REVIEW

Nutritional Factors Affecting Adult Neurogenesis

and Cognitive Function
Shibu M Poulose, Marshall G Miller, Tammy Scott, and Barbara Shukitt-Hale
USDA-ARS Human Nutrition Research Center on Aging at Tufts University, Neuroscience and Aging Laboratory, Boston, MA

ABSTRACT

Adult neurogenesis, a complex process by which stem cells in the hippocampal brain region differentiate and proliferate into new neurons and
other resident brain cells, is known to be affected by many intrinsic and extrinsic factors, including diet. Neurogenesis plays a critical role in neural
plasticity, brain homeostasis, and maintenance in the central nervous system and is a crucial factor in preserving the cognitive function and repair
of damaged brain cells affected by aging and brain disorders. Intrinsic factors such as aging, neuroinflammation, oxidative stress, and brain injury,
as well as lifestyle factors such as high-fat and high-sugar diets and alcohol and opioid addiction, negatively affect adult neurogenesis.
Conversely, many dietary components such as curcumin, resveratrol, blueberry polyphenols, sulforaphane, salvionic acid, polyunsaturated fatty
acids (PUFAs), and diets enriched with polyphenols and PUFAs, as well as caloric restriction, physical exercise, and learning, have been shown to
induce neurogenesis in adult brains. Although many of the underlying mechanisms by which nutrients and dietary factors affect adult
neurogenesis have yet to be determined, nutritional approaches provide promising prospects to stimulate adult neurogenesis and combat
neurodegenerative diseases and cognitive decline. In this review, we summarize the evidence supporting the role of nutritional factors in
modifying adult neurogenesis and their potential to preserve cognitive function during aging. Adv Nutr 2017;8:804–11.

Keywords: hippocampal neurogenesis, stem cells, cognition, polyphenols, neurodegeneration, aging brain

Introduction specialization restricted the extent to which residual

Aging is the single greatest risk factor for most neurode-
generative diseases, which often are characterized by their
irreversibility, their lack of effective treatment, and the
poor quality of life they engender, along with social and
economic burdens. Lack of effective therapies for these de-
bilitating brain disorders has been attributed to the inabil-
ity of adult mammalian brains to generate or repair
damaged neurons. Although Altman and Das (1) showed
continuous adult hippocampal neurogenesis in rat brains
in 1965, further studies to reinforce theories such as dam-
aged neuronal replacement by resident precursor cells
were conducted mainly after 1989 (2–4). The limiting fac-
tor for this delay was that the limited regenerative capacity
of the mature brain and its unusual degree of cellular
This article is a review from the session “Aging and Cognition,” presented at the 6th Annual
Advances & Controversies in Clinical Nutrition Conference, held 8–10 December 2016 at
Rosen Shingle Creek in Orlando, Florida. The conference was jointly provided by ASN and
Tufts University School of Medicine.
The authors reported no funding received for this study.
Author disclosures: SMP, MGM, TS, and BS-H, no conflicts of interest.
Address correspondence to BS-H (e-mail: barbara.shukitthale@ars.usda.gov).
Abbreviations used: AD, Alzheimer disease; BDNF, brain-derived neurotrophic factor; CNS,
central nervous system; DG, dentate gyrus; NSCs, neural stem cells; SGZ, subgranular zone;
SVZ, subventricular zone.
healthy tissue could assume the functions of damaged
brain tissue (5). Many studies since the mid-1990s, how-
ever, have established adult neurogenesis in mammalian
systems, where adult neural stem cells or precursor cells,
located in the rostral subventricular zone (SVZ) of the lat-
eral ventricles and the subgranular zone (SGZ) of the den-
tate gyrus (DG) in the hippocampus, can differentiate and
proliferate into new neurons (5–9). The process is a highly
complex, multistep process that begins with the prolifera-
tion of progenitor cells, is followed by commitment to a
neuronal phenotype and morphological and physiological
maturation with the development of functional neuronal
characteristics, and ends with the existence of a newly
functioning, integrated neuron (10). Adult neurogenesis
is an integral component of neural plasticity, brain homeo-
stasis, maintenance, and tissue remodeling in the central
nervous system (CNS). The migration and repopulation
of neural stem cells (NSCs) into other critical regions of
the brain and their maturation into functional neurons
or other brain cells is determined by both intrinsic and ex-
trinsic factors, including neurotrophins, antidepressants,
opioids, seizures, physical activity (10), glucocorticoids (11),

804 ã2017 American Society for Nutrition. Adv Nutr 2017;8:804–11; doi: https://doi.org/10.3945/an.117.016261.
sex hormones (12), growth factors (13), excitatory neuro-
transmission (14), learning (15), physical exercise (16),
stress (17), and diet (18). The prospect of continuous gene-
sis and proliferation of new neurons and glial cells and the
plastic nature of adult mammalian brains has vast therapeu-
tic potential in combating the exponential rise in the inci-
dence of neurodegenerative diseases.
Age-related decline in cognitive function has been char-
acterized by compromised neuronal plasticity, decreased
neurogenesis, and neuronal death (19). Impaired adult neu-
rogenesis also has been well characterized in patients with
neurological diseases, including Alzheimer disease (AD),
Parkinson disease, Huntington disease, epilepsy, ischemia,
autism spectrum disorders, and prion diseases, leading to
continuous loss of neurons and subsequent cognitive and
motor disabilities (20). Aberrant neurogenesis appears to
be a common hallmark for most neurodegenerative diseases,
even though distinct proteins are responsible for different
diseases and cause the loss of different neural populations
in different regions of the brain. Adult hippocampal neuro-
genesis has a direct effect on cognitive function, because the
hippocampal formation has been widely linked to memory
storage and processing (21) and, in most neuropathologies,
the hippocampal region has been shown to be the brain re-
gion that is the most affected (22). It has been shown that
neurogenesis can be induced in the SVZ and hippocampus
in response to neuronal death (23). Moreover, some neuro-
nal precursors reach these degeneration-prone areas and in
some cases replace dead neurons (24). Treatment of neuro-
logic diseases using endogenous neurogenesis is limited by
the continuous decline in number and capacity of NSCs
as a result of the disease process and aging (6, 23). Regener-
ation of damaged neurons with site-specific transplantation
of NSCs also has limitations because the transplanted NSCs
sometimes are unable to differentiate into specific types of
neurons and because of the increased risk of malignant
transformation and immune rejection after NSC transplan-
tation (6). Therefore, determination of a clear mechanism in
the development and activation of endogenous neurogenesis
may be an ideal approach to the prevention and treatment of
neurological diseases.
