The first supplement recommended to women with polycystic ovary syndrome (PCOS) is often inositol. Given the prevalence of its use, there is a large literature on inositol supplementation and PCOS. Consequently, I am breaking up my discussion of inositol into a series of posts. This first post covers some of the basics of inositol like what inositol actually is and why it might be used for PCOS. Subsequent posts will talk about scientific literature on the effectiveness of the use of inositol for PCOS and its associated health challenges.

What is inositol?

Inositol is actually a kind of sugar, which seems counterintuitive as a treatment for PCOS, a disorder with insulin resistance at its core.

Inositol includes 9 stereoisomers. What the heck is a stereoisomer?? Within a given category of stereoisomers, like inositol, all have the same number and kinds atoms, but the atoms are put together a little bit differently. The words rat, art, and tar all contain the letters A, R, and T, but in different orders. Stereoisomers are kind of like that. And because they have different arrangements of the same atoms, different inositol stereoisomers have different functions in the body.

For PCOS, there are two inositol stereoisomers that matter most: myo-inositol and d-chiro-inositol.

Myo-inositol

Myo-inositol (MI) is the most common inositol found in the human body. It is sometimes referred to as vitamin B8. However, vitamins are substances that generally cannot be produced by the human body (vitamins D and K are the primary exceptions), and we’ve learned that our kidneys produce about 2 g of inositol each day (DiNicolantonio and O’Keefe 2022). Consequently, it is no longer considered to be a vitamin, although you may still see it labeled as such.

MI is converted to inositol phosphoglycans (IPGs), which are required for the processes that convert glucose into energy our cells can use and for the uptake of glucose by our cells. A deficiency in myo-inositol leads to reduced levels of these IPGs and impaired use and uptake of glucose. This can lead to elevated blood sugar levels and increased release of insulin as the body attempts to regulate blood sugar.

In females with PCOS whose ovaries tend to be extra sensitive to insulin, this excess insulin triggers excess production of androgens like testosterone, contributing to PCOS symptoms like acne, excess body hair, and male-pattern baldness.

IPGs are also used to enhance the effects of follicle stimulating hormone (FSH). Females with PCOS tend to have low FSH levels, especially relative to luteinizing hormone (LH). LH and FSH control ovulation, and a high LH relative to FSH leads to follicles that do not reach the critical size needed for ovulation (To learn more about phases of menstrual cycles, check out this post.). Decreased concentrations of MI in follicle fluid is also associated with poorer oocyte (egg) quality and reduced likelihood of conception (Chiu et al. 2002).

Consumption of MI can also help to stabilize blood sugar levels because its presence in the small intestine slows absorption of glucose (Haneda et al. 1990).

D-Chiro-inositol

Like myo-inositol, d-chiro-inositol (DCI) is converted to IPGs, but its associated IPGs help with the creation of glycogen. Glycogen is one form of glucose storage that occurs in muscle cells and the liver. Stored glycogen can then be accessed and used quickly by muscle cells when we are active. Glucose is also stored as fat in fat cells for longer term energy needs. With impaired glycogen creation, more glucose will be converted to and stored as fat.

DCI is created from MI, but it requires insulin to do so. In people with insulin resistance, such as females with PCOS, this insulin resistance impedes the conversion of MI to DCI. Ideally, muscle cells with have a high rate of conversion of MI to DCI, leading to higher DCI concentrations relative to MI concentrations. People with insulin resistance tend to have low levels of DCI in their muscle tissues because this conversion is impaired.

While muscle cells can become insulin resistant, ovary cells cannot become insulin resistant. In females with PCOS and insulin resistance, chronically elevated levels of insulin prompt increased conversion of MI to DCI in the ovary, leading to low levels of MI in the ovary, impeding ovulation and lowering egg quality, as discussed above.

In females without PCOS, the ratio of MI to DCI in ovary cells is about 100 to 1. In females with PCOS, it is about 0.2 to 1.

The first trial of supplementation with any form of inositol tested the use of DCI alone to address insulin resistance, elevated testosterone levels, high blood pressure, and irregular menstrual cycles (Nestler et al. 1999). The efficacy of the intervention prompted numerous other studies, that will be discussed in coming posts.

Food Sources of inositol

Some of the best food sources of inositol are no longer regularly consumed. These include organ meats like liver, kidney, and brains (DiNicolantonio and O'Keefe 2022). Beans, certain fruits, and certain vegetables are the next best sources. The list below includes all known sources with at least 100 mg of MI per g of food. All amounts are from Clements and Darnell 1980, the most comprehensive review available.

