BMJ Nutrition, Prevention & Health

Iron deficiency (ID) is the most common nutritional deficiency worldwide, often caused by insufficient dietary intakes. Oral supplementation is one of the means to improve iron status. This study evaluated the efficacy and safety of two low-dose iron supplements - >Your< Iron Forte Capsules (YIFC) and Ferrous Sulfate Capsules (FSC) - in individuals with dietary ID. One hundred and one participants (mean age 30.6 years; 98% women) with low iron stores (mean serum ferritin 16.1 {micro}g/L) were randomized to receive either YIFC or FSC once daily for 12 weeks. Changes in blood indices and iron-related parameters were assessed at four and 12 weeks of intervention relative to baseline. The primary outcome was the change in hemoglobin (Hb) after 12 weeks. Eighty-seven participants completed the study. Both supplements significantly increased Hb at 12 weeks (YIFC: mean 6.52 g/L, p<0.001; FSC: mean 5.71 g/L, p<0.001). Product-related adverse events (AEs) were few (17% of all AEs) and of mild to moderate intensity only. One participant receiving FSC withdrew due to a probable product-related AE. The frequencies of product-related AEs were similar between study arms, however, statistically significantly more AEs judged to be definitely related to the product occurred in in the FSC arm. While product-related AEs were confined to the gastrointestinal tract in the YIFC arm, they affected multiple organ systems in the FSC arm. Supplementation with either YIFC or FSC proved as an effective, well-tolerated, and safe strategy for improving iron status in non-anemic dietary iron deficiency. In terms of the AE profile, supplementation with YIFC may offer advantages over supplementation with FSC.

Background: Creatine monohydrate (typically 5 to 20 g/day) has a well-established safety profile across diverse populations. Creatine hydrochloride (CR-HCl) is a highly soluble creatine formulation that may allow effective supplementation at substantially lower doses (750 mg to 3 g/day); however, controlled human safety data specific to CRHCl remain limited. Objective: To evaluate the short-term laboratory safety and tolerability of low dose CRHCl supplementation administered for 28 days in healthy adults. Methods: This single center, single arm, singl blind pilot safety study enrolled 11 healthy adults (10 females, 1 male; mean age 44.6 plus/minus 7.2 years). Participants consumed 750 mg/day CRHCl for 28 consecutive days while maintaining their usual diet and physical activity patterns. Fasting blood and urine samples were collected at baseline and Day 28. Laboratory assessments included hematological, lipid, and clinical chemistry biomarkers. Pre and post changes were evaluated using paired parametric and nonparametric tests, baseline-adjusted regression models, bootstrap confidence intervals, and false discovery rate (FDR) correction. Results: All participants completed the intervention. No clinically meaningful changes were observed in lipid parameters, hematologic indices, renal markers, or most chemistry analytes after adjustment for multiple comparisons. Fasting glucose increased modestly (8.1 mg/dL) prior to multiplicity adjustment but was not statistically significant after FDR correction and remained within reference ranges. Serum bicarbonate decreased slightly (2.4 mmol/L); although statistically detectable in parametric analysis, values remained within physiological limits and were not consistently supported by nonparametric testing.

BackgroundThe surgical stress response is a predictable, physician-managed metabolic state triggered by anesthesia and tissue injury, marked by insulin resistance and hypercatabolism that create unique nutritional needs unmet by standard, pre-surgical fasting diets. We developed a multi-nutrient medical food to support perioperative metabolic homeostasis and piloted its safety/tolerability and exploratory outcomes. MethodsIn a single-center pilot trial (n=67) of adults undergoing elective abdominal, cardiac/thoracic, gynecological, or orthopedic surgery, participants were allocated to medical food or no-treatment control. The product was taken twice preoperatively (evening before and 4 h pre-op) with standard care. Primary safety outcomes were adverse events, postoperative nausea/vomiting (PONV), 30-day readmission, and infections. Exploratory outcomes were fasting glucose, HbA1c, electrolytes, cortisol, pre-operative emotional state, and post-operative pain. ResultsAll participants completed the intervention. No product-attributed adverse events occurred. Gastric clearance was achieved within 2 h in all, and there were no 30-day readmissions or infections. PONV occurred in 30.3% vs 35.3% (risk ratio 0.86, 95% CI 0.43-1.71, p=0.796). Post-operative glycemia favored the intervention; at 48 hr the intervention group showed lower glucose (HL -9 mg/dL, g=0.35, p=0.030), while earlier timepoints were nonsignificant. Post-operative magnesium was numerically lower with intervention (4.76 vs 5.10) without statistical significance; other electrolytes and cortisol showed minimal differences. Post-operative pain was 5.33 vs 5.62 (g=0.19, p=0.43). Positive pre-operative emotion was more frequent with intervention (17/33 vs 9/34; risk ratio 1.95, p=0.046). ConclusionThe medical food was safe and well tolerated without increased PONV or readmissions. Preliminary metabolic and emotional signals justify a larger, adequately powered efficacy trial. Clinical Relevancy StatementThis pilot trial demonstrates that a preoperative multi-nutrient medical food was well tolerated and feasible to administer in a routine clinical setting: all participants achieved gastric clearance within 2 hours of the pre-operative dose, with no increase in PONV and no readmissions. Exploratory findings indicate potential benefits that could nutritionally support recovery if confirmed. These results support the feasibility of administering a targeted nutrition intervention shortly before surgery and justify evaluation in a larger efficacy trial. Clinical Trial RegistrationNCT07359222

