Healthy Middle-aged Japanese Men Research Articles

Beta 1,3-1,6 Glucans Produced by Two Novel Strains of Aureobasidium Pullulans Exert Immune and Metabolic Beneficial Effects in Healthy Middle-aged Japanese Men: Results of an Exploratory Randomized Control Study.

In this pilot study, we have evaluated the specific metabolic and immune-related benefits of the AFO-202 strain and N-163 strain of black yeast Aureobasidium pullulans-produced beta 1,3-1,6 glucan in healthy human subjects. Sixteen healthy Japanese male volunteers (aged 40 to 60 years) took part in this clinical trial. They were divided into four groups (n = 4 each): Group I consumed AFO-202 beta-glucan (2 sachets of 1 g each per day), IA for 35 days and IB for 21 days; Group II consumed a combination of AFO-202 beta-glucan (2 sachets of 1 g each) and N-163 beta-glucan (1 sachet of 15 g gel each per day), IIA for 35 days and IIB for 21 days. Decrease in HbA1C and glycated albumin (GA), significant increase of eosinophils and monocytes and marginal decrease in D-dimer levels, decrease in neutrophil-to-lymphocyte ratio (NLR), with an increase in the lymphocyte-to-CRP ratio (LCR) and leukocyte-to-CRP ratio (LeCR) was observed in Group I between pre- and post-treatment. Decrease in total and LDL cholesterol, a decrease of CD11b, serum ferritin, galectin-3 and fibrinogen were profound in Group II between pre- and post-treatment. However, there was no statistically significant difference between day 21 and day 35 among the groups. This outcome warrants larger clinical trials to explore the potentials of these safe food supplements in the prevention and prophylaxis of diseases due to dysregulated metabolism, such as fatty liver disease, and infections such as COVID-19 in which balanced immunomodulation are of utmost importance, besides their administration as an adjunct to existing therapeutic approaches of both communicable and non-communicable diseases.

Longitudinal Association of Arterial Stiffness and Pressure Wave Reflection with Decline of the Cardiac Systolic Performance in Healthy Men.

Aims: This prospective observational study aimed to examine the individual longitudinal associations of the increases in the arterial stiffness and pressure wave reflection with the decline in the cardiac systolic performance during the study period in healthy middle-aged Japanese men. Methods: In 4016 middle-aged Japanese healthy men (43±9 years), the brachial-ankle pulse wave velocity (baPWV), radial augmentation index (rAI), and pre-ejection period/ejection time (pre-ejection period (PEP)/ET) were measured annually during a 9-year study period. Results: The baPWV, rAI, and PEP/ET showed steady annual increases during the study period. According to the results of multivariate linear regression analyses, both the baPWV and rAI measured at the baseline showed significant independent associations with the PEP/ET measured at the baseline (baPWV: beta=0.17,p＜0.01 and rAI: beta=0.11,p＜0.01), whereas neither showed any association with the PEP/ET measured at the end of the study period. The results of the mixed-model linear regression analysis of the repeated-measures data collected over the 9-year study period revealed that the baPWV, but not the rAI, showed a significant longitudinal association with the PEP/ET (estimate=0.69 x 10−4,p＜0.01). Conclusion: In apparently healthy middle-aged Japanese men, the annual increase of the arterial stiffness, rather than the annual increase of the pressure wave reflection, appears to be more closely associated with the annual decline of the cardiac systolic performance as assessed by the systolic time interval.

Mediation of Arterial Stiffness for Hyperuricemia-Related Decline of Cardiac Systolic Function in Healthy Men.

Background: This prospective observational study examined whether hyperuricemia may be associated with impaired left ventricular (LV) systolic function and increased cardiac load resulting from increased arterial stiffness.Methods and Results: In 1,880 middle-aged (mean [±SD] age 45±9 years) healthy men, serum uric acid (UA) levels, pre-ejection period/ejection time (PEP/ET) ratio, serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and brachial-ankle pulse wave velocity (baPWV) were measured at the start and end of the 3-year study period. Linear regression analysis revealed that serum UA levels measured at baseline were significantly associated with the PEP/ET ratio, but not with serum NT-proBNP levels, measured at baseline (β=0.73×10−1, P<0.01) and at the end of the study period (β=0.68×10−1, P<0.01). The change in the PEP/ET ratio during the study period was significantly greater in the High-UA (UA >7 mg/dL in 2009 and 2012) than Low-UA (UA ≤7 mg/dL in 2009 and 2012) group. Mediation analysis demonstrated both direct and indirect (via increases in baPWV) associations between serum UA measured at baseline and the PEP/ET ratio measured at the end of the study period.Conclusions: In healthy middle-aged Japanese men, hyperuricemia may be associated with an accelerated decline in ventricular systolic function, both directly and indirectly, via increases in arterial stiffness.

