Effect of one year krill oil supplementation on depressive symptoms and self-esteem of Dutch adolescents: A randomized controlled trial.

INTRODUCTION: Observational studies have shown a relationship between omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) and depression in adolescents. However, n-3 LCPUFA supplementation studies investigating the potential improvement in depressive feelings in adolescents from the general population are missing. METHODS: A one-year double-blind, randomized, placebo controlled krill oil supplementation trial was conducted in two cohorts. Cohort I started with 400 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or placebo, after three months this increased to 800 mg EPA and DHA per day, whilst cohort II started with this higher dose. Omega-3 Index (O3I) was monitored via finger-prick blood measurements. At baseline, six and 12 months participants completed the Centre for Epidemiologic Studies Depression Scale (CES-D) and the Rosenberg Self Esteem questionnaire (RSE). Adjusted mixed models were run with treatment allocation/O3I as predictor of CES-D and RSE scores. RESULTS: Both intention-to-treat and assessing the change in O3I analyses did not show significant effects on CES-D or RSE scores. CONCLUSION: There is no evidence for less depressive feelings, or higher self-esteem after one year of krill oil supplementation. However, due to a lack of adherence and drop-out issues, these results should be interpreted with caution.

The association of maternal polyunsaturated fatty acids during pregnancy with social competence and problem behaviours at 7 years of age: The MEFAB cohort.

BACKGROUND: The prenatal exposure to maternal n-6 and n-3 polyunsaturated fatty acids (PUFAs) might influence the development of social competence and internalizing and externalizing behaviours of the child, because of the numerous functions of PUFAs within the nervous system. METHODS: To analyse the association of selected maternal PUFAs (i.e., AA, EPA, DHA, total n-6, total n-3, and the n-6:n-3 ratio) measured during gestation with childhood social competence and problem behaviours, we examined 311 mother-child pairs from the Maastricht Essential Fatty Acid Birth (MEFAB) cohort. For each woman, PUFA-specific changes in relative concentrations were calculated by identifying the best-fitting curve of PUFA concentration by linear splines of gestational age. The associations of changes in maternal PUFAs in early and late pregnancy with childhood social competence, total problems, internalizing and externalizing behaviours, measured with the Child Behaviour Checklist 4/18 at age 7, were investigated with linear regression analyses adjusted for maternal and children's socio-demographic characteristics. RESULTS: In late gestation (i.e., from gestational week 30), an increase in AA was associated with higher social competence, while a decrease in total n-6 was associated with lower externalizing behaviours. No other significant associations were found. DISCUSSION: In this prospective study, increasing maternal AA and decreasing total n-6 were associated with improved social competence and externalizing behaviours, respectively, in 7-year old children. Nonetheless, the clinical significance of the identified associations is modest and further investigations are warranted to clarify the relationship between maternal AA and total n-6 during pregnancy and childhood social and behavioural development.

Exploring the association between whole blood Omega-3 Index, DHA, EPA, DHA, AA and n-6 DPA, and depression and self-esteem in adolescents of lower general secondary education.

PURPOSE: Depression is common in adolescents and long-chain polyunsaturated fatty acids (LCPUFA) are suggested to be associated with depression. However, research in adolescents is limited. Furthermore, self-esteem has never been studied in relation to LCPUFA. The objective here was to determine associations of depression and self-esteem with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), Omega-3 Index (O3I), n-6 docosapentaenoic acid (n-6 DPA, also called Osbond acid, ObA), n-3 docosapentaenoic acid (DPA), and arachidonic acid (AA) concentrations in blood of adolescents attending lower general secondary education (LGSE). METHODS: Baseline cross-sectional data from a krill oil supplementation trial in adolescents attending LGSE with an O3I ≤ 5% were analysed using regression models built with the BayesFactor package in R. Fatty acids and O3I were determined in blood. Participants filled out the Centre for Epidemiologic Studies Depression (CES-D) scale and the Rosenberg Self-Esteem scale (RSE). RESULTS: Scores indicative of depression (CES-D ≥ 16) were found in 29.4% of the respondents. Of all fatty acids, we found extreme evidence [Bayes factor (BF) > 100] for a weak negative association between ObA and depression score [- 0.16; 95% credible interval (CI) - 0.28 to - 0.04; BF10 = 245], and substantial evidence for a weak positive association between ObA and self-esteem score (0.09; 95% CI, - 0.03 to 0.20; BF10 = 4). When all fatty acids were put in one model as predictors of CES-D or RSE, all of the 95% CI contained 0, i.e., no significant association. CONCLUSION: No evidence was found for associations of DHA, EPA and O3I with depression or self-esteem scores in LGSE adolescents with O3I ≤ 5%. The associations of higher ObA status with lower depression and higher self-esteem scores warrant more research.