PurposeAdequate hydration is vital for health, yet many people do not meet fluid recommendations. This study aimed to characterise the role of water and sugar-sweetened beverages in hydration across different levels of socioeconomic status (SES) in the UK. MethodsIn a pre-registered cross-sectional study, participants (N = 1,112) recalled beverages consumed on the previous day and reported urine colour as an indicator of their hydration status. We analysed water intake (H1), sugar-sweetened beverage (SSB) intake (H2), and SES (education; H3) as predictors of hydration status using stepwise binomial logistic regression adjusted for health, demographic, and lifestyle covariates. ResultsForty percent of participants were classified as underhydrated. Higher water intake was associated with a greater likelihood of adequate hydration: Drinking one extra glass of water per day (250 ml) increased the odds of being adequately hydrated by about 16%. However, SSB intake was not associated with hydration unless intake from other drink sources was held constant. Having a higher versus lower level of education was not significantly associated with hydration status, although finer-grained and income-based analyses suggested modest socioeconomic differences. ConclusionWater intake--rather than SSB intake--is the primary correlate of adequate hydration in this UK sample. Public health initiatives should emphasise the importance of water for hydration, invest in ways to make water more appealing, and promote the use of urine colour as a marker of hydration status.

BackgroundDiet is central to cardiovascular disease (CVD) prevention, yet free-living studies rarely capture what people eat at home or how closely they follow an assigned diet due to limitations in self-reporting. Short-term inpatient feeding studies, with all meals provided and supervised intake, allow direct assessment of the physiological effects of dietary patterns. Objectivesi) To compare the short-term effects of a UK-National Institute for Health and Care Excellence (NICE) aligned diet versus a Western-style diet on CVD risk factors, metabolic phenotypes and microbiome; ii) To evaluate whether urinary metabolic phenotyping can objectively classify dietary adherence in adults with increased CVD risk. MethodsIn a controlled inpatient randomized crossover trial, 18 adults at elevated CVD risk completed two 72 h isocaloric diets: NICE-compliant and Western-style. Repeated-measures MCCV-PLS-DA assessed NMR fasting serum and 24 h urine metabolomic phenotypes. Univariate analyses examined CVD markers, urinary metabolites, serum SCFAs, and gut microbial richness and -diversity. ResultsDiet modulated CVD risk markers, with the NICE compliant diet lowering systolic blood pressure and atherogenic lipid parameters, whereas the Western-style diet increased these measures (all q < 0.05). The Western-style diet reduced microbial richness and tended towards lower -diversity. Urinary metabolic phenotyping identified 27 discriminatory metabolites between the diets reflecting food intake. Most diet-linked metabolites diverged from baseline within 24 h; microbiome derived metabolites demonstrated early and sustained divergence across 72 h. The urinary MCCV-PLS-DA model extended from a previously published framework in healthy adults, robustly classified dietary adherence (Q2Y=0.96), and correctly predicted allocated dietary intervention at earlier timepoints (24-48 h). ConclusionsUrinary metabolic phenotyping offers a sensitive and non-invasive tool for objectively assessing dietary intake. Short-term adherence to contrasting dietary patterns produced rapid, diet-specific metabolic and microbial effect in individuals at elevated CVD risk and differentially impacted cardiovascular risk profiles. This trial was registered at the ISRCTN registry (https://www.isrctn.com/ISRCTN44705179).

