Hydrolyzed Doesn’t Always Mean Better: Rethinking Protein for Premature Infants

If a formula is easier to digest, shouldn’t it automatically be better for a premature infant?

Working as a diet technician in the Infant Nutrition Division at Golisano Children’s Hospital, I have seen how important nutrition is for premature infants. Our team prepares and delivers breast milk and specialized formulas for infants who may receive nutrition through feeding tubes, parenteral nutrition, or breast or bottle feeding. In the NICU, nutrition is complex and a critical component of medical treatment and development.

Because premature infants have immature digestive systems and high nutritional needs, feeding decisions are made carefully and continually reassessed. One option used in some situations is hydrolyzed protein formula. But does breaking protein into smaller pieces automatically make it safer or better for every premature infant?

 

What does “hydrolyzed” actually mean?

Hydrolyzed formulas contain proteins that have been broken down into smaller peptides, which, in theory, makes them easier to digest and may improve feeding tolerance. This could be beneficial, particularly for infants whose digestive systems are still developing. However, easier digestion does not necessarily mean improved growth, nutrient absorption, or reduced risk of complications such as necrotizing enterocolitis (NEC).

Hydrolyzed formulas are sometimes selected because they are perceived to improve feeding tolerance. This belief is understandable, but the available evidence is not as conclusive as the label “hydrolyzed” might suggest.

 

What does the evidence show?

A 2022 systematic review and meta-analysis by Li et al. examined 10 studies involving 886 preterm infants. The researchers found that hydrolyzed formulas were associated with a lower rate of feeding intolerance and a shorter time to reach full enteral feeding. However, there was no statistically significant reduction in NEC. The confidence interval included the possibility of no benefit, meaning the results were not strong enough to establish whether hydrolyzed formulas prevent this complication (Li et al., 2022).

Other researchers present a more cautious perspective. A 2019 Cochrane review analyzed 11 trials involving 665 infants and found no strong or consistent evidence that hydrolyzed formulas improved digestion or changed the risk of severe bowel problems. The authors also noted that many of the studies were small and had methodological limitations (Ng et al., 2019).

Individual clinical trials further demonstrate why the evidence remains mixed. In a randomized controlled trial of 60 preterm infants, Baldassarre et al. (2019) found no differences in measures of feeding tolerance between infants receiving intact-protein and extensively hydrolyzed formulas. In a smaller subset of infants who received at least 75% of their enteral intake from the study formula, the intact-protein group reached full enteral feeding sooner, with a median of 10 days compared with 14 days in the hydrolyzed group. No cases of NEC occurred in either group. Although this was a small study, it provides another example of why hydrolyzed protein does not consistently produce better feeding outcomes.

The current professional guidance is more nuanced than simply labeling hydrolyzed formula as better or worse. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) position paper reports that hydrolyzed protein can accelerate gastrointestinal transit and enteral feeding advancement in preterm infants. However, there are no data showing that routine use improves long-term outcomes. ESPGHAN states that hydrolyzed protein may be used for early enteral feeding when human milk is unavailable, rather than recommending it as the standard choice for every formula-fed preterm infant (Embleton et al., 2023). With updated professional guidance on enteral nutrition in preterm infants and continued use of hydrolyzed formulas in neonatal care, understanding what these formulas can and cannot accomplish is important for setting health and growth goals.

There are also potential nutritional disadvantages to consider. Hydrolysis alters amino acid kinetics and may reduce nutrient utilization, particularly nitrogen. Some studies have reported slower weight gain and lower nutritional efficiency with hydrolyzed formulas, although increasing protein concentration can help compensate for reduced protein retention. Hydrolyzed formulas can also have increased osmolality (Verduci et al., 2021; Embleton et al., 2023).

Another challenge is that “hydrolyzed formula” is not one standardized product. Formulas can be partially or extensively hydrolyzed, and commercial formulas differ in the size of their remaining protein peptides. These differences may produce different functional effects, meaning results from one hydrolyzed formula cannot necessarily be applied to every hydrolyzed formula used in the NICU (Embleton et al., 2023).

 

Why does this matter in the NICU?

