The newest research clearly shows that
apple polyphenol extracts can prevent, and possibly treat, the oxidative damage associated with
Alzheimer's disease, Parkinson's disease, and other neurodegenerative
In one study, apples with skin (where the highest
concentrations of apple polyphenols
reversed age-related brain function decline in rats.
Cornell researchers found that the
higher the concentration of
extract, the greater the protection was for the nerve cells against
Association International Conference on Prevention of Dementia, June
Consumption of Fruit and Vegetable Juices Predicts a
Reduced Risk of Alzheimer's Disease: The Kame Project.
Topic: Nonpharmacological and Lifestyle
interventions Presentation Time: Sunday, 12:00 noon - 2:30 p.m. Amy R. Borenstein1, Qi Dai2,
Yougui Wu1, James C. Jackson2, Eric B. Larson3,
1University of South Florida, Tampa, FL, USA; 2Vanderbilt
University, Nashville, TN, USA; 3Group Health Cooperative of
Puget Sound, Seattle, WA, USA. Contact e-mail: firstname.lastname@example.org Presentation Number: P-161 Poster Board Number: P-161 Keyword: antioxidants, risk factor, epidemiology
Background: Chronic accumulation of reactive oxygen species in the brain
may exhaust antioxidant capacity and lead to the onset/progression of AD.
Antioxidant vitamins, particularly vitamin E from dietary fruits and
vegetables, but not from supplements, may play a role in delaying AD onset.
Objective(s): To test whether
polyphenols from consumption of fruit and vegetable juices lower AD risk.
Methods: The Kame Project cohort, 1836 of whom were dementia-free
at baseline (1992-1994) was followed through 2001. At baseline, a
semi-quantitative food frequency questionnaire (FFQ) was given, including
fruits, vegetables, tea, wine, and fruit and vegetable juices; usual dietary
intake of nutrients was calculated from a food composition database. Time to
first diagnosis of probable AD (NINCDS/ADRDA criteria) using age as the time
axis and Cox hazard regression were used, adjusting for ApoE, baseline CASI
score, gender, smoking/alcohol consumption, education, physical activity,
BMI, energy intake, antioxidant vitamin supplements, history of vascular
conditions, diabetes and cancer. Intake of antioxidant vitamins was
categorized into tertiles. Fruit and vegetable groups, tea, wine and juice
drinking were classified as “<1/week”, “1-2/week” and “≥3/week”.
Over 6.3 years follow-up (sd=2.6), 81 incident cases of probable AD were
diagnosed who had FFQ data. Mean age was 71.8; 54.4% female; 65% drank fruit
or vegetable juices at least 1/week; 32% used vitamin E supplements at least
1/week (41.8% vitamin C). No
association was observed for intake of any supplemental vitamin or for
dietary intake of vitamins E, C or β-carotene. The hazard ratio was
0.27 (95% CI 0.10-0.74) in the fully-adjusted model comparing subjects who
drank fruit and vegetable juices at least 3/week vs. those who drank less
often than 1/week (p for trend=0.01) with an HR of 0.67 (95% CI
0.21-2.13) for those drinking juices 1-2/week. Conclusions: Certain polyphenols
abundant in fruit and vegetable juices may play an important role in
delaying AD onset. Animal studies have found that a number of
polyphenols from juices have stronger protection for neuronal cells
against H2O2 and protein oxidation than vitamins E and
C. These results may lead to a new avenue of inquiry in the prevention of
November/December 2004, Vol 69, No 9
Phenolics Protect in Vitro Oxidative Stress-induced Neuronal Cell Death
Heo HJ, Kim DO, Choi SJ, Shin DH, Lee CY. 2004. Apple Phenolics
Protect in Vitro Oxidative Stress-induced Neuronal Cell Death. J Food Sci
ABSTRACT: Oxidative stress induced by reactive oxygen species may be
linked to neurodegenerative diseases. Fresh Red Delicious apples,
having 232.9 mg/100 g vitamin C equivalent antioxidant capacity,
protected the rat pheochromocytoma
neuronal (PC-12) cells from H2O2-induced oxidative
toxicity in vitro in a dose-dependent manner. MTT
(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction
assay showed significant increase in
cell viability when PC-12 cells were treated with
indicates that the applephenolics
protected oxidative stress-induced neurotoxicity. Because oxidative
stress is also known to increase neuronal cell membrane breakdown, we
further investigated by lactate dehydrogenase and trypan blue exclusion
assays. Applephenolics inhibited
oxidative stress-induced membrane damage in neuronal cells.
Therefore, these results may suggest
that naturally occurring antioxidants, such as phenolicphytochemicals in
fresh apples, may reduce the risk of neurodegenerative disorders.
