|In response to the many media reports about resveratrol, it seems like every supplement company is offering some form of grape complex for sale that claims to contain some resveratrol.
Recent attention has focused on a publication in the journal Nature that demonstrated improved health and survival in mice fed a high-fat diet supplemented with resveratrol, the same flavonoid that has been shown to increase the life span of a variety of organisms, including yeast, worms, flies, fish, and mice.1-5 This research tied the beneficial effects of resveratrol to mechanisms that underlie caloric restriction, and showed that such approaches could be used to treat certain chronic disorders and diseases of aging.
However, some popular press reports that accompanied this scientific article generated a fair amount of controversy, especially related to the dose used in the experimental mice and the estimated human-equivalent dose that may be required to exert the same biological effects. The Life Extension Foundation, however, is the only organization that has taken a grape-seed/resveratrol product already being used by health-conscious individuals and shown that the favorable biological effects of resveratrol can be achieved at a dose that is more than 10-fold lower than that used in the most-referenced study (referred to as the Harvard study).
Just recently, Life Extension reported that experimental animal studies conducted by BioMarker Pharmaceuticals were under way using the same grape extract fortified with resveratrol that is currently used by Foundation members.6 These studies were designed to evaluate the gene-expression response in mice fed resveratrol from the whole-grape extract found in the Grapeseed Extract with Resveratrol encapsulated product. The gene-expression data obtained from the grape extract group were compared to data from a group of animals subjected to caloric restriction. The preliminary data suggested a significant overlap in the favorable pattern of gene expression between the grape extract-fed mice and the calorie-restricted mice. In addition, experimental fruit flies (Drosophila) fed grape extract showed improvement in a model of Parkinson’s disease, as well as an extended life span. These findings paved the way for further analysis identifying the specific molecular pathways involved in these effects. Here we provide an update to these earlier findings.
Resveratrol and Other Health-Promoting Grape Constituents
The Life Extension Foundation constantly surveys the scientific literature in order to utilize the most important findings in promoting health and extending life. Mounting evidence demonstrates the broad-spectrum effects of biologically active molecules such as resveratrol, which is derived from natural plant extracts. In nature, molecular compounds like resveratrol are found in complex mixtures containing a diverse array of physiologically relevant molecules. Many of these constituents may be required in order to provide phytomedicinal agents with optimal bioavailability and synergistic action. Scientists must consider these points when conducting studies using either a single phytochemical (such as resveratrol alone) versus resveratrol combined with grape skin and grape seed extracts.
Classes of molecules found in natural whole grape, grape skin, and grape seed extracts include potent effectors like proanthocyanidins (in grape seed), anthocyanins (which give purple and red grapes their color), and single molecular entities such as resveratrol and quercetin. Scientific studies document the multiple health effects of these components, which can be characterized as antibiotic, anti-tumor, anti-diabetic, anti-ulcer, cardioprotective, anti-inflammatory, and anti-brain aging.7
The cardiovascular health benefits of grape seed extract include favorable effects on blood pressure, enhanced endothelial function, and decreased oxidative stress.8 The potent antioxidant activity of grape seed extract may be responsible for its reported neuroprotective effects, as observed in animal models of Alzheimer’s disease.9,10 Recently, grape seed extract combined with calcium was found to be more effective than calcium alone in building healthy bone mass.11 Grape seed extract has effectively inhibited the growth of human colorectal tumor cells in the laboratory and in animals.12
Recent findings on resveratrol’s effects in experimental animal models are attracting a great deal of interest from the scientific community, while raising many questions about resveratrol’s applications in humans. One of the most intriguing questions is what dose of resveratrol may help humans achieve the beneficial health effects that have been observed in animals. While extrapolating animal dosage to human dosage is difficult at best, scientists are using several approaches to address this question. The accumulating data from gene-expression studies in mice provide some clues. These findings are also helping to illuminate the molecular basis of the biological effects of resveratrol and grape extracts.
