(P31-020-23) Multimodal Intermittent Fasting Regimen With Protein Pacing Shifts Plasma Metabolome, Reflective of Increased Fat Mobilization and Macronutrient Metabolism

Objectives: To compare and analyze the metabolomic signatures between a calorie-matched, calorie-restricted heart-healthy control diet (CR) and IF-P.

Methods: Thirty-nine overweight/obese individuals were randomly allocated to either a 1200-1500 kcal/d CR diet (n=19) following the TLC (Therapeutic Lifestyle Changes) diet or an IF-P diet (n=20) for eight weeks. For IF-P, subjects consumed 1350-1850 kcals/d five or six days per week, targeting 35% of calories as protein. Fasting days provided approximately 400 kcals/day. Calories consumed and expended were matched weekly to account for the fasting intervention. The plasma metabolome was profiled via targeted liquid chromatography with tandem mass spectrometry at baseline (week 0), week 4, and week 8. 

Results: Clear shifts in plasma metabolome were documented for both diets; however, these did not differ between diets or time. Controlling for age and sex, we observed significant effects of IF-P on 15 metabolites, including sugar alcohols, amino acid derivatives, malonic acid, and acetylcarnitine (false discovery rate [FDR] < 0.10). Compared to CR, malonic acid and acetylcarnitine increased, suggesting greater synthesis, mobilization, and oxidation of fatty acids. Using integrating enrichment and pathway topology analysis, we determined that three interrelated amino acid pathways were significantly impacted by IF-P, whereas CR most impacted alterations in amino acid, TCA cycle intermediates, and nucleotide sugars (FDR < 0.10). 

Conclusions: These results suggest that health benefits associated with IF-P may be reflected by alterations in the plasma metabolome, which are likely influenced by the combination of protein-pacing and intermittent fasting dietary approaches.

Funding Sources: Isagenix International, LLC