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Stimulatory Effect of Whole Coffee Fruit Concentrate Powder on Plasma Levels of Total and Exosomal Brain-Derived Neurotrophic Factor in Healthy Subjects: An Acute Within-Subject Clinical Study

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DOI: 10.4236/fns.2013.49127    3,935 Downloads   5,916 Views   Citations


A pilot study by Reyes [1] previously showed that ingestion of single dose of whole coffee fruit concentrate (WCFC) powder increased blood levels of brain derived neurotrophic factor (BDNF) during the first 60 minutes after ingestion. In the present report, we performed a single dose, placebo-controlled, within-subject study to confirm and further investigate this effect. Twenty healthy subjects with ages ranging from 25 to 35 participated in this study. All fasted and resting subjects received placebo on Day 1, WCFC on Day 2, and a cup of freshly brewed coffee on Day 3. Treatment with WCFC resulted in a statistically significant increase in plasma BDNF compared to placebo (p = 0.0073) or coffee (p = 0.0219) during first 60 minutes. In addition, e isolated exosomes from serum and found that they contained BDNF. Furthermore, oral WCFC consumption acutely increased BDNF levels in serum exosomes. In summary, all presented results justify further clinical investigation of WCFC as a tool to manage BDNF-dependent health conditions.

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T. Reyes-Izquierdo, R. Argumedo, C. Shu, B. Nemzer and Z. Pietrzkowski, "Stimulatory Effect of Whole Coffee Fruit Concentrate Powder on Plasma Levels of Total and Exosomal Brain-Derived Neurotrophic Factor in Healthy Subjects: An Acute Within-Subject Clinical Study," Food and Nutrition Sciences, Vol. 4 No. 9, 2013, pp. 984-990. doi: 10.4236/fns.2013.49127.


[1] T. Reyes-Izquierdo, et al., “Modulatory Effect of Coffee Fruit Extract on Plasma Levels of Brain-Derived Neurotrophic Factor in Healthy Subjects,” British Journal of Nutrition, Vol. 110, No. 3, 2013, pp. 420-425. doi:10.1017/S0007114512005338
[2] E. E. B. Noble, C. J. Kotz and C. M. Wang, “The Lighter Side of BDNF,” American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, Vol. 300, No. 5, 2011, pp. R1053-R1069. doi:10.1152/ajpregu.00776.2010
[3] R. N. Klein, J. Venkata, L. Shuqian, T. Fabienne, B. Peter, C.-C. Sherri, J. Carlos, R. Kevin, L. F. Reichardt and M. Barbacid, “The trkB Tyrosine Protein Kinase Is a Receptor for Brain-Derived Neurotrophic Factor and Neurotrophin-3,” Cell, Vol. 66, No. 2, 1991, pp. 395-403.
[4] A. I. Su, T. Wiltshire, S. Batalov, H. Lapp, K. A. Ching, D. Block, J. Zhang, R. Soden, M. Hayakawa and G. Kreiman, “A Gene Atlas of the Mouse and Human Protein-Encoding Transcriptomes,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 16, 2004, pp. 6062-6067. doi:10.1073/pnas.0400782101
[5] R. F. A. Alderson, L. Andrea, Y.-A. Barde and R. M. Lindsay, “Brain-Derived Neurotrophic Factor Increases Survival and Differentiated Functions of Rat Septal Cholinergic Neurons in Culture,” Neuron, Vol. 5, No. 3, 1990, pp. 297-306. doi:10.1016/0896-6273(90)90166-D
[6] B. Knüsel and F. Hefti, “K-252b Is a Selective and Nontoxic Inhibitor of Nerve Growth Factor Action on Cultured Brain Neurons,” Journal of Neurochemistry, Vol. 57, No. 3, 1991, pp. 955-962.
[7] R. F. Alderson, A. L. Alterman, Y.-A. Barde and R. M. Lindsay, “Brain-Derived Neurotrophic Factor Increases Survival and Differentiated Functions of Rat Septal Cholinergic Neurons in Culture,” Neuron, Vol. 5, No. 3, 1990, pp. 297-306. doi:10.1111/j.1471-4159.1991.tb08243.x
[8] C. Grothe and K. Unsicker, “Neuron-Enriched Cultures of Adult Rat Dorsal Root Ganglia: Establishment, Characterization, Survival, and Neuropeptide Expression in Response to Trophic Factors,” Journal of Neuroscience Research, Vol. 18, No. 4, 1987, pp. 539-550. doi:10.1002/jnr.490180406
[9] M. Hofer and Y.-A. Barde, “Brain-Derived Neurotrophic Factor Prevents Neuronal Death in Vivo,” Nature, Vol. 331, No. 6153, 1988, pp. 261-262.
