BACKGROUND:Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce cardiovascular risk in obese individuals with established cardiovascular disease (CVD), potentially through modulating key risk factors. However, their benefit in primary prevention remains unclear. OBJECTIVES:This study aims to emulate GLP-1RA use for primary prevention by applying risk factor changes observed in the SELECT (Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes) trial to obese individuals at risk of but without established CVD. METHODS:In 610,789 CVD-free individuals from European and North American Global Cardiovascular Risk Consortium cohorts, a model to estimate 10-year incidence of CVD and death from any cause was fitted using prespecified risk factors: body mass index (BMI), glycosylated hemoglobin, systolic blood pressure, high-sensitivity C-reactive protein, and non-high-density-lipoprotein cholesterol. This model was applied to 200,012 individuals from 2 contemporary health examination surveys to emulate GLP-1RA therapy by using sex-stratified, placebo-adjusted changes in the 5 risk factors observed with GLP-1RA therapy in SELECT. Primary analyses included individuals with a BMI ≥27 kg/m2 and a SCORE2 (Systematic Coronary Risk Evaluation 2)-derived baseline risk ≥7.5%. Secondary analyses examined nonobese and lower SCORE2 groups and accounted for reduced compliance. RESULTS:In the surveys, 21,720 individuals had a BMI ≥27 kg/m2 and a SCORE2-derived baseline risk ≥7.5%. Observed 10-year CVD incidence was 13.82% (95% CI: 11.94%-15.71%). Emulated GLP-1RA therapy lowered projected CVD incidence to 10.83% (95% CI: 9.27%-12.39%), an absolute reduction of 2.99% (95% CI: 2.67%-3.31%) and a relative reduction of 22%. Absolute reductions were larger in men than in women (3.14% [95% CI: 2.82%-3.47%] vs 2.7% [95% CI: 2.23%-3.16%]), with similar potential relative reductions across sexes (21% vs 23%). Modeled risk reductions were attenuated in nonobese and lower SCORE2 groups and diminished further with lower compliance assumptions. CONCLUSIONS:In appropriately selected individuals at high CVD risk, GLP-1RA therapy may complement existing primary prevention strategies, supporting the rationale for future randomized studies.

Background and Aim: Dietary guidelines play a central role in shaping food and nutrition policy, food regulations, education, and food and agricultural systems worldwide. Recent controversies with the 2026 Dietary Guidelines for Americans (DGA) have highlighted inconsistencies in the processes used to develop dietary guidance, including evidence synthesis, policy formulation, and public-facing recommendations. In parallel, rising burdens from diet-related chronic diseases, environmental pressures, and health inequities underscore the need for globally relevant recommendations that address both human and planetary health. Making health and sustainable diets affordable for all is consistent with health as a human right. Given our expertise in carbohydrate nutrition, our aim here was to develop an evidence-informed International Food Guide Pyramid emphasizing optimal carbohydrate-containing staples. Methods: The International Carbohydrate Quality Consortium (ICQC) applied an evidence-review framework to identify dietary patterns, food substitution effects, and consistency across major scientific bodies, drawing on a narrative synthesis of consistent national dietary guideline sources to inform the pyramid's structure. Quantitative intake ranges from the EAT-Lancet Commission reference diet were used to guide the relative visual proportions of food groups within the pyramid, preserving rank order and magnitude. Qualitative support and contextual interpretation were derived from authoritative evidence syntheses. Results: The resulting pyramid depicts a plant-forward omnivorous dietary pattern supported by epidemiological and clinical evidence indicating benefits for cardiometabolic health and chronic disease prevention. Vegetables, fruits, whole grains, and legumes constitute foundational components of the pyramid. Nuts, seeds, and unsaturated plant oils are emphasized as primary sources of fat, while foods high in saturated fat are generally limited. Animal-source foods are included in moderate amounts, with poultry and fish preferred over red meat, and dairy incorporated in modest amounts. Carbohydrate quality is emphasized through prioritization of wholegrain foods alongside traditional low-glycemic index grain staples, favoring carbohydrate sources rich in dietary fiber, intact plant cells and micronutrients while limiting sugars consumed in low-nutrient forms, especially as beverages. The framework also accommodates plant-based dietary patterns. Conclusions: This evidence-informed International Food Guide Pyramid integrates quantitative modeling and qualitative evidence synthesis to provide a coherent, flexible, and globally adaptable dietary framework aligned with both human and planetary health.

