorry to hear that your doctor hasn’t been explaining her thoughts thoroughly, I would still strongly recommend letting her finish all of the lab tests and studies she feels are appropriate and making the diagnosis as complete and accurate as possible. She may find other explanations for your symptoms in addition to or instead of PCOS. If you do have your diagnosis of PCOS confirmed, I would recommend trying myo or DCI, but not both. I can’t really say whether DCI would interact with Goat’s Rue, but if you’re not insulin resistant and you’re not trying to lactate, why exactly are you taking the Goat’s Rue?

Chiral Balance says:

Hi Peyton,

Vitex is a very old herbal remedy for menstrual regularity. It has a number of suspected active ingredients and mechanisms of action. At the end of the day though, its traditional use was for menstrual cycles.

kaitlyn says:

I’ve been taking the myo-inositol that i picked up from a local healthfood store for almost 3 weeks now. I ordered the d-chiro a few days ago and am excited to try it out once it’s delivered. I have PCOS with normal cycles and I have never had an issue with my weight. My skin/ hair on the other hand is how PCOS likes to present itself. I’ve been struggling with breakouts and mild hair loss/ mild hair growth where i don’t want it and after taking the myo-inositol i have noticed a HUGE decrease in the rogue hairs that i would get under my belly button. This is fabulous and i’m totally happy about it but i’m also experiencing a lot of fatigue and occasional headaches. I’m taking 500mg in the am and 500mg before bed. Am i taking too much? Will these side effects subside? I eat an extremely clean, whole foods diet, gluten, dairy and sugar free with minimal fruit so I’m not sure if its causing my BS to be too low which would contribute to the fatigue…. any insight would be great. Thanks!

Valerie says:

I was sent an article on a study done on myo verses d-chiro…in the study, they state that DCI seems to lower egg quality. Is there any truth to this?

Chiral Balance says:

Hi Valerie,

Many of the studies about myo-inositol (this once included) are poorly designed and their titles and results are incredibly misleading. Let me give you an example of what I mean by poorly designed. There is an enzyme called an epimerase that is responsible for converting myo-inositol (MYO) into D-chiro-inositol (DCI). That epimerase is expressed in response to insulin, meaning the higher your insulin is, the more of this enzyme is produced. The authors then hypothesized that this would lead to a functional deficit MYO in women with PCOS, as high insulin would deplete it. This was an odd hypothesis in itself since years of research have shown that women with PCOS have a functional deficit of DCI and elevated MYO and that this is likely because they have a poorly functional or nonfunctional epimerase. However, what really made the study poorly designed is that they only included euglycemic PCOS women, meaning PCOS women without elevated insulin or blood sugar. Do you see the disconnect? If the women in the study had normal insulin, then by the authors’ own reasoning there MYO/DCI ratio should have been normal. That is the exact opposite of the population they should have been looking at. If they’re concerned that high insulin depletes MYO, they should have been looking at PCOS women with high insulin. Their hypothesis itself has other flaws and shows a fundamental lack of understanding of basic biochemistry and thermodynamics. Additionally, If you read their materials and methods section, there is a striking omission regarding the source of either inositol. They also specifically excluded the women in the DCI group who had the strongest response to treatment, yet nowhere did they discuss this as a potential source of bias. They also used a one-way ANOVA, which is simply not an appropriate statistical method for this type of study. Moreover, none of this was a true measure of fertility; the women in the trial underwent a dangerous and expensive artificial ovulation induction therapy, so generalizing the results to people trying to conceive naturally is irresponsible and unjustifiable, though the authors attempt to imply otherwise merely by the title. I could go own. Frankly, I’ve torn this particular paper (the one about oocyte quality) apart and it is a mess of flawed reasoning, poor design, broken methodology, inadequate documentation and overstated results. I’m shocked and disturbed that it passed peer review. Forgive me if I sound a little brusque, but I think the best things in the world for PCOS women are good solid facts so that they can take charge of their own health. Studies like that one do not serve that aim.

ALl of that being said, there are a some good studies about MYO. I’m not anti-MYO. In fact, I’ve even recommended it to certain people in the past. I’m just strongly opposed to junk science like that particular paper and several related papers that came from the same research group in Italy. This is probably more than you wanted to know, but I think of myself as an educator and helper first and a businessman second. Let me know if you have any further questions and if you ever find a peer reviewed article about PCOS and want a second opinion, I’ll be happy to read it (if I haven’t already) and give my two cents.

Chiral Balance says:

Hi Kaitlyn,

I’m not as versed in myo-inositol dosing regimens as I am in DCI, but most of the studies done with myo-inositol were 1,000 mg twice daily (a total of 2,000 mg). I am sorry to hear that myo-inositol has been causing you headache and fatigue, but from what you’ve said, you aren’t taking more than the amount used in most of the studies. I can’t really speak on the topic of myo-inositol side effects and when or whether they will pass. Fatigue and headache could certainly be related to low blood sugar, so the simple solution might be to add a few carbs back to your diet and see if that helps. I’m optimistic that DCI may be able to provide similar benefits without the attending side effects that you mentioned. Please let us know how D-chiro-inositol helps you versus myo-inositol.

