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MFe adipose tissue macrophages compensate for tissue iron perturbations in mice.
Hubler MJ, Erikson KM, Kennedy AJ, Hasty AH
(2018) Am J Physiol Cell Physiol 315: C319-C329
MeSH Terms: Adipocytes, Adipose Tissue, Animals, Cell Line, Dietary Supplements, Inflammation, Iron Overload, Iron, Dietary, Macrophages, Male, Mice, Mice, Inbred C57BL, Monocytes
Show Abstract · Added March 26, 2019
Resident adipose tissue macrophages (ATMs) play multiple roles to maintain tissue homeostasis, such as removing excess free fatty acids and regulation of the extracellular matrix. The phagocytic nature and oxidative resiliency of macrophages not only allows them to function as innate immune cells but also to respond to specific tissue needs, such as iron homeostasis. MFe ATMs are a subtype of resident ATMs that we recently identified to have twice the intracellular iron content as other ATMs and elevated expression of iron-handling genes. Although studies have demonstrated that iron homeostasis is important for adipocyte health, little is known about how MFe ATMs may respond to and influence adipose tissue iron availability. Two methodologies were used to address this question: dietary iron supplementation and intraperitoneal iron injection. Upon exposure to high dietary iron, MFe ATMs accumulated excess iron, whereas the iron content of MFe ATMs and adipocytes remained unchanged. In this model of chronic iron excess, MFe ATMs exhibited increased expression of genes involved in iron storage. In the injection model, MFe ATMs incorporated high levels of iron, and adipocytes were spared iron overload. This acute model of iron overload was associated with increased numbers of MFe ATMs; 17% could be attributed to monocyte recruitment and 83% to MFe ATM incorporation into the MFe pool. The MFe ATM population maintained its low inflammatory profile and iron-cycling expression profile. These studies expand the field's understanding of ATMs and confirm that they can respond as a tissue iron sink in models of iron overload.
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13 MeSH Terms
Antioxidant supplementation and atrial arrhythmias in critically ill trauma patients.
Mirhoseini MF, Hamblin SE, Moore WP, Pouliot J, Jenkins JM, Wang W, Chandrasekhar R, Collier BR, Patel MB
(2018) J Surg Res 222: 10-16
MeSH Terms: Adult, Antioxidants, Arrhythmias, Cardiac, Ascorbic Acid, Critical Care, Critical Illness, Dietary Supplements, Female, Humans, Male, Middle Aged, Oxidative Stress, Retrospective Studies, Selenium, Trauma Centers, Vitamin D, Wounds and Injuries
Show Abstract · Added June 26, 2018
BACKGROUND - The purpose of this study is to determine if antioxidant supplementation influences the incidence of atrial arrhythmias in trauma intensive care unit (ICU) patients.
MATERIALS AND METHODS - In this retrospective pre-post study, critically ill injured patients aged ≥18 years, admitted to a single-center trauma ICU for ≥48 hours were eligible for inclusion. The control group consists of patients admitted from January 2000 to September 2005, before routine antioxidant supplementation in our ICU. The antioxidant group consists of patients admitted from October 2005 to June 2011 who received an antioxidant protocol for ≥48 hours. The primary outcome is the incidence of atrial arrhythmias in the first 2 weeks of hospitalization or before discharge.
RESULTS - Of the 4699 patients, 1622 patients were in the antioxidant group and 2414 patients were in the control group. Adjusted for age, sex, year, injury severity, past medical history, and medication administration, the unadjusted incidence of atrial arrhythmias was 3.02% in the antioxidant group versus 3.31% in the control group, with no adjusted difference in atrial arrhythmias among those exposed to antioxidants (odds ratio: 1.31 [95% confidence interval: 0.46, 3.75], P = 0.62). Although there was no change in overall mortality, the expected adjusted survival of patients in those without antioxidant therapy was lower (odds ratio: 0.65 [95% confidence interval: 0.43, 0.97], P = 0.04).
CONCLUSIONS - ICU antioxidant supplementation did not decrease the incidence of atrial arrhythmias, nor alter the time from admission to development of arrhythmia. A longer expected survival time was observed in the antioxidant group compared with the control group but without a change in overall mortality between groups.
Published by Elsevier Inc.