The Harvard Study generated a great deal of enthusiasm by showing that mice fed high-fat diets (60% of calories from fat) avoided numerous diet-related health problems when supplemented with res-veratrol. Compared to mice that were not given resveratrol, the supplemented mice exhibited increased survival, increased insulin sensitivity, decreased organ pathology, and in-creased numbers of mitochondria.1 Resveratrol was also responsible for shifting the gene-expression patterns of mice on the high-fat diet towards those of mice on a standard (moderate-fat) diet. These results were achieved by feeding the mice a daily resveratrol supplement equivalent to 22.4 milligrams per kilogram of body weight.* In preliminary studies of this type, scientists often choose relatively high individual doses that are likely to generate an observable effect. Typically, more formal dose-ranging studies would be conducted later to identify optimal doses to attain specific effects. This is partly responsible for the controversy in the popular press regarding the relatively high dose of resveratrol used in this study.
While the Harvard study was under way, BioMarker Pharmaceuticals had already completed an eight-week controlled feeding study in which mice received either resveratrol (a synthetic version) or grape extract (containing resveratrol and other constituents), along with a “normal” diet. Gene-expression profiles were completed on these animals and compared to those of a group of calorie-restricted mice. Genes affected by either resveratrol formulation (synthetic or natural grape extract) or by caloric restriction were then compared. Importantly, the resveratrol dosage used in this study was much lower—approximately 12-fold lower—than that used in the Harvard study (see Table 1).
Results of Gene-Expression Analysis
Mice on normal diets were fed a daily, relatively low dose of resveratrol obtained from either a synthetic source or from a whole-grape extract enriched with resveratrol. A control group of mice fed a normal diet without resveratrol supplementation and a calorie-restricted group were also evaluated. Total calorie intake was identical in the resveratrol, grape extract, and control groups, and 40% less in the calorie-restricted group.
At the end of an eight-week feeding schedule, the animals’ livers were harvested in order to prepare RNA (the biochemical cousin of DNA) for gene-expression profiling. The samples were specially prepared for analysis with DNA microarrays, or “gene chips,” containing a full set of characterized mouse genes (the Affymetrix GeneChip® contains a total of over 45,000 probe sets, representing a complete set of over 34,000 genes of the mouse genome). Gene-expression levels were determined using statistical methods that ensure a high degree of confidence in the data.*
Both mouse groups that received resveratrol showed significant changes in the expression of key genes, confirming that even at the relatively low doses used in this study, there was a notable biological effect. The differentially expressed genes control over 100 different molecular pathways, including those related to metabolism (primarily metabolism of carbohydrates and lipids), DNA repair, and the regulation of cell death. Since the genes involved are in key biological pathways, they are likely to be responsible for at least some of resveratrol’s biological effects. Furthermore, significant results were achieved using a dose of synthetic resveratrol that was more than 10-fold lower than that used in the Harvard study.
Animals fed grape extract received resveratrol and other components of whole-grape extract.** Their gene-expression response would therefore be expected to reflect effects of both resveratrol and other grape components. Genes that significantly changed in expression in the grape extract group are found in molecular pathways involved in carbohydrate metabolism and biosynthesis (such as the creation of blood sugars), and lipid metabolism and biosynthesis (such as the creation or reduction of cholesterol and fatty acids).
Interestingly, scientists noted a significant overlap—about 65%—when they compared the gene-expression patterns of the resveratrol and grape extract groups. While expected, these results confirm the similar effects of pure synthetic resveratrol and grape extract-derived resveratrol on gene expression in animals.
The gene-expression effects of “low-dose” resveratrol were similar to those seen in calorie-restricted mice: about 55% similarity between the calorie-restricted and resveratrol groups, and 52% similarity between the calorie-restricted and grape extract-supplemented groups.
A method known as molecular pathway analysis can be applied to the gene-expression profiling results in order to identify the key regulatory pathways affected by the various treatments of resveratrol, grape extract, and caloric restriction. Displayed in Figures 1 and 2, these data show which pathways are specific to the different treatments, as well as pathways that are shared between or among the treatments.
Figure 1 shows the results for genes in pathways that are related to biological processes involving DNA; as shown by the overlap, 20 differentially expressed genes involved in DNA-related processes are regulated in the same fashion in animals receiving synthetic resveratrol, grape extract, or caloric restriction. These data suggest that the three treatments share some common features with respect to how genes involved in DNA processing are controlled through gene expression.