In my experience working in the NICU, hydrolyzed formulas are not chosen simply because they are considered better. They are used in specific clinical situations, and the infant’s tolerance, growth, medical condition, overall feeding plan, and growth goals are all factors that dietitians and providers must consider. Witnessing these decisions and preparing so many hydrolyzed formulas brought my attention to this very niche debate and made me realize how complex nutritional strategies are in pediatrics and neonatology.

In the NICU, no two infants have exactly the same medical needs. A premature infant’s nutritional plan may depend on gestational age, weight, medical conditions, tolerance, growth, and whether the infant is receiving breast milk, fortification, or formula.

This is why I believe hydrolyzed protein should not be viewed as automatically superior. It may be a useful option for certain infants, but the choice of formula should rest on more than the assumption that smaller protein molecules will solve feeding problems.

For parents and families, the most important step is to ask questions: Why was a specific formula selected? Is the goal to improve feeding tolerance, support growth, address an allergy, or manage another medical concern? What outcomes will the healthcare team monitor and report?

Nutritional decisions should be an ongoing conversation based on the infant’s individual needs and the best available evidence, not simply on the idea that a product with more specialized processing will produce better outcomes.

Premature infants deserve nutrition plans that are carefully considered and individualized. Hydrolyzed protein may benefit some infants, but “easier to digest” should not necessarily be interpreted as “better feeding outcomes.”

 

By Allison L. Kimmerer, A Master's of Medical Science student at the University of Kentucky

 

References

Baldassarre, M. E., Di Mauro, A., Fanelli, M., Capozza, M., Wampler, J. L., Cooper, T., & Laforgia, N. (2019). Shorter time to full preterm feeding using intact protein formula: A randomized controlled trial. International Journal of Environmental Research and Public Health, 16(16), 2911. https://doi.org/10.3390/ijerph16162911

Embleton, N. D., Moltu, S. J., Lapillonne, A., van den Akker, C. H. P., Carnielli, V., Fusch, C., Gerasimidis, K., van Goudoever, J. B., Haiden, N., Iacobelli, S., Johnson, M. J., Meyer, S., Mihatsch, W., Saenz de Pipaon, M., Rigo, J., Zachariassen, G., Bronsky, J., Indrio, F., Köglmeier, J., ... Domellöf, M. (2023). Enteral nutrition in preterm infants (2022): A position paper from the ESPGHAN Committee on Nutrition and invited experts. Journal of Pediatric Gastroenterology and Nutrition, 76(2), 248–268. https://doi.org/10.1097/MPG.0000000000003642

Li, M., Fang, Y., Lian, Y., Lu, X., Qiu, M., & He, Y. (2022). Effect of hydrolyzed formulas on gastrointestinal tolerance in preterm infants: A systematic review and meta-analysis. The Journal of Maternal-Fetal & Neonatal Medicine, 35(25), 10173–10180. https://doi.org/10.1080/14767058.2022.2122794

Ng, D. H. C., Klassen, J. R. L., Embleton, N. D., & McGuire, W. (2019). Protein hydrolysate versus standard formula for preterm infants. Cochrane Database of Systematic Reviews, 2019(7), Article CD012412. https://doi.org/10.1002/14651858.CD012412.pub3

Verduci, E., Salvatore, S., Bresesti, I., Di Profio, E., Pendezza, E., Bosetti, A., Agosti, M., Zuccotti, G. V., & D’Auria, E. (2021). Semi-elemental and elemental formulas for enteral nutrition in infants and children with medical complexity—Thinking about cow’s milk allergy and beyond. Nutrients, 13(12), 4230. https://doi.org/10.3390/nu13124230

Does Tylenol Cause Autism: Separating Fear from Reality

 

When I was growing up, Tylenol was the remedy for almost everything. Whenever I had a fever or a pounding headache, my parents handed me the familiar red-and-white bottle, usually after dinner, and told me to get some sleep. I always woke up feeling better. I never questioned the medicine or worried about hidden risks. So, when I recently started seeing headlines and viral posts claiming that Tylenol causes autism, I felt the same concern many parents and patients feel today: How could a medication trusted for more than half a century suddenly be dangerous?

