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Vitamin D and prebiotics for intestinal health in cystic fibrosis: Rationale and design for a randomized, placebo-controlled, double-blind, 2 x 2 trial of administration of prebiotics and cholecalciferol (vitamin D3) (Pre-D trial) in adults with cystic fibrosis.
Sivapiromrat, AK, Suppakitjanusant, P, Wang, Y, Hu, C, Binongo, J, Hunt, WR, Weinstein, S, Jathal, I, Alvarez, JA, Chassaing, B, et al
Contemporary clinical trials communications. 2024;:101278
Abstract
Individuals with cystic fibrosis (CF) have dysfunctional intestinal microbiota and increased gastrointestinal (GI) inflammation also known as GI dysbiosis. It is hypothesized that administration of high-dose cholecalciferol (vitamin D3) together with a prebiotic (inulin) will be effective, and possibly additive or synergistic, in reducing CF-related GI and airway dysbiosis. Thus, a 2 x 2 factorial design, placebo-controlled, double-blinded, pilot and feasibility, clinical trial was proposed to test this hypothesis. Forty adult participants with CF were block-randomized into one of four groups: 1) high-dose oral vitamin D3 (50,000 IU weekly) plus oral prebiotic placebo daily; 2) oral prebiotic (12 g inulin daily) plus oral placebo vitamin D3 weekly; 3) combined oral vitamin D3 weekly and oral prebiotic inulin daily; and 4) oral vitamin D3 placebo weekly and oral prebiotic placebo. The primary endpoints included 12-week changes in the microbial bacterial communities, gut and airway microbiota richness and diversity before and after the intervention. This pilot study examined whether vitamin D3 with or without prebiotics supplementation was feasible, changed airway and gut microbiota, and reduced dysbiosis, which in turn, may improve health outcomes and quality of life of patients with CF.
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Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis: Rationale and design for a randomized, placebo-controlled, double-blind, 2 × 2 trial of administration of prebiotics and cholecalciferol (vitamin D3) (Pre-D Trial) in adults with cystic fibrosis.
Sivapiromrat, AK, Suppakitjanusant, P, Wang, Y, Binongo, J, Hunt, WR, Gewirtz, A, Alvarez, JA, Hu, C, Weinstein, S, Jathal, I, et al
medRxiv : the preprint server for health sciences. 2024
Abstract
Individuals with cystic fibrosis (CF) have dysfunctional intestinal microbiota and increased gastrointestinal (GI) inflammation also known as GI dysbiosis. It is hypothesized that administration of high-dose cholecalciferol (vitamin D3) together with a prebiotic (inulin) will be effective, and possibly additive or synergistic, in reducing CF-related GI dysbiosis and improving intestinal functions. Thus, a 2 × 2 factorial design, placebo-controlled, double-blind, clinical trial was proposed to test this hypothesis. Forty adult participants with CF will be block-randomized into one of four groups: 1) high-dose oral vitamin D3 (50,000 IU weekly) plus oral prebiotic placebo daily; 2) oral prebiotic (12 g inulin daily) plus oral placebo vitamin D3 weekly; 3) combined oral vitamin D3 weekly and oral prebiotic inulin daily; and 4) oral vitamin D3 placebo weekly and oral prebiotic placebo. The primary endpoints will include 12-week changes in the reduced relative abundance of gammaproteobacteria, and gut microbiota richness and diversity before and after the intervention. This clinical study will examine whether vitamin D3 with or without prebiotics will improve intestinal health and reduce GI dysbiosis, which in turn, should improve health outcomes and quality of life of patients with CF.
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Vitamin D for glycemic control following an acute pulmonary exacerbation: A secondary analysis of a multicenter, double-blind, randomized, placebo-controlled trial in adults with cystic fibrosis.
Sivapiromrat, AK, Hunt, WR, Alvarez, JA, Ziegler, TR, Tangpricha, V
medRxiv : the preprint server for health sciences. 2024
Abstract
Individuals with cystic fibrosis (CF) often incur damage to pancreatic tissue due to a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) protein, leading to altered chloride transport on epithelial surfaces and subsequent development of cystic fibrosis-related diabetes (CFRD). Vitamin D deficiency has been associated with the development of CFRD. This was a secondary analysis of a multicenter, double-blind, randomized, placebo-controlled study in adults with CF hospitalized for an acute pulmonary exacerbation (APE), known as the Vitamin D for the Immune System in Cystic Fibrosis (DISC) trial (NCT01426256). This was a pre-planned secondary analysis to examine if a high-dose bolus of cholecalciferol (vitamin D3) can mitigate declined glucose tolerance commonly associated with an acute pulmonary exacerbation (APE). Glycemic control was assessed by hemoglobin A1c (HbA1c) and fasting blood glucose levels before and 12 months after the study intervention. Within 72 hours of hospital admission, participants were randomly assigned to a single dose of oral vitamin D3 (250,000 IU) or placebo, and subsequently, received 50,000 IU of vitamin D3 or placebo every other week, beginning at month 3 and ending on month 12. Forty-nine of the 91 participants in the parent study were eligible for the secondary analysis. There were no differences in 12-month changes in HbA1c or fasting blood glucose in participants randomized to vitamin D or placebo. A high-dose bolus of vitamin D3 followed by maintenance vitamin D3 supplementation did not improve glycemic control in patients with CF after an APE.
