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Is There a Connection between Methotrexate and Weight Gain?

By Kathleen Howard
Updated Mar 03, 2024
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Some patients experience weight gain while taking the pharmaceutical drug methotrexate, but it isn’t a common phenomenon and weight fluctuations aren’t usually listed as common side effects. This particular drug works by slowing the growth of certain types of cells. It isn’t known to impact metabolism or digestion, though. It is most frequently used in conjunction with other medications for the treatment of various cancers, and some of these other treatments, or possibly the combination of all the drugs, can sometimes lead patients to experience fluctuations in their size. In general, though, there hasn’t been enough research to draw any definitive connections.

Drug Basics

Methotrexate is a prescription medication that slows the growth of particular cells, including those in the skin and bone marrow. This makes it a good choice for the treatment of many different cancers, and it’s also commonly used for rheumatoid arthritis and certain skin conditions like psoriasis.

It’s usually considered a very aggressive medication, and people usually only take it when they are facing a serious prognosis, or when other less intensive therapies haven’t gotten good results. Like most pharmaceuticals, the precise workings of this drug are pretty complicated. In general it acts as a suppressant, slowing the body’s processes which can in turn help slow the progression of deadly or otherwise harmful growths and can also provide a chance for the body’s own immune response to catch up. It isn’t always tremendously effective all on its own, though. Most care providers include methotrexate in what’s known as a cocktail of different medications that are specially chosen to work together in a particular patient’s body.

Most Common Side Effects

Common side effects of methotrexate include nausea, vomiting, dizziness, headache, mouth ulcers, fatigue, and blurred vision. These side effects often have a negative effect on appetite, which sometimes leads to weight loss. It’s important to note here that it isn’t actually the drug causing the weight loss, but that loss is a secondary effect of the drug’s impact on appetite. In some patients, weight gain might work the same way.

Patients who notice a connection between methotrexate and weight gain are often taking a number of different medications together, many of which have known secondary effects on appetite and metabolism. Weight gain has most commonly been recorded in women taking cyclophosphomide, methotrexate, and 5-fluorouracil (CMF) for breast cancer. Most of these patients are regularly taking a high methotrexate dose, and this may be part of the cause.

Weight Gain Studies

Research has not conclusively shown a specific connection between methotrexate and weight gain. As methotrexate has been studied in combination with other medications, it is unclear as to whether one medication or the combination is to blame when patients do end up getting heavier over the course of their treatments. It is widely believed, however, that CMF therapy will increase lean muscle mass and fatty tissue in patients. Experts have not determined the cause for this increase, but it is clear that any weight gain a patient may experience is not due to reduced metabolic function.

Fluid Retention Concerns

Fluid retention may be another reason people could experience temporary weight gain while on this and other related medications. Retaining water for a short while isn’t usually too troubling, though if the problem persists it can lead to some pretty serious consequences. Fluid retention usually happens because of additional stress on the kidneys. It can cause an increase in raw weight, but in most cases it isn’t related to fat storage at all. If it isn’t treated it can cause organ swelling and possibly also rupture, which can be fatal.

Other Possible Connections

Some patients also experience weight gain due to decreased activity levels. Patients suffering from the sorts of conditions that require methotrexate might be unable to exercise as often as they once did. They might also eat more as a means of combating the stress of their diagnosis. These things might make it seem as if there is a link between methotrexate and weight gain when in fact inactivity or poor diet is the true culprit.

What Is Methotrexate Used For Currently?

Methotrexate is currently prescribed as an immunosuppressant medication to treat various inflammatory conditions. Methotrexate helps treat inflammatory conditions by slowing down the body’s immune response to reduce painful inflammation. It is often prescribed for multiple autoimmune disorders, including but not limited to:

  • Psoriasis 
  • Arthritis 
  • Lupus 
  • Crohn's disease 
  • Sarcoidosis 
  • Addison’s disease
  • Inflammatory bowel disease
  • Certain cancers 

Common Prescription Information 

Methotrexate is primarily prescribed to patients that have autoimmune disorders. Autoimmune disorders are those where the patient's immune system mistakenly attacks their own body. Long-term effects of autoimmune diseases are joint and organ damage in addition to chronic pain and loss of mobility. Methotrexate slows the mistaken immune response to give the body time to heal between flare-ups.