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Proline Precursors and Collagen Synthesis: Biochemical Challenges of Nutrient Supplementation and Wound Healing.
Albaugh VL, Mukherjee K, Barbul A
(2017) J Nutr 147: 2011-2017
MeSH Terms: Amino Acids, Animals, Collagen, Dietary Supplements, Disease Models, Animal, Humans, Proline, Wound Healing
Show Abstract · Added January 4, 2019
Wound healing is a complex process marked by highly coordinated immune fluxes into an area of tissue injury; these are required for re-establishment of normal tissue integrity. Along with this cascade of cellular players, wound healing also requires coordinated flux through a number of biochemical pathways, leading to synthesis of collagen and recycling or removal of damaged tissues. The availability of nutrients, especially amino acids, is critical for wound healing, and enteral supplementation has been intensely studied as a potential mechanism to augment wound healing-either by increasing tensile strength, decreasing healing time, or both. From a practical standpoint, although enteral nutrient supplementation may seem like a reasonable strategy to augment healing, a number of biochemical and physiologic barriers exist that limit this strategy. In this critical review, the physiology of enteral amino acid metabolism and supplementation and challenges therein are discussed in the context of splanchnic physiology and biochemistry. Additionally, a review of studies examining various methods of amino acid supplementation and the associated effects on wound outcomes are discussed.
© 2017 American Society for Nutrition.
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Effects of Vitamin D Supplementation on Vitamin D Metabolism in Health and CKD.
Batacchi Z, Robinson-Cohen C, Hoofnagle AN, Isakova T, Kestenbaum B, Martin KJ, Wolf MS, de Boer IH
(2017) Clin J Am Soc Nephrol 12: 1498-1506
MeSH Terms: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, Adult, Aged, Biomarkers, Dietary Supplements, Ergocalciferols, Female, Humans, Male, Middle Aged, Renal Insufficiency, Chronic, Time Factors, Treatment Outcome, United States, Vitamin D, Vitamin D Deficiency, Vitamin D3 24-Hydroxylase
Show Abstract · Added September 19, 2017
BACKGROUND AND OBJECTIVES - Vitamin D supplements are prescribed to correct low circulating concentrations of 25-hydroxyvitamin D. In CKD, vitamin D metabolism is complicated by decreased conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by CYP27B1 and possibly decreased conversion of 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D by CYP24A1. The aim of this study was to determine the effects of vitamin D supplementation on vitamin D metabolism in health and CKD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS - We conducted a treatment-only intervention study of 25 individuals with CKD (eGFR<60 ml/min per 1.73 m) and 44 individuals without CKD from three academic centers, all with screening 25-hydroxyvitamin D <30 ng/ml. Each participant was prescribed vitamin D (ergocalciferol) 50,000 IU orally twice weekly for 5 weeks. We tested whether changes in plasma concentrations of vitamin D metabolites and vitamin D metabolic ratios differed by CKD status. Plasma 1,25-dihydroxyvitamin D-to-25-hydroxyvitamin D ratio and 24,25-dihydroxyvitamin D-to-25-hydroxyvitamin D ratio were calculated as estimates of CYP27B1 and CYP24A1 function, respectively.
RESULTS - With treatment, plasma 25-hydroxyvitamin D and total 25-hydroxyvitamin D concentrations increased similarly for participants with and without CKD. For participants without CKD, 1,25-dihydroxyvitamin D increased (2.8±1.3-32.9±1.4 pg/ml), whereas 1,25-dihydroxyvitamin D decreased (45.6±1.9-14.6±1.9 pg/ml), resulting in no significant change in total 1,25-dihydroxyvitamin D; 1,25-dihydroxyvitamin D-to-25-hydroxyvitamin D ratio decreased (3.0±0.2-1.7±0.2 pg/ng), and 24,25-dihydroxyvitamin D-to-25-hydroxyvitamin D ratio increased (115.7±7.8-195.2±7.9 pg/ng). Individuals with CKD had lower baseline levels and smaller changes in magnitude for 1,25-dihydroxyvitamin D (2.1±1.6-24.4±1.6 pg/ml; interaction =0.01), 1,25-dihydroxyvitamin D-to-25-hydroxyvitamin D ratio (1.8±0.2-1.1±0.2 pg/ng; interaction =0.05), and 24,25-dihydroxyvitamin D-to-25-hydroxyvitamin D ratio (72.0±9.1-110.3±9.3 pg/ng; interaction <0.001). Fibroblast growth factor-23 and parathyroid hormone were not significantly changed in either group.
