Benefits
Ovulation in two placebo-controlled trials in women
In 44 women with obesity and PCOS, 1,200 mg of DCI daily for 6 to 8 weeks was followed by ovulation in 19 of 22 women versus 6 of 22 on placebo. In 20 lean women with PCOS, 600 mg daily gave ovulation in 6 of 10 versus 2 of 10, which was not statistically significant. Both short trials came from one research group and were backed in part by Insmed, the company that supplied the DCI.
Insulin response to an oral glucose test
In the 44-woman trial the insulin response to an oral glucose test fell on DCI, but not significantly versus placebo (P = 0.07), and glucose tolerance did not change. In 20 lean women it fell versus placebo (P = 0.03). In 11 women given 2,400 mg a day for 6 weeks, in a trial stopped early, insulin sensitivity did not differ from placebo.
Free testosterone and androgen levels in women
Free testosterone fell on DCI versus placebo in the 44-woman trial (from 1.1 to 0.5 ng/dL) and by 73% in 20 lean women, but did not differ from placebo in a third trial of 11 women stopped early. In a 6-month comparison in 50 women with PCOS, DCI 1 g a day lowered androgen excess more than myo-inositol 4 g.
Blood pressure and triglycerides
In both completed placebo-controlled trials of DCI alone, blood pressure and triglycerides fell compared with placebo. In the 44-woman trial triglycerides went from 184 to 110 mg/dL and systolic and diastolic pressure each fell by 4 mm Hg. In the 20 lean women both pressures and triglycerides also fell.
Combination with myo-inositol and the 40:1 ratio
Most current products pair DCI with myo-inositol. In a 3-month trial of 56 women with PCOS (8 per group) comparing DCI alone with six myo-inositol to DCI ratios, the 40:1 ratio gave the best ovulation results, and ratios richer in DCI did less well. In an IVF trial, only a myo-inositol plus DCI product, not DCI 500 mg alone, improved oocyte and embryo quality.
DCI dose and egg (oocyte) quality
One published hypothesis holds that too much DCI in the ovary lowers egg quality, which is the reasoning behind low-DCI combinations; the main human study behind it carries two editorial expressions of concern. In a 12-week trial in 11 women having ICSI, 300 mg of DCI with myo-inositol improved oocyte cytoplasm quality more than 27.6 mg. Three of its authors worked for Biosearch Life, a company that makes DCI.
Mechanism of action
Inositol phosphoglycan (IPG) messengers
DCI is part of inositol phosphoglycan messengers released when insulin acts on cells. In women with PCOS, a greater release of the DCI-containing messenger during a glucose test went along with better insulin sensitivity, regardless of treatment group.
Tissue-specific conversion from myo-inositol
An insulin-dependent epimerase enzyme converts myo-inositol to DCI, and its activity differs between tissues. One hypothesis proposes that this enzyme is overactive in the ovary in PCOS, leaving the ovary short of myo-inositol and lowering egg quality.
Aromatase gene expression in ovarian cells (lab study)
In human granulosa (ovarian) cells grown in the lab, DCI lowered gene expression of aromatase (CYP19A1), the enzyme that makes estrogen, and of other steroid-making enzymes, in a dose-dependent way. Hormone output was not measured, and this is cell work, not a result in people.
Insulin and ovarian androgen production
In the same cell work, insulin raised the expression of steroid-making genes in gonadotropin-stimulated ovarian cells and DCI countered that effect. The trial authors of the 44-woman study linked the lower free testosterone on DCI to its effect on insulin action.
Clinical trials
Randomized, double-blind, placebo-controlled trial of D-chiro-inositol 1,200 mg (INS-1, supplied by Insmed Pharmaceuticals) once daily for 6 to 8 weeks; ovulation tracked by weekly serum progesterone, with oral glucose tolerance tests and hormone measures. Supported by an NIH small-business grant and by Insmed Pharmaceuticals; the lead author had consulted for Insmed. No side effects were noted in either group. (Nestler et al. 1999, N Engl J Med)
44 women with obesity and PCOS (22 DCI, 22 placebo).