OBJECTIVES:Predicting disease progression in metabolic dysfunction-associated steatotic liver disease (MASLD) is challenging, and current non-invasive tests (NITs) lack the precision to replace liver biopsy. This study aimed to identify plasma biomarkers for different stages of fibrosis using affinity-based proteomics in two biopsy-proven cohorts. The primary objective was to identify biomarkers capable of distinguishing between low-to-no fibrosis (F0-1) and significant fibrosis (F2-4) in MASLD. MATERIALS AND METHODS:Participants in the discovery cohort were recruited from Uppsala University Hospital and Swedish CArdioPulmonary bioImage Study (SCAPIS), while the validation cohort was included from Linköping University Hospital. All participants diagnosed with MASLD underwent liver biopsy and were categorized by fibrosis stage (F0-1 or F2-4). A total of 276 plasma proteins were analyzed using Olink® panels, with biomarkers identified through ordinal logistic regression, random forest (RF) analysis and the Boruta algorithm. RESULTS:The discovery cohort included 60 participants, with 60% having fibrosis stage F0-1 and 40% having F2-4. The validation cohort had 59 participants, of whom 35 had fibrosis stage F0-1 (59.3%) and 24 had stage F2-4 (40.7%). Five biomarkers were significantly associated with fibrosis stage in the discovery cohort, with four confirmed in the validation cohort. A model combining angiotensin converting enzyme-2 (ACE2), hepatocyte growth factor (HGF) and insulin-like growth factor-binding protein-7 (IGFBP-7) demonstrated strong predictive performance for significant fibrosis (c-statistics 0.82-0.83), outperforming fibrosis-4 (FIB-4) (c-statistics 0.61-0.72). CONCLUSIONS:A biomarker model including ACE2, HGF and IGFBP7 shows promise in distinguishing between low-stage and significant fibrosis.

Aims: In addition to weight loss, obesity surgery (OS) leads to metabolic improvements that seem at least partly independent of weight loss and are also mediated by various endocrine pathways and the brain. For the first time, we compared the short-term effects of weight loss achieved by either OS or a low-energy diet (LED) on several hormonal systems, at fasting and upon an oral glucose challenge. Materials and Methods: This study presents sub-analyses from a randomized controlled trial including 24 participants with obesity but without diabetes (BMI 35-45 kg/m(2)), randomized 2:1 to either OS or 4-week LED leading to comparable weight loss. Circulating levels of gut, pituitary, adrenal, thyroid hormones, glucagon, insulin-like growth factor-1 and sex hormone-binding globulin were measured at baseline and 4 weeks after either intervention, both at fasting and during an oral glucose tolerance test (OGTT). Results: At 4 weeks, similar weight loss was achieved for the two interventions (7.7 for OS vs. 7.4% for LED). glucagon-like peptide-1 and peptide YY secretion during the OGTT increased after OS (p < 0.001 for OGTT(AUC) for both hormones), but not LED, while glucagon secretion remained unaffected. Adrenocorticotropin, cortisol and prolactin levels during OGTT were increased after OS (p = 0.04, p < 0.001, p = 0.002, respectively), while parathyroid hormone levels were decreased (p = 0.007). Fasting triiodothyronine levels were reduced after OS (p = 0.01). Fasting sex hormone-binding globulin levels decreased after both interventions (p < 0.01). Conclusion: Rapid and extensive hormonal changes occur after OS, but not LED, despite similar weight loss. Of note, few differences were seen in the fasting state, whereas multiple endocrine pathways were affected during the oral glucose challenge. The findings suggest altered responses to oral glucose after OS in several hypothalamus-pituitary endocrine axes and peripheral endocrine glands.