KEYWORDS: apple, oxidative stress, neurodegeneration, phenolicphytochemicals, reactive oxygen species Submitted 5/13/04, Revised 6/23/04, Accepted 7/7/04, Published on Web
10/28/2004 Authors Heo, Kim, and Lee are with Dept. of Food Science and Technology,
Cornell Univ., Geneva, NY 14456. Authors Choi and Shin are with Graduate
School of Biotechnology, Korea Univ., Seoul, Korea.
Direct inquiries to author Lee (E-mail: CYL1@cornell.edu).
damage of the brain resulting from oxidative stress is believed to be
responsible for the development of neurodegenerative disorders such as
"The neuronal cells of brain is especially vulnerable to ROS
(reactive oxygen species) damage as a
result of the brain’s high oxygen consumption rate, its abundant lipid
content, high levels of membrane unsaturated fatty acid that are easily
oxidizable by free radicals, and the relative paucity of antioxidant enzymes
compared with other organs."
"Our results clearly
demonstrated that applephenolics protect PC-12 cells from oxidative
H2O2 toxicity in vitro. Quercetin, one of the major flavonoids in apples,
appeared to be the main agent responsible for this beneficial effect..."
"This result suggests that applephenolics with a strong antioxidant activity may play an important role to
reduce the oxidative stress-induced risk of AD."
"Therefore, it would be proposed that natural antioxidants
from applephenolics could reduce
the risk of neurodegenerative disease such as AD."
1936, the Journal of Food Science (JFS ) has been IFT's premier science
journal, containing peer-reviewed reports of original research and critical
reviews of all aspects of food science for food professionals. Today it
publishes more than 500 papers a year -- over 3,000 pages of original
research and scientific reviews.)
American Journal of
Clinical Nutrition, Vol. 78, No. 3, 517S-520S, September 2003
Health benefits of fruit and vegetables are
from additive and synergistic combinations of phytochemicals1
Rui Hai Liu
1 From the Department of Food Science and the Institute of Comparative and Environmental Toxicology,
Cornell University, Ithaca, NY.
Cardiovascular disease and cancer are ranked as the first
andsecond leading causes of death in the United States and in
mostindustrialized countries. Regular consumption of fruit and
vegetablesis associated with
reduced risks of cancer,
cardiovascular disease,stroke, Alzheimer disease, cataracts, and
some of the functionaldeclines associated with aging.
Prevention is a more effectivestrategy than is treatment of
chronic diseases. Functional foodsthat contain significant
amounts of bioactive components mayprovide desirable health
benefits beyond basic nutrition andplay important roles in the
prevention of chronic diseases.
The key question is whether a
purified phytochemical has thesame health benefit as does the
whole food or mixture of foodsin which the phytochemical is
present. Our group found, forexample, that the vitamin C
with skin accounts foronly 0.4% of the total antioxidant
activity, suggesting thatmost of the antioxidant activity of
fruit and vegetables maycome from phenolics and flavonoids in
We propose thatthe additive and synergistic effects of
phytochemicals in fruitand vegetables are responsible for their potent antioxidantand
anticancer activities, and that the benefit of a diet rich
in fruit and vegetables is attributed to the complex mixtureof
phytochemicals present in whole foods.
We recently reported that
fruithave strong antioxidant and antiproliferative effects and
proposedthat the combination of phytochemicals in fruit and
vegetablesis critical to powerful antioxidant and anticancer
For example, the total antioxidant activity ofphytochemicals in
1 g of apples
with skin is equivalent to 83.3µmol vitamin C equivalents—that
is, the antioxidantvalue of 100 g
equivalent to 1500 mg of vitamin C.This is much higher than the
total antioxidant activity of 0.057mg of vitamin C (the amount
of vitamin C in 1 g of apples withskin). In other words, vitamin C in apples
contributed only< 0.4% of total antioxidant activity (31).
Thus, most ofthe
antioxidant activity comes from phytochemicals, not vitaminC. The natural combination of phytochemicals in fruit and vegetablesis responsible for their potent antioxidant activity.
Appleextracts also contain bioactive compounds that inhibit tumorcell growth in vitro. Phytochemicals in 50 mg
skinper milliliter (on a wet basis) inhibit tumor cell proliferationby 42%. Phytochemicals in 50 mg apple
without skin per milliliterinhibit tumor cell proliferation by
23%. The appleextractswith skin significantly reduced the tumor cell
proliferationwhen compared with the
appleextracts without skin
Eberhardt MV, Lee CY,
Liu RH. Antioxidant activity of fresh apples.