Due to a high prevalence of obesity-related chronic diseases and an increasing use of injectable weight loss medications, a need for dietary consultations by registered dietitian nutritionists (RDNs) has been increasing. However, there is a paucity in RDNs who provide weight management services. The objective of this study is to gather insight on the dietary interventions and barriers in weight loss practice as reported by RDNs specializing in weight management. The survey contained 33 questions and four domains (current practice diet interventions and protocols, client demographics, practitioner demographics, and barriers). Descriptive statistics were used to evaluate results. Survey participants, RDNs (N=739), were recruited from Weight Management Dietetic Practice Group of the Academy of Nutrition and Dietetics. Weight management occupies most (69%) of surveyed RDNs work time. App use was the most common method of food record collection (n=299), and food record accuracy was the most prevalent cited barrier to weight loss magnitude (n=233). Most (n=253) RDNs reported seeing their typical client once a month with an average continued engagement of one month being the most prevalent (n=197). Lastly, most RDNs (81%, n=595) do not have a customary program or diet they refer clients to. In conclusion, improvements in technologically enhanced platforms for accurate diet record collection and patient education may benefit RDNs weight management practice and further research into reasons for patient attrition from weight loss counselling is warranted.

BackgroundTime-restricted eating (TRE) has gained popularity for weight loss and metabolic health. While some evidence suggests greater benefits when TRE aligns with circadian rhythms--characterized by early daytime eating and avoidance of nighttime intake, often referred to as early TRE (eTRE), other studies report no meaningful differences between eTRE, other TRE approaches with or without exercise, or calorie restriction (CR), and robust comparative evidence remains limited. AimTherefore, the aim of this network meta-analysis (NMA) is to evaluate the physiological effects of eTRE, midday time-restricted eating (mTRE), late time-restricted eating (lTRE), with and without exercise, CR, and control (without prescribed energy or fasting windows) on anthropometric measures and cardiometabolic markers in adults with cardiometabolic risk factors. MethodsA comprehensive literature search was conducted in four major databases (PubMed, Web of Science, Scopus, and Embase) up to April 24, 2025. A Bayesian NMA was performed, using a control group as the reference comparator across interventions. Treatment effects were expressed as mean differences with 95% confidence intervals. The relative ranking of the included arms on the outcomes was assessed using surface under the cumulative ranking curve, values derived from the NMA, where higher values reflect a higher probability of superior effectiveness. Resultsa total of 40 trials comprising 3259 subjects were included in the analysis. There were significant reductions in most anthropometric measures in all intervention groups compared to control group. Whereas eTRE and eTRE + exercise (EX) significantly improved glucoregulatory outcomes compared to control, eTRE + EX showed superior results over other interventions. ConclusionWhile our results did not detect statistically significant differences between TRE patterns and CR, the consistent SUCRA rankings in favor of eTRE (particularly with exercise) suggest that meal timing may play an important role in metabolic regulation.

ContextVitamin B12 deficiency is common among vegans and vegetarians due to limited intake of animal-derived foods. Identifying safe, plant-based sources of vitamin B12 is essential to address this nutritional gap. AimsThis study evaluated the efficacy and safety of Chlorella vulgaris tablets in improving vitamin B12 deficiency. Settings and DesignA double-blind, randomized, placebo-controlled trial was conducted among 46 healthy adults with vitamin B12 deficiency (serum levels 107-210 pmol/L). Methods and MaterialParticipants were randomized (1:1) to receive C. vulgaris (1 g twice daily) or identical placebo for 12 weeks. Primary outcome was change in serum vitamin B12; secondary outcomes included folic acid, homocysteine, methylmalonic acid (MMA), and quality of life (WHO-QoL). Assessments were conducted at baseline and week 12, with safety monitored through liver and kidney function tests and adverse event reporting. Statistical Analysis UsedSample size (n=46) was calculated with 90% power and 10% dropout allowance. Data were analyzed using SPSS v22. Non-parametric tests were applied after normality assessment, with p<0.05 considered significant. ResultsOf 46 participants (mean age 35.5 {+/-} 11.2 years; 69.6% female), mean serum vitamin B12 levels were significantly higher in the C. vulgaris group than in the placebo group at 12 weeks (214.4 {+/-} 160.8 vs 55.9 {+/-} 15.0 ng/mL; P < .001). No significant differences were observed in folic acid, homocysteine, MMA, or QoL scores between groups. No adverse events were reported. ConclusionsSupplementation with Chlorella vulgaris significantly improved serum vitamin B12 levels, suggesting its potential as a safe, plant-based alternative for managing vitamin B12 deficiency. Key MessagesO_LIPlant-based Chlorella vulgaris improved vitamin B12 levels significantly C_LIO_LIRandomized trial in B12-deficient healthy adults over 12 weeks C_LIO_LINo adverse effects observed on liver or kidney function tests C_LIO_LIQuality of life improved across all domains in the intervention group C_LI