[10] M. Sieber-Blum, “Role of the Neurotrophic Factors BDNF and NGF in the Commitment of Pluripotent Neural Crest Cells,” Neuron, Vol. 6, No. 6, 1991, pp. 949-955. doi:10.1016/0896-6273(91)90235-R
[11] Y. Dwivedi, “Brain-Derived Neurotrophic Factor: Role in Depression and Suicide,” Neuropsychiatric Disease and Treatment, Vol. 5, 2009, pp. 433-449. doi:10.2147/NDT.S5700
[12] A. R. Brunoni, M. Lopes and F. Fregni, “A Systematic Review and Meta-Analysis of Clinical Studies on Major Depression and BDNF Levels: Implications for the Role of Neuroplasticity in Depression,” The International Journal of Neuropsychopharmacology, Vol. 11, No. 8, 2008, pp. 1169-1180.
[13] G. Maina et al., “Serum Levels of Brain-Derived Neurotrophic Factor in Drug-Naive Obsessive-Compulsive Patients: A Case-Control Study,” Journal of Affective Disorders, Vol. 122, No. 1-2, 2010, pp. 174-178. doi:10.1016/j.jad.2009.07.009
[14] I. A. Alhaider, A. M. Aleisa, T. T. Tran and K. A. Alkadhi, “Sleep Deprivation Prevents Stimulation-Induced Increases of Levels of P-CREB and BDNF: Protection by Caffeine,” Molecular and Cellular Neurosciences, Vol. 46, No. 4, 2011, pp. 742-751. doi:10.1016/j.mcn.2011.02.006
[15] T. Yamamoto, A. Hirayama, N. Hosoe, M. Furube and S. Hirano, “Effects of Soft-Diet Feeding on BDNF Expression in Hippocampus of Mice,” The Bulletin of Tokyo Dental College, Vol. 49, No. 4, 2008, pp. 185-190. doi:10.2209/tdcpublication.49.185
[16] T. Yamamoto, A. Hirayama, N. Hosoe, M. Furube and S. Hirano, “Soft-Diet Feeding Inhibits Adult Neurogenesis in Hippocampus of Mice,” The Bulletin of Tokyo Dental College, Vol. 50, No. 3, 2009, pp. 117-124. doi:10.2209/tdcpublication.50.117
[17] C. Zuccato and E. Cattaneo, “Brain-Derived Neurotrophic Factor in Neurodegenerative Diseases,” Nature Reviews. Neurology, Vol. 5, No. 6, 2009, pp. 311-322. doi:10.1038/nrneurol.2009.54
[18] Y. Muto, et al., “Age-Related Decrease in Brain-Derived Neurotrophic Factor Gene Expression in the Brain of the Zitter Rat with Genetic Spongiform Encephalopathy,” Neuroscience Letters, Vol. 271, No. 2, 1999, pp. 69-72.
[19] K. Hashimoto, “Understanding Depression: Linking BrainDerived Neurotrophic Factor, Transglutaminase 2 and Serotonin,” Expert Review of Neurotherapeutics, Vol. 13, No. 1, 2013, pp. 5-7.
[20] K. Hashimoto, “[Depression and BDNF],” Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica, Vol. 127, No. 3, 2006, pp. 201-204. doi:10.1254/fpj.127.201
[21] K. Hashimoto, “Brain-Derived Neurotrophic Factor as a Biomarker for Mood Disorders: An Historical Overview and Future Directions,” Psychiatry and Clinical Neurosciences, Vol. 64, No. 4, 2010, pp. 341-357. doi:10.1111/j.1440-1819.2010.02113.x
[22] K. Hashimoto, “Sigma-1 Receptor Chaperone and BrainDerived Neurotrophic Factor: Emerging Links between Cardiovascular Disease and Depression,” Progress in Neurobiology, Vol. 100, No. 1, 2013, pp. 15-29. doi:10.1016/j.pneurobio.2012.09.001
[23] K. Hashimoto, E. Shimizu and M. Iyo, “Critical Role of Brain-Derived Neurotrophic Factor in Mood Disorders,” Brain Research. Brain Research Reviews, Vol. 45, No. 2, 2004, pp. 104-114.
[24] E. Shimizu, et al., “Alterations of Serum Levels of BrainDerived Neurotrophic Factor (BDNF) in Depressed Patients with or without Antidepressants,” Biological Psychiatry, Vol. 54, No. 1, 2003, pp. 70-75. doi:10.1016/S0006-3223(03)00181-1
[25] M. Yamanaka, et al., “Intermittent Administration of Brain-Derived Neurotrophic Factor (BDNF) Ameliorates Glucose Metabolism and Prevents Pancreatic Exhaustion in Diabetic Mice,” Journal of Bioscience and Bioengineering, Vol. 105, No. 4, 2008, pp. 395-402. doi:10.1263/jbb.105.395
[26] M. Yamanaka, et al., “Brain-Derived Neurotrophic Factor Enhances Glucose Utilization in Peripheral Tissues of Diabetic Mice,” Diabetes, Obesity and Metabolism, Vol. 9, No. 1, 2007, pp. 59-64.
