Grapefruit is a hybrid that nobody planned. It is a chance cross between a pomelo and a sweet orange that appeared in Barbados. A recent review calls it the youngest member of the Citrus genus. Its name may come from the way the fruit hangs in grape-like clusters on the tree.
Pharmacists know grapefruit better than most cooks do. It contains furanocoumarins, such as bergamottin, that switch off CYP3A4. This enzyme in the lining of the small intestine breaks down many drugs. In 10 healthy men, six days of grapefruit juice cut that enzyme by 62%.
In an 18-person trial, juice with about 99% of its furanocoumarins removed no longer raised levels of the blood pressure drug felodipine.
The color of pink and red grapefruit follows its lycopene content. The same review says most commercial varieties arose from mutations of one white-fleshed, seedy grapefruit called Duncan. In one small trial, red grapefruit lowered LDL cholesterol (the “bad” cholesterol) about twice as much as blond grapefruit.
Health benefits of grapefruit
The top findings from 25 studies, strongest evidence first
What the stars mean
- Strong. Several randomized trials, pooled in a meta-analysis, point the same way, or regulators (FDA or EFSA) have approved the claim.
- Moderate. Good randomized trials support it, but there are fewer of them, or their results vary.
- Limited. Small, short or single trials, or mixed results. Promising, but it needs confirmation.
Population and lab studies get no stars: they show a link or a mechanism, not proof.
How we rate evidence →- ★★Changes blood levels of many medicinesGrapefruit juice raised exposure to the transplant drug cyclosporine by 53% in pooled trials, and cut aliskiren and celiprolol levels by about 80 to 90%. A review found more than 85 drugs can interact with grapefruit.
- ★★No clear weight lossAcross 3 trials in 250 overweight or obese people, body weight differed by only 0.45 kg, a gap that could be chance. In another trial, grapefruit before meals did no better than water.
- ★Lower LDL and triglycerides in heart patientsOne red grapefruit a day for 30 days cut LDL by about 20% and triglycerides by 17% in patients with high cholesterol after bypass surgery. The groups were small.
- ★Less aortic stiffness, same blood pressureIn 48 postmenopausal women, daily grapefruit juice for 6 months lowered aortic stiffness (7.36 m/s, against 7.70 m/s on a control drink). Blood pressure, blood sugar and inflammation markers did not change.
- ★No change in kidney stone risk markersA week of grapefruit juice raised urine oxalate (41.1 to 51.9 mg a day), but citrate rose too (504.8 to 591.4 mg). The authors say the two changes offset each other, in 10 healthy adults.
All 25 studies, strongest evidence first
In overweight adults, grapefruit gave no clear weight loss
This systematic review pooled 3 randomized trials (people were put into groups by chance) with 250 overweight or obese people. Body weight differed by only 0.45 kg, a gap that could be chance. Systolic blood pressure fell by 2.43 mm Hg, but that drop was borderline. The authors cite few trials, short durations and no established effective dose.
Grapefruit juice raised cyclosporine exposure by 53% in pooled trials
This systematic review pooled 7 randomized trials in healthy volunteers who took the transplant drug cyclosporine with citrus juice or with water. Peak levels rose 24%. Pomelo juice also raised exposure (by 23%), while orange juice did not. Cyclosporine has a narrow safe range, so a change like this matters.
Grapefruit juice cut aliskiren and celiprolol levels by about 80 to 90%
This meta-analysis of 51 studies, mostly small open-label crossover trials, looked at fruit juice and blood pressure drugs such as aliskiren and celiprolol. Grapefruit juice blocks CYP3A4 and transporters that carry some drugs into the body. So it can lower levels as well as raise them. Most studies did not measure blood pressure, so the clinical importance is still unclear.
Half a fresh grapefruit: 1.6 kg lost, against 0.3 kg on placebo
In this randomized trial, 91 obese people were split into groups for 12 weeks. Three times a day before meals, they took a placebo (dummy pill), grapefruit capsules, grapefruit juice or half a fresh grapefruit. The juice group lost 1.5 kg and the capsule group 1.1 kg. Only the fresh fruit group differed clearly from placebo overall, and the authors say the mechanism is unknown.
