Effects of Long-Chain Polyunsaturated Fatty Acids in Combination with Lutein and Zeaxanthin on Episodic Memory in Healthy Older Adults.

Arachidonic acid (ARA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), which are long-chain polyunsaturated fatty acids (LCPUFAs), as well as lutein (L) and zeaxanthin (Z), can potentially improve brain function. However, the effect of a combination of these components (LCPUFAs + LZ) on memory function in healthy older individuals remains unclear. This study aimed to determine if LCPUFAs + LZ-supplemented food could improve memory function. Exploratory and confirmatory trials (Trials 1 and 2, respectively) were conducted in healthy older Japanese individuals with memory complaints. We conducted randomized, double-blind, placebo-controlled, parallel-group trials. Participants were randomly allocated to two groups: placebo or LCPUFAs + LZ. LCPUFAs + LZ participants were provided with supplements containing ARA, DHA, EPA, L, and Z for 24 weeks in Trial 1 and 12 weeks in Trial 2. Memory functions were evaluated using Cognitrax before and after each trial. Combined analyses were performed for subgroups of participants with cognitive decline in Trials 1 and 2. The results showed that supplementation with LCPUFAs + LZ did not significantly affect memory function in healthy, non-demented, older individuals with memory complaints whereas it improved memory function in healthy, non-demented, older individuals with cognitive decline.

Effects of combining exercise with long-chain polyunsaturated fatty acid supplementation on cognitive function in the elderly: a randomised controlled trial.

Multifactorial lifestyle intervention is known to be more effective for ameliorating cognitive decline than single factor intervention; however, the effects of combining exercise with long-chain polyunsaturated fatty acids (LCPUFA) on the elderlies' cognitive function remain unclear. We conducted a randomised, single-masked placebo-controlled trial in non-demented elderly Japanese individuals. Participants were randomly allocated to the exercise with LCPUFA, placebo, or no exercise with placebo (control) groups. Participants in the exercise groups performed 150 min of exercise per week, comprised resistance and aerobic training, for 24 weeks with supplements of either LCPUFA (docosahexaenoic acid, 300 mg/day; eicosapentaenoic acid, 100 mg/day; arachidonic acid, 120 mg/day) or placebo. Cognitive functions were evaluated by neuropsychological tests prior to and following the intervention. The per-protocol set analysis (n = 76) revealed no significant differences between the exercise and the control groups in changes of neuropsychological tests. Subgroup analysis for participants with low skeletal muscle mass index (SMI) corresponding to sarcopenia cut-off value showed changes in selective attention, while working memory in the exercise with LCPUFA group was better than in the control group. These findings suggest that exercise with LCPUFA supplementation potentially improves attention and working memory in the elderly with low SMI.

Supplementation with Matured Hop Bitter Acids Improves Cognitive Performance and Mood State in Healthy Older Adults with Subjective Cognitive Decline.

BACKGROUND: Prevention of age-related cognitive decline and depression is becoming urgent because of rapid growing aging populations. Effects of vagal nerve activation on brain function by food ingredients are inadequately investigated; matured hop bitter acid (MHBA) administration reportedly improves cognitive function and depression via vagal nerve activation in model mice. OBJECTIVE: We investigated the effects of MHBA supplementation on cognitive function and mood state in healthy older adults with perceived subjective cognitive decline. METHODS: Using a randomized double-blind placebo-controlled trial design, 100 subjects (aged 45-69 years) were randomly assigned into placebo (n = 50) and MHBA (n = 50) groups, and received placebo or MHBA capsules daily for 12 weeks. RESULTS: Symbol Digit Modalities Test (SDMT) score assessing divided attention at week 12 was significantly higher (p = 0.045) and ß-endorphin at week 12 was significantly lower (p = 0.043) in the subjects receiving MHBA. Transthyretin in serum, a putative mild cognitive impairment marker, was significantly higher at week 12 in the MHBA group than in the placebo group (p = 0.048). Subgroup analysis classified by the subjective cognitive decline questionnaire revealed that in addition to improved SDMT scores, memory retrieval assessed using the standard verbal paired-associate learning tests and the Ray Verbal Learning Test at week 12 had significantly improved in the subgroup with perceived subjective cognitive decline and without requirement for medical assistance in the MHBA group compared with that in the placebo group. CONCLUSION: This study suggested that MHBA intake improves cognitive function, attention, and mood state in older adults.

