ArticlePDF AvailableLiterature Review

Role of Walnuts in Maintaining Brain Health with Age

  • USDA- Human Nutrition Research Center on Aging At Tufts University


Because of the combination of population growth and population aging, increases in the incidence of chronic neurodegenerative disorders have become a societal concern, both in terms of decreased quality of life and increased financial burden. Clinical manifestation of many of these disorders takes years, with the initiation of mild cognitive symptoms leading to behavioral problems, dementia and loss of motor functions, the need for assisted living, and eventual death. Lifestyle factors greatly affect the progression of cognitive decline, with high-risk behaviors including unhealthy diet, lack of exercise, smoking, and exposure to environmental toxins leading to enhanced oxidative stress and inflammation. Although there exists an urgent need to develop effective treatments for age-related cognitive decline and neurodegenerative disease, prevention strategies have been underdeveloped. Primary prevention in many of these neurodegenerative diseases could be achieved earlier in life by consuming a healthy diet, rich in antioxidant and anti-inflammatory phytochemicals, which offers one of the most effective and least expensive ways to address the crisis. English walnuts (Juglans regia L.) are rich in numerous phytochemicals, including high amounts of polyunsaturated fatty acids, and offer potential benefits to brain health. Polyphenolic compounds found in walnuts not only reduce the oxidant and inflammatory load on brain cells but also improve interneuronal signaling, increase neurogenesis, and enhance sequestration of insoluble toxic protein aggregates. Evidence for the beneficial effects of consuming a walnut-rich diet is reviewed in this article.
The Journal of Nutrition
Supplement–What Comes First: The Food or the Nutrient?
Role of Walnuts in Maintaining Brain Health with
Shibu M. Poulose, Marshall G. Miller, and Barbara Shukitt-Hale*
USDA–Agricultural Research Services, Human Nutrition Research Center on Aging, Tufts University, Boston, MA
Because of the combination of population growth and population aging, increases in the incidence of chronic neurodegenerative
disorders have become a societal concern, both in terms of decreased quality of life and increased financial burden. Clinical
manifestation of many of these disorders takes years, with the initiation of mild cognitive symptoms leading to behavioral
problems, dementia and loss of motor functions, the need for assisted living, and eventual death. Lifestyle factors greatly affect
the progression of cognitive decline, with high-risk behaviors including unhealthy diet, lack of exercise, smoking, and exposure to
environmental toxins leading to enhanced oxidative stress and inflammation. Although there exists an urgent need to develop
effective treatments for age-related cognitive decline and neurodegenerative disease, prevention strategies have been
underdeveloped. Primary prevention in many of these neurodegenerative diseases could be achieved earlier in life by consuming
a healthy diet, rich in antioxidant and anti-inflammatory phytochemicals, which offers one of the most effective and least
expensive ways to address the crisis. English walnuts (Juglans regia L.) are rich in numerous phytochemicals, including high
amounts of polyunsaturated fatty acids, and offer potential benefits to brain health. Polyphenolic compounds found in walnuts
not only reduce the oxidant and inflammatory load on brain cells but also improve interneuronal signaling, increase neurogenesis,
and enhance sequestration of insoluble toxic protein aggregates. Evidence for the beneficial effects of consuming a walnut-rich
diet is reviewed in this article. J. Nutr. 144: 561S–566S, 2014.
In many countries, growing populations and increased mean
life spans are leading to a large aging population. With this
demographic shift comes an increased incidence of neurodegen-
erative diseases. Worldwide, >35.6 million people are living with
dementia, and in the United States, nearly 7 million people have
been diagnosed with dementia and other neurologic disorders
(1). Neurodegenerative diseases are highly debilitating, severely
affecting quality of life and imposing an economic burden on
both individuals and society. Cures for most neurodegen-
erative disorders have yet to be discovered, in part due to
irreversible loss of brain cells during the covert pathogenesis
of these debilitating diseases, which often take 10–15 y to
manifest clinically, and the poorly understood familial-genetic
linkage (2).
Neurodegenerative diseases are associated with chronic
exposure to oxidative stress and inflammation, loss of protective
signaling, and the accumulation of toxic proteins. During aging,
these factors trigger a cascade of altered molecular events, which
ultimately disrupt or destroy cells within the brain. Damage to
individual cells modifies interneuronal communications, caus-
ing deficits in memory, cognition, and motor function. These
cellular modifications ultimately lead to the pathogenesis of
Supported by USDA Intramural funds and an agreement between the USDA
and the California Walnut Commission.
Author disclosures: S. M. Poulose and M. G. Miller, no conflicts of interest.
B. Shukitt-HaleÕs laboratory receives research support as part of an agreement
between USDA–Agricultural Research Services and the California Walnut
*To whom correspondence should be addressed. E-mail: barbara.shukitthale@
Presented at ‘‘What Comes First: The Food or the Nutrient?,’’ as a satellite session
to the American Society for Nutrition Scientific Sessions and Annual Meeting at
Experimental Biology held in Boston, MA, on 19 April 2013. The satellite session and
supplement publication were supported by the California Walnut Commission
(CWC). All session speakers received travel funding and/or honoraria for participation
in the meeting and manuscript preparation. The views expressed are those of the
authors. Because the symposium was held on the day of the city lockdown in the
search for the Boston Marathon bomber, presentation was to a limited audience;
Dr. Katz was not present. The recorded presentations are available at http://www.
meetings-an d-professional -development- events/asn-at-eb-2013/recorded-sessions/
satellite-session-what-comes-first-the-food-or-the-nutrient/. The CWC and all of the
presenters express their solidarity with the people of Boston, and particularly with
those killed or injured at the Boston Marathon. The Supplement Coordinator for this
supplement was David R. Jacobs Jr. Supplement Coordinator disclosures: David R.
Jacobs Jr., PhD, is a consultant at the California Walnut Commission (member of
the Scientific Advisory Council). Dr. JacobsÕtravel expense to Experimental Biology
2013 was paid by the California Walnut Commission. Dr. Jacobs is otherwise
employed by the University of Minnesota and is supported by government grants.
This supplement is the responsibility of the Guest Editor to whom the Editor of The
Journal of Nutrition has delegated supervision of both technical conformity to the
published regulations of The Journal of Nutrition and general oversight of the
scientific merit of each article. The Guest Editor for this supplement was Kevin
Schalinske. Guest Editor disclosure: Kevin Schalinske had no conflicts to disclose.
Publication costs for this supplement were defrayed in part by the payment of page
charges. This publication must therefore be hereby marked "advertisement" in
accordance with 18 USC section 1734 solely to indicate this fact. The opinions
expressed in this publication are those of the authors and are not attributable to the
sponsors or the publisher, Editor, or Editorial Board of The Journal of Nutrition.
