Myo-Inositol vs D-Chiro-Inositol: What the 40:1 Ratio Trials Compared

Myo-inositol is the form of inositol in food and in almost every trial; D-chiro-inositol is made from it inside tissues and has two small placebo-controlled trials of its own. The 40:1 combination rests on two trials by one research group, a trial from another group, with four ingredient-company authors, found a mix with more D-chiro-inositol did better, and the 2023 international guideline recommends no type, dose or combination.¹ This page is one spoke of the Wellgard inositol guide.

Evidence at a glance

• Trials: 30 randomised trials included in the 2024 guideline review (19 pooled), 2,230 women, two of them (64 women) on D-chiro-inositol against placebo; five ratio or combination trials, 543 women, counted here.
• Largest trial: 240 pregnant women with a family history of diabetes, 1.1 g myo-inositol with 27.6 mg D-chiro-inositol a day, first antenatal visit to the 24 to 28 week glucose test.
• Strongest measured outcome: 19 of 22 women ovulated on 1,200 mg D-chiro-inositol a day against 6 of 22 on placebo.
• Not tested: the 40:1 mix against myo-inositol alone in women trying to conceive; any ratio trial longer than six months.

Sources checked on 17 October 2026.

What is D-chiro-inositol, and how is it different from myo-inositol?

Inositol is a six-carbon ring with nine arrangements, two of them sold as supplements. Myo-inositol is the one in fruit, beans and grains and in every cell, and the one almost every trial used; D-chiro-inositol is made from it inside tissues. Two hypotheses, neither tested directly in women, drive the trials: that polycystic ovary syndrome involves a shortage of a D-chiro-inositol-containing messenger for insulin's signal, and that the two forms belong to different signalling cascades.^{2, 3} A label saying only "inositol" almost always means myo-inositol. The NHS renamed the condition polyendocrine metabolic ovarian syndrome (PMOS) in 2026; the trials say PCOS, so this page does too.⁴

What did the D-chiro-inositol trials find on their own?

The guideline review counted two placebo-controlled trials of D-chiro-inositol alone, both from one research group, 64 women, low certainty.⁵ In 1999, 44 women with PCOS and obesity (average BMI 31) took 1,200 mg or placebo daily for six to eight weeks: 19 of 22 on D-chiro-inositol ovulated against 6 of 22 on placebo, and free testosterone roughly halved.² In 2002, 20 lean women took 600 mg or placebo for the same time: free testosterone fell by 73%, and 6 of 10 ovulated against 2 of 10, not statistically significant.⁶ Pooled, they gave lower free testosterone, higher sex hormone binding globulin, lower insulin after glucose and a BMI 0.67 units higher than placebo.⁵ Two further D-chiro-only studies are not counted: a 2015 study of 48 women was retracted in 2026, and a 2012 dose study of 54 women has carried an expression of concern since 2018.^{7, 8}

Where does the 40:1 ratio come from?

From one Italian research group, which describes 40:1 as the ratio of the two forms in blood plasma and tested that mix in two trials.^{3, 9} In 2012, 50 overweight women with PCOS took myo-inositol alone or the 40:1 combination for six months: both groups' metabolic measures improved, the combination was ahead at three months, and at six months there was no significant difference.³ In 2019, 56 women were split eight to a group across D-chiro-inositol alone and six ratios from 1:3.5 to 80:1, 4 g of inositols a day for three months; the authors report 40:1 as best for ovulation, but the abstract gives no between-group statistics, and eight per arm settle nothing.⁹ Two more papers are not counted here. A 2013 study of 20 women from the same group, which called 40:1 a "physiological ratio" in its title, was placed under an expression of concern in 2026 over its data, ethics approval and a possible undeclared conflict of interest.¹⁰ A 2011 trial of 84 women, the origin of the claim that myo-inositol rather than D-chiro-inositol improves egg quality, was placed under an expression of concern in 2025 over a potential undeclared conflict of interest.¹¹

What did the ratio trial from another group find?

The one double-blind ratio trial from outside that group was a multicentre Spanish study in 2019: 60 women with PCOS undergoing ICSI were randomised to 1.1 g of myo-inositol a day with either 300 mg or 27.6 mg of D-chiro-inositol (3.6:1 or 40:1) for 12 weeks; 44 completed.^{12, 5} Pregnancy was recorded in 65.5% of the higher-D-chiro group against 25.9% of the 40:1 group, live birth in 55.2% against 14.8%.¹² Four of its ten authors list an ingredient company as their affiliation on the PubMed record. The two groups that have tested ratios point in opposite directions, neither trial is large, and no third group has repeated either.

Does the combination work better than myo-inositol alone?

Not shown. The 2026 umbrella review of 13 pooled analyses found that combination therapy did not consistently outperform a single form, and no outcome had high-quality evidence.¹⁴ The one direct comparison with myo-inositol alone found no significant difference at six months.³ In pregnancy, a 40:1-type mix with folic acid did not lower the rate of gestational diabetes against folic acid alone.¹³

What does the guideline say about types and ratios?