Sun J, Chu Y-F, Wu X,
Liu RH. Antioxidant and antiproliferative activities of fruits. J Agric
Food Chem. 2002;50:7449–54.[Medline]
Chu Y-F, Sun J, Wu X,
Liu RH. Antioxidant and antiproliferative activities of vegetables. J
Agric Food Chem. 2002;50:6910–16.[Medline]
J Nutr Health Aging.
prevents oxidative stress and impaired cognitive performance caused by
genetic and dietary deficiencies in mice.
Rogers EJ, Milhalik S, Orthiz D, Shea TB.
Center for Cellular Neurobiology and Neurodegeneration Research, Department
of Biological Sciences, University of Massachusetts Lowell, One University
Avenue, Lowell, MA 01854, USA.
Increased oxidative stress contributes to the
decline in cognitive performance
during normal aging
and in neurodegenerative conditions
such as Alzheimer s disease. Dietary supplementation with fruits and
vegetables that are high in antioxidant potential have in some cases
compensated for dietary and/or genetic deficiencies that promote increased
oxidative stress. Herein, we demonstrate that
apple juice concentrate,
administered ad libitum in drinking water, can
compensate for the increased
reactive oxygen species and decline in cognitive performance in maze
trials observed when normal and transgenic mice lacking apolipoprotein E are
deprived of folate and vitamin E. In addition, we demonstrate that this
protective effect is not derived from the sugar content of the concentrate.
PMID: 14978604 [PubMed - indexed for MEDLINE]
J Nutr Health
supplementation with apple juice concentrate alleviates the compensatory
increase in glutathione synthase transcription and activity that accompanies
dietary- and genetically-induced oxidative stress.
Tchantchou F, Graves M,
Ortiz D, Rogers E, Shea TB.
TB Shea, PhD, Center for Cellular Neurobiology and Neurodegeneration
Research, Department of Biological Sciences, University of Massachusetts
Lowell, One University Avenue, Lowell, MA 01854, Tel: 978-934-2881, Fax:
978-934-3044, Email: Thomas_Shea@uml.edu.
Increased oxidative stress, which can arise from dietary, environmental
and/or genetic sources, contributes to the
decline in cognitive performance
during normal agingand in
neurodegenerative conditions such as
Alzheimer's disease. Supplementation with fruits and vegetables that
are high in antioxidant potential can compensate for dietary and/or genetic
deficiencies that promote increased oxidative stress. We have recently
demonstrated that apple juice
concentrate (AJC) prevents the increase in oxidative damage to brain tissue
and decline in cognitive performance observed when transgenic mice
lacking apolipoprotein E (ApoE-/-) are maintained on a vitamin-deficient
diet and challenged with excess iron (included in the diet as a
pro-oxidant). However, the mechanism by which AJC provided neuroprotection
was not conclusively determined. Herein, we demonstrate that supplementation
with AJC also prevents the compensatory increases in glutathione synthase
transcription and activity that otherwise accompany maintenance of ApoE-/-
mice on this vitamin-free diet in the presence of iron. Inclusion of the
equivalent composition and concentration of sugars of AJC did not prevent
these increases. These findings
provide further evidence that the antioxidant potential of AJC can
compensate for dietary and genetic deficiencies that otherwise promote
PMID: 15543422 [PubMed - in process]
J Alzheimers Dis.
Apple juice prevents oxidative stress induced by
amyloid-beta in culture.
Ortiz D, Shea TB.
Center for Cellular Neurobiology and Neurodegeneration Research, Department
of Biological Sciences, University of Massachusetts Lowell, Lowell, MA
Increased oxidative stress contributes to the
decline in cognitive performance
during normal aging and
in neurodegenerative conditions such as
disease. Dietary supplementation with fruits and vegetables that are high in
antioxidant potential have in some cases compensated for oxidative stress.
Herein, we examined whether apple juice could alleviate the neurotoxic
consequences of exposure of cultured neuronal cells to amyloid-beta (Abeta),
since at least a portion of the neurotoxicity of Abeta is due to oxidative
stress. Apple juice concentrate (AJC; 70 degree brix) was diluted into
culture medium of SH-SY-5Y human neuroblastoma cells that had been
differentiated for 7 days with 5 microM retinoic acid concurrent with the
addition of 20 microM Abeta. AJC
prevented the increased generation of reactive oxygen species (ROS)
normally induced by Abeta treatment under these conditions.
AJC also prevented Abeta-induced
calcium influx and apoptosis, each of which results in part due to
increased ROS. These findings
suggest that the antioxidant potential of apple products can prevent Abeta-induced
PMID: 15004325 [PubMed - indexed for MEDLINE]
J Neurosci. 2002 Jul
enriched in foods with high antioxidant activity reverse age-induced
decreases in cerebellar beta-adrenergic function and increases in
James A. Haley Veterans Affairs Medical Center, Tampa, Florida 33612, USA.