CONCLUSIONS - Vitamin D supplementation decreases conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D and induces vitamin D catabolism as evidenced by changes in D metabolites and vitamin D metabolic ratios. These effects occur without significant changes in fibroblast growth factor-23 or parathyroid hormone and are blunted in CKD.
PODCAST - This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_08_02_CJASNPodcast_17_09.mp3.
Copyright © 2017 by the American Society of Nephrology.
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Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps.
Sun P, Zhu X, Shrubsole MJ, Ness RM, Hibler EA, Cai Q, Long J, Chen Z, Li G, Hou L, Smalley WE, Edwards TL, Giovannucci E, Zheng W, Dai Q
(2017) J Nutr Biochem 47: 35-40
MeSH Terms: Adenoma, Amino Acid Transport Systems, Basic, Calcium, Dietary, Case-Control Studies, Colonic Polyps, Colonoscopy, Colorectal Neoplasms, Diet, Healthy, Dietary Supplements, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Magnesium, Male, Middle Aged, Neoplasm Grading, Patient Compliance, Polymorphism, Single Nucleotide, Self Report, Tennessee, Tumor Burden
Show Abstract · Added April 3, 2018
Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic amino acid transporter 2, which mediates the transport of arginine, lysine and ornithine. l-Arginine is necessary for cancer development and progression, including an important role in colorectal cancer pathogenesis. Furthermore, previous studies found that both calcium and magnesium inhibit the transport of arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact with polymorphisms in the SLC7A2 gene in association with colorectal cancer. We conducted a two-phase case-control study within the Tennessee Colorectal Polyps Study. In the first phase, 23 tagging single-nucleotide polymorphisms in the SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In the second phase conducted in an independent set of 607 cases and 2113 controls, we replicated the significant findings in the first phase. We observed that rs2720574 significantly interacted with calcium:magnesium intake ratio in association with odds of adenoma, particularly multiple/advanced adenoma. In the combined analysis, among those with a calcium:magnesium intake ratio below 2.78, individuals who carried GC/CC genotypes demonstrated higher odds of adenoma [OR (95% CI):1.36 (1.11-1.68)] and multiple/advanced adenoma [OR (95% CI): 1.68 (1.28, 2.20)] than those who carried the GG genotype. The P values for interactions between calcium:magnesium intake ratio and rs2720574 were .002 for all adenomas and <.001 for multiple/advanced adenoma. Among those with the GG genotype, a high calcium:magnesium ratio was associated with increased odds of colorectal adenoma [OR (95% CI): 1.73 (1.27-2.36)] and advanced/multiple adenomas [1.62 (1.05-2.50)], whereas among those with the GC/CC genotypes, high calcium:magnesium ratio was related to reduced odds of colorectal adenoma [0.64 (0.42-0.99)] and advanced/multiple adenomas [0.55 (0.31-1.00)].
Copyright © 2017 Elsevier Inc. All rights reserved.
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Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations.
Midttun Ø, Theofylaktopoulou D, McCann A, Fanidi A, Muller DC, Meyer K, Ulvik A, Zheng W, Shu XO, Xiang YB, Prentice R, Thomson CA, Pettinger M, Giles GG, Hodge A, Cai Q, Blot WJ, Wu J, Johansson M, Hultdin J, Grankvist K, Stevens VL, McCullough ML, Weinstein SJ, Albanes D, Langhammer A, Hveem K, Næss M, Sesso HD, Gaziano JM, Buring JE, Lee IM, Severi G, Zhang X, Han J, Stampfer MJ, Smith-Warner SA, Zeleniuch-Jacquotte A, le Marchand L, Yuan JM, Butler LM, Koh WP, Wang R, Gao YT, Ericson U, Sonestedt E, Ziegler RG, Freedman ND, Visvanathan K, Jones MR, Relton C, Brennan P, Johansson M, Ueland PM
(2017) Am J Clin Nutr 105: 1314-1326
MeSH Terms: Aged, Asia, Australia, Biomarkers, Carbon, Cross-Sectional Studies, Dietary Supplements, Female, Humans, Kynurenine, Laboratories, Male, Middle Aged, Scandinavian and Nordic Countries, Tryptophan, United States, Vitamin A, Vitamin B Complex, Vitamin D, alpha-Tocopherol
Show Abstract · Added April 21, 2017
Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies. We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions. The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory. Circulating concentrations of riboflavin, pyridoxal 5'-phosphate, folate, vitamin B-12, all- retinol, 25-hydroxyvitamin D, and α-tocopherol as well as combined vitamin scores that were based on these nutrients showed that the general B-vitamin concentration was highest in the United States and that the B vitamins and lipid soluble vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-vitamin concentration in the United States appears to be driven mainly by multivitamin-supplement users. The observed differences likely reflect the variation in intake of vitamins and, in particular, the widespread multivitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.
