Benefits
Body weight when half a grapefruit is eaten before meals
In a 12-week trial of 91 adults with obesity, the group eating half a fresh grapefruit before each meal lost 1.6 kg versus 0.3 kg on placebo, a significant difference. Two later controlled trials, one with a calorie-restricted diet and one against a control diet, found no difference in weight between grapefruit and comparison groups.
Insulin levels after a glucose drink
In the same 12-week trial, insulin measured 2 hours after a glucose drink fell more with fresh grapefruit than with placebo. This was a single trial in adults with obesity. A 12-week preload trial found no change in fasting glucose or insulin, and a 6-month juice trial found no effect on glucose metabolism versus a control drink.
Arterial stiffness with daily grapefruit juice
In a double-blind crossover trial, 48 healthy postmenopausal women drank 340 mL of grapefruit juice or a matched flavanone-free drink daily for 6 months each. Pulse wave velocity, a measure of aortic stiffness, was lower after the juice. The main outcome, artery widening, and blood pressure did not differ. The trial was funded by the Florida Department of Citrus.
HDL cholesterol with grapefruit or juice before meals
In a 12-week open-label trial of 85 adults with obesity on a calorie-restricted diet, HDL cholesterol rose 6.2 percent with grapefruit and 8.2 percent with juice preloads but fell 3.7 percent with water, a significant difference. Total and LDL cholesterol did not differ. A 6-week trial found no lipid difference versus a control diet.
Blood lipid levels with fresh red grapefruit
In 57 adults with high blood lipids after coronary bypass surgery, one fresh red grapefruit a day for 30 days was followed by lower total cholesterol, LDL cholesterol and triglycerides than in a control group; white grapefruit had smaller effects. This was a single short trial in heart surgery patients, and blinding was not described.
Oxidative stress and inflammation markers
In a 6-week trial of 69 overweight or obese adults, one and a half grapefruits a day did not change urinary F2-isoprostanes, a marker of oxidative damage, or plasma CRP or sVCAM-1 compared with a citrus-free control diet. Only participants who started with high F2-isoprostane levels showed a reduction, a subgroup finding.
Vitamin C and fiber from the whole fruit
USDA data list 31.2 mg of vitamin C, 1.6 g of fiber and 42 kcal per 100 g of raw pink or red grapefruit, so half a medium fruit (123 g) supplies about 38 mg of vitamin C. In a 12-week trial, grapefruit and juice preloads raised daily vitamin C intake by about 130 mg compared with water.
Mechanism of action
Furanocoumarins inactivate CYP3A4 in the gut wall
Furanocoumarins such as 6',7'-dihydroxybergamottin are converted by intestinal CYP3A4 into reactive forms that permanently disable the enzyme. In a human study, removing about 99 percent of the furanocoumarins from grapefruit juice while keeping its flavonoids abolished the rise in felodipine levels. Repeated juice lowered small-bowel CYP3A4 protein by 62 percent without changing liver CYP3A4.
Recovery needs new enzyme, so the effect lasts days
Because the enzyme is destroyed rather than briefly blocked, activity returns only as the gut makes new CYP3A4. After one 300 mL glass, midazolam levels were still raised at 26 and 50 hours, with a recovery half-life of about 23 hours and near-complete recovery within about 3 days.
Naringin and naringenin
Grapefruit is a major dietary source of naringin, the bitter flavanone glycoside that gut bacteria convert to naringenin. A 340 mL daily serving of juice supplied about 210 mg of naringenin glycosides, and the authors suggested the 6-month arterial stiffness finding may be related to these flavanones. Naringin is not the main driver of the CYP3A4 interaction.
Low energy density before meals
Grapefruit and its juice are watery and low in calories. In a 12-week trial comparing grapefruit, juice and water preloads matched for weight and calories, all three lowered energy intake and body weight similarly, and the authors concluded that preload weight and low energy density, not fiber or flavonoid content, explained the effect.
Clinical trials
Randomized, placebo-controlled trial of half a fresh grapefruit, 237 mL grapefruit juice or grapefruit capsules three times a day before meals, against placebo capsules with apple juice, for 12 weeks. The funder is not named in the abstract; PubMed tags it as non-government research support. (Fujioka et al. 2006, J Med Food)
91 adults with obesity; a secondary analysis looked at those with metabolic syndrome.
Weight fell 1.6 kg with fresh grapefruit, 1.5 kg with juice, 1.1 kg with capsules and 0.3 kg with placebo; only the fresh grapefruit group was reported as significantly different from placebo in the full sample. In the metabolic syndrome subgroup all three grapefruit forms lost more weight than placebo. Two-hour post-glucose insulin fell more with fresh grapefruit than with placebo.