Grapefruit with meals: no clear change against a control diet
In this randomized trial, 74 overweight adults first had a 3-week washout. Then 42 ate half a grapefruit with each meal for 6 weeks, and 32 followed a control diet. From their own starting values, the grapefruit group lost 2.45 cm of waist, systolic pressure fell 3.21 mm Hg and LDL cholesterol 18.7 mg/dL. Neither these changes nor weight differed clearly from the control diet.
Grapefruit before meals did no better for weight than water
In this randomized trial, 85 obese adults had 127 g of grapefruit, grapefruit juice or water before each meal for 12 weeks. They were also cutting calories. Everyone lost weight (7.1% overall), and the groups did not differ clearly. HDL (the “good” cholesterol) rose 6.2% with grapefruit and 8.2% with juice, and fell 3.7% with water.
Red grapefruit daily cut LDL about 20%, triglycerides 17% in heart patients
This randomized trial took 57 high-cholesterol patients after coronary bypass surgery. For 30 days, 19 people each ate one red grapefruit a day, a blond grapefruit or nothing extra. Blond grapefruit gave smaller drops (LDL 10.7%, triglycerides 5.6%). The groups were small, and the same paper reported lab tests of antioxidant content.
Grapefruit juice daily lowered aortic stiffness, but not blood pressure
In this double-blind trial (nobody knew who drank what), 48 healthy postmenopausal women had juice and a matched drink for 6 months each. The juice was 340 mL of grapefruit juice a day (210 mg of naringenin glycosides), and the matched drink had no flavanones. Pulse wave velocity, a measure of aortic stiffness, was 7.36 m/s after juice against 7.70 m/s after the control drink. Artery widening, blood pressure, blood sugar and inflammation markers did not change.
Grapefruit juice plus beetroot juice lowered systolic pressure 3.3 mm Hg more
In this placebo-controlled crossover trial, 11 healthy volunteers tried each drink and were followed for 7 hours after each. Adding 250 mL of grapefruit juice to beetroot juice gave the further drop at its peak. The result went against the team’s prediction, because blood nitrite was lower with grapefruit juice. It tested one day and a combination of juices, not grapefruit alone.
More than 85 drugs can interact with grapefruit, a review found
This expert review in CMAJ has no abstract, so its figures, including 43 drugs with serious effects, come from its key points. Drugs at risk are taken by mouth, only partly absorbed (low to intermediate bioavailability) and broken down by CYP3A4. Every form of grapefruit can cause this, the authors say, and one whole fruit or 200 mL of juice is enough. Older people are most at risk.
Grapefruit juice raised simvastatin levels 16-fold in healthy volunteers
In this randomized crossover trial, 10 healthy volunteers drank 200 mL of double-strength juice three times a day for 2 days. They took 60 mg of the statin simvastatin with it, and peak levels rose about 9-fold. This was a large juice dose. The authors advise avoiding large amounts of juice with simvastatin, or lowering the dose.
Simvastatin stayed 2.1 times higher 24 hours after the last juice
In this crossover study, 10 healthy volunteers took 40 mg of simvastatin with water or with high-dose grapefruit juice. They also took it 1, 3 and 7 days after the juice. Taken with juice, exposure rose 13.5-fold, and after 3 days the rise was 1.4-fold, small enough to be chance. By day 7 there was no rise.
Grapefruit juice raised atorvastatin 2.5-fold, but not pravastatin
Two crossover trials, in 12 and 11 healthy volunteers, tested these statins. People drank 200 mL of double-strength juice three times a day for 2 days and took a 40 mg dose of each statin. Active statin activity in the blood rose 1.3-fold with atorvastatin. The interaction depends on the drug and not on the drug class.
In people aged 70 to 83, grapefruit juice raised felodipine 2.9-fold
In this study, 12 healthy older people took 5 mg of the blood pressure drug felodipine with 250 mL of juice or water. Six of them were also tested at steady state, after repeated doses. Peak levels rose 4.0-fold, and the response varied a lot between people. Blood pressure was lower with juice after one dose, but not at steady state.
