Bilberry/red grape juice decreases plasma biomarkers of inflammation and tissue damage in aged men with subjective memory impairment –a randomized clinical trial

Abstract

Background Few randomized clinical trials have explored the health effects of bilberries in humans. The aim was to test the effect of bilberry and red grape-juice consumption on visual memory, motor speed and dexterity as well as inflammatory and tissue damage biomarkers of plasma in aged men with subjective memory impairment. Methods Nine-week double-blind, placebo-controlled, dietary intervention study of aged men (n = 60, age ≥ 67 years) with subjective memory impairment randomized to consume a 50/50 mix of bilberry/red grape-juice or an iso-caloric placebo juice. A selection of Cambridge Cognition Test Battery (CANTAB), Grooved Pegboard tests and blood-sampling for biomarker analysis were performed before and after the intervention. Results Compared to placebo the selected memory and motor test scores were un-affected by the bilberry/red grape intervention. However, the plasma levels of tissue damage biomarkers decreased significantly more in the bilberry/red grape group. In particular lactate dehydrogenase (LDH) decreased from 362 U/L (median, baseline) to 346 U/L (median, post intervention) in the bilberry/red grape group. Also, several biomarkers of inflammation (EGF, IL6, IL9, IL10 and TNFα) decreased significantly more in the bilberry/red grape group. Furthermore, several plasma polyphenols; p-coumaric acid, hippuric acid, protocatechuic acid, 3HPAA and vanillic acid, increased significantly more in the bilberry/red grape group compared to placebo with the largest increase in p-coumaric acid with 116%; from 2.2 [1.0,5.5] to 4.7 [2.8,8.1] μM/L (median [95% CL]). Conclusions The results indicate that a nine-week bilberry/red grape juice intervention has no measurable effects on the selected memory scores in aged men experiencing memory problems but decreases the level of biomarkers of inflammation and tissue damage. Whether the dampening effects on inflammation and tissue damage biomarkers have relevance for neuroinflammatory brain pathology remains to be established. Trial registration Registration number (ClinicalTrials.gov: NCT00972972), September 9, 2009.

Dihydrocaffeic Acid—Is It the Less Known but Equally Valuable Phenolic Acid?

“…Dihydrocaffeic acid is a compound that is observed in samples of plasma, urine, or faeces after the consumption of products with a high content of chlorogenic and caffeic acids, which indicates, e.g., the activity of intestinal microbiota on the metabolic fate of these compounds. In recent years, scientists have examined what happens to the phenolic compounds that are ingested along with the following food products: coffee, yerba mate, cocoa, and artichoke, as well as berry, grape, and apple products [40][41][42][43][44][45][46][47][48][49][50].…”

“…Dihydrocaffeic acid derivatives evaluated as anticancer agents. Chemical structures of: isopropyl dihydrocaffeate ( 45), tert-butyl dihydrocaffeate (46), benzyl dihydrocaffeate (47), 3-phenylpropyl dihydrocaffeate (48). 3.…”

“…Cancer Cell Line IC 50 (mM) * Reference methyl dihydrocaffeate (2) mouse leukemia cell line L1210 0.024 [108] ethyl dihydrocaffeate (17) 0.023 isopropyl dihydrocaffeate (45) 0.019 butyl dihydrocaffeate (19) 0.020 tert-butyl dihydrocaffeate (46) 0.024 hexyl dihydrocaffeate (20) 0.009 octyl dihydrocaffeate (21) 0.009 benzyl dihydrocaffeate (47) 0.022 phenethyl dihydrocaffeate (25) 0.012 3-phenylpropyl dihydrocaffeate (48) 0.010 methyl dihydrocaffeate (2) breast cancer cell line MCF-7 0.115 ethyl dihydrocaffeate (17) 0.105 isopropyl dihydrocaffeate (45) 0.069 butyl dihydrocaffeate (19) 0.110 tert-butyl dihydrocaffeate (46) 0.050 hexyl dihydrocaffeate (20) 0.105 octyl dihydrocaffeate (21) 0.060 benzyl dihydrocaffeate (47) 0.120 phenethyl dihydrocaffeate (25) 0.132 3-phenylpropyl dihydrocaffeate (48) 0.129 dihydrocaffeic acid (1) human melanoma cell line SK-MEL-24 2.200 [110] dihydrocaffeic acid (1) leukemic cell line U-937 >2.000 [111] * The concentration that decreases cell viability by 50%.…”

A look beyond dietary (poly)phenols: The low molecular weight phenolic metabolites and their concentrations in human circulation

“…Studies with isotopically labeled molecules have also confirmed these observations. Albeit hippuric acids are widely recognized as biomarkers of (poly)phenol consumption (Bøhn et al., 2021; Yuan et al., 2022), they are also produced from endogenous pathways, that is, phenylalanine metabolic pathway (Zhang et al., 2021). This may lead to their continuous production in humans and the fact that it is present in longer timepoints.…”

Anti-Inflammatory Activity of Bilberry (Vaccinium myrtillus L.)

“…As free radical stress and inflammation are closely related, an inflammatory response increases ROS production, maintaining a pro-inflammatory environment. In one study, bilberry/red grape juice consumption (660 mL per day) improved oxidative stress and inflammation biomarkers in a double-blind, placebo-controlled, intervention study ( n = 60) [ 81 ]. The intervention decreased the levels of biomarkers of inflammation (epidermal growth factor [EGF], IL-6, TNF-α, macrophage inflammatory protein [Mip]1β, and vascular endothelial growth factor [VEGF]) and tissue damage (lactate dehydrogenase [LDH]); however, the memory score was unaffected.…”