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Original Research Communications

Randomized placebo-controlled study of the memory effects of

pomegranate juice in middle-aged and older adults
Prabha Siddarth,1 Zhaoping Li,2 Karen J Miller,1 Linda M Ercoli,1 David A Merril,1,3 Susanne M Henning,2 David Heber,2
and Gary W Small1
1 Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the
University of California, Los Angeles, CA, USA; 2 Center for Human Nutrition, David Geffen School of Medicine at the University of California, Los Angeles,
CA, USA; and 3 Pacific Brain Health Center at Pacific Neuroscience Institute, Santa Monica, CA, USA

ABSTRACT
Background: Antioxidant nutrients such as the polyphenols in
pomegranate juice may prevent neuronal damage from the free
radicals produced during normal metabolism. Previous research in
animals and a short-term clinical trial in middle-aged and older
adults support the potential memory benefits of pomegranate juice;
however, the long-term effects of pomegranate juice consumption on
cognition have not been studied.
Objective: In this study, we investigated the long-term effect of
pomegranate juice on memory in nondemented middle-aged and
older adults.
Methods: We performed a 12-month, randomized, double-blind,
placebo-controlled trial of pomegranate juice in middle-aged and
older adults. Two hundred and sixty-one subjects (aged 50–75 y)
were randomly assigned to consume pomegranate juice [8 oz (236.5
mL) per day] or a placebo drink (8 oz, matched constituents of
pomegranate juice except for pomegranate polyphenols). Memory
measures [Brief Visuospatial Memory Test-Revised (BVMT-R) and
Buschke Selective Reminding Test (SRT)] were assessed at 6
and 12 mo and analyzed using a mixed-effects general linear
model.
Results: Twenty-eight subjects in the pomegranate juice group and
33 subjects in the placebo group dropped out before completing
the study. Baseline variables in the 98 pomegranate juice and 102
placebo group subjects who completed the study did not differ
significantly. Group by time interaction was statistically significant
for BVMT-R Learning (F[2, 257]= 5.90, P = 0.003; between-group
effect size [ES] = 0.45): the change within the pomegranate group
was not significant (ES = 0.15), whereas the placebo group showed
a significant decline (ES = −0.35). Changes in the other BVMT-R
scores as well as the SRT measures were not significantly different
between groups.
Conclusions: Daily consumption of pomegranate juice may stabilize
the ability to learn visual information over a 12-mo period. This trial
was registered at clinicaltrials.gov as NCT02093130. Am J Clin
Nutr 2019;00:1–8.
Keywords: pomegranate juice, antioxidant polyphenol, normal
aging, memory, cognition
Introduction
Forgetfulness can be a normal part of aging as changes
including oxidative damage and inflammation occur in the brain.
Mild forgetfulness and loss of memory are among the top health
concerns of middle-aged and older adults. Memory loss can
begin as early as age 45 y (1) and as these deficits progress
with advancing age, they can interfere with daily functioning
and quality of life (2). Memory training programs are used to
maintain cognitive performance in older adults with normal aging
or mild memory challenges (3). However, there are few well-
designed prospective studies of nutritional interventions intended
to improve or stabilize memory performance during aging.
Healthy lifestyle behaviors such as engaging in aerobic
exercise, increasing mental activity, staying socially active,
avoiding tobacco and excess alcohol, and consuming a healthy
diet have also been recommended to benefit memory performance
and brain function (4–7). A promising line of research has
focused on foods that contain properties beneficial to healthy
brain functioning. Investigators have found that various nutrients
such as curcumin, sage, vitamin D, ω-3 fatty acids, and
This study was supported by The Wonderful Company, LLC, Fran and Ray
Stark Foundation Fund for Alzheimer’s Disease Research, John and Barbara
McLoughlin Gift Fundand the Parlow-Solomon Professorship (GWS).
The Wonderful Company, LLC, provided a gift for research in this area and
provided the juice and placebo drinks for the participants. The company had
no role in the design, implementation, analysis, and interpretation of the data.
Supplemental Tables 1 and 2 are available from the “Supplementary data”
link in the online posting of the article and from the same link in the online
table of contents at https://academic.oup.com/ajcn/.
Data described in the article will be made available in a de-identified form
without restriction.
Address correspondence to PS (e-mail: psiddarth@mednet.ucla.edu).
Abbreviations used: BVMT-R, Brief Visuospatial Memory Test-Revised;
CLTR, Consistent Long-Term Retrieval; ES, effect size; MCI, mild cognitive
impairment; SRT, Selective Reminding Test.
Received March 7, 2019. Accepted for publication August 29, 2019.
First published online 0, 2019; doi: https://doi.org/10.1093/ajcn/nqz241.

