Introduction
Is resveratrol a breakthrough discovery that is destined to play a more vital role in the prevention and treatment of age-related disease than antibiotics or is it a momentary diversion of finite research time and money from the development of pharmaceuticals the world needs now to treat an aging population suffering near pandemic levels of obesity, diabetes, coronary disease and cancer? Only five years ago virtually no one, including physicians, scientists and pharmaceutical companies, had even heard of this phytoalexin, and only a handful of scientists and physicians possessed any real knowledge of the molecule’s potential health and wellness effects. A few animal studies had shown the potential for increases in life span, and a few hundred investigations, primarily by researchers at universities in Japan, India and China, elucidated resveratrol’s chemo-protective properties, particularly with respect to cancer, diabetes and the so-called life style diseases. However the same could be said for thousands of other phytochemicals and synthetic drugs that had at one time or another shown promising results in the lab, only to die an ignoble death when scientists were unable to replicate the same effects in mammals, especially humans. Very little was known about the potential toxicity of resveratrol in humans or what might constitute an efficacious dose. There were also serious concerns about the low bioavailability of resveratrol and questions about its possible estrogenic effects. Some scientists speculated that women who might be best advised to avoid resveratrol for this reason. We now know that precisely the opposite is true. Resveratrol has since been shown to be a powerful protectant against breast cancer. The big missing element was published human clinical trials by major medical schools and research institutions.
As earlier studies were successfully replicated and new investigations by research teams around the world uncovered more and more transcription factors, signaling pathways and other important pharmacokinetic effects of this very small molecule, interest in resveratrol increased exponentially in Asia, the US and Europe. By late 2010 there were over 4,000 published studies on resveratrol and a remarkable consensus was developing. Not only were scientists finding unusually consistent positive results, as one institution after the other examined the molecule using different approaches and technologies, but fundamental new effects and modes of action were being discovered at an astonishing rate. Many of these diverse properties of resveratrol have potentially huge implications for the prevention and treatment of human disease.
Only time will tell if resveratrol manages to unseat antibiotics to take the top spot as contributor to human health but at this point in time it can not be counted out. Certainly in terms of its beneficial properties relative to chronic conditions such as diabetes, cardiovascular diseases, many cancers, and quality of life enhancement overall resveratrol is clearly a contender, and for resveratrol the race has just begun.
Resveratrol vs Penicillin
In an interview with a well known international technology magazine in March 2009 I told the journalist “In my opinion, resveratrol will, in the space of 20 or 30 years come to be regarded as a more important scientific development than penicillin. In this prediction I was referring to this small molecule’s potential to positively impact the health, longevity, and quality of life of the human race. Seven months after my interview a scientist researching resveratrol at Harvard University took this prediction one step further by proclaiming that resveratrol will be more important than all antibiotics. Penicillin was discovered in 1928 and has been credited with saving many thousands, if not millions of lives. Resveratrol was first isolated from a plant source in 1940 in the West but has been used as a traditional medicine in asia for more than 2,000 years. In 1970 it was first characterized as a chemo-preventative, a substance which protects healthy human tissue from the disease causing effects of various agents such as poor diet, bacteria, viruses and aging. An example of a chemoprotective would be the use of low dose aspirin to protect against heart attacks. Both penicillin and resveratrol are derived from natural sources; penicillin comes from a common fungus, and resveratrol is found in a variety of plants including grapes, peanuts, cranberries but most importantly in the Japanese Giant Knotweed plant, also known as Polygonum-cuspidatum. Giant Knotweed has been used in Asia as a traditional medicine to treat immune disorders, cancer, and neurological conditions. The plant acquired a rather unsavory reputation as a foreign invader throughout Southeast Asia and Japan owing to its ability to survive in the harshest conditions and to crowd out other plants and crops. Five years ago a Google search for giant knotweed would return hundreds of articles on how to exterminate it. The same search today would be filled with scientific studies elucidating its astonishing medical and health applications.
The Scientific Community Agrees
In September 2010 the first international conference of resveratrol researchers was held outside of Copenhagen, Denmark. At this milestone event over 120 of the world’s leading scientists from prestigious institutions in the US, Asia, India, Europe and Australia met to present their findings on resveratrol. After attending this conference and listening to the presentations of these distinguished and highly accomplished scientists I am now convinced that, if anything, my comparison of resveratrol with penicillin was extremely conservative. Resveratrol and the drugs, treatments, supplements and functional foods, based which will contain this tiny but incredibly potent molecule will eclipse penicillin’s importance within one generation. From 1940 until 2005 there were some 800 published studies on resveratrol’s biological properties and its health benefits. From 2005 until the middle of 2010 there have been more than 3,000 new studies on cells, animals, and humans. New and surprising revelations are being announced almost weekly now by the leading universities, medical schools and research organisations around the world. All of these discoveries add to our knowledge of resveratrol’s remarkable range of health and disease prevention effects and give us new ideas on how to apply this knowledge for the good of mankind. The reservations expressed by some physicians and science writers a few years ago about possible side effects or over estimation of the benefits of resveratrol have been almost entirely refuted, and new earlier unimagined benefits are being revealed as more funding is devoted to animal and human clinical trials of this remarkable natural chemical. At a time when we face multiple drug resistant bacteria, an explosion in the incidence of diabetes, pandemic levels of obesity, debilitating increases in Alzheimer’s disease and other forms of dementia, and many other diseases of aging, it is clear that Resveratrol is a chemopreventative whose time has come. No single molecule or drug known to medical science has shown the wide range of potential preventative, therapeutic, and quality of life enhancement properties of resveratrol. It has been shown to inhibit cancer, kill bacteria, viruses and fungal infections, extend life span in animals, improve energy production in cells, quench damaging free radicals, increase glucose tolerance in diabetics, improve cardiac function, enhance physical and mental fitness and concentration, repair damaged DNA, prevent cell damage from nuclear radiation, and much more. Penicillin has been shown to have one use; to combat bacterial infections. Its effectiveness has been greatly diminished over the past twenty years as many strains of harmful bacteria have acquired resistance to it. Time will tell if resveratrol does fulfill its promise as a so-called miracle molecule, but if it only proves to possess ten percent of the health and medical benefits researchers have attributed to it so far it will in deed make a greater contribution to human health then penicillin, and perhaps even all antibiotics.