The myth that has gotten the world in a chokehold, because of the misinformation that is being spread across the world. I want to address not just because it’s widespread, but because misinformation about common medicines can create real fear. Articles like “The Untold Connection Between Tylenol and Autism” paint acetaminophen as a hidden threat fueled by political statements, dramatic trend lines, and biological speculation. But when you look closely at the evidence, the story is far more complex, and ultimately more reassuring, than the rumors suggest.

This myth usually starts with a comparison of the increased autism diagnosis and the increase use of Tylenol. At first glance, the trend lines might look suspicious. However, pairing two rising curves does not prove a causal relationship: correlation does not equal causation. Autism prevalence has risen for many reasons, including expanded diagnostic criteria, increased awareness, earlier screening, and better access to developmental services. Even the FDA has repeatedly stated (most recently in 2023 and 2025) that no conclusive evidence currently links Tylenol to autism. The FDA’s job is risk evaluation of drugs used by millions.

One part of the article that is somewhat true is that the article argues that Tylenol may contribute to autism by overwhelming the body’s glutathione system its main antioxidant pathway. While it is true that acetaminophen is metabolized in part by glutathione, this does not mean that typical use during pregnancy damages the developing brain. While toxicity can happen when you take Acetaminophen, it only happens at very high dosages, not at normal levels. Autism can involve many factors like genetics, prenatal influences, and early development. Many medical organizations like FDA, CDC, ACOG, etc. have confirmed that standard dosage of Tylenol doesn’t cause autism.

              A main reason why this myth still continues with this misinformation is that fear spreads faster than nuance. A lot of people based what they believe off of political statements. They can get emotionally charged anecdotes, and misleading articles which can create the illusion of a hidden danger. And when a medication is used by pregnant women and children, the stakes feel even higher, but myths can cause real harm. Parents may blame themselves for their child’s autism, people may start mistrusting medical professionals and dosing guidelines. Alternatively parents may start blame themselves for their child’s autism. Believing these myths can do real harm to the individuals and others. The real risk is overuse or stacking medications, such as taking Tylenol, NyQuil, and an extra-strength cold medicine without realizing they all contain acetaminophen. Acknowledging uncertainty is part of good science. It is reasonable to use any medication in pregnancy thoughtfully. It is reasonable to avoid unnecessary doses. And it is reasonable to ask questions.

My own experience with Tylenol has been straightforward and positive, and more importantly, science supports its safety when used properly. Autism is a complex developmental condition that cannot be traced to a single household medicine. While research will continue. Current evidence does not support the claim that Tylenol causes autism. In a world full of overwhelming information, patients deserve clarity. So, the next time a headline or shared post suggests a hidden danger behind a familiar medicine, pause, ask questions, and look to credible medical guidance. Misinformation spreads quickly, but informed choices protect our health far more effectively than fear ever could.

By Ditri Patel, A Master's of Medical Science student at the University of Kentucky

 

No, that doesn’t give children autism. Or that.

 

What’s going on?

Critical thinking seems to be becoming more and more of a lost art with each passing year. This is especially evident in the interplay between politics and public health that has arisen in recent years. Fewer and fewer people are going in for doctors’ visits, giving their kids vaccines, and enrolling their kids in public school. Some parents are even refusing to take acetaminophen (Tylenol) while pregnant or give their kids vaccines for fear of them developing autism. These parents claim to do so because they are ”skeptical.” Healthy skepticism is important, true. However, when there is no credible evidence to back up your claim, you must learn to accept the truth with grace rather that double down and endanger your life and that of your loved ones.

How did we get here?

The modern antivaccine movement can be traced back to the late 1990s. A study by Andrew Wakefield and colleagues was published in The Lancet that purportedly linked the measles, mumps, and rubella (MMR) vaccine to autism in children (1). The study was immediately placed under scrutiny for its “small sample size (n=12), the uncontrolled design, and the speculative nature of its conclusions” (2). They also note that “a temporal link between the two is almost predestined: both events, by design (MMR vaccine) or definition (autism), occur in early childhood” (2) (as always, correlation does not equal causation). Despite this, Wakefield’s flawed conclusions made their way into the public consciousness, and he remains a figurehead among vaccine skeptics. He has never faced any criminal convictions or even charges, though his medical license was revoked.  

