Investigating Associations of Omega-3 Fatty Acids, Lung Function Decline, and Airway Obstruction.

Rationale: Inflammation contributes to lung function decline and the development of chronic obstructive pulmonary disease. Omega-3 fatty acids have antiinflammatory properties and may benefit lung health. Objectives: To investigate associations of omega-3 fatty acids with lung function decline and incident airway obstruction in a diverse sample of adults from general-population cohorts. Methods: Complementary study designs: 1) longitudinal study of plasma phospholipid omega-3 fatty acids and repeated FEV1 and FVC measures in the NHLBI Pooled Cohorts Study and 2) two-sample Mendelian randomization (MR) study of genetically predicted omega-3 fatty acids and lung function parameters. Measurements and Main Results: The longitudinal study found that higher omega-3 fatty acid levels were associated with attenuated lung function decline in 15,063 participants, with the largest effect sizes for the most metabolically downstream omega-3 fatty acid, docosahexaenoic acid (DHA). An increase in DHA of 1% of total fatty acids was associated with attenuations of 1.4 ml/yr for FEV1 (95% confidence interval [CI], 1.1-1.8) and 2.0 ml/yr for FVC (95% CI, 1.6-2.4) and a 7% lower incidence of spirometry-defined airway obstruction (95% CI, 0.89-0.97). DHA associations persisted across sexes and smoking histories and in Black, White, and Hispanic participants, with associations of the largest magnitude in former smokers and Hispanic participants. The MR study showed similar trends toward positive associations of genetically predicted downstream omega-3 fatty acids with FEV1 and FVC. Conclusions: The longitudinal and MR studies provide evidence supporting beneficial effects of higher levels of downstream omega-3 fatty acids, especially DHA, on lung health.

Investigating associations of omega-3 fatty acids, lung function decline, and airway obstruction.

Rationale: Inflammation contributes to lung function decline and the development of chronic obstructive pulmonary disease. Omega-3 fatty acids have anti-inflammatory properties and may benefit lung health. Objectives: Investigate associations of omega-3 fatty acids with lung function decline and incident airway obstruction in adults of diverse races/ethnicities from general population cohorts. Methods: Complementary study designs: (1) longitudinal study of plasma phospholipid omega-3 fatty acids and repeated FEV 1 and FVC measures in the National Heart, Lung, and Blood Institute Pooled Cohorts Study, and (2) two-sample Mendelian Randomization (MR) study of genetically predicted omega-3 fatty acids and lung function parameters. Measurements and Main Results: The longitudinal study found that higher omega-3 fatty acid concentrations were associated with attenuated lung function decline in 15,063 participants, with the largest effect sizes for docosahexaenoic acid (DHA). One standard deviation higher DHA was associated with an attenuation of 1.8 mL/year for FEV 1 (95% confidence interval [CI] 1.3-2.2) and 2.4 mL/year for FVC (95% CI 1.9-3.0). One standard deviation higher DHA was also associated with a 9% lower incidence of spirometry-defined airway obstruction (95% CI 0.86-0.97). DHA associations persisted across sexes, smoking histories, and Black, white and Hispanic participants, with the largest magnitude associations in former smokers and Hispanics. The MR study showed positive associations of genetically predicted omega-3 fatty acids with FEV 1 and FVC, with statistically significant findings across multiple MR methods. Conclusions: The longitudinal and MR studies provide evidence supporting beneficial effects of higher circulating omega-3 fatty acids, especially DHA, on lung health.

