The Effect of Acai (Euterpe spp.) Fruit Pulp on Brain Health and Performance

Abstract

The pulp of two small palm fruits found in the Amazon forests of South America-. Euterpe oleracea Mart., and Euterpe Precatoria Mart., commonly known as 'acai'-have been found to contain the most potent combination of antioxidant and anti-inflammatory polyphenolics and flavonoids of all fruits, vegetables, or nuts. Flavones in the pulp include a compound called velutin, the most potent anti-inflammatory flavonoid found in nature. Acai has been studied to determine if it has neuroprotective properties capable of preventing, mitigating, and/or treating a range of neurological diseases, including dementia, Alzheimer's, and Parkinson's diseases. The pulp's ability to attenuate the development of atherosclerosis lesions in vivo has been of particular interest to neuroscientists given the impact this disease can have on brain function. Research on the benefit of acai in supporting brain health and performance is still in the early stages, but based on the pulp's properties and the experimental outcomes reported to date, further research is warranted.

Full text

Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease
http://dx.doi.org/10.1016/B978-0-12-411462-3.00019-9 © 2015 Elsevier Inc. All rights reserved.
179
CHAPTER
19
The Effect of Acai (Euterpe spp.) Fruit Pulp on
Brain Health and Performance
Alexander G. Schauss
Senior Director of Research, Natural and Medicinal Products Research, AIBMR Life Sciences, Puyallup,
WA, USA
OUTLINE
Introduction 179
Acai Fruit Pulp 180
Conclusion 184
References 184
INTRODUCTION
Foods rich in anthocyanins and flavonoids have been
shown to be effective in reversing age-related deficits
in memory and learning (Rendeiro et al., 2013). Adult
animals fed a high-fat diet lacking in polyphenols have
been found to exhibit memory deficits associated with
a reduction in hippocampal SIRT1 gene expression
(Heyward et al., 2012) and impaired neurogenesis (Park
et al., 2010).
Mounting evidence suggests that impaired cogni-
tive function is associated with a high-fat diet, resulting
in oxidative stress and subsequent brain inflammation
(Yan et al., 1994) Similarly, high-carbohydrate diets rich
in processed and refined carbohydrates have been impli-
cated because they have been shown to increase protein
glycation, oxidative stress, and inflammation (Pistell
et al., 2010). Even small blood sugar elevations have been
associated with an increased risk of dementia in nondia-
betics, based on 35,264 clinical measurements of glucose
levels and 10,208 measurements of glycated hemoglobin
levels from 2067 participants without dementia followed
for 6.8 years; dementia developed in 524 participants,
of whom 74 had diabetes and 450 did not (Crane et al.,
2013). Even high caloric intake from carbohydrates and
low intake of fats and proteins has been associated with
an increased risk of mild cognitive impairment (MCI) or
dementia, based on the finding that individuals 70 and
older who consume foods high in carbohydrates, par-
ticularly refined sugar, have almost four times the risk
of developing MCI, as seen in a prospective study that
tracked 1,230 people aged 70 to 89 (Robets et al., 2012).
These studies suggest that a healthy balanced diet
of carbohydrates, fat, and protein, such as a low-car-
bohydrate, low-fat, Mediterranean diet (Shal et al.,
2008; Kesse-Guyot et al., 2013; Aalbers et al., 2013),
may reduce the risk associated with age-related MCI
and dementia. The Mediterranean diet has been found
to reduce cognitive decline, reduce MCI, and reduce
the risk of MCI progressing into Alzheimer’s disease
(Louridea et al., 2013). Plant-based diets, inclusive of
whole grains, fruits, and vegetables, have been found
to reduce the risk of cardiovascular disease, improve
the metabolic profile, and produce favorable gene
expression. Studies have shown that the longest liv-
ing and least dementia-prone populations subsist on
plant-based diets (Leitzmann, 2005). However, such
populations may also be less prone to stress or chemical
exposure.
New evidence suggests that chronic stress predis-
poses the brain to mental illnesses such as anxiety
and mood disorders due to increased production of

19. THE EFFECT OF ACAI (EUTERPE SPP.) FRUIT PULP ON BRAIN HEALTH AND PERFORMANCE
180
III. MOOD AND COGNITION BY NUTRACEUTICAL INTERVENTIONS
myelin-producing cells and fewer neurons, resulting in
an excess of white matter in some regions of the brain
such as the hippocampus and disruption in the balance
and timing of communications between cells (Chetty,
2014).
A small pilot study has suggested that diet can mod-
erate factors involved in clearing amyloids linked to
Alzheimer’s disease; the investigators found that a diet
with a high glycemic index and high in saturated fat
increased levels of cerebrospinal fluid unbound amy-
loid-beta (Aβ), whereas healthier diets reduced the levels
of these fractions (Hanson et al., 2013). The results sug-
gest that a high-fat diet may interfere with clearance of
amyloid fibrils.
Unfortunately, the vast majority of people in devel-
oped countries consume a diet characterized by foods
with a low density of nutrients. Although it remains
unclear why following a Mediterranean diet may protect
brain function, some speculate that healthy food choices
improve overall blood vessel health (arterial reactivity)
and reduce the production of free radicals and oxidative
stress, thereby lowering the risk of damage caused by
chronic exposure of brain cells to inflammation (Cordain
et al., 2005; Watzl, 2008).
Constant overproduction of proinflammatory mol-
ecules in the brain can lead to chronic inflammation;
left unchecked, this can contribute to a host of diseases,
including those associated with brain dysfunctions.
