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Naringenin

Evidence Level
Limited
2 Clinical Trials
4 Documented Benefits
2/5 Evidence Score

Naringenin is a citrus flavanone found mostly in grapefruit, oranges, and tomatoes. It is the aglycone (sugar-free form) of naringin, the bitter flavonoid glycoside in grapefruit, and the body also forms naringenin from naringin in the gut. It has been studied in cell, animal, and a smaller number of human studies for cardiovascular, metabolic, and antioxidant effects, with the human evidence still limited. Naringin is one of several grapefruit constituents linked to the way grapefruit juice can change the absorption of some medicines, but controlled human studies show naringin on its own is not the main driver of that effect, and furanocoumarins such as bergamottin are considered the principal contributors. Isolated naringenin is a newer supplement ingredient and its long-term effects in people are not well characterized.

Studied Dose 150-500 mg/day in human studies; isolated-naringenin doses are not yet well standardized.
Active Compound Naringenin (4',5,7-trihydroxyflavanone), the aglycone of naringin

Benefits

Cardiovascular / Lipid Effects

In a small placebo-controlled human trial in overweight adults with fatty liver, naringenin improved several blood lipid ratios and reduced body-mass index and visceral fat. Most other data come from cell and animal work suggesting it lowers fat production in the liver and supports a healthier lipid profile. Human evidence remains limited.

Supported by Trial 1

Insulin Sensitivity / Glycemic Effects

Animal models show improved insulin sensitivity and reduced hepatic glucose production. Human clinical translation modest.

Supported by Trial 1, Trial 2

Antioxidant Activity

Naringenin can scavenge free radicals directly and activates the Nrf2 pathway, which raises the cell's own antioxidant enzymes. Most of this evidence comes from laboratory and animal studies rather than human trials.

Supported by Trial 2, Trial 1

Anti-Inflammatory Effects

Reduces inflammatory cytokine production, modulates NF-κB pathway. Modest anti-inflammatory profile.

Mechanism of action

1

PPAR-Alpha Activation

Naringenin activates peroxisome proliferator-activated receptor alpha (PPAR-alpha), a nuclear receptor that is also the target of fibrate medications. Activating it lowers fat synthesis and increases fatty acid oxidation in the liver.

2

AMPK Activation

Activates AMP-activated protein kinase (AMPK), a cellular energy sensor also switched on by metformin and by exercise. This promotes glucose uptake and fat oxidation and reduces fat synthesis.

3

Naringin versus naringenin (grapefruit interaction context)

Naringin, the glycoside abundant in grapefruit, is often blamed for grapefruit's effect on drug absorption, but controlled human studies show it does not reproduce the interaction on its own and is not the major active ingredient. Furanocoumarins such as bergamottin are considered the main contributors (inhibiting intestinal CYP3A4; transporters such as OATP are also involved). Naringenin is not expected to produce grapefruit-level interactions, though human data are limited.

4

Antioxidant Pathway Activation

Direct radical scavenging plus Nrf2 transcription factor activation upregulating endogenous antioxidant enzymes.

Clinical trials

1
Naringenin RCT in Fatty Liver
PubMed

Pilot double-blind, placebo-controlled randomized trial of naringenin supplementation over 4 weeks (Naeini et al. 2022, Eur J Gastroenterol Hepatol).

Overweight or obese adults with nonalcoholic fatty liver disease.

Compared with placebo, naringenin significantly reduced the atherogenic index of plasma, non-HDL cholesterol, and several cholesterol ratios, and lowered body-mass index and visceral fat. Systolic blood pressure fell only marginally and most other outcomes did not differ. The trial was small and described as preliminary.

2
Human Pharmacokinetics of Naringenin
PubMed

Single-oral-dose pharmacokinetic study of pure naringenin and hesperetin aglycones in healthy volunteers (Kanaze et al. 2007, Eur J Clin Nutr).

Six healthy adult volunteers given 135 mg of naringenin under fasting conditions.

After a single oral dose, naringenin was absorbed and then rapidly conjugated, appearing in plasma and urine mainly as glucuronides and sulfates, with a short time to peak and relatively low systemic exposure. The study characterized basic pharmacokinetics rather than any clinical outcome.

Side effects and drug interactions

Common Potential side effects

Generally well-tolerated.
Mild GI distress.
Headache rare.
Allergic reactions to citrus rare.
Theoretical CYP enzyme effects (modest at supplemental doses; less than grapefruit juice).