Effect of Short-Term Increase in Meal Frequency on Glucose Metabolism in Individuals with Normal Glucose Tolerance or Impaired Fasting Glucose: A Randomized Crossover Clinical Trial.

Effects of meal frequency on blood glucose levels and glucose metabolism were evaluated over 3 days in adult males with normal glucose tolerance (NGT, n = 9) or impaired fasting glucose (IFG, n = 9) in a randomized, crossover comparison study. Subjects were provided with an isocaloric diet 3 times daily (3M) or 9 times daily (9M). Blood glucose was monitored on Day 3 using a continuous glucose monitoring system, and subjects underwent a 75-g oral glucose tolerance test (OGTT) on Day 4. Daytime maximum blood glucose, glucose range, duration of glucose ≥180 mg/dL, and nighttime maximum glucose were significantly lower in the NGT/9M condition than in the NGT/3M condition. Similar findings were observed in the IFG subjects, with a lower daytime and nighttime maximum glucose and glucose range, and a significantly higher daytime minimum glucose in the 9M condition than in the 3M condition. The OGTT results did not differ significantly between NGT/3M and NGT/9M conditions. In contrast, the incremental area under the curve tended to be lower and the maximum plasma glucose concentration was significantly lower in the IFG/9M condition than in the IFG/3M condition. In IFG subjects, the 9M condition significantly improved glucose metabolism compared with the 3M condition. Higher meal frequency may increase glucagon-like peptide 1 secretion and improve insulin secretion.

Effect of Supplementation of a Whey Peptide Rich in Tryptophan-Tyrosine-Related Peptides on Cognitive Performance in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Study.

Background: Previous epidemiological and clinical studies have shown that dairy products have beneficial effects on cognitive decline and dementia. Enzymatic digestion of whey protein produces a whey peptide rich in tryptophan-tyrosine-related peptides which improve cognitive performance in mice. We evaluated the effects of whey peptides on cognitive functions in healthy adults in a randomized, double-blind, placebo-controlled design. Methods: 101 healthy adults (45 to 64 years), with a self-awareness of cognitive decline received either whey peptide or placebo supplements for 12 weeks. Changes in cognitive function were assessed using neuropsychological tests at 6 and 12 weeks after the start of supplementation. Results: Verbal fluency test (VFT) score changes tended to be higher in the whey peptide group compared with the placebo at 12 weeks. Subgroup analysis classified by the degree of subjective fatigue showed that changes in the VFT as well as the Stroop and subjective memory function tests between baseline and 6 weeks of intervention were significantly better in subjects with high-level fatigue from the whey peptide group as compared to the placebo group. CONCLUSIONS: Intake of whey peptide might improve cognitive function in healthy middle- and older-aged adults with high subjective fatigue levels. Further studies will elucidate the relationship among cognitive improvement, whey peptides, and psychological fatigue.

Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study.

Kale (Brassica oleracea var. acephala), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21-64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140-187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30-120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (Cmax; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); P<0.01]. The area under the plasma glucose concentration-time curve for 0-2 h (AUC0-2 h) values (means ± SD) were significantly lower for active-L (268±43 mg/h/dl) and active-H (266±42 mg/h/dl) than for the placebo (284±43 mg/h/dl; P<0.05). No significant differences were identified in the postprandial plasma insulin levels between the three conditions. No adverse events associated with intake of either dose of kale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe.

Matured hop extract reduces body fat in healthy overweight humans: a randomized, double-blind, placebo-controlled parallel group study.