Because dietary factors can play an important role in
maintaining health, attention has been given to growing
evidence that polyphenols and other plant compounds
in certain fruits might play a role in attenuating and miti-
gating proinflammatory processes (Van Duyn et al., 2000;
Biesalski, 2007; Bhupathiraju and Tucker, 2011; Holt et al.,
2009; Gonzalez-Gallego et al., 2010; Marzocchella et al.,
2011). Foods rich in flavonoids and anthocyanins, such
as blueberries, cranberries, and strawberries, have been
shown to reverse age-related deficits in neuronal signal
transduction, learning, and memory in animals (Joseph
et al., 1999; Casadesus et al., 2004; Andres-Lacueva et al.,
2005; Joseph et al., 2005; Williams et al., 2008; DeFuria
et al., 2009; Miller and Shukitt-Hale, 2012; Rendeiro et al.,
2013). Blueberries have been shown to inhibit inflamma-
tory mediators by reducing the production of proinflam-
matory cytokines tumor-necrosis factor alpha (TNF-α)
and interluekin 6 (IL-6) production and by inhibition
of NF-κB activation and the mitogen-activated protein
kinase (MAPK) pathway (Lau et al., 2007; Xie et al., 2011).
One novel food that began receiving increasing
attention in the late 1990s due to its extraordinary anti-
oxidant and anti-inflammatory properties compared
to other antioxidant-rich foods is the fruit of two palm
trees growing in the same genus found in the Amazon
of South America: Euterpe oleracea and Euterpe precatoria,
both commonly known as ‘acai.’
ACAI FRUIT PULP
Acai (pronounced ah-sigh-ee; Euterpe oleracea Mart.) is
a small palm fruit with a diameter of 1 to 2 cm that con-
tains a single, tan-colored seed (Figure 19.1). The seed
of acai is covered by a thin layer of an edible purple-
colored pulp. The palm species is found in an area of
over 12 million hectares in the flood plains of the Ama-
zon river. In the city of Belem, in the state of Para, Brazil,
near the mouth of the Amazon river, over 120,000 tons
of the fruit is processed annually for its pulp.
The discovery of acai pulp’s extraordinary free radi-
cal scavenging capacity in vitro was discovered by this
author in 1995, followed by the revelation that it had a
high degree of nutritional density, including an unusu-
ally high concentration of mono- and polyunsaturated
fatty acids (Schauss et al., 2006a, 2006b). The oleic acid
content of the pulp is the same as that found in olive oil.
The pulp’s extraordinary antioxidant-scavenging capac-
ity compared to other fruits against hydroxyl, peroxyl,
and peroxynitrite radicals and the superoxide anion
received considerable attention by food scientists; in turn,
that laid the foundation for over a hundred subsequent
published studies to determine the pulp’s relevance in
the prevention, mitigation, and/or treatment of a range
of diseases in which oxidative processes and inflamma-
tion have been implicated. Analytical studies of the dark
purple acai pulp have found the pulp to be a rich source
FIGURE 19.1 Acai fruit. Alexander G. Schauss.

ACAI FRUIT PULP 181
III. MOOD AND COGNITION BY NUTRACEUTICAL INTERVENTIONS
of polyphenolics, including anthocyanins (e.g., cyanid-
ing, delphinidin, malvidin, pelargonidin, and peonidin),
chrysoerial (a unique flavone), and a group of flavones
with potent dual antioxidant and anti-inflammatory bio-
activities in addition to other flavonoids with known
health benefits (Odendaal and Schauss, 2014). More
recently, the chemistry and nutritional composition of
acai seed has been studied (Wycoff et al., submitted),
particularly after experimental evidence in vivo dem-
onstrated that the seed had protective effects against
emphysema caused by chronic exposure to secondhand
tobacco smoke (Soares de Moura et al., 2011).
Cerebral infarction and systemic atherosclerosis of the
intracranial arteries are known risk factors associated
with MCI and dementia (Suwanwela and Chutinetr,
2003). The role for oxidant stress and resultant endothelial
dysfunction due to inactivation of nitric oxide by super-
oxide and other reactive oxygen species as observed in
the development of atherosclerosis and other cardiovas-
cular diseases has been proposed by numerous investi-
gators (Seo et al., 2008; Dolan et al., 2010; Exel et al., 2002;
Cai and Harrison, 2000; Hoshi et al., 2008).
Whether acai pulp could attenuate atherosclerosis
in ApoE-deficient (ApoE-/-) knockout mice through its
antioxidant and anti-inflammatory bioactivities has
been studied (Xie et al., 2011). In the first study, of 20
weeks duration, and a confirmatory study of five weeks,
ApoE-/- mice were fed a high-fat diet (AIN-93G) con-
taining a 5% freeze-dried acai juice powder. Biomark-
ers of lipid peroxidation (F2-isoprostanes, isomers of
hydroxyoctadecadienoic acids [HODE], and hydroxye-
icosatetraenoic acids [HETE]) and expression of two
antioxidant enzyme genes (glutathione reductase 3
[GPX3] and glutathione reductase [GSR] and paraox-
onase 1 [PON1]) were measured, along with two proin-
flammatory cytokines (TNF-α and IL-6), in both groups
of animals. At 20 weeks, expression of GPX3 and GSR
was found to have been significantly upregulated in the
aorta of acai-fed mice, whereas the activity of GPX, GSR,
and PON1 increased in serum and liver compared to
the control group. In the second five-week study, serum
levels, gene expression, and protein levels of TNF-α
and IL-6 in resident macrophages with or without lipo-
polysaccharide (LPS) stimulation were lowered in the
acai-fed animals. NF-kB activation was also reduced, as
determined by the secreted alkaline phosphate (SEAP)
reporter gene assay. The significant finding of these two
studies was the dramatic reduction in mean lesion areas
of 58% (p<0.001) in the ApoE-/- mice fed freeze-dried
acai juice by 20 weeks, suggesting that acai pulp has the
potential to protect against atherosclerosis even when
consuming a high-fat diet, based on the hyperlipidemic
ApoE- deficient animal model used experimentally.
