LE: Life Extension Update 2001.07.13

From: Technotranscendence (neptune@mars.superlink.net)
Date: Fri Jul 13 2001 - 20:29:45 MDT

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LIFE EXTENSION UPDATE EXCLUSIVE: Crosslink-breaking drug ALT-711 to be
tested for hypertension

WHAT'S HOT: Prevention ignored in half of stroke and heart attack survivors

PROTOCOL: Hypertension


    Fats for Life
    In the News: Blood Pressure Drug Reverses Sexual Dysfunction

Crosslink-breaking drug ALT-711 to be tested for hypertension

Alteon Corporation has announced a phase 2B trial of their anti-crosslink
drug ALT-711 to be tested in patients with isolated systolic hypertension.
Systolic hypertension, characterized by a high systolic and normal
diastolic blood pressure reading, has recently gained attention as the
most common form of hypertension in individuals aged 50 and older. An
elevation in systolic blood pressure has been associated with a high risk
of cardiovascular and all cause mortality.

ALT-711 is one of a new class of compounds called advanced glycosylation
endproduct crosslink breakers. These drugs have the ability to break
crosslinks caused by glycosylation, which is the binding of sugar to
protein molecules. The resultant crosslinkage destroys the elasticity of
tissue over time, leading to a loss of function. Glycosylation-induced
damage occurs more frequently with age and with diabetes. Crosslinkage in
the vacular system creates hardening of the arteries, or arteriosclerosis.
When blood vessels cannot expand, blood pressure becomes elevated.

The new trial has been named SAPPHIRE, which stands for Systolic And Pulse
Pressure Hemodynamic Improvement by Restoring Elasticity. Four hundred
fifty patients age 50 and older with isolated systolic hypertension in
forty sites in the US will receive the drug for six months in addition to
the medications they are currently taking. In a previous trial of ALT-711
in cardiovascular disease patients, participants experienced increased
elasticity of the vascular wall and lower pulse pressure.

The drug has proven effective in all species tested. Robert C deGroof PhD,
Senior Vice President of Scientific Affairs at alteon commented, "It is
important to emphasize that our data thus far has been consistent across
all species that we have tested. In preclinical evaluations, ALT-711
reversed stiffening of the aorta in rodents,canines and non-human
primates, similar to what recently has been observed in humans. The
SAPPHIRE trial has been designed to confirm all of these results and to
further determine effects of ALT-711 over a longer period of time and a
wider range of dosages."

ALT-711 does not interfere with natural glycosylation sites or peptide
bonds, and only breaks abnormal crosslinking. As there are no approved
drugs that treat the stiffening of the arteries that leads to isolated
systolic hypertension, ALT-711 will offer a new pharmaceutical therapy for
this undertreated condition, as well as for other cardiovascular disorders
associated with aging.

Prevention ignored in half of stroke and heart attack survivors

A study published in the July 9 2001 issue of Archives of Internal
Medicine showed that many survivors of stroke and heart attack are not
taking measures to prevent a second event. The study was conducted by
researchers at the University of Buffalo Toshiba Stroke Research Center
and Department of Neurosurgery who analyzed data collected from 17,752
people from 1988 to 1996 who took part in the National Health and
Nutrition Examination Survey (NHANES III). NHANES was conducted by the CDC
to estimate the prevalence of chronic disease and identify risk factors.

The data revealed that 53% of the 1,252 stroke and heart attack survivors
who had uncontrolled hypertension prior to their cardiovascular event were
still hypertensive after the event, and 46% who had high cholesterol
previous to their heart attack of stroke failed to control it afterward.
And as testimony to the power of addiction, 18% of smokers did not give up
their habits.


A startling statistic in the May 4, 1999, edition of The New York Times
revealed that only 18% of people with high blood pressure (hypertension)
are successfully treated to achieve normotensive ranges. Untreated
hypertension carries enormous health risks, such as increased risk of
heart disease, stroke, kidney disease, and eye disease, yet fear of
medication side effects and improper prescribing by physicians are
contributing to an epidemic of hypertension-induced disease.

"Blood pressure" can be defined as the pressure or force that is applied
against the artery walls as blood is carried through the circulatory
system. It is recorded as a measurement of this force in relation to the
heart's pumping activity, and is measured in millimeters of mercury
(mmHg). The top number, or systolic pressure, is the measurement of the
pressure that occurs when the heart contracts or beats. The bottom number,
or diastolic pressure, is the measurement recorded between beats, while
the heart is at rest. The systolic number is placed over the diastolic
number. For example, 110/70 (read as "110 over 70") means a systolic
pressure of 110 mmHg and a diastolic pressure of 70 mmHg. The systolic
number is always the higher of the two numbers.

High doses of fish oil concentrates have lowered blood pressure in some
people. There are cardiovascular as well as other health benefits
associated with taking fish oil. A study published in the October 1997
American Journal of Clinical Nutrition stated that "fish oils have been
shown to lower blood pressure in hypertensive subjects." According to a
January 1999 Journal of Nutrition study, the fatty acid DHA
(docosahexaenoic acid, obtained directly from fish oil) was shown to alter
the membrane fatty acid composition as well as the amount of ATP released
from vascular endothelial cells, and also decrease plasma noradrenaline.
The doctors who conducted this study stated that these factors may
ameliorate the rise in blood pressure normally associated with advancing
age. The Journal of Vascular Research (January 1998) corroborated these
findings by showing that the EPA (eicosapentaenoic acid) fatty acid
fraction of fish oil, when administered to aged rats, increases the
release of ATP from the vascular endothelial cells, leading to repression
of the blood pressure rise seen with advancing age. The October 1997
American Journal of Clinical Nutrition stated that "fish oil has a mild
blood pressure-lowering effect in both normal and mildly hypertensive