Nontraditional Risk Factors for Progression Through Chronic Kidney Disease Risk Categories: The Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: There may be nontraditional pathways of chronic kidney disease (CKD) progression that are complementary to classical pathways. Therefore, we aimed to examine nontraditional risk factors for incident CKD and its progression. METHODS: We used the generally healthy population (n = 4382) starting at age 27-41 years in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, which is an observational longitudinal study. Nontraditional risk factors included forced vital capacity, inflammation, serum urate, and serum carotenoids. CKD risk category was classified using the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) measured in 1995-1996 and repeated every 5 years for 20 years: No CKD, low risk, moderate risk, high risk, and very high risk. RESULTS: At baseline, 84.8% had no CKD (eGFR ≥60 mL/min/1.73 m2 and UACR <10 mg/g), 10.3% were in the low risk (eGFR ≥60 and UACR 10-29), and 4.9% had CKD (eGFR <60 and/or UACR ≥ 30). Nontraditional risk factors were significantly associated with the progression of CKD to higher categories. Hazard ratios per standard deviation of the predictor for incident CKD and its progression from the No CKD and low and moderate risk into CKD were inverse for forced vital capacity and serum carotenoids and positive for serum urate, GlycA, and C-reactive protein, the first 3 even after adjustment for conventional risk factors. CONCLUSION: Several nontraditional markers were significantly associated with an increased risk of progression to higher CKD categories in generally healthy young to middle-aged adults.

Calcium Intake Is Inversely Related to Risk of Obesity among American Young Adults over a 30-Year Follow-Up.

BACKGROUND: Calcium (Ca) is an essential nutrient that may play an important role in weight maintenance through its involvement in energy or lipid metabolism. However, little is known about the long-term associations of Ca intake with obesity risk. OBJECTIVES: We aimed to prospectively examine the association between cumulative Ca intake and the incidence of obesity among American young adults over 30 y of follow-up. METHODS: Participants were from the CARDIA (Coronary Artery Risk Development in Young Adults) study. A total of 4097 of 5115 black and white individuals aged 18-30 y at baseline in 1985-1986 were included in the current analysis. Dietary and supplemental Ca intake was assessed by the validated interview-based CARDIA diet history at baseline and exam years 7 and 20. Incident cases of obesity were identified when BMI was ≥30 kg/m2 for the first time since baseline. A survival analysis was performed using Cox proportional hazards regression models to estimate the HRs and corresponding 95% CIs for obesity incidence during follow-up. RESULTS: During a 30-y follow-up (mean ± SD: 20 ± 10 y), 1675 participants developed obesity. Cumulative total Ca intake (dietary plus supplemental Ca) was inversely associated with incidence of obesity in multivariable-adjusted analysis [quintile (Q)5 (highest intake) compared with Q1 (lowest intake): HR: 0.68; 95% CI: 0.56, 0.82; P-trend < 0.01]. This inverse association persisted among Ca supplement users (Q5 compared with Q1: HR: 0.53; 95% CI: 0.40, 0.70; P-trend < 0.01), but was not seen among nonusers. CONCLUSIONS: Following a cohort of Americans from young adulthood to midlife, an inverse association between calcium intake and obesity incidence was observed. Further studies are needed to confirm our findings.

Magnesium intake was inversely associated with hostility among American young adults.

Hostility is a complex personality trait associated with many cardiovascular risk factor phenotypes. Although magnesium intake has been related to mood and cardio-metabolic disease, its relation with hostility remains unclear. We hypothesize that high total magnesium intake is associated with lower levels of hostility because of its putative antidepressant mechanisms. To test the hypothesis, we prospectively analyzed data in 4,716 young adults aged 18-30 years at baseline (1985-1986) from four U.S. cities over five years of follow-up using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Magnesium intake was estimated from a dietary history questionnaire plus supplements at baseline. Levels of hostility were assessed using the Cook-Medley scale at baseline and year 5 (1990-1991). Generalized estimating equations were applied to estimate the association of magnesium intake with hostility as repeated measures at the two time-points (baseline and year 5). General linear model was used to determine the association between magnesium intake and change in hostility over 5 years. After adjustment for socio-demographic and major lifestyle factors, a significant inverse association was observed between magnesium intake and hostility level over 5 years of follow-up. Beta coefficients (95% CI) across higher quintiles of magnesium intake were 0 (reference), -1.28 (-1.92, -0.65), -1.45 (-2.09, -0.81), -1.41 (-2.08, -0.75) and -2.16 (-2.85, -1.47), respectively (Plinear-trend<.01). The inverse association was independent of socio-demographic and major lifestyle factors, supplement use, and depression status at year 5. This prospective study provides evidence that in young adults, high magnesium intake was inversely associated with hostility level independent of socio-demographic and major lifestyle factors.