Longitudinal changes in late systolic cardiac load and serum NT-proBNP levels in healthy middle-aged Japanese men.

We determined whether any significant association exists between change in late systolic cardiac load with time, estimated by radial pressure waveform analysis, and development of cardiac hemodynamic stress in individuals with preserved cardiac function. Brachial-ankle pulse wave velocity, radial augmentation index (rAI), first peak of the radial pressure waveform (SP1), systolic and pulse pressure at the second peak of the radial pressure waveform (SP2 and PP2), and serum levels of N-terminal fragment B-type natriuretic peptide (NT-proBNP) were measured at the start (first examination) and at the end (second examination) of this 3-year study in healthy Japanese men (n = 1,851). A stepwise multivariate linear regression analysis demonstrated that among the parameters of radial pressure waveform analysis and markers of arterial stiffness analyzed, only PP2 was significantly associated with serum NT-proBNP levels in study participants at both the first and second examinations. Furthermore, among the parameters analyzed, only change in PP2 was significantly correlated with the change in serum NT-proBNP levels during the study period (beta = 0.131, P < 0.001). Sustained late systolic cardiac load might be a more significant determinant of the development of cardiac hemodynamic stress than sustained early systolic cardiac load or arterial stiffening in individuals with preserved cardiac function.

Self-reported faster eating is positively associated with accumulation of visceral fat in middle-aged apparently healthy Japanese men

Faster eating is positively associated with body mass index in apparently healthy Japanese populations. In the present study, we examined the associations between self-reported rate of eating and visceral and subcutaneous fat areas in apparently healthy middle-aged Japanese men. We conducted a cross-sectional study of men who participated in health checkups in Japan. We removed participants who were diagnosed with metabolic diseases by the time of their health checkups. A total of 320 subjects aged 30-64 years (mean ± standard deviation, 47.4 ± 8.6 years) were selected. We compared the associations between rate of eating and various clinical parameters including visceral and subcutaneous fat areas, using analysis of covariance (ANCOVA), which was adjusted by age and lifestyle factors such as alcohol intake, energy intake, smoking, and physical activity. Multivariate logistic regression analyses (MLRA) were performed with visceral fat area (cm(2)) as the dependent variable and independent variables that included self-reported rate of eating. Tukey's multiple test following ANCOVA showed that self-reported rate of eating was positively associated with visceral fat area (cm(2)), but not with subcutaneous fat area (cm(2)). MLRA showed that the odds ratio of rate of eating for visceral fat area in tertile (T) 3 (>100 cm(2)) compared with T1 (≤70 cm(2)) was 1.99 (95% CI 1.40-2.90, P < 0.01), and the association remained after adjustment for the subcutaneous fat area. The present results show that self-reported faster eating is positively associated with visceral fat accumulation, independently of subcutaneous fat accumulation, in apparently healthy Japanese men.

Is Low Testosterone Concentration a Risk Factor for Metabolic Syndrome in Healthy Middle-aged Men?

To clarify the probability of low serum testosterone level as a risk factor for metabolic syndrome (MS) in middle-aged men, we measured serum total testosterone (TT) and assessed several metabolic factors because the direct risk for MS has not been investigated fully in men. This study comprised 1150 men aged≥30 years. Physical and laboratory variables were assessed. Analyses were conducted to determine the association between serum TT level and incidence risk of MS and MS factors by a separate logistic regression model. Mean (± standard deviation [SD]) serum TT level was 5.4 ± 1.7 ng/mL in the 1150 men, and only 92 men (8.0%) were classified as having MS by the Japanese criteria. In age-adjusted analyses, higher levels of serum TT were independently associated with a lower risk of MS (odds ratio, per SD decrement of TT, 2.3; 95% confidence interval [CI], 1.7-2.9). MS risk increased by lower quintile of TT: ORs were 15.1 (95% CI, 4.6-50.0) for first quintile, 8.8 (95% CI, 2.6-29.9) for second quintile, 5.8 (95% CI, 1.7-20.5) for third quintile, and 5.0 (95% CI, 1.4-17.9) for fourth quintile compared with highest quintile of TT. Age-adjusted ORs for the incidence of dichotomous components of MS per SD decrement of TT were 1.8 (95% CI, 1.5-2.3) for waist circumference, 1.6 (95% CI, 1.1-2.2) for dyslipidemia, and 1.5 (95% CI, 1.2-1.8) for hypertension. We found that higher probability of MS was associated with lower levels of serum TT level in relatively healthy middle-aged Japanese men.

