Junk food junkies take notice. What you eat does more
than influence your gut. It also may affect your brain.
Increasing evidence shows that mom was right: You should
eat your vegetables, and your blueberries and walnuts,
Scientists are confirming that this age-old adage is
worth following. And new studies show that diet may have
implications for those who suffer from certain brain ailments.
Diets containing two percent, six percent, or nine percent
walnuts, when given to old rats, were found to reverse
several parameters of brain aging, as well as age-related
motor and cognitive deficits, says James Joseph, PhD,
of the U.S. Department of Agriculture Human Nutrition
Research Center at Tufts University in Boston.
In previous research, Joseph and his colleagues showed
that old rats maintained for two months on diets containing
two percent high antioxidant strawberry or blueberry extracts
exhibited reversals of age-related deficits in the way
that neurons function and in motor and cognitive behavior.
In the brain, antioxidant molecules wage war against molecules
known as free radicals, which can harm brain cells and
brain function. The present research extends these findings
and shows that walnuts can have a similar effect.
Walnuts contain alpha-linolenic acid (ALA), an essential
omega-3 fatty acid, and other polyphenols that act as
antioxidants and may actually block the signals produced
by free radicals that can later produce compounds that
would increase inflammation. Findings from the studies
by Joseph and his colleague Barbara Shukitt-Hale, PhD,
show for the first time that shorter chain fatty acids
found in plants, such as walnuts, may have beneficial
effects on cognition similar to those from long chain
fatty acids derived from animal sources, which have been
A six percent diet is equivalent to a person eating 1
ounce of walnuts each day, which is the recommended amount
to reduce harmful low-density lipoprotein, or LDL, cholesterol,
while a nine percent diet is equivalent to people eating
1.5 ounces of walnuts per day. "Importantly,"
Joseph says, "this information, coupled with our
previous studies, shows that the addition of walnuts,
berries, and grape juice to the diet may increase 'health
span' in aging and provide a 'longevity dividend' or economic
benefit for slowing the aging process by reducing the
incidence and delaying the onset of debilitating degenerative
Joseph and his colleagues are currently assessing whether
increased neurogenesis or alterations in stress signaling,
or both, may be involved in the mechanisms through which
the walnut diets could be producing their effects. Ongoing
research suggests that walnuts involve more than the mere
"quenching" of free radicals and may in fact
involve direct effects on blocking the deleterious "stress
signals" generated by the oxidative stressors. "The
beneficial effects of walnuts also may be the direct result
of enhancements of signals which mediate such important
functions as neuronal communication and the growth of
new neurons," says Joseph.
A great deal of data suggests that the deficits associated
with aging, for example, Alzheimer's disease and cardiovascular
diseases, arise as a result of an increasing inability
of the aging organism to protect itself against inflammation
and oxidative stress, providing fertile ground for the
development of neurodegenerative diseases. "The good
news," Joseph says, "is that it appears that
compounds found in fruits and vegetables -- and, as we
have shown in our research, walnuts -- may provide the
necessary protection to prevent the demise of cognitive
and motor function in aging."
Other research shows that walnut extract may play a role
toward developing novel treatments for Alzheimer's. Amyloid-ß
plaques are the primary physiological hallmark of Alzheimer's.
The presence of the enzyme acetylcholinesterase within
these plaques has been confirmed, and the enzyme has been
shown to induce plaque formation.
Modern Alzheimer's drugs typically target either acetylcholinesterase
activity or plaque formation, but do not simultaneously
inhibit both. "Therefore, they only have limited
success in slowing the progression of the disease,"
says Gina Wilson, of Baldwin-Wallace College in Berea,
Ohio. Wilson and her colleagues have discovered through
the use of strictly chemical techniques in the absence
of living cells that walnut extract and two of its major
components, gallic and ellagic acids, act as "dual-inhibitors"
of the enzyme acetylcholinesterase. Chemical techniques
included enzyme kinetics and colorimetric analyses of
congo red, a dye that binds to amyloid-ß aggregates.
It was found that gallic and ellagic acids not only inhibit
the site of acetylcholinesterase associated with amyloid-ß
protein aggregation, but will also inhibit the site of
acetylcholinesterase responsible for the breakdown of
"Initially, we confirmed earlier results showing
that walnut extract inhibits amyloid-ß protein aggregation
in the presence of acetylcholinesterase and breaks apart
preformed aggregates," says Wilson. "However,
the new findings have not been presented elsewhere or
replicated by other laboratories, to the best of our knowledge."
Wilson's research is the first set of data to demonstrate
inhibition of acetylcholine breakdown by walnut extract
and to isolate specific chemicals from that extract, gallic
and ellagic acids, responsible for the observed dual-inhibition.
The research is the first to suggest that ellagic acid,
and possibly gallic acid, can break up preformed aggregates.
While exact replications are needed, Wilson and her colleagues
plan to extend their research to live animals. They plan
to inject rats with an amyloid-ß protein fragments
that will aggregate in their brains. Experimental animals
will then be treated with either chemical. This will allow
for measurements of brain acetylcholinesterase activity,
plaque formation, and oxidative damage. Additionally,
this procedure will provide comparisons of cognitive-behavioral
data between treated and untreated groups.
