Rheumatoid arthritis (RA) is a chronic autoimmune, inflammatory and systemic disease that impacts the  joints and other organs. Affecting approximately 0.4-1.3% of the global population, RA leads to pain, disability, and is significant burden on individuals and society.

Disease Characteristics

RA is characterized by synovitis, the inflammation of the synovial membrane that lines the joints. This inflammation leads to the proliferation of synovial tissue, infiltration of immune cells, and the release of inflammatory mediators, ultimately resulting in the destruction of cartilage and bone. The disease typically affects the same joints on both sides of the body and can also manifest in extra-articular features like rheumatoid nodules or vasculitis that may impact other organs in the body.

Causes and Contributing Factors

I have dedicated a lengthy article discussing in details all the biological and environmental/life style factors that contribute to the development and progression of the disease but here is a short explanation; The development of RA is influenced by a complex interplay of genetic and environmental factors. Several genes, including HLA-DRB1, TNFRSF14, and PTPN22, have been strongly associated with an increased risk of RA. These genes are involved in immune system regulation and antigen presentation, suggesting a role for T cell-mediated autoimmune responses in causing RA.

Environmental factors such as smoking, diet, obesity, use of external hormones, infections, chemical exposures and air pollution can also contribute to the development of RA, potentially through epigenetic mechanisms that modify gene expression. This means that you could be genetically susceptible to the disease but those genes were not activated, then one or a number of environmental/ lifestyle factors occur and they cause activation of these genes leading RA to manifest.

Disease Progression and Complications

If left untreated, RA can lead to severe joint damage, disability, and a reduced quality of life. Chronic inflammation associated with RA can also contribute to the development of comorbidities, such as cardiovascular diseases, further increasing the risk of mortality. Even when RA is managed and clinical remission is achieved, the damage to joints is often irreversible. Therefore, early diagnosis and intervention with effective strategies for prevention (through controlling non-biologic risk factors), and treatment is imperative for achieving a positive outcome.

Current Treatment Options and Limitations

Currently, there is no cure for RA. Available treatments primarily focus on reducing pain and inflammation, slowing disease progression, and preventing joint damage. Common medications used for RA include:

• DMARDs: Disease-modifying anti-rheumatic drugs These are drugs like methotrexate and hydroxychloroquine that reduce symptoms and slow progression by inhibiting the body’s immune response reducing inflammation.
• Biological Treatments: Newer treatments such as adalimumab and etanercept, used in combination with DMARDs when they alone are not effective. They work by targeting specific immune system cells that causes the symptoms of RA.
• Pain Relief and anti-inflammatory Medication: Includes painkillers like paracetamol and NSAIDs like ibuprofen, or corticosteroids.

While these treatments can provide relief and improve disease management, they often come with significant side effects, such as immune suppression, hepatotoxicity, cardiovascular complications, and gastrointestinal issues. Additionally, a substantial proportion of patients (30-50%) do not respond effectively to standard therapies, limiting the long-term benefits of treatment.

The Potential of Herbal Medicine in Rheumatoid Arthritis Treatment

The limitations of current treatments and the desire for safer alternatives have led to increased interest in the therapeutic potential of herbal medicine for RA. Traditional medicine systems, such as traditional Chinese medicine and Indian Ayurvedic medicine, offer a vast array of plant-derived compounds with potential anti-inflammatory and immunomodulatory properties.

Herbal medicines have been used for centuries to manage various health conditions, including inflammatory and autoimmune diseases. Many modern drugs are derived from plant compounds, demonstrating the potential of natural products in drug discovery and development.

