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High-dose fish oil and antioxidants in Crohn's disease and the response of bone turnover: a randomised controlled trial
<jats:p>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 E<jats:sub>2</jats:sub>) 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) (<jats:italic>n</jats:italic> 31) or placebo (<jats:italic>n</jats:italic> 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 <jats:italic>P</jats:italic><0·01), and with a reduction in interferon-γ production by mitogen-stimulated PBMC, which demonstrated a negative correlation with deoxypyridinoline/creatinine:osteocalcin ratio (<jats:italic>r</jats:italic> −0·33, <jats:italic>P</jats:italic>=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.</jats:p>
Inhibition of tumour necrosis factor-α and interleukin 6 production by mononuclear cells following dietary fish-oil supplementation in healthy men and response to antioxidant co-supplementation
<jats:p>Increased dietary consumption of the<jats:italic>n</jats:italic>-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (20:5<jats:italic>n</jats:italic>-3; EPA) and docosahexaenoic acid (22:6<jats:italic>n</jats:italic>-6; DHA) is associated with their incorporation into circulating phospholipid and increased production of lipid peroxide metabolites. The relationship between peripheral blood mononuclear cell (PBMC) function,<jats:italic>n</jats:italic>-3 PUFA intake and antioxidant co-supplementation is poorly defined. We therefore investigated tumour necrosis factor (TNF)-α and interleukin (IL) 6 production by PBMC and phospholipid fatty acid composition in plasma and erythrocytes of healthy male subjects (<jats:italic>n</jats:italic>16) receiving supplemental intakes of 0·3, 1·0 and 2·0 g EPA+DHA/d, as consecutive 4-week courses. All subjects were randomised in a double-blind manner to receive a concurrent antioxidant supplement (200 μg Se, 3 mg Mn, 30 mg D-α-tocopheryl succinate, 90 mg ascorbic acid, 450 μg vitamin A (β-carotene and retinol)) or placebo. There was a positive dose-dependent relationship between dietary<jats:italic>n</jats:italic>-3 PUFA intake and EPA and DHA incorporation into plasma phosphatidylcholine and erythrocyte phosphatidylethanolamine, with a tendency towards a plateau at higher levels of intake. Production of TNF-α and IL-6 by PBMC decreased with increasing<jats:italic>n</jats:italic>-3 PUFA intake but tended towards a ‘U-shaped’ dose response. Both responses appeared to be augmented by antioxidant co-supplementation at intermediate supplementary<jats:italic>n</jats:italic>-3 PUFA intakes. Thus, increased dietary<jats:italic>n</jats:italic>-3 PUFA consumption resulted in defined but contrasting patterns of modulation of phospholipid fatty acid composition and PBMC function, which were further influenced by antioxidant intake.</jats:p>