I have often commented here on specific longevity interventions and why I’m skeptical of some claims that circulate in the field.
I recently wrote a piece describing the framework I use when evaluating longevity interventions.
The core idea is that many interventions fail not because the underlying biological mechanism is wrong, but because the effect does not survive translation across biological scales, from a mechanistic idea to a meaningful effect in a whole organism over long time horizons.
The article walks through several examples (apigenin, MSC therapies, IL-11 inhibition, and hyperbaric oxygen therapy) and then summarizes the recurring failure modes that often prevent promising mechanisms from producing real anti-aging effects.
Link to article:
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Which is why I like pharma drugs. You have a better chance to assess long term effects and outcomes in a rigorous fashion and it’s immediately relevant to humans on top of it. Meanwhile with supplements the data is frequently sparse and confounded. This doesn’t mean supplements are useless, just that pharma drugs get you closer to decision making results faster. I can look at a drug and more readily see if it’s likely a useful addition to my stack. The gambling odds are better. However with supplements the path to that decision is more often long and winding. Doesn’t mean drugs can’t have the same kinds of problems, just the process is easier with more data and more reliable data. Of course, ultimately there’s also individual variation to any drug/intervention effect, and also your personal profile - if you have CVD vulnerabilities, your longevity stack will look different from someone with a different profile of vulnerabilities. We all age, but we age slightly differently and need to adjust our interventions to fit our particular physiology. Individualized approach insofar as is practical, but most often it’s just a gamble based on something observed in consolidated averages from studies. Testing is essential, but the things we can test for are limited. We’re just playing the odds, over and over again. We need to get lucky quite a number of times. The more interventions, the more often we need for things to break our way. It’s all a gamble in an information constrained environment. Game theory is relevant surprisingly often.
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I agree, and many of the things I take are a gamble in the long run. My main criterion is the physicians’ “Do no harm.” There are many drugs/supplements that I don’t take because of meaningful harmful side effects, even though some people swear by them.
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You make some good points about why it’s easier to assess drugs than supplements. I would like to mention that one negative of most drugs that is less the case with some supplements is that they don’t have as much of a long term safety history and aren’t natural. I’m not saying natural is necessarily better, but if the choice is between some supplement that is part of what the body produces or is exposed to through the diet (e.g. some amino acids) and some drug that has been developed a decade ago, then the supplement usually is much safer. With drugs you have to be more careful because their effects at the indicated doses are usually more powerful than the effect of supplements, which can be a good thing if it works, but also makes it that much more risky, if it has negative effects. Also most drugs lack long term history of use and often we won’t find about some negative side-effects until decades later and that’s an extra gamble especially with newly developed drugs.
In addition, because drugs are usually more powerful, any kind of interaction between a drug and other drugs/supplements is that much more likely to be significant, which increases risk.
For those reasons, I think drugs require higher level of evidence to be incorporated into someones longevity regimen than supplements, as a general rule of thumb.
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I’m not saying natural is necessarily better, but if the choice is between some supplement that is part of what the body produces or is exposed to through the diet (e.g. some amino acids)
The human body is not usually exposed to most supplements on the market today and to the ones it is, the concentrations are much lower.
I’m actually curious how many drugs released in the past 50 years took 10, 20 or even 30 years before some long-term side effects were discovered that weren’t detected within the first 3-5 years.
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Well, apart from folk medicine anecdotal evidence many supplements, especially as sold by random brands don’t have long track records either, meanwhile many drugs have decades long clinical records, validated and studied. Drugs come in more reliable dosage and manufacturing integrity compared to supplements ( mostly). As Virilius says, current supplements are often extracts at supraphysiological levels, far from “natural”. As to “stronger” drug effects, well, that just tells me that they actually do something, vs the equivocal effects of many supplements and sometimes you can calibrate that with dosage. Again, I’m not against supplements (I take a ton of them!), just drugs are easier to handle and evaluate. YMMV.
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True. I should have been more clear and mentioned that I was talking about supplements that have been available in somewhat similar form for hundreds of years and in doses that are not far from such exposure levels and comparing them to drugs that are relatively recent and do not have decades of history of use yet. As an example, if the choice is between a supplement containng a herb at a moderate dose that has been historically used widely for hundreds of years and some drug that has only been used for ten years, then the supplement clearly has an advantage in terms of long term safety.
Drugs also in general are something one needs to be extra careful about because, unlike supplements, many of which don’t have very significant effects, drugs typically have highly significant targeted effects at the indicated doses, or else they wouldn’t have been approved for any indication. So when it comes to drugs, you can be more certain that it has a significant effect, and must be more careful to make sure that effect is not harmful. I’m pretty sure that if you picked ten random drugs and took them daily for a year at the indicated doses or picked ten random supplements daily and took them at the indicated doses for a year, your chances of harming yourself significantly are much higher with the drugs than the supplements largely because the drugs are more likely to be powerful at the inidicated doses.
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