A similar approach was used to analyze genes involved in lipid metabolism. As shown in Figure 2, 10 genes involved in pathways related to lipid metabolism are commonly regulated by resveratrol, grape extract, and caloric restriction. These data are just a subset of the entire analysis. In total, 159 different molecular pathways were found to be commonly regulated by these three different treatments.
Resveratrol and grape extract produce strongly similar effects, based on the gene-expression responses demonstrated in mice fed a relatively low dose of these compounds. Comparison of these groups with calorie-restricted mice shows a significant overlap in the three treatments’ regulation of similar biological pathways. These data add to the accumulating evidence that resveratrol triggers a biological response in mammals that is similar to that observed with caloric restriction, an intervention that is known to extend life span and protect against age-related diseases.2-5 These effects are observed even at a relatively low dose of resveratrol, indicating that a human-equivalent dose can be obtained through dietary supplementation with high-quality resveratrol products.
What This Means to Aging Humans Today
A fluid ounce of red wine averages around 90 micrograms of resveratrol.13 The resveratrol supplements used by Life Extension members contain 20 mg (20,000 mcg) of resveratrol in each capsule. Therefore, these 20-mg resveratrol supplements provide approximately 220 times the amount of resveratrol found in one fluid ounce of red wine.
Since a glass of wine is approximately 5 and 1/3 ounces, a person taking one 20-mg resveratrol supplement may ingest the equivalent amount of resveratrol found in 41 glasses of red wine. Needless to say, that is a lot of red wine.
In the studies conducted by BioMarker Pharmaceuticals, mice demonstrated favorable anti-aging gene-expression changes in response to receiving the human equivalent of 20 mg of resveratrol a day.
The very positive study results reported in the media in late 2006 used human-equivalent doses of resveratrol in the hundreds or thousands of milligrams a day.
So what we have now are extremely favorable data on resveratrol (along with other grape constituents), with a wide range of probable optimal doses for aging humans to consider.
Those who choose to consume 20 mg of resveratrol a day can take comfort in the BioMarker research showing that this potency exerted impressive changes in critically important genes involved in various aging processes and degenerative diseases.
Those who choose to consume higher doses of resveratrol can look at the media-reported studies that also showed very impressive results. The good news for consumers is that they can obtain standardized resveratrol and other grape constituents in 20 mg and 100 mg capsules, at a very moderate cost.
* Doses of drugs in experimental animals are often calculated in milligrams (mg) per kilogram (kg) of body weight. This enables the doses to be standardized among treatment groups.
** A threshold p-value of 0.001 for a minimum two-fold change in level of gene expression was used; this means that the probability that the gene-expression level is statistically significant is 99.9% or more.
*** Polyphenolic acids, flavonoids, anthocyanins, and oligomeric proanthocyanidins.
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Resveratrol is a natural remedy frequently marketed as a weight loss aid . An antioxidant found in the skin of red grapes, resveratrol is said to speed up metabolism and prevent the growth of fat cells.
The Science Behind Resveratrol and Weight Loss
To date, most of the data on resveratrol and weight loss have come from test-tube studies and animal-based research. In a 2011 study published in the journal BMC Physiology, for instance, scientists found that lemurs fed a resveratrol-enriched diet gained less weight during the winter (a period typically marked by weight gain in the small primate animals).
Study results suggest that resveratrol helped prevent weight gain by revving up the lemurs’ metabolism and decreasing their intake of calories.
Previously published animal-based research indicates that resveratrol may help stave off weight gain among rodents fed a high-fat diet. In addition, test-tube studies show that resveratrol may help counteract the formation of fat cells.
However, in a 2009 report from Nutrition Research Reviews, scientists caution that resveratrol should “not be recommended for use in the prevention and treatment of obesity” until more is known about its safety and effectiveness. The report’s authors also note that resveratrol may be toxic to the liver.
Using Resveratrol for Weight Loss
While preliminary research suggests that resveratrol shows promise for obesity prevention, given the lack of clinical trials on resveratrol and weight loss, it’s too soon to recommend resveratrol as a weight loss aid.
