Diet and lifestyle offer the potential for achieving a healthy lifespan by reducing risk for cardiometabolic diseases and cancer, as well as maintaining cognitive health and physical function. To facilitate translation and implementation of dietary practices, we have critically reviewed the justification of the current focus on single nutrients, most notably a 10% cap for dietary saturated fat intake and argue for a more holistic food-based approach. In the newly released Dietary Guidelines for Americans, 2025-2030, the recommendation for selecting low-fat dairy foods has been changed to allow full-fat dairy food consumption in recognition of the evidence for their health benefits despite their high content of saturated fat. However, the 10% cap on total saturated fat intake has been maintained, which would require reduced saturated fat consumption from other food sources. Our analysis shows that there is considerable heterogeneity in the physiological and health effects of individual saturated fatty acids, and that the health effects of foods are determined by the food matrix and the overall nutrient profile rather than their saturated fatty acid content. We therefore conclude that the 10% cap on saturated fat intake should be replaced by food-based dietary guidelines.

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.

BACKGROUND:The purpose was to test the hypothesis that exposures to organochlorine compounds are associated with body weight increases in a dietary intervention study. METHODS:In the DioGenes trial, adults with obesity who had at first lost at least 8% of their body weight then completed at least 26 weeks on a specific diet. Concentrations of major organochlorine compounds were assessed in plasma samples obtained at study baseline. RESULTS:A total of 372 participants with complete data were examined for plasma concentrations of major organochlorine compounds. A doubling in total-PCB in plasma was associated with an increase in weight (in kg) at 26 weeks by 0.43 (0.04;0.83), independent of diet group and sex. Associations for most individual organochlorines were in the same direction, though mostly not statistically significant, especially after adjustment. However, p,p'-DDE showed opposite effects. Adjustment for exposure to perfluorinated alkyl substances (PFASs) only minimally affected the findings. CONCLUSIONS:Elevated plasma concentrations of some organochlorine compounds were weakly associated with increased weight gain, although most individual associations did not reach statistical significance after adjustment for PFAS exposure. However, p,p'-DDE concentrations showed a clear association with lowered body weight. Overall, the halogenated pollutants examined are likely to contribute to the obesity pandemic. TRIAL REGISTRATION:The original RCT is with ClinicalTrials.gov number NCT00390637.

Most current dietary guidelines for the prevention of cardiovascular diseases (CVD) recommend the consumption of low-fat dairy in place of regular-fat dairy foods, one of the main sources of dietary saturated fatty acids (SFAs). Here, we summarize the data presented and discussions held-relating to the validity of such recommendations-between a panel of international nutrition research experts at a high-level closed workshop on "Saturated Fat in Dairy and Cardiovascular Diseases," which took place in Amsterdam on 15-16 April, 2024. The most recent evidence indicates that overall, consumption of milk, yogurt and cheese, irrespective of fat content, is neutrally associated with CVD risk. There is also no evidence yet from randomized controlled trials that consumption of regular-fat milk, yogurt, and cheese has different effects on a broad array of cardiometabolic risk factors when compared with consumption of low-fat milk, yogurt, and cheese. Thus, the body of evidence does not support differentiation between regular-fat and low-fat dairy foods in dietary guidelines for both adults and children. Strategies focusing primarily on reduction of energy-dense, nutrient-poor foods, the main source of SFAs in Western diets, rather than on the fat content of dairy foods, are more likely to benefit the population's cardiovascular health. Future research is needed to understand better the place of regular-fat and low-fat dairy foods within healthy eating patterns.

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Purpose (the aim of the study): To determine the benefits and harms associated with participation in a weight loss intervention in overweight and obese individuals with knee or hip osteoarthritis (OA) measured on pain, physical function, quality of life, weight loss, and adverse events. Secondarily we explored whether there was a dose-response relationships between weight loss and clinical benefit.

Scientists were chasing an incretin hormone, and when GLP-1 was finally discovered, we found that it had a pronounced satiety effect, slowed down gastric emptying, and actually reduced postprandial insulin response. These mechanisms are the basis for the highly efficacious GLP-1 analogues that today offer safe and effective treatment in millions of people living with obesity. Moreover, the combined GLP-1 mechanisms of weight loss and delayed carbohydrate absorption may also be the key drivers of remission of type 2 diabetes and reduced cardiovascular events found by GLP-1 analogues.

Nutrients serve physiological functions in a dose-dependent manner and that needs to be recognized in risk assessment. An example of the consequences of not properly considering this can be seen in a recent assessment by the European Food Safety Authority (EFSA). EFSA concluded in 2022 that the intake of added and free sugars should be “as low as possible in the context of a nutritionally adequate diet”. That conclusion of EFSA is based on the effects on two surrogate endpoints for an adverse effect found in randomized controlled trials with high sugars intake levels: fasting glucose and fasting triglycerides. The lowest intake levels in these trials were around 10 energy% and at this intake level there were no adverse effects on the two outcomes. This indicates that the adverse effects of sugars have an observable threshold value for these two endpoints. The most appropriate interpretation from the vast amount of data is that currently no definitive conclusion can be drawn on the tolerable upper intake level for dietary sugars. Therefore, EFSA's own guidance would lead to the conclusion that the available data do not allow the setting of an upper limit for added sugars and hence, that more robust data are required to identify the threshold value for intake of sugars.