Residential proximity to greenhouse crops and pesticide exposure (via acetylcholinesterase activity) assessed from childhood through adolescence.

BACKGROUND: Off-target drift of pesticides from farms increases the risk of pesticide exposure of people living nearby. Cholinesterase inhibitors (i.e. organophosphates and carbamates) are frequently used in agriculture and inhibit acetylcholinesterase (AChE) activity. Greenhouse agriculture is an important production method, but it is unknown how far pesticide drift from greenhouses can extend and expose people living nearby. METHODS: This study included 1156 observations from 3 exams (2008, Apr, 2016 and Jul-Oct 2016) of 623 children aged 4-to-17 years living in agricultural communities in Ecuador. AChE, a physiological marker of cholinesterase inhibitor exposure, was measured in blood. Geographic positioning of greenhouses and homes were obtained using GPS receivers and satellite imagery. Distances between homes and the nearest greenhouse edge, and areas of greenhouse crops within various buffer zones around homes were calculated. Repeated-measures regression adjusted for hemoglobin and other covariates estimated change in AChE relative to distance from greenhouses. RESULTS: The pooled mean (SD) of AChE activity was 3.58 U/mL (0.60). The median (25th-75th %tile) residential distance to crops was 334 m (123, 648) and crop area within 500 m of homes (non-zero values only) was 18,482 m2 (7115, 61,841). Residential proximity to greenhouse crops was associated with lower AChE activity among children living within 275 m of crops (AChE difference per 100 m of proximity [95% CI] = -0.10 U/mL [-0.20, -0.006]). Lower AChE activity was associated with greater crop area within 500 m of homes (AChE difference per 1000 m2 [95% CI] = -0.026 U/mL [-0.040, -0.012]) and especially within 150 m (-0.037 U/mL [-0.065, -0.007]). CONCLUSIONS: Residential proximity to floricultural greenhouses, especially within 275 m, was associated with lower AChE activity among children, reflecting greater cholinesterase inhibitor exposure from pesticide drift. Analyses of residential proximity and crop areas near homes yielded complementary findings. Mitigation of off-target drift of pesticides from crops onto nearby homes is recommended.

Evaluating the use of the heart age tool in community pharmacies: a 4-week cluster-randomized controlled trial.

BACKGROUND: Joint British Societies have developed a tool that utilizes information on cardiovascular disease (CVD) risk factors to estimate an individual's 'heart age'. We studied if using heart age as an add-on to conventional risk communication could enhance the motivation for adapting to a healthier lifestyle resulting in improved whole-blood cholesterol and omega-3 status after 4 weeks. METHODS: A total of 48 community pharmacies were cluster-randomized to use heart age+conventional risk communication (intervention) or only conventional risk communication (control) in 378 subjects after CVD risk-factor assessment. Dried blood spots were obtained with a 4-week interval to assay whole-blood cholesterol and omega-3 fatty acids. We also explored pharmacy-staff's (n=27) perceived utility of the heart age tool. RESULTS: Subjects in the intervention pharmacies (n=137) had mean heart age 64 years and chorological age 60 years. In these, cholesterol decreased by median (interquartile range) -0.10 (-0.40, 0.35) mmol/l. Cholesterol decreased by -0.20 (-0.70, 0.30) mmol/l (P difference =0.24) in subjects in the control pharmacies (n=120) with mean chronological age 60 years. We observed increased concentrations of omega-3 fatty acids after 4 weeks, non-differentially between groups. Pharmacy-staff (n=27) agreed that heart age was a good way to communicate CVD risk, and most (n=25) agreed that it appeared to motivate individuals to reduce elevated CVD risk factors. CONCLUSIONS: The heart age tool was considered a convenient and motivating communication tool by pharmacy-staff. Nevertheless, communicating CVD risk as heart age was not more effective than conventional risk communication alone in reducing whole-blood cholesterol levels and improving omega-3 status.