Many exogenous modulators of neural activity such as
physical activity, enriched environment (e.g., containing
tunnels, platforms, toys, and running wheels), caloric re-
striction, and vitamin E have been shown to regulate and
stimulate adult progenitor cells and neurogenesis (25–27).
Furthermore, dietary phytochemicals, which are known to
possess many neurogenic properties, play a beneficial role
in brain aging and neurodegenerative disease. Compounds
such as curcumin, resveratrol, blueberry polyphenols, sul-
foraphanes, salvionic acids, PUFAs (e.g., omega-3 and
DHA), the LMN diet (a patented diet by the company
La Morella Nuts enriched with polyphenols and PUFAs),
and flours rich in soluble fibers have been shown to induce
neurogenesis in the adult brain (20, 28–33). Although the
molecular mechanisms by which these compounds influ-
ence neurogenesis have yet be established, these compounds
reduce oxidative stress and neuroinflammation, enhance cell
signaling, activate autophagy, and affect growth factors (34).
Many of these compounds have been shown to improve
learning and memory by affecting specifically the hippo-
campal brain region. Dietary compounds also have been
shown to induce adaptive stress–response molecules and al-
ter the specific microenvironments in which adult progeni-
tor cells reside (34). These compounds enhance the ability of
the brain to resist more severe stress in the event of larger
insults by promoting cell repair and survival, via inducing
and activating trophic factors, antioxidant and DNA-repair
enzymes, and proteins involved in mitochondrial biogenesis
(20, 28–34). Although the potential roles of adult neurogen-
esis have been widely established in neurophysiologic pro-
cesses such as motor function, learning and memory,
olfaction, and the regulation of the hypothalamus-pituitary-
adrenal axis (35), its therapeutic applications have been lim-
ited because it is a complex multistep process, and accurate
biomarkers to establish each of these steps are still being
discovered.
Although the individual effects of dietary compounds on
adult neurogenesis are not yet fully understood, evidence
supports the notion that some of the bioactive compounds
from fruits and vegetables can modulate brain structure
and function, as well as cognitive ability, throughout the life-
span of an organism. In this review, we focus primarily on
studies that have investigated the effects of dietary factors
that influence hippocampal neurogenesis and brain plastic-
ity in the context of cognitive function, aging, and neurode-
generative disease.
Factors Negatively Affecting Adult
Neurogenesis
Aging negatively affects the proliferation of neural progeni-
tor cells and the survival of immature neurons, thus reduc-
ing neurogenesis (36–39). Proposed mechanisms include
the modulation of inflammation and hormonal concentra-
tions, as well as structural changes to brain vasculature.
Although the functional consequences of a decline in
neurogenesis are not understood fully, performance on
hippocampus-dependent learning and memory tasks is
closely linked to the amount of hippocampal neurogenesis
in adult rodents (24, 36, 40–43).
The aging process, and to a greater degree neurodegener-
ative disorders such as AD, are characterized by a proinflam-
matory state [(44–46), as reviewed in (47, 48)]. In rodent
models, injection of LPS to induce systemic inflammation
results in a decrease in hippocampal neurogenesis (49, 50).
Activation of microglia and the release of proinflammatory
cytokines such as TNF-a, IL-1b, and IL-6 can inhibit neu-
rogenic differentiation of neural progenitor cells (51).
With aging, blood vessels become more permeable for pro-
teins that normally would be blocked by the blood-brain
barrier, potentially initiating an inflammatory response
(52, 53). The role of inflammation in adult neurogenesis is
complex; however, there is evidence that microglia, depend-
ing on the phenotype or state of activation, may be beneficial
Nutrition affects neurogenesis and cognition 805
and support progenitor proliferation, survival, and differen-
tiation (54). Both astrocyte and microglial cells remain qui-
escent under normal physiologic conditions and respond to
an infection, injury, or neurotoxicity by releasing neuroin-
flammatory molecules. The balance between the beneficial
and harmful effects of neuroinflammation on neurogenesis
depends on the magnitude of the inflammatory response.
This response is classified as acute or chronic inflammation,
with the former being an early defensive response leading to
the protection or repair of the damaged CNS area and the
maintenance of neurogenesis as a mechanism of brain re-
pair. On the one hand, the mobilization of neural precursors
for repair, remyelination, and even axonal regeneration
could facilitate long-term neuronal survival. On the other
hand, chronic inflammation leads to long-lasting damage
to adult neurogenesis processes (55) and plays a mechanistic
role in neurodegenerative disease.
The aging process also affects a number of hormone clas-
ses. Ghrelin, an orexigenic hormone produced in the stom-
ach, has been shown to promote neurogenesis and synaptic
plasticity in the hippocampus and to have neuroprotective
effects (56, 57). Ghrelin concentrations are reduced in
aged animals (58), and young knock-out rats lacking the
ghrelin receptor growth hormone secretagogue receptor
have reduced hippocampal neurogenesis (59). Likewise,
vascular endothelial growth factor and insulin growth
factor-1 decrease with age and may contribute to a decline
in hippocampal neurogenesis (60).
Diets high in fat and refined sugars contribute to age-
related cognitive decline and dementia (61–63). Although
the negative effects of high-fat and –refined sugar diets on
brain function result in part from cardiovascular and cerebro-
vascular diseases (e.g., atherosclerosis), there appear to be di-
rect effects on the brain from diet. Lindqvist and colleagues
(64) found that feeding a high-fat (but not high-sugar) diet
for 4 wk decreased hippocampal neurogenesis and increased
serum corticosterone concentrations in male but not female
rats as compared with controls. Other studies have found
that high-fat and –refined sugar diets affect neurogenesis
and neuroplasticity through a decrease in hippocampal
brain-derived neurotrophic factor (BDNF) (65–67), a vital
mediator of neurogenesis and neuronal plasticity implicated
in the formation of long-term memory. Reduced hippocam-
pal neurogenesis (68) and impaired spatial memory (69)
also have been linked to high fructose consumption and in-
sulin resistance (66). Conversely, calorie restriction appears
to increase BDNF, neurogenesis, and the survival of newly
generated cells in the DG (70, 71). Findings from studies
by Hornsby and colleagues (72) and Kim and colleagues
(73) suggest that the beneficial effects of calorie restriction
on adult hippocampal neurogenesis and memory may be
mediated by the ghrelin receptor.
