The Great Cholesterol Con-Artist: Malcolm Kendrick

There has been a spate of studies and commentaries coming out of late related to plasma saturated fatty acid content, dietary sat fats and carbohydrates.  It gets mightly frustrating to hear the same arguments made over and over, when some basic calculations and critical radiolabel-tracer studies have shown otherwise for over 15-25 years now (and longer, I'm talking major summary papers and supporting studies).  And still ....

Kendrick is a Scottish physician, author of The Great Cholesterol Con, hence my title.  He's also a card carrying member of  and spokesman for THINCS:  THe International Network of Cholesterol Skeptics.    Sadly, his skepticism and paranoia have turned him into quite the con artist ... feet planted firmly in denial.
Professors, who shall be nameless, appear unable to admit how basic human physiology works. For example, they may concede a few steps here and there, but they will never, ever, admit to the following chain that I have described below.

Beware the preamble, and not naming names.  Many have called me brave -- or crazy! -- for naming names on this blog.  But it is important to do so most of the time.  The way I see it, show me what it is these people are really saying, so I can decide for myself what they are supposedly in denial about.    I'll show you who I'm talking about so you can assess my credibility on this point.   As written, Kendrick is setting the pole up for a giant strawman.

In truth it is more like the un-named "they" learned every pathway Kendrick is about to lay out. They teach them. It's in most/all of the textbooks. They have also learned and hopefully teach proper context. They will not "admit" to Kendrick's chain because it is distorted at best, intentionally misleading at worst. 

In Point 1, He begins with the biochemical and metabolic fact that all carbs are turned into simple sugars and then absorbed by the body.  Leaving aside some oligosaccharides and other fibers, this is correct.  No argument to be had.

And then the con begins ....

2: If you keep eating carbohydrate the resultant simple sugars will, at first, be stored. The human body can pack away around 1,500 calories of sugar. However, once this limit is reached, the liver will turn the rest into fat.

Ahhh ... this gives me the opportunity to reminisce about one of my early posts here at the Asylum ... so I will!  It ruled as most popular even over some of the "contentious posts that mentally unstable evil stalker biotch writes just to glom web traffic and page hits using fill-in-the-blank's name - yada yada" for many months.

Folks might recognize Eric Jequier as being a favorite reference of Feinman and Harcombe's metabolic manglings.  It's really too bad these people have no shame in lying to everyone so blatantly and incessantly.   But I digress ...

The bottom line here is that carbohydrate stimulates it's own oxidation -- as in when you eat a pint of white rice, roughly a cup of it is burned for energy in the following few hours.  The rest goes into glycogen, about half of that in the liver, where it will serve as a source for glucose to be released into circulation during the post-absorptive -- aka fasting -- periods of the 24 hour time cycle.   

Kendrick, and so many, like to treat glycogen stores like some sort of one way storage tank with a fill limit, the truth is that tank is being regularly drained which makes room for more glucose when you eat.  In actuality, the kinetics of glycogen turnover are not nearly as simple as even a filling & draining bathtub analogy could model, but it is better than working with a model with an invisible drain.  

What is "The Rest"?    Before moving on, however, let's presume that Kendrick's ceiling of 1500 calories represents the limit for some average human.  Despite numerous claims to the contrary, the SAD and other "Western" diets hover right around 45-55% carb, mostly around the 50% range.  This means that big-if this limit is meaningful, only those consuming roughly 3000 calories a day are flirting with excess.   Your average human consuming the calories for "normal weight" and reasonable activity isn't going to to come close, which is why from Jequier we have:
"It is to be emphasized that other metabolic pathways for disposal of dietary CHO, such as conversion into TAG or into non-essential amino acids, are not quantitatively important."
... and:
"The important point is that there was no gain of fat by de novo lipogenesis, as a small amount of net lipid oxidation was observed."
... and lastly:
 "de novo lipogenesis is not an important pathway in humans" 
And from Marc Hellerstein, I'm going to link to an image from a Nutrition textbook excerpt that I've shared many times.  You can click to enlarge in browser or click on the link to access the image.

Human hepatic (liver) de novo lipogenesis -- turning carbs to fat -- is not a quantitatively significant source of fat in the overall scheme of things in human metabolism.   Upregulated even in the "worst case scenario" we're talking hundreds of grams carbs to a few grams of fat.  

