Table 1.

Clinical trials on the efficacy of naringin, naringenin, and its enriched food sources.

Model	Dose	Mechanism	Key findings	Ref.
Hypercholesterolemic subjects	Naringin, 400mg/capsule/day	Decreased plasma total cholesterol (TC), LDL, and Apo B; increased erythrocyte SOD and CAT activity	Lowering blood lipid, antioxidant	[183]
Patients with moderate hypercholesterolemia	Naringin, 500mg/capsule/day	TC and LDL cholesterol (LDL-C) concentrations are not reduced	Naringin does not lower blood lipids in patients with moderately high cholesterol	[184]
Adult patients with dyslipidemia	Naringin. 450 mg/day	TC, LDL, and TG decreased; lipocalin increased slightly	Reducing weight in patients with dyslipidemia	[102]
Prediabetes patients	Citrus Flavonoid Supplement (4 % Naringin). 200, 400, or 800 mg/day for 12 weeks	Decreased fasting glucose, HOMA-IR, HbA1c, glucagon, C-peptide, hsCRP, IL-6, and TNF-α; increased GLP-1, lipocalin in the blood.	Anti-inflammatory, anti-hyperglycemic and antioxidant	[185]
Patients with T2DM and mixed hyperlipidemia	650 mg of the BPF powder (BPF, main ingredient naringin)	LDL particles (LDL-P), TC, LDL-C, TG, blood glucose reduction	Lowering of blood glucose and blood lipids, complementary treatment of cardiometabolic disorders	[186,187]
T2DM	Mediterranean Diet (naringenin, naringin)	Decreased IL-6, oxidative stress marker 8-hydroxy-2′-deoxyguanosine (8-OHdG)	Reducing Inflammation in T2DM	[188]
Participants with abdominal obesity/dyslipidemia	1240 mg/day total polyphenols (naringin, naringenin)	Increases fatty acid oxidation in the liver, reduces inflammation by inhibiting nuclear factor κ-light chain enhancers in activated B cells, increases lipocalin	Blood pressure lowering, diet program to treat NAFLD.	[189]
older adults experiencing subjective cognitive decline (SCD)	400 mg Citrus Peel Extract (naringenin 3 mg)	IL-10, IL1-Ra, soluble TNF receptor I, soluble TNF receptor II increased; CXCL8/IL-8, IL-1β, IL-6, IL-17, TNF-α, IP10, MIP-1α, CCL2/MCP-1, CCL5/RANTES, IL-18, NO, thiobarbituric acid reactive substances, SOD decreased	Improves immediate memory, visuospatial/structural, language, attention, and delayed memory; reduces oxidative stress and neuronal damage and anti-inflammatory effects	[190]
Healthy volunteers	Felodipine with 250 mL grapefruit juice	Significantly inhibited CYP3A4 activity	Peak concentrations were higher, but half-life was unchanged. Grapefruit juice significantly increased the bioavailability of felodipine	[[191], [192], [193]]
Healthy volunteers	aliskiren with 300 mL grapefruit juice	Naringin inhibits human intestinal organic anion transporting polypeptide (OATP) 1A2	Reducing exposure to aliskiren	[194]
Healthy volunteers	Fexofenadine with 300 ml grapefruit juice	Naringin inhibits the OATP1A2 part of the intestine	Reduces the bioavailability of oral fexofenadine	[195]
Healthy volunteers	talinolol and 1050 mg of naringin	The high dose may inhibit the efflux transporter protein P-glycoprotein (P-gp), counteracting uptake inhibition.	Short-term high-dose supplementation with naringin does not affect the pharmacokinetics of talinolol.	[196]
Healthy volunteers	Nisoldipine coated tablets with 250 ml water, 250 ml grapefruit juice		Increasing the maximum concentration of nisoldipine and decreasing the time to reach the maximum concentration	[197]