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An enantioresolution of 2-methoxy-2-(1-naphtyl)propionic acid (MαNP acid) using the diastereomeric salt with chiral (R)-phenylethylamine was achieved to give enantiopure (R)-MαNP acid in 29% yield with >99% ee based on rac-MαNP acid. X-ray crystallographic analysis of diastereomeric salt revealed that (R)-MαNP acid was tightly arranged by four independent hydrogen bonds and one CH-π interaction with (R)-phenylethylamine. [ABSTRACT FROM AUTHOR]

Background and Objectives: Total fat intake is linked to the intake of other nutrients. Little data are available on the extent to which total fat affects diet quality in Japanese people. We investigated the relationship between total fat intake and other nutrient intake using INTERLIPID/ INTERMAP data on Japanese people living in Japan.Methods and Study Design: The participants included 371 men and 401 women with a healthy body mass index and between the ages of 40 and 59 from 4 population samples in Japan. Nutrient intake data were based on four in-depth 24-hour dietary recalls per person.Results: Analysis of covariance adjusted for age revealed that total fat intake was positively related to intakes of calcium, thiamine, riboflavin, meat, eggs, and milks and dairy products for both sexes. Total fat intake was inversely associated with carbohydrate and cereals intake for both sexes. On average, men with total fat intake between 25.0 and 27.4% of total energy had saturated fatty acids above 7%, which is the upper limit recommended for preventing lifestyle-related diseases. Men with total fat intake less than 20% of total energy had a higher risk of not meeting the Dietary Reference Intakes for Japanese (2015) for some nutrients.Conclusions: Total fat intake was positively associated with calcium, thiamine, and riboflavin intakes and inversely associated with carbohydrate intake. Our results suggest that in 40-59-year-old men with a healthy body mass index, total fat intake between 20 and 27% of total energy may best support adequate intake of other nutrients. [ABSTRACT FROM AUTHOR]

Objectives: The present cohort study investigated the relationship between serum ferritin levels and indices of insulin resistance and β-cell dysfunction in a normoglycemic population without iron overload disorders. Methods: The study participants included 575 normoglycemic Japanese men aged 35-57 years with serum ferritin levels of 400 µg/L or less. Insulin resistance and β-cell dysfunction were estimated at baseline and after 3 years by the homeostasis model assessments of insulin resistance and β-cell function (HOMA-IR and HOMA-β, respectively). To compare the subsequent changes in HOMA-IR and HOMA-β over a 3-year follow-up period among 3 groups based on tertiles of baseline serum ferritin levels (4.9-87.1, 87.2-140.5, and 140.6-396.8 µg/L), the geometric mean HOMA-IR and HOMA-β values at year 3 were calculated for each group using analysis of covariance, incorporating the respective log-transformed parameters at baseline in addition to age, body mass index and major confounding factors. Results: The multivariate-adjusted geometric mean HOMA-IR at year 3 was significantly higher in those in the highest and middle serum ferritin tertiles (1.24 and 1.22, respectively), compared with the lowest tertile (1.07) (p = 0.009). When the total study participants were stratified by median body mass index (22.72 kg/m²), similar positive relationships were observed between serum ferritin levels and HOMA-IR for both obese and non-obese participants. However, the adjusted geometric mean HOMA-β at year 3 was similar among the 3 serum ferritin groups. Conclusions: Elevated serum ferritin levels predicted a subsequent increase in HOMA-IR in normoglycemic Japanese men without iron overload disorders. [ABSTRACT FROM AUTHOR]

Bien Hoa Air Base is the largest dioxin contamination hot spot in Vietnam. In 2012, we recruited 216 mothers who were living in 10 communities around Bien Hoa Air Base and had delivered newborns at a prefecture hospital, and we investigated recent exposure levels of dioxins and nonortho PCBs in their breast milk. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD) was present at 2.6 pg/g lipid in primiparae and 2.2 pg/g lipid in multiparae. Among multiparae and total subjects, significant high prevalence of 2,3,7,8-tetraCDD ⩾ 5 pg/g lipid and 2,3,7,8- tetraCDD contribution ⩾ 40% were observed in mothers living in the five communities closest to Bien Hoa Air Base. The TEQ/or nonortho PCBs was 1.6 pg-TEQ/g lipid for primiparae, and this was even lower than that in the unsprayed area. The length of residency was a strong factor to increase dioxins, including 2,3,7,8- tetraCDD. Residency in the five communities with the highest exposure was a specific risk factor for increased 2,3,7,8-tetraCDD in breast milk. Food intake might contribute partly to the increased levels of dioxin congeners other than 2,3,7,8-tetraCDD in breast milk. These results suggest that Bien Hoa Air Base has led to elevated 2,3,7,8- tetraCDD levels in breast milk of mothers in nearby areas even in the recent years. [ABSTRACT FROM AUTHOR]

