January 23, 2025
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Why grapefruit interferes with taking medicine and what to do about it
Could gene editing produce delicious citrus fruits that don’t interfere with prescription drugs?

Serhiy Tychinsky/Getty Images
Unfortunately for grapefruit lovers, mixing the appealingly bitter citrus fruit with certain medications can have dangerous side effects. At least 85 drugs, including commonly prescribed antidepressants, statins and antibiotics, have been shown to interact with grapefruit or grapefruit juice, according to the National Capital Poison Center, a nonprofit poison control organization. known or suspected. But plant researchers are currently working on possible solutions. The idea is to genetically modify a variety of fruits that are safe to use with medication.
Over the past few decades, scientists have focused on a class of chemicals called furanocoumarins that are the main culprits for grapefruit’s notorious sabotaging effects. These molecules can bind to and inactivate an enzyme called CYP3A4 in the intestines that helps metabolize certain drugs. This can lead to excessive concentrations of the drug in the bloodstream, creating a risk of a harmful overdose. (Grapefruit may have an adverse effect on some medications, such as certain antihistamines, through another mechanism.) Many popular citrus fruits, such as grapefruit, limes, and pomelo, contain It contains coumarins, but some orange varieties such as Valencia, navel, and mandarin contain furanocoumarins. Oranges have low or negligible levels of these chemicals.
In a recently published study, new botanist, Researchers at Israel’s Institute of Volcanology have discovered a gene in grapefruit that plays a key role in the production of furanocoumarins. According to the study authors, editing this gene could result in a variety of grapefruit that does not interfere with drug therapy in this way.
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“Chemical efforts have been made to remove furanocoumarins from fruit juices. Mandarin and pomelo have also been hybridized to yield a product similar to grapefruit,” said Dr. One Yoram Eyal says: “But the commercial production of grapefruit juice is so (regulated) that you can’t sell anything that resembles a grapefruit as ‘grapefruit juice.'”
Eyal and his colleagues had wanted to try a new approach by engineering grapefruit without furanocoumarins, but “now we know which genes to target,” he says.
Researchers discovered the gene by crossing grapefruit and mandarin oranges and examining the genetics of the resulting plants. “We found that 50 percent of the offspring produced furanocoumarins and 50 percent did not. This indicates that there is probably only one gene involved in this pathway of furanocoumarin biosynthesis.” said Livnat Goldenberg, a postdoctoral researcher at the Institute of Volcanology and lead author of the study. “We then examined its activity and found that it did indeed produce the first component of the furanocoumarin pathway.”
Paul Watkins, director of the Watkins Institute for Drug Safety Sciences at the University of North Carolina at Chapel Hill, previously worked with stakeholders in the Florida citrus industry to understand how grapefruit interferes with drug administration. I’ve done it before. He and his colleagues conducted experiments and found that after removing furanocoumarins from grapefruit juice, the main known grapefruit-drug interactions did not occur.
However, removing these chemicals from the juice using a process similar to that used to make lactose-free milk was expensive and affected the taste.
“Unfortunately, the process of removing the furanocoumarins also removed a lot of other things, so the juice lost its vigor,” said Watkins, who was not involved in the experiment. new botanist study. “If we could use technology like CRISPR to create an entire variety of grapefruit without the potential for drug interactions… economically, commercially, and for the people who really need it. “It’s great value.” Like grapefruit juice. ”
Identifying common genes for furanocoumarin synthesis is just the first step, and the Volcani team is currently using CRISPR to create a set of real-world trees. “We are developing this type of grapefruit,” Eyal says. But he points out that it could take about four years for the edited plants to become fruit-bearing trees.
The researchers’ ultimate goal is to produce viable grapefruit trees that can be classified as genome-edited, but not as genetically modified organisms (GMOs). In some countries, such as Israel and the United States, crops that have been CRISPR edited but do not carry new genes can be designated as non-GMO. Additionally, the lack of furanocoumarin genes does not seem to make citrus fruits such as mandarins more susceptible to disease or pests, leading Eyal and colleagues to discuss any significant health implications for grapefruit trees. says he is not worried. He also doesn’t expect it to have a major impact on grapefruit’s nutritional benefits. “Furanocoumarins are considered antioxidants, but there are many other antioxidants, such as vitamin C and flavonoids,” he added.
If the genome editing efforts bear fruit, Volcani’s team will work with researchers in the medical field to test modified fruit juices, first in the lab and eventually in human studies.
“Our long-term goal is to develop grapefruit varieties that are free of furanocoumarins and make them available to grapefruit growers,” Eyal says.