Ovulation occurred in 19 of 22 women on DCI versus 6 of 22 on placebo (P<0.001). The insulin response to oral glucose fell on DCI, but the change versus placebo was not significant (P=0.07), and glucose tolerance did not change significantly. Free testosterone fell from 1.1 to 0.5 ng/dL (P=0.006 vs placebo), triglycerides fell from 184 to 110 mg/dL (P=0.002), and blood pressure fell by 4 mm Hg (diastolic P<0.001, systolic P=0.05).
Randomized placebo-controlled trial of D-chiro-inositol 600 mg once daily for 6 to 8 weeks, with oral glucose tolerance tests, hormone, blood pressure and lipid measures. Funded in part by the same NIH small-business grant as the 44-woman trial; three authors worked at Insmed Pharmaceuticals. (Iuorno et al. 2002, Endocr Pract)
20 lean women with PCOS (BMI 20.0 to 24.4 kg/m2; 10 DCI, 10 placebo).
The insulin response to oral glucose fell on DCI compared with placebo (P=0.03). Free testosterone fell 73%, from 0.83 to 0.22 ng/dL, with essentially no change on placebo (P=0.01). Systolic and diastolic blood pressure (P=0.002 and P=0.001) and triglycerides (P=0.001) fell compared with placebo. Ovulation occurred in 6 of 10 on DCI versus 2 of 10 on placebo, which was not statistically significant (P=0.17).
Randomized placebo-controlled trial of D-chiro-inositol 1,200 mg twice daily (Insmed Pharmaceuticals) for 6 weeks, with insulin sensitivity measured by intravenous glucose tolerance test; stopped early when the study product became unavailable. Between-group results are from the PMC full text. (Cheang et al. 2008, Metabolism)
11 women with PCOS (6 DCI, 5 placebo).
Blood DCI rose on DCI compared with placebo (P=0.04), but insulin sensitivity (P=0.82), release of the DCI-containing messenger (P=0.34), fasting insulin (P=0.18) and free testosterone (P=0.17) did not differ from placebo. Pooling both groups, a rise in messenger release relative to insulin went along with a rise in insulin sensitivity (r = 0.69, P = 0.02).
Randomized two-arm comparison with no placebo group: myo-inositol 4 g or D-chiro-inositol 1 g daily, each with 400 mcg folic acid, for 6 months. The abstract reports results without numbers or P values. (Pizzo et al. 2014, Gynecol Endocrinol)
50 women with PCOS and irregular cycles (25 per group).
Both forms improved ovarian function and metabolic measures from baseline. Myo-inositol had the larger effect on metabolic measures, while D-chiro-inositol lowered androgen excess more.
Randomized, open-label comparison of D-chiro-inositol alone and myo-inositol to DCI ratios of 1:3.5, 2.5:1, 5:1, 20:1, 40:1 and 80:1, each given as 2 g of inositols twice daily for 3 months; no placebo group. Primary outcome ovulation (luteal progesterone); secondary outcomes FSH, LH, SHBG, estradiol, free testosterone, basal and postprandial insulin, HOMA index, BMI and menses. The authors declared no conflicts. (Nordio et al. 2019, Eur Rev Med Pharmacol Sci)
56 women with PCOS (8 per group).
Ovulation markers improved with the 20:1, 40:1 and 80:1 ratios, best with 40:1, while improvement was very low or not detectable with DCI alone and the DCI-rich ratios. HOMA index fell from baseline with every formulation, with no differences between groups. Results are shown only in figures, without group-level numbers in the text.
Randomized controlled trial comparing a myo-inositol 1.1 g plus D-chiro-inositol 27.6 mg product (INOFOLIC combi, Lo.Li. Pharma) with D-chiro-inositol 500 mg alone before IVF. The abstract gives no group sizes, numbers or P values. (Colazingari et al. 2013, Arch Gynecol Obstet)
Women with PCOS undergoing IVF.
Only the combination improved oocyte and embryo quality and pregnancy rates; D-chiro-inositol alone did not.
Randomized, double-blind trial of myo-inositol 550 mg plus D-chiro-inositol 300 mg or 27.6 mg daily for 12 weeks; three authors worked for Biosearch Life, a company that makes DCI from carob. (Mendoza et al. 2020, Gynecol Endocrinol)
11 women with PCOS undergoing ICSI (5 higher dose, 6 lower dose; 172 oocytes analyzed).
The higher DCI dose improved oocyte cytoplasm quality (p = 0.0067). Other oocyte features improved with either combination.