Am J Clin Nutr 2019;00:1–8. Printed in USA. Copyright © American Society for Nutrition 2019. All rights reserved. 1
2 Siddarth et al.
antioxidant foods may help to maintain cognitive function during
aging (8–11).
Some phytonutrients including pomegranate ellagitannins
may reduce oxidative stress and inflammation, and thus could
maintain brain health during aging (12). Large-scale, placebo-
controlled, randomized studies with antioxidant supplements in
nondemented adults have demonstrated better cognitive function
including 39% enhanced long-term memory performance in one
study (13). Adherence to a Mediterranean diet pattern, which
emphasizes colorful fruits and vegetables high in antioxidants,
has been linked to improved cognitive functioning (5) and
reduced rates of cognitive decline (14) in elderly subjects.
Numerous natural antioxidant compounds found in fruits and
vegetables have also been associated with neuroprotective effects
(15).
In the present study, we investigated the effect of pomegranate
juice on cognition in nondemented middle-aged and older adults.
Pomegranate juice is rich in ellagitannin polyphenols, which
have both antioxidant and anti-inflammatory properties. Animal
studies have shown that pomegranate juice and other polyphenol-
rich fruit juices protect against oxidant stress and amyloid-
induced brain injury in transgenic mouse models (16, 17).
Although some human studies on the use of polyphenols, such
as resveratrol (18–20) and flavanol (21), have provided initial
evidence that these supplements are associated with improved
memory performance, these studies were relatively short in
duration, ranging from acute interventions to 26 wk. The most
recent study (22) with 60 healthy elderly participants failed to
show significant improvements in verbal memory after 6 mo of
resveratrol use. In a pilot study of 23 subjects (aged 50–75 y) who
had mild memory complaints associated with aging, we found
that drinking 8 oz. of pomegranate juice daily for 1 mo both
improved memory performance and altered brain neural activity,
measured using functional MRI, in comparison to a control
group drinking taste-matched placebo juice without polyphenols
(23). The present study was designed to determine whether
pomegranate juice has long-term benefits over 1 y on cognitive
abilities in middle-aged and older nondemented volunteers.
Methods
Study design
Utilizing a randomized, double-blind, 2-group parallel design,
we tested memory performance in subjects consuming 8 oz.
(236.5 mL) of pomegranate juice (The Wonderful Company,
LLC) compared with those consuming a placebo drink. Eight
ounces of pomegranate juice used for the intervention contain
the following polyphenols: 368 mg punicalagins, 93 mg antho-
cyanins, 29 mg ellagic acid, and 98 mg other tannins, and we
have previously shown that plasma concentrations are similar
when consuming 8 oz. of juice or 1 g of pomegranate extract
(24, 25). The placebo drink contained the same constituents
of pomegranate juice (flavor, color, sugar, and acidity level)
except for pomegranate polyphenols. Identical packaging was
used for both the pomegranate juice and the placebo drink.
Subjects were sent weekly supplies of the study drink and
were instructed to drink 8 oz. daily for 12 mo. The statistician
prepared the randomization schedule using a computer-generated
random assignment scheme, which assigned subjects in a 1:1
ratio to each group. Group assignments were blinded to all
participants and study personnel, including care providers and
those assessing outcomes. Baseline assessments consisted of vital
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signs (blood pressure, respiratory rate, pulse, and temperature),
electrocardiogram, serum electrolytes, thyroid function, and
complete blood counts. Potential adverse events (including but
not limited to gastrointestinal difficulties, headaches, fatigue, skin
rash) and compliance with the pomegranate juice or placebo drink
consumption were assessed every 3 mo.
Subject selection and assessment
We performed baseline cognitive assessments on 261 subjects
who met study entry criteria from a pool of 995 potential
volunteers recruited through advertisements, media, and referrals
from physicians and families. Our study protocol detailed the
methods and procedures, as well as prespecified inclusion and
exclusion criteria (this trial was registered at clinicaltrials.gov
as NCT02093130). We determined a priori that a sample size
of ≥100 completers per arm was needed to detect an effect size
