— Slide 33 from Plant Positive‘s “How Much LDL?“
So, finally (!), I’m going to get into really examining the data presented in this Plant Positive video. The video is comprised of 42 slides plus a voice-over narrative. This post will begin to discuss the study mentioned at slide 33, at location 15:06 into the video. I chose this slide to open with because Plant Positive says it is devastating to the arguments of the people he calls confusionists and cholesterol deniers. Here’s the slide ID plus link to the journal abstract (in blue) and the indented Plant Positive narrative text (in green):Slide 33, 15:06 – (journal) Overall mortality, incremental life expectancy, and cause of death at 25 years in the program on the surgical control of the hyperlipidemias
I’ll briefly remind you of the amazing work of Henry Buchwald, who proved that LDL lowering through surgery led to fewer cardiac events and greater life expectancy. I think this is devastating to confusionist claims.
If this study is indeed truly “devastating to confusionist claims”, well and good! Then another controversy has been resolved and we can move along to something else!
So, first of all, what is this study?
To answer that, let’s look at two abstracts describing the study: POSCH design and methodology (1989) and POSCH entry characteristics (1991). From the abstracts, POSCH = Program on the Surgical Control of the Hyperlipidemias. The research group located 838 patients (760 men / 78 women), aged 30-64, who each had survived exactly one documented “heart attack” (called myocardial infarction (MI) in the journals). An additional requirement for entry into the study was that the patients had high cholesterol or high LDL plus their total cholesterol couldn’t be brought down to the “normal” range with dietary control.
They divided the patients into two groups, the “study” group and the “control” group. The study group would receive a surgical intervention consisting of a partial ileal bypass operation. The control group would not.
What is a “partial ileal bypass” (PIB)?
There’s a good diagram of it here. The small intestine is a digestive organ which connects the stomach to the large intestine. In PIB surgery, the small intestine is severed about 1/3 to 1/2 of the way from where it empties into the large. This final 1/3 to 1/2 of the small (called the ileum) is left hanging from the end of the large. The remaining 2/3 to 1/2 (still connected to the stomach) of the now shorter small is rejoined to the large a little higher up than where the now useless ileum portion hangs.
How could this surgery affect LDL cholesterol?
I found a very readable MedScape article written by Buchwald (who originated this procedure) here, but before it can be understood, you need to be familiar with the process of cholesterol recycling, which is part of what’s called “enterohepatic recirculation“, which I’ll try to explain below.
Cholesterol is required in order to get dietary fats and fat-soluble vitamins into your body. The problem is that without some help, fats cannot dissolve into a water-based fluid (like your last meal). You know, fat floats on the top. So, in order to get the fat “into solution”, your body makes a substance called “bile salt” by combining single molecules of cholesterol with single molecules of amino acids. This acts to “emulsify” the fats on contact in the small intestine, similar to the way that soap dissolves fat from dishes or helps remove grease from your fingers. The amino acid side of the bile salt is friendly to water and the cholesterol side is friendly to fat – so the fat globules from that last meal will now disperse and be absorbed.
The cholesterol used in the bile salts must come from one of three sources: dietary intake, your body’s internal stores and/or internal synthesis. When everything is working as it should, when you eat a little more cholesterol than your body needs, excess cholesterol is dumped in the form of bile salts that pass out in the stool. Of course, all bets are off if you consume cholesterol at a higher rate than your body has evolved mechanisms to dispose of the excess. And, on the other hand, if you aren’t in cholesterol overload, the body is thrifty and reabsorbs the bile salts when their transport work is done. As it turns out, this re-absorption occurs in the ileum – hence the name “ileal bypass surgery”. When the ileum is taken out of the loop, the cholesterol-laden bile salts can no longer be reabsorbed. They are forever lost and the recycling mechanism is defeated. If your body needs more cholesterol, it will either have to make it new or get it from diet; according to Buchwald, “cholesterol absorption is decreased by 85%” with this surgery.
So, now I think I understand enough about this study to evaluate it and I hope anyone reading this does too.
What would need to be proven for this to be “devastating to confusionist claims”?
