Intermittent fasting increases plasma arachidonic acid

Intermittent fasting (IF) has emerged as a dietary intervention with potential effects on metabolic health and inflammatory processes. However, clinical evidence for its benefits remains inconsistent, despite numerous biochemical indications. Polyunsaturated fatty acids (PUFAs), as precursors of bioactive lipid mediators, may represent a potential mechanism through which dietary interventions such as IF exert anti-inflammatory and metabolic effects. Therefore, we investigated changes in blood fatty acid (FA) composition and associated metabolic endpoints during IF.

Thirty-nine normal-weight and overweight/obese participants followed a 16:8 IF regimen. Body weight, body mass index (BMI), routine lipid and liver parameters, and blood FA composition, quantified by gas chromatography with flame ionization detection (GC-FID), with a focus on omega-6 and omega-3 PUFAs (n-6 and n-3 PUFAs), were assessed at baseline and after 4 weeks.

IF induced plasma FA mobilization and a higher n-6/n-3 ratio in normal-weight participants. Across the cohort, arachidonic acid (AA) and the Delta-5-desaturase (D5D) index increased while the eicosapentaenoic acid/AA (EPA/AA) ratio decreased. Red blood cell FA composition remained largely unchanged. In contrast, overweight/obese participants showed minimal changes in FA profiles but significant metabolic improvements, including reductions in body weight, BMI, liver fat content, and γ-glutamyl transferase (GGT).

IF results in weight-dependent alterations in plasma FAs. Normal-weight individuals showed a predominance of n-6 PUFAs, whereas FA profiles in overweight/obese participants remained stable despite metabolic improvements. Overall, IF may exert a more pronounced effect on inflammatory pathways in normal-weight individuals, reflected by increased availability of AA, whose inflammatory significance remains unclear.