Is Resveratrol the Fountain of Youth?

Byron J. Richards, Board Certified Clinical Nutritionist

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Is Resveratrol the Fountain of Youth?
There are a lot of great anti-aging and metabolism boosting nutrients: DHA, pantethine1, acetyl-l-carnitine, carnosine, r-alpha lipoic acid, grape seed extracts – the list goes on and on. In fact, most nutrients help cells function better and thus live longer. So, why is resveratrol vying for the position as King of the anti-aging nutrients – with a potent fat-burning twist thrown in for good measure?

Maybe we should ask Big Pharma, who is spending a pile of cash on metabolites of resveratrol3 that they hope to patent as weight loss drugs, diabetes drugs, and a new generation of anti-aging medicines. Part of the way resveratrol works is by activating a powerful metabolic fat-burning and anti-aging gene called SIRT1. In newly published Big Pharma animal research their resveratrol drug activated SIRT1, prevented weight gain on a high fat diet, improved blood sugar and insulin function, and doubled the exercise endurance of the mice.

Interestingly, resveratrol dietary supplements4 have been shown to do essentially the same thing. The resveratrol drug (SRT1720) is apparently six times more potent at activating SIRT1 than plain resveratrol. However, plain resveratrol operates in a number of different ways5 besides activating SIRT1, providing a broader base of potential health benefits including comprehensive cardiovascular support.

What is Resveratrol?



Interest in resveratrol research took off when it was identified as a component in red wine that may be partly responsible for the “French Paradox,” the ability to eat a higher fat diet with less heart disease than Americans. Research shows that resveratrol helps your liver metabolize fat and helps break down stored fat6 contained in your white adipose tissue.

Resveratrol is a type of polyphenol known as a stilbenoid, which is produced in grapes and blueberries to protect themselves from bacterial and fungal infection, and to a lesser extent from UV radiation. It was discovered that grapes growing in damp and moldy areas had the highest content of resveratrol of any known commonly consumed food/beverage. Resveratrol is obviously a potent anti-fungal compound and antioxidant.7

Resveratrol is a different compound than the flavonoid proanthocyanidins of grape seed extracts, which also contribute to the notion of the French Paradox. Blueberries, by comparison, also contain flavonoids and a different stilbenoid called pterostilbene8 (pronounced "tero-STILL-bean"). Significant research at the USDA has shown that pterostilbene has a powerful ability to influence the metabolism of cholesterol and the synthesis of triglycerides by improving metabolism within cells, as well as providing brain-protecting anti-aging properties.

The amount of resveratrol in a bottle of red wine varies from 2 mg to 14 mg, mostly on the lower side. Dietary supplements of resveratrol are typically derived from the roots of Japanese knotweed (Polygonum cuspidatum), a far more economical source than grapes. Doses will range from a basic protective dose of a few milligrams (like a bottle of red wine), up to 100 mg per serving or more (a therapeutic dose). It is readily absorbed, reaching peak blood levels in 30 minutes, and then rather rapidly cleared by your liver. Thus, it is better to spread out intake during the day than take a large amount all at once.

At this point, other than the colorful history and longevity benefits associated with red wine consumption, the majority of the extensive resveratrol research has been carried out with cell studies and small animals. The implications of this research are mind-boggling, clearly showing significant extension of life span.

The Fat-Burning and Anti-Aging Properties of Resveratrol



SIRT1 first drew attention as the primary gene signal involved with the longevity benefits of calorie restriction.9 A very simple explanation is that when you are in a food scarcity situation, SIRT1 is activated so as to help break down your stored fat to use as fuel as well as to boost up your energy so that you have enough energy to hunt for new food. SIRT1 is part of a famine-related survival system.

Many experiments with animals show that by restricting calorie intake SIRT1 is naturally activated, a finding that goes along with a noticeably extended lifespan, better fat and cholesterol metabolism, more efficient immune function, and better cardiovascular health. A number of humans have taken up calorie restriction experiments on themselves, and pictures of them do not portray the portrait of health. In fact, you would be hard pressed to pick out of a line-up someone on a self-induced calorie restriction diet and someone coming in for anorexia treatment. Which gets to my point, what is the difference between a calorie restriction diet and anorexia?

I have studied the calorie restriction science for 20 years and I am also the leading diet expert on the fat-derived hormone leptin, which is the overall boss hormone that controls your metabolic rate and your ability to survive a period of famine. Thus, I will give you answers in this area that you won't find elsewhere. There is a very fine line between prolonged calorie restriction and anorexia.

