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LE Magazine August 2002
Studies from throughout
the world that can help you live longer
August 2002 Table of Contents
1. Melatonin protects against
mercury-induced mortality
Mice were given methyl mercury chloride (MMC) in their diet with or without
melatonin for five weeks. In the group not given the melatonin, four of
10 mice began to show neurological signs (e.g., abnormal righting reflex,
staggering gait, falling and posture on its side) concomitant with loss
of body weight four to seven days before death. Their survival rate was
60% on the 35th day. However, the melatonin treated group, showed a 100%
of survival rate on the 35th day, although one of 10 mice began to show
the neurological signs on the 33rd day. The level of thiobarbituric acid
reactive substance (TBARS, an indication of oxidative damage) in the brain,
showed a significant decrease in the treated group compared with the control
group. Thus, the 100% survival rate in the treated group may be partly
due to the antioxidative effect of melatonin on induced neurotoxicity.
TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 2000,
Vol 191, Iss 4, pp 241-246
2. Gamma-tocopherol, not alpha-tocopherol, inhibits COX-2 activity
Gamma-tocopherol is the most abundant form of vitamin E. However, research
has found that much of it is excreted through urine after being metabolized
by the liver. The "gamma" form has been shown to be superior to the "alpha"
form for inhibiting cancer cell growth. Recent research supports the theory
that gamma-tocopherol's antioxidant role goes above and beyond that of
alpha-tocopherol by effectively entrapping and removing mutagenic (induces
genetic mutation) oxidants. It is the gamma-form that seems to disband
free radicals and force them into submission. Cyclooxygenease-2 (COX-2)
is an enzyme that causes synthesis of prostaglandin El, an inflammation-causing
chemical in the body, which plays a key role in inflammation, vascular
heart disease and cancer. It promotes tumor growth via several mechanisms,
one of which is to promote the development of blood vessels into the tumor.
It is believed that blocking the action of the COX-2 enzyme is a crucial
variable in cancer therapy. A study showed that gamma-tocopherol (gamma
T) reduced prostaglandin synthesis in both macrophages (immune cells)
and human epithelial cells with 7.5 micrometer and 4 micrometer, respectively.
In addition, gamma T's major metabolite (gamma-CEHC, produced by metabolism)
(30 micrometer), also showed an inhibitory effect. In contrast, the alpha-tocopherol
form (50 micrometer) only slightly reduced prostaglandin formation in
macrophages, and had no effect in epithelial cells. The inhibitory effects
shown by gamma-tocopherol and its metabolite came from their inhibition
of COX-2 activity, and appeared to be independent of antioxidant activity.
The metabolite also inhibited prostaglandin synthesis to COX-2-preinduced
cells after arachidonic acid was added, when exposed for only one hour.
However, gamma-tocopherol required eight to 24 hours to cause the inhibition.
The results indicate that gamma-tocopherol and its major metabolite both
possess anti-inflammatory activity, important in human disease prevention.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES
OF THE UNITED STATES OF AMERICA, 2000, Vol 97, Iss 21, pp 11494-11499
3. Adenosine vs. colorectal
cancer cells
8-Cl-adenosine represents a new nontoxic chemotherapeutic agent shown
to inhibit growth of cancer cells in the colon and rectum. Adenosine inhibited
growth by slowing cell growth at the G phase, which was associated with
an eight-fold increase in p53 protein levels and a decrease in the phosphorylation
status. (P53 is a gene that encodes a protein that regulates cell growth
and can cause potentially cancerous cells to destroy themselves.) The
cancer cells, however, did not undergo apoptosis (programmed cell death).
Adenosine also induced some degree of differentiation (increasing structural
heterogeneity of the cells). Both villin protein levels as well as alkaline
phosphatase activity rose (2- and 3.5-fold, respectively) in response
to treatment with adenosine. The results suggest that in colon and rectal
cancer cells, adenosine not only inhibits growth, but also induces differentiation.
