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Propolis Extract Improves Verbal Memory in Elderly Japanese Participants

Date 05-31-2021
HC# 042131-665
Propolis Extract

Asama T, Hiraoka T, Ohkuma A, Okumura N, Yamaki A, Urakami K. Cognitive improvement and safety assessment of a dietary supplement containing propolis extract in elderly Japanese: a placebo-controlled, randomized, parallel group, double-blind human clinical study. Evid Based Complement Alternat Med. February 24, 2021;2021:6664217. doi: 10.1155/2021/6664217.

Dementia is a chronic, progressive brain condition associated with a decline in cognitive functions. It can affect memory, thinking, orientation, understanding, calculation, learning, language, and judgment. Multiple factors contribute to age-related dementia, including inflammation, oxidative stress, neurotransmitter decline, and beta-amyloid accumulation. Drugs may be used to delay the progression. Propolis, a substance made by honeybees from plant resin to help maintain the hygienic environment of their nests, has been reported to have antioxidant and anti-inflammatory effects in humans, to inhibit beta-amyloid accumulation in vivo, and to increase the brain-derived neurotrophic factor in vitro. These authors, from Japan, where the number of people with dementia is increasing as the population ages, conducted a placebo-controlled, randomized, parallel-group, double-blind clinical study to examine the effect of propolis on the cognitive function of elderly Japanese.

Males and females were eligible for the study if they were aged 60-79 years and if they scored 24 to 29 points (indicating no dementia) on the Mini-Mental State Examination (MMSE) but were aware of being forgetful or had been told they were forgetful. Seventy-nine participants were randomly assigned to the propolis (n = 39) and placebo (n = 40) groups, distributed equally based on their ages, gender, body mass index, and MMSE scores. They were aged 66.1 ± 4.5 years in the placebo group and 66.6 ± 3.9 years in the propolis group. Baseline MMSE scores were 27.5 ± 1.4 in the placebo group and 27.5 ± 1.3 in the propolis group. The study product contained propolis extract (57.68 mg artepillin C and 0.95 mg culifolin as standard components in the daily dose). A starch placebo was used.

Baseline assessments, which were conducted from March 2019 to May 2019, included height, weight, blood pressure, pulse, MMSE, magnetic resonance imaging, a geriatric depression scale (short version-Japanese), the general cognitive test Cognitrax, and various blood and urine tests. In this study, the following parts of the Cognitrax were used: verbal memory, visual memory, finger tapping, symbol digit coding, Stroop, shifting attention, continuous performance, and four-part continuous performance tests. After those assessments, the participants started taking six placebo or propolis capsules daily for 24 weeks, from June to November 2019. At the end of the study, the participants underwent measures of height, weight, blood pressure, pulse, Cognitrax, and blood and urine markers. A daily log kept during the study recorded test product intake, presence or absence of changes in health, lifestyle routines, intake of drug and/or health foods, and state of interpersonal exchange.

One participant in the placebo group and two in the propolis group discontinued the study because of personal reasons. Seven participants (five in the placebo group and two in the propolis group) were excluded from the final analysis because of changes in lifestyle that could negatively affect cognition. One participant in the placebo group who did not meet the Cognitrax cognitive test criteria was also excluded from the analysis. At the end of the study, the final analysis included 33 and 35 participants in the placebo and propolis groups, respectfully.

A significant improvement was observed in changes of verbal memory in the propolis group compared with the placebo group at the end of the study (P = 0.028). No significant changes were observed in any of the other Cognitrax tests.

Among the blood tests, the changes in total cholesterol (P = 0.011) and low-density lipoprotein cholesterol (P = 0.004), which increased in both groups, were significantly smaller in the propolis group compared with the placebo group. Urea nitrogen (P = 0.048) and uric acid (P = 0.005) levels decreased in the propolis group and increased in the placebo group. Creatinine levels increased in both groups, but the change was significantly less in the propolis group (P = 0.045). The levels of urea nitrogen, creatinine, and uric acid remained within normal limits.

A subgroup analysis of participants who scored higher than the standardized overall Cognitrax score revealed significantly greater improvements in the propolis group compared with the placebo group in verbal memory (P = 0.007) and processing speed (P = 0.029). The 53 adverse effects reported during the study were determined to be unrelated to the products. No safety concerns were raised by the results of the blood and urine tests.

Limitations of the study include the facts that a lower effective dose and dose dependency of the propolis was not clarified and that the mechanism and associated component responsible for improving cognitive function was not detailed.

"Propolis intake improves not only verbal memory but also information processing, attention, and concentration in a group with high cognitive function" … and "no side effects were shown by propolis ingestion," write the authors.

Author K. Urakima received a medical advisory fee from Yamada Bee Company in Tomata-gun, Kagamino-cho, Japan; the other authors declare no conflicts of interest.

Shari Henson