Several plant-derived compounds have shown promise in preclinical and clinical studies for the treatment of RA. These compounds can act through multiple mechanisms, including:

• Modulating specific immune cells
• Regulating inflammatory mediators
• Inhibiting tissue-degrading enzymes

Advantages of Herbal Medicine

While Herbal medicines may not work as quick as pharmaceuticals, considering that this condition is a chronic one that requires a life-long treatment, in this case herbal medicines are often considered superior to synthetic drugs in several aspects:

• They are generally non-toxic and well-tolerated in the long-run in recommended doses.
• They can target multiple pathways involved in the disease process without impacting the healthy tissues.
• They may offer synergistic effects when used in combination together or with other synthetic pharmaceuticals.
• They are often more affordable and accessible than synthetic drugs.

As usual, it is always crucial to consult with your physician or integrative medicine specialist before taking any herbs, as despite being generally safe, if you suffer from any health condition such as liver or kidney disease, some herbs may not be suitable for you, while others their dose may need to be adjusted. Also, if you are already taking other medications or supplements, some interactions may occur so in this case your physician would advise you to ensure a certain period pass between the doses of these two.

Herbal Medicines and Supplements for Rheumatoid Arthritis (RA) Treatment

Resveratrol

Resveratrol, a natural compound found in over 70 plant species, is gaining recognition for its potential in managing rheumatoid arthritis (RA). This is largely due to its antioxidant and anti-inflammatory properties, which protect the mitochondria and contribute to overall cellular health.

Early studies in animal models provided the initial evidence for resveratrol’s therapeutic effects in RA, it was found to reduce cartilage breakdown animals with arthritis. Furthermore, one  study  showed superior results of resveratrol compared to the traditional medications in reducing RA symptoms in rat models.

Afterwards, researchers moved to prove its efficacy in humans;

• A 2018 randomized controlled trial involving 100 RA patients (68 women, 32 men) supported the use of resveratrol as an add-on therapy to conventional anti-rheumatic drugs. Resveratrol improved both the symptoms and the underlying biological markers of RA, indicating it might help slow down the disease’s progression.
• Resveratrol also demonstrated synergistic effects when used in combination with methotrexate, a common RA medication. This combination can enhance the treatment efficacy.

Effects on RA Complications

While the focus is on clinical studies related to RA itself, it’s worth noting that resveratrol has shown promise in also addressing RA-related complications:

• Resveratrol reduced the incidence and severity of atrial fibrillation (AF) in animal with arthritis.
• It also protected against lung complications and periodontal disease (gum disease) which are associated with RA.

Overall, the accumulating evidence from preclinical and clinical studies suggests that resveratrol holds a great promise as a standalone or adjunctive therapy for RA, with the potential to improve treatment outcomes and prevent complications.

Curcumae Longae Rhizoma (CLR)

CLR, commonly known as turmeric, is a traditional herbal medicine with a long history of use. Its primary active compound, curcumin, has been extensively studied for its anti-inflammatory properties. β-Elemene, another compound found in CLR, has been shown to induce apoptosis (programmed cell death) in RA fibroblast-like synoviocytes (FLS), which are cells involved in joint inflammation and damage.

Clinical trials have demonstrated the therapeutic potential of curcumin in RA. A study where patients receiving either 250 mg or 500 mg of curcumin twice daily for 90 days showed significant improvements in clinical symptoms, including reduced CRP levels and improved DAS-28 scores.

An animal study evaluated a standardized formulation containing extracts of Zingiber officinale (ginger), Boswellia serrata, Curcuma longa, and Withania somnifera, in rats with RA. The study found that the formulation improved symptoms and inflammatory markers.
In a human clinical trial to replicate these results in patients with osteoarthritis, The study involved 201 patients, it investigated the effects of 333 mg curcuminoids alone,  or (350 mg curcuminoids and 150 mg boswellic acid) taken orally three times a day for 12 weeks compared to placebo in a three-arm, randomized trial. The results show Twelve-week use of curcumin complex or its combination with boswellic acid reduces pain-related symptoms in patients with OA. Curcumin in combination with boswellic acid showed the most efficacy, presumably due to synergistic effects of curcumin and boswellic acid.

