Berberine

• Glycemic control (type 2 diabetes, prediabetes): Multiple meta-analyses of randomized trials indicate berberine may modestly lower HbA1c (~0.3–1.0%), fasting glucose, and HOMA-IR compared with placebo or as add‑on to standard therapy; magnitude is similar to some oral agents in small studies, but trial quality and heterogeneity vary (evidence: moderate). • Lipid management: Systematic reviews suggest reductions in total cholesterol, LDL-C, and triglycerides, with small increases in HDL-C; effects are enhanced when combined with lifestyle changes or statins (evidence: moderate). • Nonalcoholic fatty liver disease (NAFLD): Trials and meta-analyses report improvements in liver enzymes, hepatic fat content (imaging), and insulin resistance when used with diet/lifestyle; data are promising but vary by study design and dose (evidence: moderate). • Polycystic ovary syndrome (PCOS) with insulin resistance: Small RCTs suggest improvements in insulin sensitivity, lipids, and some androgen/ovulatory parameters, comparable in some outcomes to metformin; larger confirmatory trials are needed (evidence: moderate to emerging). • Weight and metabolic syndrome: Some meta-analyses show small reductions in body weight/BMI and waist circumference, particularly in insulin‑resistant individuals; effects are modest and inconsistent (evidence: emerging). • Diarrhea of infectious origin and IBS-D: Traditionally used; modern trials (mostly small) suggest benefit in acute infectious diarrhea and possibly IBS-D via antimicrobial and motility effects (evidence: emerging). • Blood pressure: Small decreases in systolic/diastolic BP have been observed in some studies, often alongside improvements in insulin resistance (evidence: emerging).

Common (often dose-related, 5–30% in trials): gastrointestinal upset (constipation or diarrhea), abdominal cramping, nausea, vomiting, gas, bitter taste. Occasional: headache, dizziness, fatigue, decreased appetite. Less common: hypotension, bradycardia, skin rash or pruritus. Metabolic: hypoglycemia when combined with glucose-lowering medications. Rare but serious: idiosyncratic liver enzyme elevations or drug-induced liver injury (case reports); marked bradycardia or palpitations in sensitive individuals; neonatal jaundice risk if exposed in late pregnancy or via breastfeeding. Most GI effects improve by dose reduction, dividing doses, or taking with meals.

Typical supplemental doses studied: 500–1,500 mg/day of berberine (commonly as berberine HCl), divided 2–3 times daily with meals. In clinical trials: • Glycemic/lipid/NAFLD endpoints: 900–1,500 mg/day for 8–24 weeks (often alongside diet/lifestyle). • PCOS with insulin resistance: 500 mg three times daily for 3 months in small RCTs. • Diarrhea/IBS-D: lower divided doses have been used short-term in smaller studies. Onset of metabolic effects may require 4–12 weeks; GI tolerability often improves by starting low and dividing doses. Optimal dosing varies by individual and condition; consult a clinician, especially when taking prescription medications.

• Pregnancy: Avoid—berberine may cross the placenta and has been associated with neonatal jaundice risk (bilirubin displacement). • Breastfeeding: Avoid—risk of kernicterus in newborns; berberine and related alkaloids can enter breast milk. • Neonates/infants, especially with jaundice or G6PD deficiency: Contraindicated. • Concomitant use with strong P-gp/CYP3A4 substrate drugs with narrow therapeutic index (e.g., digoxin, cyclosporine, tacrolimus): Avoid unless closely supervised due to potential for elevated drug levels. • Diabetes treated with insulin or secretagogues (e.g., sulfonylureas): Use only with medical supervision due to hypoglycemia risk. • Hypotension, bradyarrhythmias: Use caution; may mildly lower BP/HR. • Significant hepatic or renal impairment: Use caution; rare reports of hepatotoxicity and altered drug clearance. • Pre‑operative period: Stop at least 2 weeks before surgery due to potential effects on glucose control and drug metabolism.