(difference between group means as a multiple of the SD) of ≥0.4
SDs, given an alpha level of 0.05 and power of 0.8.
To be included, volunteers were required to have objective
cognitive performance scores and clinical histories consistent
with normal aging or mild cognitive impairment (MCI). Subjects
with evidence of dementia or a major neurocognitive disorder
were excluded from the study. All subjects were aged between
50 and 75 y and agreed to participate for the entire 12 mo
of the trial. Subjects had adequate visual and auditory acuity
for neuropsychological testing; and had screening laboratory
tests and electrocardiograms without evidence of significant
medical conditions that might interfere with the study. Exclusion
criteria included: significant cerebrovascular disease (i.e., strokes
limiting communication abilities and interfering with study
procedures); probable Alzheimer’s disease, other dementia;
neurological or physical illnesses associated with cognitive
deterioration; inability to undergo MRI or with any significant
abnormality on brain MRI (e.g., tumor, stroke, vasogenic edema);
a history of myocardial infarction within the previous year or un-
stable cardiac disease; uncontrolled hypertension (systolic blood
pressure >170 or diastolic blood pressure >100); significant
liver or pulmonary disease, diabetes, or cancer; major depression
or any major psychiatric disorder; history of alcoholism or
substance addiction; use of vitamins other than a standard
multivitamin supplement; or use of any cognitive enhancing
supplements (e.g., gingko biloba, phosphatidyl serine), cognitive
enhancing drugs (e.g., donepezil, rivastigmine, memantine),
any juice containing pomegranate or pomegranate juice, or
investigational drugs within the previous month or longer,
depending on drug half-life. None of the participants from the
previous pilot study (23) were included in the present study.
At baseline, all subjects completed the Montreal Cognitive
Assessment (26) and the Beck Depression Inventory (27). A
neuropsychological test battery (28) was also performed to
assist in excluding subjects with dementia, and a standardized
measure of memory self-awareness, the Memory Functioning
Questionnaire (29), confirmed the presence of mild memory
complaints.
Compliance was determined based on participant diary
records. Participants were instructed to keep diaries every week
 Memory effects of pomegranate juice
and indicate whether they followed the protocol every day. Then,
during each of their visits, the research staff inspected these
diaries and tabulated, for each participant, the number of days
elapsed and the number of days marked by the participant as not
compliant. At the end of the study, the percentage of compliance
was calculated as the percentage of the total number of days
compliant over the total number of days elapsed. If the percentage
of compliance was ≥80%, then the participant was deemed to
have followed the protocol.
Blood samples were drawn for DNA analysis for apoE
genotyping using standard techniques (30). Genetic data were
available for 241 subjects. Written informed consent was
obtained from all subjects in accordance with the University of
California, Los Angeles Human Subjects Protection Committee
procedures. The trial began in January 2014 and was completed
in May 2018 and all data were collected at the Semel Institute
for Neuroscience and Human Behavior and Center for Human
Nutrition, David Geffen School of Medicine at the University of
California, Los Angeles, CA.
Primary outcome measures
Because our previous research indicated memory effects of
pomegranates, we chose 2 memory tests, namely, the Brief
Visuospatial Memory Test-Revised (BVMT-R) (31) and the
Buschke Selective Reminding Test (SRT) (32) as the primary
outcome instruments after 6 and 12 mo of treatment; thus,
these tests were given at each time point. Performance on the
BVMT-R was the primary outcome for visual memory. The
BVMT-R is a standardized measure of visual learning and recall
that presents 6 geometric designs to the subject for 10 s. The
subject is subsequently asked to draw on a separate page as
many of the figures as possible in their correct location. This
is repeated for a total of 3 learning trials. The Delayed Recall
trial is administered after a 25-min delay. A learning score
(indicating how the participant benefited from repetition) is also
calculated by subtracting the total correct items of Trial 1 from
the highest number of correct items recalled on Trial 2 or Trial 3.
