Statistics on rheumatoid arthritis (RA) from the World Health Organization¹

• In 2019, 18 million people were reported to be living with RA worldwide
• 70% of RA cases are women and they are two to three times more likely to be affected than men
• 55% cases of RA are found in those over 55 years old

In this week's blog, we look at the signs, symptoms and risk factors associated with rheumatoid arthritis including diet, lifestyle and genetics.

What is rheumatoid arthritis?

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by the production of auto-antibodies, activated T cells, continuous synovitis and the presence of rheumatoid factor (RF), alongside chronic joint inflammation and destruction. Over time, inflammation of the synovial membrane lining the synovial joints, known as synovitis, leads to this joint destruction causing pain, swelling, stiffness and the limitation of movement.

Inflammatory conditions such as RA can lead to inflammation developing in other areas of the body such as:

• • Blood vessels (vasculitis) – this can lead to the thickening, narrowing, weakening and scarring of blood vessel walls.
  • Heart – inflammation of the tissue around the heart can lead to pericarditis, causing chest pain.
  • Eyes – inflammation of the eyes can lead to scleritis which can cause eye redness and pain.
  • Lungs – inflammation of the lungs or lung lining can lead to pleurisy or pulmonary fibrosis, which can cause shortness of breath, chest pain and a persistent cough.
  • Spinal cord – there is an increased risk of cervical myelopathy which is the compression on the cervical spinal cord.

Skip to Key Takeaways

Signs and symptoms of RA

• Joint pain is a common symptom alongside swelling in and around the joints lasting for six weeks or more. The wrists, feet, hands, ankles and knees are most commonly affected by RA, but any joint can be affected
• Stiffness first thing in the morning, lasting for several hours
• Fatigue and muscle aches
• Redness, tenderness, pain and heat around the inflamed joints. This can often be in a symmetrical pattern
• Limitation of movement such as exercise, walking or bending
• Some people find that they lose their appetite
• Low grade fever

Rheumatoid arthritis risk factors

Lifestyle

Several lifestyle factors have been shown to play a role in RA risk, including:

• Smoking—nicotine in the bloodstream can increase rheumatoid factor levels² and research has found smokers have a 30% higher risk of developing RA.³

Evidence suggests that cigarette smoking can lead to the production of antibodies that are linked to RA development.⁴ Smoking may also reduce the effect of clinical RA treatments such as disease-modifying antirheumatic drugs (DMARDs).^5,6

• Weight – Obesity is a risk factor for RA development and is associated with disease progression and poor response to treatments. Physical inactivity is both a result of and risk factor for the development of RA and can lead to further adverse health effects such as cardiovascular disease risk.⁷

It has been proposed that increasing rates of RA could potentially be related to the increase in rates of obesity, but study results have been mixed. Adipocytokines and insulin resistance and their pro-inflammatory effects have been proposed as possible mediators in RA.⁸

Genetics

The association of a particular human leukocyte antigen (HLA) with RA was first noted in the late 1970s, when the frequency of individuals with the HLA-Dw4 serotype was found to be increased among RA patients compared with healthy controls.⁹

Vitamin D deficiency

Epidemiological evidence has shown increased prevalence of several autoimmune diseases, including inflammatory bowel disease, MS, type 1 diabetes and rheumatoid arthritis at Northern latitudes where sun exposure is reduced; therefore, it has been suggested that vitamin D may be protective against autoimmune conditions.¹⁰

This is likely to be due to anti-inflammatory and immune modulating effects that vitamin D has demonstrated, such as regulating the production of inflammatory cytokines and inhibiting the proliferation of pro-inflammatory cells, both of which are crucial for the development of inflammatory and autoimmune diseases.

Research suggests that low levels of 25(OH)D may be a risk factor for RA development and disease activity, with supplementation being considered useful due to its effect on suppressing Th1 and Th17 and stimulating Treg activity, which play a role in autoimmunity and inflammation. ¹¹

Dietary sources of vitamin D only provide low levels and most is produced in the skin following sun exposure. In the UK, vitamin D can be synthesised on sunny days between April and September between 10.00 am and 2.00 pm. Although vitamin D cannot be synthesised during the winter at our latitude, it can be stored in the body, however production also depends on factors such as genetics, age, sunscreen, clothing, and skin colour.

