What is grapefruit?
Grapefruit (Citrus paradisi) is part of the citrus family of fruits and is thought to be a hybrid of sweet orange (Citrus sinensis) and pomelo (Citrus maxima). The first grapefruit tree was discovered in Barbados in the 18th century, and the fruit had yellow pulp with many large seeds at its center. Over time, several varieties have been developed, and today, grapefruits are mostly seedless with pulp ranging from white to reddish pink, depending on the content of lycopene.[7][8][9] The characteristic aroma and bittersweet flavor of grapefruit are thanks to its content of flavonoids, terpenes, furocoumarins, simple sugars, and organic acids.[10]
What are grapefruit’s main benefits?
Grapefruit can be a nutritious addition to one’s diet, providing a source of vitamin C, potassium, carotenoids, fiber, and various other health-promoting vitamins, minerals, and phytochemicals.
Only a few clinical trials have examined grapefruit's health effects in humans. Some preliminary studies have pointed to potential benefits on cardiovascular health and metabolic health, including reduced blood pressure, weight loss, and improved lipid profiles and endothelial function.[6][11][5][4] However, these effects aren’t found consistently, and more research is needed.
In observational studies, higher intakes of flavonoid-rich foods tend to be associated with a reduced risk of all-cause mortality, cardiovascular disease, and cerebrovascular disease (e.g., stroke).[12][13] However, the relationship is less robust when looking specifically at grapefruit or its main types of flavonoids (flavanones). Some studies have even reported an increased risk of all-cause mortality with higher levels of consumption.[14][15] It’s unclear why this is, but the researchers suggested it could relate to the risk of drug interactions with grapefruit or to the disproportionate consumption of fruit juice rather than whole fruit.
What are grapefruit’s main drawbacks?
Although many people assume grapefruit is a harmless fruit, it actually carries some serious safety concerns that should be considered, particularly for people who take medications regularly.
Grapefruit interacts with nearly half of all oral medications. These include medications used to manage epilepsy, high cholesterol, HIV, heart arrhythmias, high blood pressure, organ transplants, anxiety, erectile dysfunction, pain, and more.[16][17] For a list of medications that could be affected, see here. This interaction can occur with as little as 6 ounces (180 mL) of grapefruit juice or about 180 grams of fresh grapefruit and persists for at least 24 hours after consumption.[18]
Regarding side effects, grapefruit is generally considered well tolerated when consumed in appropriate amounts. Most studies have failed to report on the adverse effects of grapefruit, apart from one study that reported both constipation and diarrhea during treatment with grapefruit capsules.[4]
Consuming grapefruit in large amounts (≥1 liter of juice at once) seems to prolong the QTc interval (a measurement of the heart's electrical activity). This could increase the risk of torsades de pointes, a potentially fatal heart arrhythmia. This effect has been observed in multiple randomized controlled trials and appears greater in women and in people with pre-existing disease affecting the heart rhythm.[1][2][3] The flavanone naringenin may be the culprit. In one study, QTc prolongation was observed at doses of about 1440 µmol naringenin (equivalent to roughly 390 mg). While naringenin content in grapefruit varies, this could correspond to about 4.5 whole grapefruits.[19]
How does grapefruit work?
Grapefruit contains an abundance of phytochemicals with biological activity, including various flavonoids, carotenoids, and coumarins. Naringenin is the predominant flavonoid in grapefruit and is often considered the major bioactive compound.[7] Compounds in grapefruit have been linked to various health-promoting effects, including antioxidant, anticancer, antimicrobial, anti-obesity, and antidiabetic properties.[20][21][22]
Naringenin and a few other compounds in grapefruit activate the enzyme AMPK. AMPK helps regulate metabolism, and its activation increases the breakdown of glucose and fats and decreases their synthesis.[23][6] This may be a driver of the antidiabetic, lipid-modulating, and weight-lowering effects of grapefruit. However, fiber and other nutritional compounds in grapefruit likely also play a role.[6]
Grapefruit may lower blood pressure by promoting the dilation of blood vessels possibly by increasing the synthesis of nitric oxide.[24][6]
What are other names for Grapefruit
- Citrus paradisi
Dosage information
Dosage Information
Grapefruit is usually taken as whole fresh grapefruit, 100% grapefruit juice, freeze-dried whole grapefruit powder, or grapefruit seed extract.
