There is some merit to what you are saying…it’s all in the control reference point.
One of the big criticisms of mice studies is the “AD LIBITUM (AL)” control mice. This artificial construct results in lower longevity control mice, and thus inflates an intervention. For example, wild type mice NEVER feed ad libitum in the wild…so it’s ridiculous to call them “wild type”. They are only referenced as wild because they are a natural strain, not transgenic. NOT because of their dietary feeding habits.
So you have this wild type mouse eating massive quantities of food, outside it’s evolutionary history, ramping up all manner of aging pathways…they die YOUNG.
So then you overlay an intervention that say lowers food intake or other appetite dysregulation…and voila, the intervention looks amazing…relative to the control.
The basic premise of control fed mice is ERRONEOUS.
Makes you wonder about the biggest lifespan intervention in mice…CR. The intervention is all about restricting calories relative to AL mice?
Thus, this could explain a significant issue with human translation impact. The effect is much larger in mice, and humans have a tightly controlled set point that is much harder to shift to a new homeostasis.
Great! We are all here to listen and learn and improve.
Very informative summary. Also interesting is the review of IP6 + inositol at the very end of the page.
Not only is it cytotoxic to cancer cells but it also lowers A1C levels and at 4 grams of inositol there’s a very sig drop in cholesterol and triglycerides.
Some life extension as well.
I’m not sure set point theory really makes sense to me - or at least there is much more going on. Personally, I’ve fluctuated between ~145-205 lbs give or take (several years), depending on adaptation and food intake if I really pushed my stomach as I did in earlier years. Just never went above 14% body fat, as I suspect there is some cutoff range.
The classic example is the Standard American Diet - it appears to be obesogenic enough to disrupt this theorized homeostatic process. Our genes barely changed over 200 years.
It’s interesting that ramipril+statin is beneficial but ramipril and statin alone are not. Is there any evidence that taken together, they would add up to something greater=ramipril+statin+metformin+acarbose would be beneficial?
Thanks, this summary helps to pick and choose which supplements to take.
I simply cannot take all of the supplements that are apparently beneficial.
Keeping track of dose, timing, with or without food, avoiding negative interactions with medications, etc., is just too much.
I have to choose carefully the few I choose to take based on my age, medications I take, etc.,
It would be interesting to know how many supplements the average person on this site takes daily.
Mine is now approximately 20! I simply have to downsize. I take ~10 reliably, the other 10 varies on what I am doing or feeling on a particular day
I can handle them all except astaxanthin. My body just does not get along with it. It gives me dull pain on both sides of my body just below the ribcage at any dosage above 10 mg. Maybe my kidneys are revolting against it or GI bloating. Either way, I hate having dull constant pain.
NAC is OK. I do believe that combined with glycine (which tastes like sugar and is very pleasant), the benefit to glutathione levels is helpful. But maybe I am putting too much stock in the Baylor human tests. I am running a test of n=3 with my family now. Will share results once I get them.
It sounds like the TRT numbers if they are legit would be for those treated for hypogonadism, which would not be surprising.
It’s hard to tell with TRT studies from abstract/title - I suspect it’s not on “healthy” men. I’m still “wait and see” for now. I’m not an expert at TRT but I do know endocrinology can get pretty complex and my observation is I don’t see many practitioners even thinking about pharmacogenetics to treat a continuum of what I currently consider hypogonadism. Endocrinologist professional recs are hard cutoffs for subnormal morning serum T at 3 different times which seems too fixed, while other practitioners are highly variable which seems too loose when I see enough middle-aged “healthy” men with vague symptoms (attributed to something else) going on TRT. That’s enough to give me pause on it personally when it seems there’s not enough precision.
I’ll probably get back to reviewing it when there’s more precision involved, as I don’t expect to even consider TRT anytime soon and it’s too hard of a call if a patient without clear hypogonadism asked me about it. I’d also be wary if I see the words “bioidentical” or compounded pharmacy. There’s enough data to be wary of potential quality control issues.
The neuroendocrine system has even more unknowns as we see in the lack of literature describing exogenous high levels of 17aE2 on the brain, while “low estrogen” in men could be mistaken for “low T”. I don’t really see any signs of discernment among practitioners (measuring estradiol levels isn’t done afaik) but hard to say for sure.
I think getting to “normal levels” and staying there can be reasonable - but hard to say if intermittent supra-physiological doses based on the delivery method are potentially harmful, so if I was on TRT I’d be careful about getting the titration right. If I was on it, I’d avoid oral form and certain injections - but there’s probably way too much variability on an individual level. The studies out there are non-uniform and there are so many different options that can make it confusing to navigate until one digs really deep.
Richard miller of the ITP program was going to do lifespan studies with spermidine - but said in this recent interview that they tested it for 8 weeks, but could not find any evidence that it was even getting into the bloodstream, and they felt that if it wasn’t even getting into the bloodstream, there was little hope it was going to effect lifespan… so yes, spermidine is still a big question mark and may be of little value as its currently delivered: Longevity Supplements - Interventions Testing Program Results | Dr. Richard Miller - YouTube