Bifidobacterium adolescentis SBT2786 Improves Sleep Quality in Japanese Adults with Relatively High Levels of Stress: A Randomized, Double-Blind, Placebo-Controlled Study.

Sleep disorders associated with lifestyle changes and unhealthy habits are major public health concerns. Our previous study showed that Bifidobacterium adolescentis SBT2786 has a potent sleep-promoting effect on fruit flies. Fruit flies share many similarities with mammals, making them suitable model organisms for studying sleep. Thus, in the present study, we conducted a randomized, double-blind, placebo-controlled clinical trial to test whether SBT2786 has sleep-enhancing effects in humans. In this study, 61 participants in the SBT2786 group and 65 participants in the placebo group were analyzed. The results showed that SBT2786 increased sleep time; however, it predominantly increased light sleep and did not improve subjective sleep quality. Interestingly, mood improvement was observed. A subgroup analysis was conducted on participants with high stress levels, and results showed that these participants experienced an increase in sleep duration and an improvement in sleepiness upon waking up and reported feeling well-rested during the day. We concluded that SBT2786 may improve sleep quality, particularly in individuals experiencing high levels of stress, and that SBT2786 can be used as a dietary supplement to improve sleep and mood.

Ingestion of ß-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind randomized, placebo-controlled study.

The study evaluated how ingestion of nicotinamide mononucleotide (NMN) for 12 weeks by older adults affected blood nicotinamide adenine dinucleotide (NAD +) levels and physical function, particularly walking function. Information concerning sleep, and stress was also collected as secondary endpoints. In this randomized, placebo-controlled, double-blind, parallel-group comparison study, 60 participants were randomly allocated into a placebo group or NMN group. Members of the NMN group consumed 250 mg/day NMN for 12 weeks. Motor function tests, blood NAD metabolite analysis, and questionnaires were conducted at the start of the study and 4 and 12 weeks after intake. This trial was registered at umin.ac.jp/ctr as UMIN000047871 on June 22nd, 2022.At primary outcome, at both 4 weeks and 12 weeks, the NMN and placebo groups had no significant differences in a stepping test. At secondary outcomes, after 12 weeks of NMN intake, the NMN group had a significantly shorter 4-m walking time than the placebo group as well as significantly higher blood levels of NAD + and its metabolites. A significant negative correlation was observed between the change in the 4-m walking time and the change in blood NAD + , N1-methyl-2-pridone-5-carboxamide (2-PY), and N1-methyl-4-pridone-3-carboxamide (4-PY) at 12 weeks. The NMN group had improved sleep quality at 12 weeks relative to the placebo group as evidenced by lower scores for "Daytime dysfunction" and "Global PSQI" on the Pittsburgh Sleep Questionnaire. No adverse effects related to test substance consumption were observed. Together, these results indicate that NMN intake could increase blood NAD + levels, maintain walking speed, and improve sleep quality in older adults. Interventions involving NMN aimed at maintaining walking speed could contribute to extended healthy life expectancy.

Piceatannol Upregulates SIRT1 Expression in Skeletal Muscle Cells and in Human Whole Blood: In Vitro Assay and a Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Trial.

Piceatannol (PIC), a polyphenol abundant in passion fruit seeds, is reported to promote fat metabolism. This study investigated whether PIC affects sirtuin 1 (SIRT1) expression and metabolic factors in C2C12 skeletal muscle cells. C2C12 myotubes were stimulated with PIC, and alterations in gene expression, protein levels, mitochondrial DNA content, and fatty acid levels were assessed using real-time PCR, Western blotting, and Nile red staining. Furthermore, we examined changes in SIRT1 expression following the consumption of a test food containing 100 mg PIC for 2 weeks among adults with varying age and body mass index ranges. Both PIC and passion fruit seed extract induced SIRT1 expression in C2C12 myotubes to a greater extent than resveratrol. PIC also increased the expression of genes associated with mitochondrial biogenesis and fatty acid utilization, increased mitochondrial DNA content, and suppressed oleic acid-induced fat accumulation. Moreover, participants who consumed PIC exhibited significantly higher SIRT1 mRNA expression in whole blood compared to those in the placebo group. These findings suggest that PIC induces SIRT1 expression both in vitro and in the human body, which may promote mitochondrial biosynthesis and fat metabolism.