Wine Vs. Weed
Given all of the recent publicity about the health benefits of drinking wine and the so-called French Paradox one would logically assume that the principal source of resveratrol used by scientists and supplement makers is the red wine grape. Although the skin of red grapes does contain small amounts of resveratrol, the concentration is much too low to make grapes an economical source of this compound. Another problem with the extraction of resveratrol from grapes is the difficulty in removing the residues from pesticides, fungicides, and other agricultural chemicals needed to protect the fruit while it ripens. The application of agricultural chemicals not only poses a serious problem from contamination by toxins but also tends to reduce the natural production of resveratrol and other antioxidants by the grape. The highest concentration of resveratrol is found in organic grapes that are stressed by fungus, unfavorable weather, too little or too much water and a lack of pesticides. These conditions also lower the wine production levels but often result in a wine of outstanding quality.
If the amount of resveratrol in red wine is inadequate to explain the French Paradox then what is the reason the French suffer 40% less heart disease than the average westerner? As anyone who has spent time in France knows, the typical French urban diet is high in fats and salt and other less than ideal ingredients from a health standpoint, but in spite of this fact the French people tend to have far lower rates of cancer and cardiovascular disease then do Americans. Even lung cancer rates are relatively low amongst the tobacco loving French citizens. Furthermore, France has more people over the age of 100 than any other European country. Many scientists now believe that it is the full range of polyphenols, not only resveratrol, which accounts for the chemo-protective effects of drinking wine.
There is another paradox and that is the American Paradox. The American Paradox refers to the fact that even though Americans are amongst the best fed and most affluent people in the world their rate of mortality from cancer and heart disease, and more recently, diabetes and the effects of obesity, is extraordinarily high compared to many other developed countries. Wine consumption in the US is relatively low and the typical American and UK diet is heavy on bad fats, red meat raised on antibiotics, growth hormones and other chemicals, high fructose corn syrup, processed foods and chemical laden burgers and other fast foods. These factors along with too little exercise, too much stress, not enough sound sleep, and a heavy reliance on pharmaceuticals to treat chronic conditions surely account for much of the incidence of serious diseases in the US. They also result in a shorter health span, the number of years a person lives free of the so-called diseases of aging. A person who dies at the age of 85 who manages to avoid cancer, diabetes, heart disease and neurological conditions such as Alzheimer’s and dementia has a far longer health span than a person who dies at the same age after many years of intensive medical treatment and a dramatically impaired quality of life due to disease and incapacity.
So, if grape skins are not the preferred source of resveratrol what is? The answer is the Japanese Giant Knotweed plant, aka Polygonum-cuspidatum. If there were a master ninja of the plant kingdom it would surely be Japanese Giant Knotweed. This voracious predator is one of the toughest and most aggressive plants in existence. Above the ground it appears to be much like any other relatively harmless flowering green perennial but under the surface its roots tell a different story. If you can imagine a gnarly, hard, dense, thick brown mass that resembles the roots of a mature oak tree you have a good idea of what the roots of this plant look like. It thrives just as well in high and low altitudes, and in hot and cold, and wet or arid climates. It seems to actually grow stronger in more hostile environments. It is an aggressive invader and, once established in an area, will overwhelm existing vegetation within a few years. It is so tough it has been known to grow up through concrete building foundations. In Japan and parts of Europe a perpetual battle is waged by farmers and local councils to eliminate or at least control it. In mid 2010 the government of the United Kingdom took the extreme measure of approving the importation of a worm known to thrive on the roots of the Polygonum-cuspidatum plant in a rather desperate attempt to rid England and Wales of the invasive weed. British and Asian farmers who have tried to remove infestations of Giant Knotweed will tell you that if even one centimeter of the root of one plant is left in the ground the plant will return with a vengeance within a year or two. This obnoxious plant is the principal source of the resveratrol used in thousands of studies on cells, animals and humans. It is also a 2,000 year old traditional medicine in China and Tibet. Resveratrol functions as the immune and defense systems for this plant and many others. Although resveratrol is found in peanuts, blueberries, and many other plants, the concentration of resveratrol is highest in Knotweed. Not only is the plant rich in resveratrol, it is also a source of other natural protective compounds with names like polydatin, pterostilbene, and emodin, which western scientists are only beginning to investigate. Some of these compounds appear to be even more potent than resveratrol in fighting specific diseases and improving health. Pterostilbene, for example, a compound closely related chemically to resveratrol, has been shown to reverse decline in mental function in rats even better than resveratrol or any pharmaceutical. It also has potent cholesterol lowering properties. Many scientists believe that the optimum health and medical effects will follow from combining resveratrol with other chemoprotective plant extracts such as pterostilbene, fruit-based polyphenols, and other natural compounds. As one physician and researcher recently stated, “Antioxidants are not solo acts, they perform best as players in a diverse symphony orchestra”
That which Protects the Plant Protects He Who Consumes the plant
In 2006 scientists working at Harvard began referring to resveratrol as a hormetic. A hormetic is a substance which is produced by a plant in response to stresses such as fungus, bacteria, insects, heat, and too much sunlight, which protects the plant against damage or infection. The theory of zenohormesis is that these substances also provide protection and early warning of environmental threats to the animals in their vicinity who consume them, either by eating the whole plant or in the case of humans, a concentrated form of the plant compounds, such as in a supplement. Hormetics, such as resveratrol, do not normally act directly on the illness or biological stressor as do most drugs. They do not function like conventional medicines such as antibiotics, pain killers, cancer drugs, and blood pressure regulators; nor do they generally possess the toxicity of synthetic drugs. These natural plant derived compounds work by kick starting processes within the animals’ own cells and organs which attack disease or protect against the stress of harmful environmental factors. One example of a way in which resveratrol protects animals is its ability to prevent and reduce inflammation by suppressing certain proteins produced by the body in response to infection, injury, and other stresses. It is well known that inflammation, rather then simply being a symptom of disease as once though, is itself the cause of many human adverse medical conditions. We have very compelling evidence for example that inflammation plays a key role in auto immune diseases such as arthritis, allergies, multiple sclerosis and other illnesses including heart disease, diabetes and Alzheimer’s disease and many other maladies. When