Grapefruit showed how a plant can change your drug dose, and herbs can too

Key takeaways

• In 2012 national survey data, about 1 in 4 adults whose main complementary practice was an herb or supplement hadn’t told their primary care doctor, and the top reason nondisclosers gave was that the doctor never asked.
• Grapefruit juice raises blood levels of some drugs by blocking a gut enzyme called CYP3A4, and in a small 2023 study of healthy volunteers, goldenseal raised levels of a sedative by roughly 40% to 60%.
• In a 2020 comparison, all eight interaction checkers tested, free and paid, caught fewer than 1 in 5 known interactions between herbs and cancer drugs.
• An anesthesiologist may ask you to stop supplements at least two weeks before surgery, so bring up your bottles as soon as an operation is booked.
• Every Medicare Part D plan must offer a medication therapy management program to members who qualify, and if you qualify, you can bring your herbs to the review.

In the late 1980s, a Canadian pharmacologist named David Bailey had a taste problem. He was testing whether alcohol changed the effects of felodipine, a blood pressure drug, and he needed a drink that would hide the alcohol from volunteers¹. He picked grapefruit juice.

The blood tests came back strange. The alcohol didn’t matter. Instead, volunteers in both groups carried roughly triple the felodipine the team had predicted².

Bailey, who had run the mile for Canada at the 1968 Olympics, tested himself. With grapefruit juice, his drug level was five times what it was with water¹. The work appeared in The Lancet in 1991¹. Later research traced the effect to compounds in the juice that block a gut enzyme that normally breaks the drug down¹².

That enzyme, called CYP3A4, handles many medicines³. Today the Food and Drug Administration (FDA) requires grapefruit warnings on the labels of some prescription and over-the-counter drugs³.

Grapefruit is breakfast food, not medicine, and that is the lesson for anyone who uses herbs. Plants are chemically active, which is part of why people value them. Most herb and drug pairs have no known problem. A few can change how a medicine works in ways that are serious and predictable, and knowing how that happens tells you which ones to ask about.

Most people who use herbs are never asked about them

Researchers at the University of Minnesota looked at 2012 national survey data on 7,493 U.S. adults who used a complementary health approach and had a primary care doctor⁴. About 42% hadn’t told that doctor about the approach they used most⁴.

Herb and supplement users were the most likely to speak up. Even so, about 1 in 4 people whose main approach was an herb or supplement had kept quiet⁴.

The top reason wasn’t fear of a lecture. It was that the doctor never asked, cited by 57%⁴. Nearly half didn’t think the doctor needed to know⁴.

People with cancer showed the same pattern. In a 2019 study in JAMA Oncology, herbal supplements were the most common complementary therapy among cancer patients and survivors⁵. Only about 12% of herbal supplement users hadn’t told a doctor, but “my doctor didn’t ask” again topped the list of reasons for silence⁵.

Surgery has its own gap. The American Society of Anesthesiologists (ASA) says half of people who use herbal supplements don’t mention them before an operation⁶.

So don’t wait for the question. NIH’s National Center for Complementary and Integrative Health (NCCIH) advises telling every provider about every supplement and medicine, prescription and over-the-counter, and updating the list at each visit⁷. Our article on what happens when you don’t tell your doctor covers that conversation.

Plants change drugs in three main ways, plus one shortcut

Your body treats most medicines as something to clear out. Enzymes in the gut wall and liver break drugs down. Proteins called transporters act like doors and pumps, moving drugs into or out of cells. A plant compound can interfere at either step.

1. Slowing the cleanup. Grapefruit blocks CYP3A4 in the small intestine, so more of a drug slips into the blood³. The effect can last up to 24 hours, so taking the pill and the juice at different times doesn’t solve it².

Goldenseal, an herbal supplement, works in a similar way. In a 2023 study in the Journal of Pharmacology and Experimental Therapeutics, goldenseal raised blood levels of midazolam, a sedative cleared by this enzyme family, by roughly 40% to 60% in healthy volunteers⁹. Most of the blocking happened in the gut, and computer models suggest it lasts about a day after one dose⁹.

2. Speeding up the cleanup. Some herbs do the opposite. They switch on extra enzymes and pumps, so a drug leaves the body faster and works less well. St. John’s wort is the classic example, and our profile of it explains the transplant, HIV and birth control failures it has caused.

3. Blocking the door. Transporters also help some drugs get into the body. The allergy drug fexofenadine (Allegra) is a good example. Taken with grapefruit, orange or apple juice, less of it gets absorbed, so it may work less well²³. The label tells you to skip fruit juice with it³, and McGill University’s Office for Science and Society puts the blocking window at roughly four hours².

