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“To kill an error is as good a service as, and sometimes even better than, the establishing of a new truth or fact”
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Thursday, March 1, 2012

Live Blogging from the Paleo Summit IX: Chris Kresser

Link:  Chris Kresser
Title:  An Update on Cholesterol


☼ ☼ ☼ ☼   Entertainment Value
☼ ☼ ☼ ☼  Content
☼ ☼ ☼ ☼  Informational Accuracy
☼ ☼ ☼ ☼  Overall


Hands down the most informative and important presentation yet.  Go listen.  NOW.  You can read this later!  This one trumps O'Bryan's gluten presentation because I don't think any of us escape the insidious reach of "cholesterol".  Whether it's our doctor pressuring us to take statins, or diet and exercise not working, etc.etc. Chris Kresser lays out a thorough and concise summary of all things LDL these days.  I sincerely hope that those in the low carb wing of paleo ... ahem ... Jimmy Moore ... will listen to this and dial back their "protective fluffy LDL" cheerleading, as well as the "my LDL caused my doctor to have a heart attack" jeering and snickering about the paleo web.   Chris discusses the meaning of cholesterol test results, the possible underlying causes, further testing you should seek if you have high cholesterol and treatments.  He also briefly discusses low LDL.    It is well worth the listen.
My Notes
The Pendulum:
Chris touches on a phenomenon that occurs in many areas with paleo.  The conventional cholesterol = heart disease hypothesis has been pretty thoroughly trounced by now to the degree that, despite insistence to the contrary, most docs no longer really adhere to it.  The over-reaction, however has been to embrace high cholesterol levels as OK, because that's all BS anyway (and Taubes has a little blood on his hands for this one with his cholesterol is meaningless schtick).   As Chris says, a phrase I use often, the truth probably lies somewhere in between.  So if your cholesterol levels are high, or they get that way when you adopt a paleo lifestyle, don't ignore it, but investigate it.  A total cholesterol level of 350 is not  (again, ahem Jimmy Moore) some stellar number to crow over.  The probem is when cholesterol gets oxidized.  Kresser goes on to lay the case for elevated cholesterol being due to reduced clearance which means it's hanging around longer and thus susceptible to oxidative damage.  

The Possible Underlying Causes:
  • Leptin resistance: --  Leptin signals LDL uptake by LDL receptors.  If you are LR, the receptor signaling is blocked.
  • Thyroid -- Hypothyroid can elevate LDL because T2 activates  the LDL receptorI
  • Infection -- LDL rises with infection
  • Inflammation -- LDL repairs damage, so if you have damage that is in need of repair, LDL goes up
  • Micronutrient deficiency -- Specifically Fe, Cu and I (in the case of hypothyroid)
  • Genetic Mutation -- familial hypercholesterolemia associated with  increased all cause mortality and CVD
Old Hypothesis / New Hypothesis:
  • Infiltrative Hypothesis:  The old "artery clogging cholesterol" theory where elevated sticky LDL builds up on the vessel walls leading to obstruction and eventual heart attack.  Pretty much bunk.
  • Degenerative Hypothesis:  LDL is oxidized or "degenerates" and unable to perform its beneficial roles in the body
  • Chris discusses a condition called SLOS where not enough cholesterol  is made.  These fetuses almost never reach birth, but those that are born suffer all sorts of deformities and problems.  We see issues with cholesterol below 150 as well.
  • LDL is the precursor to all hormones, UV light generation of VitD, myelin sheath formation, etc.etc.
Dietary/Lifestyle Factors : 
  • Excessive PUFA consumption, includes excessive Omega 3's because they are fragile fatty acids,  as all PUFA oxidize more readily.
  • You need antioxidants with LDL which you should be getting from anti-oxidant rich foods not a medicine cabinet full of pills.
  • Oxidative risk factors:  toxins, inflammation, infection, stress, lack of physical activity
It's Only a Matter of Time:
  • Lot of LDL + Lot of oxidative  factors (listed above)  = Problems!
  • Time is key -- The longer the LDL is exposed to these factors (due to slow clearance), the greater the chance of oxidation
  • LDL receptor activity controls time LDL spends in circulation.  High activity (or proper activity) = normal LDL, reduced activity = buildup of LDL 
Getting Smaller Every Day
  • For your LDL particle, enzymes remove triglycerides making the particle smaller and denser,
  • Oxidation makes them even smaller and denser
  • Then LDL and HDL particles interact.  Triglycerides are transferred from LDL to HDL and cholesterol is transferred from HDL to LDL, and -- you guessed it -- the LDL particles become even smaller and denser
The Bottom Line:
  • 80% of people by gel test, vs only 8% of people by VAP test will be found to have large LDL -- that's quite a difference!
  • The NMR & GGE methods give results somewhere in between 
  • Prospective studies have yielded pretty ambiguous results especially once controlling for confounding variables like smoking. 
  • Bottom line:  The theories on particle size are not proven
  • HOWEVER:  Small LDL is a marker for poor LDL receptor function and LDL oxidation
What is Best Predictor? (edited -- see comments)
  • LDL to HDL ratio is the most predictive measure
  • Preferably under 3, optimally under 2  
  • But remember ... it's a marker! 
Your Levels May Vary  
  • The standard deviation for TC is 17 mg/dL.  I'm not sure exactly what that is but it sounds like he's saying that if I ate a consistent diet for a month and tested each day, my levels would vary with a standard deviation of 17 mg/dL.  Now I have a quibble with Chris' statistics after this, because that doesn't naturally extend to a +/- 2 SD swing of 70 points, as the probability that you test one day and it's way up in the tail of the normal distribution that day, and way down in the other tail the next day is pretty slim, but his point is nonetheless well taken.
  • Levels vary, get consistent levels on multiple tests before doing anything drastic.
  • He lists the following for other things (presumably 4X the SD):  HDL 10, LDL 30, Trigs 40 , TC/HDL 0.8 up or down
When Should You Be Concerned?
  • 250-275 and above is high  for TC.
  • 240 used to be normal but the down revision of marker thresholds has caused this to now be considered high.  
What Should Look For/Get Tested For?
  • Infection 
  • Inflammation
  • Micronutrient deficiency  (copper, iron)  
  • Order a thyroid panel TSH, free T3, free T3 rT3, TPO, TGB
  • 24 hr iodine/bromide loading test 
  • Investigate leptin resistance     
  • Screen for familial hypercholesterolemia
  • low dose thyroid activates LDL
  • statins good for familial hypercholerolemia

