High-Protein Diet Reduces Hunger After Weight Loss, Linked to Gut Peptide PYY and Endocannabinoid Changes | Research

The takeaway

A high-protein/moderate-carbohydrate diet reduced hunger perception nearly 34 months after weight loss, with the effect linked to increased gut peptide PYY and the endocannabinoid 2-AG.

56.6% hunger reduction
The high-protein diet reduced hunger perception by over half compared to the moderate-protein diet, even 34 months after weight loss, linked to increased PYY and 2-AG levels.

What the researchers found

The high-protein/moderate-carbohydrate (HP/MCHO) diet reduced hunger perception by 56.6% compared to the moderate-protein/high-carbohydrate (MP/HCHO) diet (p<0.05), measured approximately 34 months after initial weight loss.

The decreased hunger on the HP/MCHO diet was significantly associated with increased 2-AG (endocannabinoid) concentrations (p<0.05) and increased PYY (satiety peptide) concentrations (p<0.01). However, ad libitum food intake, insulin resistance (HOMA-IR), and incremental areas under the curve for GLP-1 and PYY were not significantly different between the two diet conditions.

Why it matters

Weight regain after dieting is extremely common, and persistent hunger is a key driver. This study shows that maintaining a higher protein intake can reduce hunger even years after weight loss, and identifies specific biological mechanisms — involving the gut peptide PYY and the endocannabinoid system — that mediate this effect. Understanding these pathways could help design better long-term weight management strategies.

How the study worked

Crossover study in a 48-hour respiration chamber with 38 participants (22 female, 16 male; mean age 64.5 years; BMI 28.9 kg/m²) approximately 34 months after weight loss. Participants were fed in energy balance with either a HP/MCHO diet (25:45:30 protein:carb:fat) or MP/HCHO diet (15:55:30). Researchers measured endocannabinoids and related compounds, postprandial GLP-1 and PYY levels, subjective hunger and satiety, and ad libitum food intake.

What this study cannot tell us

The sample size of 38 participants is relatively small. The study measured hunger perception but found no difference in actual ad libitum food intake, raising questions about the practical significance of the hunger reduction. The respiration chamber setting may not reflect real-world eating behavior. The study was conducted in post-obese older adults, so results may not generalize to younger populations or those currently losing weight. The 48-hour measurement window may not capture longer-term effects.

How to read the evidence

This is a controlled crossover study conducted in a respiration chamber, providing well-controlled metabolic data. However, the small sample size (38 participants) and the disconnect between hunger perception and actual food intake somewhat limit the clinical implications.

When this study was published

Published in 2019 as part of the PREVIEW study, a large European diabetes prevention project. The findings contribute to ongoing understanding of macronutrient effects on appetite regulation.

The bigger picture

This study connects three important areas: dietary macronutrient composition, gut peptide signaling (PYY, GLP-1), and the endocannabinoid system. While GLP-1 receptor agonists are transforming obesity treatment pharmacologically, understanding how diet naturally modulates these same peptide pathways could inform complementary nutritional strategies for weight management. The interaction between PYY and endocannabinoids in appetite regulation is a growing area of research.

Questions still open

If hunger is reduced but actual food intake isn't different, does the high-protein diet truly help with long-term weight maintenance?
Could the PYY-endocannabinoid interaction be targeted pharmacologically to enhance appetite suppression?
Do these hunger-reducing effects of high-protein diets persist indefinitely, or do they diminish over longer periods?

Common questions

Does eating more protein really help control hunger after weight loss?

This study found that a diet with 25% of calories from protein reduced hunger perception by nearly 57% compared to a 15% protein diet, even almost 3 years after weight loss. The effect was linked to changes in gut peptides (PYY) and endocannabinoids (2-AG) — biological signals that help regulate appetite.

What is PYY and how does it affect appetite?

PYY (peptide YY) is a gut peptide released after eating that signals satiety — the feeling of being full. Higher PYY levels are associated with reduced hunger. In this study, the high-protein diet increased PYY concentrations, which correlated with the participants feeling less hungry.

Read the original research

Effects of a High-Protein/Moderate-Carbohydrate Diet on Appetite, Gut Peptides, and Endocannabinoids-A Preview Study.

Nutrients, 11(10)

View on PubMed ↗Publisher’s paper ↗

Citation

Tischmann, Lea; Drummen, Mathijs; Gatta-Cherifi, Blandine; Raben, Anne; Fogelholm, Mikael; Hartmann, Bolette; Holst, Jens J; Matias, Isabelle; Cota, Daniela; Mensink, Ronald P; Joris, Peter J; Westerterp-Plantenga, Margriet S; Adam, Tanja C. (2019). Effects of a High-Protein/Moderate-Carbohydrate Diet on Appetite, Gut Peptides, and Endocannabinoids-A Preview Study.. Nutrients, 11(10). https://doi.org/10.3390/nu11102269