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Background: The measurement of micronutrient status is essential to understand the health of individuals and populations, but there are limited data on the stability of micronutrients in whole blood.Objectives: The objective was to investigate the effects of delayed processing of whole blood on the stability of 25 micronutrient and selected clinical biomarkers.Methods: Blood from 16 healthy adults was collected into EDTA, lithium heparin (LH), or serum tubes. Samples were processed within 2 hours of collection ("2-hour processed") or mailed overnight (boxed with frozen cold packs) before processing ("24-hour processed"). Micronutrient and clinical biomarker concentrations were quantified with validated methods. The concentration percentage difference between the 2- and 24-hour processed samples was calculated and was compared against quality specifications determined from intra- and interindividual variations.Results: All analytes had a sample type where the percentage difference concentration between 2-hour and 24-hour processed samples was ≤4% and was acceptable based on calculated limits, including for biomarkers of vitamin A, vitamin D, thiamin, folate, vitamin B-12, iron (ferritin), and zinc status and for selected clinical markers, C-reactive protein, HDL and total cholesterol, and triglycerides. EDTA plasma vitamin C was lower compared to the 2-hour processed sample (geometric mean, 43%; 95% CI: 36%-49%). Pyridoxal-5-phosphate (vitamin B-6 biomarker) decreased, with differences from the 2-hour processed samples of -8% (95% CI: -13% to -2%) and -14% (95% CI: -18% to -9%) in LH plasma and serum, respectively.Conclusions: In blood collected from adult participants, delayed processing of chilled whole blood for 24 hours did not materially affect the measured concentrations of the majority of micronutrients and selected clinical biomarkers. This suggests that for these analytes, adherence to a 2-hour processing protocol may be unnecessary. This knowledge is valuable and may help to simplify logistics for sample transport and processing of blood samples for micronutrient status assessment. [ABSTRACT FROM AUTHOR]

Micronutrient (MN) deficiencies can produce a broad array of adverse health and functional outcomes. Young, preschool children and women of reproductive age in low- and middle-income countries are most affected by these deficiencies, but the true magnitude of the problems and their related disease burdens remain uncertain because of the dearth of reliable biomarker information on population MN status. The reasons for this lack of information include a limited understanding by policy makers of the importance of MNs for human health and the usefulness of information on MN status for program planning and management; insufficient professional capacity to advocate for this information and design and implement related MN status surveys; high costs and logistical constraints involved in specimen collection, transport, storage, and laboratory analyses; poor access to adequately equipped and staffed laboratories to complete the analyses reliably; and inadequate capacity to interpret and apply this information for public health program design and evaluation. This report describes the current situation with regard to data availability, the reasons for the lack of relevant information, and the steps needed to correct this situation, including implementation of a multi-component MN Data Generation Initiative to advocate for critical data collection and provide related technical assistance, laboratory services, professional training, and financial support. [ABSTRACT FROM AUTHOR]

Background: Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to coronavirus disease 2019 (COVID-19) infection, progression to symptoms, likelihood of severe disease, and survival.Objective: The aim was to review the latest evidence on how malnutrition across all its forms (under- and overnutrition and micronutrient status) may influence both susceptibility to, and progression of, COVID-19.Methods: We synthesized information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity, and diabetes; protein-energy malnutrition; anemia; vitamins A, C, D, and E; PUFAs; iron; selenium; zinc; antioxidants; and nutritional support. For each section we provide: 1) a landscape review of pertinent material; 2) a systematic search of the literature in PubMed and EMBASE databases, including a wide range of preprint servers; and 3) a screen of 6 clinical trial registries. All original research was considered, without restriction to study design, and included if it covered: 1) severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2), Middle East respiratory syndrome CoV (MERS-CoV), or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16 May and 11 August 2020.Results: Across the 13 searches, 2732 articles from PubMed and EMBASE, 4164 articles from the preprint servers, and 433 trials were returned. In the final narrative synthesis, we include 22 published articles, 38 preprint articles, and 79 trials.Conclusions: Currently there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery. However, results of clinical trials are eagerly awaited. Given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. Furthermore, there is strong evidence that prevention of obesity and type 2 diabetes will reduce the risk of serious COVID-19 outcomes. This review is registered at PROSPERO as CRD42020186194. [ABSTRACT FROM AUTHOR]

