Vitamin D may help reduce the risk of colorectal cancer (CRC) by exerting an anti-inflammatory or modulatory effect on biomarkers associated with the disease. While previous studies have investigated individual biomarkers, our approach evaluates their combined effects. We investigated the association between 25-hydroxyvitamin D (25(OH)D) levels, measured using MS, and the expression of 92 inflammatory biomarkers assessed using the Olink Target 96 inflammation panel. This analysis was conducted in women from the Norwegian Women and Health Study (NOWAC), utilising plasma samples taken 1–6 years prior to CRC diagnosis (n = 163) and 163 matched cancer-free controls. Factor analysis was used to identify biomarker patterns, and linear regression examined the association of each factor with 25(OH)D levels. Women with 25(OH)D deficiency (≤30 nmol/L) had significantly higher Factor 1 scores compared to those with sufficient levels (≥50 nmol/L) (β = 0.72, 95% CI: 0.26–1.18). This association was specific to pre-diagnostic CRC cases (β = 0.97, 95% CI: 0.33–1.60) and was not observed in cancer-free controls (β = 0.22, 95% CI: −0.50–0.93). Factor 1 represents a cluster of biomarkers, many of which are pro-inflammatory (TNFSF14, S100-A12, IL-8, IL-18) and many that play key roles in processes such as cell growth, angiogenesis, and apoptosis (OSM, TGF-alpha, VEGF-A, CASP-8). Several of these biomarkers have been independently linked to CRC, exhibiting both unfavourable and favourable roles. The observed association between 25(OH)D deficiency and Factor 1 in pre-diagnostic CRC cases supports the hypothesis that sufficient levels of vitamin D could potentially contribute to prevention of CRC development.

The biologically active form of vitamin D (1,25(OH)2D) is involved in the regulation of calcium and phosphorus, influencing bone formation and probably fetal growth and development. However, 1,25(OH)2D has a very short half-life, and 25(OH)D is the main circulating metabolite, making it the ideal clinical indicator. Given the lack of prospective epidemiological cohort studies exploring the relationship between maternal 25(OH)D and fetal growth and adiposity, the aim of this study was to evaluate the association of maternal 25(OH)D concentrations with fetal biometry and adiposity at three periods of pregnancy. This prospective study included 330 women participating in the Araraquara Cohort Study, Brazil, who were evaluated at gestational ages ≤19, 20–28 and ≥30 weeks. 25(OH)D concentrations were measured by chemiluminescence. The following fetal outcomes were assessed by ultrasound: biometric (estimated fetal weight, femur length, abdominal circumference, head circumference and biparietal diameter) and adiposity parameters (subcutaneous tissue of the abdomen and subcutaneous areas of the thigh and arm). Generalised estimating equation models adjusted for maternal sociodemographic, lifestyle, nutritional, clinical and biochemical factors were used. In the unadjusted analysis, 25(OH)D ≥ 75 nmol/l was associated with higher fetal biometry and adiposity measures. After adjusting for potential confounders, for each increase of 10 nmol/l in 25(OH)D, there was a 0·0046 cm increase in fetal head circumference (β = 0·0046 [95 % CI 0·0003, 0·0089]; p = 0·04). Maternal 25(OH)D was associated with greater head circumference, suggesting a possible role of 25(OH)D in fetal cranial development and reinforcing the importance of implementing prenatal monitoring of 25(OH)D concentrations.