Outcome measures from BVMT-R included the following: Total
Recall (number of designs recalled over the 3 learning trials;
measures Immediate Recall [i.e., short-term memory]); Delayed
Recall (number of designs recalled during the 25-min delayed
trial; reflects delayed recall for new information); and Learning
scores.
The Buschke SRT (32) performance was the primary outcome
for verbal memory. The SRT is a standardized measure of verbal
learning that presents 12 unrelated words to the subject, who
is then asked to immediately recall as many words as possible.
The examiner then selectively re-presents words (i.e., reminds)
that the subject was unable to recall on all subsequent trials,
although subjects must attempt to recall the entire word list.
This procedure is repeated until either the respondent attempts
all 12 learning trials, or until the respondent recites the entire list
on 2 consecutive trials without reminders (32). The Consistent
Long-Term Retrieval (CLTR) score is the number of words that
the subject recalls consecutively over trials without receiving
reminders and indicates how well the subject consolidates
the new information during the learning phase (encoding). In
addition to CLTR, we used the Buschke SRT Total Recall
(number of words recalled over the 12 trials) and Delayed Recall
3
(number of words recalled during the 30-min delayed trial) scores
as outcome measures.
To minimize practice effects, alternate versions of the Buschke
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SRT and the BVMT-R were administered and counterbalanced.
All tests were administered by trained psychometrists.
Statistical analysis
Before statistical analyses, all data were inspected for outliers,
skewness, kurtosis, and homogeneity of variance to ensure their
appropriateness for parametric statistical tests. The pomegranate
juice and placebo groups were compared on baseline demo-
graphic and clinical characteristics with chi-square statistics for
categorical measures and t-tests for continuous measures. All
subjects with baseline data were included in the examination of
all outcomes in intent-to-treat analyses. Our outcome measures
are continuous and were analyzed using a mixed-effects general
linear model, as implemented in PROC MIXED in SAS v 9.4
(SAS Institute, Cary, NC). Mixed models allow the use of all
available data from all subjects, thereby minimizing the effects
of loss to follow-up (33). We included treatment group as the
between-subject factor, time as the within-subject factor, and the
interaction term between time and treatment group as predictors.
Age, sex, and education level were used as covariates. We also
estimated separate moderation models for apoE-4 genetic risk,
overweight/obesity, and MCI status by including the interaction
term of apoE-4 or overweight/obesity or MCI by treatment group
by time, all respective lower-order interactions and main effects,
and the same covariates as the basic model. Post-hoc analyses
determined the significance of between-group differences and
within-group changes. We present test scores and statistics as
well as effect sizes (Cohen’s d) for group differences and within-
group changes. Because we had 6 outcome measures (3 scores
for BVMT-R and 3 scores for Buschke SRT), the significance
threshold for each of the outcome measures was set at 0.008
(0.05/6; 2-tailed).
Results
Participant flow and follow-up
Of the 261 subjects who met the study inclusion criteria for
randomization, 130 were assigned to the pomegranate group and
131 to the placebo condition. Nearly a quarter (23%) of the
randomized participants dropped out before completion. Neither
the drop-out rate (pomegranate: 22%; placebo: 25%) nor the
reasons for dropping out differed between the pomegranate and
the placebo groups (Figure 1). Subjects who withdrew did not
differ significantly from those who completed the study in mean
age or baseline cognitive measures. Of the 200 subjects who
completed the study, 98 belonged to the pomegranate group and
102 to the placebo group. For the pomegranate group, mean (SD)
follow-up was 12.4 (1.3) mo; for the placebo group it was 12.6
(1.7) mo. Based on participant diaries, compliance rates for both
treatment groups were equal (89%).
Treatment groups did not differ significantly in baseline demo-
graphic variables, including age, sex, family history of dementia,
apoE-4 risk status, or in scores on the Montreal Cognitive
Assessment, Beck Depression Inventory, and Wechsler Test of
Adult Reading (Table 1). Educational level was significantly
4 Siddarth et al.

