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As	humans	age,	the	neuronal	architecture	that	makes	up	the	memory	begins	to	deteriorate,	
with	neuronal	popula8ons	or	synap8c	connec8ons	decreasing	over	8me,	leaving	the	systems	
less	efficient	in	the	processing	and	storage	of	sensory	informa8on.	One	of	the	possible	effects	
flavonoids	have	in	the	brain	is	an	ability	to	induce	the	development	of	new	neuronal	8ssue.	7	
Flavonoids	and	their	metabolites	that	reach	the	brain	are	thought	to	exert	ac8vity	at	receptors,	
kinases,	and	transcrip8on	factors.	8	More	research	is	needed	to	determine	more	precisely	
where	and	how	these	interac8ons	occur,	however	by	affec8ng	such	pathways	they	have	the	
poten8al	to	induce	new	protein	synthesis	in	neurons	and	and	an	ability	to	cause	physical	
changes	which	have	a	direct	influence	on	memory	acquisi8on,	consolida8on	and	storage.	8		
	
Cogni8on	is	thought	to	be	improved	by	increasing	and	improving	cerebral	func8on.	Epicatechin,	
is	a	type	of	flavanol	that	acts	on	blood	vessels	in	the	brain	and	s8mulates	the	ac8vity	of	the	
enzyme	nitric	oxide	synthase	(NOS),	which	increases	the	produc8on	of	nitric	oxide.9	Nitric	oxide	
is	known	to	increase	vasodila8on	in	local	arteries	which	results	in	an	increase	in	cerebral	blood	
flow	(CBF).10	In	smooth	muscle	cells	like	blood	vessels,	nitric	oxide	helps	to	ac8vate	the	enzyme	
guanylate	cyclase	leading	to	the	conversion	of	guanosine	5’-triphosphate	(GTP)	to	cyclic	
guanosine	3’,5’-monophosphate	(cGMP)	which	induces	smooth	muscle	relaxa8on	and	therefore	
vasodila8on	of	local	arteries.5,11	For	op8mal	brain	func8oning,	CBF	needs	to	be	well	maintained	
to	support	constant	oxygen	and	glucose	supply	to	neurons	as	well	as	waste	excre8on.	Increase	
in	CBF	represents	a	poten8al	means	to	improve	cerebral	func8on.	12			
	
Cocoa Flavonoid Consump0on and the Effects on Short-Term MemoryLaurenHebert,RachelMostek,andJakeReinbold
DepartmentofFoodScience&HumanNutri0on,ColoradoStateUniversity,FortCollins,CO 
Spring	2016	
Abstract:		 Physiological	Aspects:		
Objec8ves:		
Related	Nutri8on:		 References:		
Applica8ons/Conclusions:		
Flavonoids	in	cocoa	have	been	shown	to	have	beneficial	effects	to	the	human	
brain.	Research	suggests	that	the	consump8on	of	dark	chocolate	can	increase	
short	term	memory	in	which	flavonoids	can	increase	and	improve	cerebral	
func8on.	Studies	have	suggested	that	by	maintaining	cerebral	blood	flow	by	
processes	of	relaxa8on	and	conversion	of	phosphates,	improved	cerebral	
func8on	has	been	shown.	The	purpose	of	this	research	is	to	conclude	how	the	
substances	in	dark	chocolate	affect	the	human	brain	and	its	effects	on	short	
term	memory.	
	
