LW - in defense of Linus Pauling by bhauth

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Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: in defense of Linus Pauling, published by bhauth on June 4, 2024 on LessWrong.
Linus Pauling was a chemist who won a Nobel Prize in Chemistry in 1954. He later became well-known for advocating large doses of Vitamin C.
I've heard that advocacy referred to as a cautionary tale, but I've long had a bit of sympathy for Linus, and I'm writing this post to explain how and why.
mainstream nutrition
One reason for my sympathy for Linus is that I've heard him used as an example of why you shouldn't go off on your own instead of trusting mainstream views in a field, yet his advice, while not particularly helpful, caused much less harm than contemporary "mainstream nutritional advice", such as:
the food pyramid
"partially hydrogenated vegetable oil is healthier than butter"
"a very-low-fat diet is healthy"
"eating very little salt is healthy"
I certainly wouldn't suggest trying to independently compete with the conceptual framework of, say, semiconductor physics or structural engineering, but when a field is rotten enough (nutrition, psychology, education, and economics come to mind) history indicates to me that someone smart from another field is often more correct than specialists on that topic, when they have an interest in it.
my view of Vitamin C
To be clear, I'm not advocating for the very high doses of Vitamin C that Linus did. I do think the World Health Organization's RDA (45 mg/day) is a bit low, but the RDA of Japan and the EU (~100 mg/day) seems entirely reasonable to me.
Amounts above that generally don't have much effect on blood levels of Vitamin C, because it's absorbed less and the excess is expelled. Thus, some people have advocated administering it by IV, but one has to consider the possibility that there's a good reason for a specific level being naturally maintained.
Research since Linus first advocated for Vitamin C megadoses has supported oxidative stress being a major cause of aging. It's associated with many problems (Alzheimer's comes to mind) and there's a good theoretical basis (DNA I-compounds) for its long-term harms. We've also seen that previous suggestions for Vitamin D doses were much too low, so there's also precedent for that.
Where, then, did Linus go wrong?
Vitamin C is an antioxidant, but it's also a pro-oxidant. It can reduce iron and copper, which can then react with hydrogen peroxide or oxygen to form hydroxyl radicals or peroxide ions. It can also form some complexes with metal ions that could conceivably have some harmful catalytic effects.
(Its ability to interact with metal ions in certain ways is the main reason it's used in cells rather than some other compound: it's a cofactor.) The normal levels of free Fe and Cu ions are low, but my view is that the natural blood level of Vitamin C is a compromise set by pro-oxidant effects.
When an infection happens that causes hypochlorite production by immune cells, it's logical that the optimal level of Vitamin C would be higher. And indeed, there's evidence that extra Vitamin C during infections (especially bacterial infections) helps somewhat. But the main antioxidant in mammals seems to be glutathione rather than Vitamin C, and it has to be used in combination with superoxide dismutase.
So, Linus was one the right track. He was trying to solve the right problem, and he found a reasonable solution to it, but he overlooked some complicated side effects. That's a mistake I consider forgivable. He should have realized that there was a reason for homeostasis of Vitamin C levels, but the ideology of his time was that biological regulatory systems were so ineffective that any deliberate management by people would be better.
There were, thus, people optimizing the balance of purified starch/fat/protein diets they fed rats, and being puzzled when the rats kept dying. Then, as soon as they discov...