Arthritis remains among the top chronic conditions in the world, encompassing a variety of signs and symptoms including inflammation, pain, and loss of function. Moreover, Rheumatoid Arthritis, also referred to as “RA”, is one of the most prevalent forms of arthritis, affecting 0.5-1% of the population in developed countries.1-3 In addition, it seems that women have a higher risk of developing the disease than men (3:1), and it is most prevalent in those between 40 and 60 years of age.1,4 RA is defined by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) as an autoimmune disorder characterized by joint tenderness and swelling throughout multiple joints of the upper and lower extremities and destruction of synovial joints that lead to decreased function and immobility.5,6 Left uncontrolled, these symptoms can severely impact a person’s quality of life.
Although the pathogenesis of the disease is unclear, there are several possible causes for the disease, including genetic and environmental factors, that may play a strong role in developing rheumatoid arthritis.2 Studies have demonstrated a link between particular cytokines and RA, and the biological effects that are correlated with relative serum concentrations, such as elevated erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and rheumatoid factor (RF), and inflammatory cytokines (TNF- and IL-6) and their inhibitors. These interactions play an important role in inflammation and disease activity.7
Currently, the goal for treatment of RA is to decrease the symptoms with no active inflammation and loss of function caused by the disease. Standard treatment utilizes “disease-modifying anti-rheumatic drugs”, known as DMARDs, incorporating a wide variety of medications with differing mechanisms of action.1 However, like many prescribed therapies, there is always a potential for unpleasant adverse effects, and the therapies may actually be more difficult to manage than the disease.6 Therefore, patients have an increased potential to demonstrate poor adherence to their treatment due to the side effects and tedious maintenance of the disease.
Reports have revealed that 33-75% of RA patients believe that food plays an important role to the extent of their disease activity and 20-50% have previously tried dietary manipulation to alleviate their suffering.7 These manipulations are often accomplished in various forms, from eliminating a single substance or complete dietary lifestyle changes. It has been noted that higher levels of antioxidants may protect against and neutralize toxins from the environment or infectious agents that are often correlated to the development of RA.8 Due to the potential role that oxidative stress plays in disease exacerbation in patients with rheumatoid arthritis, there are many studies examining the inhibitory effects of antioxidants on inflammatory cytokine and serum concentrations related to RA.
In 2014, an 8-week trial was conducted on male rats with collagen-induced arthritis to observe the effects of vitamin A and vitamin E on serum leptin and other cytokines correlated with rheumatoid arthritis. Subjects were assigned to one of the four following subgroups based on their four paw scores indicating the severity of paw swelling: 1. Untreated/control group, 2. Ibuprofen group receiving 50 mg/kg daily, 3. Vitamin E group receiving 200 mg/kg daily, and 4. Vitamin A group receiving 42.86 μg retinol equivalents/kg daily. The subjects received their assigned treatment for a total of 4 weeks. Results showed that administration of vitamin A and E significantly reduced serum leptin (P<0.05), TNF‐α (P<0.05), IL‐6 (P<0.01), ESR (P<0.05), and CRP (P<0.05) compared to the untreated subgroup. Further, levels of anti-inflammatory cytokines (IL-10 and IL-4) were higher in subjects with antioxidant supplementation than those in the untreated group, although not statistically significant in regard to IL-4 markers. However, levels of RF of subject assigned to the Vitamin A and E subgroups were not significantly reduced in comparison to the untreated subgroup.7
Similarly, a study conducted in Iran in 2014 demonstrates the effects of antioxidant supplementation on 39 female participants, ages 40-60 years old, with RA. The subjects were instructed to take a “selenplus” capsule, containing 50 μg selenium, 8 mg zinc, 400 μg vitamin A, 125 vitamin C, and 40 mg vitamin E, once daily for 12 weeks. In comparison to baseline results, end-of-study results exhibited a significant improvement in DAS-28 scores and serum CRP levels, both (P <0.01). In addition, antioxidant markers, such as total antioxidant capacity (TAC), glutathione peroxidase (GPX), superoxide mutase (SOD), and catalase (CAT), increased significantly (P <0.01). Although there were no statistically significant improvements in swollen and tender joints counts, the study does demonstrate that there may be use for antioxidants, particularly zinc and selenium, at higher doses to improve disease activity. Although no control/placebo group was recorded, the results remain significant to include as a basis for further experimentation.3
Additionally, a study examining the effects of fish oil and primrose oil on oxidative stress was conducted in 2016 with a subject population that included 60 postmenopausal, female patients with rheumatoid arthritis in Serbia. Both fish oil and primrose oil are well known for their antioxidant containing properties and are often used in supplementation. Patients were assigned (1:1:1) to one of three cohorts. In Group I (the control group), patients were instructed to continue their medication regimen with no antioxidant supplementation. Group II was characterized by patients receiving five gel capsules of Omega-3 Cardio daily, which contained 1000 mg concentrated fish oil and 300 mg DHA, 200 mg EPA, and 10 mg other omega-3 fatty acids. Group III received two gel capsules of Omega-3 Cardio and two gel capsule of evening primrose oil, which contained 130 mg evening primrose oil, 949 mg linoleic acid, and 117 mg gamma linolenic acid (GLA). All patients remained on an identical medication therapy utilizing low dose steroids (<10 mg/day), oral methotrexate (mean dose 15 mg/week) with folic acid supplementation, and NSAIDs, on occasion, throughout the entirety of the 12-week trial. Results demonstrated that supplementation of antioxidant containing substances (i.e. fish oil and primrose oil) effectively reduced oxidative stress in patients with RA. Whereas, Groups II and III showed statistically significant increases in plasma levels of TBARS (P <0.05 in Group II, P<0.001 in Group III) and NO2- (P <0.001), but a significant decrease in H2O2 plasma levels (P <0.001) in comparison to Group I who showed no significant changes in any of the serum markers and antioxidants. However, Group II did not show a statistically significant difference in SOD in contrast to Group III with a statistically significant increase (P <0.05). Also, CT and O2- showed no significant change in all three groups.9
A study was conducted in 2012 investigating the relationship between nutritional status, oxidative stress, and disease activity in 37 patients (34 females, 3 males) with rheumatoid arthritis. Patients were divided into a high or low disease activity group based on their DAS-28 scores at baseline. They were instructed to complete diet records for two months via food frequency questionnaires (FFQ) and a 3-day diet record. This study confirmed similar findings mentioned in previous studies. For instance, leptin levels were significantly lower and serum CRP and ESR concentrations were statistically higher in patients from high disease activity group compared to those in the low disease activity group (P <0.01). The high disease activity group also reported significantly lower intakes of fish oil in comparison to the low disease activity group (P <0.05). Reactive oxygen species (ROMs,) present in sera and saliva samples, correlated with the DAS-28 and CRP indicating a significant oxidative stress value (P <0.05). Therefore, this study suggests that lower disease activity and inflammation may be associated with dietary intake of fish oil antioxidants.10
This collection of literature discusses the potential benefit of antioxidant supplementation on disease activity in patients with rheumatoid arthritis. Continued research is highly encouraged due to the limited number of large-scale studies available for review, short trial timelines (<12 weeks), and varied doses and forms of antioxidants administered to produce a response. Also, there is a necessity for a standardized methodology in further research regarding specific antioxidants chosen for review.