Why Grapefruit Interferes with Medication, and What to Do about It

Why grapefruit interferes with medication and what to do about it

Who Charlotte Hu edited by Lewis asked

Unfortunately for grapefruit lovers, mixing the tantalizingly bitter citrus with certain medications can lead to dangerous side effects. According to the National Capital Poison Center, a nonprofit poison control organization, at least 85 drugs—including commonly prescribed antidepressants, statins and antibiotics known or suspected interactions grapefruit or grapefruit with juice. But plant researchers are now working on a possible solution: genetically engineering a variety of fruits that are safe for medication.

In recent decades, scientists have studied the main culprit behind grapefruit’s well-known interference effect: a class of chemicals. furanocoumarins. These molecules can bind to and deactivate a helpful intestinal enzyme called CYP3A4. metabolizing certain drugs. This results in excessive levels of the drug in the blood and therefore the risk of a harmful overdose. (By another mechanism, grapefruit can have an adverse effect on some medications, such as certain antihistamines.) Many popular citrus fruits—such as grapefruit, limes, and pomelo—contain furanocoumarins, but some orange varieties, including Valencia, navel, and tangerine. oranges have low or negligible levels of these chemicals.

In a study published recently The new phytologist, Researchers at the Volcani Institute in Israel have discovered a gene that plays a key role in the production of furanocoumarins in grapefruit. According to the authors of the study, editing this gene in this way could produce grapefruit that is not interfered with by drugs.

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“They have been chemical efforts to remove furanocoumarins from juice. People too cross mandarin and grapefruitwhich yielded products like grapefruit,” says Yoram Eyal, a professor at the Volcani Center and a co-author of the paper. “But the commercial production of grapefruit juice is highly (regulated), so you can’t call something that looks like a grapefruit ‘grapefruit juice’ sell as”.

Eyal and his colleagues wanted to try a new approach by engineering a furanocoumarin-free grapefruit, and “now we know which genes to target,” he says.

The researchers discovered the gene by crossing grapefruit and mandarin oranges, then analyzed the genetics of the resulting plants. “In the progeny, we saw that 50 percent of them produced furanocoumarins and 50 percent did not. This indicated that perhaps only one gene is involved in this furanocoumarin biosynthesis pathway,” says Livnat Goldenberg, a postdoctoral researcher at the Volcani Institute and first author of the study. “Then we checked the activity, and we found that it produces the first component of the furanocoumarin pathway.”

Paul Watkins, director of the Watkins Laboratory for Drug Safety at the University of North Carolina at Chapel Hill, has been working with stakeholders in the Florida citrus industry to learn how grapefruit interferes with medications. He and his colleagues he did the experiments and found that after furanocoumarins were removed from grapefruit juice, the main grapefruit-drug interactions did not occur.

But extracting the juice from these chemicals, using a process similar to that used to make lactose-free milk, was expensive and affected the taste.

“Unfortunately, the juice also lost its potency because it took out a lot of other things in the process of extracting the furanocoumarins,” says Watkins, who was not involved. The new phytologist to analyze “If you could use a technique like CRISPR (a gene editing method) and create a line of grapefruit that didn’t have that potential for drug interactions … that has a lot of value economically, commercially, and actually for the people who have it. like grapefruit juice”.

Identifying a gene common to furanocoumarin synthesis is just the first step, and the Volcani team is using CRISPR to create a real-world set of trees. “We are in the process of developing this type of grapefruit,” says Eyal. But he pointed out that it can take about four years for the edited plant to become a fruit-bearing tree.

Ultimately, the researchers’ goal is to produce a viable grapefruit tree that can be classified as a genome-edited but not genetically modified organism (GMO); in some countries, including Israel and the US, they may be CRISPR-edited crops but without the new genes. designated non-GMO. And since the lack of the furanocoumarin gene doesn’t seem to make citrus plants such as mandarins more susceptible to disease or insects, Eyal says, he and his colleagues aren’t worried about a major impact on the health of grapefruit trees. Also, don’t expect a big impact on the nutritional benefits of grapefruit. “Furanocoumarins are considered antioxidants,” he added, “but there are many other antioxidants, (such as) vitamin C and flavonoids.”

If its genome-editing efforts bear fruit, the Volcani team plans to collaborate with medical researchers to test the fruit juice, first in the lab and eventually in human studies.

“The long-term goal is to develop furanocoumarin-free grapefruit varieties,” says Eyal, “and offer them to grapefruit growers.”