resveratrol is consumed it does not directly reduce inflammation, instead it activates systems in the body’s cells and proteins which reduce inflammation naturally. This is why resveratrol is called a regulator or a potentiator, and not a drug as such. A regulator works by activating or deactivating various enzymes, proteins and even genes to prevent or treat the cause of a problem, not simply mask its symptoms. When is the last time you heard of a synthetic drug that actually cured any disease? Resveratrol inhibits inflammation by activating many of the same processes that are activated by anti-inflammatory drugs, but in a more sophisticated and precisely targeted manner. Comparing resveratrol with the NSAIDS, non-steroidal anti-inflammatory drugs, is analogous to comparing a scalpel to a blunt kitchen knife. Resveratrol reduces inflammation without also interfering with the beneficial processes that the anti-inflammatory drugs inhibit. It also does not have the side effects of drugs such as aspirin, ibuprofen, and the more recently released next generation anti-inflammatory drugs. The manner in which resveratrol attacks cancer is another example of its selective, almost intelligent effects on cells. Resveratrol inhibits the growth of cancerous cells through a number of different actions. It inhibits the growth of small blood vessels that feed a tumor, but does not stimulate the spread of the tumor to other areas of the body, a process referred to as metastasis, which is one side effect of the anti-cancer drugs which also inhibit the supply of blood to a cancerous tumor. It also works by activating or deactivating certain proteins such as Tumor Necrosis Factor, TNF, an important immune system molecule that characterizes many tumors, and by suppressing a protein called NF-κB, a which is linked to almost all cancers in humans. Many of these anti-cancer effects of resveratrol are the same effects that the pharmaceutical companies are spending billions of dollars to reproduce in new pharmaceuticals. Unfortunately, many of the more effective drugs being used today are also highly poisonous. Often it is a death race for the patient between the drugs’ toxic effects and the growth and spread of the cancer. One oncologist I spoke to at M.D, Anderson Hospital in Houston said “Very few people are actually dying of cancer these days, with aggressive treatments such as chemo, radiation and surgery most die of the therapy first, or if they are lucky they survive both the cancer and the treatment.” This is not to propose the use of resveratrol as a treatment against cancer, or any other disease for that matter. We need much more actual human clinical data and confirmation of the results seen in the 3500 studies, trials and investigation already completed before we can say with confidence that resveratrol is as effective as the laboratory studies indicate it should be against any specific disease. It may well turn out that some combination of resveratrol and the more effective anti-cancer drugs will be the best strategy to pursue. We know for example that, in the case of some chemo therapy agents, resveratrol improves their effectiveness and reduces the severity of their side effects. It may also turn out that some other phytochemical, such as Pterostilbene or Picead, may be even more effective than resveratrol. There is presently an enormous amount of research being undertaken to answer these questions.
Why Smaller is Better
The larger and more complex a molecule is the harder it is for the molecule, be it a drug or nutrient, to be taken up by the cell, and very often the less effective it is against the basic process or disease being targeted. Larger molecules are also more likely to have unpredictable side effects. Smaller molecules are better able to pass through the cell membranes which, act as barriers surrounding all cells. They are also better able to precisely target individual disease components at the cellular level. The effects of large molecules, which constitute most pharmaceutical drugs on the market today, vs small molecules, such as resveratrol, is the difference between using a laser to remove a tumor versus removing the entire organ or limb surgically. The major drug companies, such as Biotica and Genentech, as well as research organizations, including the National Institutes of Health, consider small molecule drug candidates to have the greatest potential as treatments for diseases such as arthritis, Alzheimer’s disease, cancer. In the areas of gene therapy, and neurological diseases such as Alzheimer’s disease, larger molecules are essentially ineffective due to their inability to pass through the blood brain barrier, the protective barrier which prevents potentially damaging chemicals from entering the brain. Only small molecules can pass through this protective filter. Resveratrol is an exceptionally small molecule that has shown astonishing effects in thousands of animal and laboratory studies. In the past few years many of the health and longevity effects seen in the laboratory have also been confirmed in human clinical trials. We now know in much finer detail how resveratrol operates at the cellular level to affect the body’s systems and functions. Going forward the emphasis of researchers will shift from cell and animal trials to clinical trials on humans. Results from these limited human studies so far have been nothing short of astonishing. It is expected that progress in discovering new medical and health enhancement applications for resveratrol over the coming decade will be rapid and dramatic.
Resveratrol and Aging, Life span versus health span.
Increases in the maximum and average life span of humans from the beginning of the 20th century until now have not been particularly impressive compared to the advances made in other areas of science and technology; and some countries, such as Russia, life spans have actually declined. Predictions by demographers of a drop in US life span in this century are based upon compelling evidence of declining health amongst the present generation of teens and twenty somethings. Our poor record in extending maximum life span is attributable to the fact that medical technologies and pharmaceutical research have focused more on keeping sick people alive rather than on preventing the diseases and disabilities related to aging. Drug companies may far more money selling drugs that treat disease then they on cures to diseases. This is one reason why virtually no cures have been offered by any major pharmaceutical company in the last 25 years. One result of corporate medicine has been that the average person spends more than 90% of the his or her lifetime medical expenditures during the last five years of life. Although average life spans have increased moderately over the past two decades, Health Span, the number of years one enjoys a healthy, independent, and productive life, has not kept pace. In fact, Health Span appears to be decreasing in the US and the UK and in much of Asia as the citizens of these countries forsake traditional diet and remedies for the western lifestyle; and parents aged 45 to 60 may, on average, outlive their children for the first time in history. At the current rate of increase of medical costs the policy of treating disease rather then preventing disease is unsustainable. At some point during the next ten to twenty years the result will be that health care, and consequently life span, will be severely rationed, or national budgets for health care will consume more than the total government revenues for all public services. Preventable diseases such as type 2 diabetes, many cancers, and cardiovascular diseases are increasing in incidence at unprecedented rates in the developed world. It appears that resveratrol can play a critical strategic role in reducing run away health care costs by preventing, delaying or treating many of the health conditions associated with poor diet, lack of exercise, and obesity.
