Rheumatoid factor is an antibody that usually signals an autoimmune attack in the body. Although useful in diagnosing rheumatoid arthritis and monitoring disease activity, this marker may also be produced in other inflammatory diseases and certain infections. We break down all the possible causes of high levels and outline the steps you can take to naturally lower them.
What Is Rheumatoid Factor?
Rheumatoid factor (RF) is an autoantibody produced by the immune system. Autoantibodies trigger autoimmunity and inflammation responses by mistakenly mounting an attack against the body’s own tissues.
This marker got its name from its initial discovery in people with rheumatoid arthritis. Since then, it became evident that other conditions can also trigger its production. Detectable levels of the rheumatoid factor were uncovered in people with other autoimmune diseases, chronic infections, cancer, liver disease, and parasites [R, R].
The rheumatoid factor is a curious autoantibody that attacks other antibodies. It mostly takes the form of an IgM antibody (the largest antibody type) and specifically targets a region on IgG antibodies. It can alternatively exist as other antibody types (IgG, IgA, IgE, or IgD), but the IgM form is usually the first to appear in the blood and is most closely linked to disease activity [R, R, R].
Healthy people may produce beneficial forms of rheumatoid factors, which are part of the body’s normal defense against bacterial toxins (lipopolysaccharides) and viruses such as the Epstein Barr Virus (EBV). These don’t attack the body’s own tissues but instead help fight infections and clear away immune cells that are no longer needed. Once the threat is over, their levels naturally drop [R, R, R].
In contrast, the rheumatoid factor produced in people with rheumatoid arthritis remains high for longer and attaches to the target (IgG) more strongly. It probably doesn’t directly cause the disease, but it does worsen the symptoms by increasing inflammation and destroying the joints [R, R].
The rheumatoid factor is mainly used to help diagnose rheumatoid arthritis and determine how the disease will progress. Levels often rise many years before the first symptoms appear and may stay high shortly after, in the early course of the disease. However, the rheumatoid factor is not an exclusive marker – some people with rheumatoid arthritis never test positive for it [R, R, R].
Rheumatoid Factor Testing
- Joint pain, tenderness, redness, and swelling
- Joint stiffness
- Fatigue and weakness
- Slight fever
- Eye or mouth dryness
When combined with a test called anti-citrullinated peptide antibodies (ACPA), the rheumatoid factor is very accurate in diagnosing rheumatoid arthritis [R].
Normal Rheumatoid Factor Levels
If you’re positive for the rheumatoid factor, your other lab tests may show false values. The rheumatoid factor can interfere with the following lab tests:
- Malaria (false positive) [R]
- HIV (false positive) [R]
- Hepatitis C (false positive) [R]
- Cardiolipin (a mitochondrial phospholipid) antibodies (false positive) [R]
- TSH (falsely elevated) [R, R, R]
- Cytokines, including IL-1 beta, IL-4, IL-6, and IL-8 (falsely elevated) [R]
Causes of High Rheumatoid Factor Levels
Rheumatoid arthritis (RA) is the most common systemic autoimmune disease, marked by joint inflammation and destruction.
Between 70 – 90% of people with RA produce rheumatoid factors, which can further drive inflammation and tissue damage. This subset of rheumatoid factor-positive patients experiences a more intense inflammatory response and worse outcomes than those who are negative for it [R, R, R, R].
Lowering this marker may play a role in successful therapy. A drop in rheumatoid factor levels has been closely linked to improvements in response to medication in people with RA [R].
Other Types of Arthritis
Levels of the rheumatoid factor may rise in other less common forms of arthritis, although less consistently so.
Psoriatic arthritis occurs in people with psoriasis and rheumatoid factor is found in 15% of the patients [R].
Juvenile idiopathic arthritis (JIA) is a form of autoimmune arthritis that affects children under 16 years of age. The cause is still unknown, while the rheumatoid factor is found in 5% of children with this disease [R].