Several studies suggest that garlic may have protective effects against
cardiovascular diseases. One cross-sectional observational study reported
in Circulation, October 1997, tested the hypothesis that regular garlic
intake would delay the stiffening of the aorta related to aging. Chronic
garlic powder intake was shown to attenuate age-related increases in
aortic stiffness. Arterial stiffening with age is one cause of
hypertension. The doctors conducting this study stated, "These data
strongly support the hypothesis that garlic intake had a protective effect
on the elastic properties of the aorta related to aging in humans. Garlic
supplements can be found at a wide range of prices and potencies, some not
even standardized and containing no certifiable amounts of active

Pure-Gar with EDTA

The Foundation makes available Pure-Gar's highest potency extracts which
contain 10,000 ppm of allicin, a key component of non-aged garlic involved
in disease prevention.In addition to potent amounts of garlic extract,
this Pure-Gar product contains the chelating agent EDTA
(ethylene-diamine-tetra-acetic acid) for additional heavy-metal chelating
and anti-thrombotic benefits.

Garlic will:

Slightly reduce cholesterol when taken in large doses
Significantly inhibit abnormal platelet aggregation
Reduce cancer risk by neutralizing dietary mutagens and inhibiting free
Help to remove iron and other toxic heavy metals from the body
Protect neurons from aging damage
Boost immune function
Inhibit oxidation of LDL and VLDL cholesterol
Lower blood pressure in some people



Most people fail to obtain the optimal balance of essential fatty acids
from their diet. That is why dietary supplements such as fish, primrose
and borage oils have become so popular among health conscious people.
Fatty acids serve as building blocks of nerve cells and cell membranes.
Without adequate levels of the friendly fats, dangerous saturated fats
will replace essential fatty acids within cell membranes, reducing
membrane fluidity and efficiency, and thereby starting a process of
premature aging and disease development. By taking the right proportions
of essential fatty acids, we can maximize the production of beneficial
prostaglandins while minimizing production of harmful ones (such as
prostaglandin E2).

Deficiencies of essential fatty acids have been linked to a wide range of
common disorders including:

Cardiovascular disease
Elevated LDL cholesterol
Elevated triglycerides
Insulin resistance (leading to type II diabetes)
Memory Loss

To assure optimal fatty acid intake, the Life Extension buyers' Club has
designed a combination supplement consisting of GLA and DHA.

Life Extension Magazine, July 2001

Fats for Life

Imagine a kind of fat that could help reduce cholesterol levels, lower
blood pressure, fight dementia and slow down the aging process. This fat
would be better than any known drug. Best of all, it is not a fantasy but
a reality. We are talking about certain polyunsaturated, natural fatty
acids, whose beneficial effects have been documented in thousands of
studies over the last decade. Of crucial importance, however, is taking
the right essential fatty acids in the correct balance.

Fat is necessary for life. It is a key component in body chemistry and
energy storage. Knowing the difference between the beneficial essential
fatty acids (EFAs) and the harmful fats is of crucial importance for
health and longevity. Extensive research has made it clear that a reduced
or imbalanced intake of EFAs plays a significant role in the development
of many cardiovascular, neurological, metabolic and other age-related
degenerative diseases.

This research has singled out two particularly beneficial fatty acids, GLA
and DHA, and pointed to an ideal balance between them that could guard
against disease and age-related disorders in many-fold ways. These key
fatty acids protect the cardiovascular system, lowering blood pressure,
raising good (HDL) cholesterol while lowering bad (LDL) cholesterol and
triglyceride levels. They reduce stress reactions, and may ameliorate
insulin resistance. GLA helps reverse the effects of aging on fatty acid
metabolism, while DHA is essential to the development and maintenance of
brain functions, being of crucial importance for children, as well as for
the elderly in prevention and treatment of dementia.

The richest known source of GLA is borage oil (23% GLA), while DHA is
plentiful in cold water fish. GLA and DHA make a wonderful team for health
and longevity.

In the News: Blood Pressure Drug Reverses Sexual Dysfunction

When treating blood pressure using drug therapy, The Life Extension
Foundation long ago recommended that members ask their doctors to
prescribe either Cozaar or Hyzaar. These drugs are known as angiotension
II receptor antagonists because of their unique mechanism to block the
receptor sites of cells involved in inducing vascular constriction.
Hypertension is often caused by arterial inelasticity, also known as
vascular constriction.

While old-line anti-hypertensive drugs such as the calcium channel
blockers continue to be heavily promoted to doctors, Life Extension
members were told years ago that Cozaar or Hyzaar were the superior class
of drugs. Some studies suggest that short acting calcium channel blockers
increase mortality,(1-3) while the angiotension II receptor antagonist
drugs like Cozaar and Hyzaar are remarkably safe and effective.

A new study has just come out indicating that the active ingredient in
Cozaar and Hyaar (losartan) can significantly improve sex lives of men who
suffer from sexual dysfunction. This makes sense based on the beneficial
mechanism of action these drugs induce on the vascular system.

It is important to note that these improvements only occurred in those who
reported sexual dysfunction to begin with. In other words, Cozaar does not
act as an aphrodisiac in those with normal sexual function, but for those
whose sex lives are compromised by hypertension, Cozaar was shown in this
study to produce significant sexual-enhancing effects.

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If you have questions or comments concerning this issue or past issues of
Life Extension Update, send them to ddye@lifeextension.com

For longer life,

Dayna Dye
Editor, Life Extension Update
Life Extension Foundation
1 800 841 LIFE

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