Blog - The Eating Academy | Peter Attia, M.D.

The straight dope on cholesterol – Part II

The straight dope on cholesterol – Part II
Share

In this post I’m going to tackle the next set of logical (at least in my mind) questions to follow up on last week’s post, Part I in this series.

Last week we addressed these 3 concepts:

     #1What is cholesterol?

     #2What is the relationship between the cholesterol we eat and the cholesterol in our body?

     #3Is cholesterol bad?

This week we’ll address the following concept:

      #4 How does cholesterol move around our body?

I want to thank folks for doing their best to resist the following two urges:

  1. Please resist asking me questions beyond the scope of this post.  If it’s not in here, it will probably be in a subsequent post in this series.
  2. Please resist sending me your cholesterol numbers.  Share your story with me and others, but understand that I can’t really comment other than to say what I pretty much say to everyone: standard cholesterol testing (including VAP) is of limited value and you should have a lipoprotein analysis using NMR spectroscopy (if you don’t know what I mean by this, that’s ok… you will soon). I can’t practice medicine over the internet.

 

Remember last week’s take away messages:

  1. Cholesterol is “just” another fancy organic molecule in our body but with an interesting distinction: we eat it, we make it, we store it, and we excrete it – all in different amounts.
  2. The pool of cholesterol in our body is essential for life.  No cholesterol = no life.
  3. Cholesterol exists in 2 formsunesterified or “free” (UC) and esterified (CE) – and the form determines if we can absorb it or not, or store it or not (among other things).
  4. Much of the cholesterol we eat is in the form of CE. It is not absorbed and is excreted by our gut (i.e., leaves our body in stool). The reason this occurs is that CE not only has to be de-esterified, but it competes for absorption with the vastly larger amounts of UC supplied by the biliary route.
  5. Re-absorption of the cholesterol we synthesize in our body (i.e., endogenous produced cholesterol) is the dominant source of the cholesterol in our body. That is, most of the cholesterol in our body was made by our body.
  6. The process of regulating cholesterol is very complex and multifaceted with multiple layers of control.  I’ve only touched on the absorption side, but the synthesis side is also complex and highly regulated. You will discover that synthesis and absorption are very interrelated.
  7. Eating cholesterol has very little impact on the cholesterol levels in your body. This is a fact, not my opinion.  Anyone who tells you different is, at best, ignorant of this topic.  At worst, they are a deliberate charlatan. Years ago the Canadian Guidelines removed the limitation of dietary cholesterol. The rest of the world, especially the United States, needs to catch up.  To see an important reference on this topic, please look here.

 

Concept #4 – How does cholesterol move around our body?

To understand how cholesterol travels around our body requires some understanding of the distinction between what is hydrophobic and hydrophilic.  A molecule is said to be hydrophobic  (also called nonpolar) if it repels water, while a molecule is said to be hydrophilic (also called polar) if it attracts water.  I could spend a lot of time getting in to the nuances of these properties, but I think it’s best to just focus on the major issues.  Think of your veins, arteries, and capillaries as the “waterways” or rivers of your body.

BONUS concept: Another important concept is that cell membranes are lipid bilayers (which are hydrophobic) as I wrote about last week.  Hence, a hydrophilic substance cannot pass through lipid membranes. Substances that can pass through lipid membranes are said to be lipophilic. A substance that has both polar (hydrophilic) and nonpolar (hydrophobic) properties is called amphipathic. The fact that unesterified cholesterol (UC) is an amphipathic molecule is a crucial property for its location in cell membranes. CE in which the –OH group has been replaced by a long chain fatty acid is a very nonpolar or hydrophobic molecule.

If a molecule needs to travel from your gastrointestinal tract (A) to, say, a cell in your quadriceps muscle (B) it needs to get on the river and travel from point A to point B.  Because blood is effectively water, (the “water” part of blood is called plasma, an aqueous solution with a bunch of “stuff” in it (e.g., red blood cells, white blood cells, other proteins, ions) there are two ways to move down the river – swim or hitch a ride on a boat.

If a molecule is hydrophilic, it can be transported in our bloodstream without any assistance – sort of like swimming freely in the river – because it is not repelled by water.  Conversely, if a molecule is hydrophobic, it must have a “transporter” to move about the river because the plasma (water) wants to repel it.  I know this seems like a strange concept, but if you think about it, you’ve already seen great examples in your day-to-day life:

Sugar and salt will easily dissolve in water.  They are, therefore, hydrophilic.  Oil does not dissolve in water.  It is, therefore, hydrophobic.

By extension, a molecule of glucose (sugar) or sodium and chloride ions (salt), because of their chemical properties which I won’t detail here, will travel through plasma without assistance.  A lipid will not.

All of this is a long way of saying that sterol lipids (of which cholesterol ester is the predominant form in plasma), because they are hydrophobic, need to be carried around our bloodstream.  They can’t move from one place to the next without a protein transporting molecule.

In other words, cholesterol doesn’t exist in our bloodstream without something to carry it from point A to point B.


So what are these “transporting molecules” called?

The proteins that traffic collections of lipids are called apoproteins. Once bound to lipids they are called apolipoproteins, and the protein wrapped “vehicle” that transports the lipids are called lipoproteins.  Many of you have probably heard this term before, but I’d like to ensure everyone really understands their important features.  A crucial concept is that, for the most part, lipids go nowhere in the human body unless they are a passenger inside a protein wrapped vehicle called a lipoprotein. As their name suggests lipoproteins are part lipid and part protein.   They are mostly spherical structures which are held together by a phospholipid membrane (which, of course, contains free cholesterol).  The figure below shows a schematic of a lipoprotein.

 

lipoprotein

 

You will also notice variable-sized proteins on the surface of the lipid membrane that holds the structure together.  The most important of these proteins are called apolipoproteins, as I alluded to above.   The apolipoproteins on the surface of lipoprotein molecules serve several purposes including:

  1. Assisting in the structural integrity and solubility of the lipoprotein;
  2. Serving as co-factors in enzymatic reactions;
  3. Acting as ligands (i.e., structures that help with binding) for situations when the lipoprotein needs to interact with a receptor on a cell.

Apolipoproteins come in different shapes and sizes which determine their “class.”  Without getting into the details of protein structure and folding, let me focus on two important classes: apolipoprotein A-I and apolipoprotein B.  Apoprotein A-I (abbreviated apoA-I), which is composed of alpha-helicies, form lipoproteins which are higher in density.  (The “A” class designation stems from the fact that apoA’s migrate with alpha-proteins in an electrophoretic field).  Conversely, apoprotein B (abbreviated apoB), which is predominantly composed of beta-pleated-sheets, form lipoproteins which are lower in density.  (The “B” class designation stems from the fact that apoB’s migrate with beta-proteins in an electrophoretic field.)

Virtually all apoB in our body is found on low-density lipoproteinLDL, while most apoA-I in our body is found on high-density lipoproteinHDL.  Going one step further, the main structural apoprotein on the LDL is called apoB100 (though we often shorten this to just “apoB”), and there is only one apoB molecule per particle. It’s starting to come together now with “high” and “low” density lipoproteins, isn’t it?

But there’s actually more to it.

Everything I just described above deals with the structure and surface of the lipoprotein molecule – sort of the like the hull of the ship.  But, what about the cargo?  Remember what started this discussion.  It’s all about transporting cholesterol (and lipids) which can’t freely travel in the bloodstream.  The “cargo” of these ships, what they actually carry both on their surface [molecules of cholesterol and phospholipids] and in their core [cholesteryl esters (CE) and triglycerides (TG, or triacylglycerols)] is what we’ll now turn our attention to.

The ratio of lipid-to-protein in the lipoprotein structure determines its density – which is defined as mass per unit volume.  Something that has a high density is heavier for a given volume than something with a low density.  The table in this link (which I’ve also included below) shows the relative density of the five main classes of lipoproteins (from most dense to least dense) as they were originally discovered using ultracentrifugation: high density lipoprotein (HDL), low density lipoprotein (LDL), intermediate density lipoprotein (IDL), very low density lipoprotein (VLDL), and chylomicron.

Note the very subtle difference in density between the most and least dense lipoprotein – about 10 or 15%.  Conversely, note the very large difference in diameter between each lipoprotein – as much as 2 orders of magnitude.  Later in this series, when we start to talk about the volume of a lipoprotein particle, this difference will be amplified 1,000 times (because volume is calculated to the third power of diameter).

Density table

Below is a figure I’ve borrowed graciously from one of Tom Dayspring’s remarkable lectures which gives you a sense of the diversity of each of these classes of lipoproteins as well as the subclasses within each class.  If this topic wasn’t confusing enough, there are actually multiple nomenclatures for the HDL subparticles.  Originally, nomenclature was based on their buoyancy.  Today nomenclature is based on the following methods, dependent on the technology used to measure them:

  1. Particle separation using gradient gel electrophoretic fractionation (deployed by Berkeley Heart Lab).
  2. Magnetic resonance assaying of lipid terminal methyl groups, called Nuclear Magnetic Resonance, or NMR (deployed by Liposcience).
  3. Two-dimensional gradient gel electrophoresis and apoA-I staining (deployed by Boston Heart Lab).

