Inositol: Benefits, Dosage, PCOS & Guide

Quick Facts

Inositol is one of the most well-researched yet underappreciated compounds in integrative medicine. It spans hormonal health, metabolic function, and neuroscience, with rigorous clinical trial data supporting its use for conditions ranging from polycystic ovary syndrome (PCOS) to panic disorder. Despite being classified as a sugar alcohol, it behaves nothing like table sugar; instead, it functions as a critical secondary messenger inside your cells, relaying signals from insulin receptors and neurotransmitter systems alike.

This guide covers everything the evidence actually says: what inositol is, how it works at a molecular level, the clinical data behind its major uses, how to dose it properly, and what the emerging research looks like.

Watch: Inositol in 60 Seconds

What Is Inositol?

Inositol is a six-carbon cyclic sugar alcohol (cyclohexane-1,2,3,4,5,6-hexol) that was once classified as vitamin B8. Although it lost its official vitamin status when researchers discovered the body can synthesize it endogenously from glucose-6-phosphate, inositol remains an essential part of human physiology, and dietary intake is still important for maintaining optimal tissue concentrations.

The Nine Stereoisomers

Inositol exists in nine distinct stereoisomeric forms, differing only in the spatial orientation of their hydroxyl groups. Of these nine, two are biologically dominant:

• Myo-inositol (MI): The most abundant form, accounting for roughly 99% of total inositol in human cells. It is the primary form involved in insulin signaling, neurotransmitter modulation, and cell membrane structure.
• D-chiro-inositol (DCI): A minor form produced by enzymatic conversion (epimerization) of myo-inositol in specific tissues. It plays a specialized role in glycogen synthesis and androgen production in the ovaries.

The remaining seven stereoisomers (scyllo-, muco-, neo-, allo-, epi-, cis-, and L-chiro-inositol) are present in trace amounts and have limited known biological roles, though scyllo-inositol has attracted some research interest in Alzheimer’s disease.

Where Inositol Comes From

The body produces approximately 2–4 g of myo-inositol per day, primarily in the kidneys. Dietary intake provides an additional 0.25–1 g/day from sources such as:

• Fruits: Cantaloupe, citrus (especially grapefruit)
• Grains: Whole wheat, bran, oats
• Legumes: Beans, peas, lentils
• Nuts: Almonds, walnuts, peanuts
• Organ meats: Liver, heart

In plants, inositol is predominantly stored as phytic acid (inositol hexaphosphate), which has limited bioavailability until liberated by phytase enzymes during digestion.

The Role of Inositol as a Secondary Messenger

Inositol’s primary biological function is as a precursor to phosphoinositides — a family of signaling lipids embedded in cell membranes. When a hormone or neurotransmitter binds to its receptor on the cell surface, an enzyme called phospholipase C (PLC) cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into two secondary messengers:

1. Inositol 1,4,5-trisphosphate (IP3): Triggers calcium release from the endoplasmic reticulum, activating a cascade of intracellular events.
2. Diacylglycerol (DAG): Activates protein kinase C (PKC), which phosphorylates downstream target proteins.

This signaling mechanism is not niche. It is one of the most fundamental communication pathways in human biology, affecting insulin action, serotonin signaling, dopamine regulation, thyroid hormone function, and oocyte maturation.

How Inositol Works

Understanding inositol’s mechanisms helps explain why a single compound can have meaningful effects across such different conditions.

Insulin Signaling and the PI3K Pathway

When insulin binds to its receptor on a cell surface, it triggers a signaling cascade involving phosphoinositide 3-kinase (PI3K). PI3K phosphorylates PIP2 to produce PIP3, which in turn activates Akt (protein kinase B), the master switch for glucose uptake, glycogen synthesis, and metabolic regulation.

Myo-inositol is the substrate for this entire process. When myo-inositol levels are depleted (as they are in insulin-resistant states), the PI3K/Akt pathway becomes sluggish. Cells respond poorly to insulin, glucose uptake falls, and the pancreas compensates by producing even more insulin (hyperinsulinemia). This is the core metabolic dysfunction in PCOS, type 2 diabetes, and metabolic syndrome.

