I am in the UK. I have used a range of labs. Normally now it is a mixture of London Medical, Randox and Nationwide Pathology. All are in the range of GBP 150-200.
Annually, of course that is in the territory of GBP 10K note exactly Bryan Jones territory, but still not petty cash.
Incidentally I have used Medicheks, but because they are a postal service rather than a courier service there are metabolism issues.
Thanks John. Medichecks give me the option to get the blood draw done at a local pharmacy where the sample is couriered same day and I usually get my result with 48-72hrs. I’ve been on 5mg rapa for 3 months. Will be interesting to see any changes from baseline.
His book is worth reading/listing{audiobook].
https://www.amazon.com/Ignorance-Drives-Science-Stuart-Firestein/dp/0199828075
The problem is that these studies actually tell us how much there is to know. If there is a treatment that lowers risk for a disease by 96%, that means there is little room for anything else.
“I use that term [ignorance] purposely to be a little provocative. But I don’t mean stupidity. I don’t mean dumb. I don’t mean a callow indifference to facts or data or any of that” - Firestein
To be clear, I am not advocating very low LDL levels
It was amusing to me, that way back in the day when I took a forensics (debate) class, it did not matter which side of the debate I was on, I could find plenty of ammo for my cause.
I think we have debated this issue many times in this and other threads in this forum.
My stance is: High LDC is not acceptable, rapamycin notwithstanding.
On average, there was a 20% drop in CVD risk seen for every 39 mg/dL drop in LDL cholesterol. In other words, a drop in LDL from 70 mg/dL down to 31 mg/dL was associated with 20% fewer CVD events such as heart attack or stroke.
“Very low cholesterol levels may be a sign of an underlying disease. Some potential causes of low overall or LDL cholesterol include chronic infections, inflammation, and malnourishment”
LDL cholesterol: How low can you (safely) go? - Harvard Health.
I found this study earlier which is a bit interesting, showing the causal relationship of apoB and lifespan:
Amount of apoB studied
Every 1 SD (standard deviation) of increase of apoB, at 0.24 g/L or 24 mg/dl was studied:
Estimates were inferred causal effects per 1 SD elevated lipoprotein trait (for apoB, 1 SD=0·24 g/L).
Effects of every increase of 24 mg/dl of apoB
For every 24 mg/dl (1 SD) increase in apoB, there was a 60% less chance of reaching the 90th percentile of lifespan:
(odds ratio [OR] of surviving to the 90th centile of lifespan: 0·38 per 1 SD higher apoB in offspring, 95% CI 0·22–0·65).
Our findings support apoB as being the major lipoprotein entity implicated in the aetiology of coronary heart disease and stroke and identify that higher apoB decreases lifespan and increases the risk of type 2 diabetes. These findings highlight the crucial role of apoB in causing cardiometabolic disease, which collectively shortens the lifespan.
Not surprising, and very significant considering rapamycin increases apoB, and by a lot higher than 24 mg/dl. Tell me if I missed something with this study.
The real magnitudes of effect, in terms of duration of life lost due to elevated apoB, are likely to be greater, as indicated in the effect estimates from the GWAS of 90th centile of survival. Our findings further strengthen the suggestion that it is the number of circulating apoB particles, rather than their lipid content, that is the critical element for atherogenesis, manifested as coronary heart disease and ischaemic stroke.5, 6, 8 The cholesterol within LDL particles does play a causal role in atherogenesis but it is within the physiological framework of the trapping of apoB particles within the arterial wall.
You need to know the time between blood draw and the various aspects of the testing process.
I wonder if the study I linked above will convince people that an above mean (50th percentile) apoB is very dangerous.
Consistently lost in the wash of this debate is whether rapamycin can protect against CAD despite an increase in lipids. As I’ve pointed out numerous times, there’s considerable evidence that this is the case.
In a rabbit study, rapamycin resulted in zero plaque rupture and a decrease in plaque burden while increasing lipids. This was in contrast to a 56% incidence of plaque rupture in the control group. The mechanism seems to be an increase in the thickening and stability of the fibrous cap. A similar effect has been seen with gotu kola.
This was also seen in humans
So again, is there evidence that the low risk person with elevated lipids from rapamycin needs to resort to statin therapy? If concerned , there’s statin alternatives. A good therapeutic target seems to be an ApoB to ApoA ratio < 0.8. I’m very close to that with just adding citrus bergamot at 1000 mg per day. I’m going to see if pantethine 600 mg is additive. Best of both worlds without the risk of diabetes or cognitive impairment.
cIMT is useless, so that human study is bunk.
