SoCalGuy wrote:Here's Peter Attia's latest email article. Very interesting read with regard to lowering LDL-C and blood pressure. It also ties in nicely with his interview with Francisco Gonzalez-Lima.
Email link: https://peterattiamd.com/191110/
Podcast link: https://peterattiamd.com/franciscogonzalezlima/
If this is the case ApoE 4 caused increases in CVD risk and Cerebrovascular risk would explain Alzheimer’s risk. I don’t see the risk ratios as the same unless the heart disease cerebrovascular risk is linear and the Alzheimer’s risk is geometric or exponential because the size of the vasculature in AD is geometrically smaller.Having two copies (i.e., rs7412 T;T) means you’re an APOE 2/2, which is associated with a reduced risk for AD. So, if we were looking at AD risk and LDL-C levels in a Mendelian randomization study, it’s possible we might conclude that reduced risk of AD from this SNP is entirely due to its effect on LDL-C levels, when there are a number of other plausible mechanisms (though the evidence is pretty solid that lower LDL-C, which improves vascular health, lowers AD risk by reducing the risk of vascular disease in the brain, which was covered in my podcast with Francisco Gonzalez-Lima).
... should be impressed enough by the effort he invested to agree with his conclusions.I had to print it out, put a spreadsheet together, and build my own model to fully digest it. It took a lot longer than I expected.
The evidence suggests otherwise.Kenny4/4 wrote:all things equal a lower LDL equates to a lower CHD-CVD risk.
MarcR wrote:So, "all things equal", higher LDL-C = longer life in relatively healthy populations.
The purpose of this review is to elucidate how low blood cholesterol promotes mitochondrial dysfunction and mortality by the loss of thioretinaco ozonide from opening of the mitochondrial permeability transition pore (mPTP). Mortality from infections and cancer are both inversely associated with blood cholesterol, as determined by multiple cohort studies from 10 to 30 years earlier. Moreover, low-density lipoprotein (LDL) is inversely related to all-cause and/or cardiovascular mortality, as determined by followup study of elderly cohorts. LDL adheres to and inactivates most microorganisms and their toxins, causing aggregation of LDL and homocysteinylated autoantibodies which obstruct vasa vasorum and produce intimal microabscesses, the vulnerable atherosclerotic plaques. The active site of mitochondrial oxidative phosphorylation and adenosine triphosphate (ATP) biosynthesis is proposed to consist of thioretinaco, a complex of two molecules of thioretinamide with cobalamin, oxidized to the disulfonium thioretinaco ozonide and complexed with oxygen, nicotinamide adenine dinucleotide (NAD+), phosphate, and ATP. Loss of the active site complex from mitochondria results from the opening of the mPTP and from decomposition of the disulfonium active site by electrophilic carcinogens, oncogenic viruses, microbes, and by reactive oxygen radicals from ionizing and non-ionizing radiation. Suppression of innate immunity is caused by the depletion of adenosyl methionine because of increased polyamine biosynthesis, resulting in inhibition of nitric oxide and peroxynitrite biosynthesis. Opening of the mPTP produces a loss of thioretinaco ozonide from mitochondria. This loss impairs ATP biosynthesis and causes the mitochondrial dysfunction observed in carcinogenesis, atherosclerosis, aging and dementia. Cholesterol inhibits the opening of the mPTP by preventing integration of the pro-apoptotic Bcl-2-associated X protein (BAX) in the outer mitochondrial membrane. This inhibition explains how elevated LDL reduces mitochondrial dysfunction by preventing loss of the active site of oxidative phosphorylation from mitochondria.
Puzzled ... seems the paper explains that high LDL is a desirable functional response to infection or toxins. We don't want infection or toxins, but if we do have them, we also want high LDL, right?SusanJ wrote:So there might be a corollary that you don't want high LDL with the presence of infection or toxins.
MarcR wrote:We don't want infection or toxins, but if we do have them, we also want high LDL, right?
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