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High-Dose Vitamin D3 Administration Is Associated With Increases in Hemoglobin Concentrations in Mechanically Ventilated Critically Ill Adults: A Pilot Double-Blind, Randomized, Placebo-Controlled Trial.
Smith, EM, Jones, JL, Han, JE, Alvarez, JA, Sloan, JH, Konrad, RJ, Zughaier, SM, Martin, GS, Ziegler, TR, Tangpricha, V
JPEN. Journal of parenteral and enteral nutrition. 2018;42(1):87-94
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Plain language summary
Anaemia is common in critically ill patients and is associated with increased mortality and potentially an extended need for a ventilator. Treatment for anaemia can be invasive and carries a level of risk; therefore further studies on complementary therapies are warranted. Vitamin D has the potential to decrease anaemia through decreasing the production of the iron-regulatory hormone hepcidin. The study aimed to test whether high dose vitamin D would affect haemoglobin concentrations in critically ill patients. In this pilot double-blind randomised control trial, 30 critically ill patients were assigned 250,000 IU vitamin D, 500,000 IU vitamin D or placebo split over 5 doses in 5 days. Blood was taken weekly for up to four weeks and analysed for vitamin D and hepcidin concentrations. Vitamin D concentrations increased significantly in both groups that received vitamin D, compared to no change in the placebo group. Compared to placebo, haemaglobin concentrations significantly increased by 8% in the group receiving 500,000 IU vitamin D but not in the lower dose group. After one week, hepcidin concentrations were significantly decreased in the 500,000 IU vitamin D group, however this was not sustained and no differences between either group and placebo were observed at the end of the study. This did not translate into a reduction in anaemia in either group at any point throughout the study. Extremely high dose vitamin D supplementation was shown to significantly increase circulating vitamin D concentrations and acutely reduce hepcidin. Although anaemia was not affected, clinicians could use this study as an example of safe usage of high dose vitamin D in critically ill patients to improve haemaglobin concentrations, which could reduce the need for invasive treatments, reduce hospital stay duration and treatment costs.
Abstract
BACKGROUND Anemia and vitamin D deficiency are highly prevalent in critical illness, and vitamin D status has been associated with hemoglobin concentrations in epidemiologic studies. We examined the effect of high-dose vitamin D therapy on hemoglobin and hepcidin concentrations in critically ill adults. MATERIALS AND METHODS Mechanically ventilated critically ill adults (N = 30) enrolled in a pilot double-blind, randomized, placebo-controlled trial of high-dose vitamin D3 (D3 ) were included in this analysis. Participants were randomized to receive placebo, 50,000 IU D3 , or 100,000 IU D3 daily for 5 days (totaling 250,000 IU D3 and 500,000 IU D3 , respectively). Blood was drawn weekly throughout hospitalization for up to 4 weeks. Linear mixed-effects models were used to assess change in hemoglobin and hepcidin concentrations by treatment group over time. RESULTS At enrollment, >75% of participants in all groups had plasma 25-hydroxyvitamin D (25(OH)D) concentrations <30 ng/mL, and >85% of participants across groups were anemic. In the 500,000-IU D3 group, hemoglobin concentrations increased significantly over time (Pgroup × time = .01) compared with placebo but did not change in the 250,000-IU D3 group (Pgroup × time = 0.59). Hepcidin concentrations decreased acutely in the 500,000-IU D3 group relative to placebo after 1 week (P = .007). Hepcidin did not change significantly in the 250,000-IU D3 group. CONCLUSION In these critically ill adults, treatment with 500,000 IU D3 was associated with increased hemoglobin concentrations over time and acutely reduced serum hepcidin concentrations. These findings suggest that high-dose vitamin D may improve iron metabolism in critical illness and should be confirmed in larger studies.
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A nutrient-wide association study on blood pressure.
Tzoulaki, I, Patel, CJ, Okamura, T, Chan, Q, Brown, IJ, Miura, K, Ueshima, H, Zhao, L, Van Horn, L, Daviglus, ML, et al
Circulation. 2012;126(21):2456-64
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Elevated blood pressure (BP) is a major risk factor for coronary heart disease and stroke. This study aims to examine the association between a wide range of nutrients and BP using a systematic nutrient-wide association study (NWAS) approach. Data obtained from the cross-sectional International Study of Macro/Micro-nutrients and Blood Pressure (INTERMAP) were analysed. All foods and drinks, including supplements, from 24-hours dietary recalls as well as analytes from urine collection were recorded. Statistical analyses were then performed for the associations of 82 nutrients from food only, 73 nutrients from foods plus supplements, as well as 3 urinary electrolytes/electrolyte ratios with systolic and diastolic BP. The study found: direct associations between alcohol and urinary sodium/potassium ratio with systolic BP; inverse associations between dietary phosphorus, magnesium, non-heme iron, thiamin, folacin, and riboflavin with systolic BP; inverse associations between dietary folacin and riboflavin with diastolic BP; and inclusion of nutrients from supplements intake decreased the associations of folacin, thiamin and riboflavin intake with BP. Authors emphasised the importance of NWAS approach to identify the complex array of nutritional correlates of systolic and diastolic BP. Findings have a potential to represent causative relations that need to be further examined in observational and interventional studies.
Abstract
BACKGROUND A nutrient-wide approach may be useful to comprehensively test and validate associations between nutrients (derived from foods and supplements) and blood pressure (BP) in an unbiased manner. METHODS AND RESULTS Data from 4680 participants aged 40 to 59 years in the cross-sectional International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) were stratified randomly into training and testing sets. US National Health and Nutrition Examination Survey (NHANES) four cross-sectional cohorts (1999-2000, 2001-2002, 2003-2004, 2005-2006) were used for external validation. We performed multiple linear regression analyses associating each of 82 nutrients and 3 urine electrolytes with systolic and diastolic BP in the INTERMAP training set. Significant findings were validated in the INTERMAP testing set and further in the NHANES cohorts (false discovery rate <5% in training, P<0.05 for internal and external validation). Among the validated nutrients, alcohol and urinary sodium-to-potassium ratio were directly associated with systolic BP, and dietary phosphorus, magnesium, iron, thiamin, folacin, and riboflavin were inversely associated with systolic BP. In addition, dietary folacin and riboflavin were inversely associated with diastolic BP. The absolute effect sizes in the validation data (NHANES) ranged from 0.97 mm Hg lower systolic BP (phosphorus) to 0.39 mm Hg lower systolic BP (thiamin) per 1-SD difference in nutrient variable. Inclusion of nutrient intake from supplements in addition to foods gave similar results for some nutrients, though it attenuated the associations of folacin, thiamin, and riboflavin intake with BP. CONCLUSIONS We identified significant inverse associations between B vitamins and BP, relationships hitherto poorly investigated. Our analyses represent a systematic unbiased approach to the evaluation and validation of nutrient-BP associations.