Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies

BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance–weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88–0.99), 0.78 (0.70–0.85), and 0.88 (0.79–0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88–1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86–0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention

In vivo multiphoton fluorescence imaging: a novel approach to oral malignancy.

Background and objectiveCurrent techniques for oral diagnosis require surgical biopsy of lesions, and may fail to detect early malignant change. Non-invasive, sensitive tools providing early detection of oral cancer and a better understanding of malignant change are needed. These studies evaluated in vivo multiphoton excited fluorescence (MPM) techniques to (1) map epithelial and subepithelial changes through out oral carcinogenesis and (2) serve as an effective diagnostic modality.Study design/materials and methodsIn the hamster model (n = 70), epithelial and subepithelial change was imaged in vivo throughout carcinogenesis. MPM- and histopathology-based diagnoses on a scale of 0 (healthy)-6 (squamous cell carcinoma [s.c.c.]) were scored by two pre-standardized investigators.ResultsCollagen matrix and fibers, cellular infiltrates, blood vessels, and microtumors were clearly visible. MPM agreed with the histopathology for 88.6% of diagnoses.ConclusionsIn vivo MPM images provide (1) high resolution information on specific components of the carcinogenesis process (2) an excellent basis for oral diagnostics

In vivo multiphoton fluorescence imaging: a novel approach to oral malignancy.

Background and objectiveCurrent techniques for oral diagnosis require surgical biopsy of lesions, and may fail to detect early malignant change. Non-invasive, sensitive tools providing early detection of oral cancer and a better understanding of malignant change are needed. These studies evaluated in vivo multiphoton excited fluorescence (MPM) techniques to (1) map epithelial and subepithelial changes through out oral carcinogenesis and (2) serve as an effective diagnostic modality.Study design/materials and methodsIn the hamster model (n = 70), epithelial and subepithelial change was imaged in vivo throughout carcinogenesis. MPM- and histopathology-based diagnoses on a scale of 0 (healthy)-6 (squamous cell carcinoma [s.c.c.]) were scored by two pre-standardized investigators.ResultsCollagen matrix and fibers, cellular infiltrates, blood vessels, and microtumors were clearly visible. MPM agreed with the histopathology for 88.6% of diagnoses.ConclusionsIn vivo MPM images provide (1) high resolution information on specific components of the carcinogenesis process (2) an excellent basis for oral diagnostics

Linking sustainability to the healthy eating patterns of the Dietary Guidelines for Americans: a modelling study

Summary: Background: Evidence-based nutrition policy is a key mechanism to promote planetary health. In the USA, the Dietary Guidelines for Americans are the foundation of nutrition policy and guide more than US$80 billion in federal spending. Recent attempts have been made to incorporate sustainability into the development of the Dietary Guidelines. However, the sustainability of the 2015–20 Dietary Guidelines remains unclear; research has not yet assessed the environmental impacts of the distinct healthy patterns recommended by the policy. Methods: In this modelling study done at the University of New Hampshire (Durham, NH, USA), we analysed the healthy US-style (US), healthy Mediterranean-style (MED), and healthy vegetarian (VEG) patterns recommended in the 2015–20 Dietary Guidelines for Americans. Food groups and subgroups consisted of 321 commonly consumed foods, with group composition predetermined by the US Department of Agriculture. We compiled and used multiple datasets to assign environmental burdens to foods, focusing on six impact categories of policy importance: global warming potential, land use, water depletion, freshwater and marine eutrophication, and particulate matter or respiratory organics. We did life cycle impact assessments for each of the three diet patterns and compared the six impact categories between the patterns. We also analysed the proportion contribution of the food groups to each impact category in each of the diet patterns. Findings: The US and MED patterns had similar impacts, except for freshwater eutrophication. Freshwater eutrophication was 31% lower in the US pattern than the MED pattern, primarily due to increased seafood in the MED pattern. All three patterns had similar water depletion impacts, with fruits and vegetables as major contributors. For five of the six impacts, the VEG pattern had 42–84% lower burdens than both the US and MED patterns. Reliance on plant-based protein and eggs in the VEG pattern versus emphasis on animal-based protein in the other patterns was a key driver of differences, as was a lower overall protein foods recommendation in the VEG pattern. Interpretation: The recommended patterns in the Dietary Guidelines for Americans might have starkly different impacts on the environment and other dimensions of human health beyond nutrition. Given the scale of influence of the Dietary Guidelines for Americans on food systems, incorporating sustainability into their development has the potential to have great benefit in terms of long-term food security. Funding: None

Evaluation of tracheal imaging by optical coherence tomography.

BackgroundOptical coherence tomography (OCT) is a new technology capable of generating high resolution cross-sectional images of complex tissue in real time. Analogous to ultrasound, OCT measures backscattered light intensity using coherence interferometery to construct topographical images of complex tissue. Since OCT uses infrared light rather than acoustic waves, its spatial resolution is exceptionally high (2-10 microm). Recent advances in data acquisition, analysis, and processing enable real-time imaging, and make OCT a potentially valuable tool for pulmonary airway diagnostic applications, including assisting directed airway biopsies.ObjectiveThis study evaluates feasibility of OCT for delineating proximal airway microstructures in various animal as well as human tracheas.MethodsExcised trachea samples from New Zealand white rabbits, Duroc pigs, and human trachea were imaged using a compact, 1,300-nm broad-band superluminescent-diode-based prototype fiber OCT device we constructed. The resulting structural OCT images were compared to conventional hematoxilin and eosin (HE) stained histological sections from the same samples.ResultsOCT was able to delineate microstructures such as the epithelium, mucosa, cartilage, and glands in all samples.ConclusionThese findings suggest that integration of OCT with flexible fiberoptic bronchoscopy could enhance pulmonary diagnostic medicine and detection of pathologic tissue changes in various respiratory diseases

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.In supplementary material: Drs Imamura, Forouhi and Wareham acknowledge support from the core Medical Research Council Epidemiology Unit Programmes (MC_UU_12015/1 and MC_UU_12015/5)