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Prediagnostic Calcium Intake and Lung Cancer Survival: A Pooled Analysis of 12 Cohort Studies.
Yu D, Takata Y, Smith-Warner SA, Blot W, Sawada N, White E, Freedman N, Robien K, Giovannucci E, Zhang X, Park Y, Gao YT, Chlebowski RT, Langhammer A, Yang G, Severi G, Manjer J, Khaw KT, Weiderpass E, Liao LM, Caporaso N, Krokstad S, Hveem K, Sinha R, Ziegler R, Tsugane S, Xiang YB, Johansson M, Zheng W, Shu XO
(2017) Cancer Epidemiol Biomarkers Prev 26: 1060-1070
MeSH Terms: Aged, Calcium, Dietary, Diet Surveys, Dietary Supplements, Feeding Behavior, Female, Follow-Up Studies, Humans, Lung Neoplasms, Male, Middle Aged, Neoplasm Staging, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors, Survival Rate
Show Abstract · Added March 26, 2018
Lung cancer is the leading cause of cancer death. Little is known about whether prediagnostic nutritional factors may affect survival. We examined the associations of prediagnostic calcium intake from foods and/or supplements with lung cancer survival. The present analysis included 23,882 incident, primary lung cancer patients from 12 prospective cohort studies. Dietary calcium intake was assessed using food-frequency questionnaires at baseline in each cohort and standardized to caloric intake of 2,000 kcal/d for women and 2,500 kcal/d for men. Stratified, multivariable-adjusted Cox regression was applied to compute hazard ratios (HR) and 95% confidence intervals (CI). The 5-year survival rates were 56%, 21%, and 5.7% for localized, regional, and distant stage lung cancer, respectively. Low prediagnostic dietary calcium intake (<500-600 mg/d, less than half of the recommendation) was associated with a small increase in risk of death compared with recommended calcium intakes (800-1,200 mg/d); HR (95% CI) was 1.07 (1.01-1.13) after adjusting for age, stage, histology, grade, smoking status, pack-years, and other potential prognostic factors. The association between low calcium intake and higher lung cancer mortality was evident primarily among localized/regional stage patients, with HR (95% CI) of 1.15 (1.04-1.27). No association was found for supplemental calcium with survival in the multivariable-adjusted model. This large pooled analysis is the first, to our knowledge, to indicate that low prediagnostic dietary calcium intake may be associated with poorer survival among early-stage lung cancer patients. This multinational prospective study linked low calcium intake to lung cancer prognosis. .
©2017 American Association for Cancer Research.
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Hot Topics in Pharmacogenetics of Age-Related Macular Degeneration.
Schwartz SG, Brantley MA, Kovach JL, Grzybowski A
(2017) Curr Pharm Des 23: 547-550
MeSH Terms: Age Factors, Angiogenesis Inhibitors, Dietary Supplements, Humans, Macular Degeneration, Pharmacogenetics, Vascular Endothelial Growth Factors
Show Abstract · Added February 23, 2017
Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss and is primarily treated with nutritional supplementation as well as with anti-vascular endothelial growth factor (VEGF) agents for certain patients with neovascular disease. AMD is a complex disease with both genetic and environmental risk factors. In addition, treatment outcomes from nutritional supplementation and anti-VEGF agents vary considerably. Therefore, it is reasonable to suspect that there may be pharmacogenetic influences on these treatments. Many series have reported individual associations with variants in complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), and other loci. However, at this time there are no validated associations. With respect to AMD, pharmacogenetics remains an intriguing area of research but is not helpful for routine clinical management.
