Does Methotrexate Cause Weight Gain?

Methotrexate is a medication used to treat inflammatory types of arthritis such as rheumatoid arthritis. Originally developed as a cancer drug, it is also used to treat different types of cancer, including breast cancer and lung cancer, as well as severe forms of psoriasis. As helpful as this medication is, those taking methotrexate may experience some side effects, including nausea and vomiting, mouth sores and ulcers, headaches, and fatigue. Research has shown that using this drug can also result in weight gain.

Caucasian woman's feet standing on scale

Blend Images/John Fedele / Getty Images

Weight Fluctuations and Arthritis

Weight fluctuations occur in many people with arthritis. In the case of rheumatoid arthritis, studies have shown that even modest weight fluctuations can lead to worse overall health. One particular study looked at how people with arthritis would be affected by both weight loss and gain, and found that those who either lost or gained 5% to 10% of their body weight experienced heightened disease activity and worse physical function and were more likely to be disabled.

Weight loss and gain can happen in those with arthritis for many reasons. When it comes to weight gain, inactivity could be to blame because having severe pain and swelling in the joints can discourage or prevent a person from exercising. On the other hand, arthritis has been shown to affect appetite and lead to gastrointestinal issues such as diarrhea, nausea, and vomiting, which contribute to weight loss.   

Arthritis Medication and Weight

In those who gain weight, their arthritis can be more difficult to manage because of the extra pressure being put on their already damaged joints. Those who lose weight or have a low BMI have been shown to be at an increased risk of developing cardiovascular disease and cancer and have a higher mortality rate.

Weight Management on Methotrexate

Maintaining a healthy weight is especially important for those who have arthritis and are taking methotrexate. Extra weight or not enough muscle mass can affect the outcome and progression of the disease.  

For those who are overweight, losing the extra weight can help relieve the pain associated with the condition, and those who are underweight may benefit from gaining some to decrease the risk of developing adverse health outcomes associated with a low BMI. Being overweight is also associated with lower rates of remission. The good news is that there are ways a person can maintain a healthy weight to help cope with and manage their arthritis.


Studies have shown that people with inflammatory rheumatic diseases who lost up to 10% of their body mass had fewer symptoms and a reduction in disease activity.  For those who need to lose weight, cutting back on calories can be a great help. It's important to figure out how many calories you need to sustain healthy levels of energy and nutrition throughout the day. Using a weight loss calculator can help you determine that number.

For those who need to gain weight, they will need to increase their caloric intake. This can be done by calculating maintenance calories and then increasing that number gradually to see results. Gaining weight should be done using whole foods. Often calorie-dense foods contain specific ingredients that can lead to increased inflammation, and that is not ideal for those with arthritis. An anti-inflammatory diet can help with losing and gaining weight. Evidence suggests that disease symptoms such as pain and joint stiffness can be reduced by eating the right foods.

Eating foods that are high in antioxidants and omega-3 fatty acids has been shown to reduce inflammation levels in the body. Avoiding foods that cause inflammation is just as important as eating ones that lower levels of inflammation. Some foods that can lead to an increase in inflammation include high-sugar foods, processed meats, and foods with trans fats or refined carbohydrates.  


Exercise is a key component of health. For those who are underweight, exercise can help them maintain muscle mass, and for those who are overweight, exercise can lead to weight loss. It can also help reduce joint pain and stiffness. Exercising with arthritis can be difficult, so it’s important to participate in the right types of exercise.

The best types of exercise for those with arthritis are range-of-motion exercises, which encourage normal joint movement; strengthening exercises to increase muscle strength and mass; and aerobic or endurance exercises to improve movement and cardiovascular fitness.

Managing Stress

Stress has been proven to make symptoms of arthritis, specifically rheumatoid arthritis, worse. Practicing stress-relieving techniques such as meditation can help people with arthritis manage their stress and their condition. Meditation has been shown to be a great help in managing stress and maintaining overall health.

Developing positive self-talk can also be a great way to improve stress levels. By talking to yourself the way you would to a friend in a similar position, you can reap the benefits of experiencing less stress throughout the day. Practicing gratitude has also been shown to have a positive impact on stress levels, and a daily gratitude practice can improve mental health and quality of life.

8 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Arthritis Foundation. Methotrexate: Managing Side Effects.

  2. Baker JF, Reed G, Kremer J. Weight Fluctuation and the Risk of Cardiovascular Events in Patients with Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2020 Oct 1;1(1) doi:10.1002/acr.24469

  3. England BR, Baker JF, Sayles H, Michaud K, Caplan L, Davis LA, Cannon GW, Sauer BC, Solow EB, Reimold AM, Kerr GS, Mikuls TR. Body Mass Index, Weight Loss, and Cause-Specific Mortality in Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2018 Jan;70(1):11-18. doi: 10.1002/acr.23258

  4. Schulman E, Bartlett SJ, Schieir O, Andersen KM, Boire G, Pope JE, Hitchon C, Jamal S, Thorne JC, Tin D, Keystone EC, Haraoui B, Goodman SM, Bykerk VP. Overweight, Obesity, and the Likelihood of Achieving Sustained Remission in Early Rheumatoid Arthritis: Results From a Multicenter Prospective Cohort Study. Arthritis Care Res (Hoboken). 2018 July;27(8):1185-1191. doi:10.1002/acr.23457

  5. Weijers JM, Müskens WD, van Riel PLCM. Effect of significant weight loss on disease activity: reason to implement this non-pharmaceutical intervention in daily clinical practice. RMD Open. 2021 Jan;7(1):e001498. doi: 10.1136/rmdopen-2020-001498

  6. Khanna S, Jaiswal KS, Gupta B. Managing Rheumatoid Arthritis with Dietary Interventions. Front Nutr. 2017 Nov;8(4):52. doi:10.3389/fnut.2017.00052

  7. Finan, P., Zautra, A. Stress affects rheumatoid arthritis, but via what mechanisms?. Nat Rev Rheumatol. 2013 Sept;10(9):569–570. doi:10.1038/nrrheum.2013.139

  8. O'Connell BH, Killeen-Byrt M. Psychosocial health mediates the gratitude-physical health link. Psychol Health Med. 2018 Oct;23(9):1145-1150. doi:10.1080/13548506.2018.1469782 

By Angelica Bottaro
Angelica Bottaro is a professional freelance writer with over 5 years of experience. She has been educated in both psychology and journalism, and her dual education has given her the research and writing skills needed to deliver sound and engaging content in the health space.