Polyunsaturated fatty acid levels at birth and child-to-adult growth: Results from the MEFAB cohort.

BACKGROUND: Prenatal exposure to polyunsaturated fatty acids (PUFAs) may influence childhood growth. However, available evidence mostly derived from short-term studies is inconsistent. OBJECTIVE: To assess whether fetal PUFA exposure is associated with height and body mass index (BMI), a common measure of adiposity, from 6 months to 23 years of age. METHODS: In the MEFAB cohort, we assessed cord blood phospholipid n-3 and n-6 PUFA levels, reflecting fetal exposure in late pregnancy. For 250 (45.2% females) participants, we collected a total of 1770 (n= 802 for females) repeated growth measurements from infancy to young adulthood. We examined sex-specific associations of PUFAs with height and BMI at different developmental ages (infant: 6 months; toddler: 2 years; pre-schooler: 4 years; school-aged child: 7 years; adolescent: 12 years; and young adult: 23 years) using fractional polynomial mixed models adjusted for important covariates. RESULTS: Higher n-3 PUFA levels were associated with higher infant length in males (ß= 0.44cm [95% CI: 0.07, 0.82] per SD increase), whereas, for females, higher n-6 PUFA concentrations were associated with lower length in infancy (ß= -0.69cm [95% CI: -1.08, -0.30] per SD increase). A higher ratio of n-3 to n-6 PUFAs was associated with higher infant length in both sexes (ß= 0.40cm [95% CI: 0.01, 0.78] and 0.42cm [95% CI: 0.05, 0.79] per unit increase for males and females, respectively). These associations were not detectable later in childhood and young adulthood. No associations with BMI were found at any time point examined. CONCLUSIONS: Our findings suggest a small sex-specific influence of PUFA status at birth on length in infancy, but this does not persist in later life up to young adulthood. PUFA status at birth does not seem to affect BMI from infancy till young adulthood.

Association between prenatal and current exposure to selected LCPUFAs and school performance at age 7.

INTRODUCTION: Long-chain polyunsaturated fatty acids (LCPUFAs) are important for brain functioning and might, thus, influence cognition and school performance. However, research investigating LCPUFAs relationships with school performance is limited. The objective of this study was to determine the association between levels of the LCPUFAs docosahexaenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and n-6 docosapentaenoic acid (Osbond acid, ObA) at study entry, 22 weeks of pregnancy, 32 weeks of pregnancy, at partus, in umbilical cord plasma and child's plasma at age 7 and school performance scores at age 7. METHODS: Data from the Maastricht Essential Fatty Acid Birth cohort (MEFAB) were used for this study. Fatty acid levels of plasma phospholipids were measured in maternal blood plasma at study entry, 22 weeks of pregnancy, 32 weeks of pregnancy and partus. Childs fatty acid levels of plasma phospholipids were measured a in umbilical cord blood plasma, and in blood plasma of the child at age 7. Scores on national standardised tests for spelling, reading and arithmetic at age 7 were obtained via the school (scores were available for 149, 159 and 155 children, respectively). Associations between LCPUFA levels and school performance scores were analysed with categorical regression analyses with correction for covariates (smoking, maternal education, sex, breastfeeding, maternal intelligence, birth weight and BMI at age 7). RESULTS: Significant (p<0.001) associations between DHA level at age 7 and both reading (ß=0.158) and spelling (ß=0.146) were found. Consistent significant negative associations were observed between all maternal DHA plasma levels and arithmetic scores at age 7 (all p<0.001, all ß<-0.019). Additional significant negative associations were observed between maternal LCPUFA plasma levels at study entry and both reading and spelling scores at age 7; these associations were less consistent. CONCLUSION: Plasma DHA levels at age 7 were positively associated with reading and spelling scores at age 7. Consistent significant negative associations between maternal plasma DHA levels and arithmetic scores of the child at age 7 were found. Although this is an observational study, which cannot proof causality, the consistent negative associations observed between maternal plasma DHA levels and the arithmetic scores of the children at age 7 calls upon prudence when considering DHA supplementation during pregnancy.

Effect of maternal n-3 long-chain polyunsaturated fatty acid supplementation during pregnancy and/or lactation on adiposity in childhood: a systematic review and meta-analysis of randomized controlled trials.

