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Flavonoids inhibit MCT1-mediated transport of GHB, altering its pharmacokinetics and reducing sleep time in rats

In vitro, flavonoids such as luteolin, morin, and phloretin competitively inhibited MCT1-mediated uptake of GHB in rat MCT1-transfected cells, with IC50 values of 0.41, 6.41, and 2.57 μM, respectively. In vivo, intravenous luteolin (10 mg/kg) co-administered with GHB (1000 mg/kg) in rats significantly increased renal and total clearance of GHB and reduced sleep time from 165 ± 10 minutes to 121 ± 5 minutes.

Last updated: Jul 7, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score26/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo.

observational

Wang Q, Morris ME · Drug metabolism and disposition: the biological fate of chemicals (2007)

Participants: N/A
Duration: Acute (single dose)
Intervention: Intravenous administration of luteolin (10 mg/kg) with or without GHB (1000 mg/kg) in rats
Outcome: Sleep time, renal clearance, total clearance of GHB
Effect Size: Sleep time reduction: 44 minutes (121 ± 5 vs 165 ± 10 min)
Population: Male Sprague-Dawley rats

Result:

PubMed: 17108059DOI: 10.1124/dmd.106.012369

Mechanism Graph

Flavonoids (e.g., luteolin) competitively inhibit MCT1 transporter at the renal tubule
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Inhibition reduces MCT1-mediated renal reabsorption of GHB
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Increased renal clearance of GHB leads to lower systemic exposure
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Result: Reduced GHB-induced sleep time in rats

Limitations

  • ⚠Animal study (rats) with limited generalizability to humans
  • ⚠Only one flavonoid (luteolin) tested in vivo; effects of other flavonoids not confirmed in living animals

Frequently Asked Questions

What flavonoids were found to inhibit GHB transport?▼

Apigenin, biochanin A, chrysin, diosemin, fisetin, genistein, hesperitin, kaempferol, luteolin, morin, narigenin, phloretin, and quercetin inhibited MCT1-mediated GHB uptake in vitro; flavonoid glycosides phloridzin and rutin had no effect.

How much did luteolin reduce sleep time in rats?▼

Luteolin (10 mg/kg i.v.) reduced GHB-induced sleep time from 165 ± 10 minutes to 121 ± 5 minutes, a reduction of about 44 minutes.

What is the mechanism by which flavonoids affect GHB?▼

Flavonoids competitively inhibit the monocarboxylate transporter 1 (MCT1), which is responsible for renal reabsorption of GHB. This inhibition increases GHB clearance from the body, reducing its duration of action.

Are flavonoids substrates for MCT1?▼

No, the study found that [3H]kaempferol and [3H]biochanin A did not exhibit MCT1-mediated uptake, indicating these flavonoids are inhibitors but not substrates of MCT1.

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References

  1. 1.Wang Q, Morris ME. "Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo.." Drug metabolism and disposition: the biological fate of chemicals, 2007. PMID: 17108059 DOI: 10.1124/dmd.106.012369
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.