do specific dietary constituents and supplements affect ... · the data were summarized and...

Do specific dietary constituents and supplements affect mentalenergy? Review of the evidence

Heather E Gorby, Amy M Brownawell, and Michael C Falk

The numbers of marketing claims and food, beverage, and drug products claimingto increase mental energy have risen rapidly, thus increasing the need for scientificspecificity in marketing and food label claims. Mental energy is a three-dimensionalconstruct consisting of mood (transient feelings about the presence of fatigue orenergy), motivation (determination and enthusiasm), and cognition (sustainedattention and vigilance). The present review focuses on four dietary constituents/supplements (Ginkgo biloba, ginseng, glucose, and omega-3 polyunsaturated fattyacids) to illustrate the current state of the literature on dietary constituents andmental energy. The strongest evidence suggests effects of Ginkgo biloba on certainaspects of mood and on attention in healthy subjects, as well as associationsbetween omega-3 polyunsaturated fatty acids and reduced risk of age-relatedcognitive decline. Limitations of the current data and challenges for future researchare discussed.© 2010 International Life Sciences Institute

INTRODUCTION

Lack of energy and motivation is often associated withdiminished work productivity and reduced quality oflife.1 Dietary supplements as well as food and beverageproducts reported to increase energy are well-establishedin the marketplace.2 Product claims regarding “energy”and/or “mental energy” have risen rapidly in recent years,thus increasing the need for scientific specificity. Untilrecently, the term mental energy was only loosely definedand appropriate assessment methods to study changes inmental energy status were not clearly described.

A series of workshops sponsored by the NorthAmerican branch of the International Life Sciences Insti-tute (ILSI) resulted in the development of a scientificdefinition of mental energy as “the ability to performmental tasks, the intensity of feelings of energy andfatigue, and the motivation to accomplish mental andphysical tasks”.3,4 Mental energy is a three-dimensionalconstruct consisting of mood (transient feelings aboutthe presence of fatigue or energy), motivation (determi-nation and enthusiasm), and cognition (sustained atten-tion and vigilance).3 However, all three do not need to be

altered by a substance to affect mental energy. Appropri-ate techniques to measure mood,5 motivation,6 and cog-nition7 in relation to mental energy have been identifiedand reviewed. Following the recent definition of the term“mental energy”, a limited amount of published researchhas applied that definition. Previously, researchersreferred to central nervous system arousal and activationin relation to foods and dietary constituents in place of adefined mental energy concept. While the current reviewfocuses on the effects of specific foods, dietary constitu-ents, and/or dietary supplements on mental energy, thereare other approaches toward enhancing mental energy,such as exercise, adequate sleep, and brief afternoonnaps.8,9

The present review stems from a project undertakenby ILSI to describe the scope of the published scientificliterature on mental energy and to provide an assessmentof the state of the science related to the effects of foods,dietary constituents, and/or dietary supplements onmental energy, as currently defined. A literature searchwas performed, as described in detail below, and relevantdata were extracted. It was evident that insufficient datawere available to perform a systematic review. Therefore,

Affiliations: HE Gorby, AM Brownawell, and MC Falk are with the Life Sciences Research Organization, Bethesda, Maryland, USA.

Correspondence: AM Brownawell, Life Sciences Research Organization, 9650 Rockville Pike, Bethesda, MD 20814-3998, USA. E-mail:[email protected], Phone: +1-301-634-7030, Fax: +1-301-634-7876.

Key words: cognition, memory, mental energy, mood, motivation

Lead Article

doi:10.1111/j.1753-4887.2010.00340.xNutrition Reviews® Vol. 68(12):697–718 697

the data were summarized and limitations of the pub-lished studies were identified. The present review articledescribes the findings related to four select dietaryconstituents/supplements (Ginkgo biloba, ginseng,glucose, and omega-3 polyunsaturated fatty acids) toillustrate the state of the science regarding mental energyas a defined concept and to discuss the challenges forimproving future research.

THE MENTAL ENERGY LITERATURE

Criteria for studies

At the request of ILSI, the Life Sciences Research Orga-nization (LSRO) conducted a literature search and reviewon the relationships between the intake of foods, dietaryconstituents, and/or dietary supplements and mentalenergy. Studies were restricted to those with human sub-jects only and included both prospective and observa-tional studies. Study subjects were limited to healthyadults aged 18 years and older, including seniors withmanaged disease (e.g., diabetes). Studies of seniors diag-nosed with Alzheimer’s disease or other dementia wereexcluded. Both oral ingestion and gastric infusion deliv-ery methods were considered. Review articles and reportsof original research evaluating the effects of genetics,pain, sleep, and/or disease on mental energy wereexcluded. Studies examining the effects of caffeine werealso excluded from the current review, because caffeinehas a clear dose-dependent effect on cognitive functionthat has been extensively reviewed elsewhere.10

Search methods for identification of studies

LSRO conducted the literature search using the PubMedand PsychInfo databases for articles cited through May2010. Searches were conducted using Medical SubjectHeadings (MeSH) combined with key-word searches to

capture all indexed studies (Table 1). Bibliographicsearches were also conducted to ensure inclusion of allrelevant studies. The initial search strategy retrievedapproximately 2,500 primary articles. The abstracts werereviewed and studies were included if they investigatedfood, dietary constituent, or dietary supplement intakeand used at least one measure of mood, cognition, and/ormotivation. Full-text copies of the articles meeting thosecriteria were then screened for their suitability for inclu-sion and those meeting the inclusion criteria were manu-ally cross-referenced. Two-hundred and sixty-five articlesmet the initial search criteria.

Data were extracted and entered into a database.Extracted information included study population,number of subjects, type and duration of the study,dosage/amount and timing of treatment or ingestion offood, and outcome measures for mood, cognition, and/ormotivation. Timing and duration of ingestion of dietaryconstituents were categorized into five groups: short-term acute (<2 h), long-term acute (2–24 h), short-termchronic (2–7 days), moderate-term chronic (1–26 weeks),and long-term chronic (>26 weeks).

Outcome measures

Previous reviews recommended several instruments formeasuring mental energy based on their prevalence inthe literature.5–7 Studies included in the current reviewfrequently evaluated mood using the Profile of MoodStates (POMS) questionnaire (42 studies) and the VisualAnalog Scale (VAS) (49 studies), but 25 additional instru-ments were also used. The cognitive measures most fre-quently used were tests of attention and vigilance; 12different testing instruments were used to evaluate atten-tion and 6 were used to evaluate vigilance. Cognitive per-formance outcomes were also included, such as memoryand speed of information processing. Out of the initial265 studies retrieved for the review, only two attemptedto measure motivation. The measures used in these

Table 1 Search strategy used to identify the studies evaluated in the present review.Search terms used in PubMed search engine PubMed search terms Total hits(brain OR cognition OR fatigue OR motivation

OR mood OR affect) AND (food OR diet ORnutrition OR micronutrient OR supplementOR vitamin) Limits: Human, English, MESHterms Major Topics

(“brain”[MeSH Major Topic] OR “cognition”[MeSH Major Topic]OR “fatigue”[MeSH Major Topic] OR “motivation”[MeSHMajor Topic] OR “affect”[MeSH Major Topic] OR“affect”[MeSH Major Topic]) AND (“food”[MeSH MajorTopic] OR “diet”[MeSH Major Topic] OR (“nutritionalsciences”[MeSH Major Topic] OR “nutritionphysiology”[MeSH Major Topic]) OR (“traceelements”[MeSH Major Topic] OR “micronutrients”[MeSHMajor Topic]) OR “dietary supplements”[MeSH Major Topic]OR (“vitamins”[MeSH Major Topic] OR “vitamin k”[MeSHMajor Topic] OR “vitamin d”[MeSH Major Topic] OR “vitamina”[MeSH Major Topic])) AND (“humans”[MeSH Terms] ANDEnglish[lang])

2,488

Nutrition Reviews® Vol. 68(12):697–718698

studies, i.e., “time spent trying to remember words”11 andpupil size,12 are not generally accepted measures of moti-vation. Given the lack of available data, no conclusionscan be drawn about associations between dietaryconstituents/supplements and motivation, so this mentalenergy component is not discussed further in this review.

Description of included studies

The literature search revealed that changes in mentalenergy had been evaluated for 35 foods, dietary constitu-ents, dietary supplements, and dietary factors (e.g., mealtiming, caloric load, macronutrient composition). For 26of these 35 foods/supplements/constituents, 10 or fewerstudies were published for each. For 19 of those 26, fewerthan 5 studies were published. As a result, insufficientevidence is available to evaluate mental energy claims fornumerous foods, dietary constituents, and dietary supple-ments. The greatest amount of literature was available forGinkgo biloba, glucose, carbohydrate, and ginseng. Toillustrate the state of the mental energy literature, thisreview provides a detailed discussion of Ginkgo biloba(Table 2), ginseng (Table 3), and glucose (Table 4), as wellas a popular supplement, omega-3 polyunsaturated fattyacids (PUFAs) (Table 5).

FOUR SPECIFIC DIETARY SUPPLEMENTS ANDDIETARY CONSTITUENTS

Ginkgo biloba

Medicinal products derived from the maidenhair tree,Ginkgo biloba, are some of the most widely used of allplant-based products. The active components of Ginkgobiloba consist of flavonoids, terpenoids, and terpene lac-tones (i.e., ginkgolides and bilobalide). A well-definedextract, EGb 761, which is produced from ground-upleaves, contains 24% w/w flavone glycosides and 6% w/wterpene lactones. It is marketed as Tanakan, Tebonin, andRokan. Kaveri (L1 1370) is similar but with 25% w/wflavone glycosides. Ginkgo biloba is available without pre-scription in the United Kingdom, Europe, Canada, China,and the United States, where it is marketed as a dietarysupplement.

Ginkgo biloba has been used in China as a traditionalmedicine for a range of conditions for many centuries.The medicinal properties of Ginkgo biloba are likely dueto several biological effects including increased cerebralblood flow, modification of neurotransmitter systems,reduced blood viscosity, and free radical scavenging.91

Single cases of bleeding (i.e., intracranial hemorrhaging)have been reported in relation to intake of Ginkgo bilobapreparations.92 However, a review of controlled studies

indicated EGb761 does not influence blood clotting forbleeding time and is unable to potentiate the effects ofanticoagulant or antiplatelet drugs.93

The main use of Ginkgo biloba is in the treatment ofcerebral dysfunction. Ginkgo biloba extract has beeninvestigated for clinical efficacy in patients with age-related cognitive decline and dementia related to Alzhe-imer’s disease. A 2007 Cochrane Collaboration Reviewfound that evidence for the benefit of Ginkgo biloba oncognition in individuals with dementia was not convinc-ing.91 The results of two recent randomized, placebo-controlled trials support the Cochrane conclusion29,30,37;compared to placebo, 240 mg daily intake of Ginkgobiloba extract did not reduce the incidence of dementia orAlzheimer’s disease, nor did it protect against cognitivedecline in elderly populations. Fewer studies have evalu-ated whether Ginkgo biloba enhances cognitive functionin younger healthy populations. The effects on mood andcognition in healthy adults administered Ginkgo bilobaare discussed below.