Introduc8on:		
•  	According	to	the	USDA,	a	100	gram	bar	of	dark	chocolate	contains	about	55	
milligrams	of	flavonoids.13	
•  In	order	to	see	an	improvement	short-term	memory,	one	study	has	shown	that	
250	mg	of	flavonoids	would	have	to	be	consumed	to	induce	significant	
vasodilla8on.14	
•  To	consume	250	mg	of	flavonoids	in		the	form	of	dark	chocolate,	a	person	would	
have	to	consume	approximately	1	pound	of	dark	chocolate	per	day.	
•  To	conclude,	the	benefits	the	flavonoids	would	have	on	cogni8on	likely	do	not	
outweigh	the	risks	because	1	pound	of	chocolate	would	possibly	lead	to	other	
nega8ve	health	consequences.	
•  More	research	is	needed	to	determine	if	flavonoid	supplements	can	be	used	as	
an	alterna8ve.14	
•  Ea8ng	a	variety	of	flavonoid	containing	foods,	aside	from	just	chocolate,	is	likely	
the	healthiest	way	to	ensure	adequate	intake.	
Another	reason	chocolate	has	been	thought	to	increase	cogni8on	is	because	
of	its	s8mulant	effects.	Chocolate	ocen	contains	caffeine,	which	could	play	a	
role,	but	another	substance	that	has	been	shown	to	have	a	s8mula8ng	
effect	is	theobromine.	
	
