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Ask the Mental Health Expert Archives 2001-2004

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Grapefruit and Lithium

Q. A friend of mine recently brought me an article from his cardiologist warning against the combination of lithium and grapefruits/grapefruit juice. I'm just wondering if anyone has ever heard of this and whether it can be further substantiated?

A. Grapefruit juice, to the best of my knowledge, has not been reported to interact with lithium in any published scientific report that I can locate. However, if your friend has an article stating otherwise, I would not dismiss this out of hand--there is sometimes a gap between what clinicians report and what is published.

To be sure, grapefruit juice contains chemicals called naringens that can inhibit the metabolisim of several drugs, including triazloam (Halcion), alprazolam (Xanax), and nefazodone (Serzone). These are medications that are broken down via an enzyme system
in the liver and intestine known as CYP 3A4. The effect of grapefruit juice on these medications--i.e., increasing their levels in the blood--is thought to occur mainly in the small intestine. In contrast, lithium is not broken down by the liver, but is almost entirely eliminated via the kidneys; furthermore, I am not aware of any interaction between lithium and the CYP 3A4 system in the intestine.

Thus, it would be surprising if grapefruit juice would affect lithium metabolism in any significant way. In contrast, beverages that tend to promote urination, such as caffeine-containing drinks, may cause a reduction in blood lithium levels. But...in the field of medicine, we "never say never"!

September 2003

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