Resveratrol
seems to mimic the effects of caloric restriction,
which activates a protein family that exerts myriad
effects on the body. It stabilizes chromosomes and
DNA molecules, promotes DNA repair and regulates genetic
functions that control every activity of the living
cell. In doing so, it promotes health and increases
longevity.
There is
strong evidence that Resveratrol can also protect
the auditory system from noise-induced hearing loss,
which will discussed in detail further in this article.
It has
been known for over 70 years that a drastic reduction
in caloric intake slows the pace of aging and increases
maximum life span in many lower organisms such as
yeast, worms and fruit flies. More recently, this
form of drastic dieting has been shown to have similar
effects on mammals.1
Decreased
activity in this protein family is intimately connected
with the changes that typically occur with aging and
that lead to many of the diseases we label as “chronic,
age-related conditions,” such as cancer, diabetes,
cardiovascular disease and neurodegenerative disorders
such as Alzheimer’s and Parkinson’s disease.
At the
forefront of cutting-edge investigations into resveratrol’s
effect on health and longevity are Christoph Westphal,
MD, PhD, and David Sinclair, PhD. Together, they have
started the biotechnology firm Sirtris Pharmaceuticals,
based on their discoveries, in Cambridge, MA. The
name, Sirtris, is based on the activated protein family,
sirtuins.
Sirtris
Pharmaceuticals is developing a synthetic analog of
resveratrol that they hope to patent and sell as an
anti-age medication and for diseases such as cardiovascular,
diabetes, cancer and neurodegenerative disturbances.
Drs. Westphal and Sinclair were recently featured
on a segment of “60 Minutes” on CBS. The
segment can be viewed here:
The medication
Sirtris Pharmaceuticals is working on will, if approved,
have several benefits. One will be a higher dosage
using fewer pills. The disadvantages will be those
common to all patented prescription medications, potential
side effects and high cost. For those people without
health insurance or whose insurer refuses to pay for
the medication, the cost may be prohibitively high.
Organic resveratrol is currently available as an over-the-counter
supplement obtainable without a prescription.
History
Resveratrol
was first discovered in the 1940’s in the root
of Japanese knotweed (polygonum cuspidatum). Extracts
of this plant had been used in traditional Japanese
and Chinese medicine to treat a wide range of afflictions,
including fungal infections, skin inflammations, and
liver and cardiovascular disease.
In
1976, researchers found resveratrol in the skin and
seeds of grapes. Concentrations range from 50 to 100
mg resveratrol per gram of skin or seeds. The concentration
in red wine ranges from 0.2 mg/liter to 7.7 mg/liter.
There is no resveratrol in white wine, as the grape
skin is not used to make white wine. It is also found
in peanuts, blueberries and cranberries. Currently,
most commercial extract is produced from the root
of Japanese knotweed.
Studies
that compared alcohol consumption to the risk of death
from coronary heart disease revealed that those with
the lowest risk drank red wine, while those who preferred
other alcoholic beverages had the highest risk.2
They also discovered that when healthy subjects were
given pure alcohol or red wine for 15 days, pure alcohol
increased platelet aggregation (a cause of heart attack
and stroke); however red wine decreased platelet aggregation
while, at the same time, elevating HDL (good) cholesterol.
It is important
to note when discussing "healthy" red wine
consumption most doctors and scientists agree that
men will benefit from consuming one to two servings
(4 oz.) per day. Women should consume only one serving
per day. These recommended amounts, while helpful,
do not contain enough reveratrol to be truly therapeutic.
To obtain similar dosages of resveratrol, taken in
the form of a dietary supplement, one would need to
consume 50-100 bottles of read wine per day!
As scientists
began to appreciate the cardiovascular benefits of
drinking red wine, they also began to seriously investigate
red wine polyphenols, especially resveratrol. Below
is a limited sampling of the many clinical trials
on resveratrol.
Hearing
Loss and Tinnitus
Tinnitus
authority, Michael Seidman, MD, has been investigating
the effects of resveratrol for 15 years and has several
published studies. He has received several grants
to look at the effects of this compound on noise-induced
hearing loss and, more recently, the National Institutes
of Health (NIH) awarded him a grant to examine resveratrol’s
effects on aging.
He and
his team have conducted a series of experiments in
their lab on noise-induced hearing loss in laboratory
rats. The most widely cited of these was published
in Otolaryngology-Head and Neck Surgery in 2003.3
Ten rats were divided into an experimental and a placebo
group. The experimental group was fed 430 ug/kg/day
resveratrol while the placebo group was given saline.
This dosage is equivalent to 35 mg per day for a normal,
170 lb man.
Auditory
brainstem responses were determined for each animal
beforehand. After 21 days, the animals were exposed
to noise for 24 hours and brainstem responses were
conducted immediately afterward, at 3 days, 7 days
and 4 weeks after noise exposure. Results showed that
hearing loss in the animals was significantly lowered
in the resveratrol group compared to the control group.
The study “demonstrates a protective effect
of resveratrol on noise-induced hearing loss.”
It is important to remember that 90% of individuals
with tinnitus also have some level of hearing loss
and prevention from further damage to one’s
hearing is critical.
Author’s
note: I am not aware of any studies to determine if
resveratrol can restore hearing loss after it has
already occurred. There will be more investigation
into this in the future. For now, it is a demonstrated
fact that resveratrol can prevent hearing loss and
help maintain healthy hearing.
Longevity
Colleagues
of David Sinclair, Phd, at the National Institute
on Aging fed resveratrol to laboratory mice, producing
the same changes in gene expression as those induced
by caloric restriction.4
Elderly mice fed resveratrol along with a normal diet
also showed a dramatic reduction in signs of aging.
