Naringin: What to Expect from Citrus Fruits for the Heart and Blood Pressure

Naringin, the main flavonoid in grapefruit and tangerine, has long been featured in talk about the “benefits of citrus.” But behind the general words “antioxidant” and “anti-inflammatory,” there are few specifics: does it affect the endothelium (the inner lining of blood vessels), is it able to protect the heart during ischemia and reperfusion, and is there evidence in people, not just in vitro and in mice? A team of researchers conducted a systematic review according to the PRISMA standard and collected everything that is known about the cardiovascular effects of naringin for 2000-2025. The result included 62 studies: 28 cellular, 29 on animals, and 5 clinical in humans. Conclusion: the picture is in favor of vascular-cardioprotective action, but larger and “cleaner” trials are needed for the clinic.

Background of the study

Cardiovascular disease begins long before a heart attack, with endothelial dysfunction, when the inner lining of blood vessels loses the ability to produce and retain nitric oxide (NO), oxidative stress and inflammation increase, and white blood cells “stick” more easily to the arterial wall. This early breakdown is one of the key predictors of atherosclerosis and vascular stiffness, so any nutrients that can reduce inflammation, quench reactive oxygen species, and support the NO signal are considered potential vascular “adjuvants” to lifestyle and therapy.

Against this background, it is logical to pay attention to citrus flavanones - primarily to naringin, the main glycoside of grapefruit/bitter oranges. In the body, it is converted into naringenin and in preclinical models shows antioxidant, anti-inflammatory and vasoprotective effects: from suppression of the NF-κB cascade and NADPH oxidases to activation of Nrf2 and maintenance of eNOS/NO. But to what extent these mechanisms translate into clinical benefit in humans is an open question and requires systematization of disparate studies.

A limiting factor is the low oral bioavailability of naringin: it is poorly soluble, poorly passes through the intestinal barrier and is extensively metabolized during the “first pass”, so that typical bioavailability is estimated at <5%. Hence the interest in improved delivery forms (nanocapsules, complexes with cyclodextrins, etc.) and in the selection of target groups where the effect will be more noticeable.

Finally, citrus biology runs into a practical “landmine”: grapefruit (and related citrus fruits) can inhibit intestinal CYP3A4 and alter the exposure of a number of drugs (statins, calcium channel blockers, etc.). So when discussing naringin as a dietary component or supplement, it is important to consider drug interactions, lest the potential vascular benefit turn into pharmacological risks. Against this background, a new systematic review in Nutrients attempts to soberly weigh the preclinical and small clinical studies to understand where naringin has realistic therapeutic potential and where the limits of the evidence are.

How they searched and what they included

The authors sifted through PubMed, Scopus, Web of Science, and EMBASE, excluded duplicates and irrelevance, and then assessed the risk of bias for each type of paper. In the final PRISMA tree: of the 2884 records, after removing duplicates, 165 were included in the full-text analysis, and 62 were included in the review.

• Cell models (n=28): endothelial cells, cardiomyocytes, vascular smooth muscle cells.
• Animals (n=29): atherosclerosis, hypertension, diabetes/dyslipidemia, ischemia-reperfusion.
• Humans (n=5): naringin drinks/capsules or grapefruit flavonoids, 4-24 weeks.

The main thing in one paragraph

In all three “model worlds”—cells, animals, and humans—naringin exhibited antioxidant, anti-inflammatory, and vasoprotective effects. In animals, it improved endothelium-dependent vasorelaxation, reduced infarct size, and preserved cardiac contractility. Small human studies showed improved lipid profiles, decreased arterial stiffness, and increased adiponectin; effects on blood pressure and flow-dependent dilation were inconsistent.

What happens at the cellular level

In the endothelium, naringin dampens the inflammatory cascade of NF-κB and reduces the expression of “sticky” molecules (VCAM-1/ICAM-1/selectins), thereby preventing leukocytes from adhering to the vascular wall. It reduces the activity of superoxide anion sources (NADPH oxidase), and therefore preserves nitric oxide (NO), the main vasodilator mediator. In parallel, survival pathways (PI3K/Akt) are activated, and cell death signals (apoptosis/ferroptosis/excessive autophagy) are suppressed. The result is a viable, calm endothelium and less reactive smooth muscle cells.

