Amyloid-β (Aβ) is formed by the cleavage of amyloid precursor protein (APP) and is characterized by the deposition of Aβ in the brain. A high plasma Aβ40/42 ratio is associated with an increased incidence of dementia. In the present study, we analyzed the effect of aging markers on Aβ40/42 from the data of an anti-aging medical check-up conducted in 2019. The subjects included 21 university faculty and staff (FS; 49.3 ± 12.9 years) and 36 independent elderly (Yurin elderly, YE; 79.3 ± 6.4 years) living in the Yurin area of Kyoto, Japan. Statistical analysis was performed using stepwise multiple regression analysis for a total of 13 items, including gender, age, BMI and anti-aging medical check-up items (muscle age, neural age, bone age, blood vessel age, hormone age, glycative stress, oxidative stress, immune stress, physical and mental stress and lifestyle) as independent variables and Aβ40/42 as a dependent variable. For FS, the dependent variable Y (Aβ40/42) was expressed with the equation "Y = −0.131 X1(lifestyle score) + 19.7", where poor lifestyle was a risk factor for elevated Aβ40/42. Neural age was a risk factor for YE, while blood vessel age and glycative stress were risk factors to analyze all subjects for elevated Aβ40/42. We can conclude that neural age, blood vessel age, glycative stress and poor lifestyle may affect the plasma Aβ40/42 ratio and may be risk factors for exacerbating dementia.

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Purpose: "Sleep quality" plays an important role in maintaining the homeostasis of the body, and deterioration in sleep quality causes various lifestyle-related diseases. In the present study, we verified the effects of a mat with a "Distinctive 4-Layer 3-Dimensional Structure" as the study product on sleep quality and gut microbiota through a non-controlled open-label study. Methods: The Pittsburgh Sleep Quality Index (PSQI-J) was used to assess 36 men and women who were not satisfied with their sleep quality, and 12 subjects (age 50.1 ± 4.9 years) with a marked decrease in "sleep quality" were included in the study. A non-controlled open-label study was conducted for changes in physical data when the study product (Nishikawa Co., Ltd., Chuo-ku, Tokyo) was used for 8 weeks. Analysis of gut microbiota by PSQI-J and T-RFLP, and measurement of plasma amyloid-β (Aβ) 40/42 ratio were conducted before commencement and 8 weeks after the start of the study. The present study was conducted with the approval of the ethics review committee. Results: PSQI-J showed a significant improvement in sleep quality, time to fall asleep, difficulty sleeping and daytime difficulty waking after 8 weeks. The PSQI global score improved significantly from 8.2 ± 1.4 to 4.2 ± 2.2 (p < 0.01). Gut microbiota analysis showed a significant increase in the percentage of genus Bacteroides and short-chain fatty acid (SCFA)-related bacteria. Plasma Aβ40 was slight but significantly elevated, and there were no changes in the Aβ40/42 ratio. Conclusion: The use of the study product improved "sleep quality, " affecting the gut microbiota through the gut-brain connection, increasing bacteria belonging to genus Bacteroides, suggesting that the study product may contribute to the maintenance of homeostasis in glycolipid metabolism and immune defense mechanisms.

