Omega-3 Free Fatty Acids for the Maintenance of Remission in Crohn Disease

Feagan, Brian G.; Sandborn, William J.; Mittmann, U.; Bar‐Meir, Simon; D’Haens, Geert R.; Bradette, Marc; Cohen, Albert; Dallaire, Chrystian; Ponich, Terry; McDonald, John W.D.; Hébuterne, Xavier; Paré, Pierre; Klvaňa, Pavel; Niv, Yaron; Ardizzone, Sandro; Alexeeva, Olga; Rostom, Alaa; Kiudelis, Gediminas; Spleiss, Johannes; Gilgen, D.; Vandervoort, Margaret K.; Wong, Cindy J.; Zou, Guang Yong; Donner, Allan; Rutgeerts, Paul

doi:10.1001/jama.299.14.1690

Cited by 243 publications

(171 citation statements)

References 42 publications

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“…Indeed, some of the studies that have reported such benefit have been conducted in populations where the fish consumed are lean and relatively deficient in -3 PUFAs (36,37). Interventional prospective trials of fish oil supplements have given encouragement that there might be benefit (38 -40), although the results have varied (41)(42)(43)(44). Because EPA and DHA possess more double bonds than AA, they may be more susceptible to oxidation by free radicals than is AA.…”

Section: Discussionmentioning

confidence: 99%

Novel Eicosapentaenoic Acid-derived F3-isoprostanes as Biomarkers of Lipid Peroxidation

Song

Paschos

Fries

et al. 2009

Journal of Biological Chemistry

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Isoprostanes (iPs) are prostaglandin (PG) isomers generated by free radical-catalyzed peroxidation of polyunsaturated fatty acids (PUFAs). Urinary F 2 -iPs, PGF 2␣ isomers derived from arachidonic acid (AA) are used as indices of lipid peroxidation in vivo. We now report the characterization of two major F 3 -iPs, 5-epi-8,12-iso-iPF 3␣ -VI and 8,12-iso-iPF 3␣ -VI, derived from the -3 fatty acid, eicosapentaenoic acid (EPA). Although the potential therapeutic benefits of EPA receive much attention, a shift toward a diet rich in -3 PUFAs may also predispose to enhanced lipid peroxidation. Urinary 5-epi-8,12-iso-iPF 3␣ -VI and 8,12-iso-iPF 3␣ -VI are highly correlated and unaltered by cyclooxygenase inhibition in humans. Fish oil dose-dependently elevates urinary F 3 -iPs in mice and a shift in dietary -3/-6 PUFAs is reflected by an increasing slope [m] of the line relating urinary 8, 12-iso-iPF 3␣ -VI and 8,12-iso-iPF 2␣ -VI. Administration of bacterial lipopolysaccharide evokes a reversible increase in both urinary 8,12-iso-iPF 3␣ -VI and 8,12-iso-iPF 2␣ -VI in humans on an ad lib diet. However, while excretion of the iPs is highly correlated (R 2 median ‫؍‬ 0.8), [m] varies by an order of magnitude, reflecting marked inter-individual variability in the relative peroxidation of -3 versus -6 substrates. Clustered analysis of F 2 -and F 3 -iPs refines assessment of the oxidant stress response to an inflammatory stimulus in vivo by integrating variability in dietary intake of -3/-6 PUFAs. Isoprostanes (iPs),2 a family of prostaglandin isomers, are generated initially in situ by free radical attack on polyunsaturated fatty acids (PUFAs) in cell membranes. There, they can be immunodetected and quantified by mass spectrometry (1). They are then cleaved by phospholipases (2), circulate in plasma, and are excreted in urine (3). F 2 -iPs, isomers of PGF 2␣ (3), derived from peroxidation of arachidonic acid (AA), are the most studied species. F 2 -iPs can be quantified in normal animal and human biological fluids and tissues, implying ongoing lipid peroxidation under physiological conditions, despite replete and diversified endogenous antioxidant defense systems (4). The measurement of urinary F 2 -isoprostanes has been used to reflect lipid peroxidation noninvasively in several human diseases (5-8). In addition to their utility as markers of oxidant stress (OS), high concentrations of some F 2 -iPs also possess biological activity in vitro, including bronchoconstriction (9), vasoconstriction (10), platelet aggregation (11, 12), and adhesion (13). These effects result from iPs acting as incidental ligands at prostaglandin receptors. It is unknown whether this capacity of individual iPs to ligate prostanoid receptors has relevance to the concentration of the multiple endogenous iP species likely to be formed simultaneously under conditions of oxidant stress in vivo.iPs analogous to the F 2 -iPs may be formed from other fatty acid substrates (14 -19), including the fish oil constituent, eicosapentaenoic acid (EPA) (20). Pote...

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Section: Discussionmentioning

confidence: 99%

Novel Eicosapentaenoic Acid-derived F3-isoprostanes as Biomarkers of Lipid Peroxidation

Song

Paschos

Fries

et al. 2009

Journal of Biological Chemistry

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“…A randomized controlled trial of 738 patients found no effect of n-3 fatty acid supplementation during 1 year in prevention of CD relapse [53], whereas other studies have found n-3 fatty acid (fish oil) supplementation to be associated with absence of relapse in CD [54]. In UC, no effect of n-3 fatty acid supplementation has been found in a meta-analysis or in a systematic review [43].…”

Section: Impact Of Diet On Disease Course and Treatment Resultsmentioning

confidence: 99%

Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease

Andersen¹,

Hansen²,

Heitmann³

2017

Preprint

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Abstract:We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73-4.31, p < 0.01, OR 2.93; 95% CI: 1.66-5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.

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“…The soundest result was the potential of n-3 PUFA to maintain the patients of Crohn's disease in remission (Belluzzi et al, 1996). However, this observation was not confirmed in a recent larger study using a similar protocol (Feagan et al, 2008). One reason why dietary lipids might be more effective in animal models than in human patients is the different dose of assay.…”

Section: Trials In Human Patientsmentioning

confidence: 98%