Most of what you think you know about aging is wrong. This applies whether you are a laymen, physician, political leader, science journalist, social scientist or author of books and articles on the subject. To begin the process of dismantling the prevailing myths and misconceptions here are a few facts to consider.
- Aging and the widely recognized diseases of aging are the inevitable consequences of living longer. False
Aging is not in itself the cause of diabetes, obesity, heart disease, cancer or Alzheimer’s. Nor does aging necessarily lead to impairment of emotional health, physical capacity, libido, cognition, memory or intelligence. Aging is merely the name given to the constellation of adverse health and medical conditions normally associated with the elapse of time since one is born. The diseases and disabilities associated with advancing age all have specific causes. One’s age is simply a measurement of time lived, and time is not a cause of any disease. By modifying one’s diet and daily routine, staying physically and mentally active, adopting preventative life style practices, and seeking appropriate medical interventions to repair, replace and renovate deteriorated body parts and capabilities virtually all of the diseases normally associated with chronological aging can be either delayed, prevented or even reversed. The mortality rate from disease can be radically lowered by adopting preventative strategies at the individual level and one such strategy is the intelligent use of supplements such as resveratrol. Unfortunately, the institutionalized profit motive driving the emphasis on treatment versus prevention deprives the majority of the world’s population of the benefits of increased longevity and improved health during later life. Only those individuals who take personal responsibility for their health can expect to achieve improved Health and Life spans.
- An aging population will be a drag on society, the young and the economy.
- False
Precisely the opposite scenario to this almost universally predicted calamity will actually ensue.
The science commentators and social scientists who contend that an increased population of older citizens will be a burden on the younger members of society fail to understand one very simple fact; many people will live longer because they are free of the disabling medical conditions which presently drain the wealth, vitality, and productivity from society. It is foolish to presume that people will somehow magically live substantially longer without concurrent improvements in their health and vitality. An elderly professional man of woman, for example, who is still healthy, energetic, and mentally sharp is advantaged over a younger colleague by virtue of his or her additional years of work experience, judgement, and maturity. Think about it. Given the choice between two surgeons, both of whom are fit and healthy, would you prefer the doctor with 40 years of experience and thousands of operations under this belt to remove your ruptured appendix or the surgeon with 5 years and only 100 operations? Industry and the professions are already seeing a surge in demand for older workers over their less experienced colleagues in all developed countries. As Health Span increases we will see people taking up new careers and starting university at the age of 50 and greater, professional athletes in their 40s and 50s will challenge competitors who are decades younger, and the average retirement age will increase dramatically, which means that many more people will be paying taxes and contributing to the GNP for five to twenty years longer during their life times. Importantly, many fewer people will be drawing retirement and disability payments or requiring costly medical treatments. If prevention and personal responsibility for health become a reality the improvements in Health Span could be the single largest contributor to the US and UK economies twenty years from now. Resveratrol and other natural compounds related to resveratrol may have the potential to add many productive years to the life of westerners by extending health span and inhibiting conditions such as dementia, diabetes, cardiovascular disease, and cancer.
- There is an intrinsic biological limit to the number of years humans can live healthy, vital, independent lives.
- False
Scientists have yet to identify a ticking “biological clock” that predetermines the maximum life span for a human. Humans are not “programmed” to die at a certain age. We know what the principal causes of aging are, and we are rapidly closing in on solutions to these causes. Some, such as the corruption of one’s DNA, and decreasing telemere length, which occur as cells divide and are replaced, are a bit more complex than others, but none are impossible to solve given the application of sufficient resources. A Manhattan Project styled attack on aging would probably solve all of these challenges in less than ten years. Now that the medical and research communities are beginning to treat aging as any other disease, rather then accepting it as inevitable, and simply focusing on making older people more comfortable, we can expect dramatic breakthroughs in life extension. Each new breakthrough will give humans a bit more time during which new discoveries will be made that will create stepping stones to the final goal of indefinite life span.
Resveratrol is known to be a chemo protective agent which can play a critical role in delaying or possibly even preventing the most serious causes of mortality in the developed world. Serious consideration should be given to incorporating resveratrol and other natural chemo preventative supplements into a more rational, humane and effective national health plan in every developed country. Unless the priority shifts from treatment to prevention the health, wealth and life span of citizens will continue to decline and national health care budgets will be unable to provide cope.
- There is no silver bullet on the horizon that will dramatically extend human life span.
- True
The increase will come in small steps which will turn aging from a debilitating terminal
disease into a treatable condition just as the case has been with diseases such as diabetes,
HIV-AIDS, malaria, and many others.
Resveratrol is not a magic elixer that will prevent the diseases of aging or compensate for poor health habits. Like stem cell therapy, genetic engineering, organ replacement, natural and synthetic drugs, exercise, diet, and medical technology, it has an important part to play in any longevity program. As we collect more data from human clinical trials we will be better able to define just what this role should be. Resveratrol is only the first in what will likely be a long list of similar compounds with extensive health benefits. Other compounds related to resveratrol, such as Pterostilbene, Polydatin, and various analogs of resveratrol, will be intensively investigated over the coming few years and it is almost certain that researchers will find a treasure trove of genetic and other biological effects even more impressive than those of resveratrol. Pterostilbene, a natural compound found in blueberries, for example, has been shown in rats to actually reverse declines in decision making abilities and appears to improve intelligence. It also lower bad cholesterol more effectively than resveratrol does. Polydatin is more effective than resveratrol in preventing the damage to heart tissue which occurs when a heart attack victim is resuscitated or a heart is restarted following some types of cardiac surgery. Emodin, an antioxidant found in the Japanese Giant Knotweed plant is a potent anti-cancer agent. The more we learn about these astonishing molecules the more we are awed by their benefits to human health. Many researchers have noted a synergistic effect when resveratrol is combined with other polyphenols such as curcumin however not all combinations of polyphenols are synergistic. For example, a negative effect on Sirt gene activation has been observed when resveratrol is combined with the antioxidant quercetin.
