BMJ Nutrition, Prevention & Health

BackgroundCreatine monohydrate (typically 5-20 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 - 3 g/day); however, controlled human safety data specific to CR-HCl remain limited. ObjectiveTo evaluate the short-term laboratory safety and tolerability of low-dose CR-HCl supplementation administered for 28 days in healthy adults. MethodsThis single-center, single-arm, single-blind pilot safety study enrolled 11 healthy adults (10 females, 1 male; mean age 44.6 {+/-} 7.2 years). Participants consumed 750 mg/day CR-HCl 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-post changes were evaluated using paired parametric and nonparametric tests, baseline-adjusted regression models, bootstrap confidence intervals, and false discovery rate (FDR) correction. ResultsAll 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. ConclusionsSupplementation with 750 mg/day CR-HCl for 28 days was well tolerated and was not associated with clinically meaningful alterations in routine laboratory biomarkers. These preliminary findings support the short-term tolerability of low-dose CR-HCl and provide a basis for larger randomized, placebo-controlled studies to further evaluate its safety profile.

BackgroundCirculating lipid levels are influenced by both genetic and environmental factors. While vegetarianism has been linked to improved lipid profiles, it remains unclear whether these beneficial effects persist across individuals with varying genetic capacity for lipid metabolism. ObjectiveWe hypothesized that genetic capacity and vegetarianism interact to influence the circulating levels of four lipids, including total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TG). MethodsOur study included UK Biobank participants of European (EUR, n = 182,300), Central/South Asian (CSA, n = 2,627), African (n = 2,143), and East Asian (n = 1,031) ancestry. Utilizing polygenic scores (PGS) for four circulating lipids, we employed multivariable regression models to assess PGS-by-vegetarianism interactions for each lipid. ResultsVegetarianism is associated with reduced levels of TC, LDL cholesterol, and HDL cholesterol, and with elevated levels of TG in the EUR cohort (p-value < 0.001). The same significant association patterns were observed for HDL cholesterol and TG in the CSA cohort. We did not detect significant PGS-by-vegetarianism interactions for any lipid traits (Interaction p-value > 0.05). There is a lack of evidence supporting that PGS modifies the associations between vegetarianism and lipid levels, nor that vegetarianism alters the effects of PGS on lipid levels. ConclusionsVegetarianism is associated with reduced TC, LDL cholesterol, and HDL cholesterol, as well as elevated TG among EUR participants, with similar patterns for HDL cholesterol and TG in CSA participants. These association effects of vegetarianism on circulating lipids are similar across individuals with varying genetic capacity for lipid metabolism.

Aim: The global population of older adults is growing, and older age is linked to higher bleeding risk. Although guidelines discourage aspirin for primary prevention in healthy older adults due to bleeding harms outweighing benefits, many continue taking it without a clear indication. It remains unclear whether all older adults face uniform aspirin-related bleeding risk or if certain subgroups are more vulnerable. Methods: We analyzed data from 19,114 ASPREE trial participants to develop machine learning models using 116 baseline variables. Random forest (RF) and random survival forest (RSF) models predicted 5-year bleeding risk, and participants were stratified into low, intermediate, and high-risk groups based on the 20th and 80th percentiles of predicted risk. We assessed heterogeneity of treatment effect (HTE) by testing treatment-by-risk group interactions on the relative scale using Fine-Gray models, and on the absolute scale using observed 5-year cumulative incidence rates. Results: Over a median follow-up of 4.7 years, 626 major bleeding events occurred. The RF model had moderate discrimination (AUC = 0.65, 95% CI: 0.63-0.67) and good calibration (Brier = 0.032, 95% CI: 0.029-0.034). Statistically significant HTE was observed on the relative scale, with the greatest relative increase in bleeding risk seen in the low-risk group (subdistribution hazard ratio = 2.26, 95% CI: 1.27-4.01). On the absolute scale, low-risk participants experienced higher bleeding with aspirin (absolute risk difference (ARD) = 1.17%, 95% CI: 0.37-1.95), but heterogeneity in ARDs was not statistically significant (Cochran's Q p > 0.45). Similar findings were observed when using the RSF model. Conclusion: Participants at lowest baseline bleeding risk experienced the greatest relative increase in bleeding risk with aspirin therapy. We found statistically significant heterogeneity in treatment effects on the relative but not absolute scale. These findings support an individualized, risk-based approach to aspirin therapy decision-making in older adults.

