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LE Magazine February 2003
ACAM
Convention 2002
at Broward county convention
center,
Ft. Lauderdale, Florida May 2002
Stress and brain aging
David Perlmutter, M.D., the medical
director of Perlmutter Health Center, is currently involved in
research at the National Parkinson's Disease Foundation,
studying the effectiveness of glutathione treatment in
Parkinson's disease. He is also widely known as an author and
lecturer on the broader subject of brain aging and
regeneration. At this conference, he presented a lecture on
the effects of chronically elevated cortisol on the
hippocampus, an area of the brain important in the formation
of memory, as well as in the regulation of the
hypothalamic-pituitary-adrenal (HPA) axis.
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In a dramatic slide, the audience saw the
neuroprotective effects of cortisol reduction. Aged rats whose
cortisol was kept down through adrenalectomy showed no more
damage in their hippocampus than young rats, in sharp contrast
to intact aged rats. Perlmutter also pointed out that dominant
monkeys do not suffer the kind of hippocampal atrophy that is
seen in subordinate monkeys. Humans with pathologically
elevated cortisol, such as the victims of Cushing's syndrome,
have overactive adrenals, and show much more cognitive decline
than individuals with lower cortisol levels. Likewise,
Alzheimer's disease patients show elevated levels of cortisol
in their cerebrospinal fluid; in these patients, the degree of
hippocampal atrophy accurately reflects cognitive decline.
How does cortisol damage the hippocampus?
Perlmutter explained that glucocorticoids (cortisol is our
main glucocorticoid hormone) increase levels of glutamate, an
excitatory neurotransmitter. Excess glutamate causes neural
mitochondria to produce defective ATP (ATP, adenosine
triphosphate, is our energy molecule). This defective ATP
eliminates the "magnesium block" guarding the neuron against
excess influx of calcium ions, followed by generation of free
radicals and cell damage or cell death.
Elevated evening cortisol indicates damage
to the HPA axis. Evening cortisol elevation is related to
sleep fragmentation (frequent awakenings) and less REM sleep.
Even modest elevation in cortisol has been found to correlate
with memory deficit. Unfortunately, our cortisol levels
increase with aging, a problem that definitely needs to be
addressed by anti-aging medicine.
Women who have been raped show higher
cortisol, Perlmutter said. Likewise, stress in childhood may
set the HPA axis at an over-reactive level, so that the
individual reacts to even minor stressors with an exaggerated
cortisol response.
Is there a remedy? Stress reduction has
been much talked about, but Perlmutter thinks that we need to
go beyond that, into positive feelings, including love.
Supplements that have been shown to reduce cortisol levels are
4000 mg a day of vitamin C and DHEA.
We also need to stimulate neurogenesis in
order to regenerate the brain. Dr. Perlmutter mentioned that
lithium is both neuroprotective and neurotrophic. It inhibits
neuronal death induced by beta amyloid. Lithium users were
also found to have significant increases in gray matter.
Stimulation of the vagus nerve also increases neurogenesis. On
a practical level, physical exercise, which improves
circulation and tends to lower emotional stress, also promotes
neurogenesis.
Meditation, positive emotions and physical
exercise are all effective tools in protecting the brain, and
especially the hippocampus, against the deadly effects of
chronic stress.
Magnesium, lipoic acid and flavonoids help
protect against exitotoxicity
Russell Blaylock, M.D. assistant professor at the
University of Mississippi Medical Center and a retired
neurosurgeon, spoke about ways to protect the aging brain with
diet and supplements. Because of its high (60%) content of
polyunsaturated fat and high metabolism, the brain is
especially vulnerable to damage. One mechanism of damage is
called excitotoxicity. This term describes a process during
which excessive extracellular glutamate promotes excessive
influx of calcium ions into nerve cell, inducing a generation
of free radicals, lipid peroxidation, and inflammation. This
so-called excitotoxic cascade leads to damage and even cell
death.
Fortunately, we know that magnesium is a natural calcium
antagonist, and helps protect the neurons against
excitotoxicity. Low levels of magnesium have been found in the
hippocampus of Alzheimer's disease patients. Magnesium
deficiency is extremely common.
Magnesium protects the brain in other ways as well: it
lowers blood pressure and helps prevent atherosclerosis, and
thus the risk of stroke. Magnesium also helps increase
glutathione levels; magnesium deficiency has been found to
cause a drastic decrease in glutathione. Glutathione, our key
cellular antioxidant, is enormously important in defending
neurons against free-radical damage. Besides magnesium, lipoic
acid, acetyl-cysteine, vitamin C, and various flavonoids
increase glutathione levels.