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Micronutrient status and protein-energy malnutrition in free-living older adults: a current perspective.
Alvarez-Nuncio, MDC, Ziegler, TR
Current opinion in gastroenterology. 2024;(2):99-105
Abstract
PURPOSE OF REVIEW This review addresses the newest findings on micronutrient status and protein-energy malnutrition in the increasingly aging global population; understanding the nutritional challenges they face is vital for healthcare, well being, and public health. RECENT FINDINGS The review examines deficiencies in macro- and micronutrients among nonhospitalized, free-living older adults, revealing significant associated health consequences, including frailty, cognitive decline, and reduced quality of life. Deficiencies in fat-soluble vitamins such as A, D, and E, are common in older populations, emphasizing the need for close monitoring for status of these. Furthermore, water-soluble vitamin deficiencies, especially vitamins B12 and C are also common, and pose health risks, including neurological disorders and cognitive decline. Iron and iodine deficiencies contribute to anemia, and neurocognitive disorders. Finally, protein-energy malnutrition is common in older adults living in high-resource countries and may occur concomitant with depletion of one or more micronutrients. SUMMARY Addressing specific nutritional deficiencies is fundamental to enhancing the wellbeing and quality of life for free-living older adults. Protein-energy malnutrition, impacting over 25% of those aged 65 and above, results in a range of health issues, including poor wound healing, susceptibility to infections, anemia, and delayed convalescence. These concerns are aggravated by inadequate energy, macronutrient, and micronutrient intake, affecting muscle strength and overall health. Future research should focus on tailored appropriate monitoring of at-risk individuals, specific nutritional interventions, and dietary strategies to mitigate these issues and improve health outcomes among older adults.
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Correction: The effect of a single, large bolus of vitamin D in healthy adults over the winter and following year: a randomized, double-blind, placebo-controlled trial.
Kearns, MD, Binongo, JNG, Watson, D, Alvarez, JA, Lodin, D, Ziegler, TR, Tangpricha, V
European journal of clinical nutrition. 2023;(6):698
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Impact of a specialized oral nutritional supplement on quality of life in older adults following hospitalization: Post-hoc analysis of the NOURISH trial.
Baggs, GE, Middleton, C, Nelson, JL, Pereira, SL, Hegazi, RM, Matarese, L, Matheson, E, Ziegler, TR, Tappenden, KA, Deutz, N
Clinical nutrition (Edinburgh, Scotland). 2023;42(11):2116-2123
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Plain language summary
Malnutrition in hospitalised adults is recognized as a challenging health concern that is associated with many adverse outcomes. Malnutrition screening and assessment are essential for all patients admitted to the hospital and are particularly important for adults who are vulnerable. The aim of this study was to determine whether specialised oral-nutritional supplements (S-ONS) benefits were further associated with measurable improvements in quality of life (QoL) domains during the post-hospitalisation period. This study was a post-hoc analysis of NOURISH trial data. The NOURISH trial was a multicentre, prospective, randomised, double-blind, placebo-controlled, parallel-group study. Six-hundred and twenty-two patients were included in the intent-to-treat analysis. Results showed that malnourished, older patients who received daily interventions with S-ONS (during hospital stay and for 90-day post-discharge) had significantly better QoL domain scores compared to those who received only placebo intervention. Specifically, there were significant differences in the QoL domains of mental health/ cognition, vitality, social functioning, and general health. Further, there were significant QoL differences for physical component, physical functioning, bodily pain, and emotional role. Authors concluded that among malnourished, hospitalised patients (aged 65 years and over), supplementation with S-ONS during the hospitalisation and 90-days post discharge resulted in improvements in QoL.