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.

ABSTRACT Background: Self medication with analgesics and non steroidal anti inflammatory drugs (NSAIDs) is common in low- and middle income countries and may expose users to preventable adverse outcomes. Evidence from Guinea remains scarce. This study aimed to estimate the prevalence of self medication with analgesics and NSAIDs among pharmacy clients in urban Conakry, identify associated factors, and describe clinical risk situations. Methods: We conducted a pharmacy based analytical cross sectional study in 30 private pharmacies across Conakry, Guinea. A total of 1,032 participants seeking analgesics or NSAIDs were enrolled between November 3, 2012, and April 5, 2013. Self-medication was defined as acquisition or use without a valid medical prescription. Factors associated with self-medication were analysed using multivariable logistic regression. Results: Among 1,032 participants, 603 reported self medication (prevalence 58.4%). Previous unsupervised use was reported by 78.7%. The most frequently used medicines were paracetamol (56.9%, n=587), diclofenac (21.3%, n=220), ibuprofen (17.9%, n=185), and aspirin (3.9%, n=40). Overall, 68.0% (n=702) reported no knowledge of potential adverse effects. Clinical risk situations were frequent: gastrointestinal disorders (41.3%, n=426), hypertension (9.2%, n=95), and pregnancy exposure among reproductive age women (26.0%). In multivariable analysis, self medication was independently associated with previous analgesic/NSAID use (aOR = 2.8, 95% CI: 2.1 to 3.6), lack of knowledge of adverse effects (aOR = 1.9, 95% CI: 1.4 to 2.5), informal occupation (aOR = 1.6, 95% CI: 1.2 to 2.2), and age 18 to 59 years (aOR = 1.5, 95% CI: 1.1 to 2.1). Conclusions: In this pharmacy based study conducted in urban Conakry, self medication with analgesics and NSAIDs was common and frequently associated with limited awareness of potential adverse effects. These findings support the need for strengthened pharmaceutical regulation, pharmacist-led counselling, health literacy interventions, and improved access to primary care. Keywords: self medication; analgesics; NSAIDs; paracetamol; diclofenac; ibuprofen; pharmacy; Guinea; Conakry; drug safety; public health.

Background: An increasing demand for organic food has risen due to perceived health benefits. Current evidence for the health effects of organic food is limited. Objective: To evaluate the association between organic food purchase as a proxy for organic food consumption and hypertension in a nationally representative population of the US. Methods: This was a cross-sectional study that included 9173 participants aged >= 18 and had available data of both organic food purchase and hypertension from the National Health and Nutrition Examination Survey 2007-2010. Organic food purchase and frequency were obtained from survey questionnaires. Hypertension was defined as having either a systolic BP >= 130 mm Hg/ diastolic BP >= 80 mm Hg, currently taking antihypertensive medication, or self-reported diagnosis of hypertension. We used multivariable logistic regression with sample weights and adjustment of potential confounders to assess associations (adjusted odds ratio [aOR] and 95% confidence intervals [CI]) between organic food purchase and hypertension status. Results: Findings suggest an 11% decrease in odds of hypertension (aOR = 0.89, 95% CI: 0.75-1.06) among organic food purchasers compared to non-purchasers. Lower odds of hypertension were observed across all categories of organic food purchasing frequency, with 13% lower among rarely purchasing organic food (aOR = 0.87, 95% CI: 0.67-1.14), 9% lower (aOR = 0.91, 95% CI: 0.71-1.16) among sometimes purchasing organic food, and 17% lower (aOR = 0.83, 95% CI: 0.55-1.27) among always or mostly purchasing organic food, as compared to those who never purchased organic food. Conclusion: Our findings suggest that organic food purchase, a proxy for organic food consumption, may be associated with lower odds of hypertension. These findings may reflect either the true benefits of organic food consumption, including lower pesticide amounts and higher nutrient content, or the health-seeking behaviors among health-conscious, healthy, and highly educated individuals.

Introduction: Menstrual cycle phase has been proposed as a source of intra-individual variability in resting energy expenditure and the thermic effect of food in premenopausal females, yet studies examining the thermic effect of food across menstrual cycle phases report conflicting findings. Methods: This protocol describes a secondary analysis of prespecified outcomes from a non-randomized, two-period crossover trial primarily designed to assess postprandial plasma triglyceride concentrations across menstrual cycle phases (ClinicalTrials.gov: NCT07459465) in 12 premenopausal females aged 18-30 years, free of chronic disease and hormonal contraceptive use, recruited in Ottawa, Canada. Participants complete two experimental sessions: one in the early follicular phase and one in the mid-luteal phase, each involving consumption of a high-fat meal. Eleven secondary outcomes will be reported: fasting resting energy expenditure, thermic effect of food, respiratory exchange ratio, carbohydrate oxidation rate, lipid oxidation rate, desire to eat, hunger, fullness, prospective food consumption, serum beta-estradiol, and serum progesterone. Masked outcome analyses are performed using linear mixed-effects models. Results: Recruitment began on 26 March 2026; results will be reported in the Stage 2 manuscript. Discussion: Findings from this trial may help clarify whether menstrual cycle phase constitutes a meaningful source of intra-individual variability in energy metabolism, with implications for the design of metabolic research in premenopausal females.

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

BackgroundThe 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. ObjectiveWe 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. MethodsWe 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. ResultsThe 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. ConclusionsDistinct multidimensional meal timing patterns emerged in early adolescence, with the delayed start, condensed eating period pattern potentially associated with higher adiposity. Clinical Trials Registry Site and NumberN/A

Background: GLP-1 receptor agonists (GLP1-RAs) are an established treatment for type 2 diabetes mellitus (T2DM) and obesity. Their widespread use is set to increase through both indication expansion and patent expiry. As well as efficacy, it is crucial to understand the safety of this drug class to enable optimal use. Here we demonstrate how a genetic approach can augment signal-detection and post-market authorization surveillance. Methods: We used single nucleotide polymorphisms (SNPs) in GLP1R to recapitulate the effect of agonism with GLP1RAs on circulating glucose, glycated hemoglobin (HbA1c), body mass index (BMI) and risk of type 2 diabetes (T2DM) using Mendelian randomisation. We then tested if the adverse effect highlighted by medicines regulators of pancreatitis and the emerging effect of sarcopenia were causally related to GLP1R agonism, using this approach. Analyses were conducted in UK biobank and replicated in FinnGen and All of Us, results being combined using meta-analysis. Analyses were further stratified by a priori risk factors of age and alcohol consumption. Results: Genetically proxied GLP-1R agonism was associated with a reduction in glucose (exp({beta}) = 0.95 95% CI [0.94, 0.97]), HbA1c (exp({beta}) = 0.94 95% CI [0.92, 0.95]), and BMI (exp({beta})=0.98 95% CI [0.97, 0.99]); and a reduced risk of T2DM (OR = 0.82 95% CI [0.79 to 0.86]). Risk of acute and chronic pancreatitis was however increased (OR = 1.10 95% CI [1.01 to 1.20] and OR = 1.05 95% CI [0.95, 1.17], respectively), which varied as a function of age with risk most pronounced in those aged 50-59 years-old (OR = 1.79 95% CI [1.43, 2.24], OR = 1.57 95% CI [1.16, 2.12]) and in drinkers (OR = 1.32 95% CI [1.12, 1.54], OR = 1.36 95% CI [1.12, 1.65]). Risk of sarcopenia also increased (OR 1.34; 95% CI 1.05,1,71). Conclusions: Genetically proxied agonism with GLP-1RAs recapitulated the pharmacological effects of GLP1-1RAs on glycaemic traits, BMI and T2DM risk. This approach supports a causal effect of GLP-1RAs on the well reported adverse effects of pancreatitis and further indicates age and alcohol consumption as risk modifying effects. The less well reported but emerging effect of sarcopenia appears to also be casually related to agonism at GLP-1R. These analyses suggest a genetic approach could be used as an adjunct to signal detection studies to enhance safety regulation as well as personalisation of the use of these drugs.