These results suggest that acai pulp may con-
tain both potent antioxidant and anti-inflammatory
phytochemical compounds working in unison, worth
identifying for their cardiovascular disease protective
properties. Not long after these results were reported,
further characterization and elucidation of freeze-dried
acai pulp was carried out among several collaborative
laboratories, led by investigators affiliated with the
United States Department of Agriculture (USDA) and
the University of Arkansas School for Medical Sciences;
this research led to the discovery of the most potent
anti-inflammatory flavonoid found in nature among a
class of flavones, including a particularly potent novel
flavone, velutin (Kang et al., 2010, 2011; Xie et al., 2012).
This systematic search for anti-inflammatory flavonoids
in acai pulp also resulted in isolation of 13 flavonoids
with greater than expected anti-inflammatory and anti-
oxidant activities. In the case of velutin, assays deter-
mined that the flavone exhibited a superior inhibitory
effect on nuclear factor kappa-light-chain-enhancer of
activated B cells activation compared to other flavones
within the same class (Xie et al., 2012). The anti-inflam-
matory properties and underlying mode of action of
velutin revealed an ability to reduce LPS-induced TNF-α
and IL-6 production in RAW 264.7 peripheral mac-
rophages and mice peritoneal macrophages (Xie et al.,
2012). As assessed by the SEAP assay, velutin not only
showed a significant inhibitory effect on NF-κB activa-
tion, but also exhibited the greatest effect by blocking
the degradation of IkB as well as inhibiting c-Jun N-ter-
minal kinase (JNK) phosphorylation and p38 MAPK,
involved in signaling pathways that led to production
of TNF-α and IL-6.
Recent studies have suggested that a higher intake of
antioxidants such as flavones and anthocyanins might
benefit insulin sensitivity and inflammation. In one
study, women who had the highest intake of flavones
(4.21 mg/d) had 8.3% higher levels of the hormone adi-
ponectin, which is elevated in lean, healthy individu-
als, 7.8% lower levels of insulin, and 8.3% lower levels
of the homeostasis model assessment-estimated insulin
resistance (HOMA-IR) index, compared to those with
the lowest 20% (0.59 mg/d) of intake (Jennings, 2014).
Among those with the highest 20% of intake (39.9 mg/d)
of anthocyanins, 9.5% had lower levels of insulin, 18.25
had lower levels of the inflammatory protein hs-C-
reactive protein (hs-CRP), and 8.3% had lower levels of
HOMA-IR than those with the lowest 20% of anthocy-
anin intake. Although the highest group intake levels of
flavones and anthocyanins can be readily consumed by
eating oranges, grapes, strawberries, blueberries, rasp-
berries, or blackberries, acai pulp has been shown in a
human pharmacokinetic study involving healthy adult
volunteers to result in up to an eight- to ten-fold higher
absorption of anthocyanins compared to berries with
higher concentrations of the compounds (Mertens-Talc-
ott et al., 2008).

19. THE EFFECT OF ACAI (EUTERPE SPP.) FRUIT PULP ON BRAIN HEALTH AND PERFORMANCE
182
III. MOOD AND COGNITION BY NUTRACEUTICAL INTERVENTIONS
That these antioxidant and anti-inflammatory com-
pounds are absorbed is but one step in demonstrating
their utility insofar as promoting any health benefits. To
determine if acai pulp does provide a measurable benefit
in humans, a 12-week study of 48 to 84 year olds with
an impaired range of motion (ROM) that affected daily
living was carried out (Jensen et al., 2011). Participants
were asked to consume 120 ml/day of an anthocyanin-
rich juice, whose predominant ingredient was freeze-
dried and frozen acai pulp. Study participants were
assessed at baseline and 2, 4, 8, and 12 weeks by a struc-
tured nurse interview, pain and activities of daily living
(ADL) questionnaires, blood samples, and ROM assess-
ment using dual digital inclinometry as recommended
by American Medical Association guidelines. Consump-
tion of the juice resulted in significant reduction in pain
and improved ROM and ADLs. At the end of 12 weeks,
hs-CRP was reduced, as well as lipid peroxidation. Most
notably, serum antioxidant status improved within two
weeks after consuming the acai beverage and continued
to improve through the 12th week, as seen in the cell-
based antioxidant protection in erythrocytes (CAP-e)
assay (Honzel et al., 2008).
The results of this human study confirmed benefits
seen in a randomized, double-blind, placebo-controlled
crossover study of the same acai-rich beverage in healthy
19 to 52 year olds for antioxidant uptake and changes in
inflammatory markers (Jensen et al., 2008). In the ran-
domized controlled trial, subjects under imposed oxida-
tive stress produced by fasting consumed 120 ml of the
beverage; blood samples were thereafter taken at 30, 60,
and 120 minutes. Participants consuming the acai-rich
beverage had significantly increased protection from
oxidative damage based on the CAP-e assay (p<0.001),
reduced formation of ROS in polymorphonuclear cells
(p<0.003), and reduced migration of three proinflamma-
tory chemoattractants (bacterial peptide f-Met-Leu-Phe
[fmlp; p<0.001], leukotriene B4 [p<0.05], and interleu-
kin 8 [IL-8; p<0.03]). The investigators commented that
given the high levels of polyphenols in the beverage due
to acai pulp, the increased antioxidant protection in vivo
after consumption, and the anti-inflammatory capacity
in vitro, further research was warranted to evaluate the
pulp on compromised cognitive function.