BACKGROUND: Hops are the main components of beer that provide flavor and bitterness. Iso-α-acids, the bitter components of beer, have been reported to reduce body fat in humans, but the bitterness induced by effective doses of iso-α-acids precludes their acceptance as a nutrient. The matured hop bitter acids (MHBA) of oxidized hops appear to have a more pleasant bitterness compared to the sharper bitterness of iso-α-acids. While there has been little information concerning the identity of the MHBA compounds and their physiological effects, MHBA was recently found to be primarily composed of oxides derived from α-acids, and structurally similar to iso-α-acids. Here, we investigated the effects of matured hop extract (MHE) containing MHBA on reducing abdominal body fat in healthy subjects with a body mass index (BMI) of 25 to below 30 kg/m(2), classified as "obese level 1" in Japan or as "overweight" by the WHO. TRIAL DESIGN: A randomized, double-blind, placebo-controlled parallel group study. METHODS: Two hundred subjects (male and female aged 20 to below 65 years with a BMI of 25 or more and less than 30 kg/m(2)) were randomly assigned to two groups. During a 12-week ingestion period, the subjects in each group ingested daily 350 mL of test-beverage, either containing MHE (with 35 mg MHBA), i.e. the namely active beverage, or a placebo beverage without MHE. The primary endpoint was reduction of the abdominal fat area as determined by CT scanning after continual ingestion of MHE for 12 weeks. RESULTS: Compared to the placebo group, a significant reduction was observed in the visceral fat area after 8 and 12 w, and in the total fat area after 12 w in the active group. There was also a concomitant decrease in body fat ratio in the active group compared to the placebo group. No adverse events related to the test beverages or clinically relevant abnormal changes in the circulatory, blood and urine parameters were observed in either group. CONCLUSIONS: The present study suggests that continual ingestion of MHE safely reduces body fat, particularly the abdominal visceral fat of healthy overweight subjects. TRIAL REGISTRATION: UMIN-CTR UMIN000014185.

Improvement of liver function by the administration of oyster extract as a dietary supplement to habitual alcohol drinkers: A pilot study.

Alcoholic liver disease (ALD) is characterized by elevated serum γ-glutamyltransferase (GGT) activity with hepatic steatosis, hepatitis or occasionally fibrosis that may progress to cirrhosis. The potential therapeutic role of oyster extract (OE) or OE-containing dietary supplements (OE supplement) in ALD has seldom been evaluated. In the present study, 84 adults who had an alcohol-drinking habit and marginally high serum GGT levels were enrolled in a randomized, double-blind, placebo-controlled feeding trial to study the effect on alcohol-impaired liver function as reflected by an increased serum level of GGT, as well as the safety, of an OE supplement. The subjects were randomized to receive either an OE supplement (OE group) or placebo (placebo group). There were 42 subjects (31 males and 11 females) in each group, and all the enrolled subjects entered the study. Four individuals (5%) dropped out for reasons unassociated with the study and 6 other subjects were excluded from the efficacy analysis because they did not maintain the required frequency of alcohol intake. As a result, 38 subjects in the placebo group and 36 in the OE group underwent efficacy assessment. Assays of GGT and other liver enzymes were performed at baseline (week 0) and at weeks 4, 8 and 12 of the intervention period. The mean serum levels of GGT in the placebo group gradually increased, while those in the OE group tended to decrease, although no significant within-group differences were observed for either group. A significant between-group difference in the change of mean GGT from baseline was, however, found at week 12 (P=0.049). No OE supplement-associated untoward side-effects nor any abnormal changes in routine laboratory tests and anthropometric parameters were observed throughout the 12-week intervention. An OE supplement shows promise in reducing risk factors associated with ALD in adults with an alcohol intake habit.

The effects of natural S-equol supplementation on skin aging in postmenopausal women: a pilot randomized placebo-controlled trial.

OBJECTIVE: The aim of this study was to investigate the effects of the natural S-equol supplement on skin aging in equol-nonproducing Japanese postmenopausal women. METHODS: A randomized, double-blind, placebo-controlled trial examined the use of the natural S-equol supplement for 12 weeks in 101 postmenopausal Japanese women who were equol nonproducers. They were randomly assigned to one of three groups: placebo (n = 34), 10 mg S-equol/day (EQL10; n = 34), or 30 mg S-equol/day (EQL30; n = 33). Skin parameters of crow's-feet wrinkles (area and depth), hydration, transepidermal water loss, and elasticity were measured at baseline and at monthly intervals during treatment. Vaginal cytology, endometrial thickness, and mammography were performed before and after treatment. Serum hormone concentrations were measured at the same time as skin parameters. RESULTS: The EQL10 and EQL30 groups showed significant reductions in wrinkle area compared with the placebo group (P < 0.05). There was a significant difference in wrinkle depth between the placebo group and the EQL30 group (P < 0.05). Other skin parameters did not show significant differences after the treatment in any group. There were no abnormal results in hormone status or gynecological examinations. CONCLUSIONS: Our data suggest that natural S-equol supplementation (EQL10 and EQL30) may have a beneficial effect on crow's-feet wrinkles in postmenopausal women without serious adverse events.