This study looked to identify determinants of exposure to dioxin in breast milk from breast-feeding women in a hot spot of dioxin exposure in Vietnam. Breast milk was collected from 140 mothers 1 month after delivery. The risk factors investigated included length of residency, drinking of well water and the frequency of animal food consumption. Cluster analysis was performed to identify dietary patterns of fish and meat portions, fish variety and egg variety. Residency, age and parity were clearly associated with increased dioxin levels. Drinking well water and the consumption of marine crab and shrimps were related to higher levels of furans in breast milk. The consumption of quail eggs also appeared to be associated with increased levels of some dioxin isomers in this area. Some mothers who ate no or less meat than fish and mothers who consumed more freshwater fish than marine fish had lower levels of dioxins in their breast milk. However, the type of water and the eating habits of mothers contributed only partly to the increased dioxin levels in their breast milk; the length of residency was the most important risk factor associated with increased dioxin body burdens of mothers. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the mortality and causes of deaths of inhabitants with renal dysfunction induced by cadmium (Cd) exposure caused by heavy environmental contamination. Methods: We conducted a 26-year follow-up survey targeting 7529 inhabitants of the Cd-polluted Jinzu River basin and 2149 controls from non-polluted areas who participated in urinary examinations for proteinuria and glucosuria conducted in 1979 to 1984. When the residents were divided into 4 groups, no finding group, glucosuria group, proteinuria group, glucoproteinuria group, mortality risk ratios for all and specific causes of these groups in the polluted area were compared with that of controls without glucosuria and/or proteinuria after adjustments for age at baseline, smoking status, and history of hypertension using Cox’s proportional hazard model. Results: The mortality risk ratios for all causes of proteinuria and glucoproteinuria in men and glucosuria, proteinuria, and glucoproteinuria in women of the polluted areas significantly increased compared with those of the controls with no urinary findings. Respiratory, renal, and cardiovascular diseases and diabetes in men, and all diseases except cerebrovascular diseases in women contributed toward an increased mortality of exposed glucoproteinuria groups, which involved chronic Cd toxicosis with renal tubular dysfunction. In women, the mortality risks for cancer of the colon and rectum, uterus and kidney and urinary tract were significantly higher in the exposed proteinuria and glucoproteinuria groups, suggesting associations between renal damage and cancer risk. In exposed women, the no finding group and glucoproteinuria group also showed increased mortality from ischemic heart diseases, indicating that all exposed women may be at risk for ischemic heart diseases. Although the control glucosuria and/or proteinuria group also showed high mortality for diabetes and renal diseases, the increased risk ratio for renal disease mortality was much higher in exposed subjects with urinary findings, particularly in women. Conclusions: These findings indicate that inhabitants with renal effects caused by Cd exposure had a poor life prognosis over long-term observation in both genders. Particularly in women, renal tubular dysfunction indicated by glucoproteinuria may increase mortality from cancer, ischemic heart diseases, and renal diseases. [ABSTRACT FROM AUTHOR]