A 2022 systematic review and meta-analysis of 29 randomized controlled trials concluded that curcumin and Curcuma longa extract, administered in doses ranging from 120 mg to 1500 mg for 4-36 weeks, were safe and effective in improving inflammation and pain in arthritis patients.

Ginger

Ginger ((Zingiber officinale Roscoe), a member of the Zingiberaceae family, has been used for thousands of years as both a spice and a traditional medicine, such as Ayurvedic and Chinese medicine. Modern scientific research is now confirming its potential benefits, particularly in managing inflammation and pain associated with conditions like rheumatoid arthritis (RA) and osteoarthritis (OA).

Anti-inflammatory Effects

Studies have shown that ginger can reduce inflammation in the body. In one study, consuming 750mg of ginger powder twice daily lowered the activity of genes linked to inflammation in patients with RA. Similar effects were seen in OA patients, where 500 mg of ginger powder daily for three months reduced the production of inflammatory substances. The study reported lowered specific markers of inflammation (NO and CRP) in the OA patients, with effects lasting even after 12 months.

Pain Relief

Ginger has also demonstrated pain-relieving properties. In OA patients, oral ginger powder and topical ginger gel (5% concentration) were both effective in reducing pain and improving function. In one clinical trial, The gel provided pain relief for up to three months after just two weeks of application.

Combining Ginger with Other Herbs

Research also suggests that ginger can be effectively combined with other plants known for their anti-inflammatory properties, such as turmeric (Curcuma longa) and galangal (Alpinia galanga). One study found that a combination of ginger and galangal reduced knee pain in OA patients, with reduction in the number of occasions patients had to resort to taking rescue medications such as powerful painkillers. Another study showed that a blend of ginger, turmeric, and black pepper had similar effects to administering 250 mg of naproxen four times daily in reducing prostaglandin E2 (PGE2), which is directly linked to increased pain perception as it is a key mediator of inflammation, causing pain signals to be amplified in the body, essentially making you feel more pain.

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Safety and Side Effects

Importantly, ginger appears to be safe with minimal side effects. In the studies reviewed, ginger did not cause any serious adverse effects. Only a few instances of mild gastrointestinal symptoms was reported. Studies have shown ginger to be safe for use over several years, which is particularly relevant for individuals with chronic conditions like OA and RA who often require long-term pain management.

Piperine

Piperine, a compound found in black pepper, has shown potential benefits in managing rheumatoid arthritis (RA) due to its anti-inflammatory properties.

Studies have shown that piperine can:

• Reduce inflammation: It inhibits molecules involved in inflammation and oxidative stress
• Alleviate symptoms: A study in rats reported that piperine significantly reduced arthritis-related pain and swelling.
• Impact RA cells: A study of the cells of 68 RA patients and 30 healthy controls showed that piperine decreased the growth and increased the death of fibroblast-like synoviocytes (RA-FLSs), cells involved in RA joint damage. The study also found that peperine regulates the expression of genes, increasing the expression/activation of genes that can cause death to harmful cell, while reducing the expression of others related to the proliferation of these cells and inflammation. The study suggested that this compound could be a suitable alternative for pharmaceutical treatment of RA.
• Improve curcumin absorption: Piperine was also found to enhance the bioavailability of curcumin, therefore, it is always recommended to combine both for best results.

Sinomenine

Sinomenium acutum is a herb that has been long used in Asia in traditional medicine, particularly in Japan and China, as it is well-known for its medicinal properties. It has been used to treat rheumatism and arthritis due to its anti-inflammatory and immunosuppressive effects. The plant’s main active compound, Sinomenine, has shown promising neuroprotective and anti-arthritic effects in research studies. The exact mechanisms through which sinomenine exerts its therapeutic effects are still being investigated. However, research suggests that it interacts with multiple targets and pathways, contributing to its multi-faceted effects in managing RA.