A diet high in antioxidants is also highly recommended. The
catechins found in green tea are highly neuroprotective, as
are the flavonoids found in blackberries, blueberries,
cranberries and berries in general, in prunes and raisins, as
well as deep green vegetables such as kale and spinach.
Quercetin, found in tea, onion and apples, has been found to
inhibit the initiation of the inflammatory cascade. Quercetin
also powerfully inhibits the production of peroxynitrite.
Ginkgo has also been found to be very neuroprotective,
improving circulation and increasing glucose uptake.
Other vitamins and nutrients that protect the brain include
CoQ10, acetyl-l-carnitine, vitamin C (which helps control
brain glutamate), vitamin E, and the anti-inflammatory omega-3
fats, especially DHA, found in fish oil. Phosphatidylserine
also helps block glutamate excitotoxicity.
Dr. Blaylock is the author of Excitotoxins: the Taste
that Kills, a book warning the public about MSG and
aspartate.
Flavonoids synergize with antioxidants to
fight cancer and heart disease
Jeffrey Blumberg, Ph.D., Associate Director and Chief of
the Antioxidant Research Laboratory at the USDA Nutrition
Research Center on Aging at Tufts University in Boston,
presented a fascinating lecture that explained the puzzling
contradiction in many studies on phenolic compounds found in
fruits, vegetables, tea, coffee, chocolate, red wine and other
plant-derived food products.
Over 4,000 flavonoids have been identified, including
anthocyanins found in fruits and flowers; flavans, also known
as catechins and found in tea; flavones such as apigenin,
luteolin and tangeretin; flavonols such as quercetin,
myricetin, and kaempherol; and isoflavones, including soy
isoflavones, genistein and daidzein, and equol, a metabolite
of daidzein produced by the intestinal flora.
Certain flavonoids have been shown to have anti-viral as
well as an anti-cancer activity. They can also suppress the
growth of new blood vessels by tumor tissue (anti-angiogenetic
activity) and inhibit adhesion molecules. Many flavonoids
chelate iron, help prevent blood clots, and show
anti-inflammatory and antioxidant activity. In addition,
certain flavonoids, such as those found in purple grape juice,
can improve blood flow; pycnogenol has been shown to lower
blood pressure in mild hypertension.
Epidemiological research has found that high consumption of
phenolics is associated with lower cardiovascular disease,
cancer, osteoporosis and Alzheimer's disease. Most notably, a
well-known Dutch study found a 50% reduction in cardiovascular
disease in subjects who consumed the most flavonoids, mainly
those found in apples, onions and black tea. Likewise,
Japanese studies found a 50% reduction in coronary stenosis
(narrowing of coronary arteries) in patients who drank four or
more cups of green tea a day. Some in-vitro studies on
isolated flavonoids, however, have found no effect. The main
reason for this, Blumberg argued, is that phenolic compounds
act in synergy with other antioxidants such as vitamins E and
C. The resulting synergy can provide powerful protection
against disease.
To support his thesis, Blumberg presented the findings of
studies done at Tufts University, investigating the protection
of LDL cholesterol against oxidation. Oxidized LDL cholesterol
plays a huge role in atherogenesis, Blumberg stated. It
promotes inflammation and stimulates the proliferation of
smooth muscle cells. Of the flavonoids tested, quercetin,
luteolin, and epigallocatechin gallate (found in green tea)
showed the highest ability to protect LDL cholesterol,
especially when combined with vitamins C and E.
Blumberg also tested oat extract. It turned out that oat
extract provided no antioxidant protection when used by
itself. However, when vitamin E was added, its action was 20%
to 36% more effective; there was even more synergy with
vitamin C. Similarly, almond-skin extract, a rich source of
quercetin and other polyphenols, was found to be an excellent
LDL protector when combined with a small amount of vitamin
E.
Actually, it has been known since the 1930s that flavonoids
enhance the action of vitamin C. Yet, it is only now that we
are beginning to grasp the essence of this synergy. In the
body, antioxidants operate within networks rather than by
themselves. The reason is that in the process of donating
electrons to the harmful free radicals, antioxidant compounds
themselves become oxidized, and need another antioxidant to
restore them to the reduced state. Thus, the synergy of an
antioxidant network comes from its ability to maintain its
components in an antioxidant state much longer.