This umbrella review synthesised evidence from 35 meta-analyses encompassing 154 randomised controlled trials (11 newly included) and 78,175 participants to evaluate the clinical effects of calcium (Ca) and calcium plus vitamin D (CaD) supplementation on cardio-cerebrovascular outcomes and metabolic parameters. Data extracted from Embase, Web of Science, PubMed, and Cochrane Library (inception to 31 January 2025) revealed divergent outcomes: Ca supplementation demonstrated reductions in diastolic blood pressure, body fat, total cholesterol, and total/high-density lipoprotein (HDL) cholesterol ratio but was associated with increased cardio-cerebrovascular disease risk, elevated inflammatory markers (IL-6, TNF-α), two-hour postload glycemia, and waist-to-hip ratio. Conversely, CaD supplementation showed beneficial regulation of cardiovascular risk factors including decreased body fat, body mass index, fasting blood glucose, and improved lipid profiles (low-density lipoprotein, HDL, non-HDL, and total/HDL cholesterol ratios), whereas no significant effects were observed on cardio-cerebrovascular disease incidence. Limitations included exclusion of studies with an unspecified calcium source and suboptimal evidence quality. Taken together, these findings suggest that CaD supplementation may confer a more favourable cardiometabolic profile than Ca supplementation alone. Because several clinical event outcomes were supported by low-certainty evidence, the potential benefits and risks of calcium supplementation should be weighed carefully in individualised clinical decision-making.

In Switzerland, as in many other countries, national guidelines recommend individualized rather than systematic vitamin D supplementation in children beyond the age of three, making routine assessment challenging. This study aimed to examine paediatricians’ reported practices and opinions regarding vitamin D management in children aged 3–17 years in Geneva, Switzerland. A cross-sectional online survey was distributed to 193 paediatricians, of whom 59 completed the questionnaire (85% women). The questionnaire covered assessment frequency and methods, deficiency management, and views on systematic supplementation. Fewer than half reported assessing vitamin D adequacy at every check-up, with 49% (n = 29) for children aged 3–10 years and 44% (n = 26) for adolescents. Among children with clinical signs of deficiency, 76% (n = 45) reported assessment at every check-up, compared with 63% (n = 37) for children with dark skin or chronic digestive disorders and 58% (n = 34) for those with overweight or obesity. Assessments relied mainly on reported supplementation, followed by diet and sun exposure. Regarding prophylactic supplementation, 61% of paediatricians were in favour for children aged 3–10 years and 76% for those aged 11–17 years. Among those opposed, the main reason cited was the absence of clear national guidelines. Overall, this survey highlights marked variability in paediatricians’ approaches to vitamin D, with routine assessment remaining infrequent, even among children with clinical signs of deficiency. This gap may leave vulnerable children and adolescents with undetected deficiency, underscoring the need for harmonized national guidance and targeted educational initiatives to support preventive paediatric care.

Plasma levels of procollagen type 1 N-propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) are bone turnover markers (BTM) used to predict risk of fracture. We compared the effects of vitamin D supplements on plasma levels of P1NP and CTX in the Biochemical Efficacy and Safety Trial of vitamin D (BEST-D) trial (305 participants) after treatment with 2000 IU/d or 4000 IU/d vitamin D3 or placebo. The results of BEST-D were combined in a meta-analysis of all trials of vitamin D v. placebo on levels of P1NP (12 trials, 2654 participants) or CTX (16 trials, 2695 participants). In BEST-D, allocation to vitamin D3 resulted in a dose-dependent increase in 25-hydroxy-vitamin D (25(OH)D) levels but had no effects on P1NP or CTX. Geometric mean (se) levels at 12 months were similar for P1NP (41·7 (0·7) v. 42·9 (1·0) ng/ml; P = 0·29: either dose v. placebo) and likewise for CTX (0·23 (0·01) v. 0·23 (0·01) ng/ml; P = 0·98). In a meta-analysis of eighteen trials, the average difference between the within-trial change in P1NP for allocated vitamin D and control was −3·3 % (95 % CI −5·6, −1·0, P < 0·005). For CTX, this difference was slightly greater (−3·8 % (−6·8, −0·8); P = 0·01). There was no significant heterogeneity between these trials after stratifying trials with or without Ca, higher or lower doses of vitamin D, or lower v. higher pre-treatment levels of 25(OH)D. Overall, vitamin D supplementation was associated with modest reductions in both P1NP and CTX, and results provide support for further trials of vitamin D for prevention of fracture in older people.