The discourse surrounding acetaminophen and its link to autism is more recent. Since his appointment to Secretary of the Department of Health and Human Services in February of this year, Robert F. Kennedy Jr. has advised Americans to exercise caution before taking medications (3). In their article for PBS, Thomas Beaumont and Laura Ungar say that he even called women taking Tylenol during pregnancy “irresponsible” (4). Mind you, this was before saying that a woman in a TikTok disagreeing with him had a baby developing in her placenta rather than uterus (4). He has also advised physicians to prescribe the lowest possible dose of acetaminophen or even recommend pregnant women against taking it at all (5). People often take what authority figures say at face value, which can be extremely dangerous. Especially when the person in that position of power has made unsubstantiated claims about public health.

Andrew Wakefield, father of modern  vaccine skepticism (left) and RFK Jr. HHS Secretary

So, what’s the truth?

Autism diagnoses have been on the rise for the past four decades. However, this has also been accompanied by improvements in screening and diagnostic techniques. There is also no single cause of autism (6). The Mayo Clinic says both genetics and the environment can play a role (7). Researchers have found the number of genes to be associated with autism development to be in the hundreds (6). Potential environmental contributors include “viral infections, medications, complications during pregnancy, or air pollutants” (7). It is also important to know that autism is officially called autism spectrum disorder and, as the name implies, it can present in a variety of ways. There is no correlation between any risk factor and the way autism presents (7).

Moreover, there is no established link between vaccines or acetaminophen use in pregnant women and autism (4,5,7). Studies that have investigated this have found no relationship or an associative one at best. In fact, most experts believe it is more dangerous to not give vaccines to children. They are more likely to acquire and spread serious diseases such as whooping cough, measles, and mumps. The vast majority of physicians still say acetaminophen is safe to use, even while pregnant. Dr. Christopher Zahn, Chief of Clinical Practice at the American College of Obstetricians and Gynecologists, says “pregnant patients should not be frightened away from the many benefits of acetaminophen” (3). Dr. Salena Zanotti of the Cleveland Clinic commented that acetaminophen is the safest drug to take to treat pain and fever during pregnancy (3).

Autism is a complex disease with multiple potential contributing factors

 What can we do?

Educate others patiently and respectfully. Inform them of the difference between associative and causal relationships. Teach them how to do their own research. Help them understand that science is itself often not an exact science and that mistakes are usually made on the way to discovery. You should be willing to listen to others’ concerns as well. Most importantly, don’t force someone to change their view. Resolution is achieved through discussion, not coercion.

 

 By Evan Strobel, a Master's of Medical Science Student at the University of Kentucky

 

References

 1.     The Editors of The Lancet. (2010). Retraction—ileal-lymphoid-nodular hyperplasia, non-specific            colitis, and pervasive developmental disorder in children. The Lancet, 375(9713),                                    445.  https://doi.org/10.1016/s0140-6736(10)60175-4

2.     Sathyanarayana Rao, T., & Andrade, C. (2011). The MMR vaccine and autism: Sensation, refutation, retraction, and fraud. Indian Journal of Psychiatry, 53(2), 95–96. https://doi.org/10.4103/0019-5545.82529

3.     Czopek, M. (2025, September 15). 5 things to know about autism and Tylenol during pregnancy. PolitiFact. https://www.politifact.com/article/2025/sep/15/Tylenol-acetaminophen-pregnancy-autism-RFK/

4.     Beaumont, T., & Ungar, L. (2025, October 10). Reupping unproven claims about Tylenol, Kennedy claims a link between circumcision and autism. PBS. https://www.pbs.org/newshour/health/reupping-unproven-claims-about-tylenol-kennedy-claims-a-link-between-circumcision-and-autism#:~:text=Kennedy%20noted%20during%20the%20meeting,vaccine%20confidence%20as%20health%20secretary