Kendrik implies that he has had many discussions with nutrition professors, and as such implies that he has studied enough biochemistry and metabolism to hold up his end of the discussion.  To put it bluntly, he either knows these facts, or should know them.  If he has secret knowledge of copious evidence that demonstrate them to be incorrect, he needs to provide that evidence.  Instead he resorts to unsubstantiated mockery and worse:  perpetuating lies.  

On that note, let's accept steps 1 and 2, and move on:
3: The fat that is made in the liver is palmitic acid
4: The next step is that three palmitic acid molecules are attached to a glycerol molecule, to form a triglyceride.

The carbs turn to fat and fat comes from carbs people really need a summit so they can agree on their bastardized metabolic biochemistry.  

Not all that long ago the headlines were blaring about how saturated fat in the blood comes from carbs thanks to an overhyped study led by Jeff Volek.  Only the main fatty acid that was increased following ramping carbohydrate intake up after a VLC diet was palmitoleic acid -- a MUFA.  

In humans, the primary product of de novo lipogenesis is indeed palmitic acid, a 16 carbon, unbranched, saturated fatty acid.

But this is not the final fate of palmitic acid which may be elongated (e.g. to stearic acid, an 18 carbon saturated fatty acid) or desaturated (e.g. to palmitoleic acid, an 18 carbon monounsaturated fatty acid) or both.   Once again, the regulation of the various enzymes that catalyze these reactions and control the rates and amounts of product are far from easy to describe.  I won't even try in this post.    How much palmitic acid you have in the liver will depend on not only how much is made, but how much is subsequently converted.  It can further be altered by rates at which it is taken up, stored, oxidized or secreted.   Levels of palmitic acid in circulation are even more complicated, because it is transported in different forms, impacted by both release and uptake in liver and adipose tissue, and impacted by uptake into other cells.  

Typical milk fat triglyceride  link
My point is that even in making a mostly true statement, Kendrick ignores important aspects of fatty acid synthesis.   He compounds this by implying that all or most triglycerides assembled in the liver consist of three palmitic acids.   It's beyond my time and priorities at the moment to provide you with an extensive list of references, but most triglycerides are assembled from a mix of fatty acids and the positioning of different fatty acids on different carbons of the glycerol backbone is far from random.    For example, bovine milk fat (C&P this link to automatically download full text PDF: )  

But let's move on ...

5: These triglycerides will then be packed into Very Low Density Lipoproteins (VLDL) and released into the bloodstream. [Beware of confusion here. For VLDLs are also called triglycerides although, of course, they are not. VLDLs contain triglycerides but they are not the same thing – even if they are called the same thing].

The Relationship of VLDL and Triglycerides 

Kendrick's always-a-conspiracy they're-trying-to-confuse-you schtick is pretty thick.    Which is rather sad because a 2003 essay on the THINCS website provides a largely accurate accounting of the differences and relationships  between various lipoproteins.  

There's nothing really to beware of here in the diagnostic/biomarker sense, because VLDL = trigs for all intents and purposes in the fasted state.   Although I discuss NEFA = FFA = Non-Esterified or Free Fatty Acids here quite a bit, the levels of this circulating form of fat are exceedingly low.  This is by necessity, and even "free" fatty acids are found bound to proteins (albumin) so that they mix better in circulation -- long story short, it's all about finding ways to "dissolve" oil in water.   

Far greater amounts of fat are transported as lipid "drops" surrounded by a protein shell, otherwise called lipoproteins.  The different protein "shells" of these particles are recognized by various receptors on cells throughout the body so that they can "dock" and deliver their cargo.   This delivery involves breaking lipases that break down the triglyceride to fatty acids for uptake into the cell.  

The two lipoproteins that carry the bulk of triglycerids are chylomicrons and VLDL.   Chylomicrons, or chylos for short, are by far the largest lipoproteins and transport dietary fat.  Although chylos do dock and unload triglyceride directly to cells around the body, the old adage of "fat going straight to the hips" has more truth to it than most.  It is difficult to pinpoint an exact percentage, and it depends on the relative nutritional state of the person when they consume fat, but it's fair to say that a goodly portion of the chylo load is "dumped" into fat cells.  If the fat tissue is healthy, this is accomplished with little or no "leakage" or "spill over" of fatty acids into circulation during the process.  Regardless of where the triglyceride has been off loaded, what's left of the lipoprotein with residual triglycerides is called a chylomicron remnant.  These are recognized by the liver, taken up, taken apart, and remaining triglycerides are repackaged along with others, into VLDL.   

