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Drug-Nutrition Interactions and the Brain: It’s Not All in Your Head

  • Nutrition and the Brain (J Nasser, Section Editor)
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Abstract

Purpose of Review

The interactions between nutrition and medication can be numerous with potential impact on health outcomes. Several subtypes of drug-nutrition interactions exist. Each of these interaction subtypes may influence patients receiving medication for neurologic disorders. After defining drug-nutrition interactions, this review will describe the various types using a handful of widely used central nervous system agents as examples.

Recent Findings

Medication may be the object of interactions perpetrated by a specific meal, a food component, a nutrient, or nutrition status thereby altering drug disposition and clinical effect. On the other hand, drugs can influence nutrition status generally or the status of specific nutrients by any number of mechanisms.

Summary

Individuals using medication for neurologic disorders are at risk for drug-nutrition interactions of all types.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Santos CA, Boullata JI. An approach to evaluating drug-nutrient interactions. Pharmacotherapy. 2005;25:1789–800.

    Article  Google Scholar 

  2. Boullata JI, Hudson LM. Drug-nutrient interactions: a broad view with implications for practice. J Acad Nutr Diet. 2012;112:506–17.

    Article  Google Scholar 

  3. Boullata JI. Drug and nutrition interactions: not just food for thought. J Clin Pharm Ther. 2013;38:269–71.

    Article  CAS  Google Scholar 

  4. Zigmond MJ, Rowland LP, Coyle JT. Neurobiology of Brain Disorders: Biological Basis of Neurological and Psychiatric Disorders. London, UK: Academic Press; 2015.

    Google Scholar 

  5. Kantor ED, Rehm CD, Haas JS, Chan AT, Giovannucci EL. Trends in prescription drug use among adults in the United States from 1999-2012. JAMA. 2015;314:1818–31.

    Article  CAS  Google Scholar 

  6. Sibley DR, Hanin I, Kuhar M, Skolnick P. Handbook of Contemporary Neuropharmacology. Hoboken, NJ: John Wiley & Sons, Inc.; 2007.

    Book  Google Scholar 

  7. Klang M, McLymont V, Ng N. Osmolality, pH, and compatibility of selected oral liquid medications with an enteral nutrition product. JPEN J Parenter Enteral Nutr. 2013;37:689–94.

    Article  CAS  Google Scholar 

  8. Bailey DG, Dresser G, Arnold MO. Grapefruit-medication interactions: forbidden fruit or avoidable consequences? CMAJ. 2013;185:309–16.

    Article  Google Scholar 

  9. Fleisher D, Sweet BV, Parekh A, Boullata JI. Drug absorption with food. In: Boullata JI, Armenti VT, editors. Handbook of Drug-Nutrient Interactions. 2nd ed. New York: Humana Press; 2010. p. 209–41.

    Google Scholar 

  10. Benet LZ. The role of BCS (biopharmaceutics classification system) and BDDCS (biopharmaceutics drug disposition classification system) in drug development. J Pharm Sci. 2013;102:34–42.

    Article  CAS  Google Scholar 

  11. Lincoln J, Stewart ME, Preskorn SH. How sequential studies inform drug development: evaluating the effect of food intake on optimal bioavailability of ziprasidone. J Psychiatr Pract. 2010;16:103–14.

    Article  Google Scholar 

  12. • Sutton SC, Nause R, Gandelman K. The impact of gastric pH, volume, and emptying on the food effect of ziprasidone oral absorption. AAPS J. 2017;19:1084–90 Physiologically-based pharmacokinetic modeling of gut absorption, using published food effect data from a variety of test meals as additional parameter inputs, further improved prediction of ziprasidone absorption profiles based on gastric pH, volume and emptying.

    Article  CAS  Google Scholar 

  13. • Boudriau S, Hanzel C, Massicotte J, et al. Randomized comparative bioavailability of a novel three-dimensional printed fast-melt formulation of levetiracetam following the administration of a single 1000-mg dose to healthy human volunteers under fasting and fed conditions. Drugs R D. 2016;16:229–38 In a randomized, open-label, crossover study evaluating a new formulation of the antiepileptic drug levetiracetam against the conventional tablet in healthy subjects, the meal effect findings included a much slower rate of absorption without a significant influence on overall drug bioavailability.