A longitudinal study of pre-pregnancy antioxidant levels and subsequent perinatal outcomes in black and white women: The CARDIA Study.

BACKGROUND: Although protective associations between dietary antioxidants and pregnancy outcomes have been reported, randomized controlled trials of supplementation have been almost uniformly negative. A possible explanation is that supplementation during pregnancy may be too late to have a beneficial effect. Therefore, we examined the relationship between antioxidant levels prior to pregnancy and birth outcomes. METHODS AND FINDINGS: Serum carotenoids and tocopherols were assayed in fasting specimens at 1985-86 (baseline) and 1992-1993 (year 7) from 1,215 participants in Coronary Artery Risk Development in Young Adults (CARDIA) study. An interviewer-administered quantitative food-frequency questionnaire assessed dietary intake of antioxidants. Pregnancy outcome was self-reported at exams every 2 to 5 years. Linear and logistic regression modeling was used to assess relationships of low birthweight (LBW; <2,500 g), continuous infant birthweight, preterm birth (PTB; <37 weeks) and length of gestation with antioxidant levels adjusted for confounders, as well as interactions with age and race. RESULTS: In adjusted models, lycopene was associated with higher odds of LBW (adjusted odds ratio for top quartile, 2.15, 95% confidence interval 1.14, 3.92) and shorter gestational age (adjusted beta coefficient -0.50 weeks). Dietary intake of antioxidants was associated with lower birthweight, while supplement use of vitamin C was associated with higher gestational age (0.41 weeks, 0.01, 0.81). CONCLUSIONS: Higher preconception antioxidant levels are not associated with better birth outcomes.

Effects of seafood consumption and toenail mercury and selenium levels on cognitive function among American adults: 25 y of follow up.

OBJECTIVES: The aim of this study was to examine the longitudinal association between seafood and intake of long-chain ω-3 polyunsaturated fatty acids (LCω-3 PUFA) and cognitive function and to explore the possible effect modifications owing to mercury (Hg) and selenium (Se) levels. METHODS: Participants (N = 3231) from the CARDIA (Coronary Artery Risk Development in Young Adults) study underwent baseline examination and were reexamined in eight follow-up visits. Diet was assessed at baseline and in exam years 7 and 20. Toenail Hg and Se were measured at exam year 2. Cognitive function was measured at exam year 25 using three tests: Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and the Stroop test. The general linear regression model was used to examine cumulative average intakes of LCω-3 PUFA and seafood in relation to the cognitive test scores; and to explore the possible effect modifications caused by Hg and Se. RESULTS: LCω-3 PUFA intake was significantly associated with better performance in the DSST test (quintile 5 versus quintile 1; mean difference = 1.74; 95% confidence interval, 0.19-3.29; Ptrend, 0.048]), but not in the RAVLT and Stroop tests. Similar results were observed for intakes of eicosapentaenoic acid, docosahexaenoic acid, and non-fried seafood. The observed associations were more pronounced in participants with body mass index ≥25 kg/m2, but not significantly modified by toenail Hg or Se. CONCLUSION: This longitudinal study supported the hypothesis that LCω-3 PUFA or non-fried seafood intake is associated with better cognitive performance in psychomotor speed among US adults, especially those who are overweight or obese.

New approaches to cope with possible harms of low-dose environmental chemicals.