The idea of synergy in general has been gaining ground.
More and more studies show that two or more compounds tend to
be more potent than a single compound. This applies even to
combinations of chemotherapy drugs and with natural
anti-cancer compounds. Thinking in terms of a single "magic
bullet" is rapidly becoming obsolete.
On the practical level, Blumberg warned that iced tea is
less potent than strong hot tea. The research at Tufts
discovered that iced tea that has been left in the
refrigerator for more than one day, and bottled tea that has
been sitting on the shelf, have no health benefits. The
flavonoids in these beverages have become oxidized and no
longer have any antioxidant activity.
Blumberg was honored with an ACAM award for his work on
flavonoids.
Arthritis update: Glucosamine doesn't cause insulin
resistance
Jason Theodosakis, M.D., Assistant Professor at the
University of Arizona College of Medicine, presented an update
on holistic treatment of arthritis. One important point was
the effectiveness of anti-inflammatory enzymes such as
bromelain and papain. Another was the speaker's rebuttal of
the unfounded belief that glucosamine causes insulin
resistance. An indirect proof that it does not was provided by
a three-year study published in Lancet. Patients taking
glucosamine actually had lower serum glucose than controls.
Furthermore, rats given glucosamine showed no increase in
insulin resistance, and had lower blood pressure than
controls.
Glucosamine has a wide range of benefits, including
suppression of interleukin-1 and interleukin-6. Glucosamine
also suppresses the TNF alpha-induced production of nitric
oxide in chondrocytes (cartilage-producing cells). It inhibits
matrix metalloproteinases, enzymes that dissolve
cartilage.
The popular COX-2 inhibiting drug Vioxx, according to
Theodosakis, has been shown to lead to further joint
deterioration. X-ray studies reveal dose-dependent cartilage
loss with long-term use. A 25 mg dose produced greater damage
than a 12.5 mg dose.
Theodosakis also mentioned the benefits of niacinamide, a
form of niacin, in the treatment of arthritis. Niacinamide
appears to inhibit pro-inflammatory interleukin-1.
The speaker also recommended exercise. "People who have
good leg muscles have less knee arthritis; the muscles act as
shock absorbers," Theodosakis explained. Also, the right
exercise, such as working out on a stationary bicycle,
stimulates chondrocytes to produce more cartilage.
Don't sit for long periods of time without taking a break,
the speaker warned. He explained "the movie goer's knee"-When
the knee stays bent for too long, there is insufficient blood
flow to the knee, and insufficient circulation of synovial
fluid.
As Dr. Gonzalez stated, "There is change in the air."
Mainstream medicine can no longer afford to dismiss the
ever-growing research on the effectiveness of natural
therapies. Much more needs to be done; but at least the
research has begun, as seen, for instance, in the excellent
presentations of the speakers from Tufts University. Other
outstanding presentations included Dr. Gonzalez's own lecture
on the use of enzymes, nutrition, autonomic balancing and
supportive supplements in the treatment of cancer. Dr.
Perlmutter likewise excelled as usual, explaining how chronic
stress and elevated cortisol levels lead to hippocampal
atrophy and cognitive decline.
It is not easy to summarize a conference as rich in
information as this Spring's ACAM convention. For one thing,
the information tends to get more complex the more is
discovered about human physiology, the aging processes and
diseases such as cancer. It is important that both physicians
and the public keep up with this growing body of knowledge.
ACAM is a leader in providing this kind of education to
physicians.
References
Arif JM, et al. 2000. Inhibition of
cigarette smoke-related DNA adducts in rat tissues by
indole-3-carbinol. Mutat Res 452:11-18.
Bell MC, et al. 2000. Placebo-controlled
trial of indole-3-carbinol in the treatment of CIN. Gynecol
Oncol 78:123-9.
Bohlke K, et al. 1999. Vitamins A, C and
E and the risk of breast cancer: results from a case-control
study in Greece. Br J Cancer 79:23-9.
Bosetti C, et al. 2000. Fraction of
prostate cancer incidence attributed to diet in Athens,
Greece. Eur J Cancer Prev 9:119-23.
Caltagirone S, et al. 2000. Flavonoids
apigenin and quercetin inhibit melanoma growth and metastic
potential. Int J Cancer 87:595-600.
Chandra RK. 1984. Excessive intake of
zinc impairs immune responses. JAMA 252:1443-6.