Purpose of reviewTo inform about the current evidence on the potential cardiometabolic benefits of replacing saturated fatty acids with unsaturated fatty acids. This review will highlight the recent data from prospective cohort studies that have used substitution analyses to evaluate cardiometabolic [with a focus on cardiovascular disease (CVD)] and total mortality risk when replacing intakes of saturated fatty acids (SFA) with either monounsaturated fatty acids (MUFA) or polyunsaturated fatty acids (PUFA).Recent findingsResults from recent, prospective cohort studies suggest that replacing SFA (e.g. from butter, meats, or palm oil) with unsaturated fats, particularly PUFA from vegetable oils, nuts, and fatty fish, are not only associated with reduced all-cause mortality and CVD risk but also from other cardiometabolic diseases.SummaryThe current evidence supports replacing SFA with unsaturated fatty acids from MUFA and PUFA on all-cause mortality and CVD risk. Replacing foods rich in SFA such as butter, red meat, and processed red meat with either plant-based MUFA or PUFA-rich sources such as vegetable oils, nuts, or fatty fish is associated with lower risk of all-cause mortality and CVD. These recent findings accord with international dietary recommendations, and also support the use of more plant-based diets for public health.

Polyunsaturated fatty acids (PUFA) have been shown to reduce liver fat compared to saturated fat, but effects of a novel "anti-lipogenic" diet replacing carbohydrates with PUFA (LCPUFA) or a low-fat healthy Nordic diet (HND) rich in whole-grains are unknown. The objective of this study was to investigate the effects of these diets, as compared with usual care (UC), on liver fat (primary outcome) and related glycemic and lipid disorders after 12 months of intervention, in individuals with prediabetes or type 2 diabetes (T2D). A three-arm parallel ad libitum randomized trial was completed in December 2022 (NCT04527965). Outcome assessors and care providers were blinded to participants' diets. Men and women (n=150) with prediabetes or T2D (55%) were randomized in a 1:1:1 allocation ratio, stratified by sex and T2D status, and were assessed at the Uppsala Academic hospital. General linear models were employed to estimate intention-to-treat effects. Liver fat was reduced after the LCPUFA diet (n=54) and the HND (n=51) when compared to UC (n=43); -1.46% (95% CI: -2.42, -0.51)) and -1.76 % (95% CI: -2.96, -0.57), respectively. No difference in liver fat between LCPUFA and HND was observed. Body weight and HbA1c decreased more in the HND versus the other diets, whereas no differences were observed between LCPUFA and UC. LDL-cholesterol was reduced to a similar extent during the HND and LCPUFA diet, compared to UC, whereas only HND reduced triglycerides, inflammation and liver enzymes. In total, n=4 serious adverse events occurred, distributed among groups. An ad libitum mainly plant-based LCPUFA diet and HND similarly reduced liver fat and LDL-cholesterol, compared with UC. Even without intentional energy restriction, the HND further improved body weight, glycemic control, liver biochemistry, triglycerides, and inflammation, suggesting a HND as a clinically feasible diet for the management of T2D and metabolic dysfunction-associated steatotic liver disease (MASLD).