Some Final Thoughts
Quite a lot of this is discussed by Chris Masterjohn in his interviews with Kresser , Part 2 especially.
 If Kresser makes any $$ off of this, I sure do hope he'll be sharing the wealth with Masterjohn!  Also, go listen to those interviews for more. 

This is part 1 Part IPart IIPart III.
To me, the takeaway messages here were several:
  1. Particle size is far from settled science.  When you think about the differences depending on test, and any review or meta study hoping to summarize data, one can see how it would be difficult if not down right impossible to come up with anything meaningful.
  2. Absolving LDL entirely from CVD "blame" may well be premature
  3. Cholesterol is a marker -- if it's out of the ordinary, and I would add if it changes dramatically for YOU, it can be indicative that somethings going on. Ignore it at your peril
  4. Triglycerides , schmiglycerides
  5. LDL/HDL is the best predictor -- Although this is edited from TD/HDL, this indirectly means TC not so meaningless after all in the sense that LDL's contribution is often poo pooed by low carbers and paleos.   


Mario Iwakura said...

Just one caveat. There are several studies showing that, in modern societies, lower total mortality is associated with a TC around 200~240 mg/dL.

So, according to Chris, optimally, your HDL should be higher than 100~120 mg/dL? Really? Is an HDL this high really healthy? How many people have TC/HDL <= 2? I would bet that veeeery few.

TC/HDL could be a good predictor, but probably a better number is around 3~4, not 2~3.

R. K. said...

I second Mario's concern.

Nance said...

Mario, my lifelong TC/HDL ratio has been around 2.7. I'm interested in what they'll find when I'm tested tomorrow, because on the "healthy low-fat whole grains" diet my TC dropped to 134. I'm hoping it's in the good range but not TOO high now. :-))

Larry Eshelman said...

A ratio below 3, with 2 being optimal, is usually recommended for the LDL/HDL ratio, not TC/HDL. On the other hand, the suggested ratio for TC/HDL is preferably below 4 and optimally below 3.

My guess is that the LDL/HDL ratio was meant. If you read the transcript of the 3rd interview with Kresser and Masterjohn, nowhere does anyone recommend a TC/HDL ratio below 2. But Masterjohn does say the the Kitavans have an LDL/HDL between 2 and 4.

Kurt G. Harris MD said...

