The Common Food Additive Carrageenan Increases Intestinal Permeability without Affecting Whole-Body Insulin Sensitivity in Humans—Results from a Randomized, Double-Blind Crossover Study

It is not known whether food additives associated with western lifestyle, such as the widely used carrageenan, also play a role in the pathogenesis of diabetes. Animal data suggest that increased carrageenan consumption causes insulin resistance and diabetes, mainly by interfering with hepatic insulin signaling. This is the first trial in humans that tested whether carrageenan added to the diet affects key metabolic traits. We conducted a randomized, double-blind, placebo-controlled, cross-over trial (registered as NCT02629705). Healthy males (N=20) were randomly allocated to 14 days of carrageenan (250 mg twice daily) or matching placebo. After a washout-period of 30±7 days, they received the other compound. At the end of each treatment phase, participants underwent an oral glucose tolerance test (OGTT), a hyperinsulinemic-euglycemic clamp with labeled glucose, whole-body MR-tomography and 1H-MR-spectroscopy, blood immune cell phenotyping and a lactulose-mannitol test for investigating intestinal permeability. Participants had a mean (±SD) age of 27.6±4.8 years and a BMI of 24.4±2.6 kg/m2. Intestinal permeability significantly increased after carrageenan vs. placebo exposure (lactulose-mannitol-ratio 0.0196 vs. 0.015, p=0.03). Whole-body insulin sensitivity index (ISI) did not differ between placebo and carrageenan exposure (p=0.5 for both ISIclamp and ISIOGTT). No changes of hepatic fat content, body fat mass, distribution, liver transaminases and inflammatory cytokines were observed (all p>0.4). In young healthy males, short-term carrageenan intake resulted in increased gut permeability. This was not accompanied by changes of whole-body insulin sensitivity, body fat mass, distribution and liver fat content. Further investigations of hepatic and brain insulin sensitivity, immune phenotyping will reveal whether carrageenan intake affected these variables. Disclosure R. Wagner: None. J. Büttner: None. M. Heni: Research Support; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Novo Nordisk Inc.. L. Fritsche: None. S. Kullmann: None. M. Wagmüller: None. A. Peter: None. H. Preissl: None. J. Machann: None. U. Pape: None. G. van Hall: None. P. Plomgaard: None. R. Klein: None. A. Fritsche: Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH, Novo Nordisk A/S, Eli Lilly and Company, Boehringer Ingelheim GmbH. H. Haering: None. N. Stefan: Consultant; Self; Merck Sharp & Dohme Corp.. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca, OmniaMed Ltd..