Treatment of Rheumatoid Arthritis with Marine and Botanical Oils: Influence on Serum Lipids

Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2011, Article ID 827286, 9 pages doi:10.1155/2011/827286 Research Article Treatment of Rheumatoid Arthritis with Marine and Botanical Oils: Influence on Serum Lipids Barbara C. Olendzki,1 Katherine Leung,2 Susan Van Buskirk,3 George Reed,2 and Robert B. Zurier4 1 Center for Integrative Nutrition, Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA 2 Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA 3 Department of Family Medicine and Community Health, University of Massachusetts Medical School, Worcester, MA 01655, USA 4 Division of Rheumatology, University of Massachusetts Medical School, Worcester, MA 01655, USA Correspondence should be addressed to Barbara C. Olendzki, [email protected] Received 31 December 2010; Revised 6 June 2011; Accepted 25 July 2011 Copyright © 2011 Barbara C. Olendzki et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The gap in mortality between patients with rheumatoid arthritis (RA) and the general population (1.5–3.0 fold risk) is increasing. This disparity is attributable mainly to cardiovascular disease (CVD), as the CVD risk is comparable to patients with diabetes mellitus. The purpose of this study is to determine whether borage seed oil rich in gamma-linolenic acid, fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), or the combination of both oils are useful treatments for dyslipidemia in patients with RA. We randomized patients into a double blind, 18 month trial. Mixed effects models were used to compare trends over time in serum lipids. No significant differences were observed between the three groups: All three treatment groups exhibited similar meaningful improvement in the lipid profile at 9 and 18 months. When all groups were combined, these treatments significantly reduced total and LDL-cholesterol and triglycerides, increased HDL-cholesterol, and improved the atherogenic index. All improvements observed at 9 months persisted at 18 months (P<0.001 verses baseline). Conclusion. Marine and botanical oils may be useful treatment for rheumatoid arthritis patients who are at increased risk for cardiovascular disease compared to the general population. 1. Introduction [6]. In a prospective study, [7] atherogenic lipid profiles were considerably worse in people who later met criteria for RA Over the past 30 years, substantial progress has been made (as much as 10 years later) than those in matched controls. in the medical and surgical management of patients with Although recent advances in the treatment of RA, especially rheumatoid arthritis (RA). Despite this progress, there is an with agents designed to block the actions of tumor necrosis increasing gap in mortality between patients with RA (1.5– factor alpha (TNFα), have improved the course of the disease 3.0 fold risk) and the general population. The disparity is [8] and endothelial function [9], results of studies of their mainly attributable to cardiovascular disease (CVD) [1]as influence on circulating lipids are mixed, and adequate the CVD risk is comparable to patients with diabetes mellitus evidence for or against such benefit is not available [10–12]. [2, 3]. Although the reasons for this gap are not entirely Due to the lack of supporting data, patients with RA, many clear, the traditional risk of abnormalities in lipid profiles [4] of whom are limited in their ability to exercise to improve the appears to be enhanced by a chronic increase in inflamma- lipid profile and the risk of CVD [13], have an urgent need tory cytokines [5], resulting in accelerated atherosclerosis. In for other treatments to control their dyslipidemia. fact, the elevated risk of cardiovascular disease for patients It is clear that an increased intake of polyunsaturated with RA indicates that atherosclerosis may in fact begin at fatty acids can improve their lipid profile [14]. Abundant lower thresholds of lipid dysfunction and inflammation than experimental evidence supports the view that prostaglan- those in the general population, making the lipid profile and dins, thromboxanes, and leukotrienes (collectively termed other risk factors of particular concern for patients with RA eicosanoids), derived from polyunsaturated fatty acids, and 2 Evidence-Based Complementary and Alternative Medicine Omega-6-fatty acids Linoleic acid (18:2) Delta-6-desaturase Gamma-linolenic acid (18:3) Elongase Delta-5-desaturase Dihomogamma-linolenic acid (20:3) Arachidonic acid (20:4) Cyclooxygenase Lipoxygenase Cyclooxygenase Lipoxygenase − PGG PGG Peroxidase (15-OH) LTC3 LTC4 LTB4 Peroxidase PGH DGLA PGH LTD4 Synthases Synthases PGE1 TxA1 LTE4 PGE2 PGD2 PG12 TxA2 PGJ2 Figure 1 participate in development and regulation of immunological (TXA2), and leucotriene B4 (LTB4). Randomized, placebo and inflammatory responses [15–18]. The fatty acids them- controlled double blind trials