Methotrexate & Folic Acid

[Guest guest]

Here is an article I saw today. It is on a site that needs a

password so I don't think I can post the link. It is interesting to

people on methotrexate I would say.

Annette

Experts debate folic-acid supplementation during methotrexate for RA

Apr 14, 2005 Gandey

Rome, Italy - Should folate be added routinely for all patients

receiving methotrexate for rheumatoid arthritis (RA)? Response to

this question of clinical practice is mixed, but many say yes. " Folic-

acid supplementation in patients with RA receiving methotrexate

appears to be safe, inexpensive, and easily administered, " said Dr

Louis Bridges (University of Alabama at Birmingham and

www.jointandbone.org editorial board member). " It has been

consistently shown to reduce side effects of methotrexate without

adversely affecting efficacy and may have beneficial cardiovascular

effects. "

In a review article published in Rheumatology and previously reported

by rheumawire, Drs SL Whittle and RA (Ashford and St s

NHS Trust, Chertsey, Surrey, UK) advocated for folic-acid

supplementation for all RA patients on methotrexate [1]. They

write, " We recommend a pragmatic dosing schedule of 5 mg of oral

folic acid given on the morning following the day of methotrexate

administration. "

But not everyone agrees with this approach. Responding to the

article, Dr R Manna (Catholic University of the Sacred Heart, Rome,

Italy) and colleagues write, " Although folate use reduces the rate of

side effects of methotrexate treatment, the guidelines for folate

supplementation should state that folate should be added only when

its actual demand increases, such as during an infectious disease or

during antibiotic therapy " [2]. The group's letter to the editor,

published in the April 2005 issue of Rheumatology,

notes, " Supplementation should not be given routinely because a

normal diet can ensure an adequate amount of this vitamin and it can

impair methotrexate therapeutic effects. "

Conflicting opinions about the benefits of supplementation

Manna and colleagues point out that there are currently no guidelines

available outlining doses and timing of use. They write, " In our

opinion, low doses of methotrexate without concomitant folate

administration are well tolerated for long periods in the absence of

adverse events. " The authors argue that folate supplementation should

be administered only in circumstances leading to folate deficiency to

prevent methotrexate adverse effects. They cite gastroduodenal

atrophy as an appropriate example not previously described in the

literature. " Prophylactic folate for all RA patients on methotrexate

is not strictly requiredexcept in the case of increased folate

requirement. "

Responding to the group's letter in an email interview, Bridges calls

their conclusions " untenable. " He explains that while the authors

suggest that folic acid should be used only in situations where there

is an increase in demand, such as during an infectious disease or

during antibiotic therapy, it is difficult to definitively know when

there will be increased demand. Bridges notes that since folic acid

is inexpensive, safe, and easily administered, it makes sense to

encourage its routine use.

He also questions the group's assertion that folic acid can impair

methotrexate therapeutic effects. " No reference for this is provided,

and I am not aware of any studies that support this conclusion. "

Folic acid may prevent side effects other than elevated liver-

function tests

" In contrast to this study, " Bridges told rheumawire, " other studies

have shown that folic acid may prevent side effects other than

elevated liver-function tests [LFTs]. The conclusion that folic acid

does not prevent any toxicity except elevated liver-function tests

does not suggest to me that folic acid should not be routinely used.

In my opinion, the prevention of abnormal LFTs by a safe, inexpensive

medication is advisable. "

Bridges adds that while the authors' assertion that a normal diet can

provide adequate folate is true, there may be beneficial effects of

folic supplementation. " For example, the effects of methotrexate on

homocysteine can be prevented with the replacement of folic acid, " he

said.

Dr Graciela Alarcon (University of Alabama at Birmingham) says she

agrees. " The vast majority of the population does not consume a diet

that is sufficiently rich in folic acid. While this would be an

effective means to receive folate, most people do not consume the

necessary 400 g through diet alone. "

Alarcon says her clinic routinely administers folic-acid

supplementation during methotrexate treatment to prevent side

effects. " Why wait? " she says, " When negative effects can be

prevented. " Alarcon echoes Bridges's argument that supplementation is

inexpensive and easily administered.

Regional and national differences for this practice remain

pronounced. While folate supplementation has become routine in the US

since roughly the 1990s, this has widely not been the case in the UK

and Europe.