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

Siv K Bøhn, Mari C W Myhrstad, Magne Thoresen, Iris Erlund, Ann Kristin Vasstrand, Anne Marciuch, Monica H Carlsen, Nasser E Bastani, Knut Engedal, Kjell M Flekkøy, Rune Blomhoff, Siv K Bøhn, Mari C W Myhrstad, Magne Thoresen, Iris Erlund, Ann Kristin Vasstrand, Anne Marciuch, Monica H Carlsen, Nasser E Bastani, Knut Engedal, Kjell M Flekkøy, Rune Blomhoff

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.

Keywords: Aged men; Bilberry; blueberry; blueberries; Cytokines; Grape; Inflammation; Memory.

Conflict of interest statement

The following authors declare no potential competing interest; SKB, MCM, MT, IE, AKV, AM, MHC, NB, KE, KMF. RB has interests in Vitas AS.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Overview of the study design
Fig. 2
Fig. 2
Change in plama tissue damage biomarkers;  lactate dehydrogenase (LDH) (A), myocard specific creatinine kinase  (CKMB) (B), total creatinine kinase  (CK total) (C) in the bilberry/red grape juice group (blue boxes) compared to the placebo group (white boxes). P-values are obtained by non-parametric MW tests
Fig. 3
Fig. 3
Change in plasma interleukins for: (A) Interleukin 6 (IL6), (B) IL9 and (C) IL10 in the bilberry/red grape juice group (blue boxes) compared to the placebo group (white boxes). P-values are obtained by non-parametric MW tests
Fig. 4
Fig. 4
Change in plasma cytokins: (A) epidermal growth factor (EGF), (B) Vascular endothelial growth factor (VEGF), (C) Macrophage Inflammatory Protein (MIP-1β) and (D) tumor necrosis factor (TNFα)  in the bilberry/red grape juice group (blue boxes) compared to the placebo group (white boxes). P-values are obtained by non-parametric MW tests

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