The shortcut: piling on. Many herb risks have nothing to do with drug levels. Two things simply do the same job. Garlic, ginkgo, ginseng and vitamin E can each add to bleeding risk⁶.

Kava and valerian can strengthen or prolong anesthesia, and kava can cause more sedation than intended⁶¹⁰. The Institute for Safe Medication Practices (ISMP) warns that ginseng may drop blood sugar dangerously low around surgery¹⁰.

NCCIH adds two less obvious examples. Glucosamine may strengthen the blood thinner warfarin, and early evidence suggests ashwagandha may add to anti-anxiety drugs such as Valium and Xanax⁸.

People also differ. The FDA notes that the amount of CYP3A4 in the gut varies from person to person, so the same combination can affect two people differently³.

The mechanism-to-risk table

Use this table to decide which questions to bring to your pharmacist. It shows patterns, not a complete list. For specific herbs, see the profiles in this series.

What the plant does	Examples	Medicines with the most at stake	Ask this
Slows drug breakdown	Grapefruit, Seville oranges, pomelos, tangelos; goldenseal39	Some statins and blood pressure drugs, cyclosporine, buspirone, midazolam39	“Is my drug cleared by CYP3A4?”
Speeds drug breakdown	St. John’s wort (see our profile)	Warfarin, transplant drugs and some cancer drugs510; HIV and birth control drugs	“Will this weaken my medicine, and what happens if I stop?”
Blocks absorption	Grapefruit, orange and apple juice2	Fexofenadine23	“How far apart should I take them?”
Adds to bleeding	Garlic, ginkgo, ginseng, feverfew, vitamin E; glucosamine with warfarin6810	Warfarin, ibuprofen-type pain relievers, surgery610	“Do I need a clotting check?”
Adds to drowsiness	Kava, valerian, ashwagandha6810	Anti-anxiety drugs, sedatives, anesthesia68	“Is it safe to drive?”
Lowers blood sugar	Ginseng10	Diabetes medicines	“Should I check my sugar more often?”
Raises blood pressure or heart rate	Ephedra6	Blood pressure medicines6	“Is this safe with my heart drugs?”

Some medicines leave very little room for error

An interaction matters most when a drug’s dose is set tightly and failure is costly. These are the groups to raise first. For details on single herbs, use the herb profiles in this series rather than a general list.

• Blood thinners. Herbs that add to bleeding are one worry⁶⁸¹⁰, and herbs that weaken warfarin, such as St. John’s wort, are the other¹⁰. Our garlic, ginseng, ginger and chamomile profiles each cover warfarin.
• Transplant drugs. Cyclosporine is on the FDA’s grapefruit list³. ISMP says transplant patients should avoid echinacea before and after surgery¹⁰. Our peppermint, chamomile and St. John’s wort profiles flag cyclosporine too.
• Cancer and HIV treatment. NCCIH reports growing concern that herbal and dietary supplements may interfere with how well these treatments work⁷. Radiation oncologist Nina Sanford of UT Southwestern advises patients to avoid supplements during radiation, since high-dose antioxidants may blunt it, though she says a daily multivitamin can continue⁵.
• Diabetes and blood pressure drugs. Ginseng’s effect on blood sugar¹⁰ is worth raising if you take diabetes medicine, and ephedra can push blood pressure and heart rate dangerously high with some blood pressure drugs⁶. Our ashwagandha profile covers its overlap with these medicines.
• Sedatives and sleep medicines. Kava, valerian and ashwagandha can stack with them⁶⁸¹⁰. See our valerian and lavender profiles.
• Birth control pills. St. John’s wort is the main concern, and our chamomile profile notes a caution as well.

Surgery is the deadline most people miss

Anesthesia drugs are powerful, and so are some herbs. The ASA tells patients that an anesthesiologist may recommend stopping supplements at least two weeks before a procedure⁶. ISMP, citing the ASA’s one-to-two-week window, describes it as erring toward caution, since many herbs’ effects fade soon after stopping¹⁰.

Herb-by-herb timing rests on older, thinner evidence: a July 2001 review in JAMA by three University of Chicago physicians that looked at eight popular herbs¹¹. Their suggested minimum stop times ran from 24 hours for kava and ephedra, to 36 hours for ginkgo, five days for St. John’s wort and seven days for garlic and ginseng¹¹. They found no randomized trials, so the advice rested on pharmacology and case reports¹¹.

