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

Published online by Cambridge University Press:  08 March 2007

Timothy M. Trebble ,
Mike A. Stroud ,
Stephen A. Wootton ,
Philip C. Calder ,
David R. Fine ,
Mark A. Mullee ,
Caje Moniz  and
Nigel K. Arden
Timothy M. Trebble*
Affiliation:
Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
Mike A. Stroud
Affiliation:
Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
Stephen A. Wootton
Affiliation:
Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
Philip C. Calder
Affiliation:
Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
David R. Fine
Affiliation:
Division of Infection, Inflammation and Repair, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
Mark A. Mullee
Affiliation:
Medical Statistics/Southampton Statistical Sciences Research Institute, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
Caje Moniz
Affiliation:
Department of Clinical Biochemistry, King's College Hospital, London SE5 9RS, UK
Nigel K. Arden
Affiliation:
MRC Environmental Epidemiology Unit, University of Southampton, Tremona Road, Southampton SO16 6YD, UK
*
*Corresponding author: T. M. Trebble, email tt2@soton.ac.uk
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Abstract

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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.

Keywords

BoneFish oilCrohn's disease
Type
Research Article
Information
British Journal of Nutrition , Volume 94 , Issue 2 , August 2005 , pp. 253 - 261
Copyright
Copyright © The Nutrition Society 2005

