Therapeutic efficacy of Urtica dioica and evening primrose in patients with rheumatoid arthritis: A randomized double-blind, placebo-controlled clinical trial.

Abd-Nikfarjam B, Abbasi M, Memarzadeh M, Farzam SA, Jamshidian A, Dolati-Somarin A. Journal of Herbal Medicine. 2022 Mar 1;32:100556.

Reigning in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease affecting peripheral joints, particularly the small joints of the hands and feet. An estimated 456,000 (1.9%) Australians have the condition which causes joint pain and swelling, morning stiffness, fatigue and a decline in physical functioning and quality of life.^1,2

Recent research demonstrates that Nettle (Urtica dioica) and Evening Primrose Oil (EPO)(Oenothera biennis) may help improve symptoms of RA by addressing underlying drivers, potentially reducing the need for pharmaceutical interventions.³

Investigating the Effects of Nettle Leaf and Evening Primrose Oil

A randomised, double-blind, placebo-controlled trial investigated the effects of Nettle leaf extract and EPO on clinical symptoms and laboratory parameters in patients with RA.³ Ninety patients aged 24-82 years were randomly assigned to receive either dried Nettle leaf extract (400 mg TDS), EPO (500 mg TDS) or placebo for three months as an adjunct to standard treatment (NSAIDS, Methotrexate, low dose oral steroids).              

Clinical evaluations and laboratory tests were done at baseline and following treatment, measuring the effects on symptoms (Disease Activity Score 28, DAS28), antibodies (Rheumatoid Factor [RF], anti-cyclic citrullinated peptide [anti-CCP]), total antioxidant capacity (TAC), and inflammatory markers, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and interleukin 17 (IL-17).

Nettle and Evening Primrose Oil Reduce Disease Activity and Pain

Patients in the active treatment groups experienced improvements in symptoms, reduced disease activity, and less inflammation following treatment. After the three-month intervention, mean values of DAS28, RF, CRP and IL-17 were significantly reduced in the Nettle and EPO groups compared to placebo (p≤0.05). Anti-CCP and RF antibodies reduced significantly compared to baseline in both groups, and this change was greater in the Nettle group. Further, TAC significantly increased compared to placebo, indicating greater antioxidant activity.

These findings indicate that Nettle and EPO can significantly decrease disease activity and pain in RA patients when compared to placebo, helping to relieve clinical symptoms.³

Inflammation Fuels the Arthritic Fire

Inflammation drives RA symptoms and disability, and its reversal is a major therapeutic target. T lymphocytes, B lymphocytes, and inflammatory cytokines (e.g. TNF-α, IL-6, and IL-17) have major roles in developing symptoms such as bone and cartilage destruction, and synovitis. Th17 cells express IL-17 and other cytokines involved in the development of inflammation and joint injury in RA.³

Results suggest that EPO and Nettle improve pain and other symptoms by inhibiting the inflammatory cascade, supporting production of anti-inflammatory mediators in plasma, and increasing antioxidant capacity.³ Reducing inflammation can be a disease-modifying strategy, helping to slow and/or prevent joint damage and improve physical functioning.²

Nettle Leaf - a Time-Tested Remedy for Arthritis

Fresh stinging nettles were used in ancient times to flail arthritic limbs, stimulating circulation and bringing warmth to joints in a treatment known as urtication or rubefaction.³ Modern research confirms the herb’s therapeutic applications in arthritic disease.

Nettle leaf extract has significant anti-inflammatory and analgesic effects. Studies have shown its inhibitory potential on the pro-inflammatory transcription factor NF-κB, which is elevated in the synovial fluid of RA patients.⁴ Several studies have indicated Nettle extract inhibits the production of T cells cytokines and can prevent inflammation in autoimmune diseases such as RA.⁵

Anti-inflammatory and Antioxidant Effects of Evening Primrose Oil

EPO is prescribed for its antioxidant and anti-inflammatory effects in autoimmune and inflammatory diseases. Obtained from evening primrose seeds, EPO is an important source of omega-6 essential fatty acids, especially gamma-linolenic acid (GLA).

In the current study, daily EPO doses included 420 mg GLA which is likely to have contributed to its therapeutic effects.³ This study supports earlier research that showed significant and clinically relevant reductions in signs and symptoms, and considerable decreases in morning stiffness and articular index in RA patients taking GLA.^6,7

In summary

Standard pharmaceutical interventions can have side effects with long-term use and may fail to achieve complete disease improvement in some patients; therefore, new interventions are needed.

This study demonstrates that 3 month’s treatment with either Nettle leaf extract or EPO alongside standard treatment can significantly decrease the levels of inflammatory markers in patients with RA, improving pain and enhancing quality of life.³

References

1. Australian Institute of Health and Welfare (AIHW). Chronic musculoskeletal conditions: rheumatoid arthritis [Internet]. AIHW; Canberra. [cited 2023 Aug 18, updated 2023 Jun 30]. Available from: https://www.aihw.gov.au/reports/chronic-musculoskeletal-conditions/rheumatoid-arthritis-1
2. Smolen JS, Aletaha D, McInnes I. Rheumatoid arthritis. Lancet. 2016;388(10055):2023-2038.
3. Abd-Nikfarjam B, Abbasi M, Memarzadeh M, Farzam S, Jamshidian A, et al. Therapeutic efficacy of Urtica dioica and evening primrose in patients with rheumatoid arthritis: A randomized double-blind, placebo-controlled clinical trial. Herb Med. 2022;32:100556. doi: 10.1016/j.hermed.2022.100556.
4. Riehemann K, Behnke B, Schulze-Osthoff K. Plant extracts from stinging nettle (Urtica dioica), an antirheumatic remedy, inhibit the proinflammatory transcription factor NF-kappaB. FEBS Lett. 1999 Jan 8;442(1):89-94. doi: 10.1016/s0014-5793(98)01622-6.
5. Dhouibi R, Affes H, Ben Salem M, Hammami S, Sahnoun Z, Zeghal KM, et al. Screening of pharmacological uses of Urtica dioica and others benefits. Prog Biophys Mol Biol. 2020 Jan;150:67-77. doi: 10.1016/j.pbiomolbio.2019.05.008.
6. Zurier RB, Rossetti RG, Jacobson EW, DeMarco DM, Liu NY, Temming JE, White BM, Laposata M. gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. Arthritis Rheum. 1996 Nov;39(11):1808-17. doi: 10.1002/art.1780391106. 
7. Brzeski M, Madhok R, Capell HA. Evening primrose oil in patients with rheumatoid arthritis and side-effects of non-steroidal anti-inflammatory drugs. Br J Rheumatol. 1991 Oct;30(5):370-2. doi: 10.1093/rheumatology/30.5.370.