Phytochemical Friday: on the “sober” life

Resveratrol is a relatively well-known plant chemical found in the skin of grapes, and in wine. There is plenty of research that in less complex life-forms than humans, such as our friend the mouse, resveratrol lengthens life span, decreases diabetes, and keeps the friendly mouse nice and slim.

Resveratrol has been widely used in the naturopathic armatorium as an anti-aging compound, with good reason.  The hallmarks of aging are decreased oxidative phosphorylation and decreased aerobic capacity.  Decreased mitochondrial oxidative phosphorylation means that your cells do not fully oxidize fuel efficiently, and decreased aerobic capacity means that your cells do not use oxygen the same way they did when they were younger. Resveratrol helps do both. And ozone therapy  does the same (but faster, better, and usually when resveratrol doesn’t work).

Image from the journal Cell 2006

Exercise and caloric-restriction (going hungry) are both well-established ways of increasing longevity. Exercise improves quality of life, but caloric restriction likely would decrease quality of life. Interestingly enough, exercise, caloric restriction, ozone therapy, and resveratrol all work on similary pathways.

Exercise consumes “reductants” or fuel, while caloric-restriction decreases supply. The net effect is an increased NAD+/NADH ratio. Ozone therapy (see the link and scroll down to the second part of the newsletter where all the pictures are) strongly stimulates an increase in the ratio, especially in patients with diseases and in whom exercise takes too long; it is exercise at the cellular level. Resveratrol stimulates SIRT1, essentially having the same effect. The net effect? An increase in oxygen consumption happens, and more importantly, and increase in oxidative phosphorylation, or an increase in energy generation at the cellular level. That is the hallmark of anti-aging and longevity.

Contrary to popular belief, it is doubtful that resveratrol has its longevity promoting actions by being a super anti-oxidant that quences free radicals. In fact, resveratrol’s cancer preventative effects come from stimulating cell-suicide (apoptosis) in cancer cells. Apoptosis usually happens with an increase in free-radicals. Excess antioxidants are not good. Excess antioxidants decrease the NAD+/NADH ratio because they greatly increase NADH.

I use resveratrol in conjunction with ozone therapy. Resveratrol, unfortunately, is processed by the liver with remarkable efficiency, such that almost every molecule of resveratrol absorbed is detoxified by the liver by a process called glucuronidation. Obviously the resveratrol still has effects in mice and tissue cultures, and there is preliminary evidence (mostly epidemiological) that humans, though our livers sure like processing it, get some benefit as well. To bypass the liver and get the effects seen in the studies, I sometimes give it by injection so that the other tissues can have the resveratrol effect before it is processed by the liver. Remember the liver is the first organ to see anything taken by mouth.

So why the title a “sober” life? Cornaro, a Venetian Nobleman, survived to the age 102 in the 15th Century. He promoted caloric restriction and wrote “On the Sober Life”. His diet had no less than 14 oz of red wine a day. I wouldn’t recommend wine, as there are too many other options.