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CasioTheSane comments on Thermodynamics of Intelligence and Cognitive Enhancement - Less Wrong
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Perhaps sugar and glucose only cause problems in those who can't metabolize it effectively, for other reasons (or when consumed in excess of your capacity to metabolize them). I used to think high glucose intake caused metabolic syndrome but I can't reconcile that with the existence of large groups of people (Kitavans, fruitarianism, etc.) that have very high carb diets and don't develop metabolic syndrome.
In mice, high sugar diets don't cause metabolic problems or liver damage unless also coupled with high polyunsaturated fat intake. Populations of people with high carbohydrate diets and no metabolic syndrome seem to have very low polyunsaturated fat intake. Could carb restriction protect against the symptoms of metabolic disease, without addressing the underlying cause?
Fructose seems to increase T3 production in the liver, which could be a mechanism behind the sugar high. I am not sure if this is "good" or "bad."
What do you mean by "metabolize effectively"? People who have problems with metabolizing glucose are usually known as "dead" and things like insulin resistance are a problem with signalling, not a problem with cells' aerobic metabolism.
The metabolic syndrome is clearly multi-factor, there is no single cause we can point to. I am not sure PUFAs (or fructose) are the magic ingredient either, and it looks quite likely that the amount of physical exercise plays a fairly major role in all this -- but the whole thing is pretty messy at the moment. Sorting out all the causal connections leading to the metabolic syndrome is probably Nobel material :-/
There can be damage or defects in the mitochondria that inhibit it's ability to respond to hormones, for example per-oxidation of cardiolipin. Cells don't always die when they have a mitochondrial defect. An extreme example is cancer, where there is major damage to the mitochondria, but the cells continue to live via anaerobic fermentation (aka the Warburg Effect).
Some review articles that talk about these theories:
Cancer as a metabolic disease: implications for novel therapeutics
Life and Death: Metabolic Rate, Membrane Composition, and Life Span of Animals
Role of cardiolipin peroxidation and Ca2+ in mitochondrial dysfunction and disease
Sure, but what's the prevalence of this kind of problems? Sugar and/or glucose can cause problems in a significant chunk of population, maybe even the majority. Are you saying all these people have damaged mitochondria?
I need to learn more about this, I don't have a strong belief. If I understand correctly, this is basically the idea behind the free radical theory of aging (FRTA). One interesting variant of that idea is in the article I linked above, which suggests that the focus should be on "mitochondrial membrane peroxidizability index" rather than antioxidant activity or free radical production.
It seems weird that sugar seems to cause problems in certain populations of people, but not others.