Removing furanocoumarins erased grapefruit juice’s effect on felodipine
In this randomized crossover trial, 18 healthy volunteers took 10 mg of the blood pressure drug felodipine with different drinks. These were regular grapefruit juice, orange juice, or grapefruit juice with about 99% of its furanocoumarins removed. Median felodipine exposure was 110, 54 and 48 nmol h/L. The flavonoids stayed in the treated juice, so the furanocoumarins are the active ingredients.
Six days of juice cut a gut drug enzyme by 62%
Ten healthy men drank 8 oz of juice three times a day, with biopsies (small tissue samples) of the gut lining before and after. Activity in the liver stayed the same. The mRNA for CYP3A4 in the gut did not change, so the juice lowers the amount of enzyme protein. Felodipine absorption was also tested and linked to each man’s starting enzyme level.
A glass of grapefruit juice raised amlodipine by only about 16%
In this randomized crossover trial, 12 healthy men took 5 mg of the blood pressure drug amlodipine with 250 mL of juice or water. The rise was too small to change blood pressure or heart rate, unlike with felodipine. The authors say people vary, and heavier juice intake might matter more.
A week of juice left urine measures of stone risk unchanged
In this study, 10 healthy adults drank 240 mL of grapefruit juice three times a day for a week. Urine oxalate rose from 41.1 to 51.9 mg a day. But citrate also rose, from 504.8 to 591.4 mg, so the two changes offset each other. The authors note that earlier population studies linked grapefruit juice to stones, a link that remains unexplained.
Whole grapefruit raised a blood estrogen marker by up to 26%
In this pilot study, 59 postmenopausal volunteers ate whole grapefruit, juice or soda for 2 weeks. The marker, estrone sulfate, peaked 26% higher 8 hours after eating. Estrone and estradiol did not change with whole fruit, while juice and soda lowered estradiol. The authors say more research is needed because estrogen relates to breast cancer risk.
Grapefruit three or more times a week: 41% higher melanoma risk
These two US cohorts (studies that follow large groups for years) tracked 63,810 women and 41,622 men for 24 to 26 years, with 1,840 melanomas. Grapefruit had the clearest link of any citrus product, at 1.41 times the risk of people who never ate it. The authors point to light-sensitizing furocoumarins and ask for further study. A link is not proof of cause.
A quarter grapefruit a day or more: 30% higher breast cancer risk
The Multiethnic Cohort followed over 50,000 postmenopausal women, with 1,657 breast cancers (1.30 times the risk). The authors raised the idea that blocking CYP3A4 could raise estrogen. A European cohort did not confirm the link.
In 114,504 European women, grapefruit was not linked to breast cancer
The EPIC cohort had 3,747 breast cancers over a median 9.5 years. Women who ate 60 g or more a day had 0.93 times the risk of women who ate none, a difference that could be chance. Grapefruit intake was also unrelated to estradiol or estrone in postmenopausal women.
Grapefruit went with a slightly lower risk of type 2 diabetes
Three US cohorts recorded 12,198 cases of type 2 diabetes. Each 3 servings a week of grapefruit went with 0.95 times the risk, or 5% lower. Each 3 servings a week of fruit juice went with an 8% higher risk (1.08). The link differed a lot between fruits: blueberries 0.74, apples and pears 0.93, oranges 0.99, cantaloupe 1.10.
In cells, DHB blocked the enzyme 85% or more in 30 minutes
This lab study used human intestinal Caco-2 cells that make CYP3A4. It compared two grapefruit furanocoumarins, DHB and bergamottin. Bergamottin acted more slowly, reaching 70% or more inhibition after 3 hours. This is cell work, not a study in people.
Four grapefruit furanocoumarins inactivated human CYP3A4 in test tubes
This lab study isolated compounds from grapefruit juice and tested them on human enzymes. The two dimers acted most strongly. The concentration needed was 40 µM (micromoles per liter) for bergamottin and 0.13 µM for the strongest dimer. Bergamottin also blocked other enzymes, such as CYP1A2 and CYP2C9, more strongly than CYP3A4.
