F2-isoprostanes may be a marker for both oxidative stress and fat oxidation, with lower concentrations predictive of incident T2D.Whether diet composition affects F2-isoprostanes is not clear. The objective of this study is to determine the effects of a ketogenic diet (KD) vs low-fat diet (LFD) on four F2-isoprostane isomers and their association with change in fat oxidation and visceral adipose tissue (VAT) in older adults with obesity.


Eighteen men and women (60-75 yrs, BMI 30-40 kg/m2) were randomized to KD (<20:25:>55% energy from CHO:protein:fat) (N=10) or LFD(55:25:20) (N=8) for 8-wks. Body composition by DXA and VAT by MRI were assessed at baseline and post-intervention. Four isomers of F2-Isoprostanes: iPF(2α)-III (F2isoP1), 2,3-dinor-iPF(2α)-III (F2isoP2), iPF(2α)-VI(F2isoP3), and 8,12-iso-iPF(2α)-VI (F2isoP4) were assessed from 24-hour urine collected at baseline and post-intervention using liquid chromatography-tandem mass spectrometry and corrected for creatinine concentrations and expressed as the ratio to VAT. Respiratory Quotient (RQ) was measured using indirect calorimetry.


Decrease in VAT was greater in KD vs. LFD (-14.5% vs -0.2%, p<0.01). Relative to VAT, both F2isoP1 and F2isoP2 decreased in the LFD group (p=0.05) but not in the KD group (p>0.05). In the KD group, participants with the least VAT loss had the greatest decrease in F2isoP1 (r=-0.72, p<0.05) and F2isoP4 (r=-0.69, p=0.06). Change in F2isoP4 was associated with follow-up RQ (r=0.64, p<0.05) within the KD group.


A KD results in higher F2-isoprostanes than a LFD, likely due to greater fat oxidation from both greater intake of dietary % fat and greater depletion of VAT.