In the case of someone consuming too much food, their extra pounds of fat10 crank out inflammatory messengers (TNFa and IL6), in turn stimulating the liver to make the inflammatory CRP. This combination of inflammation2311 induces significant free radical damage in the circulatory system12 and all around the body. As the waistline expands the volume knob on inflammation and free radical production is turned up. At the same time the liver becomes clogged with fat, which in turn is “cooked” by free radicals from the inflammation, eventually sending the liver3213 on the path to looking like a fried piece of bacon. Arteries are also getting fat around the outside of the arterial wall structure, in turn generating more inflammation to the inside of arteries and deactivating friendly nitric oxide20 production. This makes blood pressure go up and blood not flow well and further induces free radical production in arteries that damages LDL cholesterol, promoting the formation of plaque.

In this scenario leptin levels are also high (leptin resistance), which lowers another fat-derived hormone called adiponectin, in turn causing a bad mood and insulin resistance that leads to type II diabetes14. Leptin problems cripple thyroid function as well as promoting never-ending cravings to eat more food. This is the precise metabolic profile15 of millions of Americans on the fast track to diabetes, heart disease, and poor health. Ironically, they are being poisoned to death by too much food with no easy way out of the misguided subconscious drive to continue excess eating.

It is important to understand that just about everyone who is overweight and having trouble with their cravings has high leptin in their blood (leptin resistance), and that leptin is not getting into their brains correctly (a false state of misperceived starvation). Leptin resistance is caused by consistently eating meals that are too large, by eating after dinner at night, and by snacking.

Human beings do not have the genes to deal with the abuse of eating too much food, as during evolution this was never the problem. Rather, a scarcity of food was the primary issue that constantly threatened the survival of the human race – and so it is that we have a lot of mechanisms built in to help deal with starvation. The ability to survive famine is controlled by leptin. During famine leptin levels have gone low as your fat mass that secretes leptin in the first place has been reduced in size to use the stored fat for energy, which is how your subconscious brain knows a famine is occurring. In response to this low-leptin famine issue, your liver turns on the production of SIRT1. This helps your liver know to break down fat to use as fuel, not store calories as fat, as well as to boost physical energy to be able to hunt or gather new food.

Considering all the interest in both SIRT1 and leptin, the number of studies linking the function of the two is remarkably absent from the literature. New research shows that SIRT1 is active in key regions of your brain that relate to appetite and energy16, which are governed by leptin. Leptin deficient mice do not activate SIRT1 properly, and are always obese. The details of this relationship are far from clear. It is easy to predict that low levels of leptin from true starvation are able to trigger SIRT1 activation in your liver based on messages received from SIRT1 signaling systems in your brain. It is also easy to predict that high levels of leptin in your blood (obesity-related leptin resistance) turn SIRT1 off as they would be signaling your liver that famine is over or not happening.

As you begin to diet (especially if you follow the Leptin Diet) and drop your first 10-15 pounds you will clear high leptin from your blood, which is always reflected by your cravings going away. For a while your body is set to burn more calories based on your pre-dieting metabolic set point. The problem for many people is that you hit a plateau after a month or so of dieting that is too far from your goal weight.

If you eat less you can't function. Your head is heavy, you are irritable, your sleep gets disturbed, your immune system goes on the blink, and you are much more likely to get sick. If you exercise more you must eat more or you will be completely exhausted and feel even worse. If you get stressed, unlike the stress-free monkeys practicing calorie restriction, you are in real trouble and likely to eat the house down. Yes, you are practicing calorie restriction – how on earth is this state of feeling going to help you live longer? Answer – its not. You start generating inflammation the longer you are in this condition. The inflammation is no longer coming from your extra pounds of fat. It is coming from the trauma of the diet combined with stressors in your life.

Under these circumstances you are much more likely to break down muscle, a key sign of inappropriate weight loss. If you keep trying to lose weight while you feel this way you may be able to do so, but you will progressively lose more muscle, increase inflammation, generate a lot of free radical damage, disturb digestion, get sick really easily, and presto – you are anorexic. Funny thing is, you may still be an overweight anorexic. Wow – is that any way to diet?

If you start eating more food you will feel much better. Unfortunately, you messed with leptin in the wrong way. Leptin now turns off SIRT1 and goes into a famine-recovery mode. It commands that a large portion of the calories you are now eating go back to fat storage. Most people find themselves rapidly gaining weight on formerly normal amounts of food. Once the yo-yo routine comes to a halt you are likely to find yourself 5-10 pounds heavier than when you first started, as an insurance policy in case you attempt another dieting stunt in the future.

Solving this dilemma requires that you eat in harmony with leptin, which means following the five simple rules of the Leptin Diet. In many cases you will never hit this problematic plateau. However, many people will, especially if they have a history of yo-yo dieting. Enter resveratrol. Resveratrol is an ideal nutrient to enhance weight loss and maintain energy ONCE YOU HAVE GOTTEN PAST THE INITITAL PHASE OF 10-15 POUNDS OF WEIGHT LOSS, especially if you are getting stuck at a plateau.