Acetylcholine is a brain chemical particularly important
for learning and memory. Levels of acetylcholine found
in the brains of Alzheimer's patients are significantly
depleted. However, this is not the sole event responsible
for progression of the disease. Abnormal amyloid-ß
proteins aggregate and form what are known as plaques,
another key feature found in the brains of Alzheimer's
sufferers. Amyloid-ß plaques have also been linked
to the memory impairments and cognitive decline associated
with the disease. Acetylcholinesterase is an integral
part of these plaques and accelerates plaque formation.
"It is important," Wilson says, "to investigate
'dual-inhibitors' of acetylcholinesterase in efforts to
develop more efficient pharmacological treatments for
Another avenue of research regarding a link between diet
and the brain shows that blueberries contain compounds
that can reduce inflammation in the central nervous system.
Inflammation in the central nervous system is known to
be a key issue in the progression of neurodegeneration,
and dietary intake of blueberries has been shown to alleviate
cognitive decline associated with disease and aging.
Thomas Kuhn, PhD, of the University of Alaska, Fairbanks,
and his colleagues have discovered that Alaska wild bog
blueberries contain compounds that efficiently interfere
with inflammatory processes in the central nervous system.
The study conducted in Kuhn's lab revealed an interaction
between compounds in Alaska blueberries and a specific
protein molecule in neuronal cells that reduces detrimental
effects of inflammation. Understanding the interaction
of these compounds could lead to the development of new
drug therapies that would diminish inflammation of the
brain and spinal cord.
While the health benefits of fruits and vegetables are
largely attributed to polyphenols, molecules with strong
antioxidant potential, Kuhn says that, surprisingly, the
compounds in Alaska blueberries discovered in their study
are neither antioxidants nor polyphenols, yet rather serve
as specific inhibitors.
Using a cell-based model of nueroinflammation, Kuhn's
lab exposed neuronal cells to tumor necrosis factor alpha
(TNFa), a pivotal factor mediating inflammation in the
brain and spinal cord. Exposure of neuronal cells to TNFa
rapidly stimulates a cascade of reactions, which ultimately
leads to the death of neuronal cells. The application
of Alaska blueberry extracts to neuronal cells effectively
prevented the degeneration of neuronal cells exposed to
"Expanding our knowledge of natural products' health
benefits and their molecular targets in the nervous system
would improve preventative measures and potentially reveal
new therapeutic strategies to alleviate inflammation in
the brain and spinal cord," says Kuhn. Inflammation
in the brain and spinal cord accompanies most chronic
degenerative diseases such as Alzheimer's, Parkinson's,
ALS, or multiple sclerosis, or acute injuries including
stroke and trauma. Moreover, inflammation is highly prevalent
in psychiatric disorders such as depression and autism
and in the normal aging process.
In other recent studies, Ron Mervis, PhD, of the Center
for Aging and Brain Repair at the University of South
Florida College of Medicine in Tampa, Fla., who collaborated
with Joseph and Shukitt-Hale, has discovered that supplementing
the diet of old rats with blueberries for a relatively
short period (8 weeks), resulted in maintenance and rejuvenation
of brain circuitry. These results, using a small amount
of blueberry extract, two percent, to supplement a standard
rat diet, are the first to show that a dietary intervention,
specifically blueberries, can not only protect against
the loss of dendritic branching and dendritic spines (e.g.,
synapses) seen in aged animals, but can result in neuroplastic
enhancement of brain circuitry such that it looks like
a much younger brain.
Mervis explains that age-related oxidation and inflammation
in the brain can damage neurons. He notes that blueberries
also contain various chemical compounds-flavonoids-which
have strong antioxidant and anti-inflammatory activities.
"These benefits, along with other indirect mechanisms,
may help to minimize, or reverse, the age-related breakdown
of communication between neurons," says Mervis, "and
optimize brain function in the old rat." A two percent
blueberry extract is equivalent to a human having about
half a cup of blueberries added to their daily diet.
The decrease in the amount of dendritic branching, or
atrophy, of neurons and loss of synapses on the branches
in the aging mammalian brain is correlated with memory
loss and cognitive dysfunction. Dendrites, which receive
and process incoming information from other neurons, comprise
about 95 percent of the surface area of the cell, and
the vast majority of the synapses are on dendritic spines.
Therefore, Joseph says, "analysis of dendritic branching
and dendritic spines can accurately reflect the integrity
of brain circuits and neuronal communication."
Previous research showed that blueberry-enriched diets
fed to aging rats reversed age-related declines in cognitive
function. The current data show that a diet supplemented
with blueberry extract should be able to protect against
the loss of dendritic branching and dendritic spines-in
other words, Joseph says, the blueberry supplement diet
"would enhance the neuronal circuitry back to the
status associated with a younger brain."
While these parameters have not been investigated in
humans, it is known that individuals who consume a diet
high in fruits and vegetables are less likely to develop
some of the neurodegenerative diseases associated with
aging and may not exhibit declines in motor and cognitive
function that are as great as those seen in people whose
consumption is less.