In some countries, melatonin is sold without a physician prescription and dosage is unregulated. Transdermal products have become popular including those marketed for children. We measured consumer assumptions about these products among adult residents of the United States, analyzed lot-to-lot variability, and compared the pharmacokinetics of melatonin administered in oral, lotion, and bath product forms. Survey respondents (n=199) believed oral melatonin was more effective than transdermal products and that all melatonin products were relatively safe. Melatonin lotion products analyzed by HPLC displayed lot-to-lot variability as well as changes in formulation and product claims. To determine pharmacokinetics, three different treatments (oral tablets, lotion, and bath immersion) were administered to twelve undergraduate participants in a randomized, crossover design. Five additional participants completed bath product treatment only. Participants collected saliva samples up to 48 hours after administration, which were analyzed for melatonin by enzyme-linked immunosorbent assay. Oral (n=11) and lotion formulations (n=12) caused maximum salivary melatonin levels within 30 minutes after administration, but bath immersion did not cause increases in saliva melatonin (n=17). The half-life of oral melatonin was 1.17 [0.69 -- 1.65] hours versus 5.72 [3.75 -- 7.68] hours for lotion treatment (p = 0.011, effect size r = 0.770). Melatonin lotion may pose a risk to consumers who assume it is safe and less effective than oral tablets, when in fact it may be very potent and remain at high physiological levels into the following day. This study is registered on clinicaltrials.gov (NCT06382610) and was funded by the Sleep Research Society.

Background Blood pressure (BP) regulation in individuals with sickle cell disease (SCD) is influenced by a complex interplay of genetic and physiological factors. While SCD has traditionally been associated with lower BP, there is an increased risk of hypertension. Emerging BP research suggests significant heterogeneity across genotypes, age groups, and sex. Objectives: This study investigated the longitudinal effects of population-level characteristics and continuous clinical and laboratory predictors on systolic (SBP) and diastolic blood pressure (DBP) in individuals with SCD, with emphasis on the interactions between baseline and predicted blood pressure slopes over time. Methods We retrospectively analyzed longitudinal data from a cohort of 2,739 patients with diverse SCD genotypes. Descriptive statistics were documented across sex, age range, genotype, health status and relative systemic hypertension risk categories (rHTN-risk). Linear mixed-effects models provided estimates of fixed- and random-effects of baseline BP and of time-related BP effects, respectively. Post-estimation margins provided contrasts of baseline-adjusted BP means and of pre-specified time effects on BP patterns. Results Males had significantly higher baseline SBP ({beta} = 6.64, p < 0.001) but lower baseline DBP ({beta} = -2.61, p < 0.001) compared with age-matched HbSS females. Baseline SBP was more unstable compared with baseline DBP and baseline DBP was more predictive of future BP trends than baseline SBP. Genotype was a consistent predictor of DBP (p < 0.05), but not of SBP. Similarly, we observed increased risks of relative diastolic hypertension across most genotypes, while the prevalence and magnitude of systolic hypertension was lower across all genotype compared with HbSS. Conclusions Blood pressure trajectories in SCD patients are not uniform and are significantly related to genotype, age group and sex over time. Baseline diastolic levels were less heterogenous and exhibited clear upward trajectories over time. These findings support the need for patient-specific BP surveillance in the care and management of SCD.

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

BackgroundSeveral genetic variants have been identified to modify the effects of fish oil supplementation (FOS) on increasing circulating omega-3 fatty acids, but it remains unexplored whether polygenic predisposition to low circulating omega-3 fatty acids modifies these effects. ObjectiveTo test if polygenic scores (PGS) for circulating omega-3 fatty acids modify the associations of FOS with corresponding circulating concentrations. MethodsWe developed PGS models for absolute circulating concentrations of total omega-3 fatty acids (Omega-3), docosahexaenoic acid (DHA), and their relative percentages in total fatty acids (Omega-3% and DHA%), using a multi-ethnic genome-wide association study (N=136,016). PGS models were validated in 437,803 UK Biobank participants of European (EUR), Central/South Asian (CSA), African, and East Asian genetic ancestries. Linear models tested PGS-by-FOS interactions on corresponding observed circulating concentrations. Discovery analysis was performed separately in 237,380 EUR participants and each non-EUR group. Replication analyses were performed using oily fish intake and in another 178,935 EUR participants. ResultsIn EUR participants, PGS explained 5.3-11.1% of the phenotypic variance, and significant PGS-by-FOS interactions were detected across all four circulating omega-3 traits. Among participants in the bottom 5% of the PGS distribution, FOS was significantly associated with a 0.40 SD (95% CI: 0.39-0.44) increase in Omega-3. This association effect was 11.1% larger than the population average ({beta} = 0.36; 95% CI: 0.35-0.37; PInt = 0.016) and 42.8% larger than that in participants in the top 5% of the PGS distribution ({beta} = 0.28 SD; 95% CI: 0.25-0.32; PInt = 4.03X10-10). These interaction patterns were consistently observed in CSA ancestry and confirmed in replication and sensitivity analyses. ConclusionsPGS modify the associations of FOS with circulating omega-3 fatty acids in EUR and CSA populations, with larger FOS effects in participants with lower PGS. These findings support the development of genome-informed precision nutrition.