Recently, such studies have been performed in a
series of experiments led by neuroscientists at the
USDA Human Nutrition Research Center on Aging
(HNRCA) at Tufts University in Boston in collabora-
tion with investigators at other institutions. The center
has been studying age-related diseases of the brain and
in the process has determined that a direct link exists
between oxidative stress and inflammation, and com-
promised memory, learning, and movement. Earlier
studies performed at the center showed that consump-
tion of polyphenolic-rich berries results in modulation
of signaling in primary hippocampal neurons or BV-2
mouse microglial cells. How the pulp affects neuronal
signaling has been of particular interest. Application
of acai pulp fractions to hippocampal neurons resulted
in significant recovery of depolarized brain cells from
dopamine (DA)-induced Ca+2 10 influx, an increase in
the length of basal dendrites, and attenuation of inhib-
itor-induced autophagy dysfunction (Poulose et al.,
2012, 2014). Because of the high polyphenolic content
of acai pulp, USDA’s HNRCA also explored the effect of
acai fractions on BV-2 mouse microglial cells (Poulose
et al., 2012). Treatment of BV-2 cells with acai fractions
resulted in significant (p<0.05) decreases in nitrite pro-
duction accompanied by reduced inducible nitric oxide
synthase (iNOS) expression, cyclo- oxygenase-2 (COX-2)
and iNOS produced proinflammatory mediators, such
as prostaglandin E2 (PGE2) and nitric oxide (Caolini
et al., 2002). Also observed was protection of microglial
cells by a significant concentration-dependent reduc-
tion in COX-2, p38-MAPK, TNF-α, and NF-κB. These
results infer that acai pulp may contain compounds
whose effects on brain cells could result in an improve-
ment in cognitive and motor functions by modulating
signaling, downregulating phosphorylation of NF-κB,
and transcriptionally suppressing production of COX-2
and iNO-S. The investigators also suggested that con-
sumption of acai pulp “may contribute to ‘health span’
in aging, as it is able to combat some of the inflamma-
tory and oxidative mediators of aging at the cellular
level.” (Caolini et al., 2002, p1092). To determine if acai
pulp could reverse or mitigate age-related cognitive
and motor deficits, additional experiments were carried
out in aged rats fed acai-supplemented diets, and other
studies are also bearing this out. Spada and colleagues
(2009) have reported that pretreatment with acai pulp
mitigated damage caused by hydrogen peroxide in the
cerebral cortex, cerebellum, and hippocampus of adult
rats
Before performing in vivo studies of the effect of acai
pulp on cognitive and motor function in aged animals, a
discovery was made by another group at the USDA Chil-
dren’s Nutrition Center and the University of Arkansas
in Little Rock related to acai just before further studies
on the effect of acai pulp were carried out. Although
virtually all acai fruit is harvested and processed for
domestic use and export in the lowland floodplains of
the Amazon, a different species of acai, Euterpe precatoria,
a single-stem palm tree, was found to be highly concen-
trated among millions of hectares of land in the Bolivian
Amazon, east of Santa Cruz, and into the Brazilian Ama-
zon. Therefore, characterization and elucidation of the
polyphenolics of E. precatoria fruit pulp was carried out
to determine if it too had exceptional antioxidant and
anti-inflammatory properties and, later, what effects it
might have in protecting neurons during stress.

ACAI FRUIT PULP 183
III. MOOD AND COGNITION BY NUTRACEUTICAL INTERVENTIONS
In comparing E. oleracea (EO) to E. precatoria (EP) acai,
four assays were performed: a series of oxygen radical
absorbance capacity (ORAC) assays to derive a total
ORAC value; the 2,2-diphenyl-1-picrylhydrazil (DPPH)
assay; the CAP-e assay; and the NF-κB SEAP assay. Total
phenolics were also measured as an indication of total
phenolic content. EP fruit pulp was found to be superior
to EO pulp in every assay (Kang et al., 2012). EP pulp
inhibited LPS-induced NF-κB activation by 23% (p<0.05)
at 20 microgram/ml, whereas EO pulp showed no sig-
nificant inhibitory effect at comparable doses. Although
freeze-dried EO pulp had the highest hydroxyl radical
and superoxide anion-scavenging capacity based on
antioxidant assays such as ORAC and the ferric-reducing
ability of plasma (FRAP) assay when reported in 2006,
EP pulp was found to be significantly superior, placing
it in a unique position in terms of in vitro assays of this
nature as an antioxidant-rich food when compared to all
fruits, vegetables, and nuts. Taken together, for example,
EP fruit pulp resulted in three times higher total ORAC
value than that of EO fruit pulp (7698.6 micromole Tro-
lox Equivalent [TE]/g versus 2649.1 micromole TE/g),
whereas total phenolics by the Fast Blue (FBBB) method
were three times higher in EP than in EO.
To date, systematic isolation and evaluation of puri-
fied compounds in EO and EP fruit pulp has not been car-
ried out in order to isolate the constituents and bioactive
compounds responsible for the differences in scavenging
activities. Given the mounting evidence of a benefit of
other dark-colored fruits and berries on cognitive func-
tion, the determination of the pulp’s superior ORAC and
DPPH values warrants additional feeding studies. Two
such studies have been carried out, the first of which
examined whether either of the acai pulps would attenu-
ate stressor-induced calcium dysregulation in rodent
brain cells and/or restore autophagy. Both dysregulation
of Ca+2 and homeostasis and loss of autophagy function
in the brain have been implicated in progressive neuro-
nal degeneration and death associated with acute and
chronic neuropathologies (Poulose et al., 2014).