The Effects of Black Tea Consumption on Intestinal Microflora-A Randomized Single-Blind Parallel-Group, Placebo-Controlled Study.

We previously reported that black tea consumption for 12 wk reduced the risk of acute upper respiratory tract inflammation, and improved secretory capacity in individuals with low salivary SIgA levels (Tanaka Y et al. 2021. Jpn Pharmacol Ther 49: 273-288). These results suggested that habitual black tea consumption improves mucosal immunity. Therefore, in this study we evaluated the effect of black tea intake on gut microbiota, which is known to be involved in mucosal immunity, by analyzing the bacterial flora and the short-chain fatty acids (SCFAs) concentration of feces collected during the above clinical study. The clinical design was a randomized, single-blind, parallel-group, placebo-controlled study with 72 healthy Japanese adult males and females, who consumed three cups of black tea (Black Tea Polymerized Polyphenols 76.2 mg per day) or placebo per day for 12 wk. In all subjects intake of black tea significantly increased abundance of Prevotella and decreased fecal acetic acid concentration. Particularly in the subjects with low salivary SIgA levels, the change over time of total bacteria, Prevotella, and butyrate-producing bacteria, which are involved in normalizing immune function, were higher in the black tea group than in the placebo group. In subjects with low abundance of Flavonifractor plautii a butyrate-producing bacteria, black tea consumption significantly increased salivary SIgA concentration and the absolute number of Flavonifractor plautii. In conclusion, our results suggest that improvement of mucosal immunity via an increase in butyrate-producing bacteria in the gut may partly contribute to the suppressive effect of black tea consumption on acute upper respiratory tract inflammation observed in our previous report.

Effect of Flavanol-Rich Cacao Extract on the Profile of Mood State in Healthy Middle-Aged Japanese Women: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

To investigate the effects of flavanol-rich cacao extract on healthy middle-aged women's fatigue and mood conditions, we conducted a randomized, double-blind, placebo-controlled study in women aged 40-60 years who had reported fatigue and had shown high levels of a serum oxidative stress marker. We randomized the participants (n = 60) into equal groups receiving either a beverage containing cacao flavanols (240 mg/200 mL/day) or a placebo for 8 weeks. Before and after the 8-week treatment, we determined the participants' Chalder fatigue scale (CFS) scores, various mood states, autonomic nervous system (ANS) activity levels, and their ANS balance. The results demonstrated that among the mood states, the indicators of negative mood (e.g., depression, fatigue, and anger) and the total mood disturbance score were significantly lower in the cacao group compared to the placebo group after the treatment (p < 0.05). The change in the index of positive mood (i.e., vigor) from baseline to 8 weeks was significantly higher in the cacao group versus the placebo group (p < 0.05). There were no significant between-group differences in the changes in the CFS score or ANS activity level. The consumption of flavanol-rich cacao extract both suppressed negative moods and promoted positive moods in healthy middle-aged women. These results suggest that cacao flavanols may be a useful food material that can improve variable mood conditions in middle-aged women and support their active lives.

The Potential Immunomodulatory Effect of Bifidobacterium longum subsp. longum BB536 on Healthy Adults through Plasmacytoid Dendritic Cell Activation in the Peripheral Blood.

The interaction between the gut microbiota and the host can influence the host's immune system. Bifidobacterium, a commensal genus of gut bacteria, seems to have positive effects on host health. Our previous clinical research showed that B. longum subsp. longum BB536 enhanced innate and adaptive immune responses in elderly individuals with a lower grade of immunity, but the immunomodulatory mechanism is still unclear. In this study, dendritic cell (DC) surface markers in peripheral blood mononuclear cells isolated from healthy individuals were evaluated through coculture with heat-killed BB536. DC markers, innate immune activity and cytokine levels in plasma were also evaluated by a randomized, double-blind, placebo-controlled, parallel-group study (UMIN000045564) with 4 weeks of continuous live BB536 intake. BB536 significantly increased the expression of CD86 and HLA-DR on plasmacytoid DCs (pDCs) in vitro. Compared to placebo (n = 48), a significant increase in the expression of CD86 on peripheral pDCs was detected at week 4 of live BB536 intake (n = 49; 1 × 1010 CFU/day). Furthermore, coculture with hk-BB536 significantly increased the IFNγ expression level and demonstrated trends of increased IFNα1 and IFNß expression. These findings suggest that consumption of BB536 has potential immunomodulatory effects on healthy individuals through the activation of peripheral pDCs.