Abstract
BACKGROUND & AIMS Both during and after hospitalization, nutritional care with daily intake of oral nutritional supplements (ONS) improves health outcomes and decreases risk of mortality in malnourished older adults. In a post-hoc analysis of data from hospitalized older adults with malnutrition risk, we sought to determine whether consuming a specialized ONS (S-ONS) containing high protein and beta-hydroxy-beta-methylbutyrate (HMB) can also improve Quality of Life (QoL). METHODS We analyzed data from the NOURISH trial-a randomized, placebo-controlled, multi-center, double-blind study conducted in patients with congestive heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease. Patients received standard care + S-ONS or placebo beverage (target 2 servings/day) during hospitalization and for 90 days post-discharge. SF-36 and EQ-5D QoL outcomes were assessed at 0-, 30-, 60-, and 90-days post-discharge. To account for the missing QoL observations (27.7%) due to patient dropout, we used multiple imputation. Data represent differences between least squares mean (LSM) values with 95% Confidence Intervals for groups receiving S-ONS or placebo treatments. RESULTS The study population consisted of 622 patients of mean age ±standard deviation: 77.9 ± 8.4 years and of whom 52.1% were females. Patients consuming placebo had lower (worse) QoL domain scores than did those consuming S-ONS. Specifically for the SF-36 health domain scores, group differences (placebo vs S-ONS) in LSM were significant for the mental component summary at day 90 (-4.23 [-7.75, -0.71]; p = 0.019), the domains of mental health at days 60 (-3.76 [-7.40, -0.12]; p = 0.043) and 90 (-4.88 [-8.41, -1.34]; p = 0.007), vitality at day 90 (-3.33 [-6.65, -0.01]; p = 0.049) and social functioning at day 90 (-4.02 [-7.48,-0.55]; p = 0.023). Compared to placebo, differences in LSM values for the SF-36 general health domain were significant with improvement in the S-ONS group at hospital discharge and beyond: day 0 (-2.72 [-5.33, -0.11]; p = 0.041), day 30 (-3.08 [-6.09, -0.08]; p = 0.044), day 60 (-3.95 [-7.13, -0.76]; p = 0.015), and day 90 (-4.56 [-7.74, -1.38]; p = 0.005). CONCLUSIONS In hospitalized older adults with cardiopulmonary diseases and evidence of poor nutritional status, daily intake of S-ONS compared to placebo improved post-discharge QoL scores for mental health/cognition, vitality, social functioning, and general health. These QoL benefits complement survival benefits found in the original NOURISH trial analysis. CLINICAL TRIAL REGISTRATION NCT01626742.
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Evaluation of whole blood thiamine pyrophosphate concentrations in critically ill patients receiving chronic diuretic therapy prior to admission to Turkish intensive care units: A pragmatic, multicenter, prospective study.
Gundogan, K, Sahin, GG, Ergul, SS, Ozer, NT, Temel, S, Akbas, T, Ercan, T, Yildiz, H, Dizdar, OS, Simsek, Z, et al
Journal of critical care. 2023;:154326
Abstract
BACKGROUND/OBJECTIVES Thiamine plays a pivotal role in energy metabolism. The aim of the study was to determine serial whole blood TPP concentrations in critically ill patients receiving chronic diuretic treatment before ICU admission and to correlate TPP levels with clinically determined serum phosphorus concentrations. SUBJECTS/METHODS This observational study was performed in 15 medical ICUs. Serial whole blood TPP concentrations were measured by HPLC at baseline and at days 2, 5 and 10 after ICU admission. RESULTS A total of 221 participants were included. Of these, 18% demonstrated low TPP concentrations upon admission to the ICU, while 26% of participants demonstrated low levels at some point during the 10-day study period. Hypophosphatemia was detected in 30% of participants at some point during the 10-day period of observation. TPP levels were significantly and positively correlated with serum phosphorus levels at each time point (P < 0.05 for all). CONCLUSIONS Our results show that 18% of these critically ill patients exhibited low whole blood TPP concentrations on ICU admission and 26% had low levels during the initial 10 ICU days, respectively. The modest correlation between TPP and phosphorus concentrations suggests a possible association due to a refeeding effect in ICU patients requiring chronic diuretic therapy.
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Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement.
Woodworth, MH, Conrad, RE, Haldopoulos, M, Pouch, SM, Babiker, A, Mehta, AK, Sitchenko, KL, Wang, CH, Strudwick, A, Ingersoll, JM, et al
Science translational medicine. 2023;(720):eabo2750
Abstract
Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation (FMT) can reduce MDRO colonization, but its mechanisms are poorly understood. We conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816). Eleven participants were enrolled and randomized 1:1 to FMT or an observation period followed by delayed FMT if stool cultures were MDRO positive at day 36. Participants who were MDRO positive after one FMT were treated with a second FMT. At last visit, eight of nine patients who completed all treatments were MDRO culture negative. FMT-treated participants had longer time to recurrent MDRO infection versus PREMIX-eligible controls who were not treated with FMT. Key taxa (Akkermansia muciniphila, Alistipes putredinis, Phocaeicola dorei, Phascolarctobacterium faecium, Alistipes species, Mesosutterella massiliensis, Barnesiella intestinihominis, and Faecalibacterium prausnitzii) from the single feces donor used in the study that engrafted in recipients and metabolites such as short-chain fatty acids and bile acids in FMT-responding participants uncovered leads for rational microbiome therapeutic and diagnostic development. Metagenomic analyses revealed a previously unobserved mechanism of MDRO eradication by conspecific strain competition in an FMT-treated subset. Susceptible Enterobacterales strains that replaced baseline extended-spectrum β-lactamase-producing strains were not detectable in donor microbiota manufactured as FMT doses but in one case were detectable in the recipient before FMT. These data suggest that FMT may provide a path to exploit strain competition to reduce MDRO colonization.
