This study aimed to determine the relationship between oxidative stress, DNA damage, inflammation, and metabolic biomarkers as the mediating factor between Islamic Sunnah intermittent fasting (IF) practice and cognitive function among older adults with mild cognitive impairment (MCI).

This study was a 36 months prospective cohort study.

Community-dwelling older participants recruited through a stratified random sampling method from four states representing Malaysia’s central, north-west, northeast and southern regions.

Ninety-nine Malay Muslim older adults (n= 99) aged 60 and above with MCI and no known critical illnesses were included in the current analysis. The participants were divided into regularly practicing IF (r-IF), irregularly practicing IF (i-IF) and not practicing IF (n-IF) groups.

Fasting venous blood was collected and used to determine the levels of oxidative stress, DNA damage, inflammatory and metabolic biomarkers. Mini-Mental State Examination, Montreal Cognitive Assessment, Rey Auditory Verbal Learning Test, Digit Span and Digit symbol were used to evaluate the cognitive function. Then, the mediation analysis was conducted using a multistep regression model to determine the mediating role of various biomarkers between IF practice and cognitive function.

When comparing the r-IF and n-IF groups, higher SOD activity, lower DNA damage (percentage of DNA in tail), lower CRP levels and higher HDL-cholesterol levels established partial mediation while lower insulin levels established complete mediation between IF practice and better cognitive function. Meanwhile, when comparing the r-IF and i-IF groups, higher SOD activity and lower CRP levels completely mediated the effects of IF practice on better cognitive function.

It can be concluded that changes in antioxidant function, DNA damage, inflammation and a limited set of metabolic biomarkers (insulin and HDL cholesterol) may mediate improvements in cognitive function among older participants with MCI who practice Islamic Sunnah IF.