Below is a comment I just posted on Freetheanimal blog this morning (before I saw this post). You may find the whole discussion over over the past 3 blog posts there pretty interesting.

I think we are making some progress in fighting off the attempt by low carb hucksters to swallow up and digest paleo...

My quote from there was in response to someone bragging about their blood work on a high fat diet:

"Here is what is wrong with your belief in “blood lipids”. The blood lipids you are presumably referring to are measures like HDL and fasting triglycerides. Medical research suggests that high HDL and low fasting trigs correlate with lower cardiovascular risk. True enough. But does this mean that changing your diet to increase HDL and lower fasting trigs changes your risk?

Not so fast. That conclusion so popular with the low carb proselytizers is a massive non-sequiter. The study populations are in general eating the SAD at approx. a 50% carb intake. The research tells us that these are risk factors AT THAT DIETARY COMPOSITION, it does not necessarily follow that a high HDL or low trigs at 10% carbs means the same thing as it does at 50% carbs – just like a postprandial blood glucose of 140 after a load of potatoes is normal but after a steak might mean you have diabetes. Context matters.

As proof of this, read (or re-read) the papers by Stefan Lindeberg on the Kitavans. Even Lindeberg struggled to explain the “paradoxically” low HDL and “paradoxically” high trigs in this population, who we all know have vanishingly low cardiovascular disease. But he should not have struggled as it is no paradox at all.

HDL and trigs are NOT independent of macronutrient ratios. And you cannot conclude that these lipids are the CAUSE of anything without explaining why they fail to predict the CV risk in the Kitavans.

A high HDL and low fasting trigs do seem to be a marker for low CV risk ON THE SAD. But you are not scientifically justified in concluding that raising your HDL and lowering your trigs by eating low carb lowers your risk BECAUSE of the change in these lipid markers. And there is no clinical evidence that changing these parameters via diet results in fewer CV events, just like there is no evidence that reducing LDL or total serum cholesterol does so.

Belief in the efficacy of low carb to lower CV risk based on “blood lipid” is an unjustified myth being promoted by low carb diet doctors who have simply not thought things through carefully enough.

And to the degree that people stay hyper caloric (stay fat and in energy excess) and reassure themselves that they have “great labs” they are simply whistling past the graveyard.

They would be better to have “bad” HDL and “bad” trigs and be THIN on a high carb diet – just like the Kitavans."

Chris Kresser said...

Larry is right. If I said TC:HDL ratio is optimally 2, I misspoke. As Mario pointed out, that's mathematically unlikely - and I do agree that elevated HDL (>85/90) can itself be a marker for inflammation.

I'd also agree with Kurt: there's still a lot we don't understand about the relationship between lipids and heart disease, and it's dangerous to assume causal relationships when causality hasn't been established.

Evelyn aka CarbSane said...

Welcome to the Asylum Chris! Thanks for taking the time to check in here. I double checked and the slide at @22 min says Total Cholesterol/HDL. I can only guess that Sean or someone on his team made up slides of the highlights based on what each of you said in the interviews. May want to correct this for the upgrade package. So to be certain, the ratios would be for LDL to HDL right?

Thanks for a great presentation!

ProudDaddy said...

Perhaps the elevation of HDL using niacin also illustrates your point -- i.e., no clinical benefit.

Jeff Rothschild said...

Great summary Evelyn! Thanks for doing this! It was my favorite talk so far as well, also just ahead of Dr Gluten.

Kurt G. Harris MD said...

Good Point Daddy.

Chris Kresser said...

Hi Evelyn,

Good idea - I'll contact Sean. Yes, the ideal LDL:HDL ratio would be around 2, whereas the TC:HDL ratio would be between 3-4.

Thanks for the great review, and keep up the good work fighting VLC fundamentalism.

Jeff Rothschild said...

One question regarding the statement that 'Leptin signals LDL uptake by LDL receptors. If you are LR, the receptor signaling is blocked.' Other people in the paleosphere have said a similar thing. I believe it may be true, I just haven't been able to find a reference for it..... I have found papers that say leptin downregulates HMG-CoA reductase and decreases hepatic cholesterol synthesis and promotes hepatic uptake of plasma cholesterol (VanPatten and others 2001) and is an important regulator of HDL cholesterol (Lundasen and others 2003).

Can anyone point me to a paper specifically talking about leptin's effects on regulating LDL receptor activity? I suppose it could do it indirectly via T3?


Jeff said...

