Gene-vegetarianism interactions in calcium, estimated glomerular filtration rate, and testosterone identified in genome-wide analysis across 30 biomarkers.

We examined the associations of vegetarianism with metabolic biomarkers using traditional and genetic epidemiology. First, we addressed inconsistencies in self-reported vegetarianism among UK Biobank participants by utilizing data from two dietary surveys to find a cohort of strict European vegetarians (N = 2,312). Vegetarians were matched 1:4 with nonvegetarians for non-genetic association analyses, revealing significant effects of vegetarianism in 15 of 30 biomarkers. Cholesterol measures plus vitamin D were significantly lower in vegetarians, while triglycerides were higher. A genome-wide association study revealed no genome-wide significant (GWS; 5×10-8) associations with vegetarian behavior. We performed genome-wide gene-vegetarianism interaction analyses for the biomarkers, and detected a GWS interaction impacting calcium at rs72952628 (P = 4.47×10-8). rs72952628 is in MMAA, a B12 metabolic pathway gene; B12 has major deficiency potential in vegetarians. Gene-based interaction tests revealed two significant genes, RNF168 in testosterone (P = 1.45×10-6) and DOCK4 in estimated glomerular filtration rate (eGFR) (P = 6.76×10-7), which have previously been associated with testicular and renal traits, respectively. These nutrigenetic findings indicate genotype can modify the associations between vegetarianism and health outcomes.

Effect of Daily Vitamin D Supplementation on Risk of Upper Respiratory Infection in Older Adults: A Randomized Controlled Trial.

BACKGROUND: Among individuals with vitamin D deficiency, daily vitamin D supplementation appears to lower risk of acute respiratory infection. However, recent trials, in different populations and using different regimens, have yielded null results. We investigated the effect of daily vitamin D supplementation (vs placebo) on risk of upper respiratory infection (URI) in older adults. METHODS: The VITamin D and OmegA-3 TriaL (VITAL) is a randomized, double-blind, placebo-controlled trial of supplemental vitamin D and/or omega-3 fatty acids in generally healthy men (age ≥50 years) and women (age ≥55 years). This prespecified analysis focuses on vitamin D3 (2000 IU/day) versus placebo in the 15 804 (61%) participants with baseline serum total 25-hydroxyvitamin D level. The primary outcome was self-report of a recent URI at 1-year follow-up. RESULTS: Participants had a mean age of 68 years and 51% were women; 76% were non-Hispanic White, 16% Black, and 8% other race/ethnicity. The mean 25-hydroxyvitamin D level at baseline was 31 (standard deviation, 10) ng/mL, with <12 ng/mL in 2.4%. The overall effect of vitamin D supplementation on recent URI was nonsignificant (odds ratio [OR], 0.96 [95% confidence interval {CI}, .86-1.06]). In the prespecified subgroup of primary interest (<12 ng/mL and denied taking concurrent vitamin D), which had only 255 participants, vitamin D supplementation was nonsignificant (OR, 0.60 [95% CI, .28-1.30]). Statistical power to assess effect modification in other subgroups was limited. CONCLUSIONS: In older adults not selected for vitamin D deficiency, supplemental vitamin D did not lower URI risk overall. Whether effects differ in subgroups requires further study. Clinical Trials Registration. NCT01169259.

High-dose vitamin D to attenuate bone loss in patients with prostate cancer on androgen deprivation therapy: A phase 2 RCT.

BACKGROUND: Androgen deprivation therapy (ADT) inhibits prostate cancer growth. However, ADT causes loss of bone mineral density (BMD) and an increase in fracture risk; effective interventions for ADT-induced bone loss are limited. METHODS: A phase 2 randomized controlled trial investigated the feasibility, safety, and preliminary efficacy of high-dose weekly vitamin D (HDVD, 50,000 IU/week) versus placebo for 24 weeks in patients with prostate cancer receiving ADT, with all subjects receiving 600 IU/day vitamin D and 1000 mg/day calcium. Participants were ≥60 years (mean years, 67.7), had a serum 25-hydroxyvitamin D level <32 ng/mL, and initiated ADT within the previous 6 months. At baseline and after intervention, dual-energy x-ray absorptiometry was used to assess BMD, and levels of bone cell, bone formation, and resorption were measured. RESULTS: The HDVD group (N = 29) lost 1.5% BMD at the total hip vs. 4.1% for the low-dose group (N = 30; p = .03) and 1.7% BMD at the femoral neck vs. 4.4% in the low-dose group (p = .06). Stratified analyses showed that, for those with baseline 25-hydroxyvitamin D level <27 ng/mL, the HDVD group lost 2.3% BMD at the total hip vs 7.1% for the low-dose group (p < .01). Those in the HDVD arm showed significant changes in parathyroid hormone (p < .01), osteoprotegerin (p < 0.01), N-terminal telopeptide of type 1 collagen (p < 0.01) and C-terminal telopeptide of type 1 collagen (p < 0.01). No difference in adverse events or toxicity was noted between the groups. CONCLUSIONS: HDVD supplementation significantly reduced hip and femoral neck BMD loss, especially for patients with low baseline serum 25-hydroxyvitamin D levels, although demonstrating safety and feasibility in prostate cancer patients on ADT.