Introduction: The upper limit of recommended dietary cholesterol has been abolished recently from guidelines in Japan and US even though high intake is known to increase serum cholesterol levels. Reverse causality has been involved, reflecting availability of widespread information with consequent lifestyle modifications among knowledgeable people. People with higher serum cholesterol are more likely to modify diet than those with lower serum cholesterol, especially among more educated; if enough people do this, dietary cholesterol will not relate to serum cholesterol or will relate inversely. Hypothesis: We assessed the hypothesis that lifestyle modifications separately by those with high education level and employment status reverse the positive relationship between dietary cholesterol and serum low density lipoprotein cholesterol (LDL-C); therefore, the positive relationship between dietary cholesterol and LDL-C would prevail after adjustment for education level and employment status. Methods: A population-based, random sample, cross-sectional study (INTERLIPID) which was an ancillary study of the International Study of Macronutrients and Blood Pressure (INTERMAP), conducted a survey between 1996 and 1999. Among 1,145 Japanese individuals ages 40-59 years, 106 were excluded because of special diets, use of lipid lowering drugs, hormone replacement, and missing data, leaving 1,039 individuals (533 men and 506 women). Dietary cholesterol was assessed from four 24-h dietary recalls and LDL-C was measured by enzymatic methods on an auto-analyzer. A standard questionnaire inquired about years of education and employment status. Results: Linear regression analysis revealed an inverse association between dietary cholesterol and LDL-C in men (coefficient, -0.04 [95%CI, -0.08 to -0.01]), no significant association when adjusted for education and its interaction term with dietary cholesterol in men (coefficient, 0.05 [95%CI, -0.03 to 0.14]), and a significant positive relation when adjusted for employment and its interaction term in men (coefficient, 0.13 [95%CI, 0.01 to 0.26]). With adjustment for education and employment and their interactions, a significant positive relation was recorded again in men (coefficient, 0.16 [95%CI, 0.03 to 0.29]). These relationships were not observed in women. Conclusions: In Japanese men, education, employment, and their interaction terms with dietary cholesterol reversed an observed inverse relationship between dietary cholesterol and LDL-C. A positive relation prevailed between dietary cholesterol and LDL-C after adjustment for education level and employment status. [ABSTRACT FROM AUTHOR]

Background: Immigration studies reported that dyslipidemia is more prevalent in people living in a western lifestyle. However, it is not clear what kind of lifestyle and dietary factors contribute to this difference. Aim: To investigate whether lifestyle including dietary factors could explain the difference in serum lipids between Japanese in Japan and Japanese-Americans in Hawaii living a western lifestyle. Methods: Analyses were conducted in the INTERLIPID study, where four standardized in-depth 24-h dietary recalls were performed. Non-fasting blood was drawn from the participants who included 1,087 Japanese and 176 Japanese-American. Participants' characteristics were described as means and SD, t test was used for the comparison of means between Hawaii and Japan. Multiple linear regression models were used to examine relationships between dietary and lifestyle factors and the difference in serum lipids levels (low-density lipoprotein cholesterol [LDL-C] and log transformed triglycerides [log-TG]) between Hawaii and Japan, adjusting for age, sex and site as the basic model. Other confounders were then added separately to the basic model. Percentage reduction of regression coefficient for the difference between Hawaii and Japan was calculated. Results: In men, LDL-C levels were significantly higher in Japanese-Americans (138.3 mg/dl) compared to Japanese in Japan (120.3mg/dl, P<0.0001). Similarly, in women LDL-C levels were higher in Japanese-Americans (135.5 mg/dl) than in Japanese in Japan (123.7mg/dl, P<0.001). Median levels of TG were also higher in Japanese-Americans compared to Japanese in Japan (men: 171.0mg/dl and 132.0mg/dl, P<0.001 and women: 132.0mg/dl and 94.5mg/dl, P<0.0001). Mean intakes of most nutrients were significantly different between Japan and Hawaii for both men and women. In multiple linear regression models, for LDL-C, BMI reduced the regression coefficient of site difference by 44.6% in the basic model that included age, sex and site. Added to the basic model separately, alcohol, dietary cholesterol and saturated fatty acid reduced LDL-C site difference by 11%, 15.6% and 13.4%, respectively. For log-TG, BMI reduced the regression coefficient of site difference by 55.8% and other variables tested reduced the site difference by less than 5%. With step by step addition of other variables (BMI, alcohol, dietary cholesterol, fiber and total fat) into the multiple linear regression model, the site LDL-C and log-TG coefficient further reduced from 14.4 to 3.4 (-76.6%) and 0.31 to 0.10 (-68.2%), respectively. Conclusion: BMI explained about half of the higher LDL-C and TG levels in Japanese-Americans in Hawaii compared to Japanese in Japan. BMI together with other macro-nutrients contributed to about 70% of the difference. Further investigation is required to explore the remaining difference. [ABSTRACT FROM AUTHOR]