ã2014 American Society for Nutrition.
Manuscript received September 23, 2013. Initial review completed October 17, 2013. Revision accepted November 4, 2013. 561S
First published online February 5, 2014; doi:10.3945/jn.113.184838.
by guest on September 12, 2017jn.nutrition.orgDownloaded from
neurodegenerative diseases, such as Alzheimer disease (AD),
Parkinson disease, Huntington disease, amyotrophic lateral scle-
rosis, prion disease, and dementia (2,3). Although the central
nervous system is particularly vulnerable, the mutually perpetu-
ating effects of oxidative stress and inflammation also affect other
organ systems, increasing older adultsÕrisk of developing other
diseases suchas heart disease, cancer, arthritis, diabetes, and other
age-related disorders. Therefore, systemic protection from oxi-
dative stress and inflammation could not only protect the brain
from their direct effects but also from a variety of related
Dietary interventions may be able to prevent or forestall
neurodegeneration. Epidemiologic investigation of the Mediter-
ranean diet, which consists of high amounts of fruits, vegetables,
cereals, and fish and minimal amounts of alcohol, red meat, and
dairy products revealed substantial reductions in the risk of AD
in a large community-based, case-control cohort study in 194
AD patients and 1790 non-AD patients (4). A similar investi-
gation reported a decreased risk of dementia with increased
flavonoid-rich-diet consumption in a cohort study in 1367
participants > 65 y of age (5). A few other studies also indicated
the benefits of the Mediterranean diet in reducing the risk of
dementia, as well as mortality, in AD patients, indicating the
vital role of fruit and nut bioactive compounds on cognitive
health (6,7).
English walnuts (Juglans regia L.) are rich in a-linolenic acid
(ALA; 18:3n23) and linoleic acid (LA; 18:2n26) as well as
other polyphenolics, phytosterols, and micronutrients. Feeding
studies from our laboratory have shown that dietary supple-
mentation with walnuts can improve memory, cognition, and
motor function in aged animals (8–10). Although most of these
studies have linked walnutsÕeffects to their high PUFA content,
walnutsÕnotable polyphenol content plays an important role in
reducing the inflammation and oxidative stress in the aging
brain. This review addresses contemporary research into the
effects of dietary walnuts on cognition, motor function, and
brain health.
Aging and Metabolic Effects on Brain
The central nervous system is metabolically demanding, con-
suming nearly one-fourth of total oxygen intake and accounting
for >20% of the metabolic rate at rest (11,12). The brainÕs high
metabolic rate results in the generation of disproportionate
amounts of reactive oxygen and nitrogen species (13). The
damaging effects of these free radicals are usually countered by
endogenous oxidoreductase enzymes and intrinsic proteins,
which act as molecular quenchers at the cellular level. However,
aging, as well as other factors, alters the homeostasis between
the generation and quenching of these highly reactive elemental
species, leading to increased oxidation at the cellular level.
Increased oxidative stress and lipid peroxidation initiate a
cascade of proinflammatory signals, leading to the dystrophy
and death of brain cells. Altered homeostasis of oxidation,
inflammation, and protein aggregation has been attributed to
the death of neurons, which is directly related to impairment in
various cognitive domains, such as learning, decision making,
judgment, problem solving, and memory (14–17).
The coordination and execution of cognitive processes
depends on the appropriate detection and propagation of signals
from both the environment and surrounding cells in the brain.
The responsivity of each cell depends on the composition of the
cell membrane, through which all signals must pass. FAs are
abundant within neuronal membranes, where they play a role in
maintaining structural integrity, modulating enzyme activity,
and generating secondary messengers and other signaling
molecules (9). The PUFA composition of neuronal membranes
decreases during aging and contributes to the decline of neuronal
function observed in aging. This alteration is prevalent in the
aged brain, particularly the cortex, hippocampus, striatum, and
cerebellum, where reduced PUFA concentrations contribute to
changes in neuronal morphology and a decrease in membrane
fluidity and synaptic plasticity (18–20). A number of neuronal
functions are affected by deficits in membrane FA composi-
tion, all of which reduce the cellsÕability to propagate and
transmit signals within the brain. Therefore, increased avail-
ability of PUFAs may counteract PUFA depletion in neuronal
Walnut Phytochemicals and In Vitro
Walnuts are a rich source of nutrients and bioactive phytochem-
icals. Walnuts contain large amounts of PUFAs such as ALA and
LA, which have been shown to boost brain health and function
even with an increase in age (8,21). Every 100 g of walnuts
(Juglans regia) contain 38 g of LA and 9 g of ALA, as well as 4.4
g of saturated (palmitic acid, 16:0) and 8.7 g of monounsatu-
rated (oleic acid, 18:1n–9) FAs. In humans, ALA from walnuts is
then converted through a series of sequential desaturation and
elongation reactions into essential PUFAs such as EPA (20:5n–3)
and DHA (22:6n–3) in the liver. Both EPA and DHA play an
important role in brain health not only by reducing oxidative
stress and altering the immune function but also in maintaining
synaptic plasticity, neuronal membrane stability, gene expres-
sion, and neurogenesis (8,22).
Even though PUFAs play an important role in brain health,
the presence of other phytochemical components contributes to
healthy neuronal processes. Other important nutrients in wal-
nuts include, but are not limited to, polyphenols, vitamin E,
folate, ellagitannins, ellagic acid monomers, polymeric tannins,
melatonin, pectin, flavonoids, carotenoids, alkaloids, nitrogen-
containing or organosulfur compounds, and a variety of
minerals. Along with PUFAs, other phytonutrients provide
direct neuroprotection (8,9,23–26) as well as indirect protection
through improved lipid profiles and endothelial function and
increased plasma antioxidant capacity. Polyphenols present in
walnuts include, but are not limited to, hydroxycinnamic acids
such as chlorigenic acid, caffeic acid, P-coumaric acid, ferrulic
acid, and sinapic acid; hydrobenzoic acids such as syringic acid
and ellagic acid; and compounds such as gallic acid, glansrin,
juglone, and syringaldehyde (27). Polyphenols promote neuro-
nal calcium homeostasis in the striatum and hippocampus,
regions of the brain crucial for primary and secondary memory
functions (28,29).
Melatonin is another bioactive compound found in walnuts.
Endogenous melatonin, which is primarily synthesized by the
pineal gland, plays a critical role in regulating circadian rhythms
(30). Melatonin deficiency has been linked to degeneration of
Abbreviations used: Ab, amyloid b; AD, Alzheimer disease; ALA, a-linolenic
acid; APOE4, apoliproprotein e4; BDNF, brain-derived neurotrophic factor; CREBP,
cAMP response element-binding protein; DA, 6-hydroxy dopamine, LA, linoleic
acid; NPD1, neuroprotection D1; TLR-4, Toll-like receptor 4.
