Cocoa Seed Extract

Cocoa Extract Common Name

Cocoa | Cocoa Bean | Cacao | Chocolate 

Top Benefits of Cocoa Extract

  • Supports healthy aging*
  • Supports exercise performance*
  • Supports brain function*
  • Supports visual acuity*
  • Supports mitochondrial structure, function, and biogenesis* 
  • Supports muscle structure and function* 
  • Supports antioxidant defenses* 
  • Supports healthy metabolic pathways* 
  • Supports healthy gut microbiota*
  • Supports cardiovascular function and circulation* 

What is Cocoa Extract?

Theobroma cacao has been cultivated in central and south America for at least 3,000 years. The name Theobroma cacao can be translated as chocolate, food of the gods. This tree is native to the tropical regions of the Americas. The seeds (sometimes referred to as beans) are enclosed in a pod or husk. They  are the source of the cocoa used to make chocolate. Chocolate, especially dark chocolate, has a blossoming reputation as being heart healthy. This is because of the cocoa content. Cocoa has been reported to support many health-promoting and energy-enhancing actions ranging from improving mitochondrial structure and function to enhancing cognitive performance and vision. Cocoa is one of the biggest dietary sources for polyphenol compounds, a category of plant-derived molecules that are increasingly being shown to support healthy aging. It is an especially great food source of (‐)‐epicatechin, a unique flavanol polyphenol. Cocoa is also a rich source of a bitter compound called theobromine. This compound is a weaker cousin of sorts to caffeine, influencing similar brain processes but not quite as strongly. Cocoa flavanols, especially (‐)‐epicatechin, and theobromine can cross the blood brain barrier, supporting brain performance and vision. The synergy between the cocoa flavanol and theobromine content is responsible for cocoa’s ability to support such a wide range of health processes.*

Neurohacker’s Cocoa Extract Sourcing

In general, cocoa flavanol content varies widely, because many flavanols are degraded when cocoa is processed. The result is that, although in theory cocoa-containing products should be a great source of flavanols, in practice many are not. When selecting a cocoa extract it’s important to choose a source that retains high amounts of the cocoa flavanols.

Neurohacker uses ACTICOA® cocoa created by Barry Callebaut. After years of research, and through controlled sourcing and processing, they found a way to retain high amounts of the naturally occurring flavanols found in cocoa beans.

ACTICOA® cocoa is at least 7.5% cocoa flavanols. It also contains about 2% theobromine.

ACTICOA® is non-GMO, gluten-free, and vegan.

Cocoa Extract Dosing Principles and Rationale

When deciding on a dose of a cocoa extract we think it’s important to consider the amount of cocoa flavanols and theobromine. Flavanols are a sub-group of polyphenols, and are one of the main class of active compounds in cocoa bean extracts and powders. Some polyphenols appear to produce threshold responses, while others produce biphasic responses. In either case, above a certain range, more is not better. In addition to flavanols cocoa contains a bitter alkaloid compound called theobromine. Although theobromine is a weaker cousin of sorts to caffeine, it can cause some of the same issues if consumed in excess. So, similar to caffeine we think of theobromine as having a hormetic range (i.e., a dosing range above which results could be poorer). We have selected to dose cocoa extract at an amount of theobromine that is well below the threshold amount, but sourced a cocoa extract that retains high amounts of the naturally occurring flavanols. With both of these compounds we think it’s important to generally follow hormetic dosing principles (see Neurohacker Dosing Principles). *

Cocoa Extract Key Mechanisms 

Mitochondrial biogenesis

  • Upregulates peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α) [1–6]
  • Upregulates cAMP-PKA-CREB signaling [7]
  • Upregulates nuclear transcription factors of mitochondrial biogenesis (mitochondrial transcription factor A [TFAM]) [2,5,6,8–10]
  • Promotes healthy nitric oxide (NO) pathway function [1,8,10]

Mitochondrial structure

  • Promotes inner mitochondrial membrane folding (cristae density) [1,2,8]
  • Upregulates mitochondrial membrane protein compounds (porin, mitofilin) [1,5,6,8,10]
  • Upregulates mitochondrial size/density/number [1,11]

Mitochondrial function

  • Supports electron transport chain and oxidative phosphorylation performance (mitochondrial complex I-V performance) [1,2,5,8–10,12–14]
  • Supports mitochondrial β-oxidation performance [11]
  • Supports citric acid cycle function via upregulation of citrate synthase [3,5,8–10,13]

Exercise performance (ergogenic effects)

  • Supports endurance performance [3,8,9,13,15,16]
  • Supports post-exercise recovery [17–19]
  • Supports muscle structure and function [8,16,20,21]
  • Promotes muscle angiogenesis/vascularity/capillarity [2,8,9,13]
  • Upregulates muscle carbohydrate metabolism [22]
  • Supports antioxidant capacity during exercise [23]

Antioxidant defenses

  • Upregulates antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], thioredoxin [TRX]) [4,5,21]
  • Replenishes glutathione (GSH) levels [3–5,14,21,24]
  • Supports a healthy mitochondrial redox status [3,5]