Effects of Sinomenine

• Anti-arthritic Effects: Studies have shown sinomenine’s ability to reduce arthritis severity, suppress inflammatory responses, and inhibit COX-2 production, which plays a role in pain and inflammation.
• Immunomodulatory Effects: Sinomenine has been found to regulate immune responses, which is crucial in managing autoimmune diseases like RA.
• Anti-inflammatory Effects: It helps in reducing inflammation, a key aspect of RA.
• Analgesic Effects: Sinomenine contributes to pain relief, improving the quality of life for RA patients.
• Bone Metabolism Improvement: It aids in improving bone health, which is often compromised in RA.

Side Effects

Sinomenine is generally well-tolerated. However, some cases of histamine-release-like anaphylactoid reactions (HRARs) have been observed in clinical trials. Further research is needed to fully understand and document these reactions.

Omega 3 fatty acids

Studies show that taking omega-3 fatty acids, especially those from animal sources like fish oil, can help people with inflammatory rheumatic diseases, particularly rheumatoid arthritis.

One recent systematic review of 30 clinical trials, including 1420 patients, showed that omega-3 supplements significantly improved pain, joint swelling, and overall disease activity. The benefits were most noticeable when patients took more than 2 grams of animal-sourced omega-3s per day.

Another review and meta-analysis of 23 studies confirmed these findings. Omega-3s led to small but significant reductions in pain, tender and swollen joints, and the need for taking anti-inflammatory drugs (NSAIDs). Additionally, omega-3s slightly lowered levels of c-reactive protein, a marker of inflammation in the body.

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Quercetin

Quercetin (QU), a natural compound found in many plants, has shown potential in various health applications, including anti-inflammatory, anti-platelet aggregation, and antitumor activities. It has been studied for its potential benefits in RA.

Studies have shown that QU can reduce inflammation in mice with arthritis. Specifically, it lowers the production of inflammatory mediators and inhibits the expression of inflammatory cytokines.

In a human clinical trial involving women with RA, QU did not significantly alter CRP levels, a marker of inflammation, after continuous dosage 500 mg/day for 8 weeks. However, it did significantly reduce pain (after-activity pain and morning pain) and improve overall disease activity. Compared to a placebo, QU supplementation led to a decrease in TNF-α levels, a key inflammatory cytokine involved in RA, improved symptoms and functional ability in RA patients.

Importantly, QU has shown a favorable safety profile. No side effects were reported in these studies, suggesting that QU may be a safe and effective option for managing RA symptoms and disease activity.

Green Tea Epigallocatechin-3-gallate (EGCG)

Green tea’s secret weapon, EGCG, is a potent anti-inflammatory, offering hope for those with arthritis. Studies show it can block substances that trigger joint inflammation and pain, such as PGE2, COX-2, and TNF-α.

• Cartilage protection: EGCG safeguards cartilage, by preventing the breakdown of essential proteins (MMP-13 and MMP-1). This protection increases with higher EGCG doses. In lab studies, EGCG effectively inhibited these destructive enzymes.
• Tendon health: EGCG also protects tendons, the connective tissue between muscles and bones, by inhibiting certain enzymes that can cause damage and pain.
• Reducing inflammation: Research demonstrated EGCG’s ability to suppress inflammation in human chondrocytes (cartilage cells) and tendon fibroblasts. This means potentially less pain and stiffness for arthritis sufferers.

Boswellic Acid (BA)

Boswellic acid (BA) is a natural compound found in plants that has been used for centuries to treat various health problems. Modern research suggests that BA may be effective in treating osteoarthritis (OA) and rheumatoid arthritis (RA).

Studies on BA for OA have shown promising results. In a 2003 study, all 30 participants with OA knee pain reported decreased pain and increased mobility after taking boswellia. A more recent study found that higher doses of boswellia extract led to even greater improvements in physical ability and reduced cartilage damage.

In RA patients, a study on a blend of boswellia, ginger, curcuma and ashwagandha reported a significant reduction in swollen joints and rheumatoid factor |(RF)

Boswellia may help reduce joint swelling and improve pain potentially through various anti-inflammatory and immune modulating activities. More human research is needed to determine the optimum dose for efficacy and safety.

