Nutrition Diet: What vitamins should you take with methotrexate?

October 9, 2025 •

5 min read

Between 7% and 30% of people on methotrexate for autoimmune conditions may discontinue treatment within the first year due to adverse effects, many of which stem from folate depletion. This makes understanding what vitamins should you take with methotrexate? essential for mitigating side effects and improving treatment adherence.

Quick Summary

Patients on low-dose methotrexate for autoimmune diseases are commonly prescribed folic acid to reduce specific side effects, without impacting the medication's effectiveness.

Key Points

Folic Acid (Vitamin B9): The most critical vitamin to take with low-dose methotrexate, as it helps counteract side effects like nausea and mouth sores caused by folate antagonism.
Dosage and Timing: The appropriate dosage and timing are prescribed by a doctor and should generally be taken on a different day than your methotrexate dose.
Vitamin D: Maintaining adequate levels of vitamin D is beneficial, with studies suggesting it can lower the risk of early death in RA patients and protect lipid balance in psoriasis patients on methotrexate.
Supplements to Avoid: Certain supplements, such as St. John's Wort, white willow bark, and some herbal remedies, can interact with methotrexate and should be avoided unless approved by your doctor.
Dietary Adjustments: Limit caffeine and alcohol intake, and eat a balanced diet with folate-rich foods. Avoid unpasteurized dairy and raw meat due to an increased risk of infection.
Multivitamins: Standard multivitamins are often not sufficient. It's best to rely on your doctor's specific prescription for folic acid to ensure the correct dosage.

Methotrexate is a potent medication used to treat various conditions, including rheumatoid arthritis, psoriasis, and certain cancers. While highly effective, it can interfere with the body’s folate (vitamin B9) metabolism, leading to a host of unpleasant side effects. Understanding the specific nutritional adjustments and supplement regimen required can significantly improve your quality of life while on this treatment.

The crucial role of folic acid with methotrexate

Methotrexate functions as a folate antagonist, blocking the enzyme dihydrofolate reductase that converts folate into its active form. For patients on low-dose methotrexate for autoimmune diseases, this can cause a folate deficiency, leading to side effects like mouth ulcers, nausea, vomiting, gastrointestinal upset, and elevated liver enzymes. Folic acid, the synthetic form of vitamin B9, is co-prescribed to replenish folate levels and combat these effects.

How folic acid combats side effects

Clinical studies have consistently shown that folic acid supplementation reduces the incidence of methotrexate side effects. For example, a Cochrane review found that people taking folate supplements experienced significantly fewer gastrointestinal issues and abnormal liver tests compared to those on a placebo. This reduction in side effects can help improve adherence to the treatment plan, as fewer patients feel the need to stop taking methotrexate. It's crucial to note that this supplementation does not interfere with the medication's efficacy for autoimmune conditions.

Dosage and timing guidelines

The appropriate dosage and timing of folic acid supplementation when taking methotrexate are determined by a healthcare professional based on individual needs and the specific treatment plan. Folic acid is typically prescribed in a specific amount and frequency, often taken on a different day than the methotrexate dose to potentially avoid any interference with the drug's absorption or action. For cancer patients on high-dose methotrexate, taking folic acid can be contraindicated, and patients should only follow their oncologist's specific instructions.

Other important vitamins and supplements

While folic acid is a key consideration, other vitamins can also play a supportive role for patients on methotrexate.

Vitamin B12

Methotrexate is known to affect folate metabolism, and folate is intrinsically linked to vitamin B12 metabolism. Therefore, monitoring B12 levels is often recommended. While the exact mechanisms are still being studied, some research suggests that B12 can help protect against certain toxic effects of methotrexate. A balanced diet rich in B12 is beneficial.

Vitamin D

Low vitamin D levels have been linked to an increased risk of early death in the general population and in patients with rheumatoid arthritis. A study on RA patients showed that those with adequate vitamin D levels before starting methotrexate had a 28% lower risk of early death. For psoriasis patients, vitamin D supplementation alongside methotrexate has been shown to protect lipid homeostasis. Your doctor can test your vitamin D levels to determine if supplementation is right for you.

Nutritional guidelines for patients on methotrexate

Beyond supplements, certain dietary practices can help manage methotrexate side effects and support overall health. A balanced diet focused on nutrient-dense foods is key.

