The Cognitive-Enhancing Effects of Bacopa monnieri: A Systematic Review of Randomized, Controlled Human Clinical Trials

Abstract

Traditional knowledge suggests that Bacopa monnieri enhances cognitive performance. Such traditional beliefs have now been scientifically tested through a handful of randomized, controlled human clinical trials. The current systematic review aimed to examine the scientific evidence as to whether Bacopa can enhance cognitive performance in humans.
A systematic review of randomized controlled trials is presented. Multiple databases were systematically searched by multiple authors. Relevant trials were objectively assessed for methodological quality.
The subjects studied were adult humans without dementia or significant cognitive impairment. Interventions: B. monnieri, including Bacopa extracts, were administered over long-term supplementation periods.
Any validated cognitive test, whether a primary or secondary outcome.
Six (6) studies met the final inclusion criteria and were included in review. Trials were all conducted over 12 weeks. Across trials, three different Bacopa extracts were used at dosages of 300-450 mg extract per day. All reviewed trials examined the effects of Bacopa on memory, while other cognitive domains were less well studied. There were no cognitive tests in the areas of auditory perceptual abilities or idea production and only a paucity of research in the domains of reasoning, number facility, and language behavior. Across studies, Bacopa improved performance on 9 of 17 tests in the domain of memory free recall. There was little evidence of enhancement in any other cognitive domains.
There is some evidence to suggest that Bacopa improves memory free recall with evidence for enhancement in other cognitive abilities currently lacking perhaps due to inconsistent measures employed by studies across these cognitive domains. Research into the nootropic effects of Bacopa is in its infancy, with research still yet to investigate the effects of Bacopa across all human cognitive abilities. Similarly, future research should examine the nootropic effects of Bacopa at varied dosages and across different extracts.

Full text

Review Article
The Cognitive-Enhancing Effects of Bacopa monnieri:
A Systematic Review of Randomized, Controlled
Human Clinical Trials
Matthew P. Pase, BSc, BA(Hons),
1
James Kean, BSc(Hons),
1
Jerome Sarris, MHSc, PhD,
1,2
Chris Neale, BSc, MSc,
1
Andrew B. Scholey, PhD,
1
and Con Stough, PhD
1
Abstract
Objectives: Traditional knowledge suggests that Bacopa monnieri enhances cognitive performance. Such tradi-
tional beliefs have now been scientifically tested through a handful of randomized, controlled human clinical
trials. The current systematic review aimed to examine the scientific evidence as to whether Bacopa can enhance
cognitive performance in humans.
Design: A systematic review of randomized controlled trials is presented. Multiple databases were systemati-
cally searched by multiple authors. Relevant trials were objectively assessed for methodological quality.
Subjects: The subjects studied were adult humans without dementia or significant cognitive impairment.
Interventions: B. monnieri, including Bacopa extracts, were administered over long-term supplementation periods.
Outcome measures: Any validated cognitive test, whether a primary or secondary outcome.
Results: Six (6) studies met the final inclusion criteria and were included in review. Trials were all conducted
over 12 weeks. Across trials, three different Bacopa extracts were used at dosages of 300–450 mg extract per day.
All reviewed trials examined the effects of Bacopa on memory, while other cognitive domains were less well
studied. There were no cognitive tests in the areas of auditory perceptual abilities or idea production and only a
paucity of research in the domains of reasoning, number facility, and language behavior. Across studies, Bacopa
improved performance on 9 of 17 tests in the domain of memory free recall. There was little evidence of
enhancement in any other cognitive domains.
Conclusions: There is some evidence to suggest that Bacopa improves memory free recall with evidence for
enhancement in other cognitive abilities currently lacking perhaps due to inconsistent measures employed by
studies across these cognitive domains. Research into the nootropic effects of Bacopa is in its infancy, with
research still yet to investigate the effects of Bacopa across all human cognitive abilities. Similarly, future research
should examine the nootropic effects of Bacopa at varied dosages and across different extracts.
Introduction
Bacopa monnieri (L.) Wettst.(syn.Bacopa monniera
Hayata & Matsum), from the family Scrophulariaceae, is a
perennial creeping herb that thrives in damp soils and marshes
throughout the subcontinent. Bacopa has long been renowned
for its medicinal properties. This has been documented in the
sixth-century Ayurvedic text, the Caraka Samhita,wherebyBa-
copa is recommended for the treatment of various mental con-
ditions.
1
Of late, Western medicine has shown interest in this
ancient herb as a potential cognitive enhancer.
Studies conducted on animals were among the first to
investigate the cognitive- enhancing effects of Bacopa.
2
Using
an alcoholic extract (40 mg/kg orally for 3 days), Singh and
Dhawan showed that Bacopa improved learning in a shock-
motivated brightness discrimination task and attenuated
memory deficits induced by the administration of various
neurotoxins.
3
Preclinical work suggests that Bacopa’s mech-
anisms of action on the central nervous system are varied
and include antioxidant activity (across various Bacopa ex-
tracts),
4–7
b-amyloid scavenging properties (Bacopa ethanol
extract: 40 or 160 mg/kg orally),
8
protection against b-
amyloid-induced cell death (Bacopa ethanol extract adminis-
tered to cultured neurons),
9
modulation of frontocortical and
hippocampal acetylcholine levels (5–10 mg/kg Bacopa extract
administered to animal models of Alzheimer disease),
10
and
1
Centre for Human Psychopharmacology, Faculty of Life and Social Sciences, Swinburne University of Technology, Hawthorn, Australia.
2
Department of Psychiatry, Faculty of Medicine, The University of Melbourne, Melbourne, Australia.
THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE
Volume 18, Number 7, 2012, pp. 1–6
ªMary Ann Liebert, Inc.
DOI: 10.1089/acm.2011.0367
1