995 Screened

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670 Excluded
Medical condition; excluded medication/supplement; lives too far; time
commitment; claustrophobic; MRI contraindication; age; BMI; not interested;
participating in another study; lost contact; too little compensation, etc.

325 Consented to participate

64 Dropped before randomization

Unable to get medical clearance (abnormal labs, metal in MRI) – 15; too busy
– 12; concerned about calories – 7; excluded health condition – 7; low
cognitive screening assessment – 6; lost contact – 5; no longer interested –
4; high BMI – 2; new health condition (unknown - per subject request) – 3;
will travel too much – 1; excluded medication – 1; did not want MRI – 1

261 Randomized to pom juice or placebo

61 (28 pom; 33 placebo) Dropped after randomization

Adverse event (upset stomach, heartburn, gastric irritation, diarrhea, etc.) – 8
Pom, 10 placebo; other adverse event (rash, congestion, bladder irritation,
headache, yeast infection) – 4 pom, 5 placebo; did not like taste – 3 pom, 5
placebo; new medical condition (cancer diabetes, prediabetes, etc.) – 2 pom,
4 placebo; compliance issues/ too busy – 5 pom, 3 placebo; concern about
sugar/ calories – 3 pom, 2 placebo; did not want possibility of placebo – 2
placebo; new medication use – 2 pom; worsening clinical condition – 1
placebo; moved – 1 pom, 1 placebo

200 Completed

FIGURE 1 Flow diagram of participants. pom, pomegranate.

different between groups (pomegranate group: 16.7 [2.1] y;
placebo group: 16.2 [2.0] y, t(259) = 2.0, P = 0.05; Table 1).
Treatment groups also did not differ in any of the memory
measures at baseline, both the subjective memory measures and
the primary outcome measures of verbal and visual memory
(Tables 1 and 2). In addition, the number of adverse events
for both groups was comparable, the most common being
gastrointestinal issues (19% in the pomegranate group;16% in the
placebo group). A list of all adverse events reported are tabulated
in Supplemental Table 1.
Memory outcomes
P = 0.4). For Delayed Recall, the pomegranate group improved
(t(257) = 2.31, P = 0.02), but not significant after correction,
whereas the placebo group showed no change (t(257) = 0.31,
P = 0.8).
For the primary verbal memory outcome (SRT), the group
by time interaction term was not statistically significant for any
of the 3 measures. Both the pomegranate and placebo groups
improved in Total (pomegranate: t(257) = 3.25, P = 0.001;
placebo: t(257) = 4.01, P = 0.0001; Table 2) and CLTR
(pomegranate: t(257) = 2.27, P = 0.02; placebo: t(257) = 3.50,
P = 0.001) scores, whereas neither group showed change in
Delayed Recall (pomegranate: t(257) = −0.51, P = 0.6; placebo:
t(257) = 1.46, P = 0.15).