[27] M. Yamanaka, Y. Itakura, A. Tsuchida, T. Nakagawa and M. Taiji, “Brain-Derived Neurotrophic Factor (BDNF) Prevents the Development of Diabetes in Prediabetic Mice,” Biomedical Research, Vol. 29, No. 3, 2008, pp. 147-153. doi:10.2220/biomedres.29.147
[28] M. Suwa, et al., “Brain-Derived Neurotrophic Factor Treatment Increases the Skeletal Muscle Glucose Transporter 4 Protein Expression in Mice,” Physiological Research/Academia Scientiarum Bohemoslovaca, Vol. 59, No. 4, 2010, pp. 619-623.
[29] T. Nakagawa, et al., “Brain-Derived Neurotrophic Factor Regulates Glucose Metabolism by Modulating Energy Balance in Diabetic Mice,” Diabetes, Vol. 49, No. 3, 2000, pp. 436-444.
[30] J. Gray, et al., “Hyperphagia, Severe Obesity, Impaired Cognitive Function, and Hyperactivity Associated with Functional Loss of One Copy of the Brain-Derived Neurotrophic Factor (BDNF) Gene,” Diabetes, Vol. 55, No. 12, 2006, pp. 3366-3371. doi:10.2337/db06-0550
[31] J. C. Han, et al., “Brain-Derived Neurotrophic Factor and Obesity in the WAGR Syndrome,” New England Journal of Medicine, Vol. 359, No. 9, 2008, pp. 918-927.
[32] J. D. Abbott, H. N. Ahmed, H. A. Vlachos, F. Selzer and D. O. Williams, “Comparison of Outcome in Patients with ST-Elevation versus Non-ST-Elevation Acute Myocardial Infarction Treated with Percutaneous Coronary Intervention (from the National Heart, Lung, and Blood Institute Dynamic Registry),” The American Journal of Cardiology, Vol. 100, No. 2, 2007, pp. 190-195.
[33] H. Fujimura, et al., “Brain-Derived Neurotrophic Factor Is Stored in Human Platelets and Released by Agonist Stimulation,” Thorombosis and Haemostasis, Vol. 87, No. 4, 2002, pp. 728-734.
[34] S. Tamura, et al., “Release Reaction of Brain-Derived Neurotrophic Factor (BDNF) through PAR1 Activation and Its Two Distinct Pools in Human Platelets,” Thrombosis Research, Vol. 128, No. 5, 2011, pp. e55-e61. doi:10.1016/j.thromres.2011.06.002
[35] P. Stoll, A. Plessow, K. Bratke, J. C. Virchow and M. Lommatzsch, “Differential Effect of Clopidogrel and Aspirin on the Release of BDNF from Platelets,” Journal of Neuroimmunology, Vol. 238, No. 1, 2011, pp. 104-106.
[36] P. Lalive, S. Kantengwa, M. Benkhoucha, C. Juillard and M. Chofflon, “Interferon-β Induces Brain-Derived Neurotrophic Factor in Peripheral Blood Mononuclear Cells of Multiple Sclerosis Patients,” Journal of Neuroimmunology, Vol. 197, No. 2, 2008, pp. 147-151. doi:10.1016/j.jneuroim.2008.04.033
[37] C. Hahn, A. P. Islamian, H. Renz and W. A. Nockher, “Airway Epithelial Cells Produce Neurotrophins and Promote the Survival of Eosinophils during Allergic Airway Inflammation,” Journal of Allergy and Clinical Immunology, Vol. 117, No. 4, 2006, pp. 787-794. doi:10.1016/j.jaci.2005.12.1339
[38] O. Noga, et al., “The Production, Storage and Release of the Neurotrophins Nerve Growth Factor, Brain-Derived Neurotrophic Factor and Neurotrophin-3 by Human Peripheral Eosinophils in Allergics and Non-Allergics,” Clinical & Experimental Allergy, Vol. 33, No. 5, 2003, pp. 649-654. doi:10.1046/j.1365-2222.2003.01586.x
[39] O. Noga, et al., “Regulation of NGF and BDNF by Dexamethasone and Theophylline in Human Peripheral Eosinophils in Allergics and Non-Allergics,” Regulatory Peptides, Vol. 132, No. 1, 2005, pp. 74-79. doi:10.1016/j.regpep.2005.09.023
[40] B. Rost, et al., “Monocytes of Allergics and Non-Allergics Produce, Store and Release the Neurotrophins NGF, BDNF and NT-3,” Regulatory Peptides, Vol. 124, No. 1, 2005, pp. 19-25.