ObjectivesTo investigate clinical characteristics of users of weight loss drugs in Norway. DesignNested population-based case control study SettingNationwide healthcare registers in Norway with information on all dispensed medications linked to contacts with primary and specialist healthcare services. ParticipantsAll individuals aged 18-74 years with first dispensing of a weight loss drug (WLD) in 2023-2024, classified as initiators of 1) semaglutide (only Wegovy), 2) liraglutide (only Saxenda), 3) tirzepatide, 4) bupropion-naltrexone, or 5) orlistat. We matched each WLD user by sex and age to five controls randomly selected from the general Norwegian population. Main outcome measuresType and count of number of comorbidities diagnosed in the two years preceding initiation of WLD use, comedications dispensed in the preceding year, and any previous bariatric surgery. Differences between WLD users and population controls were estimated using conditional logistic regression adjusted for country of birth and education level. ResultsDuring 2023-24, 150,036 individuals initiated semaglutide, 4,603 liraglutide, 3,596 tirzepatide, 31,172 bupropion-naltrexone, and 1,411 orlistat. Among WLD users, 22-29% were registered without any of the pre-defined comorbidities, compared to around half of population controls. Comorbidities and comedications were generally observed at similar proportions in the different WLD user groups, but at much lower proportion for controls: hypertension: 32-38% of WLD users vs. 17-20% of controls; hyperlipidaemias: 20-24% vs. 12-15%; sleep apnoea: 7-11% vs. 2-3%; back pain: 15-20% vs. 10-11%; opioids: 24-30%vs. 13-15%; antidepressants: 20-24%vs. 10-11%. ConclusionsLike other countries, Norway faces the challenge of costly pharmacological obesity treatment, and the need for measures to mitigate increasing socioeconomic health disparities to ensure access to obesity treatment for those most likely to benefit including persons with multimorbidity. What is already known on this topicO_LIObesity is increasing worldwide and is associated with increased risk of multimorbidity. C_LIO_LIThe available treatment options for obesity have been rapidly and substantially transformed by the availability of new weight loss drugs. C_LI What this study addsO_LIThis nested case-control study within the Norwegian population examined clinical characteristics of new users of five weight loss drugs: semaglutide, liraglutide, tirzepatide, bupropion-naltrexone, and orlistat. The study identified a higher proportion of weight loss drugs users with cardiovascular, endocrine, mental, and other health conditions, as well as increased usage of cardiovascular, nervous system, and chronic pain medications, compared to the general population. C_LIO_LIThe majority of WLD users had high levels of multimorbidity and medication use compared to controls. Approximately 1 in 5 WLD users had no registered comorbidity in either primary or specialist health care systems. C_LIO_LIAdditionally, we noted differences in sociodemographic factors between users and population controls, such as lower education levels among WLD users. C_LIO_LIThe rapidly expanding use of weight loss drugs necessitates close attention from public health authorities. C_LI

Abstract Objective: Frailty is an important concern in old age. Inflammation can cause frailty. Anti-inflammatory food supplements can play a role in slowing down frailty processes and consequences. This study explored the views of people (aged 50-89 years) on the need to develop a frailty supplement, preferences for its form and how older people could be encouraged to use such a supplement. Design: We conducted semi-structured qualitative interviews and used a framework method to analyse the data. Participants: 30 participants from a city in the UK. Setting: These participants were recruited from social housing, care homes, foodbanks and the wider population. Participants were from diverse ethnic, gender and age backgrounds. Results: Participants identified a strong need for the development of a food-based supplement for frailty. They expressed excitement for the supplement and viewed it as something which they would be happy to integrate in their daily food routine. In terms of preferences, our participants wanted to have multiple options, however, a biscuit-based supplement was preferred by most. The participants preferences were mainly based on taste of the supplement, its effectiveness, convenience in use and affordability. Muslim participants in the sample said they would be happy to use this supplement if it was developed using Halal ingredients. In terms of creating awareness and encouraging people to use the proposed supplement, participants suggested a variety of marketing methods. These included: word of mouth, face to face sessions with older adults, social media, especially YouTube and advertising on TV. Conclusion: The participants were generally open to the idea of a food-based supplement and felt that it could easily fit with their existing food practices and lifestyles. Keywords: older adults, frailty, food supplement, co-creation, healthy ageing

