Laura Johnson

Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk: A Systematic Review and Meta-analysis

BACKGROUND Guidelines advocate changes in fatty acid consumption to promote cardiovascular health. PURPOSE To summarize evidence about associations between fatty acids and coronary disease. DATA SOURCES MEDLINE, Science Citation Index, and Cochrane Central Register of Controlled Trials through July 2013. STUDY SELECTION Prospective, observational studies and randomized, controlled trials. DATA EXTRACTION Investigators extracted data about study characteristics and assessed study biases. DATA SYNTHESIS There were 32 observational studies (530,525 participants) of fatty acids from dietary intake; 17 observational studies (25,721 participants) of fatty acid biomarkers; and 27 randomized, controlled trials (103,052 participants) of fatty acid supplementation. In observational studies, relative risks for coronary disease were 1.02 (95% CI, 0.97 to 1.07) for saturated, 0.99 (CI, 0.89 to 1.09) for monounsaturated, 0.93 (CI, 0.84 to 1.02) for long-chain ω-3 polyunsaturated, 1.01 (CI, 0.96 to 1.07) for ω-6 polyunsaturated, and 1.16 (CI, 1.06 to 1.27) for trans fatty acids when the top and bottom thirds of baseline dietary fatty acid intake were compared. Corresponding estimates for circulating fatty acids were 1.06 (CI, 0.86 to 1.30), 1.06 (CI, 0.97 to 1.17), 0.84 (CI, 0.63 to 1.11), 0.94 (CI, 0.84 to 1.06), and 1.05 (CI, 0.76 to 1.44), respectively. There was heterogeneity of the associations among individual circulating fatty acids and coronary disease. In randomized, controlled trials, relative risks for coronary disease were 0.97 (CI, 0.69 to 1.36) for α-linolenic, 0.94 (CI, 0.86 to 1.03) for long-chain ω-3 polyunsaturated, and 0.89 (CI, 0.71 to 1.12) for ω-6 polyunsaturated fatty acid supplementations. LIMITATION Potential biases from preferential publication and selective reporting. CONCLUSION Current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats. PRIMARY FUNDING SOURCE British Heart Foundation, Medical Research Council, Cambridge National Institute for Health Research Biomedical Research Centre, and Gates Cambridge.

Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies

Objective To evaluate the extent to which circulating biomarker and supplements of vitamin D are associated with mortality from cardiovascular, cancer, or other conditions, under various circumstances. Design Systematic review and meta-analysis of observational studies and randomised controlled trials. Data sources Medline, Embase, Cochrane Library, and reference lists of relevant studies to August 2013; correspondance with investigators. Study selection Observational cohort studies and randomised controlled trials in adults, which reported associations between vitamin D (measured as circulating 25-hydroxyvitamin D concentration or vitamin D supplement given singly) and cause specific mortality outcomes. Data extraction Data were extracted by two independent investigators, and a consensus was reached with involvement of a third. Study specific relative risks from 73 cohort studies (849 412 participants) and 22 randomised controlled trials (vitamin D given alone versus placebo or no treatment; 30 716 participants) were meta-analysed using random effects models and were grouped by study and population characteristics. Results In the primary prevention observational studies, comparing bottom versus top thirds of baseline circulating 25-hydroxyvitamin D distribution, pooled relative risks were 1.35 (95% confidence interval 1.13 to 1.61) for death from cardiovascular disease, 1.14 (1.01 to 1.29) for death from cancer, 1.30 (1.07 to 1.59) for non-vascular, non-cancer death, and 1.35 (1.22 to 1.49) for all cause mortality. Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements. In randomised controlled trials, relative risks for all cause mortality were 0.89 (0.80 to 0.99) for vitamin D3 supplementation and 1.04 (0.97 to 1.11) for vitamin D2 supplementation. The effects observed for vitamin D3 supplementation remained unchanged when grouped by various characteristics. However, for vitamin D2 supplementation, increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods. Conclusions Evidence from observational studies indicates inverse associations of circulating 25-hydroxyvitamin D with risks of death due to cardiovascular disease, cancer, and other causes. Supplementation with vitamin D3 significantly reduces overall mortality among older adults; however, before any widespread supplementation, further investigations will be required to establish the optimal dose and duration and whether vitamin D3 and D2 have different effects on mortality risk.

