British Journal of Nutrition

Research Article

High-dose fish oil and antioxidants in Crohn's disease and the response of bone turnover: a randomised controlled trial

Timothy M. Trebblea1 c1, Mike A. Strouda1, Stephen A. Woottona1, Philip C. Caldera1, David R. Finea2, Mark A. Mulleea3, Caje Moniza4 and Nigel K. Ardena5

a1 Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK

a2 Division of Infection, Inflammation and Repair, University of Southampton, Tremona Road, Southampton SO16 6YD, UK

a3 Medical Statistics/Southampton Statistical Sciences Research Institute, University of Southampton, Tremona Road, Southampton SO16 6YD, UK

a4 Department of Clinical Biochemistry, King's College Hospital, London SE5 9RS, UK

a5 MRC Environmental Epidemiology Unit, University of Southampton, Tremona Road, Southampton SO16 6YD, UK


Crohn's disease is associated with altered bone turnover that may be influenced by nutritional status, the systemic inflammatory response, cytokine production by circulating (peripheral blood) mononuclear cells (PBMC) and antioxidant micronutrient intake. High-dose fish oil is associated with reductions in disease relapse and inflammatory markers, and modulates PBMC function. The effect of fish oil plus antioxidants on bone turnover and PBMC function (the production of interferon-γ and prostaglandin E2) in Crohn's disease was investigated in a randomised-controlled trial. Patients with currently or recently raised biochemical markers of inflammation (C-reactive protein ≧6·9 mg/l or erythrocyte sedimentation rate ≧18 mm/h) received fish oil (providing 2·7 g/d EPA and DHA) and antioxidants (vitamins A, C and E, and Se) (n 31) or placebo (n 30) for 24 weeks. Bone turnover was assessed by measuring the concentrations of urinary deoxypyridinoline (bone resorption) and serum osteocalcin (bone formation). Fish oil plus antioxidants were associated with increases in EPA, DHA Se in plasma (all P<0·01), and with a reduction in interferon-γ production by mitogen-stimulated PBMC, which demonstrated a negative correlation with deoxypyridinoline/creatinine:osteocalcin ratio (r −0·33, P=0·009). There were no differences between the groups at 24 weeks in the response of deoxypyridinoline or osteocalcin or their ratio, or in nutritional status. Dietary supplementation in Crohn's disease with high intakes of EPA and DHA, as fish oil, plus antioxidants was associated with a modulated production of interferon-γ by PBMC but not altered indices of bone turnover.

(Received June 14 2004)

(Revised January 14 2005)

(Accepted February 16 2005)


c1 *Corresponding author: T. M. Trebble, email