Circulating 25-hydroxyvitamin D and survival outcomes of colorectal cancer: evidence from population-based prospective cohorts and Mendelian randomisation.

BACKGROUND: To investigate the association between circulating 25-hydroxyvitamin D (25-OHD) and colorectal cancer (CRC) survival outcomes. METHODS: We conducted analyses among the Study of Colorectal Cancer in Scotland (SOCCS) and the UK Biobank (UKBB). Both cancer-specific survival (CSS) and overall survival (OS) outcomes were examined. The 25-OHD levels were categorised into three groups, and multi-variable Cox-proportional hazard models were applied to estimate hazard ratios (HRs). We performed individual-level Mendelian randomisation (MR) through the generated polygenic risk scores (PRS) of 25-OHD and summary-level MR using the inverse-variance weighted (IVW) method. RESULTS: We observed significantly poorer CSS (HR = 0.65,95%CI = 0.55-0.76,P = 1.03 × 10-7) and OS (HR = 0.66,95%CI = 0.58-0.75,P = 8.15 × 10-11) in patients with the lowest compared to those with the highest 25-OHD after adjusting for covariates. These associations remained across patients with varied tumour sites and stages. However, we found no significant association between 25-OHD PRS and either CSS (HR = 0.98,95%CI = 0.80-1.19,P = 0.83) or OS (HR = 1.07,95%CI = 0.91-1.25,P = 0.42). Furthermore, we found no evidence for causal effects by conducting summary-level MR analysis for either CSS (IVW:HR = 1.04,95%CI = 0.85-1.28,P = 0.70) or OS (IVW:HR = 1.10,95%CI = 0.93-1.31,P = 0.25). CONCLUSION: This study supports the observed association between lower circulating 25-OHD and poorer survival outcomes for CRC patients. Whilst the genotype-specific association between better outcomes and higher 25-OHD is intriguing, we found no support for causality using MR approaches.

Optimisation of vitamin D status in global populations.

Vitamin D is important for musculoskeletal health. Concentrations of 25-hydroxyvitamin D, the most commonly measured metabolite, vary markedly around the world and are influenced by many factors including sun exposure, skin pigmentation, covering, season and supplement use. Whilst overt vitamin D deficiency with biochemical consequences presents an increased risk of severe sequelae such as rickets, osteomalacia or cardiomyopathy and usually warrants prompt replacement treatment, the role of vitamin D supplementation in the population presents a different set of considerations. Here the issue is to keep, on average, the population at a level whereby the risk of adverse health outcomes in the population is minimised. This position paper, which complements recently published work from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, addresses key considerations regarding vitamin D assessment and intervention from the population perspective. This position paper, on behalf of the International Osteoporosis Foundation Vitamin D Working Group, summarises the burden and possible amelioration of vitamin D deficiency in global populations. It addresses key issues including screening, supplementation and food fortification.

Predictive value of Vitamin D levels in pregnant women on gestational length and neonatal weight in China: a population-based retrospective study.

BACKGROUND: Vitamin D deficiency, a common occurrence among pregnant women, is an emerging public health concern worldwide. According to research, prenatal vitamin D deficiency is associated with various complications. This study assessed the vitamin D status of pregnant women in Yanbian, Jilin Province, as well as the correlation and predictive value of their vitamin D levels in relation to gestational length (weeks) and fetal weight, aiming to provide a basis for clinical diagnosis and treatment. METHODS: We conducted a population-based retrospective study involving 510 pregnant women from August 2019 to October 2022. Blood samples were collected at 16-20 weeks of gestation for the detection of serum vitamin D levels. Statistical analyses were performed using SPSS 28.0 and R 4.1.0 software. Multifactorial logistic regression analysis was employed to establish whether each variable was a risk factor for deliveries at ≤ 38 gestational weeks and low fetal weight. These results were used to construct a risk prediction model, and the model's predictive efficacy was evaluated. Results or differences with p < 0.05 were considered statistically significant. RESULTS: Multifactorial logistic regression analysis revealed that vitamin D ≤ 14.7 ng/mL(OR: 1.611; 95% CI: 1.120-2.318; P = 0.010), Bone Mineral Density (BMD) T-value ≤-1(OR: 1.540; 95%CI: 1.067-2.223; P = 0.021), and gestational hypertension(OR: 7.173; 95% CI: 1.482-34.724; P = 0.014) were the independent risk factors for deliveries at ≤ 38 gestational weeks. Additionally, vitamin D ≤ 14.7 ng/mL(OR: 1.610; 95%CI: 1.123-2.307; P = 0.009), BMD T-value ≤ -1(OR: 1.560; 95%CI: 1.085-2.243; P = 0.016), and gestational hypertension(OR: 4.262; 95% CI: 1.058-17.167; P = 0.041) were the independent risk factors for low fetal weight (< 3400 g). CONCLUSION: This study revealed that low vitamin D levels are an independent risk factor for a short gestational length and low fetal weight. Prenatal low BMD T-value and comorbid hypertensive disorders were also found to increase the risk of a short gestational length and low fetal weight.