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Arginine-Dual roles as an onconutrient and immunonutrient.
Albaugh VL, Pinzon-Guzman C, Barbul A
(2017) J Surg Oncol 115: 273-280
MeSH Terms: Animals, Arginine, Dietary Supplements, Humans, Neoplasms
Show Abstract · Added January 4, 2019
Arginine is an important player in numerous biologic processes and studies have demonstrated its importance for cellular growth that becomes limiting in states of rapid turnover (e.g., malignancy). Thus, arginine deprivation therapy is being examined as an adjuvant cancer therapy, however, arginine is also necessary for immune destruction of malignant cells. Herein we review the data supporting arginine deprivation or supplementation in cancer treatment and the currently registered trials aimed at understanding these divergent strategies. J. Surg. Oncol. 2017;115:273-280. © 2016 Wiley Periodicals, Inc.
© 2016 Wiley Periodicals, Inc.
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High Dose Omega-3 Fatty Acid Administration and Skeletal Muscle Protein Turnover in Maintenance Hemodialysis Patients.
Deger SM, Hung AM, Ellis CD, Booker C, Bian A, Chen G, Abumrad NN, Ikizler TA
(2016) Clin J Am Soc Nephrol 11: 1227-35
MeSH Terms: Adult, Aged, Amino Acids, Blood Glucose, C-Reactive Protein, Dietary Supplements, Double-Blind Method, Fatty Acids, Omega-3, Female, Forearm, Humans, Inflammation, Insulin Resistance, Male, Middle Aged, Muscle Proteins, Muscle, Skeletal, Protein Biosynthesis, Renal Dialysis, Renal Insufficiency, Chronic
Show Abstract · Added July 1, 2016
BACKGROUND AND OBJECTIVES - Protein energy wasting and systemic inflammation are prevalent in maintenance hemodialysis (MHD) patients. Omega-3 (ω-3) fatty acids have anti-inflammatory properties and have been shown to improve protein homeostasis. We hypothesized that administration of high-dose (2.9 g/d) ω-3 would be associated with decreased muscle protein breakdown in MHD patients with systemic inflammation.
DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS - This is a substudy from a randomized, placebo-controlled study (NCT00655525). Patients were recruited between September 2008 and June 2011. Primary inclusion criteria included signs of chronic inflammation (average C-reactive protein of ≥5 mg/L over three consecutive measurements), lack of active infectious or inflammatory disease, no hospitalization within 1 month prior to the study, and not receiving steroids (>5 mg/d) and/or immunosuppressive agents. The primary outcomes were forearm muscle and whole body protein breakdown and synthesis before and after the intervention. The patients received ω-3 (n=11) versus placebo (n=9) for 12 weeks. Analysis of covariance was used to compare outcome variables at 12 weeks. Models were adjusted for a propensity score that was derived from age, sex, race, baseline high sensitivity C-reactive protein, diabetes mellitus, and fat mass because the groups were not balanced for several characteristics.
RESULTS - Compared with placebo, ω-3 supplementation was significantly associated with decreased muscle protein breakdown at 12 weeks (-31, [interquartile range, -98--13] versus 26 [interquartile range, 13-87] µg/100 ml per min; P=0.01), which remained significant after multivariate adjustment (-46, [95% confidence interval, -102 to -1] µg/100 ml per min). ω-3 Supplementation resulted in decreased forearm muscle protein synthesis while the rate in the placebo group increased; however, there is no longer a statistically significant difference in skeletal muscle protein synthesis or in net protein balance after multivariate adjustment. There was no statistically significant effect of ω-3 supplementation on whole body protein synthesis or breakdown.
CONCLUSIONS - High-dose ω-3 supplementation over 12 weeks in MHD patients with systemic inflammation was associated with attenuation of forearm muscle protein breakdown but did not influence skeletal muscle protein synthesis, skeletal muscle net protein balance or any component of the whole-body protein balance. These results should be interpreted cautiously given the imbalance in the two groups and the short duration of the intervention.
Copyright © 2016 by the American Society of Nephrology.
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