Outcomes from the COSMOS trial have reinforced the notion of flavanols as important plant-derived bioactives contributing to cardiovascular health. As discussions continue on whether specific dietary reference values for flavanols are warranted, it is possible that existing dietary guidelines emphasizing fruits and vegetables already yield sufficient flavanol intake levels. If this were the case, developing flavanol specific dietary reference values might be unnecessary. This study therefore aimed at assessing whether adherence to dietary recommendations for fruit and vegetable intake and overall diet quality achieves flavanol intake levels of 500 mg/day, the amount proven to mediate cardiovascular benefits in the COSMOS trial. Flavanol intake was objectively evaluated using two validated and complementary biomarkers, 5-(3{square},4{square}-dihydroxyphenyl)-{gamma}-valerolactone metabolites (gVLMB) and structurally related (-)-epicatechin metabolites (SREMB), in two geographically distinct studies: COSMOS (US; n=6,509) and EPIC-Norfolk (UK; n=24,154). The results showed that higher fruit and vegetable intakes and diet quality (assessed via the alternative healthy eating index-aHEI) were associated with increased flavanol intake in COSMOS. Nevertheless, fewer than 25% of participants meeting dietary guidelines achieved an estimated flavanol intake of [&ge;]500 mg/day. Similar findings were observed in EPIC-Norfolk as well as through flavanol intake simulations considering fruits and vegetables commonly consumed in the US diet. In conclusion, adherence to existing dietary guidelines does not yield flavanol intake levels comparable to those shown to provide cardiovascular benefits in COSMOS. Thus, specific dietary reference values for flavanols may still be necessary if aiming to increase the intake of these dietary compounds. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/26346949v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@2966f5org.highwire.dtl.DTLVardef@269232org.highwire.dtl.DTLVardef@483edborg.highwire.dtl.DTLVardef@116a957_HPS_FORMAT_FIGEXP M_FIG C_FIG

Background: The timing of energy intake could be important in the development of obesity. However, most observational evidence stems from adults, anthropometric defined obesity outcomes, single meal timing phenotyping, and traditional regression modeling. Objective: We aimed to describe meal timing patterns in adolescents and determine if they associated with fat mass by modeling the median and all other percentiles of the frequency distribution. Methods: We analyzed data from the Sleep and Growth Study 2 (S-Grow2, N=286, 12-13y). Participants completed 3-day 24-hour dietary recalls and time stamped eating occasions were used to define 8 meal timing traits, with aide from self-reported wake and bed timing. Principal component analysis (PCA) identified multi-dimensional meal timing patterns. Fat mass index (FMI) was estimated using dual energy X-ray absorptiometry. Quantile regression assessed if there were associations between meal timing traits and FMI across the entire FMI frequency distribution. Results: The typical first and last eating occasions were 8:00am (40 minutes after waking) and 8:00pm (2.7 hours before sleep), respectively, thus the eating period typically lasted 11.5 hours per day. The typical eating period midpoint was 2:15pm, and the timing when 50% of energy intake was consumed typically occurred at 3:15pm. PCA revealed three meal timing patterns: 1) Delayed Start, Condensed Eating Period (43% of variance; shorter eating period and delayed timing of first eating); 2) Late, Sleep Proximal Eating (30% of variance; later timing of last eating and extended eating period), and 3) Later Energy Intake (10% of variance; delayed energy intake midpoint). Higher scores for the Delayed Start, Condensed Eating Period pattern associated with higher body mass index and FMI at the upper tails of their distributions. Conclusions: Distinct multidimensional meal timing patterns emerged in early adolescence, with the delayed start, condensed eating period pattern potentially associated with higher adiposity.