1.  Pase	M,	Scholey	A,	Pipingas	A,	Kras	M,	Nolidin	K,	Gibbs	A,	Wesnes	K,	Stough	C.	Cocoa	polyphenols	enhance	posi8ve	mood	states	but	not	cogni8ve	
performance:	a	randomized,	placebo-controlled	trial.	Psychopharm.	2013;	27(5):	451-458.	doi:	10.1177/0269881112473791	
2.  Prastowo	NA,	Kristanto	S,	Sasmita	PK.	Dark	chocolate	administra8on	improves	working	memory	in	students.	Universa	Medicina.	2015;34:229-236.	
3.  Knezevic	B,	Komatsuzaki	Y,	Freitas	E,	Lukowiak	K.	A	flavanoid	component	of	chocolate	quickly	reverses	an	imposed	memory	deficit.	J	Exp	Biol.	2016.	doi:
10.1242/jeb.130765	
4.  Smit	H,	Gaffan	E,	Rogers	P.	Methylxanthines	are	the	psycho-pharmacologically	ac8ve	cons8tuents	of	Chocolate.	Physchopharmacology.	2004;	176:	
412-419.	Doi:	10.1007/s00213-004-1898-3	
5.  Nehlig	A.	The	neuroprotec8ve	effects	of	cocoa	flavanol	and	its	influence	on	cogni8ve	performance.	Br.	J.	Clin.	Pharmacol.	2013;	75,	716-727.	10.1111/j.
1365-2125.2012.04378.x	
6.  Ruxton,	C.	H.	S.	(2008),	The	impact	of	caffeine	on	mood,	cogni8ve	func8on,	performance	and	hydra8on:	a	review	of	benefits	and	risks.	Nutri8on	Bulle8n,	
33:	15–25.	doi:	10.1111/j.1467-3010.2007.00665.x	
7.  Food	for	thought:	the	role	of	dietary	flavonoids	in	enhancing	human	memory,	learning	and	neuro-cogni8ve	performance.	Spencer	JP	Proc	Nutr	Soc.	2008	
May;	67(2):238-52	
8.  Spencer	JPE.	Flavonoids	and	brain	health:	mul8ple	effects	underpinned	by	common	mechanisms.	Genes	Nutr.2009	Dec;	4(4):243-250.	Doi:	10.1007/
s12263-009-0136-3	
9.  Drake	CT,	Iadecola	C.	The	role	of	neuronal	signaling	in	controlling	cerebral	blood	flow.	Brain	and	Language.	2006;	I02:141-152.	Doi:	10.1016/j.bandI.
2006.08.002	
10.  Piknova	B,	Kocharyan	A,	Schechter	AN,	Silva	AC;	The	role	of	nitrite	in	neurovascular	coupling.	Brain	Research.	2011;	1407:	62-68.	Doi:	10.1016/j.brainres.
2011.06.045	
11.  Klabunde	R.	Nitric	Oxide.	Cardiovascular	Physiology	Concepts	Web	site.	hlp://www.cvphysiology.com/Blood%20Flow/BF011.htm.	Published:	1998.	
Updated	2008.	Accessed:	April	2,	2016.		
12.  Duman	RS,	Nestler	EJ.	Guanylyl	Cyclase.	In:	Siegal	GJ,	Agranoff	BW,	Albers	RW,	et	al.,	editors.	Basic	Neurochemistry:	Molecular,	Cellular	and	Medical	
Aspects.	6th	edi8on.	Philadelphia:	Lippincol-Raven;	1999.	Available	from:	hlp://www.ncbi.nlm.nih.gov/books/NBK28167/	
13.  USDA	Database	for	the	Flavonoid	Content	of	Selected	Foods,	Release	3.0.	U.S.	Department	of	Agriculture,	Agricultural	Research	Service.	hlp://
www.ars.usda.gov/SP2UserFiles/Place/80400525/Data/Flav/Flav_R03.pdf.	2011.		
14.  Egert	S,	Rimbach	G.	Which	sources	of	flavonoids:	complex	diets	or	dietary	supplements?	Advances	in	NutriAon.	2011;	7(2):	8-14.	doi:	10.3945/an.
110.000026	
15.  Massee	L,	Ried	K,	Pase	M,	et	al.	The	acute	and	sub-chronic	effects	of	cocoa	flavanols	on	mood,	cogni8ve	and	cardiovascular	health	in	young	healthy	
adults:	a	randomized,	controlled	trail.	FronAers	in	Pharmacology.	2015;	93(6):	1-14.	doi:	10.3389/fphar.2015.00093	
16.  Sorond	FA,	Hurwitz	S,	Salat	DH,	Greve	DN,	Fisher	NDL.	Neurovascular	coupling,	cerebral	white	maler	integrity,	and	response	to	cocoa	in	older	people.	
Neurology.	2013;81:904-909.	
17.  Mastroiacovo	D,	Kwik-Uribe	C,	Grassi	D,	et	al.	Cocoa	flavanol	consump8on	improves	cogni8ve	func8on,	blood	pressure	control,	and	metabolic	profile	in	
elderly	subjects:	the	Cocoa,	Cogni8on,	and	Aging	(CoCoA)	Study--a	randomized	controlled	trial.	Am	J	Clin	Nutr.	2015;101:538-48.	doi:	10.3945/ajcn.
114.092189.	
18.  Prastowo	NA,	Kristanto	S,	Sasmita	PK.	Dark	chocolate	administra8on	improves	working	memory	in	students.	Universa	Medicina.	2015;34:229-236.		
19.  Field	D,	Williams	C,	Butler	L.	Consump8on	of	cocoa	flavanols	results	in	an	acute	improvement	in	visual	and	cogni8ve	func8ons.	Elsevier.	2011;	??	:255-260.	
doi:	10.1016/j.physbeh.2011.02.013	
20.  Pase	M,	Scholey	A,	Pipingas	A,	Kras	M,	Nolidin	K,	Gibbs	A,	Wesnes	K,	Stough	C.	Cocoa	polyphenols	enhance	posi8ve	mood	states	but	not	cogni8ve	
performance:	a	randomized,	placebo-controlled	trial.	Psychopharm.	2013;	27(5):	451-458.	doi:	10.1177/0269881112473791	
21.  Camfield,	D.	Scholey,	A.	Pipingas,	A.	Silberstein	A.	Kras,	M.	Nolidin,	K.	Wesnes,	K.	Pase,	M.	Stough,	C.	Steady	State	Visually	Evoked	Poten8al	(SSVEP)	
Topography	Changes	Associated	with	Cocoa	Flavanol	Consump8on.	Journal	of	Physiology	and	Behavior.	2012;	105:	948-957.	DOI:	10.1016/j.physbeh.
2011.11.013	
	
	
	
