I began to question the “positives” of caffeine when I was reading combination therapy studies where caffeine alone was not effective but caffeine plus a therapy was more effective than the therapy alone. That raised an eyebrow for me. Perhaps it is useful to know how compounds exert their effects before we say something is good for you.
Caffeine as are most methylxanthines are potent inhibitors of respiration. There are also a number of negative hormonal side effects with the digestive system leading me to wonder e.g. if some perceived food intolerances are caused by heavy chronic coffee consumption.
When I see a compound inhibit respiration and a shift towards glycolysis I automatically think insulin. Caffeine effectively increases insulin. This would have the effect of suppressing beta-oxidation to some extent causing a stress response which would temporarily increase the RMR. Anytime respiration is suppressed acutely there is a temporary increase in the RMR to restore NAD+/NADH ratios. Caffeine probably inhibits respiration by shifting the cells towards glycolysis increasing NADH which essentially creates the Crabtree effect. It happens that the Crabtree effect causes cells to uptake calcium which eventually causes apoptosis. In cancer this would be useful. Essentially the caffeine is stressing the cell making the pharmaceutical therapy more potent.
Some people report that when they give up coffee there is a period of time where they feel excessively tired. My opinion is that when chronic stress is reduced this symptom is to be expected.
Dr. Peat mentions caffeine being an “adaptogen” he is somewhat correct in the sense that acute caffeine consumption would cause a temporary increase in RMR (stress response) causing weaker damaged cells to follow through to apoptosis. Caffeine does stimulate autophagy. Basically a sort of ripple effect through the organism i.e. a window cleaning with a squeegee. When insulin increases the thyroid hormones tend to increase as the thyroid hormones participate in degrading insulin thus restoring organization through increased beta-oxidation of fatty acids.
But chronic consumption could be maladaptive. On the surface there seems to be a loss of heavy caffeine consumers in centenarian pools. Fat, nicotine, chocolate, and alcohol (although heavy alcohol consumption does as well skew NAD+/NADH ratios) seems to be far more common with coffee consumption being a cup or two a day for those that do drink it and happen to make past their 90’s. But that observation is probably biased because I haven’t looked that hard.
Chocolate also contains methylxanthines but the stearic acid and other SFAs probably offset the negative consequences.
For those who look at metabolic rates, there are a lot of compounds that increase the metabolic rate. A lot of lethal substances are on that list. I think that it is important to look at the context when recommending chronic consumption of said substances as an adaptive stress response is something quite different then a chronically induced state of hypermetabolism. Animals that live long such as the naked mole rat have low RQs, are insulin resistant, and Vitamin D deficient. During hypoxia (e.g. altitude or underground) humans react physiologically, fatty oxidation increases and ketones increase. Fatty acids, lactate, and ketones are protective in low oxygen environments.
Then there are those who are better or worse at metabolizing caffeine and other xenobiotic compounds, I would guess this would determine tolerance to such compounds as well as what “dose” would mediate a beneficial hormetic response.
In the beginning I mentioned that I began to question the “positives” of caffeine. I want to define “positives”. Because the idea is not to recommend that you should axe coffee the idea is that just because we see good evidence of a substance with benefits doesn’t mean we turn off our brains and forget to ask why are there these benefits, how does the substance mediate its effects, how can I best use this substance without interfering in general with my enjoyment of a substance which possibly could be a double edged sword.
So having a cup or two of coffee a day is probably adaptive, but if you are drinking “50 cups of coffee per day” there is probably something extremely wrong with you.