Steroidal alkaloids may be responsible for some of the health benefits of a tomato rich diet, but little is known about their metabolic fate after consumption. The objective of this study was to elucidate the pharmacokinetic parameters of plasma steroidal alkaloids and to define their bioavailability and metabolism following a single tomato containing meal. Healthy subjects (n = 11, 6M/5F) consumed 505 g of tomato juice following a two-week tomato washout and blood plasma were collected post-prandially at 11 time points over 12-hours. Plasma steroidal alkaloids were analyzed using UHPLC-MS. The fractional absorption of steroidal alkaloids was 11.8 {+/-} 7% and over 99% of the absorbed dose were present as metabolized products. The maximum concentration of total plasma steroidal alkaloids in subjects was 406.5 {+/-} 377.0 nmol/L occurring at 6 hours after consumption, with an AUC0-12hr of 2529.0 {+/-} 1644.8 nmol*h/L. Liver S9 enzymatic synthesis of steroidal alkaloid metabolites including trihydroxy-tomatidine and sulfonated dihydroxy-tomatidine improved confidence in compound identification. This study reports the first pharmacokinetic data for tomato steroidal alkaloids, demonstrating moderate absorption and extensive metabolism after tomato juice consumption. These data provide context for future studies investigating the potential role that these compounds may play in human health.

BackgroundPacked lunches are a common feature of early childhood food provision, yet evidence describing their nutritional composition in early years settings remains limited. Understanding the foods provided during this developmental period is important, given the potential influence of early dietary exposures on later health. AimTo characterise the composition, nutritional quality, cost, and dietary patterns of packed lunches brought from home in Early Childhood Education and Care settings, and to examine variation by child age and area-level deprivation. MethodsA cross-sectional analysis was conducted using a remote food photography method to assess packed lunches provided for children aged 1-4 years attending early years settings across Essex, UK. Food items were categorised into predefined groups, and nutrient composition was estimated. Area-level deprivation was determined using the English Index of Multiple Deprivation (2019). Non-parametric tests assessed between-group differences. Principal components analysis (PCA) was used to identify patterns of co-occurring foods. ResultsA total of 389 packed lunches were analysed. Starchy foods (82%), fruit (81%), dairy or alternatives (72%), and savoury snacks (74%) were commonly provided, while vegetables were less frequent and fish was rarely observed (1.5%). Overall, 97.7% of lunches contained at least one ultra-processed food (UPF), with a median of three UPF items per lunch and 74% of total energy derived from UPFs. Median energy provision was 400 kcal (IQR 309-518). Nutrient composition was broadly similar across deprivation groups, although cake and biscuit counts and UPF item counts were modestly higher in more deprived areas. The median estimated lunch cost was {pound}1.79 and did not differ by deprivation. ConclusionsPacked lunches in early years settings frequently contained ultra-processed foods and showed considerable variability in nutritional quality. Socioeconomic differences were limited, suggesting that contemporary packed lunch practices may reflect influences operating across population groups. Further research across diverse regions is warranted to better understand the provision of packed lunches and their implications for early dietary exposure.

IntroductionMechanistic research has shown that prior obesity induces durable transcriptomic and epigenetic reprogramming in adipose tissue that persists after weight loss and predisposes individuals to weight regain. This phenomenon, termed obesogenic memory (OM), is currently conceptualized primarily as a molecular process. We propose extending OM beyond adipose tissue biology to include interacting biological and sociocultural processes through which past exposures shape present physiological regulation and health-related behavior. MethodsIn-depth qualitative interviews were conducted with individuals living with obesity (n=31) and with healthcare professionals (n=18). The data were analyzed abductively to examine participants lived experiences of obesogenesis. ResultsWe developed a three-phase model of OM comprising memorizing, remembering, and rescribing. The memorizing phase describes the initial acquisition and encoding of biological and sociocultural obesogenic influences. The remembering phase captures the persistence of these influences, contributing to long-term obesity maintenance. The rescribing phase refers to processes through which obesogenic influences may be attenuated or reversed, creating conditions for sustainable health behavior change. ConclusionExtending OM to include sociocultural dimensions provides a more comprehensive understanding of obesity persistence. This integrative framework identifies multilevel targets for obesity prevention and treatment that acknowledge past exposures while supporting resilience and long-term weight management.

