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Matthias B Schulze and colleagues discuss current knowledge on the associations between dietary patterns and cancer, coronary heart disease, stroke, and type 2 diabetes, focusing on areas of uncertainty and future research directions

Chronic kidney disease (CKD) remains a major epidemiological, clinical, and biomedical challenge. During CKD, renal tubular epithelial cells (TECs) present a persistent inflammatory and profibrotic response. Fatty acid oxidation (FAO), the main source of energy for TECs, is reduced in kidney fibrosis and contributes to its pathogenesis. To determine whether gain of function in FAO (FAO-GOF) could protect from fibrosis, we generated a conditional transgenic mouse model with overexpression of the fatty acid shuttling enzyme carnitine palmitoyl-transferase 1A (CPT1A) in TECs. Cpt1a-knockin (CPT1A-KI) mice subjected to 3 models of renal fibrosis (unilateral ureteral obstruction, folic acid nephropathy [FAN], and adenine-induced nephrotoxicity) exhibited decreased expression of fibrotic markers, a blunted proinflammatory response, and reduced epithelial cell damage and macrophage influx. Protection from fibrosis was also observed when Cpt1a overexpression was induced after FAN. FAO-GOF restored oxidative metabolism and mitochondrial number and enhanced bioenergetics, increasing palmitate oxidation and ATP levels, changes that were also recapitulated in TECs exposed to profibrotic stimuli. Studies in patients showed decreased CPT1 levels and increased accumulation of short- and middle-chain acylcarnitines, reflecting impaired FAO in human CKD. We propose that strategies based on FAO-GOF may constitute powerful alternatives to combat fibrosis inherent to CKD.

AbstractObjectiveTo evaluate the association between consumption of ultra-processed foods and all cause mortality.DesignProspective cohort study.SettingSeguimiento Universidad de Navarra (SUN) cohort of university graduates, Spain 1999-2018.Participants19 899 participants (12 113 women and 7786 men) aged 20-91 years followed-up every two years between December 1999 and February 2014 for food and drink consumption, classified according to the degree of processing by the NOVA classification, and evaluated through a validated 136 item food frequency questionnaire.Main outcome measureAssociation between consumption of energy adjusted ultra-processed foods categorised into quarters (low, low-medium, medium-high, and high consumption) and all cause mortality, using multivariable Cox proportional hazard models.Results335 deaths occurred during 200 432 persons years of follow-up. Participants in the highest quarter (high consumption) of ultra-processed foods consumption had a higher hazard for all cause mortality compared with those in the lowest quarter (multivariable adjusted hazard ratio 1.62, 95% confidence interval 1.13 to 2.33) with a significant dose-response relation (P for linear trend=0.005). For each additional serving of ultra-processed foods, all cause mortality relatively increased by 18% (adjusted hazard ratio 1.18, 95% confidence interval 1.05 to 1.33).ConclusionsA higher consumption of ultra-processed foods (>4 servings daily) was independently associated with a 62% relatively increased hazard for all cause mortality. For each additional serving of ultra-processed food, all cause mortality increased by 18%.Study registrationClinicalTrials.gov NCT02669602.

The Mediterranean diet has been linked to a number of health benefits, including reduced mortality risk and lower incidence of cardiovascular disease. Definitions of the Mediterranean diet vary across some settings, and scores are increasingly being employed to define Mediterranean diet adherence in epidemiological studies. Some components of the Mediterranean diet overlap with other healthy dietary patterns, whereas other aspects are unique to the Mediterranean diet. In this forum article, we asked clinicians and researchers with an interest in the effect of diet on health to describe what constitutes a Mediterranean diet in different geographical settings, and how we can study the health benefits of this dietary pattern.

Whereas the relationship between some components of diet, such as n-3 fatty acids and B-vitamins, and depression risk has been extensively studied, the role of fast-food or processed pastries consumption has received little attention. Consumption of fast food (hamburgers, sausages, pizza) and processed pastries (muffins, doughnuts, croissants) was assessed at baseline through a validated semi-quantitative FFQ. Participants were classified as incident cases of depression if they reported a physician diagnosis of depression or the use of antidepressant medication in at least one of the follow-up questionnaires. Cox regression models were fit to assess the relationship between consumption of fast food and commercial baked goods and the incidence of depression. The SUN (Seguimiento Universidad de Navarra - University of Navarra Follow-up) Project, Spain. Participants (n 8964) from a Spanish cohort. After a median follow-up of 6·2 years, 493 cases of depression were reported. A higher risk of depression was associated with consumption of fast food (fifth (Q5) v. first quintile (Q1): hazard ratio (HR) = 1·36; 95 % CI 1·02, 1·81; P trend = 0·003). The results did not change after adjustment for the consumption of other food items. No linear relationship was found between the consumption of commercial baked goods and depression. Participants belonging to consumption quintiles Q2-Q5 showed an increased risk of depression compared with those belonging to the lowest level of consumption (Q1; HR = 1·38; 95 % CI 1·06, 1·80). Fast-food and commercial baked goods consumption may have a detrimental effect on depression risk.