Mood. Several studies report that Ginkgo biloba improvesoverall mood (subjective intensity scale-mood,VAS),14,15,28

alertness,21,25 and calmness.22 Four weeks of treatment withGinkgo biloba (120 mg/d) in healthy older adultsimproved self-reported quality of life (VAS) and increasedpositive mood state (subjective intensity scale-mood)compared to placebo, but there were no differencesbetween groups as measured by the POMS.14 Participantscompleted baseline mood measures in addition to weeklyquestionnaires. Although Cockle et al.15 and Trick et al.28

reached similar conclusions, neither of their studiesemployed placebo-controlled designs or determined base-line mood, thus weakening their findings.

Six hours after Ginkgo biloba (360 mg/d) administra-tion to healthy young adults, participants reported greateralertness (VAS) compared to placebo.21 This study mea-sured alertness at 1, 2.5, 5, and 6 h after Ginkgo bilobaadministration, and increased alertness was found at alltime points compared to placebo. However, the samplesize was small (n = 20), and a subsequent study by thesame laboratory failed to replicate the findings over arange of doses (120–360 mg).20 A 6 h study of youngadults by the same group demonstrated that 120 mgGinkgo biloba extract was also associated with improvedcalmness.22 Rigney et al.25 administered a range of doses(120–300 mg) for 2 days to healthy adults. The partici-pants reported increased alertness on day 1, but decreasedarousal on day 2.

In contrast to the favorable effects of Ginkgo bilobaon mood discussed above, 10 studies reported no appre-ciable effect.13,16–20,23,24,26,27 In these negative studies, studyduration varied from 1 h to 12 weeks of administrationand wide-ranging doses of Ginkgo biloba (80–600 mg)

Nutrition Reviews® Vol. 68(12):697–718 699

Tabl

e2

Sum

mar

yof

stud

ies

onG

inkg

obi

loba

and

men

tale

nerg

y.Re

fere

nce

Trea

tmen

tO

utco

me

mea

sure

(s)

Resu

ltsM

ood

Burn

set

al.(

2006

)13G

inkg

obi

loba

;ext

ract

,40

mg,

Gin

gkof

orte

;24

%gi

nkgo

-flav

ongl

ycos

ides

and

6%gi

nkgo

lides

3¥/d

(120

mg)

POM

SN

oeff

ect

Clez

aet

al.(

2003

)14G

inkg

obi

loba

;ext

ract

120

mg,

EGb

761;

2¥/d

(240

mg)

Self-

rate

dde

pres

sion

scal

e;PO

MS;

subj

ectiv

ein

tens

itysc

ale-

moo

dm

enta

lhea

lth:

self-

repo

rton

VAS;

gene

ralh

ealth

:se

lf-re

port

onVA

S;qu

ality

oflif

e:se

lf-re

port

onVA

S

Subj

ects

repo

rted

am

ore

posi

tive

stat

e,be

tter

men

talh

ealth

,and

qual

ityof

life

afte

rta

king

Gin

kgo

bilo

ba

Cock

leet

al.(

2000

)15G

inkg

obi

loba

;ext

ract

120

mg,

LI13

70Se

lf-ra

ted

activ

ities

ofda

ilyliv

ing

scal

eVA

SG

inkg

obi

loba

grou

pfe

ltbe

tter

able

toco

pew

ithda

ilyliv

ing,

and

had

redu

ced

anxi

ety

and

depr

essi

onEl

saba

ghet

al.(

2005

)16G

inkg

obi

loba

;ext

ract

120

mg,

25%

gink

gofla

vono

ids

and

6%te

rpen

oids

Bond

-Lad

erVA

SN

oeff

ect

Elsa

bagh

etal

.(20

05)17

Gin

kgo

bilo

ba;e

xtra

ct12

0m

g,LI

1370

;25%

tota

lgin

kgo

flavo

noid

s,6%

tota

lter

pene

lact

ones

Hos

pita

lanx

iety

and

depr

essi

onsc

ale

Bond

-Lad

erVA

SN

oeff

ect

Har

tley

etal

.(20

03)18

Gin

kgo

bilo

ba;e

xtra

ct12

0m

g,LI

1370

;25%

gink

gofla

vono

ids

and

6%te

rpen

oids

Bond

-Lad

erVA

SN

oeff

ect

Har

tley

etal

.(20

04)19

Gin

kgo

bilo

ba;e

xtra

ct12

0m

g/d

GK5

01G

inse

ng;e

xtra

ct20

0m

g/d

G11

5Bo

nd-L

ader

VAS

No

effec

t

Kenn

edy

etal

.(20

00)20

Gin

kgo

bilo

ba;e

xtra

ct12

0,24

0,or

360

mg,

GK5

01;2

4%gi

nkgo

-flav

one

glyc

osid

esan

d6%

terp

ene

lact

ones

Bond

-Lad

erVA

SN

oeff

ect

Kenn

edy

etal

.(20

02)21

Gin

kgo

bilo

ba;e

xtra

ct36

0m

g,G

K501

Bond

-Lad

erVA

SG

inkg

obi

loba

grou

pre

port

edim

prov

edal

ertn

ess

and

cont

ente

dnes

sKe

nned

yet

al.(

2007

)22G

inkg

obi

loba

;ext

ract

120

mg,

24%

gink

go-fl

avon

olgl

ycos

ides

and

6%te

rpen

ela

cton

es

Bond

-Lad

erVA

SG

inkg

obi

loba

asso

ciat

edw

ithim

prov

edca

lmne

ss

Mix

etal

.(20

00)23

Gin

kgo

bilo

ba;e

xtra

ct18

0m

g/d,

EGb

761

Self-

repo

rtqu

estio

nnai

re,m

ood

No

effec

tM

ixet

al.(

2002

)24G

inkg

obi

loba

;ext

ract

60m

g,EG

b76

124

%fla

vone

glyc

osid

es,6

%te

rpen

ela

cton

esan

dle

ssth

an5

ppm

gink

olic

acid

s,3¥

/d(1

80m

g)

Self-

repo

rtqu

estio

nnai

re,m

ood

No

effec

t

Rign

eyet

al.(

1999

)25G

inkg

obi

loba

;ext

ract

150

mg

(50

mg

3¥/d

),30

0m

g(1

00m

g3x

/d),

240

mg,

120

mg

VAS

120,

150,

and

300

mg

incr

ease

dal

ertn

ess

onda

y1;

120

mg

and

150

mg

decr

ease

dar

ousa

lon

day

2


Sing

het

al.(

2004

)26G

inkg

obi

loba

;ext

ract

40m

g,2¥

/d(8

0m

g)M

edic

alsy

mpt

omqu

estio

nnai

reSF

-12

No

effec

tSu

bhan

etal

.(19

84)27

Gin

kgo

bilo

ba;e

xtra

ct12

0,24

0,or

600

mg

VAS

No

effec

tTr

ick

etal

.(20

04)28

Gin

kgo

bilo

ba;3

grou

ps:1

)Gin

kgo

bilo

baex

trac

tLI1

370:

120

mg

for4

mon

ths

plus

6m

onth

sco

ntin

uatio

n;2)

Gin

kgo

bilo

bafo

r4m

onth

spl

usst

opta

king

for6

mon

ths;

3)ne

wtr

eatm

entg

roup

:6m

onth

sof

Gin

kgo

bilo

ba

Self-

rate

dac

tiviti

esof

daily

livin

gsc

ale

VAS

Gin

kgo

bilo

baim

prov

edsc

ores

onm

ood

and

self-

asse

ssed

perf

orm

ance

,lon

gerd

urat

ion

(10

mon

ths)

oftr

eatm

enti

mpr

oved

scor

esev

enfu

rthe

r

Cogn

ition

Burn

set

al.(

2006

)13G

inkg

obi

loba

;ext

ract

,40

mg,

Gin

koFo

rte;

24%

gink

go-fl

avon

egl

ycos

ides

and

6%gi

nkgo

lides

3¥/d

(120

mg)

Subt

ests

from

the

Woo

dcoc

k-Jo

hnso

nPs

ycho

-Edu

catio

nalB

atte

ry-R

evis

edG

inkg

obi

loba

impr

oved

long

-ter

mm

emor

yin

olde

radu

lts(5

5–79

year

s).N

oeff

ecti

nyo

unge

rsub

ject

sCi

eza

etal

.(20

03)14

Gin

kgo

bilo

ba;e

xtra

ct12

0m

g,EG

b76

1;2¥

/d(2

40m

g)D

igit

conn

ectio

nte

st;w

ord

listt

est;

incr

emen

tth

resh

old

forv

isua

lstim

uli;

audi

tory

choi

cere

actio

ntim

e;fin

gert

appi

ngte

mpo

and

spee

d

Gin

kgo

bilo

baim

prov

edre

actio

ntim

e

DeK

osky

etal

.(20

08)29

Gin

kgo

bilo

ba;e

xtra

ct12

0m

g,EG

b76

1;2¥

/d(2

40m

g)M

MSE

;Clin

ical

Dem

entia

Ratin

g;G

inkg

oEv

alua

tion

ofM

emor

ySt

udy

Neu

rops

ycho

logi

calB

atte

ry

No

effec

t

Dod

geet

al.(

2008

)30G

inkg

obi

loba

;ext

ract

,240

mg,

6%te

rpen

ela

cton

esan

d24

%fla

vone

glyc

osid

es,p

lus

stan

dard

mul

tivita

min

with

40IU

ofvi

tam

inE

MM

SE;l

ogic

alm

emor

ysu

bsca

le:W

MS-

RN

oeff

ect

Elsa

bagh

etal

.(20

05)16

Gin

kgo

bilo

ba;e

xtra

ct12

0m

g,LI

1370

;25%

tota

lgin

kgo

flavo

noid

s,6%

tota

lter

pene

lact

ones

Spat

ialw

orki

ngm

emor

y;m

enta

lflex

ibili

tyan

dpl

anni

ngab

ility

;PAS

AT;p

atte

rnre

cogn

ition

mem

ory;

spat

ialr

ecog

nitio

nm

emor

y;de

laye

dre

call

ofw

ords

and

pict

ures

Acut

edo

seof

Gin

kgo

bilo

baim

prov

edpe

rfor

man

ceon

asu

stai

ned-

atte

ntio

nta

skan

dpa

tter

n-re

cogn

ition

mem

ory

task

.Aft

er6

wee

ksth

ere

wer

eno

effec

tson

cogn

ition

Elsa

bagh

etal

.(20

05)17

Gin

kgo

bilo

ba;e

xtra

ct12

0m

g,25

%gi

nkgo

flavo

noid

san

d6%

terp

enoi

dsCa

tego

ryge

nera

tion

Stoc

king

sof

Cam

brid

gete

st:C

ANTA

B;im

med

iate

and

dela

yed

para

grap

hre

call:

WM

S-R;

dela

yed

mat

chin

g-to

-sam

ple

task

:CAN

TAB;

pict

ure

reca

llta

sk:P

ASAT

;int

ra/e

xtra

dim

ensi

onal

shift

task

:CAN

TAB

Gin

kgo

bilo

baim

prov

edex

ecut

ive

func

tion

ina

subs

etof

part

icip

ants

(tho

sein

men

opau

se5

year

sor

mor

e)

Har

tley

etal

.(20

03)18

Gin

kgo

bilo

ba;e

xtra

ct12

0m

g,25

%gi

nkgo

flavo

noid

san

d6%

terp

enoi

dsIm

med

iate

and

dela

yed

para

grap

hre

call:

WM

S-R;

dela

yed

mat

chin

g-to

-sam

ple

test

:CA

NTA

B;PA

SAT;

com

mon

obje

cts

test

Stoc

king

sof

Cam

brid

gete

st:C

ANTA

B;in

tra/

extr

adi

men

sion

alsh

iftta

sk:C

ANTA

B

Gin

kgo

bilo

baim

prov

edpe

rfor

man

ceof

non-

verb

alm

emor

y,fr

onta

llob

efu

nctio

n,an

dsu

stai

ned

atte

ntio

n.N

oeff

ecto

nim

med

iate

orde

laye

dpa

ragr

aph

reca

llor

inde

laye

dre

call

ofpi

ctur

es


Tabl

e2

Cont

inue

dRe

fere

nce

Trea

tmen

tO

utco

me

mea

sure

(s)

Resu

ltsKe

nned

yet

al.(

2000

)20G

inkg

obi

loba

;ext

ract

120,

240,

or36

0m

g,24

%gi

nkgo

-flav

one

glyc

osid

esan

d6%

terp

ene

lact

ones

CDR

com

pute

rized

asse

ssm

entb

atte

ry:s

peed

ofat

tent

ion,

qual

ityof

mem

ory,

spee

dof

mem

ory,

accu

racy

ofat

tent

ion

Both

240

and

360

mg

impr

oved

spee

dof

atte

ntio

nat

2.5

and

6h.

Man

yot

hert

ime-

and

dose

-spe

cific

chan

ges

inpe

rfor

man

ceof

othe

rfac

tors

Kenn

edy

etal

.(20

02)21

Gin

kgo

bilo

ba;e

xtra

ct36

0m

g,G

K501

CDR

com

pute

rized

asse

ssm

entb

atte

ry:s

peed

ofat

tent

ion,

qual

ityof

mem

ory,

spee

dof

mem

ory,

accu

racy

ofat

tent

ion

seria

lThr

ees

and

seria

lSev

ens

Gin

kgo

bilo

baim

prov

edse

cond

ary

mem

ory

perf

orm

ance

and

perf

orm

ance

onse

rial

thre

esan

dse

rials

even

s

Kenn

edy

etal

.(20

07)31

Gin

kgo

bilo

ba;e

xtra

ct12

0m

g,24

%gi

nkgo

-flav

one

glyc

osid

esan

d6%

terp

ene

lact

ones

CDR

com

pute

rized

asse

ssm

entb

atte

ry:s

peed

ofat

tent

ion,

qual

ityof

mem

ory,

spee

dof

mem

ory,

accu

racy

ofat

tent

ion

120

mg

Gin

kgo

bilo

baim

prov

ed“q

ualit

yof

mem

ory”

at1

and

4h,

redu

ced

“spe

edof

atte

ntio

n”at

1an

d6

hKe

nned

yet

al.(

2007

)22G

inkg

obi

loba

;ext

ract

120

mg,

24%

gink

go-fl

avon

olgl

ycos

ides

and

6%te

rpen

ela

cton

es

CDR

com

pute

rized

asse

ssm

entb

atte

ry:s

peed

ofat

tent

ion,

qual

ityof

mem

ory,

spee

dof

mem

ory,

accu

racy

ofat

tent

ion,

seria

lse

vens

,and

seria

lthr

ees

No

effec

t

Mix

etal

.(20

00)23

Gin

kgo

bilo

ba;e

xtra

ct18

0m

g/d,

EGb

761

Logi

calm

emor

ysu

btes

t:W

MS-

R;vi

sual

repr

oduc

tion

subt

est:

WM

S-R;

trai

lmak

ing

task

part

sA

and

B;St

roop

colo

rtas

k

Gin

kgo

bilo

baim

prov

edsp

eed

ofpr

oces

sing

com

pare

dto

plac

ebo.

Part

icip

ants

wer

eal

som

ore

confi

dent

inth

eira

bilit

yto

rem

embe

r,as

mea

sure

dby

ase

lf-re

port

ques

tionn

aire

Mix

etal

.(20

02)24

Gin

kgo

bilo

ba;e

xtra

ct60

mg,

EGb

761

24%

flavo

negl

ycos

ides

,6%

terp

ene

lact

ones

and

less

than

5pp

mgi

nkgo

licac

ids,

3¥/d

(180

mg)

Face

ssu

btes

t:W

MS-

III;d

igit

sym

bolc

odin

g:W

AIS-

III;b

lock

desi

gnsu

btes

t:W

AIS-

III;

sele

ctiv

ere

min

ding

task

Gin

kgo

bilo

baen

hanc

edde

laye

dfr

eere

call

and

dela

yed

reco

gniti

onof

non-

cont

extu

alau

dito

ry-v

erba

lmat

eria

l.G

inkg

obi

loba

impr

oved

abili

tyto

rem

embe

rfac

es.G

inkg

ogr

oup

rate

dth

eiro

vera

llab

ility

tore

mem

bera

sim

prov

edM

oulto

net

al.(

2001

)32G

inkg

obi

loba

;ext

ract

60m

g,LI

1370

,2¥/

d(1

20m

g)Re

adin

gsp

anan

ddi

gits

pan

forw

ards

:W

AIS-

R;St

ernb

erg

mem

ory

scan

ning

test

No

effec

t

Nat

han

etal

.(20

02)33

Gin

kgo

bilo

ba;e

xtra

ct12

0m

g,G

ingk

ofor

teCD

Rco

mpu

teriz

edas

sess

men

tbat

tery

:sim

ple

reac

tion

time,

choi

cere

actio

ntim

e,nu

mer

icw

orki

ngm

emor

y,sp

atia

lmem

ory;

Rey

audi

tory

verb

alle

arni

ngta

sk;p

ictu

rere

cogn

ition

No

effec

t


Polic

het

al.(

2001

)34G

inkg

obi

loba

;ext

ract

40m

g,le

ssth

an5

ppm

gink

golic

acid

,plu

sfo

licac

id,L

-tyr

osin

e,D

MAE

bita

rtra

te,p

anto

then

icac

id,

ribofl

avin

,vita

min

B 6,v

itam

inB 1

,ni

acin

amid

e,vi

npoc

etin

e,ni

acin

Pict

ure

nam

ing;

cont

inuo

uspe

rfor

man

ceta

sk;

insp

ectio

ntim

e;si

mpl

ean

dch

oice

resp

onse

time

Gin

kgo

bilo

bade

crea

sed

resp

onse

time

ona

wor

king

mem

ory

task

Rign

eyet

al.(

1999

)25G

inkg

obi

loba

;ext

ract

150

mg

(50

mg

3¥/d

),30

0m

g(1

00m

g3¥

/d),

240

mg,

120

mg

Ster

nber

gm

emor

ysc

anni

ngta

sk;w

ord

reca

llte

st;c

ritic

alfli

cker

fusi

on;c

hoic

ere

actio

ntim

e;di

gits

ymbo

lsub

stitu

tion

task

;W

AIS-

R;St

roop

colo

rtas

k

Gin

kgo

bilo

ba,e

xcep

t150

mg,

perf

orm

edfa

ster

onth

eSt

ernb

erg

mem

ory

scan

ning

task

onda

y1,

and

120

mg

and

300

mg

perf

orm

edfa

ster

onda

y2

Sant

oset

al.(

2003

)35G

inkg

obi

loba

;ext

ract

80m

g,24

%fla

vono

id,

6.1%

terp

enoi

dTo

ulou

se-P

iero

nco

ncen

trat

edat

tent

ion

Wis

cons

inca

rdso

rtin

gte

st;v

erba

lfre

ere

call;

Rey-

Ost

errie

thco

mpl

exfig

ure

test

;W

AIS-

R;W

MS-

R;Co

rsib

lock

-tap

ping

test

Gin

kgo

bilo

baim

prov

edgl

obal

cogn

itive

func

tioni

ng,a

tten

tion,

and

spee

dof

info

rmat

ion

proc

essi

ng

Scho

ley

etal

.(20

02)36

Gin

kgo

bilo

ba;s

tudy

1:G

inkg

obi

loba

extr

act

(GK5

01,2

4%gi

nkgo

-flav

one

glyc

osid

esan

d6%

terp

ene

lact

ones

),60

mg

each

;6ca

psul

eda

ilydo

ses

=12

0,24

0,or

360

mg

Seria

lsev

ens;

seria

lthr

ees

Gin

kgo

bilo

baim

prov

edto

taln

umbe

rof

subt

ract

ions

durin

gse

rialt

hree

sin

ado

se-r

espo

nse

man

nera

t4h

Snitz

etal

.(20

09)37

Gin

kgo

bilo

ba;e

xtra

ct12

0m

g,EG

b76

1;2¥

/d(2

40m

g)M

MSE

;clin

ical

dem

entia

ratin

g;G

inkg

oEv

alua

tion

ofM

emor

ySt

udy

Neu

rops

ycho

logi

calB

atte

ry

No

effec

t

Solo

mon

etal

.(2

002)

38G

inkg

obi

loba

;ext

ract

40m

g,3¥

/d(1

20m

g)St

roop

colo

rtas

k;di

gits

ymbo

lsub

stitu

tion;