Background: Studies have found that HDL particle (HDL-P) concentration is inversely associated with risk of CVD, independent of HDL cholesterol (HDL-C). Dietary factors (such as fatty acid intake) have been found to affect levels of HDL-C and influence risk of CVD. However, little is known about the associations of dietary fatty acid with serum HDL-P levels. Hypothesis: We hypothesized that dietary fatty acid associations with HDL-P are independent of HDL-C in men. Methods: Data were from 463 male participants in the 1996-98 cross-sectional INTERLIPID Study, ages 40-59 years, randomly selected from five populations; four in Japan (n=386) and one in Hawaii (n=77). Fatty acid intake was estimated from the mean of four in-depth 24-hour dietary recalls (% kcal per day). Individuals were excluded due to missing data on HDL-P or HDL-C and use of lipid lowering medication. Serum HDL-P was measured using nuclear magnetic resonance and HDL-C was measured using standard methods. Multiple linear regression models were used to assess the association between dietary fatty acid and each of the lipid measures. Results: In men, HDL-P and HDL-C were moderately correlated (r = 0.52, p<0.001). In Model 1 (Table), adjusted for age, country, alcohol intake, BMI, diabetes, hypertension, smoking status, and physical activity, most dietary fatty acids were significantly (p<0.05) associated with HDL-P and HDL-C levels. In Model 2, further adjusted for HDL-C, almost all fatty acids maintained a significant association with HDL-P. In contrast, most associations of fatty acids and HDL-C ceased to be significant after adjustment for HDL-P. Total SFA and omega-3 PUFA remained associated with HDL-C. Conclusion: HDL-P was significantly associated with fatty acid intake, independent of HDL-C. Associations of dietary fatty acid intake and HDL-C level were weaker and generally not independent of HDL-P in men. [ABSTRACT FROM AUTHOR]

Background: Obesity is an established risk factor for hypertension and end stage kidney disease. There is little information on how obesity relates to risk of impaired renal function in apparently healthy individuals. We investigated associations of body mass index (BMI) with timed 24-hour creatinine clearance (Ccr) and glomerular filtration rate (GFR) in the cross-sectional population-based INTERLIPID Study, ancillary study of the International Study on Macro- and Micro-Nutrients and Blood Pressure (INTERMAP). Methods: INTERLIPID participants ages 40-59 y from 5 INTERMAP research samples (4 Japanese and 1 Hawaiian) were investigated. Participants were ethnically all Japanese. Two timed 24-hour urine specimens were collected by each participant and analyses were performed in a central laboratory. Values of serum creatinine (Scr) were assayed by Jaffe's method in a Japanese central laboratory. Data were analyzed from 1,338 Japanese, 570 men and 563 women in Japan, 100 men and 105 women in Hawaii. Measures of kidney function were 24-hour Ccr (ml/min) and GFR (ml/min/1.73m). Ccr was calculated by equation (urine creatinine urine volume)/(Scr 1440); GFR was calculated as Ccr (1.73/body surface area (BSA)). BSA was estimated by the DuBois formula. In addition, estimated GFR (eGFR) was calculated by use of the Modification of Diet in Renal Disease (MDRD) Study equation, 186 Scr-1.154 age-0.203 0.742 (if female). All statistical analyses were stratified by gender. Adjusted mean values of Ccr, GFR, and eGFR in quartiles of BMI were estimated using analysis of covariance. Model 1 was adjusted for age; model 2, for age and urine volume; model 3 for variables in model 2 plus blood pressure, pulse rate, physical activity, smoking habit, alcohol consumption, urinary sodium excretion, HbA1c, and total serum cholesterol. Results: Ccr (mean (SD)) were 107.5 (18.9) in men in Japan, 91.9 (17.0) in women in Japan, 123.4 (25.1) in men in Hawaii, and 98.5 (20.3) in women in Hawaii. BMI quartile ranges were in men Q1 16.8-22.3, Q2 22.3-24.1, Q3 24.1-26.1, and Q4 26.1-42.9; in women Q1 15.9-21.2, Q2 21.2-23.0, Q3 23.0-25.1, and Q4 25.1-47.0. In men, BMI was positively related to multivariate-adjusted Ccr and GFR (P for trend across BMI quartiles <0.001 and <0.001, respectively), however, multivariate-adjusted eGFR was inversely associated with BMI (P for trend 0.001). In women, BMI was positively related to multivariate-adjusted Ccr (P for trend across BMI quartiles <0.001); multivariate-adjusted GFR and eGFR were not significantly associated with BMI. Interactions between age and BMI were not significant in men or women. Conclusions: These results indicate that excess BMI may lead to higher Ccr, and that the MDRD equation may underestimate GFR in middle-aged overweight or obese Japanese men. [ABSTRACT FROM AUTHOR]