Chaumontet C, et al. 1997. Flavonoids (apigenin, tangeretin)
counteract tumor promoter-induced inhibition of intercellular
communication of rat liver epithelial cells. Cancer Lett
114:207-10.
"Do Not Use Celecoxib (CELEBREX) and
Rofecoxib (VIOXX) for arthritis-the misnamed and overpriced
'super aspirins'". Worst Pills, Best Pills News. Washington,
DC: April 2001; 27.
Dubois RN. 2000. Review article: cyclooxygenase-a target for
colon cancer prevention. Alimet Pharmacol Ther 14 Suppl
1:64-7.
Duchateau J, et al. 1981. Beneficial
effects of oral zinc supplementation on the immune resonse of
old people. Am J Med 70:1001-4.
Egner PA, et al. 2001. Chlorophyllin
intervention reduces aflatoxin-DNA adducts in individuals at
high risk for liver cancer. Proc NY Acad Sci USA
98:14601-6.
Elkin AC, et al. 2000. Folic acid
supplements are more effective than increased dietary folate
intake in elevating serum folate levels. Br J Obstet Gynaecol
107:285-9.
Fong LY, et al. 1987. Zinc-deficiency and
the development of malignant lymphoma in rats given a single
intragastric dose of N-methyl-N-nitrosourea. IARC Sci Publ
84:261-3.
Fraker PJ, et al. the dynamic link between the integrity of
the immune system and zinc status. J Nutr 130(5S
Suppl):1399S-06S.
Gann PH, et al. 1999 Lower prostate
cancer risk in men with elevated plasma lycopene levels:
results of a prospective analysis. Cancer Res 59:1225-30.
Giovannucci E, et al. 1998. Multivitamin
use, folate and colon cancer in women in the Nurses' Health
Study. Ann Int Med 129:517-24.
Guengerich F, et al. 1991. Cytochrome
P-450 oxidations and the generation of biologically reactive
intermediates. Biological Reactive Intermediates IV, 1991,
Plenum Press, New York.
Hatherill JR. Eat to Beat Cancer. Renaissance Books: Los
Angeles. 1998.
Regenstein L. America the Poisoned.
Acropolis Books Ltd.: Washington, DC. 1983.
Guyton KZ, et al. 1993. Oxidative mechanisms in
carcinogenesis. British Med Bull 49:523-44.
He YH, et al. 2000. Indole-3-carbinol as a chemopreventive
agent in 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine
(PhIP) carcinogenesis: inhibition of PhIP-DNA adduct
formation, acceleration of PhIP metabolism, and induction of
cytochrome P450 in female F344 rats. Food Chem Toxicol
38:15-23.
Holland MB, et al. 1995. Estrone-induced
cell proliferation and differentiation in the mammary gland of
the female Noble rat. Carcinogenesis 16:1955-61.
Hsu JT, et al. 2000. Regulation of
inducible nitric oxide synthetase by dietary phytoestrogen in
MCF-7 human mammary cancer cells. Reprod Nutr Dev
40:11-18.
Jacobsen BK, et al. 1998. Does high soy
milk intake reduce prostate cancer incidence? The Adventist
Health Study (United States) [see comments]. Cancer Causes
Control 9:553-7.
Jin Z, et al. 2002. Soy isoflavones increase latency of
spontaneou mammary tumors in mice. J Nutr 132:3186-90.
Johnson PW, et al. 1987. Enhanced lytic
susceptibility of Ha-ras transformants after oncogene
induction is specific to activated NK cells. J Immunol
138:3996-03.
Kawaii S, et al. 1999. HL-60 differentiating activity and
flavonoid content of the readily extractable fraction prepared
from citrus juices. J Agric Food Chem 47:128-35.
Kawaii S, et al. 1999. Antiproliferative activity of
flavonoids on several cancer cell lines. Biosci Biotechnol
Biochem 63:896-9.
Liang Y, et al. Suppression of inducible
cyclooxygenase and inducible nitric oxide synthase by apigenin
and related flavonoids in mouse macrophages. Carcinogenesis
20:1945-52.
Li HC, et al. 2000. Green tea polyphenols induce apoptosis in
vitro in peripheral blood T lymphocytes of adult T-cell
leukemia patients. Jpn J Cancer Res 91:34-40.
Lu LJ, et al. 2000. Decreased ovarian hormones during a soya
diet: implications for breast cancer prevention. Cancer Res
60:4112-21.
Mäkelä S, et al. 1998.