WAI

S-Rd

Dig

itsp

an;W

MS-

Rlo

gica

lmem

ory

subs

cale

;WM

S-R

visu

alre

prod

uctio

nsu

bsca

le;W

MS-

Rm

enta

lcon

trol

;WM

S-R

Calif

orni

ave

rbal

lear

ning

test

;Bos

ton

nam

ing

test

;cat

egor

yflu

ency

No

effec

t

Stou

ghet

al.(

2001

)39G

inkg

obi

loba

;ext

ract

120

mg

Spee

dof

com

preh

ensi

onte

st;d

igit

span

;tra

ilm

akin

gte

st;R

eyau

dito

ryve

rbal

lear

ning

test

;ins

pect

ion

time;

sim

ple

reac

tion

time;

wor

king

mem

ory

Gin

kgo

bilo

baex

trac

tim

prov

edsp

eed

ofin

form

atio

npr

oces

sing

,wor

king

mem

ory,

and

exec

utiv

epr

oces

sing

Subh

anet

al.(

1984

)27G

inkg

obi

loba

;ext

ract

120,

240,

or60

0m

gSt

ernb

erg

mem

ory

scan

ning

test

;cho

ice

reac

tion

time;

criti

calfl

icke

rfus

ion

test

600

mg

ofG

inkg

obi

loba

impr

oved

perf

orm

ance

onth

eSt

ernb

erg

mem

ory

test

Abbr

evia

tions

:CAN

TAB,

Cam

brid

geN

euro

psyc

holo

gica

lTes

tAut

omat

edBa

tter

y;CD

R,Co

gniti

vedr

ugre

sear

ch;M

MSE

,Min

i-Men

talS

tate

Exam

inat

ion;

PASA

T:Pa

ced

Audi

tory

Seria

lAdd

ition

Test

;PO

MS,

Profi

lein

Moo

dSt

ates

;VAS

,Vis

ualA

nalo

gSc

ale;

WAI

S,W

echs

lerA

dult

Inve

ntor

ySc

ale;

WAI

S-R,

Wec

hsle

rAdu

ltIn

vent

ory

Scal

e-Re

vise

d;W

MS-

R,W

echs

lerM

emor

ySc

ale-

Revi

sed.


Tabl

e3

Sum

mar

yof

stud

ies

ongi

nsen

gan

dm

enta

lene

rgy.

Refe

renc

eTr

eatm

entd

escr

iptio

nO

utco

me

mea

sure

(s)

Resu

ltsM

ood

Card

inal

etal

.(20

01)40

Gin

seng

;ext

ract

200

mg

or40

0m

g,Pa

nax

gins

eng

G11

5PA

NAS

;PO

MS

No

effec

t

Kenn

edy

etal

.(20

01)41

Gin

seng

;ext

ract

200

mg,

400

mg

or60

0m

g,Pa

nax

gins

eng

G11

5VA

SBo

thth

e20

0an

d40

0m

gdo

ses

ofgi

nsen

gsi

gnifi

cant

lyre

duce

dal

ertn

ess

Kenn

edy

etal

.(20

04)42

Gin

seng

;ext

ract

200

mg,

Pana

xgi

nsen

gG

115

VAS

No

effec

t

Reay

etal

.(20

06)43

Gin

seng

;ext

ract

200

mg,

Pana

xgi

nsen

gG

115

VAS

Gin

seng

decr

ease

dfa

tigue

Uss

here

tal.

(199

5)44

Gin

seng

;ext

ract

40m

g,Pa

nax

gins

eng

G11

5PO

MS

Gin

seng

incr

ease

dvi

gor

Cogn

ition

D’A

ngel

oet

al.(

1986

)45G

inse

ng;e

xtra

ct10

0m

g,Pa

nax

gins

eng

G11

5,2¥

/dCa

ncel

latio

nte

st;m

enta

larit

hmet

ic;l

ogic

alde

duct

ion;

choi

cere

actio

ntim

e;au

dito

ryre

actio

ntim

e;ta

ppin

gte

st;d

igit

sym

bol

subs

titut

ion

test

Gin

seng

impr

oved

perf

orm

ance

form

enta

lar

ithm

etic

proc

essi

ng

Kenn

edy

etal

.(20

01)41

Gin

seng

;ext

ract

200

mg,

400

mg,

or60

0m

g,Pa

nax

gins

eng

G11

5CD

Rco

mpu

teriz

edas

sess

men

tbat

tery

:spe

edof

atte

ntio

n,qu

ality

ofm

emor

y,sp

eed

ofm

emor

y,ac

cura

cyof

atte

ntio

n

Gin

seng

impr

oved

“qua

lity

ofm

emor

y”at

400

and

600

mg;

200

and

600

mg

ofgi

nsen

gca

used

decr

emen

tsin

perf

orm

ance

on“s

peed

ofat

tent

ion”

fact

orKe

nned

yet

al.(

2004

)42G

inse

ng;e

xtra

ct20

0m

g,Pa

nax

gins

eng

G11

5CD

Rco

mpu

teriz

edas

sess

men

tbat

tery

:spe

edof

atte

ntio

n,qu

ality

ofm

emor

y,sp

eed

ofm

emor

y,ac

cura

cyof

atte

ntio

n;se

rialt

hree

san

dse

rials

even

s;lo

gica

lrea

soni

ng;s

ente

nce

verifi

catio

nta

sk

Gin

seng

impr

oved

task

perf

orm

ance

,enh

ance

dsp

eed

ofm

emor

y,in

crea

sed

reac

tion

times

Reay

etal

.(20

05)46

Gin

seng

;ext

ract

200

mg

or40

0m

g,Pa

nax

gins

eng

G11

5Se

rialt

hree

san

dse

rials

even

s;ra

pid

visu

alin

form

atio

npr

oces

sing

task

Gin

seng

incr

ease

dnu

mbe

rofs

ubtr

actio

nsin

seria

lthr

ees

subt

ract

ion

task

and

decr

ease

dfa

lse

alar

ms

inra

pid

visu

alin

form

atio

npr

oces

sing

task

Reay

etal

.(20

06)43

Gin

seng

;ext

ract

200

mg,

Pana

xgi

nsen

gG

115

Seria

lthr

ees

and

seria

lsev

ens;

rapi

dvi

sual

info

rmat

ion

proc

essi

ngta

skG

inse

ngen

hanc

edpe

rfor

man

ceof

am

enta

lar

ithm

etic

task

,and

impr

oved

perf

orm

ance

onth

era

pid

visu

alin

form

atio

npr

oces

sing

task

Scho

ley

(200

2)36

Gin

seng

;ext

ract

200

mg,

400

mg,

or60

0m

g,Pa

nax

gins

eng

G11

5Se

rialt

hree

san

dse

rials

even

sG

inse

ngha

dno

effec

ton

seria

lthr

ees,

butt

here

wer

esi

gnifi

cant

time-

dose

inte

ract

ions

for

serie

sse

vens

Søre

nson

etal

.(19

96)47

Gin

seng

;ext

ract

400

mg,

Pana

xgi

nsen

gG

115

Sim

ple

audi

tive

reac

tion

times

test

;sim

ple

visu

alre

actio

ntim

este

st;fi

nger

-tap

ping

test

;D2

test

;flue

ncy

test

;sel

ectiv

ere

min

ding

task

;lo

gica

lmem

ory

and

repr

oduc

tion

test

;Re

y-O

ster

rieth

com

plex

figur

ete

st;W

isco

nsin

card

sort

ing

test

Gin

seng

sped

uppe

rfor

man

ceon

the

sim

ple

audi

tive

reac

tion

times

test

and

impr

oved

perf

orm

ance

onth

eW

isco

nsin

card

sort

ing

test

Abbr

evia

tions

:CD

R,co

gniti

vedr

ugre

sear

ch;P

ANAS

,Pos

itive

Affec

tNeg

ativ

eAff

ectS

ched

ule;

POM

S,Pr

ofile

inM

ood

Stat

es;V

AS,V

isua

lAna

log

Scal

e.


Tabl

e4

Sum

mar

yof

stud

ies

ongl

ucos

ean

dm

enta

lene

rgy.

Refe

renc

eTr

eatm

entd

escr

iptio

nO

utco

me

mea

sure

(s)

Resu

ltsM

ood

Gre

enet

al.(

2001

)48G

luco

se;5

00m

Lgl

ucos

e.4

grou

ps:i

n2

sess

ions

(1gl

ucos

ean

d1

aspa

rtam

e),

subj

ects

wer

eco

rrec

tlyin

form

edof

drin

k;in

the

othe

r2se

ssio

ns,t

hey

wer

eto

ldth

eyre

ceiv

edth

eot

her

drin

k.

VAS

No

effec

t

Reay

etal

.(20

06)43

Glu

cose

;25

gdr

ink

VAS

Glu

cose

decr

ease

dm

enta

lfat

igue

Scho

ley

etal

.(20

02)49

Glu

cose

;25

ggl

ucos

epl

us20

0m

Lw

ater

POM

SN

oeff

ect

Win

dere

tal.

(199

8)50

Glu

cose

;250

mL

beve

rage

swee

tene

dw

ith50

ggl

ucos

epo

wde

r(Bo

ots’

“Glu

cose

C”)b

alan

ced

fort

aste

and

acid

ityw

ithle

mon

drin

kco

ncen

trat

e(B

oots

’“U

nsw

eete

ned

Lem

on”)

POM

SN

oeff

ect

Cogn

ition

Aza

riet

al.(

1991

)51G

luco

se;3

00m

L(w

ater

)bev

erag

eco

ntai

ning

30or

100

ggl

ucos

eM

emor

yre

cogn

ition

;mem

ory

reca

llN

oeff

ect

Bent

onet

al.(

1993

)52G

luco

se;e

xper

imen

t1:g

luco

sebe

vera

ge:5

0g

Expe

rimen

t1:w

ord

list;

spat

ialm

emor

yte

stN

oeff

ect

Bent

onet

al.(

1993

)52G

luco

se;e

xper

imen

t2:g

luco

sebe

vera

ge:5

0g

Expe

rimen

t2:w

ord

list;

WM

SN

oeff

ect

Craf

teta

l.(1

994)

53G

luco

se;5

0g

oran

gefla

vore

dbe

vera

geM

odifi

edCV

LT;S

troo

pco

lort

ask;

PASA

T;w

ord-

listg

ener

atio

n;pa

tter

nre

call

and

reco

gniti

on;p

arag

raph

reca

ll;se

rialr

eact

ion

time

task

Glu

cose

enha

nced

perf

orm

ance

onth

ede

clar

ativ

em

emor

ym

easu

re,

para

grap

hre

call,

forb

oth

olde

rmal

esw

ithgo

odre

cove

ryan

dyo

unge

rm

ales

with

poor

reco

very

.You

nger

mal

esw

ithgo

odre

cove

rysh

owed

impa

ired

mem

ory

afte

rglu

cose

Don

ohoe

etal

.(19

99)54

Glu

cose

;exp

erim

ents

1an

d2:

gluc

ose

drin

k:50

ggl

ucos

epo

wde

radd

edto

250

mL

wat

er,2

tbsp

Robi

nson

’sw

hole

oran

gesq

uash

(sug

ar-f

ree)

,2ts

ple

mon

juic

e

Embe

dded

figur

este

st;t

ime

take

nto

solv

ecr

itica

lpro

blem

s;w

ater

jars

test

;ver

balfl

uenc

y;bl

ock

desi

gnte

st;

Port

eus

maz

e;lo

gica

lrea

soni

ngte

st

Glu

cose

incr

ease

dve

rbal

fluen

cy.