The results of this acai pulp study showed that pre-
treatment of rodent primary hippocampal neurons
in vitro up to 1 mg/ml significantly increased the length
of basal dendrites while attenuating inhibitor-induced
autophagy dysfunction. Acai pulp was found to activate
phosphorylation of mammalian target of rapamycin
(mTOR), increase the turnover of authophagosomes and
microtubule-associated protein 1B (MAP1B-Ls-II), and
decrease accumulation of LC3-ubiquitin binding P62/
SQSTM1 (also known as sequestosome1). The ubiquitin-
proteasome system and autophagy are two major mech-
anisms for protein degradation, as shown in eukaryotic
cells (Gao et al., 2010). Surprisingly, even though the
polyphenolic concentration of EP pulp was found to be
significantly higher in major flavonoids compared to
EO’s pulp, both species of fruit pulp showed essentially
the same effect. However, EP pulp’s scavenging ability
against the superoxide anion and single oxygen (1O2)
and inhibition of LPS-induced NF-κB activation were
found to be superior to EO fruit pulp. This may be due to
EP pulp containing significantly stronger water-soluble
antioxidants able to enter cells and inhibit ROS forma-
tion compared to EO pulp, which is richer in mono- and
polyunsaturated fatty acids (Schauss et al., 2006).
A study of the pulp’s effects against amyloid-β (AB)
in vitro has been carried out. The study found that acai
protected against AB-mediated loss of cell viability
and oxidative stress associated with antifibrillar effects
(Wong et al., 2013). Compared to other phenolics, acai
was found to be more effective at inhibiting amyloid
aggregation. Such inhibition may provide further insight
into how acai exerts its neuroprotective effect and might
mitigate the progression of Alzheimer’s disease.
Acai pulp’s properties and bioactivities have been
studied at the National Center on Aging of the US
National Institute of Health (NIH) in Baltimore. Studies
in fruit flies (Drosophila melanogaster) showed that adding
just 2% freeze-dried acai pulp to a high-fat diet resulted
in a significant positive life extension effect via modu-
lation of the c-Jun N-terminal kinase (JNK)-signaling
pathway, an increase in the transcript level of the heat-
shock-related protein (l(2)efl), a decrease in transcription
of phosphoenol-pyruvate carboxykinase (Pepck)—a key
gene involved in gluconeogenesis—a reduction in TNF-
α, IL-6, and NF-κB, and an increase in the production of
glutathione S transferase (GstD1) and metallothionein A
(MtnA)—both endogenous antioxidant enzymes—com-
pared to controls (Sun et al., 2010). Previous studies have
shown that high-fat diets in flies are just as detrimental
to their health as they are in humans (Driver et al., 1986),
so attention to these findings is warranted.
In another study by USDA HNRCA, 19-month-old
(aged) F344 rats were fed either a diet containing 2%
freeze-dried pulp from Euterpe oleracea (EO) or Euterpe
precatoria (EP), or a control diet for seven weeks, prior to
cognitive testing (Miller et al., 2013). Cognitive function
was performed using the Morris water maze (MWM)
to test memory and spatial learning. Serum collection
at the end of the study was performed. BV2 microglial
cells were cultured, and nitrite was quantified to assess
production of nitric oxide (NO) and nitrite (NO2) as
well as quantification of TNF-α by ELISA and inducible
nitrous oxide (iNOS) and COX-2 by Western blots. The
results showed that acai significantly improved working
and reference memory compared to controls. BV2 cells
treated with serum from aged rats from each group indi-
cated that the EO-fed rats showed significantly reduced
nitrite levels relative to aged control or EP-fed rats
(Poulose and Shukitt-Hale, 2013). Cells treated with serum
from EO- and EP- fed rats both showed significantly

19. THE EFFECT OF ACAI (EUTERPE SPP.) FRUIT PULP ON BRAIN HEALTH AND PERFORMANCE
184
III. MOOD AND COGNITION BY NUTRACEUTICAL INTERVENTIONS
reduced TNF-α and reduced iNOS levels compared to
control-fed rats. It was also determined that extracel-
lular nitrite levels and TNF-α levels significantly cor-
related with performance. Rats who improved the least
from trial to trial on the MWM showed the highest TNF-
α levels. The study came to the conclusion that dietary
acai improves working and reference memory in aged
rats. Pretreatment with serum from aged, acai-fed rats
reduced nitrite, iNOS, and TNF-α production, but not
COX-2, in BV2 cells. Although EO acai was determined
to have lower levels of total phenolics than EP acai, over-
all each acai pulp was equally effective in enhancing
working memory.
CONCLUSION
A substantial number of studies have demonstrated
that diets rich in fruits, vegetables, and nuts, especially
those foods rich in polyphenols, improve brain health
via reducing oxidative stress and oxidative damage to
cells and neuroinflammation, while modulating increas-
ing expression of neuronal-signaling molecules that
have been seen in vivo to improve behavior as well as
cognitive and motor function (Galland, 2010; Masters
et al., 2010; Bakker et al., 2010; Wu and Schauss, 2012).
There nevertheless remains an inadequate body of evi-
dence based on long-term studies in humans to show
that these polyphenolics preserve brain function once
they cross the blood–brain barrier.
Acai fruit pulp, rich in polyphenols and with supe-
rior antioxidant and anti-inflammatory bioactivity com-
pared to other polyphenolic-rich foods (Odendaal and
Schauss, 2014), deserves long-term study to determine
its position as a fruit with neuroprotective properties.
The observed dose-dependent inhibition of mTOR by EP
and EO fruit pulp suggests a potential role in providing
neuronal protection. Further evidence to support inves-
tigations on the effect of acai in neuroprotection comes
from a study of the pulp’s effects against AB in vitro. A
study found that acai protected against AB-mediated
loss of cell viability and oxidative stress associated with
antifibrillar effects. Compared to other phenolics, acai
was found to be more effective at inhibiting amyloid
aggregation. Such inhibition may provide insight into
how acai exerts its neuroprotective effect.
