The Evolutionary Argument Against Antioxidants

In the wake of more attention being drawn to the general ineffectiveness of ingested antioxidants as even a marginal tool for health and longevity, Randall Parker remarks in passing:

Biogerontologist Aubrey de Grey makes what to to my mind is a persuasive argument against the expectation that antioxidants will deliver large health benefits: The metabolic cost of making and retaining antioxidants in the body is pretty low. If antioxidants could deliver benefits as large as some of their advocates claim then natural selection would long ago have selected for mutations that boost body antioxidant levels. So why expect consumed antioxidants to deliver a big benefit?

So (I hear you asking) why wouldn't the body make more detoxifying enzymes even in the absence of foods consumed that up-regulate detoxifying enzymes? My guess is that those enzymes are more metabolically expensive to keep around.

Human metabolism certainly isn't the most effective possible from a perspective of longevity, but one would expect that any easily attainable and practical change that benefits health in youth would already have been selected over the generations. On the other side of the coin, simple changes that benefit health in old age and extend longevity do in fact exist, and have not been selected for - for example, mutations to boost the level of naturally occuring antioxidants in the mitochondria:

The catalase soaks up some portion of free radicals before they can attack your vulnerable mitochondrial DNA. Damage to this [DNA] leads to an unfortunate chain of events that causes entire cells to rabidly produce damaging free radicals and export them throughout the body. But stop a fraction of the original mitochondrial free radicals from attacking their birthplace, and you have slowed the rate at which one cause of aging happens - you have slowed down aging, and extended healthy life.

Evolution cares not for your old age - if you're past the point of reproductive fitness, you're on your own. So mutations that might help your longevity, but have little benefit in youth, are unlikely to have prospered and spread in the dark days of cave living, disease, parasites and short, brutish lives.

It seems there is something to be done with antioxidants and advanced biotechnology in combination, given the evidence to date of the effectiveness of targeting to the mitochondria via gene therapy or other clever science. But the salesmen of the "anti-aging" marketplace - those folk energetically waving pills and potions in your face today - are most likely sitting on a pile of junk and nonsense rather than any even marginally effective product.

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With due respect to Dr. de Gray I have to say I'm suprised that he would make such a statement. Most advocates of antioxident supplementation claim that they may extend life, not that will significantly enhance it at earlier ages(aside from those who say it helps the symptoms of the common cold etc) If anxtioxidents extend life after reproductive age there would be no selective advantage to enhancing their action. I know many people who have had their reproductive fitness enhanced by smoking or skydiving or doing lots of drugs and playing loud rock music, all of which will negatively effect lifespan. Evolution simply is blind to enhancing lifespan unless it is somehow related to increasing reproductive fitness.


Posted by: Thomas at March 10th, 2007 7:13 AM

Evolution, huh. Let's go back in time, back when humanoids were able to manufacture their own antioxiedent, namely l-ascorbic acid (vitamin C). At some point in our distant history a mutation occured since then humans have been carrying a defective gene for the production of the liver enzyme, L-gulonolactone oxidase. The pathway of the biosynthesis of ascorbic acid was elucidated at the end of the sixties (Nishikimi and Udenfriend, 1977):
D-glucose =>(1)=> D-glucuronic acid =>(2)=> L-gulonic acid =>(3)=> L-gulonolactone =>(4)=> L-ascorbic acid
Steps 2 and 3 are catalysed by enzymes in the liver. Step 4 is catalysed by L-gulonolactone oxidase, an enzyme in little microsomes. Animals which are scurvy-prone lack this L-gulonolactone oxidase activity

The lack of this enzyme in the human liver produces an inborn error of carbohydrate metabolism which prevents us from synthesising our own ascorbic acid (vitamin C) in our livers. This synthesis is common and normal to all but a very few mammals and they produce large amounts each day. It is a stress-responsive process, and, under stress, mammals produce even greater amounts of ascorbic acid. The main function of this large ascorbic acid production during the evolution of the mammals was to maintain homeostasis during biochemical stress. Because of this defective human gene, man, through out his entire history, has been deprived of this important mammalian protective mechanism.

We evovolved to survive with the mutation, which in and of it's self is pretty cool, because usually a mutation means that you've been selected against.

The only animals on earth that get heart disease are those that don't manufacture their own l-ascorbic acid, humans, guinea pigs, a couple of monkeys and a couple of bats.

Animals that do manufacture their own l-ascorbic acid do so in great volumes, typical l-ascorbic acid production is between 80-180mg/kg. That means a 160 pound man would need somewhere between 6 and 14 *grams* of l-ascorbic acid a day for optimal health. If that 160 pound man had any type of health problem his l-ascorbic acid requirements would skyrocket, 50, 100 grams, just like animals that make their own l-ascorbic acid. 300mg of l-ascorbic acid a day will just keep you from dying of scurvy.

L-ascorbic acid is a stereoisomer, which means there is a mirror image, r-lascorbic acid, when vitamin C is made in a lab, you get both l and r, r is unusable by our bodies, which means when you buy vitamin C and it does not say l-ascorbic acid it means its a racemic, and you are getting both l and r, so a bottle of vitamin C that claim it's 500mg per tablet, you are only getting 250mg of usable vitamin C.

The two people behind the majority of our understanding of l-ascorbic acid are Dr. Irwin Stone, and Dr. Linus Pauling the only two time solo noble prize winner and the father of modern chemistry. Until someone comes along who is a) as smart as Dr. Pauling, b) has the credentials of Dr. Pauling, and c) doesn't have a vested interest one way or the other I'm sticking with Dr. Pauling, and his theories.

If you want to learn more about the biochemistry of l-ascorbic acid, check out my sources for this post:

Posted by: Jay at March 10th, 2007 9:33 PM
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