Methotrexate is a commonly prescribed medication for a range of chronic conditions, including rheumatoid arthritis, psoriasis, and cancer. While effective, this medication has numerous side effects that can impact quality of life. Weight gain is one of the possible side effects of methotrexate that has left many patients wondering about this connection. Understanding this relationship is crucial in deciding whether methotrexate treatment is still the best option for patients. In this article, we will explore the connection between methotrexate and weight gain, providing you with the necessary knowledge to make an informed decision.

Research-based article

Research has been conducted on whether methotrexate causes weight gain. A review of existing studies shows that the relationship between methotrexate and weight gain is uncertain. Some studies suggest that methotrexate is associated with weight gain, while others suggest that it may lead to weight loss. Still, others show no significant association between methotrexate and weight change. The conflicting findings in these studies make it difficult to provide a definitive answer to the question of whether methotrexate causes weight gain.

One potential explanation for the mixed results is that methotrexate affects different people in different ways. Factors such as age and genetic predisposition can also play a role in how the medication affects weight. Additionally, many of the studies examining methotrexate and weight gain have limitations, such as small sample sizes and a lack of diversity in participants. As a result, more research is needed to understand the relationship between methotrexate and weight gain fully.

Personal experience article

Real-life experiences from patients who have taken methotrexate can provide valuable insight into the connection between methotrexate and weight gain. Many patients report weight gain as a side effect of the medication. “When I started methotrexate, I noticed that my weight started creeping up slowly,” said one patient. “Eventually, I gained about 10 pounds over six months. I’ve had to work hard to lose the weight, but it’s been a struggle.”

Patients’ experiences with methotrexate and weight gain vary. Some patients report no weight gain at all, while others experience significant increases in weight. However, one common theme among patients is the challenge of managing weight while on methotrexate. “I’ve tried everything to lose weight, but it seems impossible. It’s frustrating because I’m doing everything I’m supposed to, but the weight just won’t come off,” said another patient.

Patients also share insights on how they manage their weight gain while on methotrexate. Some patients have found success with healthy lifestyle changes, such as exercise and a balanced diet. Others have found that alternative treatments that do not cause weight gain, such as biologics, have been more effective for them.

Mechanism of Action article

Methotrexate’s mechanism of action may be the key to understanding weight gain associated with the medication. Methotrexate works by inhibiting an enzyme called dihydrofolate reductase (DHFR). This enzyme is essential for the formation of nucleotides, the building blocks of DNA. By inhibiting DHFR, methotrexate slows down cell division, which is especially crucial in rapidly dividing cells like cancer cells.

In addition to its impact on cell division, methotrexate also affects metabolic pathways associated with weight gain. Specifically, methotrexate can affect the metabolism of purines, which are compounds that play a role in energy metabolism. This alteration in metabolic pathways may indirectly contribute to weight gain.

Methotrexate treatment alternatives and their effects on weight gain

Alternative treatments to methotrexate exist for many chronic conditions, including biologics and nonsteroidal anti-inflammatory drugs (NSAIDs). Biologics target specific proteins that play a role in the inflammatory process. While they can be more expensive and have more severe side effects than methotrexate, biologics may not cause weight gain.

NSAIDs are a class of pain relievers that also have anti-inflammatory properties. Unlike methotrexate, NSAIDs aren’t disease-modifying drugs and cannot slow down disease progression. However, they may be an effective alternative for managing pain related to chronic conditions.

These alternatives to methotrexate may have different side effects and may impact weight gain differently than methotrexate. A healthcare provider can help determine which treatment plan is best for individuals based on their medical history, symptoms, and lifestyle.

Holistic approach to weight gain and methotrexate treatment

A holistic approach emphasizes treating the whole person, not just the disease. This method includes addressing physical, mental, and emotional health, as well as lifestyle factors such as stress management and nutrition. This approach may provide additional benefits for individuals on methotrexate by addressing weight gain as part of a larger wellness plan.

Practices such as yoga, meditation, and cognitive-behavioral therapy (CBT) can help reduce stress and promote emotional wellness. Eating a healthy diet and exercise can improve overall physical health and promote healthy weight loss. A holistic approach may not only address the physical symptoms of chronic conditions but also provide long-term solutions to weight gain.


The relationship between methotrexate and weight gain is complex and not well understood. Some patients may gain weight while on methotrexate, while others may not. Despite the conflicting results of research, real-life experiences and methotrexate’s mechanism of action do suggest that weight gain is possible. Understanding the risks and benefits of methotrexate treatment and alternative treatments can help individuals make informed decisions about their care.

A holistic approach that addresses weight gain as part of a larger wellness plan may be a valuable tool for individuals on methotrexate. A healthcare provider can provide guidance on the best treatment plan for each individual, taking into account their medical history, symptoms, and lifestyle.

By Riddle Reviewer

Hi, I'm Riddle Reviewer. I curate fascinating insights across fields in this blog, hoping to illuminate and inspire. Join me on this journey of discovery as we explore the wonders of the world together.

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