Oxidative stress has been considered one of the most po-
tent environmental factors negatively affecting neurogenesis
because it inhibits various stages of adult neurogenesis
(74, 75). Oxidative stress is known to suppress the prolifer-
ation of precursor cells, migration, integration, and survival
806 Poulose et al.
of newly formed cells (74, 75). Oxidative stress has been
shown to diminish neurogenesis in aged animals to a
much greater extent than in their younger counterparts
(76). Oxidative stress in the CNS, marked by an increased
release of reactive oxygen species, is a critical factor in cellu-
lar injury and in the activation of both acute and chronic
neuroinflammation, thereby inhibiting the adult neurogen-
esis process (77). Many dietary components have been
shown to reduce oxidative stress and neuroinflammation,
provide protection from cellular damage, and improve cog-
nitive function (78); therefore, improving the neuronal at-
mosphere could be the key to enhancing adult hippocampal
neurogenesis.
Dietary Enhancement of Adult Neurogenesis
During the last decade there has been a steady increase in re-
search into the dietary factors that affect the brain. Although
the overall diet can have profound effects on the brain, accu-
mulating evidence suggests that consumption of specific di-
etary compounds can improve cognition. Many of these
compounds have antioxidant and anti-inflammatory prop-
erties; however, increases in adult neurogenesis may also
contribute to some of the observed cognitive improvements.
Investigations into improving adult neurogenesis have thus
far focused primarily on vitamins B-9 and E, v-3 PUFAs,
and nonnutrient phytochemicals.
Vitamins
Folic acid and folate (vitamin B-9) can be found in a wide va-
riety of plant and animal foods and is a necessary regulator of
CNS development. As such, many grain-based foods are forti-
fied with folates and the intake of folic acid and folate by
women of childbearing age is encouraged. In later life, low con-
centrations of folates are associated with reduced cognitive abil-
ity (79). Supplementation with folic acid has been shown to
slow cognitive and clinical decline in people with mild cogni-
tive impairment, in particular in those with elevated homocys-
teine, which is a risk factor for AD (80). In a randomized,
double-blind, placebo-controlled study by Durga and co-
workers in 2007 (81), folic acid supplementation for 3 y
greatly improved domains of cognitive function that tend
to decline with age. In vivo studies have shown that folate
plays a critical role in DNA methylation and epigenetic phe-
nomenon in the CNS along with vitamins B-6 and B-12,
which is critical for the maintenance of adult neuro-
genesis (82). Folate deficiency substantially affects adult
hippocampal neurogenesis and depletes neurotransmitter
concentrations in the hippocampus (82); therefore, it may
be inferred that folic acid plays a critical role in the cognitive
function through the regulation of neurogenesis.
Vitamin B-12 (cobalamin) is known to play a major role
in proper brain development and function. Many clinical
studies have indicated that “low-normal” (150–300 pmol/L)
vitamin B-12 status in the serum is strongly correlated with
cognitive impairment. One plausible mechanism for this
cognitive impairment extrapolates the white matter damage
in the spinal cord characteristic of vitamin B-12 deficiency
to the white matter in the brain, damage which is known to
be associated with cognitive deficits. Another possible mech-
anism is related to DG being one of the few regions of the
adult brain where neurogenesis occurs; because vitamin
B-12 is needed for DNA replication, an inadequate supply
could impair neurogenesis. A potential third mechanism is
the impairment of methylation caused by insufficient vita-
min B-12, leading to loss of myelin from axons of the perfo-
rant path (83).
In a 2012 study (84), male Sprague-Dawley rats were ad-
ministered folic acid (0, 4, or 12 mg $ kg21 $ d21) for 28 d
before middle cerebral artery occlusion. Neurogenesis was in-
creased following occlusion; however, folic acid potentiated
this response, further increasing hippocampal neurogenesis
and attenuating ischemia-induced cognitive impairments by
improving cognitive performance following occlusion to the
level of sham controls.
Vitamin E is a fat-soluble vitamin found in nuts, seed oil,
and leafy green vegetables. Along with vitamin C, it is known
for its antioxidant and anti-inflammatory properties (85).
Preclinical studies have shown that vitamin E can regulate
adult neurogenesis (85). In an initial study (86), Sprague-
Dawley rats (age 1 mo; male) were fed a standard diet or
one that lacked vitamin E. After 5 mo, vitamin E–deficient
rats showed increased cell proliferation and density in the
DG, relative to diet controls. In a subsequent study (87), it
was determined that, although vitamin E deficiency in-
creased cell proliferation, it also increased cell death in the
DG. Furthermore, supplementation with a-tocopherol
(2 mg $ kg21 $ d21; subcutaneously) reversed these effects,
decreasing cell proliferation but increasing cell survival in
the DG (88). Vitamins are a key component of the diet; how-
ever, not all vitamins are consumed adequately. In the
United States (89), both folates and vitamin E are undercon-
sumed; therefore, supplementation with these vitamins may
help individuals achieve recommended intake amounts and
improve neurogenesis.
v-3 FAs
v-3 FAs are a form of PUFA commonly found in fatty fish,
walnuts, flaxseed, and their respective oils. v-3 FAs are nec-
essary to the structure and function of the brain, and their
role in brain health has been studied extensively. Supple-
mentation trials with v-3 FAs suggest, however, that their
effects on cognition may be beneficial only in certain com-
promised populations and not in healthy older adults (90–
97). These clinical studies indicate an improvement in
cognitive function with DHA or PUFA supplementation in
the population with habitual diets low in DHA (98). Preclin-
ical research suggests that one mechanism by which v-3 FAs
could improve cognition is by increasing adult neurogenesis.
In an early study (99), aged Wistar rats (age 18 mo; male)
were administered a 5% gum arabic solution with or without
DHA (300 mg $ kg21 $ d21; per os). After 7 wk, rats in the
DHA group showed increased neurogenesis in the DG. When
aged Wistar rats (25–26 mo; male) were compared with young
Wistar rats (age 3–4 mo; male) (100), 12 wk of feeding with a
diet containing v-3 FAs (EPA:DHA: 1.5:1; 270 mg $ kg21 $ d21;
per os) partially attenuated age-related declines in adult neuro-
genesis, relative to diet controls. A systematic meta-analysis
by Yurko-Mauro and colleagues in 2015 (101), using clinical
trials and observational studies to establish the relation
between DHA intake and cognitive outcomes, showed a sub-
stantial improvement in specific memory domains such as
episodic, working, and semantic memory, linking the possible
role of adult neurogenesis to improved cognitive function.
Phenolics
Polyphenols are a class of phytochemicals present in a wide va-
riety of plant foods. Polyphenols have received increasing atten-
tion in recent years, both as bioactive compounds underlying
the health benefits of fruits and vegetables and for their poten-
tial utility as dietary supplements. In addition to their known
antioxidant and anti-inflammatory properties, polyphenols
and polyphenol-rich whole foods can increase neurogenesis.