[41] R. M. Johnstone, “Exosomes Biological Significance: A Concise Review,” Blood Cells, Molecules, and Diseases, Vol. 36, No. 2, 2006, pp. 315-321. doi:10.1016/j.bcmd.2005.12.001
[42] M. P. Hunter, et al., “Detection of microRNA Expression in Human Peripheral Blood Microvesicles,” PloS ONE, Vol. 3, No. 11, 2008, Article ID: e3694. doi:10.1371/journal.pone.0003694
[43] M. Simons and G. Raposo, “Exosomes: Vesicular Carriers for Intercellular Communication,” Current Opinion in Cell Biology, Vol. 21, No. 4, 2009, pp. 575-581. doi:10.1016/
[44] Y. Lee, S. E. Andaloussi and M. J. Wood, “Exosomes and Microvesicles: Extracellular Vesicles for Genetic Information Transfer and Gene Therapy,” Human Molecular Genetics, Vol. 21, No. R1, 2012, pp. R125-R134. doi:10.1093/hmg/dds317
[45] A. Lakkaraju and E. Rodriguez-Boulan, “Itinerant Exosomes: Emerging Roles in Cell and Tissue Polarity,” Trends in Cell Biology, Vol. 18, No. 5, 2008, pp. 199-209. doi:10.1016/j.tcb.2008.03.002
[46] K. K. Jain, “Nanobiotechnology-Based Strategies for Crossing the Blood-Brain Barrier,” Nanomedicine, Vol. 7, No. 8, 2012, pp. 1225-1233. doi:10.2217/nnm.12.86
[47] M. J. Wood, A. J. O’Loughlin and S. Lakhal, “Exosomes and the Blood-Brain Barrier: Implications for Neurological Diseases,” Therapeutic Delivery, Vol. 2, No. 9, 2011, pp. 1095-1099.
[48] X. Zhuang, et al., “Exosomes Are Endogenous Nanoparticles That Can Deliver Biological Information between Cells,” Advanced Drug Delivery Reviews, Vol. 65, No. 3, 2012, pp. 342-347.
[49] S. M. van Dommelen, et al., “Microvesicles and Exosomes: Opportunities for Cell-Derived Membrane Vesicles in Drug Delivery,” Journal of Controlled Release, Vol. 161, No. 2, 2012, pp. 635-644. doi:10.1016/j.jconrel.2011.11.021
[50] I. B. Borecki, et al., “Evidence for Multiple Determinants of the Body Mass Index: The National Heart, Lung, and Blood Institute Family Heart Study,” Obesity Research, Vol. 6, No. 2, 1998, pp. 107-114. doi:10.1002/j.1550-8528.1998.tb00323.x
[51] W. Duan, Z. Guo and M. P. Mattson, “Brain-Derived Neurotrophic Factor Mediates an Excitoprotective Effect of Dietary Restriction in Mice,” Journal of Neurochemistry, Vol. 76, No. 2, 2001, pp. 619-626. doi:10.1046/j.1471-4159.2001.00071.x
[52] N. Maswood, et al., “Caloric Restriction Increases Neurotrophic Factor Levels and Attenuates Neurochemical and Behavioral Deficits in a Primate Model of Parkinson’s Disease,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 52, 2004, pp. 18171-18176. doi:10.1073/pnas.0405831102
[53] J. B. Johnson, et al., “Alternate Day Calorie Restriction Improves Clinical Findings and Reduces Markers of Oxidative Stress and Inflammation in Overweight Adults with Moderate Asthma,” Free Radical Biology & Medicine, Vol. 42, No. 5, 2007, pp. 665-674. doi:10.1016/j.freeradbiomed.2006.12.005
[54] L. R. Guimaraes, et al., “Serum Levels of Brain-Derived Neurotrophic Factor in Schizophrenia on a Hypocaloric Diet,” Progress in Neuro-Psychopharmacology & Biological Psychiatry, Vol. 32, No. 6, 2008, pp. 1595-1598. doi:10.1016/j.pnpbp.2008.06.004
[55] G. Muller, “Novel Target Identification Technologies for the Personalised Therapy of Type II Diabetes and Obesity,” Immunology, Endocrine & Metabolic Agents-Medicinal Chemistry, Vol. 12, No. 3, 2012, pp. 183-207.
[56] S. Lakhal and M. J. Wood, “Exosome Nanotechnology: An Emerging Paradigm Shift in Drug Delivery,” BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology, Vol. 33, No. 10, 2011, pp. 737-741. doi:10.1002/bies.201100076
[57] S. Lakhal, S. El Andaloussi, A. J. O’Loughlin, J. H. Li and M. M. Wood, “RNAi Therapeutic Delivery by Exosomes,” Springer, Berlin, 2013. doi:10.1007/978-1-4614-4744-3_9

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