Mean memory scores from both BVMT-R and Buschke SRT

at baseline, 6 mo, and 12 mo by treatment group are presented
in Table 2 for all participants. In addition, we present these scores
for completers only in each treatment group in Supplemental
Table 2. For the primary visual memory outcome (BVMT-R),
the group by time interaction was statistically significant for
the Learning score: the change in the pomegranate group was
not significant (t(257) = 1.67, P = 0.1), whereas the placebo
group showed significant decline (t(257) = −3.19, P = 0.002)
(Figure 2 and Table 2). Changes in the BVMT-R Total and
Delayed Recall scores were not significantly different between
groups. Neither group showed change in BVMT-R Total Recall
(pomegranate: t(257) = 1.11, P = 0.2; placebo: t(257) = 0.86,
Moderation models
There was no significant group by time by apoE-4 status
interaction for any of the outcome measures (P = 0.3–0.9). Thus,
apoE moderation of treatment effect was not indicated. Similarly,
being overweight/obese or MCI status did not moderate treatment
effect (P = 0.2–0.8).
Discussion
In this 12-mo randomized controlled trial, visual memory
performance, specifically the ability to learn visual information
 Memory effects of pomegranate juice 5
TABLE 1 Baseline demographic characteristics of participants1

Pomegranate juice Placebo drink

(n = 130) (n = 131)

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Age, y 60.8 (6.5) 59.9 (6.4)
Education,2 y 16.7 (2.1) 16.2 (2.0)
Sex, female, n (%) 85 (65) 89 (68)
BMI 25.3 (4.6) 25.6 (4.5)
Overweight/obese, n (%) 35 (27)/21 (16) 44 (33)/21 (16)
Montreal Cognitive Assessment 27.3 (2.0) 27.4 (2.0)
Wechsler Test of Adult Reading 42.0 (7.1) 40.3 (7.8)
Mild cognitive impairment, n (%) 67 (52) 59 (45)
Beck Depression Inventory 4.5 (4.3) 5.2 (5.4)
Family history of dementia, n (%) 55 (42) 55 (42)
apoE-4 carriers,3 n (%) 35 (29) 28 (23)
Memory Functioning Questionnaire
Frequency of forgetting 166.7 (29.1) 168.9 (35.1)
Seriousness of forgetting 83.7 (26.2) 85.4 (25.3)
Retrospective functioning 15.7 (4.5) 16.0 (5.3)
Mnemonics usage 23.1 (9.5) 23.3 (8.1)
1 Values are means with SDs in parentheses, unless otherwise noted.
2 t(259)= 2.0, P = 0.05.
3 Not available for 11 pomegranate juice and 9 placebo subjects.