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cholinergic neurons in the basal forebrain and the deposition of
aggregated proteins, such as amyloid b(Ab) peptides, leading
to cognitive impairment and dementia (31). Reiter et al. (30)
reported that consumption of walnuts increased blood mela-
tonin concentrations, which correlated with an increase in ‘‘total
antioxidant capacity’’ of the serum with ‘‘total antioxidant
capacity,’’ indicating the ability of the blood to detoxify free
Walnut extract is neuroprotective against a variety of
stressors. Previously, we showed that treating cells with walnut
oil protected the cells from increases in inflammation and
oxidative stress by inhibiting LPS-induced activation of micro-
glial cells (32). When BV-2 mouse microglial cells were treated
with walnut extract prior to LPS stimulation, production of NO
and expression of inducible NO synthase were substantially
reduced. In the same study, walnut extract also reduced the
production of TNF-a, a proinflammatory mediator. We have
also shown that calcium buffering in hippocampal cells was
substantially altered by LPS and 6-hydroxy dopamine (DA)
stressors (33). Walnut extract protected against LPS-induced,
but not DA-induced, loss of calcium recovery (34). Another
study showed that walnut extract counteracted Ab-induced
oxidative stress and cytotoxicity in PC12 cells of rat adrenal
medulla (35). In a recent study from our laboratory, we
examined the cellular mechanisms underlying walnutsÕprotec-
tive effects on neuronal health and functioning in aging brain
(34). Primary hippocampal neurons were pretreated with walnut
extract or with the PUFAs found in walnuts. The cells were then
exposed to DA and LPS, and cell death and calcium buffering
dysregulation were measured (34). Results indicated that walnut
oil extract, ALA, and DHA provided substantial protection
against cell death and calcium dysregulation; the effects were
pretreatment concentration-dependent and stressor-dependent.
Conversely, LA and EPA were not as effective at protecting
hippocampal cells from these insults. The whole-walnut extract
was most beneficial because it does not contribute the cellular
toxicity effects. We have also reported that PUFAs found in
walnuts attenuate neuroinflammation by modulating microglial
reactivity. In a study using mouse microglial cells, walnut extract
altered the response stimuli to the chemically induced inflam-
matory stress through phospholipase D2–mediated internaliza-
tion of Toll-like receptor 4 (TLR-4) (32).
Mechanistic Animal Studies Supporting
Walnut Effects on Cognitive Function
In an effort to determine the bioavailability of FAs in the diet,
at the site of action, rats fed diets containing 15% LA and 3%
ALA were examined for whole-body distribution of deuterated
LA and ALA after a single-dose oral administration (36). The
brain concentration of LA peaked at 8 h post-administration.
Although ALA was not detected in brain tissue, ALA metabolites
including EPA, DPA, and DHA remained elevated up to 25 d
post-administration (36). Studies have also shown a decline in
FA enzyme activity in the liver of aged animals (37), potentially
allowing the presence of ALA and LA in the blood, where it
could be taken up in the brain. Additionally, Davis et al. (38)
found that mice fed a whole-walnut diet comprising 155 g of
whole walnuts/kg diet, which is the equivalent of 80 g (;3
ounces) of walnuts/d in humans, to provide 20% of energy from
fat, had changes in plasma markers, which were echoed in the
liver metabolomics results. It was concluded that the walnut
dietÕs beneficial effects probably represent the effects of whole
walnutsÕmultiple constituents and not a specific FA or tocoph-
erol (38).
In isolation, dietary DHA can improve learning and memory
in rodent models of aging. Aged mice (9 mo) whose diet
contained 20% DHA in the form of the green algae Chlorella
vulgaris for 8 wk made fewer working memory errors in an 8-
arm radial water maze (39). Dietary walnuts can also improve
cognition. In 1 study, rats that ingested 80 mg/d of walnuts, in
addition to their standard diet, for 28 d had enhanced learning
and memory in the radial arm maze and reduced anxiety on the
elevated plus maze (40). In a recent study from our laboratory
(9), 19-mo-old Fischer (F344) rats were fed diets containing
0, 2, 6, or 9% (wt:wt) ground walnuts with skin for 8 wk. Rats
fed a diet containing 2 or 6% walnuts had improved balance,
coordination, and strength; however, rats fed the 9% diet had
impaired motor performance relative to controls. Working
memory in the water maze was also enhanced in rats fed diets
containing walnuts; however, rats fed the 9% walnut diet had
impairments in reference memory. The 6% walnut diet pro-
duced the best overall results among the aged rats. The 6% diet
contained 5.4 g of ALA and 22.9 g of LA/kg, which, interestingly,
is equivalent to the recommended dietary intake of 1 ounce/d
(;28 g) of walnuts for humans (8,22,25). We subsequently found
that walnut consumption was associated with substantially lower
acetylcholinesterase activity in the striatum brain region of aged
animals (22).
Older adults are at a higher risk of seizure disorders, the
incidence and prevalence of which increase after 60 y of age (41).
Acute symptomatic seizures among older adults are often the
result of acute neural insults or metabolic disturbances. Asadi-
Shekaari et al. (42) also showed that the addition of walnut
kernels to the diet of male rats was preventive against experi-
mentally induced epilepsy. In one of our recent studies on aged
rats that were supplemented with 6–9% walnuts, walnuts
substantially inhibited the activation/phosphorylation of P38
MAPK and the transcription factor NF-kB (43). The results also
showed that 6% walnut supplementation activated cAMP
response element-binding protein (CREBP), a constitutively
expressed nuclear transcription factor that plays a critical role in
neuronal survival in the hippocampus and striatum (43). n–3
FAs that are rich in walnuts are converted to EPA and DHA,
which act as precursors for anti-inflammatory eicosanoids and
neuroprotection D1 (NPD1), respectively. NPD1 has been
shown to attenuate the activation of inflammatory signaling
mediators such as prostaglandins synthesized from arachidonic
acid (long-chain n–6 PUFAs) by cyclooxygenase-2 (44). There-
fore, walnut phytochemicals, which can effectively inhibit pro-
oxidant and proinflammatory mediators, may be 1 method of
reducing the risk of dementia, seizure, and other neurologic
disorders among older adults.