References

Aghdassi, E, Wendland, BE, Steinhart, AH, Wolman, SL, Jeejeebhoy, K & Allard, JP (2003) Antioxidant vitamin supplementation in Crohn's disease decreases oxidative stress. a randomized controlled trial. Am J Gastroenterol 98, 348–353.Google ScholarPubMed
Andreassen, H, Rungby, JDahlerup, JF & Mosekilde, L (1997) Inflammatory bowel disease and osteoporosis. Scand J Gastroenterol 32, 1247–1255.CrossRefGoogle ScholarPubMed
Arron, JR & Choi, Y (2000) Bone versus immune system. Nature 408, 535–536.CrossRefGoogle ScholarPubMed
Barker, ME & Blumsohn, A (2003) Is vitamin A consumption a risk factor for osteoporotic fracture? Proc Nutr Soc 62, 845–850.CrossRefGoogle ScholarPubMed
Bassey, EJ, Littlewood, JJ, Rothwell, MC & Pye, DW (2000) Lack of effect of supplementation with essential fatty acids on bone mineral density in healthy pre- and postmenopausal women: two randomized controlled trials of Efacal v. calcium alone Br J Nutr 83, 629–635.CrossRefGoogle Scholar
Belluzzi, A, Brignola, C, Campieri, M, Pera, ABoschi, S & Miglioli, M (1996) Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. N Engl J Med 334, 1557–1560.CrossRefGoogle ScholarPubMed
Best, WR, Becktel, JM, Singleton, JW & Kern, F Jr (1976) Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastroenterology 70, 439–444.CrossRefGoogle ScholarPubMed
Brignola, C, Campieri, M, Bazzocchi, G, Farruggia, P, Tragnone, A & Lanfranchi, GA (1986 a) A laboratory index for predicting relapse in asymptomatic patients with Crohn's disease Gastroenterology 91, 1490–1494.CrossRefGoogle ScholarPubMed
Brignola, C, Lanfranchi, GA, Campieri, M, Bazzocchi, G, Devoto, M, Boni, P, Farruggia, P, Veggetti, S & Tragnone, A (1986 b) Importance of laboratory parameters in the evaluation of Crohn's disease activity J Clin Gastroenterol 8, 245–248.CrossRefGoogle ScholarPubMed
British Nutrition Foundation (1999) Briefing Paper: n-3 Fatty Acids and Health. London: British Nutrition Foundation.Google Scholar
Calder, PC (2001) n-3 polyunsaturated fatty acids, inflammation and immunity: pouring oil on troubled waters or another fishy tale? Nutr Res 21, 309–341.CrossRefGoogle Scholar
Clowes, JA & Eastell, R (2000) The role of bone turnover markers and risk factors in the assessment of osteoporosis and fracture risk. Baillieres Best Pract Res Clin Endocrinol Metab 14, 213–232.CrossRefGoogle ScholarPubMed
Crosbie, OM, Freaney, R, McKenna, MJ & Hegarty, JE (1999) Bone density, vitamin D status, and disordered bone remodeling in end-stage chronic liver disease. Calcif Tissue Int 64, 295–300.CrossRefGoogle ScholarPubMed
Department of Health (1991) Dietary Reference Values for Food Energy and Nutrients for the United Kingdom. Report of the Panel on Dietary Reference Values of the Committee on Medical Aspects of Food Policy London: HMSO.Google Scholar
De Vos, M, De Keyser, FMielants, H, Cuvelier, C & Veys, E (1998) Review article: bone and joint diseases in inflammatory bowel disease. Aliment Pharmacol Ther 12, 397–404.CrossRefGoogle ScholarPubMed
Endres, S, Meydani, SN, Ghorbani, R, Schindler, R & Dinarello, CA (1993) Dietary supplementation with n-3 fatty acids suppresses interleukin-2 production and mononuclear cell proliferation. J Leuk Biol 54, 599–603.CrossRefGoogle ScholarPubMed
Eritsland, J (2000) Safety considerations of polyunsaturated fatty acids. Am J Clin Nutr 71, 197S–201S.CrossRefGoogle ScholarPubMed
Fernandes, G, Lawrence, R & Sun, D (2003) Protective role of n-3 lipids and soy protein in osteoporosis. Prost Leukot Essent Fatty Acids 68, 361–372.CrossRefGoogle ScholarPubMed
Granato, D, Blum, SRossle, C, Le Boucher, J, Malnoe, A & Dutot, G (2000) Effects of parenteral lipid emulsions with different fatty acid composition on immune cell functions in vitro. J Parenter Enteral Nutr 24, 113–118.CrossRefGoogle ScholarPubMed
Green, KH, Wong, SC & Weiler, HA (2004) The effect of dietary n-3 long-chain polyunsaturated fatty acids on femur mineral density and biomarkers of bone metabolism in healthy, diabetic and dietary-restricted growing rats. Prost Leuk Essent Fatty Acids 71, 121–130.CrossRefGoogle ScholarPubMed
Grisham, MB (1994) Oxidants and free radicals in inflammatory bowel disease. Lancet 344, 859–861.CrossRefGoogle ScholarPubMed
Habtezion, A, Silverberg, MS, Parkes, R, Mikolainis, S & Steinhart, AH (2002) Risk factors for low bone density in Crohn's disease. Inflamm Bowel Dis 8, 87–92.CrossRefGoogle ScholarPubMed
Horowitz, MCXi, Y, Wilson, K & Kacena, MA (2001) Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands. Cytokine Growth Factor Rev 12, 9–18.CrossRefGoogle ScholarPubMed
Horwood, NJ, Kartsogiannis, V, Quinn, JM, Romas, E, Martin, TJ & Gillespie, MT (1999) Activated Tlymphocytes support osteoclast formation in vitro. Biochem Biophys Res Commun 265, 144–150.CrossRefGoogle Scholar
Katagiri, T & Takahashi, N (2002) Regulatory mechanisms of osteoblast and osteoclast differentiation. Oral Dis 8, 147–159.CrossRefGoogle ScholarPubMed
Kotake, S, Udagawa, N, Hakoda, M et al. , (2001) Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients. Arth Rheum 44, 1003–1012.3.0.CO;2-#>CrossRefGoogle Scholar
Kruger, MC, Coetzer, H, de Winter, R, Gericke, G & Van Papendorp, DH (1998) Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging (Milano) 10, 385–394.Google ScholarPubMed
Mazlam, MZ & Hodgson, HJ (1992) Peripheral blood monocyte cytokine production and acute phase response in inflammatory bowel disease. Gut 33, 773–778.CrossRefGoogle ScholarPubMed
Miura, M & Hiwatashi, N (1985) Cytokine production in inflammatory bowel disease J Clin Lab Immunol 18, 81–86.Google ScholarPubMed
