Part of the intrigue of research is the often unanticipated findings encountered. The current study was not designed to detect differences in lipids in patients with RA; hence, we lack a control group. Because marine and botanical oils given individually reduce joint inflammation in RA patients [14
], and because the groups in this study showed improvement in the lipid profile, a trial of these oils with a placebo arm is warranted.
RA is a chronic systemic inflammatory disease. Mediators of inflammation and prothrombotic factors contribute to endothelial dysfunction and development of cardiovascular disease in RA patients [33
]. There is little evidence that therapy for inflammation also leads to cardiovascular risk reduction in this group. Marine and botanical oils represent an excellent primary or secondary therapy for improvement of cardiovascular risk management in patients with rheumatoid arthritis.
Results of studies presented in this paper indicate that a GLA-enriched botanical oil (borage seed oil), an EPA/DHA-enriched fish oil, or a combination of these oils are useful for correcting dyslipidemia in patients with RA. Since there were no differences observed between the groups, with the notable exception of triglycerides and the AIP (shown separately in ), all 3 treatment groups were analyzed as a single group. Although lipid profiles of most patients were acceptable at baseline, patients taking these oils exhibit significant additional reductions in total and LDL cholesterol, triglycerides, the TC/HDL ratio, and the atherogenic index, and experience a significant increase in HDL cholesterol. All of these improvements in the lipid profile were seen after 9 months of therapy and increased after 18 months of oils administration. Particularly noteworthy is the group treated with both oils, as they experienced a significantly greater reduction in serum triglyceride concentrations and in the AIP than the groups on either oil alone. Oils enriched in GLA affect inflammation differently than oils enriched in EPA/DHA, and the anti-inflammatory and joint protective effects of the combination of these oils are synergistic in animal models [23
]. Thus, it is possible that these different oils influence different aspects of TG synthesis or metabolism. Indeed, fish and botanical oils that provide EPA both reduce hepatic synthesis of TG in rats [34
]. In humans the delta-5-desaturase that converts DGLA to arachidonic acid (AA) is sluggish, and we have not seen increases in circulating arachidonic acid after administration of GLA for 24 weeks [17
]. Nonetheless, the possibility of increased circulating AA must be considered if treatment is to be long term. When fish oil is administered with borage oil to healthy individuals, bioconversion of GLA to AA is prevented [34
], perhaps another reason for administering both GLA- and EPA-rich oils together.
All treatments were safe. Rates and types of adverse events were similar across all treatment groups, and as anticipated, were due entirely to mild to moderate gastrointestinal distress. The main reason for the large drop-out rate (in excess of 45%) was the large size and the number of capsules ingested each day over the 18-month-study period. It is possible to deliver much larger amounts of the individual polyunsaturated fatty acids (GLA, EPA, and DHA) in far smaller capsules than are needed to accommodate the natural marine and botanical oils, a strategy which should substantially reduce the dropout rate.
Alterations in diet can influence serum lipid concentrations [35
]. However, the patients in our study did not change their diets over the course of the trial, suggesting that the improvements in their lipid profiles, including the significant increase in HDL cholesterol, are due to administration of the study oils. Most pharmacological treatments of dyslipidemia address reduction of LDL cholesterol [36
]. Since improvement in HDL cholesterol depends to a large extent on an exercise regimen [13
], many patients with RA are denied this manner of therapy. Thus, treatment with one or a combination of these oils could aid in the reduction of cardiovascular risk in RA patients whose disability impairs or prevents a prescribed exercise program.
Although LDL-C is the primary target of lipid-lowering therapy, other measures of the lipoprotein lipid profile, as reflected in the AIP and the TC/HDL-C ratios, are also associated with CVD risk. The AIP is a useful monitor of the lipid profile and its subsequent impact on the progression of cardiovascular risk [39
]. In the study presented here, the AIP is significantly and beneficially altered at both 9 and 18 months compared to baseline. Patients in this study also exhibit a significant reduction in the TC/HDL ratio at 9 and 18 months, another indication of reduced CVD risk [40
]. The safety of marine and botanical oils, and their remarkable impact observed in this study on the lipid profile of RA patients who are at increased risk for dyslipidemia and cardiovascular disease [1
], suggest that these oils should have a prominent role in therapy of patients with RA.
Additionally, there is some evidence [41
] that these oils can substitute for treatment of RA patients with nonsteroidal anti-inflammatory drugs (NSAIDs). The adverse gastrointestinal and renal events associated with NSAID therapy are well known [42
]. In addition, macrophages treated with a cyclooxygenase inhibitor in vitro exhibit greater vulnerability to formation of foam cells, a key element in development of atheromatous plaques [43
]. Neither borage oil nor fish oil is associated with serious gastrointestinal events (ulceration, bleeding, perforation). In addition, whereas NSAIDs increase the incidence of myocardial infarction and stroke [44
], fish oil reduces the risk of cardiovascular events in patients at risk, including those with RA [45
]. The efficacy of omega-3-fatty acids in reducing mortality after a myocardial infarction [46
] is further reason to recommend their use in patients with RA. Although studies in humans of the influence of GLA on serum lipids are scant, GLA administration appears to prevent increases in TC and LDL-C [47