DIGESTIVE DISEASES AND SCIENCES, 2001, Vol 46,
Iss 4, pp 757-764
4. NSAIDs, telomeres and
tumor growth
Indomethacin is part of a group of NSAIDs (ibuprofen, sulindac sulfone,
etc., anti-inflammatory agents that work by inhibiting the production
of prostaglandins). It is well recognized that such inhibitors of the
cyclooxygenase enzyme (produces prostaglandins from arachidonic acid)
weaken tumor growth. A study showed that indomethacin weakens tumor growth
in mice by inducing apoptosis/necrosis (cell death) and inhibiting the
lengthening of telomeres (ends of chromosomes). Human colon cancer cells
showed both slowed growth and slowed telomerase activity, even though
there was a low level of prostaglandins present. Sulindac sulfone decreased
growth and telomerase activity in colon cancer cells, without any effects
on prostaglandin production. Ibuprofen reduced prostaglandin production
but had no effect on growth or telomerase activity. The results demonstrate
that cyclooxygenase inhibitors can slow growth in human tumor cells by
inhibiting the activity of the enzyme, telomerase.
INTERNATIONAL JOURNAL OF ONCOLOGY, 2001, Vol 18,
Iss 5, pp 929-937
5. Alternative to HRT for hot flashes
Hot flashes are a major problem for many postmenopausal women. Women with
unrelieved hot flashes suffer negative psychosocial consequences. The
relief of hot flashes may improve mood, affect daily activities such as
sleep, concentration, and sexuality, and overall quality of life. Findings
concerning concentration are consistent with research showing decreased
cerebral blood flow during hot flashes in healthy women. In women without
breast cancer, hormone replacement therapy (HRT) involving estrogen is
the typical treatment prescribed to relieve the problem. However, hot
flashes are a significant problem in women following treatment for breast
cancer presumably because of the effects of chemotherapy and tamoxifen
and the inability to take HRT. In comparison to naturally menopausal healthy
women of the same age, the chemotherapy used to treat the cancer causes
the woman to go into early menopause and experience hot flashes that were
significantly more frequent, severe, bothersome, and of greater duration.
Because of the concern that estrogen may lead to the growth of breast
cancer cells, these women are often denied estrogen for hot flashes. Recent
findings suggest that currently available nonhormonal hot flash treatments
may be ineffective, underutilized, or not acceptable to breast cancer
survivors. Although these women have tried nonhormonal prescription medications
(e.g., clonidine) in the past compared to healthy women, few breast cancer
survivors were using these medications at the time of the survey despite
frequent, severe, and bothersome hot flashes. This implies that although
women may have tried these medications in the past, they may have discontinued
the medications for reasons such as failure to obtain relief, cost, or
side effects. Although many prescription medications are effective in
reducing hot flashes, they can be associated with significant side effects.
However, in a Mayo Clinic study, long-term use of the new antidepressant
drug, venlafaxine, provided women treated for breast cancer with safe
and effective relief from hot flashes. This antidepressant can be an alternative
to estrogen for women who want a nonhormonal treatment for their hot flashes.
The study showed that 102 postmenopausal women receiving extended-release
venlafaxine (75 mg/day) over eight weeks maintained approximately a 60%
reduction in their hot flashes and its severity. Venlafaxine works to
control various neurotransmitters in the brain. Some of those neurotransmitters
are thought to trigger hot flashes. It was found that venlafaxine is a
safe, effective, and well tolerated nonhormonal treatment for postmenopausal
cancer patients and over a longer period. The side effects of venlafaxine
include mild appetite loss, dry mouth and, in some women, nausea. Only
a minority of women in this study experienced nausea from venlafaxine,
and most rated their nausea as relatively mild and transitory. In about
10% of the women, nausea was a more prominent problem. Thus, the study
provides the most comprehensive assessment available of the symptom experience
of hot flashes in breast cancer survivors. In addition, this study is
the only one to include a comparison group of healthy women.