over repeated learning trials, was shown to be maintained
in individuals who drank pomegranate juice compared with
a placebo drink. This finding is consistent with our earlier
pilot study showing greater levels of activity in brain regions
controlling visual memory functions in subjects consuming
pomegranate juice over 1 mo compared with subjects consuming
a placebo drink (23). In the 1-mo pilot study, a significant
between-group improvement in a verbal memory measure was
found, which this larger study did not replicate. The briefer
duration of the intervention in the pilot study—4 wk compared
with 12 mo in the current investigation—could explain the
discrepancy in these results. It is thus possible that pomegranate
juice consumption has short-term effects on verbal memory
that are not sustained long term. We also emphasize that only
1 cognitive measure (of the 6 that were examined) showed
a significant between-group difference, and thus the effect of
pomegranate juice is relatively narrow. However, pomegranate
juice is a safe, easy-to-consume antioxidant nutrient beverage,
and any memory benefits that it may offer to an aging population
are worth noting.
Other investigations have documented memory benefits of
pomegranate polyphenol consumption. A 2013 study (34)
reported that in patients undergoing heart surgery, a pomegranate
extract administered 1 wk before and 6 wk after the surgery
protected against memory loss. In a mouse model of Alzheimer’s
disease (35), mice consuming pomegranate juice not only learned
water maze tasks more quickly and swam faster, but also had
50% less accumulation of soluble amyloid-β42 and amyloid
deposition in the hippocampus compared with control mice.
These studies demonstrate improvements in a spatial learning
and memory task as the result of pomegranate juice consumption
consistent with our finding of visual memory benefits in humans
consuming pomegranate juice.
The ability of dietary manipulation to influence memory and
learning is well recognized. In addition to possible direct effects
of dietary constituents on the central nervous system, the role
of dietary modification on gut bacterial populations and the
possibility of affecting the production of biologically active
compounds such as urolithins, and relating the microbial shifts
to memory and learning have been an active area of study. For
example, Li and associates (36) reported a correlation between
dietary-induced shifts in bacterial diversity and animal learning
that may indicate a role for gut bacterial diversity in memory and
learning.
The currently available data are insufficient to postulate an
exact mechanism of action for pomegranate juice on memory;
however, several possibilities exist. Yuan and colleagues (37)
found that although polyphenols are unable to cross the
blood–brain barrier, urolithins, produced by gut bacteria from
pomegranate polyphenols, are able to cross the blood–brain bar-
rier, and such pomegranate metabolites could have an impact on
memory neural circuits. Further, in a previous study, Olajide and
co-workers (38) demonstrated that freeze-dried pomegranates
inhibited inflammation, as well as amyloidogenesis in IL-1β-
stimulated SK-N-SH cells (39), and such anti-inflammatory
effects may support cognitive health. Other investigators have
found (40, 41) that in patients with atherosclerosis, a year
of pomegranate juice supplementation reduced clogging in the
carotid arteries compared with a control group, where the
blockage increased. It is thus possible that regular pomegranate
consumption could result in improved blood flow to brain regions
controlling memory.
Several limitations of the present study deserve comment.
Only 26% of the screened volunteers were included in the study,
and it is possible that our recruitment method yielded a sample of
motivated, educated, physically healthy subjects concerned about
age-related memory problems, which is not representative of
the general population. Also, ∼23% of the enrolled participants
dropped out before study completion. Although such completion
rates are comparable to those of other similar trials, this too
6 Siddarth et al.

Between-group statistics 2 ; effect size (95%

F(2, 257) = 5.90, P = 0.003; 0.45 (0.17, 0.73)

F(2, 257) = 1.12, P = 0.3; 0.01 (−0.26, 0.29)
F(2, 257) = 1.47, P = 0.2; 0.15 (−0.13, 0.43)

F(2, 257) = 0.14, P = 0.9; 0.09 (−0.19, 0.37)

F(2, 257) = 1.02, P = 0.4; 0.20 (−0.07, 0.48)
F(2, 257) = 0.38, P = 0.7; 0.07 (−0.21, 0.35)

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CI)3

FIGURE 2 Mean BVMT-R Visual Memory Learning Score compared

statistics from general linear models, with treatment group, time, and time × treatment group as predictors and age, sex, and education level as covariates.
with time in the pomegranate (baseline N = 130; 6 mo N = 103; 12 mo
% Change

N = 98) and placebo (baseline N = 131; 6 mo N = 104; 12 mo N = 102)

0.5
− 1.2
− 26.3
2.6

groups. Horizontal bar lines indicate 95% CIs of the means. Group by time
1
8

interaction is statistically significant, F(2, 257) = 5.90, P = 0.003; between-

group ES = 0.45. Change in the pomegranate group was not significant,
t(257) = 1.67, P = 0.1, whereas the placebo group showed significant decline,
t(257) = −3.19, P = 0.002. BVMT-R, Brief Visuospatial Memory Test-
119.3 (14.3)

86.0 (33.7)
Brief Visuospatial Memory Test-Revised; CLTR, Consistent Long-Term Retrieval; SRT, Buschke Selective Reminding Test.
(n = 102)

2.9 (1.6)
21.3 (6.0)

10.1 (2.3)
8.0 (2.3)

Revised; ES, effect size; Pom, pomegranate.