Given the ‘epidemic’ growth of diabetes and the rise
in obesity worldwide, the known role of blood glucose
in regulating autophagy, and its ability to significantly
inhibit phosphorylated mTOR by acai pretreatment,
further studies of the fruit seem warranted. Insulin
resistance is characterized by a marked increase in ROS
production and oxidative stress, both processes that
might be attenuated by acai pulp in vivo, given the effect
of the pulp in sequestering p62 (sequestosome), and a
distinguishing characteristic of type 2 diabetes is poor
performance on measures of memory and learning.
Microvascular disease associated with chronic hyper-
glycemia in both type 1 and type 2 diabetes has also
been shown to impair measures of attention, executive
function, and motor performance. The observed benefit
seen in ApoE-deficient mice on a high-fat diet and the
dramatic reduction in the formation of atherosclerotic
lesions in those animals given a small amount of freeze-
dried acai would suggest the possibility that acai pulp
consumption could play a role in mitigating the damag-
ing effect of diabetes in general, and in time could play a
role in mitigating damage to the brain.
References
Aalbers, T., Baars, L., Rikkert, M.O., 2013. The Mediterranean diet as
prevention strategy for dementia as a multicausal geriatric syn-
drome. [letter to the editor]. Am. J. Clin. Nutr. 97, 1411.
Andres-Lacueva, C., Shukitt-Hale, B., Galli, R.L., et al., 2005. Antho-
cyanins in aged blueberry-fed rats are found centrally and may
enhance memory. Nutr. Neurosci. 8, 111–120.
Bakker, G.C., van Erk, M.J., Pellis, L., et al., 2010. An antiinflammatory
dietary mix modulates inflammation and oxidative and metabolic
stress in overweight men: a nutrigenomics approach. Am. J. Clin.
Nutr. 91, 1044–1059.
Bhupathiraju, S.N., Tucker, K.L., 2011. Greater variety in fruit and veg-
etable intake is associated with lower inflammation in Puerto Rican
adults. Am. J. Clin. Nutr. 2011 (93), 37–46.
Biesalski, H.K., 2007. Polyphenols and inflammation: basic interac-
tions. Curr. Opin. Clin. Nutr. Metabol. Care 10, 724–728.
Cai, H., Harrison, D.G., 2000. Endothelial dysfunction in cardiovascu-
lar diseases: the role of oxidant stress. Circul. Res. 87, 840–844.
Casadesus, G., Shukitt-Hale, B., Stellwagen, H.M., et al., 2004. Modu-
lation of hippocampal plasticity and cognitive behavior by short-
term blueberry supplementation in aged rats. Nutr. Neurosci. 7,
309–316.
Casolini, P., Catalani, A., Zuena, A.R., et al., 2002. Inhibition of COX-2
reduces the age-dependent increase of hippocampal inflammatory
markers, corticosterone secretion, and behavioral impairments in
the rat. J. Nutr. Neurosci. 68, 337–343.
Chetty, S., Friedman, A.R., Tarovosh-Lahn, K., et al., 2014. Stress
and glucocoroids promote oligodendrogenesis in the adult hip-
pocampus. Molecul. Psychiatry. http://dx.doi.org/10.1038/
mp.2013.190.
Cordain, L., Eaton, S.B., Sebastian, A., et al., 2005. Origins and evolu-
tion of the Western diet: Health implications for the 21st century.
Am. J. Clin. Nutr. 81, 341–354.
Crane, P.K., Walker, R., Hubbard, R.A., et al., 2013. Glucose levels and
risk of dementia. N. Engl. J. Med. 369, 540–548.
DeFuria, J., Bennett, G., Strissel, K.J., et al., 2009. Dietary blueberry
attenuates whole-body insulin resistance in high fat-fed mice by
reducing adipocyte death and its inflammatory sequelae. J. Nutr.
139, 1510–1516.
Dolan, H., Crain, B., Troncoso, J., et al., 2010. Atherosclerosis, dementia,
and Alzheimer disease in the Baltimore longitudinal study of aging
cohort. Ann. Neurol. 68, 231–240.
Driver, C.J., Wallis, R., Cosopodiotis, G., et al., 1986. Is a fat metabolite
the major diet dependent accelerator of aging? Exp. Gertonol. 1986
(21), 497–507.
Exel, E.V., Gussekloo, J., Houx, P., et al., 2002. Atherosclerosis and
cognitive impairment are linked in the elderly. the leiden 85- plus
study. Atherosclerosis 165, 353–359.

REFERENCES 185
III. MOOD AND COGNITION BY NUTRACEUTICAL INTERVENTIONS
Galland, L., 2010. Diet and inflammation. Nutr. Clin. Pract. 25, 634–640.
Gao, Z., Gammoh, N., Wong, P.M., et al., 2010. Processing of autopha-
gic protein LC3 by the 20S proteasome. Autophagy 6, 126–137.
Gonzalez-Gallego, J., Garcia-Mediavilla, M.V., Sanchez-Campos, S.,
et al., 2010. Fruit polyphenols, immunity and inflammation. Br. J.
Nutr. 104 (Suppl. 3), S15–S27.
Hanson, A.J., Bayer-Carter, J.L., Green, P.S., et al., 2013. Effect of apo-
lipoprotein E genotype and diet on apolipoprotein E lipidation
and amyloid peptides: randomized clinical trial. JAMA Neurol. 70,
972–980.
Heyward, F.D., Walton, R.G., Carle, M.S., 2012. Adult mice maintained
on a high-fat diet exhibit object location memory deficits and
reduced hippocampal SIRT1 gene expression. Neurobiol. Learn.
Memory 98, 25–32.
Holt, E.M., Steffen, L.M., Moran, A., et al., 2009. Fruit and vegetable
consumption and its relation to markers of inflammation and oxi-
dative stress in adolescents. J. Am. Diet. Assoc. 109, 414–421.
