Folic Acid Reduces Side Effects of Methotrexate Liver Treatment

by | Nov 25, 2008 | 2008, Folic Acid & Folate, Vitamins

Written by Greg Arnold, DC, CSCS.

As a medication used to help regulate cell growth by blocking an enzyme needed by cells to divide (1), methotrexate is a popular medication for cancer and also a “standard” treatment for inflammatory disorders like rheumatoid arthritis and psoriasis. Methotrexate sales exceeded $157 million in 2003 (2).

But as with most prescription medications, methotrexate is not without its side effects. With five years of use, 5–35% of patients have adverse side effects that include digestion problems (nausea, vomiting, mouth sores, loss of appetite), hair loss, malaise and liver damage (3, 4). It is methotrexate’s liver-damaging effects that cause the most concern, since the liver has many jobs, including changing food into energy, cleaning alcohol and poisons from the blood, and making bile, a yellowish-green liquid that helps with digestion (5).

Now a new study (6) has found that folic acid may help with liver health. In the study, researchers analyzed data from nine studies conducted between 1988 and 2007. In these studies, patients took 7.5 mg of methotrexate per week for at least 12 weeks for either psoriasis or rheumatoid arthritis. They also took folic acid as a way to counter the liver effects of methotrexate since folic acid has been suggested to reduce side effects in patients taking methotrexate (7).

With folic acid supplementation ranging from 1 mg to 5 mg per day, patients taking folic acid had “a slight reduction” (8.6% reduction) in digestive side effects and “a trend” that produced a 7.2% reduced risk of mouth symptoms (mouth ulcerations) and rash symptoms. Regarding liver damage, the researchers found that patients taking folic acid had a 35.8% reduced risk of liver damage from methotrexate.

For the researchers, “Supplementation with folic acid is an effective measure to reduce [liver] adverse effects associated with methotrexate treatment.”

Source: Prey, S., and C. Paul. “Effect of folic or folinic acid supplementation on methotrexate‐associated safety and efficacy in inflammatory disease: a systematic review.” British Journal of Dermatology 160.3 (2009): 622-628.

© 2008 British Association of Dermatologists

Posted November 25, 2008.

References:

  1. van Ede AE, Laan RF, De Abreu RA et al. Purine enzymes in patients with rheumatoid arthritis treated with methotrexate. Ann Rheum Dis 2002; 61:1060–4.
  2. “Top 200 Generic Drugs By Retail Sales in 2003” posted on the Drug Topics website.
  3. Bologna C, Viu P, Picot MC et al. Long-term follow-up of 453 rheumatoid arthritis patients treated with methotrexate: an open, retrospective, observational study. Br J Rheumatol 1997; 36:535–40.
  4. Wluka A, Buchbinder R, Mylvaganam A et al. Longterm methotrexate use in rheumatoid arthritis: 12 year follow up of 460 patients treated in community practice. J Rheumatol 2000; 27:1864–71.
  5. “Liver Disease” posted on the US National Library of Medicine website.
  6. Prey S. Effect of folic or folinic acid supplementation on methotrexate-associated safety and efficacy in inflammatory disease: a systematic review. Br Jou Dermatol 2008. Published Online: Oct 20 2008 DOI: 10.1111/j.1365-2133.2008.08876.x.
  7. Ortiz Z, Shea B, Suarez Almazor M et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev 2000; 2:CD000951.