By supplementing myo-inositol, you effectively restore the raw material needed for proper insulin signal transduction. Downstream effects include:

• Improved GLUT4 translocation to the cell membrane (increased glucose uptake)
• Reduced compensatory hyperinsulinemia
• Decreased hepatic glucose output
• Improved lipid profiles

Neurotransmitter Modulation

The same phosphoinositide signaling system underpins neurotransmission. Serotonin (5-HT2) receptors, muscarinic acetylcholine receptors, and certain dopamine receptor subtypes all signal through PLC and the IP3/DAG pathway.

In the brain, inositol concentrations are remarkably high, approximately 100-fold greater than in plasma. This reflects its importance for neural function. When brain inositol levels are reduced (as has been observed in cerebrospinal fluid studies of patients with depression), neurotransmitter signaling becomes impaired, particularly serotonin reuptake and postsynaptic serotonin receptor sensitivity.

High-dose inositol supplementation appears to restore this signaling, which is why it has demonstrated effects in conditions characterized by serotonergic dysfunction: panic disorder, obsessive-compulsive disorder, and depression.

Ovarian Function

In the ovaries, myo-inositol mediates follicle-stimulating hormone (FSH) signaling, which is critical for follicular development and oocyte maturation. D-chiro-inositol, by contrast, mediates insulin-driven androgen (testosterone) synthesis in thecal cells.

In women with PCOS, a phenomenon called the “inositol paradox” occurs: excessive insulin drives overconversion of myo-inositol to D-chiro-inositol in the ovaries, depleting the myo-inositol pool that is needed for FSH signaling while simultaneously increasing the DCI pool that drives androgen production. The result is a double hit: impaired ovulation and excess testosterone.

How does inositol help with PCOS?

Inositol is the most evidence-supported non-pharmaceutical intervention for polycystic ovary syndrome — a 2017 meta-analysis by Unfer et al. confirmed that myo-inositol supplementation produces statistically significant improvements in ovulation rates, insulin sensitivity, testosterone levels, and metabolic markers across multiple randomized controlled trials, with efficacy comparable to metformin and significantly fewer side effects [1]. Research shows inositol’s effectiveness in PCOS is strong enough that several international gynecological guidelines now recognize inositol as a legitimate therapeutic option for PCOS management.

The Evidence

A 2017 meta-analysis by Unfer et al., one of the most cited papers in this space, pooled data from multiple randomized controlled trials and concluded that myo-inositol supplementation in women with PCOS led to statistically significant improvements in [1]:

• Ovulation rates: Restoration of regular menstrual cycles and spontaneous ovulation
• Insulin sensitivity: Reduced fasting insulin, lower HOMA-IR scores
• Hormonal balance: Decreased total and free testosterone, reduced LH/FSH ratio
• Metabolic markers: Improved fasting glucose, triglycerides, and total cholesterol

The effect sizes were clinically meaningful, not marginal. Many of the trials compared myo-inositol directly to metformin (the standard pharmaceutical treatment for insulin-resistant PCOS) and found comparable efficacy with significantly fewer side effects.

How It Addresses the Root Cause

Most pharmaceutical treatments for PCOS address symptoms: oral contraceptives suppress androgens, metformin forces glucose uptake, spironolactone blocks androgen receptors. Inositol, by contrast, targets the upstream signaling dysfunction, restoring the insulin sensitivity and FSH responsiveness that are impaired in PCOS.

This is an important distinction. When insulin sensitivity improves through restored phosphoinositide signaling, the downstream hormonal consequences correct themselves: the ovaries produce less testosterone, the LH/FSH ratio normalizes, follicles mature properly, and ovulation resumes.

What to Expect

Clinical trials typically show measurable improvements within 3–6 months of consistent supplementation at 2–4 g/day of myo-inositol. Menstrual regularity often improves first (within 1–3 cycles), followed by hormonal changes visible on bloodwork, and finally improvements in metabolic markers.

How does inositol support mental health?

Inositol demonstrates clinically meaningful psychiatric benefits at high doses — analysis of controlled trials confirms significant effects for panic disorder and OCD, with the psychiatric applications of inositol supported by some of the most compelling clinical comparisons in nutritional psychiatry research. The working hypothesis is that inositol’s psychiatric effects are mediated through the phosphoinositide second-messenger system, amplifying serotonergic signaling through 5-HT2A and 5-HT2C receptors at the 12–18 g/day doses used in clinical trials.