Glucose levels during oral glucose tolerance tests and gamma-glutamyl transpeptidase are predictors of change from normal to impaired glucose tolerance in healthy middle-aged Japanese men

We evaluated the predictors of the development from normal to impaired glucose tolerance (IGT) in healthy middle-aged Japanese men. Forty male subjects who showed normal glucose tolerance (NGT) levels based on WHO criteria and who had undergone 75-g OGTT annually for 10 years were selected in the database of medical checkups retrospectively, and divided into two groups: those retaining NGT and those that developed IGT. Gamma-glutamyl transpeptidase (GGT) and the glucose levels at 30 and 60 min were significantly associated with the development of IGT in the Cox proportional hazard model. However, other clinical characteristics and the glucose levels at pre-load and at 120 min were not significantly associated with the development of IGT. GGT and the glucose levels at 30 and 60 min after the 75-g glucose load were predictors of development from NGT to IGT in healthy middle-aged Japanese men.

Administration of dietary fish oil capsules in healthy middle-aged Japanese men with a high level of fish consumption

The nutritional effects of fish oil, which is rich in the n-3 polyunsaturated fatty acids, have been reported. In this randomized, placebo-controlled, double-blind, crossover study, we evaluated the effects of dietary fish oil capsules on the hematological parameters of healthy middle-aged Japanese men with a high level of fish oil consumption. Over a 4-week period, subjects were administered five fish oil or olive oil (placebo) capsules with every meal (1,260 mg eicosapentaenoic acid and 540 mg docosahexaenoic acid/day). There was a 4-week washout period between the treatment phases. The results did not demonstrate a decrease in plasma triacylglycerol, cholesterol, low-density lipoprotein cholesterol, and whole-blood viscosity. Further, no changes in the fatty acid composition of plasma and erythrocyte phospholipids were noted. These results suggested that the supplementation of fish oil might be effective only for those subjects who have a lower level of fish oil consumption.

Overweight Body Mass Index Classification Modifies Arterial Stiffening Associated with Weight Gain in Healthy Middle-Aged Japanese Men

The present study was conducted to clarify whether body mass index (BMI [kg/m(2)]) classifications (i.e., without excess weight, overweight, and obese) modify the rate of progression of arterial stiffening, a cardiovascular risk factor associated with weight gain. A 3-year observational study was conducted in 2,080 healthy middle-aged Japanese men (aged 42+/-10 years). Brachial-ankle pulse wave velocity (baPWV) was measured at the beginning and end of the study period. In overweight subjects (30>BMI>or=25), the estimated annual rate of increase of baPWV (ARbaPWV) in subjects with weight gain (>or=5% weight gain; ARbaPWV, 21.8+/-4.4 cm/s/year) was significantly higher than in those without weight gain (<5% weight gain; ARbaPWV, 12.5+/-1.6 cm/s/year), after adjustments for changes in blood pressure and other variables (p<0.05). This change was not observed in subjects without excess weight (BMI<25) or in obese subjects (BMI>or=30). The increase in the ARbaPWV associated with weight gain in the overweight group was also higher than that in the without excess body weight or obese groups. Our study revealed that the BMI classifications modified the annual rate of increase in arterial stiffening associated with weight gain. Weight gain seemed to accelerate arterial stiffening in overweight subjects, but not in subjects without excess weight. The weight gain in overweight subjects seemed to worsen the cardiovascular risk related to arterial stiffness in middle-aged healthy Japanese men. Thus, the prevention of weight gain should be emphasized in overweight subjects.

Longevity-associated NADH dehydrogenase subunit-2 polymorphism and serum electrolyte levels in middle-aged obese Japanese men

Mitochondrial DNA 5178 cytosine/adenine polymorphism, which is also called NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with Japanese longevity. This polymorphism is widely associated with blood pressure, serum lipid levels, hematological parameters, intraocular pressure, and serum protein fraction levels. However, there have been no reports on the association between ND2-237 Leu/Met polymorphism and serum electrolyte levels. To investigate this relationship, we performed an association study in 321 healthy middle-aged Japanese men. Crude data showed that serum sodium levels and serum chloride levels were significantly lower in men with ND2-237 Met than in those with ND2-237 Leu ( P = 0.021 and 0.003, respectively). Cigarette consumption and body mass index were significantly and positively associated with serum chloride levels ( P = 0.002 and 0.008, respectively) and hemoglobin levels were significantly and negatively associated with them ( P = 0.007) in ND2-237 Leu genotypic men. In men with ND2-237 Met, only hemoglobin levels were significantly and negatively associated with serum chloride levels ( P = 0.025). After adjusting for covariates, only in male obese (body mass index ≥ 25) subjects, serum sodium and chloride levels remained significantly lower, and serum calcium levels appeared to be significantly higher in ND2-237 Met than in ND2-237 Leu ( P = 0.013, <0.001, and 0.046, respectively). Longevity-associated NADH dehydrogenase subunit-2 polymorphism may influence serum electrolyte levels in middle-aged obese Japanese men.