The loss of protein homeostasis in the brain, whereby brain
cells accumulate insoluble, misfolded, or damaged protein or
organellar structures, is the hallmark of many age-related neuro-
degenerative diseases. In a separate study, which used the brains
of rats supplemented with 6 and 9% walnut diets, our labo-
ratory showed substantially reduced aggregation of polyubiqui-
tinated proteins and activated the neuronal housekeeping
function, known as autophagy, in the striatum and hippocampus
(43). The clearance of polyubiquitinated protein aggregates such
as p62/sequestosome 1 was more pronounced in the hippocam-
pus, a critical region in the brain involved in memory function
(43). Importantly, the clearance of toxic protein aggregates was
in conjunction with reductions in oxidative stress and inflam-
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Human Studies Linked to Walnut
Most human studies associate walnuts and walnut PUFAs with
their cardiovascular benefits (45–48). Reductions in cardiovas-
cular disease risk factors may be associated with better brain
health because cardiovascular disease is also associated with
the development of cerebrovascular disease, stroke, and mild
cognitive impairment (49,50). A walnut- and walnut-oil–rich
diet reduced inflammatory and cardiovascular risk factors
among hypercholesterolemic men and women (51). A walnut-
enriched diet can also improve endothelium-dependent vasodi-
latation in type 2 diabetic individuals (24) and overweight adults
with visceral adiposity (52). Increased vasculature and improved
endothelial function have direct bearing on cerebral health and
cognitive function.
Generally, increased nut intake, and walnut intake in
particular, has been shown to improve cognition among older
adults. Recently, the Doetinchem Cohort Study reported that
higher nut intake at baseline was associated with improved
processing speed, cognitive flexibility, memory, and global
cognitive function (7). Another large, parallel-group, multicen-
ter randomized, controlled clinical trial (PREDIMED, Pre-
venci ´
on con Dieta Mediterr´
anea) recently provided compelling
evidence for the ability of nuts to counteract depression and age-
related cognitive decline. This study, spanning 7 y with a minimum
follow-up of 5 y, enrolled 7447 persons (55–80 y of age), with 3
randomized intervention arms (53). The first group received the
Mediterranean diet supplemented with virgin olive oil (1 L/wk),
the second group received the Mediterranean diet supplemented
with 30 g/d of mixed nuts (15 g walnuts, 7.5 g almonds, 7.5 g
hazelnuts), and the third group received a low-fat control diet.
After 3 y, participants who were on the Mediterranean diet
supplemented with nuts had substantially improved concentrations
of plasma brain-derived neurotrophic factor (BDNF), particularly
among the individuals with a history of depression (53). BDNF, a
member of the neurotrophin family, is highly expressed in cortical
and hippocampal neurons and promotes the induction of long-
term potentiation, synaptic plasticity, neuronal survival and
differentiation, axonal elongation, and neurotransmitter release
(54). BDNF can cross the blood-brain barrier, and lower plasma
and brain BDNF protein concentrations have been implicated
in enhanced aggressiveness, hyperactivity, and hyperphagia, as well
as in an array of brain disorders, such as epilepsy, AD, Huntington
disease, autism, schizophrenia, and major depression (55). A subset
of PREDIMED participants were assessed for neuropsychological
testing, which revealed that higher intakes of both total olive oil
and virgin olive oil, coffee, walnuts, and wine improved both
memory and overall cognitive functions (56). Furthermore, the
study found that walnuts, among all other nuts included in the
study, were associated with substantial improvements in working
memory (56). The study also reported that the Mediterranean diet
with nuts reduced the risk of stroke by 46%, which indirectly
establishes the benefits of nuts on age-associated cognitive decline
caused by vascular deterioration.
Further supporting the benefits of walnuts on cognitive
function, Pribis et al. (57) reported that daily supplementation
with 60 g of walnuts for 8 wk substantially improved inferential
verbal reasoning in a double-blind, randomized, placebo-
controlled cross-over (6-wk washout) study in young college
students. The study was conducted in healthy, cognitively intact
young adults, which may explain why no differences in memory,
mood, or nonverbal reasoning were detected between the
control and diet group.
Walnuts may also play a role in preventing AD. Dai et al. (58)
reported that supplementation with fruit and vegetable juice,
rich in polyphenols, at least 3 times/wk was attributed to a
slower onset of AD, particularly in patients who are apolipro-
protein e4(APOE4) carriers (58). APOE4 plays a critical role in
promoting amyloid accumulation, neurotoxicity, oxidative
stress, and neurofibrillary tangles (59). In 2 longitudinal cohort
studies, the Washington Heights and Inwood Columbia Aging
Project (WHICAP; population-based) and the Predictors
Study (clinic-based), which followed people for an average of
4 y, researchers showed that the presence of at least 1 APOE4
allele was associated with faster cognitive decline in the earliest
stages of AD (60). In another study, Yasuno et al. (61)
supplemented 41 participants aged $65 y with n–3 PUFAs
from fish, lycopene, and Ginkgo biloba extracts daily for 3 y
and compared them with 622 participants of a similar age
group without supplementation. They showed that the com-
bination of antioxidants improved cognitive function in aged
persons after 3 y, and the improvement in cognitive function
with supplementation was observed both in APOE4 noncar-
rier (E42)andAPOE4 carrier (E4+) groups (61). Although
n–3 PUFAs from animal sources differ from n–3 PUFAs from
walnuts, because humans convert ALA from walnuts into EPA
combination with other high-antioxidant compounds, may
delay the cognitive decline associated with AD.
In conclusion, age-related increases in oxidative stress
and inflammation, especially when coupled with metabolic
and cardiovascular dysfunction, lead to neurodegeneration and
cognitive decline. This process of brain aging occurs even in the
absence of specific neurodegenerative diseases. Although most
chronic neurodegenerative diseases cannot currently be cured,
preventive measures earlier in life can protect cognitive function
in old age and may prevent or delay the onset of debilitating
neurodegenerative diseases. Dietary interventions provide a safe
and palatable means of modifying the bodyÕs internal environ-
ment and, importantly, the neuronal environment within the
brain. Walnut polyphenols and tocopherols can reduce oxidative
stress and inflammation; furthermore, PUFAs help maintain
neuronal membrane integrity and attenuate protein aggregation
involved in AD. In rodent studies, the addition of dietary walnuts,
equivalent to a single serving of walnuts for humans, was sufficient
to improve both motor and cognitive behavior in aged animals. In
humans, the inclusion of walnuts in the diet improved cardiovas-
cular health, which is itself a risk factor for neurodegenerative
diseases and age-related cognitive decline. Taken together, this
evidence suggests that the integration of walnuts into a healthy
diet could be an effective means of prolonging health spans,
slowing the processes of brain aging, and reducing the risk of
chronic neurodegenerative disease.
S.M.P. and M.G.M. wrote the manuscript, and B.S.-H. had
primary responsibility for the final content. All authors read and
approved the final manuscript.
