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.

IntroductionThere is no comparison of iron phenotypes and menses, pregnancies, and live births reports of women with HFE-related hemochromatosis (HFE p.C282Y (rs1800562) homozygosity) and HFE wt/wt (absence of p.C282Y and HFE p.H63D (rs1799945)). Subjects and MethodsWe compared phenotypes and reports of non-Hispanic white women women aged [&ge;]25 y in post-population screening evaluations using univariable methods. ResultsThere were 153 p.C282Y/p.C282Y and 273 wt/wt. Median ages were 50 y (25, 86) and 55 y (25, 92), respectively (p=0.0019). Median transferrin saturation (TS), median serum ferritin (SF), and provisional iron overload prevalence were higher in p.C282Y/p.C282Y (p [&le;]0.0001, each comparison). Prevalences of documented iron overload (3.3% p.C282Y/p.C282Y vs. 0.7% wt/wt), iron overload-related disease (2.0% vs. 0.4%, respectively), and iron deficiency (3.9% vs. 2.6%, respectively) were not significantly different. Median ages at menarche (13 y p.C282Y/p.C282Y vs. 13 y wt/wt) and menopause (50 y vs. 49 y, respectively) were not significantly different. Reports of "in-between bleeding?" (24.2% p.C282Y/p.C282Y vs. 25.2% wt/wt, respectively), "early stopping of periods?" (11.8% vs. 13.9%, respectively), and "had a hysterectomy?" (30.1% vs. 35.9%, respectively) were not significantly different. Respective percentage pairs of women with p.C282Y/p.C282Y and wt/wt who reported 0, 1, 2, 3, or [&ge;]4 pregnancies (or live births) did not differ significantly. Live births/pregnancies were 287/363 (79.1%, p.C282Y/p.C282Y) and 534/673 (79.3%, wt/wt) (p=0.7549). ConclusionsMedian TS, median SF, and provisional iron overload prevalence are greater in women with HFE p.C282Y/p.C282Y than those with wt/wt, although reports of menses, pregnancies, and live births are similar.

BackgroundVariables that influence mean corpuscular volume (MCV) in HFE p.C282Y (rs1800562)/p.H63D (rs1799945) compound heterozygotes are inadequately defined. MethodsWe retrospectively studied self-reported non-Hispanic white adult compound heterozygotes with transferrin saturation (TS) >50% and serum ferritin (SF) >300 g/L (men) or TS >45% and SF >200 g/L (women) who participated in primary care-based screening. In post-screening evaluations, we excluded participants with anemia, pregnancy, or medication use that increases MCV. We defined heavy alcohol intake as >28 g/d men and >14 g/d women. We determined associations of MCV with 11 clinical and laboratory variables. ResultsThere were 74 participants (37 men, 37 women) of mean age 59{+/-}12 (SD) y. Mean screening TS and SF were 65{+/-}13% and 529{+/-}169 {micro}g/L (men) and 59{+/-}14% and 376{+/-}195 {micro}g/L (women). Post-screening values did not differ significantly. Mean MCV was 95.7{+/-}4.0 fL. There was a negative correlation of MCV with body mass index (p=0.0488) and positive correlations of MCV with age (p=0.0098), daily heme iron intake (p=0.0333), and daily alcohol intake (p=0.0113). Mean MCVs of 19 participants with and 55 without heavy alcohol intake were 97.8{+/-}3.8 g/d and 95.0{+/-}3.9 g/d, respectively; p=0.0074). Linear regression on MCV confirmed positive associations with age (p=0.0064) and daily alcohol intake (p=0.0151). MCV was not significantly associated with sex, diabetes, daily intakes of non-heme and supplemental iron, swollen or tender 2nd/3rd metacarpophalangeal joints, TS, or SF. ConclusionMCV in HFE p.C282Y/p.H63D compound heterozygotes with high iron phenotypes is positively associated with age and daily alcohol intake, after adjustment for other variables.