Those figures are 25 years old. Treat them as background, and follow the timing your own surgical team gives you.

Valerian is the exception to “just stop.” The same team suggested tapering it¹¹, and ISMP advises lowering the dose over one to two weeks to avoid withdrawal symptoms¹⁰.

This is the trap. Back in 2001, the university’s announcement of the review flagged a timing problem with the ASA’s two-week advice: most pre-surgery checkups took place just days before the operation¹¹. Raise your herbs the day the surgery is booked, and tell both the surgeon and the anesthesiologist what you took and when you stopped¹⁰.

Free interaction checkers miss most herb problems

Online checkers are handy, but herbs are their weak spot. A 2020 study, whose summary and data the journal publisher SAGE posted online, ran herbs paired with cancer drugs through eight tools. Four were subscription products and four were free websites. A natural-products reference database served as the answer key¹².

Every tool flagged fewer than 1 in 5 of the interactions that the reference rated as clinically relevant¹². Lexicomp, a paid tool, scored highest overall, and Medscape led the free group¹². Even the lowest-scoring subscription tool matched or beat the top free one¹². The researchers rated herb-drug screening poor overall and well below what these tools manage for drug-drug pairs¹².

For a free, noncommercial starting point, NCCIH points readers to NIH’s MedlinePlus website, whose Drugs, Herbs and Supplements section describes known side effects and interactions¹³.

Use these tools to learn, not to get cleared. A blank result means “no warning found,” not “safe.”

Bring the whole cabinet: a brown-bag review kit

A brown-bag review is simple. You put everything you take into a bag and sit down with a pharmacist or clinician who goes through it item by item. NCCIH recommends a written list with doses and how often you take each product, and bringing the bottles themselves⁷. The ASA asks for the bottles at pre-surgery visits for the same reason: labels show exactly what and how much⁶.

What goes in the bag

• Prescription medicines, including inhalers, patches and injectables
• Over-the-counter pain relievers, antacids, allergy and sleep aids
• Every herb, tincture, powder and capsule, plus teas you drink daily
• Vitamins, minerals, protein or “wellness” drinks and any mixed formulas

Your one-page list. Make one row per product, with these columns:

Product and maker	Plant name and part, if listed	Amount and how often	Why I take it	Start date	Who suggested it
(example row)

Questions to ask

1. “Does anything here change how my drugs are cleared, or add to bleeding, drowsiness or low blood sugar?”
2. “Which of my medicines has the least room for error?”
3. “If I stop an herb, does any dose need to change?”
4. “What should stop before a surgery or procedure, and when?”
5. “Which warning signs should make me call you?”

If you’re on Medicare. The Centers for Medicare & Medicaid Services (CMS) requires every Part D drug plan to run a medication therapy management program, built with pharmacists and physicians, to improve how medicines are used and lower the risk of harmful drug events¹⁴. It targets people with several chronic conditions, many Part D drugs and high drug costs¹⁵.

A 2024 CMS rule widened eligibility starting January 1, 2025. HIV/AIDS became the 10th core chronic condition, and the cost bar is now tied to the average cost of eight generic drugs, replacing a 2024 threshold of $5,330¹⁵. CMS noted that eligibility had fallen to 8% of enrollees by 2020¹⁵.

The full review is a live conversation, in person or by real-time telehealth¹⁵. Ask your plan whether you qualify, and bring your herbs.

What the evidence shows

Claim	Evidence rating	What it rests on
Grapefruit can raise blood levels of some drugs	Strong evidence	Human studies starting with Bailey’s; FDA-required label warnings123
Goldenseal can raise levels of drugs cleared by CYP3A	Promising but early	Small human studies that measured blood levels, not health outcomes9
Ashwagandha adds to anti-anxiety drugs	Promising but early	Preliminary evidence, per NCCIH8
Stopping herbs one to two weeks before surgery prevents complications	Not enough evidence	A sensible precaution based on pharmacology and case reports; a 2001 review found no trials1011
A free online checker can clear your herb and drug combination	Evidence says no, or unsafe	All eight tools tested caught fewer than 1 in 5 interactions12

Respecting a plant’s power means asking how it acts

Many herbalists teach that plants are medicine. Interactions are the evidence that the teaching is right. A plant strong enough to help is strong enough to collide with a drug.

That makes interaction checks part of herbal tradition, not a rejection of it. Careful practitioners ask what else a person is taking. A brown-bag review is the modern version of that question, and it lets you keep using herbs with your eyes open.