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... In a nutshell, the findings of this study indicated that Walnut kernel extract was effective at increasing the needed dose to the first myoclonic jerk, at reducing the severity of seizures, and the high efficacy of the extracts at preventing mortality was considerable, 100% of animals were protected (Asadi-Shekaari et al., 2014). The results are also supported by the study by Poulose et al. (2014). ...
... This evidence has not yet been proven and needs further investigation (Djedjibegovic et al., 2020). The results are consistent with Poulose et al. (2014) and Fisher et al. (2017). ...
Full-text available
Global and regional trends of population aging spotlight major public health concerns. As one of the most common adverse prognostic factors, advanced age is associated with a remarkable incidence risk of many non-communicable diseases, affecting major organ systems of the human body. Age-dependent factors and molecular processes can change the nervous system’s normal function and lead to neurodegenerative disorders. Oxidative stress results from of a shift toward reactive oxygen species (ROS) production in the equilibrium between ROS generation and the antioxidant defense system. Oxidative stress and neuroinflammation caused by Amyloid-ß protein deposition in the human brain are the most likely pathogenesis of Alzheimer’s disease (AD). Walnut extracts could reduce Amyloid-ß fibrillation and aggregation, indicating their beneficial effects on memory and cognition. Walnut can also improve movement disabilities in Parkinson’s disease due to their antioxidant and neuroprotective effect by reducing ROS and nitric oxide (NO) generation and suppressing oxidative stress. It is noteworthy that Walnut compounds have potential antiproliferative effects on Glioblastoma (the most aggressive primary cerebral neoplasm). This effective therapeutic agent can stimulate apoptosis of glioma cells in response to oxidative stress, concurrent with preventing angiogenesis and migration of tumor cells, improving the quality of life and life expectancy of patients with glioblastoma. Antioxidant Phenolic compounds of the Walnut kernel could explain the significant anti-convulsion ability of Walnut to provide good prevention and treatment for epileptic seizures. Moreover, the anti-inflammatory effect of Walnut oil could be beneficial in treating multiple sclerosis. In this study, we review the pharmaceutical properties of Walnut in age-related neurological disorders.
... Like in numerous other crops, phenolics are present in nuts. Many studies are reporting the beneficial effects of nut consumption on human health, including cardioprotective, neuroprotective, antidiabetic, anti-inflammatory, and antioxidant properties [99][100][101][102][103]. Studies have shown that the consumption of nuts improves flood lipoprotein profile [104,105] and gut microbiota [106]. ...
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The possibility that nut intake may defend human health is an interesting point of view and has been investigated worldwide. Consequently, nuts are commonly promoted as healthy. In recent decades, the number of investigations proposing a correlation between nut consumption and a decrease in the risk of key chronic diseases has continued to increase. Nuts are a source of intake of fiber, and dietary fiber is associated with a reduced occurrence of obesity and cardiovascular diseases. Nuts likewise provide minerals and vitamins to the diet and supply phytochemicals that function as antioxidant, anti-inflammatory, and phytoestrogens agents and other protective mechanisms. Therefore, the main goal of this overview is to summarize current information and to describe the utmost new investigation concerning the health benefits of certain nuts.
... To this end, consumption of coffee [21] as well as total nut consumption [22], have been associated with a reduction in total and cause-specific mortality. Regarding the link between tree nut consumption and mortality, the potential role of walnuts is specifically intriguing given their link to reduced risk for developing many diseases of aging, including type 2 diabetes [23], cardiovascular disease [24], cognitive decline [25], and certain cancers [26]. Moreover, a potential advantage of whole walnuts is that they are uniquely enriched in many bioactive constituents purported to have protective effects, including polyunsaturated fatty acids (e.g., ALA), ᵧ-tocopherol, phytosterols, several polyphenolic compounds, and fiber [26][27][28], of which similar compounds have been previously tested for aging effects as single agents. ...
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Evidence continues to accrue that aging and its diseases can be delayed by pharmacologic and dietary strategies that target the underlying hallmarks of the aging process. However, identifying simple, safe, and effective dietary strategies involving the incorporation of whole foods that may confer some protection against the aging process is also needed. Recent observational studies have suggested that nut consumption can reduce mortality risk in humans. Among these, walnuts are particularly intriguing, given their high content of n-3 fatty acids, fiber, and antioxidant and anti-inflammatory compounds. To this end, 12-month-old male CB6F1 mice were provided either a defined control low-fat diet (LFD), a control high-fat diet (HFD), or an isocaloric HFD containing 7.67% walnuts by weight (HFD + W), and measures of healthspan and related biochemical markers (n = 10–19 per group) as well as survival (n = 20 per group) were monitored. Mice provided the HFD or HFD + W demonstrated marked weight gain, but walnuts lowered baseline glucose (p < 0.05) and tended to temper the effects of HFD on liver weight gain (p < 0.05) and insulin tolerance (p = 0.1). Additional assays suggested a beneficial effect on some indicators of health with walnut supplementation, including preservation of exercise capacity and improved short-term working memory, as determined by Y maze (p = 0.02). However, no effect was observed via any diet on inflammatory markers, antioxidant capacity, or survival (p = 0.2). Ingenuity Pathway Analysis of the hippocampal transcriptome identified two processes predicted to be affected by walnuts and potentially linked to cognitive function, including estrogen signaling and lipid metabolism, with changes in the latter confirmed by lipidomic analysis. In summary, while walnuts did not significantly improve survival on a HFD, they tended to preserve features of healthspan in the context of a metabolic stressor with aging.
... Nowadays, walnut consumption is considered a key element that can improve human health [1,2] . Several clinical trials have been devoted to highlighting the benefits of walnut seed consumption on human health and, in particular, on the brain and cardiovascular health [3][4][5][6][7] , blood lipids and pressure [1,[8][9][10][11] , along with its effect on improving insulin resistance [12] . All these properties related to the consumption of walnut seeds are related to their composition in unsaturated fatty acids and bioactive compounds. ...