Probiotics and Rheumatoid Arthritis (RA)

Gut Dysbiosis and Rheumatoid arthritis

An imbalance in gut bacteria, known as dysbiosis, can contribute to the development of RA through various mechanisms, including molecular mimicry, leaky gut, and metabolic dysregulation. Studies have shown that individuals with RA have an increased presence of Bacteroides, Escherichia, and Shigella bacteria in their gut, along with a significant decrease in beneficial Lactobacillus species.

Role of Probiotics

Probiotics, which are live microorganisms that offer health benefits, have emerged as potential tools for managing RA. They can counteract the negative effects of dysbiosis by:

• Displacing harmful bacteria in the gut.
• Producing anti-inflammatory metabolites, such as short-chain fatty acids (SCFAs).
• Directly influencing immune cells.
• Modifying host metabolism.

Lactobacillus spp. and Gut Integrity

Adequate colonization of Lactobacillus spp. can improve the integrity of the gut lining, making it less susceptible to infections and the translocation of harmful bacteria into the intestinal lumen. These bacteria also secrete SCFAs and vitamins that provide nutritional support and help maintain a healthy gut environment.

Clinical Studies:

• An 8-week randomized clinical trial found that daily administration of L. casei in women with RA reduced joint swelling, disease activity scores, and levels of pro-inflammatory markers, while also improving insulin levels. However, it did not change oxidative stress indicators or lipid profiles of RA patients.
• Another study with a similar L. casei treatment protocol showed similar improvement of disease activity and inflammation in RA patients.
• Regular consumption of L. casei preserves the gastrointestinal diversity and prevents gastrointestinal dysbiosis, physiological stress, RA, and other inflammatory disorders
• The consumption of L. casei and L. acidophilus might sometimes, but rarely, produce harmful effects, this was observed in an animal study, possibly due to an excessive increase in the population of these bacteria in their gut.

Vitamin-B6 Deficiency

A well-balanced gut microflora provides essential vitamins, including vitamin B6. Low plasma vitamin B6 has been observed in inflammatory conditions like RA. And long-term treatment with NSAIDs such as Ibuprofen, Naproxen, Diclofenac and Aspirin, can hinder vitamin B6 metabolism, further reducing vitamin B6 levels in the blood. Impaired levels of essential vitamins, especially vitamin B6 deficiency, can contribute to RA and cardiovascular complications.

It is important to note that the randomized clinical trials on probiotics in RA are not easily comparable due to variations in patient selection, probiotic formulation, experimental parameters, dose, and frequencies of probiotic treatment.
Further research is necessary to optimize probiotic strains, dosages, and treatment protocols for personalized and effective management of RA.

Other complementary Rheumatoid Arthritis Treatments:

Acupuncture

Acupuncture is a traditional Chinese medicine technique that involves inserting thin needles into specific points on the body. It has been studied as a complementary therapy for rheumatoid arthritis.

Benefits and Mechanisms

A 2018 systematic review of 43 studies indicated that acupuncture, used alone or in conjunction with conventional treatments, can be beneficial for people with RA. The review found that acupuncture may improve symptoms like pain and stiffness, enhance physical function, and boost overall quality of life. Notably, no adverse effects were reported in the reviewed studies. Researchers believe these benefits may stem from acupuncture’s anti-inflammatory and antioxidant effects, as well as its ability to regulate the immune system.

Types of Acupuncture and Effectiveness

A 2022 meta-analysis delved deeper into the effectiveness of different types of acupuncture for RA. This analysis, which included 32 randomized controlled trials and 2,115 RA patients, found that combining electroacupuncture with standard drug therapy (DMARDs) was the most effective approach for improving disease activity scores. However, when it came to alleviating pain and improving blood markers of inflammation, fire needle acupuncture and moxibustion, both combined with DMARDs, showed the greatest promise.