Inhibition of 17 -hydroxysteroid oxireductase by flavonoids in
breast and prostate cancer cells. Proc Soc Exp Biol Med
217:310-16.
McMillan DC, et al. 2000. Changes in
micronutrient concentrations following anti-inflammatory
treatment in patients with gastrointestinal cancer. Nutr
16:425-8.
Michaud DS, et al. 2000. Intake of
specific carotenoids and risk of lung cancer in 2 prospective
US cohorts [see comments]. Am J Clin Nutr 72:990-97.
Mills PK, et al. 1989. Cohort study of diet, lifestyle and
prostate cancer in Adventist men. Cancer 64:598-04.
Miodini P, et al. 1999. The two
phyto-estrogens genistein and quercetin exert different efects
on oestrogen receptor function. Br J Cancer 1150-55.
Nakachi K, et al. 1998. Influence of
drinking green tea onbreast cancer malignancy among Japanese
patients. Jpn J Cancer Res 89:254-61.
Noroozi M, et al. 1998. Effects of
flavonoids and vitamin C on oxidative DNA damage to human
lymphocytes. Am J Clin Nutr 67:1210-17.
Ong T, et al. 1989. Comparative
antimutagencity of 5 compounds against 5 mutagenic complex
mixtures in Salmonella typhimurium strain TA98. Mutat Res
222:19-25.
Otsuka T, et al. 1998. Growth inhibition of leukemic cells by
(-)-epigallocatechin gallate, the main constituent of green
tea. Life Sci 63:1397-403.
Parazzini F, et al. 2000. Population
attributable risk for ovarian cancer. Eur J Cancer
36:520-4.
Porrini M. et al. 2000. Lymphocyte lycopene concentration and
DNA protection from oxidative damage is increased in women
after a hort period of tomato consumption. J Nutr
130:189-92.
Post JFM, et al. 1992. Growth inhibitory effects of
bioflavonoids and related compounds on human leukemic CEM-C1
and CEM-C7 cells. Cancer Lett 67:207-13.
Reddy KB, et al. 1999. Mitogen-activated
protein kinase (MAPK) regulates the expression of
progelatinase B (MMP-9) in breast epithelial cells. Int J
Cancer 82:268-73.
Sadakata S, et al. 1992. Mortality among
female practitioners of Chanoyu (Japanese "tea-ceremony").
Tohoku J Exp Med 166:475-77.
Schecter A, et al. 1997. Dioxins,
dibenzofurans, dioxin-like PCBs, and DDE in U.S. fast food,
1995. Chemosphere 34:1449-57.
Seo YR, et al. 2002. Selenomethionine
induction of DNA repair response in human fibroblasts.
Oncogene 21(23):3663-9.
Sharpe CR, et al. 2000. Nested
case-control study of the effects of non-steroidal
anti-inflammatory drugs on breast cancer risk and stage. Br J
Cancer 83:112-20.
Shao Z, et al. 1998. Genistein exerts multiple suppressive
effects on human breast carcinoma cells. Cancer Res
58:4851-57.
Slattery ML, et al. 2000. Carotenoids and
colon cancer. Am J Clin Nutr 71:575-82.
Smith ML, et al. 2000. The effect of
non-steroidal anti-inflammatory drugs on human colorectal
cancer cells: evidence of different mechanisms of action. Eur
J Cancer 36:664-74.
Smith WA, et al. 2001. Effect of
chemopreventive agents on DNA adduction induced by the potent
mammary carcinogen dibenzo[a]pyrene in the human breast cells
MCF-7. Mutat Res 480:97-108.
Solomons NW. 1996. Plant sources of
vitamin A and human nutrition: renewed strategies. Nutr Rev
54:89-91.
Song J, et al. Chemopreventive effects of
dietary folate on intestinal polyps in Apc+/-Msh2-/-mice.
Cancer Res 60:3191-9.
Voorrips LE, et al. 2000. A prospective
cohort study on antioxidant and folate intake and male lung
cancer risk. Cancer Epidem Biomarkers Prev 9:357-65.
Zhang S, et al. 1999. A prospective study
of folate intake and the risk of breast cancer. JAMA
281:1632-7.
Zhang S, et al. 1999. Dietary carotenoids
and vitamins A, C, and E and risk of breast cancer. J Natl
Cancer Inst 91:547:56.
Zhou J, et al. 2002. Inhibition of
orthotopic growth and metastasis of androgen-sensitive human
prostate tumors in mice by bioactive soybean components.
Prostate 53:743-53.
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