BackgroundChildren with congenital heart disease (CHD) have an increased risk of developing thrombosis. Coagulation markers are used to guide clinical anti-coagulation decisions. We aimed to identify circulating metabolites that are associated with coagulation markers in children with CHD. MethodsPlasma samples were separated from whole blood under consistent conditions (consistent timing of blood draws and the same processing procedures). Untargeted metabolomic data were measured by Metabolon in plasma from young patients (age range: 0 days-24 years) with CHD before cardiac surgery. Coagulation markers included activated partial thromboplastin time (aPTT), prothrombin time (PT), activated clotting time (ACT), and international normalized ratio. Associations of individual metabolites with four coagulation markers were assessed with multivariable regression models, with false discovery rate (FDR) correction for multiple comparison. ResultsOut of 1,115 metabolites measured in samples from 203 patients, 776 met the quality control criteria. In total, 418 metabolites were associated with at least one marker, with one (valine) associated with ACT, three (gamma-CEHC, retinol, and behenoyl sphingomyelin) with PT, and 415 with aPTT (FDR q value < 0.05); among these, behenoyl sphingomyelin was associated with both PT and aPTT. Among the metabolites associated with aPTT, the top three were ornithine, X-21364 (identity unknown), and androstenediol disulfate. Metabolic pathway analysis based on the 415 metabolites significantly associated with aPTT suggested three pathways with an FDR q value<0.05: valine, leucine and isoleucine biosynthesis; histidine metabolism; and arginine and proline metabolism. ConclusionWe have identified promising novel metabolites and metabolic pathways associated with coagulation markers in children with CHD. Future studies are warranted to confirm these findings and examine the implications of the links between these metabolites and coagulation markers. HIGHLIGHTSO_LIIn this metabolomic study, we identified 418 metabolites associated with coagulation markers in young patients with CHD; C_LIO_LIThese metabolites indicated three novel metabolic pathways in this patient population; C_LIO_LIPlasma metabolites clustered into eight modules that were also associated with coagulation markers. C_LI

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.

Background & AimsCirculating proteins are integral to many biological processes and could be influenced by diet. We aimed to assess differences in the plasma proteome between people of different dietary groups, defined by degree of animal food consumption. MethodsThe UK Biobank recruited middle-aged adults (mostly 40 to 69 years) throughout the UK between 2006-2010. Relative concentrations of 2920 plasma proteins were quantified using the Olink Proximity Extension Assay on blood samples from 49,615 participants, who were also asked to report their ethnicity and consumption of red and processed meat, poultry, fish, dairy and eggs. We defined six diet groups among the white British participants (23,243 regular meat eaters, 23,472 low meat eaters, 486 poultry eaters, 1081 fish eaters, 721 vegetarians, and 54 vegans), and two diet groups among the British Indians (391 meat eaters and 167 vegetarians). We used multivariable-adjusted linear regressions to assess the cross-sectional differences in protein concentrations between diet groups, with correction for multiple testing. ResultsWe observed significant differences in many plasma proteins by diet group (920 proteins in white British participants, 2 in British Indians). Of the biggest differences, compared with regular meat eaters, the non-meat eaters had significantly higher FGF21 (e.g. +0.40 SD in vegetarians), CKB (+0.34), GUCA2A (+0.33), FOLR1 (+0.32), IGFBP2 (+0.31) and DSG2 (+0.30); all groups except the vegans had lower HAVCR1 (-0.38 in vegetarians). Vegetarians also had significantly lower SELENOP (-0.46), while the vegans had lower FGFBP2 (-0.68). The observed differences were generally similar in direction in both ethnicities. ConclusionsIn this first comprehensive assessment of plasma proteins by diet group, we identified many differences in proteins between vegetarians, vegans and meat eaters; this variation in protein levels suggests differences in various biological activities, including gastrointestinal tract and kidney function, which may relate to differences in future disease risk.

