Supplement
Naringenin is a flavanone, a plant pigment abundant in grapefruit and other citrus, which can influence enzymes and transporters that handle food compounds and medicines. Grapefruit juice containing it raised blood levels of several medications by slowing an intestinal enzyme, and in one six-month trial postmenopausal women's arterial stiffness eased. The evidence is limited, though: other grapefruit compounds may drive the drug effect, and most heart and cholesterol findings come from animal or lab studies.
Sources: PMID 9565737; PMID 26016866
- Updated
- How we grade
- 20 studies cited
- Best evidence
- Grade C
- Conditions studied
- 3
- Outcomes
- 11
- Graded outcomes
- 0056
Evidence by condition
- Strong
- Moderate
- Limited
- Very limited
General
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Drug Bioavailability (CYP3A4 Inhibition) Grapefruit juice containing naringenin and furanocoumarins is well-documented to inhibit intestinal CYP3A4, increasing bioavailability of many medications by >70% for felodipine, nisoldipine, and saquinavir (PMID 9565737). Naringenin also inhibits P-glycoprotein transport (PMID 17542018). However, furanocoumarins rather than naringenin may be the primary CYP3A4 inhibitors (PMID 8809221). Multiple human pharmacokinetic studies confirm significant drug interactions. | Improves (the measure goes up) | Large effect | 6 studies | 50 people | ||
Studies that measured drug bioavailability (cyp3a4 inhibition)
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| Triglycerides Multiple preclinical studies consistently show naringenin reduces plasma and hepatic triglycerides. In rats, dietary naringenin decreased plasma triglycerides and adiposity via PPARalpha activation (PMID 20567977). In vitro studies demonstrate naringenin inhibits hepatocyte apoB-lipoprotein secretion through MTP inhibition (PMID 12564931) and induces a fasted-like hepatic metabolic state via PPARalpha/PPARgamma activation and LXRalpha inhibition (PMID 20811644). No direct human trials for lipid outcomes. | Improves (the measure goes down) | Moderate effect | 5 studies | |||
Studies that measured triglycerides
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| Liver Protection In a rat model, oral naringenin (20-50 mg/kg/day for 4 weeks) prevented dimethylnitrosamine-induced liver damage, reducing serum liver enzymes, oxidative stress, collagen deposition, and hepatic stellate cell activation (PMID 14709902). In vitro studies show naringenin modulates hepatic lipid metabolism via PPARalpha activation (PMID 20811644), suggesting potential hepatoprotective benefit. No human trials exist. | Improves (the measure goes up) | Moderate effect | 3 studies | |||
Studies that measured liver protection | ||||||
| Glucose Uptake In L6 muscle cells, naringenin (75 microM for 2 hours) stimulated glucose uptake by 192.8%, comparable to insulin, via AMPK activation. siRNA knockdown of AMPK abolished the effect, confirming the mechanism (PMID 20558145). No human studies have evaluated naringenin's effect on glucose metabolism. | Changes; see studies | Moderate effect | 2 studies | |||
Studies that measured glucose uptake | ||||||
| Intestinal Inflammation In a mouse model of DSS-induced colitis, naringenin significantly reduced disease severity and inflammatory markers via suppression of TLR4/NF-kappaB signaling. In vitro studies confirmed naringenin blocked inflammatory responses in macrophage and intestinal epithelial cell lines (PMID 23506745). No human data available. | Improves (the measure goes down) | Moderate effect | 2 studies | |||
| Neuropathic Pain In rats with spinal nerve ligation-induced neuropathic pain, intrathecal naringenin dose-dependently attenuated mechanical allodynia and thermal hyperalgesia by reducing spinal glial cell activation and inflammatory mediators (PMID 24944810). No human studies have evaluated analgesic effects. | Improves (the measure goes down) | Moderate effect | 2 studies | |||
| Estrogen Metabolism In a crossover trial of 8 postmenopausal women receiving micronized estradiol, grapefruit juice significantly increased peak estrone concentrations by inhibiting oxidative estrogen degradation (PMID 7715468). This suggests grapefruit flavonoids including naringenin may alter hormone levels, relevant to both drug interactions and estrogen-dependent conditions. | Improves (the measure goes up) | Small effect | 2 studies | 8 people | ||
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Atherosclerosis Risk A review of literature (PMID 25483717) summarizes consistent preclinical evidence that naringenin reduces LDL and triglycerides, increases HDL, suppresses macrophage inflammation, and inhibits foam cell formation. In mice, naringin reduced atherosclerotic plaque by 41% over 18 weeks (PMID 21684135). One human RCT showed reduced arterial stiffness (PMID 26016866), supporting vascular benefit. | Improves (the measure goes down) | Moderate effect | 5 studies | 48 people | ||