When fresh grapefruit, grapefruit juice, and freeze-dried grapefruit capsules were directly compared in one study, fresh grapefruit seemed the most promising for various cardiometabolic outcomes. However, the only effect that reached statistical significance was weight loss.[4]
Most studies have provided one-half of a fresh grapefruit or an 8-oz glass of grapefruit juice three times a day before meals. When it was reported, the daily dose of naringenin (the major flavonoid in grapefruit) has ranged from 81 to 142 mg daily.[5][6]
For regular dietary intake, the US Dietary Guidelines suggest consuming whole fruit over juice, but either one can help you meet the recommended 2 cups of fruit per day.
Frequently asked questions
Grapefruit (Citrus paradisi) is part of the citrus family of fruits and is thought to be a hybrid of sweet orange (Citrus sinensis) and pomelo (Citrus maxima). The first grapefruit tree was discovered in Barbados in the 18th century, and the fruit had yellow pulp with many large seeds at its center. Over time, several varieties have been developed, and today, grapefruits are mostly seedless with pulp ranging from white to reddish pink, depending on the content of lycopene.[7][8][9] The characteristic aroma and bittersweet flavor of grapefruit are thanks to its content of flavonoids, terpenes, furocoumarins, simple sugars, and organic acids.[10]
Grapefruit can be a nutritious addition to one’s diet, providing a source of vitamin C, potassium, carotenoids, fiber, and various other health-promoting vitamins, minerals, and phytochemicals.
Only a few clinical trials have examined grapefruit's health effects in humans. Some preliminary studies have pointed to potential benefits on cardiovascular health and metabolic health, including reduced blood pressure, weight loss, and improved lipid profiles and endothelial function.[6][11][5][4] However, these effects aren’t found consistently, and more research is needed.
In observational studies, higher intakes of flavonoid-rich foods tend to be associated with a reduced risk of all-cause mortality, cardiovascular disease, and cerebrovascular disease (e.g., stroke).[12][13] However, the relationship is less robust when looking specifically at grapefruit or its main types of flavonoids (flavanones). Some studies have even reported an increased risk of all-cause mortality with higher levels of consumption.[14][15] It’s unclear why this is, but the researchers suggested it could relate to the risk of drug interactions with grapefruit or to the disproportionate consumption of fruit juice rather than whole fruit.
The nutritional content of grapefruit varies depending on the cultivar (Marsh, Thompson, Ruby Red, Rio Red, etc.) and whether it’s consumed as a whole fruit or as juice. Grapefruit cultivars with red or pink pulp usually contain more carotenoids and other phytochemicals and may have higher antioxidant activity.[11] Marsh grapefruits have white/yellow pulp and have about half the amount of sugar than other grapefruit varieties.[9]
Juicing grapefruit can reduce the amount of fiber and some phytochemicals, as these tend to be concentrated in the pith of the grapefruit (the white spongy layer beneath the peel).[10] Juicing can also increase the amount of sugar, calories, and micronutrients within a serving.
Average nutritional content of pink/red grapefruit (whole or juiced)
| Nutrient | Whole Grapefruit (0.5 fruit / 123 g) | Grapefruit Juice (8 oz / 240 mL) |
|---|---|---|
| Calories | 51.7 kcal | 96 kcal |
| Protein | 0.9 g | 1.2 g |
| Total fat | 0.2 g | 0.3 g |
| Total carbohydrates | 13.2 g | 22.5 g |
| Sugar | 8.5 g | 17.6 g |
| Dietary Fiber | 2 g | 0.5 g |
| Calcium | 27.1 mg | 22.2 mg |
| Folate | 16 µg | 24.7 µg |
| Magnesium | 11.1 mg | 29.6 mg |
| Phosphorus | 22.1 mg | 37 mg |
| Potassium | 166 mg | 400 mg |
| Vitamin C | 38.4 mg | 93.9 mg |
| Vitamin A, RAE | 71.3 µg | 54.3 µg |
Obtained from U.S. Department of Agriculture, FoodData Central (ID 174673, 167774, and 2003595)
Although many people assume grapefruit is a harmless fruit, it actually carries some serious safety concerns that should be considered, particularly for people who take medications regularly.