I think Kurt hits on something important here...CONTEXT. All of this research is on populations on SAD diets. What would similar studies indicate on a paleo/real food cohort show or might indicate? Might be similar or not...but I guess that is something impossible to test or know at this moment.

Tomas said...

This is the original podcast

I can attest that lot of information found in the podcast appeared on the talk, probably the best value primer on cholesterol you can ever get.

This is part 1
and part 3 (I haven't listened to these)

Evelyn aka CarbSane said...

Thanks Tomas!

Evelyn aka CarbSane said...

Awww Daddy, what a cutie you got there!

Ya know, alcohol raises HDL too. :D

Evelyn aka CarbSane said...

Well said Kurt. I've been following those discussions. Context is EVERYTHING. I believe low trigs on LC are prematurely celebrated.

Evelyn aka CarbSane said...

Good catch!

Lisa Lawrence said...

Is there any scientific research I should be reading about the harms of "VLC fundamentalism"?

I appreciate the need to have differing points of view (to learn and grow) but I also appreciate the value in backing up claims with evidence

I have come across so many differing opinions on grain free carb consumption though and at this point, the more I read, the more I am confused.

ProudDaddy said...

Thanks for the compliment on my precious daughter. You've probably guessed that she gets her looks from her mother and her brains, well, also from her mother.

Evelyn aka CarbSane said...

I'm not really all that up on this topic, although it's nice to chat some specifics on leptin for a change rather than pie-in-the-sky theories, eh? I'll try to put this on the list and see if I don't get to it at some point. I've really got such a backlog of stuff I want to blog on.

Evelyn aka CarbSane said...

Welcome Lisa! I don't think one is going to find scientific evidence on the harms of VLC fundamentalism as it's not a recognized condition (grin). I will share a few sentiments I hear from people both publicly here and behind the scenes, one of the strongest being trapped in a LC mentality with diminishing health or returns. Quite a few of these began to once again achieve weight loss and feel better after adding carbs back to their diets. We even have quite a few grain eaters here. A peeve of mine is those who sing the glories of LC but are struggling with health issues nonetheless. There's little evidence that humans are optimized on a VLC diet, which doesn't mean it's not therapeutic or safe in some contexts.

Lisa Lawrence said...

a very helpful answer. I was looking for any evidence (aside from anecdotal) that LC in general is harmful.I am doing so much better LC, but if I start to backslide, I will be open to all options.

Lerner said...

And so the house of cards that Taubes built continues to fall. Some of the people who used to make the argument that "Taubes says so-and-so" will now declare "but Richard did so-and-so".

Roughly 15 years ago I'd seen a small newspaper article with the headline, "Scientists discover the main cause of obesity is overeating". Back then the evasion was "slow metabolism". Today it's "evil carbs". Tomorrow there will be something else.

Lerner said...

wrt to thin Kitavans, one of the two things that really stood out for me was Lindberg's instinctive conclusion that their health was due in large part to their "leanness". It very much had the ring of truth. But posting about that on macro-obsessed Paleo forums was met only with [free range] crickets.

Still, what is known about CVD status in Kitavans? We know they don't have events. But without a scan or autopsy, we don't know what is going on inside. They might be like the Masai, who have "extensive atheroma" discovered on autopsy but don't have events because they don't get eventual plaque rupture (men) or erosion (more typical in women and diabetics).

I'd guess nobody is doing CAC or IVUS but what about a simple portable b-mode sono CIMT? I've just been looking for a few minutes for anything on that but can't find anything.

Also, then what about that presumably small number of people who are thin but still get MI? If we subtract out the skinny-fat ones, there will still presumably be some left. Are there? If so, what's the culprit there (aside from genetic pathologies like FH)? The possible explanation that leaps out is inflammation -- but there was a recent registry study from Emergency Rooms in Italy, Scotland and China which showed that 40% of cases had 'normal' CRP.

The inflammation angle also leads to that second thing which stood out to me about the Kitavans: they "smoked like chimenys".

Lerner said...

if the talk about niacin and HDL is referring to AIM-HIGH, then it should be noted that there were a lot of odd things about that study. Foremost to me was that the 'control' group also showed a marked rise in HDL - as did the niacin group. I put 'control' in quotes because they also got niacin, though a low dose (so that they supposedly got some flush.)

Dawn said...

Lisa, have you checked out Paul Jaminet and the Perfect Health Diet? He addresses some of that science and explains his rationale behind the low but not-too-low carb content he recommends.

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