Berry fruit has been shown to improve cognition in both
animals (102) and humans (103–106). Blueberry has been
shown to increase neurogenesis (107). Aged F344 rats (age
19 mo; male) were fed a modified NIH-31 control diet
or a diet containing 2% blueberry (;20 g/kg). After 8 wk,
blueberry-fed rats showed improved performance (fewer er-
rors) on a spatial memory task, which was associated with an
increased proliferation of precursor cells in the DG, relative
to control-fed rats. Recently, strawberry also has been shown
to improve neurogenesis (31); in this study, aged F344 rats
(age 19 mo; male) were randomly assigned to a 2% blueberry
diet, a 2% strawberry diet, or a control diet (NIH-31). After
8 wk, blueberry-fed rats showed increased coordination,
and rats in both diet groups showed improved spatial working
memory, relative to diet controls. Strawberry-fed rats showed
increased survival in the precursor cells in the DG, relative to
controls. No substantial improvements in cell survival were
achieved in blueberry-fed rats in the study by Shukitt-Hale
et al. (31); however, changes in cognition were positively cor-
related with changes in cell proliferation in blueberry-fed rats.
Similarly, grapeseed extract has been shown to improve
adult neurogenesis. Middle-aged C57BL/6 mice (age 12 mo;
male) were administered grapeseed extract (0, 25, 50, or
100 mg $ kg21 $ d21) for 28 d. Grapeseed extract increased
proliferation, differentiation, and integration in the DG,
in a dose-dependent manner, relative to controls. Although
the effect of grapeseed extract on neurogenesis has not been
assessed in humans, acute administration has been shown
to increase serum concentrations of BDNF, which plays a reg-
ulatory role in neurogenesis (108).
Curcumin is a polyphenol found in turmeric, a staple of
Asian cuisine. Curcumin has been studied widely for its po-
tential health benefits (109); however, research shows that it
may promote brain health by increasing or stabilizing adult
neurogenesis. Aged Sprague-Dawley rats (age 15 mo; male)
were administered a 0.048% curcumin diet or unpurified
diet for 6 or 12 wk (110). Curcumin-fed rats showed im-
proved performance on an olfactory cortex–based social
Nutrition affects neurogenesis and cognition 807
recognition memory task at both 6 and 12 wk, and on a
hippocampus-dependent spatial learning and memory task
after 12 wk, relative to controls. Curcumin-fed rats also
showed increased proliferation in the DG at 12 wk, relative
to diet controls. Similarly, Xu et al. showed that curcumin
can reverse stress-induced reductions in neurogenesis
(111). In this study, Sprague-Dawley rats (190–200 g) were
administered a peanut oil solution containing curcumin
(0, 5, 10, or 20 mg $ kg21 $ d21; per os) during 20 d of un-
predictable chronic stress. Whereas control rats showed de-
creased proliferation and BDNF concentrations in the DG,
curcumin-fed rats showed attenuated amounts of proliferation
and BDNF, in a dose-dependent manner, with the highest dose
(20 mg $ kg21 $ d21) being consistent with the amount of pro-
liferation seen in imipramine hydrochloride–treated positive
controls (110 mg $ kg21 $ d21; intraperitoneally).
Resveratrol is a stilbene found in peanuts, tree nuts, grapes,
cocoa, wine, and berry fruits (112). Resveratrol is well known
for its activation of sirtuin 1 (113), and it can also induce neu-
rogenesis. In one study (114), 2-mo-old female BALB/c mice
were administered Brucella abortus antigen to induce chronic
fatigue, which reduced the amounts of cell proliferation in the
SGZ of the DG and hippocampal BDNF mRNA, relative to
controls. Subsequent treatment with resveratrol (40 mg $
kg21 $ d21) for 1 mo fully attenuated the reduction of cell
proliferation and normalized the amounts of hippocampal
BDNF mRNA, relative to vehicle controls.
Synergy
As in other areas of nutritional research, an emerging line of
inquiry is whether the combination of specific foods or their
constituent compounds can produce a synergistic effect
when combined in the diet or through supplementation.
One study (28) examined the effect of a specially formulated
diet, the LMN, that includes both FA and phenolic compo-
nents, specifically nuts, cocoa, vegetable oils, and high-fiber
flour. Ten-week-old 129S1/SvImJ mice that consumed a
9.27% LMN diet for 40 d showed increased cell prolifer-
ation and differentiation in the subventricular rostral mi-
gratory stream and olfactory bulb, and in the SGZ of the
DG, relative to age-matched diet controls. A subsequent
study (115) examined the effect of the LMN diet on 18-
mo-old Tg2576 transgenic mice, which develop amyloid
(Ab) plaques at 12 mo. Both Tg2576 mice and wild-type
controls that were fed the LMN diet showed improved spa-
tial learning and memory at 18 mo, and these improvements
were correlated with increases in cell proliferation in the
SVZ of the DG. Dietary compounds, both individually and
in combination, can improve adult neurogenesis. Combin-
ing whole foods or their bioactive constituent compounds
may result in additive or synergistic (or both) improvement
in adult neurogenesis and thereby further increase their ther-
apeutic potential.
Summary
This review has highlighted the latest evidence that hippo-
campal neurogenesis and brain plasticity can be improved
808 Poulose et al.
by dietary factors, leading to possible improvement in age-
related cognitive deficits. The US population is experiencing
an increase in the proportion of older people, such that
;20% of the US total population will be >65 y by 2050,
which is almost double what it is today. As people age, the
incidence of age-related pathologies, including decreases in
cognitive function, will also increase, with a concomitant in-
crease in health care costs. As shown in this review, neuro-
genesis also decreases with age, and because of its role in
neural plasticity, brain homeostasis, maintenance, and tissue
remodeling, it plays a critical role in cognitive function. Al-
though factors associated with aging, such as oxidative stress
and inflammation, have been shown to decrease neurogen-
esis, dietary compounds that mitigate aging and age-related
behavioral declines have been shown to increase neurogen-
esis. Some of these food compounds include the folates,
vitamin E, v-3 FAs, and polyphenols found in fruits, vege-
tables, nuts, and spices. Because these studies have been con-
ducted in animal models, it is unclear whether the results
will translate to humans. Although these studies are needed
for proof of concept, the difficulty of assessing neurogenesis
in human intervention studies precludes their feasibility in
clinical trials. Given that increasing intake of these foods
and food components is relatively safe and easy, however,
their potential beneficial effects on neurogenesis should be
considered for the prevention of or delay in age-related neu-
rological dysfunction and cognitive decline.