    Article  CAS  Google Scholar 

  14. Dutta S, Reed RC. Distinct absorption characteristics of oral formulations of valproic acid/divalproex available in the United States. Epilepsy Res. 2007;73:275–83.

    Article  CAS  Google Scholar 

  15. Wilder BJ, Leppik I, Hietpas TJ, Cloyd JC, Randinitis EJ, Cook J. Effect of food on absorption of Dilantin Kapseals and Mylan extended phenytoin sodium capsules. Neurology. 2001;57:582–9.

    Article  CAS  Google Scholar 

  16. Bass DJ, Miles MV, Tennison MB, et al. Effects of enteral tube feeding on the absorption and pharmacokinetic profile of carbamazepine suspension. Epilepsia. 1989;30:364–9.

    Article  CAS  Google Scholar 

  17. Troy SM, Parker VP, Hicks DR, Pollack GM, Chiang ST. Pharmacokinetics and effect of food on the bioavailability of orally administered venlafaxine. J Clin Pharmacol. 1997;37:954–61.

    Article  CAS  Google Scholar 

  18. Kvernelend M, Taubøll E, Selmer KK, et al. Modified Atkins diet may reduce serum concentrations of antiepileptic drugs. Acta Neurol Scand. 2015;131:187–90.

    Article  Google Scholar 

  19. Manrique YJ, Lee DJ, Islam F, et al. Crushed tablets: does the administration of food vehicles and thickened fluids to aid medication swallowing alter drug release? J Pharm Pharmaceut Sci. 2014;17:207–19.

    Article  Google Scholar 

  20. Bailey DG. Grapefruit and other fruit juices interactions with medicines. In: Boullata JI, Armenti VT, editors. Handbook of drug-nutrient interactions. 2nd ed. New York: Humana Press; 2010. p. 267–302.

    Google Scholar 

  21. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC. The effects of grapefruit juice on sertraline metabolism: an in vitro and in vivo study. Clin Ther. 1999;21:1890–9.

    Article  CAS  Google Scholar 

  22. Kumar N, Garg SK, Prabhakar S. Lack of pharmacokinetic interaction between grapefruit juice and phenytoin in healthy male volunteers and epileptic patients. Methods Find Exp Clin Pharmacol. 1999;21:629–32.

    CAS  PubMed  Google Scholar 

  23. • Johnson EJ, Won CS, Köck K, Paine MF. Prioritizing pharmacokinetic drug interaction precipitants in natural products: application to OATP inhibitors in grapefruit juice. Biopharm Drug Disp. 2017;38:251–9 A well-designed study evaluated seven active compounds found in grapefruit and their relative influence on an important gut uptake transporter using a probe drug in cell culture. Simulated intestinal absorption modeling provided an interesting approach to more widely applying the data.

  24. • Chen M, Zhou S-Y, Fabriaga E, Zhang P-H, Zhou Q. Food-drug interactions precipitated by fruit juices other than grapefruit juice: an update review. J Food Drug Anal. 2018;26:S61–71 A recent review that reiterates the findings that juices other than grapefruit juice, including apple, orange and grape juice, may impact drug bioavailability by influencing specific metabolizing enzymes and/or transporters.

    Article  CAS  Google Scholar 

  25. • Ronis MJJ, Pedersen KB, Watt J. Adverse effects of nutraceuticals and dietary supplements. Annu Rev Pharmacol. 2018;58:583–601 A recent review of dietary supplement products and adverse effects associated with the most commonly used ingredients, and highlighting interactions with medication.

    Article  CAS  Google Scholar 

  26. Egert S, Rimbach G. Which sources of flavonoids: complex diets or dietary supplements? Adv Nutr. 2011;2:8–14.

    Article  CAS  Google Scholar 

  27. Dreiseitel A, Oosterhuis B, Vukman KV, Schreier P, Oehme A, Locher S, et al. Berry anthocyanins and anthocyanidins exhibit distinct affinities for the efflux transporters BCRP and MDR1. Br J Pharmacol. 2009;158:1942–50.