ObjectivesTo determine how menorrhagia is managed in people with bleeding disorders. DesignA systematic review and thematic synthesis. Data sourcesPubMed, Medline, Scopus, Cochrane library, google scholar and CINAHL complete (via EBSCO). MethodsSearches were conducted on articles published from 1st January 2000 until 6th May 2024. Following deduplication, the titles and abstracts were screened for relevance. 244 primary studies were then assessed for eligibility based on inclusion and exclusion criteria. Studies were included if they were based on primary articles and focussed on people with inherited bleeding disorders and heavy menstrual bleeding. Included studies were appraised for risk of bias and quality assurance using the Newcastle Ottawa Scale, following which data was systematically coded to generate descriptive and analytical themes. ResultsWe identified 16 eligible articles of which 13 were included in a thematic synthesis. These included prospective and retrospective clinical studies, cross-sectional studies and randomised control trials encompassing over 893 participants. Thematic synthesis identified hormonal treatments, such as the levonorgestrel-releasing intrauterine system (LNG-IUS), to be largely effective in the symptom management of HMB in IBD and associated with improved quality of patient life. Treatment of HMB patients with LNG-IUS, followed by tranexamic acid (TA) or 1-deamino-8-d-arginine vasopressin (DDAVP), the trade name for desmopressin, commonly led to amenorrhea. Technological approaches to the management of HMB in IBD included the use of mobile technology to encourage treatment compliance. These management strategies led to an improvement in reported QoL by patients with IBD. This review had limitations including the exclusion of some articles that may have limited generalisability. The Medical Subject Heading (MeSH) terms used focussed on HMB as opposed to abnormal menstrual bleeding, potentially directing the identified recommendations for clinical practice. Based on the findings of this thematic review, the use of LNG-IUS as first line therapy for those with HMB, followed by the use of combination therapy such as TA and desmopressin, would be recommended. These measures should be adopted in both primary and secondary care settings. We identified the need to strengthen counselling and communication between specialists involved in the care of those with HMB and IBD, and the need to increase awareness of HMB in IBD through public and patient education. Data availability statementAll data presented is secondary to published studies and available within the public domain. RegistrationPROSPERO registration number: CRD42023452533 Key MessagesO_LIWhat is already known on this topic - Heavy menstrual bleeding (HMB) is often a symptom of inherited bleeding disorders (IBD) in females and can have a significant impact on the quality of life of an individual. C_LIO_LIWhat this study adds - A systematic review and thematic analysis of the currently available literature allowed the identification of best practise management options for patients with IBD and HMB. A thematic synthesis was used to identify best practice for IBD patient treatment and management of HMB, which will improve patient quality of life. C_LIO_LIHow this study might affect research, practice or policy - This study of existing literature and thematic synthesis has been used to provide recommendations to haematologists and gynaecologists to support evidence based best practise recommendations on how to treat patients with HMB consequent to IBDs. C_LI

IntroductionRanitidine is a member of the H2-blocker class of medications, commonly used in the treatment gastroesophageal reflux and peptic ulcer disease. Recent laboratory analyses have demonstrated that ranitidine may yield the probable carcinogen, N-Nitrosodimethylamine (NDMA). Here, we characterized the kinetics of NDMA production from ranitidine under various simulated gastric conditions. Moreover, we conducted a cross-sectional epidemiologic analysis to evaluate potential associations between ranitidine use and various cancer presentations. MethodsThe formation of NDMA in the presence of ranitidine was studied in a series of experiments conducted in simulated gastric fluid (SGF), while varying pH, nitrite concentration, and time of reaction. Chemical analyses of NDMA yield were performed by liquid chromatography-high resolution mass spectrometry per FDA guidelines on the detection of NDMA from ranitidine drug products. To evaluate potential associations between ranitidine use and cancer diagnoses, we conducted a cross-sectional analysis among a population of oncology patients, following institutional review board approval. Analyses were limited to those reporting use of ranitidine or an active comparator (i.e. proton-pump inhibitor [PPI] or other H2-blocker) to partially mitigate potential confounding. Multivariable logistic regression was employed to identify associations between ranitidine and certain cancers, adjusted for age, sex, race, ethnicity, and body-mass index. ResultsIncreasing sodium nitrite concentrations in SGF at pH 1.2 were associated with increasing NDMA yield. At a pH of 2.5, previously identified as the optimal reaction condition, samples collected at incubation times of 1, 2 and 4 hours (approximating typical gastric emptying conditions) showed a continued increase in NDMA over time. Notably, the reaction trajectory suggests NDMA may have continued to form beyond the last observed timepoint of 4 hours. On cross-sectional analysis of an oncology population, use of ranitidine (versus active comparators) was associated with increased odds of presenting with cancers of the breast (OR=1.58; 95%CI: 1.23-2.01) as compared to presentation with another cancer. Similar positive associations were observed for cancers of the thyroid (OR=1.89; 95%CI: 1.18-2.92), bladder (OR=1.58; 95%CI: 1.10-2.21), and prostate (OR=1.80; 95%CI: 1.34-2.39). Conversely, ranitidine was inversely associated with cancers of the colorectum (OR=0.48; 95%CI: 0.30-0.74) and brain (OR=0.56; 95%CI: 0.33-0.89). ConclusionUnder simulated gastric conditions, ranitidine yields increasing amounts of NDMA over time (up to, and likely beyond 4 hours) and with increasing concentrations of sodium nitrite. In addition, among a cohort of cancer patients reporting use of H2-blockers or PPIs at the time of diagnosis, we found an association between ranitidine use and cancers of the breast, thyroid, bladder and prostate. We further observed unexplained inverse associations with cancers of the brain and colorectum. These associations reflect the odds of presenting with different cancers exclusively among an oncology population, and do not directly represent risk in a general population (as there were no cancer-free individuals in this study). Moreover, these exploratory analyses are to be viewed as hypothesis generating and should prompt analyses of larger cohorts with longer follow-up.