The interaction between 25-hydroxyvitamin D [25(OH)D] and physical activity (PA) in influencing hypertension remains underexplored. This study aimed to examine their independent and joint associations with hypertension risk among 5327 participants aged ≥ 50 years from the English Longitudinal Study of Ageing. Participants were categorised by 25(OH)D status (sufficient, ≥ 50 nmol/l; insufficient, ≥ 30 to < 50 nmol/l; deficient, < 30 nmol/l) and self-reported PA levels. Multivariable logistic regression, adjusting for the season of measurement and sociodemographic confounders, showed that sufficient 25(OH)D (OR = 0·66, 95 % CI 0·56, 0·78) and higher PA (OR = 0·82, 95 % CI 0·71, 0·94) were independently associated with reduced hypertension prevalence. In joint analyses, the group combining higher PA and sufficient 25(OH)D exhibited the lowest odds of hypertension (OR = 0·55, 95 % CI 0·43, 0·70) compared with the lower PA and deficient group. A significant synergistic interaction was identified, indicating that the combined protective effect of these factors was greater than the sum of their individual associations. These results were corroborated by Mendelian randomisation analysis, which identified inverse causal associations between genetically predicted 25(OH)D, vigorous PA and hypertension risk across independent datasets. These findings emphasise that vitamin D sufficiency acts in synergy with an active lifestyle to enhance cardiovascular protection. This relationship underscores the critical importance in nutritional science of integrating micronutrient status with PA to develop more effective, multifaceted lifestyle-based strategies for hypertension management in middle-aged and older populations.

Vitamin D has been associated with depression, potentially via anti-inflammatory mechanisms, yet data are scarce, particularly in adolescence. We investigated (1) whether lower vitamin D status is associated with greater depression severity and (2) whether this association is statistically moderated by inflammation in patients of a child and adolescent psychiatry department. At admission, fasting morning venous blood was drawn. Serum vitamin D (25-hydroxy-cholecalciferol (25(OH)D)) and C-reactive protein (CRP) were analysed in all participants (n 465 (64·7 %♀; 11·3–18·9 years)). In a subsample (n 177), we additionally measured tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin (IL)-1β, IL-6, IL-8 and IL-10. Depression severity was assessed by the Beck Depression Inventory II (BDI-II) (n 450), the Diagnostic System for Mental Disorders in Childhood and Adolescence via self-assessment (DISYPS Self) (n 441) and parent-assessment (DISYPS Proxy) (n 422). Overall, 43·2 % (n 201) were at risk for vitamin D deficiency (< 30 nmol/l), and 73·5–83·2 % – depending on assessment tool – showed at least mild depression. Linear regression revealed an inverse association between 25(OH)D and BDI-II in both crude and CRP-adjusted full-sample models. Logistic regressions showed a robust inverse association between 25(OH)D and DISYPS Proxy, but not for DISYPS Self. Although 25(OH)D was inversely correlated with some pro-inflammatory markers, neither their inclusion in regression models nor formal mediation analyses supported inflammation as a mediator of the vitamin D–depression association. Overall, our results suggest that vitamin D relates modestly to both depression and inflammation in adolescence. However, based on the measured parameters, we cannot confirm that anti-inflammatory effects are the link between vitamin D and depression.

Nutrient gaps are differences between recommended and actual intakes and are often based on the estimated average requirement (EAR), the average daily intake estimated to meet the requirement of 50% of healthy individuals. While nutrient gaps have been established in the general population, their presence in exercising adults has not been extensively investigated. In the present analyses, 681 dietary recalls were obtained from 226 healthy exercising adults (154 F, 72 M) using the Automated Self-Administered 24-h (ASA24®) Dietary Assessment Tool. Intakes of seventeen vitamins and minerals were compared to corresponding EAR values to determine if nutrient gaps were present. Additionally, the potential for sex differences in absolute and relative nutrient intakes was examined. Median intakes of vitamin D fell below the EAR in both female and male adults, with the median intake of vitamin E below the EAR in female adults only (p ≤ 0.003 for each). In female participants, >50% exhibited intakes below the EAR for calcium, folate, magnesium, vitamin A, vitamin C, vitamin D, and vitamin E. In male participants, >50% exhibited intakes below the EAR for vitamin C, vitamin D, and vitamin E. Sex differences were present for intakes in sixteen of seventeen micronutrients (p < 0.001 for each), with lower intakes observed in female adults. Collectively, the present analyses indicate underconsumption of some micronutrients, particularly in exercising female adults. The potential to improve vitamin and mineral intakes and attendant health and performance outcomes through targeted interventions in exercising adults should be explored in future research.