Background Infantile beriberi–related mortality is still common in South and Southeast Asia. Interventions to increase maternal thiamine intakes, and thus human milk thiamine, are warranted; however, the required dose remains unknown. Objectives We sought to estimate the dose at which additional maternal intake of oral thiamine no longer meaningfully increased milk thiamine concentrations in infants at 24 wk postpartum, and to investigate the impact of 4 thiamine supplementation doses on milk and blood thiamine status biomarkers. Methods In this double-blind, 4–parallel arm randomized controlled dose–response trial, healthy mothers were recruited in Kampong Thom, Cambodia. At 2 wk postpartum, women were randomly assigned to consume 1 capsule, containing 0, 1.2 (estimated average requirement), 2.4, or 10 mg of thiamine daily from 2 through 24 weeks postpartum. Human milk total thiamine concentrations were measured using HPLC. An Emax curve was plotted, which was estimated using a nonlinear least squares model in an intention-to-treat analysis. Linear mixed-effects models were used to test for differences between treatment groups. Maternal and infant blood thiamine biomarkers were also assessed. Results In total, each of 335 women was randomly assigned to1 of the following thiamine-dose groups: placebo (n =  83), 1.2 mg (n =  86), 2.4 mg (n =  81), and 10 mg (n =  85). The estimated dose required to reach 90% of the maximum average total thiamine concentration in human milk (191 µg/L) is 2.35 (95% CI: 0.58, 7.01) mg/d. The mean ± SD milk thiamine concentrations were significantly higher in all intervention groups (183 ± 91, 190 ± 105, and 206 ± 89 µg/L for 1.2, 2.4, and 10 mg, respectively) compared with the placebo group (153 ± 85 µg/L; P  < 0.0001) and did not significantly differ from each other. Conclusions A supplemental thiamine dose of 2.35 mg/d was required to achieve a milk total thiamine concentration of 191 µg/L. However, 1.2 mg/d for 22 wk was sufficient to increase milk thiamine concentrations to similar levels achieved by higher supplementation doses (2.4 and 10 mg/d), and comparable to those of healthy mothers in regions without beriberi. This trial was registered at clinicaltrials.gov as NCT03616288. [ABSTRACT FROM AUTHOR]

Background Fibroblast growth factor-23 (FGF23) regulates body phosphate homeostasis primarily by increasing phosphaturia. It also acts as a vitamin D-regulating hormone. Maternal iron deficiency is associated with perturbed expression and/or regulation of FGF23 and hence might be implicated in the pathogenesis of hypophosphatemia-driven rickets in their offspring. Objectives We aimed to determine the effect of antenatal oral iron supplementation on FGF23 concentration and maternal and infant markers of bone-mineral regulation. Methods We performed a secondary analysis of a trial in which 470 rural Kenyan women with singleton pregnancies and hemoglobin concentrations ≥ 90 g/L were randomly allocated to daily, supervised supplementation with 60 mg elemental iron as ferrous fumarate or placebo from 13–23 weeks of gestation until 1 mo postpartum. As previously reported, iron supplementation improved iron status in mothers and neonates. For the present study, we reanalyzed all available plasma samples collected in mothers and neonates at birth, with primary outcomes being concentrations of FGF23, measured by 2 assays: 1 that detects intact hormone and C-terminal cleavage products (total-FGF23) and another that detects the intact hormone only (intact-FGF23). Results Analysis was performed on 433 women (n  = 216, iron group; n  = 217, placebo group) and 414 neonates (n  = 207, iron group; n  = 207, placebo group). Antenatal iron supplementation reduced geometric mean total-FGF23 concentrations in mothers and neonates by 62.6% (95% CI: 53.0%, 70.3%) and 15.2% (95% CI: −0.3%, 28.4%, P  = 0.06), respectively. In addition, it increased geometric mean neonatal intact-FGF23 concentrations by 21.6% (95% CI: 1.2%, 46.1%), increased geometric mean maternal hepcidin concentrations by 136.4% (95% CI: 86.1%, 200.3%), and decreased mean maternal 25-hydroxyvitamin D concentrations by 6.1 nmol/L (95% CI: −11.0, −1.2 nmol/L). Conclusions Analysis of this randomized trial confirms that iron supplementation can reverse elevated FGF23 production caused by iron deficiency in iron-deficient mothers and their neonates. Further investigations are warranted to assess to what extent iron supplementation can prevent FGF23-mediated hypophosphatemic rickets or osteomalacia. [ABSTRACT FROM AUTHOR]