BackgroundSkeletal muscle wasting is a major determinant of physical functional disability in critical illness survivors, and contributes to post-intensive care syndrome. As yet, no therapies exist to address this major public health issue. Intramuscular bioenergetic failure and inflammation are understood to be the underpinning mechanisms, and carbohydrate and lipid oxidation are impaired. This systematic review synthesises the evidence that peroxisome proliferator-activated receptor gamma agonists may be a therapeutic option to optimise clinical nutrition in critically ill patients. MethodSystematic review and meta-analysis. ResultsFourteen studies over 19 publications were included. Lean body mass was unaffected (n=174). Pioglitazone treatment resulted in periperal insulin sensitivity increasing 30-71% (Standardised mean change 0.97 (95%CI 0.36-1.58; n=213). Intramuscular Tumour Necrosis Factor Alpha concentrations decreased in treatement arms (n=29) as did circulating interlukin-6 and Tumour Necrosis Factor Alpha (n=53). Intramyocellular Lipid concentrations decreased by 34-40% with pioglitazone therapy (n=60). Treatment increased intramuscular markers of Oxidative Phosphorylation (n=55), mitochondrial biogenesis(PGC1 and PGC1{beta}; n=26) and {beta}-oxidation (n=29) ConclusionsPioglitazone therapy increases skeletal muscle insulin sensitivity, decreases intramyocellular lipid accumulation and systemic and intramuscular inflammation. Where lean body mass was measured, this was seen to increase. Pioglitazone may be an adjunctive therapy to optimise clinical nutrition in acutely unwell patients. Clinical relevancy statementPioglitazone may optimise clinical nutrition therapy in critically ill patients by normalising carbohydrate and lipid metabolism.

Decreased handgrip-strength has become an increasingly important measure of overall health status and fitness. This was a cross-sectional analysis among adult participants in the 2011-2012 NHANES survey. Handgrip-strength was assessed using a digital dynamometer and a standard protocol, and medication use was assessed by self-report and verification by the interviewer. Mean handgrip-strength among participants with no medication use was 87.2kg in males and 57.2kg in females. Handgrip strength decreased significantly in both men and women (ptrend<0.001 for both) with increasing medication use after adjustment for age, sex, height, arm circumference, and BMI. Statins, ACE-inhibitors, ARBs, diuretics, calcium channel blockers, and sulfonylureas showed a consistent and significant decrease in grip strength in linear regression models. In this nationally representative survey of adults in the US, we observed a negative relationship between handgrip strength and polypharmacy. Further, several specific medications, mostly cardiovascular drug classes, were associated with reduced handgrip-strength.