AIMS:Diet is a determinant of cardiovascular diseases (CVD) with coronary disease as predominant cause of pre-mature death. To analyse how diet was associated with coronary atherosclerosis, including plaque features. METHODS AND RESULTS:The cross-sectional population-based study using data from the Swedish CArdioPulmonary BioImage Study (SCAPIS) included 24 079 adults aged 50-64 years, recruited in 2013 to 2018 who were free of clinical cardiovascular disease. The recruitment and comprehensive examinations were conducted at six locations in Sweden. A dietary index (DI) based on a previously published anti-inflammatory DI including high proportion of plant-based foods, and low in red or processed meat and sugar-sweetened beverages was constructed. The reference group was within lowest DI tertile. Coronary atherosclerosis assessed by coronary computed tomography angiography, including any-, significant-, and adverse or high-risk coronary plaque, which is non-calcified with a significant stenosis ≥50%. Lowest, compared to highest DI tertile was associated with younger age, more often men (62.2% vs. 32.9%), higher high-sensitive C-reactive protein, more cardiometabolic risk and smokers, higher alcohol-, and higher energy-intake. In the highest and lowest tertile, coronary plaques were present in 36.3% and 44.3%, respectively, stenosis ≥ 50% in 3.7% and 6.0%. Non-calcified coronary plaques with stenosis ≥50% were present in 0.9% and 1.5% in highest and lowest tertiles. In multivariable analyses, the lowest tertile of DI was associated with high-risk plaque features after adjusting for age, sex, smoking, with waist circumference, triglycerides (TGs), and hypertension as possible mediators. CONCLUSION:A low-fibre diet with high red meat content was associated with high-risk plaques features, increased coronary calcification and significant stenosis. Waist circumference, TGs, and hypertension emerged as potential mediators of these associations, underscoring the role of metabolic and hemodynamic factors in the dietary impact on coronary atherosclerosis. Our findings strengthen the importance of cardioprotective dietary recommendations.

Background: PUFAs, especially from vegetable fat sources, have been suggested to contribute to weight regulation and be protective to cardiometabolic health. However, a few longitudinal studies on childhood exposure are available, with short follow-up time and conflicting results. Objectives: To study the relationship between plasma proportions of PUFA in childhood and adolescence and cardiometabolic risk factors in young adulthood, such as obesity, body composition, blood pressure (BP), and blood lipids in a prospective cohort study. Methods: We included n = 688 participants of the BAMSE (Barn, Allergi, Miljo, Stockholm, Epidemiologi) cohort in Stockholm, Sweden, with data on plasma phospholipid proportions of n-3 and n-6 fatty acids [alpha-linolenic acid (ALA), EPA, docosapentaenoic acid, DHA, linoleic acid (LA), and arachidonic acid (AA)] at 8 and 16 y and body mass index (BMI), waist circumference, fat mass %, BP, and blood lipids at 24 y. Associations between PUFAs and cardiometabolic health outcomes were assessed with sex-stratified multivariable-adjusted linear and logistic regression models. Results: In females, LA and ALA at 16 y were inversely associated with BMI [B:-0.35 (-0.54,-0.17) and B:-6.1 (-11,-1.5), respectively], and similarly with waist circumference and fat mass at 24 y. Also in females, LA was inversely associated with BP, triglycerides, LDL-cholesterol), and total cholesterol (e.g., B-0.044 [-0.079,-0.0099] for LA at 16 y and LDL-cholesterol), whereas ALA was only inversely associated with LDL-cholesterol. No associations were found between long chain n-3 fatty acids or AA and any of the studied outcomes. Conclusions: Plasma phospholipid proportions of LA and ALA, biomarkers of vegetable oil intake, during childhood and adolescence were inversely associated with measures of obesity and cardiometabolic health in young adulthood, with a potential sex difference. These findings accord with short-term feeding trials suggesting a possible preventive role of LA on body fat accumulation.