Important Drug interactions

Drugs affected by grapefruit juice: mainly a theoretical concern. Naringin on its own does not reproduce the grapefruit interaction in human studies, and naringenin is not expected to; still, if you take drugs known to interact with grapefruit (for example simvastatin, atorvastatin, some calcium channel blockers, or certain immunosuppressants), discuss supplementation with your prescriber.
Statins: theoretical only, expected to be far less than grapefruit juice.
Calcium channel blockers: theoretical only, expected to be far less than grapefruit juice.
Cyclosporine and tacrolimus: theoretical only, expected to be far less than grapefruit juice.
Blood-pressure medications: possible minor additive effect in theory.
Diabetes medications: possible additive blood-sugar lowering in theory.

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Frequently asked questions about Naringenin

What is naringenin used for?

Naringenin is a flavonoid found in grapefruit and citrus. It is studied for antioxidant, metabolic, and liver support, including effects on cholesterol and blood sugar in laboratory research.

Is naringenin related to grapefruit drug interactions?

Naringin, a grapefruit flavonoid, is often named as the cause of grapefruit's drug interactions, but controlled human studies show it is not the main driver; furanocoumarins such as bergamottin are considered the principal contributors. Naringenin is the aglycone form and is not expected to reproduce that effect, though data are limited, so use caution with interacting medicines if unsure.

How much naringenin should I take?

Isolated naringenin doses are not well standardized; follow product labeling. Citrus fruits provide it naturally as part of a healthy diet.

Is naringenin safe?

Dietary amounts from citrus are very safe. As a supplement, the main caution is potential interactions with medications (like the grapefruit effect), so check with your doctor if you take prescription drugs.

What is Naringenin?

Naringenin is a citrus flavanone found mostly in grapefruit, oranges, and tomatoes. It is the aglycone (sugar-free form) of naringin, the bitter flavonoid glycoside in grapefruit, and the body also forms naringenin from naringin in the gut.

Does Naringenin interact with any medications?

Possible interactions include: Drugs affected by grapefruit juice: mainly a theoretical concern. Naringin on its own does not reproduce the grapefruit interaction in human studies, and naringenin is not expected to; still, if you take drugs known to interact with grapefruit (for example simvastatin, atorvastat… If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Naringenin?

NutraSmarts rates the evidence for Naringenin as Limited (2 out of 5). It is backed by 2 study summaries and 5 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(5 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Naeini F, Namkhah Z, Tutunchi H, Rezayat SM, Mansouri S, Yaseri M, Hosseinzadeh-Attar MJ Effects of naringenin supplementation on cardiovascular risk factors in overweight/obese patients with nonalcoholic fatty liver disease: a pilot double-blind, placebo-controlled, randomized clinical trial. European Journal of Gastroenterology and Hepatology. 2022;34(3):345-353. doi: 10.1097/MEG.0000000000002323.PubMedUsed to support: Human double-blind placebo-controlled RCT of naringenin supplementation measuring cardiovascular risk factors in overweight/obese NAFLD patients; primary human evidence for Cardiovascular / Lipid Effects and Anti-Inflammatory benefits.
  2. Alam MA, Subhan N, Rahman MM, Uddin SJ, Reza HM, Sarker SD Effect of citrus flavonoids, naringin and naringenin, on metabolic syndrome and their mechanisms of action. Advances in Nutrition. 2014;5(4):404-17. doi: 10.3945/an.113.005603.PubMedUsed to support: Review of naringenin/naringin effects on metabolic syndrome components including lipids, insulin resistance, and inflammation; supports Cardiovascular / Lipid Effects, Insulin Sensitivity / Glycemic Effects, and Anti-Inflammatory Effects benefits.
  3. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR Grapefruit juice-felodipine interaction: effect of naringin and 6',7'-dihydroxybergamottin in humans. Clin Pharmacol Ther. 1998;64(3):248-56. doi: 10.1016/S0009-9236(98)90173-4.PubMedUsed to support: Randomized crossover study in healthy men testing grapefruit juice fractions against felodipine; concluded that naringin is not a major active ingredient of the interaction although it may contribute, supporting the page's contribute-not-cause framing of naringin.
  4. Nguyen MA, Staubach P, Tamai I, Langguth P High-dose short-term administration of naringin did not alter talinolol pharmacokinetics in humans. Eur J Pharm Sci. 2015;68:36-42. doi: 10.1016/j.ejps.2014.12.001.PubMedUsed to support: Crossover study in healthy volunteers found that high-dose naringin from a supplement did not significantly change the pharmacokinetics of talinolol, an OATP transporter substrate, supporting that isolated naringin does not reproduce grapefruit-level interactions.
  5. Kanaze FI, Bounartzi MI, Georgarakis M, Niopas I Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects. Eur J Clin Nutr. 2007;61(4):472-7. doi: 10.1038/sj.ejcn.1602543.PubMedUsed to support: Single-dose human pharmacokinetic study of pure naringenin and hesperetin aglycones; backs the clinical-trial card describing naringenin's low systemic exposure and rapid conjugation to glucuronides and sulfates.