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The increasing demand for plant-based medicines makes plant research attractive to find natural alternatives that can replace synthetic products or at least reduce their use. Saponins are a group of natural phytochemical compounds in most herbs, vegetables, and legumes. There are two different types of saponin compounds, which can be classified based on the nature of the aglycone bound to the oligosaccharide fragments, whether it is a steroid or triterpenoid. This paper is devoted to saponins with triterpenoid aglycone and aims to study the relationship between their content and several biological activities in different Juglans regia kernel extracts, including antioxidant, antimicrobial and antibacterial activities. Antioxidant activity was assessed against two free radicals: DPPH and ABTS. Oleanolic acid was used as a standard to quantify triterpenoid saponins, measured by the vanillin method, whereas Acarbose and Tetracycline were used as positive controls to evaluate the α-glucosidase inhibitory and antimicrobial activities, respectively, of walnut kernel extracts. Findings show that hydroalcoholic extract (EtOH 70%) has a considerable content of phenolic compounds, with 59.51 ± 0.26 mg GAE/g in total polyphenol contents, while the content of total flavonoids and condensed tannins were 3.14 ± 0.27 mg QE/g and 85.65 ± 0.37 mg CE/g of crude extract, respectively. In terms of antioxidant activity, the butanolic extract proved to be the most effective against DPPH with IC50 = 7.74 ± 1.49 µg/mL, while the precipitated extract showed the highest scavenging activity against the ABTS free radical with IC50 = 33.14 ± 2.96 µg/mL. In addition, butanolic and hydroalcoholic extracts of Juglans regia kernels showed an α-glucosidase inhibitory activity even more efficiently than synthetic drugs such as Acarbose, with IC50 values of 11.66 µg/mL and 16.17 µg/mL, respectively, versus 18.01 µg/mL in Acarbose. The evaluation of the antimicrobial activity against Bacillus subtilis, Escherichia coli and Klebsiella pneumoniae strains revealed that some extracts could inhibit these bacteria. This study successfully assessed the bioactivities of the extracts, suggesting that the extracts of medicinal plants can demonstrate stronger bioactivity than pure synthetic compounds.
... In the present study, WE and juglone decreased brain and liver oxidative stress in rats compared to the control group. Poulose et al. concluded that phenolic compounds in walnuts could reduce oxidants, prevent inflammation in the brain, increase interneuron signaling and promote neurogenesis (Poulose et al., 2014). It was determined that juglone was more effective than WE in reducing oxidative stress. 1 mg/kg juglone was the most effective dose. ...
... For example, polyphenols have been well-established for their ability to interact with various proteins, enzymes, and membrane receptors, resulting in modulating various biological processes. Among these biological properties, strong antioxidant and anti-inflammatory properties have been well-studied for many polyphenols such as curcumin (Cur), resveratrol (RSV), quercetin (QUE), and tannins for treatment of various inflammatory disorders [8,9], obesity-mediated inflammation [10,11], inflammatory bowel disease [12][13][14], Alzheimer disease [15,16], diabetes [17], and skin inflammation [18,19]. ...
Owing to their eco-friendliness, natural abundance, cost-effectiveness, and organic nature, numerous phyto- chemicals are being traditionally used for treatment of different diseases. Despite their great potency, clinical translation of phytoconstituents is constrained due to their intrinsic physicochemical properties (i.e., low aqueous solubility, low permeation coefficient, and chemical instability), poor bioavailability, short plasma half- life, and ultimate sub-therapeutic efficacy. To mitigate these shortcomings, nanotechnology has been employed in the past few decades. In this review, we have mainly focused on significance of different nanodelivery systems in improving the physicochemical properties and targeted delivery of anti-inflammatory phytochemicals for treatment of inflammatory diseases. The encapsulation of anti-inflammatory phytochemicals in various nano- delivery systems (phytonanomedicine) has resulted in significant improvement in physicochemical properties, biocompatibility, pharmacokinetic profile, and therapeutic efficacy. Moreover, many recent adaptations including, PEGylation, surface functionalization with targeting ligand(s), and stimuli-responsive behavior of phytonanomedicines have also been pondered to maximize targeted biodistribution, cell uptake efficiency, prolonged localization, and therapeutic efficacy. Convincingly, phytonanomedicines have modernized thera- peutic value of anti-inflammatory phytochemicals for treatment of various inflammatory disorders; however, one of the restrictions to clinical translation of phytonanomedicines is lacking of substantial evidences on their prerequisite safety and efficacy in human which needs further exploration
... This study showed that GC effectively protected neuronal cells against H 2 O 2 and high glucose-induced neurotoxicity and reduced ROS production in PC12 and HT22 cells. Walnut, which has an abundance of polyunsaturated fatty acids (PUFAs) and polyphenolic compounds, reduced cerebral oxidative stress and inflammatory reaction by enhancing neuronal signaling [30,50]. According to Muthaiyah et al., walnut extract protected neuronal cells against Aβ-mediated cytotoxicity by increasing the capacity of endogenous antioxidant defenses and modulating the cellular redox state [51]. ...
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This study was conducted to evaluate the protective effect of Juglans regia (walnut, Gimcheon 1ho cultivar, GC) on high-fat diet (HFD)-induced cognitive dysfunction in C57BL/6 mice. The main physiological compounds of GC were identified as pedunculagin/casuariin isomer, strictinin, tellimagrandin I, ellagic acid-O-pentoside, and ellagic acid were identified using UPLC Q-TOF/MS analysis. To evaluate the neuro-protective effect of GC, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2′,7′-dichlorodihydrofluorecein diacetate (DCF-DA) analysis were conducted in H2O2 and high glucose-induced neuronal PC12 cells and hippocampal HT22 cells. GC presented significant cell viability and inhibition of reactive oxygen species (ROS) production. GC ameliorated behavioral and memory dysfunction through Y-maze, passive avoidance, and Morris water maze tests. In addition, GC reduced white adipose tissue (WAT), liver fat mass, and serum dyslipidemia. To assess the inhibitory effect of antioxidant system deficit, lipid peroxidation, ferric reducing antioxidant power (FRAP), and advanced glycation end products (AGEs) were conducted. Administration of GC protected the antioxidant damage against HFD-induced diabetic oxidative stress. To estimate the ameliorating effect of GC, acetylcholine (ACh) level, acetylcholinesterase (AChE) activity, and expression of AChE and choline acetyltransferase (ChAT) were conducted, and the supplements of GC suppressed the cholinergic system impairment. Furthermore, GC restored mitochondrial dysfunction by regulating the mitochondrial ROS production and mitochondrial membrane potential (MMP) levels in cerebral tissues. Finally, GC ameliorated cerebral damage by synergically regulating the protein expression of the JNK signaling and apoptosis pathway. These findings suggest that GC could provide a potential functional food source to improve diabetic cognitive deficits and neuronal impairments.
... Reviews examining the health effects of walnut consumption published in the last 30 years have largely focused on CVD risk markers and end points. [45][46][47][48][49][50][51][52] Additionally, more limited research relates to other major global health concerns, including obesity [53][54][55] and age-related cognitive decline, [56][57][58] which is likely to become increasingly important for aging populations. 59 There is a lack of recent systematic reviews that amalgamate many different areas of walnut and health research, ie, including both more established and emerging risk markers and outcomes, and some reviews have focused on particular walnut components such as polyphenols or micronutrients rather than consumption of whole nuts. ...