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Objective: Accumulation of advanced glycation end products (AGEs) produced by glycative stress promotes the progression of age-related diseases. We conducted an exploratory study in humans using mixed herb extracts that have both enhancing action of oxidized protein hydrolase (OPH) activity in the body and AGEs crosslink cleaving activity. Method: The subjects were 24 women 40 years or older and less than 65 years of age with high levels of skin AGEs deposits. Three kinds of the following herbs were extracted in hot water: fenugreek (Trigonella foenum-graecum) seeds, fennel (Foeniculum vulgare) seeds, and hibiscus (Hibiscus sabdariffa) calyxes and bracts. Solid contents of the extracts and dextrin were mixed in a ratio of 6:4 to produce mixed herb extract (MHE) powder (brand name: Satonaceil). The test food was a food product in a capsule form. The daily intake of the test food was 100 mg/day for the L group (n = 12) and 300 mg/day for the H group (n = 12) as MHE. The ingestion period was 12 weeks. Before ingestion, and at 6 and 12 weeks post-ingestion, physical examination, blood test, urine test, skin-related tests, and a questionnaire were performed. Note that this study was conducted upon approval by an ethics review committee. (UMIN Clinical Trial ID: UMIN000025986). [Results] Because two subjects violated the exclusion criteria after the start of the study, 11 subjects each were to be analyzed in the L group and the H group. Significant reductions were observed in the levels of pentosidine and fasting blood glucose in both groups at 12 weeks post-ingestion compared to those pre-ingestion. Significant reductions were also observed in the score of wrinkle (on the left and right) measured with VISIA in the L group and HOMA-IR in the H group. In addition, there was a tendency for 3-deoxyglucosone (3DG) to decrease in the L group and for carboxymethyl lysine (Nε-(carboxymethyl)lysine: CML) to decrease in the H group. Further, significant reductions in several liver-function-related indices were observed. In the safety evaluation, no adverse events or abnormal variations in laboratory parameters attributable to the test food were observed. [Conclusion] Effects of MHE ingestion on the reduction of AGEs seen in basic studies can be expected in humans, as demonstrated by the significant decrease or tendency to decrease of glycative-stress-related parameters. Furthermore, ingestion of this MHE was confirmed to be safe.

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Purpose: One of the measures against glycative stress is a method of promoting the decomposition and metabolism of accumulated advanced glycation end products (AGEs). We screened a large number of plants using indicators such as the action of directly cleaving the AGE crosslinks and the enhancing action for the oxidized protein hydrolase (OPH) activity that is involved in the decomposition of the glycated proteins. As a result, we identified that Trigonella foenum-graecum (fenugreek, seeds), Foeniculum vulgare (fennel, seeds) and Hibiscus sabdariffa (hibiscus, calyxes and bracts) have both actions. In addition, it has been reported that the mixed herb extract (MHE) consisting of these 3 herbs demonstrated various anti-glycation effects and physiological functions in our exploratory clinical trial with two groups, 100 mg/day (low-dose group) and 300 mg/day (high-dose group), in the previous study. Therefore, in this study, we conducted a randomized, placebo-controlled parallel-group study with the same amount of MHE as the low-dose group in the previous study to verify its anti-glycation effect and its effects on the skin. Method: The subjects were 40 Japanese women (20 in the MHE group, 20 in the placebo group) aged 40 to 64 years who had high amounts of AGEs deposits on the skin (as measured by AGE Reader mu). MHE was used as the test food, which was administered in soft capsules of 100 mg per day for 12 weeks. The subjects underwent blood tests, urine tests, skin-related tests, physical tests, body measurements and medical interviews before administration as well as after 6 and 12 weeks of administration. Note that this study has been conducted upon approval by an ethics review committee. (UMIN Clinical Trial ID: UMIN000037855). Results: During the study, 4 subjects withdrew and 1 was subject to the trial exclusion criteria, therefore, the number of subjects analyzed was 19 in the MHE group and 16 in the placebo group. A subgroup analysis was performed for pentosidine, the primary outcome, with 10 subjects in the MHE group and 6 subjects in the placebo group who were below the mean value of all the subjects for analysis, excluding 1 subject whose result was judged to be an outlier using the interquartile range. A significant decrease was observed only in the MHE group when comparing the results from pre-administration to after 12 weeks of administration. A significant decrease was also observed in the group compared to the placebo group. A subgroup analysis was conducted for Nε-(carboxymethyl) lysine (CML) with 7 subjects in the MHE group and 5 subjects in the placebo group whose BMI were 22.0 or higher, excluding 1 subject whose result was judged to be an outlier using the interquartile range. A tendency to decrease was observed only in the MHE group when comparing the results from pre-administration to after 12 weeks of administration. In the results of imaging analysis by VISIA for all cases, only the MHE group showed a decrease in the wrinkle parameter after administration compared to the pre-administration levels, and the group also indicated a significant tendency to decrease against the placebo group. In addition, improvement effects were observed in the MHE group in the secondary outcomes of skin texture and brown spots. Conclusion: Administration of MHE improved glycation indices as well wrinkles, texture and brown spots of the skin. It is considered that the AGE crosslink cleaving activity and the OPH activity enhancing action of the MHE may have contributed to these effects.