BackgroundThe gut microbiome has been implicated in exercise performance and, more recently, in neural pathways that govern exercise motivation. Veillonella atypica--a lactate-utilizing bacterium enriched in elite athletes-- enhances forced treadmill performance in mice through lactate-to-propionate metabolism, yet effects on voluntary physical activity, the clinically relevant behavior, remain unknown. We tested whether supplementation with V. atypica reduces fatigue burden and increases voluntary physical activity in humans, with mechanistic validation in mice. MethodsWe conducted a randomized, placebo-controlled, app-mediated trial in healthy adults (8-week protocol: 2-week baseline, 4-week supplementation, 2-week washout; n=151 meeting compliance criteria). Participants received high-dose V. atypica, low-dose V. atypica, or placebo; dose groups were pooled after confirming similar responses. Primary endpoints were Multidimensional Fatigue Inventory (MFI-20) subscales assessed pre- and post-supplementation; secondary endpoints included weekly surveys (fatigue interference, physical activity hours) and daily surveys (sleep quality, energy). In parallel, we profiled voluntary wheel running in mice randomized to PBS, V. atypica, or Lactobacillus johnsonii (peanut butter delivery), with striatal dopamine quantification at endpoint. ResultsIn humans (n=146-149 depending on outcome), weekly longitudinal assessments revealed V. atypica-specific benefits not captured by endpoint comparisons. Relative to placebo, V. atypica produced a faster decline in fatigue interference (-0.097 days/week; 95% CI -0.175 to -0.018; p=0.016) and a faster increase in self-reported physical-activity hours (+0.357 h/week; 95% CI +0.031 to +0.684; p=0.032). Model-predicted effects by week 6 corresponded to approximately 0.6 fewer days with fatigue interference and 2 additional activity hours per week if linear trends continued. By contrast, MFI-based fatigue scores improved over time in both arms without between-group differences (treatmentxtime interactions all p>0.40). Daily measures indicated improved sleep quality during washout in V. atypica versus placebo (difference-in-differences +0.197 Likert units; p=0.0039), with no differences in sleep duration; odds of high-energy days trended higher with V. atypica during washout (OR{approx}2.36; p=0.07). In mice, mixed-effects models revealed a significant groupxtime interaction for daily running distance (F=13.31; p=2.1x10-): V. atypica maintained running across 12 weeks (slope not significantly different from zero), whereas PBS and L. johnsonii declined significantly. During the final 5 weeks (days 49-84), baseline-adjusted mean running distance was approximately 2.86 km/day higher in V. atypica versus PBS (p=2.2x10-). Striatal dopamine concentrations were elevated in V. atypica-treated mice relative to both controls (one-way ANOVA p=0.05; V. atypica vs PBS p=0.03, approximately 30% higher). ConclusionsAcross complementary human and murine experiments, V. atypica was associated with reduced day-to-day fatigue interference and increased voluntary physical activity, with convergent evidence of sustained behavioral engagement in mice. Preliminary findings of elevated striatal dopamine are consistent with emerging evidence that gut microbiome regulates exercise motivation through dopaminergic signaling, though mechanistic causality remains to be established. These data extend Veillonella biology beyond performance physiology to motivational domains and support continued investigation of precision microbiome approaches to address barriers to physical activity.

In the UK, black African-Caribbeans (ACs) and South Asians (SAs) have 3-6 times greater risks of developing diabetes than white Caucasians do. East London is among the areas with the highest prevalence of type 2 diabetes and the highest proportion of minority groups. This ethnic health inequality is ascribed to socioeconomic standing, dietary habits, culture, and attitudes, while biological diversity has rarely been investigated. The evidence shows that the postprandial glucose peak values in SAs are 2-3 times greater than those in white Caucasians after the same carbohydrate loads; however, the mechanism is poorly understood. In the UK, 50% of SAs and 33% of ACs have vitamin D (vitD) deficiency, whereas 18% of white Caucasians have vitamin D deficiency. There is evidence that vitD status is inversely associated with insulin resistance in healthy adults and diabetic patients and that vitD supplementation may help improve glycaemic control and insulin resistance in type 2 diabetes patients. However, little evidence is available on minority groups or East London. This study will investigate the postprandial glycaemic response (PGR) in three ethnic groups (white Caucasians, SAs and ACs) in East London and link PGR to plasma 25(OH)D (an indicator of vitD status). Ninety-six healthy adults (n=32 per group) will be recruited. Two test drinks will be provided to the participants (300 ml of glucose drink containing 75 g glucose, and 300 ml of pure orange juice) on different occasions. PGR is monitored before and after drinking every 30 min for up to 2 hours via finger prick. A fasting blood sample obtained via phlebotomy will be used for 25(OH)D and relevant tests. A knowledge/perception questionnaire about vitD and a 4-day food diary (analysing vitD dietary intake) will also be collected. The findings of the study will be shared with participants, published in journals, disseminated via social media, and used to inform a randomized controlled trial of the effects of vitD supplementation on PGR in minority groups. The study complies with the Helsinki Declaration II and was approved by the Senate Research Ethics Committee at City, University of London (ETH2223-2000). The study findings will be published in open access peer-reviewed journals and disseminated at national and international conferences. ClinicalTrials.gov Identifier: NCT06241976