When to get help. Call your prescriber or pharmacist if you notice unusual bleeding or bruising, more drowsiness than usual, or signs of low blood sugar after starting or stopping an herb⁶¹⁰. Call 911 for trouble breathing, fainting, a seizure or collapse.

Questions readers ask

The bottom line

Most herbs and most medicines get along. The exceptions follow patterns: a plant that slows or speeds the body’s cleanup of a drug, one that blocks its way in, or one that adds to bleeding, drowsiness or low blood sugar. Those patterns matter most with blood thinners, transplant, HIV and cancer drugs, diabetes and blood pressure medicines, sedatives and birth control.

Don’t wait to be asked. Bag up everything you take, write one page, and go through it with a pharmacist, especially before surgery. Treat app results as a first look, and use the herb profiles in this series for specifics.

Related reading

• What happens when you don’t tell your doctor about supplements
• St. John’s wort may ease mild depression, but it can undercut your other medicines
• A stack of safe supplements can add up to an unsafe dose
• Some healthy habits clash with your medicines, so check these goals first
• What to bring, write down and ask before a doctor visit

Sources

1. The Globe and Mail. Obituary of David Bailey, Olympian and pharmacologist (headline, byline and date not shown in the accessed text; he died August 27, 2022). The Globe and Mail, accessed October 2026. theglobeandmail.com
2. Schwarcz J. “When It Comes to Taking Medicine, It’s Not Only a Matter of ‘What,’ but Also ‘How.'” McGill University Office for Science and Society, September 27, 2023. mcgill.ca
3. U.S. Food and Drug Administration. “Grapefruit Juice and Some Drugs Don’t Mix.” FDA Consumer Update, content current as of July 1, 2021. fda.gov
4. Jou J, Johnson PJ. “Nondisclosure of Complementary and Alternative Medicine Use to Primary Care Physicians: Findings From the 2012 National Health Interview Survey.” JAMA Internal Medicine, 2016;176(4):545-546. pubmed.ncbi.nlm.nih.gov
5. Bath C. “Are Your Patients Using Complementary and Alternative Therapies? You Might Not Know If You Don’t Ask” (on Sanford NN, et al., JAMA Oncology, 2019). The ASCO Post, June 25, 2019. ascopost.com
6. American Society of Anesthesiologists. “Herbal and Dietary Supplements and Anesthesia.” ASA patient brochure, 2020. madeforthismoment.asahq.org
7. National Center for Complementary and Integrative Health. “Talk With Your Health Care Providers.” Know the Science: How Medications and Supplements Can Interact. NCCIH, site updated 2026. nccih.nih.gov
8. National Center for Complementary and Integrative Health. “Some Supplements May Increase the Effects—and Side Effects—of Medications.” Know the Science. NCCIH, site updated 2026. nccih.nih.gov
9. Nguyen JT, Tian DD, Tanna RS, et al., Paine MF. “An Integrative Approach to Elucidate Mechanisms Underlying the Pharmacokinetic Goldenseal-Midazolam Interaction.” Journal of Pharmacology and Experimental Therapeutics, 2023;387(3):252-264. pmc.ncbi.nlm.nih.gov
10. Institute for Safe Medication Practices. “Stop Taking Herbal Medicines 1 to 2 Weeks Before Surgery.” ConsumerMedSafety.org, accessed October 2026. consumermedsafety.org
11. UChicago Medicine. “New Recommendations Proposed for Safe Use of Herbal Medications by Patients Having Surgery” (on Ang-Lee MK, Moss J, Yuan CS, JAMA, July 11, 2001). University of Chicago Medical Center, July 9, 2001. uchicagomedicine.org
12. SAGE Journals. “Comparison of Eight Screening Tools to Detect Interactions Between Herbal Supplements and Oncology Agents” (study summary and data collection; authors and journal not named on the page). SAGE figshare, posted February 21, 2020. sage.figshare.com
13. National Center for Complementary and Integrative Health. “Introduction.” Know the Science: How Medications and Supplements Can Interact. NCCIH, site updated 2026. nccih.nih.gov
14. Centers for Medicare & Medicaid Services. “Medication Therapy Management.” CMS, last modified May 4, 2026. cms.gov
15. Centers for Medicare & Medicaid Services. “Medicare Program; Changes to the Medicare Advantage and the Medicare Prescription Drug Benefit Program for Contract Year 2024 – Remaining Provisions and Contract Year 2025 Policy and Technical Changes” (final rule, CMS-4205-F). Federal Register, April 23, 2024;89 FR 30448. govinfo.gov