We’ll cover this later, but I want to point this out now to avoid (unnecessary) confusion in the figure below, which uses the first two of these.

 

Lipoprotein sizes

 

A few things probably jump out as you look at this figure:

  1. ApoA-I lipoproteins (i.e., HDLs) are tiny compared to ApoB lipoproteins (i.e., VLDL’s, IDL’s, and LDL’s) [this figure is not actually to scale – the “real” difference is even more pronounced.]
  2. As a general rule (with pathological exceptions), as particles move from being larger to smaller, the relative content of triglycerides (TG) goes down while the relative content of protein goes up, hence the density change.
  3. Actual cholesterol mass is greatest in the LDL particle.
  4. Each specific lipoprotein has a different core make up – meaning the variable ratio of TG to cholesterol ester changes. A particle of VLDL has 5 times more TG than CE whereas a particle of LDL typically has 4 or more times more CE than TG (i.e., ratio > 4:1), and an HDL has 90-95% CE and < 10% TG in its core.
  5. The TG trafficking lipoproteins are chylomicrons from the intestine and VLDLs from the liver.

Deep breath. Anyone left wondering why this topic is NOT covered in medical school? I think I can conservatively say 95% to 99% of physicians do not know what you have just learned — not because they aren’t “smart,” but because this topic is simply not covered in medical school, and the pace at which the field is developing is too great for most doctors to keep up with.

 

Why is cholesterol concentration increasing and triglyceride concentration decreasing as lipoproteins progress from larger to smaller?

The liver exports VLDL which, after chylomicrons (used to get triglycerides to muscles and adipocytes and cholesterol from the gut to the liver) are the largest of the lipoprotein particles.  VLDL particles “give up” some of their triglycerides in the form of free fatty acids and shrink as they also release surface phospholipids. Once a certain size or buoyancy is reached it is called a “VLDL remnant” and ultimately an IDL.  Some (though not all) of the IDL particles undergo continued lipolysis to reduce in size and become the famous (or infamous) LDL particles.  However, most of the IDL particles are actually cleared by liver LDL receptors and do not become LDL particles. 

All along this process, the larger particles “shed” phospholipids and fatty acids and thus become cholesterol-rich.  It is the LDL particle that is the ultimate delivery vehicle of cholesterol back to the liver in a process now called “indirect reverse cholesterol transport.” However, under certain circumstances the LDL will penetrate and deliver its cholesterol load to the artery walls.  THIS IS EXACTLY WHAT WE DON’T WANT TO HAPPEN.  (Sorry for the bold ALL CAPS – I know some of you may have fallen asleep by now, but I didn’t want anyone missing the punch line.)  Because almost all cells in the body de-novo synthesize all the cholesterol they need, LDLs are not actually needed to deliver cholesterol to most cells.

The final important point I want to make about cholesterol transport is that it goes BOTH ways.  Lipoprotein particles carry triglycerides and cholesterol from the gut and liver to the periphery (muscles and adipocytes – fat cells) for energy, cellular maintenance, and other functions like steroid creation (called “steroidogenic” purposes – remember the figure last week showing a cholesterol molecule and steroid molecule).  Historically this process of returning cholesterol to the liver was thought to be performed only by HDL’s and has been termed reverse cholesterol transport, or RCT (you’ll need to subscribe — for free — to lecturepad.org to access this last link, which is well worth the time).

This RCT concept is outdated as we now know LDL’s actually perform the majority of RCT. While the HDL particle is a crucial part of the immensely complex RCT pathway, a not-so-well-known fact is that apoB lipoproteins (i.e., LDL’s and their brethren) carry most of the cholesterol back to the liver.  In other words, the “bad” lipoprotein, LDL, does more of the cleaning up (i.e., taking cholesterol back to the liver) than the “good” lipoprotein, HDL!

The problem, as we’ll discuss subsequently, is that LDL’s actually do the bad stuff, too – they dump cholesterol into artery walls.

 

Cholesterol trafficking

 

Let’s put this all together to summarize how cholesterol gets around our body

  1. Cholesterol and triglycerides are not soluble in plasma (i.e., they can’t dissolve in water) and are therefore said to be hydrophobic.
  2. To be carried anywhere in our body, say from your liver to your coronary artery, they need to be carried by a special protein-wrapped transport vessel called a lipoprotein.
  3. As these “ships” called lipoproteins leave the liver they undergo a process of maturation where they shed much of their triglyceride “cargo” in the form of free fatty acid, and doing so makes them smaller and richer in cholesterol.
  4. Special proteins, apoproteins, play an important role in moving lipoproteins around the body and facilitating their interactions with other cells.  The most important of these are the apoB class, residing on VLDL, IDL, and LDL particles, and the apoA-I class, residing on the HDL particles.
  5. Cholesterol transport occurs in both directions, towards the periphery and back to the liver.
  6. The major function of the apoB-containing particles is to traffic energy (triglycerides) to muscles and phospholipids to all cells. Their cholesterol is trafficked back to the liver. The apoA-I containing particles traffic cholesterol to steroidogenic tissues, adipocytes (a storage organ for cholesterol ester) and ultimately back to the liver, gut, or steroidogenic tissue.
  7. All lipoproteins are part of the human lipid transportation system and work harmoniously together to efficiently traffic lipids. As you are probably starting to appreciate, the trafficking pattern is highly complex and the lipoproteins constantly exchange their core and surface lipids. This is a big reason why measuring how much cholesterol is within various lipoprotein species will in many circumstances be so misleading, as we’ll discuss subsequently in this series.

This was a bit of a tough one, so let’s stop there.  Next week we’ll discuss how to actually measure cholesterol levels.  In other words, if you’re looking at the river, with all its floating ships carrying their cargo, how do we measure the amount of cargo actually contained within the ships?  Furthermore, is this the most important thing to be measuring?  Ironically, it’s easier to measure the cargo in the ships, but more important to know the number of ships in the river. But now I’m getting ahead of myself.

P.S. Happy Birthday Dad (now I’ll know if you’re reading my blog!)

(To Part III »)

174


About the Author:

Peter Attia, M.D., is the co-founder and President of the Nutrition Science Initiative (NuSI), a non-profit based in San Diego, CA. He received his B.Sc. from Queen's University in Canada and his M.D. from Stanford Medical School in California. After his surgical residency in general surgery at Johns Hopkins he worked as a consultant at McKinsey & Company. He founded NuSI with scientific journalist Gary Taubes in 2012.

Discussion

  1. Johannes Oecolampadius  May 3, 2012

    This guy’s a national treasure.

    (reply)
    • James K Boyer  May 3, 2012

      Agreed! It’s awesome to have Peter making all of this accessible.

    • Eric  May 3, 2012

      I couldn’t agree more.

    • marie  May 3, 2012

      Absolutely! Thank you for the up-to-date education Peter – have you thought of maybe a lecture series/videos? You’ve done the hard work and from the way you’ve organized it, looks like it can move to slides/animations naturally.

    • Peter Attia  May 3, 2012

      I think the content that Tom Dayspring and Tara Dall have on lecturepad.org and fhit.org is really great. Not sure I could do better!

    • Nina  May 3, 2012

      I agree.

  2. greensleeves  May 3, 2012

    Hi Peter:

    But why do we have so many kinds of these “ships?” Why do we need so many of these different sizes? The body is usually economical in its functioning. I honestly can’t understand why we need more than 1 kind – 1 big, which would just naturally get small as it “sheds.”

    Any idea? Ty!

    (reply)
    • Peter Attia  May 3, 2012

      It’s a great question. As the ships dump their TG cargo, they don’t “need” to be as big. Perhaps that’s the efficiency?

  3. PaulaM  May 3, 2012

    Wow. I did doze off. Can’t wait for tomorrow when I’ll be fresh and awake so my brain will pay closer attention. Cool the way you are teaching this as a sort of virtual class(room). Thank you.

    (reply)
  4. Laura  May 3, 2012

    So, do chylomicrons only (or predominantly) travel from the intestine to the liver, or also from the intestine to other tissues? And what happens to them when they deliver TG to liver and/or other tissues? Do they become something else when they shrink?
    Thanks!

    (reply)
    • Peter Attia  May 3, 2012

      Chylos main goal is the transport of fat from the gut to periphery and the liver. Once they get rid of their TG content they shrink in size and become “remnants,” which are taken back up by the liver.

  5. LeonRover  May 3, 2012

    Very nice explanation.

    Maybe a med school would benefit from taking you on in a teaching role.

    It would certainly benefit the students.