To increase your resveratrol intake without using supplements, try adding resveratrol-rich foods like grapes, blueberries, cranberries, and pomegranate to your diet. Although these foods may not have a significant effect on weight loss, they do offer a range of antioxidants and other nutrients.
Following a weight-management plan that pairs healthy eating with regular exercise is the best approach to weight loss, according to the National Institutes of Health. Keeping a food diary, getting eight hours of sleep each night, keeping your stress in check, and natural weight remedies may also help you reach and maintain a healthy weight.
If you’re considering the use of resveratrol supplements for weight loss (or any other health purposes), talk to your doctor before starting your supplement regimen.
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Resveratrol is a brilliant solution to many age-related health problems:
Heart Health: The World Health Organisation suggests that resveratrol single-handedly reduces cardiovascular risk by 40%! Resveratrol is more effective than Vitamin E at protecting against a wider range of free radicals to prevent oxidation of low-density lipoprotein (LDL). It inhibits platelet aggregation by blocking the action of thrombin and several other aggregating factors. It promotes production of nitric oxide, which relaxes and dilates the arteries. It reduces blood triglyceride and cholesterol levels as well as the intrinsic hypertensive agent endothelin-1.
Brain Health: Preliminary studies suggest that resveratrol—administered solely, and in combination with other antioxidants—protects the brain against oxidative stress. Oxidative stress is known to play a major role in most neurodegenerative diseases.
Inflammation: A Chinese study has recently shown that, when injected immediately after injury, Resveratrol is as effective as the drug, prednisone at protecting against inflammation of the spinal cord, but with additional benefit of antioxidant protection. A study of rats pre-supplemented with Resveratrol for 21 days has shown to improve prognosis and reduce the permanent effects of stroke.
Longevity: According to a study at Harvard Medical School, Resveratrol activates a longevity gene in certain strains of yeast and extends life expectancy by 70%! It works in the same way as calorie restriction (the only scientifically-proven way of increasing longevity) by activating SIR genes. Research to date has been restricted to yeasts, flies and nematodes but it’s worth noting that humans also possess these genes.
The French Paradox
Resveratrol, a compound found in red wine, first gained publicity in the early nineties when the CBS television show, 60-Minutes investigated why people living in France, despite eating diets high in saturated fats, had lower rates of coronary heart disease than people living in the United States. The report concluded that a higher consumption of red wine may play a role in lowering coronary heart disease. Since then, researchers have pointed to resveratrol, a substance contained in grape skins (and other plants such as Japanese knotweed), as the compound with the possibility of preventing or delaying coronary heart disease and many other health conditions.
The potential benefits of resveratrol are based on hundreds of studies, and include assisting with the cardiovascular system, liver, calorie restrictions and mimetic and athletic endurance; prevention against cancer, joint disease, Alzheimer’s, aging, cataracts, macular degeneration, Lyme disease, Neurodegenerative diseases, Parkinson’s, Multiple Sclerosis, and cell damage, as well as having anti-aging and anti-inflammatory properties.
Resveratrol Health Benefits
Resveratrol: The most effective and best-researched phytonutrient for maintaining and protecting health.
• Supports colon health
• An all natural powerful antioxidant that protects DNA
• Restores glutathione (our most important antioxidant) levels
• Increases levels of quinone reductase (the liver uses this enzyme to detoxify carcinogens)
• Supports prostate health
• Acts as a beneficial phytoestrogen
• Shown to reduce LDL (bad cholesterol) oxidation
• Enhances healing of skin wounds
What Should You Know Before Purchasing Resveratrol?
Its not surprising that consumers are confused about resveratrol. Resveratrol is a general name for a product that is available in various prices and purities: 5%, 10%, 20%, 50%, and 99%. It’s all about labeling. If a manufacturer does not indicate the purity on the label (which most do not), then there is no way of knowing the amount of trans-resveratrol in the product, or if it has any health benefits at all. Resveratrol can provide great health benefits ONLY if it contains sufficient amounts of trans-resveratrol, the active ingredient and beneficial substance in resveratrol. “Resveratrol” does not mean trans-resveratrol.