12-mo
Placebo drink

could have had an impact on the results. While we corrected

for multiple comparisons in our analyses, it is important to note
119.8 (14.5)

87.1 (34.5)
(n = 104)

3.5 (1.9)
20.4 (5.5)

10.2 (2.0)
8.1 (2.0)

that we detected a significant between-group difference in only

6-mo

one of the memory measures that we examined. In addition, we

controlled for education in all the analyses, but we cannot rule out
the possibility that the relatively small but significant difference
116.3 (14.2)

79.6 (33.2)

in educational level between the 2 treatment groups may have had

(n = 131)

3.8 (1.8)
21.2 (5.7)

10.0 (2.2)
8.1 (2.2)
Baseline

an influence on the results. Finally, measures such as cholesterol,

blood, or imaging biomarkers, which may have shed light on
mechanistic aspects, were not collected during this trial.
Despite such limitations, the study had several strengths,
% Change

including the double-blind placebo-controlled design, large

1.4

14.3
3.3
0
5

10

sample size, the relatively long (12 mo) treatment duration, and
the high compliance rates in both arms of the study. Further, we
included subjects with a range of cognitive abilities, thus allowing
119.2 (14.4)

88.1 (34.4)

for generalizability of results to all nondemented individuals aged

21.4 (5.0)

4.0 (2.2)

10.0 (2.1)
8.4 (1.9)
(n = 98)
12-mo

50–75 y.
Pomegranate juice
TABLE 2 Baseline, 6-mo, and 12-mo memory scores, and % changes1

Forgetfulness and memory loss are common experiences of

aging. Most people develop mild age-related cognitive challenges
that remain relatively stable, whereas others develop MCI, a more
120.1 (14.5)

90.8 (35.5)
(n = 103)
21.4 (5.1)

10.2 (2.0)
8.5 (1.9)
3.7 (2.0)

serious form of cognitive decline that is a risk factor for dementia.

6-mo

Even intense memory training interventions in nondemented

people have yielded only modest effect sizes in terms of
maintaining memory performance and have demonstrated only
115.4 (15.4)

80.1 (34.6)

limited transfer of training (42). Further, there is a significant

(n = 130)
21.1 (5.4)
8.0 (2.2)
3.5 (1.8)

10.0 (2.3)
Baseline

gap between the development of effective cognitive intervention

programs and convenient availability to the general population,
and a simple nutritional supplementation, such as pomegranate
juice, may be more accessible to many individuals. Thus, these
findings that pomegranate juice maintains visual memory skills
BVMT-R Delayed Recall

in middle-aged and older adults could have a potential impact on

BVMT-R Total Recall

visual memory issues commonly associated with aging.

SRT Delayed Recall
BVMT-R Learning
SRT Total Recall

3 Cohen’s d.
1 BVMT-R,

The authors’ contributions were as follows—PS, ZL, DH, and GWS:

Memory tests

SRT CLTR

designed the research; KJM, LME, DAM, and SMH: conducted the research;
PS: analyzed data; PS, ZL, DH, and GWS: wrote the manuscript; PS
2F

and GWS: had primary responsibility for final content; and all authors
read and approved the final manuscript. The University of California, Los
 Memory effects of pomegranate juice
Angeles, owns a US patent (6,274,119) entitled “Methods for Labeling ß-
Amyloid Plaques and Neurofibrillary Tangles;” which has been licensed to
Ceremark Pharma, LLC. GWS is among the inventors and has financial
interest in Ceremark Pharma, LLC. GWS also reports having served as an
advisor to and/or having received lecture fees from AARP, Acadia, Allergan,
Avanir, Axovant, Handok, Herbalife, Lundbeck, Lilly, Genentech, Novartis,
Otsuka, Recruitment Partners, Roche, and Theravalues. DH reports receiving
consulting fees from Herbalife and the McCormick Science Institute. All
other authors declare no conflicts of interest.
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