Recently we reported similar performances in both progressive tests to exhaustion (VO 2 max) and 5km running time trials (5KTT) after consuming low-carbohydrate, high-fat (LCHF) or high-carbohydrate, low-fat (HCLF) diets. Accordingly, we tested the null hypothesis that the metabolic responses during both tests would be similar across diets. In a randomized, counterbalanced, cross-over design, seven male athletes (VO 2 max: 61.9 ± 6.1 mL/kg/min; age: 35.6 ± 8.4 years; height: 178.7 ± 4.1 cm; mass: 68.6 ± 1.6 kg; body fat: 5.0 ± 1.3%) completed six weeks of LCHF (6/69/25% energy carbohydrate/fat/protein) and HCLF (57/28/15% energy carbohydrate/fat/protein) diets, separated by a two-week washout. Substrate utilization and energy expenditure were measured during VO 2 max tests and 5KTTs. The LCHF diet markedly increased fat oxidation and reduced carbohydrate oxidation, with no associated impairment in either the VO 2 max tests or the 5KTTs. Following the LCHF diet, athletes generated 50% or more of their energy requirements from fat at exercise intensities up to 90% VO 2 max and reached the crossover point for substrate utilization at ~85% VO 2 max. In contrast, following the HCLF diet, carbohydrate provided more than 50% of the total energy consumption at all exercise intensities. During the 5KTT, ~56% of energy was derived from fat following the LCHF diet whereas more than 93% of the energy came from carbohydrate following the HCLF diet. This study provides evidence of greater metabolic flexibility following LCHF eating and challenges the popular doctrines of “carbohydrate dependence” for high intensity exercise and the role dietary macronutrients play in human performance.
A growing number of endurance athletes have considered switching from a traditional high-carbohydrate/low-fat (HCLF) to a low-carbohydrate/high-fat (LCHF) eating pattern for health and performance reasons. However, few studies have examined how LCHF diets affect blood lipid profiles in highly-trained runners. In a randomized and counterbalanced, cross-over design, athletes (n = 7 men; VO2max: 61.9 ± 6.1 mL/kg/min) completed six weeks of two, ad libitum, LCHF (6/69/25% en carbohydrate/fat/protein) and HCLF (57/28/15% en carbohydrate/fat/protein) diets, separated by a two-week washout. Plasma was collected on days 4, 14, 28, and 42 during each condition and analyzed for: triglycerides (TG), LDL-C, HDL-C, total cholesterol (TC), VLDL, fasting glucose, and glycated hemoglobin (HbA1c). Capillary blood beta-hydroxybutyrate (BHB) was monitored during LCHF as a measure of ketosis. LCHF lowered plasma TG, VLDL, and TG/HDL-C (all p < 0.01). LCHF increased plasma TC, LDL-C, HDL-C, and TC/HDL-C (all p < 0.05). Plasma glucose and HbA1c were unaffected. Capillary BHB was modestly elevated throughout the LCHF condition (0.5 ± 0.05 mmol/L). Healthy, well-trained, normocholesterolemic runners consuming a LCHF diet demonstrated elevated circulating LDL-C and HDL-C concentrations, while concomitantly decreasing TG, VLDL, and TG/HDL-C ratio. The underlying mechanisms and implications of these adaptive responses in cholesterol should be explored.
Diamond-Blackfan anemia (DBA) is a rare bone marrow failure syndrome usually caused by heterozygous variants in ribosomal proteins (RP) and which leads to severe anemia. Genetic studies in DBA rely primarily on multigene panels that often result in variants of unknown significance. Our objective was to optimize polysome profiling to functionally validate new large subunit RP variants. We determined the optimal experimental conditions for B-cell polysome profiles then performed this analysis on 2 children with DBA and novel missense RPL5 (uL18) and RPL26 (uL24) variants of unknown significance. Both patients had reduced 60S and 80S fractions when compared with an unaffected parent consistent with a large ribosomal subunit defect. Polysome profiling using primary B-cells is an adjunctive tool that can assist in validation of large subunit RP variants of uncertain significance. Further studies are necessary to validate this method in patients with known DBA mutations, small RP subunit variants, and silent carriers.
Introduction: The main goal of Hemophilia A treatment has been to restore secondary hemostasis, whether through direct factor VIII replacement or through a combination of bypassing agents and immune tolerance induction in cases of inhibitor activity. In pediatric populations, these treatments are frequently given through a central venous access device (CVAD) for ease of access, convenience, and mitigation of pain. However, these devices carry the risk of infection and thromboembolism (Cost & Journeycake, 2011). The new Hemophilia treatment emicizumab (Hemlibra) has the benefits of less frequent dosing (weekly to every 4 weeks) and does not require central venous access since it is given subcutaneously. There have been cases in the literature of patients developing thromboemboli when using both emicizumab and high doses of inhibitor bypassing agents such as activated prothrombin complex concentrate (aPCC) (Weyand, Dorfman, Shavit, & Pipe, 2019). There have been no reported cases of patients developing thromboemboli who were on emicizumab alone. We present a patient with severe Hemophilia A with no inhibitor who developed a central line-associated venous thromboembolism (VTE) while on emicizumab. Case Summary: A nine-year-old boy with Hemophilia A, factor VIII activity <1%, and no known inhibitor was managed for several years with prophylactic recombinant antihemophilic factor VIII (Advate). A left subclavian CVAD was placed at 15 months of age. A fluoroscopic port study revealed retrograde infusion secondary to a fibrin sheath at the tip of the catheter when the patient was three years old. A right subclavian CVAD was subsequently placed. At the age of seven, the patient's right subclavian port also developed a fibrin sheath. This was removed and multiple attempts to access the subclavian vein again were unsuccessful, leading to right femoral CVAD placement. Two years later, the patient was transitioned to emicizumab. His last dose of recombinant factor VIII was two weeks after initiation of emicizumab. Emicizumab loading doses were completed, and the patient continued with every 28-day dosing. Line removal was scheduled for summer months for the family's convenience. Three months after starting emicizumab, the patient experienced right ankle pain and leg swelling. Venous ultrasound revealed an acute on chronic VTE in the right distal external iliac vein. The patient had not received any aPCC prior to or during emicizumab therapy. Management: The femoral CVAD was removed, and the patient received two doses of recombinant factor VIII during the admission. The patient was started on enoxaparin titrated to a therapeutic anti-Xa level while continuing emicizumab. At approximately one month of follow up, the venous ultrasound showed resolution of the acute portion of his VTE and persistence of chronic VTE. Thereafter, patient was to continue eight more weeks of enoxaparin prior to further venous ultrasound imaging. This patient's family then moved, and the patient was transferred to another hemophilia treatment center. Conclusions: Patients with central venous catheters on emicizumab alone without may develop clinically significant thromboemboli. We propose that guidelines should be developed for patients with CVAD receiving emicizumab. Patients transitioned to emicizumab with central lines in place may require more urgent removal. Furthermore, standardized therapy for anticoagulation is needed for patients on emicizumab who develop VTE. References 1. Cost, C. R., & Journeycake, J. M. (2011). Deep venous thrombosis screening in patients with inherited bleeding disorders and central venous catheters. Haemophilia,17(6), 890-894. doi:10.1111/j.1365-2516.2011.02515.x 2. Weyand, A. C., Dorfman, A. L.,Shavit, J. A., & Pipe, S. W. (2019).Emicizumab prophylaxis to facilitate anticoagulant therapy for management of intra‐atrial thrombosis in severe haemophilia with an inhibitor. Haemophilia,25(3). doi:10.1111/hae.13721 Disclosures No relevant conflicts of interest to declare.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.