Health Span and Life Span will increase at a steady but ever increasing rate as discoveries are made and knowledge is created that will lead to cures and therapies to treat the so-called diseases of aging. Natural chemo-preventatives such as resveratrol, curcumin and a wide range of other polyphenols may take over much of the role synthetic drugs now play in treating disease after the fact rather than focusing on preventing disease naturally.
- Technology advances will lead to longer life spans and elimination of many diseases.
True
Dr. Sinclair at Harvard discovered the gene activation properties of resveratrol only because he had the help of a new computerized chemical screening system that could examine thousands of molecules for their anti-aging gene activation properties in the time it previously took to investigate only a handful of compounds. Advances in computing power are rapidly increasing our ability to comprehend the intricacies of the metabolic process and to realistically simulate critical biological pathways. The past decade saw the development of genomics. The coming ten years will consolidate this knowledge and move on to unraveling the role of the proteins which are encoded by our genes. This will represent an enormous advance in our ability to design drugs that turn on beneficial genes and switch off the genes responsible for diseases such as multiple sclerosis, asthma, mental illness and hundreds of other diseases that are caused by either a specific genetic abnormality or a combination of genetic factors. We will also begin to solve the mystery of what function the 95% of the genome which does not code for proteins plays in human development. This will lead to the design of new strategies to prevent orreverse aging and result in quantum leaps in human longevity.
By 2020 computers and other medical devices will be powerful and cheap enough to give scientists the tools they have needed to virtually stop the aging process in animals. This goal has already been achieved in the lab. The convergence of thousands of independent discoveries and incremental breakthroughs by dedicated professionals working in diverse fields are creating synergies and mutually reinforcing discoveries that are the key to extending life span and eventually eliminating aging altogether. Developments in advanced prosthetics, stem cell therapy, organ replacement, and the prevention and treatment of cancer, heart disease, and neurological conditions such as Alzheimer’s and dementia will mean that those persons who are presently under 60 years of age and in excellent health will have a reasonably good chance of living indefinitely. This assumes that they are financially able to afford the treatments, drugs, and therapeutic procedures which will become available over the next 30 years. Beyond 2040 aging will be simply a chronic condition treatable or preventable at a reasonable cost to the patient. The timing of one’s death will become for many people a matter of individual choice. Accidents and needless wars over resources will become the main causes of death in the developed world. Unless we stop destroying our planet through the plundering of its resources and poisoning its air and water, climate change and scarcity of usable water and breathable air will negate any increases we make in average life spans.
It is not necessary to fully understand the cell’s incredibly complex metabolic process to develop effective drugs and other preventatives and treatments for the disease we call aging.
True
Many of the safest and most successful drugs in use today work by targeting, unidentified biological processes they were not initially designed to target. Luck plays a part in drug discovery. Serendipity and persistency on the part of researchers and physicians resulted in the discovery of penicillin, aspirin, pain killers and many other valuable drugs. Partial knowledge of the cellular-level biological processes being targeted coupled with the intelligent application of trial and error is an effective and rational life extension strategy. It probably offers the greatest potential to conquer aging in the near to mid term. When Dr Sinclair discovered the ability of resveratrol to activate the so-called anti-aging genes it was due to serendipity as much as to science. Sinclair discovered this previously unknown ability of resveratrol because he was able to quickly screen thousands of chemicals for this property due to advances which had just been made in laboratory analysis technology. His discovery did not come about because he had some reason to believe that resveratrol might fit any receptor on a cell or it might have anti-inflammatory or antioxidant properties.
Why are we aging faster but living longer?
The decline in the health status of the average British or American citizen is not principally a natural or inevitable consequence of human evolution nor is it due to the rise of new diseases or the deterioration of the quality of the environment in which we live, although environmental factors do militate against increasing life spans. The causes are simple and well known.
- Life span increases so far have come about only because advances in medical technology and pharmaceuticals are keeping sick people alive longer, but at a very high and untenable cost; not because diseases and disabilities are being prevented or that people are staying healthy longer. Further increases in both health span and life span must come from adopting prevention as our primary focus. We have yet to begin to exploit the advantages of prevention at the institutional level. Resveratrol is one molecule that may play an important part in both prevention and treatment.
Obesity and life style factors, not aging, are the principal cause of diabetes, hypertension, most heart conditions, and most cancers. Obesity is also a major causal factor for gastric reflux disease, gall bladder disease, degeneration of L-Sacral Spine and weight-bearing joints, asthma and hundreds of other adverse medical conditions. Resveratrol was shown to increase the life span and health span in obese mammals. In his now famous study published in the journal Nature, obese rats lived 31% longer and managed to avoid all of the diseases normally contracted by aging animals. Their organs resembled those of young, lean, health rats.
Lack of regular exercise compounds the negative medical consequences of obesity, and is a risk factor for osteoporosis as well as a wide range of adverse physical, emotional and neurological conditions. Mitochondria are the cells’ energy factory. Resveratrol increases mitochondrial density and enhances mitochondrial function. Rats fed resveratrol in the study by Dr Auwerx and published in the journal Cell, were able to run twice as far as rats not fed resveratrol.
Probably the largest contributor to early aging and the diseases associated with aging is poor diet. Excessive consumption of red meat, processed foods, sugars and high fructose corn syrup, as well as trans fats and the lack of omega 3 rich foods and polyphenols from fruits and green leafy vegetables, and overeating in general are all enemies of human Health Span and longevity. Resveratrol has been shown to counter many of the adverse effects of poor diet.
Chronic unresolved stress, results in endocrine imbalances, immune system dysfunction, inflammation, sleep disorders and neurological impairment. Resveratrol is a natural anti-inflammatory agent and may have important neuroprotective properties.
A prescription for longevity.