  28. Sand PG, Dreiseitel A, Stang M, Schreier P, Oehme A, Locher S, et al. Cytochrome P450 2C19 inhibitory activity of common berry constituents. Phytother Res. 2010;24:304–7.

  29. • Bahramsoltani R, Rahimi R, Farzaei MH. Pharmacokinetic interactions of curcuminoids with conventional drugs: a review. J Ethnopharmacol. 2017;209:1–12 A review that delves into in vitro, in vivo, clinical and mechanistic data on interactions between the popular curcuminoid compounds of turmeric and medication.

    Article  CAS  Google Scholar 

  30. • Hyrsova L, Vanduchova A, Dusek J, et al. Trans-resveratrol, but not other natural stilbenes occurring in food, carries the risk of drug-food interaction via inhibition of cytochrome P450 enzymes or interaction with xenosensor receptors. Toxicol Lett. 2019;300:81–91 An elegant mechanistic study in human cell cultures to examine over one dozen stilbenes including resveratrol and describe their influence on a wide range of phase I drug metabolizing enzymes.

    Article  CAS  Google Scholar 

  31. Kodali M, Parihar VK, Hattiangady B, Mishra V, Shuai B, Shetty AK. Resveratrol prevents age-related memory and mood dysfunction with increased hippocampal neurogenesis and microvasculature, and reduced glial activation. Sci Rep. 2015;5:8075.

    Article  Google Scholar 

  32. • Alharbi MH, Lamport DJ, Dodd GF, et al. Flavonoid-rich orange juice is associated with acute improvements in cognitive function in healthy middle-aged males. Eur J Clin Nutr. 2016;55:2021–9 A randomized controlled trial of one serving of flavonoid-enriched orange juice, compared with a calorie-matched placebo, in healthy, middle-aged adults suggests acute cognitive benefits (objective and subjective) over a 6-hour time frame.

    Article  CAS  Google Scholar 

  33. Anderson KE. Effects of specific foods and dietary components on drug metabolism. In: Boullata JI, Armenti VT, editors. Handbook of drug-nutrient interactions. 2nd ed. New York: Humana Press; 2010. p. 243–65.

    Google Scholar 

  34. Ronis MJJ, Chen Y, Liu X, Blackburn ML, Shankar K, Landes RD, et al. Enhanced expression and glucocorticoid-inducibility of hepatic cytochrome P450 3A involve recruitment of the pregnane-X-receptor promoter elements in rats fed soy protein isolate. J Nutr. 2011;141:10–6.

  35. Lewis DP, Van Dyke DC, Willhite LA, Stumbo PJ, Berg MJ. Phenytoin-folic acid interaction. Ann Pharmacother. 1995;29:726–35.

    Article  CAS  Google Scholar 

  36. Berg MJ, Stumbo PJ, Chenard CA, et al. Folic acid improves phenytoin pharmacokinetics. J Am Diet Assoc. 1995;95:352–6.

    Article  CAS  Google Scholar 

  37. Walter-Sack I, Klotz U. Influence of diet and nutritional status on drug metabolism. Clin Pharmacokinet. 1996;31:47–64.

    Article  CAS  Google Scholar 

  38. Boullata JI. Drug disposition in obesity and protein-energy malnutrition. Proceed Nutr Soc. 2010;69:543–50.

    Article  CAS  Google Scholar 

  39. Jacques KA, Erstad BL. Availability of information for dosing injectable medications in underweight or obese patients. Am J Health-Syst Pharm. 2010;67:1948–50.

    Article  Google Scholar 

  40. Pai MP. Drug dosing based on weight and body surface area: mathematical assumptions and limitations in obese adults. Pharmacotherapy. 2012;32:856–68.

    Article  Google Scholar 

  41. Janmahasatian S, Duffull SB, Ash S, Ward LC, Byrne NM, Green B. Quantification of lean body-weight. Clin Pharmacokinet. 2005;44:1051–65.

    Article  Google Scholar 

  42. • Beckman LM, Boullata JI, Fisher PL, Compher CW, Earthman CP. Evaluation of lean body weight equation by dual-energy X-ray absorptiometry measures. JPEN J Parenter Enteral Nutr. 2017;41:392–7 A pilot study that suggests that a validated, body composition-based, predictive equation for lean body weight performs much better based on DEXA measures than a commonly used empiric equation in a small group of patients with a wide range of body mass index.

