Inositols are signalling molecules found in almost all human tissues with 99% of them being in the myo-inositol form, while the remainder exist as d-chiro inositol. With each form having a particular function, different tissues maintain specific ratios of myo- to d-chiro-inositol based on their associated activity. Myo-inositol is most known for its role in the signalling pathways of follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH), while d-chiro inositol is most well-known for its ability to increase androgen levels in the ovaries. However, these two versions of inositol have one thing in common: they both play a role in insulin signalling and improve insulin sensitivity.1
Higher amounts of d-chiro inositol are found in body tissues that store glycogen such as the liver, but the ratio is always in favour of the myo-inositol form. For example, the liver and adipose tissue maintain a ratio of about 2:1 of myo to d-chiro forms, while the heart and brain maintain a 200:1 ratio. The follicular fluid of the ovaries contains a 100:1 ratio while inositol levels in blood are closer to a 40:1 ratio.1 These functions and ratios are an important consideration when dosing inositol therapeutically.
The clinical spotlight is often on myo-inositol since it’s the form the majority of our inositol is in and it’s involved in more cellular processes, but d-chiro inositol has its own particular functions that make it clinically useful in certain circumstances. In addition to supporting insulin regulation, d-chiro inositol acts as an aromatase inhibitor. Aromatase is the enzyme, found in both adipose tissue and the ovaries, that facilitates the conversion of testosterone into estradiol. By inhibiting this action, d-chiro inositol can slow the hormonal conversion, saving and increasing testosterone while decreasing the production of estrogen. This can be clinically helpful in a few scenarios:
Low Testosterone in Men
In hypogonadotropic hypogonadism, low levels of FSH, luteinizing hormone (LH) and testosterone can cause symptoms such as low sex drive, erectile dysfunction, weight gain, fatigue, depression, and infertility. Aromatase inhibitors are often used in these cases to help improve testosterone levels when hypothalamus-pituitary signalling is under functioning. Since d-chiro inositol decreases aromatase expression, downregulating the conversion of testosterone to estrogen, it can be used to rescue testosterone levels. Meanwhile, by decreasing elevated estradiol, this affects the feedback of estrogen on the pituitary gland and would increase LH and FSH, making d-chiro inositol a useful hormonal modulator in hypogonadotropic hypogonadism.
In one preliminary study of elderly hypogonadal men, supplementing with 1.2g d-chiro inositol daily for 30 days led to a 20% boost in testosterone levels, while estradiol levels declined by a similar percentage on average.1 That said, it would not be advisable to use d-chiro inositol in cases where LH and FSH levels are elevated (primary hypogonadism), since lower estrogen levels will cause a boost in LH and FSH secretion, and could further elevate them above normal levels.
High Estrogen Levels in Obese Men
Adipose tissue contains the aromatase enzyme, therefore high amounts of adipose tissue (high body fat percentage) means increased aromatase activity and increased estrogen levels. In men, this can cause gynecomastia and drives even more adipose accumulation.
Excess adipose tissue is also associated with hyperinsulinemia. As found in one study, d-chiro inositol can improve androgen levels from excess aromatase activity while also improving glucose balance, HOMA index and hyperinsulinemia.2 In this study, supplementing with 1g per day for one month led to a 14% reduction in estradiol levels, and increased testosterone by 23%.
Women with Excess Estrogen Disorders
Excess estrogens are associated with gynaecological cell proliferation such as in fibroids and endometriosis. These conditions may be asymptomatic or may cause heavy menstrual bleeding, pelvic pain and/or painful periods. In endometriosis, lesions themselves express aromatase, allowing local estrogen production to maintain the pathology. D-chiro inositol can downregulate aromatase activity in situ to rob lesions of that estrogen and slow their growth.
Even though there may be a role for d-chiro inositol in excess estrogen disorders, prescribing it in women (or those with ovaries) should be done cautiously due to its androgen-enhancing actions.
One example of this is androgen-excess polycystic ovarian syndrome (PCOS). In this form of PCOS androgen production is already abnormally high and can be exacerbated by high insulin levels. Although both d-chiro- and myo-inositol can improve insulin sensitivity, the androgen enhancing effect of the d-chiro form would not be favourable in the case of hyperandrogenism, exacerbating the disorder and interfering with ovarian follicle development.
In general, d-chiro inositol should not be used on its own (ie. Without myo-inositol and in the proper ratio) by women who are trying to conceive. In one study, women with non-obese PCOS who were undergoing in vitro fertilization (IVF) were given d-chiro inositol at a daily dose of 300mg, 600mg, 1200mg or 2400mg, or were given a placebo.3 The two highest doses of d-chiro inositol (1200mg and 2400mg) given daily for 8 weeks led to greater requirements of FSH treatment, and less oocytes retrieved. There were also significantly less mature oocytes, more immature oocytes and less high-grade embryos in those given the higher doses of d-chiro inositol, compared to placebo.3
In a small study of non-obese egg donors undergoing IVF, higher quality embryos were found when the oocyte’s follicular fluid contained higher ratios of myo-inositol to d-chiro inositol. Reducing this ratio was associated with significantly poorer quality embryos.4
D-chiro inositol may be found in smaller amounts and ratios in the body, but it does indeed have its own particular functions. Due to the negative effect it has on ovarian egg quality, it should be avoided or used very cautiously (with myo-inositol in a 40:1 to 100:1 ratio) in women trying to conceive.
With its androgen-enhancing effects, a person’s whole hormonal picture should be assessed and dosing and duration of therapy should also be carefully prescribed. The most clinically therapeutic role of d-chiro inositol is likely in men with elevated estrogen levels and low testosterone, especially with coinciding hyperinsulinemia.
- Gambioli R, Forte G, Aragona C, et al. (2021). The use of D-chiro-Inositol in clinical practice. Eur Rev Med Pharmacol Sci. 25(1):438-446
- Dinicola S, Unfer V, Facchinetti F, et al. (2021). Inositols: From Established Knowledge to Novel Approaches. Int J Mol Sci. 22(19):10575
- Isabella R, Raffone E. (2012). CONCERN: Does ovary need D-chiro-inositol? J Ovarian Res. 5(1):14
- Ravanos K, Monastra G, Pavlidou T, et al. (2017). Can high levels of D-chiro-inositol in follicular fluid exert detrimental effects on blastocyst quality? Eur Rev Med Pharmacol Sci. 21(23):5491-5498