Peter Attia is a big proponent of getting ApoB as low as possible (as low as 20–30!) which usually requires the use of Rx meds (statins, PCSK9, etc). As far as I understand, this is contrary to the standard guidelines. An average doctor would be more than happy with a level 60–100.
Peter talks about this in his book Outline, but this clip provides a nice summary:
An interesting point he makes is that ApoB is mechanistically linked to atherosclerosis, but I don’t have sufficient education to evaluate that claim. Nor can I understand whether the benefit of using multiple rx meds would outweigh potential risks, especially with regard to the long-term all-cause mortality (not just CVD mortality. I’m curious what you think about this!
Also, if you believe that this is a smart strategy, have you taken action? If so, how did you find a doctor that is willing to work with you on this, prescribe the right meds, and monitor the results?
Yeah, I’m taking rosuvastatin but that won’t be enough. So I have started using canola oil too and eat a more Mediterranean diet. I will look to add ezetimibe as well.
It’s a really interesting question. And the jury is still out. There are 3 types of study looking at this and each has it’s limitations:
1.RCTs show lower apob is better for heart disease. But only marginally so below about 65 apo b. They are limited because they are generally underpowered for all cause mortality and so rely on classifying whether a death is cardio or non-cardio ( which can be controversial). They also look at secondary prevention only (the subjects have pre-existing heart disease) so they may not be generalizable to healthy people. They also tend to be limited in time to a few years rather than long term. So they may not tell us anything about the long term risks and the long term safety data
2. Population cohort studies show a u curve. With a best outcome well above 65 mg/dl apo b. They look at longer period, all cause mortality and larger size. But these are limited because they only show association not causation. And importantly, many deadly diseases impact/lower apob levels. The studies try to factor these out but it’s a limitation.
3. Mendelian randomization studies show lower apo b is better, but again not dramatically below about 65 apo b. These look at people with genetic variation around psk9 which leads them to naturally have very low apo b. But the limitation is that we have no idea whether other protective/compensatory genes have evolved which correlate to the psk9 gene. I.e. a person with mutated psk9 may have a very different overall generic/health profile compared to someone simply taking psk9 inhibitors all their life.
Taking all that together I aim for about 50-60 mg/dl apo b. Going lower (20-30) has marginal benefit and unknown sides from the pharma (over decades). But I’m guessing like everyone else and I can do that (60 ish mg/dl) mainly without pharma, just using lifestyle. Exercise, fibre, nuts, olive oil, low frying collectively make a massive difference. (Canola oil doesn’t seem to help apo b, it seems to lower ldl cholesterol volume by shrinking the particle size, so you end up with the same number of apob particles and possibly more oxidized cholesterol as well). I’m also currently experimenting with 1mg of rosuvastatin on top to go from about 65 to hopefully lower.
One thing to add, inflammation, blood pressure, blood sugar and oxidation of cholesterol are all important for both Cardiovascular health and other organs (esp. kidneys and brain!). The lifestyle measures listed above all benefit these on top of apob. So I believe it’s much better to do the heavy lifting with these rather than focus on pharma initially. It also minimises pharma side effect risk. But age and health may preclude that strategy.
The apo b mechanism does seem to be widely accepted now. Tom Dayspring is the expert Attia relies on in this area. But there will be more research needed to understand why vessel lining is sometimes more/less prone to disruption by apo b. Quality of the lining will no doubt be important.
I am taking action. I have been taking Bempedoic Acid and I’ll be able to see how much it lowers my ApoB in March. If it’s still not low enough, I’ll add Ezetemibe back in.
What did you decide re policosanol in the end?
I’m tempted to stop my 1mg of rosuvastatin experiment. And try a self experiment with 1g a day of my bee honeycomb instead. So many self experiments to consider, and so little time!!
I’m already on Repatha (PCSK9i) and ezetimibe, soon to add bempedoic acid. This is the ultimate 3-med combo that Attia promotes for maximal efficacy in lowering ApoB with the least risk of side effects, and it makes sense to me (barring any as-yet undiscovered side effects of bempedoic acid, since it’s relatively new). Will be eager to see just how low I can get my ApoB after a couple of months!
Agree with your points. There are still a lot of unknowns. There are also other supplements that have shown efficacy at reducing arterial calcification (though studies are limited) such as Kyolic Aged Garlic Extract. The mechanism of action may be preventing the oxidation of LDL particles, which suggests the culprit causing CVD may not be the number of particles (ApoB) but the number of OXIDIZED particles, which are not being measured.
The study in question did not show that AGE prevented oxidation of apoB particles though other beneficial effects were detected.
The aim of this study was to test the effect of treatment with AGE on brachial artery flow mediated endothelium-dependent dilation (FMD) and circulating markers of oxidative stress and systemic inflammation. The trial included 15 men with angiographically proven CAD in a randomized, placebo-controlled, cross-over design with 2-week treatment and washout periods. During AGE supplementation, FMD increased (44%) significantly (p = 0.04) from the baseline and mainly in men with lower baseline FMD. Levels of FMD at the end of AGE treatment were significantly (p = 0.03) higher compared with the corresponding levels at the end of placebo treatment when the variation in baseline body weight was taken into account. Markers of oxidant stress (plasma oxidized low density lipoprotein and peroxides), systemic inflammation (plasma C-reactive protein ad interleukin-6) and endothelial activation (VCAM-1) did not change significantly during the study. These data suggest that short-term treatment with AGE may improve impaired endothelial function in men with CAD treated with aspirin and a statin. Whether improvement in endothelial function decreases the risk of future cardiovascular events remains to be determined.
“Using an in vitro model in which copper sulfate (CuSO4) was used to oxidize LDL”
This kind of study has been criticized for its potential lack of physiologic relevance, since it is done ex vivo and the large flux of free radicals generated from CuSO4 is higher than what you’d see in vivo. Sorry no reference, this is from memory. Not saying garlic is useless by any means, just suggesting to take the ex vivo LDL oxidizability studies with a grain of salt.
Yes, I realize this was an in vitro study, but I posted it to address the LDL oxidation issue.
However, there are many clinical studies and RCTs (albeit relatively small) showing the benefits of Kyolic Aged Garlic specifically. These include reductions in the growth rate of soft and calcified plaque. It has been repeatedly noted that keeping the growth in CAC to below 15% reduces MI risk tremendously.
Ideally we would want to have larger and more extended RCTs, but the reality of our medical system is that there is little funding for treatments that can’t be patented by pharmaceutical companies.
Here is a link to a good PDF that summarizes the benefits of Aged Garlic Extract and references the appropriate studies.
