Me time The lowdown on folic acid Studies show that folic acid can reduce the side effects of methotrexate Words: peter stannett I n 2014, a Cochrane review was published looking at the evidence for using low doses of folic or folinic acid as a supplement in the treatment of rheumatoid arthritis specifically, for reducing the side-effects of methotrexate. Folic and folinic acids are forms of vitamin B9, which are chemically different, but work in the body in similar ways. The paper reviewed a number of studies that met the inclusion criteria. The review included six double-blind, placebo-controlled, randomised-controlled trials, involving more than 600 adults with rheumatoid arthritis. About half of these took low-dose folic acid supplementation. did you know? What is methotrexate? Methotrexate is an effective disease-modifying anti-rheumatic drug used for treating rheumatoid arthritis. It can be used alone or with biological therapies. How it works is not clear, but we know that certain metabolites of methotrexate affect folate-dependent enzymes. A build-up of these folate-dependent enzymes releases adenosine. This occurs naturally in the body and is involved in the production of cellular energy and many other functions. Adenosine interacts with receptors on mononuclear cells and neutrophils, and it is thought this may contribute to the anti-inflammatory effect of methotrexate. Gastrointestinal problems such as nausea, vomiting and abdominal pain are common side effects of taking methotrexate. Other side effects include oral ulcers, changes in liver function and bone-marrow suppression. A common method of reducing these is to supplement with folic or folinic acid. This can be taken in tablet form, but it also occurs naturally in foods such Peter Stannett is the as broccoli and peas. information officer at Arthritis Care. How folic acid helps Find out more The review showed that the use of folic acid or folinic acid taken about how folate in addition to methotrexate significantly reduced: interacts with n gastrointestinal toxicity medicines n higher than usual serum transaminase a sign of liver damage n the number of people with rheumatoid arthritis who stopped taking methotrexate for any reason by 61 per cent, compared with the control group. The review provides very strong evidence for the use of low-dose supplements (7mg per week) of folic and folinic acid when taken with methotrexate. This means that a single daily folic acid tablet can reduce the above side effects dramatically. Multivitamins often contain folic acid, and are available over the counter. Folic acid has almost no side effects, and may reduce the potential for cardiovascular disease. It is not known whether a higher dose of folic or folinic acid would give an extra reduction in the side effects of methotrexate. In another study, there was found to be no benefit or harm in taking a higher dose of folic acid (30mg per week) over a usual dose (10mg per week), even with the high doses of methotrexate. Folic acid supplements are usually taken on a non-methotrexate day. Folic acid interacts with medicines used to treat other conditions, such as diabetes, epilepsy and Alzheimers, so its important to tell your doctor if you plan to take folic acid or folinic acid. Metabolites are the intermediaries or products of metabolism and have various functions. These include cell signalling, and stimulating or restricting the function of enzymes.