Eicosanoids and other oxylipins represent a superfamily of bioactive lipids involved in the regulation of crucial biological processes such as inflammation, blood clotting or endothelial reactivity. Oxylipins are generated from polyunsaturated fatty acids (PUFAs) through various enzymatic and free-radical-mediated reactions. Interestingly, each metabolic step (PUFA availability, enzyme activity and oxidative stress) can be influenced by diet. Oxylipins could therefore be important mediators of the effects of diet on human health. To provide new insights into the relationships between oxylipins, fatty acids (FAs) and diet, we conducted two independent cohort studies nested in the Polish branch of the PURE international cohort and in the French Nutrinet-Santé cohort, respectively. The selected participants (n = 318) were healthy and fully characterized for their dietary intake. Our first objective was to determine if a healthy diet was associated with a specific oxylipin signature. Our secondary objective was to comprehensively investigate the relationships between diet, FAs and oxylipins. Participants were distributed into two groups according to the quality of their diet (based on the Alternative Healthy Eating Index (AHEI)). Targeted lipidomics was performed to comprehensively quantify plasma oxylipins and FAs. The association between oxylipins, FAs and the quality of the diet was modeled using conditional logistic regression. The relationships between oxylipins, FAs and diet were investigated using an unsupervised multiblock analysis (Multiblock Factorial Analysis (MFA)). We generated a unique database revealing unsuspected associations between diet, FAs and oxylipins. Validation studies are now required to further explore the potential of oxylipins to monitor the health effects of diet.

Background/Objective Insulin resistance is more prominent in men than women. If this involves adipose tissue is unknown and was presently examined. Subjects/Methods AdipoIR (in vivo adipose insulin resistance index) was measured in 2344 women and 787 men. In 259 of the women and 54 of the men, insulin induced inhibition of lipolysis (acylglycerol breakdown) and stimulation of lipogenesis (glucose conversion to acylglycerols) were determined in subcutaneous adipocytes; in addition, basal (spontaneous) lipolysis was also determined in the fat cells. In 234 women and 115 men, RNAseq expression of canonical insulin signal genes were measured in subcutaneous adipose tissue. Messenger RNA transcripts of the most discriminant genes were quantified in 175 women and 109 men. Results Men had higher AdipoIR values than women but only when obesity (body mass index 30 kg/m 2 or more) was present ( p < 0.0001). The latter sex dimorphism was found among physically active and sedentary people, in those with and without cardiometabolic disease and in people using nicotine or not ( p = 0.0003 or less). In obesity, adipocyte insulin sensitivity (half maximum effective hormone concentration) and maximal antilipolytic effect were tenfold and 10% lower, respectively, in men than women ( p = 0.005 or less). Basal rate of lipolysis was two times higher in men than women ( p > 0.0001). Sensitivity and maximum effect of insulin on lipogenesis were similar in both sexes ( p = 0.26 and p = 0.18, respectively). When corrected for multiple comparison only RNAseq expression of insulin receptor substrate 1 ( IRS1 ) was lower in men than women ( p < 0.0001). The mRNA transcript for IRS1 was 60% higher in women than men ( p < 0.0001). Conclusions In obesity, adipose tissue insulin resistance is more pronounced in men than in women. The mechanism involves less efficient insulin-mediated inhibition of adipocyte lipolysis, increased basal rate of lipolysis and decreased adipose expression of a key element of insulin signaling, IRS1 .

Introduction Behavioural weight loss programmes are generally accepted as being beneficial in reducing cardiometabolic risk and improving patient-reported outcomes. However, prospective data from large real-world cohorts are scarce concerning the mid-term and long-term impact of such interventions. The objective of this large prospective cohort study (n>10 000 participants) is to demonstrate the effectiveness of the standardised Nutritional and Psycho-Behavioural Rehabilitation programme (RNPC Programme) in reducing the percentage of subjects requiring insulin and/or other diabetes drug therapy, antihypertensive drugs, lipid-lowering therapies and continuous positive airway pressure therapy for obstructive sleep apnoea after the end of the intervention. The rate of remission of hypertension, type 2 diabetes and sleep apnoea will also be prospectively assessed.Methods This is a prospective multicentre observational study carried out in 92 RNPC centres in France. Participants will follow the standardised RNPC Programme. The prospective dataset will include clinical, anthropometric and biochemical data, comorbidities, medications, body composition, patient-reported outcome questionnaire responses, sleep study data with objective measurements of sleep apnoea severity and surrogate markers of cardiovascular risk (ie, blood pressure and arterial stiffness). About 10 000 overweight or obese participants will be included over 2 years with a follow-up duration of up to 5 years.Ethics and dissemination Ethical approval for this study has been granted by the Ethics Committee (Comité de protection des personnes Sud-Est I) of Saint-Etienne University Hospital, France (SI number: 23.00174.000237). Results will be submitted for publication in peer-review journals, presented at conferences and inform the design of a future randomised controlled trial in the specific population identified as good responders to the RNPC Programme.Trial registration number NCT05857319.