Frailty is an ageing-related syndrome of physiological decline, heightening vulnerability and increasing risk of adverse health outcomes. Nutritional deficiencies, particularly in vitamins B9, B12 and D, are prevalent among the elderly owing to physiological changes and reduced food intake. Research suggests a correlation between low levels of these vitamins and an elevated risk of frailty. Vitamin B9, crucial for DNA synthesis and cell division, shows potential in frailty prevention, although evidence regarding supplementation remains inconclusive. Similarly, vitamin B12, essential for nerve function and red blood cell formation, presents conflicting findings regarding its impact on frailty prevention. Vitamin D, essential for bone health and muscle function, is linked to frailty risk, yet studies on the efficacy of supplementation yielded mixed results. The mechanisms involving these vitamins, including their roles in DNA methylation and inflammation regulation, highlight the need for further research to clarify their direct impact on frailty prevention. Maintaining optimal levels of vitamins B9, B12 and D may reduce frailty, but older individuals need a complete approach that includes proper nutrition, physical activity and other preventive measures.

Blood 25-hydroxyvitamin D (25(OH)D) concentrations vary considerably by season and sex. The present study aimed to determine associations between vitamin D deficiency and mortality in Japanese adults and identify risk thresholds according to 25(OH)D concentrations. This was a cohort study with an 11-year follow-up. Participants were 8285 community-dwelling Japanese adults aged 40–74 years. Plasma 25(OH)D concentrations were measured by chemiluminescent immunoassay at baseline and divided into quintiles for each of the subgroups stratified by season and sex (denoted as season- and sex-stratified quintiles). The main outcome was all-cause mortality. Hazard ratios (HR) were calculated using a Cox proportional hazards model. Mean age and 25(OH)D concentration were 59·9 years (sd = 9·1) and 50·1 nmol/l (sd = 18·1), respectively. Lower season- and sex-stratified quintiles were associated with higher hazards of all-cause mortality (Pfor trend = 0·0015), with the first quintile (median = 28·2 nmol/l) having a higher HR (HR = 1·46, 95 % CI, 1·13, 1·88) than the highest quintile (reference). When crude quintiles were used, the overall association was similar (Pfor trend = 0·0027), with the first (median = 28·0 nmol/l) and second (median = 39·7 nmol/l) quintiles having higher HR (HR = 1·40, 95 % CI, 1·06, 1·85 and 1·38, 95 % CI, 1·07, 1·77, respectively) than the reference. The risk threshold difference was estimated to be approximately 10 nmol/l. In conclusion, low blood 25(OH)D concentrations are associated with high mortality risk. Crude blood 25(OH)D concentration may modulate the estimated risk threshold for vitamin D deficiency associated with mortality.