Studies that measured atherosclerosis risk
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Cardiovascular Health
- Arterial Stiffness: improves
- QTc Interval: worsens
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Arterial Stiffness A 6-month randomized, controlled, crossover trial in 48 postmenopausal women found that daily grapefruit juice consumption (containing ~210 mg naringenin glycosides) significantly reduced carotid-femoral pulse wave velocity, indicating decreased arterial stiffness (PMID 26016866). Preclinical studies in hypercholesterolemic mice show naringin reduces atherosclerotic plaque progression by 41% (PMID 21684135). | Improves (the measure goes down) | Moderate effect | 4 studies | 48 people | ||
Studies that measured arterial stiffness
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| QTc Interval In 10 healthy volunteers, 1L of pink grapefruit juice produced peak QTc prolongation of 12.5 +/- 4.2 ms at 5 hours via HERG channel blockade; naringenin was the most potent flavonoid inhibitor among 10 tested (PMID 15710766). In 32 participants including cardiomyopathy patients, grapefruit juice significantly increased QT variability indices comparable to sotalol (PMID 18433709). This represents a cardiac safety concern, particularly for patients with structural heart disease. | Worsens (the measure goes down) | Small effect | 3 studies | 42 people | ||
Studies that measured qtc interval
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Breast Cancer
- Breast Cancer Cell Proliferation: changes; see studies
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Breast Cancer Cell Proliferation Naringenin and other citrus flavonoids inhibited human breast cancer cell proliferation in vitro, with IC50 values of 5.9-140 microg/mL. Combined flavonoids showed synergistic effects. In rats, citrus juice delayed mammary tumorigenesis after carcinogen exposure (PMID 8875554). A separate review noted anti-mammary cancer potential of citrus flavonoids (PMID 9781306). All evidence is preclinical. | Changes; see studies | Small effect | 3 studies | |||
Key findings
- Drug Bioavailability (CYP3A4 Inhibition)Improves (the measure goes up)
- TriglyceridesImproves (the measure goes down)
- Atherosclerosis RiskImproves (the measure goes down)
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- Grade C
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Studies cited
20 studies from PubMed
- A Review on Pharmacological and Analytical Aspects of Naringenin
- Flavanones protect from arterial stiffness in postmenopausal women consuming grapefruit juice for 6 mo: a randomized, controlled, crossover trial
- Naringenin and atherosclerosis: a review of literature
- Analgesic effects of naringenin in rats with spinal nerve ligation-induced neuropathic pain
- Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-kappaB signalling
- Naringin, the major grapefruit flavonoid, specifically affects atherosclerosis development in diet-induced hypercholesterolemia in mice
- Dietary naringenin increases hepatic peroxisome proliferators-activated receptor alpha protein expression and decreases plasma triglyceride and adiposity in rats
- Naringenin, a citrus flavonoid, increases muscle cell glucose uptake via AMPK
- Transcriptional regulation of human and rat hepatic lipid metabolism by the grapefruit flavonoid naringenin: role of PPARalpha, PPARgamma and LXRalpha
- Effects of pink grapefruit juice on QT variability in patients with dilated or hypertensive cardiomyopathy and in healthy subjects
- Grapefruit juice-drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells
- QTc prolongation by grapefruit juice and its potential pharmacological basis: HERG channel blockade by flavonoids
- The flavonoid naringenin inhibits dimethylnitrosamine-induced liver damage in rats
- Hepatocyte apoB-containing lipoprotein secretion is decreased by the grapefruit flavonoid, naringenin, via inhibition of MTP-mediated microsomal triglyceride accumulation
- Bioavailability of the flavanone naringenin and its glycosides in rats
- Drug interactions with grapefruit juice. Extent, probable mechanism and clinical relevance
- Inhibition of mammary cancer by citrus flavonoids
- Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices
- Naringin and naringenin are not the primary CYP3A inhibitors in grapefruit juice
- Inhibition of 17 beta-estradiol metabolism by grapefruit juice in ovariectomized women