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Context Considering the accumulation of recent studies investigating the health effects of walnut consumption, both including and beyond cardiovascular health effects, a systematic review of this literature to investigate the strength of the evidence is warranted. Objective To investigate associations between walnut consumption and outcomes with public health relevance (specifically all-cause mortality, type 2 diabetes, CVD, metabolic syndrome, obesity, cancer, neurological and mental health, musculoskeletal, gastrointestinal, and maternal disorders) and the effect on associated disease risk markers, reported in studies published from 2017 to present. Data Sources MEDLINE, FSTA, CENTRAL, and Scopus were searched from 1 January 2017 to 5 May 2021. Data Extraction Human studies (cohort studies and RCTs) ≥3 weeks in duration comparing consumption of walnuts (whole, pieces, or 100% butter) to a control and measuring associations with relevant public health outcomes and disease risk markers were assessed. Key study characteristics were extracted independently by 2 investigators using a standardized table. The quality of the studies was assessed using the Cochrane Risk-of-Bias tool 2.0 and the Newcastle–Ottawa Scale. Data Analysis Only 1 RCT was considered to be at low risk of bias for any of its outcomes. The cohort studies were considered to be of moderate or high quality. The results were synthesized using vote counting, based on the direction of effect. Thirty-three articles, 23 describing RCTs (walnut dose ∼10–99 g/day, 1,948 subjects) and 10 describing cohort studies (∼675,928 subjects), were included. Vote counting could be performed for the blood lipids, cardiovascular function, inflammation- and hemostatic-related factors, markers of glucose metabolism, and body weight and composition outcome groupings. The results are presented in effect direction plots. With respect to blood lipids, results from 8/8 RCTs favoured walnuts, in accordance with associations with a reduced risk of CVD suggested by cohort studies; results from 6/6 RCTs favoured control with respect to body weight and composition, although most of these effects were small. This was contrary to cohort study results suggesting small benefits of walnut consumption on body weight. There was no overall consistent direction of effect for cardiovascular function, markers of glucose metabolism, or inflammation- and hemostatic-related factors. Conclusions Evidence published since 2017 is consistent with previous research suggesting that walnut consumption improves lipid profiles and is associated with reduced CVD risk. Evidence is accumulating in other areas, such as cognitive health, although more research is needed to draw firm conclusions. Systematic Review Registration PROSPERO registration no. CRD4202122.
... Walnuts contain the highest amount of ALA of all nuts [20]. Other fatty acids such as oleic acid, linoleic acid, or palmitic acid provide a natural ALA-rich n3-PUFA to n6-PUFA ratio of 1:4 [21,22]. Furthermore, this extract also includes low levels of the lipophilic vitamin E, a powerful antioxidant [23,24]. ...
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(1) Background: Mitochondria are the cells' main source of energy. Mitochondrial dysfunction represents a key hallmark of aging and is linked to the development of Alzheimer's disease (AD). Maintaining mitochondrial function might contribute to healthy aging and the prevention of AD. The Mediterranean diet, including walnuts, seems to prevent age-related neurodegeneration. Walnuts are a rich source of α-linolenic acid (ALA), an essential n3-fatty acid and the precursor for n3-long-chain polyunsaturated fatty acids (n3-PUFA), which might potentially improve mitochondrial function. (2) Methods: We tested whether a lipophilic walnut extract (WE) affects mitochondrial function and other parameters in human SH-SY5Y cells transfected with the neuronal amyloid precursor protein (APP695). Walnut lipids were extracted using a Soxhlet Extraction System and analyzed using GC/MS and HPLC/FD. Adenosine triphosphate (ATP) concentrations were quantified under basal conditions in cell culture, as well as after rotenone-induced stress. Neurite outgrowth was investigated, as well as membrane integrity, cellular reactive oxygen species, cellular peroxidase activity, and citrate synthase activity. Beta-amyloid (Aβ) was quantified using homogenous time-resolved fluorescence. (3) Results: The main constituents of WE are linoleic acid, oleic acid, α-linolenic acid, and γ- and δ-tocopherol. Basal ATP levels following rotenone treatment, as well as citrate synthase activity, were increased after WE treatment. WE significantly increased cellular reactive oxygen species but lowered peroxidase activity. Membrane integrity was not affected. Furthermore, WE treatment reduced Aβ1-40 and stimulated neurite growth. (4) Conclusions: WE might increase ATP production after induction of mitochondrial biogenesis. Decreased Aβ1-40 formation and enhanced ATP levels might enhance neurite growth, making WE a potential agent to enhance neuronal function and to prevent the development of AD. In this sense, WE could be a promising agent for the prevention of AD.
Walnut has been reported to have beneficial effects on improving cognitive performance. This randomized double-blind placebo-controlled clinical trial evaluates the clinical effectiveness and safety of walnut oligopeptide (WO) on memory enhancement, cognition, and sleep quality in teenagers and elderly people. Eighteen teenagers and 18 elderly people were, respectively, randomly allocated to placebo, low dosage (170 mg), and high dosage (340 mg) WO administration groups (n = 6 per group in each population). After 90 days of administration, the Wechsler Adult Intelligence Scale (WAIS) score was significantly increased and the global Pittsburgh Sleep Quality Index (PSQI) score was significantly decreased in the WO administration group. In addition, the average scores for test subjects of Chinese, Mathematics, and English examinations were significantly increased from the baseline for the teenagers in the WO administration group. Our results support the claim that WO has the potential to become a new option for nutritional intervention, to enhance the memory, cognitive ability, and sleep quality of teenagers and elderly people. This study was approved by the Institutional Review Board of the Shanghai Nutrition Society and registered at the Chinese Clinical Trial Registry ( ) with an ID number of ChiCTR1900028160.
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Metabolic syndrome is a precursor of diabetes and cardiovascular disease (CVD). Walnut ingestion has been shown to reduce CVD risk indices in diabetes. This randomized controlled crossover trial was performed to investigate the effects of daily walnut consumption on endothelial function and other biomarkers of cardiac risk in a population of overweight individuals with visceral adiposity. Forty-six overweight adults (average age, 57.4 years; 28 women, 18 men) with elevated waist circumference and 1 or more additional signs of metabolic syndrome were randomly assigned to two 8-week sequences of walnut-enriched ad libitum diet and ad libitum diet without walnuts, which were separated by a 4-week washout period. The primary outcome measure was the change in flow-mediated vasodilation (FMD) of the brachial artery. Secondary measures included serum lipid panel, fasting glucose and insulin, Homeostasis Model Assessment-Insulin Resistance values, blood pressure, and anthropometric measures. FMD improved significantly from baseline when subjects consumed a walnut-enriched diet as compared with the control diet (1.4% ± 2.4% versus 0.3% ± 1.5%; p = 0.019). Beneficial trends in systolic blood pressure reduction were seen, and maintenance of the baseline anthropometric values was also observed. Other measures were unaltered. Daily ingestion of 56 g of walnuts improves endothelial function in overweight adults with visceral adiposity. The addition of walnuts to the diet does not lead to weight gain. Further study of the potential role of walnut intake in diabetes and CVD prevention is warranted.