Honzel, D., Carter, S.G., Redman, K.A., et al., 2008. Comparison of
chemical and cell–based antioxidant methods for evaluation of
foods and natural products: generating multifaceted data by par-
allel testing using erythrocytes and polymorphonuclear cells. J.
Agric. Food Chem. 56, 8319–8325.
Hoshi, T., Kitagawa, K., Yamagami, H., et al., 2008. Relation between
interleukin-6 level and subclinical intracranial large-artery athero-
sclerosis. Atherosclerosis 197, 326–332.
Jennings, A., 2014. Intakes of anthocyanins and flavones are associated
with biomarkers of insulin resistance and inflammation in women.
J. Nutr. 14, 202–208.
Jensen, G.S., Ager, D.M., Redman, K.A., et al., 2011. Pain reduction and
improvement of range of motion after consumption of an antiox-
idant-rich fruit- and berry-juice blend. J. Med. Food 14, 712–717.
Jensen, G.S., Patterson, K.M., Barnes, J., et al., 2008. In vitro and in vivo
antioxidant and anti-inflammatory capacity of an antioxidant-rich
fruit and berry juice blend. Results of a pilot and randomized, dou-
ble-blind, placebo-controlled crossover study. J. Agric. Food Chem.
56, 8326–8333.
Joseph, J.A., Shukitt-Hale, B., Casadesus, G., 2005. Reversing the del-
eterious effects of aging on neuronal communication and behavior:
beneficial properties of fruit polyphenolic compounds. Am. J. Clin.
Nutr. 81, 313S–316S.
Joseph, J.A., Shukitt-Hale, B., Denisova, N.A., et al., 1999. Reversals of
age-related declines in neuronal signal transduction, cognitive, and
motor behavioral deficits with blueberry, spinach, or strawberry
dietary supplementation. J. Neurosci. 1999 (19), 8114–8121.
Kang, J., Li, Z., Wu, T., et al., 2010. Antioxidant capacities and anti-
inflammatory effects of flavonoid compounds from açai pulp
(euterpe oleracea mart.). Food Chem. 122, 610–617.
Kang, J., Xie, C., Li, Z., et al., 2011. Flavonoids from açai (euterpe oleracea
mart.) pulp and their antioxidant and anti-inflammatory activities.
Food Chem. 128, 152–157.
Kang, J., Thakali, K.M., Chenghui, X., et al., 2012. Bioactivities of açaí
(euterpe precatoria mart.) fruit pulp, superior antioxidant and anti-
inflammatory properties to euterpe oleracea mart. Food Chem. 133,
671–677.
Kesse-Guyot, E., Andreeva, V.A., Lassale, C., et al., 2013. Mediterra-
nean diet and cognitive function: a French study. Am. J. Clin. Nutr.
97, 369–376.
Lau, F.C., Bielinski, D.F., Joseph, J.A., 2007. Inhibitory effects of blue-
berry extract on the production of inflammatory mediators in
lipopolysaccharide-activated BV2 microglia. J. Neurosci. Res. 85,
1010–1017.
Leitzmann, C., 2005. Vegetarian diets: what are the advantages? In: Diet
diversification and health promotion. Forum Nutr. 57, 147–156.
Lourida, I., Soni, M., Thompson-Coon, J., et al., 2013. Mediterranean
diet, cognitive function, and dementia: a systematic review. Epide-
miol 24, 479–489.
Marzocchella, L., Fantini, M., Benvenuto, M., et al., 2011. Dietary fla-
vonoids: molecular mechanisms of action as anti-inflammatory
agents. Rec. Pat. Inflamm. Allergy Drug Disc 5, 200–220.
Masters, R.C., Liese, A.D., Haffner, S.M., et al., 2010. Whole and refined
grain intakes are related to inflammatory protein concentrations in
human plasma. J. Nutr. 140, 587–594.
Mertens-Talcott, S.U., Rios, J., Jilma-Stohlawetz, P., et al., 2008. Phar-
macokinetics of anthocyanins and antioxidant effects after the
consumption of anthocyanin-rich acai juice and pulp (euterpe olera-
cea mart.) in human healthy volunteers. J. Agric. Food Chem. 56,
7796–7802.
Miller, M.G., Shukitt-Hale, B., 2012. Berry fruit enhances beneficial sig-
naling in the brain. J. Agric. Food Chem. 60, 5709–5715.
Miller, M.G., Fisher, D.R., Carey, A.N., Poulose, S., Shukitt-Hale, B.,
2013. Dietary acai fruit improves cognition in aged rats. Proceed-
ings of the Society for Neuroscience, San Diego, CA: 252.04.
Odendaal, A.Y., Schauss, A.G., 2014. Potent antioxidant and anti-
inflammatory flavonoids in the nutrient-rich Amazonian palm
fruit, açaí (Euterpe spp.). In: Watson, R.R., Reedy, V.R., Zibadi, S.
(Eds.), Polyphenols in human health and disease. Academic Press,
San Diego, pp. 219–239.
Park, H.R., Park, M., Choi, J., et al., 2010. A high-fat diet impairs neuro-
genesis: involvement of lipid peroxidation and brain-derived neu-
rotrophic factor. Neurosci. Lett. 482, 235–239.
Pistell, P.J., Morrison, C.D., Gupta, S., et al., 2010. Cognitive impair-
ment following high fat diet consumption is associated with brain
inflammation. J. Neuroimmunol. 219, 25–32.
Poulose, S.M., Shukitt-Hale, B., 2013. Functional role of walnuts and
acai fruits on brain health. In: Patil, B., et al. (Ed.), Tropical and sub-
tropical fruits: flavors, color, and health benefits. ACS Symposium
Series; American Chemical Society, Washington, D.C, pp. 172–187.