Other Diseases and Conditions
High levels of the rheumatoid factor are also found across a diverse array of diseases and conditions, including [R]:
- Sjogren’s syndrome, an autoimmune disease that causes dry mouth and eyes (75 – 95% of the cases)
- Primary biliary cirrhosis, an autoimmune disease that destroys the bile ducts (45 – 70%)
- Mixed connective tissue disease, an autoimmune disease similar to lupus (50 – 60%)
- Viral infections including hepatitis, HIV, Epstein-Barr, cytomegalovirus (10 – 76%)
- Breast cancer (13 – 47%) [R]
- Liver cirrhosis, scarring of the liver (25%)
- Lupus erythematosus, an autoimmune disease that damages the connective tissue (15 – 35%)
- Sarcoidosis, an inflammatory disease that damages the lungs and lymph glands (5 – 30%)
- Parasitic infections such as malaria and toxoplasmosis (10 – 18%)
- Bacterial infections including chlamydia, syphilis, and tuberculosis (8 – 15%)
An observational study of 296 people found that 88% of smokers tested positive for rheumatoid factor over a period of 10 years. Also, the rheumatoid factor-positive group of people contained more smokers than the rheumatoid factor-negative group [R].
The risk of high rheumatoid factor was 4 times higher in current smokers than in people who never smoked in an observational study of 7,000 people. In another study of 100 people with rheumatoid arthritis (RA), rheumatoid factors were more than twice as high in current and former smokers than in people who never smoked [R, R].
Smoking the equivalent of 1 pack (20 cigarettes) a day for 25 years was linked to a 3-fold increase in the risk of high rheumatoid factor in a study of 336 RA patients. What’s more, rheumatoid factor levels were directly linked to the number of years smoked in two studies of 673 people with RA [R, R, R].
Too Much Coffee
The number of coffee cups drunk daily was directly linked to the risk of developing rheumatoid arthritis (RA) and testing positive for rheumatoid factors in an observational study of 19,000 people. Those drinking four or more cups a day had more than double the risk of developing rheumatoid factor-positive RA compared to those drinking less [R].
Health Effects of High Rheumatoid Factor Levels
1) Risk of Rheumatoid Arthritis
In one observational study that followed 9,700 healthy people for 30 years, slightly higher rheumatoid factor levels (25 – 50 IU/mL) were associated with a nearly 4-fold increase in the risk of developing rheumatoid arthritis (RA). Very high levels (> 100 IU/mL) were linked to a 26-fold increased risk, compared to normal levels (< 25 IU/mL) [R].
2) Risk of Deep Vein Thrombosis
Levels above 110 IU/mL were associated with a 3-fold increased risk of blood clots in deep veins of the body (deep vein thrombosis) in an observational study of 670 people [R].
2) Risk of Hardening of the Arteries
One observational study of 6,500 people found that rheumatoid factor levels above 15 IU/mL were linked to an increased risk of hardening of the arteries (atherosclerosis) in African American women [R].
3) Poor Cognitive Recovery After Stroke
Rheumatoid factor levels within the normal range (above 7.6 IU/mL) were associated with a 79% increased the risk of cognitive dysfunction compared to barely detectable levels (below 1.1 IU/mL) in a study of 582 stroke patients [R].
4) Risk of Heart Disease
Men who had rheumatoid factor levels above 6 IU/mL had a 2.9-fold increased risk of developing heart disease compared to men with levels below 6 IU/mL in an observational study of 1,100 people. This link did not hold true in women [R].
5) Death From Heart Disease, Cancer, or Any Cause
Testing negative for the rheumatoid factor has been linked to a lower risk of dying. In one observational study of 12 people, detectable rheumatoid factor was linked to a 31% increased risk of death from any cause. Detectable levels were also linked to a 45% increased risk of death from heart disease, specifically [R].
In another study of nearly 300,000 people, levels above 20 IU/mL were linked with a 50% increase in death from any cause and a 56% increase in deaths from cancer [R].
Another study of 2,900 people with rheumatoid arthritis strengthens these findings. Those who tested positive for rheumatoid factor were nearly twice as likely to die as those who tested negative over a period of 25 years [R].
Ways to Lower Rheumatoid Factor Levels
1) Quit Smoking
If you’re a smoker and have high rheumatoid factor levels (or a family history of autoimmune diseases like rheumatoid arthritis), quitting may help lower your levels while supporting your general wellness.
2) Reduce Coffee Intake
If you’re an avid coffee-drinker, gradually reducing the amount of coffee you consume on a daily basis (or avoiding coffee altogether) may help lower your rheumatoid factor levels and disease risk.
3) Vegetarian Diet
In a study of 53 people, eating a vegetarian diet for one year decreased rheumatoid factor levels better than an omnivorous diet [R].
5) Fish Oil and Olive Oil
6) Vitamin E
7) Vitamin K1
Taking 10 mg/day of vitamin K1 for eight weeks reduced rheumatoid factor levels by 16% in a trial of 64 people with rheumatoid arthritis [R].