5.     Garrison, J. (2025, November 6). RFK Jr. says his position on Tylenol use for pregnant women hasn’t changed. USA Today. https://www.usatoday.com/story/news/politics/2025/11/06/rfk-jr-tylenol-pregnant-women-autism/87127637007/

6.     Parshall, A. (2025, September 22). Autism has no single cause. here’s how we know. Scientific American. https://www.scientificamerican.com/article/autism-has-no-single-cause-research-shows/

7.     Mayo Clinic Staff. (2025, May 22). Autism spectrum disorder. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/autism-spectrum-disorder/symptoms-causes/syc-20352928

 

Mixing Alcohol and Medications: What are the Risks?

 

You’ve probably seen this warning on medications you’ve taken. Mixing alcohol with certain       medications can cause nausea and vomiting, headaches, drowsiness, fainting, or loss of coordination.   It also can put you at risk for internal bleeding, heart problems, and difficulties in breathing (1).     Alcohol (ethanol) is one of the most widely consumed psychoactive substances in the world (2).     Despite its social acceptability, simultaneous use of alcohol and medications can lead to serious         pharmacologic and clinical consequences. Alcohol use remains prevalent across populations, including  patients undergoing drug therapy. Chronic ethanol exposure alters gene expression related to mitochondrial function, immune signaling, and neurotransmitter systems (5).

How Alcohol Affects the Body

Ethanol acts as a central nervous system (CNS) depressant, by enhancing GABA activity, inhibiting glutamate, and boosting dopamine. In the liver, it’s metabolized by alcohol dehydrogenase and CYP2E1, which are both key players in drug metabolism. Alcohol disrupts the neurochemical and autonomic systems, causing irregular emotional and stress responses, decreased heart rate variability, and chronic headaches or mood swings. These effects can drive individuals to drink more to relieve stress, reinforcing addiction. Alcohol also impairs neurological functions like sleep, body temperature regulation, and coordination. It affects the hypothalamus, leading to heat loss, disrupted REM sleep, and insomnia during withdrawal (6).

Figure 1: A diagram showing the effects of ethanol on the CNS (6)

The impact of alcohol consumption on chronic and acute health outcomes is largely determined by the total volume of alcohol consumed and the pattern of drinking, especially those patterns which are associated with the frequency of drinking (3). Chronic alcohol use damages the cerebellum, resulting in poor muscular coordination, staggering, and peripheral neuropathy. Over time, alcoholics may develop nerve damage and partial paralysis. Neuropsychological tests reveal cognitive impairments such as poor learning, memory loss, and personality changes. (6)

Figure 2: A figure showing the Pharmacokinetics, Determinants of BAC and Predicting BAC (7)

When Two Drugs Collide

         Mixing alcohol with other depressants, for example benzodiazepines, opioids, or sleep aids, can lead to additive CNS effects, increasing risks of respiratory depression and overdose. Even small amounts of alcohol can quickly intensify sedation. Combining substances intensifies their effects, increasing the risk of overdose, injury, organ damage, and risky behaviors. Alcohol mixed with these depressants can cause severe health problems, including slowed breathing, impaired judgment, and brain or organ damage. These combinations also raise the likelihood of developing substance use disorders (4).

        The effects of alcohol vary across different population groups.  For example, when a woman drinks, the alcohol in her bloodstream typically reaches a higher level than a man’s even if both are drinking the same amount. This is because women’s bodies generally have less water than men’s bodies, showing that a given amount of alcohol is more concentrated in a woman’s body than in a man’s. As a result, women are more susceptible to alcohol-related damage to organs such as the liver. Older generations are also at a higher risk for alcohol-medication interactions. Aging slows the body’s ability to break down alcohol, so therefore alcohol remains in a person’s system longer. Older people also are more likely to take a medication that interacts with alcohol and oftentimes they need to take more than one of these medications. (1)

Conclusion

        Mixing alcohol and medications is more than a simple warning. It’s a pharmacologic event that can change how drugs are absorbed, metabolized, and experienced. Although alcohol is widely consumed and socially accepted, its interaction with prescription, over-the-counter, or illicit drugs can lead to dangerous physiological and neurological effects. Alcohol’s role as a central nervous system depressant amplifies the sedative properties of other substances, increasing the likelihood of respiratory depression, and addiction (8).