Acknowledgments
All authors read and approved the final manuscript.
References
1. Altman J, Das GD. Autoradiographic and histological evidence of
postnatal hippocampal neurogenesis in rats. J Comp Neurol 1965;124:
319–35.
2. Temple S. Division and differentiation of isolated CNS blast cells in
microculture. Nature 1989;340:471–3.
3. Bayer SA. Development of the hippocampal region in the rat. I.
Neurogenesis examined with 3H-thymidine autoradiography. J Comp
Neurol 1980;190:87–114.
4. Reynolds BA, Weiss S. Generation of neurons and astrocytes from
isolated cells of the adult mammalian central nervous system. Science
1992;255:1707–10.
5. Jin K, Minami M, Lan JQ, Mao XO, Batteur S, Simon RP,
Greenberg DA. Neurogenesis in dentate subgranular zone and rostral
subventricular zone after focal cerebral ischemia in the rat. Proc Natl
Acad Sci USA 2001;98:4710–5.
6. Overall RW, Paszkowski-Rogacz M, Kempermann G. The mammalian
adult neurogenesis gene ontology (MANGO) provides a structural
framework for published information on genes regulating adult hip-
pocampal neurogenesis. PLoS One 2012;7:e48527.
7. Lois C, Garcia-Verdugo JM, Alvarez-Buylla A. Chain migration of
neuronal precursors. Science 1996;271:978–81.
8. Luskin MB. Restricted proliferation and migration of postnatally
generated neurons derived from the forebrain subventricular zone.
Neuron 1993;11:173–89.
9. Ming GL, Song H. Adult neurogenesis in the mammalian brain: sig-
nificant answers and significant questions. Neuron 2011;70:687–702.
10. Balu DT, Lucki I. Adult hippocampal neurogenesis: regulation, func-
tional implications, and contribution to disease pathology. Neurosci
Biobehav Rev 2009;33:232–52.
11. Cameron HA, McKay RD. Restoring production of hippocampal
neurons in old age. Nat Neurosci 1999;2:894–7.
12. Tanapat P, Hastings NB, Reeves AJ, Gould E. Estrogen stimulates a
transient increase in the number of new neurons in the dentate gyrus
of the adult female rat. J Neurosci 1999;19:5792–801.
13. O’Kusky JR, Ye P, D’Ercole AJ. Insulin-like growth factor-I promotes
neurogenesis and synaptogenesis in the hippocampal dentate gyrus
during postnatal development. J Neurosci 2000;20:8435–42.
14. Cameron HA, Tanapat P, Gould E. Adrenal steroids and N-methyl-D-
aspartate receptor activation regulate neurogenesis in the dentate
gyrus of adult rats through a common pathway. Neuroscience 1998;
82:349–54.
15. Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ. Learning enhances
adult neurogenesis in the hippocampal formation. Nat Neurosci 1999;
2:260–5.
16. Yau SY, Lau BW, So KF. Adult hippocampal neurogenesis: a possible
way how physical exercise counteracts stress. Cell Transplant 2011;20:
99–111.
17. Veena J, Rao BS, Srikumar BN. Regulation of adult neurogenesis in
the hippocampus by stress, acetylcholine and dopamine. J Nat Sci Biol
Med 2011;2:26–37.
18. Stangl D, Thuret S. Impact of diet on adult hippocampal neuro-
genesis. Genes Nutr 2009;4:271–82.
19. Foster TC. Biological markers of age-related memory deficits: treat-
ment of senescent physiology. CNS Drugs 2006;20:153–66.
20. Winner B, Winkler J. Adult neurogenesis in neurodegenerative dis-
eases. Cold Spring Harb Perspect Biol 2015;7:a021287.
21. Bekinschtein P, Katche C, Slipczuk L, Gonzalez C, Dorman G,
Cammarota M, Izquierdo I, Medina JH. Persistence of long-term
memory storage: new insights into its molecular signatures in the hip-
pocampus and related structures. Neurotox Res 2010;18:377–85.
22. Armstrong RA, Cairns NJ. Comparative quantitative study of ‘signa-
ture’ pathological lesions in the hippocampus and adjacent gyri of 12
neurodegenerative disorders. J Neural Transm (Vienna) 2015;122:
1355–67.
23. Dokter M, von Bohlen und Halbach O. Neurogenesis within the adult
hippocampus under physiological conditions and in depression.
Neural Regen Res 2012;7:552–9.
24. Deng W, Aimone JB, Gage FH. New neurons and new memories: how
does adult hippocampal neurogenesis affect learning and memory?
Nat Rev Neurosci 2010;11:339–50.
25. Fabel K, Kempermann G. Physical activity and the regulation of neuro-
genesis in the adult and aging brain. Neuromolecular Med 2008;10:59–66.
26. Huang FL, Huang KP, Wu J, Boucheron C. Environmental enrichment
enhances neurogranin expression and hippocampal learning and
memory but fails to rescue the impairments of neurogranin null
mutant mice. J Neurosci 2006;26:6230–7.
27. Levenson CW, Rich NJ. Eat less, live longer? New insights into the role
of caloric restriction in the brain. Nutr Rev 2007;65:412–5.
28. Valente T, Hidalgo J, Bolea I, Ramirez B, Angles N, Reguant J,
Morello JR, Gutierrez C, Boada M, Unzeta M. A diet enriched in
polyphenols and polyunsaturated fatty acids, LMN diet, induces
neurogenesis in the subventricular zone and hippocampus of adult
mouse brain. J Alzheimers Dis 2009;18:849–65.
29. Beltz BS, Tlusty MF, Benton JL, Sandeman DC. Omega-3 fatty acids
upregulate adult neurogenesis. Neurosci Lett 2007;415:154–8.
30. Kim SJ, Son TG, Park HR, Park M, Kim MS, Kim HS, Chung HY,
Mattson MP, Lee J. Curcumin stimulates proliferation of embryonic
neural progenitor cells and neurogenesis in the adult hippocampus.
J Biol Chem 2008;283:14497–505.
31. Shukitt-Hale B, Bielinski DF, Lau FC, Willis LM, Carey AN, Joseph JA.
The beneficial effects of berries on cognition, motor behaviour and
neuronal function in ageing. Br J Nutr 2015;114:1542–9.
32. Torres-Pérez M, Tellez-Ballesteros RI, Ortiz-López L, Ichwan M, Vega-
Rivera NM, Castro-García M, Gómez-Sánchez A, Kempermann G,
Ramirez-Rodriguez GB. Resveratrol enhances neuroplastic changes,
including hippocampal neurogenesis, and memory in Balb/C mice at
six months of age. PLoS One 2015;10:e0145687.