Hig

heri

nitia

lblo

odgl

ucos

ele

vels

corr

elat

edto

bett

erpe

rfor

man

ceon

the

wat

erja

rste

st;h

igh

bloo

dgl

ucos

ele

vels

afte

rbev

erag

ew

ere

asso

ciat

edw

ithpe

rfor

man

cede

crem

ents

onth

ebl

ock

desi

gnte

stFl

int,

Jr.,

etal

.(20

03)55

Glu

cose

;drin

k:10

,100

,and

500

mg/

kg,

or50

gCo

ntin

uous

perf

orm

ance

task

Subj

ects

give

n10

0m

g/kg

ofgl

ucos

epe

rfor

med

wor

seon

the

atte

ntio

nta

sk


Tabl

e4

Cont

inue

dRe

fere

nce

Trea

tmen

tdes

crip

tion

Out

com

em

easu

re(s

)Re

sults

Ford

etal

.(20

02)56

Glu

cose

;25

ggl

ucos

ead

ded

to15

0m

Lof

wat

er,m

ixed

with

20m

Lof

suga

r-fr

eeor

ange

drin

k

CDR

com

pute

rized

asse

ssm

entb

atte

ryN

oeff

ect

Fost

eret

al.(

1998

)57G

luco

se;2

5g

gluc

ose

adde

dto

300

mL

wat

erM

odifi

edCV

LT;f

orw

ard

and

back

war

ddi

gits

pan;

Rey-

Ost

errie

thco

mpl

exfig

ure

draw

ing

Glu

cose

impr

oved

long

-ter

mve

rbal

free

and

cued

reca

ll,w

hich

corr

elat

edto

bloo

dgl

ucos

ele

vels

.No

effec

tsof

gluc

ose

onsh

ort-

term

verb

alm

emor

yor

long

-ter

mno

n-ve

rbal

mem

ory

Gon

der-

Fred

eric

ket

al.(

1987

)58G

luco

se;5

0g

gluc

ose,

16oz

swee

tene

dbe

vera

geN

arra

tive

mem

ory:

WM

S;di

gits

pan:

WM

S;vi

sual

mem

ory:

WM

S;pa

ired

asso

ciat

ew

ord

list:

WM

S

Glu

cose

impr

oved

tota

lsco

reon

the

Wec

hsle

rmem

ory

scal

ean

dth

ena

rrat

ive

mem

ory

test

Gre

enet

al.(

2001

)48G

luco

se;5

00m

Lgl

ucos

e.4

cond

ition

s(2

gluc

ose

and

2as

part

ame)

.In

2se

ssio

ns(1

gluc

ose

and

1as

part

ame)

subj

ects

wer

eco

rrec

tlyin

form

edab

outt

hedr

ink,

inth

eot

her2

sess

ions

they

wer

eto

ldth

eop

posi

te

Verb

alre

cogn

ition

mem

ory

task

;tw

o-fin

gert

appi

ngve

rbal

free

-rec

all;

Baka

nvi

gila

nce

task

Glu

cose

impr

oved

reco

gniti

onm

emor

y.G

luco

seim

prov

edvi

gila

nce,

buto

nly

whe

nsu

bjec

tsw

ere

told

they

wer

egi

ven

gluc

ose

Hal

leta

l.(1

989)

59G

luco

se;5

0g

gluc

ose,

16oz

lem

on-fl

avor

edbe

vera

geVi

sual

mem

ory,

WM

S;lo

gica

lmem

ory,

WM

S;pa

ired

asso

ciat

es,W

MS;

digi

tsp

anfo

rwar

dan

dba

ckw

ard,

WM

S

Glu

cose

enha

nced

mem

ory

inel

derly

and

youn

gsu

bjec

ts.G

luco

seto

lera

nce

pred

icte

dm

emor

yin

elde

rly,b

utno

tin

youn

gad

ults

Kapl

anet

al.(

2000

)60G

luco

se;2

90m

Lw

ater

,10

mL

lem

onju

ice,

50g

gluc

ose

Para

grap

hre

call;

trai

lste

stpa

rtB;

atte

ntio

nRe

yau

dito

ryve

rbal

lear

ning

test

No

effec

t

Kenn

edy

etal

.(20

00)61

Glu

cose

;25

ggl

ucos

ead

ded

to25

0m

Lof

wat

eran

d25

mL

Robi

nson

’slo

w-c

alor

ieor

ange

squa

sh

Seria

lsev

ens

and

seria

lthr

ees;

wor

dre

trie

val

Glu

cose

cons

umpt

ion

impr

oved

perf

orm

ance

onse

rials

even

s,bu

tnot

seria

lthr

ees

Man

ning

etal

.(19

90)62

Glu

cose

;50

ggl

ucos

e,le

mon

-flav

ored

beve

rage

Dig

itsp

anfo

rwar

dan

dba

ckw

ard;

logi

calm

emor

y,W

MS;

Rey-

Ost

erre

ithco

mpl

exfig

ure

draw

ing;

Amm

on’s

quic

kte

st;l

ette

rcan

cella

tion

test

;fin

gero

scill

atio

nte

st;s

elec

tive

rem

indi

ngte

st

Glu

cose

enha

nced

logi

calm

emor

ype

rfor

man

ce,b

utno

tsho

rt-t

erm

mem

ory

Man

ning

etal

.(19

92)63

Glu

cose

;50

gad

min

iste

red

befo

reor

afte

racq

uisi

tion

Mem

ory

reca

ll;na

rrat

ive

pass

age

Both

gluc

ose

grou

psim

prov

edre

call


Man

ning

etal

.(19

97)64

Glu

cose

;50

gdr

ink

Wor

dlis

trec

ogni

tion

and

reca

ll;w

ord-

stem

com

plet

ion

Inel

derly

subj

ects

,glu

cose

impr

oved

perf

orm

ance

onth

ede

clar

ativ

ete

st,

butn

otno

n-de

clar

ativ

ete

st.I

nyo

ung

adul

tsub

ject

sgl

ucos

eha

dno

effec

tM

anni

nget

al.(

1998

)65G

luco

se;5

0g

adde

dto

8oz

(236

.8m

L)le

mon

-flav

ored

beve

rage

give

nbe

fore

oraf

tera

cqui

sitio

n

Mem

ory

reca

ll;na

rrat

ive

pass

age

Subj

ects

had

bett

erre

call

perf

orm

ance

whe

ngl

ucos

ew

asin

gest

ed.R

ecal

lw

asbe

tter

whe

ngl

ucos

ew

asgi

ven

befo

reac

quis

ition

Mar

tin&

Bent

on(1

999)

66G

luco

se;5

0g

gluc

ose

diss

olve

din

250

mL

wat

erfla

vore

dw

ith2

tbsp

(29.

5m

L)su

gar-

free

Robi

nson

sW

hole

Ora

nge

Squa

sh,2

tbsp

(29.

5m

L)an

d2

tsp

(9.8

mL)

lem

onju

ice

Mem

ory;

reca

llof

trig

ram

sG

luco

sedr

ink

impr

oved

mem

ory

infa

sted

subj

ects

,but

noti

nth

ose

who

cons

umed

brea

kfas

t

Mei

kle

etal

.(20

04)67

Glu

cose

;25

or50

gof

gluc

ose

diss

olve

din

200

mL

wat

erfla

vore

dw

ith2

tbsp

(29.

5m

L)of

suga

r-fr

eew

hole

oran

gesq

uash

;and

5m

Lof

suga

r-fr

eew

hole

lem

on

Trai

lmak

ing

task

Aan

dB;

lett

erca

ncel

latio

nta

sk;v

erba

lpro

duct

ion;

mem

ory

sear

ch;v

isua

lsea

rch;

dela

yed

free

reca

ll;vi

sual

span

test

Glu

cose

impr

oved

mem

ory

sear

chin

olde

radu

lts.G

luco

seim

prov

edre

call

inbo

thag

egr

oups

.No

effec

tofd

ose

Mes

sier

etal

.(19

97)68

Glu

cose

;50

gpl

us24

0m

Lle

mon

-flav

ored

beve

rage

Canc

ella

tion

Hte

stdi

gits

pan

back

war

dan

dfo

rwar

d,W

MS-

R;lo

gica

lm

emor

y,W

MS-

R;ve

rbal

paire

das

soci

ates

,WM

S-R;

visu

alm

emor

ysp

an,W

MS-

R;di

gits

ymbo

lsu

bstit

utio

n,W

AIS-

R;co

gniti

vepo

rtio

nof

Alzh

eim

er’s

Dis

ease

Asse

ssm

entS

cale

Glu

cose

inge

stio

nim

prov

edm

emor

yin

mal

esw

ithgo

odgl

ucor

egul

atio

nfo

rth

efir

st7

item

son

the

mem

ory

test

,bu

tdec

reas

edfo

rtho

sew

ithpo

orgl

ucor

egul

atio

n

Mes

sier

etal

.(19

99)69

Glu

cose

;50

gpl

us24

0m

Lle

mon

-flav

ored

beve

rage

Imm

edia

tean

dde

laye

dw

ord

reca

llBo

thm

ales

and

fem

ales

with

poor

gluc

oreg

ulat

ion

perf

orm

edw

orse

ona

mem

ory

task

durin

gth

esa

ccha

rinco

nditi

on,b

utno

tdur

ing

gluc

ose

Met

zger

etal

.(20

00)70

Glu

cose

;lem

onad

e(2

24g)

swee

tene

dw

ithgl

ucos

e(5

0g)

Faci

alre

cogn

ition

;Com

Phot

ofit

faci

alco

nstr

uctio

nso

ftw

are

Glu

cose

enha

nced

perf

orm

ance

ona

faci

alre

cogn

ition

task

Moh

anty

etal

.(20

01)71

Glu

cose

;100

mg/

kgor

50g

drin

kSp

atia

lmem

ory

rete

ntio

n,ne

utra

land

emot

iona

l;sp

atia

lmem

ory

acqu

isiti

on,e

mot

iona

land

neut

ral

Both

100

mg/

kgan

d50

ggl

ucos

eim

paire

dpe

rfor

man

cefo

rem

otio

nal

stim

ulio

na

spat

ialm

emor

yta

sk;