It is hypothesized that prenatal and early postnatal exposure to n-3 long-chain polyunsaturated fatty acids (LCPUFAs) is negatively associated with adiposity later in life. We conducted a systematic review and meta-analysis to evaluate whether maternal n-3 LCPUFA supplementation in pregnancy and/or lactation exerts a beneficial effect on adiposity status in childhood. We searched six electronic databases till 20 May 2014 for randomized controlled trials (RCTs) of n-3 LCPUFA supplementation to pregnant and/or lactating women that reported data on body mass index (BMI), waist circumference, sum of skinfold thicknesses or body fat mass in children. Adiposity measures were grouped into three age categories: preschool children (<5 years), school-aged children (6-12 years), and adolescents (>13 years). Trial quality was assessed. We conducted fixed-effect and random-effects meta-analyses to combine study-specific estimates of differences between the supplemented and control groups. A total of 6 RCTs (9 publications) involving 2847 participants were included. Summary estimates showed no effect of maternal supplementation on BMI in preschool (standardized mean difference (SMD)=0.07, 95% confidence interval (CI)=-0.22, 0.36, P=0.65) and school-aged children (SMD=0.12, 95% CI=-0.06, 0.30, P=0.20). Because of sparse data, it was not possible to pool study results relating to other adiposity measures. There is currently no evidence to support that n-3 LCPUFA supplementation during pregnancy and/or lactation favourably affects child adiposity. Further high-quality trials are needed.

Blood pressure response to calcium supplementation: a meta-analysis of randomized controlled trials.

Calcium plays a role in blood pressure (BP) regulation, but the importance of supplemental calcium intake for the prevention of hypertension is still debated. We conducted a meta-analysis of randomized controlled trials to determine the effect of calcium supplementation on BP. A systematic search for randomized trials of calcium supplementation and BP in non-pregnant subjects was performed in Medline from 1966 to June 2003. Seventy-one trials were identified, 40 of which met the criteria for meta-analysis (total of 2492 subjects). Two persons independently extracted data from original publications on changes in calcium intake and BP. In addition, data were collected on subjects' characteristics, that is, age, gender, initial BP and initial calcium intake. A random effects model was used to obtain the effect of calcium supplementation on BP, overall and in predefined population subgroups. Calcium supplementation (mean daily dose: 1200 mg) reduced systolic BP by -1.86 mm Hg (95% confidence interval: -2.91 to -0.81) and diastolic BP by -0.99 mm Hg (-1.61 to -0.37). In people with a relatively low calcium intake (< or =800 mg per day) somewhat larger BP estimates were obtained, that is, -2.63 (-4.03 to -1.24) for systolic BP and -1.30 (-2.13 to -0.47) for diastolic BP. Our study suggests that an adequate intake of calcium should be recommended for the prevention of hypertension. More research on BP in people with calcium-deficient diets is warranted.

Oral essential fatty acid supplementation in atopic dermatitis-a meta-analysis of placebo-controlled trials.

BACKGROUND: Essential fatty acids are components of cell membranes and precursors of immunomodulating factors that may play a role in the inflammatory and immunological pathogenesis of atopic dermatitis. Trials of supplementation with essential fatty acids (EFA) to alleviate atopic dermatitis (AD) have given inconsistent results. OBJECTIVES: To summarize and quantify the results of placebo-controlled trials with EFA for AD. DESIGN: Publications of clinical trials were searched in a systematic way and the study characteristics assessed independently by three assessors. Trials were selected for inclusion in the meta-analysis when they had included a placebo group and when the outcome measure included the severity of AD. The pooled effect sizes of improvement of the overall severity of AD were calculated by random effects meta-analysis. The dependence of the results on study characteristics was studied using meta-regression analysis. RESULTS: We identified 34 publications of controlled trials in AD up to April 2002. Nineteen trials of gamma-linolenic acid (GLA) and five trials of fish oil matched our inclusion criterion of placebo-controlled trial. The effect size of GLA supplementation on the improvement of the overall severity of AD could be calculated from 11 of these trials. The pooled effect size was 0.15 [95% confidence limits (CL) - 0.02, 0.32]. The effect size of fish oil supplementation, calculated from three trials was - 0.01 (95% CL - 0.37, 0.30). For component subscales such as itch, scaling and lichenification, EFA supplementation showed no benefit. The study characteristics showed no detectable influence on the overall result. CONCLUSIONS: Supplementation with EFA has no clinically relevant effect on the severity of AD.

An asymptotically unbiased estimator of exposed versus non-exposed odds ratio from reported dose-response data.

Summary effect measures in meta-analysis of published epidemiological cohort or case control studies are often based on odds ratios reported for several exposure levels with varying arrangements and number of levels across primary studies. Usually only two-way contingency tables together with exposure specific adjusted odds ratios and corresponding standard errors are presented in articles. An asymptotically unbiased estimate of exposed versus non-exposed adjusted odds ratio from reported dose-response data is proposed. This estimate is based on the weighted sum of the exposure specific odds ratios, with the prevalences of the control group as weights. Large sample variance is derived accounting for the dependency between exposure specific adjusted odds ratios. The exposed versus non-exposed adjusted odds ratio could then be used in systematic reviewing.