Cholesterol Interference in the Assessment of Vitamin D Status: A Canadian Health Measures Survey Biobank Project.

BACKGROUND: Matrix effects are a known problem with immunoassays measuring serum 25-hydroxyvitamin D [25(OH)D]. OBJECTIVES: To determine if the inverse association between serum 25(OH)D and serum cholesterol concentrations is a function of assay method: Diasorin Liaison 25(OH) Vitamin D Total Assay (Liaison Total Assay), an immunoassay, compared with liquid chromatography tandem mass spectrometry (LC-MS/MS). METHODS: Canadian Health Measures Survey data and biobank serum (White males aged 20-79 y, n = 392) were evaluated for bias in serum 25(OH)D using Bland-Altman plots. Differences in serum 25(OH)D (Liaison Total Assay - LC-MS/MS) were compared among non-HDL-cholesterol <4.2 (n = 295) compared with ≥4.2 (n = 97) mmol/L and total cholesterol groups <5.2 (n = 256) compared with ≥5.2 (n = 136) mmol/L, and associations tested between 25(OH)D and non-HDL-cholesterol or total cholesterol concentrations, using regression. RESULTS: Serum 25(OH)D measured using Liaison Total Assay ranged from 10.7 to 137.0 nmol/L and 14.4 to 137.9 nmol/L by LC-MS/MS. Liaison Total Assay - LC-MS/MS showed a negative bias of 5.5 (95% limits of agreement -23.8, 12.7) nmol/L. Differences in 25(OH)D were -4.0 ± 9.0 (±SD) nmol/L if non-HDL-cholesterol was <4.2 mmol/L and -10.2 ± 8.7 nmol/L if ≥4.2 mmol/L (P < 0.0001). Differences in 25(OH)D, if total cholesterol was <5.2 mmol/L, were -3.4 ± 8.6 nmol/L and -9.6 ± 9.3 nmol/L if ≥5.2 mmol/L (P < 0.0001). Serum non-HDL-cholesterol (beta -3.17, P = 0.0014) and total cholesterol (beta -2.77, P = 0.0046) were inversely associated with Liaison Total Assay 25(OH)D (adjusted for age, fasting, and body mass index), but not with LC-MS/MS measured 25(OH)D. Interference by these lipoproteins was not eliminated by standardization of the Liaison Total Assay. Similar associations were observed with triglycerides as for the lipoproteins. CONCLUSIONS: Total cholesterol inversely associates with 25(OH)D, which is likely due to elevated non-HDL-cholesterol lipoprotein or triglyceride interference with the Liaison Total Assay. This is important as elevated cholesterol is common, and an underestimation of vitamin D status could be an unnecessary cause for concern.

The Relationship Between Vitamin D Intake and Serum 25-hydroxyvitamin D in Young Children: A Meta-Regression to Inform WHO/FAO Vitamin D Intake Recommendations.

BACKGROUND: This work was commissioned by the World Health Organization and Food and Agriculture Organization to inform their update on the vitamin D requirements for children aged <4 y. OBJECTIVES: The objective of this work was to undertake multilevel and multivariable dose-response modeling of serum 25-hydroxyvitamin D (25OHD) to total vitamin D intake in children aged <4 y with the goal of deriving updated vitamin D requirements for young children. METHODS: Systematically identified randomized controlled trials among healthy children from 2 wk up to 3.9 y of age provided with daily vitamin D supplements or vitamin D-fortified foods were included. Linear and nonlinear random effects multilevel meta-regression models with and without covariates were fitted and compared. Interindividual variability was included by simulating the individual serum 25OHD responses. The percentage of individuals reaching set minimal and maximal serum 25OHD thresholds was calculated and used to derive vitamin D requirements. RESULTS: A total of 31 trials with 186 data points from North America, Europe, Asia, and Australasia/Oceania, with latitudes ranging from 61°N to 38°S, and with participants of likely mostly light or medium skin pigmentation, were included. In 29 studies the children received vitamin D supplements and in 2 studies the children received vitamin D-fortified milk with or without supplements. The dose-response relationship between vitamin D intake and serum 25OHD was best fitted with the unadjusted quadratic model. Adding additional covariates, such as age, did not significantly improve the model. At a vitamin D intake of 10 µg/d, 97.3% of the individuals were predicted to achieve a minimal serum 25OHD threshold of 28 nmol/L. At a vitamin D intake of 35 µg/d, 1.4% of the individuals predicted to reach a maximal serum 25OHD threshold of 200 nmol/L. CONCLUSIONS: In conclusion, this paper details the methodological steps taken to derive vitamin D requirements in children aged <4 y, including the addition of an interindividual variability component.

Association of serum 25-hydroxy-vitamin D concentration and risk of mortality in cancer survivors in the United States.

PURPOSE: Cancer survivors have a high risk of mortality, and vitamin D (VD) is associated with the risk of mortality. This study is aim to examine the impact of VD on mortality in cancer survivors. METHODS: A prospective study was conducted using data from the National Health and Nutrition Examination Survey. Participants were obtained information on their baseline characteristics, dietary habits, comorbidities, lifestyle, and serum 25-hydroxy VD [25(OH)D] concentrations. The weighted Cox proportional hazard and competing risk regression models were used to estimate the hazard ratio and 95% confidence intervals (HR, 95% CI) of mortality for different serum 25(OH)D concentrations. Restricted cubic spline (RCS) curves were utilized to illustrate the dose-response relationship between serum 25(OH)D concentrations and mortality. RESULTS: The study encompassed 2,495 participants with cancer diagnoses. Multivariate models indicated that, compared to serum 25(OH)D concentrations below 58.5 nmol/L, concentrations exceeding 81.6 nmol/L were associated with reduced HRs for all-cause mortality (HR = 0.70; 95% CI: 0.56-0.87), cardiovascular mortality (HR = 0.53; 95% CI: 0.32-0.86), and cancer-specific mortality (HR = 0.66; 95% CI: 0.45-0.99). RCS curves revealed "L-shaped" associations between serum 25(OH)D concentration and both all-cause and cancer-specific mortality, with threshold effects at 87.9 nmol/L and 84.6 nmol/L, respectively. Conversely, the relationship between serum 25(OH)D concentration and cardiovascular mortality exhibited a more linear pattern, with a threshold at 88.7 nmol/L. Subgroup analyses highlighted a gender-specific interaction that elevated serum 25(OH)D concentrations were significantly more protective against mortality in males than in females, especially regarding cancer-specific mortality (P-interaction = 0.009). CONCLUSION: Elevated serum 25(OH)D concentrations were correlated with decreased risks of all-cause, cardiovascular, and cancer-specific mortality in cancer survivors, with benefit thresholds at 87.9, 88.7, and 84.6 nmol/L, respectively. These findings suggested that cancer survivors might benefit from higher vitamin D recommendations than the general population.

Association between Serum 25-Hydroxyvitamin D Levels and Sarcopenia in Patients Undergoing Chronic Haemodialysis.

INTRODUCTION: Sarcopenia and vitamin D deficiency are highly prevalent among patients undergoing haemodialysis. Although vitamin D deficiency, assessed using serum 25-hydroxyvitamin D (25(OH)D) levels, is known to be associated with sarcopenia in the general population, whether serum 25(OH)D levels are associated with sarcopenia in patients undergoing haemodialysis with suppressed renal activation of 25(OH)D remains unclear. This study aimed to examine the association between serum 25(OH)D levels and sarcopenia in patients undergoing haemodialysis. METHODS: Serum 25(OH)D level measurements and assessment of sarcopenia using the Asian Working Group for Sarcopenia criteria were conducted in 95 stable outpatients undergoing maintenance haemodialysis therapy. RESULTS: Sarcopenia was observed in 22 (23.1%) patients. In multiple logistic regression analysis, serum 25(OH)D levels were associated with sarcopenia (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.77-0.99, p = 0.039) independent of traditional risk factors for sarcopenia. In multiple linear regression analyses, serum 25(OH)D levels were associated with parameters of skeletal muscle mass and strength (ß = 0.145, p = 0.046, and ß = 0.194, p = 0.020, respectively). The adjusted OR for sarcopenia was 5.60 (95% CI 1.52-20.57, p = 0.009) in the vitamin D deficiency group categorized based on the cut-off serum 25(OH)D level of 10 ng/mL. Regarding model discrimination, adding vitamin D deficiency to the traditional risk factors significantly improved the integrated discrimination improvement score (0.093, p = 0.007). CONCLUSION: Lower serum 25(OH)D levels were associated with sarcopenia independent of traditional risk factors in patients undergoing haemodialysis with suppressed vitamin D activation in the kidney. This finding implies that circulating 25(OH)D may have an important relationship with the skeletal muscle function of patients undergoing haemodialysis, and its measurement may be recommended to identify patients at high risk for sarcopenia among those undergoing haemodialysis.

