To Your Health

Q. I have been taking methotrexate for rheumatoid arthritis for more than two years with good results, but now my doctor is advising me to discontinue it because he says my liver enzymes are becoming elevated. Is there a way to avoid this side effect?

A. Methotrexate is one of the most successful of the "disease modifying anti-rheumatic drugs," although like any medication, it has its limits. The most serious is liver toxicity, but upset stomach, vision problems, and dry cough are also among the reported side effects, and anemia is a possible complication. It is not known exactly how methotrexate works for rheumatoid arthritis (RA), but RA is an autoimmune disease, and methotrexate may alter some aspects of immune function.

Methotrexate is an antagonist or competitor of folic acid, one of the B-complex vitamins. Folic acid is most needed by rapidly dividing cells such as cancer cells. Methotrexate has a long history as one of the first chemotherapy or anti-cancer agents. Unfortunately, other rapidly dividing body cells, like the cells of the immune system, gut, lungs, skin, and hair are also affected, and this accounts for some of the side effects of methotrexate.

Folic acid supplements, strangely enough, do not reduce the effectiveness of methotrexate as a disease modifying anti-rheumatic drug, but does reduce the liver damage associated with methotrexate use by about half. The amount of folic acid needed to normalize liver enzymes is more than you will find in a multivitamin (1,000 to 2,000 micrograms or mcg per day), but taking two or three pills per day of the allowable potency (800 mcg) is simple enough. When you take this much folic acid, it is prudent to add a vitamin B-12 supplement of about 1,000 mcg per day to protect against the distant possibility of pernicious anemia.

There are numerous other ways to guard from liver damage while taking methotrexate. Complete avoidance of alcohol is sensible. Even though pain relievers are needed when RA flares up, the less of these the better, since these are also capable of provoking liver damage.

Supplements of antioxidant nutrients (vitamin C, vitamin E, N-acetyl cysteine, lipoic acid, selenomethionine, and S-adenosylmethionine) have all been demonstrated to protect the liver from drug-induced damage. Except for S-adenosylmethionine, all these are conveniently available in a single formula. Also, S-adenosylmethionine is rather expensive and its activity is not as well documented as the other antioxidants.

Milk thistle, an herb, has a long history as a liver protector capable of reducing raised liver enzymes such as SGPT and SGOT. Milk thistle supplements have been demonstrated to increase our most important "homemade" antioxidant, glutathione, in the liver by more than 35%.

You may also be able to slow the progression of RA by avoiding certain foods. For instance, nightshades, which include potatoes, peppers, and tomatoes, have a bad reputation for inducing RA symptoms. Tobacco is also in the nightshade family and should be avoided for many reasons. Certain essential fatty acids from fish oils have "anti-inflammatory" activity and can be used generously even if your menu already includes generous amounts of ocean fish.

Prevention of disease has always been the first choice, but once joint damage from RA has occurred, there may be no other choice than to treat the pain and inflammation with medications such as methotrexate. One of the benefits of going ahead and using folic acid and the antioxidants mentioned is that other difficulties besides RA, heart disease and cancer for instance, may be prevented by taking these supplements.