Inositol Side Effects: What Trials Reported and Who Should Ask First

In the PCOS (now called PMOS by the NHS) trials, at 2 to 4 g a day for up to six months, the recorded side effects of inositol were mild stomach ones, and stomach upsets were far less common on myo-inositol than on metformin. Most trials did not report side effects at all, and the 2023 international guideline says side effects and safety are not known for inositol in fertility treatment.^{1, 2} Glucose-lowering medicines, pregnancy and fertility treatment, under-18s and lithium are each a question for a GP, midwife, clinic or prescriber first. 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 with PCOS; 23 of 29 trials did not report adverse events.¹
• Largest trial: 464 pregnant women with PCOS, 2025, 4 g a day from 8 to 16 weeks until delivery.
• Strongest measured outcome: stomach side effects in six trials of 382 women, odds ratio 0.09 on myo-inositol against metformin, moderate certainty.
• Not tested: use beyond 12 months, an interaction with any medicine, and under-18s in a trial that still stands.

Sources checked on 12 October 2026.

What side effects did the inositol trials report?

The review written for the 2023 international PCOS guideline screened 43 trials for research integrity, set 13 aside, included 30 trials of 2,230 women and pooled 19 of them.¹ Its one side-effect comparison is myo-inositol against metformin: in six trials of 382 women, stomach side effects were about a tenth as common on myo-inositol (odds ratio 0.09, interval 0.02 to 0.37, moderate certainty), and the review calls the stomach effects that did occur typically mild and self-limiting.¹ The NHS, which now calls the condition polyendocrine metabolic ovarian syndrome (PMOS), previously PCOS, lists metformin as "a type 2 diabetes medicine to help tiredness and weight problems".³

One qualifier: the review's sensitivity analysis, limited to the two trials at low risk of bias, found no difference in stomach side effects, and "fewer than metformin" compares inositol with a medicine whose stomach effects are well known; it is not a count of what inositol itself causes.¹

The clearest dose signal comes from outside PCOS. A 2011 safety review, whose first author also wrote one of the inositol papers since retracted, found that only the 12 g a day amount produced mild stomach effects (nausea, wind and diarrhoea).⁴ A 2017 trial gave 38 adults 6 to 18 g a day for ten weeks.⁵ A 2014 pooling of seven depression trials (242 people) and four anxiety trials (70 people) found stomach upset marginally more common than on placebo (P = 0.06).⁶

What was never measured?

The guideline review notes that 23 of the 29 trials in its pooled comparisons did not report adverse events.¹ A 2019 pooling of 20 glucose trials in 1,239 people, whose included set could not be checked against the retractions, found adverse events mentioned in only 13, none serious.⁷ No trial has run beyond 12 months, and no formal interaction study has tested inositol with any medicine. Weight was measured as an outcome, not a side effect; that record is on does inositol help with weight loss. Several early trials in the pool behind "well tolerated" have since been retracted; the hub names them.

Can inositol lower blood sugar too far with diabetes medicines?

Nobody has tested it. The guideline review found benefit on some metabolic measures at low to very low certainty, and the 2019 pooling reported fasting glucose 0.44 mmol/l lower than control.^{1, 7} An additive effect with a medicine that also lowers blood glucose is plausible and unstudied. The NHS metformin page, reviewed 5 August 2026, warns of a higher risk of side effects on "more than one medicine for lowering blood sugar levels" and lists feeling sick, diarrhoea and tummy pain among its common side effects.⁹ The guideline's practice point is that women taking inositol "are encouraged to advise their healthcare professional".² On any glucose-lowering medicine the diabetes team or GP decides; the head-to-head trial record is on inositol and metformin, what the trials compared.

Is inositol safe in pregnancy, breastfeeding or fertility treatment?

On fertility, the guideline says inositol in any form "should be considered experimental therapy in women with PCOS with infertility", and its practice point reads "side effects and safety are not known for inositol".² For pregnancy, the largest trial is the 2025 Dutch one: 464 pregnant women with PCOS took 2 g of myo-inositol with folic acid twice daily, or placebo with folic acid, from 8 to 16 weeks until delivery; a composite of gestational diabetes, pre-eclampsia and preterm birth occurred in 25.0% on myo-inositol and 26.8% on placebo (relative risk 0.93), so no excess of the complications it measured, but it was not designed to find side effects.⁸ No breastfeeding data exist. The NHS pregnancy supplements page, reviewed 2 February 2026, says "if you need higher dose folic acid or other supplements, speak to a GP"; the midwife or fertility clinic decides anything taken during treatment.¹⁰

Can under-18s take inositol?

The evidence is too thin to say. A 2024 narrative review found eight studies in adolescents aged 12 to 19, two of them randomised, and called the benefit unclear; a 2021 trial of lean teenagers was retracted in 2026 and is not counted here.¹¹ The guideline's adolescent recommendations name the combined pill for irregular cycles and metformin as what "could be considered" for metabolic features, on low to moderate certainty evidence, and its no-type, no-dose, no-combination practice point covers adolescents as well as adults.^{2, 12} A teenager's symptoms are a GP question, not a label question.