Panic Disorder

In a landmark double-blind, controlled, crossover trial, Palatnik et al. (2001) compared inositol at 18 g/day to fluvoxamine (an SSRI) for the treatment of panic disorder. The results were striking: inositol was as effective as fluvoxamine in reducing the frequency and severity of panic attacks, with significantly fewer side effects [2].

Patients on inositol experienced an average reduction of 4 panic attacks per week, compared to 2.4 for fluvoxamine. Importantly, the inositol group reported no nausea, sexual dysfunction, or other SSRI-typical adverse effects.

Obsessive-Compulsive Disorder

Fux et al. (1996) conducted a double-blind, placebo-controlled crossover trial of inositol at 18 g/day for OCD. Patients showed significant improvement on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) compared to placebo, with a mean reduction of approximately 5.9 points, a clinically meaningful effect [3].

While the sample size was small (13 patients), the crossover design strengthened the findings, and the effect size was comparable to what is typically seen with SSRIs in similar study designs.

Depression

Several smaller trials have explored inositol for major depressive disorder. Results have been mixed, with some showing significant improvement over placebo, others showing no difference. The current consensus is that inositol may have modest antidepressant effects in some individuals, but it is not a reliable standalone treatment for clinical depression.

Where inositol may have a clearer role in depression is as an adjunct to SSRIs, potentially enhancing serotonergic signaling through a complementary mechanism (restoring second-messenger function rather than blocking reuptake).

Mechanism in Mental Health Conditions

The working hypothesis is that inositol’s psychiatric effects are mediated through the same phosphoinositide second-messenger system described above. Serotonin 5-HT2A and 5-HT2C receptors, which are central to the pharmacology of SSRIs, panic regulation, and OCD, signal through PLC-mediated IP3 production. By increasing intracellular inositol availability, high-dose supplementation may amplify or normalize this transduction pathway.

This mechanistic explanation is consistent with the fact that inositol’s effects in mental health appear to be dose-dependent, with significant effects emerging only at 12–18 g/day, concentrations high enough to meaningfully alter brain inositol pools.

Myo-Inositol vs D-Chiro-Inositol

One of the most common questions about inositol supplementation is whether to take myo-inositol, D-chiro-inositol, or both. The answer depends on the context, but the science points clearly toward a specific ratio.

The 40:1 Ratio

In healthy human plasma, the ratio of myo-inositol to D-chiro-inositol is approximately 40:1. This ratio is maintained by an insulin-dependent epimerase enzyme that converts myo-inositol to D-chiro-inositol in specific tissues at specific rates.

Research by Colazingari et al. (2013) demonstrated that supplementing with the combined 40:1 ratio of MI to DCI produced superior outcomes in IVF compared to DCI alone [4]. In fact, DCI supplementation alone at high doses actually worsened oocyte quality, likely because it disrupted the delicate inositol balance in the ovaries, further depleting the myo-inositol pool needed for FSH signaling.

When to Use Which

• Myo-inositol alone (2–4 g/day): Appropriate for most PCOS patients, general insulin sensitization, and mental health applications. This is the most studied form and the one with the broadest evidence base.
• MI + DCI at 40:1 ratio: The preferred approach for PCOS patients who are also trying to conceive, as it optimizes both insulin sensitivity and ovarian function simultaneously. A typical dose is 4,000 mg MI + 100 mg DCI per day.
• D-chiro-inositol alone: Generally not recommended. While DCI has specific roles in glycogen synthesis, supplementing it in isolation, especially at high doses, can paradoxically impair ovarian function and oocyte quality.

Why the Ratio Matters

The reason the ratio matters so much comes back to the ovarian inositol paradox. In PCOS, the epimerase enzyme in the ovaries is upregulated by chronic hyperinsulinemia, converting too much myo-inositol into D-chiro-inositol locally. Supplementing with high-dose DCI makes this worse. Supplementing with MI (or the 40:1 combination) helps restore the balance.

Dosage Guidelines

Inositol dosing varies substantially depending on the intended use. Here are the evidence-based ranges from clinical trials.

