Cognitive improvement by daily intake of coffee cherry pulp extract from Coffea Canephora var. Robusta in a Japanese population: A randomized, placebo-controlled, double-blind, parallel-group comparison trial

BACKGROUND: In coffee-producing regions, coffee cherry pulp is usually discarded despite its potential bioactivity. This study examined the effects of coffee cherry pulp extract from Coffea canephora var. Robusta (CCPER) on cognitive function in healthy adults and its neurite outgrowth effect on PC12 cells. METHODS: This randomized, placebo-controlled, double-blind, parallel-group trial included 66 individuals aged ≥40 years with suspected mild cognitive impairment. Participants were randomized in equal groups using a computer-generated list. They were assigned to either the high-dose CCPER, low-dose CCPER (20 or 5mg/day of dimetric B-type procyanidins (PCs) consisting of two isomers with procyanidins B1 and B3 without procyanidin B2, respectively), or placebo group, with each group receiving five capsules daily for 12 weeks (UMIN000051275). In vitro, PC12 cells were treated with either CCPER (0.1 or 0.5µg/mL) or PCs (0.0021 or 0.0105µg/mL) for 3 or 6 days. Neurite outgrowth was evaluated using a microscope. RESULTS: Sixty participants completed the intervention. After the 12-intervention, the primary outcome-a standardized composite memory score on Cognitrax-was significantly higher in the high-dose group than in the placebo group (difference: 12.1, 95% confidence interval: 0.7-23.5, P = 0.038). Contrarily, no significant difference was observed in the low-dose group. No adverse events occurred. In vitro, CCPER and PCs treatments significantly promoted neurite extension compared with the control (P < 0.05). CONCLUSION: Daily intake of CCPER (20mg/day PCs) improved cognitive function, particularly visual memory, likely due to the neurite outgrowth-promoting effects of its PCs observed in PC12 cells.