Key takeaways:
Methotrexate (Jylamvo, Rasuvo, Trexall, Xatmep) is a prescription medication that's FDA approved to treat certain types of cancer. It can also treat autoimmune conditions such as rheumatoid arthritis and psoriasis.
Methotrexate may cause modest weight gain over time. Other medications that are sometimes prescribed alongside methotrexate may also contribute to weight gain.
To help manage potential weight gain with methotrexate, do your best to maintain a nutritious diet and regular exercise routine. Talk to your healthcare team if you’re experiencing unexpected weight changes after starting methotrexate.
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Methotrexate (Jylamvo, Rasuvo, Trexall, Xatmep) is a prescription medication that's FDA approved to treat certain types of cancer, such as leukemia and lymphoma. It also treats autoimmune conditions such as rheumatoid arthritis (RA) and psoriasis.
Regardless of how it’s used, weight changes can happen with methotrexate. This is largely due to how it affects inflammation in the body. Methotrexate may also make you feel tired, and that drop in energy can make it harder to stay active. On top of that, other medications commonly taken with methotrexate can affect your appetite and energy, which may lead to weight gain.
Here, we’ll dive deeper into how methotrexate contributes to weight gain and what you can do to manage it.
Does methotrexate cause weight gain?
Yes, methotrexate can cause weight gain. But, everyone’s experience with the medication is different. It's also possible that you can experience no changes in your body weight, or even some weight loss.
Methotrexate may lead to weight gain because it can change how many calories your body burns at rest. When inflammation is high — as with rheumatoid arthritis or psoriasis — your body tends to burn more calories, even when you’re not active. Methotrexate lowers inflammation to help treat these conditions. When inflammation goes down, your body may burn fewer calories each day, which can make weight gain more likely.
What is an average weight gain with methotrexate?
The amount of weight gain with methotrexate can vary from person to person, but it tends to be modest. For instance, one study of people taking methotrexate for RA showed an average weight gain of just a few pounds over a period of 6 months.
When should you be concerned about weight changes from methotrexate?
It’s important to try to maintain your typical body weight while taking methotrexate. You don’t want to gain or lose too much weight while taking it.
One study found that you may actually experience more flare-ups of inflammatory health conditions such as RA if you lose or gain 5% to 10% of your body weight. For a person weighing 170 lbs, this means gaining or losing about 8 to 17 lbs after starting the medication.
If you’ve gained or lost more than 5% to 10% of your body weight while taking methotrexate, talk with your healthcare professional. They can help figure out whether something else may be causing the change and suggest ways to manage your weight.
How does methotrexate work?
Methotrexate is an antimetabolite medication. It works in different ways depending on the health condition you’re taking it for.
For cancer, methotrexate works by blocking a protein called dihydrofolate reductase. This protein normally helps cells make DNA and grow. When it’s blocked, methotrexate slows cell growth, which can help slow the growth of cancer.
For autoimmune conditions such as RA and psoriasis, methotrexate works by blocking the immune system from becoming too active and attacking healthy parts of the body, such as the skin and joints.
Does methotrexate affect your appetite and energy?
Yes, methotrexate can affect your appetite and energy. In fact, appetite loss and fatigue are commonly reported side effects of methotrexate. Methotrexate can make you feel tired and wiped out, a feeling commonly called the “methotrexate fog.”
Other medications, such as prednisone (a corticosteroid), that are commonly prescribed with methotrexate can also affect your appetite. Prednisone and other corticosteroids can make you feel hungrier and cause your body to hold on to more fluid (swelling) — both of which can contribute to weight gain.
What’s more, health conditions such as RA are associated with joint pain. If your condition isn’t well-managed, this discomfort can reduce your mobility and ability to exercise, which can lead to weight gain in turn.
How to lose weight while taking methotrexate
If you’re new to taking methotrexate and you’re worried about body weight changes, make sure to talk to your healthcare team. They can tell you about the best ways to manage or prevent significant weight gain depending on your health background and lifestyle.
Here are a few tips that may help you maintain your target body weight when starting methotrexate.
Exercise regularly
If weight changes have been frustrating while taking methotrexate, a strategic exercise plan can help you work toward weight loss. For instance:
Strength training exercises, such as lifting weights and using resistance bands, can improve muscle mass and overall strength.