Cardiovascular function

  • Supports healthy blood flow (endothelial function and endothelium/NO-dependent vasodilation)[25–29]
  • Supports healthy blood pressure [25–27,30–33]
  • Supports healthy cholesterol levels [25,26,34,35]
  • Supports healthy insulin sensitivity [25–27,30–32,36]

Brain function

  • Supports cognitive performance [7,31,37–45]
  • Supports exercise-induced executive function improvements [46]
  • Promotes motor activity [43]
  • Promotes cerebral blood flow,[41,47,48] cerebral oxygenation,[49] and angiogenesis in the hippocampus [45]
  • Cerebral antioxidant [37]
  • Central nervous system stimulant (theobromine) [50]
  • Adenosine receptor antagonist (theobromine);[50] regulates neurotransmitters modulated by adenosine – noradrenaline, dopamine, serotonin, acetylcholine, glutamate, and GABA [43]
  • Phosphodiesterase (PDE) inhibitor (theobromine) — upregulates intracellular cAMP [7](long-term potentiation support)
  • Upregulates BDNF signaling [7,51] (neurogenesis support) 

Gut microbiota

  • Regulates the composition of the gut microbiota [52–55]
  • Regulates gut microbial metabolism [54,56] 

Healthy aging and longevity  

  • Increases lifespan (rats, diabetic mice, Drosophila melanogaster, Caenorhabditis elegans) [41,42,57]
  • Upregulates the NAD+ Pool [58]
  • Upregulates insulin-like growth factor-1 (IGF-1) signaling [21,57]
  • Upregulates SIRT1 [1,4–6,58]
  • Upregulates SIRT3 [4–6]
  • Promotes resistance to oxidative stress [57]
  • Supports mild mitochondrial uncoupling (UCP1 increase) [6,11]
  • Upregulates signaling pathways: AMP-Activated Protein Kinase (AMPK),[3,21] liver kinase B1 (LKB1, also known as serine/threonine kinase 11 [STK11]),[3] p38 mitogen-activated protein kinases (p38 MAPK) [2]