33. Sawamoto A, Okuyama S, Yamamoto K, Amakura Y, Yoshimura M,
Nakajima M, Furukawa Y. 3,5,6,7,8,39,49-Heptamethoxyflavone, a
citrus flavonoid, ameliorates corticosterone-induced depression-like
behavior and restores brain-derived neurotrophic factor expression,
neurogenesis, and neuroplasticity in the hippocampus. Molecules
2016;21:541.
34. Poulose SM, Carey AN, Shukitt-Hale B. Improving brain signaling in
aging: could berries be the answer? Expert Rev Neurother 2012;12:
887–9.
35. Migaud M, Batailler M, Segura S, Duittoz A, Franceschini I, Pillon D.
Emerging new sites for adult neurogenesis in the mammalian brain: a
comparative study between the hypothalamus and the classical neu-
rogenic zones. Eur J Neurosci 2010;32:2042–52.
36. Seib DR, Martin-Villalba A. Neurogenesis in the normal ageing hip-
pocampus: a mini-review. Gerontology 2015;61:327–35.
37. Galvan V, Jin K. Neurogenesis in the aging brain. Clin Interv Aging
2007;2:605–10.
38. Lazarov O, Mattson MP, Peterson DA, Pimplikar SW, van Praag H.
When neurogenesis encounters aging and disease. Trends Neurosci
2010;33:569–79.
39. Varela-Nallar L, Aranguiz FC, Abbott AC, Slater PG, Inestrosa NC.
Adult hippocampal neurogenesis in aging and Alzheimer’s disease.
Birth Defects Res C Embryo Today 2010;90:284–96.
40. Marín-Burgin A, Schinder AF. Requirement of adult-born neurons
for hippocampus-dependent learning. Behav Brain Res 2012;227:
391–9.
41. Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM,
Fainberg N, Ding Z, Eggel A, et al. The ageing systemic milieu neg-
atively regulates neurogenesis and cognitive function. Nature 2011;
477:90–4.
42. Drapeau E, Mayo W, Aurousseau C, Le Moal M, Piazza PV,
Abrous DN. Spatial memory performances of aged rats in the water
maze predict levels of hippocampal neurogenesis. Proc Natl Acad Sci
USA 2003;100:14385–90.
43. Clelland CD, Choi M, Romberg C, Clemenson GD Jr., Fragniere A,
Tyers P, Jessberger S, Saksida LM, Barker RA, Gage FH, et al. A
functional role for adult hippocampal neurogenesis in spatial pattern
separation. Science 2009;325:210–3.
44. Franceschi C, Campisi J. Chronic inflammation (inflammaging) and
its potential contribution to age-associated diseases. J Gerontol A Biol
Sci Med Sci 2014;69:S4–9.
45. Simen AA, Bordner KA, Martin MP, Moy LA, Barry LC. Cognitive
dysfunction with aging and the role of inflammation. Ther Adv
Chronic Dis 2011;2:175–95.
46. Sartori AC, Vance DE, Slater LZ, Crowe M. The impact of inflam-
mation on cognitive function in older adults: implications for
healthcare practice and research. J Neurosci Nurs 2012;44:206–17.
47. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM,
Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, et al. In-
flammation and Alzheimer’s disease. Neurobiol Aging 2000;21:383–
421.
48. Wyss-Coray T, Rogers J. Inflammation in Alzheimer disease—a brief
review of the basic science and clinical literature. Cold Spring Harb
Perspect Med 2012;2:a006346.
49. Monje ML, Toda H, Palmer TD. Inflammatory blockade restores adult
hippocampal neurogenesis. Science 2003;302:1760–5.
50. Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O. Inflammation
is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci USA
2003;100:13632–7.
51. Gemma C, Bachstetter AD, Bickford PC. Neuron-microglia dialogue
and hippocampal neurogenesis in the aged brain. Aging Dis 2010;1:
232–44.
52. Farrall AJ, Wardlaw JM. Blood-brain barrier: ageing and microvascu-
lar disease–systematic review and meta-analysis. Neurobiol Aging
2009;30:337–52.
53. Weiss N, Miller F, Cazaubon S, Couraud PO. The blood-brain barrier
in brain homeostasis and neurological diseases. Biochim Biophys Acta
2009;1788:842–57.
Nutrition affects neurogenesis and cognition 809
 54. Ekdahl CT, Kokaia Z, Lindvall O. Brain inflammation and adult neu-
rogenesis: the dual role of microglia. Neuroscience 2009;158:1021–9.
55. Fuster-Matanzo A, Llorens-Martin M, Hernandez F, Avila J. Role of
neuroinflammation in adult neurogenesis and Alzheimer disease:
therapeutic approaches. Mediators Inflamm 2013;2013:260925.
56. Moon M, Kim S, Hwang L, Park S. Ghrelin regulates hippocampal
neurogenesis in adult mice. Endocr J 2009;56:525–31.
57. Kent BA, Beynon AL, Hornsby AK, Bekinschtein P, Bussey TJ,
Davies JS, Saksida LM. The orexigenic hormone acyl-ghrelin increases
adult hippocampal neurogenesis and enhances pattern separation.
Psychoneuroendocrinology 2015;51:431–9.
58. Smith RG, Sun Y, Jiang H, Albarran-Zeckler R, Timchenko N. Ghrelin
receptor (GHS-R1A) agonists show potential as interventive agents
during aging. Ann N Y Acad Sci 2007;1119:147–64.
59. Li E, Chung H, Kim Y, Kim DH, Ryu JH, Sato T, Kojima M, Park S.
Ghrelin directly stimulates adult hippocampal neurogenesis: impli-
cations for learning and memory. Endocr J 2013;60:781–9.
60. Lee SW, Clemenson GD, Gage FH. New neurons in an aged brain.
Behav Brain Res 2012;227:497–507.
61. Knopman D, Boland LL, Mosley T, Howard G, Liao D, Szklo M,
McGovern P, Folsom AR; Atherosclerosis Risk in Communities
(ARIC) Study Investigators. Cardiovascular risk factors and cognitive
decline in middle-aged adults. Neurology 2001;56:42–8.
62. Kalmijn S, White L, Ross GW, Petrovitch H, Foley D, Curb JD,
Havlik RJ, Launer LJ. The metabolic cardiovascular syndrome and the
risk of dementia in elderly men: the Honolulu-Asia aging study. Neu-
rology 2000;54:A76.
