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2026-07-03 PubMed

Continuous energy restriction alone increased ghrelin levels in obese men; probiotic blend offered no additional benefit

Effect of Continuous Energy Restriction Combined with Probiotic Supplementation on Parameters Related to Homeostatic and Hedonic Systems of Food Intake in Adult Men Living with Obesity: Data from a Randomized, Parallel, Double-Blind, Placebo-Controlled Clinical Trial.

Background

Managing obesity often involves continuous energy restriction (CER), which effectively reduces body fat. However, CER can negatively impact hunger regulation and the hedonic system of food intake, potentially compromising long-term weight maintenance. The gut microbiota is an emerging target for supporting sustained weight loss, but studies combining probiotics with CER are limited. This trial investigated if probiotic supplementation could enhance CER's metabolic and behavioral effects on appetite-related hormones like ghrelin, leptin, GLP-1, GIP, and PYY, and eating behaviors.

Study Design

This was a 12-week randomized, double-blind, placebo-controlled, parallel-group clinical trial. Adult males with obesity, aged 25 to 44 years, were included. Participants followed a continuous energy restriction (CER) diet, reducing total daily energy expenditure by 30%. The probiotic group received two 1 g sachets/day of a blend containing 1×10^9 CFU/day of Lactobacillus acidophilus NCFM, Lacticaseibacillus rhamnosus HN001, Lacticaseibacillus paracasei Lpc-37, and Bifidobacterium lactis HN019. Primary outcomes were ghrelin and leptin levels, with secondary outcomes including other appetite hormones and eating behaviors assessed via Three-Factor Eating Questionnaire.

Results

Of 49 participants randomized, 38 were included in the final analysis, with hormonal outcomes available for 25 participants. Significant time effects were observed, indicating that changes were primarily driven by the continuous energy restriction (CER), regardless of the probiotic supplementation group. Specifically, ghrelin levels increased over time in both groups, a common physiological adaptation to weight loss. This suggests that the probiotic blend did not mitigate the expected rise in ghrelin, a hormone known to stimulate appetite. The study found no significant interaction effect between the probiotic supplementation and CER on any of the measured appetite-related hormones, including leptin, GLP-1, GIP, PYY, insulin, or adiponectin. Similarly, no differential effects were observed for eating behavior dimensions such as emotional eating, cognitive restraint, or binge eating between the probiotic and placebo groups. The overall metabolic and behavioral improvements were attributable solely to the 30% energy deficit.

Significant time effects were observed, indicating that changes were primarily driven by the continuous energy restriction (CER), regardless of the probiotic supplementation group.

Key Findings

  • Continuous energy restriction (CER) alone drove changes in appetite hormones and eating behaviors.
  • Ghrelin levels increased over time in both CER groups, regardless of probiotic supplementation.
  • Probiotic supplementation offered no additional benefit for ghrelin, leptin, GLP-1, GIP, PYY, insulin, or adiponectin levels.
  • No differential effects were observed for emotional eating, cognitive restraint, or binge eating with probiotic use.
  • Hormonal outcomes were analyzed for only 25 participants.

Why It Matters

For individuals undergoing continuous energy restriction for weight loss, adding this specific multi-strain probiotic blend may not provide additional benefits for appetite regulation or eating behaviors. This finding challenges the hypothesis that gut microbiota modulation via these probiotics can mitigate the hunger-promoting hormonal adaptations, like increased ghrelin, that often accompany dieting. Clinicians and biohackers should be aware that while probiotics have diverse health benefits, their role in directly enhancing the metabolic and behavioral outcomes of CER, particularly regarding appetite control, appears limited based on this formulation and study design. Further research with different probiotic strains, dosages, or durations, or in different populations, might reveal specific contexts where gut modulation could be more impactful for weight management.


obesity weight loss continuous energy restriction probiotics ghrelin appetite
Source: pubmed:42392542 · Ingested 2026-07-03 · Digest: gemini-2.5-flash