Methotrexate is not available over the counter or by emergency prescription. Your primary care provider or specialist will administer a series of blood and other tests to confirm whether or not you have an autoimmune disorder. If it is determined that your autoimmune disease benefits from methotrexate, you will be started on a low dosage first.

Methotrexate comes in different forms depending on your dosage and medical needs. Your doctor will determine the proper dosage and form best for you. For most people with autoimmune disorders other than certain cancers, methotrexate is taken once a week in the most accessible form.

  • Liquid 
  • Tablets 
  • Pre-filled injections 
  • Localized injections 
  • Hospital injections 

How Long Does Methotrexate Stay in Your System?

Depending on your dosage, methotrexate stays in your system for anywhere from 24 hours to one week. Lower dosages might have only trace amounts left after one day, whereas larger doses could take upwards of a week to leave your body. If you have deficiently functioning kidneys, the time it takes methotrexate to leave the body is likely longer than average; you can expect it to take upwards of 10 to 12 days to evacuate your system entirely.

How Long Does It Take Methotrexate To Work?

While the time it takes the drug to leave your system is relatively low, the time it takes to manage your symptoms effectively is much longer. If you take a weekly dosage regularly and without fail, you can generally expect results within one to two months.

How Long Do Side Effects Last?

Within the one- to two-month period in which the methotrexate is beginning to take effect in your system, it is crucial to be aware of potential side effects that can disrupt your life. While the side effects are bothersome at best and bed-ridding at worst, they will subside around the one-month mark. Your doctor will prescribe additional support to combat typical side effects.

Common Side Effects 

Common side effects for methotrexate are reported from most people who have been prescribed the drug.

  • Hair loss 
  • Loss of appetite 
  • Nausea 
  • Body aches
  • Diarrhea 
  • Headaches 
  • Fatigue 
  • Decreased immune system

Severe Side Effects 

Severe side effects are reported in rare cases and should be directed to your doctor or emergency care immediately.

  • Skin rash 
  • Unexplained bleeding 
  • High temperature 
  • Swollen appendages 
  • Changes in urination 
  • Difficulty breathing 
  • Persistent cough 
  • Yellowing of skin or eyes 

How To Boost Immune System While Taking Methotrexate?

The singular job of methotrexate is to slow your body's immune response. While this slowing of immune response helps your body heal from unwarranted attacks from your own immune system, it also impairs your immune system from doing the job it was meant to do against actual foreign cells. As a result, you are vulnerable to illness.

What To Include 

Boosting your immune system while taking methotrexate is vital to staying well while living with an autoimmune disease. In addition to prescribed medicinal therapies, our doctor will have other resources to help you stay well as you regain your health.

  • Increase vitamin B9, known as folate 
  • Include omega-3 fatty acids in your diet 
  • Talk to your doctor about borage seed oil 
  • Explore calcium and vitamin D supplements 
  • Consider more fresh fruits and vegetables 
  • Cook with blood-building foods 
  • Participate in regular exercise 
  • Stay up to date on vitals and appointments 

What To Avoid 

You can also boost your immune system by avoiding certain other foods and activities for the best results. Decreasing adverse side effects will improve your overall quality of life and reduce your body's chances of receptiveness to further illness.

  • Avoid foods that are nightshades 
  • Steer clear of any alcohol 
  • Don’t take OTC pain medications 
  • Never schedule a “live” vaccination 
  • Veto pregnancy and breastfeeding 
  • Restrict participation in crowded events 
  • Refuse exposure to the sun without sunscreen 
  • Exclude sick people from events for best results
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Discussion Comments
By Grivusangel — On Mar 11, 2014

My mother was treated with the CMF chemo protocol for breast cancer and I don't recall that she gained much weight during her treatment.

However, I have known people who were on methotrexate for other conditions, like rheumatoid arthritis or psoriasis, and did gain weight. I think it all depends on the person's individual body chemistry. Everyone is different, so it stands to reason that not everyone will experience the same side effects. It’s probably cumulative, but my mom said by far the worst side effects from the CMS protocol were the nausea and having a metallic taste in her mouth.

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