Kaitlyn says:

Okay thanks, one more question. I’m 5’2 112lbs, and I know the instructions say take 1 pill for every 130lbs, would it hurt me to take 2 pills or would I just end up peeing out whatver my body doesn’t use?

Chiral Balance says:

Hi Kaitlyn,

I would stick with the label recommendation – I don’t think you’ll see any additional benefits from taking 2 a day since you’re pretty well below the cutoff.

Christine says:

Thank you so much for this information. A co-worker who what just diagnosed w/PCOS was telling me about myo just today. I was diagnosed w/PCOS about 15yrs ago and never found a treatment that worked for me in regards to fertility.

About 10yrs ago I finally agreed to a hysterectomy (at age 37) after a biopsy after a D&C revealed pre-cancer cells. My doc had wanted to save at least one ovary, but she said both of my ovaries were huge and covered with cysts and not worth saving.

I’ve had no regrets, and no adverse affects of the hysterectomy beyond dry, thin skin in my ‘lady parts’ that seems to be helped with topical estrogen.

My question is whether myo-inositol and/or D-chiro-inositol could possibly help symptoms of PCOS that I still have, such as weight issues, hair loss/growth?

Chiral Balance says:

Hi Christine,

That is a very good question. Since DCI was never studied clinically in women who have had a hysterectomy or in postmenopausal women (who have a similar hormonal profile), I don’t have any hard facts are data rely upon when answering your question. So, I’ll just say that if some of your symptoms of PCOS have persisted even after having a hysterectomy, then it might be worth trying some form of inositol. Which to try is hard to say. I generally recommend D-chiro-inositol since I find the clinical evidence for DCI more compelling. Also, the main reason that people try myo-inositol first is cost; if you factor in the fact that you have to take nearly 4 time as much myo-inositol, much of the cost difference disappears. The only time people try myo-inositol after trying D-chiro-inositol is if DCI didn’t help (it doesn’t work equally well for all people). But, back to the first part of your question, I have to add that after a hysterectomy, there are now new, different reasons that are not necessarily related to PCOS that will cause weight issues and hair growth. So, while trying some form of inositol might help, I think it also is less likely to be beneficial. I say this not to be negative, but just to set reasonable expectations. Whichever you decide to try, please feel free to let us know how it goes. We are always eager to hear new and different stories from women with PCOS.

Tomiaka says:

Hello! Today marks my 10th week taking DCI. So far, I have lost 13 lbs (that’s in conjunction with exercise and low carb diet), but continue to have facial hair growth and no period. At times, I have PMS, but nothing happens. Is this reaction common? Also, how much longer should I continue to use DCI before throwing in the towel?

Chiral Balance says:

Hi Tomiaka,

The question of whether to discontinue DCI is a difficult one. We generally recommend a 60 day trial, which it sounds like you have already completed. Some women see benefits much sooner than 60 days and for others it will be longer. If you feel that DCI has helped you to lose weight, then that in and of itself might be a reason to continue taking it. If you main goals were to manage facial hair and resume a cycle, then if DCI hasn’t helped you to reach those goals, discontinuing DCI might be the right thing to do.

Kaitlyn says:

I’ve been taking DCI since Feb 20th however, after a week or so i dropped down to half a pill a day cause I noticed too much weight loss. On march 14th i Started taking 1 pill every morning and have noticed a lot of improvment in my acne, unwanted hair growth and my period was heavier (which is good) and ontime (although my period was only slightly irregular to begin with) and my hair shedding decreased and my hair was feeling healthy and thick.About 2 weeks before my period is supposed to start I noticed the increase in hair loss again. This has happened before and once i get my period my hair shedding seems to decrease again and my hair feels thicker. It’s really discouraging and I know i haven’t been on the DCI a full 8 weeks yet. just curious if you think continued use will straighten out the hair loss issue or if I would benefit from the saw palmetto formula.

Thanks

Chiral Balance says:

Hi Kaitlyn,

That is a good question and I’m sorry to hear that you’re still dealing with shedding. It might be worth considering trying a saw palmetto formulation. But before you do that, consider that cyclic hair shedding is something some women without PCOS experience as part of their normal cycle. That doesn’t mean that hair shedding isn’t concerning and that doesn’t necessarily mean that it is normal for you, but I thought I should mention that hair shedding can be cyclic even if all of your hormones are balanced and are going through their normal variations during the course if your cycle. If the shedding does persist and it continues to be concerning, then a 5-alpha-reductase antagonist like saw palmetto could be an effective method to correct shedding.

Heni says:

Hello! I would like to get some help. I have been on paleo diet for a long time,which totally messed up my metabolism. I have become insulin resistant, but no PCOS luckily. My doctor wants to bring back my insulin sensitivity first with the help of inositol instead of Metformin (for what Im really happy). However, cant decide which is better in my case. Should I get the D-chiro or the Myo-inositol for hyperinsulinemia? Thank you for your help!

Chiral Balance says:

Hi Heni,

Your doctor likely had a specific form of inositol in mind when s/he made this recommendation. So, you should give your doctor a call for clarification. If you don’t have PCOS, then I would guess the doctor meant myo-inositol.

Ask a Question or Leave a Comment

Your email address will not be published.

 (require)