Limited data exists on the interrelationships between physical activity (PA), sedentary behaviors and sleep concerning cardiometabolic risk factors in aged adults at high cardiovascular disease risk. Our aim was to examine independent and joint associations between time spent in leisure-time PA, sedentary behaviors and sleep on the prevalence of obesity, type 2 diabetes (T2D) and components of the metabolic syndrome (MetS) in Mediterranean individuals at high cardiovascular risk. Cross-sectional analyses were performed on baseline data from 5776 Spanish adults (aged 55-75y in men; 60-75y in women) with overweight/obesity and MetS, from October 2013 to October 2016, in the PREDIMED-PLUS trial. Employing multivariable-adjusted Cox regression with robust variance and constant time (given the cross-sectional design), higher prevalence of obesity, T2D and abdominal obesity as component of the MetS were associated with greater time in TV-viewing (Relative Risk, RR: 1.02, 95%CI: 1.01, 1.03; RR:1.04, 95%CI: 1.02, 1.06 and RR: 1.01 95%CI: 1.00, 1.02; respectively, all P < .01). Conversely, greater time in moderate-vigorous PA (MVPA) was associated with lower prevalence of obesity, T2D, abdominal obesity and low HDL-cholesterol (RR: 0.95, 95%CI: 0.93, 0.97; RR: 0.94, 95%CI: 0.89, 0.99; RR: 0.97, 95%CI: 0.96, 0.98; and RR: 0.95, 95%CI: 0.91, 0.99, respectively, all P < .05). For these outcomes, theoretically substituting 1-h/day of MVPA for 1-h/day TV-viewing was also significantly associated with lower prevalence (RR 0.91 to 0.97, all P < .05). Similar lower RR in these outcomes was observed when substituting 1-h/day of MVPA for 1-h/day of sleeping. Longer time watching TV and not meeting MVPA recommendations were jointly associated with higher RR of the prevalence of obesity and T2D. We concluded that, in senior individuals at high cardiovascular risk, greater time spent on MVPA and fewer on sedentary behaviors was inversely associated with prevalence of obesity, T2D, and some of the components of MetS.

Prospective studies have consistently suggested that nut consumption is inversely related to fatal and non-fatal coronary heart disease. Limited data are available on the epidemiological associations between nut intake and cardiometabolic risk factors. To evaluate associations between frequency of nut consumption and prevalence of cardiometabolic risk factors [obesity, metabolic syndrome (MetS), type-2 diabetes, hypertension, and dyslipidemia] in a Mediterranean population at high cardiovascular risk. Cross-sectional study of 7,210 men and women (mean age, 67 y) recruited into the PREDIMED study. MetS was defined by the harmonized ATPIII and IDF criteria. Diabetes and hypertension were assessed by clinical diagnosis and dyslipidemia (high triglycerides, low HDL-cholesterol, and hypercholesterolemia) by lipid analyses. Nut consumption was assessed using a validated food frequency questionnaire and categorized as <1, 1-3, and >3 servings/wk. Control of confounding was done with multivariate logistic regression. Compared to participants consuming <1 serving/wk of nuts, those consuming >3 servings/wk had lower adjusted odds ratios (OR) for obesity (0.61, 95% confidence interval 0.54 to 0.68; P-trend <0.001), MetS (0.74, 0.65 to 0.85; P-trend<0.001), and diabetes (0.87, 0.78 to 0.99; P-trend = 0.043). Higher nut consumption was also associated with lower risk of the abdominal obesity MetS criterion (OR 0.68, 0.60 to 0.79; P-trend<0.001). No significant associations were observed for the MetS components high blood pressure, dyslipidemia, or elevated fasting glucose. Nut consumption was inversely associated with the prevalence of general obesity, central obesity, MetS, and diabetes in subjects at high cardiovascular risk.

BACKGROUND & AIMS: Metabolic syndrome (MetS) has become an important public concern due to its increasing prevalence. An altered fatty acid composition has been associated with MetS, but the Mediterranean diet has been shown to have a protective effect. The aim of the present study was to analyze the influence of a Mediterranean dietary pattern, as assessed by the biomarkers of food supplied, on the plasma fatty acid composition and its relation with MetS after 1 year of intervention. METHODS: A total of 424 subjects were randomly selected from the PREDIMED randomized dietary trial after completing a 1-year intervention program. Participants aged 55 to 80 years and at high risk of cardiovascular disease were randomly assigned to three dietary interventions: Mediterranean diet supplemented with virgin olive oil or nuts, or a low-fat diet. RESULTS: After 1 year of intervention participants in the virgin olive oil group showed significantly increased plasma concentrations of palmitic and oleic acids, but reduced proportions of margaric, stearic, and linoleic acids. In turn, subjects in the nut group showed significantly increased levels of palmitic, linoleic, and α-linolenic acids, but reduced proportions of myristic, margaric, palmitoleic, and dihommo-γ-linoleic acids. Increases in the biomarkers of foods supplied to the Mediterranean diet groups, i.e., oleic and α-linolenic acids, were beneficially associated with the incidence, reversion and prevalence of MetS. No weight changes were observed among participants. CONCLUSIONS: The nut and olive oil diets induced a fatty acid composition that has been shown to be beneficial in the face of MetS. Therefore, a Mediterranean diet rich in fats of vegetable origin may be a useful tool for the management of MetS without the need for concerns over weight gain due to its high fat content.

