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Rheumatism patients in methotrexate therapy have lower mortality if their vitamin D levels are high

Rheumatism patients in methotrexate therapy have lower mortality if their vitamin D levels are highVitamin D deficiency is a common problem among patients with rheumatoid arthritis. However, if their blood levels of vitamin D are high before they start on methotrexate therapy, it lowers their mortality. This was shown in a study published in Nutrients, where the authors looked at vitamin D’s therapeutic properties. Note that the official vitamin D recommendations are too low to optimize blood levels of the nutrient.

Rheumatoid arthritis is an autoimmune disease that causes the immune defense to attack and destroy the articular cartilage. The inflammatory process can also attack the surrounding articular capsules and the adjacent bone and spread to other tissues. Rheumatoid arthritis affects more women than men, and the disease typically occurs at 50-70 years of age. Although some people are genetically predisposed to the disease, recent studies suggest that external factors (epigenetics) play a greater role in the disease etiology, involving such factors as infections, poisoning, hormonal factors, smoking, and lack of nutrients
Therapies that involve the use of anti-inflammatory drugs such as methotrexate are linked to various side effects like e.g., nausea, abdominal pain, elevated liver enzymes, and fatal hematological complications. For that reason, there is growing interest in natural add-on therapies that can be used to treat autoimmune diseases like rheumatoid arthritis.
Vitamin D is important for bones and for regulating inflammatory processes in the body. However, the official recommendations for vitamin D intake only focus on bone health and not on optimizing blood levels of vitamin D in the blood, which can otherwise benefit the immune defense and its ability to regulate inflammatory processes.

Vitamin D lowers the risk of complications and early death

Vitamin D deficiency is linked to an increased risk of dying of cardiovascular disease, non-alcoholic fatty liver disease, diabetes, cancer, and other serious ailments. Patients with rheumatoid arthritis who have love vitamin D levels in their blood also have an increased mortality risk. In the new study, the scientists looked at the relation between blood levels of 25(OH)D and mortality in rheumatism patients scheduled to begin treatment with methotrexate.
The study authors analyzed data from a large national population study called Veterans Affairs (VA) that included 15,109 patients with rheumatoid arthritis. They compared patient survival in those with blood levels of vitamin D that were higher or lower than 50 nmol/L. Also, they adjusted for confounding factors like age, gender, ethnicity, smoking habits, BMI, use of cholesterol-lowering medication (statins), and Charlson Comorbidity Index that takes the number and severity of comorbidities into account.
The study revealed that rheumatoid patients with vitamin D levels above 50 nmol/L had a 28 percent lower risk of early death compared with patients whose levels were below 50 nmol/L.
Based on their findings, the scientists concluded that having higher vitamin D levels in the blood prior to therapy with methotrexate is linked to lower mortality in patients suffering from rheumatoid arthritis. The researchers recommend studying underlying mechanisms, and they call for future studies to see how vitamin D supplementation can affect the immune defense and the risk of dying of rheumatoid arthritis and other autoimmune diseases.

  • Vitamin D deficiency is common among patients with rheumatoid arthritis
  • Vitamin D deficiency appears to contribute to the development of the disease

Vitamin D’s role in the immune defense and its ability to regulate inflammation

Virtually all cells in the body have vitamin D receptors (VDR) that control gene activity through biological on-off switches. This also goes for the immune defense that is designed to launch an inflammatory response in the case of infections and tissue damage. As soon as things are under control, it’s vital that the inflammatory response be terminated. The new study describes how vitamin D affects various proteins and white blood cells (macrophages), effectively reprogramming them from being pro-inflammatory to anti-inflammatory. Macrophages are part of the innate immune defense that communicates with white blood cells (T and B cells) in the adaptive immune defense. This is why macrophages have a key role in the inflammatory processes.
In their study, the authors mention an earlier study (VITAL), in which it was shown that daily supplementation with 50 micrograms of vitamin D lowers the rate of autoimmune diseases and cancer mortality. They also mention the large national VA study showing that vitamin D supplementation prior to contracting COVID-19 is linked to lower mortality.
With regard to vitamin D supplementation, it is vital to optimize blood levels of the vitamin if you aim for a reliable therapeutic effect. The official threshold level for vitamin D status is 50 nmol/L, but many scientists consider this to be too low and recommend 75 nmol/L or higher as the optimal level.

  • Chronic inflammation is the common thread in most chronic diseases, including rheumatoid arthritis
  • Diet plays a major role in our health. Anti-inflammatory diets and lifestyle are the new trend, and there are many excellent recipe books on the market.


Shahdi K Malakooti et al. Higher Vitamin D Levels before Methotrexate Therapy Initiation Are Associated with Lower Subsequent Mortality in Patients With Rheumatoid Arthritis. Nutrients 2024

Abdulrazaq, Innes JK, Calder PC. Effect of ω-3 polyunsaturated fatty acids on arthritic pain: A systematic review. Nutrition 2017

Methotrexat (MTX) – Alt om bivirkninger, behandling og gode råd (

Methotrexat kan føre til fatale hæmatologiske komplikationer hos ældre |

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