Who should be careful with grapefruit
Most people can eat grapefruit freely. Take a little care if one of these applies:
- Medicines. Grapefruit and its juice block a gut enzyme, CYP3A4. This can raise the blood levels of some drugs, including certain statins such as simvastatin and the blood pressure drug felodipine. One fruit or one glass can be enough, and in one trial the effect was still there 24 hours later. Not every drug is affected, so ask your pharmacist about your own medicines before you eat it or drink the juice.
- Cancer signals. Large cohorts linked eating grapefruit three or more times a week to a higher melanoma risk. One linked it to breast cancer in postmenopausal women, but a European study of 114,504 women found no breast cancer link. These are associations, not proof, and the concern is small.
How to choose, store and eat grapefruit
- Whole fruit: half a fresh grapefruit before each meal is what the weight trials tested. In one trial it led to 1.6 kg of loss against 0.3 kg on placebo in 12 weeks. In another it made no clear difference.
- Juice: it worked about like the fruit for weight in one trial (1.5 kg lost). In another, 340 mL a day for 6 months lowered artery stiffness. It has the same medicine risk as the whole fruit.
- Red or white: in one small trial, a red grapefruit a day lowered LDL cholesterol by 20.3% against a control group. A blond one lowered it by 10.7% against the same control group.
Choose fruit that feels heavy for its size, without soft brown spots or dull, wrinkled skin. Keep it for about a week at room temperature or 2 to 3 weeks in the fridge.
Residues are not a reason to skip it. In USDA tests of 526 peeled grapefruit in 2017, the highest residue of imazalil, a fungicide applied after harvest, was 0.21 ppm (parts per million). The legal limit is 10 ppm. Only 1 sample had a residue with no US limit listed.
Sources
- Grapefruit juice and some drugs don’t mix. U.S. Food and Drug Administration, Consumer Updates.
- Bailey DG, Dresser G, Arnold JM. Grapefruit-medication interactions: forbidden fruit or avoidable consequences? CMAJ. 2013.
- Lilja JJ, Kivistö KT, Neuvonen PJ. Duration of effect of grapefruit juice on the pharmacokinetics of the CYP3A4 substrate simvastatin. Clin Pharmacol Ther. 2000.
- Wu S, Han J, Feskanich D, et al. Citrus consumption and risk of cutaneous malignant melanoma. J Clin Oncol. 2015.
- Monroe KR, Murphy SP, Kolonel LN, Pike MC. Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study. Br J Cancer. 2007.
- Spencer EA, Key TJ, Appleby PN, et al. Prospective study of the association between grapefruit intake and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Causes Control. 2009.
- Fujioka K, Greenway F, Sheard J, Ying Y. The effects of grapefruit on weight and insulin resistance: relationship to the metabolic syndrome. J Med Food. 2006.
- Silver HJ, Dietrich MS, Niswender KD. Effects of grapefruit, grapefruit juice and water preloads on energy balance, weight loss, body composition, and cardiometabolic risk in free-living obese adults. Nutr Metab (Lond). 2011.
- Gorinstein S, Caspi A, Libman I, et al. Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans. J Agric Food Chem. 2006.
- Habauzit V, Verny MA, Milenkovic D, et al. Flavanones protect from arterial stiffness in postmenopausal women consuming grapefruit juice for 6 mo: a randomized, controlled, crossover trial. Am J Clin Nutr. 2015.
- Fruit and vegetable guide series: grapefruit. Utah State University Extension.
- Pesticide Data Program annual summary, calendar year 2017. USDA Agricultural Marketing Service.
History of grapefruit
Grapefruit began as an accident in Barbados. Sweet oranges and pomelos both came to the Caribbean from Asia in the 17th century. The grapefruit appeared as a natural cross between them.
It is the youngest member of the Citrus genus. Genome work shows how tangled the family tree is, with pomelo genes spread even through mandarins.
The Welsh clergyman Griffith Hughes described a “forbidden fruit” in his Natural History of Barbados in 1750. That fruit is often linked to the grapefruit. Botanists still disagree on whether it was the same plant, because later descriptions differ from his.
The word “grapefruit” was published in 1814 by the naturalist John Lunan. He described a Jamaican tree and said the fruit tasted like a grape. Another explanation is that the name refers to the clusters it grows in. In 1830 James Macfadyen gave the Jamaican plant the botanical name Citrus paradisi, which means “citrus of paradise.”
