With an avalanche of research questioning whether LDL cholesterol (LDL-C), independently of any other factors or biomarkers, plays a role in the etiology of cardiovascular disease, it’s hard to believe studies keep coming out trying to massage and manipulate data to support a hypothesis that is increasingly being abandoned. Nevertheless, this remains a very controversial topic, so it’s worth taking a closer look when one such study appears in a prestigious journal like The American Journal of Clinical Nutrition (AJCN). So let’s do that with a paper published just last month: “Effects of red meat, white meat, and nonmeat protein sources on atherogenic lipoprotein measures in the context of low compared with high saturated fat intake: a randomized controlled trial.”
The study the paper was based on—called the APPROACH trial (Animal and Plant Protein and Cardiovascular Health)—involved subjects 21–65 years old with a body mass index (BMI) 20–35 kg/m2 randomly assigned to a diet either high or low in saturated fat, and within those parallel arms, allocated to protein from red meat, white meat, or non-meat protein consumed for 4 weeks each in random order. Primary outcomes were LDL-C, total/HDL-C, apolipoprotein B (apoB), and small + medium LDL particles.
Results showed that, independent of the saturated fat content of the diet, LDL-C and apoB were higher after consuming red and white meat compared with non-meat proteins. Total/HDL-C was not affected by the protein sources, nor were small and medium LDL-particle counts. Researchers determined that the increase in LDL-C was due mainly to increases in large LDL particles—the ones believed to be the least atherogenic. (“Large buoyant” LDL particles make up the pattern A lipoprotein profile. It is not pattern A, but rather, pattern B—characterized by small, dense LDL particles—that is associated with cardiometabolic disease.)
Primary outcomes did not differ significantly between red and white meat. According to Ronald Krauss, MD, a co-author on the AJCN paper: “When we planned this study, we expected red meat to have a more adverse effect on blood cholesterol levels than white meat, but we were surprised that this was not the case – their effects on cholesterol are identical when saturated fat levels are equivalent.”
On the surface, this finding seems to suggest that red and white meat are “equally bad” when it comes to worsening cardiovascular risk factors. (What a disappointment to all the people who spent decades passing up juicy steaks in favor of dry chicken breast!) The title of the press release from The University of California even says they are “equally bad”—but it says they’re equally bad for cholesterol, not for cardiovascular disease. Having the same effect on cholesterol and this being a “bad” thing assumes increased LDL-C is independently causal for CVD or atherosclerosis. If red and white meat increase LDL-C to a similar extent, then they are “equally bad,” but if increased LDL-C is not automatically a risk factor for CVD, then neither is bad to begin with. (Indeed, serum LDL-C often does not correlate with actual arterial calcification. The coronary artery calcium scan may be a better indicator of the actual presence of atherosclerosis—the disease in place—compared to the amount of cholesterol in the bloodstream.)
It’s essential to note that all primary outcomes of this study are surrogate markers. They are not clinical endpoints. High LDL-C is not a disease. It’s not a heart attack or other cardiovascular event, and it’s being increasingly questioned whether it’s even a risk factor for these.
Setting aside the protein sources for a moment, independent of protein source, the higher saturated fat diets increased LDL-C, large LDL particle count, and apoB compared to the diets lower in saturated fat. This might seem like a strike against saturated fat, but it’s certainly not news that consuming saturated fat tends to raise LDL-C. The part that’s up for debate is whether this is harmful for cardiovascular health—and many researchers assert that it isn’t. Some cardiologists have gone so far as to state outright that “saturated fat does not clog the arteries,” while other researchers have written that saturated fat is part of a healthy diet:
“Numerous meta-analyses and systematic reviews of both the historical and current literature reveals that the diet-heart hypothesis was not, and still is not, supported by the evidence. There appears to be no consistent benefit to all-cause or CVD mortality from the reduction of dietary saturated fat.” (Gershuni 2018)
The public has long been cautioned to reduce consumption of red meat and favor poultry, seafood and plant proteins instead. According to the UCSF press release, the study results “indicated that restricting meat altogether, whether red or white, is more advisable for lowering blood cholesterol levels than previously thought. The study found that plant proteins are the healthiest for blood cholesterol.” Again, this is based on the assumption that higher LDL-C is a causal factor in CVD, and it’s clear by now that numerous researchers and clinicians no longer believe that it is.
This is a topic that remains controversial and presents many unanswered questions. Healthcare professionals should continue to follow the science and strengthen and solidify their understanding of the biochemical and physiological mechanisms at work, rather than taking sensationalist headlines at face value.