The effects of cholecalciferol and afamelanotide on vitamin D levels in erythropoietic protoporphyria: a multicentre cohort study.

BACKGROUND: Patients with erythropoietic protoporphyria experience lifelong painful photosensitivity resulting in a lack of sunlight exposure. Previous studies have shown that 47-63% of patients with EPP suffer from vitamin D deficiency and a high prevalence of osteoporosis. An effective treatment for EPP has been available since 2016: the α-melanocyte stimulating hormone analogue afamelanotide. So far, studies on vitamin D levels in EPP have only investigated patients who have not been treated with afamelanotide. OBJECTIVES: To investigate the effects of afamelanotide treatment on vitamin D levels in EPP. METHODS: A multicentre observational cohort study in adults with EPP from the Erasmus Medical Centre, the Netherlands, and the University Hospital Düsseldorf, Germany, was carried out. Routinely collected vitamin D levels between 2005 and 2021 were used for analysis. Patient exposure to cholecalciferol or afamelanotide was categorized into four treatment groups: untreated, cholecalciferol, afamelanotide and combined treatment. A linear mixed model for longitudinal data was applied to measure the effect of the treatment groups compared with the untreated groups on vitamin D levels. RESULTS: A total of 230 patients and 1774 vitamin D measurements were included. The prevalence of vitamin D deficiency and severe deficiency remained high despite afamelanotide treatment (< 50 nmol L-1 in 71.8% of patients and < 30 nmol L-1 in 48.1%, respectively). Afamelanotide treatment alone did not lead to a significant average increase in vitamin D levels [ß = 0.5, 95% confidence interval (CI) -3.2 to 4.2]. In contrast, cholecalciferol and combined therapy with afamelanotide led to a significant increase in vitamin D levels [ß = 11.6 (95% CI 7.2-15.9) and ß = 15.2 (95% CI 12.3-18.1), respectively]. CONCLUSIONS: Cholecalciferol remains essential for the treatment of vitamin D deficiency in EPP, irrespective of new treatment options like afamelanotide. Afamelanotide treatment did not affect vitamin D levels. We suggest that future guidelines include continuous monitoring of vitamin D and a prescription for cholecalciferol in all patients with EPP, including those treated with afamelanotide.

Erythropoietic protoporphyria (EPP) is a rare inherited condition. People with EPP experience severe pain after their skin has been exposed to sunlight. To avoid this severe pain, people with EPP avoid going out in the sun by limiting outdoor activities or by wearing protective clothing. As sunlight is needed for our skin to produce vitamin D, approximately half of people with EPP in Europe do not have enough of it. In 2016, a new treatment called afamelanotide (SCENESSE®) became available, which allows people with EPP to go outside and expose themselves to sunlight longer without pain. In this study, we looked at how afamelanotide and vitamin D supplements affect vitamin D levels in people with EPP. We included information from patients treated in Rotterdam in the Netherlands and Düsseldorf in Germany and analysed levels of vitamin D in their blood. We also examined electronic patient files and collected questionnaires on the use of vitamin D supplements. In total, information from 230 patients was included. We found that afamelanotide alone did not raise vitamin D levels, but in combination with vitamin D supplements, vitamin D levels did go up. Even though afamelanotide is now available, our findings suggest that people with EPP may need more time to adapt to an outdoor lifestyle, after being conditioned to avoid sunlight since their childhood. Overall, our study demonstrates that vitamin D supplements remain crucial for people with EPP, with or without afamelanotide treatment.

Effect of vitamin D on pregnancy in women with polycystic ovary syndrome: retrospective and prospective studies.

RESEARCH QUESTION: Does vitamin D affect the pregnancy rate of patients with polycystic ovary syndrome (PCOS) receiving ovulation-induction therapy? DESIGN: The retrospective study included 200 patients with PCOS and 200 healthy women. The prospective study included 160 patients with PCOS receiving vitamin D or placebo supplementation. Pregnancy rates were assessed after a maximum of three cycles of ovulation induction. Serum concentrations of 25-hydroxycalciferol [25-(OH)D3], LH, FSH, progesterone, oestradiol, testosterone and fasting insulin; LH/FSH ratio; and body mass index were evaluated. RESULTS: In the retrospective study, patients with PCOS had lower 25-(OH)D3 concentrations than healthy women, pregnant patients with PCOS had higher 25-(OH)D3 concentrations than non-pregnant patients with PCOS (both P = 0.000), and the pregnancy rate was lower in the vitamin-D-deficient group compared with the non-vitamin-D-deficient group (P = 0.022). In the prospective study, compared with placebo supplementation, vitamin D supplementation increased the serum concentration of 25-(OH)D3 (P = 0.000), and reduced the LH/FSH ratio, and concentrations of LH and testosterone significantly (all P ≤ 0.049). After the intervention, it was found that the LH/FSH ratio, and concentrations of LH and testosterone were significantly lower in both groups compared with pre-intervention (P = 0.000). After ovulation induction, the pregnancy rate was higher in patients in the vitamin D supplementation group compared with the placebo supplementation group (P = 0.049). CONCLUSIONS: Vitamin D deficiency is common in patients with PCOS, and vitamin-D-deficient patients with PCOS have lower pregnancy rates after ovulation induction compared with non-vitamin-D-deficient patients with PCOS. Vitamin D supplementation can improve the pregnancy rate and mitigate basic hormone disorders. Therefore, monitoring vitamin D supplementation and checking vitamin D concentrations before and during interventions are essential for patients with PCOS.

