Potassium Citrate
Effect: Possible Harmful Interaction
Potassium citrate and other forms of citrate (such as calcium citrate and
magnesium citrate) may be used to prevent kidney
stones. These agents work by making the urine less acidic. This
effect on the urine may lead to decreased blood levels and therapeutic effects of
methotrexate. It may be advisable to avoid these citrate compounds during
methotrexate therapy except under medical supervision.
St. John’s Wort, Dong Quai
Effect: Possible Harmful Interaction
St. John’s
wort (Hypericum perforatum) is used
primarily to treat mild to moderate depression. The herb dong quai
(Angelica sinensis) is often recommended for menstrual
disorders such as dysmenorrhea, premenstrual syndrome (PMS), and irregular
menstruation. Methotrexate has been reported to cause increased sensitivity to the
sun, amplifying the risk of sunburn or skin rash. Because St. John’s wort and dong
quai may also cause this problem, taking these herbal supplements during
methotrexate therapy might add to this risk. It may be a good idea to use
sunscreen or to wear protective clothing during sun exposure if taking one of
these herbs while using methotrexate.
White Willow
Effect: Possible Harmful Interaction
The herb white
willow (Salix alba), also known as willow
bark, is used to treat pain and fever. White willow contains a substance that is
converted by the body into a salicylate similar to aspirin. Case reports suggest
that salicylates can increase methotrexate blood levels and toxicity. For this
reason, one should avoid combining white willow with methotrexate.
Ipriflavone
Effect: Possible Harmful Interaction
The supplement ipriflavone is used to treat osteoporosis. A three-year
double-blind trial of almost five hundred women, as well as a small study, found
worrisome evidence that ipriflavone can reduce white blood cell count in some
people. For this reason, anyone taking medications that suppress the immune system
should avoid taking ipriflavone.
Citrate
Effect: Possible Harmful Interaction
Potassium citrate, sodium citrate, and potassium-magnesium citrate are sometimes used to prevent kidney stones. These supplements reduce urinary acidity and can therefore lead to decreased blood levels and effectiveness of methotrexate.
Folate
Effect: Supplementation Possibly Helpful
Folate (also known as folic acid) is a B vitamin that plays
an important role in many vital aspects of health, including preventing neural
tube birth defects and possibly reducing the risk of heart disease. Because
inadequate intake of folate is widespread, if one is taking any medication that
depletes or impairs folate even slightly, one may need supplementation.
Methotrexate is called a folate antagonist because it prevents the body from converting folate to its active form. In fact, this inactivation of folate plays a role in methotrexate’s therapeutic effects. This leads to an interesting Catch-22: Methotrexate use can lead to folate deficiency, but taking extra folate could theoretically prevent methotrexate from working properly. However, evidence suggests that people who take methotrexate for rheumatoid arthritis, juvenile rheumatoid arthritis, or psoriasis can safely use folate supplements. Not only does the methotrexate continue to work properly, but also its usual side effects may decrease.
For example, in a forty-eight-week double-blind, placebo-controlled trial of 434 persons with active rheumatoid arthritis, use of folate helped prevent liver inflammation caused by methotrexate. Other side effects did not improve. A slightly higher dose of methotrexate was needed to reach the same level of benefit as taking methotrexate alone, but researchers felt this was worth it.
In the study just described, folate supplements did not help reduce the incidence of mouth sores and nausea. However, in other studies, folate supplements did reduce these side effects, both in persons receiving methotrexate for rheumatoid arthritis and in those with psoriasis. In addition, two studies of persons with rheumatoid arthritis found that use of folate supplements corrected the methotrexate-induced rise in homocysteine without affecting disease control.
Folate supplements have been found safe only as supportive treatment in the specific conditions noted above. It is not known, for example, whether folate supplements are safe for use by persons taking methotrexate for cancer treatment.
Bibliography
Alexandersen, P., et al. “Ipriflavone in the Treatment of Postmenopausal Osteoporosis.” Journal of the American Medical Association 285 (2001): 1482-1488.
Griffith, S. M., et al. “Do Patients with Rheumatoid Arthritis Established on Methotrexate and Folic Acid 5 Mg Daily Need to Continue Folic Acid Supplements Long Term?” Rheumatology 39 (2000): 1102-1109.
Hunt. P. G., et al. “The Effects of Daily Intake of Folic Acid on the Efficacy of Methotrexate Therapy in Children with Juvenile Rheumatoid Arthritis.” Journal of Rheumatology 24 (1997): 2230-2232.
Van Ede, A. E., et al. “Effect of Folic or Folinic Acid Supplementation on the Toxicity and Efficacy of Methotrexate in Rheumatoid Arthritis.” Arthritis and Rheumatology 44 (2001): 1515-1524.
_______. “Homocysteine and Folate Status in Methotrexate-Treated Patients with Rheumatoid Arthritis.” Rheumatology 41, no. 6 (2002): 658-665.
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