If all manufacturers would disclose the purity content of their product, there would be no confusion at all. In principle buying resveratrol is as straightforward as buying gold: Both are available in a variety of purities, but with gold there is no confusion. Why? In order to protect the consumer, the law requires the dealer/jeweler to indicate the purity content by stamping the purity on each item they sell (e.g. 5K, 14K, 24K etc.). Unfortunately, the same law does not apply to dietary supplements and essentially leaves the door open to fraud.
Since the FDA does not require the purity content of dietary supplements to be indicated on the label, it is not surprising that manufacturers who offer low-purity resveratrol do it solely for financial gain, and therefore do not disclose the purity content of their products. Instead, they go a few steps further by using misleading descriptions such as “Extra Strength”, “Super Potency”, “High Purity”, “Pure Resveratrol” and other intentionally deceptive statements while offering low purity resveratrol. It is important to note that most resveratrol sold in the USA and abroad (about 90% of the market) is of a low purity: 20%-50% or less. Remember, if the label does not clearly indicate the amount (or percentage) of trans-resveratrol, then there is no way of knowing its purity content, or if it even has any health benefits. It is important to note that based on recent scientific studies, 500 mg – 1000 mg of trans-resveratrol is the minimum daily amount that is needed to promote the benefits of this product for healthy individuals (an even higher dosage may be required for individuals with certain health conditions). Every label should include the purity information. Below are examples of valid and invalid supplement fact labels in regards to purity.
Consumers should be aware that even though the initial cost of lower purity resveratrol supplements may seem lower, the actual cost can work out significantly higher than the cost of pure trans resveratrol. For instance, consumers who purchase supplements of 50 percent purity must take double the dosage to achieve the same results. Consumers who take supplements of 20 percent purity must take five capsules to match the effectiveness of a single pure trans resveratrol capsule.
Below are samples of “Supplement Facts” labels. In order to emphasis on the purity content, certain information which does not relate to the subject matter (e.g. “Inactive Ingredients”, “Directions”, etc., but legally must be posted as a part of every label), was purposely omitted from the sample labels below.
When total “Resveratrol” or “Trans-Rresveratrol” content is not disclosed, its impossible to calculated or establish purity content. (Unless indicated as “standardized to ‘x’ Percent” as disclosed in the first two sample labels above.)
If you and your partner are thinking about making babies soon, then it’s time to start eating the right foods to boost your chances of conception.
What you eat and drink can directly impact your nutrient levels and therefore your ability to conceive. A preconception plan should not just be about taking a multivitamin. Your diet should focus on only consuming foods that are packed full of fertility-enhancing nutrients and avoiding those that can negatively affect your chances of a healthy conception.
And guys, these tips aren’t just for the woman. You also need to be eating a healthy diet for healthy sperm. But once the job has been done, don’t go back to your old ways! You’ll need all the vitality you can get to enjoy your baby once they arrive.
Fertility-boosting foods and drinks
Fresh leafy greens – Aim to have some sort of green leafy vegetable (baby spinach, rocket, English spinach kale, broccoli, bok choy) with at least 2 meals each day. This is easy if you have a salad for lunch and then have some steamed broccoli for dinner. These vegetables contain lots of folate essential for a healthy conception and early stage fetal development.
Lean red meat – Have 2-3 serves of lean red meat each week to ensure you get your boost of iron. Only have fresh, unprocessed meats such as lamb or beef and organic is best. Try not to have too much red meat though. It’s important to vary your sources of protein with fish and poultry to get a range of nutrients.
Protein with every meal and snack – Protein contains the building blocks for growth to happen. It also balances your blood sugar levels and is important for healthy hormone production. Healthy protein sources include eggs, meat, fish, poultry, nuts and seeds, legumes, hummus and natural yoghurt.
Fish – Aim for 3 serves of fish per week to provide healthy omega 3 fatty acids. Choose your fish carefully to avoid heavy metal contaminants found in some species of fish. The safest fish to eat when preparing for pregnancy are salmon, flathead, bream, john dory, sardines, anchovy, whiting and blue-eyed cod.
Complex grains and carbohydrates – Getting your daily carbohydrate intake from whole grains is much better for your fertility than getting it from sugars and white, refined flours. Choose brown rice, breads and pastas instead of white options.
2 litres of water everyday – Keeping hydrated is essential to proper health and will make sure toxins are eliminated.
