Live Blogging from the Paleo Summit IX: Chris Kresser

Link:  Chris Kresser
Title:  An Update on Cholesterol

Ratings:

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☼ ☼ ☼ ☼ ☼  Informational Accuracy

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Summary:

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

 LDL is GOOD!

• 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:

SMALL DENSE LDL IS A MARKER FOR POOR LDL RECEPTOR FUNCTION

But What About Particle Size?   PARTICLE SIZE TESTS ARE UNRELIABLE

• 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

Treatment?

• 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 I ,  Part II,  Part 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.