Low-grade inflammation from prenatal period to age 6-8 years in a Vitamin D trial.

BACKGROUND: Low-grade systemic inflammation measured as high sensitivity C-reactive protein (hs-CRP) has been associated with non-communicable disease risk. We assessed whether prenatal inflammation and early-childhood vitamin D are associated with inflammation until age 6-8. METHODS: We analyzed blood hs-CRP and 25-hydroxy vitamin D [25(OH)D] in pregnancy, at birth from umbilical cord blood (UCB), from offspring at ages 1, 2, and 6-8 years in the Vitamin D Intervention in Infants (VIDI) study. VIDI was a randomized-controlled trial of vitamin D supplementation of 10 µg/day or 30 µg/day from age 2 weeks until 2 years in 975 infants recruited in 2013-14, with follow-up at age 6-8 in 2019-21 (n = 283). RESULTS: Pregnancy hs-CRP was associated with UCB hs-CRP (r = 0.18, p < 0.001) but not independently with childhood hs-CRP (Estimate [95% CI] 0.04 [<-0.00, 0.09]). Higher UCB hs-CRP was associated independently with higher hs-CRP until 6-8 years (0.20 [0.12, 0.29]). Infant vitamin D dose had no effect on longitudinal hs-CRP (6-8 years, 0.11 [-0.04, 0.25]). Childhood 25(OH)D were associated positively with hs-CRP until age 6-8 (0.01 [>0.00, 0.01]). CONCLUSION: Our results indicate that in children, inflammation, assessed by hs-CRP, persists from birth until 6-8 years. We observed positive associations between 25(OH)D and hs-CRP in vitamin D-sufficient children. IMPACT: High sensitivity C-reactive protein (hs-CRP) concentrations tract from birth to age 8 years Our novel finding suggests a long-lasting pro-inflammatory phenotype in the child Higher vitamin D concentration - but not dose - is associated with higher childhood hs-CRP Chronic disease risk related to inflammation may in part originate from the prenatal period or early childhood Further studies are needed to investigate the effects of inflammation on long-term clinical health outcomes.

Relationship of serum and dietary vitamin D with high cardiometabolic risk in Mexican systemic lupus erythematosus patients: A cross-sectional study.

Objetive: Serum and dietary vitamin D could influence clinical disease activity and cardiometabolic outcomes in systemic lupus erythematosus (SLE). This study aimed to assess the relationship of serum and dietary vitamin D with cardiometabolic risk in Mexican SLE patients and healthy subjects (HS).Methods: 224 SLE patients and 201 HS were included in this cross-sectional study. Serum calcidiol was measured using a competitive enzyme-linked immunosorbent assay (ELISA). Vitamin D dietary intake was assessed by collecting three 24h food records. Dietary patterns (DPs) were identified using principal component analysis (PCA). Cardiometabolic status was analyzed through biochemical measurements and cardiometabolic indexes.Results: Calcidiol deficiency (<20 ng/mL) was associated with 1.66-fold higher risk of excess weight by body mass index (BMI) (≥25 kg/m2) (p = .02), 2.25-fold higher risk to low high-density lipoprotein-cholesterol (HDL-C) (<40 mg/dL) (p < .001), and 1.74-fold higher risk to high triglycerides (TG) ≥150 mg/dL (p = .02). Inadequate vitamin D dietary intake was associated with 1.92-fold higher risk of presenting non-healthy waist circumference (WC) (>80 cm) (p < .01), 2.05-fold higher risk of android waist to hip ratio (WHR ≥85) (p < .01), and 1.72-fold higher risk to excess weight (p = .02). Non-adherence to a DP rich in vitamin D food sources was associated with higher WC, WHR, triglycerides, and lower high-density lipoprotein-cholesterol (HDL-C); furthermore, in HS, non-adherence to the DP rich in vitamin D food sources provided 2.11-fold higher risk to calcidiol deficiency.In Cconclusion: A pattern of Calcidiol deficiency, inadequate vitamin D dietary intake, and non-adherence to a DP rich in vitamin D food sources was related to high cardiometabolic risk in SLE patients and HS.