For PCOS and Insulin Resistance

• Standard dose: 2,000–4,000 mg (2–4 g) of myo-inositol per day
• With DCI: 4,000 mg MI + 100 mg DCI (40:1 ratio)
• Divided into: Two doses per day (morning and evening), taken with meals
• Timeline to effect: 3–6 months for full hormonal and metabolic benefits

For Mental Health (Panic Disorder, OCD)

• Target dose: 12,000–18,000 mg (12–18 g) per day
• Titration: Start at 2–4 g/day and increase by 2–4 g every 3–5 days to minimize GI discomfort
• Divided into: Two to three doses per day
• Timeline to effect: 4–6 weeks at full dose

For Fertility and IVF

• Standard dose: 4,000 mg MI per day (or 4,000 mg MI + 100 mg DCI)
• Begin: At least 3 months before IVF cycle to allow oocyte maturation effects
• Continue: Through stimulation and retrieval

General Titration Advice

Because inositol powder at high doses can cause transient gastrointestinal discomfort (bloating, loose stools), it is advisable to start at the lower end of the dose range and increase gradually. Most individuals tolerate 4 g/day without issue from day one. When working up to 12–18 g/day for psychiatric applications, adding 2–4 g every several days allows the GI system to adapt.

Safety and Side Effects

Inositol has one of the best safety profiles of any supplement studied in clinical trials. It is a naturally occurring compound present in virtually every cell in the body, and supplemental doses, even at the high end, are well-tolerated by most people.

Side Effects

• Mild GI discomfort: The most common side effect, typically observed at doses above 12 g/day. Symptoms include bloating, loose stools, flatulence, and mild nausea. These usually resolve within a few days or with dose reduction.
• No serious adverse events: Across dozens of clinical trials involving thousands of patients, no serious adverse events have been attributed to inositol supplementation.
• No hormonal disruption in men: Despite its effects on androgen levels in women with PCOS (where androgens are pathologically elevated), inositol does not suppress normal testosterone levels in men.

Safety in Pregnancy

Myo-inositol has been studied specifically in pregnant women. D’Anna et al. (2013) conducted a randomized controlled trial of myo-inositol supplementation in pregnant women at risk for gestational diabetes and found it to be safe and well-tolerated, with no adverse effects on maternal or fetal outcomes [5]. Several subsequent trials have confirmed this safety profile.

Given that inositol is a natural component of the human diet and is present in breast milk, its safety during pregnancy and lactation is considered well-established at standard supplemental doses (2–4 g/day).

Drug Interactions

Inositol has no well-documented clinically significant drug interactions. However, because it shares mechanistic territory with SSRIs (both modulate serotonergic signaling), individuals taking SSRIs should discuss high-dose inositol use with their prescriber, not because of a known dangerous interaction, but out of prudent caution when combining agents with overlapping mechanisms.

Inositol for Fertility and IVF

Beyond its role in PCOS-related fertility, inositol has attracted significant research attention in the context of assisted reproduction.

Egg Quality and Oocyte Maturation

Myo-inositol is critical for oocyte maturation because it mediates FSH signaling within the follicular cells. Adequate MI concentrations in the follicular fluid are associated with higher-quality oocytes, better fertilization rates, and improved embryo development.

Colazingari et al. (2013) demonstrated that the combined therapy of myo-inositol plus D-chiro-inositol at the 40:1 ratio improved IVF outcomes, including the number of mature oocytes retrieved and the quality of resulting embryos, compared to DCI alone [4]. This finding was particularly important because it clarified that it is not simply “more inositol” that helps, but the right balance of inositol forms.

Practical Recommendations for IVF

Women undergoing IVF are commonly advised to begin myo-inositol supplementation (4 g/day) at least 3 months before their stimulation cycle. This timeframe aligns with the approximately 90-day window of oocyte development (from primordial follicle recruitment to mature oocyte). Starting earlier allows the inositol to influence the full maturation cycle.

Some fertility clinics have now incorporated inositol into their standard pre-IVF protocols, particularly for patients with PCOS or diminished ovarian reserve.

Other Emerging Uses

The research on inositol continues to expand into new therapeutic areas. Several of these emerging applications are backed by early but promising clinical data.