Grapefruit interacts with nearly half of all oral medications. These include medications used to manage epilepsy, high cholesterol, HIV, heart arrhythmias, high blood pressure, organ transplants, anxiety, erectile dysfunction, pain, and more.[16][17] For a list of medications that could be affected, see here. This interaction can occur with as little as 6 ounces (180 mL) of grapefruit juice or about 180 grams of fresh grapefruit and persists for at least 24 hours after consumption.[18]
Regarding side effects, grapefruit is generally considered well tolerated when consumed in appropriate amounts. Most studies have failed to report on the adverse effects of grapefruit, apart from one study that reported both constipation and diarrhea during treatment with grapefruit capsules.[4]
Consuming grapefruit in large amounts (≥1 liter of juice at once) seems to prolong the QTc interval (a measurement of the heart's electrical activity). This could increase the risk of torsades de pointes, a potentially fatal heart arrhythmia. This effect has been observed in multiple randomized controlled trials and appears greater in women and in people with pre-existing disease affecting the heart rhythm.[1][2][3] The flavanone naringenin may be the culprit. In one study, QTc prolongation was observed at doses of about 1440 µmol naringenin (equivalent to roughly 390 mg). While naringenin content in grapefruit varies, this could correspond to about 4.5 whole grapefruits.[19]
Grapefruit is an irreversible inhibitor of the major drug-metabolizing enzyme CYP3A4. CYP3A4 is a cytochrome P450 enzyme found predominantly in the liver and intestines. It is involved in the breakdown and elimination of around half of all available medications. Medications metabolized by CYP3A4 are called CYP3A4 substrates.[17]
Grapefruit contains certain compounds — furanocoumarins — that can form strong and stable covalent bonds with CYP3A4, primarily in the intestine. This renders the enzyme inactive and impairs the body’s ability to metabolize the medication.[17] Most of the time, this leads to higher-than-intended levels of the drug in the body, which can cause side effects and even toxicity. Additionally, some medications called prodrugs rely on CYP3A4 to convert them into an active form. In these cases, the medications may be less effective, which could result in treatment failure.
Because the inhibition of CYP3A4 by grapefruit is irreversible, CYP3A4 enzyme activity remains suboptimal until the body makes new enzymes or until the epithelial lining of the intestine is shed, which usually takes upwards of 24 hours.[25]
To complicate matters further, grapefruit also seems to inhibit the drug efflux pump p-glycoprotein (P-gp) and the organic anion-transporting polypeptide (OATP) transporters OATP1A2 and OATP2B1. However, these effects are not consistently found and likely contribute only minorly to grapefruit’s drug interactions.[17][26][27]
The relationship between grapefruit and breast cancer risk is highly speculative and has to do with how estrogen is metabolized in the body. Elevated levels of estrogen are associated with an increased risk of breast cancer.[28] Normally, the cytochrome P450 enzyme CYP3A4 metabolizes estrogen into a form that is more easily removed from the body. However, grapefruit inhibits this enzyme, raising the question of whether grapefruit might lead to elevated estrogen in the body and potentially an increased risk of breast cancer.
Although biologically plausible, research has not provided a clear answer. In one observational study, higher grapefruit consumption was associated with an increased risk of breast cancer. However, in two other studies, no association was found.[29][30] Furthermore, a study examining the effects of grapefruit on endogenous estrogen levels in postmenopausal women reported unclear and contradictory effects. Whole grapefruit did not affect levels of estrone (E1) or estradiol (E2), while fresh grapefruit juice, bottled juice, and soda all lowered E2 — the opposite of what was hypothesized.[18]
Grapefruit has been reported to increase the plasma concentration of estrogen taken orally.[31] Because grapefruit inhibits CYP3A4 primarily in the intestines rather than the liver,[31] the interaction between grapefruit and estrogen might only be relevant when estrogen is being taken orally, rather than being produced naturally in the body.
Grapefruit contains an abundance of phytochemicals with biological activity, including various flavonoids, carotenoids, and coumarins. Naringenin is the predominant flavonoid in grapefruit and is often considered the major bioactive compound.[7] Compounds in grapefruit have been linked to various health-promoting effects, including antioxidant, anticancer, antimicrobial, anti-obesity, and antidiabetic properties.[20][21][22]
Naringenin and a few other compounds in grapefruit activate the enzyme AMPK. AMPK helps regulate metabolism, and its activation increases the breakdown of glucose and fats and decreases their synthesis.[23][6] This may be a driver of the antidiabetic, lipid-modulating, and weight-lowering effects of grapefruit. However, fiber and other nutritional compounds in grapefruit likely also play a role.[6]
Grapefruit may lower blood pressure by promoting the dilation of blood vessels possibly by increasing the synthesis of nitric oxide.[24][6]
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References
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