100

mg/

kgen

hanc

edm

emor

ydu

ring

neut

rals

timul

i,50

gsh

owed

noeff

ect

Ow

ens

etal

.(19

94)72

Glu

cose

;50

gdr

ink

Reac

tion

time;

insp

ectio

ntim

eIn

crea

sing

bloo

dgl

ucos

ele

vels

resu

lted

infa

ster

deci

sion

times


Tabl

e4

Cont

inue

dRe

fere

nce

Trea

tmen

tdes

crip

tion

Out

com

em

easu

re(s

)Re

sults

Pars

ons

etal

.(19

92)73

Glu

cose

;10

g+

38.8

mg

sacc

harin

,25

g+

24.9

mg

sacc

harin

,or5

0g

mix

edw

itha

240

mL

lem

on-fl

avor

edbe

vera

ge

Amm

on’s

quic

kte

st;l

ogic

alm

emor

y;W

MS

25g

gluc

ose

enha

nced

logi

calm

emor

y

Reay

etal

.(20

06)43

Glu

cose

;25

gdr

ink

Seria

lthr

ees

and

seria

lsev

ens;

rapi

dvi

sual

info

rmat

ion

proc

essi

ngta

skG

luco

seen

hanc

edpe

rfor

man

ceof

am

enta

larit

hmet

icta

skan

dth

era

pid

visu

alin

form

atio

n-pr

oces

sing

task

Scho

ley

etal

.(20

01)74

Glu

cose

;25

gluc

ose

pow

der,

250

mL

wat

er,a

nd25

mL

flavo

ring

Verb

alflu

ency

;wor

dm

emor

y;se

rial

seve

nsG

luco

seim

prov

edpe

rfor

man

ceon

seria

lsev

ens,

butn

otw

ord

retr

ieva

lor

wor

dm

emor

y.Se

rials

even

sta

skal

sosi

gnifi

cant

lyre

duce

dbl

ood

gluc

ose,

indi

catin

gth

athi

ghco

gniti

velo

aden

hanc

esgl

ucos

eut

iliza

tion

Scho

ley

etal

.(20

02)49

Glu

cose

;25

ggl

ucos

epl

us20

0m

Lw

ater

Kine

sthe

ticm

emor

y;m

aze

test

Glu

cose

impr

oved

kine

sthe

ticm

emor

ype

rfor

man

ceSü

nram

-Lea

etal

.(20

01)75

Glu

cose

;25

gin

300

mL

wat

er;3

food

cond

ition

s:fa

stin

g,br

eakf

ast,

and

lunc

h

Rey-

Ost

errie

thco

mpl

exfig

ure

draw

ing;

mod

ified

digi

tspa

n;CV

LTG

luco

seen

hanc

edlo

ng-t

erm

spat

ial

mem

ory

perf

orm

ance

.No

diffe

renc

esin

time

ofda

yof

gluc

ose

adm

inis

trat

ion,

orfa

stin

gco

nditi

onSü

nram

-Lea

etal

.(20

02)76

Glu

cose

;25

gdi

ssol

ved

in30

0m

Lof

wat

erRe

y-O

ster

rieth

com

plex

figur

edr

awin

g;se

rials

even

s;CV

LTG

luco

seim

prov

edim

med

iate

reca

llpe

rfor

man

cean

dde

laye

dre

call

perf

orm

ance

Sünr

am-L

eaet

al.(

2002

)77G

luco

se;d

elay

edan

tero

grad

e:25

gof

gluc

ose

15m

inbe

fore

;im

med

iate

ante

rogr

ade:

25g

gluc

ose

imm

edia

tely

befo

rete

stin

g;im

med

iate

retr

ogra

de:2

5g

gluc

ose

give

nim

med

iate

lyaf

terw

ord

list

CVLT

;Rey

-Ost

errie

thco

mpl

exfig

ure

draw

ing;

seria

lsev

ens

Glu

cose

give

nbe

fore

oraf

terw

ord

list

impr

oved

mem

ory

Sünr

am-L

eaet

al.(

2004

)78G

luco

se;4

cond

ition

s:25

ggl

ucos

epl

usfu

ll-fa

tyog

urt(

200

g);g

luco

sepl

usfa

t-fr

eeyo

gurt

(200

g);0

.2g

aspa

rtam

epl

usfu

ll-fa

tyog

urt

(200

g);0

.2g

aspa

rtam

epl

usfa

t-fr

eeyo

gurt

(200

g)

CVLT

;Rey

-Ost

errie

thco

mpl

exfig

ure

draw

ing;

seria

lsev

ens

Glu

cose

drin

kpl

usfa

t-fr

eeyo

gurt

impr

oved

perf

orm

ance

onsh

ort-

and

long

-del

ayre

call

Win

dere

tal.

(199

8)50

Glu

cose

;250

mL

beve

rage

with

50g

gluc

ose

pow

der(

Boot

s’“G

luco

seC”

)pl

usle

mon

drin

kco

ncen

trat

e(B

oots

’“U

nsw

eete

ned

Lem

on”)

Nam

efa

ceas

soci

atio

nta

sk;s

elec

tive

rem

indi

ngta

skN

oeff

ect

Abbr

evia

tions

:CVL

T,Ca

lifor

nia

Verb

alLe

arni

ngTe

st;P

ASAT

,Pac

edAu

dito

rySe

rialA

dditi

onTe

st;P

OM

S,Pr

ofile

inM

ood

Stat

es;V

AS,V

isua

lAna

log

Scal

e;W

MS,

Wec

hsle

rMem

ory

Scal

e;W

MS-

R,W

echs

lerM

emor

ySc

ale-

Revi

sed.


Tabl

e5

Sum

mar

yof

stud

ies

onom

ega-

3PU

FAs

and

men

tale

nerg

y.Re

fere

nce

Trea

tmen

tdes

crip

tion

Out

com

em

easu

re(s

)Re

sults

Moo

dFo

ntan

ieta

l.(2

005)

79O

meg

a-3;

4g

caps

ules

,2.8

gom

ega-

3PU

FA,

EPA

+D

HA

ratio

2:1

POM

SO

meg

a-3

supp

lem

ents

incr

ease

dPO

MS

inde

x;vi

gori

ncre

ased

and

ange

rde

crea

sed

Font

anie

tal.

(200

5)80

Om

ega-

3;4

gca

psul

es,2

.8g

omeg

a-3

PUFA

,EP

A+

DH

Ara

tio2:

1PO

MS

Om

ega-

3in

crea

sed

vigo

rand

redu

ced

ange

r,an

xiet

y,fa

tigue

,con

fusi

on,a

ndde

pres

sion

John

son

etal

.(20

08)81

Om

ega-

3;80

0m

gD

HA

Neu

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were given to both young and elderly participants. A doseof 120 mg/d for 12 weeks had no effect on mood (POMS)in either older or younger adults.13 Three studies by thesame laboratory reported no effect of 120 mg/d Ginkgobiloba on mood (VAS) given to either healthy young par-ticipants or older women for 6 weeks.16–18 Ginkgo biloba ata range of doses (120, 240, and 360 mg/d) given to healthyolder women for 7 days had no effect on mood (VAS).19

Administration of a range of Ginkgo biloba doses (120,240, or 360 mg) for just 6 h did not affect mood in healthyyoung adults, but this study had a very small sample size(n = 20).20 Two studies that administered 180 mg/d ofGinkgo biloba to healthy older adults reported no effecton mood after 6 weeks using an unvalidated self-reportquestionnaire created by the authors.23,24 Ginkgo biloba(80 mg/d) given to healthy adults did not affect mood, asmeasured by the Medical Symptom Questionnaire, after 6weeks of treatment.26 A range of Ginkgo biloba doses (120,240, or 600 mg/d) administered to healthy adults did notaffect mood after 1 h.27 Definitive conclusions cannot bedrawn regarding the effects of Ginkgo biloba on mooddue to a combination of poor study design elements andinconsistent findings.

Cognition. Numerous studies have examined the rela-tionship between Ginkgo biloba and cognition in healthysubjects, with variable results. Many studies focused onminor components of mental energy (i.e., learning andmemory), although more relevant cognitive domains likeattention and vigilance were also investigated. Improvedspeed of processing was reported in three studies thatadministered Ginkgo biloba at 40–180 mg/d for 14 d to 8months to both young39 and older adults.23,24,35,39 Stoughet al.39 conducted a randomized, double-blind placebo-controlled clinical trial that lasted for 30 days. A neuro-psychological test battery, including the digit symbolsubstitution test, was performed before and after treat-ment, adding validity to the results. Similar designs wereused by Santos et al.35 and Mix et al.23 Cieza et al.14 alsoobserved enhanced motor performance in older subjects(50–65 years) after 240 mg/d Ginkgo biloba extract for 4weeks.

The relationship between Ginkgo biloba and atten-tion has also been investigated. Ginkgo biloba improvedattention in younger16,20,31 and older participants18,35 infive studies, while one study of older women reported noeffect.17,24 Elsabagh et al.16 measured sustained attentionafter 4 h and again after 6 weeks of treatment (120 mg/d).Improved attention was reported 4 h after intake ofGinkgo biloba (120 mg/d) by young subjects (18–26years), but not after 6 weeks. A follow-up study in post-menopausal women (51–67 years) found no effect ofGinkgo biloba on attention.17 However, both studieslacked baseline data. Kennedy et al.20 reported improved

speed of attention in young subjects (19–24 years) at 2.5and 6 h after administration of either 240 or 360 mgGinkgo biloba extract using the Cognitive Drug Researchcomputerized assessment battery. A subsequent study bythe same laboratory with a similar subject group31 dem-onstrated that a lower dose of Ginkgo biloba extract(120 mg) also improved speed of attention at 1 and 6 hafter administration using the same assessment battery.Hartley et al.18 reported improved performance in healthyolder females (53–65 years) on measures of frontal lobefunction (rule shifting) and attention (Paced AuditorySerial Addition Test) after 7 days of Ginkgo biloba treat-ment (120 mg/d). Santos et al.35 reported improved atten-tion and speed of information processing in healthy oldermen (60–70 years) taking 80 mg/d Ginkgo biloba extractfor 8 months. These results suggest a potential effect ofGinkgo biloba extract on attention after short-termadministration in both young and older subjects.