BackgroundCOVID-19 is a major pandemic that has killed more than 196,000 people. The COVID-19 disease course is strikingly divergent. Approximately 80-85% of patients experience mild or no symptoms, while the remainder develop severe disease. The mechanisms underlying these divergent outcomes are unclear. Emerging health disparities data regarding African American and homeless populations suggest that vitamin D insufficiency (VDI) may be an underlying driver of COVID-19 severity. To better define the VDI-COVID-19 link, we determined the prevalence of VDI among our COVID-19 intensive care unit (ICU) patients. MethodsIn an Institutional Review Board approved study performed at a single, tertiary care academic medical center, the medical records of COVID-19 patients were retrospectively reviewed. Subjects were included for whom serum 25-hydroxycholecalcifoerol (25OHD) levels were determined. COVID-19-relevant data were compiled and analyzed. We determined the frequency of VDI among COVID-19 patients to evaluate the likelihood of a VDI-COVID-19 relationship. ResultsTwenty COVID-19 patients with serum 25OHD levels were identified; 65.0% required ICU admission.The VDI prevalence in ICU patients was 84.6%, vs. 57.1% in floor patients. Strikingly, 100% of ICU patients less than 75 years old had VDI. Coagulopathy was present in 62.5% of ICU COVID-19 patients, and 92.3% were lymphocytopenic. ConclusionsVDI is highly prevalent in severe COVID-19 patients. VDI and severe COVID-19 share numerous associations including hypertension, obesity, male sex, advanced age, concentration in northern climates, coagulopathy, and immune dysfunction. Thus, we suggest that prospective, randomized controlled studies of VDI in COVID-19 patients are warranted.

Aims and objectiveAnemias are a burden for management because they are associated with the worsening of the pathophysiology of diseases. They can be multifactorial, including micronutrient deficiencies including iron deficiencies. This study aimed to biologically characterize anemias and iron deficiency anemias during diabetes and to identify the associated factors. MethodsOver 4 months, we conducted an analytical cross-sectional study from August to November 2024. 210 diabetic patients, attending the diabetology unit of the regional hospital in West Cameroon were studied, their age range between <20 and > 70 years. Blood samples were taken for biological tests including blood count, glycemia, glycated hemoglobin, ferritin, and serum following standard assay protocols. The results obtained were analyzed using the R statistical tool version 4.1.1. ResultsThe sex ratio was 0.89 and the mean age was 48.32{+/-}18.19 years. 48.6% of patients were overweight. The frequency of anemia was observed in 72 females (53%) and 63 males (46.7%) with a total frequency of 64.3%. 11.4% were found to have iron deficiency anemias. The blood count revealed hematological abnormalities characterized by leukopenia (41.4%), granulocytopenia (35.7%), and thrombocytopenia (2.86%) with macroplateletosis (40.0%). Anemias were characterized by microcytosis (11.1% in anemic patients versus none in non-anemic patients (p<0.001), hypochromia (88.9% in anemic patients versus 72% in non-anemic patients (p<0.001)) and greater regeneration in anemic patients versus non-anemic patients (p<0.001). Macroplateletosis and high Hb1AC were identified as predictive factors for iron deficiency anemia in diabetes with (Or=2.83, 95% CI= [1.17;6.80]; p=0.021) and Or=2.38, 95% CI= [0.14;3.09], p=0.045, respectively. ConclusionThis study reports a significant frequency of anemia and iron deficiency anemia in diabetic patients; the latter is associated with worsening clinical manifestations in patients. This study raises the need for regular exploration of iron status in diabetics to prevent complications related to iron deficiency.

Vitamin D is essential for bone and metabolic health. Deficiency remains a global health issue, particularly among older adults and ethnic minorities with darker skin pigmentation. Data on circannual variation these groups remain sparse. This study reports vitamin D status in older adults ([&ge;]65 years) and ethnic adults ([&ge;]18 years, Fitzpatrick classes IV-VI) in northern Britain during the screening phase of a supplementation trial. Participants were screened for inclusion between December 2024 and August 2025. Serum 25-hydroxyvitamin D (25(OH)D) was assessed in dried blood spots followed by LC-MS/MS analysis. 299 participants were screened. Vitamin D insufficiency or deficiency (<50 nmol/L) was noted in 54.8% of older adults and 72.1% of ethnic individuals. These rates did not decline during summer months. These findings highlight persistently high rates of vitamin D insufficiency across high-risk groups in northern Britain and underscore the inadequacy of sunlight exposure as a corrective measure.