Gestational Diabetes Prevention

D’Anna et al. (2013) conducted a key trial showing that myo-inositol supplementation (4 g/day) starting in the first trimester significantly reduced the incidence of gestational diabetes mellitus (GDM) in pregnant women with a family history of type 2 diabetes. The incidence of GDM was 6% in the myo-inositol group compared to 15.3% in the placebo group, a clinically and statistically significant reduction [5].

This finding has prompted multiple follow-up trials, and a growing body of evidence now supports myo-inositol as a safe, low-cost intervention for GDM prevention in at-risk populations.

Metabolic Syndrome

Because inositol improves insulin sensitivity, reduces hyperinsulinemia, and favorably modifies lipid profiles, it has natural applicability to metabolic syndrome. Early studies have shown improvements in fasting glucose, triglycerides, HDL cholesterol, and waist circumference with myo-inositol supplementation. Larger trials are underway.

Skin Health and Acne

Hormonal acne, particularly acne driven by hyperandrogenism in PCOS, often improves with inositol supplementation as a downstream consequence of androgen reduction. Some dermatology-focused studies have reported clinically meaningful improvements in acne severity and sebum production after 3–6 months of myo-inositol therapy in women with PCOS.

Thyroid Function

Emerging evidence suggests myo-inositol may support thyroid function, particularly in the context of subclinical hypothyroidism and autoimmune thyroiditis (Hashimoto’s). Inositol is involved in TSH signaling in the thyroid gland through the same phosphoinositide pathway. Preliminary trials combining myo-inositol with selenium have shown improvements in TSH levels and thyroid antibody markers, though this area requires further study.

How to Take Inositol

Powder vs. Capsules

Inositol is most commonly and practically taken as a powder. At therapeutic doses (2–18 g/day), capsule form is impractical; you would need to swallow 8–70+ capsules daily. Myo-inositol powder has a mildly sweet taste (it is technically a sugar alcohol, after all), making it easy to mix into water, juice, smoothies, or other beverages.

Timing and Meals

• With food: Taking inositol with meals is generally recommended, as it integrates naturally with the postprandial insulin signaling process it is designed to support.
• Divided doses: Split your daily dose into two or three servings. For PCOS doses (4 g/day), take 2 g with breakfast and 2 g with dinner. For higher psychiatric doses, divide into two or three approximately equal portions spread throughout the day.
• Consistency matters: Inositol’s effects are cumulative and require sustained daily intake. Skipping doses or irregular use significantly reduces efficacy.

Storage

Myo-inositol powder is stable at room temperature and does not require refrigeration. Keep it in a cool, dry place away from direct sunlight. It has a long shelf life and is not prone to degradation under normal storage conditions.

Frequently Asked Questions

Is inositol the same as vitamin B8?

Historically, inositol was classified as vitamin B8. It lost this designation when researchers determined the body can synthesize it endogenously. However, the term “vitamin B8” still appears in some older references and supplement labels. Functionally, inositol behaves similarly to a B-vitamin (it is a water-soluble cofactor involved in essential metabolic processes), but it is no longer officially classified as one.

How long does it take for inositol to work?

This depends on the condition being treated. For PCOS, menstrual cycle improvements often appear within 1–3 months, with full hormonal and metabolic benefits emerging over 3–6 months. For panic disorder and OCD, effects at high doses (12–18 g/day) typically become apparent within 4–6 weeks. For fertility and IVF preparation, a minimum of 3 months is recommended before an IVF cycle to influence oocyte maturation.

Can men take inositol?

Yes. While most research has focused on women with PCOS, inositol’s insulin-sensitizing and neurotransmitter effects are not sex-specific. Men can benefit from inositol for insulin resistance, metabolic health, and mental health applications. There is no evidence that inositol lowers normal testosterone levels in men. Its androgen-reducing effects are specific to the pathological hyperandrogenism seen in PCOS.

Can I take inositol with metformin?

Yes. Multiple clinical trials have used myo-inositol alongside metformin in PCOS patients, and the combination appears safe. Some studies suggest additive benefits on insulin sensitivity. However, because both compounds affect glucose metabolism, blood sugar should be monitored, and the combination should be discussed with a healthcare provider, particularly in patients with type 2 diabetes who may be at risk for hypoglycemia.