Nicotinamide riboside (NR), an endogenous precursor to the essential coenzyme nicotinamide adenine dinucleotide (NAD+), is characterized as safe and effective at longitudinally elevating NAD+ in blood and tissues, when administered orally. Preclinical research on NR as an augmenter of NAD+ has demonstrated great promise in support of healthy aging, metabolic health, and several diseases, though clinical translation of thesefindings has been limited. Interest in alternative routes of administration of NR has increased in recent years and led to the development of pharmaceutical-grade NR for intravenous and injectable administration. Two separate Phase 1 pilot clinical trials were conducted evaluating NR via bolus injections. While the designs of the two studies are different, the similarities warrant combined presentation to note the similarities, particularly with regards to safety-related outcomes. Trial 1 involved 45 participants that were randomized to a 3x3 design, accounting for three interventions, placebo, NR, and NAD+ and three routes of administration, intramuscular (IM), intravenous (IV), and subcutaneous (SC), resulting in a 9-arm study (placebo IM, n=5; placebo IV, n=5; placebo SC, n=5; NR IM, n=6; NR IV, n=5; NR SC, n=4; NAD+ IM, n=4; NAD+ IV, n=5; and NAD+ SC, n=6). Participants were administered NR once daily for three days, followed by a 7-day washout period. In Trial 2 (n=39), the 2x2 study design incorporated 4-arms for phase 1, where the participants were randomized to 50 or 100 mg of NR, administered either IM or SC in-clinic for 3 consecutive days, followed by a 7-day washout (50 mg IM, n=7; IM, 100 mg IM, n=11; 50 mg SC, n=11; and 100 mg SC, n=10). Phase 2 of Trial 2 involved participants self-administering either 50 or 100 mg of NR subcutaneously. Safety assessments for both trials included vitals, blood biomarkers, participant reported outcomes regarding the experience, and adverse event monitoring. Participant retention for both studies was 100%, and the injections did not result in any attributable unexpected adverse events or experiences. The experiences described by the participants regarding the actual injection varied. In Trial 2, pain more than two minutes after the injection and muscle soreness and tightness were reported by 45.9 and 43.2% of the participants, respectively, regardless of the route of administration or dose. Vitals remained generally consistent throughout both trials, and reductions in systolic blood pressure observed in both trials should be evaluated in larger, properly powered studies. Blood chemistry biomarkers for both trials did not elicit treatment-related patterns. Both trials presented within-group reductions in hsCRP in the NR SC arms, however, given baseline imbalance and small samples size, this finding should be considered hypothesis-generating, only. Overall, in both trials, the interventions, regardless of route of administration were associated with some discomfort but were well tolerated and did not produce any concerning safety signals. It is recommended that comprehensive metabolic and inflammatory panels should continue to be employed in future studies and clinical settings to assess whether consistent patterns emerge in larger populations.

Background: Over half of U.S. women have hypertension, a strong but modifiable risk factor for cardiovascular diseases. Personal care products (PCPs) are widely used in daily life and contain endocrine disrupting chemicals that can alter hormonal regulation of blood pressure. However, the relationship between PCPs and hypertension has not been well studied. We investigated whether patterns of PCP use were associated with incident hypertension in a large prospective cohort study of U.S. women. Methods: Sister Study participants were recruited in 2003-2009 and followed until September 30, 2021. Usage frequency of 41 PCPs in the 12 months before baseline was self-reported. Latent class analyses identified groups with similar PCP use patterns ("infrequent," "moderate," or "frequent"). At baseline, we excluded women with prevalent hypertension, antihypertensive medication users, or those missing hypertension status. Multivariable Cox regression was used to estimate associations between PCP use and incident self-reported hypertension. Results: During a mean follow-up of 11.4 years, 10,099 women developed hypertension. Frequent PCP use was associated with higher hypertension risk [HR=1.08 (95% CI: 1.03, 1.13); p-trend=0.003], with a 4.1% population attributable risk. Frequent users of beauty products had higher risk than infrequent users [HR=1.11 (95% CI: 1.05, 1.16)]. Moderate and frequent users of hygiene products also had increased risk [HR=1.07 (95% CI: 1.01, 1.13); HR=1.13 (95% CI: 1.08, 1.19)]. Conclusions: Frequent PCP use, especially beauty and hygiene products, was associated with incident hypertension. Our findings implicate everyday chemicals as modifiable cardiovascular risk factors and highlight the need to identify pathogenic components in widely used consumer products.