Does inositol interact with other medicines or supplements?

Lithium has a mechanism behind the question. Laboratory work shows lithium lowers the myo-inositol concentration inside cells, and "inositol depletion" was proposed as the way the medicine works; the hypothesis "still remains to be either proven or refuted", and no clinical study has tested inositol supplements in people on lithium.¹³ The NHS lithium page says "there's not enough information to say that complementary medicines, herbal remedies and supplements are safe" and asks patients to tell a doctor or pharmacist about any supplement.¹⁴ Berberine: no trial has given the two together; its cautions are on berberine side effects and who should avoid it. Magnesium: the claim that inositol depletes it has no study behind it.

Why does an infant trial come up in searches?

A 2018 US trial in 638 infants born before 28 weeks was stopped early: myo-inositol given by injection and then feeding tube at 40 mg per kilogram every 12 hours for up to 10 weeks was followed by death or severe retinopathy in 29% against 21% on placebo, and death in 18% against 11%.¹⁵ It concerns intravenous and tube-fed dosing in intensive care, not adults taking inositol by mouth.

Why does the guideline mention quality control?

Its practice point 4.7.5 says discussion should include "that regulatory status and quality control of inositol in any form (like other nutrient supplements) can differ from those for pharmacological products and doses and qualities may vary".² In Great Britain inositol is a food supplement with no authorised health claim on the nutrition and health claims register.¹⁶ The label's serving and cautions direct the dose; the trials' 2 to 4 g a day is a fact about the trials, not an instruction.

What we don't know

• No trial has followed anyone on inositol for longer than 12 months.
• No trial has recorded thrush, hair loss or weight gain as an adverse event, so the reports that circulate can be neither confirmed nor excluded.
• No study has given inositol with metformin, insulin or lithium and measured the interaction.
• No trial has tested D-chiro-inositol alone beyond eight weeks for side effects.

Frequently asked questions

Who should not take inositol?

Four groups ask first: anyone on a glucose-lowering medicine (the diabetes team or GP), anyone pregnant, breastfeeding or in fertility treatment (the midwife or clinic), under-18s (the GP) and anyone on lithium (the prescriber).^{2, 9, 10, 14}

Can inositol cause thrush?

No trial has recorded it; the reports are forum ones. Recurrent thrush is a GP question whatever is being taken.

Does inositol make you tired or cause headaches?

Neither was recorded in the trials that reported side effects, and most reported none, so neither can be excluded.^{1, 7}

Can you take too much inositol?

The depression and anxiety trials used far higher amounts than the PCOS trials, and stomach upset was marginally more common than on placebo; a 2017 trial went to 18 g a day.^{5, 6} The label's serving is the limit on a product.

Sources

1. Fitz V et al. Journal of Clinical Endocrinology and Metabolism 2024. Systematic review for the 2023 guideline, 30 randomised trials included (19 pooled), 2,230 women. PubMed 38163998
2. Teede HJ et al. Human Reproduction 2023. International guideline, 254 recommendations. PubMed 37580037
3. NHS. Polyendocrine metabolic ovarian syndrome (PMOS). Page last reviewed 30 June 2026. nhs.uk/conditions/polyendocrine-metabolic-ovarian-syndrome-pmos
4. Carlomagno G, Unfer V. European Review for Medical and Pharmacological Sciences 2011. Narrative safety review. PubMed 21845803
5. Leppink EW et al. International Clinical Psychopharmacology 2017. Randomised trial, 38 adults, 10 weeks. PubMed 27824633
6. Mukai T et al. Human Psychopharmacology 2014. Pooled analysis of 11 randomised trials, 312 people. PubMed 24424706
7. Miñambres I et al. Clinical Nutrition 2019. Pooled analysis of 20 randomised trials, 1,239 people. PubMed 29980312
8. van der Wel AWT et al. JAMA 2025. Randomised trial, 464 pregnant women, to delivery. PubMed 40920401
9. NHS. Metformin. Page last reviewed 5 August 2026. nhs.uk/medicines/metformin
10. NHS. Pregnancy vitamins and supplements. Page last reviewed 2 February 2026. nhs.uk/pregnancy/keeping-well/pregnancy-vitamins-and-supplements
11. Sairally BZF et al. Journal of Pediatric Endocrinology and Metabolism 2024. Narrative review, 8 studies in adolescents. PubMed 38117862
12. Peña AS et al. BMC Medicine 2025. Adolescent recommendations of the 2023 guideline. PubMed 40069730
13. Harwood AJ. Molecular Psychiatry 2005. Review of the inositol-depletion hypothesis. PubMed 15558078
14. NHS. Taking lithium with other medicines and herbal supplements. Page last reviewed 9 August 2023 (review overdue). nhs.uk/medicines/lithium/taking-lithium-with-other-medicines-and-herbal-supplements
15. Phelps DL et al. JAMA 2018. Randomised trial, 638 infants born before 28 weeks, up to 10 weeks. PubMed 30357297
16. Department of Health and Social Care. Great Britain nutrition and health claims (NHC) register. gov.uk

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