modulation of cholinergic neuron densities (Bacopa ethanol
extract: 20–80 mg/kg orally ).
11
Such effects of Bacopa have
been attributed to the saponins contained within Bacopa,
most notably that of bacoside A.
1
Of late, there have been a large number of studies ex-
ploring the cognitive-enhancing effects of Bacopa in humans.
Although a previous review has provided an excellent
general overview of Bacopa’s reputed health benefits,
1
to the
authors’ knowledge, no study has systematically reviewed
the cognitive-enhancing effects of Bacopa in humans. Fur-
thermore, since the review by Russo and Borrelli,
1
several
key trials in the area have surfaced. Consequently, this re-
view aimed to qualitatively examine the cognitive-enhanc-
ing effects of Bacopa in humans. A qualitative systematic
review of relevant trials was performed to explore the long-
term effects of Bacopa extracts on any validated cognitive
outcome.
Methods
Database searching
The electronic databases SCOPUS, PubMed, and the
Cochrane Library were searched until April 2011 by com-
bining the following key words and truncations: cognit* or
memory or neuropsycholog* or neurocognit* or executive
function* with bacopa or brahmi or bacoside* or water
hyssop. Searching was limited to randomized controlled
trials conducted in adult humans. Forward searchers were
performed on all trials meeting the inclusion criteria using
SCOPUS.
Trial selection
Located trials were considered appropriate for review if
they used Bacopa as a monotherapy, examined the effects of
Bacopa on valid cognitive outcomes, used a randomized and
controlled design, and had adequate methodologic quality as
defined by a score of at least 5 on the augmented Jadad scale.
To limit heterogeneity at the study level, trials were only
considered appropriate for review if they were conducted in
adult samples without cognitive impairment and if they
administered Bacopa daily over a long-term supplementation
period, defined as 4 or more weeks. Articles of all languages
were considered appropriate for review.
Quality rating
Each trial was analyzed for methodologic quality using a
purpose-designed modified Jadad scale
12
as first developed
in Sarris and Byrne.
13
Using the modified Jadad scale, studies
were objectively assessed for quality and given 1 point when
each of the following criteria was satisfied: (1) Was the study
described as randomized? (2) Was the randomization pro-
tocol detailed and appropriate? (3) Was the study described
as double-blind? (4) Was the blinding process detailed and
appropriate? (5) Did the study have a control group? (6) Was
the control detailed and appropriate? (7) Were there ade-
quate exclusion criteria? (8) Was the intervention used at a
therapeutic dose? (9) Was there a description of withdrawals
and dropouts? and (10) Were the data clearly and adequately
reported? Using this scale, each trial was given a score be-
tween 0 and 10, with higher scores reflecting superior
methodologic quality.
Outcomes
Any valid test of cognitive performance was considered ap-
propriate for review, whether a primary or secondary outcome.
Cognitive tests were grouped into true cognitive abilities, as
guided by the extensive factor analytic work by Carroll.
14
These
cognitive abilities include the following: (1) reasoning, which
includes general, quantitative, syllogistic, and verbal reasoning
as well as induction; (2) language behavior, which includes
vocabulary, spelling ability, phonetic coding, and verbal com-
prehension; (3) memory, which includes associative memory,
free recall, visual memory, and memory span; (4) visual per-
ception, which includes figural relations, closure speed, and
perceptual speed; (5) auditory perception, which includes pitch
discrimination; (6) number facility, which includes the ability to
compute basic numerical operations; (7) mental speed, which
includes processing speedand simple reaction time; and (8) idea
production, which includes abilities in producing words, ideas,
and figural creations such as originality and word fluency.
Data handling
The systematic review process, including article searching
and assessment of inclusion criteria, was completed indepen-
dently by 3 researchers (JK, CN, and MPP) with disagree-
ments resolved according to consensus of the entire research
group. Four (4) authors (MPP, JK, CN, and JS) independently
rated the methodologic quality of each study using the mod-
ified Jadad scale again, with results later compared and a final
score agreed upon according to group consensus. The data
gathered from each study included general study descriptives
as well as all cognitive outcomes and their reported signifi-
cance. Cognitive outcomes from each study were grouped into
the true cognitive abilities by 2 neuroscientists (MPP and CS).
To limit the likelihood of a Type I error, the following protocol
was followed. First, when a study had multiple testing time
points, only the results from the longest follow-up time point
were included in review. Second, a single cognitive test, from
any given study, was only grouped into the one cognitive
ability most representative of the original task.
Results
Of the 64 located studies, 10 were deemed to be relevant
randomized controlled trials (Fig. 1). Of these 10 trials, 4
were excluded for not meeting the inclusion criteria, leaving
6 studies for review.
The characteristics of the six studies included in this review
are shown in Table 1. Studies were relatively homogeneous. All
were conducted over an intervention period of 12 weeks and all
were randomized, parallel group, double-blind, and placebo-
controlled trials. Sample populations were comparable both in
age range and in that subjects tended to be healthy without any
chronic illnesses. Although one study recruited a sample with
subjective memory complaints, the sample was apparently free
from cognitive impairment.
15
Despite no studies using intention-
to-treat analysis, the average quality of trials was high (modified
Jadad scale mean score =8.5/10).
With respect to the interventions, three studies used
KeenMindBacopa supplements, two used BacoMind,

