Science Update

Investigating Collagen Peptides Supplementation on Appetite and GLP-1 Status: A Randomized Controlled Trial

Collagen peptides (CP) have long been associated with connective tissue support and musculoskeletal health. A new randomized, double-blind, placebo-controlled crossover trial by Reynolds and colleagues suggests that CP supplementation may also influence post-exercise appetite physiology, specifically through changes in glucagon-like peptide-1 (GLP-1), insulin, and ghrelin. These findings are consistent with prior research showing that protein ingestion, including whey, milk, and gelatin, can reduce post-exercise energy intake and elevate GLP-1 and insulin concentrations. Although the observed effect size in this specific RCT was modest, the hormonal pattern is intriguing and adds a new dimension to practitioners' consideration of collagen supplementation. 

To date, this is the first study to examine whether short-term CP supplementation affects appetite regulation after exercise in humans. The participants were 15 physically active females (mean age 23), all free from medications or conditions that could influence appetite. Eleven used hormonal contraception and completed both trial arms in the same contraceptive phase; four were naturally menstruating and completed trials in the early follicular phase. This design helps control for sex hormone-related variability in appetite and metabolic signaling. 

Study Design in Brief

Participants consumed either 15 g/day of bovine CP or a taste-matched placebo (water with flavoring) for seven days, with a minimum seven-day washout between conditions. On day 7 of each arm, they arrived fasted, consumed a standardized breakfast, and completed a 45-minute cycling session at ~55% Wmax. Ten minutes after exercise, they consumed their final supplement.  

Exactly 60 minutes later, they were provided an ad libitum pasta meal and instructed to eat ‘until they were comfortably full.’ Energy intake was measured by weighing food before and after the meal. Subjective appetite ratings and gastrointestinal (GI) symptoms were collected repeatedly, and blood samples were taken at multiple time points to assess glucose and appetite-related hormones: GLP-1, insulin, ghrelin, leptin, peptide YY (PYY), cholecystokinin (CCK), and soluble dipeptidyl peptidase4 (sDPP4). One participant’s blood draws were unsuccessful, so hormonal analyses include n = 14. 

Key Findings of the RCT 

1. Collagen peptides reduced energy intake (modestly, but significantly).

Participants consumed ~10% fewer calories (~41 kcal) at the ad libitum pasta meal in the CP condition compared with placebo (P = 0.037). Eating rates did not differ, and subjective appetite ratings (hunger, fullness, desire to eat, prospective consumption) were unchanged. This suggests that the reduction in intake occurred without participants experiencing less hunger and was a physiological rather than a perceptual driver.

The magnitude of reduction (~41 kcal) is smaller than that observed in previous protein-based appetite clinical studies, which used higher doses of whey or milk proteins (~100 kcal). This may reflect the lower protein serving size (15 g versus 20 to 30 g), collagen’s unique amino acid profile, differences in supplement energy content, sex-specific responses, or differences in exercise modality and meal composition. 

2. GLP-1 and insulin increased after CP supplementation.

Total GLP-1 concentrations were significantly higher in the CP condition at every post-supplement and post-mealtime point (P < 0.001), except at 0 minutes (the fasted pre-breakfast baseline) and 100 minutes (immediately post-exercise, before supplementation). Notably, GLP-1 remained elevated for two hours after the meal, suggesting that the effect was not simply a response to caloric intake. Insulin also rose sharply, with an ~80% higher peak compared with placebo.

3. Ghrelin and leptin were lower with CP supplementation. 

Ghrelin is a fast-acting hunger hormone, and leptin is the satiety hormone involved in ongoing energy balance. Both hormones showed lower overall concentrations in the CP condition (P ≤ 0.032). The authors note that the decrease in leptin is less associated with satiety or subsequent energy intake, “likely in part because leptin concentrations do not tend to change until several hours post food intake, with fluctuations more associated with longer-term regulation of energy balance.”

4. No differences were observed in PYY, CCK, glucose, or GI symptoms.

This supports the idea that appetite-related outcomes were most likely driven by GLP-1, insulin, and possibly ghrelin.

Potential Mechanisms

The authors propose several hypotheses to explain the association between CP supplementation and reduced post-exercise energy intake, drawing from both their hormonal data and prior protein research. First, one possibility is that the increases in GLP-1 and insulin served as the primary mediators, as differences in these hormones correlated with differences in energy intake (r ≥ –0.477). Second, reduced ghrelin concentrations may also have contributed, although the effect size was smaller and correlations were weaker than those observed for GLP-1 and insulin. Third, while in vitro studies have suggested that collagen hydrolysates may inhibit DPP-4 and thereby increase GLP-1 availability, this mechanism does not appear to explain the current findings, as sDPP-4 was slightly higher (not lower) in the CP condition. Lastly, the researchers also note that amino acid-driven signaling may be involved. Glycine, one of the primary amino acids in collagen, has been shown in preclinical models to stimulate GLP-1 secretion, and specific bioactive peptides derived from collagen may exert insulinotropic effects. The precise mechanisms remain to be clarified in future research.

Main Takeaway for Practitioners

This study provides early evidence that collagen peptides may modestly reduce post-exercise energy intake, potentially through increased GLP-1 and insulin and decreased ghrelin. The authors note several limitations, including a small, homogeneous sample (young, active females), a short intervention duration (seven days), and the use of only one ad libitum meal to assess intake. Future studies will need to explore dose-response relationships, longer-term supplementation, diverse populations, and mechanistic pathways to determine whether these early signals translate into meaningful outcomes. For now, this study suggests that practitioners who already recommend or use collagen for musculoskeletal benefits can consider these findings as a preliminary addition to its potential clinical benefit.

Read more about the latest findings in GLP-1 research: 

4 Surprising Botanicals to Promote Normal GLP-1 Production

GLP-1 Begins in the Gut: Clinical Clues From Microbiome Testing

Foundations of GLP-1 Support: Nutritional and Lifestyle Strategies for Healthy Glucose Metabolism

GLP-1s and Hydration: What You Need to Know

By Danielle C. Male, MS, CNS, LDN