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Oxidative stress is known to contribute to the progression of cerebrovascular disease. Additionally, oxidative stress may be increased by, but also augment inflammation, a key contributor to cerebral aneurysm development and rupture. Oxidative stress can induce important processes leading to cerebral aneurysm formation including direct endothelial injury as well as smooth muscle cell phenotypic switching to an inflammatory phenotype and ultimately apoptosis. Oxidative stress leads to recruitment and invasion of inflammatory cells through upregulation of chemotactic cytokines and adhesion molecules. Matrix metalloproteinases can be activated by free radicals leading to vessel wall remodeling and breakdown. Free radicals mediate lipid peroxidation leading to atherosclerosis and contribute to hemodynamic stress and hypertensive pathology, all integral elements of cerebral aneurysm development. Preliminary studies suggest that therapies targeted at oxidative stress may provide a future beneficial treatment for cerebral aneurysms, but further studies are indicated to define the role of free radicals in cerebral aneurysm formation and rupture. The goal of this review is to assess the role of oxidative stress in cerebral aneurysm pathogenesis.
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Increasing evidence suggests that synaptic dysfunction is a key pathophysiological hallmark in neurodegenerative disorders, including Alzheimer's disease. Understanding the role of brain-derived neurotrophic factor (BDNF) in synaptic plasticity and synaptogenesis, the impact of the BDNF Val66Met polymorphism in Alzheimer's disease-relevant endophenotypes - including episodic memory and hippocampal volume - and the technological progress in measuring synaptic changes in humans all pave the way for a 'synaptic repair' therapy for neurodegenerative diseases that targets pathophysiology rather than pathogenesis. This article reviews the key issues in translating BDNF biology into synaptic repair therapies.
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Epilepsy is a chief communal health problem. Antiepileptic drugs only provide symptomatic treatment. Walnut Kernels (WK) have high concentrations of phenolic compounds, which have beneficial effects on human health because of their antioxidant and anti-atherogenic properties. The present study was designed to evaluate the efficacy of WK supplementation for the prevention of experimental epilepsy in male rats. WISTAR ADULT MALE RATS WERE DIVIDED INTO THREE GROUPS: a control group (PTZ injection, fed with ordinary food), experimental group (PTZ injection, fed with WK) and a sham group (no PTZ injection, only for histological studies). Pentylenetetrazole (PTZ) was administered after the prescribed time. WKs displayed anti-epileptogenic properties, and WK supplementation was associated with increased seizure threshold and reduced mortality in the experimental group versus controls. Use of WK may be helpful in prevention of PTZ-induced seizure and its further neurodegeneration in male rats.
There is converging evidence that composite dietary patterns such as the Mediterranean diet (MeDi) is related to lower risk for a series of nonneurological medical conditions and diseases. We investigated the association between MeDi and risk for Alzheimer's Disease (AD) in a community-based study of 2,258 nondemented individuals, who were prospectively evaluated every 1.5 years for 4 (± 3.0, 0.2- 13.9) years. Adherence to the MeDi (0-9 point scale with higher scores indicating higher adherence) was the main predictor in Cox models. Adjusting for multiple potential confounders, higher adherence to the MeDi was associated with lower risk of AD (Hazard Ratio [HR], 0.91, 95% CI, 0.83-0.98; p = 0.015). Compared to subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had a HR of 0.85 (0.63-1.16) and those at the highest tertile a HR of 0.60 (0.42-0.87) for AD (p for trend 0.007). We conclude that higher adherence to the MeDi is associated with a reduction in risk for AD in a dose-responsive manner.
Walnut consumption improves cardiovascular disease risk; however, to our knowledge, the contribution of individual walnut components has not been assessed. This study evaluated the acute consumption of whole walnuts (85 g), separated nut skins (5.6 g), de-fatted nutmeat (34 g), and nut oil (51 g) on postprandial lipemia, endothelial function, and oxidative stress. Cholesterol efflux (ex vivo) was assessed in the whole walnut treatment only. A randomized, 4-period, crossover trial was conducted in healthy overweight and obese adults (n = 15) with moderate hypercholesterolemia. There was a treatment × time point interaction for triglycerides (P < 0.01) and increased postprandial concentrations were observed for the oil and whole walnut treatments (P < 0.01). Walnut skins decreased the reactive hyperemia index (RHI) compared with baseline (P = 0.02) such that a difference persisted between the skin and oil treatments (P = 0.01). The Framingham RHI was maintained with the oil treatment compared with the skins and whole nut (P < 0.05). There was a treatment effect for the ferric reducing antioxidant potential (FRAP) (P < 0.01), and mean FRAP was greater with the oil and skin treatments compared with the nutmeat (P < 0.01). Cholesterol efflux increased by 3.3% following whole walnut consumption in J774 cells cultured with postprandial serum compared with fasting baseline (P = 0.02). Walnut oil favorably affected endothelial function and whole walnuts increased cholesterol efflux. These 2 novel mechanisms may explain in part the cardiovascular benefits of walnuts.
Unlabelled: Previous research from our lab has demonstrated that dietary walnut supplementation protects against age-related cognitive declines in rats; however, the cellular mechanisms by which walnuts and polyunsaturated fatty acids (PUFAs) may affect neuronal health and functioning in aging are undetermined. Objectives: We assessed if pretreatment of primary hippocampal neurons with walnut extract or PUFAs would protect cells against dopamine- and lipopolysaccharide-mediated cell death and calcium dysregulation. Methods: Rat primary hippocampal neurons were pretreated with varying concentrations of walnut extract, linoleic acid, alpha-linolenic acid, eicosapentaenoic acid, or docosahexaenoic acid prior to exposure to either dopamine or lipopolysaccharide. Viability was assessed using the Live/Dead Cellular Viability/Cytotoxicity Kit. Also, the ability of the cells to return to baseline calcium levels after depolarization was measured with fluorescent imaging. Results: Results indicated that walnut extract, alpha-linolenic acid, and docosahexaenoic acid provided significant protection against cell death and calcium dysregulation; the effects were pretreatment concentration dependent and stressor dependent. Linoleic acid and eicosapentaenoic acid were not as effective at protecting hippocampal cells from these insults. Discussion: Walnut extract and omega-3 fatty acids may protect against age-related cellular dysfunction, but not all PUFAs are equivalent in their beneficial effects.