Low-dose environmental chemicals including endocrine-disrupting chemicals can disturb endocrine, nervous and immune systems. Traditional chemical-focused approaches, strict regulation and avoidance of exposure sources, can help protect humans from individual or several chemicals in the high-dose range, but their value in the low-dose range is questionable. First, exposure sources to problematic environmental chemicals are omnipresent, and many common pollutants present no safe level. In this situation, the value of any effort focusing on individual chemicals is very limited. Second, critical methodological issues, including the huge number of environmental chemicals, biological complexity of mixtures and non-linearity, make it difficult for risk assessment-based regulation to provide reliable permissible levels of individual chemicals. Third, the largest exposure source is already internal; human adipose tissue contains the most complex chemical mixtures. Thus, in the low-dose range, a paradigm shift is required from a chemical-focused to a human-focused approach for health protection. Two key questions are (1) how to control toxicokinetics of chemical mixtures to decrease their burden in critical organs and (2) how to mitigate early harmful effects of chemical mixtures at cellular levels. Many lifestyles can be evaluated for these purposes. Although both the chemical-focused and human-focused approaches are needed to protect humans, the human-focused holistic approach must be the primary measure in the low-dose range of environmental chemicals.

Intake of niacin, folate, vitamin B-6, and vitamin B-12 through young adulthood and cognitive function in midlife: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Background: Epidemiologic evidence regarding niacin, folate, vitamin B-6, and vitamin B-12 intake in relation to cognitive function is limited, especially in midlife.Objective: We hypothesize that higher intake of these B vitamins in young adulthood is associated with better cognition later in life.Design: This study comprised a community-based multicenter cohort of black and white men and women aged 18-30 y in 1985-1986 (year 0, i.e., baseline) from the Coronary Artery Risk Development in Young Adults (CARDIA) study (n = 3136). We examined participants' CARDIA diet history at years 0, 7, and 20 to assess nutrient intake, including dietary and supplemental B vitamins. We measured cognitive function at year 25 (mean ± SD age: 50 ± 4 y) through the use of the Rey Auditory Verbal Learning Test (RAVLT) for verbal memory, the Digit Symbol Substitution Test (DSST) for psychomotor speed, and a modified Stroop interference test for executive function. Higher RAVLT and DSST scores and a lower Stroop score indicated better cognitive function. We used multivariable-adjusted linear regressions to estimate mean differences in cognitive scores and 95% CIs.Results: Comparing the highest quintile with the lowest (quintile 5 compared with quintile 1), cumulative total intake of niacin was significantly associated with 3.92 more digits on the DSST (95% CI: 2.28, 5.55; P-trend < 0.01) and 1.89 points lower interference score on the Stroop test (95% CI: -3.10, -0.68; P-trend = 0.05). Total folate was associated with 2.56 more digits on the DSST (95% CI: 0.82, 4.31; P-trend = 0.01). We also found that higher intakes of vitamin B-6 (quartile 5 compared with quartile 1: 2.62; 95% CI: 0.97, 4.28; P-trend = 0.02) and vitamin B-12 (quartile 5 compared with quartile 1: 2.08; 95% CI: 0.52, 3.65; P-trend = 0.02) resulted in better psychomotor speed measured by DSST scores.Conclusion: Higher intake of B vitamins throughout young adulthood was associated with better cognitive function in midlife.

Invited Commentary: Can Estimation of Sodium Intake Be Improved by Borrowing Information From Other Variables?

Estimation of dietary sodium intake is problematic. The most accurate measure is average sodium excretion from multiple 24-hour urine collections, but such an approach is impractical. Using data from the Women's Health Initiative, Prentice et al. (Am J Epidemiol. 2017;186(9):1035-1043) assessed the relationship of calibrated estimates of sodium and potassium excretion with cardiovascular outcomes. The calibrated estimates were a function of self-reported sodium-to-potassium ratio from a food frequency questionnaire, age, body mass index, race, supplement use, smoking status, educational level, income, and aspirin use. In general, associations with outcomes using the calibrated estimates were in the expected direction: direct for the sodium-to-potassium ratio and sodium intake and indirect for potassium. The unexpected associations were an increased risk of hemorrhagic stroke with lower sodium-to-potassium ratio and sodium intake and increased risk with higher potassium intake, along with a null relationship of sodium intake with ischemic stroke. Overall, our assessment is that the authors have improved the estimation of mean dietary sodium and potassium intakes. However, more work is needed to show that calibrated estimates actually improve estimation of future clinical events. If this methodological issue can be successfully addressed, their approach has the potential to improve estimation of dietary sodium and potassium intakes in observational studies.