The 2023 international PCOS guideline, which assessed every trial for research integrity before pooling, makes four points. Inositol in any form could be considered, noting limited harm, potential improvement in metabolic measures and limited clinical benefit in ovulation, hirsutism or weight. Metformin should be considered over inositol for hirsutism and central adiposity. Specific types, doses or combinations cannot currently be recommended, for lack of quality evidence. And the regulatory status and quality control of inositol can differ from those of medicines, so doses and qualities may vary.¹ Its review's one myo-versus-D-chiro comparison rests on the 2011 trial flagged above and is not used here; the inositol and metformin trials are on inositol and metformin, what the trials compared.⁵ In Great Britain inositol has no authorised health claim for either form or any ratio.

How do you read the two numbers on a label?

As amounts a day against what the trials used, never as a verdict on a ratio. A label listing only myo-inositol matches the form in most of the trial evidence, including the guideline review's metformin comparisons; the myo-inositol arms above used 1.1 g to 4 g a day.⁵ A label adding a smaller amount of D-chiro-inositol matches the combination trials, 27.6 mg to 300 mg a day; a label listing D-chiro-inositol alone matches the two placebo trials, 600 to 1,200 mg a day. The head-to-head comparisons of these designs are the 50-woman and 56-woman trials and a 2015 three-arm comparison of 137 women, none longer than six months; the guideline ranks none.¹⁵ If you take a glucose-lowering medicine, are pregnant or in fertility treatment, ask your GP, pharmacist or clinic before adding either form; the trial side-effect record is on inositol side effects.

What we don't know

• No trial has tested whether the ratio of the two forms in blood says anything about what the ovary needs; the plasma figure has been an assumption, never an outcome.
• Neither placebo-controlled D-chiro-only trial ran longer than eight weeks; months of the form alone are untested against placebo.
• No trial has compared the 40:1 mix with myo-inositol alone on pregnancy or live birth.

Frequently asked questions

Is 40:1 the right ratio?

No trial establishes one. The 40:1 mix did not differ from myo-inositol alone at six months in the one trial that compared them, a mix with more D-chiro-inositol did better in the one trial from another group, and the guideline recommends no type, dose or combination.^{1, 3, 12}

Can you take D-chiro-inositol on its own?

It has two placebo-controlled trials alone, 64 women at 600 to 1,200 mg a day for six to eight weeks, at low certainty; a 2015 study of 48 women was retracted in 2026 and is not counted.^{5, 7} Anyone on a glucose-lowering medicine should ask their GP or pharmacist first: the trials measured insulin, and no interaction study exists.

Which is better for PCOS, myo-inositol or D-chiro-inositol?

Neither has been shown better. Myo-inositol carries most of the evidence, including the trials against metformin; the 137-woman comparison reported both improved cycle regularity, acne score and insulin resistance; the one trial claiming myo-inositol better for egg quality is under an expression of concern.^{5, 11, 15}

Sources

1. Teede HJ et al. Human Reproduction 2023. International guideline, 254 recommendations. PubMed 37580037
2. Nestler JE et al. New England Journal of Medicine 1999. Randomised trial, 44 women, 6 to 8 weeks. PubMed 10219066
3. Nordio M et al. European Review for Medical and Pharmacological Sciences 2012. Randomised trial, 50 women, 6 months. PubMed 22774396
4. NHS. Polyendocrine metabolic ovarian syndrome (PMOS). Page last reviewed 30 June 2026. nhs.uk/conditions/polyendocrine-metabolic-ovarian-syndrome-pmos
5. Fitz V et al. Journal of Clinical Endocrinology and Metabolism 2024. Systematic review for the 2023 guideline, 30 trials included (19 pooled), 2,230 women. PubMed 38163998
6. Iuorno MJ et al. Endocrine Practice 2002. Randomised trial, 20 women, 6 to 8 weeks. PubMed 15251831
7. Laganà AS et al. Archives of Gynecology and Obstetrics 2026. Retraction note, 2015 single-arm study of 48 women. PubMed 42449055
8. Isabella R, Raffone E. Journal of Ovarian Research 2018. Expression of concern, 2012 dose study of 54 women. PubMed 29976256
9. Nordio M et al. European Review for Medical and Pharmacological Sciences 2019. Randomised comparison, 56 women, 3 months. PubMed 31298405
10. European Review for Medical and Pharmacological Sciences 2026. Expression of concern, 2013 uncontrolled study of 20 women. PubMed 42237957
11. European Review for Medical and Pharmacological Sciences 2025. Expression of concern, 2011 trial of 84 women. PubMed 40748343
12. Mendoza N et al. Gynecological Endocrinology 2019. Randomised trial, 60 women, 12 weeks; four authors at an ingredient company. PubMed 30880505
13. Farren M et al. Diabetes Care 2017. Randomised trial, 240 women, to 24 to 28 weeks. PubMed 28325784
14. Duan M et al. Frontiers in Endocrinology 2026. Umbrella review of 13 pooled analyses. PubMed 41757236
15. Formuso C et al. Minerva Ginecologica 2015. Randomised comparison, 137 women, 6 months. PubMed 25670222

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