Session 3: Joint Nutrition Society and Irish Nutrition and Dietetic Institute Symposium on ‘Nutrition and autoimmune disease’ PUFA, inflammatory processes and rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease manifested by swollen and painful joints, bone erosion and functional impairment. The joint lesions are characterised by infiltration of T lymphocytes, macrophages and B lymphocytes into the synovium and by synovial inflammation involving eicosanoids, cytokines and matrix metalloproteinases. In relation to inflammatory processes, the main fatty acids of interest are the n-6 PUFA arachidonic acid, which is the precursor of inflammatory eicosanoids such as PGE2 and leukotriene B4, and the n-3 PUFA EPA and DHA, which are found in oily fish and fish oils. Eicosanoids derived from the n-6 PUFA arachidonic acid play a role in RA, and the efficacy of non-steroidal anti-inflammatory drugs in RA indicates the importance of pro-inflammatory cyclooxygenase pathway products of arachidonic acid in the pathophysiology of the disease. EPA and DHA inhibit arachidonic acid metabolism to inflammatory eicosanoids. EPA also gives rise to eicosanoid mediators that are less inflammatory than those produced from arachidonic acid and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving. In addition to modifying the lipid mediator profile, n-3 PUFA exert effects on other aspects of immunity relevant to RA such as antigen presentation, T-cell reactivity and inflammatory cytokine production. Fish oil has been shown to slow the development of arthritis in an animal model and to reduce disease severity. Randomised clinical trials have demonstrated a range of clinical benefits in patients with RA that include reducing pain, duration of morning stiffness and use of non-steroidal anti-inflammatory drugs.

Implications for eicosapentaenoic acid- and docosahexaenoic acid-derived resolvins as therapeutics for arthritis

“…Olson et al (2013) suggested that doses of 42 g/day of DHA may be required to reduce disease in humans. Which is in agreement with doses of fish oils used in human trials (1.6-7.1 g/day and averaged 3.5 g/day) that showed improvement in reducing duration of morning stiffness, number of tender or swollen joints, decreasing pain and time to fatigue, increasing grip strength, and decreasing use of non-steroidal anti-inflammatory drugs (reviewed in Calder (2008), and Miles and Calder (2012)). Until the necessary clinical trials are performed utilizing resolvins for inflammatory arthritis it is difficult to predict the dose required for beneficial outcome in humans, although based on their potency we would predict far lower amounts would be required in comparison to the parent compounds DHA or EPA.…”

“…Such benefits include reduced duration of morning stiffness, reduced number of tender or swollen joints, decreased pain and time to fatigue, increased grip strength, and decreased use of non-steroidal antiinflammatory drugs (reviewed in Calder (2008), and Miles and Calder (2012)). The dose range of omega-3 polyunsaturated fatty acids reported in these trials varied from 1.6 to 7.1 g/day and averaged 3.5 g/day (Calder, 2008;Miles and Calder, 2012). Thus, evidence-based reports implicate fish oil supplementation as an useful complementary therapy for rheumatoid arthritis.…”

Resolution of inflammation: targeting GPCRs that interact with lipids and peptides

“…Indeed, population studies suggest that these lipids have a preventative effect in rheumatoid arthritis (RA), with lower prevalence observed in the Japanese and Inuit population, who consume large amounts of oily fish rich in omega-3 PUFA. In corroboration, clinical studies have revealed that dietary supplementation with omega-3 PUFA is efficacious in reducing joint pain, morning stiffness, and nonsteroidal anti-inflammatory drugs (NSAID) usage in patients with RA [17]. Additionally, consumption of omega-3 PUFA has favorable effects for cardiovascular health [18], which can become compromised in patients with RA.…”

Role of Fatty Acids in the Resolution of Autoimmune and Inflammatory Diseases

“…A number of randomized, placebo-controlled, double-blind studies of fish oil treatments have been reported. In different reviews Calder have summarized the results of studies with a dose of fatty acids between 1.6 and 7.1 g/d (average of 3.5 g/day EPA + DHA) and almost of them reported some benefit (Calder, 2006;Calder, 2008b;Galli et al, 2009). Clinical symptoms were improved, including reduced duration of morning stiffness, number of tender or swollen joints, joint pain, time of fatigue and increased grip strength.…”