    (reply)
  6. Colleen  May 3, 2012

    Agreed. What a service to be able to pull up this blog and get such a great education on an important topic. THANK YOU PETER!

    (reply)
  7. Alan Veeck  May 3, 2012

    “Dr Attia, may I be excused? My brain is full.” (smile)
    http://www.flickr.com/photos/untergeek/8454334/

    A “big picture” question just to make sure I am tracking – the transport of TGs (and cholesterol with them) is all about providing energy to our cells via fat metabolism; where does carb/glucose metabolism fit into the picture? Separate path, or tied into this picture somehow?

    Also, it doesn’t seem as if cholesterol does much in this story; in most of your analogies, it seems to be along for the ride, with the TGs giving the fuel source. Can you give a high-level description of how/why our bodies use cholesterol?

    And Happy Birthday to your Dad! (Now we’ll know if he reads the comments, too!)

    (reply)
    • Peter Attia  May 3, 2012

      Great way to think of this. If I had to distill it down to the highest order points, I’d say the following: lipoproteins transport vital “stuff” from sources to sinks. Muscle cells need fat for energy; fat cells need fat to store fat (we obviously prefer when the muscles get fat to oxidize, rather than fat cells getting fat to store). Most cells can make their own cholesterol for membranes, hormones, etc. but the lipoproteins can also deliver incremental amounts, especially if cellular amounts are insufficient. And of course, lipoproteins take cholesterol back to the liver to prevent it from doing “bad” stuff in the periphery.

    • moreporkplease  May 3, 2012

      Hi again Peter:

      “Most cells can make their own cholesterol for membranes, hormones, etc. but the lipoproteins can also deliver incremental amounts, especially if cellular amounts are insufficient.”

      How does the body know how much it needs? So, say I scrape my shin and have to grow some new skin or something, and my skin there grows some new cells, but then finds out it’s a bit short of cholesterol to make them with. How do the skin cells on my shin tell the liver “hey! send me some honkin’ freighters of cholesterol ASAP!” Is something in my reptile brain controlling this or what? Where is my internal main “cholesterol meter?”

    • Peter Attia  May 4, 2012

      Big question. Beyond scope of this post. Cell signalling and homeostasis are huge fields in science.

    • lupo  May 4, 2012

      What I found:
      “[...] it appears that cells set their cholesterol at equivalence with the complexing capacity of their polar membrane lipids. Because cholesterol molecules that exceed this threshold have enhanced chemical activity or fugacity, they move to and inform homeostatic pathways based in the ER and mitochondria.” (Steck and Lange (2010): “Cell cholesterol homeostasis: mediation by active cholesterol.” Trends Cell Biol, 20(11):680-7.)

      So there is no body-wide setpoint of cholesterol. It seems plausible that cholesterol is “just cruisin around” and dropped where needed.

    • JohnJ  May 4, 2012

      If you want to learn more about heart disease and statins from an alternate sources you can read and hear;

      Heart Surgeons Dr. Lundell and Dr. Rob Carlson On Heart Disease, Cholesterol & Inflammation

      http://truthaboutheartdisease.org/two-heart-surgeons-views/

      Statin Drugs – the JAMA Debate

      http://www.jonbarron.org/heart-health/statin-drugs-jama-lower-ldl-cholesterol?utm_source=iContact&utm_medium=email&utm_campaign=Jon%20Barron&utm_content=NL+Statin+Drugs+4%2F23%2F12

      Atherosclerosis and Lipoproteins

      http://atvb.ahajournals.org/content/21/5/844.abstract

      High Cholesterol And Heart Disease — Myth or Truth?

      http://www.cholesterol-and-health.com/Does-Cholesterol-Cause-Heart-Disease-Myth.html

      Post-Meal Blood Sugar and A1c Predict Cardiovascular Events and Deaths

      http://www.phlaunt.com/diabetes/15945839.php

      Statin Drug Side Effects Articles

      http://www.spacedoc.com/statin_side_effects

  8. Richard J.  May 3, 2012

    I am so thankful that you are addressing this vital issue Dr. Attia. I have just read Dr Malcolm Kendrick’s brilliant (and funny) book, The Great Cholesterol Con, from which it is clear that the public (and most doctors) are hopelessly misinformed about this topic. Please keep up the good work!

    (reply)
    • greensleeves  May 5, 2012

      @lupo:

      “So there is no body-wide setpoint of cholesterol. It seems plausible that cholesterol is “just cruisin around” and dropped where needed.”

      Now this seems key. The body regulates everything with great care. But not cholesterol! It lets the individual cells decide how much they want, right? And they can have it any time. This seems to me like a very powerful argument that we shouldn’t ourselves try to lower or restrict our cholesterol at all. Because we have no way to determine any proper level or setpoint – there’s no way to know how much could possibly be “optimal.” These conventional cholesterol targets could be starving our brains and cells of a fundamental component for all we know, right?

    • lupo  May 5, 2012

      @greensleeves:

      Great point.

      Cholesterol in the cell itself is tightly regulated. As all lipid-processing cells retrieve lipids AND cholesterol from lipoproteins, their need for cholesterol is reduced. So *total* cholesterol in serum lipoproteins should not matter at all, from a theoretical point of view (anyone with hard data on this? Peter?).

      Another noteworthy point here is that “everything is in flux”. The body does not “store” lipids nor does it “store” cholesterol or “dump cholesterol somewhere”. There is a constant influx and efflux of substances in all tissues. If the tissues are unhealthy (i.e. overcrowed adipocytes, damaged endothelial wall cells, …) due to local damage or misguided hormonal signaling, you can see it in the blood, but that does not have to mean that the cause of the problem is in the blood.

  9. Mark Breckenridge  May 3, 2012

    The new testament on Cholesterol.

    (reply)
  10. Thomas Dayspring aka "Dr Lipid"  May 3, 2012

    Comment: Peter is doing the world a great service in educating all on the complexities of how the body traffics lipids. There is no way to truly understand CV risk without mastering lipoprotein biology. Tragically most healthcare providers have little clue about this topic. Keep up the good work my friend.

    TD

    (reply)
    • Peter Attia  May 3, 2012

      Tom, it’s only possible that I can write about this topic because of how generous folks like you have been in teaching me. Thank you. It’s a pleasure to expand the audience for this most important topic.

    • Ed  May 3, 2012

      Dr Dayspring-

      I am so glad you chimed in. I listed to your awesome lecture on HDL on Lecturepad and I will search for something related to LDL. Judging from the graphic in Peter’s posting, it appears you have something on that as well.

      One area of discussion that would be EXTREMELY HELPFUL for someone like you to tackle and start to talk about is cholesterol in the brain.

      I understand why the focus of the discussion tends to be on the bloodstream/arteries/atherosclerosis because the vast majority of research on cholesterol was driven by cardio-vascular disease, but when we consider that cholesterol as a vital substance is even more pronounced in nervous tissue (I have read that the brain is approx 2% of body mass yet 25% of cholesterol), one has to wonder what the impact of interventions on blood levels of lipids might have on the brain.

      I think it would be very useful in this context to discuss cholesterol transport / endogenous production in neural tissues. The liver seems to be the big producer of cholesterol in the body, although as I understand all cells have the basic machinery to produce it on their own. So, is the brain producing it for itself or does it need to be transported from the liver?

      I also know that there is a blood brain barrier, so it doesn’t seem like the mechanisms governing lipoprotein transportation into and out of the brain cells would be as straight forward.

      There is some anecdotal evidence that statins might have
      unintended negative consequences for cognitive function, surprise, surprise (http://query.nytimes.com/gst/fullpage.html?res=9401E0DB1139F935A35750C0A9649D8B63&ref=statinscholesterolloweringdrugs)

      Anyway, Peter is doing a fantastic service in making this information accessible but I think it’s time we start to expand the discussion of cholesterol and its transport from a Cardiovascular perspective to a “whole body” perspective… including the brain… since after all, that’s where the highest concentration of cholesterol is.

    • DHackam  May 3, 2012

      Ed, I will not answer on behalf of Dr Dayspring but from the data I have seen, which is highly conflicting, there are no adverse effects of statins on cognitive function – I am talking here about randomized, placebo-controlled trials with rigorous testing of cognitive function in both groups at baseline and follow-up. Some of these trials have even been done in Alzheimer’s patients, who would be highly susceptible to any worsening of cognate function.

      Larger studies, such as the 25k HPS study or the still large (3k) PROSPER trial, did not show any effect on cognitive outcomes, although they typically used much less sophisticated tools such as the modified mental status examination (MMSE).

