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

Robert Wagner*, Janine Buettner, Martin Heni, Louise Fritsche, Stephanie Kullmann, Moritz Wagmüller, Andreas Peter, Hubert Preissl, Jürgen Machann, Reiner Jumpertz von Schwartzenberg, Andreas L. Birkenfeld, Ulrich Frank Pape, Gerrit van Hall, Peter Plomgaard, Hans Ulrich Häring, Andreas Fritsche, Kelsey N. Thompson, Reinhild Klein, Norbert Stefan

*Corresponding author for this work

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Abstract

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/m2) 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.

Original languageEnglish
Article number558
JournalBMC Medicine
Volume22
Issue number1
Number of pages11
ISSN1741-7015
DOIs
Publication statusPublished - 2024

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Publisher Copyright:
© The Author(s) 2024.

Keywords

  • Carrageenan
  • Emulsifiers
  • Gut microbiome
  • Insulin sensitivity
  • Intestinal permeability
  • Type 2 diabetes

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