Plasma Ascorbic Acid, A Priori Diet Quality Score, and Incident Hypertension: A Prospective Cohort Study.

Vitamin C may reduce risk of hypertension, either in itself or by marking a healthy diet pattern. We assessed whether plasma ascorbic acid and the a priori diet quality score relate to incident hypertension and whether they explain each other's predictive abilities. Data were from 2884 black and white adults (43% black, mean age 35 years) initially hypertension-free in the Coronary Artery Risk Development in Young Adults Study (study year 10, 1995-1996). Plasma ascorbic acid was assessed at year 10 and the diet quality score at year 7. Eight-hundred-and-forty cases of hypertension were documented between years 10 and 25. After multiple adjustments, each 12-point (1 SD) higher diet quality score at year 7 related to mean 3.7 µmol/L (95% CI 2.9 to 4.6) higher plasma ascorbic acid at year 10. In separate multiple-adjusted Cox regression models, the hazard ratio of hypertension per 19.6-µmol/L (1 SD) higher ascorbic acid was 0.85 (95% CI 0.79-0.92) and per 12-points higher diet score 0.86 (95% CI 0.79-0.94). These hazard ratios changed little with mutual adjustment of ascorbic acid and diet quality score for each other, or when adjusted for anthropometric variables, diabetes, and systolic blood pressure at year 10. Intake of dietary vitamin C and several food groups high in vitamin C content were inversely related to hypertension, whereas supplemental vitamin C was not. In conclusion, plasma ascorbic acid and the a priori diet quality score independently predict hypertension. This suggests that hypertension risk is reduced by improving overall diet quality and/or vitamin C status. The inverse association seen for dietary but not for supplemental vitamin C suggests that vitamin C status is preferably improved by eating foods rich in vitamin C, in addition to not smoking and other dietary habits that prevent ascorbic acid from depletion.

Effect of black tea intake on blood cholesterol concentrations in individuals with mild hypercholesterolemia: a diet-controlled randomized trial.

Habitual intake of black tea has been associated with relatively lower serum cholesterol concentrations in observational studies. However, clinical trial results evaluating the effects of black tea on serum cholesterol have been inconsistent. Several factors could explain these mixed results, in particular, uncontrolled confounding caused by lifestyle factors (eg, diet). This diet-controlled clinical trial estimates the effect of black tea flavonoid consumption on cholesterol concentrations in 57 borderline hypercholesterolemic individuals (total cholesterol concentrations between 190 and 260 mg/dL [4.9 and 6.7 mmol/L]). A double-blind, randomized crossover trial was conducted in Minneapolis, MN, from April 2002 through April 2004 in which key conditions were tightly controlled to minimize possible confounding. Participants consumed a controlled low-flavonoid diet plus 5 cups per day of black tea or tea-like placebo during two 4-week treatment periods. The flavonoid-free caffeinated placebo matched the tea in color and taste. Differences in cholesterol concentrations at the end of each treatment period were evaluated via linear mixed models. Differences among those treated with tea vs placebo were 3.43 mg/dL (0.09 mmol/L) (95% CI -7.08 to 13.94) for total cholesterol, -1.02 mg/dL (-0.03 mmol/L) (95% CI -11.34 to 9.30) for low-density lipoprotein cholesterol, 0.58 mg/dL (0.02 mmol/L) (95% CI -2.98 to 4.14) for high-density lipoprotein cholesterol, 15.22 mg/dL (0.17 mmol/L) (95% CI -40.91 to 71.35) for triglycerides, and -0.39 mg/dL (-0.01 mmol/L) (95% CI -11.16 to 10.38) for low-density lipoprotein plus high-density lipoprotein cholesterol fraction. The low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio decreased by -0.1 units (95% CI -0.41 to 0.21). No results were statistically or clinically significant. The intake of 5 cups of black tea per day did not alter the lipid profile of borderline hypercholesterolemic subjects significantly.

