|Date: 02-28-2017||HC# 071653-563|
Hadi V, Kheirouri S, Alizadeh M, Khabbazi A, Hosseini H. Effects of Nigella sativa oil extract on inflammatory cytokine response and oxidative stress status in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled clinical trial. Avicenna J Phytomed. 2016;6(1):34-43.
Rheumatoid arthritis (RA) is a progressive, inflammatory autoimmune disease that causes pain, swelling, stiffness, and deformity of the joints. It is thought that the pathogenesis of RA involves chronic oxidative stress and chronic inflammation. Hence, treatments that have anti-inflammatory and antioxidant effects may be beneficial. Black cumin (Nigella sativa, Ranunculaceae) seed oil is used in Iranian traditional medicine. It has been shown to have anti-inflammatory and antioxidant activity in animal models of inflammation by suppressing the elevated levels of pro-inflammatory cytokines and pro-oxidants. The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the effects of black cumin seed oil on the concentration of selected inflammatory cytokines and oxidative stress markers in women with RA.
Patients (n = 42, aged 20-50 years) were recruited from Sheykholrayis Outpatient Clinic, affiliated with Tabriz University of Medical Sciences, in Tabriz, Iran, from May 2012 to November 2013. Included patients had mild to moderate RA according to the 2010 American College of Rheumatology/European League Against Rheumatism (ACR-EULAR) criteria; were being treated with methotrexate, hydroxychloroquine, or prednisolone; were not receiving any non-steroidal anti-inflammatory drugs or cytokine inhibitors for ≥ 2 months prior to study entry; and had body mass index (BMI) < 40. Excluded patients were pregnant or lactating; were taking hormone therapy or oral contraceptives; had metabolic disorders such as diabetes mellitus, lactose intolerance, Cushing's syndrome, or thyroid dysfunction; had kidney or liver disease; had chronic inflammatory disease including inflammatory bowel diseases; had a history of taking antioxidant or anti-inflammatory supplements 4 weeks prior to the study; or had a history of being on weight-reduction diets or smoking.
Patients received placebo (paraffin) or 1000 mg/day black cumin seed oil capsules for 8 weeks. Both placebo and black cumin seed oil soft gels were formulated, developed, and produced by Barij Asans of Kashan (Barij Essence Pharmaceutical Company); Kashan, Iran. The authors do not describe the composition or concentration of the black cumin seed oil. Physical activity level and psychological stress were assessed via International Physical Activity Questionnaire and State-Trait Anxiety Inventory Form Y (STAI-Y), respectively. Dietary intake was evaluated using a 3-day dietary record before and after the intervention, and the data was analyzed using Nutritionist IV software. Disease activity was monitored via the Disease Activity Score Calculator for Rheumatoid Arthritis. Fasting blood was collected at baseline and after 8 weeks of treatment. Serum levels of the inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) and the oxidative stress indicators total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), and nitric oxide (NO) were measured.
Groups were similar at baseline. Fifty women were enrolled in the study and 42 completed the study. Of the 25 women in the placebo group, 7 dropped out for reasons not related to the intervention and 2 were excluded from the analysis due to infection or medication change, leaving 16 patients in the per-protocol analysis. In the black cumin group, 1 patient dropped out for reasons not related to the intervention and 1 was excluded due to medication change, leaving 23 patients in the per-protocol analysis. The author's power calculation indicated that 18 patients in each group were required for statistical significance. Compared with baseline, at 8 weeks, there were no significant changes in BMI, STAI-Y, physical activity, micronutrient intake, energy intake, or macronutrient intake.
At study end, disease activity score was significantly decreased in the black cumin group compared with baseline (P < 0.05), while there was no significant change in the placebo group (data not shown; between-group difference was not reported). The black cumin group had a significant increase in IL-10 (P < 0.01) and significant decreases in malondialdehyde (MDA; P = 0.04) and NO (P = 0.01) compared to baseline; however, the difference between groups was not statistically significant. There were no significant effects on TNF-α, SOD, CAT, or TAC.
The authors conclude that black cumin "could improve inflammation and reduce oxidative stress in patients with RA … ." However, the data presented do not support their conclusion. Black cumin significantly increased the level of the inflammatory cytokine IL-10, indicating a pro-inflammation effect. Although black cumin decreased the levels of the oxidative stress markers MDA and NO compared to baseline, there was no significant difference in these parameters between the black cumin and placebo groups, and black cumin had no effect on the other 4 oxidative stress markers. Limitations of this study include the following: the size of the placebo group was too small to detect statistically significant treatment effects; relatively short study duration; lack of safety/adverse event and compliance reporting; and chemical composition and concentration of the black cumin seed oil was not reported. The authors declare no conflicts of interest; however, one of the authors (Hosseini) is an employee of Barij Essence Pharmaceutical Company.—Heather S. Oliff, PhD