Miyamoto, T, Ohneda, O, Arai, F, Iwamoto, K, Okada, S, Takagi, KAnderson, DM & Suda, T (2001) Bifurcation of osteoclasts and dendritic cells from common progenitors. Blood 98, 2544–2554.CrossRefGoogle ScholarPubMed
Mutchnick, MGLee, HH, Hollander, DI, Haynes, GD & Chua, DC (1988) Defective in vitro gamma interferon production and elevated serum immunoreactive thymosin beta 4 levels in patients with inflammatory bowel disease. Clin Immunol Immunopathol 47, 84–92.CrossRefGoogle ScholarPubMed
Parhami, F (2003) Possible role of oxidized lipids in osteoporosis: could hyperlipidemia be a risk factor?. Prost Leuk Essent Fatty Acids 68, 373–378.CrossRefGoogle ScholarPubMed
Pietschmann, P, Grisar, J, Thien, R, Willheim, M, Kerschan-Schindl, K, Preisinger, E & Peterlik, M (2001) Immune phenotype and intracellular cytokine production of peripheral blood mononuclear cells from postmenopausal patients with osteoporotic fractures. Exp Gerontol 36, 1749–1759.CrossRefGoogle ScholarPubMed
Poulsen, RC & Kruger, MC (2004) Detrimental effect of high dose eicosapentaenoic acid supplementation on bone density in ovariectomised Sprague Dawley rats. Asia Pac J Clin Nutr 13, S49.Google Scholar
Sakaguchi, K, Morita, I & Murota, S (1994) Eicosapentaenoic acid inhibits bone loss due to ovariectomy in rats. Prost Leuk Essent Fatty Acids 50, 81–84.CrossRefGoogle ScholarPubMed
Sasaki, T, Hiwatashi, N, Yamazaki, H, Noguchi, M & Toyota, T (1992) The role of interferon gamma in the pathogenesis of Crohn's disease. Gastroenterol (Japan) 27, 29–36.Google ScholarPubMed
Schlemmer, CK, Coetzer, H, Claassen, N & Kruger, MC (1999) Oestrogen and essential fatty acid supplementation corrects bone loss due to ovariectomy in the female Sprague Dawley rat. Prost Leuk Essent Fatty Acids 61, 381–390.CrossRefGoogle ScholarPubMed
Schreiber, S, Nikolaus, S, Hampe, J, Hamling, JKoop, I, Groessner, B, Lochs, H & Raedler, A (1999) Tumour necrosis factor alpha and interleukin 1beta in relapse of Crohn's disease. Lancet 353, 459–461.CrossRefGoogle ScholarPubMed
Shaheen, SO, Sterne, JA, Thompson, RL, Songhurst, CE, Margetts, BM & Burney, PG (2001) Dietary antioxidants and asthma in adults: population-based case-control study. Am J Respir Carit Care Med 164, 1823–1828.CrossRefGoogle ScholarPubMed
Simmonds, NJ & Rampton, DS (1993) Inflammatory bowel disease – a radical view. Gut 34, 865–868.CrossRefGoogle ScholarPubMed
Sun, D, Krishnan, A, Zaman, K, Lawrence, R, Bhattacharya, A & Fernandes, G (2003) Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice. J Bone Miner Res 18, 1206–1216.CrossRefGoogle ScholarPubMed
Takahashi, M, Naitou, K, Ohishi, T & Nagano, A (2003) Comparison of biochemical markers of bone turnover and bone mineral density between hip fracture and vertebral fracture. J Clin Densitom 6, 211–218.CrossRefGoogle ScholarPubMed
Takayanagi, H, Kim, S & Taniguchi, T (2002) Signaling crosstalk between RANKL and interferons in osteoclast differentiation. Arthritis Res 4 Suppl. 3, S227–S232.CrossRefGoogle ScholarPubMed
Terano, T (2001) Effect of omega 3 polyunsaturated fatty acid ingestion on bone metabolism and osteoporosis. World Rev Nutr Diet 88, 141–147.CrossRefGoogle Scholar
Theill, LE, Boyle, WJ & Penninger, JM, (2002) RANK-L and RANK: T cells, bone loss, and mammalian evolution Ann Rev Immunol 20, 795–823.CrossRefGoogle Scholar
Trebble, Te, Arden, NK, Stroud, MA, Wootton, SA, Burdge, GC, Miles, EA, Ballinger, AB, Thompson, RL & Calder, PC (2003 a) Inhibition of tumour necrosis factor-alpha and interleukin 6 production by mononuclear cells following dietary fish-oil supplementation in healthy men and response to antioxidant co-supplementation. Br J Nutr 90, 405–412.CrossRefGoogle ScholarPubMed
Trebble, TM, Arden, NK, Wootton, SA, Calder, PC, Mullee, MA, Fine, DR & Stroud, MA (2004 a) Fish oil and antioxidants alter the composition and function of circulating mononuclear cells in Crohn disease. Am J Clin Nutr 80, 1137–1144.CrossRefGoogle ScholarPubMed
Trebble, TM, Arden, NK, Wootton, SA, Mullee, MA, Calder, PC, Burdge, GCFine, DR & Stroud, MA (2004 b) Peripheral blood mononuclear cell fatty acid composition and inflammatory mediator production in adult Crohn's disease Clin Nutr 23, 647–655.CrossRefGoogle ScholarPubMed
Trebble, TM, Wootton, SA, Miles, EA, Mullee, M, Arden, NK, Ballinger, AB, Stroud, MA, Burdge, GC & Calder, PC (2003 b) Prostaglandin E2 production and T cell function after fish-oil supplementation: response to antioxidant cosupplementation. Am J Clin Nutr 78, 376–382.CrossRefGoogle Scholar
Trebble, TM, Wootton, SA, Stroud, MA, Mullee, MA, Calder, PC, Fine, DR, Moniz, C & Arden, NK (2004) Laboratory markers predict bone loss in Crohn's disease: relationship to blood mononuclear cell function and nutritional status. Aliment Pharmacol Ther 19, 1063–1071.CrossRefGoogle ScholarPubMed
Van Staa, TP, Cooper, C, Brusse, LS, Leufkens, H, Javaid, MK & Arden, NK (2003) Inflammatory bowel disease and the risk of fracture. Gastroenterology 125, 1591–1597.CrossRefGoogle ScholarPubMed
Wigmore, SJ, Fearon, KC, Maingay, JP, Garden, OJ & Ross, JA (2002) Effect of interleukin-2 on peripheral blood mononuclear cell cytokine production and the hepatic acute phase protein response. Clin Immunol 104, 174–182.CrossRefGoogle ScholarPubMed
Wigmore, SJ, Maingay, JP, Fearon, KC, O'Riordain, MG & Ross, JA (1998) Effect of interleukin-4 on pro-inflammatory cytokine production and the acute phase response in healthy individuals and in patients with cancer or multiple organ failure. Clin Sci 95, 347–354.CrossRefGoogle ScholarPubMed
Yaqoob, P (1998) Monounsaturated fats and immune function. Proc Nutr Soc 57, 511–520.CrossRefGoogle ScholarPubMed