Moxibustion is a form of heat therapy often used in conjunction with acupuncture. It involves burning dried mugwort, a type of herb, near specific acupuncture points. I know this may sound a woo woo land non-scientific application, however, this method of applying heat is believed to stimulate these points and enhance the flow of energy, or “Qi,” in the body, promoting healing and well-being.

I would definitely recommend trying acupuncture with a highly qualified and experienced practitioner, as improvement in symptoms and inflammation is very likely with a number of sessions that would vary from a person to another.

Physical Exercise

Yoga

Yoga can be a beneficial exercise for people with rheumatoid arthritis;

• A 2020 meta-analysis of 10 trials including 840 patients with RA found that yoga may be beneficial for improving physical function, disease activity, and grip strength. However, it did not find significant effects on pain, tender joints, swollen joints count, or inflammatory cytokines.
• Another 2023 clinical trial involving 64 participants found that an 8-week yoga program significantly improved disease activity scores, and improved epigenetic and inflammatory markers.
• The study concluded that yoga reduced the rate of immunological aging in T cells of RA patients, helping to regulate the immune system response, and lowered the  severity of the disease, therefore, it is beneficial to utilize as an adjunct therapy.

Water Sports

Exercising in warm water, also known as hydrotherapy, can be very beneficial for people with rheumatoid arthritis (RA).

• Individuals with RA may show great improvements in health after participating in hydrotherapy, Water-based exercises, such as swimming and water aerobics, can also help improve the use of affected joints and decrease pain.
• A systematic review of studies found that people with RA who participated in hydrotherapy experienced less pain and joint tenderness, as well as improved mood and overall well-being.

Tai Chi

Tai chi is a gentle form of exercise that can help improve flexibility, strengthen muscles, and reduce pain and stiffness in people with arthritis. It can also improve balance, coordination, and body awareness, as well as relieve stress.

• The American College of Rheumatology strongly recommends tai chi for people with osteoarthritis of the hips or knees.
• A 2021 study found that four specific tai chi movements (Wave Hands Like Clouds, Diagonal Flying, Brush Knee and Twist Step, and Repulse Monkey) are particularly beneficial for people with arthritis, as they use a wide range of motions in the lower limbs, slowly increase joint loading, and engage strong muscle activity.
• However, a 2023 systematic review found that tai chi is unlikely to improve physical function or provide pain relief for people with rheumatoid arthritis. More research is needed in this area.

The Low Down

Living with rheumatoid arthritis (RA) presents daily challenges, but a holistic approach offers a path toward a more fulfilling life. When dealing with chronic conditions, some may choose to opt for a fully natural approach while others may look to integrating these holistic approaches alongside conventional treatments, which can help reduce your reliance on pharmaceuticals and minimize their long-term side effects. Herbal remedies like extracts from turmeric, ginger, pepper, green tea and boswellia possess anti-inflammatory properties that may help soothe joint pain and stiffness, some also exhibit anti-arthritic properties, which protect the joints and prevent further damage and progression of the disease. Supplements such as Resveratrol and Probiotics show promise in regulating the immune system and reducing inflammation, potentially easing RA symptoms and reduce complications.

Regular physical activity, tailored to your abilities, can improve joint flexibility, strengthen muscles, and boost your overall well-being. Incorporate low-impact exercises like swimming, yoga, or tai chi to keep your body moving without excessive strain.

As always, consult with your physician before integrating any new supplement or exercise into your regimen.

Stress can exacerbate RA symptoms, making relaxation techniques like meditation and deep breathing essential tools for managing your condition. These practices promote mental and emotional well-being, reducing stress hormones that can trigger inflammation.

It’s important to acknowledge that managing RA is an ongoing process. Be patient with yourself, celebrate your successes, and seek support from healthcare professionals and fellow individuals with RA. By embracing a holistic approach, you can navigate the challenges of RA and live a fulfilling life.