and
one used Mediherb

. Across supplements, extract dosages
ranged from 300 to 450 mg per day. The KeenMind Bacopa
supplement is derived from the stems, leaves, and roots of
2 PASE ET AL.

Bacopa and is extracted with 50% ethanol. BacoMind is a
Bacopa supplement, extracted from alcohol and standardized
to contain nine active constituents.
16
Both KeenMind and
BacoMind have an herb-to-extract ratio of 20:1, and both
provide a daily oral dosage equivalent to 6000–9000 mg of
dried herb. The Mediherb supplement is manufactured from
the dried aerial portions of Bacopa extracted with a methanol-
to-water ratio of 70:30. The one study to use the Mediherb
Bacopa extract supplemented at 300 mg extract per day. The
dry extract ratio is 50:1, providing a daily oral dosage
equivalent to 1500 mg of dried herb.
Table 2 outlines the cognitive tests used in each study
grouped into the true cognitive abilities defined by Carroll.
14
This method of grouping allows for all cognitive outcomes to
be compared across studies. As seen in Table 2, bold font is
used to indicate when performance on a cognitive test was
significantly improved by Bacopa, as reported in the original
study. Across trials, there were no cognitive tests in the areas
of auditory perceptual abilities or abilities in producing and
retrieving words, ideas, and figural creations. Only two
studies examined the effects of Bacopa on reasoning abilities,
with no evidence of any enhancement following Bacopa
supplementation.
17,18
Only one study investigated the effects
of Bacopa on language behavior
17
and one study investigated
its effects on number facility,
15
again without any evidence of
improvement in either of these cognitive abilities following
Bacopa. Five (5) studies used a total of nine cognitive tests
indicative of visual perceptual abilities.
15,17–20
The only two
of these tasks to show any enhancement following Bacopa
were the Stroop (reduced reaction time)
19
and rapid visual
information-processing tasks (fewer false alarms).
20
Three (3)
studies (six cognitive tests in total) measured the effects of
Bacopa on mental speed.
17,20,21
The only task showing im-
provement after Bacopa was inspection time,
17
with no re-
ductions evident in choice or simple reaction time.
Every study included in this review administered tests of
memory. Given the richness of information available, this
factor was subdivided into the more specific facets of
memory identified by Carroll.
14
These domains include (1)
memory span: the quantity of information one can recall in
order following a single exposure to the information; (2)
associative memory: the ability to recall or recognize infor-
mation paired (associated) with other arbitrary information;
(3) free recall memory: recall of arbitrary information when
the information to be recalled exceeds the quantity of one’s