Anyone can substantially enhance both Health Span and Life Span by adopting the following measures:
- Stop using tobacco products of all types and limit alcohol use to no more then 3 glasses of wine or three ounces of spirits per day.
- Reduce, or better yet eliminate, all processed foods, fast foods, and sweetened beverages. Make green leafy vegetables your primary food group. Reduce or eliminate red meat from your diet.
- Take a pill. Add the below supplements to your daily routine:
Biotivia or other quality Resveratrol, 250mg to 1,000mg
Pterostilbene, a molecule closely related to resveratrol, 250mg
- Non fish oil derived Omega 3, such as Green Omega 3, with EPA and DHA, at least 1,000mg
A multi-antioxidant complex such as Bio Quench, 500mg to 1,000mg
Vitamin D, 10,000 IU
Acetyl L-Carnitine and Alpha Lipoic Acid supplements, 250mg of each Curcumin, also known as the spice tumeric, 1 to 2 grams per day Vitamin C, preferably the oil soluble form called ascorbyl palmitate There are, of course, many other supplements that may have a beneficial impact on Health Span and longevity but the published scientific evidence best supports the above nutrients. The majority of over the counter supplements are of no value whatsoever.
- Incorporate at least 30 minutes of moderate to intense exercise, at least 3 times each week, into your routine. Get up from your computers, video games, Ipads, email, and Facebook accounts and do something physical, preferably out of doors. Even if you are overweight you can be fit. In fact, it is healthier to be fit and fat then unfit and thin.
- Meditate or at least take a one hour mental and physical break from your daily grind once each day. Midday naps of 20 to 45 minutes are extremely beneficial.
- Maintain a healthy weight, which is best measured by dividing your height in inches by your waist circumference. The result should be no less than 2.0. The popular BMI measurement is basically worthless as it makes no distinction between lean and fat body mass.
- Use high quality air and water purifiers in your home and office. Lobby your political leaders to take environmental protection and clean energy seriously. At some point the limit on life span will be the determined by the ability of the Earth’s climate and resources to support life at all.
- See a physician at least once per year and repair failing parts just as you do with your automobile or any other complex machine. If your eyesight is deteriorating consider having a corrective procedure by an eye surgeon, if you have dental or periodontal issues see your dentist. Gum infections can cause serious heart conditions and other life threatening conditions. Do not ignore symptoms of an underlying problem. Your chances of surviving cancer, as we all know, are dramatically enhanced if you begin treatment early, the same rule applies to diabetes and most other chronic diseases.
- Drive sensibly, wear seat belts and control your anger. It would be a pity to live a healthy life and then die at the age of 40 on the motorway.
I will expand the below summary of the more recent and interesting studies in the final document. This section will be about fifteen pages when finished.
What the Science Says
The most recent research results by scientists and physicians working at prestigious medical schools and other institutions around the world were presented in September of this year at the Resveratrol 2010, the first international science conference on resveratrol and health. There is not enough space in this paper to discuss all of the remarkable results presented by the experts at this conference. I have chosen to summarize the high points of some of the more interesting and authoritative studies below. It should be noted that no study was presented in which any toxic or serious adverse effect of oral administration of resveratrol to animals was observed, and no study or trial was stopped due to the presence of such negative effects.
Resveratrol Human Clinical Trials
Over the past three years a substantial number of medical schools and research institutions have undertaken studies of resveratrol’s ability to prevent or treat disease in humans. The number of such clinical trials is increasing weekly. A few of the more important ones are described.
Diabetes
Albert Einstein Medical College conducted two human clinical trials in which the ability of resveratrol to enhance mitochondrial function and improve insulin sensitivity, two important functions the drug companies are attempting to target with a new generation of drugs.
The results were extremely positive and thes
The Phenomemon of Resveratrol: Redefining the Virtues of Promiscuity
John M Pezzuto
College of Pharmacy, University of Hawaii at Hilo, Hilo Hawaii
*There are presently over 3500 papers which have been published in various scientific and medical journals which concern some aspect of resveratrol. This represents a huge and accelerating increase in the interest in this compound by the scientific community from 2000 to the present.
*Resveratrol is contained in significant amounts in the red wine grape, which may explain the so-called “French Paradox”, the low incidence of cancer and heart disease in France in spite of a diet that is high in saturated fats, salt and other dietary risk factors for heart disease.
• Cancer chemoprotection “entails the ingestion of dietary or pharmaceutical agents that can prevent, delay or reverse the process of carcinogenesis (cancer). Resveratrol is classified as a chemo-protective.
**The low amounts of resveratrol available in wine and foods are not likely to have a major beneficial impact on human health. This suggests that a concentrated resveratrol supplement is required to produce the health effects of resveratrol as seen in the thousands of trials and investigations. In most of these studies the resveratrol dose used, in human equivalent values, ranged from 100mg to over 2,000mg for a 70kg person.
*Study observation
**Author’s analysis or comment
A definitive guide to selecting a quality resveratrol supplement
Since the study by Dr. David Sinclair was published in the journal Nature a plethora of New companies have sprung into existence offering resveratrol supplements. Evalualating resveratrol sellers and their products has become a confusing and frustrating process. This guide is meant to elucidate the most important factors one should use to discriminate one resveratrol supplement from another based upon their relative quality, value and likelyhood of being effective.
Unlike most dietary supplements, hundreds of well managed scientific studies and trials have upheld resveratrol’s potentially critical health properties as a treatment for diabetes, cancer, inflammatory and autoimmune diseases and neurological conditions. Without passing judgement on resveratrol’s actual efficacy or effectiveness it is clear that many people purchase resveratrol as a preventative or treatment for a serious medical condition. If the resveratrol these consumers purchase is not a high quality, properly manufactured, bio active compound they are not only wasting their money but are also failing to obtain whatever benefits resveratrol may offer for the amelioration of their condition.
The criteria below are based upon valid scientific principals and accepted standards for the evaluation of either a of a functional dietary supplement such as resveratrol. The standards can also be used in judging other supplements.