Stiffening Our Resolve Against Adult Weight Gain

Increasing adiposity with a clinical endpoint of obesity is associated with a progressive increase in risk of cardiovascular diseases (CVD). However, we are only beginning to understand the physiological and pathophysiological mechanisms by which excessive body fat storage causes CVD. In this issue of Hypertension , the findings of Wildman et al1 extend and strengthen previous observations2–5 by showing that changes in arterial stiffness, as measured by aortic pulse-wave velocity (PWV), are related to changes in body weight over a 2-year follow-up period in healthy men and women aged 20 to 40 years. Weight gain was associated with an increase, whereas weight loss was associated with a decrease in aortic PWV, independent of changes in blood pressure. The greatest increases in aortic PWV were observed in those subjects who gained the most weight (≥4.5 kg). Importantly, the changes in aortic PWV were related to changes in body mass index (BMI), indicating that the associations with body weight were mediated by changes in adiposity (rather than fat-free mass). Changes in aortic PWV over time also were related to baseline body weight, BMI, and waist circumference (an indirect measure of abdominal adiposity), providing evidence that higher initial levels of total and abdominal body fatness are associated with greater future increases in arterial stiffness. The study included subjects with a broad range of BMI, suggesting that the findings are applicable to both nonobese and obese adults in the general population. An important finding was that black adults demonstrated greater increases in weight gain-adjusted and blood pressure-adjusted aortic PWV over time, suggesting that they undergo greater increases in arterial stiffness in response to the same age-associated weight gain compared with whites. These observations provide further support for the emerging concept that adiposity-driven weight gain during adulthood contributes significantly to the adverse changes …

Longevity-associated mitochondrial DNA 5178 A/C polymorphism modulates effects of daily drinking and cigarette consumption on serum triglyceride levels in middle-aged Japanese men

Mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism is one of the longevity-associated mitochondrial DNA polymorphisms. The frequency of the mt5178A genotype is significantly higher in Japanese centenarians than in the general population. We previously reported that serum high-density lipoprotein cholesterol levels were significantly higher in men with mt5178A than in those with mt5178C. However, this significant difference disappeared after adjusting for drinking frequency. To investigate the interaction between mt5178 A/C polymorphism and habitual drinking on serum lipid levels, we performed an association study in 321 healthy middle-aged Japanese men. Interaction between mt5178 A/C polymorphism and daily drinking on serum triglyceride (TG) levels was observed ( P=0.019). Moreover, interaction between mt5178 A/C polymorphism and cigarette consumption on serum TG levels was also observed ( P=0.022). Multiple regression analysis showed that, in men with mt5178A, daily drinking decreased TG levels ( P=0.025), and cigarette consumption increased TG levels ( P<0.001), while in men with mt5178C, the effects of daily drinking and cigarette consumption on TG levels were unclear. No interaction was observed on other lipid levels. Longevity-associated mitochondrial DNA 5178 A/C polymorphism thus influences the effects of daily drinking and cigarette consumption on TG levels in middle-aged Japanese men.

Genetic differences in ethanol metabolizing enzymes and blood pressure in Japanese alcohol consumers.

Orientals have unique genetic polymorphisms in ethanol metabolizing enzymes, such as alcohol dehydrogenase-2 (ADH2), aldehyde dehydrogenase-2 (ALDH2) and cytochrome P450-2E1 (CYP2E1). Of the three studies conducted to clarify the influence of ALDH2 genotypes on sensitivity to the pressor effects of alcohol in Japanese, only one was suggested, though indirectly, higher sensitivity in drinkers having the genotype of inactive ALDH2. This discrepancy prompted us to determine ADH2, ALDH2 and CYP2E1 genotypes in the genomic DNA extracted from white blood cells of 855 healthy middle-aged Japanese men, and to analyse the associations with the alcohol-blood pressure (BP) relationship. No marked differences were found in the relationship among the genotypes of ALDH2, although the subjects with intact ALDH2 showed a slightly higher BP than those with inactive ALDH2 probably due to under-reporting of alcohol consumption in those with intact ALDH2 who could thus drink more. No significant influence of ADH2 genotypes was observed. A higher BP was noted in large volume alcohol consumers having c2/c2 genotype of CYP2E1. Multivariate regression analysis adjusting for the effects of age, body mass index and the volume of alcohol consumed, all of which are strong determinants of BP levels, showed only a marginal effect of c2 allele of CYP2E1 on diastolic BP elevations with increases in alcohol consumption. Thus it is concluded that the genetic polymorphisms in ethanol-metabolizing enzymes do not greatly influence the alcohol-BP relationship in Japanese men.