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A comprehensive scientific evidence‐based impact of yoga in patients with rheumatoid arthritis

2023; Wiley; Volume: 26; Issue: 12 Linguagem: Inglês

10.1111/1756-185x.14874

1756-185X

A. Mooventhan, Pavithra, N. Meha, S. Monisha, R. Deepika, Poorani Rengachar, L. Nivethitha,

Mindfulness and Compassion Interventions

Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease characterized by inflammation1 of small joints (metacarpophalangeal joint, proximal interphalangeal joints), progressing to larger joints (knee joint, elbow joint).2 The worldwide prevalence of RA is about 0.24%. It is more prevalent in women with a lifetime risk of 3.6% compared with men with a lifetime risk of 1.7%.1 It is typically treated with disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs, and glucocorticoids.3 Unfortunately, long-term medication has potent side effects, which often are not well tolerated.1 To avoid such side effects, patients often seek non-pharmacological treatments. As an important non-pharmacological treatment approach, yoga has received increasing attention in RA treatment.3 Several studies report the effects of yoga in patients with RA,4-15 but there is no wide-ranging review reporting yoga's effect on RA. Hence, this comprehensive review was performed (using available literature) with the objective of providing a detailed scientific evidence-based description of the effect of yoga on all the parameters studied in RA. To find the relevant articles in English, we performed a literature search using PubMed/Medline, and Cochrane Library electronic databases up to 14 July 2022. Keywords "(Yoga (OR) pranayama (OR) meditation (AND) Rheumatoid arthritis)" were used in PubMed/Medline and "Yoga and Rheumatoid arthritis" was used in Cochrane Library. Articles available from the literature search (n = 136) were screened and the potentially eligible articles were included (n = 18). Clinical trials, controlled trials, randomized controlled trials (RCTs), quasi-experimental, observational studies, and qualitative studies dealing with yoga in combination with/without conventional medicine and RA were included. Review articles including meta-analyses, research protocols, articles that did not have either an abstract or full-text in English, similar articles, and articles with a lack of information were excluded. A total of 18 studies were included in this review—8 (44.44%) RCTs, 3 (16.67%) quasi-experimental studies, 2 (11.11%) mixed methods pilot studies, 2 (11.11%) qualitative studies, 2 (11.11%) controlled trials, 1 (5.56%) single group trial, 1 (5.56%) cross-sectional study, and 1 (5.56%) clinical trial. A total of 1196 patients (average n = 66.44, range 8–398) with RA were studied. Of the 18 studies, 3 (16.67%) used Iyengar yoga, 2 (11.11%) used Patanjali's raja yoga, 1 (5.56%) used hatha yoga, 1 (5.56%) studied the participant who underwent any of the following yoga: Vinyasa, Bikram, Hatha, Iyengar, or restorative yoga, and 11 (61.11%) did not specify the style of yoga they followed. The average duration of yoga practice per day was 81.11 min with a minimum of 25 min to a maximum of 180 min. The average frequency of yoga sessions was 3.36 days/week with a minimum of 1 session/day to a maximum of everyday. The average study period was 6.84 weeks with a minimum of 1 week to a maximum of 16 weeks (Table 1). SG: Patanjali's raja yoga for 120 min/day, 5 days/week for 8 weeks along with DMARDs. CG: DMARDs alone ESR, CRP, IL-6, IL-17A, TNF-α, ROS, 8OHdG, HAQ-DI, DAS28 ESR, BDI are decreased. TGF-β, HLA-G, BDNF, Serotonin, β endorphin, TAC, SIRT 1, Telomerase activity are increased. No significant changes in telomere length SG: Yoga (30 min/day, 3 days/week for 12 weeks). CG: DMARDs alone n = 66, SG n = 33, CG n = 33 SG: Patanjali's ashtanga yoga (120/day, 5 days/week for 8 weeks) along with DMARDs. CG: DMARDs alone n = 47, SG n = 26 CG n = 21 SG: Structured program (1 h/day, 2 days/week for 6 weeks). CG: DMARDs SG: Yoga along with DMARDs (120/day, 5 days/week for 8 weeks) CG: DMARDs n = 57, SG n = 30, CG n = 27 SG: Guided relaxation, asanas, breathing exercises, self-inquiry meditation, and OM chant (90 min/day, 2 days/week for 12 weeks) CG: Lecturing for 1 h/week by a rheumatologist At 12 weeks: HADS and fatigue are improved with change in SF-36. At 24 weeks: Significant improvement in SF-36 and fatigue, with no changes in HADS. No significant changes were observed at any time points for DAS-28, CRP, VAS-pain, and PSS SG: Iyengar yoga postures (1.5 h/day, 2 days/week for 6 weeks) CG: DMARDs SG: IRT, Kriya, anti-rheumatic series asanas, Pranayama, Meditation for (1.30 h/day for 40 days) CG: DMARDs n = 398, YG n = 35, NYG n = 329, n = 27 NR n = 8, SG n = 8 n = 20, SG n = 10, CG n = 10 SG: Yoga (2 h/day, 5 days/week for 6 weeks) CG: DMARDs n = 64, SG n = 64 n = 286, SG = 37A, 86C, 20RA CG = 37A, 86C, 20RA SG: Yoga (1 h/day, 1 month for adults, 10 days for children, 14 days for RA patients) CG: Under regular routine Yoga (1–1 for 16 weeks) Two group review by fifth and nineth month n = 26, SG n = 13, CG n = 13 SG: Yoga (75 min/day, 1 day/week for 8 week) and Home yoga practice (20 min/day, 3 days/week) CG: Usual medical care The effect of yoga on RA disease activity has been studied using the Disease Activity Score-28 (DAS-28), along with any one of the following parameters: erythrocyte sedimentation rate, C-reactive protein, or visual analogue scale. Previous studies suggest that practice of yoga produces reductions in inflammation, joint stiffness,4 and DAS-28 scores in patients with RA.5-9 Yoga helps to reduce disease progression and promote recovery in RA. Pain is one of the most common symptoms of RA. As the disease progresses, there is a destruction of the joints with cartilage and bone erosion that leads to disability and pain. Yoga practice produces a significant reduction in pain and disability, assessed using the Health Assessment Questionnaire Disability Index,5, 9-12 pain disability scale,11, 13 visual analogue scale,14 Health Assessment Questionnaire of pain15 Chronic Pain Acceptance Questionnaire, Arthritis Self-efficacy Scale13 and Simple Descriptive Pain Intensity Scale.4 Inflammation is one of the major symptoms that worsens the quality of life (QoL) in RA. It is analyzed by measuring the inflammatory markers (pro- and anti-inflammatory markers). Studies suggest that yoga significantly reduces pro-inflammatory markers such as interleukin-1α,6 interleukin-6,5-7 interleukin-17A,5, 7 erythrocyte sedimentation rate,5 tumor necrosis factor-α,5-7 cortisol,6 C-reactive protein,5, 15 and cytotoxic T-lymphocyte-associated antigen 4,7 and increases anti-inflammatory markers such as tumor growth factor-β7 and human leukocyte antigen-G5 in RA. Cellular integrity is essential for cellular homeostasis and it is affected by a multitude of stressors in the extra- and intra-cellular environments. Cellular health and longevity are achieved by maintaining optimal oxidative stress (OS) levels. OS is a pathogenic hallmark in RA, as evidenced by increased reactive oxygen species (ROS) and reduced antioxidant levels. Yoga practice helps to increase sirtuin1 (SIRT1), and reduce ROS, total antioxidant capacity (TAC), and 8-hydroxy-2-deoxyguanosine (8OHdG) levels.5 An increased SIRT1 level indicates a reduction in the progression of inflammation by regulating pro-inflammatory cytokines whereas decreased ROS, TAC, 80HdG levels indicate reduced OS. This indicates that yoga helps to maintain an intricate balance between ROS and TAC, with downregulation of highly mutagenic oxidative product (8OHdG) and upregulation of cell regulator (SIRT1), which promotes longevity. Cellular aging is the result of a progressive decline in the proliferative capacity and lifespan of cells. Shorter telomeres and decreased telomerase activity have been associated with increased cellular aging. In RA, telomere erosion and a reduction in telomerase activity appear to proceed more rapidly, whereas yoga increases telomerase activity5 and promotes a positive impact on cellular aging. Mitochondrial ROS are essential for signaling in antigen-specific T-cell activation. Supra-physiological levels of ROS lead to the damage of cellular components, inactivation of essential metabolic enzymes, and disruption of signal transduction pathways. Studies suggest that yoga improves cyclooxygenase-2 (COX-II) activity, upregulates mitochondrial DNA copy number, optimizes OS markers and circadian rhythm markers, and elevates nicotinamide adenine dinucleotide (NAD+) levels. Improvement in COX-II activity helps to maintain mitochondrial membrane potential and increases the expression of genes (monophosphate-activated protein kinase, tissue inhibitor of metalloproteinases, KLOTHO, SIRT-1, and transcription factor A mitochondrial) associated with maintenance of mitochondrial integrity. Elevated NAD+ indicates an increase in mitochondrial bioenergetics and functions.9 It suggests that yoga helps to enhance mitochondrial health in RA. Brain-derived neurotrophic factor (BDNF), is a cardinal biomarker of neuroplasticity that possesses neurotrophic and neuroprotective abilities. Yoga increases BDNF levels,5, 7 which in turn helps to improve mind–body communications that regulate neuroplasticity and reduce associated stress cascades. Literature suggests that there is dysregulation of dehydroepiandrosterone sulfate (DHEAS) (which has neuroprotective, antioxidant and anti-inflammatory properties) levels in RA patients, whereas yoga increases DHEAS levels and helps to improve emotional regulation, neurocircuits, and memory, and to reduce depression severity in RA.7 Likewise, yoga increases β-endorphin (an endogenous morphine secreted by the pituitary gland that acts as a neuroregulator) levels,5, 7 serotonin (a neurotransmitter that is involved in regulating behavior, mood, and memory)5 and develops a positive feeling with a sense of happiness, well-being, and security with improvement in anxiety and depression in RA patients.5, 7 Studies suggest that yoga significantly reduces serum uric acid levels and average lymphocyte count in RA4 thereby playing a crucial role in reducing systemic inflammation. Rheumatoid arthritis is associated with an