Objective Meat intake is suggested to affect gut microbiome composition and the risk of chronic diseases. We aimed to identify meat-associated gut microbiome features and their association with host factors. Design Gut microbiota species were profiled by deep shotgun metagenomics sequencing in 9,669 individuals. Intake of white meat, unprocessed red meat, and processed red meat was assessed using a food frequency questionnaire. The associations of meat intake with alpha-diversity and relative abundance of gut microbiota species were tested using linear regression models with adjustment for dietary fiber intake, body mass index, and other potential confounders. Meat-associated species were further assessed for association with enrichment of microbial gene function, meat-associated plasma metabolites, and clinical biomarkers. Results Higher intake of processed red meat was associated with reduced alpha microbial diversity. White meat, unprocessed, and processed red meat intakes were associated with 36, 14, and 322 microbiota species, respectively. Species associated with processed red meat were enriched for bacterial pathways like amino acid degradation, while those negatively linked were enriched for pathways like homoacetogenesis. Furthermore, species positively associated with processed red meat were to a large extent associated with reduced trimethylamine N-oxide and glutamine levels but increased creatine and carnitine metabolites, fasting insulin and glucose, C-reactive protein, apolipoprotein A1, and triglyceride levels and higher blood pressure. Conclusion This largest to date population-based study on meat and gut microbiota suggests that meat intake, particularly processed red meat, may modify the gut microbiota composition, functional capacity, and health-related biomarkers.

BACKGROUND AND AIMS:The relationship between uncommon phenotypes, such as metabolically healthy obesity and normal weight with metabolic syndrome (MetS), and cardiovascular disease (CVD) risk, remains unclear. We investigated how different combinations of body mass index (BMI) and MetS are associated with overall and specific CVDs and how the number of MetS components influences CVD risk in individuals with obesity. METHODS AND RESULTS:We performed separate analyses and a meta-analysis of 36,233 individuals from four Swedish cohorts to assess the risk of incident CVDs across BMI/MetS combinations (normal-weight, overweight or obese/MetS yes or no). Participants were followed for CVDs and death through linkage to the Swedish National Registers. Compared to normal weight without MetS, overweight and obesity without MetS had most pronounced association with the risk of heart failure [multivariable hazard ratios, HR (95 % CI) = 1.37 (1.16-1.63) and 1.85 (1.37-2.48), respectively, p < 0.001]. In obese individuals, the risk of incident CVD (composite endpoint) increased with an increasing number of MetS components, but this relationship was not statistically significant in obese participants without additional MetS components, likely due to the small at-risk group. Normal-weight individuals with MetS had an increased risk of myocardial infarction [HR (95 % CI) 2.0 (1.51-2.64)], p < 0.001, and stroke [HR (95 % CI) 1.63 (1.17-2.28), p = 0.004]. CONCLUSIONS:Overweight and obesity without MetS showed a greater impact on the risk of heart failure, whereas normal-weight individuals with MetS had a higher risk of myocardial infarction and stroke. In obese individuals, CVD risk increased as the number of MetS components increased.

Lipid droplets (LDs) are crucial for energy homeostasis, but are also involved in a wide spectrum of other cellular processes. Accumulating data identifies LDs as an important player in inflammation. However, the underlying mechanisms and the impact of LDs on neuroinflammation remain unclear. Here, we describe a novel function of LDs in human astrocytes, in the context of Alzheimer’s disease (AD). Although, the overall lipid profile was unchanged in astrocytes with AD pathology, our data show a clear effect on LD metabolism and specific fatty acids involved in neuroinflammation. Importantly, we found astrocytes to be in close contact with infiltrating CD4 + T cells in the AD brain. Moreover, PLIN3 + LDs in astrocytes co-localize with major histocompatibility complex II (MHCII), indicating a role of LDs in adaptive immunity. Comprehensive analysis of human induced pluripotent stem cell (hiPSC)-derived astrocytes revealed that MHCII is in fact loaded within PLIN3 + LDs and forwarded to neighboring cells via tunneling nanotubes and secretion. Notably, the MHCII molecules are cleaved into its active form prior to packing, indicating an alternative route of MHCII shuttling through LDs, transporting functional immune complexes between cells. Quantification of PLIN3 + LDs in astrocytic cultures, human brain tissue and cerebral organoids indicates that AD pathology initially stimulates PLIN3 + LD formation, but in the long-run results in PLIN3 + LD consumption, which may have consequences on the astrocytes’ MHCII distribution capacity. Taken together, our findings present a novel function of PLIN3 + LDs that can be of relevance for AD and other inflammatory conditions.

