Cardiometabolic and molecular adaptations to 6-month intermittent fasting in middle-aged men and women with overweight: secondary outcomes of a randomized controlled trial.

Intermittent fasting produced significant reductions in body weight and body fat over 6 months.

• IF led to an 8% reduction in body weight.
• IF led to a 16% decrease in body fat.
• 41 participants were randomized to either IF intervention or habitual diet control.
• Participants were middle-aged (30–65 years) with overweight (BMI 24.8–35 kg/m²).
• Trial duration was 6 months.

Intermittent fasting significantly improved lipid profiles including LDL-cholesterol, non-HDL-cholesterol, and triglycerides.

• Substantial reductions were observed in plasma LDL-cholesterol, non-HDL-cholesterol, and triglycerides (p = 0.001).
• These lipid improvements were among the most notable cardiometabolic outcomes of the intervention.
• No significant changes were observed in other cardiometabolic risk factors beyond lipid profile.

Untargeted plasma metabolomics revealed significant multi-omic changes particularly in lipid metabolism, bile acid signaling, and enteroendocrine regulation.

• Exploratory analyses included untargeted plasma metabolomics and transcriptomic analysis of colon mucosa biopsies.
• Significant changes were identified in lipid metabolism pathways.
• Bile acid signaling was among the significantly altered molecular pathways.
• Enteroendocrine regulation was also significantly affected by the IF intervention.

Intermittent fasting led to downregulation of transcripts related to glucagon-like peptide 1 (GLP-1) and related enteroendocrine hormones in colon mucosa.

• Transcriptomic analysis of colon mucosa biopsies was performed.
• Downregulation of GLP-1-related transcripts was a notable finding described as 'notable' by the authors.
• Related enteroendocrine hormone transcripts were also downregulated.
• These changes were identified in colon mucosal tissue specifically.

PPAR-α and B-cell-mediated immune processes were significantly associated with changes in non-HDL cholesterol.

• Correlation analysis was used to identify key molecular pathways.
• PPAR-α signaling was significantly associated with non-HDL cholesterol changes.
• B-cell-mediated immune processes were also significantly associated with changes in non-HDL cholesterol.
• These pathway associations provide mechanistic insight into IF-mediated lipid improvements.

The primary outcome of circulating CRP concentration was previously reported in a separate publication.

• The current paper presents exploratory/secondary analyses focusing on metabolomic and transcriptomic responses.
• 41 participants were randomized in the parent trial (ClinicalTrials.gov NCT01964118).
• The study was a randomized controlled trial design with a habitual diet control group.