Poulose, S.M., Fisher, D.R., Bielinski, D.F., et al., 2014. Restoration of
stressor-induced calcium dysregulation and autophagy inhibi-
tion by polyphenolics-rich acai (Euterpe spp.) fruit pulp extracts in
rodent brain cells in vitro. Nutr. http://dx.doi.org/10.1016/j.nut.
2013.11.011.
Poulose, S.M., Fisher, D.R., Larson, J., et al., 2012. Attenuation of
inflammatory stress signaling by açai fruit pulp (euterpe oleracea
mart.) extracts in BV-2 mouse microglial cells. J. Agric. Food Chem.
60, 1084–1093.
Rendeiro, C., Vauzour, D., Rattray, M., et al., 2013. Dietary levels of pure
flavonoids improve spatial memory performance and increase hip-
pocampal brain-derived neurotrophic factor. PLoS One 8, e63535.
Robets, R.O., Roberts, L.A., Geda, Y.E., et al., 2012. Relative intake
of macronutrients impacts risk of mild cognitive impairment or
dementia. J. Alzheimers. Dis. 32, 329–339.
Schauss, A.G., Wu, X., Prior, R.L., et al., 2006a. Antioxidant capacity
and other bioactivities of the freeze-dried Amazonian palm berry,
euterpe oleraceae mart. (Açai). J. Agric. Food Chem. (54), 8604–8610.
Schauss, A.G., Wu, X., Prior, R.L., et al., 2006b. Phytochemical and
nutrient composition of the freeze–dried Amazonian palm berry,
euterpe oleraceae mart. (Açai). J. Agric. Food Chem. (54), 8598–8603.
Seo, W.K., Yong, H.S., Koh, S.B., et al., 2008. Correlation of coronary
artery atherosclerosis with atherosclerosis of the intracranial cere-
bral artery and the extracranial carotid artery. Eur. Neurol. (59),
292–298.
Shal, I., Schwarzfuchs, D., Henkin, Y., et al., 2008. Weight loss with a
low-carbohydrate, Mediterranean, or low-fat diet. N. Eng. J. Med.
359, 229–241.
Soares de Moura, R., Pires, K.M.P., Ferreira, T.S., et al., 2011. Addition
of açai (E. oleracea) seed to cigarettes has a protective effect against
emphysema in mice. Food Chem. Toxicol. 49, 855–863.
Spada, P.D., Dani, C., Bortolini, G.V., et al., 2009. Frozen fruit pulp of
euterpe oleracea mart. (acai) prevents hydrogen peroxide-induced
damage in the cerebral cortex, cerebellu, and hippocampus of rats.
J. Med. Food 12, 1084–1088.

19. THE EFFECT OF ACAI (EUTERPE SPP.) FRUIT PULP ON BRAIN HEALTH AND PERFORMANCE
186
III. MOOD AND COGNITION BY NUTRACEUTICAL INTERVENTIONS
Sun, X., Seeberger, J., Albericol, T., et al., 2010. Açai palm fruit (euterpe
oleracea mart.) pulp improves survival of flies on a high fat diet.
Exp. Gerontol. 45, 243–251.
Suwanwela, N.C., Chutinetr, A., 2003. Risk factors for atherosclerosis
of cervicocerebral arteries: intracranial versus extracranial. Neuro-
epidemiol 22, 37–40.
Van Duyn, M.A., Pivonka, E., 2000. Overview of the health benefits
of fruit and vegetable consumption for the dietetics professional:
selected literature. J. Am. Diet. Assoc. 100, 1511–1521.
Watzl, B., 2008. Anti-inflammatory effects of plant-based foods and of
their constituents. Int. J. Vit. Nutr. Res. 78, 293–298.
Williams, C.M., El Mohsen, M.A., Vauzour, D., et al., 2008. Blueberry-
induced changes in spatial working memory correlate with
changes in hippocampal CREB phosphorylation and brain-
derived neurotrophic factor (BDNF) levels. Free Rad. Biol. Med.
45, 295–305.
Wong, D.Y., Musgrave, I.F., Harvey, B.S., et al., 2013. Acai (euterpe olera-
cae mart.) berry extract exerts neuroprotective effects against beta-
amyloid exposure in vitro. Neurosci. Lett. 556, 221–226.
Xie, C., Kang, J., Burris, R., et al., 2011. Açaí juice attenuates atheroscle-
rosis in ApoE deficient mice through antioxidant and anti-inflam-
matory activities. Atherosclerosis 216, 327–333.
Xie, C., Kang, J., Li, Z., et al., 2012. The açai flavonoid velutin is a potent
anti-inflammatory agent: Blockade of LPS-mediated TNF-α and
IL-6 production through inhibiting NF-κB activation and MAPK
pathway. J. Nutr. Biochem. 23, 1184–1191.
Xie, C., Kang, J., Ferguson, M.E., et al., 2011. Blueberries reduce pro-
inflammatory cytokine TNF-alpha and IL-6 production in mouse
macrophages by inhibiting NF-kappaB activation and the MAPK
pathway. Molecul. Nutr. Food Res. 2011 (55), 1587–1591.
Wu, X., Schauss, A.G., 2012. Mitigation of inflammation with foods. J.
Agric. Food Chem. 60, 6703–6717.
Wycoff, W., Luo, R., Schauss, A.G., et al. Chemical and nutritional analysis
of seeds from purple and white acai (euterpe oleracea mart.). Submitted.
Yan, S.D., Schmidt, A.M., Anderson, G.M., et al., 1994. Enhanced cel-
lular oxidant stress by the interaction of advanced glycation end
products with their receptors/binding proteins. J. Biol. Chem. 1994
(269), 9889–9897.