After 12 kg weight loss, the hunger hormone ghrelin increased and satiety hormones leptin and insulin decreased regardless of whether people ate a higher-protein/fiber or lower-satiety diet — with ghrelin tracking muscle mass changes and leptin/insulin tracking fat mass changes.
12 kg lost, but ghrelin still increased (P<0.001)Neither high-protein/fiber nor standard diets could prevent the hunger-promoting hormonal adaptation after weight loss
What the researchers found
After 7 weeks of very-low-energy dieting producing 12 kg weight loss (P < 0.001), participants were randomized to higher-satiety food (HSF, more protein/fiber, less fat) or lower-satiety food (LSF) diets for 24-week weight maintenance. Key findings:
- Diet composition made no difference: HSF and LSF groups showed identical changes in fasting ghrelin, leptin, insulin, and glucose
- Weight regain was modest: only 1.3 kg (P = 0.004) over 24 weeks
- Hormonal adaptations persisted: ghrelin increased, leptin/insulin/glucose decreased vs. pre-diet (all P < 0.001)
- Peptide YY (PYY) did not differ from pre-diet levels
- Body composition tracking: ghrelin inversely correlated with fat-free mass changes (P = 0.002); leptin and insulin positively correlated with fat mass changes (P < 0.05)
Why it matters
Weight regain after dieting is one of the biggest challenges in obesity treatment. The hormonal adaptations that drive regain — increased ghrelin and decreased leptin — are powerful and persistent. This study shows that even a well-designed high-protein, high-fiber diet cannot override these hormonal changes. This has important implications for understanding why dietary approaches alone often fail for long-term weight maintenance and supports the rationale for pharmacological interventions (like GLP-1RA drugs) that can counteract these hormonal adaptations.
The numbers in context
N=82; -12 kg (p<0.001); +1.3 kg regain; ghrelin up; leptin, insulin, glucose down (p<0.001); PYY unchanged; HSF vs LSF: no hormone differences
How the study worked
Registered randomized controlled trial (ISRCTN 67529475). 82 men and women with obesity completed a 7-week very-low-energy diet (VLED), then were randomized to consume isoenergetic higher-satiety or lower-satiety foods with different macronutrient compositions for 24 weeks of weight maintenance. Fasting appetite-related hormones (ghrelin, leptin, insulin, PYY) and glucose were measured at multiple timepoints. Body composition (fat mass and fat-free mass) was assessed. Associations between hormone changes and body composition changes were analyzed.
Who was studied
82 men and women with obesity undergoing structured weight loss and maintenance
What this study cannot tell us
Moderate sample size (82 participants) limits subgroup analyses. Only fasting hormone levels were measured — postprandial peptide responses (which may differ more between diets) were not assessed. The 24-week maintenance period may be too short to capture longer-term hormonal adaptation. Dietary compliance was self-reported. PYY was measured only in the fasting state, where it may be less informative than postprandial PYY responses.
How to read the evidence
This is a registered randomized controlled trial — strong study design. The 82-participant sample provides adequate power for the primary between-group comparison, and the longitudinal design with multiple timepoints strengthens the hormonal tracking analysis. The negative finding (no diet effect) is informative and well-supported.
When this study was published
Published in 2021, this study remains relevant as the hormonal challenges of weight maintenance continue to be a central topic in obesity research, particularly in understanding why pharmacological interventions are often needed alongside dietary changes.
The bigger picture
This study illustrates a fundamental challenge in obesity: the body's hormonal defense of its higher weight setpoint. The finding that diet macronutrient composition doesn't affect these hormonal adaptations helps explain why dietary approaches alone have high failure rates for long-term weight maintenance. It also provides context for why GLP-1 receptor agonists — which directly override the appetite signaling these hormones mediate — have been so successful for sustained weight management.
Questions still open
- Would GLP-1 receptor agonists prevent the adverse hormonal adaptations observed after diet-induced weight loss?
- Do postprandial peptide hormone responses differ between high-protein and lower-protein diets even when fasting levels are the same?
- Could preserving fat-free mass during weight loss prevent ghrelin from increasing?
Common questions
Why does the body increase hunger hormones after weight loss?
Why didn't a higher-protein diet help prevent these hormonal changes?
Read the original research
Post-weight loss changes in fasting appetite- and energy balance-related hormone concentrations and the effect of the macronutrient content of a weight maintenance diet: a randomised controlled trial.
European journal of nutrition, 60(5), 2603-2616
Citation
Näätänen, Mari; Kolehmainen, Marjukka; Laaksonen, David E; Herzig, Karl-Heinz; Poutanen, Kaisa; Karhunen, Leila. (2021). Post-weight loss changes in fasting appetite- and energy balance-related hormone concentrations and the effect of the macronutrient content of a weight maintenance diet: a randomised controlled trial.. European journal of nutrition, 60(5), 2603-2616. https://doi.org/10.1007/s00394-020-02438-3