The contribution of milk substitutes to the nutritional status of children with cow's milk allergy.

BACKGROUND: The impact of alternative milk substitutes on the nutritional status of children with cow's milk allergy (CMA), the prevailing cause of food allergies, is unresolved. METHODS: A cross-sectional study was performed in children older than 2 years with IgE-mediated CMA. Patients' clinical characteristics, anthropometric measurements, dietary intake (by 3-day food diary), and biochemical markers of nutritional status were assessed. RESULTS: One hundred two children with CMA (68.6% boys; median age, 3.7 years; 51% multiple food allergies) were evaluated. 44.1% of the children consumed plant-based beverages (PBB), 19.6% therapeutic formula and 36.3% did not consume any milk substitutes. In all age groups, dietary calcium, riboflavin, and vitamin D intake of those who did not use milk substitutes were lower than those who consumed formula or PBB (p < .01). Also in the 2-3 years old age group, dietary zinc (p = .011) and iron intake (p = .004) of the formula-fed group was higher. Formula-fed patients had higher levels of 25-OH vitamin D (µg/L) and serum vitamin B12 (ng/L) than PBB-fed patients (respectively; p < .001, p = .005) and those who did not consume any milk substitute (p < .001). Patients of all ages who did not utilize a milk substitute failed to obtain an adequate amount of dietary calcium. CONCLUSION: The use of milk substitutes positively affects dietary calcium, riboflavin, and vitamin D intake in CMA, but their contribution is variable. Those who do not use milk substitutes are at greater risk inadequate of dietary calcium intake. Personalized nutritional advice, given the clinical diversity and the impact of individual differences, is required.

Associations Between Vitamin D Deficiency/Insufficiency and Depression Expose Health Disparities in Older Rural West Texans: A Project FRONTIER Study.

OBJECTIVE: To determine associations between Vitamin D (VD) levels and clinical depression through the Geriatric Depression Scale (GDS) and its questions and subdomains, stratified by demographics and Hispanic/Latino ethnicity (HLE). DESIGN, SETTING, AND PARTICIPANTS: A cohort of 299 Project FRONTIER participants aged 62.6 ± 11.7 years old, 70.9% female, and 40.5% HLE were used. Standard correlation and regression analyses were employed. MEASUREMENTS: The main outcome measures were VD (serum 25(OH)-VD) level, GDS-30 (30-item questionnaire), GDS-30 subfactors and questions, and HLE status. VD categories were defined as VD deficiency (VDD; ≤20 ng/mL), VD insufficiency (VDI; 21-29 ng/mL), VD sufficiency (30-38 ng/mL) and high VD sufficiency (>38 ng/mL). RESULTS: The majority (61.5%) of samples fell into VDD/VDI categories. A significant negative association was found between VD level and GDS-30 total score. VD level was negatively correlated with Dysphoria and Meaninglessness GDS-30 subfactors. Although GDS subfactors were similar between HLE and non-HLE groups, VD levels were significantly lower in HLE samples. Finally, HLE/non-HLE groups were differentially stratified across VD categories. Only 4% of HLEs fell into the high VD sufficient category, suggesting low VD supplementation. CONCLUSION: A significant negative association between VD level and depressive symptoms was revealed in our aging Project FRONTIER participants. HLE individuals were overrepresented in VDD/VDI samples, and VDD/VDI was associated primarily with the Dysphoria GDS subdomain. Regression analysis predicted high VD sufficiency (95.5 ng/mL) to be associated with no depressive symptoms (GDS=0). Our results underscore troubling disparities in VD-related depressive symptoms between HLE and non-HLE populations.

Effect of different nutrients on blood glucose, inflammatory response and oxidative stress in gestational diabetes mellitus: a network meta-analysis.

We searched PubMed, Web of Science, Embase, The Cochrane Library, China Biomedical Literature Database and other databases from inception to June 2023. The included studies were randomised controlled trials (RCT). The studies were screened by four authors, divided into two independent pairs. A total of eighteen studies were included, including 1362 patients, involving twelve intervention measures. The different nutrients had a significant effect on improving blood glucose, reducing inflammation levels and reducing oxidative stress compared with placebo (P < 0.05). Cumulative probability ranking showed that vitamin A + vitamin D + vitamin E ranked first in lowering fasting blood glucose (standardised mean difference (SMD) = 41.30, 95 % CI (2.07, 825.60)) and postprandial 2-h blood glucose (SMD = 15.19, 95 % CI (4.16, 55.53)). In terms of insulin resistance index, the first highest probability ranking is vitamin D (SMD = 5.12, 95 % CI (0.76, 34.54)). In terms of reducing the high-sensitivity C-reactive protein level, the first in probability ranking is VE (SMD = 2.58, 95 % CI (1.87,3.55)). The results of cumulative probability ranking showed that Mg + Zn + Ca + VD ranked first in reducing TNF-α (SMD = 1.90, 95% CI (0.40, 9.08)) and IL-6 (SMD = 1.83, 95 % CI (0.37, 9.12)). In terms of reducing malondialdehyde levels, the first ranked probability is VB1 (SMD = 4.99, 95 % CI (1.85, 13.46)). Cumulative probability ranking results showed that Ca + VD ranked first in reducing total antioxidant capacity (SMD = 0.66,95 % CI (0.38, 1.15)) and glutathione (SMD = 1.39, 95 % CI (0.43, 4.56)). In conclusion, nutritional interventions have significant effects on improving blood glucose, inflammatory levels and oxidative stress in patients with gestational diabetes. Due to the high uncertainty in the results and differences in the number and quality of studies included, the reliability of the conclusions still needs to be validated by conducting large-sample, high-quality RCT studies.