Instant coffee consumption may be associated with higher risk of metabolic syndrome in Korean adults.

AIMS: Cumulative evidence suggests that coffee consumption may have beneficial effects on metabolic diseases; however, few previous studies have considered the types of coffee consumed and the additives used. We investigated the relationship between coffee consumption and metabolic syndrome (MetSyn) and its components. METHODS: We analyzed 17,953 Korean adults, aged 19-65 years, using cross-sectional data from the Korean National Health and Nutrition Examination Survey (KNHANES, 2007-2011). Coffee consumption level, types of coffee consumed, and the additives used were assessed based on a food frequency questionnaire and 24-h recall. Demographic and lifestyle factors were assessed using self-administered questionnaires. Data on metabolic biomarkers were obtained from a health examination. Multivariable logistic regression was used to determine the odds ratios of prevalent metabolic syndrome and its components according to frequency and type of coffee consumption. RESULTS: We found that 76% of the subjects were habitual coffee drinkers, most of whom consumed instant coffee mix containing sugar and powder creamer. After multivariable adjustment, the odds ratios (95% CI) comparing those who consumed coffee ≥3 times/day with those who consumed coffee <1 time/week were 1.37 (1.15-1.63) for obesity, 1.33 (1.11-1.59) for abdominal obesity, 1.28 (1.09-1.51) for hypo-HDL cholesterolemia, and 1.37 (1.10-1.72) for metabolic syndrome. Instant-coffee drinkers were observed to have elevated risks of these metabolic conditions. CONCLUSIONS: Consumption of coffee, particularly instant coffee mix, may have harmful effects on MetSyn, perhaps partly deriving from excessive intake of sugar and powder creamer.

Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Dietary guidelines support intake of polyunsaturated fatty acids (PUFAs) in fish and vegetable oils. However, some controversy remains about benefits of PUFAs, and most prior studies have relied on self-reported dietary assessment in relatively homogeneous populations. METHODS AND RESULTS: In a multiethnic cohort of 2837 US adults (whites, Hispanics, African Americans, Chinese Americans), plasma phospholipid PUFAs were measured at baseline (2000-2002) using gas chromatography and dietary PUFAs estimated using a food frequency questionnaire. Incident cardiovascular disease (CVD) events (including coronary heart disease and stroke; n=189) were prospectively identified through 2010 during 19 778 person-years of follow-up. In multivariable-adjusted Cox models, circulating n-3 eicosapentaenoic acid and docosahexaenoic acid were inversely associated with incident CVD, with extreme-quartile hazard ratios (95% CIs) of 0.49 for eicosapentaenoic acid (0.30 to 0.79; Ptrend=0.01) and 0.39 for docosahexaenoic acid (0.22 to 0.67; Ptrend<0.001). n-3 Docosapentaenoic acid (DPA) was inversely associated with CVD in whites and Chinese, but not in other race/ethnicities (P-interaction=0.01). No significant associations with CVD were observed for circulating n-3 alpha-linolenic acid or n-6 PUFA (linoleic acid, arachidonic acid). Associations with CVD of self-reported dietary PUFA were consistent with those of the PUFA biomarkers. All associations were similar across racial-ethnic groups, except those of docosapentaenoic acid. CONCLUSIONS: Both dietary and circulating eicosapentaenoic acid and docosahexaenoic acid, but not alpha-linolenic acid or n-6 PUFA, were inversely associated with CVD incidence. These findings suggest that increased consumption of n-3 PUFA from seafood may prevent CVD development in a multiethnic population.

Plant extracts of spices and coffee synergistically dampen nuclear factor-κB in U937 cells.