BACKGROUND:Five risk factors account for approximately 50% of the global burden of cardiovascular disease. How the presence or absence of classic risk factors affects lifetime estimates of cardiovascular disease and death from any cause remains unclear. METHODS:We harmonized individual-level data from 2,078,948 participants across 133 cohorts, 39 countries, and 6 continents. Lifetime risk of cardiovascular disease and death from any cause was estimated up to 90 years of age according to the presence or absence of arterial hypertension, hyperlipidemia, underweight and overweight or obesity, diabetes, and smoking at 50 years of age. Differences in life span (in terms of additional life-years free of cardiovascular disease or death from any cause) according to the presence or absence of these risk factors were also estimated. Risk-factor trajectories were analyzed to predict lifetime differences according to risk-factor variation. RESULTS:The lifetime risk of cardiovascular disease was 24% (95% confidence interval [CI], 21 to 30) among women and 38% (95% CI, 30 to 45) among men for whom all five risk factors were present. In the comparison between participants with none of the risk factors and those with all the risk factors, the estimated number of additional life-years free of cardiovascular disease was 13.3 (95% CI, 11.2 to 15.7) for women and 10.6 (95% CI, 9.2 to 12.9) for men; the estimated number of additional life-years free of death was 14.5 (95% CI, 9.1 to 15.3) for women and 11.8 (95% CI, 10.1 to 13.6) for men. As compared with no changes in the presence of all risk factors, modification of hypertension at an age of 55 to less than 60 years was associated with the most additional life-years free of cardiovascular disease, and modification of smoking at an age of 55 to less than 60 years was associated with the most additional life-years free of death. CONCLUSIONS:The absence of five classic risk factors at 50 years of age was associated with more than a decade greater life expectancy than the presence of all five risk factors, in both sexes. Persons who modified hypertension and smoking in midlife had the most additional life-years free of cardiovascular disease and death from any cause, respectively. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov number, NCT05466825.).

Genetic risk variants for obesity and metabolic syndrome (MetS) have been identified, but their link to relevant metabolic health parameters warrants further attention. This study aimed to investigate the extent to which single-nucleotide polymorphisms (SNPs) associated with obesity are linked to changes in fatty acid (FA) profiles in serum cholesteryl esters, lipid metabolism, and MetS risk. Data from the Uppsala Longitudinal Study of Adult Men (ULSAM), conducted in men at age 50 (N = 1973) and age 70 (N = 982), were used to investigate SNPs associated with body mass index (BMI) in genome-wide association studies with metabolic parameters at age 50. The significant SNPs and associated lipid parameters were then used as predictors of MetS over a 20-year follow-up period, at age 70 in binary regression models. The two genes, the brain-derived neurotrophic factor gene (BDNF) (rs7103411) and the fat mass and obesity-associated gene (FTO) (rs1558902), together with delta-5-desaturase (D5D) activity, 20:5n-3 in serum cholesteryl esters (CE), fasting blood glucose, abdominal skinfold thickness, apolipoprotein-B, and high-density lipoprotein cholesterol (HDL-C) at age 50, significantly predicted the risk of MetS at age 70. The findings suggest a considerable contribution of the SNPs BDNF rs7103411, FTO rs1558902, and ETV5 rs9816226, along with low D5D activities and serum levels of HDL-C in men at age 50, to the risk for MetS 20 years later.