Is inositol safe to take long-term?

Current evidence supports long-term safety. Inositol is a naturally occurring compound in the body and diet. Clinical trials lasting 6–12 months have reported no cumulative toxicity or adverse effects. Many women with PCOS take inositol continuously for years. That said, periodic review with a healthcare provider is always good practice for any long-term supplementation.

Does inositol cause weight gain?

No. Despite being classified as a sugar alcohol, inositol at supplemental doses does not contribute meaningful calories and does not cause weight gain. In fact, by improving insulin sensitivity and reducing hyperinsulinemia, inositol may support weight management efforts, particularly in individuals with insulin-resistant conditions like PCOS or metabolic syndrome, where hyperinsulinemia promotes fat storage.

Why Choose WHYZ

WHYZ Inositol is a single-ingredient product with no fillers, no artificial additives, and no proprietary blends. It contains pure myo-inositol — the form used in the majority of clinical PCOS and metabolic health research. Every batch is third-party tested for purity and potency.

• Pure myo-inositol — the clinically studied form at research-grade purity
• No blends, no fillers — no added D-chiro-inositol ratios unless you want them
• Third-party tested — Certificate of Analysis available for every batch
• Transparent labeling — what’s on the label is what’s in the container

Related Ingredients

• Monk Fruit Extract — Zero-calorie sweetener for a low-glycemic lifestyle
• Stevia — Zero-calorie sweetener with blood pressure support; metabolic health companion

Related Guides

• Inositol for PCOS: Complete Evidence-Based Guide: A focused deep dive into the clinical trial data, dosing protocols, and practical advice for using inositol to manage PCOS.

Source in Bulk

Looking to source bulk inositol powder for manufacturing or formulation? WHYZ supplies wholesale quantities with COA documentation and free evaluation samples. Request a quote →

References

1. Unfer V, Facchinetti F, Orrù B, Giordani B, Nestler J. Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials. Endocr Connect. 2017;6(8):647-658. doi:10.1530/EC-17-0243. PMID: 29042448

2. Palatnik A, Frolov K, Fux M, Benjamin J. Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder. J Clin Psychopharmacol. 2001;21(3):335-339. doi:10.1097/00004714-200106000-00014. PMID: 11386498

3. Fux M, Levine J, Aviv A, Belmaker RH. Inositol treatment of obsessive-compulsive disorder. Am J Psychiatry. 1996;153(9):1219-1221. doi:10.1176/ajp.153.9.1219. PMID: 8780431

4. Colazingari S, Treglia M, Najjar R, Bevilacqua A. The combined therapy myo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is able to improve IVF outcomes. Results from a randomized controlled trial. Arch Gynecol Obstet. 2013;288(6):1405-1411. doi:10.1007/s00404-013-2855-3. PMID: 23708322

5. D’Anna R, Scilipoti A, Giordano D, et al. 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. Diabetes Care. 2013;36(4):854-857. doi:10.2337/dc12-1371. PMID: 23340885

6. van der Wel AWT, Frank CMC, Bout-Rebel R, et al. Myo-inositol supplementation to prevent pregnancy complications in polycystic ovary syndrome: a randomized clinical trial. JAMA. 2025. doi:10.1001/jama.2025.5467. PMID: 40920401

7. Lin L, Chen G, Qiao X, et al. Comparative efficacy and safety of metformin, anti-obesity agents, and myoinositol in improving IVF/ICSI outcomes in PCOS: a systematic review and network meta-analysis. J Ovarian Res. 2024;17(1):232. doi:10.1186/s13048-024-01554-w. PMID: 39702393

8. Payer J, Jackuliak P, Kužma M, et al. Supplementation with myo-inositol and selenium improves the clinical conditions and biochemical features of women with autoimmune thyroiditis. Front Endocrinol (Lausanne). 2022;13:1094439. doi:10.3389/fendo.2022.1094439. PMID: 36465640

9. Asimakopoulos G, Pergialiotis V, Antsaklis P, et al. Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus in overweight and obese pregnant women: a systematic review. Arch Gynecol Obstet. 2024;310(4):1757-1769. doi:10.1007/s00404-024-07680-8. PMID: 39141124