Why Grapefruit Interferes with Medication, and What to Do about It
www.scientificamerican.com
January 23, 20254 min readWhy Grapefruit Interferes with Medication, and What to Do about ItCould gene editing produce a tasty citrus fruit that doesnt interfere with prescription drugs?By Charlotte Hu edited by Tanya Lewis Serhii Tychynskyi/Getty ImagesUnfortunately for lovers of grapefruit, mixing the appealingly bitter citrus with certain medications can lead to dangerous side effects. According to the National Capital Poison Center, a not-for-profit poison control organization, at least 85 drugsincluding commonly prescribed antidepressants, statins and antibioticshave known or suspected interactions with grapefruit or grapefruit juice. But plant researchers are now working on a possible solution: genetically engineering a variety of the fruit that is medication-safe.Over the past few decades, scientists have zeroed in on the main culprit responsible for grapefruits notorious interfering effect: a class of chemicals called furanocoumarins. These molecules can bind to and inactivate an enzyme in the intestines called CYP3A4 that helps metabolize certain drugs. This leads to excessive levels of the drug in the bloodstream and thus to a risk of harmful overdose. (Through a different mechanism, grapefruit can have the opposite effect on some drugs, such as certain antihistamines.) Many popular citrus fruitssuch as grapefruit, limes and pomeloscontain furanocoumarins, but some varieties of oranges, including Valencia, navel and mandarin oranges, have low or negligible levels of these chemicals.In a study published recently in New Phytologist, researchers at Israels Volcani Institutefound a gene that plays a key role in producing furanocoumarins in grapefruit. According to the study authors, editing out this gene could potentially yield a variety of grapefruit that doesnt interfere with medication in this way.On supporting science journalismIf you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.There have been chemical efforts to remove the furanocoumarins from the juice. People also crossed mandarin and pomelo, which yielded grapefruit like products, says Yoram Eyal, a professor at the Volcani Center and a co-author of the paper. But the commercial production of grapefruit juice is very [regulated], so you cant sell something that resembles a grapefruit as a grapefruit juice.Eyal and his colleagues wanted to try a new approach by designing a grapefruit without furanocoumarinsand now we know which gene to target, he says.The researchers found the gene by crossing grapefruit and mandarin orange, then examining the genetics of the resulting plants. We saw in the progeny that 50 percent of them produce furanocoumarins and 50 percent do not. That indicated that maybe theres only one gene involved in this pathway of furanocoumarin biosynthesis, says Livnat Goldenberg, a postdoctoral researcher at the Volcani Instituteand the studys first author. Then we checked it for activity, and we saw it does produce the first component of the furanocoumarin pathway.Paul Watkins, director of the Watkins Lab for Drug Safety Sciences at the University of North Carolina at Chapel Hill, has previously worked with stakeholders in the Florida citrus industry to figure out how grapefruit interferes with medication. He and his colleagues conducted experiments and found that after removing the furanocoumarins from grapefruit juice, the main known grapefruit-drug interactions didnt occur.But ridding the juice of these chemicals, using a process similar to the one used to make lactose-free milk, was expensiveand it impacted the taste.Unfortunately, the juice also lost its spunk because in the process of taking out the furanocoumarins, [it] took out a lot of other stuff, says Watkins, who was not involved in the New Phytologist study. If you could use a technique like CRISPR [a method of editing genes] and create a whole line of grapefruit that didnt have this potential for drug interactions... theres substantial value in that economically, commercially, and for people who really like grapefruit juice.Identifying a gene common to furanocoumarin synthesis is just the first step, and the Volcani team is currently using CRISPR to create a set of real-world trees. Were in the process of developing this kind of grapefruit, Eyal says. But he notes that it can take around four years for the edited plant to become a tree that produces fruit.Ultimately, the researchers goal is to produce a viable grapefruit tree that can be classified as genome-edited but not as a genetically modified organism (GMO); in some countries, including Israel and the U.S., crops that are CRISPR-edited but dont have a new gene can be designated non-GMO. And because a lack of the gene for furanocoumarins doesnt seem to make citrus plants such as mandarins more susceptible to disease or insects, Eyal says, he and his colleaguesarent worried about significant impacts on grapefruit trees health. He also doesnt expect big impacts to grapefruits nutritional benefits. Furanocoumarins are considered antioxidants, he adds, but there are a lot of other antioxidants, [such as] vitamin C and flavonoids.If its genome-editing efforts bear fruit, the Volcani team intends to collaborate with researchers in the medical field to test the modified fruit juice, first in the lab and eventually in human studies.The long-term goal is developing varieties of grapefruit that are furanocoumarin-free, Eyal says, and providing them to growers of grapefruit.
0 Σχόλια ·0 Μοιράστηκε ·41 Views