The fruit reached Florida in 1823, when the French businessman Count Odet Philippe brought it to what is now Safety Harbor. For much of the 19th century, “grape-fruit” was also used for pomelos. A California report from 1895 recommended dropping the name in favor of pomelo.
The red grapefruit came from a lucky find. The 1929 ‘Ruby Red’ patent followed the discovery of a red grapefruit growing on a pink variety. Texas later made it the state fruit, in 1993.
Breeders then used radiation to stop the red from fading to pink. The ‘Rio Red’ variety, registered in Texas in 1984, came from bud sticks treated with thermal neutrons.
Sources
- Louzada ES, Ramadugu C. Grapefruit: history, use, and breeding. HortTechnology. 2021.
- Wu GA, Terol J, Ibanez V, et al. Genomics of the origin and evolution of Citrus. Nature. 2018.
- Grapefruit. Wikipedia.
Frequently asked questions about grapefruit
Is grapefruit good for you?
For most people, yes, but check your medicines first. Half a medium grapefruit (128 g) has 41 calories, 1.4 g of fiber and 44 mg of vitamin C. That vitamin C is 49% of the Daily Value, the FDA’s daily target. The best-supported finding, though not strong evidence, is a drug interaction: grapefruit juice raised cyclosporine exposure by 53% in a pooled analysis of 7 trials.
Does grapefruit help you lose weight?
Not clearly: a pooled analysis of 3 trials with 250 overweight adults found no clear difference in weight (0.45 kg). One 91-person trial found 1.6 kg lost on fresh grapefruit against 0.3 kg on placebo. Trials of 74 and 85 people found no difference from a control diet or from water before meals. At 32 calories per 100 g it can fill a plate cheaply, which is a swap effect and not a proven effect of grapefruit.
Why can’t you eat grapefruit with some medicines?
Grapefruit blocks CYP3A4, an enzyme in the small intestine that breaks down many drugs, so more of the drug reaches your blood. Juice raised simvastatin 16-fold in a high-dose trial and felodipine 2.9-fold in people aged 70 to 83. A review counts more than 85 drugs that can interact, 43 of them with serious effects. It can also lower levels of a few drugs, such as aliskiren and celiprolol, by about 80 to 90%. Ask your pharmacist about your own medicines.
How long does the grapefruit effect on medicines last?
Longer than most people expect: in 10 volunteers, simvastatin exposure was still 2.1 times higher 24 hours after the last glass of juice. It was 1.4-fold after 3 days (small enough to be chance) and back to normal after 7 days. So taking your pill at a different time of day does not fully avoid the interaction. Your pharmacist can tell you whether your drug is affected.
Is red grapefruit healthier than white?
Red may have a small edge, but the evidence is one small trial. The trial ran for 30 days in 57 patients after bypass surgery. Against a control group, a red grapefruit a day lowered LDL cholesterol by 20.3%, and a blond one by 10.7%. Red and pink varieties get their color from lycopene.
Is grapefruit good for cholesterol and blood pressure?
Possibly a little, but trials disagree. In 74 overweight adults, half a grapefruit per meal for 6 weeks did not change blood fats or blood pressure against a control diet. LDL did fall 18.7 mg/dL from the group’s starting value, and a pooled analysis found a 2.43 mm Hg lower systolic pressure. If you take a statin or blood pressure drug, check with your pharmacist first.
Is grapefruit high in sugar?
Not very: raw grapefruit has 6.98 g of sugars per 100 g, or 8.93 g in half a medium fruit. It also has 1.1 g of fiber per 100 g. In three large US cohorts, each 3 servings a week of grapefruit went with a 5% lower risk of type 2 diabetes. That is a link and not proof.
How much vitamin C is in a grapefruit?
Half a medium grapefruit (128 g) has 44 mg of vitamin C, or 49% of the Daily Value, and 100 g has 34.4 mg (38%). No other vitamin or mineral in that serving reaches more than 7% of the Daily Value. So it is a fruit to eat for vitamin C, and not for much else.