Another Devastating Blow to the Cholesterol Deniers

A new study powerfully validates important points I repeatedly asserted in my cholesterol videos - heart disease risk is strongly mediated by lifetime cholesterol levels (rather than end-of-life levels) and LDL in particular is a key causal factor in heart disease. This elegant research by Dr Brian Ference of Wayne State University also further damages the claims of the few vocal cholesterol deniers that statins work through effects other than lipid lowering. How can a single study accomplish all this? It examined the effects of multiple cholesterol-lowering genotypes on heart disease risk.

Viewers of my videos will recall that genetic variations affecting LDL dramatically influence cardiac mortality, from homozygous hypercholesterolemia at one end of the spectrum (in one case causing a fatal heart attack in a fifteen year old) to hypobetalipoproteinemia on the other. These conditions are compelling evidence for the lipid hypothesis as they eliminate confusion which may arise from other methods of inquiry into the clinical significance of high cholesterol (off-target drug effects, the limitations of various animal models, confounding effects of various nutritional factors, patient comorbidities, LDL phenotype, etc.). With genetic research in humans, we can now bypass all that in favor of a clean look at the specific effects of LDL concentrations, pure and simple. We don't need to be distracted by failed $800 million drug trials that crackpots like Mark Sisson can use to confuse and endanger people.

Dr Ference's team studied nine single nucleotide polymorphisms which influence LDL levels. Paleo followers might appreciate Ference's clever use of a mechanistic principle that underlies evolution (Mendelian inheritance) to uncover the natural randomized trial being conducted all around us, allowing those SNP's to act as stand-ins for lipid-lowering therapies. As these SNP's are present from birth, this approach allowed for a comparison to be made between the effectiveness of statins administered later in life with low LDL levels maintained from childhood. The results are powerful: a threefold-greater benefit for natural early-life low LDL versus later statin-lowerd LDL. Ference stated, "the effect of each of the included SNPs on risk of CHD is mediated largely or entirely through effect on circulating levels of LDL, rather than through some other pleiotropic effect." This should cause us all to appreciate the potential for genetic variation to blur the effects of lifestyle factors like diet on disease. Because we are infinitely complicated homeostatic biochemical machines, there will always be a way for the cholesterol deniers to find superficial exceptions to the lipid hypothesis. With this study, you may once again be assured that the lipid hypothesis is rock solid.

Dr Ference is due credit not just for his ingeneous research, but for his responsible interpretation of his findings. He stated, "We are not suggesting that everyone take statins from childhood; rather, that lowering LDL through more attention to healthy diet and exercise from a young age could make a big difference to public health." His work strongly supports a prevention and public health strategy, and places LDL directly in the spotlight where it belongs. Dr Ference is not content with a general population with subclinical atherosclerosis. I couldn't agree more. I hope his work will bring clarity to this heretofore needlessly muddled issue.