Carrageenan and insulin resistance in humans: a randomised double-blind cross-over trial.

Autor: Wagner R; Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany. robert.wagner@uni-duesseldorf.de.; Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany. robert.wagner@uni-duesseldorf.de.; German Center for Diabetes Research (DZD), Neuherberg, Germany. robert.wagner@uni-duesseldorf.de.; Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich Heine University, Moorenstr 5, Düsseldorf, 40225, Germany. robert.wagner@uni-duesseldorf.de.; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany. robert.wagner@uni-duesseldorf.de.; Department of Biostatistics, Microbiome Analysis Core, Harvard T.H. Chan School of Public Health, Boston, USA. robert.wagner@uni-duesseldorf.de., Buettner J; Department of Hepatology and Gastroenterology, Charité Universitätsmedizin, Berlin, Germany., Heni M; Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany.; Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany.; Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany., Fritsche L; Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Kullmann S; Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany., Wagmüller M; Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany.; Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany., Peter A; Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany., Preissl H; Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.; Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry; Interfaculty Centre for Pharmacogenomics and Pharma Research at the Eberhard Karls University Tübingen, Tübingen, Germany., Machann J; Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Section On Experimental Radiology, Department of Diagnostic and Interventional Radiology, University Hospital of Tübingen, Tübingen, Germany., Jumpertz von Schwartzenberg R; Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany.; Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Birkenfeld AL; Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany.; Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Pape UF; Department of Hepatology and Gastroenterology, Charité Universitätsmedizin, Berlin, Germany.; Department of Internal Medicine and Gastroenterology, Asklepios Klinik St. Georg, Hamburg, Germany., van Hall G; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark., Plomgaard P; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark., Häring HU; Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany.; Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Fritsche A; Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany.; Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Thompson KN; Department of Biostatistics, Microbiome Analysis Core, Harvard T.H. Chan School of Public Health, Boston, USA., Klein R; Department of Internal Medicine II, Division of Haematology, Oncology, Immunology and Rheumatology, University Hospital of Tübingen, Tübingen, Germany., Stefan N; Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany.; Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.
Jazyk: angličtina
Zdroj: BMC medicine [BMC Med] 2024 Nov 26; Vol. 22 (1), pp. 558. Date of Electronic Publication: 2024 Nov 26.
DOI: 10.1186/s12916-024-03771-8
Abstrakt: Background: The potential impact of specific food additives, common in Western diets, on the risk of developing type 2 diabetes is not well understood. This study focuses on carrageenan, a widely used food additive known to induce insulin resistance and gut inflammation in animal models, and its effects on human health.
Methods: In a randomised, double-blind, placebo-controlled, cross-over trial conducted at a university hospital metabolic study centre, 20 males (age 27.4 ± 4.3 years, BMI 24.5 ± 2.5 kg/m 2 ) participated. The intervention involved oral intake of carrageenan (250 mg) or placebo in the morning and in the evening and each intervention lasted 2 weeks. The primary outcome measured was insulin sensitivity (using oral glucose tolerance test [OGTT] and hyperinsulinaemic-euglycaemic clamp). Additional end-points included whole body and hepatic insulin sensitivity, MRI-measured brain inflammation and insulin resistance, intestinal permeability (via lactulose-mannitol test and plasma zonulin levels), and gut microbiome composition. Immune-cell activation and pro-inflammatory cytokine release from peripheral blood mononuclear cells were measured.
Results: Overall insulin sensitivity did not show significant differences between the treatments. However, interactions between BMI and treatment were observed (OGTT-based insulin sensitivity index: p=0.04, fasting insulin resistance: p=0.01, hepatic insulin sensitivity index: p=0.04). In overweight participants, carrageenan exposure resulted in lower whole body and hepatic insulin sensitivity, a trend towards increased brain inflammation, and elevated C-reactive protein (CRP) and IL-6 levels compared to placebo. Additionally, carrageenan was associated with increased intestinal permeability. In vitro natural killer (NK-)cell activation and increased pro-inflammatory cytokine release were found after carrageenan exposure in the participant's peripheral blood mononuclear cells.
Conclusions: These findings suggest that carrageenan, a common food additive, may contribute to insulin resistance and subclinical inflammation in overweight individuals through pro-inflammatory mechanisms in the gut. Further investigation into the long-term health impacts of carrageenan and other food additives is warranted.
Trial Registration: NCT02629705.
Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Ethical Committee of the Medical Faculty of the University of Tübingen, Germany (project number 359/2012BO1). All participants provided written informed consent. Consent for publication: All authors have reviewed and approved the manuscript for submission. Competing interests: RW reports lecture fees from NovoNordisk, Eli Lilly, Boehringer-Ingelheim and Sanofi, and travel grants from Eli Lilly, Sanofi and NovoNordisk. He served on the advisory board of Akcea Therapeutics, Daiichi Sankyo, Sanofi and NovoNordisk. Outside of the current work, MH reports research grants from Boehringer Ingelheim and Sanofi to the University Hospital of Tübingen, participation in advisory board for Boehringer Ingelheim and Sanofi and lecture fees from Amryt, Bayer, Sanofi, Eli Lilly, Novo Nordisk and Boehringer Ingelheim.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje