Table 3: Summary of the included in vitro, animal and clinical studies on interactions between carbamazepine and dietary supplement/food.

Dietary supplement (DS)/foodDietary productsStudy typeSubject/model (number)Study designOutcome measuresEffectMechanismReferences

FoodAlcoholAnimalMale CD-1 mice (10 in each group)Randomized parallel designPD parametersAdditive neurotoxicity (ethanol-induced motor incoordination and loss of righting reflex potentiated )Nonadenosinergic action Dar et al. 1989 [54]

FoodAlcoholHumanHealthy volunteers (8)Open label crossover studyPK parametersNo effect on pharmacokinetics of CBZLow ethanol level in subjects Sternebring et al. 1992 [55]

FoodAlcoholHumanAlcoholics (7)Open label crossover studyPK parametersIncreased AU of CBZ and decreased AU of CBZ 10,11-epoxide Acute inhibition of CBZ metabolism and/or accelerated CBZ metabolism in abstinence phase due to enzyme induction by previous ethanol abuse Sternebring et al. 1992 [55]

FoodButterAnimalNew Zealand white rabbit
(8 in each group)
Crossover studyPK parametersIncreased bioavailability of CBZImproved solubility and dissolution of poorly soluble CBZ Sidhu et al. 2004 [56]

FoodCaffeineHumanHealthy male volunteers (6)Open label crossover studyPK parametersDecreased bioavailability and increased of CBZInvolving metabolism by mixed function oxidaseVaz et al. 1998 [57]

FoodCaffeineAnimalAlbino Swiss male mice with maximal electroshock seizure model
(7 in each group)
Randomized controlled parallel studyPK and PD parametersAcute caffeine decreased antiepileptic efficacy of CBZ but had no effect on plasma level of CBZN.D.Czuczwar et al. 1990 [58]

FoodCaffeineAnimalSwiss male mice with maximal electroshock seizure model
(8 in each group)
Randomized controlled studyPK and PD parametersChronic caffeine dose-dependently decreased anti-epileptic efficacy of CBZ but had no effect on plasma level of CBZMay induce changes in neurotransmitter system causing sensitization effectGasior et al. 1996 [59]

FoodCoca-ColaHumanHealthy male volunteers (10)Randomized two-way crossover designPK parametersIncreased bioavailability of CBZ; no change in elimination Enhanced dissolution of CBZ by its acidityMalhotra et al. 2002 [60]

DSFolinic acidAnimalMale Sprague-Dawley rats
(4 in each group)
Randomized parallel controlled designPK parametersNo effect on plasma or brain level of CBZN.D. Simth and Carl 1982 [61]

FoodGrapefruit juiceHumanPatients with epilepsy (10)Randomized crossover studyPK parametersIncreased bioavailability of CBZInhibited CYP3A4-mediated intestinal and hepatic metabolism of CBZGarg et al. 1998 [62]

FoodHoneyAnimalAngora grey rabbit
(6 in each group)
Nonrandomized designPK parametersDecreased bioavailability of CBZDecreased metabolism of CBZ by inducing CYP enzymes Koumaravelou et al. 2002 [63]

FoodHoneyHumanHealthy volunteers
(10)
Randomized crossover studyPK parametersSingle dose of honey has no effect on pharmacokinetics of CBZN.D.Malhotra et al. 2003 [64]

FoodHoneyHumanHealthy male volunteers (12)Open label crossover studyPK parametersMultiple doses of honey have no effect on pharmacokinetics of CBZ Flavanoids in honey may not affect human CYP3A4 activityThomas et al. 2007 [65]

FoodKinnow JuiceHumanHealthy male volunteers (9)Randomized crossover studyPK parametersIncreased bioavailability of CBZInhibited CYP3A activityGarg et al. 1998 [66]

DSMelatoninAnimalFemale Swiss mice
(12 in each group)
Randomized parallel designPK and PD parameters Potentiated the anticonvulsant activity of CBZ but impair long-term memory but no effect on plasma and brain levels of CBZEnhanced GABAergic transmission in CNSBorowicz et al. 1999 [67]

DSMelatoninHumanChildren with epilepsy (28)Double-blind randomized control studyPK and PD parametersIncreased glutathione reductase (antioxidant) activity but no effect on plasma level of CBZ and its metaboliteAntagonized CBZ-triggered reactive oxygen species accumulationGupta et al. 2004 [68]

DSMelatoninAnimalMale Swiss albino mice with maximal electroshock seizure model
(7 in each group)
Randomized parallel designPK and PD parametersSynergistic anti-epileptic effect but no effect on plasma level of CBZN.D.Gupta et al. 2004 [69]

DSNicotinamideHumanChildren with epilepsy (2)Case reportPK parametersIncreased plasma level of CBZ and decreased clearance of CBZN.D.Said et al. 1989 [70]

FoodPomegranate juiceAnimalMale Wistar rats (5-6 in each group)Randomized parallel designPK parametersIncreased and AUC of CBZ; no change in elimination and AUC ratio of CBZ 10,11-epoxide to CBZInhibited enteric but not hepatic CYP3A activityHidaka et al. 2005 [71]

FoodPomegranate juiceEx vivo Male Wistar rats (3 in each group)In vitro everted and noneverted sac methodPK parametersDecreased intestinal transport of CBZInduced enteric CYP3A4Adukondalu et al. 2010 [72]

FoodSoybeanAnimalAlbino Wistar rats
(6 in each group)
Randomized parallel designPK parametersDecreased bioavailability of CBZ, increased plasma clearance and of CBZDecreased gastric emptying and enhanced elimination of CBZ Singh and Asad 2010 [73]

FoodStar Fruit JuiceAnimalMale Wistar rats (6 in each group)Randomized parallel designPK parametersIncreased and AUC of CBZ; no change in elimination and AUC ratio of CBZ 10,11-epoxide to CBZInhibited enteric but not hepatic CYP3A activityHidaka et al. 2006 [74]

N.D.: not determined by authors.