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Updated: Mar 12, 2026
Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
Published on: May 16, 2016
Postprandial serum endotoxin in healthy humans is modulated by dietary fat in a randomized, controlled, cross-over
Joshua M Lyte1,2,3, Nicholas K Gabler4, James H Hollis5
1Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, 50011, USA. joshua.lyte@ucc.ie.
Background:
High-fat diets may contribute to metabolic disease via postprandial changes in serum endotoxin and inflammation. It is unclear how dietary fat composition may alter these parameters. We hypothesized that a meal rich in n-3 (ω3) fatty acids would reduce endotoxemia and associated inflammation but a saturated or n-6 (ω6) fatty acid-rich meal would increase postprandial serum endotoxin concentrations and systemic inflammation in healthy adults.
Methods:
Healthy adults (n = 20; mean age 25 ± 3.2 S.D. years) were enrolled in this single-blind, randomized, cross-over study. Participants were randomized to treatment and reported to the laboratory, after an overnight fast, on four occasions separated by at least one week. Participants were blinded to treatment meal and consumed one of four isoenergetic meals that provided: 1) 20 % fat (control; olive oil) or 35 % fat provided from 2) n-3 (ω3) (DHA = 500 mg; fish oil); 3) n-6 (ω6) (7.4 g; grapeseed oil) or 4) saturated fat (16 g; coconut oil). Baseline and postprandial blood samples were collected. Primary outcome was defined as the effect of treatment meal on postprandial endotoxemia. Serum was analyzed for metabolites, inflammatory markers, and endotoxin. Data from all 20 participants were analyzed using repeated-measures ANCOVA.
Results:
Participant serum endotoxin concentration was increased during the postprandial period after the consumption of the saturated fat meal but decreased after the n-3 meal (p < 0.05). The n-6 meal did not effect a different outcome in participant postprandial serum endotoxin concentration from that of the control meal (p > 0.05). There was no treatment meal effect on participant postprandial serum biomarkers of inflammation. Postprandial serum triacylglycerols were significantly elevated following the n-6 meal compared to the n-3 meal. Non-esterified fatty acids were significantly increased after consumption of the saturated fat meal compared to other treatment meals.
Conclusions:
Meal fatty acid composition modulates postprandial serum endotoxin concentration in healthy adults. However, postprandial endotoxin was not associated with systemic inflammation in vivo.
Trial Registration:
This study was retrospectively registered at clinicaltrials.gov as NCT02521779 on July 28, 2015.
