Search This Site!
Nutrition Past and Future

26 Cholesterol Confusion 9 "Brown and Goldstein Were Wrong" 

The cholesterol confusionists usually give a wide berth to Mike Brown and Joe
Goldstein and their transformational research investigating atherosclerosis and
cell biology. The confusionists would like for you to believe that the lipid
hypothesis is merely the cooked-up fantasy of Ancel Keys and that it is only
supported by a few old animal studies and some low-quality epidemiology.
Attempts to besmirch the accomplishments of these two guys, however, would just
prove to be fruitless and embarrassing for them. Most confusionists know better
than to bring attention to their insights, which are so damning of high blood
cholesterol. A couple confusionists have attempted to take them on anyway, and
in this video we will gawk and wince and cringe at their ill-considered remarks.

I have two such examples to show you in this video. The first is this excerpt from
Uffe Ravnskov's The Cholesterol Myths. In this passage he is writing about the
work of Brown and Goldstein that won them a Nobel Prize in 1985. They had been
trying to understand what caused the tragically swift and severe heart disease
of the unlucky few with familial hypercholesterolemia when they discovered and
then described the LDL receptor. Your cells have receptors that connect to the
apoB protein on the LDL particle. It is with that receptor that the cell
connects to the LDL particle, sucks it in, and incorporates its lipid contents.
People with the most severe form of FH lack these receptors entirely. With
nowhere else to go, LDL cholesterol concentrates in the blood stream and
collects on the walls of arteries, causing plaques to form. One of the early
steps in plaque formation is the collection of cholesterol-filled foam cells on
the artery wall. Here you see that Ravnskov believes he has found a simple
logical problem with all this. FH patients have foam cells. But they have no or
few working LDL receptors. How can cholesterol get into their foam cells if FH patients
have no LDL receptors?, he wonders. Please read this so that you can see that
this is exactly what he is saying here. I am not mischaracterizing his
criticism. He says he has come up with a crucial question. He thinks he is
undermining the lipid hypothesis with this observation. He thinks the answer to
this is not known, and he thinks he knows better about all this than Brown and

Ravnskov apparently doesn't know what foam cells are. Low-carb lipidologist Thomas Dayspring does know what they are. Foam cells are macrophages that gobbled up a bunch of cholesterol.

I found an unintimidating educational web page for Ravnskov which features cartoons so he will feel more comfortable learning about them. Macrophages are a part of the innate
immune system. It is their job to attack and gobble up what your immune system
thinks are foreign invaders.

Dr. Ravnskov, you are the one who has overlooked something crucial and obvious.
Allow me to explain. Atherosclerosis is an unregulated process. It's bad. It's
a disease. It’s not what is supposed to happen. Your cells use LDL receptors to
regulate the delivery of cholesterol. Your cells can only use so much, though.
Cholesterol shouldn’t accumulate on the artery wall. It therefore has to get
there without the LDL receptor. It has to bypass the usual regulation. A diet
full of saturated fat causes the production of excess cholesterol, some of
which attaches to the artery wall and passes into it, without ever being
managed by the LDL receptor. Don’t blame the LDL receptor for this disease.

Saturated fat even causes this uptake of cholesterol into the artery wall in mice that
were genetically engineered to be resistant to atherosclerosis.

Those macrophages of yours get very aggressive toward those lipoproteins that are
full of saturated fat. Saturated fat drives this process faster. It causes an
immune response that leads to chronic inflammation. I should mention that
macrophages are not the only carriers of cholesterol into (the walls of) your arteries, but
they are the best understood.

Something that should also interest Ravnskov is that saturated fat also causes a
down-regulation of the LDL receptors in his liver. This makes him a little more
like an FH patient, and so just like with them, his LDLs become more
concentrated in his blood. For those who doubt why the work of Brown and Goldstein
pertains to diet, there it is.

Ravnskov really blew that one. He demonstrated that he doesn’t even understand the
basics of atherosclerosis. He didn't even try to address the important
lessons we’ve learned from Brown and Goldstein's research. He should be
thoroughly ashamed by his attempt to undermine their life-saving contributions, if he is
indeed capable of that emotion. But I must say, he did do a couple things right
in that passage. He kept that section short which limited the extent of his display
of ignorance, and he buried that nonsense deep in a book that very few serious
people would read beyond the first few pages. Our next would-be debunker of
Brown and Goldstein didn’t have even that much judgment.

I learned about the following article from this eloquent and dignified defender
of cholesterol and saturated fat known as Anthony Colpo. He said that he found
a journal article that showed us that Brown and Goldstein were wrong. They made
assumptions that, in his learned opinion, were idiotic. Mr Colpo didn’t know
enough about heart disease to recognize the many problems with this wretched
article which we are about to examine. No surprise there.

This is Duncan Adams. He is a retired faculty member at the University of Otago in New
Zealand. When he wrote his editorial criticizing Brown and Goldstein he must
have anticipated some polite disagreement. He probably didn’t expect that his
piece would be ridiculed in a YouTube video. Nobody expects the Spanish

Here is the article. Brown and Goldstein made a mistake, he wrote. The lipid hypothesis
is a myth. You would think that, realizing he was attempting to overturn
bedrock research under the skeptical observation of the highly educated
readership of this journal, he would have presented some major insights into
this field, all bolstered by top-quality research. If you would think that, you
would think wrong. This piece is so laughably lame, it’s almost as if he wrote
it just to furnish me with great material for a video. I wish I could show you
the whole thing, but to stay on the right side of copyright law, I will only
show you excerpts.

Here Adams lays out his premise. In the same sentence that he acknowledges their
Nobel award, he says Brown and Goldstein misunderstood the mechanisms of heart
disease. Think about this. Brown and Goldstein have published prolifically on
this subject for decades, always at the leading edge of knowledge. They won a
Nobel for their LDL receptor discovery, and their subsequent description of
receptor-mediated endocytosis, which is the process that the cell uses to pull
the LDL inside itself, was worthy of an award as well. Adams, on the other
hand, has never made a single discovery in this field, as far as I can tell.
It’s not even his area of expertise. All his published writings on heart
disease that I found were just letters to the editor. Has he even researched this? Why does he assume that he knows what he is talking about? As you will see, he doesn’t. The third sentence on the left is his big hypothesis about familial hypercholesterolemia. He says, “In reality, the accelerated arterial damage is likely to be a consequence of
more brittle arterial cell walls, as biochemists know cholesterol to be a
component of them which modulates fluidity...” Adams says FH patients experience heart disease not because their blood reaches cholesterol concentrations 6 or 10 times
higher than what is normal, but because their cell walls are brittle from a
lack of cholesterol. He goes on to say that not eating
cholesterol will cause malnutrition, especially with regard to vitamin D, a
nutrient supplied best by sun exposure. Notice there are no references to
support his claims at all. He has just proposed an entirely new model for the
worst form of heart disease, this idea that it is caused by brittle cells. He
offers absolutely no support for this belief. None at all. Do you not believe

Here is a response to him published in the same journal by J. Paul Miller. As you can
see, he states that Adams has presented no evidence for his hypothesis. He’s
right. Adams offers nothing. Dr. Miller’s response to this was good but it was
too incomplete and polite to satisfy me.

In his response to Adams, Miller did point out the success of partial ileal bypass
surgery as a tactic to lower LDL cholesterol and consequently prevent heart
disease. This is a reference to the work of Henry Buchwald.

My channel viewers may remember my discussion of Dr. Buchwald’s work in another
video. I won’t repeat myself here. Dr. Miller was very smart to remind us of
this important research. There was so much more he could have said, though.

For example, Adams says that the cells of FH patients can’t get enough cholesterol
into their membranes without an LDL receptor, so these membranes become hard
and brittle.

He pretends that something as basic as the need for cholesterol in cell walls was
something overlooked by Brown and Goldstein. As you can see, they are well
aware of how the body uses cholesterol, including with respect to the formation
of functional cell walls. The assertion that FH patients have stiffened cell
walls due to a lack of cholesterol is so bizarre, I decided to look further
into the idea. What I found isn’t good for Adams.

Yes, cell membrane fluidity can be modulated by changes in lipids, but not in the
way that he thinks. As Undurti Das has explained, “Increased incorporation of
saturated fatty acids and cholesterol into the cell membrane phospholipids will
render the membrane more rigid.” In other words, this factor works in the
opposite direction of what Adams believes. Moreover, this increased rigidity
from excess cholesterol and saturated fat causes insulin resistance.

Ira Tabas has put out some great papers explaining the problems created by excess
cholesterol at the level of the cell. He, too, states that excess cholesterol
causes an increase in membrane stiffness. This can become such a severe problem
that it might kill the cell.

Read this slide and you will see that if cell membranes become depleted of
cholesterol, we might also expect a state of insulin resistance to result. With
a lack of cholesterol in the cell walls, insulin resistance may set in under this scenario, too.

Knowing this, we might expect that if FH patients really did suffer from a lack of
cholesterol in their cell membranes, they would be insulin resistant.

But instead their glucose metabolism and insulin sensitivity appear to be normal.
They aren’t unusual in either direction. Therefore, doubt is cast upon Dr.
Adams’ hypothesis. Their cell walls are probably closer to normal. It is more likely that the obese, who I have shown you store excess cholesterol in their fatty tissues, will be insulin resistant, and you just saw that excess cholesterol in the cell membrane can promote insulin resistance. Dr. Adams’ hypothesis does not predict insulin resistance as it should.

When Adams writes that FH patients can’t get adequate cholesterol into their cells,
he is proving that he is totally ignorant about the very experiments he is
attempting to criticize. Brown and Goldstein worked with skin fibroblasts.
They demonstrated that cells outside the liver can produce their own
cholesterol. Their use of skin cells rather than liver cells was part of what
made their research so brilliant. Their research was premised on the fact that
all cells can make cholesterol. Cells are not completely dependent on the liver
for that. This was apparently not understood by Adams. Here is Daniel Steinberg
explaining this in plain English if Dr. Adams doesn’t believe me.

Moreover, there are other ways of getting cholesterol into the cell beside the LDL
receptor. The cell has other sterol-regulating binding proteins that can pull
in cholesterol. This is very dense writing but this is what is being explained
here, at least in regard to one type of FH. There are at least 1100 different
mutations associated with FH.

Adams should have reviewed the ways that FH patients are therapeutically treated
before he went public with his wild speculation. Had he done so, he would have
seen that treatments to lower their cholesterol have been successful in
managing their symptoms. What you are looking at are called xanthomas. FH
patients get these. A xanthoma is a deposit of macrophages loaded with
cholesterol underneath the skin.

These xanthomas appear in little kids with FH. This is why homozygotes can have heart
attacks in childhood. They have excesses of cholesterol that are this extreme.
This is one of the unfortunate children who Brown and Goldstein met when they
decided to look for a solution to this very terrible condition.

Patients with severe FH have serious problems and they need very aggressive treatments to lower their cholesterol. If Adams is right about their cholesterol-starved
membranes, then these extreme efforts to remove their cholesterol should only
worsen their problems. That is not what we see. There are four primary
interventions that can be used to radically lower their LDL. In this first case,
liver transplantation was undertaken. This patient had cholesterol scores over
1100 along with xanthomas not quite as unsightly as the ones you just saw.
After transplantation, his cholesterol levels fell to less than 200. His
xanthomas quickly smoothed out. His reduction in cholesterol did not lead to
brittle cell walls and heart attacks.

Liver transplantation is a most extreme measure and livers are hard to come by, so
other approaches are used more often. The second technique is called plasma
exchange. Here, the plasma is removed and replaced with a substitute in a
procedure performed outside the patient’s body. This paper indicates its
effectiveness. Severe FH patients were given plasma exchange. Their cholesterol
fell 37% due to this treatment. They survived an average of 5 and a half years
longer than their siblings, who all died suddenly due to heart disease. Once again,
Adams is contradicted.

Another approach is, of course, the use of lipid-lowering drugs like statins. This
doesn’t work well enough with the most severe FH patients because they have no
working LDL receptors at all and so their isn’t much these drugs can do for
them. This trial was carried out on children with the less-severe form of FH.

These researchers measured the plaques in their carotid arteries during this trial.
As the drugs lowered their cholesterol, their plaques regressed. This had to
have been due to their lowered LDL because their other major lipoproteins
didn’t change much. Here too, the lowering of cholesterol makes FH patients
healthier. There was no problem with brittle cells.

Lastly, severe forms of FH can be treated using apheresis. In this technique as well,
the blood is processed outside the body, but this time to selectively remove
LDL. In the example you see here, a 22-year-old woman with FH was treated. She
had incredibly high concentrations of cholesterol despite her low-fat diet. At
six years old her cholesterol was over 1000. She had cousins who died of heart
attacks at 14 and 18 years old. Apheresis and statin therapy lowered her
cholesterol from 840 to only 122. Her xanthomas disappeared as well, and the
photos that accompany this paper provide dramatic evidence of her progress.

Here is an account of another patient treated with statins and apheresis. He had three
siblings who died between 3 and 10 years of age from heart disease. With treatment,
he was still alive at 34 years of age. His membranes seemed to be doing fine.
Now cholesterol confusionists, please note the following. FH children treated
with the most aggressive form of LDL-lowering therapy grow and develop normally.

Intriguingly, they have measurable improvements in their LDL oxidation, endothelial function, and inflammation, along with other biomarkers, as their cholesterol drops.
Once again, we see that high cholesterol in fact worsens all the biomarkers
that the low carbers claim to prioritize.

Adams says that human-like heart attacks have not been produced in animals. His
reference for this, believe it or not, is from 1924.

Nevertheless, there is some truth to this. There has been a lack of fully analogous animal models of human myocardial infarction. Our species is unique this way.

However, there are now animal models of plaque rupture thanks to genetic manipulation.
The plaques in these animals are induced by high-fat feeding, of course.

Adams chose to focus on the fact that the final event in the disease process, the
plaque rupture and the ensuing clot, could not be recreated in animals for the
longest time despite high-fat and high-cholesterol feeding. However, all those animals
did die of heart disease from such diets, only in different ways.

I think it would have been a bit more honest of Adams to add that atherosclerosis has never been induced in an animal without raising its blood cholesterol. Dr. Adams, do you disagree? How do you give an animal atherosclerosis without raising its lipids? He will have no answer for this. This is one more example of the odd confusionist tendency to suppress important details. All cholesterol deniers seem to be afflicted by this need for self-censorship. I wonder why they display such a pervasive pattern of concealment and misdirection in their arguments. Could it be because they know they are frauds?

Adams’ favored explanation for heart disease is high blood pressure, and hypertension
is certainly a risk factor. Look to the right at how he argues this. In his
points 2 and 3, he says that blood pressure explains the location of plaques,
which don’t form in areas of low pressure. What he doesn’t offer is how he
expects us to avoid the high fluidic pressures in the coronary arteries that
result from being a living person with a powerful beating heart. I can never
figure out where the confusionists are going with this argument. Maybe they
just want us to know that zombies are safe from heart disease. I feel
reassured. Lastly, check out his point number 4. It is an unreferenced claim
that horses with high blood pressure that are made to race die sooner than
horses that are not made to race. I guess he means to imply that we should
avoid exercise if we want to live a long time. And yes, he really wrote that for
a medical journal.

Adams has been a believer in the false dichotomy of cholesterol versus hypertension for a long time. With the advent of more effective hypertension medications in 1985, he predicted that protection from coronary disease might at last be at hand. That prediction hasn’t worked out very well. He remains unmoved.

Adams closes out his absurd opinion piece with this list of what he calls the “unfortunate consequences” of the mistakes of Brown and Goldstein. These are the basis for his title so this section is his big payoff. He thinks statins are a waste of money. I would agree to some extent. Had people been advised of the most effective diets to prevent heart disease – healthy plant-based diets – we wouldn’t have needed so many statins. Then he claims there is a problem with malnutrition which has resulted from the lipid hypothesis. Please note the lack of a reference for this one. You can read the next couple claims on pause, which are laughable. But lastly, notice that he thinks the lipid hypothesis has harmed us by distorting the meat and dairy industries. Usually authors in medical journals hide their loyalties to industry a bit more than this. Like the rest of his article, it is lacking in any appropriate references or support, but at least he is being clear about where his priorities lay.

Brown and Goldstein don’t know everything. No one does. They may well one day have their findings substantially modified or corrected, but that will never diminish the importance and quality of their work. You see here there are those who argue that the LDL receptor hypothesis is incomplete. Time will tell if these authors are right but they hardly think Brown and Goldstein have made an unfortunate mistake. It is quite difficult to find anything resembling criticism of them from serious and knowledgeable people, with good reason.

The opponents of the lipid hypothesis project so much certainty. They pretend it is
only they who have considered all the evidence. They have arrived at the only
reasonable conclusion. For all their transparent attempts at distraction and
for all their blatant displays of ignorance, they don’t seem to have ever taken
a moment to try to figure out the cholesterol levels we as a species have
almost certainly maintained over our long evolutionary history. In light of their
full-throated support of the ridiculous and juvenile Paleo fad, this is a
glaring omission. In the next chapter, I will use their paleologic against them.
I’ll show you how low our ancestral cholesterol really was.