Oncology Nursing Forum, April 2002, Volume 29,
Number 3
6. Procyanidins may decrease platelet activation
Polyphenolic phytochemicals inhibit the vascular and inflammatory processes
that contribute to disease. (Phytochemicals are plant chemicals such as
carotenoids, which may impart health benefits such as better protection
from cancer.) The positive effects of phytochemicals are thought to result
from polyphenol-mediated alterations in the synthesis of eicosanoids (such
as leukotrienes, prostacyclin, prostaglandins, and thromboxanes). A study
determined the ability of cocoa procyanidins to alter the synthesis of
eicosanoids in human and cultured human aortic endothelial cells. After
an overnight fast, 10 healthy adults consumed 37 g low-procyanidin (0.09
mg/g) and high-procyanidin (4.0 mg/g) chocolate. Relative to the effects
of the low-procyanidin chocolate, high-procyanidin chocolate induced increases
in blood prostacyclin (32%) and decreases in blood leukotrienes (29%).
After the in vitro (culture) procyanidin treatments, aortic endothelial
cells synthesized twice as much prostaglandin and 16% less leukotriene
as did the control group of cells. The in vitro and in vivo (body) effects
of procyanidins on blood leukotriene-prostacyclin ratios in culture were
also comparable: decreases of 58% and 52%, respectively. The data from
this short-term investigation support the concept that certain flavonoids
derived from food, can favorably alter eicosanoid synthesis in humans.
This provides a plausible hypothesis for a mechanism by which flavonoids
can decrease platelet activation in humans.
AMERICAN JOURNAL OF CLINICAL NUTRITION, 2001, Vol
73, Iss 1, pp 36-40
7. Life-style factors and
risk of aneurysm
A study looked at the association of life-style factors with risk for
aneurysm in the aortic artery (main artery that distributes blood to the
whole body except the lungs) in the abdominal area among 29,133 male smokers
(50 to 69 years of age). (An aneurysm is a sac formed by the dilation
of the wall of an artery, vein or the heart.) During a follow-up of six
years, 181 were diagnosed with ruptured abdominal aortic aneurysm or nonruptured
abdominal aortic aneurysm plus aneurysmectomy (excision of an aneurysm).
The risk for abdominal aortic aneurysm was positively associated with
age for smoking years, systolic blood pressure, diastolic blood pressure,
and total cholesterol. High-density lipoprotein cholesterol (HDLC) was
strongly oppositely associated with risk for aortic aneurysm. High-energy
intake was associated with lower risk for aortic aneurysm, but there were
no associations with nutrients. Thus, the classical risk factors for atherosclerotic
diseases are important in development of large abdominal aortic aneurysms.
EPIDEMIOLOGY, 2001, Vol 12, Iss 1, pp 94-100
8. Vitamin C supplements
and BMD in postmenopausal women
Vitamin C is known to stimulate procollagen, enhance collagen synthesis,
and stimulate alkaline phosphatase activity (a marker for bone cell formation).
A study evaluated the independent relation of daily vitamin C supplement
use with bone mineral density (BMD) in 994 postmenopausal women, 277 of
whom were regular vitamin C supplement users. Daily vitamin C supplement
intake ranged from 100 to 5000 mg. The average daily dose was 745 mg,
and the average duration of use was 12.4 years. (Eighty-five percent had
taken vitamin C supplements for more than three years.) The results showed
that vitamin C users had BMD levels approximately 3% higher at the midshaft
radius, femoral neck, and total hip. In a fully adjusted model, significant
differences remained at the femoral neck and marginal significance was
observed at the total hip. Women taking both estrogen and vitamin C had
significantly higher BMD levels at all sites. Women who took vitamin C
plus calcium and estrogen had the highest BMD at the femoral neck, total
hip, ultradistal radius, and lumbar spine. Thus, vitamin C supplement
use appears to have a beneficial effect on levels of BMD, especially among
postmenopausal women using concurrent estrogen therapy and calcium supplements.
JOURNAL OF BONE AND MINERAL RESEARCH, 2001, Vol
16, Iss 1, pp 135-140
9. Antioxidant properties of carvedilol in heart failure
Carvedilol, the first beta-blocker labeled in the United States for the
treatment of heart failure, has been shown to improve left ventricular
function and may reduce mortality. Beta-blockers work by affecting the
response to some nerve impulses in certain parts of the body. As a result,
they decrease the heart's need for blood and oxygen by reducing its workload.