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A 24-hour patch test was performed to verify the safety of stable sodium hypochlorite (test sample material, 200 ppm, AirRish) with twenty healthy research participants ranging from 20-60 years old (four males and nineteen females, age: 39.5±10.7). The safety evaluation was performed in accordance with the determination criteria of a research group for patch tests in Japan. It was indicated that the rating score was 0.0 and that no adverse events were observed. This product was judged to be classified as "anzen-hin," a safe product by the skin irritation index in perfumery and cosmetics. It was suggested that there were no safety issues regarding contact with this test sample product for the disinfection of hands and fingers.

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Objectives: A financial crisis has been induced by the immense increase of national medical care expenditures in Japan, while investigations of causes and introductions of countermeasures have not yet been conducted. It has been reported that nutrients in brown rice and processed brown rice would contribute to the retention and promotion of health for citizens in Japan. The present study examined impacts of staple food replacement from polished rice to processed brown rice, concerning the reduction of public medical expenditures. Methods: Test sample products were a sub-aleurone layer residual rinse-free rice (SARFR) or a dewaxed brown rice (DBR). SARFR was a processed brown rice where sub-aleurone layer (white deep layer bran of brown rice) remains with a polished white rice-like appearance (patent number: 4708059). DER was a processed brown rice where only the wax bran layer was removed with a brown rice-like appearance (patent number: 6850526). Research targets were three companies located in Wakayama Prefecture and public medical expenditure information was obtained through medical expenditure information, which was issued by each company’s health insurance society. Consumption rates were calculated with annual average rice consumption per person (2016), quantity of delivered processed brown rice and the number of subscribers. Control targets were medical expenses of residents in Wakayama Prefecture. The number of insured persons (subscribers) in 2018 fiscal year (FY) in health insurance societies were 169 (373) in Company T, 64 (98) in Company A, 53 (125) in Company B, and 170,939 (297,088) in Wakayama Prefecture. Mean age was 45.4 at Company T, 45.4 at Company A, and 44.5 at Company B. The number of subscribers is the total number of insured persons (staff) and dependents (family members). Results: At Company T, which had a large number of regular consumers of test sample products (consumption rate: 66.1% [DBR 14.3%, SARFR 85.7%]), annual medical expenses were 120,108 yen for the 2016 FY, 119,264 yen for the 2017 FY, and 127,248 yen for the 2018 FY. Average medical expenses in Wakayama Prefecture were 175,683 yen for the 2016 FY, 180,966 yen for the 2017 FY, and 183,372 yen for the 2018 FY. Average annual medical expenses in Company T were approximately 68% that in Wakayama Prefecture. After the introduction of the test product ingestion, Company A (consumption rate: 39.1% [DBR 13.5%, SARFR 86.5%]) reduced the average of annual medical expenses by approximately 40% to 224,335 yen for the 2017 FY and 134,354 yen for the 2018 FY. Company B (consumption rate: 29.4% [DBR 13.3%, SARFR 86.7%]) reduced expenses by approximately 39% to 198,892 yen for the 2017 FY and 121,172 yen for the 2018 FY. Conclusion: It was suggested that the ingestion of the test products would lead to the improvement in health condition, the decrease in disease incidence rates, and the reduction of public medical expenses through the increase of nutrient ingestion quantity, which is contained in the sub-aleurone layer and bran layer of Japanese short-grain rice.

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