Effect of vitamin D supplementation or fortification on bone turnover markers in women: a systematic review and meta-analysis.

Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was performed to investigate the effects of vitamin D supplementation/fortification on bone turnover markers in women. All human randomised clinical trials reported changes in bone resorption markers (serum C-terminal telopeptide of type-I collagen (sCTX) and urinary type I collagen cross-linked N-telopeptide (uNTX)) or bone formation factors (osteocalcin (OC), bone alkaline phosphatase (BALP) and procollagen type-1 intact N-terminal propeptide (P1NP)) following vitamin D administration in women (aged ≥ 18 years) were considered. Mean differences (MD) and their respective 95 % CI were calculated based on fixed or random effects models according to the heterogeneity status. Subgroup analyses, meta-regression models, sensitivity analysis, risk of bias, publication bias and the quality of the included studies were also evaluated. We found that vitamin D supplementation had considerable effect on sCTX (MD: -0·038, n 22) and OC (MD: -0·610, n 24) with high heterogeneity and uNTX (MD: -8·188, n 6) without heterogeneity. Our results showed that age, sample size, dose, duration, baseline vitamin D level, study region and quality of studies might be sources of heterogeneity in this meta-analysis. Subgroup analysis also revealed significant reductions in P1NP level in dose less than 600 µg/d and larger study sample size (>100 participants). Moreover, no significant change was found in BALP level. Vitamin D supplementation/fortification significantly reduced bone resorption markers in women. However, results were inconsistent for bone formation markers.

The association of milk and multiple food avoidance with growth parameters in infants and children.

BACKGROUND: Recent studies reported that strict avoidance of milk products in cow's milk allergy (CMA) affects growth and bone turnover, causing negative calcium balance and changes in bone metabolism. OBJECTIVE: To investigate biochemical parameters to predict bone turnover and its relations with height and weight measurements and nutritional intake. METHODS: Height, weight, and body mass index z scores were plotted for age according to the World Health Organization. A 3-consecutive day food record was analyzed for nutritional values of foods. The blood levels of calcium, phosphorus, alkaline phosphatase, vitamin D, and parathyroid hormone (PTH) were determined. RESULTS: The study included 69 controls, 66 children with isolated CMA, and 59 children with multiple food allergy (FA). The z scores for weight, height, and body mass index were lower in isolated CMA and multiple FA groups than controls (P < .001, P = .004, and P = .002, respectively). The nutritional intakes of protein, fat, carbohydrates, vitamins B2 and B12, niacin, calcium, and phosphorus were significantly lower in isolated CMA and multiple FA than controls. In infants (≤2 years of age), although blood calcium level was in normal range, it was significantly lower in isolated CMA and multiple FA than in controls (P < .001). In children older than 2 years, PTH level was significantly higher in isolated CMA and multiple FA groups than in controls (P = .003). CONCLUSION: Our study revealed that children with isolated CMA and multiple FA had a high nutrition gap, growth deceleration, and unbalanced bone metabolism, as illustrated by low blood calcium and elevated PTH levels.

Environment and arthritis.

The present narrative review explores the multifactorial aetiology of rheumatoid arthritis (RA) and other immunemediated inflammatory disorders (IMIDs), emphasising the significant role of various environmental factors in disease development and exacerbation. Key modifiable environmental factors such as cigarette smoking and air pollution are identified as major contributors to RA. We will also focus on the influence of weather, seasonality, and particularly vitamin D levels, on RA activity, suggesting potential for seasonal management and supplementation to mitigate disease severity. The emerging role of diet and the gut microbiome in RA pathogenesis and progression is discussed as well, with dietary interventions and specific nutrients like omega-3 fatty acids offering protective benefits against inflammation. Despite the mounting evidence around these factors, further research is needed, to better understand the clinical impacts on RA, including well-designed randomised clinical trials.