Resveratrol will help turn on the SIRT1 gene, which will promote fat-burning in the presence of lower calorie intake. This is a terrific use of this nutrient. How do you know its working? You have energy to exercise, you feel good, and your weight is trending downward while you are happy eating less food. This either is or isn't happening, thus it isn't very hard to figure out if resveratrol helps you.

One of the real values of this nutrient in the weight management context is helping you to not slide into an inflammatory anorexic-like metabolic problem as you try to lose weight. It is also a tool to help you break through weight loss plateaus should they occur. Resveratrol will work best when you are eating less food and have already cleared surplus leptin out of your blood through initial dieting efforts. However, you don't need to eat so little that you are on the scarecrow diet.

Research indicates that resveratrol will still help you out17 even if you aren't dieting or you don't need to lose weight. After all, the French had resveratrol in their diet when they were mostly thin. I might point out, however, that while the French were eating a higher saturated fat diet they were not overeating, their food was fresh and mostly organic, and they did not snack. The effects of resveratrol will be easily overloaded by overeating. Even the French Paradox has been doomed by an epidemic of leptin-disrupting snacking and junk food consumption.

Having a large waistline is clearly linked to premature death, a risk that goes up in direct proportion to your waistline's rate of expansion. Anything safe and natural that can help you get it back to optimal and keep it that way qualifies as life extending.

Cardiovascular and Other Benefits of Resveratrol



Simply losing weight healthfully will improve your cardiovascular health. If resveratrol is able to help you in this endeavor, regardless of any other cardiovascular help it provides, then it is a success as a cardio-friendly nutrient.

There is plenty of animal and cell science to predict that resveratrol assists the healthy structure and function of your cardiovascular system in multiple ways. It has been found to reduce the stickiness or adherence of immune cells to the walls of arteries18, prevent adverse changes in the smooth muscle cells19 of arteries that lead to plaque accumulation, boost friendly nitric oxide20 levels (eNOS) that relax arteries and improve blood flow, help keep platelets21 from sticking together, reduce irregular heart beats22, and reduce circulatory inflammation2311. It even helps protect against circulatory damage from high blood sugar24. Keep in mind that in “modern” medicine, each one of these points requires a different drug that has other adverse side effects.

One of the first human resveratrol studies shows that resveratrol improved heart function25 in type II diabetic patients following a heart attack.

Resveratrol, like grape seed extract, operates in part as a protector of human body structure. This is clearly related to its anti-oxidant and anti-inflammatory properties, which include regulation of the primary inflammatory gene switch NF-kappaB26. New animal and cell studies shows it helps bone health, reduces cataracts27, helps coordination, reduces disc deterioration28 and protects joints29, guards against Parkinson's30, improves erectile performance31, protects the liver, protects the pancreas, and helps regulate cell health while protecting against adverse33 cell changes.

This is a rather impressive array of science-backed support for any one nutrient. Maybe the anti-aging promise is real. The explosion of scientific interest in the compound ensures that you will be hearing a lot more about it in the very near future.

Common doses of resveratrol that show benefit and safety in animal studies range from 2.5 mg – to 10 mg per kilogram. This translates to an approximate dose range of 150 mg – 700 mg per day for a 150 pound adult, a sensible and safe dose range until more data is in.