Randomized, open-label, parallel trial of 127 g grapefruit, grapefruit juice or water before each meal for 12 weeks after a 2-week calorie-restriction phase. Funded mainly by the State of Florida Department of Citrus, with NIH support. (Silver et al. 2011, Nutr Metab (Lond))
85 adults with obesity (BMI 30 to 39.9); 17 dropped out.
Participants lost 7.1 percent of body weight overall, but weight, body fat and waist size did not differ between the three preload groups. HDL cholesterol rose 6.2 percent with grapefruit and 8.2 percent with juice and fell 3.7 percent with water, a significant between-group difference; total and LDL cholesterol did not differ.
Randomized controlled trial of half a fresh Rio Red grapefruit three times a day for 6 weeks versus a control diet, after a 3-week low-bioactive washout diet. The companion paper from the same registered trial lists USDA grant funding. (Dow et al. 2012, Metabolism)
74 healthy overweight adults (42 grapefruit, 32 control).
There were no between-group differences in weight, blood pressure or lipids. Within the grapefruit group, waist size fell 2.45 cm, systolic blood pressure fell 3.21 mmHg and LDL cholesterol fell 18.7 mg/dL from baseline, these are within-group changes from baseline, not differences from the control group.
Randomized controlled trial (same registered trial, NCT01452841, as the 6-week weight study by Dow et al. 2012, reporting different outcomes) of a low-bioactive diet plus 1.5 grapefruits a day versus the same diet without citrus for 6 weeks. Funded by USDA grants; authors declared no conflicts. (Dow et al. 2013, J Nutr)
69 overweight or obese adults, 29 of them with metabolic syndrome.
Urinary F2-isoprostanes, plasma hsCRP and sVCAM-1 did not differ significantly between groups after 6 weeks (hsCRP P = 0.09). Participants with high baseline F2-isoprostanes showed a significant fall with grapefruit, a subgroup finding.
Double-blind, randomized, controlled crossover trial of 340 mL/day grapefruit juice (about 210 mg naringenin glycosides) versus a matched flavanone-free control drink, 6 months each with a 2-month washout. Funded by the Florida Department of Citrus. (Habauzit et al. 2015, Am J Clin Nutr)
48 healthy postmenopausal women aged 50 to 65 with a waist over 88 cm.
Carotid-femoral pulse wave velocity was lower after the juice than after the control drink (7.36 vs 7.70 m/s, P = 0.019). The primary outcome, flow-mediated dilation, did not change, nor did blood pressure, body measures, glucose metabolism or inflammation and oxidative stress markers.
Randomized three-group trial adding one fresh red or white grapefruit a day to the diet for 30 days versus a control group, with laboratory analysis of the fruit. Funding was not stated in the abstract. (Gorinstein et al. 2006, J Agric Food Chem)
57 adults aged 39 to 72 with high blood lipids after coronary bypass surgery (19 per group).
After 30 days, total cholesterol, LDL cholesterol and triglycerides were lower in the red grapefruit group than the control group (triglycerides 1.69 vs 2.32 mmol/L), with smaller differences for white grapefruit. Lipids did not change in the control group. Blinding was not described.
Open, three-way randomized crossover study of the blood-pressure drug felodipine taken with 240 mL of regular grapefruit juice, orange juice or grapefruit juice with about 99 percent of its furanocoumarins removed. (Paine et al. 2006, Am J Clin Nutr)
18 healthy volunteers.
Felodipine exposure (AUC) was about twice as high with regular grapefruit juice (median 110 nmol h/L) as with orange juice (54) or furanocoumarin-free juice (48). The authors concluded that furanocoumarins are the active ingredients behind the interaction.
Study in which volunteers took midazolam alone, then 2 hours after one 300 mL glass of grapefruit juice, and were then randomized to a third dose at 26, 50 or 74 hours; plus laboratory tests of bergamottin and 6',7'-dihydroxybergamottin in human liver microsomes. (Greenblatt et al. 2003, Clin Pharmacol Ther)
25 healthy volunteers.
Midazolam exposure was 1.65 times control 2 hours after the juice, 1.29 times at 26 and 50 hours and 1.06 times at 74 hours, a recovery half-life of about 23 hours. In the laboratory, 6',7'-dihydroxybergamottin was a potent mechanism-based CYP3A inhibitor and bergamottin was much weaker.