      However, it does seem a certain proportion of individuals, probably a very low number, report “fuzzy thinking” and other cognitive issues on statins (e.g. poor memory). I do wonder if this is related to the hydrophobicity (fat solubility) of the molecule they have been prescribed. For example, atorvastatin and simvastatin are liked oil-based paint – high solubility and crossing of the blood-brain-barrier. Rosuvastatin and pravastatin are essentially hydrophilic rather than hydrophobic and do not cross the BBB. On the other hand, statins tend to be prescribed to people who already have risk factors for cognitive deterioration over time, such as hypertension, atrial fibrillation, diabetes and hyperlipidemia – so which is the chicken and which is the egg?

    • Ed  May 3, 2012

      I probably should have just omitted the comment about statins, which I am sure we will have time to discuss when Peter (hopefully) turns his attention to the clinical applications for this series of postings. Until then, Dan, I think you made good points.

      I just wanted to point out that since cholesterol is much more important in the brain relative to other tissues, it would be worthwhile to make some mention of the transport mechanisms there, and if they relate at all to the transport mechanisms in blood… which seems better understood.

      For example, we are discussing lipoproteins in blood. Since we are all paranoid about heart disease, we study this… but how about the brain?

      a) are the same lipoproteins in “brain blood”, do they call it cerebrovascular fluid or something to that effect (apologies… last bio class in 9th grade).
      b) is there a measurable cholesterol level in the brain fluid?
      c) if so do those values correlate to serum levels?
      d) do lipoproteins cross the barrier?

    • John M  May 6, 2012

      @Ed, @DHackam

      Add my voice to the call to hear more about brain cholesterol, but here is the thing: I’m thinking that Peter may be responding only or mostly to first level posts, and so he has not responded to this. Maybe try posting as a top level comment? Just thinkin’…

  11. Scott  May 3, 2012

    Great post! A couple questions:
    1. Will you be discussing lipoprotein particle synthesis?
    2. Do you have a textbook you would recommend for those of us who would like to do some further research? (The internet can only teach us so much, sadly.)

    (reply)
    • Peter Attia  May 3, 2012

      I was not planning to go into much depth on lipoprotein synthesis, as it’s quite complex, and I’m not sure it will help folks understand the problem. I could be wrong, though. I don’t have any textbooks to recommend on this topic, but I can’t recommend lecturepad.org enough. Any article written by Tom Dayspring, Tara Dall, Bill Cromwell, Jim Otvos will be very helpful. Perhaps Tom can weigh in on the best textbook. Obviously, he’s written many chapters in various texts.

    • moreporkplease  May 3, 2012

      Hi DHackam:

      “Larger studies, such as the 25k HPS study or the still large (3k) PROSPER trial, did not show any effect on cognitive outcomes,”

      Dr. Uffe Ravnskov destroyed the PROSPER trial in his most recent book. It’s apparently quite a poor quality study.

    • John M  May 6, 2012

      I’m NOT an expert, but I have been finding the following book to be quite useful:
      Elliot and Elliot, “Biochemistry and Molecular Biology”, 2009 (4th edition), Oxford University Press. I would peg it at about the college Freshman/Sophomore level. Good chapters on both lipid synthesis and lipid metabolism.
      http://www.amazon.com/Biochemistry-Molecular-Biology-William-Elliott/dp/0199226717

  12. Jim  May 3, 2012

    “…number of ships in the river.” I suppose this is represented by LDL-P in an NMR profile. I’m in trouble then. Probably getting ahead again, but what’s the “number of ships” before you’d start to worry?

    Your detailed explanation of cholesterol is incredible, thanks so much. I can’t wait for next week.

    (reply)
    • Peter Attia  May 3, 2012

      We’ll get there, Jim. The 20th percentile for LDL-P is about 1,000 nmol/L; The 95th percentile is about 2,000 nmol/L.

  13. Alexandra M  May 3, 2012

    That was fantastic! Maybe YOU should be presenting this as one of those Teaching Company courses. It would be a nice antidote to the nutrition course that advises “drink your cereal milk” and “avoid shiny foods because they contain fat.”

    (reply)
    • Alexandra M  May 3, 2012

      (Although thanks to their biology lectures, I actually knew what a “beta-pleated sheet” was.)

    • Peter Attia  May 3, 2012

      Ok, so some good, some bad…

    • Peter Attia  May 3, 2012

      Oh, brother… is it really that bad?

  14. Bob Johnston  May 3, 2012

    I think what bugs me is the idea that the vast majority of doctors don’t know this stuff. Cholesterol should be one of the most fundamental things a doctor should know – what right do they have to give advice if they’re not keeping up on the latest knowledge about something every one of them should know?

    And thank you for your hard work, this stuff is fascinating.

    (reply)
    • Peter Attia  May 3, 2012

      Yes, the parallel between lipid physiology and obesity/diabetes/IR is upsetting. The medical establishment really SHOULD know this! And they SHOULD know what regulates fat accumulation, too…more work to do…

  15. KevinF  May 3, 2012

    Now if you can just do this in comic book format.

    (reply)
  16. lorraine  May 3, 2012

    Happy Birthday to your dad!

    I went back and looked at my graduate physiology textbooks, and realized that what is currently given as conventional wisdom on lipids is still based on the state of the knowledge when I was in grad school (a very long time ago, decades). The state of the art proceeds way too slowly down the chain to the medical student and practicing physician; the very people who hold in their hands the fate of their patients.

    This series is really well done so far. Our whole lives are a minute-by-minute interaction with science and so everyone, from lay person to student to clinician, can relate to scientific concepts if they are approached from a place of common sense. You succeed really well at this, and I hope the exercise of writing this series serves as a template for textbook revision by you and your colleagues.

    I await the take home on what potentially signals LDL-P to drop off its load in the artery.

    (reply)
    • Peter Attia  May 3, 2012

      Yes, this really is one of the difficulties in medicine. Even if we are taught everything correctly at a point in time, 15 years later it is almost certain to be outdated, at best, or even wrong.

  17. Jeffry N. Gerber, M.D.  May 3, 2012

    Peter – Great job trying to explain these difficult concepts. I agree most doc’s do not spend enough time understanding advanced lipo-protein science, and yet have no problem prescribing lots of medication treating high cholesterol as dictated by their local drug reps. I have been reading about this complicated topic for over 10 years and what’s apparent is that total LDL-C and total cholesterol carries less weight. LDL particle size, number of particles, Apo-B total, Triglyceride / HDL ratio are much better predictors of inflammation, atherogenisis and plaque formation. You must be smart, I could not learn all this in just 9 short months, way to go! I would suggest that the readers spend some time on this material. Lipoprotein science also teaches us a lot about nutrition, how dietary carbohydrates, rather then saturated fat, is more of a problem. You might enjoy reading a brief post on my Facebook page from yesterday http://www.facebook.com/Denversdietdoctor I anxiously await part III! – Jeff Gerber MD

    (reply)
    • Peter Attia  May 3, 2012

      Jeff, thank you so much. I look forward to reading your post. It’s a real challenge to learn this material. When I get on the phone with Tom Dayspring, I can’t write it down quick enough…

  18. Nina  May 3, 2012

    Peter, I am so grateful to you (and Gary Taubes and Dr. Dayspring) for all of your work and generosity in sharing your knowledge. Thank you.

    (reply)
  19. Adam  May 3, 2012

    Peter, thank you for not “talking down” to your readers. You assume we are intelligent people who want to know the scientific details and you are correct in that assumption. For that, you are unique in the blogosphere and will continue to amass a loyal following. Keep it up!

    BTW – typo alert… below the diagram of the lipoprotein (11 lines down), you say “Aproprotein A-1″ where I think you meant just Apoprotein. an extra R in there.

    (reply)
    • Peter Attia  May 3, 2012

      Thank you (for both the compliment and the correction!).

  20. steve  May 3, 2012

    In defense of many doctors(i am not one)they have moved away from avoid cholesterol(ok to eat eggs and seafood that may be high in cholesterol) but strongly warn patients to avoid saturated fat which somehow(which I assume you will discuss at some point)raises cholesterol levels in the body(indirectly i suppose?) Even some Lipidoligists still warn to stay away from saturated fat particlularly for those who have some CAD. Be nice for Dr. Dayspring to weigh in on this as well; be interested in his dietary views

    (reply)
  21. Ryan  May 3, 2012

    Holy friggin crap!!! MY head just exploded!!!

    I’m quite confident I’ll have to read that everyday for a month for it to make sense a little bit…

    (reply)
    • Peter Attia  May 3, 2012

      Nah, just 2 more times and you’ll be fine. I bet you know more than you think, already.

  22. Sam Y  May 3, 2012

    “However, under certain circumstances LDL will penetrate and deliver its cholesterol load to the artery walls.”

    What is this situation called?

    I realize this is probably outside the scope of the post, as you probably are planning a whole part of the series to CV disease, but I’d just like to know more about the unique circumstances that lead to cholesterol being delivered to artery walls.

    Thanks.

    (reply)
    • Peter Attia  May 4, 2012

      This is called atherosclerosis.

  23. Bharte  May 3, 2012

    I am a Norwegian management consultant and I appreciate your contribution. I enjoy reading especially because of the excellent logic in your arguments. Thanks.

    I only have one question for you:
    What step-by-step process would you recommend for identifying the degree of insulin resistance a person has?

    I believe outlining such a process would enable people, including myself, to make a better choice with regards to how much we should reduce our carbs intake.

    Thanks,

    Bjarte

    (reply)
    • Peter Attia  May 4, 2012

      Many things together: fasting glucose and insulin levels (HOMA-IR), glucose challenge response, euglycemic clamp, lipoprotein analysis, body composition, family history, other signs of metabolic syndrome.

  24. David Nelsen  May 4, 2012

    Another excellent post. I watched Tara Dall’s video’s on Lecturepad.org – and this re-inforces them and also gives me time to “digest” them so to speak.

    On a positive note, it appears that you won’t run out of subjects to write about any time soon. Finding the time to write, workout, and family time is the larger challenge.

    (reply)
  25. Alexandra M  May 4, 2012

    What happened to the “latest comments?” It’s the only way I can keep up with things!

    (reply)
    • Peter Attia  May 4, 2012

      Hey, good point! Site crashed yesterday, so perhaps it got dropped. Let me see if I can dig it up.

  26. tim  May 4, 2012

    You recently indicated you had thought about or did some fasting. Did you notice any effects on your cholesterol numbers? Appears some of the studies go both ways tc and ldl either rise or fall. Be curious what ldl-p did and how long after the fast until numbers return or if they do. Any studies your aware of?

    (reply)
    • Peter Attia  May 4, 2012

      Yes, I’ve been playing with fasting, but didn’t do lipid testing on either end. Perhaps next time.

  27. George Henderson  May 4, 2012

    How does HCV (hepatitis C virus) replicate? By hijacking triglyceridde synthesis (DGAT1).

    When does HCV spread into serum from infected hepatocytes?
    When VLDL is expressed.

    How does HCV infect naive hepatocytes?
    Via LDL receptors (to some extent?)

    How did I lower my HCV viral load from 400,000 to 26,000?
    If you’re reading Peter’s blog, you can probably guess.

    For more about the connection between crbohydrate, PUFA and HCV, see my website link (apologies in advance for poor presentation on my blog).

    Any advice about improving the protocol I propose is welcome.

    (reply)
  28. Mike Hurley  May 4, 2012

    The worst part about this is we have to wait a whole week for part III. The diagrams and pictures are super helpful, by the way. I always conceptualize things better with visuals. Took me a few hours to get through this post, but very enjoyable.

    (reply)
    • Peter Attia  May 4, 2012

      Mike, THAT is dedication! A career in lipidology may be in your future…

  29. Jessica Apple  May 4, 2012

    Another terrific post, Peter. Thank you. This information really helps me.

    (reply)
  30. barbara  May 4, 2012

    Peter, you are the money!!! I listened to your interview with ben and jimmy yesterday and am excited by the example you set as an endurance athlete who is looking for better solutions. I am 56yr old cyclist. I have been paleo for 2+ yrs. I am hypothyroid and on med’s for that. I am pretty low carb, 100 grms a day some days less. I plan to go keto in the fall /winter so as to not disrupt my season now. I am trying the super starch you suggested to see how it feels on the bike.

    Here are my questions:
    1. will going keto mess me up re thyroid?
    2. can i use gels for long distance rides (ie 60+ miles )with the super starch?
    3. in july i do a benefit ride that is a week long, 550 miles, 4 sates in new england, how should i think about fuelign for that one?

    You are fab and this site is golden.

    Thaks.

    (reply)
    • Peter Attia  May 4, 2012

      Sounds like your thyroid is already an issue, so not sure how keto will change it. For most people – not an issue. I would not touch a gel under any circumstance. Read post on interplay of exercise and ketosis for fueling ideas on long rides.

  31. lupo  May 4, 2012

    Hello Peter!

    I’d like to point out one thing: Cholesterol isn’t dumped to the arterial walls because there is too much of it. It is quite probably deposited there because of arterial wall inflammation. Lipoproteins are drawn to damaged endothelia because they contain antioxidant enzymes such as platelet-activating factor acetylhydrolase or paraoxonase.
    Funny thing is, statins seem to act as antiinflammatory drugs independent of LDL reduction (for an overview and relevant citations, cf. Libby et al. (2002): “Inflammation and Atherosclerosis.” Circulation, 105: 1135-1143), which could much better explain their protective effects in high-risk populations than dumb number lowering. If you remember guidelines for post-MI medical care, you prescribe aspirin, which is an antiinflammatory drug, too.

    BTW, if you plan to write an article on hypertension and insulin, I now know a little bit about the effects of insulin on arterial walls and the kidneys. With references! :-) Just drop me a mail.

    (reply)
    • Irina  November 23, 2013

      Hi there Lupo,

      I have high cholesterol but extremely low c-rp, which measures inflammation in the body. What gives?

      Cheers,
      Irina

  32. Bob Johnston  May 4, 2012

    Hi Peter,

    This question is a bit off topic so if you’re planning on covering it later in the series by all means tell me to hold my horses.

    The use of statins and their effect on cholesterol is controversial in my eyes; my impression is that the evidence they’re effective in improving all-cause mortality rates just isn’t there. So it confuses me a bit when I see conflicting information from a couple of your mentors on statin use.

    In a video I posted in the comment section of Part 1 of the cholesterol series Dr. Dayspring would have put the Reno cop on a statin as part of his treatment to lower LDL particle count (Starting at 17:45). Quite honestly I was surprised at his insistence a statin be used.

    http://www.youtube.com/watch?v=an6L9VY0v8A&feature=g-user-a&list=PL713AF033659DFAD4

    But yesterday I was checking out Lecturepad and ran across a video series from Tara Dall where she says that statins aren’t effective at lowering LDL particle count (starting at 5:30)

    http://www.lecturepad.org/index.php?option=com_content&view=article&id=950:advanced-lipid-testing-comes-alive-part-1-of-4&catid=150:live-lectures&Itemid=384

    So what am I missing here? Am I misunderstanding what is being said or is there a difference in opinion on the effectiveness of statins to lower LDL-P counts?

    Thanks,

    Bob

    (reply)
    • Peter Attia  May 4, 2012

      Bob, great questions and, obviously, very important. I will absolutely be addressing these later on in the “straight dope on cholesterol” series.

  33. barbara  May 4, 2012

    Thanks Peter, will do, I did not think Keto would change hypo condition I just wondered if it would worsen it with less carbo’s. I listened again to what you told ben about road racers vs tri athletes and there need for carbo’s /keto states and I will not dabble with keto until the end of the season.

    Many thanks.

    (reply)
  34. Janknitz  May 4, 2012

    I hope at some point you will address the physiological effects of having very low levels of LDL and low total cholesterol. The vegans seem to think that’s a desireable thing, but I suspect it’s not.

    (reply)
  35. Larry Sumners  May 4, 2012

    It appears that the $64,000 question is how you get the lipids to return it’s load to the liver instead of depositing it load on artery walls and to find a way to measure such.
    I have been working on my cholesterol for years but have learned more in these two posts than in all my study for 30 years. There is the frustration however of understanding but then not knowing what to do to make things better. It is obvious that the solution is not just to reduce cholesterol and TG, you need to change the composition and nature of the lipids. Looking forward to more info. Thanks

    (reply)
    • Peter Attia  May 4, 2012

      Wow, Larry. That’s a huge compliment. I’m honored, but the credit goes to those who taught me. I’m more than happy to share it.

  36. Mike  May 5, 2012

    Perfectly written. Very clear and concise! Also, Happy Birthday to your Father.

    (reply)
  37. Dan  May 5, 2012

    Hi Peter, I have a quick question for you. If one wanted to reduce one’s intake of coconut oil and butter but still wanted a decent oil to cook with (with optimal omega 3:6 ratio and high smoke point), what would be the best choice of oil to use? Please humor me on this, as I realize the normal recommendation of low carb diets is not to reduce one’s intake of coconut oil or butter, but for those of us who are hyper-absorbers and are trying to limit our saturated fat intake, which type of oil would you recommend? Thanks in advance. Dan.

    (reply)
    • Peter Attia  May 5, 2012

      You may be picking the wrong spot to limit your SFA intake. Besides, does being a hyper-absorber of cholesterol, which is what I assume you mean (e.g., having a defecting ABC,G5/G8), translate to problems with SFA, specifically?

    • KevinF  May 6, 2012

      Dan, take a look at a “high-heat safflower” oil .. this is a high-oleic (monounsaturated fat) version of safflower that’s supposedly good for high heat. It’s nearly all monounsaturated fat — ones I’ve seen have about an 11:2 ratio of Monounsaturad vs. PUFA’s. Recommended btw in Volek, Phinney & Westman’s “New Atkins for a New You”.

      Something like that is not going to have any Omega 3, but the point is that it won’t have much 0mega 6 either, so it’s fairly neutral. One brand I’ve seen out there is Spectrum.

    • Dan  May 6, 2012

      @Peter: I had read in UpToDate monographs, or somewhere else, that limitation of dietary cholesterol is actually trivial compared to limitation of SFA – in terms of reducing serum cholesterol and LDL-C levels (I can’t say for certain about LDL-P but will check in Medline and EMBASE later today). That is, that the emphasis for those who are truly hyperlipidemic should be, besides drugs and exercise, based on SFA limitation.

      @KevinF: Where do you get your high heat safflower oil? Would it be superior to olive oil?

    • Peter Attia  May 6, 2012

      This is simply untrue, but we can certainly thank Ancel Keys for it.

    • KevinF  May 7, 2012

      @Dan, I haven’t actually bought that high oleic safflower — although I might, in order to do more stir fry veggies. My motivation would simply be to get a high smoke point for high heat, which presumably is the only advantage of this type of safflower oil (and similarly, canola oil) over olive oil. I gather that the worst kind of oil is burnt oil.

      If you have a Super Target near you, they tend to have a variety of fancy oils and that Spectrum brand. Also might find it at a Whole-Foods type of store if you have one. Alternatively I buy most such non-standard things from Amazon (that’s where I get my Nutiva coconut oil for example).

    • Dan  May 7, 2012

      @KevinF: Thanks for the tip! I saw Spectrum at my local grocery store but they did not have safflower – I know it’s online at “vitacost.com”. Perhaps I’ll order a case through amazon to save on shipping costs. Thanks again.
      Respectfully,
      Dan

  38. steve  May 6, 2012

    A couple of comments/questions:
    1. It is starting to appear to me that if there is a material discordance between LDL-C and LDL-P with a much higher LDL-P the problem is likely to be genetic; and not so much if at all diet
    2. I know you have not covered it yet, but it seems to me there will always be penetration of the artery wall by LDL-P and if so the real issue is how fast this will occur: the more particles the faster; the fewer particles the slower. Secondly, as relates to this, the inflammatory environment or anti-inflammatory environment will affect to some extent what happens after the LDL-P penetrates the artery wall. I say this as one day all of us will die if we live long enough of either heart disease or cancer.
    3. I wonder about the predictive power of heart disease of LDL-P. After all, in low heart disease nations such as Japan, it is hard to imagine that their genetics are so different from Americans that you don’t see the same poor discordance of LDL-P with LDL-C; and yet they have very very low rates of heart disease. I would also add certain populations that eat lots of carbs where heart disease is virtually absent
    4. Are there people whose numbers are discordant but do not have atherosclerosis? If not, then there must be more to it than particles.
    I know I am getting ahead in some ways of the story, and if so hope you will cover in next post; or provide me with your thoughts to these comments/questions.

    (reply)
    • Peter Attia  May 6, 2012

      All great questions, Steve. This cholesterol “series” may end up having to become its very own blog. This topic is really overwhelming.

  39. Garry  May 6, 2012

    Peter,

    Have you now switched from VAP to NMR? In your ‘personal journey’ posts, you mention that you use VAP, but in the current post you mention the limitations of VAP and the superior reliability of NMR. Just curious. Great info, by the way!

    (reply)
    • Peter Attia  May 6, 2012

      Yes, I switched over exclusively to NMR by Liposcience about 8 months ago for me, my clients, friends, and family. I work with Health Diagnostics Laboratory for all laboratory work. In subsequent posts I’ll review some cases so folks can get a sense of how powerful this test is.

  40. steve  May 6, 2012

    Thank you Peter: I was thinking the same- about its becoming its own blog. Maybe you can get some of your mentors to assist in a cholesterol blog. My questions come as a result of your tackling this subject matter and expressing complicated science in a very clear manner. Trying to understand the presentations on Launch pad has also be of great help. Once we understand, we then have to implement strategies to minimize risk. I am sure you will be tackling that as part of this series.
    Thanks.

    (reply)
  41. Anthony  May 6, 2012

    I have benefited from increasing my fat for sure. A big however – it appears the foods you choose will certainly keep your body running. Are they healing? There are countless papers touting the benefits of plant food and their healing benefits. Fat from meat, heavy cream, salami, bacon and eggs…are not exactly repair foods.

    Your diet does not seem healing at all….or is it?

    Thx

    (reply)
    • Peter Attia  May 6, 2012

      What are the data supporting the healing nature of plant foods, or the absence of “healing” properties in animal products? By “data,” of course, I don’t mean epidemiological reports like the China Study, but rather actual science.

    • Dan  May 7, 2012

      Agreed. I think we need to get away from the whole notion of foods as “nutraceuticals” – “healing benefits” of plants, “repair foods”, “harmful effects of animal fat”, etc. These are simplistic, outdated notions which just lead to fadism. In fact, human physiology is diverse enough that it can adapt to virtually any diet, so long as the essential micronutrient vitamins and minerals are provided (A, B, C, D, E, K, zinc, iron and a few other trace minerals).

      Deficiency diseases are incredibly rare even in impoverished settings in Western countries. What is not so rare are diseases of overnutrition, in particular carbohydrate intolerance and excess. The question is whether replacing carbohydrates with SFA has a long-term beneficial effect on our overall cardiovascular and oncological health – I think the jury is still out on that. However, the surrogate markers look really promising (unfortunately, even diabetes is a surrogate marker, subject to an arbitrary cutpoint on the oral glucose tolerance test – a cutpoint which predicts risk for vascular events, incidentally – which is how it was chosen). I think there are some individuals who may be harmed by an excess of saturated fat and dietary cholesterol, but they are a small (yet still significant) minority. With carbohydrate replacement by fat, they will be less diabetogenic, dysmetabolic, hypertensive, and “inflamed”, but they might still develop the long-term consequences of dietary hyperlipidemia akin to that seen in genetic conditions like familial hypercholesterolemia and familial polygenic hyperlipidemia.

    • Alexandra M  May 7, 2012

      “…plant food and their healing benefits.”

      Food is not medicine. Medicine is not food. Food is fuel. Proper fuel keeps you healthy.

      Could you please list the “countless” papers (links will be acceptable)”touting” the benefits of plant foods and their healing benefits (redundancy alert)?

      How do you KNOW that fats from meat, eggs, etc., are not “repair” foods? I and a lot of other people have found that they are (having stupidly avoided them for years on the advice of the USDA). On what scientific basis do you claim that they are not? (Dr. Attia asked pretty much the same thing, but he’s being polite. I don’t feel any such obligation, since he can delete my comment).

  42. Anthony  May 7, 2012

    I always lump together POLITICS, RELIGION and FOOD. All three will get people crazy. I am no different – I want all the information…even the info I disagree with.

    To say food is not healing counters most research I have looked at. There are vast amounts of research stating the healing benefits from food. “Food is not medicine. Medicine is not food.” Can you cure scurvy with an orange?

    My question is exactly what you are asking me back – “Fat from meat, heavy cream, salami, bacon and eggs…are not exactly repair foods.
    Your diet does not seem healing at all….or is it?” I have not found much stating this food repairs and heals – I may certainly be wrong here – I am simply looking for guidance.

    I have increased my fat intake from 10% to 30% partly based on Dr Attia’s research. I am simply asking if this food heals and if there is research behind it?

    Thank you again for all your positive contributions – I started experimenting with UCan with great results. I now train with the thought of not raising my insulin – it really seams to be working out well.

    Apples
    Boyer J, Liu RH. Apple phytochemicals and their health benefits Nutr J 2004; 3:5.
    Jung M, Triebel S, Anke T, Richling E, Erkel G. Influence of apple polyphenols on
    inflammatory gene expression. Mol Nutr Food Res 2009; 53(10):1263-80.
    Wojdy?o A, Oszmia?ski J, Laskowski P. Polyphenolic compounds and antioxidant
    activity of new and old apple varieties. J Agric Food Chem 2008; 56(15):6520-30.

    Apricots
    Enomoto S, Yanaoka K, Utsunomiya H, et al. Inhibitory effects of Japanese apricot
    (Prunus mume Siebold et Zucc.; Ume) on Helicobacter pylori-related chronic gastritis.
    Eur J Clin Nutr 2010; 64(7):714-9.
    Fujita K, Hasegawa M, Fujita M, et al. [Anti-Helicobacter pylori effects of Bainiku-ekisu
    (concentrate of Japanese apricot juice)] Nippon Shokakibyo Gakkai Zasshi 2002;
    99(4):379-85. [Article in Japanese]

    Bananas
    Chow J. Probiotics and prebiotics: A brief overview. J Ren Nutr 2002; 12(2):76-86.
    Rashidkhani B, Lindblad P, Wolk A. Fruits, vegetables and risk of renal cell carcinoma: a
    prospective study of Swedish women. Int J Cancer 2005; 113(3):451-5.