•  Discuss	the	rela8onship	between	cocoa	flavonoids	and	cogni8on	
•  Differen8ate	between	the	effects	of	caffeine	and	theobromine	on	cogni8on	
•  Explain	physiological	effects	cocoa	flavonoids	have	on	increasing	
vasodila8on	in	the	brain	
Flavonoids	are	compounds	that	are	a	class	of	polyphenols	which	are	
tradi8onally	found	in	plants.	1	Flavanols	are	a	subcategory	of	flavanoids.	These	
flavonoids	can	be	found	in	common	food	sources	such	as	dark	chocolate.	
Specifically,	epicatechin	is	a	flavanol	that	can	be	found	in	dark	chocolate	made	
from	Theobroma	cacao	or	cacao	beans.	2		Epicatechin	can	have	physiological	
consequences	on	the	brain	which	could	possibly	lead	to	an	increase	in	short-
term	memory.	3		
		
Epicatechin	
		
GTP	
		
Nitric	Oxide	
		
Nitric	Oxide	
Synthase	
		
cGMP	
		
Smooth	
muscle	cell	
relaxa8on	
		
Vasodilla8on	
Guanylate	
cyclase	
Future	Research:		
Numerous	studies	have	been	done	on	the	effects	of	flavonoids	in	dark	
chocolate	and	how	it	affects	the	human	brain.	Only	a	few	studies	showed	that	
the	flavonoids	in	dark	chocolate	improved	short-term	memory.	5	More	studies	
should	be	conducted	on	the	correla8on	between	short-term	memory	and	
flavonoids	specifically.	Numerous	studies	did	show	that	flavonoids	improved	
calmness	and	contentedness,	increased	reac8on	8me,	increased	working	
memory,	or	a	decrease	in	mental	fa8gue.15-21	These	alterna8ve	effects	could	
possibly	lead	to	improvements	in	short-term	memory	but	more	research	is	
needed	to	determine	if	this	is	the	case.		
Caffeine:	
•  Found	in	small	amounts	in	cocoa	beans	(50	g	bar	of	dark	chocolate	
17-36	mg)4	
•  Effects	of	caffeine	are	more	established	than	theobromine5		
•  Numerous	studies	showed	when	caffeine	was	consumed	75-150	mg	
then	there	was	improvement	in	memory6	
Theobromine:	
•  Found	in	high	amounts	in	cocoa	beans	(50	g	bar	of	dark	chocolate	
237-519	mg)	4	
•  Metabolite	of	caffeine		
•  Has	lille	effects	on	the	central	nervous	system5	
•  Too	few	studies	have	been	done	to	conclude	any	effects	on	cogni8on6