Several studies investigating the effects of Ginkgobiloba on memory suggest a favorable effect. In one study,Ginkgo biloba (120 mg/d) improved long-term memoryin older participants after 12 weeks of treatment;however, no effect was found in younger participants.13 Awell-designed 4-week study in healthy elderly subjectsreceiving 120 mg/d39 and an acute high-dose study inyoung adults receiving 600 mg/d27 reported improvedworking memory (digit span backwards, Sternbergmemory scanning test) after administration of Ginkgobiloba. Mix et al.23 observed enhanced delayed free recalland delayed recognition of non-contextual auditory-verbal material in healthy older subjects (60 years orolder; 127 treatment/122 controls) administered180 mg/d Ginkgo biloba extract for 6 weeks. Polich et al.34

reported improved working memory when 40 mg/dGinkgo biloba/vinpocetine compound was administeredto a group (n = 24) of healthy subjects (22–59 years) for14 days. Subhan and Hindmarch27 also reportedimproved working memory (Sternberg memory scanningtest) after administering a range of doses (120–600 mg/d), but a poorly described product was used for a shortduration (1 h) in a small subject group (n = 8), weakeningthese findings.

Three studies also evaluated concentration andmemory using the Serial Threes and Serial Sevens tasks.Kennedy et al.21 administered 360 mg Ginkgo bilobaextract to 20 healthy young participants (mean age, 21.2years) and found improved performance on Serial Threesand Serial Sevens tests after 6 h. Scholey et al.36 found adose-dependent improvement in speed of respondingduring Serial Threes in young subjects following Ginkgobiloba administration. However, in a subsequent study bythe same group,22 a lower dose of Ginkgo biloba extract(120 mg) did not markedly improve performance on theSerial Subtraction tasks.


In contrast to the generally positive results discussedabove, additional studies report no detectable effects ofGinkgo biloba on different aspects of memory (patternrecognition, working, spatial, and logical).16,17,32,33,38 In adouble-blind, placebo-controlled study, Nathan et al.33

found no effect 90 min after administration of 120 mg/dGinkgo biloba to a small subject group (n = 11) using theCognitive Drug Research battery in addition to tests ofworking memory. In another double-blind, placebo-controlled study, Moulton et al.32 found no effect onworking memory in young subjects administered120 mg/d Ginkgo biloba for 5 days using the Sternbergmemory-scanning test. Solomon et al.38 found no changesin memory or learning in elderly participants adminis-tered 120 mg/d for 6 weeks using the California VerbalLearning Test, logical memory, visual reproduction, digitsymbol subscales of the Wechsler Memory Scale-Revised,the Stroop test, or other tests. Elsabagh et al.16 measuredepisodic and working memory and pattern recognition inyoung subjects after 4 h and again after 6 weeks of Ginkgobiloba treatment (120 mg/d); improved pattern recogni-tion memory was reported after 4 h, but no effect onepisodic or working memory was reported after 6 weeks.These findings are weakened, however, by the absence ofbaseline testing. A follow-up study in older adult womenfound no effect of Ginkgo biloba on episodic memory.17

At this time, insufficient evidence is available to deter-mine whether Ginkgo biloba improves memory, althoughmemory is a minor component of mental energy.

Summary. Several studies suggest Ginkgo biloba mayimprove aspects of mood14,15,28 including alertness21,25 andcalmness22 in healthy subjects. Aspects of cognition mayalso be affected; Ginkgo biloba extract consistentlyimproved speed of processing in both younger and olderadults23,35,39 and appears to have favorable effects on atten-tion after short-term administration.16,18,20,31,35 However,conflicting evidence prohibits any clear association frombeing made between Ginkgo biloba and memory inhealthy participants.

Ginseng

The root of Panax ginseng is commonly used either byitself or in combination with other herbal ingredients inChinese medicine. Ginsenosides, the major active com-ponents of ginseng, are triterpene saponins that modulateplatelet aggregation, blood pressure, immune function,and hypothalamic-pituitary-adrenal axis activity.94

Ginseng is unsafe in pregnant or breastfeeding womendue to estrogenic activity,95 and in patients taking antico-agulants because it may reduce blood concentrations ofthese drugs.96

The quality and composition of ginsenosides arehighly variable and are dependent on multiple factors

including the species, age, and part of the plant, the cul-tivation method, preservation method, season of harvest,and extraction method.97 To avoid variability amongpreparations, researchers often use the standardizedextract (G115) with total ginsenoside adjusted to 4%(Pharmaton SA, Switzerland).

Mood. One study found that 2 months of supplementa-tion with a multivitamin containing ginseng (40 mg)improved vigor (POMS).44 Two acute studies found thatginseng decreased fatigue (400 mg)43 and increased alert-ness (VAS) (200 or 400 mg).41 However, two additionalstudies found no effect of ginseng on mood.40,42

Kennedy42 conducted a 6-h crossover study that admin-istered 3 doses of ginseng (200, 400, or 600 mg) and testedmood using a VAS. Cardinal and Engels40 conducted adouble-blind, placebo-controlled, randomized clinicaltrial that administered 200 or 400 mg ginseng for 8 weeksand found no effect on mood as measured by the POMSor the Positive Affect–Negative Affect scale. Based onthese studies, consistent evidence is lacking that ginsengaffects mood in healthy subjects.

Cognition. Two chronic studies of ginseng reported con-flicting effects on mental energy. A well-designed12-week study of ginseng (200 mg) improved mentalarithmetic processing but had no effect on attention, rec-ognition memory, or reaction time.45 In another study,400 mg/d of ginseng improved abstract thinking andincreased auditory reaction times but had no effect onlearning and memory or speed of processing after 9weeks.47

Several acute studies also report conflicting results.Three single doses of ginseng (200, 400, or 600 mg) wereadministered in a 6-h acute study,41 but only the 400 mgdose improved memory and both the 200 and 600 mgdoses caused decrements in performance on an attentiontask. A 200 mg dose of ginseng improved attention andreaction time and enhanced memory 6 h after adminis-tration.42 The same group also reported that 400 mg ofginseng improved accuracy and a 200 mg dose slowedspeed of processing on serial sevens but had no effect onserial threes.36 An acute dose of ginseng (200 or 400 mg)improved accuracy on a task of concentration (serialsevens) after 2 h, but it did not affect concentration (serialthrees) or speed of processing.46 However, in a subse-quent study from the same authors,43 the opposite effectwas reported; the same dose of ginseng improved con-centration (serial threes) and improved speed of process-ing but did not affect serial sevens. On the basis of thesestudies, no consistent evidence is available to substantiatethe claim that ginseng affects cognition in healthysubjects.


Summary. The literature is inconsistent regarding theeffects of ginseng on mood and cognition. Althoughseveral studies report that it improves cognitive tasks, onestudy reports both positive and negative findings at dif-ferent doses and time points41; the effect also variesbetween different studies from the same authors.46,43 Reayet al.43 postulated that possible differences in performancemight stem from inconsistencies in ginsenosides in theextract.

Glucose

Glucose, a simple sugar, is the main energy source for thebrain. It is required to perform cognitive tasks,98 but thepotential benefit of supplementation beyond normaldietary intake is unclear. Although memory is a minorcomponent of mental energy, a large body of data con-cerns the relationship between glucose and memory.Mood was occasionally included in these studies to ascer-tain differences in arousal and tension, which have indi-rect effects on memory. The effects of glucose on othercognitive functions, such as attention, are not as welldocumented.

Mood. Several investigators have studied the relationshipbetween glucose and mood. In one study, a glucose drink(25 g) decreased fatigue (VAS) in healthy young adultsafter 120 min.43 In another study, glucose (500 mL)enhanced vigilance (VAS) in healthy adults 30 min afteradministration, but this was only when subjects knewthey were given glucose.48 Two studies found no effect ofglucose on mood (POMS).49,50 All of the studies usedsimilar dosing and timing. The differences in the reportedeffects of glucose on mood may be due to differing testinginstruments; the two studies reporting positive moodeffects used a VAS, while the two studies reporting noeffects administered the POMS.

Cognition. Glucose is an energy substrate for the brainand glucose supplementation may influence cognitivefunction. Raising blood glucose levels may increaseacetylcholine synthesis and cholinergic drugs influ-ence attention. Numerous studies have examined therelationship between glucose and cognitive functionbut have primarily focused on memory. Glucose has beenreported to improve some aspects of memory (spatial,logical, word list recall, short- and long-termmemory).48,49,53,54,57–59,62–71,73,75–78 However, additionalstudies report that glucose does not enhance certainaspects of memory (recall, visual, short- and long-termmemory).48,50–52,55–58,60–62,71,74,75 Discrepancies in thereported findings may derive from the age of thesubjects (young versus elderly), the type of memorytested (declarative versus short-term memory), testing

instrument, glucose dose, time of testing, and duration oftreatment. The available studies lack consistency in thetype of memory-testing instrument used. These inconsis-tencies prohibit the formation of any conclusions regard-ing the memory effects of glucose.

Subject age may be particularly relevant in studies ofglucose administration. Older adults are more likely tohave poor blood glucoregulation; thus, glucose adminis-tration may be more likely to affect cognition in thispopulation. Glucose increased performance on someaspects of declarative recall and logical memory in olderparticipants,53,59,62–65,67 but it had no effect in younger par-ticipants.64 A 50 g glucose beverage given to healthyelderly and young adult subjects improved logicalmemory in elderly adults and improved immediate recall(digit span forward) in young adults when subjects weretested immediately after administration.59 Additionally,the same authors replicated this finding of improvedlogical memory in older adults but found no effect ofglucose on short-term memory.62 A 50 g glucose beverageresulted in greater improvements in memory when givenbefore task acquisition than before memory retrieval taskin elderly participants.63,65 Manning et al.62 also reportedno effect of glucose in the elderly on other tests of cogni-tion, such as attention (letter cancellation test). Thesestudies all used the same glucose dose (50 g), but cogni-tion was tested at different times after administration andhad small sample sizes. These findings in the elderly seemlimited to certain types of memory (i.e., logical anddeclarative) and do not extend to other cognitive func-tions, such as attention. Since the currently available evi-dence for the memory effect is from the same group ofauthors, replication by separate laboratories is needed toconfirm the observed effects.

Blood glucose regulation might influence the efficacyof glucose supplementation in enhancing memory. Bloodglucose levels after glucose supplementation were associ-ated with better long-term verbal memory.57,75 Fosteret al.57 administered 25 g of glucose to healthy youngadults and measured short- and long-term verbal andnonverbal memory immediately after glucose adminis-tration; they found that blood glucose correlated withimproved long-term verbal memory but not with short-term verbal memory or long-term nonverbal memory.Performance on a recall task was positively correlatedwith blood glucose levels.75 A correlation was observed 15and 30 min after glucose administration (50 g) betweenblood glucose levels and improved short-term memoryperformance using a word recall task, but no effect onspatial memory was found.52 Owens et al.72 observedfaster decision times in healthy young subjects (mean age,21.2 years) 30 min after receiving 50 g of glucose. Reayet al.43 found that 25 g of glucose enhanced performanceon the serial threes and sevens tasks 120 min after admin-


istration in young subjects (mean age, 21.9 years). In con-trast, higher-than-baseline blood glucose levels measured30 and 60 min after glucose administration were associ-ated with poor performance on memory tasks measuredby the Wechsler Memory Scale.58 At this time, no conclu-sions can be drawn regarding blood glucose levels andcognitive function; variation in time of blood draw andcognitive task testing may contribute to the disparateresults. Blood glucose levels may impact long-term verbalmemory, but more research is needed.