I don’t know if I have to say this but obviously rabbit studies are near useless as well, except for one’s pet rabbit.
I find it unlikely that we will ever know whether rapamycin can offset the extreme risks from elevated apoB, or another mTOR inhibitor. In the meanwhile I don’t see the problem in trying to alleviate that with supplements as you do, or medications that lower apoB. If apoB goes down all is well.
You seem to be very confident that MR studies imply that any treatment that changes {LDL, APO-B} must correspondingly change [AS]CVD risk, even when, in the case of rapamycin, this is not supported by animal studies. Why are you so confident in this one line of evidence?
Rabbits, Mice, Rats.
In the end Humans are not all the same, but studies on mammals are not IMO “near useless”. I am into n~8 biohacking studies with humans which are useful because we have some vague idea as to what happens with Homo Sapiens, but “near useless” is not a conclusion I agree with.
Because it is a different animal, you are not a rabbit, which is an entirely different complex system. What works in one tend to not work in another because there are so many different moving, causal parts.
Here’s some examples and a good article on this topic:
Approximately 100 vaccines have been shown effective against an HIV-like virus in animal models, however, none have prevented HIV in humans.
Likewise, up to one-thousand drugs have been shown effective for neuroprotection in animal models but none have been effective for humans.
Along the same lines, of twenty two drugs tested on animals and shown to be therapeutic in spinal cord injury, none were effective in humans.
The success of the animal model in basic research can also be questioned based on the fact that, according to one report, only 0.004% of basic research papers in leading journals led to a new class of drugs.
For example, in part because the targets derived from animal models are not predictive for humans, the percentage of new drugs in development, after initial evaluation, that ultimately make it to market is somewhere in the area of 0.0002%.
Mendelian randomization is done on humans, also with a study design that eliminates most confounders due to the natural randomization of gene variants. Those same gene variants that in many cases only do one thing, for example increase apoB a little.
Here is an observational study showing rapamycin/everolimus being associated with more cardiovascular events and atherosclerosis.
nguyen2021.pdf (875.0 KB)
Interestingly, statins appear to have mTOR inhibiton too via AMPK activation, I don’t know how strong:
The table shows Tacrolimus, not Rapamycin. Or is Rapamycin maybe under “mTOR inhibitors”?
Yes it’s comparing rapamycin and everolimus with tacrolimus which is not a mTOR inhibitor.
It’s not a good quality study, but mTOR inhibitors also had 12 times higher rate of dyslipidemia compared to tacrolimus, so association is consistent there at least.
I’d be crazy to me to not control lipids with rapa because of some crap animal studies, just my opinion. Hopefully the increase in apoB isn’t as atherogenic as without rapa, but I wouldn’t bet on it as lipids can be decreased so safely IMO.
Because it is a different animal, you are not a rabbit, which is an entirely different complex system. What works in one tend to not work in another because there are so many different moving, causal parts.
Yes, in general animal models don’t recapitulate the details of the corresponding human disease – although the situation is less bad than often suggested. I recall, however, that most of our experimental understanding of cholesterol metabolism and its relation to atherosclerosis comes from rabbits. Statins were developed in rabbits. To the extent we can say that cholesterol (in whatever form) causes CVD in any animal, we can say it for rabbits. So rabbit evidence is worth quite a lot.
Those same gene variants that in many cases only do one thing, for example increase apoB a little.
This is the crux. The studies I’ve seen usually use a GWAS or similar to find genetic regions of interest. They literally have no idea what those regions do. I’m not sure how reliable causal inference can be with such methodology. Some studies do use variation in known genes – which leads to better conclusions. For example, MR suggests that alterations in the mevalonate pathway affects CVD, which is good evidence for the utility of statins (at least to the extent they mimic the natural variation), but isn’t as directly applicable to rapamycin.
I don’t know the literature well enough to know how to interpret it in this situation though, which is why I asked.
Of course, the reason for increased cardiovascular events could be the fact that the mTor-inhibited groups failed to keep their lipids within the normally accepted bounds.
It would be nice to see a study (which I don’t think we are going to see anytime soon) that compares for instance; rapamycin users taking statins or some other lipid control measures vs those that don’t.
Can you share a bit more about the autoimmune part?