increased burden of cardiovascular disease, which is partially attributed to classical risk factors such as hypertension. Yoga produces a significant reduction in systolic blood pressure, diastolic blood pressure, and pulse rate in RA patients4 and helps to improve cardiovascular functions in RA. Increased sympathetic activity promotes the secretion of inflammatory markers that favor inflammation in RA. Yoga reduces sympathetic activity and improves parasympathetic activity (i.e. significantly increases high-frequency and total power, and significantly reduces low-frequency, and the low to high frequency ratio in RA.6 Handgrip muscle strength describes the power or strength of hand muscles used to grasp or grip. RA preferentially affects the hands resulting in a reduction in muscle strength and mobility, whereas yoga improves hand grip strength11, 12, 15, 16 and ring size12 in RA. People with RA typically have inflammation that leads to general physical weakness, exhaustion, and fatigue. Studies suggest that yoga reduces fatigue assessed by Functional Assessment of Chronic Illness Therapy-Fatigue Subscale (FACIT-fatigue).13, 14 People with RA are more likely to experience psychological disturbances. Studies suggest that yoga produces a reduction in the scores of Hospital Anxiety Depression Scale,14, 17, 18 Beck Depression Inventory-II scale,5, 19 Brief Symptom Inventory,11, 13 Weekly Monitoring Form,13 Patient-Reported Outcomes Measurement Information System,10 and an increase in the scores of Five Factor Mindfulness Questionnaire.11, 13 It indicates that yoga helps to improve the psychological health of RA patients. Quality of life is a subjective evaluation of one's perception of reality relative to one's goals. RA causes impairment in QoL of patients in all aspects (limitation of physical function, physical disability, and pain). Studies suggest that yoga improves QoL measured using WHO QoL BREF,7 Global Improvement Scale,13 General health questionnaire,12 EuroQol-5D,17 Health-related QoL,11, 13 Short Form-36.8, 11, 14 It indicates that yoga helps to improve the physical, mental, emotional, social, and environmental health of RA patients. Patients with RA consistently reported that yoga helped with energy, relaxation, and mood and they discussed perceived mechanisms for how yoga impacted well-being. Mechanisms included physical changes such as range of motion and physiological awareness, and psycho-spiritual developments such as acceptance, coping, self-efficacy, and mindfulness. The mechanisms and outcomes reported by participants support a biopsychosocial model, which proposes that yoga benefits patients through both physiological and psychospiritual changes.20 First, participants perceived yoga as linked to physical, mental, and social well-being; second, the management of their RA was perceived to be prescriptive, medicalized, and failing to address their wider health concerns; third, yoga is a safe and adaptable therapy in the management of RA, although functional limitations inhibit the ability to practice; fourth, requirements for a yoga intervention were feasible.21 A summary of the impact of yoga on RA is provided in Figure 1. Of the 18 included studies, only 5 were registered in the clinical trial registry, 10 were not RCT, and only 5 studies were performed on populations other than Indian or US populations. Sample size varied from 8 to 398, and 16 studies had small sample size (10 with <50 participants, 6 with <100 participants), 11 studies did not specify the type of yoga they followed, and the duration of yoga practice varied from 25 min to 180 min/day, 1 day to daily/week for 1 to 16 weeks. There were inconsistencies in the findings of the studies on various parameters including pain, fatigue, cortisol level, Health Assessment Questionnaire Disability Index , etc (Table 1). As an adjuvant, yoga may help to reduce disease activity and improve QoL in RA by reducing DNA damage, inflammation, and oxidative stress, and by improving mobility, cardiovascular function, and psychological well-being by acting through various biomarkers. However, the type, duration, and frequency of the yoga practices varied among the studies and many studies had small sample size and weak study design. Future studies, particularly RCTs using a validated yoga protocol, are recommended with a larger sample size to find yoga's effects with precise mechanisms for better clinical practice. We thank Dr N. Manavalan (Principal) and Dr Dharani (PG Scholar, Department of Acupuncture and Energy Medicine), Government Yoga and Naturopathy Medical College, Chennai, India for their moral support. Study conception: A. Mooventhan, L. Nivethitha. Study Design: A. Mooventhan, L. Nivethitha. Data collection: S. Pavithra, N. Meha, S. Monisha, R. Deepika, R. Poorani. Analysis and interpretation of results: A. Mooventhan, L. Nivethitha, S. Pavithra, N. Meha. Manuscript preparation: A. Mooventhan, S. Pavithra, N. Meha, L. Nivethitha. Manuscript editing: A. Mooventhan, L. Nivethitha. None declared. Data sharing is not applicable to this article as no new data were created or analyzed in this study.