A recent randomized, double-blinded, controlled study published in Journal of Clinical Rheumatology has found that supplementation with vitamin D2 has no effect on disease activity in rheumatoid arthritis. The researchers also found that vitamin D2 had a negative impact on symptoms.
Past epidemiological research on rheumatoid arthritis (RA) has shown that low vitamin D levels are associated with an increased risk of developing the autoimmune disease. There are also a few randomized controlled trials that have shown that increasing vitamin D levels decreases the severity of the disease. However, all of these RCTs used supplemental vitamin D3 as the intervention, not vitamin D2.
The current study is novel in that it used supplemental vitamin D2 as the intervention. A total of 22 participants were recruited from local rheumatology clinics in Madison, Wisconsin. All participants had vitamin D levels lower than 25 ng/ml.
The participants were randomly assigned to an intervention group or a control group. Those in the intervention group (n=11) received 50,000 IU of D2 three times weekly for the first 4 weeks of the study, and then 50,000 IU twice monthly for 11 months. The control group (n=11) received a matching placebo at the same intervals. All participants received 500 mg of calcium three times daily throughout the study and were asked to apply sunscreen between May and September.
The researchers performed various tests on the participants at the start of the study to determine baseline levels, then at two and five months into the study, and, finally, at the end of the study 12 months later. These tests included measurements of vitamin D levels and tumor necrosis factor α (TNF-α), as well as the Patient Assessment of Global Health, Patient Global Assessment of RA, and self-reported pain.
TNF-α is a signaling protein that regulates immune cells and inflammation. Patient Assessment of Global Health is a questionnaire that involves self-assessment on a variety of health parameters such as sleep, activity levels, and emotion. Patient Global Assessment of RA is a self-assessment that measures the overall way RA affects the patient at one point in time.
The researchers found:
- Vitamin D repletion was reached by month two in the vitamin D2-treated group.
- TNF-α levels increased significantly from baseline levels in the vitamin D2-treated group.
- Measures of Patient Assessment of Global Health, Patient Global Assessment of RA, and pain increased significantly, meaning health in general and symptoms relating to RA worsened.
In their conclusion, the researchers stated, “In this small study, we did not detect improvement in health outcomes following high-dose vitamin D for 1 year in RA patients, although power limited firm conclusions.”
They study is limited by the use of vitamin D2. There is research that shows that vitamin D3 is more effective in raising serum vitamin D levels and promotes greater storage of vitamin D in the body than vitamin D2. Another limitation is the very small sample size.
These results are interesting. An increase in TNF-α, especially within the context of an autoimmune disease such as RA, means an increase in inflammation and worsening of the disease. Research supporting the role of vitamin D3 supplementation in reducing inflammation is abundant, but the effects of vitamin D2 supplementation on inflammation is less clear.
In order to differentiate between the effects of vitamin D2 and vitamin D3 on rheumatoid arthritis, large trials comparing vitamin D2 and D3 are needed.