Microbiome and leaky gut

The fundamental role the gut microbiota play in health and disease is well established and research strongly suggests that the gut microbiota plays a vital role in RA development and progression. The gut microbiome, in partner with the gut-associated lymphoid tissue maintain immune homeostasis and can influence inflammatory and autoimmune conditions.¹²

Dysbiosis impacts innate immunological pathways and may trigger the activation of innate immune cells and the production of pro-inflammatory cytokines such as IL-12, IL-23 and type 1 interferons among others, paired with a down regulation of anti-inflammatory cytokines such as transforming growth factor B and IL-10. Studies show that the balance between Th17 and Treg cells is closely related to RA and that this is regulated by the gut microbiota and their metabolites.^13,14

Healthy intestines are naturally permeable, allowing tiny nutrient particles to flow through their lining and enter the bloodstream.¹⁴ Problems arise if the intestinal lining becomes damaged.  For more information, please read our blog –   Leaky Gut Syndrome – causes, symptoms and routes to repair - Cytoplan

It is understood that celiac disease, type 1 diabetes, multiple sclerosis, rheumatoid arthritis, Crohn’s and several other autoimmune diseases have all been associated with leaky gut.  This allows the passage of antigens from the intestinal flora into the bloodstream which challenges the immune system.¹⁵

What foods to eat for rheumatoid arthritis?

Nutritional quality has been shown to impact RA with diet playing a role in the pathogenesis, symptom severity and management of the condition.

The typical western diet, associated with being low in plant foods and high in fat and animal products, alongside a higher ratio of omega 6 to omega 3 fatty acids has been found to be associated with an increased risk of RA.¹⁶

Nutritional intervention aims to attenuate inflammation and support antioxidant status by increasing omega 3 fatty acid and plant foods and reducing high intakes of omega 6, animal fats and refined carbohydrates, alongside the reduction or elimination of diary and gluten.

A recent meta-analysis showed significant reduction in pain in RA patients who followed an anti-inflammatory diet¹⁷ which is typical of the mediterranean way of eating.

A mediterranean diet (MD) is a predominantly plant-based diet including an abundance of vegetables, fruits, wholegrains, seeds, olive oil and fish, with a lower intake of animal products, processed and refined foods. Adherence to this way of eating has been found to have health promoting, anti-inflammatory and immune modulating effects and is recommended to support cardiovascular function, obesity and inflammatory conditions such as RA.¹²

High fibre intake is a fundamental aspect of a MD and has been linked to reduced disease activity, potentially in part due to the increase in short chain fatty acids, which are associated with a healthier gut environment and play a part in modulation of dysbiosis, alongside regulating inflammatory markers such as IL-6, TNF-a and plasma CRP, all of which have been found to be triggers of RA.¹⁸

Gluten-free diet

Gluten, a food-derived antigen, is the driver of the autoimmunity seen in coeliac disease. Increased intestinal permeability found in coeliac patients, coupled with a genetic predisposition and altered immunological response, may result in a systemic immune response that is directed against sites other than the gut.

Food or gut-derived antigens may have a role in the pathogenesis of other autoimmune disorders including RA.¹⁹ While research has found mixed results, a gluten-free diet may offer benefits to patients with RA.²⁰

Flavonoids

Flavonoids, found abundantly in foods and beverages of plant origin, such as fruits, vegetables, tea, cocoa and wine, possess antioxidant, antimicrobial, and anti-inflammatory properties. These compounds can play a protective role against atherosclerosis, RA, and other inflammatory conditions. ²¹

Good dietary sources of flavonoids:

• Red, blue, and purple berries; red and purple grapes
• Teas (particularly white, green, and oolong), cocoa-based products
• Apples
• Onions, kale, broccoli, apples, berries, teas
• Parsley, thyme, celery, hot peppers
• Citrus fruit such as oranges, grapefruits and lemons
• Legumes