Vitamin D deficiency is common in the UK, especially in certain ethnic minority populations. There is limited information on childhood vitamin D status in the UK, or factors associated with vitamin D deficiency. Using a cross-sectional study of 4650 children of South Asian, Black African and Caribbean and White European origins (9–10 years old) surveyed between 2004 and 2007, we investigated measurements of circulating 25(OH)D concentrations (a measure of vitamin D status) and anthropometric measurements. Overall, 68 % of children had 25(OH)D concentrations ≤ 50 nmol/L and were either insufficient (25–50 nmol/L) (45 %) or deficient (< 25 nmol/L) (23 %). Mean 25(OH)D concentrations were lowest in South Asian (especially Bangladeshi) children, intermediate in Black African and Caribbean and highest in White European children. Mean values were ≤ 50 nmol/L for all children during the winter months and ≤ 50 nmol/L throughout the year for South Asian, Black African and Caribbean children. In analyses adjusted for season, age, sex, ethnicity, socio-economic status and fat mass index, girls had a higher risk of being vitamin D deficient or insufficient (OR 1·49, 95 % CI 1·32, 1·68) compared with boys. South Asian children (OR 25·49, 95 % CI 19·95, 32·57) and Black African and Caribbean children (OR 10·31, 95 % CI 10·31, 17·52) had the highest risks of being deficient or insufficient compared with White European children. Childhood vitamin D deficiency was common in this study population. In the UK, targeted and novel interventions are needed to increase 25(OH)D concentrations, particularly South Asian and Black African and Caribbean children and reduce the health risks associated with low vitamin D status.

Pregnant women are at higher risk of vitamin D deficiency due to increased nutritional requirements and limited dietary sources. Fish is the major source of vitamin D, but its availability varies by region. This study aims to assess the availability of vitamin D-rich fish and develop food-based recommendations (FBR) for pregnant women in East Lombok, Indonesia. This comparative cross-sectional study was conducted in East Lombok, Indonesia, which is part of Action Against Stunting cohort of pregnant women. Twenty-five village markets in the area were scored based on availability of vitamin D-rich fish and number of fish sellers in each market and were categorised into high availability (HD) for the highest quartile and low availability (LD) for the lowest quartile. Quantum Geographic Information System software was used to identify each of respondents’ houses using 2·4 km buffer zones to either HD or LD markets. Dietary intake data were collected from 24-h dietary recalls and linear programming analysis using Optifood was used to identify problem nutrient and dietary inadequacy. No significant difference in vitamin D intake was found between HD and LD areas (P = 0·633). While both groups’ FBR ensure adequacy of Fe, Zn, vitamins A, B1, B2, B3, B6 and B12, Ca remain as dietary inadequacy in the LD group, suggesting that availability play a role in ensuring dietary adequacy. Future studies to develop nutrient-dense foods and improved fish availability mapping which consider non-static position of market (mobile vendor) are recommended.

Low vitamin D associated with high parathyroid hormone (PTH) is common in HIV infection. We determined the association between total 25(OH)D and PTH in adolescents living with HIV, in Zambia and Zimbabwe. Adolescents (11–19 years) perinatally infected with HIV and established on antiretroviral therapy for ≥ 6 months were recruited into a cross-sectional study. Socio-demographic and clinical characteristics were recorded, anthropometry measured and fasted serum concentrations of 1,25(OH)2D, total 25(OH)D and intact PTH measured. The association between total 25(OH)D and PTH was examined using natural cubic spline regression. 842 participants (female: 53·2%) with a median age of 15·5 (IQR: 13·2–17·9) years were enrolled. Median antiretroviral therapy duration was 9·8 (IQR: 6·3–12·3) years, and 165/841 had an HIV viral-load >60 copies/ml. Stunting (height-for-age z-score <–2) and underweight (weight-for-age z-score <–2) were observed in 29·9 and 30·0%, respectively. Three-quarters reported daily Ca intakes <150 mg/d. The mean (sd) concentrations of total 25(OH)D and 1,25(OH)2D were 66·1(16·5) nmol/l and 210·6 (70·4) pmol/l, respectively, and median PTH level was 4·3 (IQR: 3·3–5·5) pmol/l. There was an inverse non-linear relationship between total 25(OH)D and PTH, 25(OH)D levelling off at 74·6 nmol/l (95 % CI: 74·5, 75·2). Results were consistent in those taking tenofovir disoproxil fumarate and virally unsuppressed participants. In this population with extremely low habitual Ca intakes, the lack of association between 25(OH)D and PTH when 25(OH)D exceeded 75 nmol/l potentially suggests that levels of 25(OH)D >75 nmol/l may need to be achieved to improve bone health; investigation is needed in future research studies.