IntroductionDepression is highly prevalent among young adults worldwide. While research links health behaviours, such as dietary intake, to depression, few studies have examined these associations among young adults in low- and middle-income countries, including South Africa. This study investigated whether dietary intake was associated with an increased risk of depression in a cohort of young South African adults, aged 20-30 years, as part of the Global burden of disease Lifestyle And mental Disorder (GLAD) project. MethodsThis five-year prospective cohort study was conducted in the North West Province of South Africa in accordance with the GLAD project protocol (DERR1-10.2196/65576). Dietary exposures were evaluated using three non-consecutive 24-hour dietary recalls, measuring daily intake of various food groups and nutrients as defined by the Global Burden of Disease study. Depression outcomes were assessed at baseline (N=1039) and follow-up (N=551) using the Patient Health Questionnaire (PHQ-9, cut-off [&ge;]10). Logistic and Poisson regression analyses were performed, with results presented as odds ratios (OR) and relative risk ratios (RR), respectively. Four models were run: unadjusted, sociodemographic-adjusted, total energy (TE) intake-adjusted and fully adjusted (including sociodemographic information and TE intake). For longitudinal analyses of incident depression, baseline depression cases were additionally excluded (n=403). ResultsParticipants (average age 24.55 years) had a balanced distribution of sex (51.4% female) and race (48.6% Black), and a 29.45% baseline prevalence of depression. Higher milk intake was associated with a lower risk of incident depression (RR=0.94, 95% CI 0.91-0.98) in the TE-adjusted longitudinal model. Cross-sectionally, higher sugar-sweetened beverage consumption associated with higher odds of depression, while higher calcium intake (OR=0.48, 95% CI 0.31; 0.76) and vegetable consumption (OR=0.74, 95% CI 0.61, 0.91) were associated with lower odds of depression after TE intake adjustment. Higher fibre intake was associated with lower odds of depression in the unadjusted model. ConclusionHigher daily milk intake was associated with a lower risk of depression, while higher calcium, vegetable, and fibre intake were associated with a lower prevalence of depression in young adults. These findings suggest that prevention strategies for common mental disorders could include dietary approaches within mental health care.

BackgroundDrug suitability is determined by safety, efficacy, and pathological appropriateness. The pharmacogenomics of drug suitability can be assessed by analyzing drug response and drug choice in large population cohorts. MethodsWe investigated drug response and drug choice for dyslipidemia and hypertension using genetic, phenotypic, and prescribing data from the UK Biobank and the All of Us Research Program. Drug response was reassessed with rigorous biomarker scaling, while genome-wide association studies (GWAS) and polygenic scores were used to examine genetic factors influencing drug choice. ResultsConventional analyses showed that variants influencing baseline LDL cholesterol (LDL-C) were inversely associated with absolute LDL-C change but concordant with relative change following statin therapy; these signals disappeared after applying a variance-stabilizing Box-Cox transformation, indicating a methodological artifact in biomarker scaling. GWAS for drug choice identified several significant loci and unique genetic correlation patterns with cardiometabolic traits. Polygenic scores for drug choice yielded statistically significant predictive performance, which was enhanced by incorporating demographic factors, though prediction strength in clinical settings remains modest. ConclusionVariance-stabilizing transformation corrects spurious pharmacogenetic associations introduced by biomarker scaling. Genetic variation informs drug choice for dyslipidemia and hypertension, but current polygenic scores provide only modest benefits in clinical application.

Key pointsO_LIWe report findings from a phase 2 study of MY008211A among Chinese men and women aged [&ge;]18 years with paroxysmal nocturnal hemoglobinuria C_LIO_LIIncreases in hemoglobin of [&ge;]20 g/L were maintained for up to 44 weeks of treatment with MY008211A in all 34 patientsiv C_LI Explanation of noveltyParoxysmal nocturnal hemoglobinuria is characterized by red blood cell (RBC) destruction and a prothrombotic state.v Treatments exist such as complement 5 inhibitors but these carry the risk for iatrogenic extravascular hemolysis and anemia.vi As reported here, the novel, oral complement factor B inhibitor MY008211A yielded increases in hemoglobin and RBC levels, while adverse events over 44 weeks were largely mild to moderate in severity, and infections generally consisted of respiratory infections.vii Paroxysmal nocturnal hemoglobinuria (PNH) is a life-threatening disease characterized by red blood cell (RBC) destruction, blood clots, and impaired bone marrow function.viii We evaluated the efficacy and safety of 3 dosages of MY008211A, a novel complement factor B inhibitor,ix for treating PNH.x This was a multicenter, open-label, phase 2, dose-finding study of MY008211A among Chinese men and women with complement inhibitor-naive PNH and signs of active hemolysis.xi Patients with hemoglobin <100 g/L were assigned to oral MY008211A 400 mg twice daily (BID), 600 mg BID, or 800 mg once daily (QD) for 12 weeks and could then continue treatment with 400 mg BID during a 32-week extension.xii The primary endpoint was the proportion of patients achieving an increase in hemoglobin concentration of [&ge;]20 g/L vs baseline on day (D)84, without RBC transfusions after 4 weeks of dosing.xiii Safety assessments included adverse events (AEs).xiv Fifteen, 9, and 10 patients were assigned to MY008211A 400 mg BID, 600 mg BID, and 800 mg QD, respectively.xv All patients completed the study and its 32-week extension.xvi On D84, all 34 patients achieved increases in hemoglobin concentration of [&ge;]20 g/L from baseline;xvii all patients maintained this increase at D308.xviii Through D308, grade [&ge;]3 AEs occurred in 5 (33%), 5 (56%), and 4 (40%) patients in the 400-, 600-, and 800-mg groups, respectively.xix There were no deaths.xx In this multicenter, open-label study of 3 dosages of MY008211A for PNH, all patients achieved and maintained increases in hemoglobin of [&ge;]20 g/L from baseline without RBC transfusions.