These included decreased protein loss in urine, decreased
inflammation, beneficial changes in blood vessel lining,
greater motor coordination, reduced cataract formation
and preserved bone mineral density.
Pathologists,
collaborating with Dr. Sinclair at Harvard, have demonstrated
increased survival of mice on a high calorie diet
when supplemented with resveratrol.5
This study provided a group of middle-aged mice with
a high calorie diet plus resveratrol and examined
a host of physiological parameters that are affected
by age, diet and obesity. The supplemented mice had
changes associated with increased life span, increased
insulin sensitivity, increased numbers of mitochondria
in the cells and improved motor function. In fact,
the researchers discovered that resveratrol reversed
the effect of the high calorie diet in 144 out of
153 biochemical pathways. They concluded resveratrol
“points to new approaches for treating obesity
related disorders and diseases of aging.”
Cardiovascular
Korean
scientists demonstrated the relationship between resveratrol
and the cells lining arterial walls. In this study,
researchers supplemented atherosclerosis-prone mice
with either resveratrol, the prescription lipid lowering
drug clofibrate, or a control diet. The resveratrol-supplemented
mice had consistently lower total cholesterol and
LDL levels than animals in either of the control groups.6
Resveratrol
also diminished levels of adhesion molecules in blood
vessel walls that are responsible for promoting plaque
and clot formation. The most exciting finding from
this study was that resveratrol actually reduced the
number of atherosclerotic changes and the amount of
fat deposition in the arteries in the supplemented
animals.7
Turkish
cardiac surgeons applied resveratrol to cross-sectional
pieces of blood vessels obtained from 38 men undergoing
cardiac bypass operations. They found the treatment
produced relaxation of the vessels by 35%, which represented
a dramatic increase in their capacity to carry blood
efficiently.8
Cancer
It is
only in the past three years that significant attention
has been paid by oncologists to cancer-preventive
effects of resveratrol, but that is being rapidly
remedied through an outpouring of new research.
Italian
biologists have discovered that trans-resveratrol,
the most active form of the molecule, causes human
breast cancer cells in culture to commit the “orderly
suicide” referred to as apoptosis. This is one
of the most important and effective means of treating
cancers and of preventing their progression.9
Editor’s
Note: For more information about this process and
how Ginkgo biloba assists in cancer prevention please
the article in our Tinnitus Library.
Oncologists
at the Northeastern Ohio University found they could
use resveratrol to inhibit liver cancer cells from
proliferating and cause them to undergo death by apoptosis,
ultimately reducing the size and number of liver tumors
in rats given a potent carcinogen.10
Diabetes
Since
cellular uptake of glucose is impaired in diabetes,
Canadian researchers decided to examine the effects
of resveratrol on enhancing muscle cells ability to
absorb sugar, and insulin-like function.11
In a laboratory culture of skeletal muscle, the researchers
found the addition of resveratrol stimulated glucose
uptake to more than 200% of baseline, similar to the
action of insulin itself. Interestingly, similar improvement
in insulin-glucose function occurs in response to
calorie restriction.
In a remarkable
set of studies, biochemist in Madras, India reported
on a direct comparison of resveratrol with an oral
glucose-lowering drug, glyclazide, in control of blood
sugar levels in diabetic rats.12,
13 The animals were treated
with resveratrol for 30 days and experienced a significant
decrease in blood sugar; the targeted outcome.
The animals
were also found to have lower levels of biomarkers
of inflammation and liver injury. The researchers
noted that these effects are comparable with those
of glyclazide and concluded, “resveratrol my
be considered as an effective therapeutic agent for
the treatment of diabetes.”
Neurodegenerative
Diseases
Nowhere
are the ravages of unhealthy aging more visible than
in the terribly destructive neurodegenerative disorders
such as Alzheimer’s and Parkinson’s diseases.
And because these diseases are linked to oxidative
damage and inflammation, resveratrol researchers hold
high hopes for the molecule’s potential impact
in these areas. It has been suggested that, like caloric
restriction, resveratrol helps to preserve and regulate
energy levels in brain and nerve cells, prolonging
their active lives through effects on mitochondria,
the cellular powerhouses.
Direct
evidence of a resveratrol-mediated neuroprotective
effect in Alzheimer’s disease was published
in 2009 by Cornell neuroscientists who studied mice
given an experimental version of human Alzheimer’s.14
The mice were given resveratrol over a 45-day period.
Their brains were then examined for the damaging inflammatory
beta-amyloid plaques characteristic of Alzheimer’s
disease.
Despite
finding no resveratrol directly in the brain tissue,
the scientists reported reductions in plaque formation
of 48% to 90% in specific and important regions of
the brain. These dramatic changes were accompanied
by substantial increases in brain antioxidant molecules.
The researchers concluded, “onset of neurodegenerative
disease may be delayed or mitigated with use of dietary
chemopreventive agents that protect against beta-amyloid
plaque formation and oxidative stress.”
Resveratrol
continues to be studied for its effects on the fundamental
processes associated with aging. It stabilizes DNA
to prevent cancerous changes, switches on anti-oxidant
and anti-inflammation defense mechanisms and even
instructs cancer dells to commit organized destruction
by apoptosis. The end result is an incredible array
of health benefits. It is being studied now by big
pharmaceutical companies desiring to create new drugs
from the molecule. However, high quality trans-resveratrol,
the most active form of the molecule, is available
in health food stores now.
For those
of us living with tinnitus, it is important to recognize
how important it is to maintain a healthy lifestyle
in order to keep the ear ringing at its lowest possible
level. In addition to proper diet and exercise, supplements
like resveratrol could prove invaluable toward that
goal.