63. Kalmijn S, Launer LJ, Ott A, Witteman JCM, Hofman A,
Breteler MMB. Dietary fat intake and the risk of incident dementia in
the Rotterdam Study. Ann Neurol 1997;42:776–82.
64. Lindqvist A, Mohapel P, Bouter B, Frielingsdorf H, Pizzo D,
Brundin P, Erlanson-Albertsson C. High-fat diet impairs hippocampal
neurogenesis in male rats. Eur J Neurol 2006;13:1385–8.
65. Molteni R, Barnard RJ, Ying Z, Roberts CK, Gomez-Pinilla F. A high-
fat, refined sugar diet reduces hippocampal brain-derived neurotro-
phic factor, neuronal plasticity, and learning. Neuroscience 2002;
112:803–14.
66. Stranahan AM, Norman ED, Lee K, Cutler RG, Telljohann RS,
Egan JM, Mattson MP. Diet-induced insulin resistance impairs hippo-
campal synaptic plasticity and cognition in middle-aged rats. Hippo-
campus 2008;18:1085–8.
67. Park HR, Park M, Choi J, Park KY, Chung HY, Lee J. A high-fat diet
impairs neurogenesis: involvement of lipid peroxidation and brain-
derived neurotrophic factor. Neurosci Lett 2010;482:235–9.
68. van der Borght K, Kohnke R, Goransson N, Deierborg T, Brundin P,
Erlanson-Albertsson C, Lindqvist A. Reduced neurogenesis in the rat
hippocampus following high fructose consumption. Regul Pept 2011;
167:26–30.
69. Ross AP, Bartness TJ, Mielke JG, Parent MB. A high fructose diet impairs
spatial memory in male rats. Neurobiol Learn Mem 2009;92:410–6.
70. Lee J, Duan WZ, Long JM, Ingram DK, Mattson MP. Dietary re-
striction increases the number of newly generated neural cells, and
induces BDNF expression, in the dentate gyrus of rats. J Mol Neurosci
2000;15:99–108.
71. Lee J, Seroogy KB, Mattson MP. Dietary restriction enhances neuro-
trophin expression and neurogenesis in the hippocampus of adult
mice. J Neurochem 2002;80:539–47.
72. Hornsby AKE, Redhead YT, Rees DJ, Ratcliff MSG, Reichenbach A,
Wells T, Francis L, Amstalden K, Andrews ZB, Davies JS. Short-term
calorie restriction enhances adult hippocampal neurogenesis and re-
mote fear memory in a Ghsr-dependent manner. Psychoneuroendoc-
rinology 2016;63:198–207.
73. Kim Y, Kim S, Kim C, Sato T, Kojima M, Park S. Ghrelin is required
for dietary restriction-induced enhancement of hippocampal neuro-
genesis: lessons from ghrelin knockout mice. Endocr J 2015;62:269–
75.
74. Yuan TF, Gu S, Shan C, Marchado S, Arias-Carrion O. Oxidative stress
and adult neurogenesis. Stem Cell Rev 2015;11:706–9.
810 Poulose et al.
75. Santos R, Ruiz de Almodovar C, Bulteau AL, Gomes CM. Neuro-
degeneration, neurogenesis, and oxidative stress. Oxid Med Cell
Longev 2013;2013:730581.
76. Simon M, Czeh B, Fuchs E. Age-dependent susceptibility of adult hip-
pocampal cell proliferation to chronic psychosocial stress. Brain Res
2005;1049:244–8.
77. Taylor JM, Main BS, Crack PJ. Neuroinflammation and oxidative
stress: co-conspirators in the pathology of Parkinson’s disease. Neu-
rochem Int 2013;62:803–19.
78. Miller MG, Thangthaeng N, Poulose SM, Shukitt-Hale B. Role of
fruits, nuts, and vegetables in maintaining cognitive health. Exp
Gerontol 2017;94:24–8.
79. Kado DM, Karlamangla AS, Huang M-H, Troen A, Rowe JW, Selhub J,
Seeman TE. Homocysteine versus the vitamins folate, B 6, and B 12 as
predictors of cognitive function and decline in older high-functioning
adults: MacArthur Studies of Successful Aging. Am J Med 2005;118:161–7.
80. de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and
clinical outcomes of homocysteine-lowering B-vitamin treatment in
mild cognitive impairment: a randomized controlled trial. Int J Ger-
iatr Psychiatry 2012;27:592–600.
81. Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolles J, Katan MB,
Verhoef P. Effect of 3-year folic acid supplementation on cognitive
function in older adults in the FACIT trial: a randomised, double
blind, controlled trial. Lancet 2007;369:208–16.
82. Kronenberg G, Harms C, Sobol RW, Cardozo-Pelaez F, Linhart H,
Winter B, Balkaya M, Gertz K, Gay SB, Cox D, et al. Folate deficiency
induces neurodegeneration and brain dysfunction in mice lacking
uracil DNA glycosylase. J Neurosci 2008;28:7219–30.
83. Smith AD. Hippocampus as a mediator of the role of vitamin B-12
in memory. Am J Clin Nutr 2016;103:959–60.
84. Zhang X, Huang G, Liu H, Chang H, Wilson JX. Folic acid enhances
notch signaling, hippocampal neurogenesis, and cognitive function
in a rat model of cerebral ischemia. Nutr Neurosci 2012;15:55–61.
85. Oyarce K, Bongarzone ER, Nualart F. Unconventional neurogenic
niches and neurogenesis modulation by vitamins. J Stem Cell Res
Ther 2014;4:184.
86. Ciaroni S, Cuppini R, Cecchini T, Ferri P, Ambrogini P, Cuppini C,
Del Grande P. Neurogenesis in the adult rat dentate gyrus is enhanced
by vitamin E deficiency. J Comp Neurol 1999;411:495–502.
87. Ciaroni S, Cecchini T, Ferri P, Cuppini R, Ambrogini P, Santi S,
Benedetti S, Del Grande P, Papa S. Neural precursor proliferation and
newborn cell survival in the adult rat dentate gyrus are affected by
vitamin E deficiency. Neurosci Res 2002;44:369–77.
88. Cuppini R, Ciaroni S, Cecchini T, Ambrogini P, Ferri P, Del Grande P,
Papa S. a-Tocopherol controls cell proliferation in the adult rat
dentate gyrus. Neurosci Lett 2001;303:198–200.
89. USDA and US Department of Health and Human Services. Scientific
report of the 2015 dietary guidelines advisory committee. Washington
(DC): USDA and US Department of Health and Human Services;
2015.