memory span; (4) meaningful memory: the ability to recall or
recognize information when the information to be remem-
bered has meaning; and (5) visual memory: recall or recog-
nition of visual material that cannot be easily recoded into a
nonvisual modality.
14
The long-term effects of Bacopa ad-
ministration on these abilities of memory are also presented
in Table 2. Again, a cognitive task is highlighted in bold font
if performance on the task was improved by Bacopa, as re-
ported in the original study.
As displayed in Table 2, the majority of tests were in the
domain of free recall memory, with the most frequently used
test being the auditory verbal learning test. Of the 17 tasks in
this domain, 9 reported a significant effect of Bacopa on free
recall memory.
15,17–19
Of the six tests representative of mem-
ory span, performance on only one task was significantly
improved by Bacopa.
15
There were four tasks in the domain of
meaningful memory involving the recall of short stories and
passages.
15,21
None of these tasks was improved by Bacopa.In
thedomainofvisualmemory,therewereninetasksacross
FIG. 1. Systematic review
flowchart. RCT, randomized
controlled trial.
COGNITIVE-ENHANCING EFFECTS OF BACOPA MONNIERI 3

Table 1. Study Characteristics of Trials Included in Review
1st
Author/year Herb/daily dose
Bacoside
content Design
Duration
(wk)
a
N
Dropout
(%) Sample
Cognitive
outcomes
b
Age
(mean)
Male
(%) ITT
Quality
rating
c
Barbhaiya 2008
16
BacoMind

450 mg
Bacoside
A
3
>5%
w/w
DB
PC
PG
12 65 5 Memory complaints but no
severe cognitive problems
Visual P
Number F
Memory
65 yr 66 N 9/10
Calabrese 2008
19
MediHerb

300 mg
Min. 50% DB
PC
PG
12 54 11 Adults over 65 without
memory complaints or
signs of dementia
Visual P
Memory
74 yr 40 N 9/10
Morgan 2010
18
BacoMind
300 mg
40%–50% DB
PC
PG
12 98 17 Healthy adults over 55 yr
without neurological or
psychiatric illness
Reasoning
Visual P
Memory
65 yr 47 N 10/10
Roodenrys 2002
21
KeenMind
300 mg if subject <90 kg
& 400 mg if >90 kg
55% DB
PC
PG
12 84 10 Healthy adults not taking
medications or herbal
supplements
Mental S
Memory
49 yr 37 N 6/10
Stough 2001
17
KeenMind
300 mg
Min. 55% DB
PC
PG
12 46 NS Healthy. No physical or
psychiatric conditions and
no medications
Reasoning
Language B
Visual P
Mental S
Memory
39 yr 24 N 8/10
Stough 2008
20
KeenMind
300 mg
Min. 55% DB
PC
PG
12 107 42 Healthy. No neurological or
psychiatric disease. No
cognitive enhancing drugs
Visual P
Mental S
Memory
43 yr 34 N 9/10
a
Duration of supplementation.
b
All cognitive abilities investigated are listed, regardless of significance.
c
Quality rating based on augmented Jadad scale.
BM, Bacopa monnieri; DB, double-blind; PC, placebo-controlled; PG, parallel groups; ITT, intention-to-treat analysis used; NS, not specified; yr, years; Visual P, Visual perception; Mental S, mental
speed; Language B, language behavior; Number F, number facility.
4