Ethical labeling is essential. The labels of many resveratrol suppliers do not disclose the exact form of resveratrol or the quantity which is contained in their supplement. Some simply call their main ingredient “red wine complex” or a “proprietary blend”. Given that red wine contains less than 1% resveratrol it seems a bit strange that a company would use this description to label a resveratrol product unless the purpose was to conceal the actual ingredients in the product. A proprietary blend can be almost anything, but is unlikely to consist of pure resveratrol given the relatively high cost of quality resveratol versus other possible ingredients.
Resveratrol is composed of two principal isomers, trans-resveratrol and cis-resveratrol. Only the trans-isomer has been associated with health benefits. The cis isomer actually acts to nullify the effects of trans-resveratrol. Unless the seller states on the label that the product consists entirely of the trans-resveratrol form it is highly likely that it contains either some or all of cis-resveratrol, which is, by an order of magnitude, the less costly form of resveratrol.
Capsule size makes a difference. A size zero capsule is able to contain about 500mg of resveratrol, if the base material is processed using pharmaceutical technology and equipment. This is the largest size capsule that is quite easily swallowed by most people. Sellers who use larger capsules do so to compensate for the fact that they are simply stuffing lower potency raw extract into a capsule without going through the time and expense of purifying and granulating the resveratrol extract. A larger capsule size also allows for the use of various fillers and chemicals such as silicon, magnesium sterate, cellulose, and other additives. The best quality resveratrol supplements are contained in a size zero, all vegetable capsule and contain no additives or fillers at all. There is no reason why you should have to consume sand, chemicals, and other unwanted ingredients in your supplement simply because your supplier can not be bothered with using more sophisticated processing and filling technology.
Is red wine the best source of resveratrol? Although much of the news about resveratrol mentions the red wine grape as its source, wine grapes are not a practical or desirable source of resveratrol for two important reasons. First grapes are subjected to a wide range of toxic chemicals in the cultivation process. Fungicides, pesticides, chemical fertilizers and many more chemicals are sprayed directly on wine grapes. Since resveratrol comes from the skins it is very difficult to eliminate contamination in the resveratrol concentrate. The second reason wine grapes are not a good source of resveratrol is that it is impossible to produce a high potency supplement using grape extract. The concentration of resveratrol in grape skins is simply too low. This is why, in virtually all of the animal and tissue studies on the health benefits of resveratrol, the source of the resveratrol was the Giant Knotweed plant, which grows without fertilizers or agricultural chemicals in the wild.
Capsule ingredients and packaging The capsules themselves should be all vegetable such as Pfizer Vcaps rather than clear gelatin, which is made from an animal product. Not only is an all vegetable capsule healthier to consume than an animal by product but it is designed to better regulate the release of the active ingredients into your digestive tract when taken orally. What is the use of taking a natural supplement if the capsule it is contained in is made from the collagen inside animals’ skin and bones?
Resveratrol is highly susceptible to deterioration by oxidation and exposure to ultraviolet light. A quality supplement will be protected from oxidation during manufacture through the use of nitrogen gas filled processing lines. The bottle in which the supplement is contained should also use an inert gas to prevent oxidation during shipment. However once the bottle is opened oxygen is allowed to enter. If active packaging technology is not employed to protect against this damage the shelf life of the product will be seriously degraded. Only one company uses an oxygen absorber system to capture the oxygen which enters the bottle when a capsule is retrieved.
Dosage The appropriate dosage of trans-resveratrol is a highly contentious issue, with respect to the rhetoric of resveratrol suppliers that is. The science regarding dosage is relatively clear however. Although doses of around 100mg appear from some studies to have potentially important preventative effects, the consensus is that at least 250mg is required to reach the threshold for efficacy as demonstrated in most animal and in vitro studies undertaken to date. This equates to the human equivalent of the dosage used in the Dr. Sinclair study and many other studies. The dose recommended by most clinicians for treatment of an existing condition ranges from 1,000mg to 4,000mg. however it is recommended that one consult a physician before taking a dose over 1,000mg daily. No toxicity or serious adverse effects were observed in several animal and human studies in which up to 5,000mg was given on a daily basis for an extended period of time. In animal studies dosages up to the human equivalent of 30,000mg have been tolerated with only minor adverse effects. Products which offer less than 250mg of pure trans-resveratrol are of dubious value.
Natural versus synthetic resveratrol? Synthetic resveratrol can be produced using one of two methods, fermentation and chemical engineering. In the case of fermentation a yeast or bacteria is genetically modified to produce resveratrol. Chemically engineered resveratrol is constructed from a broth of compounds using organic chemistry to engineer the molecule. Both processes are fraught with potential pitfalls. In the case of fermentation often what occurs is that bits of the bacteria or yeast DNA used to produce the resveratrol show up in the finished material. This means that if you use this product you are consuming a novel substance, that is a compound that has never been previously consumed by a human, with potentially toxic or other other unknown effects. In the case of a chemically engineered resveratrol product the issue is contamination by small amounts of the chemicals used to produce the synthetic resveratrol. On a typical HPLC graph of a synthetic resveratrol there will almost always be spikes on the chart of what are referred to as “unknowns”. These trace chemicals are by-products of the creation of the resveratol which are unidentified and assumed, or hoped, to be non toxic. Furthermore, naturally extracted resveratrol from the polygonum cuspidatum plant is known to be effective and non toxic. Neither properties have been definitively verified in regard to synthetic resveratrol. When a natural compound such as resveratrol is copied using chemicals, yeast or bacteria often the final product is not truly identical to the natural compound. There is only one reason why some suppliers use synthetic resveratrol in place of natural resveratrol from polygonum cuspidatum. The reason is the far lower cost of synthetic resveratrol. If a supplier does not disclose which type of resveratrol is contained in its products you can normally assume that it is the synthetic variety.
Gimmicks to avoid
Micronized Resveratrol. There is absolutely no published scientific evidence that micronization improves the bioavailability of resveratrol. In fact, it may have a negative effect by reducing the half life of resveratrol in blood plasma. There is no reason to pay extra for a micronized resveratrol product, which offers no practical advantage to the user.