BackgroundThe human metabolome is influenced by diet, and studying circulating metabolites may help clarify underlying mechanisms linking diet groups and disease outcomes, but few large studies have been conducted. This study investigated differences in plasma metabolites across diet groups in the UK Biobank. MethodsThe UK Biobank recruited 500,000 adults (aged 40-69) across the UK in 2006-2010. At recruitment, participants reported ethnicity and diet, from which we defined six diet groups in white British participants (regular meat eaters, low meat eaters, poultry eaters, fish eaters, vegetarians, vegans) and two in British Indian participants (meat eaters, vegetarians). Metabolomics profiling (249 plasma metabolites) was performed using nuclear magnetic resonance (NMR) in a random subset of [~]275,000 participants. We used multivariable-adjusted linear regression to estimate differences in adjusted geometric means of metabolite levels by diet group. ResultsSignificant differences between diet groups were observed in 241 (97%) metabolites in white British participants after multiple testing correction. Compared with regular meat eaters, vegetarians and vegans had lower concentrations of n-3, DHA, and their ratios to total fatty acids. However, they had higher n-6, linoleic acid, and their ratios to n-3 and total fatty acids. Additionally, non-meat eaters had higher glycine but lower branched-chain amino acid concentrations. Large differences were also seen in many lipoprotein subclasses. Similar patterns were observed in British Indian participants. ConclusionsMarked differences in metabolite profiles across diet groups signify variations in fatty acid, amino acid, and lipid intake and metabolism, which may help explain associations with long-term health outcomes. HighlightsO_LIPeople on different diets showed substantial differences in metabolomic profiles. C_LIO_LILargest differences were seen in several fatty acids and their ratios. C_LIO_LISimilar patterns were found in white British and British Indian populations. C_LI

PurposeChronic inflammation is integral to Myeloproliferative Neoplasm (MPN) pathogenesis. JAK inhibitors reduce cytokine levels, but not without significant side effects. Nutrition is a low-risk approach to reduce inflammation and ameliorate symptoms in MPN. We performed a randomized, parallel-arm study to determine the feasibility of an education-focused Mediterranean diet intervention among MPN patients. Experimental DesignWe randomly assigned participants to either a Mediterranean diet or standard US Dietary Guidelines for Americans (USDA). Groups received equal but separate education with registered dietician counseling and written dietary resources. Patients were prospectively followed for feasibility, adherence, and symptom burden assessments. Biological samples were collected at four time points during the 15-week study to explore changes in inflammatory biomarkers and gut microbiome. ResultsThe Mediterranean diet was as easy to follow for MPN patients as the standard USDA diet. Over 80% of the patients in the Mediterranean diet group achieved a Mediterranean Diet Adherence Score of [&ge;]8 throughout the entire active intervention period, whereas less than 50% of the USDA group achieved a score of [&ge;]8 at any time point. Improvement in symptom burden was observed in both diet groups. No significant changes were observed in inflammatory cytokines. The diversity and composition of the gut microbiome remained stable throughout the duration of the intervention. ConclusionsWith dietician counseling and written education MPN patients can adhere to a Mediterranean eating pattern. Diet interventions may be further developed as a component of MPN care, and potentially even be incorporated into the management of other chronic clonal hematologic conditions. STATEMENT OF TRANSLATIONAL RELEVANCEChronic clonal hematologic disorders, such as myeloproliferative neoplasm (MPN), lie at the intersection between malignancy and chronic inflammatory disease. Chronic inflammation is responsible for many of the clinical consequences of MPN. Diet is a central tenant of management of chronic conditions characterized by subclinical inflammation, such as cardiovascular disease, but has not entered the treatment algorithm for clonal hematologic disorders. Here, we establish that a Mediterranean diet intervention is feasible in the MPN patient population and can improve symptom burden. These findings warrant large dietary interventions in patients with clonal hematologic disorders to test the utility of diet in improvement of clinical outcomes.

