This fascinating blog post by Josh Mittledorf points out that antioxidants, once believed to reduce aging by reducing oxidative damage, have turned out to have the opposite effect. By reducing a hormetic effect, they make things worse. I’m a friend of Bruce Ames, one of main proponents of the free radical theory of aging. I’ve heard him talk about it a dozen times. The turning point — the beginning of the realization that this might be wrong — was this 1994 study, which found that beta-carotene, a potent antioxidant, increased mortality. Bruce did not have a good explanation for the counter-theoretical result. However, Mittledorf doesn’t mention an important fact which doesn’t fit his picture. Selenium, a potent antioxidant, also powerfully reduces cancer. Don’t stop taking selenium.
I also like this theoretical paper by Mittledorf about why aging evolved (turning off certain genes reduces aging) and how its evolution — not easily explained by conventional evolutionary ideas — is part of a range of phenomena that the conventional ideas cannot explain. One reason, maybe the main reason, that aging is adaptive is very Jane Jacobsian: it makes the community more flexible. Less likely to repeat old ways of doing things.
Thanks to Ashish Mukarji.
Hi Seth,
I think there is more to this than just anti-oxidants = bad. That trial with beta carotene is confounded by the addition of synthetic alpha tocopherol. We know from other trials that synthetic fat soluble vitamins are bad news.
The effect of vitamin e is not even that consistent:
https://www.ncbi.nlm.nih.gov/pubmed/19267994
I personally take a low dose natural vitamin e supplement that includes mixed tocotrienols (which balance tocopherols) and ultrathione, a highly absorbable version of glutathione, the so-called ‘master anti-oxident’, I’ve had great results with both. Namely glowing skin and good stable mood.
I think hormetic stress is important, in fact that is how polyphenols found in vegetables and exercise benefits are now thought to come about, but that doesn’t mean the chronic oxidative stress we experience in modern life is not to be avoided and mitigated where possible.
Seth: The trial was not confounded. Betacarotene and vitamin e were varied separately. There were four groups, on other words.
Three take-away lessons that I get from all these changing and contradictory studies — and all the drug recalls — are very simple:
1. All the smug self-proclaimed experts are not as smart as they think they are.
2. We should be very careful about interfering with biological processes that have been selected for over millions of years of Darwinian evolution.
3. We should be especially careful about all the highly profitable new drugs, devices and surgeries. As for me, I’m perfectly happy to let other people be the guinea pigs taking — and dying from — all the addictive painkillers, antidepressants, prpton pump inhibitors, and other magic BigPharma potions.
Does the 1994 study and the vast majority of all vitamin studies show that supplementing with isolated chemically derived vitamins is neutral at best and negative at worst? One wonders if the 1994 study results would have been different had one group eaten carrots and the other not eaten carrots.
Seth: If you include animal (usually rat or mouse) experiments, I believe the answer is no, they don’t show that. The vast majority of vitamin experiments with isolated chemicals (lab chow with chemical X vs lab chow without chemical X) have produced positive results. That’s where the concept of vitamin came from. In these studies the animals were made sure to have a deficiency in the vitamin. Whereas human studies often fail to make sure there is a deficiency.
If I remember correctly, the idea that antioxidants would slow aging was very abstract. The takeaway might be that biology is sufficiently complex that experiments and knowledge of specific mechanisms are essential.
O/T: the flu.
https://www.independent.co.uk/life-style/health-and-families/health-news/scientists-urge-ministers-tell-truth-on-overhyped-flu-vaccine-8336184.html
“The vast majority of vitamin experiments with isolated chemicals (lab chow with chemical X vs lab chow without chemical X) have produced positive results. That’s where the concept of vitamin came from. In these studies the animals were made sure to have a deficiency in the vitamin. Whereas human studies often fail to make sure there is a deficiency. ”
Good point, Seth. The argument I’ve heard for why the CARET study possibly failed, from the Eades, is that the immune system system uses free radicals and that supplying one specific anti-oxidant could actually compromise that process. Hence the need to supply a natural smorgasbord of anti-oxidants and their raw materials to let the body select what it wants to use. But I’ve heard the same argument used for vitamins, whereas it’s clear that extracted or isolated vitamins will always cure their associated deficiency diseases.
I’m pretty much agnostic on anti-oxidants at this point.
Seth – I can’t get through to Mittledorf’s theoretical paper. Is that generelised or just from here.
Seth: I fixed the link. It should be easier now.
I once read a book by the professor who called himself the “Father of Antioxidants” and he wrote about the anti- and pro-oxidant effects. He boosted the notion of 5 antioxidants that work in concert: one would produce oxidants that another would gobble onto, and so on in a ring. C, E, selenium I think were 3 of the 5.
According to this notion, doing a study of one antioxidant alone would lead to contradictory results, depending on whether the other antioxidants were being consumed in diet in enough quantities.
The synergistic notion makes sense in evolutionary biology terms, since traditionally we consumed all vitamins in our diet.