Effects of Yeast Mannan Which Promotes Beneficial Bacteroides on the Intestinal Environment and Skin Condition: A Randomized, Double-Blind, Placebo-Controlled Study.

Yeast mannan (YM) is an indigestible water-soluble polysaccharide of the yeast cell wall. In vitro fecal fermentation studies showed that YM could exhibit a notable prebiotic effect. The aim of this randomized, double-blind, placebo-controlled study was to assess the efficacy of YM intake on the intestinal environment and skin condition. One hundred and ten healthy female subjects aged 30-49 years were supplemented with YM or placebo for eight weeks. Skin dryness was set as the primary endpoint. No side effects were observed during the study. Microbiota analyses revealed that YM intake selectively increased the relative abundance of Bacteroides thetaiotaomicron and Bacteroides ovatus compared to that by placebo. Feces and urine analyses showed that YM intake lowered the concentration of fecal p-cresol, indole, and skatole, and elevated urinal equol levels compared to those in placebo. Furthermore, YM supplementation ameliorated subjective skin dryness. This study suggests that YM intake could promote beneficial Bacteroides and improve the intestinal environment and skin condition.

Possible benefits of singing to the mental and physical condition of the elderly.

BACKGROUND: The evaluation and management of stress are important for the prevention of both depression and cardiovascular disease. In addition, the maintenance of the oral condition of the elderly is essential to enable them to stay healthy, especially to prevent aspiration pneumonia and improve mental health in an aging society. Therefore, we examined the efficacy of singing on the oral condition, mental health status, and immunity of the elderly to determine if singing could contribute to the improvement of their physical condition. METHODS: Forty-four subjects (10 men, 34 women), aged 60 years or older, participated in this study. The efficacy of singing on mental health status and immunocompetence was examined by swallowing function, oral condition, blood, and saliva tests, as well as through questionnaires taken before and after singing. RESULTS: The results showed that the amount of saliva increased and the level of cortisol, a salivary stress marker, decreased after singing. The Visual Analog Scale (VAS) scores for feeling refreshed, comfortable, pleasurable, light-hearted, relieved, and relaxed; the tension and confusion subscale score; and the total mood disturbance (TMD) score of the Profile of Mood States (POMS) all showed improvements. Furthermore, the same tendencies were shown regardless of whether or not the subjects liked singing. CONCLUSIONS: Our results suggest that singing can be effective in improving the mental health and oral condition of the elderly.

The maximum single dose of resistant maltodextrin that does not cause diarrhea in humans.

The objective of the present study was to determine the maximum dose of resistant maltodextrin (Fibersol)-2, a non-viscous water-soluble dietary fiber), that does not induce transitory diarrhea. Ten healthy adult subjects (5 men and 5 women) ingested Fibersol-2 at increasing dose levels of 0.7, 0.8, 0.9, 1.0, and 1.1 g/kg body weight (bw). Each administration was separated from the previous dose by an interval of 1 wk. The highest dose level that did not cause diarrhea in any subject was regarded as the maximum non-effective level for a single dose. The results showed that no subject of either sex experienced diarrhea at dose levels of 0.7, 0.8, 0.9, or 1.0 g/kg bw. At the highest dose level of 1.1 g/kg bw, no female subject experienced diarrhea, whereas 1 male subject developed diarrhea with muddy stools 2 h after ingestion of the test substance. Consequently, the maximum non-effective level for a single dose of the resistant maltodextrin Fibersol-2 is 1.0 g/kg bw for men and >1.1 g/kg bw for women. Gastrointestinal symptoms were gurgling sounds in 4 subjects (7 events) and flatus in 5 subjects (9 events), although no association with dose level was observed. These symptoms were mild and transient and resolved without treatment.