Association between fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease: systematic review and meta-analysis

Objective To clarify associations of fish consumption and long chain omega 3 fatty acids with risk of cerebrovascular disease for primary and secondary prevention. Design Systematic review and meta-analysis. Data sources Studies published before September 2012 identified through electronic searches using Medline, Embase, BIOSIS, and Science Citation Index databases. Eligibility criteria Prospective cohort studies and randomised controlled trials reporting on associations of fish consumption and long chain omega 3 fatty acids (based on dietary self report), omega 3 fatty acids biomarkers, or supplementations with cerebrovascular disease (defined as any fatal or non-fatal ischaemic stroke, haemorrhagic stroke, cerebrovascular accident, or transient ischaemic attack). Both primary and secondary prevention studies (comprising participants with or without cardiovascular disease at baseline) were eligible. Results 26 prospective cohort studies and 12 randomised controlled trials with aggregate data on 794 000 non-overlapping people and 34 817 cerebrovascular outcomes were included. In cohort studies comparing categories of fish intake the pooled relative risk for cerebrovascular disease for 2-4 servings a week versus ≤1 servings a week was 0.94 (95% confidence intervals 0.90 to 0.98) and for ≥5 servings a week versus 1 serving a week was 0.88 (0.81 to 0.96). The relative risk for cerebrovascular disease comparing the top thirds of baseline long chain omega 3 fatty acids with the bottom thirds for circulating biomarkers was 1.04 (0.90 to 1.20) and for dietary exposures was 0.90 (0.80 to 1.01). In the randomised controlled trials the relative risk for cerebrovascular disease in the long chain omega 3 supplement compared with the control group in primary prevention trials was 0.98 (0.89 to 1.08) and in secondary prevention trials was 1.17 (0.99 to 1.38). For fish or omega 3 fatty acids the estimates for ischaemic and haemorrhagic cerebrovascular events were broadly similar. Evidence was lacking of heterogeneity and publication bias across studies or within subgroups. Conclusions Available observational data indicate moderate, inverse associations of fish consumption and long chain omega 3 fatty acids with cerebrovascular risk. Long chain omega 3 fatty acids measured as circulating biomarkers in observational studies or supplements in primary and secondary prevention trials were not associated with cerebrovascular disease. The beneficial effect of fish intake on cerebrovascular risk is likely to be mediated through the interplay of a wide range of nutrients abundant in fish.

Chocolate consumption and cardiometabolic disorders: systematic review and meta-analysis

Objective To evaluate the association of chocolate consumption with the risk of developing cardiometabolic disorders. Design Systematic review and meta-analysis of randomised controlled trials and observational studies. Data sources Medline, Embase, Cochrane Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal, reference lists of relevant studies to October 2010, and email contact with authors. Study selection Randomised trials and cohort, case-control, and cross sectional studies carried out in human adults, in which the association between chocolate consumption and the risk of outcomes related to cardiometabolic disorders were reported. Data extraction Data were extracted by two independent investigators, and a consensus was reached with the involvement of a third. The primary outcome was cardiometabolic disorders, including cardiovascular disease (coronary heart disease and stroke), diabetes, and metabolic syndrome. A meta-analysis assessed the risk of developing cardiometabolic disorders by comparing the highest and lowest level of chocolate consumption. Results From 4576 references seven studies met the inclusion criteria (including 114 009 participants). None of the studies was a randomised trial, six were cohort studies, and one a cross sectional study. Large variation was observed between these seven studies for measurement of chocolate consumption, methods, and outcomes evaluated. Five of the seven studies reported a beneficial association between higher levels of chocolate consumption and the risk of cardiometabolic disorders. The highest levels of chocolate consumption were associated with a 37% reduction in cardiovascular disease (relative risk 0.63 (95% confidence interval 0.44 to 0.90)) and a 29% reduction in stroke compared with the lowest levels. Conclusions Based on observational evidence, levels of chocolate consumption seem to be associated with a substantial reduction in the risk of cardiometabolic disorders. Further experimental studies are required to confirm a potentially beneficial effect of chocolate consumption.