Are retinol, vitamin C, vitamin E, folate and carotenoids intake associated with bladder cancer risk? Results from the Netherlands Cohort Study.

In the Netherlands Cohort Study among 120 852 subjects aged 55-69 years at baseline (1986), the association between vitamins and carotenoids intake, vitamin supplement use, and bladder cancer incidence was examined. Exposure status was measured with a food-frequency questionnaire. After 6.3 years of follow-up, data from 569 cases and 3123 subcohort members were available for case-cohort analyses. The age-, sex-, and smoking-adjusted relative risks (RRs) for retinol, vitamin E, folate, a-carotene, b-carotene, lutein and zeaxanthin, and lycopene were 1.04, 0.98, 1.03, 0.99, 1.16, 1.11, and 1.08, respectively, comparing highest to lowest quintile of intake. Only vitamin C (RR: 0.81, 95% CI: 0.61-1.07, P-trend = 0.08), and b-cryptoxanthin intake (RR: 0.74, 95% CI: 0.53-1.03, P-trend < 0.01) were inversely associated with bladder cancer risk. The association with vitamin C disappeared after adjustment for b-cryptoxanthin but not vice versa. The RRs for supplemental use of vitamin A, C or E compared to no use were around unity. We conclude that dietary or supplemental intake of vitamin A, vitamin C, vitamin E, and intake of folate, and most carotenoids are not associated with bladder cancer. In this study, only b-cryptoxanthin intake appeared to be inversely associated.

Are coffee, tea, and total fluid consumption associated with bladder cancer risk? Results from the Netherlands Cohort Study.

OBJECTIVES: Coffee, tea, and fluid consumption have been thought to influence bladder cancer incidence. In a large prospective study, these associations were investigated. METHODS: In 1986, cohort members (55-69 years) completed a questionnaire on cancer risk factors. Follow-up was established by linkage to cancer registries until 1992. The multivariable case-cohort analysis was based on 569 bladder cancer cases and 3,123 subcohort members. RESULTS: The incidence rate ratios (RR) for men consuming <2 cups of coffee/day was 0.89 (95% CI 0.51-1.5) using the median consumption category (4-<5 cups/day) as reference. This RR increased to 1.3 (95% CI 0.94-1.9) for men consuming >7 cups/day, although no clear dose response association was found. The RRs decreased from 1.2 (95% CI 0.56-2.7) for women consuming <2 cups of coffee/day to 0.36 (95% CI 0.18-0.72) for women consuming >5 cups/day compared to the median consumption category (3-<4 cups/day). Men and women who abstained from drinking tea had a RR of 1.3 (95% Cl 0.97-1.8) compared to those consuming 2-<3 cups of tea per day (median consumption category). The RR for men and women comparing highest to lowest quintile of total fluid consumption was 0.87 (95% CI 0.63 1.2). CONCLUSION: The data suggest a possible positive association between coffee consumption and bladder cancer risk in men and a probable inverse association in women. Tea consumption was inversely associated with bladder cancer. Total fluid consumption did not appear to be associated with bladder cancer.

Are coffee and tea consumption associated with urinary tract cancer risk? A systematic review and meta-analysis.

BACKGROUND: Narrative reviews have concluded that there is a small association between coffee consumption and an increased risk of urinary tract cancer, possibly due to confounding by smoking. No association for tea consumption has been indicated. This systematic review attempts to summarize and quantify these associations both unadjusted and adjusted for age, smoking and sex. METHOD: Thirty-four case-control and three follow-up studies were included in this systematic review. Summary odds ratios (OR) were calculated by meta-regression analyses. RESULTS: The unadjusted summary OR indicated a small increased risk of urinary tract cancer for current coffee consumers versus non-drinkers. The adjusted summary OR were: 1.26 (95% CI : 1.09-1.46) for studies with only men, 1.08 (95% CI : 0.79-1.46) for studies with only women and 1.18 (95% CI : 1.01-1.38) for studies with men and women combined. Neither unadjusted nor adjusted summary OR provided evidence for a positive association between tea consumption and urinary tract cancer. Even though studies differed in methodology, the results were rather consistent. We did not perform dose-response analyses for coffee and tea consumption due to sparse data. CONCLUSIONS: In accordance with earlier reviews, we found that coffee consumption increases the risk of urinary tract cancer by approximately 20%. The consumption of tea seems not to be related to an increased risk of urinary tract cancer.