Omega-3 fatty acids

Long-term intake of omega-3 fatty acids have been reported to be protective against the development of RA.  Some studies support the role of omega-3 fatty acid supplementation as a valuable therapeutic option to improve symptoms, tender joint count, duration of morning stiffness, and the requirement for non-steroidal anti-inflammatories in RA.²²

Good sources of omega-3 fatty acids:

• Wild caught salmon (tinned or fresh)
• Sardines (tinned in olive oil)
• Herring (tinned or fresh)
• Flaxseeds
• Hempseeds
• Chia seeds
• Walnuts

Supplements for rheumatoid arthritis

Vitamin D

Vitamin D has been widely studied on its effect on the immune system and evidence suggests that low vitamin D status may be implicated in the pathogenesis of RA. The relationship between vitamin D and RA is complex, with vitamin D deficiency being common, researchers also highlight the increased risk of osteoporosis in RA.²³

Omega 3 fatty acids

Omega 3 fatty acids have anti-inflammatory properties that can help to ease symptoms associated with arthritic pain, with many studies demonstrating improvements in pain and morning stiffness after an increase in omega 3 fatty acids. A 2021 systematic review found that dietary interventions in combination with omega 3 supplementation provided additional benefit in symptom management in RA than through dietary change alone.²⁴

Live native bacteria

RA is an autoimmune disease in which probiotics appear to have an immune modulating action, alongside decreasing the inflammatory process. Current evidence supports the role of probiotics as adjunctive therapy in RA, with one study finding that probiotics lowered pro-inflammatory cytokines IL-6.²³ Probiotics have been found to reduce inflammation of the intestinal wall, reduce intestinal permeability, modulate the microbiota and have been found to lower inflammatory markers such as CRP.^14,26

Anti-inflammatory nutrients

Herbs such as Boswellia serrrata and turmeric have been shown to inhibit pro-inflammatory processes through effects on inflammatory enzymes, suppression of NF-KB activation and the reduction of pro-inflammatory cytokines.

Curcumin has been found in research to improve clinical symptoms of RA and can be used therapeutically to reduce inflammation, pain and swelling. It has also been found to improve dysfunction of the immune cells Th1, Th17, Treg and B cells which all play a role in autoimmunity and enhance anti-rheumatic immunity.²⁷

Boswellia is an Ayruvedic herb that has shown significant activity as a therapeutic tool in RA. Research has shown its use as an anti-inflammatory and anti-arthritic agent that can improve pain, improve mobility and reduce the expression of inflammatory factors such as THF-a and IL-6.²⁸

Bridge the nutrition gap

A deficiency of certain nutrients can have an impact on innate and adaptive immunity, for example, a deficiency in zinc can alter immune cells and contribute to inflammation,²⁹ while vitamin D deficiency is thought to play a role in autoimmune conditions.²³

Research has also looked into the role of other nutrients such as vitamin E’s ability to enhance the quality of life for those with RA by reducing joint discomfort and stiffness.³⁰

Therefore, an anti-inflammatory diet alongside a multivitamin and mineral formulation can help bridge the nutrition gap and ensure adequate nutritional status.

What is the difference between rheumatoid arthritis and osteoarthritis?

Rheumatoid arthritis and osteoarthritis are both conditions that share similar symptoms such as joint pain, inflammation, stiffness and loss of movement.

The pathogenesis of RA is autoimmune in nature and occurs when the immune system attacks the synovium leading to swelling and inflammation, this can then impact the health of the individual outside of the joints.

In a healthy joint, cartilage covers the surface of the bones, acting as a shock absorber to allow the bones to move against each other freely. In Osteoarthritis, there is a gradual deterioration and thinning of this cartilage, meaning bones start to rub together. The tissues within the joint become more active in an attempt to repair the damage which can alter the joint structure, in some cases this allows the joint to work without pain, but in many these changes cause pain, swelling and reduces movement.

The causes of OA are unclear with multiple factors such as age, gender, genetics, obesity and injury contributing to the development. You can read more about OA in our blog Osteoarthritis: causes, drivers & interventions for protection | Cytoplan blog

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References

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All of our blogs are written by our team of expert Nutritional Therapists. If you have questions regarding the topics that have been raised, or any other health matters, please do contact them using the details below: nutrition@cytoplan.co.uk 01684 310099

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