Background Research on the role of diet in the prevention of depression is scarce. Some evidence suggests that depression shares common mechanisms with cardiovascular disease. Discussion Before considering the role of diet in the prevention of depression, several points need to be considered. First, in general, evidence has been found for the effects of isolated nutrients or foods, and not for dietary patterns. Second, most previous studies have a cross-sectional design. Third, information is generally collected though questionnaires, increasing the risk of misclassification bias. Fourth, adequate control of confounding factors in observational studies is mandatory. Summary Only a few cohort studies have analyzed the relationship between overall dietary patterns, such as the Mediterranean diet, and primary prevention of depression. They have found similar results to those obtained for the role of this dietary pattern in cardiovascular disease. To confirm the findings obtained in these initial cohort studies, we need further observational longitudinal studies with improved methodology, as well as large randomized primary prevention trials, with interventions based on changes in the overall food pattern, that include participants at high risk of mental disorders.

[...]precision nutrition should contemplate the implementation of an efficient individualised nutritional status and assessment of strategies based on validated indices and metrics for metabolic care in every person, being not only restricted to patients suffering chronic diseases but also to healthy subjects.7 Thus, it is a good mandate to recognise individual′s differences and to develop new genetic and transcriptomic indicators, inclusive of proteomic, lipidomic and metabolomic approaches and nutrigenomic and metagenomic tools related to nutrient metabolism.8 Nevertheless, personalised clinical and phenotypical features including one’s own psychological/personality patterns, specific food allergies and intolerances, differential cultural, social and environmental backgrounds, drug side effects, personal dietary preferences as well as singular lifestyle and environmental factors such as cold weather or warm, and very warm climates need to be addressed for a robust precision nutrition and medical approaches. Regulatory issues are needed to be developed and implemented for a smooth growth of nutrition and personalised endeavours and methodologies, where important achievements, recommendations and challenges are expected for combining public and personal health benefits including ethical issues.9 Precision population nutrition A number of policies and public efforts are being currently devoted to generate evidence for health promotion and disease risk reduction supported by food-based dietary guidelines (FBDG) in order to instruct populations about healthy dietary habits.10 These messages are better interpreted than nutrient intakes only and easier to make recommendations on primary prevention of noncommunicable diseases (NCDs) when they are based on Mediterranean dietary components and other regional foods from Oriental, Latin American and Indian diets with spices rich in bioactive compounds.11 12 Of equal importance are the traditional African foods and diets which have not received global dimensions even though these are rich in their diverse nutrient quality such as nutrients provided insect foods. The adverse impact of ultraprocessed foods and discretionary food consumption involving red and processed meats, added sugars, confectionery and other detrimental food ingredients need to be explicitly disclosed on the packaged food labels and scores following the dietary guidelines.13 On the contrary, some myths on fats, oils and nuts need to be dispelled, given the strong available scientific evidence of their cardiovascular benefits and the dangers of overconsumption beyond a level without proper exercise to metabolise them adequately in the body.14 Information sourced from the FBDG repository of the FAO or articulated by WHO reveals that FBDG are currently available for about 100 countries or regions, where the incorporation of bioactive compounds occurring on foods and the analysis of environmental sustainability information, climate change data and considerations to sociocultural factors and swiftly varying dietary tendencies are fairly documented.15 It is not the intent of this article to serve as advise to different countries, but to highlight the parameters to be considered in nutrition and health of the population depending on the climate and the nature of agricultural nutritious products that they are growing and which are used within traditional food practices over thousands of years. Furthermore, epidemiological investigations concerning the impacts of Japanese, Nordic, Latin American and Mediterranean diets or African, Indian and Oriental plant-based nutritional patterns on NCDs have positioned evidences with remarkable benefits in health outcomes and life expectancy compared with westernised food intake habits of high fatty food and meat-rich diets.16 Furthermore, some well-conducted trials such as PREDIMED or DASH and Diabetes Prevention Programs implemented in USA, Europe, China, India or Japan have confirmed the role of lifestyle and dietary practices on health maintenance or prevention/management of obesity, diabetes and cardiovascular events.17 Additionally, specific population-oriented public health-nutrition communication should reflect the specific physiological needs across the life cycle, including infancy and pregnancy or lactation status, which require tailored nutritional supplies to balance particular nutrient requirements and to account for cultural and socioeconomic differences among areas, countries and regions.