indicated that fish oil treatment selves, by virtue of their incorporation into cell membranes of patients with RA result in clinical improvement, and those and signal transduction elements, also have effects on cells that monitored NSAID use suggest that fish oil treatment has involved in inflammation and immune responses that are an NSAID sparing effect [22]. independent of eicosanoids [18, 19]. A disease such as RA, A combination of EPA- and GLA-enriched oils exhibits characterized by abnormal immune responses, persistent synergy in reduction of synovitis in animal models [23], and inflammation, and joint tissue injury [20], may, therefore, be administration of black currant seed oil, which contains the amenable to control by treatment with oils rich in specific n-3 fatty acid alpha-linolenic acid (which is converted to polyunsaturated fatty acids. EPA) and the n-6 GLA, suppresses active synovitis in patients Gamma-linolenic acid (GLA: 18:3 omega 6, see Figure 1) with RA [24]. Taken together, these studies suggest that both is an essential fatty acid found in certain plant seed oils, inc- EPA and GLA are beneficial therapies for patients with RA. luding borage seed oil. GLA is metabolized to dihomoga- With this knowledge, we carried out an 18-month, multi- mma-linolenic acid (DGLA; 20:3 omega 6), the immediate center, randomized, double-blind, phase 3 trial of borage precursor of prostaglandin E1 (PGE1), an eicosanoid with seed oil, fish oil, and a combination of both oils in patients anti-inflammatory and immunoregulatory properties [18]. with RA and active synovitis, to determine whether the In addition, GLA cannot be converted to inflammatory combination of oils is superior to either oil used alone for leucotrienes by 5-lipoxygenase. Instead, it is converted to the treatment of RA. Clinical outcomes of that study will be 15-hydroxy-DGLA which has the additional virtue of sup- presented elsewhere. The object of the study presented here is pressing 5-lipoxygenase activity [21]. GLA and DGLA also to assess the influence of marine and botanical oils on serum modulate immune responses in an eicosanoid-independent lipids in patients with RA. manner by acting directly on T lymphocytes [18]andGLA suppresses acute and chronic inflammation, including arth- 2. Methods and Materials ritis, in animal models [18]. In addition, fish oil, rich in eicosapentaenoic acid (EPA; 20:5 omega 3, see Figure 2)and The study was an 18-month randomized double-blind docosahexanoic acid (DHA; 22:6 w-3), suppresses formation comparison of borage oil, fish oil, or a combination of both of the inflammatory eicosanoids PGE2, thromboxane A2 oils in RA patients with active joint inflammation. Evidence-Based Complementary and Alternative Medicine 3 Alpha-linolenic acid (18:3) Omega-3-fatty acids Delta-6-desaturase Stearadonic acid Eicosapentaenoic acid (20:5) Delta-5-desaturase 8,11,14,17-eicosatetraenoic acid (20:4) Cyclooxygenase Lipoxygenase PGG LTB5 LTC5 PGH LTD5 Synthases LTE5 PGE3 PG13 TxA3 Figure 2 Patients received 3.5 gm omega-3 fatty acids daily in a Patients were ineligible for the study if they had been 2.1gmEPA/1.4gmDHAratio(7fishoiland6sunfloweroil treated with any investigational drug within 1 month of capsules daily), 1.8 gm/d GLA (6 borage oil and 7 sunflower entry. If a patient was taking a fish oil supplement, the dose oil capsules/d), or 7 fish oil and 6 borage oil capsules was stable and ≤2000 mg/d for 2 months before screening. If daily (combination therapy). All capsules were identical in a patient was taking a borage oil supplement, the dose was appearance and color and were purchased from the manufac- stable and ≤2000 mg/d for 2 months before screening. An turer, Bioriginal Food and Service Corp, Saskatoon, Canada, AST, ALT, or creatinine >1.5 times the upper limit of normal who shipped the capsules in opaque plastic bottles to the or a total bilirubin >1.8 mg/dL excluded patients from the University of Massachusetts University Hospital pharmacy, trial. Patients were instructed to maintain their typical diet. from whence they were distributed to participating centers. The lipid profile was assessed at baseline, 9, and 18 Capsules were taken in 2 or 3 divided doses with meals. months. Diet was assessed by 24-hour dietary assessment The protocol was reviewed and approved initially by calls (24-HR), performed at baseline and 18 months. Both the Committee for the Protection of Human Subjects at laboratory evaluation and 24-HR were obtained in most the University of Massachusetts Medical School and the patients who dropped out of the study before 18 months and Food and Drug Administration. Subsequent approvals were after 3 months. These results are included in the analysis, and obtained from the Review Boards at the University of were assigned to the closest 9-month interval to the date of Alabama, Geisenger Clinic, Fallon Health Care, and the New patient’s termination in the study.

Load more