Effect of Anserine/Carnosine Supplementation on Verbal Episodic Memory in Elderly People

Abstract

Our goal in this study was to determine whether or not anserine/carnosine supplementation (ACS) is capable of preserving cognitive function of elderly people. In a double-blind randomized controlled trial, volunteers were randomly assigned to an ACS or placebo group at a 1:1 ratio. The ACS group took 1.0 g of an anserine/carnosine (3:1) formula daily for 3 months. Participants were evaluated by psychological tests before and after the 3-month supplementation period. Thirty-nine healthy elderly volunteers (60-78 years old) completed the follow-up tests. Among the tests, delayed recall verbal memory assessed by the Wechsler Memory Scale-Logical Memory showed significant preservation in the ACS group, compared to the placebo group (p = 0.0128). Blood analysis revealed a decreased secretion of inflammatory cytokines, including CCL-2 and IL-8, in the ACS group. MRI analysis using arterial spin labeling showed a suppression in the age-related decline in brain blood flow in the posterior cingulate cortex area in the ACS group, compared to the placebo group (p = 0.0248). In another randomized controlled trial, delayed recall verbal memory showed significant preservation in the ACS group, compared to the placebo group (p = 0.0202). These results collectively suggest that ACS may preserve verbal episodic memory and brain perfusion in elderly people, although further study is needed.

Keywords: Alzheimer’s disease; anserine and carnosine; cognitive function; dementia; elderly people; inflammatory cytokine; perfusion MRI; randomized controlled trial; verbal memory.

Fig.1

Flow diagram showing the number of elderly participants (≥60 years old) during the study. 1st test: baseline. 2nd test: 3 months after supplementation.

Fig.2

Chemical structures of anserine and carnosine. Anserine (β-Alanyl-L-Methyl-Histidine) and carnosine (β-Alanyl-L-Histidine) are sometimes called as imidazole-containing dipeptides.

Fig.3

Longitudinal change in score of WMS-LM2 between the two groups. Box plot of WMS-LM2 data described in Table 3. Each black dot represents the change of score in each volunteer. Active (n = 19), Placebo (n = 20). Solid bar shows median, and box shows 25–75 percentile. BL, Baseline; FU, Follow-up. We observed a significant improvement of WMS-LM2 score in the ACS group before (F[1,37] = 9.067, p = 0.0047), after adjusting for age (F[1] = 6.8588, p = 0.0128).

Fig.4

Significant decreases in inflammatory cytokines in the ACS Group. Of 26 cytokines tested, three (IL-8, CCL-2 (MCP-1), and IL-5) were significantly decreased (p <  0.01, after FDR) in the sera of the ACS group. No cytokines significantly decreased in the placebo group. Each black dot represents the concentration of cytokine in each volunteer at the indicated test. Active (n = 19), Placebo (n = 20). Red bar shows median, and red error bar shows 25–75 percentile. BL, Baseline; FU, Follow-up.

Fig.5

Analysis and location of longitudinal brain perfusion changes. Color indicates the brain region that showed a difference in brain perfusion changes between the two groups, after repeated two-way ANOVA, interaction Time×Variant (active >  placebo, p <  0.01, Voxel threshold >  500). Due to low image quality, we eliminated one individual from the ACS group; therefore, we compared 38 participants in the ACS (n = 18) and placebo (n = 20) groups. Inverse calculation showed no plot. The locations are plotted on a template human brain. Red arrows with PCC (BA29) shows a cluster of perfusion preservation after supplementation (Cluster Size: 797; Peak (x, y, z) = (–8, –58, 16) at Z-score of 3.51).

Fig.6

Longitudinal change in PCC perfusion change between the two groups. We used a PCC ROI defined by a public domain program for the SPM software: toolbox, wfu_pickatlas, and performed a ROI analysis. We observed a significant preservation of the brain perfusion of the PCC in the ACS group (p = 0.0228). After adjusting for age, we detected a significant difference between the two groups (F(1) = 5.5051, p = 0.0248).

Fig.7

Longitudinal change in score of WMS-LM2 between the two groups in another RCT. Each black dot represents the change of score in each volunteer between the baseline score and the 6 month follow-up score. Active (n = 42), Placebo (n = 42). Solid bar shows median, and box shows 25–75 percentile. BL, Baseline; FU, 6 Month Follow-up. We observed a significant improvement of WMS-LM2 score in the ACS group before (F[1,82] = 5.509, p = 0.0213), and after adjusting for age (F[1] = 5.6125, p = 0.0202).