A prospective analysis of dietary energy density at age 5 and 7 years and fatness at 9 years among UK children

Objective:To analyse whether high dietary energy density (DED) is associated with increased fat mass and risk of excess adiposity in free-living children.Design:Longitudinal, observational cohort study.Subjects:Six hundred and eighty-two healthy children from the Avon Longitudinal Study of Parents and Children.Measurements:Diet was assessed at age 5 and 7 years using 3-day diet diaries, and DED (kJ g−1) was calculated excluding drinks. Fat mass was estimated at age 9 years using Dual-Energy X-ray Absorptiometry. To adjust for body size, fat mass index (FMI) was calculated by dividing fat mass (kg) by height (m5.8). Excess adiposity was defined as the top quintile of logFMI.Results:Mean DED at age 5 years was higher among children with excess adiposity at age 9 years compared to the remaining sample (8.8±0.16 vs 8.5±0.07 kJ g−1), but there was no evidence of an association with excess adiposity at age 9 years (odds ratio (OR)=1.14, 95% confidence interval (CI) 0.90–1.44) after controlling for potential confounders. Mean DED at age 7 years was higher among children with excess adiposity compared to the remaining sample (9.1±0.12 vs 8.8±0.06 kJ g−1) and a 1 kJ g−1 rise in DED increased the odds of excess adiposity at 9 years by 36% (OR=1.36, 95% CI 1.09–1.69) after controlling for potential confounders.Conclusion:Higher DED at age 7 years, but not age 5 years, is a risk factor for excess adiposity at age 9 years, perhaps reflecting deterioration in the ability to compensate for extra calories in an energy-dense diet. DED tracks strongly from age 5 to 7 years suggesting intervention to alter dietary habits need to commence at younger ages to prevent the formation of preferences for energy dense foods.

Dietary Energy Density Affects Fat Mass in Early Adolescence and Is Not Modified by FTO Variants

Background Dietary energy density (DED) does not have a simple linear relationship to fat mass in children, which suggests that some children are more susceptible than others to the effects of DED. Children with the FTO (rs9939609) variant that increases the risk of obesity may have a higher susceptibility to the effects of DED because their internal appetite control system is compromised. We tested the relationship between DED and fat mass in early adolescence and its interaction with FTO variants. Methods and Findings We carried out a prospective analysis on 2,275 children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). Diet was assessed at age 10 y using 3-day diet diaries. DED (kJ/g) was calculated excluding drinks. Children were genotyped for the FTO (rs9939609) variant. Fat mass was estimated at age 13 y using the Lunar Prodigy Dual-energy X-ray Absorptiometry scanner. There was no evidence of interaction between DED at age 10 y and the high risk A allele of the FTO gene in relation to fat mass at age 13 y (β = 0.005, p = 0.51), suggesting that the FTO gene has no effect on the relation between DED at 10 y and fat mass at 13 y. When DED at 10 y and the A allele of FTO were in the same model they were independently related to fat mass at 13 y. Each A allele of FTO was associated with 0.35±0.13 kg more fat mass at 13 y and each 1 kJ/g DED at 10 y was associated with 0.16±0.06 kg more fat mass at age 13 y, after controlling for misreporting of energy intake, gender, puberty, overweight status at 10 y, maternal education, TV watching, and physical activity. Conclusions This study reveals the multi-factorial origin of obesity and indicates that although FTO may put some children at greater risk of obesity, encouraging a low dietary energy density may be an effective strategy to help all children avoid excessive fat gain.

Reflections from a systematic review of dietary energy density and weight gain: Is the inclusion of drinks valid?

The association between dietary energy density, increased energy intake and weight gain is supported by experimental evidence, but confirmation of an effect in free‐living humans is limited. Experimental evidence supports a role of energy density in obesity through changes in food composition, not drinks consumption. The inclusion of drinks in the calculation creates a variable of questionable validity and has a substantive impact on the estimated energy density of the diet. We posit, based on the experimental evidence, that calculating the energy density of diets by excluding drinks and including calories from drinks as a covariate in the analysis is the most valid and reliable method of testing the relationship between energy density and weight gain in free‐living humans. We demonstrate, by systematically reviewing existing observational studies of dietary energy density and weight gain in free‐living humans, how current variation in the method for calculating energy density hampers the interpretation of these data. Reaching an a priori decision on the appropriate methodology will reduce the error caused by multiple comparisons and facilitate meaningful interpretation of epidemiological evidence to inform the development of effective obesity prevention strategies.

