Exploring cocoa properties: is theobromine a cognitive modulator?
Nutritional qualities of cocoa have been acknowledged by several authors; a particular focus has been placed on its high content of flavanols, known for their excellent antioxidant properties and subsequent protective effect on cardio- and cerebrovascular systems as well as for neuromodulatory and neuroprotective actions. Other active components of cocoa are methylxanthines (caffeine and theobromine). Whereas the effects of caffeine are extensively researched, the same is not the case for theobromine; this review summarizes evidence on the effect of theobromine on cognitive functions. Considering animal studies, it can be asserted that acute exposition to theobromine has a reduced and delayed nootropic effect with respect to caffeine, whereas both animal and human studies suggested a potential neuroprotective action of long-term assumption of theobromine through a reduction of Aβ amyloid pathology, which is commonly observed in Alzheimer’s disease patients’ brains. Hence, the conceivable action of theobromine alone and associated with caffeine or other cocoa constituents on cognitive modulation is yet underexplored and future studies are needed to shed light on this promising molecule.
KeywordsCocoa Theobromine Cognitive modulator Cognition
We thank the Associazione per la Ricerca sulle Demenze (ARD) ONLUS.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
- Chen J-F, Chern Y (2011) Impacts of methylxanthines and adenosine receptors on neurodegeneration: human and experimental studies. Handb Exp Pharmacol:267–310. https://doi.org/10.1007/978-3-642-13443-2_10
- del Rosario Brunetto M, Gutiérrez L, Delgado Y et al (2007) Determination of theobromine, theophylline and caffeine in cocoa samples by a high-performance liquid chromatographic method with on-line sample cleanup in a switching-column system. Food Chem 100:459–467. https://doi.org/10.1016/j.foodchem.2005.10.007 CrossRefGoogle Scholar
- Fernández-Fernández L, Esteban G, Giralt M, Valente T, Bolea I, Solé M, Sun P, Benítez S, Morelló JR, Reguant J, Ramírez B, Hidalgo J, Unzeta M (2015) Catecholaminergic and cholinergic systems of mouse brain are modulated by LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids. Food Funct 6:1251–1260. https://doi.org/10.1039/c5fo00052a CrossRefPubMedGoogle Scholar
- Fredholm BB (ed) (2011) Methylxanthines. Springer Verlag, BerlinGoogle Scholar
- Hetherington MM (2001) Food cravings and addiction. Leatherhead food RA publ., LeatherheadGoogle Scholar
- Marriott BM, Institute of Medicine (U.S.), Committee on Military Nutrition Research (1994) Food components to enhance performance: an evaluation of potential performance-enhancing food components for operational rations. National Academy Press, Washington, D.C.Google Scholar
- Mendiola-Precoma J, Padilla K, Rodríguez-Cruz A, Berumen LC, Miledi R, García-Alcocer G (2017) Theobromine-induced changes in A1 purinergic receptor gene expression and distribution in a rat brain Alzheimer’s disease model. J Alzheimers Dis JAD 55:1273–1283. https://doi.org/10.3233/JAD-160569 CrossRefPubMedGoogle Scholar
- Panza F, Solfrizzi V, Barulli MR, Bonfiglio C, Guerra V, Osella A, Seripa D, Sabbà C, Pilotto A, Logroscino G (2015) Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: a systematic review. J Nutr Health Aging 19:313–328. https://doi.org/10.1007/s12603-014-0563-8 CrossRefPubMedGoogle Scholar
- Rabin LA, Smart CM, Amariglio RE (2017) Subjective cognitive decline in preclinical Alzheimer’s disease. Annu Rev Clin Psychol 13:369–396. https://doi.org/10.1146/annurev-clinpsy-032816-045136 CrossRefPubMedGoogle Scholar
- Romero-Cortes T, Salgado-Cervantes MA, García-Alamilla P, García-Alvarado MA, del C Rodríguez-Jimenes G, Hidalgo-Morales M, Robles-Olvera V (2013) Relationship between fermentation index and other biochemical changes evaluated during the fermentation of Mexican cocoa (Theobroma cacao) beans. J Sci Food Agric 93:2596–2604. https://doi.org/10.1002/jsfa.6088 CrossRefPubMedGoogle Scholar
- Schindler CW, Karcz-Kubicha M, Thorndike EB, Müller CE, Tella SR, Ferré S, Goldberg SR (2005) Role of central and peripheral adenosine receptors in the cardiovascular responses to intraperitoneal injections of adenosine A 1 and A 2A subtype receptor agonists. Br J Pharmacol 144:642–650. https://doi.org/10.1038/sj.bjp.0706043 CrossRefPubMedPubMedCentralGoogle Scholar
- Smit HJ (2011) Theobromine and the pharmacology of cocoa. Handb Exp Pharmacol:201–234. https://doi.org/10.1007/978-3-642-13443-2_7
- Sugimoto N, Miwa S, Hitomi Y, Nakamura H, Tsuchiya H, Yachie A (2014) Theobromine, the primary methylxanthine found in Theobroma cacao, prevents malignant glioblastoma proliferation by negatively regulating phosphodiesterase-4, extracellular signal-regulated kinase, Akt/mammalian target of rapamycin kinase, and nuclear factor-kappa B. Nutr Cancer 66:419–423. https://doi.org/10.1080/01635581.2013.877497 CrossRefPubMedGoogle Scholar
- Travassos M, Santana I, Baldeiras I, Tsolaki M, Gkatzima O, Sermin G, Yener GG, Simonsen A, Hasselbalch SG, Kapaki E, Mara B, Cunha RA, Agostinho P, Blennow K, Zetterberg H, Mendes VM, Manadas B, de Mendon A (2015) Does caffeine consumption modify cerebrospinal fluid amyloid-β levels in patients with Alzheimer’s disease? J Alzheimers Dis JAD 47:1069–1078. https://doi.org/10.3233/JAD-150374 CrossRefPubMedGoogle Scholar
- Valente T, Hidalgo J, Bolea I, Ramirez B, Anglés N, Reguant J, Morelló JR, Gutiérrez C, Boada M, Unzeta M (2009) A diet enriched in polyphenols and polyunsaturated fatty acids, LMN diet, induces neurogenesis in the subventricular zone and hippocampus of adult mouse brain. J Alzheimers Dis JAD 18:849–865. https://doi.org/10.3233/JAD-2009-1188 CrossRefPubMedGoogle Scholar
- van den Bogaard B, Draijer R, Westerhof BE, van den Meiracker AH, van Montfrans GA, van den Born BJH (2010) Effects on peripheral and central blood pressure of cocoa with natural or high-dose theobromine: a randomized, double-blind crossover trial. Hypertension 56:839–846. https://doi.org/10.1161/HYPERTENSIONAHA.110.158139 CrossRefPubMedGoogle Scholar
- von Linné (Linneaus) (1741) C. Om chokladdrykenGoogle Scholar
- Watson RR, Preedy VR, Zibadi S (eds) (2013) Chocolate in health and nutrition. Humana Press/Springer Verlag, New YorkGoogle Scholar
- Yoneda M, Sugimoto N, Katakura M, Matsuzaki K, Tanigami H, Yachie A, Ohno-Shosaku T, Shido O (2017) Theobromine up-regulates cerebral brain-derived neurotrophic factor and facilitates motor learning in mice. J Nutr Biochem 39:110–116. https://doi.org/10.1016/j.jnutbio.2016.10.002 CrossRefPubMedGoogle Scholar