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poster final

  • 1. As humans age, the neuronal architecture that makes up the memory begins to deteriorate, with neuronal popula8ons or synap8c connec8ons decreasing over 8me, leaving the systems less efficient in the processing and storage of sensory informa8on. One of the possible effects flavonoids have in the brain is an ability to induce the development of new neuronal 8ssue. 7 Flavonoids and their metabolites that reach the brain are thought to exert ac8vity at receptors, kinases, and transcrip8on factors. 8 More research is needed to determine more precisely where and how these interac8ons occur, however by affec8ng such pathways they have the poten8al to induce new protein synthesis in neurons and and an ability to cause physical changes which have a direct influence on memory acquisi8on, consolida8on and storage. 8 Cogni8on is thought to be improved by increasing and improving cerebral func8on. Epicatechin, is a type of flavanol that acts on blood vessels in the brain and s8mulates the ac8vity of the enzyme nitric oxide synthase (NOS), which increases the produc8on of nitric oxide.9 Nitric oxide is known to increase vasodila8on in local arteries which results in an increase in cerebral blood flow (CBF).10 In smooth muscle cells like blood vessels, nitric oxide helps to ac8vate the enzyme guanylate cyclase leading to the conversion of guanosine 5’-triphosphate (GTP) to cyclic guanosine 3’,5’-monophosphate (cGMP) which induces smooth muscle relaxa8on and therefore vasodila8on of local arteries.5,11 For op8mal brain func8oning, CBF needs to be well maintained to support constant oxygen and glucose supply to neurons as well as waste excre8on. Increase in CBF represents a poten8al means to improve cerebral func8on. 12 Cocoa Flavonoid Consump0on and the Effects on Short-Term MemoryLaurenHebert,RachelMostek,andJakeReinbold DepartmentofFoodScience&HumanNutri0on,ColoradoStateUniversity,FortCollins,CO Spring 2016 Abstract: Physiological Aspects: Objec8ves: Related Nutri8on: References: Applica8ons/Conclusions: Flavonoids in cocoa have been shown to have beneficial effects to the human brain. Research suggests that the consump8on of dark chocolate can increase short term memory in which flavonoids can increase and improve cerebral func8on. Studies have suggested that by maintaining cerebral blood flow by processes of relaxa8on and conversion of phosphates, improved cerebral func8on has been shown. The purpose of this research is to conclude how the substances in dark chocolate affect the human brain and its effects on short term memory. Introduc8on: •  According to the USDA, a 100 gram bar of dark chocolate contains about 55 milligrams of flavonoids.13 •  In order to see an improvement short-term memory, one study has shown that 250 mg of flavonoids would have to be consumed to induce significant vasodilla8on.14 •  To consume 250 mg of flavonoids in the form of dark chocolate, a person would have to consume approximately 1 pound of dark chocolate per day. •  To conclude, the benefits the flavonoids would have on cogni8on likely do not outweigh the risks because 1 pound of chocolate would possibly lead to other nega8ve health consequences. •  More research is needed to determine if flavonoid supplements can be used as an alterna8ve.14 •  Ea8ng a variety of flavonoid containing foods, aside from just chocolate, is likely the healthiest way to ensure adequate intake. Another reason chocolate has been thought to increase cogni8on is because of its s8mulant effects. Chocolate ocen contains caffeine, which could play a role, but another substance that has been shown to have a s8mula8ng effect is theobromine. 1.  Pase M, Scholey A, Pipingas A, Kras M, Nolidin K, Gibbs A, Wesnes K, Stough C. Cocoa polyphenols enhance posi8ve mood states but not cogni8ve performance: a randomized, placebo-controlled trial. Psychopharm. 2013; 27(5): 451-458. doi: 10.1177/0269881112473791 2.  Prastowo NA, Kristanto S, Sasmita PK. Dark chocolate administra8on improves working memory in students. Universa Medicina. 2015;34:229-236. 3.  Knezevic B, Komatsuzaki Y, Freitas E, Lukowiak K. A flavanoid component of chocolate quickly reverses an imposed memory deficit. J Exp Biol. 2016. doi: 10.1242/jeb.130765 4.  Smit H, Gaffan E, Rogers P. Methylxanthines are the psycho-pharmacologically ac8ve cons8tuents of Chocolate. Physchopharmacology. 2004; 176: 412-419. Doi: 10.1007/s00213-004-1898-3 5.  Nehlig A. The neuroprotec8ve effects of cocoa flavanol and its influence on cogni8ve performance. Br. J. Clin. Pharmacol. 2013; 75, 716-727. 10.1111/j. 1365-2125.2012.04378.x 6.  