Effects of fish oil on the neuro-endocrine responses to an endotoxin challenge in healthy volunteers.
OBJECTIVE
Fish oil (FO) has been shown to modulate the acute and chronic inflammatory responses. Endotoxin (LPS) has been shown to mimic several aspects of sepsis. The study aimed at testing the effects of oral FO supplements in healthy subjects submitted to intravenous LPS on systemic and endocrine response.


METHODS
Fifteen healthy men (aged 26.0+/-3.1 years, BMI 23.8+/-1.9 kg/m2), were enrolled. Subjects were randomised to 3-4 weeks of oral FO supplementation (7.2 g/day, providing 1.1 g/day of 20:5 (n-3) and 0.7 g/day of 22:6 (n-3) fatty acids) or no supplementation and then submitted to endotoxin challenge: 2 ng/kg of LPS. All subjects were studied twice (placebo and LPS).


METHODS
vital signs, energy expenditure (EE), glucose and lipid metabolism ((2)H2-glucose), plasma cytokines and stress hormones for 6 h after LPS or placebo.


RESULTS
LPS caused cytokine release, fever, increases in heart rate, resting EE and substrate oxidation, plasma glucagon and glucose concentrations; the neuro-endocrine response was characterised by increased plasma stress hormones. FO significantly blunted fever, ACTH and cortisol plasma levels (no effect on cytokine release). FO blunted the peak norepinephrine after LPS.


CONCLUSIONS
FO supplements blunted the endocrine stress response and the increase in body temperature, but had no impact on cytokine production after LPS. These findings conflict with the postulated anti-inflammatory effects of FO on arachidonic acid metabolism and cytokine release. These results suggest that FO may exert beneficial effects in sepsis though non-inflammatory which require further investigations.
Michaeli
Burkhard
B
Department of Intensive Care Medicine, CHUV, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland.
Berger
Mette M
MM
Revelly
Jean-Pierre
JP
Tappy
Luc
L
Chioléro
René
R
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D001831:Body Temperature / Q000187:drug effects; D018592:Cross-Over Studies; D016207:Cytokines / Q000096:biosynthesis; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005395:Fish Oils; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control; D050356:Lipid Metabolism / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D018805:Sepsis / Q000097:blood / Q000517:prevention & control*
D016207:Cytokines; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D008070:Lipopolysaccharides; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone