For many years, lowering blood levels of low density lipoprotein cholesterol (LDL-C) has been a key target for individuals with cardiovascular disease (CVD) and healthy people at increased risk for developing such disease.
Statin drugs play a key role for risk reduction and are prescribed to millions of people worldwide. Apart from lowering blood cholesterol, these drugs have a number of effects that are potentially beneficial. For example, their anti-inflammatory effect may be of importance.
The death rate from CVD has declined rapidly during the last few decades in most developed countries. Research indicates that this may partly be due to statin therapy. However, despite the widespread use of statin drugs, CVD still contributes importantly to morbidity and mortality around the world.
A new class of drugs, so-called PCSK-9 inhibitors, appears to significantly lower LDL-cholesterol among individuals not taking statins as well as those already on statin therapy. Many experts believe these drugs may be helpful for individuals who don’t tolerate statins as well as those not achieving target levels of LDL-C on statin therapy. The new PCSK9 inhibitors are so-called monoclonal antibodies which are developed by biologic methods. They can not be administered orally and are usually given by a subcutaneous injection with a two to four weeks interval.
Cholesterol and Atherosclerosis
Atherosclerosis is a form of chronic inflammation resulting from complex interactions between lipoproteins, white blood cells, different components of the immune system and the normal elements of the arterial wall. This process can lead to formations of atherosclerotic lesions or plaques that often protrude into the lumen of the artery causing vessel narrowing which may ultimately affect blood flow. If this occurs in the coronary arteries, it may cause damage to the heart muscle and induce serious irregularities of heart rhythm. Rupture of an atherosclerotic plaque may lead to thrombosis causing an acute occlusion of the artery resulting in heart attack.
There are many factors that contribute to atherosclerosis, one of which is elevated blood cholesterol. Although cholesterol is important for many bodily functions, elevated plasma levels appear to play an important role in the initiation and progression of atherosclerosis. In animal models, atherosclerosis will not occur in the absence of greatly elevated levels of plasma cholesterol. High levels of plasma cholesterol also appear to be an important contributor to atherosclerosis in humans, although the threshold level that must be exceeded to produce clinically relevant disease appears much lower than that in animal models, possibly because lesion formation occurs over many decades. Atherosclerotic clinical events are uncommon among people with lifelong very low plasma cholesterol levels. It must be emphasised however, that it is lipoprotein that interact with the arterial wall and initiate the cascade of events that leads to atherosclerosis. Cholesterol is only one of many components of lipoproteins.
The Role of LDL and the LDL-Receptor
A causative role for cholesterol in itself has never been proven, although it appears that atherosclerosis will not occur without it being present in the arterial wall. Measurements of total cholesterol only indirectly reflect the lipoproteins that transport the bulk of cholesterol and are the most atherogenic. In fact, measuring the number of LDL-particles (LDL-P) appear more predictive of risk than the measurements of the cholesterol mass within these particles (LDL-C).
When inside the arterial wall, LDL can undergo a variety of modifications including oxidation, uptake by white blood cells called macrophages, formation of so-called foam cells and the initiation of inflammation. This cascade of events may ultimately result in an atherosclerotic plaque within the vessel wall. Obviously, cholesterol is not the cause of all this, but it is always involved. So, is it true that atherosclerosis is more likely to occur if plasma concentration of LDL-cholesterol is high than if it is low. The answer is yes, and it is supported by a number of scientific studies.
The liver is the gatekeeper for LDL and is responsible for its clearance. Liver cells express LDL-receptors on their surface, that bind LDL and remove it from the blood stream. After binding to the LDL-receptor, the LDL/LDL-receptor complex is moved to endosomes within the liver cells, where the LDL is released from the complex. The LDL receptor then moves back to the cell surface where it can bind to additional LDL-particles. This circle leads to removal of LDL-particles from the circulation which can be measured as a reduction in LDL-cholesterol levels. The free LDL left within the cells is transported to lysosomes and degraded into lipids, free fatty acids and amino acids.
PCSK9 (Proprotein convertase subtilisin-like/kexin type 9) is a protein that regulates the expression of LDL-receptors in the liver. PCSK9 is produced by liver cells and released into the blood stream. PCSK9 binds to the LDL-receptor on the surface of liver cells, together with LDL. It moves into the cell, together with the LDL-receptor/LDL complex. After LDL is released from this complex, the LDL – receptor/PCSK9 complex is taken up by lysosomes for degradation, preventing the recycling of the LDL-receptor to the cell surface. Thus, PCSK9 is responsible for the degradation of LDL-receptors and therefore plays a critical role in the regulation of LDL-cholesterol levels.
Interestingly, mutations on the human PCSK gene expression that lead to a loss of PCSK9 function are found in 1 – 3 percent of the population. These mutations have been associated with lower LDL-C and a significantly lower incidence of coronary heart events. Inhibition of the interaction between PCSK9 and the LDL receptor may potentially lower LDL-C. A monoclonal antibody directed against PCSK9 could potentially lower LDL cholesterol if it blocks the interaction of PCSK9 with the LDL – receptor on the surface of liver cells. This may allow LDL- receptors to recycle to the cell surface, after releasing LDL within the cell, instead of being taken up and degraded in lysosomes. Increased concentration of LDL receptors on the surface of liver cells may lead to increased clearance of LDL, which will be reflected as reduced levels of LDL-cholesterol.
PCSK-9 Inhibitors – Are They the New Wonder Drugs?
Whatever we think of cholesterol we have to keep an open mind about the new PCSK-9 inhibitors. There are large ongoing randomized clinical trials testing whether these drugs will prolong life and reduce the risk of future cardiovascular events among individuals with CVD. The results of these studies are eagerly awaited. The may provide answers to a lot of unresolved questions regarding the lipid hypothesis.
Some of the popular “internet doctors” have slammed the PCSK9 inhibitors before they are scientifically tested. Many of them believe that lowering cholesterol is always harmful and that statins drugs are always bad. Of course, if you believe so, you won’t like the idea of PCSK-9 inhibition. But remember, don’t let cognitive dissonance steer your thought processes.
I’ve written a lot about statin drugs on my blog and I worry that they are prescribed to millions of individuals who don’t need them. I also fear that adverse effects of statins are underreported. However, statins are very important drugs for many patients and they are unfortunately often not prescribed when they should be. The world is not black and white and neither is the art and practice of medicine.
Apart from lowering LDL-cholesterol, the new PCSK-9 inhibitors also lower blood levels of non-HDL cholesterol, triglycerides, apolipoprotein B and lipoprotein(a). However, it is important to keep in mind that a change in these biomarkers induced by therapy does not always incur clinical benefit. Ezetimibe, a potent inhibitor of intestinal cholesterol absorption, has been shown to be safe, tolerable and effective at lowering LDL-C, non-HDL cholesterol andapolipoprotein B, each of which has been correlated with improved clinical outcomes, alone or in combination with a statin. However, randomized clinical rials have shown mixed results and with a few rare exceptions, the use of the ezetimibe is not recommended for cardiovascular risk prevention.
Whether treatment with PCSK9 inhibitors will positively influence the atherosclerotic process and reduce risk among individuals with CVD remains to be seen. It is also important to learn if there is any collateral damage. We will not know the answer to these questions unless they are tested by scientific methods. Until then, I won’t believe anyone who pretends to know the answer.
45 thoughts on “Can Further Lowering of Blood Cholesterol Save Lives?”
The money quote from the good doctor
“In animal models, atherosclerosis will not occur in the absence of greatly elevated levels of plasma cholesterol. High levels of plasma cholesterol also appear to be an important contributor to atherosclerosis in humans, although the threshold level that must be exceeded to produce clinically relevant disease appears much lower than that in animal models, possibly because lesion formation occurs over many decades.
Atherosclerotic clinical events are uncommon among people with lifelong very low plasma cholesterol levels.”
Dr. Mercola is incorrect as early as the 2nd paragraph:
“In order to obtain the incredibly low LDL levels now recommended, you typically have to take a cholesterol-lowering statin drug, and sometimes two or three of them in combination.”
I’ve never heard of people taking more than one statin drug. They might switch you from a less potent one to a more potent one or vice versa, but it would be nonsensical to use them in combination.
You’re absolutely right. Here‘s the link if someone wants to read Dr. Mercola’s article.
Thank you. A thoughtful and well-reasoned approach.
What do you think of calcium testing? Reading lipid panels these days seems so indirect, and with them we’re left trying to guess the odds of bad outcomes. I’ve read that calcium tests can tell us whether our arteries have plaque build-up or not, and how much. For those at risk, that would seem to be a more logical and direct approach, to determine whether they really are at risk, or not.
I’d like to hear your thoughts on that. Thanks!
That’s a highly relevant question Richard. Coronary artery calcification (CAC) assessed by computerized tomography (CT scan) is a very strong predictor of future risk. For a variety of reasons including expense and radiation exposure concerns, routine CAC testing is not currently advocated. Whether CAC outperforms parameters lipid or lipoprotein testing such as LDL-C, Non HDL-C, LDL particle number (LDL-P) or Apolipoprotein B is still debated. Here is a very nice overview on the CAC, lipids and lipoproteins if you are interested. You may have to register fore Lecture-pad but I think everyone can do that, and it’s free.
I have a cac calcium test of 0 , I weigh 110 pounds and eat basically no cholesterol. No meat of any kind in 10 years? Basically nothing that walks on the Planet. My Cadiogist wants me to take a statinfor my high cholesterol! Im 75 years old! No aches or pains!
Another great balanced post Axel. PCSK9 inhibitors increase the clearance of LDL-C (and its surrogates) and Ezetimibe decrease absorption. Net effect is the same to lower blood cholesterol, yet Ezetmibe has not been shown to reduce CV risk. It will be interesting to see if the PCSk9 reduces risk or not.
I would love to see research looking at new therapies directly addressing the inflammatory component of atherosclerosis and CV disease. For instance therapies targeting the CV immune response, superoxide, etc.. Do you know of any research?
There is an ongoing randomized placebo controlled trial, called The CANTOS trial testing the efficacy of Canakinumab in patients with a history of myocardial infarction (MI) and raised levels of hsCRP suggesting chronic low grade inlfammation. Canakinumab is a fully human antihuman IL-1 beta antibody. It is administered by a subcutaneous injection every three months. Canakinumab is expected to reduce the risk of future occurence of major cardiovascular events in patients with past MI by preventing IL-1 beta mediated vascular wall inflammation. Ten thousand patients have been randomized in the trial.
There is also an ongoing study with methotrexate but I don’t know the exact inclusion criteria for that one but it is also aimed at testing the question whether reducing inflammation associated with the atherosclerotic process will translate into clinical benefit.
“Net effect is the same to lower blood cholesterol, yet Ezetmibe has not been shown to reduce CV risk.”
Isn’t this at least partially because ezetimibe has – mainly – been compared to other medication (e.g. niacin) and examined in study populations already on statins & with quite good lipid levels? Of course you need to compare any new potential treatment to the best existing option, but the outcome of that doesn’t necessarily mean that the drug per se doesn’t work. E.g. people who don’t tolerate statins may benefit from taking ezetimibe as these people benefit from LDL lowering.
Despite lowering LDL-cholesterol, Ezetimibe alone or in the presence of statins has not been shown to have any irrefutable beneficial effects on atherosclerosis or cardiovascular morbidity and mortality. Studies have shown that statins are much more effective than Ezetimibe when it comes to atherosclerois regression as well as clinical end-points. That may be due to the fact that statins lower LDL-cholesterol (or LDL-particle number, independent of cholesterol mass) more than Ezetimibe, or because statins partly (or mainly, if you prefer) work through other mechanisms (anti-inflammatory, vasodilatory, antithrombotic).
one the few reads from you that I actually like and find useful. As for Ezetimibe, a top-snotch lipid expert Evan Stein shares his views here:
As for saying that it has not been proved that cholesterol is the causal agent in influencing CHD, that’s like saying that the theory of evolution has never been proved. Are there actually any other people apart from the mathematicians that can prove something, is science even about proving something in the end? Scientists work with hypothesis. However, I think its rather compelling evidence for the lipid theory that that once an atherosclerotic artery is transplanted from a mouse to another mouse with low levels of cholesterol, the artery will heal quickly, the opposite is true when the damaged artery is transplanted to a mouse with high serum cholesterol.
Moreover, I feel that you left of unsaid about the HMG-CoA reductase inhibitors. A recent meta-analysis of mendelian randomized studies with over 312,000 participants found that inheriting any of the nine studied genetic variants associated with life-long reduced LDL, but which do not alter other known risk factors equally predicted a three-fold greater decreased risk of coronary heart disease per unit lower of LDL than statins do when started later in life. Furthermore, this study and others found that individuals who inherit a variant of the statin drug targeted HMGCR gene that is associated with life-long reduced LDL, have an equal degree lower risk of coronary heart disease as individuals who inherited any of the other 8 studied gene variants.
what studies do you have in mind? In ENHANCE -trial Ezetemibe was administered on a group of well-treated FH patients.
As Evan Stein basically concluded, LDL reduction has shown to yield decreased risk of CHD independent of the mechanism used, everything seems to work: hormone therapy (although this carry some serious side effects), bile-acid sequestrants, bypass of the illeal, diet (Ornish, Morrison, Pritikin, Esselstyn, etc) and genes (so far at least the effect of 9 different LDL lowering polymorphism have been studied including a gene that lower cholesterol via HMG-CoA). Why would Ezetemibe not work when given a chance? In other words, ENHANCE should work in a context of proper study design (non-treated people, meaningful LDL reduction, proper duration of the trial).
And, BTW, the PCSKY-9 blocking antibodies do not just “potentially” lower LDL. These drug result in staggering reduction in LDL as short-term clinical trials have already shown. Even Stein carried the first such trial, I cannot recall what was the name of it, though. But, it’s presented here:
E. Stein – Goal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects (GAUSS): Interim Results from a Randomized, Double-blind, Placebo-controlled Study
Annual Session of the American Heart Association November 4, 2012, Los Angeles
What are the trials which have studied the efficacy of ezetimibe treament vs plasebo, without prior/ongoing statin treament? Could you name a few? I can’t think of any studies in which ezetimibe would’ve been studied in e.g. 4S setting, that is, among CVD patients who can be expected to benefit the most.
In addition, yes, statins do lower LDL more efficiently than ezetimibe. Which is precisely why they work. The pleiotropic effects of statins are more like icing on the cake, as the statins which lower LDL the most have consequently been proven to be the most efficient drugs in reducing CVD events. Let’s leave the “mainly” remark out of evidence-based discussion until there’s actual PROOF of the pivotal role of the aforementioned pleiotropic effects, shall we?
I’m not aware of any studies that have assessed the efficacy of ezetimibe in patiens with CVD not taking statins. It world be unethical not to give statins in this situation unless those are statin intolerant patiens. Ezetimibe added to statin therapy further lowers LDL-C compared with statins alone, but plaque volume is not reduced (ENHANCE)and this is not translated intolerant fewer cardiac events.
Mia, yes to what Axel said above about other mechanisms. I was comparing the net effect of Ezetimibe to PCSK9 inhibitors to suggest that if these medications only work by lowering blood cholesterol concentration and have no other mechanisms of action, perhaps that is why they might NOT reduce cardiovascular risk. There is still much to learn about PCSK9 inhibitors.
Mi(k)e has it goin’, I agree,
well done, Mie. I like that we can agree at least 1% of the time. It’s hard to make a point against the LDL theory by concluding that Ezetemibe doesn’t reduce the amount of plaque in arteries of well-treated FH patients (who as a consequence already have rather low LDL). And, as my medpage -today youtube source revealed, there are atherosclerosis experts out there who claim that ezetimibe has unwanted properties that potentially jeopardize any benefits that are gained by LDL lowering. I cannot judge whether this is correct or not, but at least this issue ought be brought to table if we are about to question the notion that LDL reduction is beneficial by itself. A view that is held by most of the prominent atherosclerosis experts around the word, if I’ve understood it correctly.
BTW, Doc, this is what your American colleague, the chief inspector of TNT trial, John LaRosa concluded about a healthy diet judged from a statin -trial context. Certainly this line of evidence must also be taken into account when discussing about dietary issues, (although not the direct topic of this thread):
“Chimpanzees eat very little fat. They have LDL levels in the range of 40 to 70, and they don’t get atherosclerosis. He noted that levels of LDL below 70 are on a par with those of nonhuman primates who don’t develop atherosclerosis, adding that, like these primates, humans were designed to be vegetarians. “Our dental anatomy suggests that we are not meant to be meat eaters. Animals that eat meat have sharp tearing teeth, while we have flatter teeth more similar to vegetarian animals. I believe humans are not anatomically or metabolically designed to be meat eaters, and because we do consume animal fat that’s why we get atherosclerosis. Chimpanzees don’t eat meat; they eat very little fat. They have LDL levels in the range of 40 to 70, and they don’t get atherosclerosis. Maybe we wouldn’t get atherosclerosis either if we had levels this low.”
Neal Barnard on an exceptionally well written commentary on the SFA meta-analysis (Chudrowy, 2014), I warmly recommend this piece, good read.
Medpage today did a 3-piece short-clip of the whole ezetimibe debate: I already posted the first part, but here’s 2 & 3. Good material.
“I’m not aware of any studies that have assessed the efficacy of ezetimibe in patiens with CVD not taking statins. It world be unethical not to give statins in this situation unless those are statin intolerant patiens.”
Well then, there you go. Precisely my point. What this means is that there’s no need to favour ezetimibe therapy in people who tolerate statins. What this doesn’t mean is that ezetimibe doesn’t work and/or that it shouldn’t be used in patients who need to lower their LDL levels but cannot handle statins.
“Ezetimibe added to statin therapy further lowers LDL-C compared with statins alone, but plaque volume is not reduced (ENHANCE)and this is not translated intolerant fewer cardiac events.”
ENHANCE was not powered to inspect CVD events – it was powered to study whether Vytorin, a combination drug containing simvastatin and ezetimibe, could stop/reverse plaque growth, the primary outcome being the possible reduction in intima–media thickness of the carotid-artery wall. The study population consisted of FH patients which meant that the LDL levels achieved, although considerably lower in the intervention group, where nowhere near the values in which you could expect the reversal of atherosclerosis.
Just because there’s a trial showing X doesn’t mean it’s valid in inspecting Y, right? 🙂
“Chimpanzees don’t eat meat; they eat very little fat. They have LDL levels in the range of 40 to 70, and they don’t get atherosclerosis. Maybe we wouldn’t get atherosclerosis either if we had levels this low.”
I eat meat, full fat diary AND I take 10mgs Atorvastatin/day + other targeted supplements an my last blood work (2/24/14) shows LDL of 47!
for “natural” and effective LDL-lowering therapy, check out some of these dishes at Forks Over Knives website. This stuff looks absolutely delicious. And, it’s very cheap to pull it off, very affordable foods. Who would not eat this?
Regardless – why would it matter how my LDL of 47 was achieved? That’s way lower than Dr. Esselstyn achieved with his patients and they were on a very low fat diet + statins!
My food is affordable – raw goat milk, kefir, grass fed beef purchased at the farm.
I don’t know whether it matters or not, probably not. But there are other chronic diseases that have been connected with the intake of animal foods. Although, in many of these diseases LDL cholesterol seem to play out a pivotal role (prostate cancer progression, Alzheimer, etc). Moreover, Esselstyns and Ornish patients seem to enjoy immunity from atherosclerotic events even with sub-optimal LDL numbers. Nevertheless, drinking raw goat milk seems like a very stupid idea already from a sheer food hygiene perspective.
Esselstyn’s own colleague at the Cleveland heart clinic achieved much lower LDL that you did, and without statins. He had his digit somewhere around 38mg/dl. Anyways, you seem to have genetically very efficient cholesterol clearance, but why would we even make any an issue out of this? I would be surprised if John LaRosa is not aware that there some people who can eat lot of animal fat and still have low LDL at midlife. Sorry, but you don’t come out as a rational thinker.
One of the first things Dr. Hyman did was to wean Mr. Clinton off his previously prescribed vegan diet. Despite persistent news media reports that he is vegan, Mr. Clinton does occasionally eat fish and lean protein. “It’s hard being a vegan to eat enough good, quality protein and not have too much starch,” Dr. Hyman said over lunch at the Four Seasons restaurant in New York. “I know a lot of fat vegans.”
“drinking raw goat milk seems like a very stupid idea already from a sheer food hygiene perspective”
Do a Google search and see how many people die from food poisoning from veggies as to the number who die from drinking raw milk.
As to the safety – sine my wife and I live in NY
To sell raw cow milk directly from the farm to consumers, a producer is required to obtain a Raw Milk Sales Part 2 permit. Even if the farmer gives away one gallon of milk, a permit is required. To receive a permit the farmer must have:
A Brucellosis ring test on file with the Department’s Division of Animal Industry.
A Tuberculosis test performed on each animal.
The farm operation must be enrolled in the Quality Milk Production Services (QMPS) program and must have a report showing that each animal was tested for pathogens, including but not limited to Staph. Aureus and E. Coli.
The farm operation must have a milk sample tested for the following pathogens: Salmonella, Listeria, Escherchia coliform, E. Coli 0157:H7, Campylobacter, and Staphylocci. These tests are required initially and monthly.
Satisfactory farm water test must be on file
In regards to the Clinton’s fair,
yes, Clinton no longer takes advice from a cardiologist, professor and a highly acclaimed clinical researcher, Dr. Dean Ornish whose studies have been published in some of the most prestigious scientific journals and whose program is covered by the Medicare, instead he seem to listen GP who likes functional medicine whose program is not covered by Medicare (this is our and Clinton’s loss):
Dr. Hyman carries packets of macadamia nut, walnut or coconut butter in his jacket pocket, and he advises busy patients like Mrs. Clinton to do the same. Grass-fed beef and turkey jerky and cans of wild salmon are also recommended travel snacks”.
Now, what do we make about this; every single prospective cohort study ever published looking the issue, shows that vegans have the most healthiest BMI out of all dietary groups, probably the most informative ones are the seventh day adventists cohorts, and even if most vegans were fat we ought to legitimately ask did they got fat by eating quinoa, oats, kale and strawberries or is there possible something else join’ on.
“Do a Google search and see how many people die from food poisoning from veggies as to the number who die from drinking raw milk”.
That’s like saying that scuba diving carries absolute no risks because people die more often in car accidents. Most Americans eat at least some vegetables every day, whereas pretty only the Western Price Foundation people a drink raw milk, that’s like what, 0,001% of the US population?
As I said, you don’t come out as a very rational thinker, but at least you doing something right, taking 10mgs of atorvastatin daily, that is.
Raw milk sickens more than widely reported, study says
Again I ask – if my current TC is 100, LDL is 47, HDL is 44, Triglycerides are 43 then HOW I go to those levels should be irrelevant – correct?
“Chimpanzees don’t eat meat; they eat very little fat. They have LDL levels in the range of 40 to 70, and they don’t get atherosclerosis. Maybe we wouldn’t get atherosclerosis either if we had levels this low.”
Maybe..? He doesn’t seem to share your absolute faith ROFL.. he must be an heretic 😛
As for Chimpanzees not eating meat: as ever, you are playing fast and loose with the truth…
Chimps Hunting Monkeys
Chimpanzees team up to attack a monkey in the wild – BBC wildlife
Spear-Wielding Chimps Studied
“Unlike other apes such as gorillas and orangutans which are almost entirely herbivorous (plant-eating), chimps are classified as omnivores. This means that, like humans, they eat a variety of plant and animal foods.
While the vast bulk of the chimpanzee’s diet is made up of plant foods including fruits, seeds, nuts, leaves and flowers, they will also eat insects and even larger animals that they have hunted and killed themselves.”
Remember – according to ROTF I’m not a rational thinker – maybe you’re not one either?? If so welcome to the club!
you are so fervently interested in proving me wrong that you loose every drop of logical consistency. I am not bending the truth, I quoted John LaRosa, who told to the press that chimps eat very little fat, you took this as straw man and insisted that I claim that chimps eat no animal fat at all. I am very aware of the fact that chimps are highly opportunistic omnivorous. I also know that it has been shown that when diets rich in cholesterol and saturated fat are fed to monkeys of the genus Macaca, including the rhesus monkey and the crab-eating macaque, they experience heart attacks at approximately the same rate as high-risk populations living in developed nations.
Be kind to yourself, stop banging your head on the wall.
@ROFL… on the contrary, I have little need to prove you wrong, as you do such a fine job of contradicting yourself at every turn.
I was well aware that you were quoting LaRosa… in fact I used the portion that you bolded “Chimpanzees don’t eat meat…” which is clearly baloney… so either he is an idiot, or you are an idiot for quoting him in support of your position.
Stop banging your own head against the wall… you cannot possibly think that you have any credibility here?
Again I ask – if my current TC is 100, LDL is 47, HDL is 44, Triglycerides are 43 then HOW I go to those levels should be irrelevant – correct? Or do I have to it a certain way for it to count?
“He (LaRosa) noted that levels of LDL below 70 are on a par with those of nonhuman primates who don’t develop atherosclerosis, adding that, like these primates, humans were designed to be vegetarians. “Our dental anatomy suggests that we are not meant to be meat eaters. Animals that eat meat have sharp tearing teeth, while we have flatter teeth more similar to vegetarian animals. I believe humans are not anatomically or metabolically designed to be meat eaters.”
This is so pathetically stupid on so many levels it’s pathetic. If humans were designed to be vegetarian how come there is no evidence of any society doing that??
for somehow Charles managed to come up with the bullet-proof money quote from Doc’s article, see the first comment on this text. You again could not grasp the take home message of LaRosa’s postulation. Thus, let me help you. John LaRosa’s point was that LDL levels under 70s are physiologically normal (lower the better), and that the closest relatives to humans have very low LDLs as a result for eating “very little fat”. Avoiding artery clogging saturated fats is a no-brainer given the whole Darwinian foundation of our biomedical research paradigm.
take it easy, I am sure you are fine with your LDL score and yes, the choice of the mechanism used to lower LDL seems to be irrelevant in regards to protection from CHD (and possible host of other chronic disease). Statins probably work in reducing the risk of dementia and prostate cancer as well (via the LDL lowering properties).
“Considerable evidence supports the plausibility of an association between low cholesterol and reduced risk of high-grade prostate cancer. Several studies have reported an association between statin use and reduced risk of advanced or high-grade prostate cancer (15, 16). In addition, an inhibitory effect of low cholesterol on prostate cancer progression is biologically plausible. Laboratory evidence suggests that lowering cholesterol levels could inhibit cell-signaling pathways that are important for prostate cancer progression (17). This hypothesis is supported by experiments in mice in which lowering serum cholesterol with dietary modification or a cholesterol-lowering drug reduced the cholesterol content, size, and vascularity of human xenograft prostate tumors (18).
@ROFL.. again, on the contrary it seems that you are the one in need of help and clarification…
If you really think that folks here will accept “science”, or even medical advice from someone (or a person who quotes them) who evidently gets his knowledge of the natural world from Disney Studios, then you’re every bit as much of an idiot as I suggested above.
“…and that the closest relatives to humans have very low LDLs as a result for eating “very little fat”.”
Do you really need to be reminded that correlation does not show causation? Yes Chimpanzees may ingest less fat than many humans, yes they may on average have low LDL values (as measured). You may be utterly convinced that one causes the other… I am not. If saturated animal fat is so damned dangerous to humans, then why is that the way we (and pretty much every animal) have evolved to store our major energy reserves? What would Darwin have to say about that?
Chimpanzees may well be our closest living relatives but there are also significant differences such as brain size (at least in some of us). Adequate fat intake is vital to the growth and maintenance of an healthy brain.. perhaps therein lies your problem.
the causal relationship of dietary (animal) fat to the serum lipids of chimps has been demonstrated in utterly and rigorously controlled feeding experiments. There is as much of discussion about this in the scientific community as there is discussion or debate about validity of theory of evolution.
I am all favor of adequate fat intake for growth and maintenance of healthy brain, the farmers in Korean peninsula had their TC cholesterol around 117mg/dl during the 1950s as a result of eating a diet with very little fat. They did not get CHD as expected.
Catalyst Corrected 4 (The Preset Mindset)
@ROFL… utterly and rigorously unconvincing, without more than just the word of someone utterly lacking credibility like yourself. You’re telling us that chimps had saturated animal fat (in what form?) added to their diet without ANY other changes to diet or lifestyle and started dropping dead with CVD?
As for yet another link to one of Pee Pee’s awful videos? Seriously, this is what he sounds like…
Here’s an interesting discussion about the Chimpanzee diet from Miki Ben-Dor, self-described as, “I am 61 old Ph.D candidate writing a thesis about human evolution and nutrition at the archaeology department of Tel Aviv University.”
Notably… “For some reason nutrients percentage numbers by weight pervade the ancestral nutrition scientific literature but they really mean very little…”
[my comment] One has to question the motivation of this tactic, which clearly bumps up the percentage (by weight) of carbohydrates) but anyhow once converted to the more normally used and more meaningful percentage of calories…
‘In summary, the chimp diet is 50-55% fats, 24-29% glucose and 21% protein – not “one that contains high amounts of complex carbohydrates and only small amounts of fat” quite the opposite. Luckily for the chimps their diet has no resemblance whatsoever to the SAD diet and if analyzed properly may indeed show the way to “the healthiest human diet” – high in fats and moderate in protein, and carbs with some fruits included for old time’s sack.’
AND these numbers don’t even seem to include the occasional monkey meat, insects, eggs, birds, reptiles (pretty much anything they can lay their hands on) which evidently wild Chimpanzees include …despite what Disney would have us think, LOL
Miki Ben-Dor seems like a top-notch researcher to me 🙂
Again, I would dearly love to see the methodology and in particular the diets fed to both groups of Chimpanzees in ROFL’s “utterly and rigorously controlled feeding experiments”
I am sure Miki Ben dorm as a 61 year old student is an excellent choice to pick nutrition information (and obviously he is world class scholar), where do we need the WHO and AHA anyway when he has already figured out the optimal diet for us? So, the chimps eat a lot of animal fat (unlike everyone else including John LaRosa seems to think), have simultaneously very low LDL levels and are protected from the CHD? You got to love the internet….LOL!
Armstrong and colleagues conducted an experiment ‘designed to demonstrate a null point of the effect of dietary cholesterol on the arterial intima’, by comparing a group of rhesus monkeys fed a cholesterol-free diet with a group fed cholesterol equivalent to that found in only half of a small egg in the average human diet of 2,000 calories per day (43µg/kcal). However, even when fed in very small amounts dietary cholesterol still had a significant adverse effect on these monkeys arteries after a period of only 18 months. Armstrong and colleagues concluded:
No null point for the effect of dietary cholesterol on arterial intima was found even at an intake level far below that conventionally used for the induction of experimental atherosclerosis in the nonhuman primate. The intimal changes found in response to very low cholesterol intake imply that subtle qualitative alterations in lipoproteins are of critical importance to our understanding of lesion induction
It has also been demonstrated that the cessation of a cholesterol-rich diet and the subsequent lowering of serum cholesterol results in the regression of atherosclerosis in various mammalian and avian species, including herbivores, omnivores, carnivores and nonhuman primates. In one experiment Armstrong and colleagues induced severe atherosclerosis in rhesus monkeys by feeding a diet with 40% of calories from egg yolks for 17 months. The egg yolks were then removed from the monkeys diet and replaced with a cholesterol-free diet with either 40% of calories from corn oil or low-fat chow with 77% calories from sugar for three years, resulting in a reduction of serum cholesterol to <140 mg/dl and a marked regression of atherosclerosis.
Again, I would dearly love to see the methodology and in particular the diets fed to both groups of Chimpanzees in ROFL’s “utterly and rigorously controlled feeding experiments”
…as in your assertion that “…the causal relationship of dietary (animal) fat to the serum lipids of chimps has been demonstrated in utterly and rigorously controlled feeding experiments.”
As for a PhD candidate being 61, I personally see maturity and life-experience being a benefit to such studies. But then of course it speaks to the weakness of your position that you immediately leap to ad hominem to try and discredit him, rather than what he writes.
“the choice of the mechanism used to lower LDL seems to be irrelevant in regards to protection from CHD (and possible host of other chronic disease).”
SO – an Ornish type diet is not needed after all!
Here’s the crux of this whole post: many people have been ripping off Taubes’s work. They have been ripping him off without attribution and making money doing it. You know how I know they are ripping him off? It’s not just that their verbiage and syntax are eerily similar. Much like my old professor the clincher is that these journalists and bloggers and charlatans all make the exact same mistake Taubes made with respect to the Y&H paper. In fact, in many of these authors make it painfully obvious that they haven’t read ANY of the papers that they are making claims about.
Now it’s one thing to blog about, say, toasters and misinform your readers, but when you are dispensing health advice and you have no idea what you talking about… well, that can impact people’s lives in a very real way. And a very negative way.”
that’s a good article. Paleo community is no different from any other pseudoscience sect who end up creating their own parallel reality. The Cremlin revisionists did the same.
CONCLUSIONS: Genetically reduced concentrations of nonfasting plasma triglycerides are associated with reduced all-cause mortality, likely through reduced amounts of cholesterol in remnant lipoproteins.