In a trial of 12 people with rheumatoid arthritis, taking 1,000 mg/day of curcumin reduced rheumatoid factor levels over the course of 90 days. If considering a curcumin supplement, make sure to choose bioavailable forms that are better absorbed [R].
9) Ashwagandha, Ginger, Boswellia, and Turmeric (RA-1)
RA-1 is an Ayurvedic herbal combination of ashwagandha, ginger, boswellia, and turmeric. In a trial of 165 people with rheumatoid arthritis, supplementing with RA-1 for 16 weeks reduced rheumatoid factor levels [R].
Andrographis is a popular herb used as a remedy for stomach aches, inflammation, and fever in traditional Chinese medicine and Ayurveda. In a trial of 60 people with rheumatoid arthritis, andrographis extracts for 14 weeks reduced rheumatoid factor levels [R].
11) Artemisia Annua
Extracts of Artemisia annua (sweet wormwood) for six months reduced rheumatoid factor levels in 159 people with rheumatoid arthritis [R].
12) Tripterygium wilfordii
Tripterygium wilfordii, also known as thunder god vine, is an herb used in traditional Chinese medicine as a remedy for various autoimmune and inflammatory diseases.
In a meta-analysis of 6 trials and 643 people with rheumatoid arthritis, this herb reduced rheumatoid factor levels [R].
Certain water extracts of this vine may cause adverse effects such as gut disturbances, rash, low white blood cells, and missing periods. Nearly all the adverse effects (except missed periods) can be avoided using safer alcohol extracts and sticking to the appropriate dosage [R, R].
13) Pine Pollen
Extracts of pine pollen reduced rheumatoid factor and other markers inflammation in arthritic mice [R].
15) Alginic Acid (Brown Seaweed)
16) Arisaema Rhizomatum
Arisaema rhizomatum (also known as Xuelijian) is a traditional Chinese medicine herb, used to alleviate joint pain and inflammation. It markedly reduced rheumatoid factor levels in arthritic rats [R].
Rheumatoid Factor Genetics
North American Indians tribes have the highest rheumatoid factor levels, with to up to 30% testing positive [R].
The SNPs rs2476601 (of the PTPN22 gene) and rs1980422 (of the CD28 gene) are associated with an increased risk of developing rheumatoid factor-positive rheumatoid arthritis (RA). Having two copies of the rs1980422 mutation more than doubles the risk of developing rheumatoid factor-positive RA [R, R, R, R, R, R].
Other SNPs linked with an increased risk of developing rheumatoid arthritis (independent of rheumatoid factors) include [R]:
SNPs associated with a decreased risk of developing rheumatoid arthritis include [R]:
Drugs That Decrease Rheumatoid Factor Levels
Some of the following drugs are used to treat rheumatoid arthritis, while others were discovered to lower rheumatoid factor in addition to their main use:
- Methotrexate (Trexall, Rasuvo) [R]
- Fenofibrate (Trilipix, Triglide, Antara) [R]
- Losartan (Cozaar) [R]
- Paroxetine (Paxil, Pexeva) [R]
- Rivastigmine (Exelon) [R]
- Monoclonal antibodies such as rituximab (Rituxan) and tocilizumab (Actemra) [R, R]
- Ramipril (Altace) [R]
- NSAIDs (ibuprofen, Tylenol) [R]
- Haloperidol (Haldol) [R]
- TNF inhibitors such as etanercept (Enbrel) [R]
- Abatacept (Orencia) [R]
- Cyclophosphamide (Endoxan, Cytoxan) [R]
Please discuss your medications with your doctor.
Irregular Rheumatoid Factor Levels?
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Rheumatoid factor is an antibody that mounts an autoimmune attack against your own antibodies (IgG). Testing positive to it is linked to more severe joint inflammation and destruction in people with rheumatoid arthritis, which is why it is commonly used to diagnose and monitor this disease. Its levels can also rise in other autoimmune, inflammatory, and infectious diseases.
Overall, it’s associated with poorer health and an increased risk for various chronic diseases. You will need to work with your doctor to holistically manage high rheumatoid factor levels. In addition, quitting smoking, reducing your coffee intake, eating plant-based foods, supporting your body with healthy oils (fish and olive oil), and supplementing with anti-inflammatory herbs like Curcumin and Boswellia are all safe natural strategies for lowering your levels.