Socioeconomic status and weight gain in early infancy

Context:The association between low socioeconomic status (SES) and childhood obesity foreshadows lifelong inequalities in health. Insight into the causal mechanisms linking childhood adversity to long-term health could be provided by discovering when the negative SES gradient in weight emerges and what early life experiences are associated with it.Objective:SES differences in infant weight gain in the first 3 months of life were examined, and contributions of parental body mass index, maternal smoking and feeding method to this association were assessed.Design:Observational study using longitudinal weight data from 2402 families taking part in the Gemini Study; a twin birth cohort recruited from all twin births between March and December 2007 in England and Wales.Outcome measures:Infant weights at birth and 3 months converted to standard deviation scores (SDS), change in weight SDS and rapid growth. SES was indexed by occupation and maternal education.Results:There were no SES differences in birth weight, but lower SES was associated with higher 3-month weight, greater change in weight and a higher prevalence of rapid growth (all P<0.01), with graded associations across levels of SES. Including parental overweight or smoking in pregnancy in the regression model did not affect the association between SES and weight gain, but including feeding method attenuated the SES effect on weight gain by at least 62% and rendered it nonsignificant.Conclusion:The foundations for lifelong socioeconomic inequalities in obesity risk may be laid in early infancy, with infant-feeding practices having a part in the diverging weight trajectories.

Prospective associations between appetitive traits and weight gain in infancy

BACKGROUND Differences in appetitive traits such as food-cue or satiety responsiveness have been hypothesized to contribute to variability in weight gain. However, existing data were largely cross-sectional and could not exclude the possibility that differences in appetitive traits were consequences of differences in weight. OBJECTIVE We tested whether prospective associations between appetitive traits and subsequent weight were stronger than associations between weight and subsequent appetitive traits. DESIGN Data were from Gemini, which is a population-based cohort of 2402 families with twins. Parents completed a Baby Eating Behavior Questionnaire to assess 4 appetitive traits for each twin at ages 3 and 15 mo. We obtained infant weights at 3, 9, and 15 mo from records of health professionals. Weight SD scores were calculated by using UK 1990 reference data. A path analysis was used to examine prospective associations in each direction over sequential 6-mo intervals and over the same 12-mo period, with the significance of differences between the 2 paths established with bootstrapping. RESULTS Path analyses included 2213 infants. For each appetitive trait, the path to subsequent weight (standardized coefficients: 0.17-0.33) was significantly larger than the path from weight to subsequent appetite (coefficients: 0.07-0.13). Results were confirmed when both associations were analyzed by using changes from 3 to 15 mo. CONCLUSION Longitudinal analyses showed that associations between appetitive traits and subsequent weight were stronger than between weight and subsequent appetite, which supports the idea that differences in appetitive traits, in conjunction with environmental opportunities to overeat, influence weight gain in early childhood.

Gemini: a UK twin birth cohort with a focus on early childhood weight trajectories, appetite and the family environment

Gemini is a cohort study of young twins in the United Kingdom designed to assess genetic and environmental influences on early childhood weight trajectories with a focus on infant appetite and the family environment. A total of 2402 families with twins born in England and Wales between March and December 2007 agreed to participate and returned completed baseline questionnaires. The sample includes 1586 same-sex and 816 opposite-sex twins. The study is currently funded for 5 years of follow-up, but is planned to continue into early adolescence and beyond, pending funding. With current funding of the study, families will be followed up when twins are: 8 months old (baseline), and then at 15, 20, 24, 36 and 48 months of age. Gemini is in its early stages, with baseline and first follow-up data collection completed. This is the first twin cohort to focus on childhood weight gain with detailed and repeated measures of childrens appetite, food preferences, activity behavior and parental feeding styles, alongside detailed and repeated collection of anthropometrics. This article reviews the rationale for the Gemini study, its representativeness and the main measures.