1. Canned great Northern beans, 440 mg/g

2. Fresh cantaloupe, 355 mg/g

3. Fresh orange, 307 mg/g

4. Stone ground whole wheat bread, 288 mg/g

5. Dried great Northern beans, 283 mg/g

6. Canned rutabaga, 252 mg/g

7. Canned red kidney beans, 249 mg/g

8. Canned large English peas, 235 mg/g

9. Fresh grapefruit, 199 mg/g

10. Fresh lime, 194 mg/g

11. Fresh shelled green beans, 193 mg/g

12. Canned blackberries, 173 mg/g

13. Canned small English peas, 170 mg/g

14. Canned mandarin oranges, 149 mg/g

15. Canned green lima beans, 146 mg/g

16. Fresh kiwi, 136 mg/g

17. Dried green split peas, 128 mg/g

18. Fresh great Northern beans, 124 mg/g

19. Fresh nectarine, 118 mg/g

20. Canned grapefruit, 117 mg/g

21. Canned black eyed peas, 117 mg/g

22. Fresh black eyed peas, 116 mg/g

23. Frozen pole beans, 175 mg/g

24. Canned wax beans, 144 mg/g

25. Fresh artichokes, 120 mg/g

26. Canned okra, 117 mg/g

27. Canned artichoke hearts, 116 mg/g

28. Fresh green beans (not shelled), 105 mg/g

Inositol supplementation

Later posts will discuss the specific research on inositol supplementation, but I will include common recommendations here.

First, while supplementation with either MI or DCI has been tested in the literature and found to have benefits, the general recommendation is to supplement with both MI and DCI with a MI to DCI ratio of 40 to 1 (Nordio et al. 2019). This ratio was originally determined using animal models, but then confirmed in a study of 56 females with PCOS who received ratios ranging from 0 MI to 1 DCI up to 80 MI to 1 DCI. Among all of the ratios considered, 40 to 1 led to the greatest improvements across a broad range of reproductive hormone levels and metabolic health markers, as well as menstrual cycle regularity. In this study, each participant received 2 g of total inositol, with the amount of MI and DCI varying based on the ratio assigned.

Most studies testing the efficacy of a fixed dose of MI per day use between 1 to 4 g of MI per day, and most common supplements contain 2g of MI per daily dose. Those supplements that contain both MI and DCI often include them in 40 to 1 ratios.

Inositol is relatively flavorless, so it is available in powder form, for those of you who (like me!) don’t like swallowing pills. I personally use this powdered form that also includes vitamin D and folate, two other nutrients females with PCOS tend to lack.

If you were paying attention to the amounts of MI in the foods listed above, you might have realized that it would be tricky to get the common supplemental dosage through diet alone.

This doesn’t, however, mean that diet is not important here!

Our food choices over time either worsen or help mitigate insulin resistance. Supplementing with inositol should not be seen as a free pass on making good dietary choices most of the time.

references

Chiu TT, Rogers MS, Law EL, Briton-Jones CM, Cheung LP, Haines CJ. 2002. Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Human Reproduction 17:1591-1596. https://doi.org/10.1093/humrep/17.6.1591

Clements RS and Darnell B. 1980. Myo-inositol content of common foods: Development of a high-myo-inositol diet. The American Journal of Clinical Nutrition, 33:1954-1967 https://doi.org/10.1093/ajcn/33.9.1954

DiNicolantonio JJ and O'Keefe JH. 2022. Myo- inositol for insulin resistance, metabolic syndrome, polycystic ovary syndrome and gestational diabetes. Open Heart, 9:e001989. https://doi.org/10.1136/openhrt-2022-001989

Haneda M, Kikkawa R, Arimura T, Ebata K, Togawa M, Maeda S, Sawada T, Horide N and Shigeta Y. 1990. Glucose inhibits myo-inositoluptake and reduces myo-inositol content in cultured rat glomerular mesangial cells. Metabolism 39:40–5 https://doi.org/10.1016/0026-0495(90)90145-3

Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, and Allan G. 1999. Ovulatory and metabolic effects of d-chiro-inositol in the polycystic ovary syndrome. The New England Journal of Medicine, 340(17):1314 - 1320.

Nordio M, Basciani S, and Camajani E. 2019. The 40:1 myo-inositol/D-chiro-inositol plasma ratio is able to restore ovulation in PCOS patients: Comparison with other ratios. European Review for Medical and Pharmacological Sciences, 23:5512-5521 doi: 10.26355/eurrev_201906_18223

Disclaimer: This post is not intended to diagnose or treat any medical issues. It is intended for informational purposes only. I am not a medical practitioner. Always consult a trusted healthcare provider with any questions you may have about a medical condition or treatment and before starting any new health care regimen.