Referenced Studies

  1. ^ Pantethine Helps Clear Up Fatty Liver Problems  J Atheroscler Thromb.   Osono Y, Hirose N, Nakajima K, Hata Y.
  2. ^ Resveratrol's Anti-Aging Hope   Curr Med Chem.  Orallo F.
  3. ^ Big Pharma is Very Interested in Resveratrol  Cell Press  
  4. ^ Resveratrol Protects Against High Fat Diet, Improves Insulin Resistance  Biochem Biophys Res Commun.  Jiang WJ.
  5. ^ Resveratrol Assists Weight Loss In A Variety of Ways  The Endocrine Society's 90th Annual Meeting in San Francisco.  
  6. ^ Resveratrol Helps Break Down Stored Fat in White Adipose Tissue  J Anim Sci.  Shan T, Wang Y, Wu T, Liu C, Guo J, Zhang Y, Liu J, Xu Z.
  7. ^ Stilbenoids Are Potent Anti-Oxidants   Neuro Endocrinol Lett.  Perecko T, Jancinova V, Drabikova K, Nosal R, Harmatha J.
  8. ^ Blueberries Contain the Anti-Aging Compound Pterostilbene  J Agric Food Chem.  Joseph JA, Fisher DR, Cheng V, Rimando AM, Shukitt-Hale B.
  9. ^ SIRT1 Is Central to Calorie Restriction and Anti-Aging Theory  Genes Nutr.   Wenzel U.
  10. ^ Swollen Fat Cells Make More Inflammation  J Clin Endocrinol Metab.  Skurk T, Alberti-Huber C, Herder C, Hauner H.
  11. ^ Swollen Fat Cells Make More Inflammation  J Clin Endocrinol Metab.  Skurk T, Alberti-Huber C, Herder C, Hauner H.
  12. ^ Obesity, Inflammation, and Heart Failure    
  13. ^ Fatty Liver Links Insulin Resistance and Abdominal Fat  American Journal of Clinical Nutrition  Juraj Koska, Norbert Stefan, Paska A Permana, Christian Weyer, Mina Sonoda, Clifton Bogardus, Steven R Smith, Denis R Joanisse, Tohru Funahashi, Jonathan Krakoff and Joy C Bunt
  14. ^ How Obesity Leads to Type II Diabetes is Now Very Clear  Int J Obes (Lond).   Zamboni M, Di Francesco V, Garbin U, Fratta Pasini A, Mazzali G, Stranieri C, Zoico E, Fantin F, Bosello O, Cominacini L.
  15. ^ Too Much Fat Drives Inflammatory Disease  Minerva Endocrinol.  Kralisch S, Sommer G, Deckert CM, Linke A, Bluher M, Stumvoll M, Fasshauer M.
  16. ^ SIRT1 and Leptin, An Important Relationship  J Neurosci.  Ramadori G, Lee CE, Bookout AL, Lee S, Williams KW, Anderson J, Elmquist JK, Coppari R.
  17. ^ Resveratrol Protects Against Fat Accumulation in the Liver   J Hepatol.  Ahn J, Cho I, Kim S, Kwon D, Ha T.
  18. ^ Resveratrol Prevents Immune Cells from Sticking to Arteries  Am J Clin Nutr.   Ferrero ME, Bertelli AE, Fulgenzi A, Pellegatta F, Corsi MM, Bonfrate M, Ferrara F, De Caterina R, Giovannini L, Bertelli A.
  19. ^ Resveratrol Selectively Inhibits Only Abnormal Cell Growth in Artery Walls  Biochem Biophys Res Commun.   Mnjoyan ZH, Fujise K.
  20. ^ Resveratrol Boosts Friendly Nitric Oxide (eNOS)  Circulation.  Wallerath T, Deckert G, Ternes T, Anderson H, Li H, Witte K, Förstermann U.
  21. ^ Resveratrol Helps Platelets Not Stick Together   Br J Haematol.   Shen MY, Hsiao G, Liu CL, Fong TH, Lin KH, Chou DS, Sheu JR.
  22. ^ Resveratrol Reduces Irregular Heart Beats  Cardiovasc Drugs Ther.  Chen YR, Yi FF, Li XY, Wang CY, Chen L, Yang XC, Su PX, Cai J.
  23. ^ Resveratrol Reduces Inflammatory NF-kappaB Gene Signalling  Br J Pharmacol.   Tsai SH, Lin-Shiau SY, Lin JK.
  24. ^ Resveratrol Protects Against Glucose Induced Circulatory Damage  Diabetes, Obesity and Metabolism.  
  25. ^ Resveratrol Helps Recovering Heart Patients  Metab Syndr Relat Disord.  Cacciapuoti F.
  26. ^ Resveratrol Regulates Primary Anti-Inflammatory Gene Switch, NF-kappB  Diabetes  Lee JH, Song MY, Song EK, Kim EK, Sung Moon W, Han MK, Park JW, Kwon KB, Park BH
  27. ^ Resveratrol Improves Bone Health, Reduces Cataracts, & Improves Coordination    
  28. ^ Resveratrol Helps Discs in the Spine  Spine.   Li X, Phillips FM, An HS, Ellman M, Thonar EJ, Wu W, Park D, Im HJ.
  29. ^ Resveratrol Protects Against Osteoarthritis  Arthritis Rheum.  Dave M, Attur M, Palmer G, Al-Mussawir HE, Kennish L, Patel J, Abramson SB.
  30. ^ Resveratrol Helps Protect Against Parkinson's  Department of Pharmacology, Zunyi Medical College, Zunyi 563000,PR China.  Jin F, Wu Q, Lu YF, Gong QH, Shi JS.
  31. ^ Resveratrol May Help Erectile Function  Arch Pharm Res.   Shin S, Jeon JH, Park D, Jang MJ, Choi JH, Choi BH, Joo SS, Nahm SS, Kim JC, Kim YB.
  32. ^ Resveratrol Protects Your Liver from Damage  Eur J Pharmacol.  Sha H, Ma Q, Jha RK, Xu F, Wang L, Wang Z, Zhao Y, Fan F.
  33. ^ adverse    

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