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Randomized trial of two maintenance doses of vitamin D in children with chronic kidney disease.
Nadeem, S, Tangpricha, V, Ziegler, TR, Rhodes, JE, Leong, T, Xiang, Y, Greenbaum, LA
Pediatric nephrology (Berlin, Germany). 2022;(2):415-422
Abstract
BACKGROUND Correction of nutritional vitamin deficiency is recommended in children with chronic kidney disease (CKD). The optimal daily dose of vitamin D to achieve or maintain vitamin D sufficiency is unknown. METHODS We conducted a phase III, double-blind, randomized trial of two doses of vitamin D3 in children ≥ 9 years of age with CKD stages 3-5 or kidney transplant recipients. Patients were randomized to 1000 IU or 4000 IU of daily vitamin D3 orally. We measured 25-hydroxvitamin D (25(OH)D) levels at baseline, 3 months and 6 months. The primary efficacy outcome was the percentage of patients who were vitamin D replete (25(OH)D ≥ 30 ng/mL) at 6 months. RESULTS Ninety-eight patients were enrolled: 49 randomized into each group. Eighty (81.6%) patients completed the study and were analyzed. Baseline plasma 25(OH)D levels were ≥ 30 ng/mL in 12 (35.3%) and 12 (27.3%) patients in the 1000 IU and 4000 IU treatment groups, respectively. At 6 months, plasma 25(OH)D levels were ≥ 30 ng/mL in 33.3% (95% CI: 18.0-51.8%) and 74.4% (95% CI: 58.8-86.5%) in the 1000 IU and 4000 IU treatment groups, respectively (p = 0.0008). None of the patients developed vitamin D toxicity or hypercalcemia. CONCLUSIONS In children with CKD, 1000 IU of daily vitamin D3 is unlikely to achieve or maintain a plasma 25(OH)D ≥ 30 ng/mL. In children with CKD stages 3-5, a dose of vitamin D3 4000 IU daily was effective in achieving or maintaining vitamin D sufficiency. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01909115.
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Serum micronutrient levels in critically ill patients receiving continuous renal replacement therapy: A prospective, observational study.
Gundogan, K, Yucesoy, FS, Ozer, NT, Temel, S, Sahin, S, Sahin, GG, Sungur, M, Esmaoglu, A, Talih, T, Yazici, C, et al
JPEN. Journal of parenteral and enteral nutrition. 2022;(5):1141-1148
Abstract
BACKGROUND Acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) may deplete micronutrient levels. Patients are also at risk for micronutrient depletion due to underlying illness(s), poor nutrient intake prior to intensive care unit (ICU) admission and/or increased requirements. We determined vitamin and trace element status before, during and after CRRT in critically ill patients. METHODS This prospective observational study performed in mixed medical and surgical ICU patients. Serial serum vitamin B6 and vitamin C concentrations were measured by HPLC and folic acid by ECLIA. Serum chromium, copper, selenium, and zinc were measured using ICP-MS. Serum ceruloplasmin was measured by the Erel method. RESULTS Fifty adult ICU patients with AKI were recruited. The median APACHE II score on ICU admission was high at 24.0 (6.0-33.0). The median days on CRRT was 2.0 (2.0-4.0) days. At baseline (within 10-15 minutes of CRRT initiation), serum vitamin C, selenium and zinc were below normal. Serum vitamin B6 levels at 72 hours on CRRT were significantly lower than at 24 hours (p = 0.011). Serum vitamin C values fell significantly at 24 and 72 hours during CRRT (p = 0.030 and p = 0.001), respectively, and remained low 24 and 48 hours after CRRT was stopped (p = 0.021). At baseline and during CRRT, 96% of participants had at least two or more micronutrient levels below the normal range. CONCLUSION Serum vitamin C, selenium and zinc concentrations were below the normal range at baseline. CRRT was associated with a significant further decrease in levels of vitamin C, selenium and zinc.