A large array of bioactive plant compounds (phytochemicals) has been identified and synergy among these compounds might contribute to the beneficial effects of plant foods. The transcription factor nuclear factor-κB (NF-κB) has been suggested as a target for many phytochemicals. Due to the complexity of mechanisms involved in NF-κB regulation, including numerous feedback loops, and the large number of phytochemicals which regulate NF-κB activity, we hypothesize that synergistic or antagonistic effects are involved. The objectives of our study were to develop a statistical methodology to evaluate the concept of synergy and antagonism and to use this methodology in a monocytic cell line (U937 expressing an NF-κB-luciferase reporter) treated with lipopolysaccharide and phytochemical-rich plant extracts. Both synergistic and antagonistic effects were clearly observed. Observed synergy was most pronounced for the combinations of oregano and coffee, and thyme and oregano. For oregano and coffee the synergistic effect was highest at 5 mg/mL with 13.9% (P < .001), and for thyme and oregano the highest synergistic effects was at 3 mg/mL with 13.7% (P < .001). Dose dependent synergistic and antagonistic effects were observed for all combinations tested. In conclusion, this work presents a methodological tool to define synergy in experimental studies. Our results support the hypothesis that phytochemical-rich plants may exert synergistic and antagonistic effects on NF-κB regulation. Such complex mechanistic interactions between phytochemicals are likely to underlie the protective effects of a plant-based diet on life-style related diseases.

Prospective study of particulate air pollution exposures, subclinical atherosclerosis, and clinical cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air).

The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) was initiated in 2004 to investigate the relation between individual-level estimates of long-term air pollution exposure and the progression of subclinical atherosclerosis and the incidence of cardiovascular disease (CVD). MESA Air builds on a multicenter, community-based US study of CVD, supplementing that study with additional participants, outcome measurements, and state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, and black carbon. More than 7,000 participants aged 45-84 years are being followed for over 10 years for the identification and characterization of CVD events, including acute myocardial infarction and other coronary artery disease, stroke, peripheral artery disease, and congestive heart failure; cardiac procedures; and mortality. Subcohorts undergo baseline and follow-up measurements of coronary artery calcium using computed tomography and carotid artery intima-medial wall thickness using ultrasonography. This cohort provides vast exposure heterogeneity in ranges currently experienced and permitted in most developed nations, and the air monitoring and modeling methods employed will provide individual estimates of exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand and reduce uncertainty in health effect estimation regarding long-term exposure to air pollution and CVD.

Dietary supplements and mortality rate in older women: the Iowa Women's Health Study.

BACKGROUND: Although dietary supplements are commonly taken to prevent chronic disease, the long-term health consequences of many compounds are unknown. METHODS: We assessed the use of vitamin and mineral supplements in relation to total mortality in 38,772 older women in the Iowa Women's Health Study; mean age was 61.6 years at baseline in 1986. Supplement use was self-reported in 1986, 1997, and 2004. Through December 31, 2008, a total of 15,594 deaths (40.2%) were identified through the State Health Registry of Iowa and the National Death Index. RESULTS: In multivariable adjusted proportional hazards regression models, the use of multivitamins (hazard ratio, 1.06; 95% CI, 1.02-1.10; absolute risk increase, 2.4%), vitamin B(6) (1.10; 1.01-1.21; 4.1%), folic acid (1.15; 1.00-1.32; 5.9%), iron (1.10; 1.03-1.17; 3.9%), magnesium (1.08; 1.01-1.15; 3.6%), zinc (1.08; 1.01-1.15; 3.0%), and copper (1.45; 1.20-1.75; 18.0%) were associated with increased risk of total mortality when compared with corresponding nonuse. Use of calcium was inversely related (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94; absolute risk reduction, 3.8%). Findings for iron and calcium were replicated in separate, shorter-term analyses (10-year, 6-year, and 4-year follow-up), each with approximately 15% of the original participants having died, starting in 1986, 1997, and 2004. CONCLUSIONS: In older women, several commonly used dietary vitamin and mineral supplements may be associated with increased total mortality risk; this association is strongest with supplemental iron. In contrast to the findings of many studies, calcium is associated with decreased risk.