Foods to include

Folate-rich foods: Continue to consume foods naturally high in folate, such as dark leafy greens (spinach, kale), legumes (beans, lentils), citrus fruits, and avocados. This helps maintain natural folate stores.
Vitamin B12 sources: Ensure adequate intake of B12 from sources like lean meats, dairy products, fortified cereals, and salmon.
Balanced diet: Prioritize whole, unprocessed foods to help combat potential gastrointestinal issues.

Supplements to avoid or be cautious with

Certain supplements can interact with methotrexate and should be avoided unless approved by your doctor.


Supplement/Food	Potential Interaction with Methotrexate	Reason for Caution
Multivitamins	Contains folic acid at potentially inadequate or interfering levels.	Could contain insufficient folic acid or interact with your prescribed dose. Consult your doctor first.
Herbal supplements (e.g., St. John's Wort)	May increase sensitivity to sunlight.	These are not regulated and could cause adverse reactions. Stick to prescribed medications.
High-dose Folate (over-the-counter)	Risk of taking an unregulated or incorrect dosage, interfering with your prescribed dose.	Prescription folic acid is recommended to ensure correct dosage and monitoring.
White Willow Bark	Contains salicylates, which can increase methotrexate toxicity.	Avoid due to the risk of increased methotrexate blood levels and toxicity.
Potassium Citrate	Can decrease methotrexate blood levels.	May reduce the drug's effectiveness. Avoid unless medically supervised.

Foods and lifestyle factors to consider

In addition to supplements, certain dietary and lifestyle choices can help manage side effects and support your treatment:

Limit alcohol intake: Alcohol and methotrexate both affect liver function. Limiting or avoiding alcohol is often advised to reduce the risk of liver damage.
Avoid excessive caffeine: Some studies suggest that high caffeine intake can reduce the effectiveness of methotrexate in treating arthritis. Talk to your doctor about your caffeine consumption.
Prioritize rest and hydration: Methotrexate can cause fatigue and dehydration, so getting enough rest and drinking plenty of fluids is important.
Manage nausea: Opt for small, frequent meals and avoid rich or spicy foods. Staying hydrated with small sips of water can also help.

A note on multivitamins

While a multivitamin might seem like an easy way to cover your nutritional bases, it’s not the best approach when taking methotrexate. Many standard multivitamins contain a low dose of folic acid, which may not be enough to counter the drug's effects. Taking a separate, prescribed folic acid supplement is generally more effective and safer. Always check with your doctor before adding any new supplement to your routine.

Conclusion

For patients on low-dose methotrexate, taking a prescribed folic acid supplement is standard practice to help prevent side effects like mouth sores, nausea, and liver issues. While folic acid (vitamin B9) is the most critical supplement, vitamins D and B12 may also offer supportive benefits. Crucially, supplements like St. John's Wort and white willow bark, and foods high in caffeine should be avoided. As every patient's needs are different, it is vital to consult your healthcare provider to create a personalized nutrition and supplementation plan that supports your health while on methotrexate.

For more information on managing chronic conditions with medication, consider this resource.

Frequently Asked Questions

Methotrexate interferes with your body's ability to process folate (vitamin B9), which can cause a deficiency and lead to side effects. Folic acid supplementation replaces this lost folate, reducing side effects like nausea and liver enzyme issues.

It is generally recommended to take your folic acid on a different day from your methotrexate dose. This avoids any potential interference with the medication's absorption, although conclusive evidence on this is mixed.

The dosage varies and is determined by your doctor based on your individual needs and treatment plan.

No, studies show that taking folic acid supplements with methotrexate for autoimmune conditions like rheumatoid arthritis or psoriasis does not reduce the drug's effectiveness.

You should not take a multivitamin containing folic acid unless your doctor approves it, as the dose may be insufficient or could interfere with your prescribed folic acid. Rely on your doctor's guidance for supplementation.

Some evidence suggests that vitamin D may be beneficial. Adequate vitamin D levels have been associated with better health outcomes for RA patients, and supplementation may protect lipid balance in psoriasis patients.

Missing one or two doses is unlikely to have a major effect. If you miss a dose, consult with your healthcare provider for guidance on how to proceed.