Obesity surgery (OS) and diet-induced weight loss rapidly improve insulin resistance. We aim to investigate the impact of either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with a diet low in energy (low-calorie diet; LCD) on body composition, glucose control and insulin sensitivity, assessed both at the global and tissue-specific level in individuals with obesity but not diabetes. In this parallel group randomised controlled trial, patients on a waiting list for OS were randomised (no blinding, sealed envelopes) to either undergo surgery directly or undergo an LCD before surgery. At baseline and 4 weeks after surgery (n=15, 11 RYGB and 4 SG) or 4 weeks after the start of LCD (n=9), investigations were carried out, including an OGTT and hyperinsulinaemic–euglycaemic clamps during which concomitant simultaneous whole-body [18F]fluorodeoxyglucose-positron emission tomography (PET)/MRI was performed. The primary outcome was HOMA-IR change. One month after bariatric surgery and initiation of LCD, both treatments induced similar reductions in body weight (mean ± SD: −7.7±1.4 kg and −7.4±2.2 kg, respectively), adipose tissue volume (7

BACKGROUND:Short-term trials have shown a reduction in liver fat when saturated fatty acids (SFAs) are substituted with polyunsaturated fatty acids (PUFA), or with low-glycemic carbohydrates. However, few cohort studies have been conducted to investigate the associations of replacing SFA and SFA-rich foods with different macronutrients and foods in more severe stages of liver disease; nonalcoholic fatty liver disease (NAFLD) cirrhosis and hepatocellular carcinoma (HCC). OBJECTIVES:To investigate associations between the substitution of SFA and SFA-rich foods with other macronutrients and foods and NAFLD cirrhosis and HCC in a middle-aged to elderly Swedish population of n = 77,059 males and females. METHODS:Time-to-event analyses were performed to investigate associations between the food and macronutrient substitutions and NAFLD cirrhosis and HCC. Multivariable Cox regression models were constructed to estimate hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Statistical isocaloric and equal-mass substitutions were performed using the leave-one-out method. Prespecified nutrient and food substitutions of interest were SFA with carbohydrates, SFA with fiber, SFA with PUFA, butter with margarine and vegetable oils, unprocessed red meat with fish, and milk with fermented milk. RESULTS:Over a median follow-up of 24 y, 566 cases of NAFLD cirrhosis and 205 cases of HCC were registered. Overall, dietary substitutions showed no clear associations with either NAFLD cirrhosis or HCC. Substituting SFA with carbohydrates showed an HR of 0.87 (95% CI: 0.74, 1.02) for HCC and 1.00 (95% CI: 0.89, 1.11) for NAFLD cirrhosis. Substituting milk with fermented milk showed an HR of 0.93 (95% CI: 0.85, 1.01) for HCC and 0.97 (95% CI: 0.92, 1.03) for NAFLD cirrhosis. CONCLUSIONS:No clear associations were observed between diet and NAFLD cirrhosis or HCC. Although accompanied by low precision, possible lowered risks of HCC by substituting SFA with carbohydrates or milk with fermented milk might be of interest, but needs replication in other cohorts.

Current cardiometabolic disease prevention guidelines recommend increasing dietary unsaturated fat intake while reducing saturated fats. Here we use lipidomics data from a randomized controlled dietary intervention trial to construct a multilipid score (MLS), summarizing the effects of replacing saturated fat with unsaturated fat on 45 lipid metabolite concentrations. In the EPIC-Potsdam cohort, a difference in the MLS, reflecting better dietary fat quality, was associated with a significant reduction in the incidence of cardiovascular disease (-32%; 95% confidence interval (95% CI): -21% to -42%) and type 2 diabetes (-26%; 95% CI: -15% to -35%). We built a closely correlated simplified score, reduced MLS (rMLS), and observed that beneficial rMLS changes, suggesting improved dietary fat quality over 10 years, were associated with lower diabetes risk (odds ratio per standard deviation of 0.76; 95% CI: 0.59 to 0.98) in the Nurses' Health Study. Furthermore, in the PREDIMED trial, an olive oil-rich Mediterranean diet intervention primarily reduced diabetes incidence among participants with unfavorable preintervention rMLS levels, suggestive of disturbed lipid metabolism before intervention. Our findings indicate that the effects of dietary fat quality on the lipidome can contribute to a more precise understanding and possible prediction of the health outcomes of specific dietary fat modifications.