They also help the heart to beat more regularly. Carvedilol is used to
treat high blood pressure (hypertension). High blood pressure adds to
the workload of the heart and arteries. If it continues for a long time,
the heart and arteries may not function properly. This can damage the
blood vessels of the brain, heart, and kidneys, resulting in a stroke,
heart failure, or kidney failure. High blood pressure may also increase
the risk of heart attacks. These problems may be less likely to occur
if blood pressure is controlled. Carvedilol is also used to prevent further
worsening of congestive heart failure, and for other conditions. Animal
and human studies have shown that carvedilol has significant antioxidant
properties compared with other beta-blockers. A 12-week study determined
if these antioxidant effects were detectable in 24 individuals with heart
failure. The results showed that the need for, and thus, the levels of
endogenous antioxidants superoxide dismutase (SOD) and glutathione peroxidase
(GSH) in red blood cells were significantly reduced in those treated with
carvedilol. Thus, in addition to improving symptoms in heart failure,
carvedilol also possesses significant antioxidant properties. Whether
this additional action influences long-term outcome is unknown at the
present time.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2001, Vol
37, Iss 1, pp 48-54
10. Air pollution and
emergency hospital admissions for CVD
A study looked at the short-term association between air pollution levels
and emergency hospital admissions for cardiovascular diseases in Valencia,
Spain (between 1994 to 1996). The pollutants were black smoke, sulphur
dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO) and ozone
(O-3). Estimations were calculated according to the hottest (May to October)
and the coldest (November to April) periods. It was found that a rise
in SO2 levels of 10 microgram/m3 was associated with an increment of 3%
in the expected number of cardiovascular admissions. A significant association
for black smoke, SO2 (24 hours), SO2 (one hour), and CO (one hour) was
found in the hottest semester. NO2 was independently associated with cerebrovascular
admissions. There were no significant associations between air pollution
and admissions for digestive diseases. Thus, current levels of air pollution
and emergency cardiovascular admissions are significantly related.
JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH, 2001,
Vol 55, Iss 1, pp 57-65
11. Raloxifene and estrogen reduces atherosclerosis
A study investigated the effect of raloxifene, a selective estrogen receptor
modulator (SERM), on atherosclerosis of the aorta in 80 cholesterol-fed
rabbits with pre-induced atherosclerosis, and with ovaries removed. They
were fed an atherogenic diet (accelerates the formation of lipid deposits
in arteries) containing 240 mg cholesterol/day for 15 weeks. Thereafter,
they were given oral estradiol (estrogen) 4 mg/day, raloxifene (210 mg/day)
or placebo. In the treatment period of 39 weeks, the dietary cholesterol
content was reduced to 80 mg cholesterol/day. There was a significant
increase in uterine weight induced by estradiol treatment (10.3g), but
raloxifene intervention caused a decreased uterus weight (1.21g) when
compared to placebo (2.48 g). Blood lipids increased in all groups to
levels seen in very high-risk humans. After 58 weeks, the cholesterol
content in the aorta was reduced 38% in the estradiol group, and 29% in
the raloxifene group. Thus, both estradiol and raloxifene significantly
reduced the progression of atherosclerosis.
ATHEROSCLEROSIS, 2001, Vol 154, Iss 1, pp 97-102
12. Kidneys, homocysteine and atherosclerosis in elderly
Studies suggest that people with minor impairment of the kidneys are at
higher risk of stroke and coronary heart disease. One explanation may
lie with observations that deterioration in the kidneys is accompanied
by a rise in blood homocysteine concentrations. There is evidence that
moderately elevated homocysteine may cause atherosclerosis. A study investigated
the relations between the kidneys, blood homocysteine and atherosclerosis
of the carotid arteries in 128 men and women aged 69 to 74 years. The
severity of atherosclerosis of the carotid artery was greatest in men
and women with the poorest kidney function. Small decrements in kidney
function were associated with increased risk. Blood homocysteine concentrations
were significantly higher in people with poorer kidney function.
ATHEROSCLEROSIS, 2001, Vol 154, Iss 1, pp 141-146
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