        Chronic consumption further harms the brain, liver, and nervous system, impairing coordination, memory, and emotional regulation (4). These risks are heightened in vulnerable populations, such as women and older adults, whose bodies process alcohol differently or more slowly. Understanding these interactions is crucial for preventing health complications and consulting with healthcare professionals is best practice. Different doses affect different people, and it should be recognized that even moderate alcohol use can have severe consequences when combined with other drugs.

By Alyssa Colemen, a Master’s of Medical Science student at the University of Kentucky.

References

 1.  Harmful interactions: Mixing alcohol with medicines. (n.d.-b). https://www.niaaa.nih.gov/sites/default/files/publications/Harmful_Interactions.pdf

2.  MacKillop, J., Agabio, R., & Feldstein Ewing, S. W. (2022, December 22). Hazardous drinking and Alcohol Use Disorders. Nature reviews. Disease primers. https://pmc.ncbi.nlm.nih.gov/articles/PMC10284465/

3.  World Health Organization. (n.d.). Alcohol. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/alcohol

4.  Centers for Disease Control and Prevention. (n.d.). Drinking alcohol while using other drugs can be deadly. Centers for Disease Control and Prevention.  https://www.cdc.gov/alcohol/about-alcohol-use/other-drug-use.html

 

5.  Ethanol metabolism - an overview | sciencedirect topics. (n.d.-a). https://www.sciencedirect.com/topics/neuroscience/ethanol-metabolism

6.  Griffith, C. (n.d.). The Neural Effects of Alcohol. Open Access Text. https://www.oatext.com/the-neural-effects-of-alcohol.php

7.  Goldman, M. R., Molina-Castro, M., & Etkins, J. C. (2025, October 1). Recent advances in alcohol metabolism: From the gut to the brain. Physiological reviews. https://pmc.ncbi.nlm.nih.gov/articles/PMC12345593/

    8.  U.S. Department of Health and Human Services. (n.d.). Alcohol-medication interactions:         Potentially dangerous mixes. National Institute on Alcohol Abuse and             Alcoholism.https://www.niaaa.nih.gov/health-professionals-communities/core-resource-on-    alcohol/alcohol-medicatio n-interactions-potentially-dangerous-mixes

Bitter Fruit, Bad Mix: Why Grapefruit and Meds Don’t Get Along

         Grapefruit and grapefruit juice are often praised as a healthy, tasty addition to the diet. They’re rich in vitamin C, potassium, and fiber, among other nutrients (1). But what many people don’t realize is that grapefruit juice can also interfere with a surprising number of medications, including common treatments for high blood pressure, high cholesterol, and certain psychiatric conditions, sometimes with serious or even dangerous consequences (1).

 Origins of the Grapefruit Effect

        It may be surprising, but the interaction between grapefruit and medications was discovered not long ago. The first clues came from an accidental finding 36 years ago by Dr. David Bailey and colleagues while studying the blood-pressure drug felodipine (3). In their experiment, grapefruit juice was used simply to mask the taste of alcohol, but follow-up research revealed that the juice itself was dramatically increasing the drug’s bioavailability. This happened because compounds in grapefruit juice were blocking the normal breakdown of felodipine in the gut, mainly by reducing the activity of a key drug-metabolizing enzyme called CYP3A4 in the intestinal wall (2).

Figure 1.  Dr. David Bailey, who first accidentally discovered the interaction between grapefruit and felodipine.  Since his initial finding, Dr. Bailey and his colleagues have published numerous studies on grapefruit's effects on drug metabolism (5).  

 Inside the Body: How the Interaction Works

When you swallow a pill, your body has several ways of making sure the drug doesn’t hang around forever. The most important of these is metabolism, especially by enzymes in the cytochrome P450 family. One member, CYP3A4, does a lot of heavy lifting; it helps break down roughly half of all prescription drugs (4). You’ll find this enzyme both in the cells lining your small intestine and colon (enterocytes) and in the main cells of the liver (hepatocytes). Because of that, many oral drugs go through a sort of “double pass” of metabolism, first in the gut wall and then again in the liver, before they ever reach your bloodstream. This “first-pass” effect can dramatically reduce how much of a drug actually gets into circulation. For instance, only about 15% of a swallowed dose of felodipine survives this process unchanged, which means it has naturally low oral bioavailability (4).

