Dietary intervention of freeze-dried black raspberries (BRBs) in a group of human
colorectal cancer patients has demonstrated beneficial effects, including proapoptosis, antiproliferation, and antiangiogenesis. The aim of this study was to investigate BRB-mediated metabolite changes from this same cohort of patients. Twenty-eight
colorectal cancer patients were given 60 g BRB
powder daily for 1 to 9 weeks. Urine and plasma specimens were collected before and after BRB intervention. A mass spectrometry-based nontargeted metabolomic analysis was conducted on each specimen. A total of more than 400 metabolites were annotated in each specimen. Of these 34 and 6 metabolites were significantly changed by BRBs in urine and plasma, respectively. Increased levels of
4-methylcatechol sulfate in both post-BRB urine and post-BRB plasma were significantly correlated with a higher level of apoptotic marker (TUNEL) in post-BRB
tumors. One
tricarboxylic acid (TCA) cycle metabolites, cis-
aconitate, was increased in post-BRB urine. Furthermore, BRB-derived
polyphenols were absorbed and metabolized to various
benzoate species, which were significantly increased in post-BRB specimens. Increased
benzoate levels were positively correlated with enhanced levels of
amino acid metabolite. These results suggest that BRBs induce significant metabolic changes and affect energy generating pathways.This study supports the hypothesis that BRBs might be beneficial to
colorectal cancer patients through the regulation of multiple metabolites.