Resveratrol with Quercetin. Quercetin is a potent antioxidant in its own right, however it should not be combined with resveratrol or even taken within at least 8 hours of taking a resveratrol supplement. The reason, which was only recently discovered, is that quercetin blocks the metabolites of resveratrol from entering your blood stream. Quercetin also deactivates sirtuins, precisely the opposite effect of resveratrol. Until a few years ago it was assumed that adding quercetin was a good thing since the importance of the metabolites was not understood. Before the latest studies revealed otherwise it was assumed that the metabolites were not responsible for the biological and longevity gene activation effects of resveratrol. Based upon several highly regarded studies we now know that it is very likely that the beneficial effects of resveratrol actually derive mainly from these metabolites rather then from the free resveratrol. These metabolites are bioactive products of the breakdown of resveratrol by the liver and layer of cells lining the small intestine. By blocking these sulphates and glucordinates quercetin interferes with the ability of resveratrol to activate the sirtuins, specifically Sirt-1 and 2, the so called anti aging genes, and blocks other signaling pathways through which resveratrol operates, and which are responsible for many of the desirable health effects of resveratrol. Moreover, the half life of the metabolites in human tissue is several hours whereas the half life of free resveratrol is only about 12 minutes. In a 2009 study of resveratrol’s effects on inducing the creation of hemoglobin cells in be patients’ blood it was found that quercetin totally blocked the ability of resveratrol to create the new red blood cells. Quercetin also nullified the anti inflammatory property of resveratrol in an informal trial of resveratrol’s palliative effect on arthritis. There is no scientific justification for adding quercetin to a resveratrol supplement. If one wishes to take quercetin it is readily available as a low cost supplement that may be taken by itself.
Red Wine Complex. Some supplement makers attempt to confuse the buyer into thinking that he is buying a resveratrol product by using this misleading description. There is no standard for “Red Wine Complex”. Red wine contains only very small amounts of resveratrol, less than 5% as a rule.
Dr. Oz or Oprah Recommended Resveratrol. Neither Dr Oz nor Oprah recommend any brand of resveratrol. If you are interested in knowing which brand they use in their presentations on resveratrol you can find this by searching for Resveratrol on their respective web sites.
The credentials of your supplier are important. The media coverage of the studies demonstrating the potential benefits of resveratrol has attracted a flood of new and clearly disreputable resveratrol sellers to the market. These companies have no experience in producing a food or health supplement, no scientific staffs, testing labs, or other technical resources. Most have no established quality control standards and no history by which one can judge their reliability and integrity. Many of these companies use a form of the word resveratrol in their names and sell only via a web site. The lawyers for Dr. Mehmet Oz and Oprah Winfrey recently filed federal law suits against over 50 of these companies for illegally using their trademarks and making false claims that their products were endorsed by these well known personalities. A copy of the litigation can be downloaded by clicking on the below link.
Your resveratrol supplier should be a manufacturer rather than simply a reseller. Many suppliers buy raw material from Asian sources at the lowest possible price and simply fill capsules, rather then collect the plant and process it in their own GMP certified facility. `legitimate resveratrol supplements will have passed Consumer Lab’s recently updated evaluation of resveratrol brands, and its web site should provide easy methods to contact the company if you have any questions, complaints or a request for a refund.
Your resveratrol provider should have a history of at least ten years, preferably more, of ethical business operations with no unresolved Better Business Bureau complaints. It should offer a range of products not only one or two virtually identical products. If the company offers a monthly recurring order program a clear and convenient means of canceling your subscription should be offered. Before you give your credit card information to an on line seller be sure that the company is legitimate. This can usually be established by contacting your local BBB and doing a bit of on line due diligence.
The company should offer its product through respected retail shops. If the company’s products are not available in brick and mortal stores such as GNC, Walgreens, The Vitamin Shop and other reputable resellers it should probably be avoided. Anyone can sell a product over the Internet but to have one’s products accepted by major Health and Supplement stores requires liability insurance, thorough testing of the products’ quality and vetting of the company and its principals. Shops that carry supplements carry out thorough due diligence of both the product itself and the company supplying and manufacturing the product. You have no such assurance with most on line suppliers. This is not to say that all on line suppliers sell inferior quality supplements. There are some very reputable and ethical Internet merchants and manufactures. Unfortunately however, with any new supplement comes a raft of brand new suppliers with no history or experience in manufacturing advanced nutritional products who buy from lost cost, low quality brokers and whose products consistently fail independent evaluation. These companies usually employ highly unethical business practices or compete entirely on the basis of price. More often than not their products are virtually worthless, their customer service is non existent and their lifespan is measured in months if not weeks.
The gold standard for a manufacturer is for its products to win widespread acceptance by the medical and research communities. Resveratrol used in human trials at institutions such as the Albert Einstein Medical School, Ottawa Hospital, Harvard, international institutes such as the University of Ferrara, University of Queensland in Australia and the NIH are the purest and most thoroughly tested supplements available to the general public. These institutions must put any product used in human trials through a rigorous and extensive series of tests for purity and possible toxicity. Their endorsement is far more valuable than any test done by the manufacturer themselves or by the so-called independent labs. One company whose products satisfy all of these criteria, and which have been used in National Institutes of Health, Health Canada and other health ministry funded studies is Biotivia, who introduced the original resveratrol supplement over six years ago. The company has been in operation in the US and Europe for over 20 years. On the opposite end of the scale are the companies who have sprung into existence to take advantage of the hundreds of news articles about resveratrol’s potential health benefits. In mid 2010 Oprah Winfrey hosted Dr. Mehmet Oz on her program to talk about extreme life extension. He extolled the virtues of resveratrol in his presentation and shortly thereafter literally dozens of new suppliers materialized offering free bottles of resveratrol and claiming an endorsement by Dr Oz. Not only were they deceiving customers with their sleazy marketing schemes their product were found, in many cases, not to contain resveratrol at all. The lawyers for Dr Oz and Oprah’s production company filed suit against most of these companies, and the states attorney general in several states launched criminal investigations.
