Omega-3 Fatty Acids and Vitamin D Improves Inflammatory Biomarkers in Rheumatoid Arthritis

The chronic, systemic autoimmune illness known as rheumatoid arthritis (RA) is characterized by joint degeneration, synovial inflammation, and a substantial decline in quality of life. Although biologics and pharmacologic treatments, such as disease-modifying antirheumatic medications (DMARDs), continue to be the mainstay of management, interest in supplemental medicines that may lower inflammation and enhance clinical results has increased. A recent systematic review and meta-analysis that was published in Food Science & Nutrition assessed the use of vitamin D and omega-3 fatty acids in patients with RA and determined that both supplements were linked to improvements in inflammatory biomarkers, pain, and disease activity markers.¹

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The immunomodulatory effects of omega-3 polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are well recognized. They function by modifying the synthesis of cytokines, reactive oxygen species, and proinflammatory eicosanoids.² The meta-analysis's clinical studies showed that taking omega-3 supplements decreased morning stiffness, the number of sensitive joints, and the need for NSAIDs. Another meta-analysis found that consuming 2.7 g of EPA/DHA daily for three months significantly decreased inflammatory indicators like IL-6 and C-reactive protein (CRP) as well as disease activity.³

Vitamin D and Immune Modulation in RA

Immune system control and skeletal health are both significantly impacted by vitamin D. T and B lymphocytes have their receptors, indicating direct immunomodulatory actions.^4,5 According to the comprehensive analysis, vitamin D supplementation was linked to slight improvements in inflammatory biomarkers like CRP and erythrocyte sedimentation rate (ESR), visual analog scale (VAS) pain ratings, and Disease Activity Score-28 (DAS-28).¹

A separate randomized controlled trial involving 75 patients with RA found that 60,000 IU/week of vitamin D3 for 8 weeks significantly improved DAS-28 scores and reduced IL-17 and TNF-α levels compared to placebo.⁶ However, not all trials report consistent benefits, and heterogeneity remains high due to differences in baseline vitamin D levels, dosing regimens, and disease severity.¹ Pharmacists should recommend testing 25(OH)D levels before initiating high-dose regimens and monitor serum calcium to avoid hypercalcemia, especially in patients on diuretics or calcium supplements.

Practical Considerations for Pharmacists

Pharmacists play a key role in helping patients with RA safely incorporate omega-3 fatty acids and vitamin D into their treatment plans. Recommended dosing includes 1.8 to 3g per day of combined EPA and DHA, and 1000 to 2000 IU per day of vitamin D3 for maintenance, or up to 50,000 IU per week for repletion based on lab values.⁶ It is recommended that patients on warfarin or clopidogrel should be monitored for bleeding risks when starting omega-3s, and pharmacists should watch for additive effects with anti-inflammatory drugs. Regular monitoring is essential; vitamin D levels should be checked every 8 to 12 weeks, and disease activity measures like DAS-28, VAS, and CRP should be tracked. Patients should be counseled that supplements take 2 to 3 months to show benefits and are intended to support, not replace, prescribed RA medications.

Future Research

Although vitamin D and omega-3 fatty acids both show promise as adjuvant treatments, the available data is constrained by brief trial periods, small sample sizes, and research heterogeneity. More high-powered standardized studies are required to evaluate long-term clinical outcomes, dose-response relationships, and effects in individuals with different illness severity, according to the meta-analysis's authors.¹

Omega-3 fatty acids and vitamin D are promising adjuncts for managing inflammation and improving outcomes in patients with RA. Pharmacists can play a pivotal role in guiding safe, evidence-based supplementation by recommending appropriate dosages, monitoring for interactions, and reinforcing adherence. These strategies complement pharmacologic treatment and align with holistic, patient-centered care in autoimmune disease management.

REFERENCES

1. Xu B, Liang D, Chen G. Evaluation of the Clinical Outcomes Associated With the Use of Fatty Acids and Vitamin D in Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis. Food Sci Nutr. 2025;13(7):e70473. Published 2025 Jul 21. doi:10.1002/fsn3.70473

2. Calder PC. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans. 2017;45(5):1105-1115. doi:10.1042/BST20160474

3. Miles EA, Calder PC. Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis. Br J Nutr. 2012;107 Suppl 2:S171-S184. doi:10.1017/S0007114512001560

4. Wachira JK, Larson MK, Harris WS. n-3 Fatty acids affect haemostasis but do not increase the risk of bleeding: clinical observations and mechanistic insights. Br J Nutr. 2014;111(9):1652-1662. doi:10.1017/S000711451300425X

5. Chandrashekara S, Patted A. Role of vitamin D supplementation in improving disease activity in rheumatoid arthritis: An exploratory study. Int J Rheum Dis. 2017;20(7):825-831. doi:10.1111/1756-185X.12770

6. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-281. doi:10.1056/NEJMra070553