… all of the following:
- Following their surgery, the surgical group must have permanently lowered LDL cholesterol as compared to the control group.
- The surgical group must experience significantly reduced mortality and/or morbidity as compared to the control group, ie “improved outcomes”.
- It must be shown that the LDL cholesterol lowering itself was responsible for the improved outcomes.
- It must be shown that the results from this study can be extrapolated to the population at large.
- The source of funding for the study must be examined for possible conflict of interest.
I have no problem with with items 1, 2, and 5, above; those criteria were all met to my satisfaction.[see 1] It’s only the 3rd and 4th that I have issues with.
Can the LDL cholesterol lowering be shown to be the primary cause of the improved outcomes?
That would require eliminating all other possible confounding causes (for the better outcomes). One of the strengths of this study is how few confounders there are. Reduced triglyceride levels for the surgery were mentioned, but that can’t be relevant considering all the other research. Obesity reduction is also ruled out.[see 2]
Firstly, it must be acknowledged that this is a very cleanly designed study. Yet there’s one factor that I can see that’s been mentioned but not discussed: cholesterol turnover. According to the author, the “partial ileal bypass resulted in
- “a 60% reduction in cholesterol absorption;
- “an increase of 380% in the fecal sterols, both in the neutral sterols and in the bile acid fraction;
- “a 450% increase in cholesterol synthesis;
- “a 300% increase in cholesterol turnover and
- “a 35% reduction in the body cholesterol pools”
If the cholesterol is turning over three times faster, then it is not sitting around as long degrading into toxic oxidized forms. Many (if not all) of these patients are heterozygous for familial hyperlipidemia. That means their LDL receptors which are normally supposed to clear LDL cholesterol from the blood stream are either dysfunctional or of insufficient number. So, for these people, their LDL cholesterol (LDLc) just sits around getting old. Their whole cholesterol recycling program comes to a screeching halt. This LDLc just gets pumped around their body forever – the body never being able to get to it to use it for something – until the cholesterol finally lodges someplace.
It could be a situation somewhat like meat left sitting around on the counter; you know after a while, it’s gonna get rotten. But you wouldn’t say the meat was at fault. True, meat spoils more rapidly and to our greater detriment than vegetative material and so requires greater care in handling than vegetables. But, still, the cause of the problem was the idiot who left the meat on the counter, not the meat!
If the too-long-on-the-counter hypothesis is correct, then the proper item of concern is not how much cholesterol is being carried by LDL particles at the moment of the lab blood draw, but rather how long the cholesterol molecules have been in circulation and how well they’ve been protected from degradation. This would affect vegans and non-vegans alike, although, generally vegans will have lower circulating levels of cholesterol and so, lower levels of damaged LDLc. I hope everyone can appreciate the distinction between indicting LDLc and, instead finding ways to measure degradated LDLc and get rid of it.
This is as far as I want to go with part 1 of this discussion of slide 33. Part 2 will continue with a few more confounding possibilities and then I’ll discuss item 4 in the “prove it” list. Sorry, this is so long and complicated. Hopefully subsequent slides will be easier to analyze, now that I’ve explained so much about cholesterol.
- Letter to the Editor pub 2001:”… this study was funded solely by the National Heart, Lung, and Blood Institute and received no funding from the pharmaceutical industry. … .The lipid modifications in POSCH were equal to or greater than those achieved in the later statin trials.2 POSCH demonstrated statistically significant reductions in overall mortality, atherosclerotic coronary heart disease mortality, atherosclerotic coronary heart disease mortality combined with recurrent myocardial infarction, the incidence of coronary artery bypass grafting and percutaneous transluminal coronary angioplasty, and peripheral arterial disease.2,3 POSCH, an arteriographic as well as a clinical trial, also confirmed arrest and regression of atherosclerotic coronary artery disease on sequential arteriograms with up to 10 years of follow-up.4“
Partial ileal bypass surgery – Wiki claims “Ileal bypass surgery was mainly performed prior to the introduction of effective oral medication for the most common hypercholesterolemias. It is occasionally used in the surgical treatment of obesity.“, but in this case the study author states that weight loss was not significant.