Safety and pharmacokinetics of naringenin: A randomized, controlled, single-ascending-dose clinical trial

Candida J. Rebello, Robbie A. Beyl, Juan J.L. Lertora, Frank L. Greenway, Eric Ravussin, David M. Ribnicky, Alexander Poulev, Brandon J. Kennedy, Hector F. Castro, Shawn R. Campagna, Ann A. Coulter, Leanne M. Redman

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Aims: To evaluate the safety and pharmacokinetics of naringenin in healthy adults consuming whole-orange (Citrus sinensis) extract. Methods and methods: In a single-ascending-dose randomized crossover trial, 18 adults ingested doses of 150 mg (NAR150), 300 mg (NAR300), 600 mg (NAR600) and 900 mg (NAR900) naringenin or placebo. Each dose or placebo was followed by a wash-out period of at least 1 week. Blood safety markers were evaluated pre-dose and 24 hours post-dose. Adverse events (AEs) were recorded. Serum naringenin concentrations were measured before and over 24 hours following ingestion of placebo, NAR150 and NAR600. Four- and 24-hour serum measurements were obtained after placebo, NAR300 and NAR900 ingestion. Data were analysed using a mixed-effects linear model. Results: There were no relevant AEs or changes in blood safety markers following ingestion of any of the naringenin doses. The pharmacokinetic variables were: maximal concentration: 15.76 ± 7.88 μM (NAR150) and 48.45 ± 7.88 μM (NAR600); time to peak: 3.17 ± 0.74 hours (NAR150) and 2.41 ± 0.74 hours (NAR600); area under the 24-hour concentration–time curve: 67.61 ± 24.36 μM × h (NAR150) and 199.05 ± 24.36 μM × h (NAR600); and apparent oral clearance: 10.21 ± 2.34 L/h (NAR150) and 13.70 ± 2.34 L/h (NAR600). Naringenin half-life was 3.0 hours (NAR150) and 2.65 hours (NAR600). After NAR300 ingestion, serum concentrations were 10.67 ± 5.74 μM (4 hours) and 0.35 ± 0.30 μM (24 hours). After NAR900 ingestion, serum concentrations were 43.11 ± 5.26 μM (4 hours) and 0.24 ± 0.30 μM (24 hours). Conclusions: Ingestion of 150 to 900 mg doses of naringenin is safe in healthy adults, and serum concentrations are proportional to the dose administered. Since naringenin (8 μM) is effective in primary human adipocytes, ingestion of 300 mg naringenin twice/d will likely elicit a physiological effect.

Original languageEnglish (US)
Pages (from-to)91-98
Number of pages8
JournalDiabetes, Obesity and Metabolism
Issue number1
StatePublished - Jan 1 2020

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


  • clinical trial
  • insulin resistance
  • obesity therapy
  • pharmacokinetics
  • type 2 diabetes


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