Background: Vitamin D is important to maternal, fetal, and infant health, but quality data on vitamin D status in low- and middle-income countries and response to cholecalciferol supplementation in pregnancy are sparse.Objective: We characterized vitamin D status and vitamin D metabolite change across pregnancy and in response to cholecalciferol supplementation in rural Gambia.Methods: This study was a secondary analysis of samples collected in a 4-arm trial of maternal nutritional supplementation [iron folic acid (FeFol); multiple micronutrients (MMN); protein energy (PE) as lipid-based supplement; PE + MMN]; MMN included 10 μg/d cholecalciferol. Plasma 25-hydroxycholecalciferol [25(OH)D3], 24,25-dihydroxycholecalciferol [24,25(OH)2D3], and C3-epimer-25-hydroxycholecalciferol [3-epi-25(OH)D3] were measured by LC-MS/MS in 863 women [aged 30 ± 7 y (mean ± SD)] in early pregnancy (presupplementation) and late pregnancy, (gestational age 14 ± 3 and 30 ± 1 wk). Changes in 25(OH)D3 and vitamin D metabolite concentrations and associations with pregnancy stage and maternal age and anthropometry were tested.Results: Early pregnancy 25(OH)D3 concentration was 70 ± 15 nmol/L and increased according to pregnancy stage (82 ± 18 and 87 ± 17 nmol/L in the FeFol and PE-arms) and to cholecalciferol supplementation (95 ± 19 and 90 ± 20 nmol/L in the MMN and PE + MMN-arms) (P < 0.0001). There was no difference between supplemented groups. Early pregnancy 25(OH)D3 was positively associated with maternal age and gestational age. Change in 25(OH)D3 was negatively associated with late pregnancy, but not early pregnancy, triceps skinfold thickness. The pattern of change of 24,25(OH)2D3 mirrored that of 25(OH)D3 and appeared to flatten as pregnancy progressed, whereas 3-epi-25(OH)D3 concentration increased across pregnancy.Conclusion: This study provides important data on the vitamin D status of a large cohort of healthy pregnant women in rural Africa. Without supplementation, vitamin D status increased during pregnancy, demonstrating that pregnancy stage should be considered when assessing vitamin D status. Nutritionally relevant cholecalciferol supplementation further increased vitamin D status. These data are relevant to the development of fortification and supplementation policies in pregnant women in West Africa. [ABSTRACT FROM AUTHOR]

Vitamin D binding protein (DBP) concentration is known to influence the availability and bioactivity of vitamin D metabolites but its diurnal rhythm (DR), its inter-relationships with the DRs of vitamin D metabolites and its influence on free vitamin D metabolite concentrations are not well described. The DRs of plasma total 25(OH)D, total 1,25(OH) 2 D, DBP, albumin and calculated free 25(OH)D and free 1,25(OH) 2 D were measured in men and women aged 60–75 years and resident in the UK ( n 30), Gambia ( n 31) and China ( n 30) with differences in lifestyle, dietary intake and vitamin D status. Blood samples were collected every 4 h for 24 h and DRs statistically analysed with Fourier regression. Gambians had significantly higher plasma concentrations of vitamin D metabolites and lower albumin concentration compared to the British and Chinese. Significant DRs were observed for all analytes and calculated free vitamin D metabolites (P < 0.01). The pattern of DRs was similar between countries. The magnitude of the DRs of free 1,25(OH) 2 D was attenuated compared to that of total 1,25(OH) 2 D whereas it was not different between total and free 25(OH)D. Relationships between the DRs were generally weak. There was no phase shift between 1,25(OH) 2 D and DBP with the strongest cross correlation at 0 h time lag ( r = 0.15, P = < 0.001). In comparison, 25(OH)D correlated less well with DBP (1 h time lag, r = 0.07, P = 0.12). These data demonstrate a relationship between the DRs of 1,25(OH) 2 D and DBP, possibly to maintain free 1,25(OH) 2 D concentrations. In contrast, the DRs of total and free 25(OH)D appeared to be less influenced by DBP, suggesting that DBP has comparatively less effect on 25(OH)D concentration and 25(OH)D availability. This work highlights the importance of standardisation in timing of sample collection particularly for the assessment of plasma protein concentrations. [ABSTRACT FROM AUTHOR]

