Long Live the Mice!

By Alice R. Laule MD

About a year ago, a news story aired about a product that made mice live extra long lives. Up until that time, the only experimental evidence available was that calorie restriction was making mice live longer, although  Dr.  Bruce Ames was doing some research with alpha lipoic acid and another agent in a “cocktail” that he said “made rats get younger.” As senescence settled in, and rats forgot how to run their mazes, Dr. Ames would give them his cocktail and they would run the mazes well again. I heard this in an interview with him, and it was preliminary at that time. For more information, see page five of this newsletter.

          The data that have been published about mice is for resveratrol, a compound found in grape products, particularly red wine. The news reporters seemed to be entirely naïve to the fact that this compound is available as a supplement, and has been previously studied.

          Here’s the rest of the story:

The amount of resveratrol given to the ageless mice in this study would be the equivalent of drinking about 300 glasses of wine a day for a human, given that a glass of wine contains in the range of 0.5 to 1 mg. of the substance. Therefore, it will probably be quite some time before we slow aging in humans with wine alone. The supplement form of resveratrol, available right now in the health food stores, can contain widely varying amounts. The most potent one I have found is actually an extract of red wine, standardized to the resveratrol amount, and contains 125 mg. per capsule of resveratrol. Three of those per day puts us in the ball park of the dose the mice took, adjusted for human weight.

          Resveratrol is also found in very small amounts in peanuts and peanut butter (about 0.25 mg per cup), red grapes (0.25 to 1.25 approximately per cup), and in similar low amounts per 5 ounce glass of other wines (rose, pinot noir, white wines).

          Clearly these amounts aren’t enough to stop aging, but they do seem to be enough to create some of the other benefits of resveratrol that have been much better studied. In fact a more recent study with fish showed that a really short lived breed of fish lived more than 50% longer when fed a somewhat lower dose than the mice got. Human studies (and aren’t we really more interested in those?) abound for the lower doses. The doses in these studies vary hugely, but many of them are studies based on the benefits of red wine, so are using the types of doses one would get in a glass of red wine — namely about 1 mg. And don’t forget, more than one glass of wine a day has other health risks, including increased risk for stroke.

          Resveratrol is mildly antidepressant, in that it has the same action on the neurotransmitters in the brain as many of the currently prescribed anti-depressants.

          It promotes the production of nitric oxide, which helps lower blood pressure and promotes proper blood flow in the small blood vessels in the body, allowing them to dilate and stay open. At the same time it helps keep the circulation from clogging by stopping the oxidation of the “bad” LDL cholesterol, a primary cause of plaque formation in arteries. Actually this is a common reason I recommend it as a supplement, is to lower LDL. Oxidized LDL can be considered in some ways a marker for the amount of free radical damage the body is suffering overall, so giving a potent free radical fighter like resveratrol makes sense, to protect the whole body from oxidative stress.

          Along the same vein, resveratrol helps prevent the oxidation of dietary fats, another enormous source of free radicals in the body. This study from 2002, looked at red wine consumed with meals.  Ordinarily when we eat a meal that contains a lot of fat,  some of those fats turn into free radicals in the digestive tract. Of course, some have already become free radicals in the cooking process, like foods fried in vegetable oil. These fatty free radicals are then absorbed into the blood stream, where they are free to spread through the body and wreak havoc. The polyphenols in red wine, of which resveratrol is one, reverse the oxidation by a chemical process called reduction, and also stop further oxidation in the gut. Thus when red wine was taken with a meal, the flood of oxidized fats into the blood stream after eating did not occur.

          Homocysteine is also a risk factor for heart disease, altogether independent from cholesterol issues. Lowering homocysteine has been proven to lower the risk for heart disease of 33%. Resveratrol now is shown to be yet another compound, in addition to folic acid, B-12, B-6 and betaine, which lowers this risk factor.

          When you put all of the above together, it becomes easier to explain the French Paradox — the fact that the French eat foods that are quite high in fats, have a high rate of smoking that should be causing heart problems, yet they have a 42% lower rate of heart disease than the USA. I would add, since the French also eat very slowly, as well as sipping red wine with their food, that part of the French paradox is simply the time they take to enjoy their food. They also eat a lot of whole grains and high fiber foods.

          Resveratrol has also been studied in cancer. It appears to be able to reduce the initial formation of cancer, perhaps by its free radical fighting ability. But additionally, it helps kill off cancer cells that do occur, reduces blood vessel growth into the cancer, and helps stop metastatic spread. Specific studies have been done to show that it is helpful as an adjunct in the treatment of prostate cancer, as well as breast, colon, lung, esophagus, skin, lymph node, brain and testicular cancer, and others. Many of these are human studies. Some of the skin cancer studies have been done in mice, and the resveratrol was actually applied topically, not taken internally, and still helped.

          Resveratrol is also anti-inflammatory, reducing inflammation by means of the same enzyme that aspirin and most NSAID’s inhibit, the cyclo-oxygenase enzyme (COX-1, 2 and 3).   At first resveratrol was thought to work primarily with COX-1, but now more recent studies show it also suppresses COX-2.  It was powerful enough in animal studies to reduce the damaging effects of arthritis on the cartilage in joints.

          Lastly, resveratrol also helps protect neurons from the toxicity of beta-amyloid, the agent believed to be the main cause of Alzheimer’s Disease. This was studied in mice, and I for one would surely like to see some human studies done. Nevertheless, resveratrol is non-toxic, safe, and compared to many drugs out there, not horribly expensive. I see no reason not to try it for our own health, for those of us with inflammation, heart disease or Alzheimer’s risk.

Until later, stay healthy.

Alice R. Laule, M.D.

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