 

Figure 2.  First-pass metabolism of felodipine.  After absorption in the small intestine, the drug is broken down first by the intestinal cells (enterocytes) and then by liver cells (hepatocytes).  Although 100% of felodipine is absorbed from the gut, only about 15% reaches the bloodstream unchanged  (CYP3A4 = cytochrome P450 enzyme 3A4)(4).

That’s where grapefruit becomes important. Grapefruit contains furanocoumarins, compounds that don’t just slow down CYP3A4, they permanently inactivate the enzyme in your intestinal lining by binding to its active site (a process called mechanism-based inhibition) (4). The enzyme then has to be newly synthesized before activity returns to normal. This results in much less drug breakdown in the gut, and much higher peak blood levels and greater overall exposure for affected medications (4). Notably, the elimination half-life and the handling of intravenous drugs remain unchanged, because the liver’s metabolism is less affected (4).

This interaction isn’t limited to one form of grapefruit. Fresh juice, frozen concentrate, or even a whole fruit can all knock down CYP3A4 activity, and just one whole grapefruit or a glass (about 200 mL) of juice may be enough to produce a clinically significant effect. Other citrus fruits like Seville oranges (used in marmalade), limes, and pomelos contain similar compounds and can cause the same problem. In contrast, sweet oranges such as navel or Valencia lack furanocoumarins and don’t interfere with CYP3A4 (4).

 

Conclusion

     Grapefruit is packed with nutrients and tastes great, but its interaction with common medications can end up causing unwanted side effects. By knocking out a key drug-metabolizing enzyme in the gut, it can quietly push the levels of many common medications far higher than intended, sometimes to dangerous levels. And because even a single glass of juice can have an effect that lasts a day or more, there is a real risk to patients taking drugs broken down by CYP3A4 (4).

So the next time you’re prescribed a new medication, ask your doctor or pharmacist whether grapefruit (or related citrus) is safe to have with it. A quick conversation can prevent deadly consequences. And if you’re craving citrus with breakfast? Pick up a sweet orange instead, your taste buds and your medications will thank you.

  By Madeline Sutherland, a Master's of Medical Sciences Student at the University of Kentucky

References

1. Publishing, H. H. (2021, March 30). Grapefruit and medication: A cautionary note. Harvard Health.https://www.health.harvard.edu/staying-healthy/grapefruit-and-medication-a-cautionary-n ote

2. Bailey, D. G., Malcolm, J., Arnold, O., & David Spence, J. (1998). Grapefruit juice–drug interactions. British Journal of Clinical Pharmacology, 46(2), 101–110. https://doi.org/10.1046/j.1365-2125.1998.00764.x

3. Bailey, D. G., Spence, J. D., Edgar, B., Bayliff, C. D., & Arnold, J. M. (1989). Ethanol enhances the hemodynamic effects of felodipine. Clinical and Investigative Medicine, 12(6), 357–362. https://pubmed.ncbi.nlm.nih.gov/2612087/

4. Bailey, D. (2013). Appendix 1: Grapefruit Interacting Drugs and Associated Oral Bioavailability, Adverse Event(s), Risk Ranking and Potential Alternative Medications Interacting Drugs Innate Oral Bioavailability* Dose-Related Drug Adverse Event(s) Predicted Interaction Risk Rank ** Potential Alternative Medication(s)*** Anti-Cancer. Canadian Medical Association Journal. https://doi.org/10.1503/cmaj.120951

5. Stewart, M. (2022, September 23). David Bailey, Olympian and pharmacologist who discovered the grapefruit effect, dead at age 77. The Globe and Mail. https://www.theglobeandmail.com/canada/article-david-bailey-olympian-and-pharmacolo gist-who-discovered-the-grapefruit/