Effect of a Fibroin Enzymatic Hydrolysate on Memory Improvement: A Placebo-Controlled, Double-Blind Study

Abstract

The consumption of a specifically prepared silk fibroin protein enzymatic hydrolysate (FPEH) has been reported to improve cognitive function in healthy humans. The objective of the current study is to evaluate the dose-dependent effects of the FPEH on memory. Healthy adults with an average age of approximately 55 years were administered doses of 0, 280, 400 and 600 mg of FPEH per day in two divided doses for 3 weeks. The Rey-Kim Auditory Verbal Learning Test and the Rey-Kim Complex Figure Test of the Rey-Kim Memory Test were used to evaluate memory at baseline and after 3 weeks. The scores for each test were combined into the memory quotient score (MQ). Learning gradient, memory maintenance, retrieval efficacy, and drawing/recall scores were also compared. After 3 weeks of FPEH, dose-dependent increases were observed for the MQ, the learning gradient, the numbers of words remembered, the retrieval efficiency, and drawing/recall. The optimal dose for FPEH was 400 or 600 mg, depending on the end point measured. No adverse effects were reported. FPEH significantly improved measurements of memory in healthy adults by 3 weeks at doses over 280 mg daily, with an apparent plateau effect at 400-600 mg daily.

Keywords: Bombyx mori (silkworm); auditory verbal learning; complex figure test; dose response; drawing/recall; fibroin enzymatic hydrolysate; learning gradient; memory quotient; memory retention; retrieval efficiency.

Figure 1

Changes in memory quotient (MQ) before and after silk fibroin protein enzymatic hydrolysate (FPEH) intake at daily doses of 0, 280, 400 and 600 mg for 3 weeks. Each value is the mean with the standard error of the mean (SEM). Groups with a different alphabetical letter are statistically significantly different on the basis of group tests following ANOVA (F = 32.97; df_total = 62; p < 0.00013). Between group p values were the following: placebo: 280 mg, p < 0.00015; placebo: 400 mg, p < 0.0001; placebo: 600 mg, p < 0.0001; 280 mg: 400 mg, p < 0.0001; 280 mg: 600 mg, p < 0.0001; 480 mg: 600 mg, p < 0.0378.

Figure 2

Learning gradient as the percentage of words remembered per trial after intake of daily doses of 0, 280, 400 and 600 mg of fibroin protein enzymatic hydrolysate (FPEH) for 3 weeks is exhibited on the y-axis. The data are presented as mean values with the standard error of the mean (SEM). On the basis of ANOVA (F = 2.8164; df_total = 62; p = 0.7440), the learning gradient changes with increasing dose were not statistically significant.

Figure 3

Changes in numbers of words remembered, before and after 3 weeks of fibroin protein enzymatic hydrolysate (FPEH), in Trials 1 (black bars) and 5 (gray bars) of the Korean version of the Rey Auditory Verbal Learning Test (KAVLT) is exhibited on the y-axis. The change in each group in the number of words remembered was assessed by ANOVA and was significant for Trials 1 (p = 0.0126) and 5 (p = 0.0463). Each value is the mean with the SEM.

Figure 4

Memory retention measured as change in number of words remembered before and after 3 weeks of daily ingestion of fibroin protein enzymatic hydrolysate (FPEH) is exhibited on the y-axis. Significant differences between groups were assessed by ANOVA (p < 0.0001). Groups with different alphabetical letters are statistically significantly different (p < 0.05). The data are presented as means ± SEM.

Figure 5

Retrieval efficiency calculated using the Korean version of the Rey Auditory Verbal Learning Test (KAVLT) delayed recognition raw score minus delayed remembrance raw score followed by conversion using the age conversion table is exhibited on the y-axis. The change in retrieval efficacy before and after intake of fibroin protein enzymatic hydrolysate (FPEH) for 3 weeks was not significant between groups by ANOVA (p = 0.3959). Each value is the mean with the SEM.

Figure 6

Korean version of the Rey Complex Figure Test (KCFT) memory test scores (as percentage of correct copying/recall) are exhibited on the y-axis. Baseline scores (black bars) for each group were similar. The percent change in drawing/recall score between groups before and after 3 weeks of daily fibroin protein enzymatic hydrolysate (FPEH) intake was increased in a dose-dependent manner (ANOVA = 0.0092). The 280 mg group change was not different from the placebo change (p = 0.5493); however, 400 mg (p = 0.0497) and 600 mg (p = 0.0032) group changes were significantly increased over the placebo group and were similar to each other (p = 0.1492). Each value is the mean with the SEM. Groups with a different alphabetical letter are statistically significantly different on the basis of t-tests.