studies.
15,18–21
Performance on only one of these tasks was
significantly enhanced by Bacopa supplementation.
15
Discussion
The current systematic review of randomized, controlled
trials revealed some evidence to suggest that Bacopa is effica-
cious in improving the learning and free recall of information.
This suggests that Bacopa could potentially be clinically pre-
scribed as a memory enhancer. At present, there is insufficient
evidence to suggest that Bacopa improves other domains of
cognitive performance in healthy nondemented subjects. Al-
though this may reflect heterogeneity in the cognitive tests used
across studies, available evidence suggests that Bacopa is more
efficacious in improving memory free recall than other aspects
of cognitive performance. This review also highlights the focus
on testing the memory-enhancing effects of Bacopa at the ex-
pense of other cognitive domains.
The focus toward testing memory over other cognitive
domains most probably stems from Bacopa’s long-standing
Ayurvedic reputation as a potent ‘‘memory enhancer.’’ Al-
though the first randomized controlled human clinical trial
to explore the long-term effects of Bacopa on cognition re-
ported both enhancement in memory and cognitive speed,
17
follow-up research has not given mental speed (or other
cognitive domains) the same attention as memory.
Between studies, there was remarkable homogeneity in
the durations of supplementation and dosage sizes with all
trials supplementing for 12 weeks. Studies using the same
Bacopa extracts tended to supplement at comparable dosages,
with KeenMind used at 300–400-mg extract across three
studies and BacoMind used at 300–450-mg extract across two
studies. This indicates that trials in the area have generally
adhered to the recommended daily dosages. To advance
current knowledge, future research in the area is required to
manipulate dosage sizes and supplementation durations.
Given that studies using Bacopa acutely have not produced
significant findings
22
and that long-term studies have all
been of short duration (3 months), future studies are needed
to explore the effects of Bacopa on human cognition over
longer supplementation periods. The implementation of
longer supplementation periods may also allow for exami-
nation of the effects of Bacopa on cognitive decline.
The current review provides future studies with the jus-
tification for examining the effects of Bacopa on memory free
recall. However, future research is also required to investi-
gate the effects of Bacopa on those cognitive abilities that have
been overlooked, including reasoning, mental speed, idea
production, language behavior, and number facility.
Strengths of the current review include the breadth of
literature searched, the conformity to Preferred Reporting
Items for Systematic Reviews and Meta-Analyses (PRISMA)
standard,
23
the objective assessment of trial quality by nu-
merous authors, and the stringent inclusion criteria em-
ployed. Importantly, trials were rather homogeneous in
terms of sample populations, supplementation periods, and
administered dosages. Furthermore, included trials were of
high quality and all were randomized, placebo-controlled,
and double-blind, extending confidence to the cumulative
results. The following limitations warrant discussion. This
review was limited to qualitative analysis, given the varia-
tion in cognitive tests used between studies and the fact that
different extracts of Bacopa were compared. An objective
meta-analysis in this area is impractical, given that most
Table 2. Neuropsychologic Tests of Each Study Grouped into True Cognitive Abilities
Ability Cognitive tests
Reasoning Trail-making test B (Stough, 2001); Trail-making test B (Morgan, 2010)
Visual Perception DS coding & Digit cancellation (Barbhaiya, 2008); Stroop** & Divided attention task (Calabrese,
2008); Trail-making A (Morgan, 2010); Trail-making A & DS coding (Stough, 2001); Digit
vigilance & RVIP* (Stough, 2008)
Language behavior Speed of comprehension test sentences (Stough, 2001)
Number Facility Serial subtraction (Barbhaiya, 2008)
Mental Speed Inspection time,* SRT, CRT (Stough, 2001); SRT & CRT (Stough, 2008); speeded coding task
(Roodenrys, 2002)
Memory
Free recall Memory AVLT IR & AVLT DR* (Barbhaiya, 2008); AVLT DR* & AVLT IR (Calabrese, 2008); AVLT trial 1,
AVLT trial 2, AVLT trial 3, AVLT trial 4,*** AVLT trial 5,* AVLT trial 6*** & AVLT trial 7
(DR)** (Morgan, 2010); AVLT learning rate,* AVLT forgetting rate,* AVLT proactive
interference* & AVLT retroactive interference (Stough, 2001); immediate word recall & delayed
word recall (Stough, 2008)
Associative Memory Paired associates similar IR, Paired associates dissimilar IR, Paired associates similar DR & Paired
associates dissimilar DR* (Barbhaiya, 2008); Word pairs DR,* Word pairs trial 1, Word pairs
trial 2 & Word pairs trial 3 (Roodenrys, 2002)
Memory Span DS backward** & DS forward (Barbhaiya, 2008); DS forward & DS backward (Roodenrys, 2002);
DS forward, DS backward
Visual Memory Visual retention I,* Visual retention II (Barbhaiya, 2008); WAIS letter-digit (Calabrese, 2008); Rey
complex figure copy, Rey complex figure IR, Rey complex figure DR (Morgan, 2010); Visual
span (Roodenrys, 2002); Spatial WM, Numeric WM, Delayed Picture rec (Stough, 2008)
Meaningful Memory Passages IR & Passages DR (Barbhaiya, 2008); Short story DR & Short story IR (Roodenrys, 2002)
DS, digit symbol; RVIP, rapid visual information processing; SRT, simple reaction time; CRT, choice reaction time; AVLT, auditory verbal
learning test; IR, immediate recall; DR, delayed recall; WAIS, Wechsler Adult Intelligence Scale; WM, working memory; rec, recognition.
*p<0.05, **p<0.01, ***p<0.001. Bold font is used to indicate when performance on a cognitive test was significantly improved by bacopa, as
reported in the original study.
COGNITIVE-ENHANCING EFFECTS OF BACOPA MONNIERI 5