    Blueberries
    Joseph JA, Shukitt-Hale B, Casadesus G. Reversing the deleterious effects of aging on
    neuronal communication and behavior: beneficial properties of fruit polyphenolic
    compounds. Am J Clin Nutr 2005; 81(1 Suppl):313S-316S.
    Krikorian R, Shidler MD, Nash TA, et al. Blueberry supplementation improves memory
    in older adults. J Agric Food Chem 2010; 58(7):3996-4000.
    Paul S, DeCastro AJ, Lee HJ, et al. Dietary intake of pterostilbene, a constituent of
    blueberries, inhibits the beta-catenin/p65 downstream signaling pathway and colon
    carcinogenesis in rats. Carcinogenesis 2010; 31(7):1272-8.
    Torri E, Lemos M, Caliari V, et al. Anti-inflammatory and antinociceptive properties of
    blueberry extract (Vaccinium corymbosum). J Pharm Pharmacol 2007; 59(4):591-6.17

    Broccoli
    Kim HJ, Barajas B, Wang M, Nel AE. Nrf2 activation by sulforaphane restores the agerelated decrease of T(H)1 immunity: role of dendritic cells. J Allergy Clin Immunol
    2008; 121(5):1255-1261.e7.
    Le HT, Schaldach CM, Firestone GL, Bjeldanes LF. Plant-derived 3,3′-Diindolylmethane
    is a strong androgen antagonist in human prostate cancer cells. Biol Chem 2003;
    278(23):21136-45.
    Li Y, Zhang T, Korkaya H, et al. Sulforaphane, a dietary component of broccoli/broccoli
    sprouts, inhibits breast cancer stem cells. Clin Cancer Res 2010; 16(9):2580-90.
    Murugan SS, Balakrishnamurthy P, Mathew YJ. Antimutagenic effect of broccoli flower
    head by the ames salmonella reverse mutation assay. Phytother Res 2007; 21(6):545-7.

    Carrots
    Coleman AL, Stone KL, Kodjebacheva G, et al. Glaucoma risk and the consumption of
    fruits and vegetables among older women in the study of osteoporotic fractures. Am J
    Ophthalmol 2008; 145(6):1081-9.
    Fernandes I, Faria A, Azevedo J, et al. Influence of anthocyanins, derivative pigments
    and other catechol and pyrogallol-type phenolics on breast cancer cell proliferation. J
    Agric Food Chem 2010; 58(6):3785-92.
    Khachik F, Beecher GR, Smith JC Jr. Lutein, lycopene, and their oxidative metabolites in
    chemoprevention of cancer. J Cell Biochem Suppl 1995; 22:236-46.
    Nicolle C, Cardinault N, Aprikian O, et al. Effect of carrot intake on cholesterol
    metabolism and on antioxidant status in cholesterol-fed rat. Eur J Nutr 2003; 42(5):254-
    61.
    Nurk E, Refsum H, Drevon CA, et al. Cognitive performance among the elderly in
    relation to the intake of plant foods. The Hordaland Health Study. Br J Nutr 2010;
    104(8):1190-201.

    Garlic
    Duda G, Suliburska J, Pupek-Musialik D. Effects of short-term garlic supplementation on
    lipid metabolism and antioxidant status in hypertensive adults. Pharmacol Rep 2008;
    60(2):163-70.
    Gorinstein S, Jastrzebski Z, Namiesnik J, et al. The atherosclerotic heart disease and
    protecting properties of garlic: contemporary data. Mol Nutr Food Res 2007;
    51(11):1365-81.18
    Yeh YY, Liu L. Cholesterol-lowering effect of garlic extracts and organosulfur
    compounds: human and animal studies. J Nutr 2001; 131(3s):989S-93S.

    Ginger
    Ali BH, Blunden G, Tanira MO, Nemmar A. Some phytochemical, pharmacological and
    toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent
    research. Food Chem Toxicol 2008; 46(2):409-20.
    Alizadeh-Navaei R, Roozbeh F, Saravi M, et al. Investigation of the effect of ginger on
    the lipid levels. A double blind controlled clinical trial. Saudi Med J 2008; 29(9):1280-4.
    Park M, Bae J, Lee DS. Antibacterial activity of [10]-gingerol and [12]-gingerol isolated
    from ginger rhizome against periodontal bacteria. Phytother Res 2008; 22(11):1446-9.
    Priya Rani M, Padmakumari KP, Sankarikutty B, et al. Inhibitory potential of ginger
    extracts against enzymes linked to type 2 diabetes, inflammation and induced oxidative
    stress. Int J Food Sci Nutr 2010 Sep 28. [Epub ahead of print]

    Goji Berry
    Amagase H, Sun B, Borek C. Lycium barbarum (goji) juice improves in vivo antioxidant
    biomarkers in serum of healthy adults. Nutr Res 2009 Jan; 29(1):19-25.
    Amagase H, Sun B, Nance DM. Immunomodulatory effects of a standardized Lycium
    barbarum fruit juice in Chinese older healthy human subjects. J Med Food 2009;
    12(5):1159-65.
    Cao GW, Yang WG, Du P.[Observation of the effects of LAK/IL-2 therapy combining
    with Lycium barbarum polysaccharides in the treatment of 75 cancer patients]. [Article in
    Chinese] Zhonghua Zhong Liu Za Zhi 1994;16(6):428-31.
    Potterat O. Goji (Lycium barbarum and L. chinense): Phytochemistry, pharmacology and
    safety in the perspective of traditional uses and recent popularity. Planta Med 2010;
    76(1):7-19.

    Green Tea
    Cooper R, Morré DJ, Morré DM. Medicinal benefits of green tea: Part I. Review of
    noncancer health benefits. J Altern Complement Med 2005; 11(3):521-8.
    Dou QP. Molecular mechanisms of green tea polyphenols. Nutr Cancer 2009; 61(6):827-
    35.
    Mandel SA, Avramovich-Tirosh Y, Reznichenko L, et al. Multifunctional activities of
    green tea catechins in neuroprotection. Modulation of cell survival genes, iron-dependent
    oxidative stress and PKC signaling pathway. Neurosignals 2005; 14(1-2):46-60.19

    Legumes
    Itoh T, Furuichi Y. Lowering serum cholesterol level by feeding a 40% ethanol-eluted
    fraction from HP-20 resin treated with hot water extract of adzuki beans (Vigna
    angularis) to rats fed a high-fat cholesterol diet. Nutrition 2009; 25(3):318-21.
    Kim JM, Kim JS, Yoo H, et al. Effects of black soybean [Glycine max (L.) Merr.] seed
    coats and its anthocyanidins on colonic inflammation and cell proliferation in vitro and in
    vivo. J Agric Food Chem 2008; 56(18):8427-33.
    Yang Y, Zhou L, Gu Y, et al. Dietary chickpeas reverse visceral adiposity, dyslipidaemia
    and insulin resistance in rats induced by a chronic high-fat diet. Br J Nutr 2007;
    98(4):720-6.

    Leafy Vegetables
    Carter P, Gray LJ, Troughton J, et al. Fruit and vegetable intake and incidence of type 2
    diabetes mellitus: systematic review and meta-analysis. BMJ 2010; 341:c4229. doi:
    10.1136/bmj.c4229.
    Hecht SS, Chung FL, Richie JP Jr, et al. Effects of watercress consumption on
    metabolism of a tobacco-specific lung carcinogen in smokers. Cancer Epidemiol
    Biomarkers Prev 1995; 4(8):877-84.
    Kim SY, Yoon S, Kwon SM, et al. Kale juice improves coronary artery disease risk
    factors in hypercholesterolemic men. Biomed Environ Sci 2008; 21(2):91-7.
    Riby JE, Xue L, Chatterji U, et al. Activation and potentiation of interferon-gamma
    signaling by 3,3′-diindolylmethane in MCF-7 breast cancer cells. Mol Pharmacol 2006;
    69(2):430-9.

    Mushrooms
    Akihisa T, Franzblau SG, Tokuda H, et al. Antitubercular activity and inhibitory effect on
    Epstein-Barr virus activation of sterols and polyisoprenepolyols from an edible
    mushroom, Hypsizigus marmoreus. Biol Pharm Bull 2005; 28(6):1117-9.
    Akramiene D, Kondrotas A, Didziapetriene J, Kevelaitis E. Effects of beta-glucans on the
    immune system. Medicina (Kaunas) 2007; 43(8):597-606.
    Gao L, Sun Y, Chen C, et al. Primary mechanism of apoptosis induction in a leukemia
    cell line by fraction FA-2-b-ss prepared from the mushroom Agaricus blazei Murill. Braz
    J Med Biol Res 2007; 40(11):1545-55.20
    Lu X, Chen H, Dong P, et al. Phytochemical characteristics and hypoglycaemic activity
    of fraction from mushroom Inonotus obliquus. J Sci Food Agric 2010; 90(2):276-80.
    Wasser SP. Medicinal mushrooms as a source of antitumor and immunomodulating
    polysaccharides. Appl Microbiol Biotechnol 2002; 60(3):258-74.