Antioxidants and diets supplemented with foods high in oxygen radical
absorbance capacity (ORAC) reverse
age-related decreases in cerebellar
beta-adrenergic receptor function. We examined whether this effect was
related to the antioxidant capacity of the food supplement and whether an
antioxidant-rich diet reduced the levels of proinflammatory cytokines in the
cerebellum. Aged male Fischer 344 rats were given
apple (5 mg dry weight), spirulina (5 mg), or cucumber (5 mg) either in 0.5 ml water by oral gavage
or supplied in the rat chow daily for 14 d. Electrophysiologic techniques
revealed a significant decrease in beta-adrenergic receptor function in aged
control rats. Spirulina reversed this effect.
Apple (a food with
intermediate ORAC) had an intermediate effect on cerebellar beta-adrenergic
receptor physiology, and cucumber (low ORAC) had no effect, indicating that
the reversal of beta-adrenergic receptor function decreases might be related
to the ORAC dose. The mRNA of the proinflammatory cytokines tumor necrosis
factor-alpha (TNFalpha) and TNFbeta was also examined. RNase protection
assays revealed increased levels of these cytokines in the aged cerebellum.
Spirulina and apple significantly downregulated this
age-related increase in proinflammatory cytokines, whereas cucumber had no effect, suggesting that
one mechanism by which these diets work is by modulation of an age-related
increase in inflammatory responses. Malondialdehyde (MDA) was measured as a
marker of oxidative damage. Appleand spirulina but not cucumber
decreased MDA levels in the aged rats. In summary, the
receptor function in aged rats induced by diets rich in antioxidants is
related to the ORAC dose, and these diets reduce proinflammatory cytokine
flavonoid, and flavonoid-sugarcompounds, and quercetin is
major dietary flavonoid. There aremore
phenolics in the skin
of apples than in the flesh, and quercetinglycosides are
found only in the skins. The antioxidant effectsof
apple extracts with
skin and apple extracts
without skin havebeen tested on the proliferation of several
kinds of cancer celllines. The
either with skin or without skininhibits the growth of colon and
cancer cells in vitro in a dose-dependentmanner,
suggesting that the combination of phytochemicals includingphenolic acid
and flavonoids present in the skin and flesh are
responsible for the antioxidant effects of apple..."
PMID: 12122072 [PubMed - indexed for MEDLINE]
Free Radic Biol
Med. 2005 Jan 15;38(2):258-61.
Mice transgenic for Alzheimer disease beta-amyloid
develop lens cataracts that are rescued by antioxidant treatment.
Melov S, Wolf N, Strozyk D, Doctrow SR, Bush AI.
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945,
Alzheimer disease is characterized by
cerebral Abeta deposition, which we
have recently discovered occurs also in the lens as cataracts in
Alzheimer disease patients. Here we
report the presence of significantly increased cataracts in the lenses of an
Abeta-transgenic mouse model for Alzheimer disease and their amelioration
upon treatment with EUK-189, a synthetic SOD/catalase mimetic. These data
support an oxidative etiology for AD-associated lens cataracts and
their potential to be treated
preventatively with antioxidants.
PMID: 15607908 [PubMed - in process]
Nutritional factors in cerebral aging and dementia:
epidemiological arguments for a role of oxidative stress.
Deschamps V, Barberger-Gateau P, Peuchant E, Orgogozo JM.
INSERM U330, Universite Victor Segalen, Bordeaux, France. Valerie.Deschamps@dim.u-bordeaux2.fr
There is increasing evidence that
oxidative stress is involved in cerebral aging and dementia. The
objective of this review is to give a progress report on the more recent
results of the various epidemiologic cohorts studied for the association
between nutrition of older people, the evolution of cognitive performances
and the risk of later occurrence of dementia or stroke.
The oxidative theory of pathological
brain ageing is supported by animal laboratory experiments.
Furthermore, experimental research has consistently suggested that
diet-related factors play an important role in cognitive functions in
ageing. In humans, a number of epidemiological case-control and prospective
studies analyzed the association between nutrition, particularly fatty acids
and antioxidant molecules (vitamins A, E, C, beta-carotene and
polyphenols) and cognition.
In the context of evidence already available, further studies are needed to
identify the specific role of various nutrients, their interactions and the
influence of genetic factors and living habits on cerebral aging and
dementia. Vascular dementia and Alzheimer's disease,
that share several risk factors, might be targets for
primary prevention through
nutritional recommendations and/or supplementation.