Summary. At this time, little evidence links glucoseintake to enhanced mood. A variety of studies haveexplored the relationship between glucose and memory,but the results are inconsistent. Contributing to thisinconsistency are variations in timing, dosing, and studypopulation. Other potentially relevant cognitive tasks,such as attention and vigilance, have not been substan-tially evaluated. Certain populations, such as the elderlyor those with poor glucoregulation, are more likely toshow improvements after glucose intake.99,100

Omega-3 polyunsaturated fatty acids

PUFAs are integral membrane lipids that serve to main-tain both the structure and function of neuronal mem-branes, membrane-associated proteins, and proteincomplexes. Increased PUFA incorporation leads toincreased membrane fluidity that can increase thenumber and affinity of receptors in the synapse andimprove neurotransmission. Such fluidity is importantfor promoting synaptic plasticity that is essentialfor learning, memory, and other complex cognitiveprocesses.101

Docosahexaenoic acid (DHA, 22:6 n-3) is consideredto be an essential PUFA because it cannot be created denovo in humans.101 a-linolenic acid (ALA, 18:3 n-3) andeicosapentaenoic acid (EPA, 20:5 n-3) are converted toDHA by some cell types and organs to a minor extent.DHA and EPA are initially produced by photosyntheticmicroalgae and are exclusively derived from marineanimals. Little EPA or ALA is found in the brains ofhumans. In contrast, DHA is found predominantly inneuronal membranes in the gray matter and constitutesthe major omega-3 PUFA in the brain. DHA may alsoplay a key role in both the structure and function of brainregions involved in the formation of new memories. Hip-pocampal DHA levels have been associated with dietaryintake in rats, and higher levels have been shown toenhance hippocampal-dependent learning processes.102

Omega-3 PUFAs may also act as mood stabilizers andhave beneficial effects in several neuropsychiatric disor-ders, such as depression,103–105 schizophrenia,106 and age-related cognitive decline.107 Chronic use of high-dose

omega-3 PUFAs (>3 g/d) must be monitored becauseimpaired blood coagulation and immune responsedepression may result.108

Mood. Researchers have investigated associationsbetween omega-3 PUFAs and mood because of theireffects on neuropsychiatric disorders. Two similar studiesby Fontani et al. found that 2.8 g/d of omega-3 PUFAs(EPA + DHA, 2:1, fish oil) increased vigor and decreasedfatigue (POMS) in young participants at 5 weeks80 and at10 weeks,79 but the results have not been replicated byother researchers. In contrast, another study reported thatomega-3 supplementation (EPA + DHA, source notspecified) had no effect on depressed mood.82 The differ-ent mood instruments used in the studies (i.e., POMSversus a depression inventory) may contribute to the con-flicting results. At this time, there is not enough evidenceto determine if omega-3 PUFAs alter mood in healthyadults.

Cognition. Several observational studies of fish intake viadietary recall suggest an association exists between highfish intake (but not necessarily omega-3 intake) andreduced cognitive decline in older subjects. High dietaryfish intake improved scores of global cognitive functionon the Mini-Mental State Examination and preventeddecline in older adults in three studies.83,84,89 A study of2,031 subjects aged 70–74 years in Norway reported thatsubjects whose mean daily intake of fish and fish productswas �10 g/d had significantly better mean test scores andlower prevalence of poor cognitive performance thanthose whose intake was <10 g/d.86 The associationsbetween seafood consumption and cognition were dose-dependent and the effect was more pronounced for con-sumption of nonprocessed lean fish and fatty fish. In astudy of elderly subjects (65 years and older) participatingin the Chicago Health and Aging Project, Morris et al.85

observed reduced cognitive decline in subjects consum-ing fish at least once per week, but the reduction was notassociated with estimates of omega-3 PUFA intake.

Two prospective studies of fish consumption andcognitive decline in older subjects reached opposite con-clusions. In the Zutphen Elderly Study, fish consumers(aged 70–80 years) had significantly lower 5-year subse-quent cognitive decline than nonconsumers.87 In oldermen (mean age, 68 years) participating in the VeteransAffairs Normative Aging Study, no significant associa-tions between fatty fish or omega-3 PUFA intake andcognitive performance or change were observed.88

Intervention studies of omega-3 PUFA supplemen-tation reveal effects on differing cognitive outcomes. One30-month observational study in older adults (each 64years old) reported that fish-oil supplement use was asso-ciated with better speed of processing, as measured by the


digit symbol subtest (Wechsler Adult Intelligence Scale-revised), but had no effect on verbal memory.90 However,a study administering omega-3 supplements to healthyadults (age range, 18–70 years) for 12 weeks reported noeffect on speed of information processing or workingmemory.82 Verbal fluency scores improved significantlyin older women (age range, 60–80 years) receiving800 mg/d DHA for 4 months, but measures of mentalprocessing speed and accuracy were not affected bysupplementation.81 Omega-3 PUFA supplementation inyoung and middle-aged adults (age range, 22–51 years)for 5 weeks improved reaction times but had no effect onattention.80

Summary. The available evidence suggests that fish con-sumption and omega-3 PUFAs might delay or reducecognitive decline in the elderly. Despite the strength ofmuch of these data, fish consumption patterns and thetiming and duration of omega-3 PUFA supplementationhave yet to be determined. Some data suggest thatomega-3 supplementation is more beneficial if adminis-tered prior to the onset of cognitive decline. Lifelongdietary habits may also be necessary to observe a favor-able effect of fish intake and/or omega-3 PUFA supple-mentation on age-related cognitive outcomes.101

Additional well-designed trials of omega-3 supplementa-tion implementing a comprehensive battery of cognitivetests are required to clarify what cognitive tasks may bealtered.

LIMITATIONS OF THE CURRENT DATA

The presently available literature suggests Ginkgo bilobaaffects certain aspects of mood and attention in healthysubjects, and associations exist between fishconsumption/omega-3 PUFAs and reduced risk of age-related cognitive decline. However, additional studies arerequired to substantiate the existing data. The literaturefor glucose could also benefit from well-designed studiesthat evaluate cognitive tasks that are major componentsof mental energy, such as attention and vigilance.

For many foods, dietary constituents, and dietarysupplements (including ginseng), little consistent evi-dence is available to confirm their effects on mentalenergy, even though claims are currently being made forconsumer products. The usefulness of the existing data islimited by poor study designs with limitations thatinclude varied populations, differing study durations,small sample sizes, inadequate accounting of baselineconsumption, inadequate dosing and/or food intakeinformation, and lack of accounting for natural productvariation, as well as the lack of a uniform battery of teststo detect effects.

The composition of natural products may varygreatly between manufacturers and even batches of thesame product. These variations often stem from varia-tions in raw plant material (varietal factors and the partsof plant products derived), climate, growing season, soil,rainfall, and other growing conditions, method of prepa-ration, and types of solvents used in the extractionprocess. Differing sources may also create variationamong products. For example, different omega-3 PUFAsor combinations of omega-3 PUFAs can be sourced fromfatty fish (EPA + DHA), algae (DHA), or seed oil (ALA).Additionally, observational studies cannot control for thewide variety of dietary sources of a particular nutrient,and dietary recall by participants may be inaccurate.

CONCLUSION

One of the greatest obstacles for interpreting the mentalenergy literature is the use of an immense variety oftesting instruments, which makes it difficult (or impos-sible) to compare results across studies and to identify thereasons for inconsistent findings. A challenge for futureresearch is, therefore, to promote the use of standardizedmethods with adequate sensitivity for measuring mentalenergy and to advocate the consistent use of thosemethods. Failure to find robust effects for many dietaryconstituents and supplements may partially result from alack of method sensitivity, rather than a true absence ofeffect. Standardized methods would allow comparisons tobe made of the relative potency of different supplementsand foods and provide greater clarity regarding the natureof the observed effects. Ideally, experiments would use apost-training design with time-dependent effects mea-sured; however, few of the current studies employ thisdesign.

Double-blind and placebo-controlled studies withadequate numbers of subjects to provide sufficient statis-tical power are needed as are controls for circadian varia-tion in performance and practice effects.109 Individualdifferences in response to dietary constituents and/orsupplements may require larger sample sizes to increasethe statistical power. Multiple doses/intakes should alsobe tested, when feasible, to obtain more complete dose-response data. Meal composition studies should includebaseline tests and control for nutritional history (i.e., useof a within-subjects design). Subjects with a low baselineintake will likely show greater improvement than thosewho already consume the dietary constituent at adequateor high levels. Future cognitive research also needs tocontrol for population effects due to demographic char-acteristics such as age, gender, socioeconomic status, andeducational level.110

Motivation is an important aspect of any neuropsy-chological testing. A subject’s willingness to engage in a


task and complete all trials with the same level of engage-ment depends on many factors, including motivation.Differences in motivation can result in wide variations intask performance between subjects.110 Therefore, studiesevaluating mood and cognition should also include mea-sures of motivation.

At this time, the neurobiological mechanisms under-lying mental energy are not clearly elucidated. Ideally,future research should measure biomarkers of exposure/intake (e.g., measure the amount of the dietary constitu-ent in blood, saliva, or urine) and possibly of effect. Avariety of techniques are used to study human brainmetabolism, neurotransmission, and regional blood flow.Some of these techniques including functional magneticresonance imaging, single-photon emission computedtomography, and positron emission tomography mayallow investigation of the neurobiological mechanismsunderlying changes in mood, motivation, and cognition.

Acknowledgments

HE Gorby and AM Brownawell contributed equally to thepreparation of this manuscript.

Disclaimer. This independent review was developedunder a contract between the Life Sciences ResearchOrganization (LSRO), Bethesda, MD, and the Interna-tional Life Sciences Institute (ILSI) North America,Wash-ington, DC. The conclusions drawn do not represent theofficial views of LSRO or ILSI. The mention of tradenames, commercial products, or organizations does notimply endorsement by LSRO or ILSI North America. Theopinions expressed herein are those of the authors and donot necessarily represent the views of the InternationalLife Sciences Institute (ILSI).

Declaration of interest. HE Gorby, AM Brownawell, andMC Falk are employees of the Life Sciences ResearchOrganization and received compensation for servicesperformed in researching and writing this review. Thereare no other pending financial interests or conflicts ofinterest.

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