Ruxton, C. H. S. (2008), The impact of caffeine on mood, cogni8ve func8on, performance and hydra8on: a review of benefits and risks. Nutri8on Bulle8n, 33: 15–25. doi: 10.1111/j.1467-3010.2007.00665.x 7.  Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cogni8ve performance. Spencer JP Proc Nutr Soc. 2008 May; 67(2):238-52 8.  Spencer JPE. Flavonoids and brain health: mul8ple effects underpinned by common mechanisms. Genes Nutr.2009 Dec; 4(4):243-250. Doi: 10.1007/ s12263-009-0136-3 9.  Drake CT, Iadecola C. The role of neuronal signaling in controlling cerebral blood flow. Brain and Language. 2006; I02:141-152. Doi: 10.1016/j.bandI. 2006.08.002 10.  Piknova B, Kocharyan A, Schechter AN, Silva AC; The role of nitrite in neurovascular coupling. Brain Research. 2011; 1407: 62-68. Doi: 10.1016/j.brainres. 2011.06.045 11.  Klabunde R. Nitric Oxide. Cardiovascular Physiology Concepts Web site. hlp://www.cvphysiology.com/Blood%20Flow/BF011.htm. Published: 1998. Updated 2008. Accessed: April 2, 2016. 12.  Duman RS, Nestler EJ. Guanylyl Cyclase. In: Siegal GJ, Agranoff BW, Albers RW, et al., editors. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edi8on. Philadelphia: Lippincol-Raven; 1999. Available from: hlp://www.ncbi.nlm.nih.gov/books/NBK28167/ 13.  USDA Database for the Flavonoid Content of Selected Foods, Release 3.0. U.S. Department of Agriculture, Agricultural Research Service. hlp:// www.ars.usda.gov/SP2UserFiles/Place/80400525/Data/Flav/Flav_R03.pdf. 2011. 14.  Egert S, Rimbach G. Which sources of flavonoids: complex diets or dietary supplements? Advances in NutriAon. 2011; 7(2): 8-14. doi: 10.3945/an. 110.000026 15.  Massee L, Ried K, Pase M, et al. The acute and sub-chronic effects of cocoa flavanols on mood, cogni8ve and cardiovascular health in young healthy adults: a randomized, controlled trail. FronAers in Pharmacology. 2015; 93(6): 1-14. doi: 10.3389/fphar.2015.00093 16.  Sorond FA, Hurwitz S, Salat DH, Greve DN, Fisher NDL. Neurovascular coupling, cerebral white maler integrity, and response to cocoa in older people. Neurology. 2013;81:904-909. 17.  Mastroiacovo D, Kwik-Uribe C, Grassi D, et al. Cocoa flavanol consump8on improves cogni8ve func8on, blood pressure control, and metabolic profile in elderly subjects: the Cocoa, Cogni8on, and Aging (CoCoA) Study--a randomized controlled trial. Am J Clin Nutr. 2015;101:538-48. doi: 10.3945/ajcn. 114.092189. 18.  Prastowo NA, Kristanto S, Sasmita PK. Dark chocolate administra8on improves working memory in students. Universa Medicina. 2015;34:229-236. 19.  Field D, Williams C, Butler L. Consump8on of cocoa flavanols results in an acute improvement in visual and cogni8ve func8ons. 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DOI: 10.1016/j.physbeh. 2011.11.013 •  Discuss the rela8onship between cocoa flavonoids and cogni8on •  Differen8ate between the effects of caffeine and theobromine on cogni8on •  Explain physiological effects cocoa flavonoids have on increasing vasodila8on in the brain Flavonoids are compounds that are a class of polyphenols which are tradi8onally found in plants. 1 Flavanols are a subcategory of flavanoids. These flavonoids can be found in common food sources such as dark chocolate. Specifically, epicatechin is a flavanol that can be found in dark chocolate made from Theobroma cacao or cacao beans. 2 Epicatechin can have physiological consequences on the brain which could possibly lead to an increase in short- term memory. 3 Epicatechin GTP Nitric Oxide Nitric Oxide Synthase cGMP Smooth muscle cell relaxa8on Vasodilla8on Guanylate cyclase Future Research: Numerous studies have been done on the effects of flavonoids in dark chocolate and how it affects the human brain. Only a few studies showed that the flavonoids in dark chocolate improved short-term memory. 5 More studies should be conducted on the correla8on between short-term memory and flavonoids specifically. Numerous studies did show that flavonoids improved calmness and contentedness, increased reac8on 8me, increased working memory, or a decrease in mental fa8gue.15-21 These alterna8ve effects could possibly lead to improvements in short-term memory but more research is needed to determine if this is the case. Caffeine: •  Found in small amounts in cocoa beans (50 g bar of dark chocolate 17-36 mg)4 •  Effects of caffeine are more established than theobromine5 •  Numerous studies showed when caffeine was consumed 75-150 mg then there was improvement in memory6 Theobromine: •  Found in high amounts in cocoa beans (50 g bar of dark chocolate 237-519 mg) 4 •  Metabolite of caffeine •  Has lille effects on the central nervous system5 •  Too few studies have been done to conclude any effects on cogni8on6