Concerning Leptin Levels in Anorexia Nervosa
Leptin levels below 3 ng/mL (or μg/L) are consistently concerning in anorexia nervosa patients, as all patients with severe malnutrition demonstrate values under this threshold. 1
Critical Threshold Values
All anorexia nervosa patients at diagnosis demonstrate leptin levels under 3 ng/mL, with mean values around 2.2-3.6 ng/mL compared to 9-19 ng/mL in normal-weight controls 1, 2
Leptin levels are reduced by approximately 77% compared to healthy controls, representing severe depletion that correlates with the degree of malnutrition 3
Values below 5.6 ng/mL are pathologically low, as this represents the mean level in anorexia nervosa cohorts with BMI around 16 kg/m² 4
Clinical Context and Interpretation
The concerning aspect is not just the absolute value, but the relationship to body weight:
Anorexia nervosa patients paradoxically have inappropriately high leptin levels for their percent ideal body weight (%IBW) when compared to the expected %IBW/leptin curve 5
This relative elevation (despite absolute low values) may contribute to resistance to dietary treatment by blunting the normal physiologic response to underweight status 5
Leptin levels remain detectable even below 5% body fat, showing linear correlation with progressive weight loss, but drop to 20-30% below baseline during acute starvation 1, 6
Prognostic Indicators
Leptin response to refeeding predicts recovery potential:
Patients with BMI below 14.5 kg/m² may show no increase in leptin despite weight gain, indicating a critical threshold below which leptin regulation fails 1
Short-term refeeding (3 days) does not restore leptin levels or circadian rhythm in anorexia nervosa patients, unlike the rapid rise seen in healthy individuals after fasting 3
After partial weight recovery (BMI increasing from 15.3 to 17.1 kg/m²), leptin increases modestly (from 2.2 to 3.3 ng/mL) but remains significantly below normal range 1
Key Clinical Pitfalls
Do not use leptin as a standalone marker for nutritional assessment:
While IGF-I normalizes completely after partial recovery, leptin remains suppressed, indicating it reflects true adipose stores rather than recent energy intake 1
Circadian rhythm of leptin is completely abolished in anorexia nervosa, contrasting with preserved cortisol rhythms 3
The correlation between leptin and BMI becomes non-significant after refeeding, limiting its utility for monitoring recovery 2