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 discovered essential vitamins and the rats weren't dying anymore, they immediately declared victory and recommended people follow their new scientific diet.

conclusion

Different antioxidants are not fungible. Some are enzyme cofactors, there are different side effects, there are membrane-bound antioxidants, specific enzymes some antioxidants need to be used with, and so on. But when I see people even today pushing quinoa or "raw water" or burnt food or fad diets, I can't blame Linus Pauling too much for not having understood that.

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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.

Economics seems out of place here. Why do you think its rotten?

[-]bhauth166
  1. Lobbyists influence politicians, who decide policies based on politics. They then find economists who will justify the things they want to do. Those economists become high status, and other economists imitate them.
  2. Appointment of economics faculty has been influenced by big donors with ideological agendas.
  3. The predictions have been bad, even beyond the difficulty of predicting market movements. "Transitory inflation", for example.
  4. Macroeconomics is mostly about making a model and working out its implications, and selects for people good at doing the math involved, but there are no pressures towards making sure the assumptions are actually correct.
  5. see this post
[-]dr_s20

About the post linked, mostly agree, but I don't see the need to move away from utility maximisation as a framework. We just have a piss poor description of the utility function. "I enjoy being like that rich and successful dude" is a value.

I don't think so. How about if what people want depends on the current weather, or if people end up wanting whatever they were able to get in the past?

[-]dr_s20

Seems a restrictive definition of "utility function". It can have the weather as one of its inputs. It can have state (because really, that only means its input is not just the present but the whole past trajectory).

"Function" is an incredibly broad mathematical term.

quinoa or "raw water" or burnt food or fad diets

What's wrong with quinoa?

I wonder if maybe the rate of infections is vastly underestimated (most fungus/bacteria/protozoa/archaea/animals don't show up on most tests) and just keeping your body very acidic indefinitely could be worth it overall. If most of the benefit comes from preventing initial infection from a handful of nasty permanent things (eg toxoplasmosis) then you probably wouldn't observe benefits to vitamin C supplementation in studies except over very long time scales or with very young children