BACKGROUND:Fatty acids may influence lean tissue volume and skeletal muscle function. We previously reported in young lean participants that overfeeding PUFA compared with SFA induced greater lean tissue accumulation despite similar weight gain. OBJECTIVES:In a double-blind randomized controlled trial, we aimed to investigate if the differential effects of overfeeding SFA and PUFA on lean tissue accumulation could be replicated in individuals with overweight and identify potential determinants. Further, using substitution models, we investigated associations between SFA and PUFA concentrations with lean tissue volume in a large population-based sample (UK Biobank). METHODS:Sixty-one males and females with overweight [BMI (kg/m2): 27.3 (interquartile range (IQR), 25.4-29.3); age: 43 (IQR, 36-48)] were overfed SFA (palm oil) or n-6 (ω-6) PUFA (sunflower oil) for 8 wk. Lean tissue was assessed by MRI. We had access to n = 13,849 participants with data on diet, covariates, and MRI measurements of lean tissue, as well as 9119 participants with data on circulating fatty acids in the UK Biobank. RESULTS:Body weight gain mean (SD) was similar in PUFA (2.01 ± 1.90 kg) and SFA (2.31 ± 1.38 kg) groups. Lean tissue increased to a similar extent [0.54 ± 0.93 L and 0.67 ± 1.21 L for PUFA and SFA groups, respectively, with a difference between groups of 0.07 (-0.21, 0.35)]. We observed no differential effects on circulating amino acids, myostatin, or IL-15 and no clear determinants of lean tissue accumulation. Similar nonsignificant results for SFA and PUFA were observed in UK Biobank, but circulating fatty acids demonstrated ambiguous and sex-dependent associations. CONCLUSIONS:Overfeeding SFA or PUFA does not differentially affect lean tissue accumulation during 8 wk in individuals with overweight. A lack of dietary fat type-specific effects on lean tissue is supported by specified substitution models in a large population-based cohort consuming their habitual diet. This trial was registered at clinicaltrials.gov identifier as NCT02211612.

BackgroundVery long-chain (VLC) polyunsaturated fatty acids (PUFA) have been hypothesized to influence the risk of allergic disease. The aim of the study was to investigate the role of plasma levels of omega-3 (n-3) and omega-6 (n-6) PUFA in childhood and adolescence, for the development of rhinitis and allergic sensitization up to young adulthood.MethodsThe study included n = 933 participants from the BAMSE cohort. Proportions of n-3 and n-6 PUFA in plasma phospholipids were analyzed at 8 and 16 years using gas chromatography. Associations between PUFA and rhinitis as well as allergic sensitization, analyzed by IgE reactivity against airborne allergens, up to age 24 years were analyzed by generalized estimating equations and logistic regression models.ResultsHigh plasma levels of VLC n-3 PUFA as well as the n-6 PUFA arachidonic acid (AA) at 8 years were inversely associated with rhinitis (overall OR up to 24 years: 0.72, 95% CI 0.55, 0.0.93 and 0.69 [0.53, 0.89], respectively) and aeroallergen sensitization (0.64 [0.49, 0.83] and 0.71 [0.54, 0.92], respectively). However, excluding prevalent cases at 8 years attenuated the associations.ConclusionPlasma levels of n-3 and certain n-6 PUFA in childhood were inversely associated with allergic sensitization and allergic rhinitis up to young adulthood. The association may to some extent be explained by persistent childhood disease, rather than new incident cases in adolescence and young adulthood. To what extent these associations are driven by dietary PUFA intake versus metabolism remains to be clarified for the prevention of rhinitis and allergic sensitization.