Can trying to cheat death paradoxically kill you sooner? - The Niche (Paul Knoepfler)


I agree. You don’t want the bleeding edge of technology to be a guillotine.

However, keeping your biomarkers in tip-top shape and proactively preventing disease seems like a reasonable goal with a lot of potential gain for minimal risk.

I don’t give this article a lot of credit due to its harping on Metformin. Metformin is a very useful intervention to treat and prevent diabetes. It’s hardly a dangerous drug even though lactic acidosis is a potential side-effect. I feel the same way about Rapamycin if you are informed about the potential pitfalls.


I agree its good to be thoughtful, do a lot of research and do regular blood testing (and have doctor engagement) to make sure things are going in the right direction… its always a balancing act, and everyone had different risk/reward profiles.

But yes - that guy who thinks metformin is risky… its the most prescribed drug in the world I think, and has probably the most benign side effect profile you can get. If he thinks thats risky, and just wants to follow the blue zones diet, thats fine. But most of us here are more aggressive than that, and want more than just 100 healthy years.

Everyone has to make the right choice for themselves. The goal here is that by sharing information, results and personal trial data, we help de-risk things for ourselves and others at the same time.

And, always a good idea to keep these threads in mind:

Here: Detrimental effects of overdoing longevity interventions?

Here: Deeply disturbing information on combining longevity supplements


I know, I’m only linking b/c he is a respected stem cell biologist (his blog is one of the the most useful in a field that’s so hard to get a traction in), but also overly conservative and not especially inclined to charity


He does make some good points. I think the risk goes up the more interventions you have (especially if you are not working closely with a doctor, like Bryan Johnson is).

Its about managing risk, and reducing the unknowns. Supplements frequently represent a significant unknown… what’s the active ingredient, what is the actual dose, what are possible contaminants, and what are possible interactions with other things you are taking…

So this statement is right on:

Supplements do have risks even though they aren’t regulated as drugs. I remember when the first study showed that Vitamin E increases cancer risk. People were shocked. Now after more research the association between Vitamin E and cancer is not so consistent but the point is that there are real and potentially major risks to supplements, especially when taken in extreme doses and in combination with other supplements and drugs.

And when you start taking pharmaceuticals like rapamycin and others, I think its important to track your blood markers closely. Simpler is probably better (and lower risk).

For example - this should be something that people should be aware of, that would be caught via regular blood testing:

Case Report: Severe Asymptomatic Hypertriglyceridemia Associated with Long-Term Low-Dose Rapamycin Administration in a Healthy Middle-Aged Labrador Retriever

Rapamycin is an mTOR inhibitor that has been shown to extend the lifespan of laboratory model organisms. In humans, rapamycin is used at higher doses as an immunosuppressive medication to prevent organ rejection. Numerous adverse effects are seen with rapamycin treatment in humans, with one of the most common being dysregulation of lipid metabolism. In humans, this often manifests as mild to moderate serum lipid elevations, with a small subset developing extreme triglyceride elevations. This case report describes an 8-year-old, castrated male, clinically healthy Labrador retriever who developed severe hypertriglyceridemia associated with low-dose rapamycin administration over a six-month period. During this time, the dog was asymptomatic and displayed no other clinical abnormalities, aside from a progressive lipemia. Within 15 days of discontinuing rapamycin treatment, and with no targeted lipemic intervention, the dog’s lipemia and hypertriglyceridemia completely resolved.


I think it is helpful to have opposing points of view presented some of the time so I can keep a balanced perspective. This particular article is not well done but he makes an important point: there can be consequences to being too aggressive. I also like the perspective that there are well known consequences for doing nothing. I know where that path ends.


Our favorite MD Alan Green experienced this recently. His ideal Mediterranean diet gave him gout which led to a nearly lethal upper GI bleed. He has fully recovered.


I doubt much that a diet was a culprit. Mediterranean diet would not contribute to uric acid accumulation.


Ray, I don’t know if you’re this mistaken, but it was a low carbohydrate diet he was following - certainly not a Mediterranean diet, as eating a 1 lb of codfish a day is not it, and neither is the Med diet low in carbs.

Dear Friends,

I had a massive Upper GI bleed on Sunday, 11/5/23.

It started with Codfish. I thought a low carbohydrate diet would be good. I thought codfish was the perfect food; low calories, almost all protein, low fat. Was eating about a pound of codfish (boiled, no sauce) almost every day. Codfish is very high in purines. As a result of a very high purine diet from codfish, I developed gout.


Now it explains it! It’s 1 lb of cod per day and every day! It’s a lot.


I think frequent measurement is a good thing. I feel a lot happier with my weekly blood tests in that if anything is going wrong I will see it quite quickly.

I am currently running an enhanced metabolism session. This tends to drive up blood pressure, but it drops back when I stop (which will probably be on friday - this is an 8 day session enhancing AMPK and ATP).