• Antioxidant: direct ROS/RNS scavenger + Nrf2 activation → increase in protective enzymes (catalase, SOD, GPx).
• Anti-inflammatory: inhibition of IKK→NF-κB→cytokines (TNF-α, IL-6), ↓MMP-9.
• NO effect: ↑eNOS (via Akt phosphorylation) and ↓NO destruction (less superoxide).
• Antiremodeling: effect on RAS (↓AT1R/ACE, shift in balance to ACE2), ↑KATP in cardiomyocytes.

What animal models show

In rats and rabbits the picture is more stable and vivid than in humans:

• Atherosclerosis/dyslipidemia: less oxidative stress in the aorta, endothelial protection and less plaque accumulation/progression; locally decreased LOX-1 and NADPH oxidase.
• Hypertension/hypertrophy: pressure is normalized (L-NAME model), less LV hypertrophy and fibrosis, better endothelium-dependent relaxation even with inhibited NO.
• Ischemia-reperfusion: smaller infarction, lower CK-MB/LDH/troponin, better EF and fraction shortening; key - PI3K/Akt, cGAS-STING, Nrf2/GPx4.

What we see in people (figures with reservations)

Only five small RCTs/crossover studies - so the "signal" is modest, but it is there:

• Lipids/body weight/adiponectin: capsules 450 mg/day for 90 days → ↓total and LDL-cholesterol (~−25% and ~−100 mg/dL, respectively), moderate ↓BMI; ↑adiponectin.
• Arterial stiffness: 340 ml/day grapefruit juice (~210 mg naringin glycosides) for 6 months in postmenopausal women → ↓pulse wave velocity (central stiffness); FMD unchanged.
• Waist circumference/BP in overweight: 1.5 grapefruit/day 6 weeks → ↓waist and systolic BP; weight − small.
• Negative/neutral results: 500 mg/day for 4-8 weeks did not improve lipids in moderately hypercholesterolemic adults - likely insufficient dose/duration and low bioavailability.

Why the effect may be “lost” in people

Naringin has a problem: low oral bioavailability (<5%) due to solubility, permeability and metabolism in the intestine/liver. Hence the interest in liposomes, nanoemulsions, mikeles, etc., which in preclinical studies increase its "visibility" for the body. Plus, interindividual differences in microbiota affect the conversion of naringin into active naringenin.

• Solutions on the horizon: improved delivery forms; dose selection to bring exposure closer to “animals”; target groups (by microbiome/genetics).

Mechanisms: "many targets - one result"

The authors reduce the action map (see the diagram in the article) to several pillars: Nrf2-antioxidant axis, NF-κB inhibition, NO-signal rescue (eNOS/Akt), RAAS modulation (↓AT1R/ACE, ↔ACE2), antiapoptosis/anti-ferroptosis/anti-autophagy-stress, plus the AMPK/PPARγ metabolic block (less lipotoxicity). Together, this protects the endothelium and myocardium and reduces vascular “stiffness.”

Practical meaning

Overall, naringin appears to be a promising nutraceutical/dietary adjuvant for the prevention of vascular dysfunction and mitigation of ischemic heart damage. No adverse effects have been reported in clinical studies, but one should be aware of grapefruit drug interactions (CYP3A4 inhibition, etc.) and avoid self-medication when taking statins/calcium channel blockers, etc.

• Who is especially interested: people with dyslipidemia, metabolic syndrome, increased arterial stiffness;
• What to realistically expect now: Improvement in lipids and inflammation/stiffness markers with regular consumption of native sources or capsules (if discussed with your doctor).
• What we don't know yet is whether naringin reduces hard endpoints (heart attacks/strokes/mortality). Large RCTs and "smart" delivery systems are needed.

Viewing Limitations

Most of the strong effects are preclinical. Human studies are small, heterogeneous in dose/formulation/duration, and bioavailability is low in classic forms. Hence the cautious optimism and call for large trials with vascular/cardiac imaging and long-term follow-up.

Conclusion

• Naringin is a multi-target protector of the endothelium and myocardium: it dampens oxidative stress and inflammation, preserves NO, interferes with the RAAS and inhibits cell death.
• In preclinical studies it works brilliantly; people see metabolic and vascular improvements, but the clinic needs larger RCTs and forms with better bioavailability.

Source: Adams JA, Uryash A, Mijares A, Eltit JM, Lopez JR Endothelial and Cardiovascular Effects of Naringin: A Systematic Review. Nutrients 2025;17(16):2658. Open access. https://doi.org/10.3390/nu17162658