Oleoylethanolamide for Health & Longevity - Quick Reference Sheet

Oleoylethanolamide for Health & Longevity

Created on 08/25/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5 Audit

A fat-derived gut signal, also sold as a capsule. About a dozen short trials, mostly in people carrying extra weight or fatty liver, link it to smaller waistlines, less body fat without lean-tissue loss, lower blood fats and fasting blood sugar. Lean adults have little documented room to gain, and the appetite-damping action threatens muscle. Nothing beyond four months studied. (Full Review)

Protocol

Standard dose
250 mg daily
Threshold at which pooled body-weight, body mass index and fasting-glucose effects reached significance. Trials span 125–600 mg/day.
Best time of day
With the largest fat-containing meal
With or shortly before it; endogenous release is meal-triggered.
Single versus split dosing
Two 125 mg capsules daily
The most common schedule. Splitting suits the short plasma residence.
Time to effect
Body mass index
At least 8 weeks
Required at least eight weeks in pooled analysis.
Triglycerides and glucose
By 8 weeks
Triglyceride and glucose shifts appeared by eight weeks.
Appetite
15 minutes to hours
Appetite and incretin changes after a single dose.

Benefits

Contraindications
  • Pregnant or breastfeeding women
  • Current or past restrictive eating disorder (anorexia nervosa, bulimia nervosa, avoidant/restrictive food intake disorder), or body mass index below 18.5 kg/m²
  • Unintentional weight loss exceeding 5% of body weight in six months, or diagnosed sarcopenia (appendicular lean mass index below 7.0 kg/m² in men, 5.5 in women)
  • Decompensated liver disease (Child-Pugh Class B or C), or unexplained ALT above three times the upper limit of normal
  • Untreated moderate-to-severe obstructive sleep apnea (apnea–hypopnea index ≥ 15 events/hour)
  • Children and adolescents under 18
  • Known allergy to olive-derived or oleic-acid-derived ingredients
Key Interactions
  • GLP-1 receptor agonists and dual incretin agonists (semaglutide, liraglutide, tirzepatide)
  • Fibrates (fenofibrate, gemfibrozil, bezafibrate)
  • Glucose-lowering drugs (metformin, sulfonylureas such as glimepiride and gliclazide, insulin)
  • Orlistat (over-the-counter alli, prescription Xenical)
  • Palmitoylethanolamide
  • Supplements with additive metabolic effects (fish oil, conjugated linoleic acid, berberine, glucomannan)
  • Calorie-restricted diets
  • Alcohol

Risk & Side Effects

  • High:
  • Medium: Unintended reduction in energy and carbohydrate intake
  • Low: Incompletely characterized tolerability and absent long-term safety data; inconsistent effect on high-density lipoprotein cholesterol; higher endogenous levels track worse metabolic and sleep states
  • Speculative: Peroxisome proliferation from sustained PPAR-α activation; locomotor slowing and malaise at high doses; raised anandamide tone through competition for FAAH

Monitoring

Marker Target Why
Fasting triglycerides < 80 mg/dL (< 0.9 mmol/L) The blood lipid with the highest-certainty response
Fasting glucose 75–86 mg/dL (4.2–4.8 mmol/L) Detects the glycemic shift seen in prediabetes and fatty-liver trials
Fasting insulin 2–5 µIU/mL More sensitive than glucose to early insulin resistance
HOMA-IR < 1.0 Composite index of insulin resistance, the outcome with the largest pooled effect
hs-CRP < 0.5 mg/L The inflammation marker with the largest pooled response
ALT and AST ALT < 20 U/L (women < 17 U/L); AST < 20 U/L Fatty-liver trials showed the clearest response here
Waist circumference < 94 cm men, < 80 cm women The body measurement with the largest pooled effect
Body composition (fat mass, fat-free mass) No established target; track change from own baseline, fat mass falling and fat-free mass flat Confirms that any weight change is fat rather than lean tissue
Hemoglobin A1c 4.8–5.2% Shows whether short-term glucose shifts persist over three months

Cadence: Baseline draw before starting; repeat metabolic panel at 8 weeks, then at 6 months, then every 6–12 months if continued. Waist circumference and body composition monthly.

Qualitative Assessment

  • Hunger, fullness and sweet craving, rated daily on a simple 0–10 scale
  • Fatigue and general energy through the afternoon
  • Mood stability and social engagement
  • Digestive comfort in the first two weeks
  • Whether protein and total food intake are being met without conscious effort