    Article  Google Scholar 

  43. Caraco Y, Zylber-Katz E, Berry EM, Levy M. Significant weight reduction in obese subjects enhances carbamazepine elimination. Clin Pharmacol Ther. 1992;51:501–6.

    Article  CAS  Google Scholar 

  44. Caraco Y, Zylber-Katz E, Berry EM, Levy M. Carbamazepine pharmacokinetics in obese and lean subjects. Ann Pharmacother. 1995;29:843–7.

    Article  CAS  Google Scholar 

  45. Abernathy DR, Greenblatt DJ. Phenytoin disposition in obesity: determination of loading dose. Arch Neurol. 1985;42:468–71.

    Article  Google Scholar 

  46. Olsen KM, Marx MA, Monoghan MS, et al. Phenytoin and plasmapheresis: importance of sampling times and impact of obesity. Ther Drug Monitor. 1994;16:624–8.

    Article  CAS  Google Scholar 

  47. de Oca GM, Gums JG, Robinson JD. Phenytoin dosing in obese patients: two case reports. Drug Intell Clin Pharm. 1988;22:708–10.

    Article  Google Scholar 

  48. Kim YG, Cho MK, Kwon JW, Kim SG, Chung SJ, Shim CK, et al. Effects of cysteine on the pharmacokinetics of phenytoin in rats with protein-calorie malnutrition. Int J Pharm. 2001;229:45–55.

  49. Greenblatt DJ, Friedman H, Burstein ES, Scavone JM, Blyden GT, Ochs HR, et al. Trazodone kinetics: effect of age, gender, and obesity. Clin Pharmacol Ther. 1987;42:193–200.

  50. Abernathy DR, Greenblatt DJ, Divoll M, et al. Enhanced glucuronide conjugation of drugs in obesity: studies of lorazepam, oxazepam, and acetaminophen. J Lab Clin Med. 1983;101:873–80.

    Google Scholar 

  51. Ling P, Lee DJ, Yoshida EM, Sirrs S. Carnitine deficiency presenting with encephalopathy and hyperammonemia in a patient receiving chronic enteral tube feeding: a case report. J Med Case Report. 2012;6:227.

    Article  Google Scholar 

  52. Piccolo KM, Boullata JI. The influence of polypharmacy on nutrition. In: Bendich A, Deckelbaum RJ, editors. Preventive nutrition. 5th ed. New York: Humana Press; 2016. p. 83–113.

    Google Scholar 

  53. Heuberger RA, Caudell K. Polypharmacy and nutritional status in older adults: a cross-sectional study. Drugs Aging. 2011;28:315–23.

    Article  Google Scholar 

  54. Said HM, Redha R, Nylander W. Biotin transport in the human intestine: inhibition by anticonvulsant drugs. Am J Clin Nutr. 1989;49:127–31.

    Article  CAS  Google Scholar 

  55. Mock DM, Dyken ME. Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants. Neurology. 1997;49:1444–7.

    Article  CAS  Google Scholar 

  56. Farhat G, Yamout B, Mikati MA, Demirjian S, Sawaya R, el-Hajj Fuleihan G. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology. 2002;58:1348–53.

    Article  CAS  Google Scholar 

  57. Fitzpatrick LA. Pathophysiology of bone loss in patients receiving anticonvulsant therapy. Epilepsy Behav. 2004;5(Suppl 2):S3–S15.

    Article  Google Scholar 

  58. Souverein PC, Webb DJ, Weil JG, Van Staa TP, Egberts AC. Use of antiepileptic drugs and risk of fractures: case control study among patients with epilepsy. Neurology. 2006;66:1318–24.

    Article  CAS  Google Scholar 

  59. Kim SH, Lee JW, Choi KG, Chung HW, Lee HW. A 6-month longitudinal study of bone mineral density with antiepileptic drug monotherapy. Epilepsy Behav. 2007;10:291–5.

