Naringenin is a citrus compound from food or oral extract. One small trial found improvement in blood fats and liver-fat grade in overweight adults with fatty liver. Weight and insulin claims rest on that trial plus one case; lifespan claims rest on animals. Main constraint is grapefruit-type drug handling and laboratory block of a heart-reset channel at high blood levels. (Full Review)

Protocol

Tehran fatty-liver regimen

100 mg twice daily

Isolated naringenin for 4 weeks in ultrasound NAFLD

Time of day

With daytime meals

Before lunch and dinner; half-life about 3 hours

Pennington extract regimen

300 mg twice daily

Whole-orange extract; single doses 150–900 mg were safe

Time to effect

Blood fats

4 weeks

Lipid changes measured in the fatty-liver trial

Liver-fat grade

4 weeks

Ultrasound grade; liver-injury enzymes did not fall

Body mass and visceral fat

4 weeks

Trial at 4 weeks; one case also reported loss at 8 weeks

Benefits

Medium: Improved atherogenic lipid profile

Low: Reduced hepatic steatosis grade; lower body mass and visceral fat; lower central arterial stiffness

Speculative: Higher insulin sensitivity and acute metabolic rate; longer lifespan and slower brain aging; less vascular senescence; greater muscle endurance in aging; lower cancer-cell viability; lower inflammatory and oxidative-stress markers; lower depression-like behavior

Contraindications

Narrow-therapeutic-index CYP3A4 or OATP drugs (tacrolimus, cyclosporine, some antiarrhythmics) unless a clinician is tracking drug levels

Congenital long-QT syndromes, baseline QTc above about 450–470 ms, or combination QT-prolonging therapy

Known citrus-flavonoid allergy

Pregnancy and lactation

Decompensated cirrhosis (Child-Pugh C) or advanced kidney failure (eGFR <30 mL/min/1.73 m²)

Key Interactions

CYP3A4 substrate medicines (simvastatin, atorvastatin, felodipine, buspirone, some benzodiazepines)

OATP substrates (fexofenadine, some statins, aliskiren)

P-gp substrates (digoxin, some direct oral anticoagulants)

QT-prolonging medicines (amiodarone, dofetilide, moxifloxacin, some antipsychotics, methadone)

Oral estrogens and tamoxifen

Over-the-counter antihistamines (fexofenadine) and acetaminophen

Other flavonoids and berberine

Metformin, berberine, and high-dose niacin

Risk & Side Effects

Medium: Altered exposure of CYP3A4 and OATP substrate drugs

Low: QTc interval prolongation at high exposure

Speculative: Weak estrogen-receptor activity; uncharacterized long-term high-dose toxicity; blunting of exercise-induced redox adaptation

Monitoring

Marker	Target	Why
Fasting triglycerides	<100 mg/dL	Primary lipid signal in the fatty-liver trial
LDL cholesterol	<70–100 mg/dL, individualized	Atherogenic fraction that moved in the trial
HDL cholesterol	>50 mg/dL (men), >60 mg/dL (women)	Rose versus placebo at 4 weeks
ALT	<25–30 U/L (men), <19–25 U/L (women)	Safety and liver-fat context
AST	<25–30 U/L	Safety companion to ALT
Fasting insulin	3–8 μIU/mL	Case-level insulin drop; metabolic context
Fasting glucose	70–85 mg/dL	Metabolic context
hs-CRP	<1.0 mg/L	Inflammatory tone
QTc (ECG)	<430 ms (men), <450 ms (women)	Heart-reset channel overlap at high peak

Cadence: Baseline fasting panel and, if high-dose or QT-active drugs are present, an electrocardiogram; repeat the same fasting panel at 4 weeks, then every 3–6 months if use continues; recheck QTc after dose increases or when a new QT-active drug is added

Qualitative Assessment

Afternoon energy and post-meal fullness
Training endurance and recovery (mouse signal, human unproven)
New muscle aches if a statin is co-used
Palpitations, syncope (fainting), or new-onset dizziness (stop and obtain an ECG)

Naringenin for Health & Longevity

Protocol

Benefits

Risk & Side Effects

Monitoring

Qualitative Assessment