Background: The mechanism and clinical significance of low circulating 25-hydroxyvitamin D [25(OH)D] in obese people are unknown. Low total 25(OH)D may be due to low vitamin D-binding proteins (DBPs) or faster metabolic clearance. However, obese people have a higher bone mineral density (BMD), which suggests that low 25(OH)D may not be associated with adverse consequences for bone. Objective: We sought to determine whether 1) vitamin D metabolism and 2) its association with bone health differ by body weight. Design: We conducted a cross-sectional observational study of 223 normal-weight, overweight, and obese men and women aged 25-75 y in South Yorkshire, United Kingdom, in the fall and spring. A subgroup of 106 subjects was also assessed in the winter. We used novel techniques, including an immunoassay for free 25(OH)D, a stable isotope for the 25(OH)D3 half-life, and high-resolution quantitative tomography, to make a detailed assessment of vitamin D physiology and bone health. Results: Serum total 25(OH)D was lower in obese and overweight subjects than in normal-weight subjects in the fall and spring (geometric means: 45.0 and 40.8 compared with 58.6 nmol/L, respectively; P < 0.001) but not in the winter. Serum 25(OH)D was inversely correlated with body mass index (BMI) in the fall and spring and in the winter. Free 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] were lower in obese subjects. DBP, the DBP genotype, and the 25(OH)D3 half-life did not differ between BMI groups. Bone turnover was lower, and bone density was higher, in obese people. Conclusions: Total and free 25(OH)D and 1,25(OH)2D are lower at higher BMI, which cannot be explained by lower DBP or the shorter half-life of 25(OH)D3. We speculate that low 25(OH)D in obesity is due to a greater pool of distribution. Lower 25(OH)D may not reflect at-risk skeletal health in obese people, and BMI should be considered when interpreting serum 25(OH)D as a marker of vitamin D status. [ABSTRACT FROM AUTHOR]

On a population basis, there is a gradual decline in vitamin D status (plasma 25(OH)D) throughout winter. We developed a mathematical model to predict the population winter plasma 25(OH)D concentration longitudinally, using age-specific values for 25(OH)D expenditure (25(OH)D 3 t 1/2 ), cross-sectional plasma 25(OH)D concentration and vitamin D intake (VDI) data from older (70+ years; n = 492) and younger adults (18–69 years; n = 448) participating in the UK National Diet and Nutrition Survey. From this model, the population VDI required to maintain the mean plasma 25(OH)D at a set concentration can be derived. As expected, both predicted and measured population 25(OH)D (mean (95%CI)) progressively declined from September to March (from 51 (40–61) to 38 (36–41) nmol/L (predicted) vs 38 (27–48) nmol/L (measured) in older people and from 59 (54–65) to 34 (31–37) nmol/L (predicted) vs 37 (31–44) nmol/L (measured) in younger people). The predicted and measured mean values closely matched. The predicted VDIs required to maintain mean winter plasma 25(OH)D at 50 nmol/L at the population level were 10 (0–20) to 11 (9–14) and 11 (6–16) to 13(11–16) μg/d for older and younger adults, respectively dependent on the month. In conclusion, a prediction model accounting for 25(OH)D 3 t 1/2 , VDI and scaling factor for the 25(OH)D response to VDI, closely predicts measured population winter values. Refinements of this model may include specific scaling factors accounting for the 25(OH)D response at different VDIs and as influenced by body composition and specific values for 25(OH)D 3 t 1/2 dependent on host factors such as kidney function. This model may help to reduce the need for longitudinal measurements. [ABSTRACT FROM AUTHOR]

The Department of Nutrition for Health and Development of the World Health Organization (WHO) in collaboration with the Executive Committee of the 18th Vitamin D Workshop (VDW), organised a joint symposium on the prevention and consequences of vitamin D deficiency in pregnant women and children, convening experts on vitamin D, clinicians and policy-makers. The overall aim was to identify priority areas for research and to discuss the need for global options for policy, with a focus on the prevention of rickets in infants and children and vitamin D deficiency in pregnant women. The scope and purpose were: (i) to present the WHO research strategy for health, addressing vitamin D-related public health problems and the process for the development of evidence-informed guidelines in general and how vitamin D interventions in diverse populations could be prioritised; (ii) to provide an overview of vitamin D status in children and pregnant and lactating women across the world; (iii) to review the health risks associated with vitamin D deficiency in children and in pregnant women and their offspring; (iv) to understand the aetiology of vitamin D deficiency in pregnant women and children; (v) to identify and interpret biomarkers to assess vitamin D status and to consider possible clinical and biochemical screening tools for determining the prevalence of nutritional rickets in at risk groups or communities; and (vi) to provide an overview of policies and recommendations on vitamin D across the world. The format of the symposium was a composite of comprehensive scientific presentations and a panel debate with international experts on WHO guidelines, nutritional rickets, nutritional policy and consequences of vitamin D deficiency during pregnancy. This paper summarizes the content and outcomes of the panel debate. [ABSTRACT FROM AUTHOR]