Effects of high‐dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs clinical and immune correlates

Kremer, Joel M.; Lawrence, David A.; Petrillo, Gayle F.; Litts, Laura L.; Mullaly, Patrick M.; Rynes, Richard I.; Stocker, Ralph P.; Parhami, N; Greenstein, Neal S.; Fuchs, Betsy R.; Mathur, Anupum; Robinson, Dwight R.; Sperling, Richard I.; Bigaouette, Jean

doi:10.1002/art.1780380813

Cited by 229 publications

(120 citation statements)

References 28 publications

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“…2 (Espersen et al 1992) Serum IL-6 levels were unchanged in the same study (Sundrarjun et al 2004) and following 7 . 1 g EPA + DHA/d (Kremer et al 1995). In addition, no effects on serum IL-8 and IL-2 concentrations were found following fish oil supplementation in the latter study.…”

Section: Rheumatoid Arthritiscontrasting

confidence: 47%

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Differential immunomodulation with long-chainn-3 PUFA in health and chronic disease

Sijben¹,

2007

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The balance of intake of n-6 and n-3 PUFA, and consequently their relative incorporation into immune cells, is important in determining the development and severity of immune and inflammatory responses. Some disorders characterised by exaggerated inflammation and excessive formation of inflammatory markers have become among the most important causes of death and disability in man in modern societies. The recognition that long-chain n-3 PUFA have the potential to inhibit (excessive) inflammatory responses has led to a large number of clinical investigations with these fatty acids in inflammatory conditions as well as in healthy subjects. The present review explores the presence of dose-related effects of long-chain n-3 PUFA supplementation on immune markers and differences between healthy subjects and those with inflammatory conditions, because of the important implications for the transfer of information gained from studies with healthy subjects to patient populations, e.g. for establishing dose levels for specific applications. The effects of long-chain n-3 PUFA supplementation on ex vivo lymphocyte proliferation and cytokine production by lymphocytes and monocytes in healthy subjects have been studied in twenty-seven, twenty-five and forty-six treatment cohorts respectively, at intake levels ranging from 0 . 2 g EPA + DHA/d to 7 . 0 g EPA + DHA/d. Most studies, particularly those with the highest quality study design, have found no effects on these immune markers. Significant effects on lymphocyte proliferation are decreased responses in seven of eight cohorts, particularly in older subjects. The direction of the significant changes in cytokine production by lymphocytes is inconsistent and only found at supplementation levels ‡ 2 . 0 g EPA + DHA/d. Significant changes in inflammatory cytokine production by monocytes are decreases in their production in all instances. Overall, these studies fail to reveal strong dose-response effects of EPA + DHA on the outcomes measured and suggest that healthy subjects are relatively insensitive to immunomodulation with longchain n-3 PUFA, even at intake levels that substantially raise their concentrations in phospholipids of immune cells. In patients with inflammatory conditions cytokine concentrations or production are influenced by EPA + DHA supplementation in a relatively large number of studies. Some of these studies suggest that local effects at the site of inflammation might be more pronounced than systemic effects and disease-related markers are more sensitive to the immunomodulatory effects, indicating that the presence of inflamed tissue or 'sensitised' immune cells in inflammatory disorders might increase sensitivity to the immunomodulatory effects of long-chain n-3 PUFA. In a substantial number of these studies clinical benefits related to the inflammatory state of the condition have been observed in the absence of significant effects on immune markers of inflammation. This finding suggests that conditionspecific clinical end points might be more sensitive markers...

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Section: Rheumatoid Arthritiscontrasting

confidence: 47%

“…9 g EPA + DHA/d in the same study. Espersen et al (1992) and Kremer et al (1995) have reported decreased serum IL-1b following 3 . 2 and 7 .…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Differential immunomodulation with long-chainn-3 PUFA in health and chronic disease

Sijben¹,

2007

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“…The fluctuations in absolute levels in all groups, including the placebo group, demonstrate the need for a proper control group in studies of this nature, and for a proper analysis that compares the effect of fish oil with that of placebo. Statistical testing of changes from baseline within the fish oil group may lead to the faulty conclusion that fish oil does decrease cytokine levels or production [3,27] In two controlled studies, no effect of dietary fish-oil on ex vivo production of IL-1b or TNF-a was found at 7 weeks and 4 months of supplementation [17,18]. Effects of n-3 fatty acids that are apparent at 6 weeks may thus 1006 W. L. BLOK et al have disappeared at 26 weeks of dietary fish oil supplementation.…”

Section: Discussionmentioning

confidence: 99%

Pro‐ and anti‐inflammatory cytokines in healthy volunteers fed various doses of fish oil for 1 year