90. Burckhardt M, Herke M, Wustmann T, Watzke S, Langer G, Fink A.
Omega-3 fatty acids for the treatment of dementia. Cochrane Data-
base Syst Rev 2016 4:CD009002.
91. Jackson PA, Forster JS, Bell JG, Dick JR, Younger I, Kennedy DO.
DHA supplementation alone or in combination with other nutrients
does not modulate cerebral hemodynamics or cognitive function in
healthy older adults. Nutrients 2016;8:86.
92. Phillips MA, Childs CE, Calder PC, Rogers PJ. No effect of omega-3
fatty acid supplementation on cognition and mood in individuals with
cognitive impairment and probable Alzheimer’s disease: a randomised
controlled trial. Int J Mol Sci 2015;16:24600–13.
93. Lee LK, Shahar S, Chin A-V, Yusoff NAM. Docosahexaenoic acid-
concentrated fish oil supplementation in subjects with mild cognitive
impairment (MCI): a 12-month randomised, double-blind, placebo-
controlled trial. Psychopharmacology (Berl) 2013;225:605–12.
94. Karr JE, Grindstaff TR, Alexander JE. Omega-3 polyunsaturated fatty
acids and cognition in a college-aged population. Exp Clin Psycho-
pharmacol 2012;20:236–42.
 95. Jackson PA, Deary ME, Reay JL, Scholey AB, Kennedy DO. No effect
of 12 weeks’ supplementation with 1 g DHA-rich or EPA-rich fish oil
on cognitive function or mood in healthy young adults aged 18–35
years. Br J Nutr 2012;107:1232–43.
96. Stough C, Downey L, Silber B, Lloyd J, Kure C, Wesnes K, Camfield D.
The effects of 90-day supplementation with the omega-3 essential fatty
acid docosahexaenoic acid (DHA) on cognitive function and visual acu-
ity in a healthy aging population. Neurobiol Aging 2012;33:824.e1–e3.
97. Mazereeuw G, Lanctôt KL, Chau SA, Swardfager W, Herrmann N.
Effects of omega-3 fatty acids on cognitive performance: a meta-analysis.
Neurobiol Aging 2012;33:1482.e17–e29.
98. Stonehouse W, Conlon CA, Podd J, Hill SR, Minihane AM, Haskell C,
Kennedy D. DHA supplementation improved both memory and re-
action time in healthy young adults: a randomized controlled trial.
Am J Clin Nutr 2013;97:1134–43.
99. Kawakita E, Hashimoto M, Shido O. Docosahexaenoic acid promotes
neurogenesis in vitro and in vivo. Neuroscience 2006;139:991–7.
100. Dyall SC, Michael GJ, Michael-Titus AT. Omega-3 fatty acids reverse
age-related decreases in nuclear receptors and increase neurogenesis in
old rats. J Neurosci Res 2010;88:2091–102.
101. Yurko-Mauro K, Alexander DD, Van Elswyk ME. Docosahexaenoic
acid and adult memory: a systematic review and meta-analysis. PLoS
One 2015;10:e0120391.
102. Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, McEwen JJ,
Bickford PC. Reversals of age-related declines in neuronal signal transduc-
tion, cognitive, and motor behavioral deficits with blueberry, spinach, or
strawberry dietary supplementation. J Neurosci 1999;19:8114–21.
103. Krikorian R, Shidler MD, Nash TA, Kalt W, Vinqvist-Tymchuk MR,
Shukitt-Hale B, Joseph JA. Blueberry supplementation improves
memory in older adultsy. J Agric Food Chem 2010;58:3996–4000.
104. Miller MG, Hamilton DA, Joseph JA, Shukitt-Hale B. Dietary blue-
berry improves cognition among older adults in a randomized,
double-blind, placebo-controlled trial. Eur J Nutr 2017 Mar 10 (Epub
ahead of print; DOI: 10.1007/s00394-017-1400-8).
105. Whyte AR, Williams CM. Effects of a single dose of a flavonoid-rich
blueberry drink on memory in 8 to 10 y old children. Nutrition
2015;31:531–4.
106. Whyte AR, Schafer G, Williams CM. Cognitive effects following acute
wild blueberry supplementation in 7-to 10-year-old children. Eur J
Nutr 2016;55:2151–62.
107. Casadesus G, Shukitt-Hale B, Stellwagen HM, Zhu X, Lee H-G,
Smith MA, Joseph JA. Modulation of hippocampal plasticity and
cognitive behavior by short-term blueberry supplementation in aged
rats. Nutr Neurosci 2004;7:309–16.
108. Reyes-Izquierdo T, Nemzer B, Shu C, Huynh L, Argumedo R, Keller R,
Pietrzkowski Z. Modulatory effect of coffee fruit extract on plasma
levels of brain-derived neurotrophic factor in healthy subjects. Br J
Nutr 2013;110:420–5.
109. Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Ramirez-
Tortosa M. Curcumin and health. Molecules 2016;21:264.
110. Dong S, Zeng Q, Mitchell ES, Xiu J, Duan Y, Li C, Tiwari JK, Hu Y,
Cao X, Zhao Z. Curcumin enhances neurogenesis and cognition in
aged rats: implications for transcriptional interactions related to
growth and synaptic plasticity. PLoS One 2012;7:e31211.
111. Xu Y, Ku B, Cui L, Li X, Barish PA, Foster TC, Ogle WO. Curcumin
reverses impaired hippocampal neurogenesis and increases serotonin
receptor 1A mRNA and brain-derived neurotrophic factor expression
in chronically stressed rats. Brain Res 2007;1162:9–18.
112. Poulose SM, Thangthaeng N, Miller MG, Shukitt-Hale B. Effects of
pterostilbene and resveratrol on brain and behavior. Neurochem Int
2015;89:227–33.
113. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV,
Allard JS, Lopez-Lluch G, Lewis K. Resveratrol improves health and sur-
vival of mice on a high-calorie diet. Nature 2006;444:337–42.
114. Moriya J, Chen R, Yamakawa J-i, Sasaki K, Ishigaki Y, Takahashi T.
Resveratrol improves hippocampal atrophy in chronic fatigue mice by
enhancing neurogenesis and inhibiting apoptosis of granular cells.
Biol Pharm Bull 2011;34:354–9.
115. Fernández-Fernández L, Comes G, Bolea I, Valente T, Ruiz J,
Murtra P, Ramirez B, Anglés N, Reguant J, Morelló JR. LMN diet, rich
in polyphenols and polyunsaturated fatty acids, improves mouse
cognitive decline associated with aging and Alzheimer’s disease. Behav
Brain Res 2012;228:261–71.
Nutrition affects neurogenesis and cognition 811