By Barry Keate
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 be 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.
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 2003.3Ten 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.
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.”
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
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
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.”
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.