Aerobic exercises — such as running, cycling, or swimming — can improve your fitness and strengthen your heart and lung capacity.
Flexibility and other range-of-motion exercises can help you maintain your mobility.
You don’t need a gym or personal trainer to start exercising. But there are resources to consider to help keep you motivated to exercise and show you how to exercise safely.
Follow a nutritious diet
A nutritious diet is another part of reaching or maintaining your target body weight. A few tips to help maintain a balanced diet include:
Keep healthy foods you like readily available at home.
Prepare nutritious meals ahead of time (“meal prepping”).
Make more health-conscious versions of your favorite foods.
Incorporate more vegetables and fiber into your diet.
Don’t skip meals, even if it seems counterintuitive.
Choose lighter options when eating out at restaurants.
Eat mindfully by reducing distractions while eating, such as watching videos or playing on your phone.
Frequently asked questions
The most common side effect of methotrexate is mouth sores, or ulcerative stomatitis. Methotrexate can cause mouth sores because it affects rapidly dividing cells in the body, such as those in the lining of the mouth.
Mouth sores can be painful. They can also cause oral bleeding and discomfort while eating, chewing, or swallowing. Your healthcare professional may recommend taking folic acid to help prevent mouth sores from forming, but this supplement may not be appropriate for everyone.
Methotrexate itself doesn’t necessarily make your face puffy. But other medications commonly prescribed with methotrexate, particularly corticosteroids, can contribute to facial puffiness. A common side effect of long-term corticosteroid use is facial roundness and puffiness — also known as “moon face.” This is due to corticosteroids causing fat deposits on the sides of the face and jaw, which make the face appear rounder.
Try your best to avoid drinking alcohol while taking methotrexate. Methotrexate itself can cause liver harm, and drinking alcohol at the same time may raise your risk of liver toxicity. Alcohol can also have inflammatory effects, which can exacerbate the health condition you’re trying to treat.
Speak with your prescriber before drinking any amount of alcohol while taking methotrexate.
The most common side effect of methotrexate is mouth sores, or ulcerative stomatitis. Methotrexate can cause mouth sores because it affects rapidly dividing cells in the body, such as those in the lining of the mouth.
Mouth sores can be painful. They can also cause oral bleeding and discomfort while eating, chewing, or swallowing. Your healthcare professional may recommend taking folic acid to help prevent mouth sores from forming, but this supplement may not be appropriate for everyone.
Methotrexate itself doesn’t necessarily make your face puffy. But other medications commonly prescribed with methotrexate, particularly corticosteroids, can contribute to facial puffiness. A common side effect of long-term corticosteroid use is facial roundness and puffiness — also known as “moon face.” This is due to corticosteroids causing fat deposits on the sides of the face and jaw, which make the face appear rounder.
Try your best to avoid drinking alcohol while taking methotrexate. Methotrexate itself can cause liver harm, and drinking alcohol at the same time may raise your risk of liver toxicity. Alcohol can also have inflammatory effects, which can exacerbate the health condition you’re trying to treat.
Speak with your prescriber before drinking any amount of alcohol while taking methotrexate.
The bottom line
Methotrexate (Jylamvo, Rasuvo, Trexall, Xatmep) is a medication that's FDA approved to treat certain types of cancer and autoimmune conditions. Methotrexate can sometimes cause weight gain, possibly due to its effects on inflammation in the body. It may also be caused by side effects such as fatigue that make you move less. Other medications, such as prednisone, that are commonly prescribed with methotrexate may contribute to weight gain, too.
To avoid weight gain from methotrexate, try to maintain a nutritious diet and exercise regularly. If you gain a meaningful amount of body weight while taking methotrexate despite making positive lifestyle adjustments, speak to a healthcare professional.
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References
Arthritis Foundation. (n.d.). Methotrexate: Managing side effects.
Baker J. F., et al. (2016). Changes in body mass related to the initiation of disease-modifying therapies in rheumatoid arthritis. Arthritis & Rheumatology.
Baker J. F., et al. (2022). Weight fluctuation and the risk of cardiovascular events in patients with rheumatoid arthritis. Arthritis Care & Research.
Chartwell RX. (2025). Methotrexate- methotrexate tablet [package insert].