    Article  Google Scholar 

  60. Ali FE, Al-Bustan MA, Al-Busairi WA, Al-Mulla FA. Loss of seizure control due to anticonvulsant-induced hypocalcemia. Ann Pharmacother. 2004;38:1002–5.

    Article  Google Scholar 

  61. Pedrera JD, Canal ML, Carvajal J, Postigo S, Villa LF, Hernandez ER, et al. Influence of vitamin D administration on bone ultrasound measurements in patients on anticonvulsant therapy. Eur J Clin Investig. 2000;30:895–9.

  62. Elliott JO, Jacobson MP, Haneef Z. Homocysteine and bone loss in epilepsy. Seizure. 2007;16:22–34.

    Article  Google Scholar 

  63. Schwaninger M, Ringleb P, Winter R, Kohl B, Fiehn W, Rieser PA, et al. Elevated plasma concentrations of homocysteine in antiepileptic drug treatment. Epilepsia. 1999;40:345–50.

  64. Apeland T, Mansoor MA, Pentieva K, McNulty H, Seljeflot I, Strandjord RE. The effect of B-vitamins on hyperhomocysteinemia in patients on antiepileptic drugs. Epilepsy Res. 2002;51:237–47.

    Article  CAS  Google Scholar 

  65. Sener U, Zorlu Y, Karaguzel O, Ozdamar O, Coker I, Topbas M. Effects of common anti-epileptic drug monotherapy on serum levels of homocysteine, vitamin B12, folic acid and vitamin B6. Seizure. 2006;15:79–85.

    Article  Google Scholar 

  66. Tamura T, Aiso K, Johnston KE, Black L, Faught E. Homocysteine, folate, vitamin B-12 and vitamin B-6 in patients receiving antiepileptic drug monotherapy. Epilepsy Res. 2000;40:7–15.

    Article  CAS  Google Scholar 

  67. Melegh B, Kerner J, Kispal G, et al. Effect of chronic valproic acid treatment on plasma and urine carnitine levels in children. Acta Paediatr Hung. 1987;28:137–42.

    CAS  PubMed  Google Scholar 

  68. Opala G, Winter S, Vance C, Vance H, Hutchison HT, Linn LS. The effect of valproic acid on plasma carnitine levels. Am J Dis Child. 1991;145:999–1001.

    CAS  PubMed  Google Scholar 

  69. Van Wouwe JP. Carnitine deficiency during valproic acid treatment. Int J Vit Nutr Res. 1995;65:211–4.

    Google Scholar 

  70. Moreno FA, Macey H, Schreiber B. Carnitine levels in valproic acid-treated psychiatric patients: a cross-sectional study. J Clin Psych. 2005;66:555–8.

    Article  CAS  Google Scholar 

  71. Tein I, DimAuro S, Xie ZW, et al. Valproic acid impairs carnitine uptake in cultured human skin fibroblasts: an in vitro model for pathogenesis of valproic acid-associated carnitine deficiency. Pediatr Res. 1993;34:281–7.

    Article  CAS  Google Scholar 

  72. Farkas V, Bock I, Cseko J, Sandor A. Inhibition of carnitine biosynthesis by valproic acid in rats: the biochemical mechanism of inhibition. Biochem Pharmacol. 1996;52:1429–33.

    Article  CAS  Google Scholar 

  73. Lheureux PER, Penaloza A, Zahir S, Gris M. Science review: carnitine in the treatment of valproic acid-induced toxicity—what is the evidence? Crit Care. 2005;9:431–40.

    Article  Google Scholar 

  74. Segura-Bruna N, Rodriguez-Campello A, Puente V, Roquer J. Valproate-induced hyperammonemic encephalopathy. Acta Neurol Scand. 2006;114:1–7.

    Article  CAS  Google Scholar 

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  1. Department of Nutrition Sciences, Drexel University, Philadelphia, PA, USA

    Joseph I. Boullata

  2. Pharmacy Specialist in Clinical Nutrition, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

    Joseph I. Boullata

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Boullata, J.I. Drug-Nutrition Interactions and the Brain: It’s Not All in Your Head. Curr Nutr Rep 8, 92–98 (2019). https://doi.org/10.1007/s13668-019-0273-2

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