BackgroundType 2 diabetes mellitus (T2DM) induces a hypercoagulable state, increasing thrombotic risk. However, data characterizing hemostatic abnormalities in T2DM patients from conflict zones with crippled healthcare systems, like Yemen, are profoundly scarce. The interplay between type 2 diabetes mellitus (T2DM) and hemostasis in conflict settings with widespread malnutrition remains unexplored. ObjectivesThis study aimed to evaluate coagulation parameters and platelet indices among Yemeni adults with T2DM and to correlate these hemostatic markers with the degree of glycemic control. MethodsA hospital-based cross-sectional study was conducted on 140 T2DM patients and 100 healthy controls in Aden, Yemen. Prothrombin time (PT), activated partial thromboplastin time (APTT), mean platelet volume (MPV), and platelet distribution width (PDW) were measured using standardized analyzers (STA-R Evolution and Sysmex XN-550). Glycemic control was assessed via HbA1c. ResultsA significant majority (86%) of patients had poor glycemic control (HbA1c [&ge;] 7%). T2DM patients exhibited a distinct coagulation profile characterized by prolonged PT (13.4 {+/-} 1.8 vs. 12.1 {+/-} 1.2 sec, p < 0.01) and shortened APTT (32.5 {+/-} 4.1 vs. 35.2 {+/-} 3.5 sec, p = 0.02) compared to controls. Platelet indices were markedly elevated, with higher MPV (10.2 {+/-} 1.5 vs. 8.7 {+/-} 1.1 fL, p < 0.001) and PDW (16.8 {+/-} 2.1 vs. 15.2 {+/-} 1.8%, p = 0.01). A strong positive correlation was observed between HbA1c and MPV (r = 0.52, p < 0.001). ConclusionThese findings advocate for the urgent integration of affordable coagulation (PT/APTT) and platelet indices screening into diabetic care protocols in conflict-affected and low-resource settings to guide targeted nutritional and anti-thrombotic interventions.

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

BACKGROUNDRegular blood donation is associated with an increased risk of iron deficiency (ID; ferritin <15 {micro}g/L). Oral iron supplementation is known to shorten iron store recovery time and could serve as a more effective alternative to extended donation intervals. We aimed to determine the optimal ferritin-guided iron supplementation protocol in terms of donor health, side-effects, donor return, and treatment adherence. METHODSIn this prospective randomized placebo-controlled trial donors with ferritin levels [&le;]30 {micro}g/L were enrolled in the study and randomly assigned to one of six groups, stratified for sex and age. Depending on the study arm, donors were asked to adhere to a ferrous bisglycinate supplementation protocol for 56 days, taking capsules containing 0 mg (i.e. placebo), 30 mg or 60 mg of elemental iron, either on alternate days or daily. The primary outcome was iron deficiency (ID) at 56 days follow-up, while secondary outcomes included low ferritin ([&le;]30 {micro}g/L), low Hb ([&le;]135 g/L for men and [&le;]125 g/L for women), iron deficiency-related symptoms, side effects, treatment adherence, and evaluations of all outcomes at 122 and 180 days follow-up. This trial is registered in the Dutch trial registry (NL73283.018.20). FINDINGSOf the 2,052 donors who provided their informed consent, 830 donors (464 women) had ferritin levels [&le;]30 {micro}g/L and were included in the trial. Compared to placebo, all iron supplementation groups exhibited similar significantly lower odds of ID at 56 days, with odds ratios (OR) ranging from 0.60 (95% CI [0.55-0.66]) to 0.65 (95% CI [0.59-0.72]). Similarly, for low Hb, the ORs ranged from 0.74 (95% CI [0.64-0.86]) to 0.80 (95% CI [0.68-0.93]) For low ferritin, 60 mg of daily iron supplementation yielded an OR of 0.52 (95% CI [0.47-0.57]), markedly lower than those of other protocols, which ranged from 0.61 (95% CI [0.55-0.68]) to 0.82 (95% CI [0.74-0.91]). Iron supplementation did not result in any significant differences compared to placebo in ID-related symptoms, gastrointestinal side effects, intention to return to donate, or treatment adherence. INTERPRETATIONIn regular donors, 60 mg iron supplements taken daily was shown to be the most effective strategy for mitigating ID, low Hb, and especially low ferritin without introducing gastrointestinal discomfort or changes in the donors intention to return to donate. Ferritin-guided iron supplementation is an effective iron management strategy as an alternative or supplement to extended donation intervals.