Blok

Deslypère

Demacker

et al. 1997

Eur J Clin Investigation

120

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Abstract. Dietary supplementation with n-3 fatty acids from fish oil alleviates inflammation in various chronic inflammatory disease states. Reductions in the production of pro-inflammatory cytokines interleukin 1b (IL1b), tumour necrosis factor alpha (TNF-a), and interleukin 6 (IL-6) have been seen in humans after short-term n-3 fatty acid supplementation. We investigated longterm effects of dietary n-3 fatty acids on circulating cytokine concentrations and on ex vivo stimulated whole-blood production of IL-1b, TNF-a and interleukin 1 receptor antagonist (IL-1Ra), the naturally occurring antagonist of IL-1. A total of 58 monks with a mean age of 56 years were randomized into four groups and their diets were supplemented with 0, 3, 6, or 9 g of fish oil, providing 0, 1·06, 2·13 or 3·19 g of n-3 fatty acids per day. Subjects received equal amounts of saturated fatty acids, vitamin E and cholesterol. Compliance was excellent and erythrocyte fatty acid profiles closely reflected the amounts of n-3 fatty acids ingested. In the group receiving 9 g of fish oil per day, no influence of n-3 fatty acids on circulating cytokine concentrations was observed relative to placebo. Endotoxin-stimulated whole-blood cytokine production was measured at 26 and 52 weeks after the start and at 4, 8 and 26 weeks after cessation of supplementation. In all groups, the production of IL-1b and IL-1Ra was higher during supplementation than afterwards. However, no differences in cytokine production were noted between the placebo group and the various treatment groups at any point in time. Our results suggest that long-term supplementation of fish oil does not affect ex vivo cytokine production in man.

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“…Supplementation trials have been conducted for most of these diseases. Clinical trials provide good evidence of the antiinflammatory and clinical improvement effects of fish oil on rheumatoid arthritis [252][253][254] and inflammatory bowel diseases (Crohn's disease and ulcerative colitis) (ref. 255,256 ).…”

Section: Immune System Disordersmentioning

confidence: 99%

Fatty Acids as Biocompounds: Their Role in Human Metabolism, Health and Disease - A Review. Part 2: Fatty Acid Physiological Roles and Applications in Human Health and Disease

Kremmyda¹,

Tvrzická²,

Staňková³

et al. 2011

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

152

134

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Background. This is the second of two review parts aiming at describing the major physiological roles of fatty acids, as well as their applications in specific conditions related to human health.Results. The review included the current literature published in Pubmed up to March 2011. In humans, fatty acids are a principle energy substrate and structural components of cell membranes (phospholipids) and second messengers. Fatty acids are also ligands of nuclear receptors affecting gene expression. Longer-chain (LC) polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid are precursors of lipid mediators such as eicosanoids (prostaglandins, leukotrienes, thromboxanes), resolvins and neuroprotectins. Lipid mediators produced by EPA and DHA (LC n-3 PUFA; mainly found in oily fish) are considered as inflammation-resolving, and thus, fish oil has been characterised as antiinflammatory. Recommendations for EPA plus DHA intake from oily fish vary between 250-450 mg/day. Dietary reference values for fat vary between nutrition bodies, but mainly agree on a low total and saturated fat intake. The existing literature supports the protective effects of LC n-3 PUFA (as opposed to n-6 PUFA and saturated fat) in maternal and offspring health, cardiovascular health, insulin sensitivity, the metabolic syndrome, cancer, critically ill patients, and immune system disorders.Conclusion. Fatty acids are involved in multiple pathways and play a major role in health. Further investigation and a nutrigenomics approach to the effects of these biocompounds on health and disease development are imperative and highlight the importance of environmental modifications on disease outcome.humans. Thus, these FA may be characterised as conditionally essential depending on EFA availability. Genetic variation in human desaturase genes affects FA metabolism, plasma lipid profiles, and risk of disease development [5][6][7] . Recommendations for minimum dietary intake of EPA plus DHA vary between 250-450 mg/day 8 , especially for pregnant women and those of reproductive age. Rich sources of LC n-3 PUFA are fish oils and the flesh of oily fish, whereas non-oily (white) fish contain them but in lower amounts.Long-chain PUFA with 18-20 carbon atoms, including EPA and AA, are precursors of eicosanoids (prostaglandins, leucotrienes and thromboxanes), which have a broad scale of regulatory, autocrine and paracrine effects. Long-chain PUFA with 20 and 22 carbon atoms are precursors of autacoids -resolvins (resolution phase interaction products), lipoxins and neuroprotectins 9 . FA are also ligands of nuclear receptors which take part in the subcellular control of metabolic pathways. Covalent modification of proteins by FA acylation enables their incorporation into membranes. Hydroxy FA are activators of some nuclear factors and are responsible for the expression of proinflammatory cytokines (interleukin (IL)-1,

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Effects of high‐dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs clinical and immune correlates

Cited by 229 publications

References 28 publications

Differential immunomodulation with long-chainn-3 PUFA in health and chronic disease

Differential immunomodulation with long-chainn-3 PUFA in health and chronic disease

Pro‐ and anti‐inflammatory cytokines in healthy volunteers fed various doses of fish oil for 1 year

Fatty Acids as Biocompounds: Their Role in Human Metabolism, Health and Disease - A Review. Part 2: Fatty Acid Physiological Roles and Applications in Human Health and Disease

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