It Started with Grapefruits

In 1991, Canadian scientists discovered that the level of certain prescription drugs was affected by drinking grapefruit juice. The drugs were blood pressure medications, while the study in question involved just six men who had borderline high blood pressure. Yet the authors confidently declared:

  • “Their diastolic blood pressure was lower, and their heart rate higher with grapefruit juice than with water. Vasodilatation-related side-effects were more frequent.” (Bailey 1991, edited)

It is now almost universally agreed that grapefruit juice can interfere with calcium channel blockers and some other drugs. To quote

Other Foods, Supplements, and Botanicals

To be clear, this interference of grapefruit juice usually consisted of unintentionally increasing the effectiveness of a medication. Thus,

Grapefruit juice was only one food out of thousands. But this realization about grapefruit juice led to a reconsideration of many other fruits, vegetables, herbs, and botanicals. Grapefruit juice turned out to be an inhibitor of cytochrome P450, specifically  the CYP3A4 enzyme. Cytochrome P450 plays a key role in the metabolism of drugs and other chemicals. So it became a matter of concern if other nutrients were having a similar effect on the absorption of anticancer drugs.

Next, scientists at Harvard University Medical School, Boston, found that two common anticancer drugs, cyclophosphamide and ifosfamide, were also activated in the liver by a P450 enzyme:

  • “The present study identifies the specific human cytochrome P450 (CYP) enzymes …leading to activation of the anticancer drug cyclophosphamide and its isomeric analog, ifosfamide” (Chang 1993).

Office of Alternative Medicine (OAM)

By coincidence, this happened at a time when “alternative medicine” was making headlines. In the 1990s, the NIH Revitalization Act established the Office of Alternative Medicine (OAM) within the Office of the NIH Director, “to facilitate the study and evaluation of complementary and alternative medical practices.” As a result, the eyes of the nation (and even the world) were focused on the question of alternative medicine. And, to put it mildly, some of that attention was highly critical. We remember how some people were looking for a stick to beat back the CAM movement. For example, we recall how a scientist appeared on TV, practically in tears, complaining that the OAM was “taking food out of the mouths” of the children of legitimate scientists. (The OAM budget at the time was 2.2 million, while the total NIH budget at the time was about $12 billion. )

At that very moment, the “grapefruit effect” struck and, by coincidence, rippled out to challenge the use of many substances that were championed by complementary practitioners. The first in the line of fire was an herb, St. John’s Wort (Hypericum perforatum, abbreviated SJW). Scientists at the Medical University of South Carolina had given SJW a clean bill of health. In a clinical study, they showed that “St. John’s wort, when taken at recommended doses for depression, is unlikely to inhibit “ P450 activity.

But this was quickly followed by a report from the research division of Pfizer, Inc., no less, that St. John’s Wort might inhibit key enzymes:

  • “St. John’s Wort preparations contain constituents that can potently inhibit the activities of major human drug-metabolizing enzymes and suggest that these preparations should be examined for potential pharmacokinetic drug interactions in vivo” (Orbach 2000).

Variation in the Amount of P450

What complicates matters is that there is considerable variation in the amount of P450 in each individual. Some people produce a lot of it in their system. These people are called ultrarapid metabolizers, while others, called poor metabolizers, process some drugs more slowly. So the same substance could have varied, or contradictory, effects from the same substance.

The Full List

Nonetheless, this topic is likely to come up if you discuss the use of complementary treatments, especially supplements, with your oncologist. You might even be given a list of things you cannot take. It used to be because these supplements contained antioxidants, which conflicted with pro-oxidant chemotherapy (and radiation therapy). But that excuse was pretty much exposed and exploded by careful meta-analyses that showed a lack of harm (and frequently a benefit) from taking supplements during chemotherapy. To quote one of the best of those papers:

  • “None of the [clinical] trials reported evidence of significant decreases in efficacy from antioxidant supplementation during chemotherapy. Many of the studies indicated that antioxidant supplementation resulted in either increased survival times, increased tumor responses, or both, as well as fewer toxicities than controls…” (Block 2007).

Once the “antioxidant conflicts with chemo” canard was exposed, the basis of opposition to concurrent supplement use switched, and it became all about P450. We believe that, too, by and large, will prove to be a non-issue, at least on the clinical level. But because you are likely to hear about this, it is best to be prepared. Forewarned is forearmed! So the Moss Report is proud to present a detailed list of Cancer Drug and Supplement Conflicts. As you can imagine, a great many hours of research went into its creation. This is a must-read among our many posts, and it could become an important part of your cancer fight!


  • Bailey DG, Spence JD, Munoz C, Arnold JM. Interaction of citrus juices with felodipine and nifedipine. Lancet. 1991 Feb 2;337(8736):268-9. doi: 10.1016/0140-6736(91)90872-m. PMID: 1671113.
  • Block KI, Koch AC, Mead MN, et al. Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review of the evidence from randomized controlled trials. Cancer Treat Rev. 2007 Aug;33(5):407-18. doi: 10.1016/j.ctrv.2007.01.005. Epub 2007 Mar 23. PMID: 17367938.
  • Chang TK, Weber GF, Crespi CL, et al Differential activation of cyclophosphamide and ifosfamide by cytochromes P-450 2B and 3A in human liver microsomes. Cancer Res. 1993 Dec 1;53(23):5629-37. PMID: 8242617.
  • Obach RS. Inhibition of human cytochrome P450 enzymes by constituents of St. John’s Wort, an herbal preparation used in the treatment of depression. J Pharmacol Exp Ther. 2000 Jul;294(1):88-95. PMID: 10871299.