[1] Taub PR, et al. Clin Transl Sci. 2012;5(1):43-47. doi:10.1111/j.1752-8062.2011.00357.x
[2] Hüttemann M, et al. Clin Sci . 2013;124(11):663-674. doi:10.1042/CS20120469
[3] Taub PR, et al. Food Funct. 2016;7(9):3686-3693. doi:10.1039/c6fo00611f
[4] Ramirez-Sanchez I, et al. Int J Cardiol. 2013;168(4):3982-3990. doi:10.1016/j.ijcard.2013.06.089
[5] Ramirez-Sanchez I, et al. FEBS J. 2014;281(24):5567-5580. doi:10.1111/febs.13098
[6] Gutiérrez-Salmeán G, et al. Eur J Pharmacol. 2014;728:24-30. doi:10.1016/j.ejphar.2014.01.053
[7] Yoneda M, et al. J Nutr Biochem. 2017;39:110-116. doi:10.1016/j.jnutbio.2016.10.002
[8] Nogueira L, et al. J Physiol. 2011;589(Pt 18):4615-4631. doi:10.1113/jphysiol.2011.209924
[9] Lee I, et al. Front Pharmacol. 2015;6:43. doi:10.3389/fphar.2015.00043
[10] Moreno-Ulloa A, et al. Bioorg Med Chem Lett. 2013;23(15):4441-4446. doi:10.1016/j.bmcl.2013.05.079
[11] Watanabe N, et al. Lipids Health Dis. 2014;13:64. doi:10.1186/1476-511X-13-64
[12] Silva Santos LF, et al. J Arrhythm. 2017;33(3):220-225. doi:10.1016/j.joa.2016.09.004
[13] Hüttemann M, et al. FASEB J. 2012;26(4):1413-1422. doi:10.1096/fj.11-196154
[14] Rowley TJ 4th, et al. J Nutr Biochem. 2017;49:30-41. doi:10.1016/j.jnutbio.2017.07.015
[15] Patel RK, et al. J Int Soc Sports Nutr. 2015;12:47. doi:10.1186/s12970-015-0106-7
[16] Taub PR, et al. Clin Sci . 2013;125(8):383-389. doi:10.1042/CS20130023
[17] Papacosta E, et al. Appl Physiol Nutr Metab. 2015;40(11):1116-1122. doi:10.1139/apnm-2015-0243
[18] Potter J, Fuller B. J Sports Med Phys Fitness. 2015;55(12):1438-1444. PMID: 25286886.
[19] McBrier NM, et al. J Strength Cond Res. 2010;24(8):2203-2210. doi:10.1519/JSC.0b013e3181e4f7f9
[20] Gutierrez-Salmean G, et al. J Nutr Biochem. 2014;25(1):91-94. doi:10.1016/j.jnutbio.2013.09.007
[21] Si H, et al. J Nutr. 2011;141(6):1095-1100. doi:10.3945/jn.110.134270
[22] Stellingwerff T, et al. Appl Physiol Nutr Metab. 2014;39(2):173-182. doi:10.1139/apnm-2013-0152
[23] Decroix L, et al. J Int Soc Sports Nutr. 2017;14:28. doi:10.1186/s12970-017-0186-7
[24] Barragán Mejía G, et al. Naunyn Schmiedebergs Arch Pharmacol. 2011;384(6):499-504. doi:10.1007/s00210-011-0676-0
[25] Grassi D, et al. Hypertension. 2005;46(2):398-405. doi:10.1161/01.HYP.0000174990.46027.70
[26] Grassi D, et al. J Nutr. 2008;138(9):1671-1676. doi:10.1093/jn/138.9.1671
[27] Davison K, et al. Int J Obes . 2008;32(8):1289-1296. doi:10.1038/ijo.2008.66
[28] Fisher NDL, et al. J Hypertens. 2003;21(12):2281-2286. doi:10.1097/01.hjh.0000084783.15238.eb
[29] Schroeter H, et al. Proc Natl Acad Sci U S A. 2006;103(4):1024-1029. doi:10.1073/pnas.0510168103
[30] Grassi D, et al. Am J Clin Nutr. 2005;81(3):611-614. doi:10.1093/ajcn/81.3.611
[31] Desideri G, et al. Hypertension. 2012;60(3):794-801. doi:10.1161/HYPERTENSIONAHA.112.193060
[32] Hooper L, et al. Am J Clin Nutr. 2012;95(3):740-751. doi:10.3945/ajcn.111.023457
[33] Ried K, et al. Cochrane Database Syst Rev. 2012;(8):CD008893. doi:10.1002/14651858.CD008893.pub2
[34] Mellor DD, et al. Diabet Med. 2010;27(11):1318-1321. doi:10.1111/j.1464-5491.2010.03108.x
[35] Neufingerl N, et al. Am J Clin Nutr. 2013;97(6):1201-1209. doi:10.3945/ajcn.112.047373
[36] Esser D, et al. PLoS One. 2018;13(4):e0194229. doi:10.1371/journal.pone.0194229
[37] Rozan P, et al. J Food Sci. 2007;72(3):S203-S206. doi:10.1111/j.1750-3841.2007.00297.x
[38] Field DT, et al. Physiol Behav. 2011;103(3-4):255-260. doi:10.1016/j.physbeh.2011.02.013
[39] Nurk E, et al. J Nutr. 2009;139(1):120-127. doi:10.3945/jn.108.095182
[40] Scholey AB, et al. J Psychopharmacol. 2010;24(10):1505-1514. doi:10.1177/0269881109106923
[41] Sorond FA, et al. Neuropsychiatr Dis Treat. 2008;4(2):433-440. PMID: 18728792.
[42] Bisson J-F, et al. Br J Nutr. 2008;100(1):94-101. doi:10.1017/S0007114507886375
[43] Burnstock G. Adv Exp Med Biol. 2013;986:1-12. doi:10.1007/978-94-007-4719-7_1
[44] Camfield DA, et al. Physiol Behav. 2012;105(4):948-957. doi:10.1016/j.physbeh.2011.11.013
[45] van Praag H, et al. J Neurosci. 2007;27(22):5869-5878. doi:10.1523/JNEUROSCI.0914-07.2007
[46] Tsukamoto H, et al. Nutrition. 2018;46:90-96. doi:10.1016/j.nut.2017.08.017
[47] Fisher NDL, et al. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S210-S214. PMID: 16794460.
[48] Francis ST, et al. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S215-S220. PMID: 16794461.
[49] Decroix L, et al. Appl Physiol Nutr Metab. 2016;41(12):1225-1232. doi:10.1139/apnm-2016-0245
[50] Franco R, et al. Nutrients. 2013;5(10):4159-4173. doi:10.3390/nu5104159
[51] Cimini A, et al. J Cell Biochem. 2013;114(10):2209-2220. doi:10.1002/jcb.24548
[52] Camps-Bossacoma M, et al. Oxid Med Cell Longev. 2017;2017:7417505. doi:10.1155/2017/7417505
[53] Tzounis X, et al. Am J Clin Nutr. 2011;93(1):62-72. doi:10.3945/ajcn.110.000075
[54] Fogliano V, et al. Mol Nutr Food Res. 2011;55 Suppl 1:S44-S55. doi:10.1002/mnfr.201000360
[55] Massot-Cladera M, et al. Arch Biochem Biophys. 2012;527(2):105-112. doi:10.1016/
[56] Martin F-PJ, et al. J Proteome Res. 2009;8(12):5568-5579. doi:10.1021/pr900607v
[57] Martorell P, et al. J Agric Food Chem. 2011;59(5):2077-2085. doi:10.1021/jf104217g
[58] Duarte DA, et al. J Nutr Biochem. 2015;26(1):64-74. doi:10.1016/j.jnutbio.2014.09.003