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.

Potassium-containing low-sodium salt substitutes (LSSS) may lower sodium intake, increase potassium intake, and reduce cardiovascular risk in mixed adult populations, but the review literature is overlapping and methodologically heterogeneous. This umbrella review assessed the efficacy, safety, and evidence quality of potassium-containing LSSS for blood pressure, cardiovascular outcomes, and adverse events. Following a registered PROSPERO protocol (CRD420261294404), we searched PubMed, Embase, Web of Science, Global Health (EBSCO) and the Cochrane Database of Systematic Reviews from inception to 6 March 2026 for systematic reviews, meta-analyses and umbrella reviews of potassium-containing LSSS. Eleven reviews met eligibility criteria. Methodological confidence was high in one review, moderate in three, low in five and critically low in two. Primary-study overlap was very high (corrected covered area 28.5%). Review-level pooled estimates consistently favoured potassium-containing LSSS for systolic blood pressure (mean differences -4.61 to -8.87 mmHg) and diastolic blood pressure (-1.42 to -4.04 mmHg). Later reviews also reported lower all-cause mortality (RR 0.88-0.89), cardiovascular mortality (RR 0.72-0.87), composite cardiovascular events and selected stroke outcomes; however, clinical-outcome estimates were heavily influenced by the Salt Substitute and Stroke Study. Serum potassium changed minimally (-0.02 to 0.18 mmol/l), and pooled estimates for hyperkalaemia and serious adverse events showed no clear excess risk in trial populations that largely excluded participants at higher risk of impaired potassium handling. Potassium-containing LSSS consistently lower blood pressure and may improve cardiovascular outcomes, but further trials are needed outside Eastern Asia, with clearer formulation reporting, prespecified baseline CVD-history strata, and stronger safety data in higher-risk populations.

Background: Black adults bear a disproportionate burden of cardiometabolic dysfunction, yet most dietary trial evidence comes from predominantly White cohorts. Objective: To evaluate whether a personalized whole-food dietary intervention improves cardiometabolic outcomes more in Black than White young adults with overweight or obesity. Methods: In this 8-week randomized, controlled trial (ClinicalTrials.gov: NCT04635917), 112 Black and White adults (18-35 years; BMI 25-45 kg/m2) were block-randomized by race to a personalized dietary intervention providing whole foods (PD, n=57) or conventional dietary counseling at baseline (BL) using MyPlate guidelines (CD, n=55). Primary outcomes were Matsuda Index and fasting and OGTT-derived glucose, insulin, and non-esterified fatty acids. Other glucoregulatory, cardiovascular, anthropometric, appetite, and cognitive outcomes were also assessed. Outcomes were analyzed using baseline-adjusted linear models with sensitivity analyses adjusting for baseline BMI and food security score. Results: Compliance with study food consumption was 85-91%. Diet quality was higher in PD than CD (P < 0.05), with larger gains in vegetable-related outcomes among Black participants (group x race, P < 0.05). HOMA-{beta} was lower in PD than CD overall (P < 0.05). In sensitivity analyses, Black PD participants had greater fasting insulin reductions than White, especially in the latter half of intervention (week x group x race, P < 0.05), with a similar tendency for HOMA-IR. Glucose AUC 0-30 min was higher in White than Black PD participants (group x race, P < 0.05). Concentration performance was higher in PD than CD overall (P < 0.05), with larger gains in processing speed and accuracy among Black than White participants (group x race, P < 0.05). No effects were observed for cardiovascular or appetite outcomes. Conclusions: The personalized whole-food intervention produced differential effects in fasting insulin and early-phase glucose handling, and greater benefits in attention, in Black compared with White young adults with overweight or obesity during weight maintenance.