Impact of marine oils in inflammatory bowel disease and psoriatic arthritis. With focus on effects of seal oil and whale oil on joint pain
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The Western diet has changed significantly over the last century, e.g. by an increased ratio of omega-6 (n-6) to n-3 polyunsaturated fatty acids (PUFA), particularly due to an increase in the use of vegetable oils like soy oil, rich in the n-6 PUFA linoleic acid (18:2n-6, LA), the precursor of arachidonic acid (20:4n-6, AA). Dietary fatty acids are incorporated into cell membranes of blood and tissues, where AA prevails as a result of the Western diet. AA and the long-chain (LC) n-3 PUFA eicosapentaenoic acid (20:5n-3, EPA), found in fatty fish and marine oils, compete as substrate for the synthesis of eicosanoids like e.g. prostaglandins by cyclooxygenase (COX) enzymes. AA-derived eicosanoids are generally more pro-inflammatory than their EPA-derived counterparts, and the former may be involved in both pathogenesis and exacerbation of chronic inflammatory diseases like inflammatory bowel disease (IBD) and rheumatic disorders. Both IBD and psoriatic arthritis (PsA) patients suffer joint pain, but in contrast to PsA patients, IBD-patients commonly have arthralgia, i.e. joint pain without arthritis. Nevertheless, arthralgia substantially reduces the health related quality of life (HRQOL) of patients. Both IBD and PsA patients need safe alternative or adjuvant treatment for joint pain, as COX-inhibitory drugs for joint pain have adverse effects, particularly in IBD-patients. Long-term oral administration of fish oil reduces the levels of nociceptive prostaglandin E2 (PGE2) and is considered a moderately effective and safe strategy for ameliorating joint pain. In a recent pilot study in IBD-patients, 10 days administration of seal oil (SO), self-administrated as 10 mL × 3 daily by nasoduodenal feeding tube, reduced joint pain and IBD-disease activity. In the present thesis, eventual health benefits of administrating SO or whale oil (WO), 10 mL × 3 daily, with focus on joint pain relief, in patients with IBD and PsA, were investigated in explorative pilot studies. Duodenal administration of SO for 10 days normalised n-6 to n-3 PUFA and AA to EPA ratios in rectal mucosa of IBD-patients as compared with controls. In a later similar study in IBD-patients, SO ameliorated joint pain and HRQOL, the former with prolonged effects, as compared with soy oil, which tended to exacerbate the condition. In another similar study, both SO and WO reduced joint pain and IBDdisease activity and improved quality of life (QoL) in IBD-patients, with no significant group differences. The pain relief after SO and WO administration might in part be mediated by COX-inhibition as suggested by reduced PGE2 levels in plasma (tendency only with WO) as analysed by liquid chromatography tandem mass spectrometry. The application of experimental design enabled estimating the interaction PGE2/internal standard (IS) and selecting confidently an optimal amount of IS and a constant response factor in order to perform a reliable eicosanoid quantification. In a rat model of IBD, short-term (seven days) pre-treatment with SO or cod liver oil (1 mL/day by gastric gavage) as supplement to a standard diet did not protect against subsequent dextran sulfate sodium (DSS) induced colitis, while soy oil aggravated the condition. In PsA patients, 14 days oral administration of SO reduced patients global assessment of disease four weeks post-treatment, but did not improve joint pain compared with soy oil. Twenty three % of PsA patients had elevated levels of faecal calprotectin suggesting asymptomatic, non-active colitis. In conclusion, the present thesis suggests that short-term duodenal administration of blubber oils from marine mammals, like SO and WO, reduce joint pain and IBD-disease activity and improve QoL without significant adverse effects in IBD-patients with moderate disease activity, while short-term oral administration of SO does not improve joint or skin affections in PsA patients.
Paper I: Scandinavian Journal of Gastroenterology 39(11), Bjorkkjar, T.; Brunborg, L. A.; Arslan, G.; Lind, R. A.; Brun, J. G.; Valen, M.; Klementsen, B.; Berstad, A.; Froyland, L., Reduced Joint Pain after Short-term Duodenal Administration of Seal Oil in Patients with Inflammatory Bowel Disease: Comparison with Soy Oil, pp. 1088-1094. Copyright 2004 Taylor & Francis. Reproduced with permission. Accepted version. The published version is available at: http://dx.doi.org/10.1080/00365520410009429Paper II: Lipids in Health and Disease 5(6), Bjorkkjar, T.; Brun, J. G.; Valen, M.; Arslan, G.; Lind, R.; Brunborg, L. A.; Berstad, A.; Froyland, L., Short-term duodenal seal oil administration normalised n-6 to n-3 fatty acid ratio in rectal mucosa and ameliorated bodily pain in patients with inflammatory bowel disease. Copyright 2006 Bjørkkjær et al; licensee BioMed Central Ltd. Reproduced with permission. Published version. The published version is also available at: http://dx.doi.org/10.1186/1476-511X-5-6Paper III: Journal of Rheumatology 33(2), Madland, T. M.; Bjorkkjar, T.; Brunborg, L. A.; Froyland, L.; Berstad, A.; Brun, J. G., Subjective Improvement in Patients with Psoriatic Arthritis After Short-Term Oral Treatment with Seal Oil. A Pilot Study with Double Blind Comparison to Soy Oil, pp. 307-310. Full text not available in BORA due to publisher restrictions. The published version is available at: http://www.jrheum.org/content/33/2/307.abstractPaper IV: Integrative Medicine Insights 2, Arslan, G.; Erichsen, K.; Milde, A. M.; Helgeland, L.; Bjorkkjar, T.; Froyland, L.; Berstad, A., No Protection against DSS-induced Colitis by Short-term Pretreatment with Seal or Fish Oils in Rats, pp. 25-34. Copyright 2007 Arslan et al. Published by Libertas Academica. Reproduced with permission. Published version. The published version is also available at: http://www.la-press.com/no-protection-against-dss-induced-colitis-by-short-term-pretreatment-w-a216Paper V: Prostaglandins, Leukotrienes and Essential Fatty Acids 77(1), Araujo, P.; Bjorkkjar, T.; Berstad, A.; Froyland, L., Improved quantification of prostaglandins in biological samples by optimizing simultaneously the relationship eicosanoid/internal standard and using liquid chromatography tandem mass spectrometry, pp. 9-13. Copyright 2007 Elsevier Ltd. Reproduced with permission. Accepted version. The published version is available at: http://dx.doi.org/10.1016/j.plefa.2007.04.007Paper VI: Prostaglandins, Leukotrienes and Essential Fatty Acids 81(5-6), Bjorkkjar, T.; Araujo, P.; Madland, T. M.; Berstad, A.; Froyland, L., A randomized double blind comparison of short-term duodenally administrated whale and seal blubber oils in patients with inflammatory bowel disease and joint pain, pp. 425-432. Copyright 2009 Elsevier Ltd. Reproduced with permission. Accepted version. The published version is available at: http://dx.doi.org/10.1016/j.plefa.2009.07.005