Inositol Research Database
The clinical studies behind our guides — organised by dose, duration, population and outcome. Every entry links to its PubMed source, and the summaries keep study findings separate from their limitations.
A study design describes how research was done; it does not establish certainty or a universal dose. Read the result alongside its population and limitations. These entries do not rank products or treatments.
Showing 33 of 33 studies
| Study | Type | Population | Dose / protocol | Duration | Key finding |
|---|---|---|---|---|---|
A 3.6:1 myo-inositol to D-chiro-inositol ratio and antioxidant-based food supplement before IVF improves fertility in women with PCOS: a pilot observational retrospective cohort study Belchín Fernández P, Calvente V, Gómez Roso MJ, et al. · 2026 · J Obstet Gynaecol | Retrospective cohort (pilot) | 92 women with PCOS (Rotterdam criteria) undergoing IVF-ICSI | MYO:DCI 3.6:1 + antioxidants ≥1 month before ovarian stimulation | ≥1 month pre-IVF | Pilot cohort: higher fertilization rate (77.7% vs 71.6%, P=0.03) and fewer cycles without a good-quality blastocyst in the supplemented group. Oocyte yield and MII rates were comparable. Observational design limits causal claims. Limitations: Retrospective pilot comparison with 92 participants; confounding and combined antioxidants prevent isolating an inositol-ratio effect. Fertilization and embryo measures do not establish a live-birth benefit. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Effects of inositol in women with polycystic ovary syndrome: an umbrella review of meta-analyses from randomized controlled trials Duan M, Yang M, Li C, et al. · 2026 · Front Endocrinol (Lausanne) | Umbrella review of 13 meta-analyses | PCOS women; 13 meta-analyses, 85 evidence items | Inositol (MI, DCI, or combined) vs placebo/folic acid | — | Inositol improved LH, SHBG, androstenedione, HOMA-IR, fasting insulin, triglycerides, ovulation (RR 2.75) and live birth (RR 2.29) vs placebo/folic acid. But GRADE found no high-quality evidence (18.9% moderate, 41.1% very low) and DCI monotherapy should be used with caution; MI/MI+FA looked superior for metabolic and reproductive outcomes. Limitations: Meta-analyses can contain overlapping trials and heterogeneous outcomes. Certainty varies by outcome, and the authors found no high-quality evidence items. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
The effect of myo-inositol supplementation on gestational diabetes mellitus prevention: a systematic review and meta-analysis Poyatos-León R, Martínez-Vizcaíno V, Sequí-Domínguez I, Sanabria-Martínez G · 2026 · Am J Obstet Gynecol | SR & meta-analysis | 4,765 women without preexisting diabetes (12 RCTs) | Myo-inositol vs placebo or standard care, during pregnancy or preconception | Varied | Myo-inositol substantially reduced the risk of gestational diabetes across 12 RCTs (4,765 women). Most trials rated moderate to high quality with some bias concerns. Limitations: Pooled pregnancy populations and protocols vary. The positive average should be interpreted alongside the large negative 2025 trial in PCOS pregnancy; it does not establish benefit of a particular commercial blend. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Metformin and Myo-Inositol: A Comparative Analysis Russo M, Oliva MM, Nordio M, et al. · 2026 · Gynecol Obstet Invest | Narrative review | Comparative review (PCOS focus) | — | — | Argues myo-inositol has a more acceptable safety profile than metformin (which carries GI side effects and rare lactic acidosis risk) and is a naturally occurring molecule. Authors note metformin's safety in pregnancy remains controversial. Interpret with caution: several authors are affiliated with inositol manufacturers/EGOI-PCOS. Limitations: Narrative interpretation rather than a randomized comparison; reported manufacturer affiliations require attention. Naturally occurring does not establish safety or equivalence to prescribed treatment. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Efficacy of inositol supplementation for the prevention and treatment of gestational diabetes in pregnant women: Results from an umbrella meta-analysis Lin L, Zhou L, Zhang X, et al. · 2026 · Int J Gynaecol Obstet | Umbrella meta-analysis | 19 studies, 17,932 participants | Inositol (myo or D-chiro) vs placebo | — | Inositol linked to lower GDM risk (RR 0.42), less insulin therapy, hypertension, preterm birth and neonatal hypoglycemia. Umbrella analyses pool heterogeneous prevention and management trials — and a large 2025 JAMA RCT found no benefit in PCOS pregnancy, so treat the direction as promising but contested. Limitations: Umbrella estimates can overlap underlying trials and mix prevention with management. The reported participant total should not be assumed to represent a separate set of unique participants; the summary also needs to account for the negative PCOS-pregnancy trial. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Oral myo-inositol plus D-chiro-inositol (3.6:1) reduces insulin resistance pathway biomarkers in acne-involved skin among subjects with metabolic comorbidities: A gene expression study Vaccaro M, Emanuele E, Minoretti P, et al. · 2026 · Neuro Endocrinol Lett | Open-label, pre-post biopsy study | 45 adults with acne and PCOS or metabolic syndrome | MI/DCI 1,100 mg + 300 mg daily (3.6:1) | 12 weeks | Exploratory evidence: MI/DCI increased FOXO1 and reduced MTOR and IGF1 in acne-involved skin, with clinical improvement in 82.2% of participants. Uncontrolled single-arm design — useful mechanistic support for the acne/IR link, not proof of clinical efficacy. Limitations: Uncontrolled, exploratory gene-expression study with 45 participants and mixed comorbidities. It cannot separate treatment effects from other changes or establish general acne efficacy. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Comparison of metformin with inositol versus metformin alone in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials Kelly FA, et al. · 2025 · Endocrine | SR & meta-analysis | 388 women with PCOS (6 RCTs) | Metformin + inositol vs metformin alone | 3–6 months | Combination improved cycle regularity (RR 1.56) and hirsutism and LH/FSH; no significant difference in glucose or HOMA-IR. Limitations: Small combination trials and varied protocols; changes in selected outcomes do not establish a universal add-on regimen or live-birth benefit. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Myo-inositol Supplementation to Prevent Pregnancy Complications in Polycystic Ovary Syndrome: A Randomized Clinical Trial van der Wel AWT, Frank CMC, Bout-Rebel R, et al. · 2025 · JAMA | RCT (double-blind) | 464 pregnant women with PCOS (13 Dutch hospitals) | Myo-inositol 2 g + folic acid 0.2 mg twice daily vs placebo (folic acid only) | 8–16 weeks' gestation until delivery | Negative result: myo-inositol did not reduce the composite of gestational diabetes, preeclampsia or preterm birth in PCOS pregnancy (25.0% vs 26.8%; RR 0.93, P=0.67). The largest rigorous RCT in this setting — important counterweight to the positive meta-analyses. Limitations: Applies to the tested myo-inositol regimen during pregnancy in participants with PCOS; it does not answer every non-pregnancy PCOS outcome or test each branded combination. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Efficacy of N-Acetylcysteine in Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis Viña I, Viña JR, Carranza M, Mariscal G · 2025 · Nutrients | SR & meta-analysis | 2,515 women with PCOS (22 studies) | N-acetylcysteine vs placebo, metformin or clomiphene | Varied | NAC increased progesterone and endometrial thickness; no significant differences in estradiol, SHBG or FSH. Two authors are affiliated with a supplement company. Limitations: Heterogeneous NAC trials, selected outcomes and reported supplement-company affiliations limit certainty. Findings do not establish universal benefit of NAC or any specific brand. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines Fitz V, et al. · 2024 · J Clin Endocrinol Metab | SR & meta-analysis | 2,230 participants with PCOS across 30 trials | Myo-inositol, D-chiro-inositol and combinations across 13 comparisons | Varied across trials | The review informing the international guideline concluded that overall evidence for inositol in PCOS is limited and inconclusive. Some metabolic measures may improve; effects on other outcomes remain uncertain. Limitations: Formulations, comparators and outcomes varied; only 19 trials were pooled. The review does not establish a universal 40:1 regimen or a superior branded product. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Different supplements improve insulin resistance, hormonal functions, and oxidative stress on overweight and obese women with polycystic ovary syndrome: a systematic review and meta-analysis Ren X, et al. · 2024 · Front Endocrinol | SR & meta-analysis | Overweight and obese women with PCOS | Various supplements compared | — | Several supplements improved insulin resistance and hormonal markers in overweight/obese PCOS; effect sizes vary by supplement. Limitations: Different supplements, small studies and variable quality limit comparative conclusions; biochemical changes do not automatically establish meaningful clinical benefits. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials Greff D, et al. · 2023 | SR & meta-analysis | Women with PCOS (pooled RCTs) | Various inositol protocols | Varied | This review reported improvements in selected PCOS outcomes and fewer adverse events than metformin, and its authors concluded favourably about inositol. Limitations: Trial quality, varied formulations and outcome definitions constrain the conclusion. A later guideline-informing review judged the overall evidence limited and inconclusive; absence of a difference does not itself prove clinical equivalence. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome International PCOS Guideline Network · 2023 | Clinical guideline | Women with PCOS | Inositol among the options considered | — | Inositol may be considered according to individual preferences, with possible metabolic benefits but limited clinical benefit. Specific forms, doses or combinations cannot currently be recommended; its use for infertility is considered experimental. Limitations: Recommendations reflect limited and uncertain evidence. Ingredient guidance does not establish efficacy or quality of an individual commercial product. Source checked: Primary guideline text. This is not an independent clinical appraisal. |
Comparison of nutritional supplements in improving glycolipid metabolism and endocrine function in polycystic ovary syndrome: a systematic review and network meta-analysis Hu X, et al. · 2023 · PeerJ | SR & meta-analysis | Women with PCOS (network meta-analysis of supplements) | Nutritional supplements compared (incl. chromium, inositol, omega-3) | — | In the network meta-analysis, chromium improved insulin and HOMA-IR; supplement effects on metabolic markers vary by agent. Limitations: Network comparisons include indirect evidence, different supplements and possible publication bias. Rankings of markers do not establish the best treatment for an individual. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
A randomized controlled trial comparing myoinositol with metformin versus metformin monotherapy in polycystic ovary syndrome Nazirudeen R, et al. · 2023 · Clin Endocrinol | RCT | 53 overweight/obese women with PCOS (18–35 y) | Myo-inositol + metformin vs metformin alone | 6 months | Better cycle regularity and quality-of-life scores with the combination; pregnancy rates equal between arms. Limitations: Small, selected 53-participant trial with background metformin. It cannot establish pregnancy benefit or justify unsupervised changes to medication. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation Statement US Preventive Services Task Force · 2023 · JAMA | Recommendation statement | People planning or possibly becoming pregnant | Folic acid 400–800 mcg daily | — | USPSTF recommends 400–800 mcg of folic acid daily for anyone planning or possibly becoming pregnant (A recommendation). Limitations: This recommendation concerns folic acid for neural-tube-defect prevention, not inositol efficacy or an automatic substitution with every other folate form. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
The effect of magnesium alone or its combination with other supplements on the markers of inflammation, OS and metabolism in women with polycystic ovarian syndrome (PCOS): A systematic review Li R, et al. · 2022 · Front Endocrinol | Systematic review | 363 participants with PCOS across 9 RCTs | Magnesium alone or combined with other supplements | Varied | Magnesium alone did not show significant improvements in the reviewed inflammatory, oxidative-stress or metabolic markers. Some combinations with other nutrients improved selected markers. Limitations: Combination studies cannot isolate magnesium’s contribution; few studies examined magnesium alone. Results do not establish a general PCOS benefit for every magnesium product. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Effectiveness of inositol, metformin and their combination in women with PCOS undergoing assisted reproduction: systematic review and meta-analysis Unanyan A, et al. · 2022 · Gynecol Endocrinol | SR & meta-analysis | 4,668 women with PCOS undergoing assisted reproduction (35 RCTs) | Metformin, inositol, or combinations | — | No significant inositol vs control difference in clinical pregnancy; metformin improved clinical pregnancy in ART; combination arms too few to pool. Limitations: Heterogeneous assisted-reproduction trials and too few combination arms; clinical pregnancy is distinct from live birth, and product-specific superiority is not established. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Inositol Treatment for PCOS Should Be Science-Based and Not Arbitrary Roseff S, Montenegro M · 2020 · Int J Endocrinol | Narrative review / commentary | Women with PCOS | Discussion of formulations; no new treatment allocation | Not a new trial | The authors argue for a 40:1 formulation and criticise arbitrary inositol combinations, drawing on earlier clinical and mechanistic work. Limitations: This is an interpretive review, not a new randomized trial or independent certainty assessment. Later international guidance does not recommend a specific universal type, dose or combination. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials Facchinetti F, Orrù B, Grandi G, Unfer V · 2019 · Gynecol Endocrinol | SR & meta-analysis | 355 women with PCOS (6 RCTs directly comparing metformin vs myo-inositol) | Metformin vs myo-inositol | Short-term (trials 1994–2017) | No significant difference between metformin and myo-inositol on fasting insulin, HOMA-IR, testosterone or SHBG over the short term — key context for inositol vs metformin comparisons. Limitations: Six small short-term trials; a non-significant difference does not prove equivalence or justify replacing prescribed metformin. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
The Effects of Probiotics or Synbiotics Supplementation in Women with Polycystic Ovarian Syndrome: a Systematic Review and Meta-Analysis of Randomized Clinical Trials Heshmati J, et al. · 2019 · Probiotics Antimicrob Proteins | SR & meta-analysis | Women with PCOS (7 RCTs, 236 women) | Probiotics or synbiotics | Varied | Clinical effect judged negligible and not clearly significant — a second-layer decision, not an automatic add. Limitations: Small, heterogeneous probiotic and synbiotic trials. Findings cannot be transferred automatically to a different strain combination or commercial product. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
The 40:1 myo-inositol/D-chiro-inositol plasma ratio is able to restore ovulation in PCOS patients: comparison with other ratios Nordio M, Basciani S, Camajani E · 2019 · Eur Rev Med Pharmacol Sci | Small comparative clinical trial | 56 women with PCOS (8 per ratio group) | Seven formulations / ratios; 2 g total inositols twice daily | 3 months | In this small seven-group trial, the authors reported better ovulatory and selected hormonal results in the 40:1 group than in the other ratio groups. Limitations: Only 56 participants, eight per group, and a short follow-up. The abstract does not establish robust randomization or blinding. The result cannot establish an ideal ratio for everyone or a live-birth benefit. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Inositol for subfertile women with polycystic ovary syndrome Showell MG, Mackenzie-Proctor R, Jordan V, Hodgson R, Farquhar C · 2018 · Cochrane Database Syst Rev | Cochrane review | 1,472 subfertile women with PCOS (13 trials) | Myo-inositol, mostly as pre-treatment to IVF | Varied | Evidence rated low to very low quality; authors could not confirm improvements in live birth or clinical pregnancy rates. Limitations: Very low-quality fertility evidence with imprecision and bias concerns; effects on live birth and clinical pregnancy remain uncertain. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility Morley LC, Tang T, Yasmin E, Norman RJ, Balen AH · 2017 · Cochrane Database Syst Rev | Cochrane review | 4,451 women with PCOS (48 RCTs) | Metformin, clomiphene citrate, rosiglitazone, pioglitazone, D-chiro-inositol | Varied | Metformin may improve live birth vs placebo (low-quality evidence) with more GI side effects. For D-chiro-inositol and the other non-metformin agents, no included studies reported the primary outcomes — no conclusions could be drawn. Limitations: Most evidence concerns metformin. No primary-outcome conclusions could be drawn for D-chiro-inositol; do not transfer the metformin findings to inositol. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials Unfer V, Facchinetti F, Orrù B, et al. · 2017 · Endocr Connect | SR & meta-analysis | Women with PCOS (9 RCTs; 247 cases, 249 controls) | Myo-inositol alone or combined with D-chiro-inositol | Varied | Meta-analysis of 9 RCTs: myo-inositol (alone or with D-chiro) significantly lowered fasting insulin and HOMA-IR in women with PCOS. Modest sample size. Limitations: Modest pooled sample with different regimens. Metabolic and hormonal markers do not establish clinical benefit for every PCOS phenotype or commercial formulation. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
myo-Inositol supplementation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: a prospective, randomized, placebo-controlled study D'Anna R, Scilipoti A, Giordano D, et al. · 2013 · Diabetes Care | RCT | 220 pregnant women with a parent with type 2 diabetes | Myo-inositol 2 g + folic acid 200 mcg twice daily, from the end of the first trimester | Until delivery | Gestational diabetes onset was significantly lower with myo-inositol (6% vs 15% in the placebo group). Limitations: Open-label prevention study in a selected family-history group; findings may not generalise to PCOS pregnancy or to other formulations. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone Nordio M, Proietti E · 2012 · Eur Rev Med Pharmacol Sci | RCT | 50 overweight participants with PCOS | Myo-inositol + D-chiro-inositol vs myo-inositol alone | 6 months | Both myo-inositol alone and the combination improved metabolic parameters by six months, without significant between-group differences at that point. The combination showed earlier improvement at three months. Limitations: Small trial using metabolic markers, not proof of fewer future cases of metabolic syndrome. The title and authors’ first-line recommendation are stronger than the measured long-term disease evidence. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
The effect of a combination therapy with myo-inositol and a combined oral contraceptive pill versus a combined oral contraceptive pill alone on metabolic, endocrine, and clinical parameters in polycystic ovary syndrome Minozzi M, Costantino D, Guaraldi C, Unfer V · 2011 · Gynecol Endocrinol | Clinical study (open-label) | 155 women with PCOS | OCP alone vs OCP + myo-inositol 4 g/day | 12 months | Adding myo-inositol 4 g/day to an oral contraceptive improved hirsutism score, reduced hyperinsulinaemia and androgens, and improved the lipid profile vs OCP alone. Open-label design. Limitations: Open-label study of one combined pill and one myo-inositol regimen. It was not a contraceptive-reliability trial and does not establish compatibility with every contraceptive method. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Myo-inositol rather than D-chiro-inositol is able to improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial Unfer V, Carlomagno G, Rizzo P, Raffone E, Roseff S · 2011 · Eur Rev Med Pharmacol Sci | RCT | 84 euglycemic women with PCOS undergoing ICSI | Myo-inositol 2 g twice daily vs D-chiro-inositol 0.6 g twice daily | — | More mature oocytes and top-quality embryos with myo-inositol than with high-dose D-chiro-inositol. Caution: the journal issued an Expression of Concern for this paper in 2025 — treat as preliminary. Limitations: The journal issued an Expression of Concern in 2025. Treat the findings with particular caution; oocyte and embryo measures do not establish live-birth effects. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial Costantino D, Minozzi G, Minozzi E, Guaraldi C · 2009 · Eur Rev Med Pharmacol Sci | RCT (double-blind) | 42 women with PCOS | Myo-inositol + folic acid vs folic acid alone | — | Myo-inositol significantly lowered total and free testosterone, triglycerides, blood pressure and the insulin response to oral glucose vs folic acid alone. Small sample. Limitations: Small 42-participant trial; short-term metabolic and ovulatory measurements do not establish long-term fertility or branded-product benefits. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome Genazzani AD, Lanzoni C, Ricchieri F, Jasonni VM · 2008 · Gynecol Endocrinol | RCT | Overweight patients with PCOS | Myo-inositol supplementation | — | Myo-inositol improved hyperinsulinemia and hormonal parameters in overweight PCOS. Limitations: Small selected population and surrogate hormonal/metabolic outcomes; results do not establish pregnancy or live-birth benefits. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction Papaleo E, Unfer V, Baillargeon JP, et al. · 2007 · Gynecol Endocrinol | Uncontrolled pilot study | 25 women with PCOS-related oligo/amenorrhea | Myo-inositol with folic acid; 2 g twice daily | 6 months | Among 25 participants, 22 had at least one spontaneous menstrual cycle and 18 maintained ovulatory activity during follow-up; 10 pregnancies were reported. Limitations: No concurrent randomized control group and only 25 participants. Changes during follow-up cannot establish that the supplement caused the pregnancies or that the rates generalise. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome Nestler JE, Jakubowicz DJ, Reamer P, et al. · 1999 · N Engl J Med | RCT (double-blind, placebo-controlled) | 44 obese women with PCOS | D-chiro-inositol 1,200 mg once daily vs placebo | 6–8 weeks | Landmark trial: 19 of 22 women ovulated on D-chiro-inositol vs 6 of 22 on placebo (P<0.001). Insulin AUC fell substantially, free testosterone dropped, and blood pressure and triglycerides improved. A foundational study, though note it used DCI monotherapy at 1,200 mg — a dose and format most modern products do not replicate. Limitations: Small 44-participant trial of high-dose D-chiro-inositol alone; the regimen differs substantially from most modern myo/DCI combination products. Source checked: PubMed abstract and citation. This is not an independent clinical appraisal. |
This database is a desk-research summary of peer-reviewed sources (PubMed/PMC), maintained under our editorial policy. We have not independently graded the certainty of every outcome. Any certainty assessment shown is attributed to its source. Study findings do not replace professional medical advice.