Application of the physical laws of energy and mass conservation at the whole-body level is not necessarily informative about causal mechanisms of weight gain and the development of obesity. The energy balance model (EBM) and the carbohydrate-insulin model (CIM) are two plausible theories, among several others, attempting to explain why obesity develops within an overall common physiological framework of regulation of human energy metabolism. These models have been used to explain the pathogenesis of obesity in individuals as well as the dramatic increases in the prevalence of obesity worldwide over the past half century. Here, we summarize outcomes of a recent workshop in Copenhagen that brought together obesity experts from around the world to discuss causal models of obesity pathogenesis. These discussions helped to operationally define commonly used terms; delineate the structure of each model, particularly focussing on areas of overlap and divergence; challenge ideas about the importance of purported causal factors for weight gain; and brainstorm on the key scientific questions that need to be answered. We hope that more experimental research in nutrition and other related fields, and more testing of the models and their predictions will pave the way and provide more answers about the pathogenesis of obesity than those currently available.

ObjectiveDespite scarce evidence, guidelines recommend weight loss as a management strategy for patients with gout. We investigated the effect of an intensive dietary intervention on body weight and clinical measures of gout severity in individuals with obesity and gout.MethodsWe conducted a 16‐week randomized nonmasked parallel‐group trial in Denmark, randomly assigning (one‐to‐one) individuals with obesity and gout to a low‐energy diet or a control diet. The primary outcome was change in body weight. Key secondary outcomes were changes in serum urate (SU) level and visual analog scale–assessed pain and fatigue.ResultsBetween December 1, 2018, and June 1, 2019, 61 participants were included in the intention‐to‐treat population and randomly assigned to the intensive diet group (n = 29) or control diet group (n = 32). Participants had a mean age of 60.3 (SD 9.9) years and mean body mass index of 35.6 (SD 5.0), and 59 (97%) were men. After 16 weeks, there was a significant difference in change in body weight between the diet and control groups (−15.4 vs −7.7 kg; difference −7.7 kg [95% confidence interval −10.7 to −4.7], P < 0.001). Despite results being potentially in favor of a low‐energy diet, we could not confirm differences in SU level changes and fatigue between groups. No differences in pain and gout flares were observed between groups. No serious adverse events or deaths occurred during the trial.ConclusionAn intensive dietary intervention was safe and effectively lowered body weight in people with obesity and gout, but the weight loss did not directly translate into effects on SU level, fatigue, and pain.

The New Nordic Renal Diet (NNRD) is a whole-food approach, tailored to meet recommended guidelines in patients with moderate chronic kidney disease (stage 3b–4). The NNRD improved various metabolic and physiological endpoints during a 26-week randomized controlled study. Here, we examined the effect of dietary intervention on health-related quality of life (HRQoL). Sixty participants were recruited (NNRD group n = 30, control group n = 30) and 58 completed the study. During the intervention, the NNRD group received food boxes, and recipes once a week. The control group continued their habitual diet. HRQoL was examined at baseline and at the end of the intervention using the validated EuroQol-5D-5L, including a 5-point scale Likert questionnaire at the end of the intervention. Assessed by the EuroQol-5D-5L questionnaire, the NNRD group experienced a reduction in pain/discomfort during the intervention by 26% [−0.44 points (95% CI; −0.73, −0.16)], compared with no change in the control group [0.25 points (95% CI; −0.02, 0.53)] and a between-group difference of −0.70 points (95% CI; −1.03, −0.37, p < 0.001). A larger decrease of body fat mass was associated with a larger decrease in pain/discomfort (p = 0.014). In addition, the NNRD group reported an overall improvement in conducting usual daily activities by 23% [−0.30-point (95% CI; −0.50, −0.11)], while no change was seen in the control group [−0.02 points (95% CI; −0.21, 0.17)], with a between-group difference −0.28 points (95% CI; −0.51, −0.06, p = 0.014). A larger decrease in 24 h urine phosphorus excretion, used as a marker of compliance, was associated with a larger improvement in conducting usual daily activities (p = 0.036). The NNRD group had a clinically relevant improvement in various HRQoL outcomes.

The New Nordic Renal Diet (NNRD) is a meal pattern reduced in phosphorus, protein, and sodium for patients with moderate chronic kidney disease. The NNRD showed improvements in metabolic, and physiological outcomes after 26-weeks intervention. In the original study, participants were randomized to NNRD (n = 30), or control (habitual diet) (n = 30). The aim of this study was to explore adherence to the NNRD 3 months after cessation of intervention (follow-up). Fifty-seven participants completed the follow-up visit, which consisted of fasting blood samples and 24 h urine samples. At follow-up, there was no longer a significant reduction in 24 h urine phosphorus excretion in the NNRD group. From intervention to follow-up, 24 h urine phosphorus increased by 63 mg in the NNRD group, vs. −24.1 mg in the control group, between-group difference 87.1 mg (−10.1, 184.3, p = 0.08). Our findings show that more active intervention is needed to support adherence and maintain beneficial effects of the NNRD.