Foods and drinks that reduce your fertility
Alcohol – Avoid alcohol as much as possible as it eliminates a number of crucial fertility nutrients such as folate and zinc.
Coffee – Limit coffee intake to a minimum. Caffeine constricts blood vessels which can reduce blood flow to important reproductive organs.
Soft drinks, especially “Diet” drinks – Avoid all soft drinks as they deplete crucial fertility nutrients. They contain very high amounts of sugar which can affect insulin levels resulting in changes to the female reproductive cycle if consumed in too high amounts. Diet soft drinks also contain artificial sweeteners that may have unwanted side effects.
Processed, fatty foods – Your preconception diet should be fresh and rich in nutrients. Processed and high fat foods only deplete you of nutrients and may therefore reduce your baby making power.
High amounts of soy – Too much soy can affect male and female fertility so keep it to a minimum. Soy milk can be replaced with oat, almond or rice milk; and keep tofu intake to once a week. Soy is now in a huge amount of processed foods (check labels) so keeping to fresh foods is best.
Exercise – we know it’s good for us, we know we should be doing it regularly, but did you know that staying active is essential for ageing well and staying in good health later in life?
Being physically active is essential throughout life for good health. Staying active as we get older helps to maintain independence, prevent chronic disease, ensure healthy body mass, maintain emotional health and cognitive function.
The benefits of regular exercise
Regular exercise has benefits for many areas of our health including:
- Bone health – weight bearing exercise is important in preventing osteoporosis and improves our balance and coordination, reducing the risk of falls and fractures as a result of falling.
- Muscle health – sarcopenia is a (usually age-related) decline in muscle mass which leads to a decline in muscle strength. Its impact on our health ranges from difficulty performing everyday tasks, to an increased risk of chronic disease such as type 2 diabetes.
- Heart health – The benefits of exercise for cardiovascular health include decreasing LDL-cholesterol and increasing HDL-cholesterol, maintaining healthy blood pressure and decreasing resting heart rate.
- Metabolic health – many areas of health are affected by what’s known as metabolic syndrome. By keeping active we can maintain metabolic health with a healthy waistline, decreasing blood triglycerides, and cholesterol decreasing insulin resistance and decreasing inflammation.
- Mental health – getting older and moving into a different stage of life can be challenging and may affect our emotional wellbeing. Regular exercise helps to boost the production of serotonin and endorphins, which are feel good brain chemicals and function to ‘lift’ mood.
What type of exercise is best?
There are essentially two types of exercise: aerobic and resistance.
Aerobic or cardio exercise involves activities that get the heart going and your breathing rate up to meet the body’s increased demand for oxygen. Running, swimming, cycling and walking are examples of this type of exercise.
Resistance or strength training involves activities that build muscle strength and work against an opposing force. Lifting weights, weight machines, Pilates, and exercise with resistance bands are all resistance ad strength building activities.
Your current health will determine if you need one or the other, or both, and which type is better to start with. For example, if your muscle strength isn’t so great and needs to be improved, it’s best to start with some strength training before you get started on cardio so that you aren’t at risk of a fall when your balance isn’t quite right.
For most people, a combination of both aerobic and resistance training will provide a broad range of health benefits. It will also help to keep your routine varied and more interesting, meaning you’re likely to stay motivated to keep moving.
How much exercise is enough?
The National Physical Activity Guidelines for Adults recommends:
- Think of movement as an opportunity, not an inconvenience.
- Older people should do some form of physical activity, no matter what their age, weight, health problems or abilities
- Put together at least 30 minutes of moderate-intensity physical activity on most, preferably all, days
- Older people should accumulate at least 30 minutes of moderate intensity physical activity on most, preferably all, days
If you’re not already exercising regularly, it’s a must that you consult with your healthcare professional before you get started on a new routine, especially if you do suffer from any health conditions that mean certain exercises should be avoided.
Enlisting the help of a personal trainer is also great when getting started as they can help make sure that you are working within your capabilities and tailor a program to suit your needs.
And keep it fun. Getting and staying fit does not have to mean slogging away in a gym! Do activities that you enjoy and make it social by exercising with friends or joining a group activity.