relevant studies have utilized multiple cognitive tests indic-
ative of a single cognitive ability. Thus, hand picking one of
many cognitive tests to include in meta-analysis, in order to
satisfy the independence of samples assumption, would be a
subjective and therefore flawed exercise. As variations in
quality and bacoside content exist between Bacopa products,
different products may differentially affect cognitive out-
comes. This is something not accounted for when results were
pooled in the current review. Only through continued re-
search into the cognitive-enhancing effects of Bacopa will any
differential effects between supplements become evident.
Conclusions
ThereissomeevidencetosuggestthatBacopa enhances
memory free recall in nondemented subjects, and thus Bacopa
could potentially be clinically prescribed as a memory en-
hancer. At present, there is insufficient evidence to suggest that
Bacopa can enhance other domains of cognitive performance.
This may reflect heterogeneity in the measures employed by
studies across these cognitive domains. Research into the cog-
nitive-enhancing effects of Bacopa is still in its infancy, with
future research required to explore the cognitive-enhancing
effects of Bacopa at different dosages, over longer supplemen-
tation periods, and in specific populations. Future research is
also required to explore the effects of Bacopa on those cognitive
domains shown to be under-researched in the current review.
Acknowledgments
Matthew P. Pase is funded by a Menzies Foundation
Scholarship in Allied Health Science. Jerome Sarris is funded
by an Australian National Health & Medical Research
Council Trainee Fellowship (NHMRC funding ID 628875).
The review was funded in part by an Australian Research
Council (ARC DP1093825) Discovery grant to Con Stough
and Andrew B. Scholey.
Disclosure Statement
No competing financial interests exist for any authors. All
authors declare no conflicts of interest.
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Address correspondence to:
Matthew P. Pase, BSc, BA(Hons)
Centre for Human Psychopharmacology
Faculty of Life and Social Sciences
Swinburne University of Technology
Hawthorn 3122
Australia
E-mail: matthewpase@gmail.com
6 PASE ET AL.