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Deep Lipidomics in Human Plasma: Cardiometabolic Disease Risk and Effect of Dietary Fat Modulation.
Eichelmann, F, Sellem, L, Wittenbecher, C, Jäger, S, Kuxhaus, O, Prada, M, Cuadrat, R, Jackson, KG, Lovegrove, JA, Schulze, MB
Circulation. 2022;146(1):21-35
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The level of fats in the blood has been implicated as a causal factor in the development of diseases such as heart attack, stroke, and type 2 diabetes. Fat levels are therefore used as a predictor for disease and targeted in treatments. However, recent studies on the involvement of fats in diseases related to metabolic disorder have shortcomings. This secondary analysis of participants in the European Prospective Investigation into Cancer and Nutrition study aimed to determine the association of blood lipids with heart related metabolic diseases and a second randomised control trial aimed to determine the effect of modifying dietary fat intake on fats associated with risk for disease development. The results showed that 69 lipids mostly in the cholesterol ester, free fatty acid, triacylglycerol, phosphatidylcholine, monoacylglycerol, and sphingolmyelin classes were associated with heart disease and type 2 diabetes most of which were specific to one disease. The consumption of a diet rich in unsaturated fats compared to a saturated fat diet altered the blood lipid profile of participants to a one more favourable for metabolic risk. It was concluded that lipids are associated with metabolic disease and that substituting high dietary saturated fats to largely unsaturated fats may prevent the development of disease. Most lipids were specific to either type 2 diabetes or heart disease highlighting potential differing causes. This study could be used by healthcare professionals to better understand the lipids associated with heart disease and type 2 diabetes and that switching to a diet high in unsaturated fat may be of benefit to those suffering from these diseases.
Abstract
BACKGROUND In blood and tissues, dietary and endogenously generated fatty acids (FAs) occur in free form or as part of complex lipid molecules that collectively represent the lipidome of the respective tissue. We assessed associations of plasma lipids derived from high-resolution lipidomics with incident cardiometabolic diseases and subsequently tested if the identified risk-associated lipids were sensitive to dietary fat modification. METHODS The EPIC Potsdam cohort study (European Prospective Investigation into Cancer and Nutrition) comprises 27 548 participants recruited within an age range of 35 to 65 years from the general population around Potsdam, Germany. We generated 2 disease-specific case cohorts on the basis of a fixed random subsample (n=1262) and all respective cohort-wide identified incident primary cardiovascular disease (composite of fatal and nonfatal myocardial infarction and stroke; n=551) and type 2 diabetes (n=775) cases. We estimated the associations of baseline plasma concentrations of 282 class-specific FA abundances (calculated from 940 distinct molecular species across 15 lipid classes) with the outcomes in multivariable-adjusted Cox models. We tested the effect of an isoenergetic dietary fat modification on risk-associated lipids in the DIVAS randomized controlled trial (Dietary Intervention and Vascular Function; n=113). Participants consumed either a diet rich in saturated FAs (control), monounsaturated FAs, or a mixture of monounsaturated and n-6 polyunsaturated FAs for 16 weeks. RESULTS Sixty-nine lipids associated (false discovery rate<0.05) with at least 1 outcome (both, 8; only cardiovascular disease, 49; only type 2 diabetes, 12). In brief, several monoacylglycerols and FA16:0 and FA18:0 in diacylglycerols were associated with both outcomes; cholesteryl esters, free fatty acids, and sphingolipids were largely cardiovascular disease specific; and several (glycero)phospholipids were type 2 diabetes specific. In addition, 19 risk-associated lipids were affected (false discovery rate<0.05) by the diets rich in unsaturated dietary FAs compared with the saturated fat diet (17 in a direction consistent with a potential beneficial effect on long-term cardiometabolic risk). For example, the monounsaturated FA-rich diet decreased diacylglycerol(FA16:0) by 0.4 (95% CI, 0.5-0.3) SD units and increased triacylglycerol(FA22:1) by 0.5 (95% CI, 0.4-0.7) SD units. CONCLUSIONS We identified several lipids associated with cardiometabolic disease risk. A subset was beneficially altered by a dietary fat intervention that supports the substitution of dietary saturated FAs with unsaturated FAs as a potential tool for primary disease prevention.
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Consumption of ultra-processed foods and cancer risk: results from NutriNet-Santé prospective cohort.
Fiolet, T, Srour, B, Sellem, L, Kesse-Guyot, E, Allès, B, Méjean, C, Deschasaux, M, Fassier, P, Latino-Martel, P, Beslay, M, et al
BMJ (Clinical research ed.). 2018;360:k322
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Foods that are heavily processed tend to have high levels of total fat, sugar and salt and low levels of fibre and vitamins. They also tend to have high levels of contaminants (caused for example by high heat treatment), food additives and plastic packaging exposure. This large prospective population-based cohort study assessed the association between ultra-processed food consumption and the incidence of cancer. The study found that ultra-processed food intake was associated with a higher overall cancer risk and a higher breast cancer risk. A 10% increase in the consumption of ultra-processed foods was associated with an increase of more than 10% greater risk of overall and breast cancer risk. The authors call for further studies to better understand the different elements of food processing and their association to cancer risk.
Abstract
OBJECTIVE To assess the prospective associations between consumption of ultra-processed food and risk of cancer. DESIGN Population based cohort study. SETTING AND PARTICIPANTS 104 980 participants aged at least 18 years (median age 42.8 years) from the French NutriNet-Santé cohort (2009-17). Dietary intakes were collected using repeated 24 hour dietary records, designed to register participants' usual consumption for 3300 different food items. These were categorised according to their degree of processing by the NOVA classification. MAIN OUTCOME MEASURES Associations between ultra-processed food intake and risk of overall, breast, prostate, and colorectal cancer assessed by multivariable Cox proportional hazard models adjusted for known risk factors. RESULTS Ultra-processed food intake was associated with higher overall cancer risk (n=2228 cases; hazard ratio for a 10% increment in the proportion of ultra-processed food in the diet 1.12 (95% confidence interval 1.06 to 1.18); P for trend<0.001) and breast cancer risk (n=739 cases; hazard ratio 1.11 (1.02 to 1.22); P for trend=0.02). These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet (lipid, sodium, and carbohydrate intakes and/or a Western pattern derived by principal component analysis). CONCLUSIONS In this large prospective study, a 10% increase in the proportion of ultra-processed foods in the diet was associated with a significant increase of greater than 10% in risks of overall and breast cancer. Further studies are needed to better understand the relative effect of the various dimensions of processing (nutritional composition, food additives, contact materials, and neoformed contaminants) in these associations. STUDY REGISTRATION Clinicaltrials.gov NCT03335644.