ObjectivePost-thrombotic syndrome (PTS), a common complication of deep vein thrombosis, lacks objective diagnostic biomarkers and its molecular mechanisms remain poorly understood. This study aimed to identify plasma biomarkers and clarify pathways using integrated multi-omics and machine learning. MethodsProteomic and metabolomic profiling of 75 PTS patients and 75 controls was performed. Differential expression analysis, pathway enrichment, and protein-metabolite network analysis were conducted. A multi-algorithm machine learning with 8 feature selection methods prioritized biomarkers. Validations and 14 models were assessed. Results1,104 proteins and 1,891 metabolites were differentially expressed. Citrate cycle and unsaturated fatty acid biosynthesis were enriched. Three proteins, namely DIP2B, KNG1, and SUCLG2, were consistently selected as core biomarkers. All of these proteins were significantly downregulated in PTS and externally validated. A random forest model utilizing these proteins achieved an accuracy of 97.7% in independent testing, with SUCLG2 being the most influential predictor. ConclusionThis study identifies a novel three - protein biomarker panel for the diagnosis of PTS and reveals an immunometabolic axis in the pathogenesis of PTS, which links inflammatory regulation with mitochondrial energy metabolism. These findings provide valuable insights into the development of diagnostic tools and targeted therapeutic approaches.

BackgroundPrevious research on diet and hip fracture risk focused on selected foods and nutrients. ObjectiveTo conduct a diet-wide association study of hip fracture risk. MethodsThe study population comprised 541,887 postmenopausal women in the Million Women Study. Dietary information was assessed using a validated food frequency questionnaire in 2000-2004, and calibrated using a 24-hour dietary recall from a subset 10 years later. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between 99 dietary factors and risk of incident hip fracture, ascertained through linkage to hospital admission data. ResultsAfter an average of 19.7 years of follow-up, 27,318 incident hip fractures occurred. In multivariable-adjusted models, 60 dietary factors were associated with hip fracture risk after correction for multiple testing (False Discovery Rate p-value <0.05). The five foods most significantly associated with hip fracture risk (based on p-value) were chicken (HR and 95% CI = 0.84, 0.80-0.87 per 20 g/day), vegetables (0.88, 0.85-0.91 per 100 g/day), pasta (0.87, 0.83-0.91 per 20 g/day), chips (1.14, 1.10-1.18 per 25 g/day), and fizzy drinks (1.18, 1.12-1.24 per 50 g/day). The five nutrients with the strongest associations were protein (0.79, 0.75-0.84 per 15 g/day), zinc (0.81, 0.77-0.86 per 2 mg/day), carotene (0.91, 0.88-0.94 per 1000 {micro}g/day), fiber (0.89, 0.85-0.92 per 5 g/day), and niacin (0.82, 0.77-0.87 per 10 mg/day). The results were consistent across subgroups of body mass index, smoking, alcohol consumption, health status, physical activity, menopausal hormone use, deprivation status, and in analyses excluding the first five years of follow-up. ConclusionsMany "healthy" foods were associated with lower risk of hip fracture, and "unhealthy" foods with higher risk. Further research is needed to assess whether these associations reflect causal relationships, are indicators of a healthier overall diet, or represent confounding from other lifestyle factors.