After a short delay, for a few hours after eating fat, the vast majority of triglycerides in circulation are carried by chylos.  As the chylos offload triglycerides and the liver mops up the excess, overall triglyceride levels fall and are carried by a mix of remaining chylos, chylo remnants and VLDL.  In the fasted state, there won't be any meaningful amounts of chylo (and chylo remnants should be at low level if any are still around at all), and overall triglyceride levels should be low.  Effectively all triglycerides are carried in VLDL in the fasted state.   

When "we" (including doctors) speak of triglycerides, this is almost always referring to fasting levels in circulation.  When fasting, almost all triglycerides are carried in VLDL.  Hence, while it is technically incorrect to call VLDL by the term triglycerides, and vice versa, for all intents and purposes they are equivalent.  Malcolm Kendrick surely knows this, but for some reason would rather you remain confused.  It helps the conspiracy theorizing ....

6: When VLDLs reach fat cells (adipose tissue), the triglyceride is stripped out and absorbed into fat cells. Which means that VLDLs gradually shrink.
7: Once a VLDL has lost a large amount of triglyceride it becomes a new, smaller, lipoprotein, which is often referred to as ‘bad cholesterol’ a.k.a. LDL (Low Density Lipoprotein).
8: LDL is taken out of the circulation, primarily, by the liver. Some LDLs are removed from the circulation by other cells around the body that need the cholesterol contained in them.

The VLDL-IDL-LDL Cascade

What Kendrick has just described is commonly called the VLDL-LDL cascade.   The "I" in IDL stands for Intermediate.  Triglycerides are less dense than the other components of the lipoproteins, just as oil is less dense than water and floats on it.  Thus as VLDL loses it's triglycerides, the particles become progressively smaller and denser (greater mass per volume).      What is written above is largely correct, except that Kendrick again ignores the transfer of triglycerides in VLDL to muscle cells.  As with chylos, the offload sites for VLDL trigs depend on the nutritional state of a person and other factors, and it is difficult to find any accountiong as to the percentage of VLDL-trigs that are offloaded to each.  But clearly, being packaged into a VLDL particle is not a non-stop trip to an adipocyte.
9: As can be seen, the only source of LDL is VLDL.
Leaving aside the fact that there is evidence for direct LDL synthesis, this last enumerated point is correct.  With this Kendrick plants the seed that LDL levels are directly linked to VLDL levels.   This simply isn't true.  While the source of most LDL is "delipidated" VLDL, the factors involved in circulating levels of each are much more complicated than more VLDL → more LDL.   Kendrick knows better than this, and yet, inexplicably the rest of his article uses this to make a bizarre case for carbohydrate consumption being the true cause of heart disease if you believe LDL has anything to do with it, which he does not, but it's the carbs anyway ... or something like that.

This next statement comes after some other stuff, but it generally relates to lipoproteins and their metabolism and the involvement of the liver, so I'll put it here:

Of course, (1) if you actually eat saturated fat, this gets nowhere near the liver.  It is digested, packed into chylomicrons, and these very large lipoproteins enter the bloodstream directly through the thoracic duct.  Which is a secret passage from the gut that opens out in one of the veins in your neck.  (2) When chylomicrons encounter fat cells, the fats/triglycerides are sucked out, and the chylomicron shrinks down to virtually nothing.  (3) Chylomicrons, however, do not convert to LDL and have nothing whatsoever to do with heart disease – even according to those who think saturated fat in the diet is deadly.
(1) Dietary Sat Fat gets nowhere near the liver:  While on a "first pass" basis this may be mostly, technically true, taken together with Kendrick's contentions about VLDL, we are left to conclude something totally erroneous about VLDL.  That is, if dietary saturated fat gets nowhere near the liver, neither should any other dietary fat as there are no subclasses of chylo specifically for packing up MUFA and PUFA separately.  Indeed, as mentioned previously, most triglycerides are themselves are of mixed fatty acid composition making segregation next to impossible.  

Kendrick is saying that VLDL particles consist solely of triglycerides assembled from palmitic acid molecules manufactured from carbohydrates in the liver.  Dietary fat, according to Kendrick, "gets nowhere near the liver".  FALSE.  

(2)  Chylo triglycerides all get sucked up by fat cells:  What's this?  Fat cells are chylo magnets that suck the last drop of triglyceride right up and out of those chylo leaving empty protein casings left and right?    So tell me Dr. Kendrick.  If what you say is true to the extent you describe, where pray tell, do most of the triglycerides in body fat come from?  Hmmmm?  Could the answer be:  dietary fat?!  Why yes!    As it turns out, the most efficeint way for your body to store energy as fat is to sequester it right away from the diet and release it on an as needed basis.  Dietary fat has the added benefit to the body of not needing to be converted from any other kind of molecule into a long chain fatty acid.   No energetically expensive process needed ... just suck it up and pack it away.  NICE admission there Doc!   But again as I've mentioned previously, it is difficult to pinpoint -- I have a reference here somewhere but I cannot put my finger on it at the moment --  chylo do deliver triglycerides to both muscle and adipose tissue, and chylo remnants have been investigated as a biomarker in their own right.  It is not true that the chylo shrink down to nothing!

(3)  Chylo do not convert to LDL:   Again, we find that Malcolm has made a technically true statement in the course of trying to confuse people into believing his blatant lies.   This point is kinda funny, because Kendrick said exactly the opposite a dozen years ago:
Chylomicrons are then released into the bloodstream and travel through the body losing chunks of triglyceride all the while as they pass fat cells. (Fat cells attack chylomicrons with a ‘lipase' enzyme, chopping bits off). As this happens chylomicrons shrink, turning into Very Low Density Lipoproteins (VLDLs), which are otherwise known as… ‘triglycerides.' How confusing is that?
Ahh but he's apparently learned "new information" and now knows that chylo don't actually turn into VLDL so that they can shrink down to LDL.  BUT, the residual fat that chylo remnants contain IS extracted by the liver and repackaged into VLDL.    This is one way in which dietary fat encounters the liver directly.  A second route -- more critical in metabolic dysfunction -- is through free fatty acid spillover into "general circulation" during the uptake process.

Of Breast Milk, Body Fat, and Bad Things

Kendrick now takes us to Wikipedia to learn about palmitic acid and drags out one of the most intellectually devoid arguments out there.
It seems that we are being asked to believe that the body naturally synthesizes a substance, palmitic acid, that actively damages our health.
Come on, already.  You will die in very short order if your body stopped producing glucose and yet we all know that to some degree too much glucose is detrimental to the body.  I say "to some degree" because the hyperglycemia of either Type 1 or classic Type 2 diabetes does not exist without concurrent dysregulated lipid metabolism.  Quality diabetes research has produced substantial evidence of this, and it's not even controversial.   Dysregulated lipid metabolism precedes glucose dysregulation in the progression of Type 2.  

The fatty acid composition of body fat is highly influenced by diet.  This is because the vast majority of fats in adipocytes originated from the diet, not from carbs being converted to fat.  Further, although the quantity of DNL in fat cells is far less than in some animal models, rodents in particular, there is significant evidence that DNL serves a critical beneficial function within the adipocyte itself, without requiring substantial, or indeed apparently any, caloric surplus.  Lastly, there is evidence for preferential uptake, incorporation and release of different fatty acids from adipocytes, and this may even differ between various fat depots.  All combined these pretty much obliterate any logic in Kendrick's argument, but if that's not enough, just ruminate on the idea that fruit turns to fat turns to LDL ... according to Kendrick anyway.

Where Do VLDL Triglycerides Come From?

Using radioactive tracers, Marc Hellerstein's research group investigated the source of triglycerides in VLDL.  I blogged on this in some depth in this three part series:  Where Do Triglycerides Come From?  The vast majority of triglycerides assembled into VLDL by the liver come from "excess" fatty acids in circulation, NEFA.    

Note the teeny slivers indicating the contribution of de novo lipogenesis to the fatty acids incorporated into VLDL-trigs.  I would note that the study this information comes from was co-authored by none other than Ronald "Large and Fluffy LDL" Krauss, so it should be common knowledge amongst his fans.  

Hasn't Kendrick been following the "groundbreaking" research of Jeff Volek?  Palmitic acid was only roughly one-quarter of the fasting plasma triglycerides in that recent study.  Where ever did the 75% of fatty acids come from if not from the diet?    They don't "originate" from NEFA because NEFA came largely from dietary fat, subsequently mobilized from fat cells.  It's just a longer route to the same destination.  Going around the loop, a much smaller percentage of triglycerides taken up by fat cells come from VLDL, most come from the diet via chylo.

But IF It's LDL, It's The Carbs Fault!

Here is why we had to suffer through Kendrick's pedantic trip down metabolic lane.  I do believe that he, like so many diet-heart-lipid denialists, errr ... "skeptics" ... recognize at some level that LDL has *something* to do with atherosclerosis.    So going down a most unusual logical path, Malcolm writes:
When people ask me why I don’t believe in the diet/heart hypothesis, I tend to shrug and move the conversation on.
However, if I am feeling a bit stroppy I tend to reply that ‘Even if you were to believe that a raised LDL levels causes heart disease, the current diet/heart hypothesis does not, and cannot make any sense from a biological or physiological perspective.’ If you were actually looking for a substance that really could raise LDL/cholesterol levels it would have to be carbohydrates a.k.a. sugars. After all the only source of LDL is VLDL, and it is eating too much sugar that raises VLDL levels.
In short, how can it not be that carbohydrates raise LDL levels? This is what a basic understanding of lipid physiology tells us must be true.
What has Kendrick been doing this past decade or so?   Following along at all with low carb "science"??  He was a contributor towards the abominable book Cholesterol Clarity by low carb scientific-know-nothing Jimmy Moore.  Did he read the book he was erstwhiley (is that a word?) quoted in?   This guy is all over the map, because he seems oblivious to the disconnect between VLDL and LDL levels in some people.  Has he paid NO attention to the rampant reports of people like Jimmy Moore with astronomical LDL and saturated fat intake often accompanied by sub-50 mg/dL triglycerides (coinciding with low VLDL levels)?

Let's revisit a study specifically to look at VLDL itself -- back to the Hellerstein paper.  The control diet was 50% carb, the HCLF diet almost 70% carb.  Both were 45% simple sugar carbs.  

VLDL concentrations increased with TG (not highlighted) as carbohydrate intake was increased.  But LDL went down -- nominally in the normal subjects, almost 25% in the hypertriglyceridemic ones.     Clearly, amounts of VLDL and the triglycerides they're packing do not track with the levels of LDL in circulation.  This is because the kinetics are far more complicated than higher VLDL = more particles secreted = more LDL when trigs are off loaded.  Per the article:
Increased secretion of TG was not the primary kinetic mechanism responsible for this carbohydrate-induced TG elevation, ...
... reduced TG clearance from the plasma was the major metabolic mechanism involved.
If there's one thing that's predictable about the various clinical trials, it's that if anything, LDL decreases on the higher carb lower fat diet, while it either flatlines or mildly increases on high fat low carb.    Occasionally you'll see LDL decrease slightly on the low carb arm if significant caloric reductions and weight loss are seen.   

Oh but here's another step-in-it moment for Kendrick, because he chides folks for writing articles about this like this one.  Saying stuff like:

This author, writing for the Journal of Nutrition, finds it paradoxical that… increased dietary carbohydrate usually comes at the expense of dietary fat….but the content of fat (triglycerides) in the blood rises. Well, what did they think would happen? That carbohydrates would turn into fairies at the bottom of the garden?
The sole author, Elizabeth Parks, is also the lead author on this paper I've just been talking about.  Apparently Kendrick hasn't bothered to read too thoroughly of late?  His own source even?  
We found no evidence that carbohydrate-induced HPTG resulted from elevated free fatty acid flow or de novo lipogenesis (12). The primary phenomenon of carbohydrate-induced HPTG could be explained by a 37% reduction in TG clearance from the blood.
Care to guess what reference 12 there is?

Man these people are just so boldly dishonest it is maddening.    

Kendrick is telling his audience that carbs raise LDL (which they do not) because they cause more VLDL production from de novo lipogenesis.  Meanwhile his own source contradicts him.   Here I thought it was statins that were supposed to cause memory and cognition problems ....

Once the liver and muscles are full of sugar (stored as glycogen – a polymer of glucose) the body can do absolutely nothing else with it, but turn it into fat – through the processes I have described earlier. This is basic, incontrovertible science.
Ummm .... no, not so much.
When you understand the science you find yourself looking at the diet heart hypothesis (fat in the diet raises LDL levels, which causes heart disease) and thinking. This does not make any sense at all. Yet, such is the determination of the nutritional experts to defend their position that they never, ever, talk about ‘what happens to the carbs?’
Oh yes they do, you just haven't bothered to listen to them, read the science, or apparently understand one iota of what you've read. 
What happens to the carbs is that they are all turned into saturated fat. This then raises VLDL levels and these, in turn becomes LDL.
No, not even close.
Yet eating carbs is supposed to be healthy, and eating saturated fat is unhealthy. Go figure.
Mo butta mo butta.
The world of nutrition is, I am afraid, nuts.
I agree.   As I post this,  I see there's a Part 2.  Perhaps there'll be one here too.