Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease that affects all joints, connective tissues, muscles, tendons and fibrous tissues of the body. This leads to pain, atrophy, and deformation of joints, muscle distortion, bones erosion, and osteoporosis, ultimately resulting in functional impairment, disability, decreased quality of life and risk of early death.¹ Despite the development of many conventional RA therapies, they often come with a multitude of adverse side effects and low rates of effectiveness. Recently, many researchers have been trying to develop additional, more natural solutions for the management of RA symptoms which have lower toxicity and less side-effects.²  

Epidemiological studies have repeatedly shown an inverse association between the risk of chronic human diseases and the consumption of polyphenolic rich diets.³ Flavonoids such as quercetin, comprise the most studied group of polyphenols and are believed to act as health-promoting substances due to their antioxidant, anti-inflammatory and anti-nociceptive properties.⁴  

In order to investigate the effect of quercetin as an adjunctive treatment on the clinical symptoms and disease activity in patients with RA, a randomised, double-blind, placebo-controlled clinical trial was conducted whereby 50 women with RA were allocated to receive quercetin (500 mg/day) or placebo for 8 weeks.¹ Disease activity and functional disability were assessed by Disease Activity Score 28 (DAS-28), physician global assessment (PGA), and a health assessment questionnaire (HAQ) at the beginning and end of the study. Plasma levels of high-sensitivity tumour necrosis factor-alpha (hs-TNFα), erythrocyte sedimentation rate (ESR), clinical symptoms including early morning stiffness (EMS), morning and after-activity pain, and tender (TSC) and swollen joint counts (SJC) were also determined.

At the end of the trial period, quercetin supplementation significantly reduced EMS, morning pain, and after-activity pain (p < 0.05). DAS-28 and HAQ scores decreased in the quercetin group compared to placebo and the number of patients with active disease significantly decreased in the quercetin group. Plasma hs-TNFα level was significantly reduced in the quercetin group compared to placebo (p < 0.05). There were no significant differences in TJC and SJC between groups but TJC significantly decreased in the quercetin group after the intervention. Supplementation had a non-significant effect on ESR (p > 0.05).

Quercetin may have anti-nociceptive effect through different mechanisms, such as by influencing the L-arginine-nitric oxide, serotonin, GABAergic, and opioid systems, as well as inhibiting pronociceptive cytokine production and the free radical generation that accompanies inflammatory pain.^1,5

While more studies in larger populations and over longer time periods are needed to confirm these results, these findings highlight the need for practitioners to consider quercetin as a suitable nutritional supplement for the support of clinical symptoms and disease activity in patients with rheumatoid arthritis. Practitioners should consider the following supportive options:

• Prescribe between 500-1,500 mg of quercetin per day in divided doses.^1,6
• Consider additional sources of anti-inflammatory and antioxidant support such as a concentrated fish oil with high EPA and DHA content (30-40 mg/kg bw/day EPA + DHA)⁶, highly bioavailable Curcuma longa (turmeric), Zingiber officinale (ginger), bromelain, grape seed extract and vitamin C.
• A potent combination of evidence-based nutrients, including vitamin K2, calcium, vitamin D3, and key cofactors including magnesium, manganese, zinc and boron can be clinically prescribed to promote bone health throughout the life stages.
• Educate patients on the importance of consuming a diet rich in nutrient dense whole foods. Fruits, such as berries, citrus fruits and pomegranates, are particularly rich sources of a variety of bioactive compounds, especially the polyphenolic flavonoids that have been associated with antioxidant, anti-inflammatory and analgesic effects.⁷

 

References

1. Javadi, F., et al., The Effect of Quercetin on Inflammatory Factors and Clinical Symptoms in Women with Rheumatoid Arthritis: A Double-Blind, Randomized Controlled Trial. J Am Coll Nutr, 2017. 36(1): p. 9-15.
2. Sung, S., et al., Could Polyphenols Help in the Control of Rheumatoid Arthritis? Molecules (Basel, Switzerland), 2019. 24(8): p. 1589.
3. Pandey, K.B. and S.I. Rizvi, Plant polyphenols as dietary antioxidants in human health and disease. Oxidative Medicine and Cellular Longevity, 2009. 2(5): p. 270-278.
4. Carullo, G., et al., Quercetin and derivatives: useful tools in the inflammation and pain management. Future Medicinal Chemistry, 2016. 9.
5. Kelly, G.S., Monograph: Quercetin. Alt Med Rev, 2011. 16(2): p. 172-94.
6. Braun, L. and M. Cohen, Herbs & Natural Supplements: An Evidence-Based Guide. 4th ed. 2015, Sydney: Churchill Livingstone/Elsevier.
7. Basu, A., J. Schell, and R.H. Scofield, Dietary fruits and arthritis. Food & Function, 2018. 9(1): p. 70-77.