Chlorogenic acid, a coffee polyphenol and antioxidant, hastens clinical onset of disease but prolongs life span in the G93A mouse, an animal model of ALS, as compared with caffeine

Abstract

The G93A mouse, an animal model of amyotrophic lateral sclerosis, exhibits elevated markers of oxidative stress (malondialdehyde, protein carbonyls) and a compensatory upregulation of antioxidant enzyme activity (Mn‐SOD, catalase) in the gastrocnemius, compared with wildtype control. We aimed to study the effects of chlorogenic acid (CHLA, an antioxidant) and caffeine (CAFN), both ingredients in coffee, on functional and disease outcomes. We hypothesized that CHLA would prolong life span as compared with CAFN. Starting at age 40 d, 20 female and 15 male separately‐caged G93A mice were randomly divided into two groups: CHLA (9 females; 7 males) and CAFN (11 females; 8 males). CHLA and CAFN were provided in the food mix, equivalent to amounts found in 5–10 cups of coffee/day (mg/g body weight). Differences in disease outcomes were evident in females, but not males. Clinical onset was attained 11 d sooner in the CHLA (97 ± 5 d) vs. CAFN (108 ± 2 d) group, a 10% difference (P = 0.036). Disease progression was 20 d longer in the CHLA (39 ± 9 d) vs. CAFN (19 ± 2 d) group, a 2 fold difference (P = 0.037). Life span was 9 d longer in the CHLA (136 ± 5 d) vs. CAFN (127 ± 2 d) group, a 7% difference (P = 0.048). Compared with CAFN, CHLA hastens onset of disease but prolongs life span in female G93A mice. (Supported by the Hamilton Health Sciences Foundation and NSERC).