    Onions
    Arai Y, Watanabe S, Kimira M, et al. Dietary intakes of flavonols, flavones and
    isoflavones by Japanese women and the inverse correlation between quercetin intake and
    plasma LDL cholesterol concentration. J Nutr 2000;130(9):2243-50.
    Kook S, Kim GH, Choi K. The antidiabetic effect of onion and garlic in experimental
    diabetic rats: meta-analysis. J Med Food 2009;12(3):552-60.
    Mayer B, Kalus U, Grigorov A, et al. Effects of an onion-olive oil maceration product
    containing essential ingredients of the Mediterranean diet on blood pressure and blood
    fluidity. Arzneimittelforschung 2001;51(2):104-11.
    Wagner H, Dorsch W, Bayer T, et al. Antiasthmatic effects of onions: inhibition of 5-
    lipoxygenase and cyclooxygenase in vitro by thiosulfinates and “Cepaenes.”
    Prostaglandins Leukot Essent Fatty Acids 1990; 39(1):59-62.

    Oranges
    Heo HJ, Choi SJ, Choi SG, et al. Effects of banana, orange, and apple on oxidative stressinduced neurotoxicity in PC12 cells. J Food Sci 2008; 73(2):H28-32.
    Jin YR, Han XH, Zhang YH, et al. Antiplatelet activity of hesperetin, a bioflavonoid, is
    mainly mediated by inhibition of PLC-gamma2 phosphorylation and cyclooxygenase-1
    activity. Atherosclerosis 2007; 194(1):144-52.
    Kurowska EM, Spence JD, Jordan J, et al. HDL-cholesterol-raising effect of orange juice
    in subjects with hypercholesterolemia. Am J Clin Nutr 2000; 72(5):1095-100.
    Peppers (Capsicum)
    Ahuja KD, Ball MJ.Effects of daily ingestion of chilli on serum lipoprotein oxidation in
    adult men and women. Br J Nutr. 2006; 96(2):239-42.
    Luo XJ, Peng J, Li YJ. Recent advances in the study on capsaicinoids and capsinoids. Eur
    J Pharmacol 2011; 650(1):1-7.
    Mori A, Lehmann S, O’Kelly J, et al.Capsaicin, a component of red peppers, inhibits the
    growth of androgen-independent, p53 mutant prostate cancer cells. Cancer Res. 2006;
    66(6):3222-9.21
    Schumacher MA.Transient receptor potential channels in pain and inflammation:
    therapeutic opportunities. Pain Pract 2010; 10(3):185-200.

    Tomatoes
    Bhuvaneswari V, Nagini S. Lycopene: a review of its potential as an anticancer agent.
    Curr Med Chem Anticancer Agents 2005; 5(6):627-35.
    Rodríguez-Muñoz E, Herrera-Ruiz G, Pedraza-Aboytes G, Loarca-Piña G. Antioxidant
    capacity and antimutagenic activity of natural oleoresin from greenhouse grown tomatoes
    (Lycopersicon esculentum). Plant Foods Hum Nutr 2009; 64(1):46-51.
    Sedjo RL, Papenfuss MR, Craft NE, Giuliano AR. Effect of plasma micronutrients on
    clearance of oncogenic human papillomavirus (HPV) infection (United States). Cancer
    Causes Control 2003 May;14(4):319-26.
    Silaste ML, Alfthan G, Aro A, Kesäniemi YA, Hörkkö S. Tomato juice decreases LDL
    cholesterol levels and increases LDL resistance to oxidation. Br J Nutr 2007
    Dec;98(6):1251-8.

    Whole Grains
    Murtaugh MA, Jacobs DR Jr, Jacob B, et al. Epidemiological support for the protection
    of whole grains against diabetes. Proc Nutr Soc 2003; 62(1):143-9.
    Lee SH, Chung IM, Cha YS, Park Y. Millet consumption decreased serum concentration
    of triglyceride and C-reactive protein but not oxidative status in hyperlipidemic rats. Nutr
    Res 2010; 30(4):290-6.
    Okarter N, Liu RH. Health benefits of whole grain phytochemicals. Crit Rev Food Sci
    Nutr 2010; 50(3):193-208.
    Pa?ko P, Zagrodzki P, Barto? H, et al. Effect of quinoa seeds (Chenopodium quinoa) in
    diet on some biochemical parameters and essential elements in blood of high fructose-fed
    rats. Plant Foods Hum Nutr 2010; 65(4):333-8.
    Slavin J. Why whole grains are protective: biological mechanisms. Proc Nutr Soc 2003;
    62(1):129-34.

    (reply)
    • Peter Attia  May 7, 2012

      Anthony, have you read all of these studies? I’ll be honest with you, hell will freeze over and I will win the lottery before I will ever read a paper titled, “Epidemiological support for the protection of whole grains against diabetes.” I’m not blowing this off to be rude, but because it’s not possible for me to read and critique every study out there. That’s WHY I write this blog. I’m trying to teach YOU the principles of HOW to read them and to understand why they are of little to no value.

      You’ve got some work ahead of you. I’d recommend starting with my post titled “Is red meat killing us?” Once you understand exactly these common flaws, I think you’ll have a better understanding of why I have little regard for this notion that plant diets are “healing.”

    • Anthony  May 8, 2012

      I have been studying diets for over 10 years (not in a lab but I read everything I can) – Agree to disagree on the plants front and the “benefits” from most meat, heavy cream, salami, bacon.

      Blood work done every six – eight months.

      Could not agree more with the controlling of insulin levels.

      Thanks for the info! Looking forward to your future work.

    • Peter Attia  May 8, 2012

      Nothing wrong with differing views, of course. Just be sure to understand the WHY part of it. Always ask yourself, “Is the effect I’m seeing because I’ve added X, or because I’ve removed Y, or some combination of both?” All of the studies that “prove” plants are healing are not designed to answer this, so it’s very difficult to draw a conclusion. This problem is the essence of all nutrition science, but hopefully we’ll change it. Thanks for fostering the discussion.

    • Alexandra M  May 8, 2012

      “Can you cure scurvy with an orange?”

      Of course. But if you were eating a traditional Inuit diet you wouldn’t get scurvy and you wouldn’t need the orange. Edible oranges are a cultivated crop that didn’t exist until about 2500 BCE. They weren’t available in Europe until after 1400 CE.Scurvy, though it had been known since ancient times, only became an issue when sailors on long ocean voyages had no fresh food of any kind, so oranges were the equivalent of a vitamin supplement.

      The fact that you can use a plant as a treatment for something doesn’t mean that the plant is an essential preventive that must be included in the diet, otherwise we’d be trying to get more willow bark into our diet to prevent headaches.

    • Peter Attia  May 8, 2012

      This is actually a fantastic example, and one worth an entire blog post. I’ll add it to the ever-growing list… Thanks for flagging it. That said, I still have yet to a credible source of data to demonstrate the antioxidants in certain foods actually have any clinical impact on disease states. It’s always the same problem: Is it the presence of X or the absence of Y?

      With out CONTROLLED experiments is it impossible to know. Enter NuSI….stay tuned.

    • Anthony  May 8, 2012

      Understanding what our species originally ate is the million dollar question. Our deficiencies “scurvy” could certainly be avoided by eating our “original” diet. I would argue that most diseases today are created by the very same reason scurvy was created – a lack of something or too much of something else (fast food as one example).

      My argument has nothing to do with an orange – it has to do with when deficiencies are created via diet, stress, pollution etc we get sick. Fill those deficiencies in with proper food (My belief Green Food as part of it) we get better. I have seen absolutely miraculous healing via lifestyle changes (food, exercise, stress mgmt etc). We can all argue the finer points of my experiences which is OK. Me pushing my beliefs on Peter is only to get him to look at the big picture from my experiences (which is unfair)…but it was worth a shot:)

      I would love to see good intelligence on what was available 10,000 years ago? Thx!

    • Peter Attia  May 9, 2012

      “I would love to see good intelligence on what was available 10,000 years ago?” As would I. Absent that, however, we need to use the best judgement we have today to make the best decisions we can.

    • JohnJ  May 9, 2012

      Well even do there is a lot of baloney in nutritional science, there is no denying that what we eat, breath and drink has a great effect on our well being as we already know some can be pretty bad like excess fructose and sugar. There is no reason not to believe that some may be good for you including nutrient in good meat and other nutrients found in foods.

      Flavonoid Compound Found in Foods and Supplements May Prevent the Formation of Blood Clots, Study Suggests

      http://www.sciencedaily.com/releases/2012/05/120508124545.htm

      “Rutin proved to be the most potently anti-thrombotic compound that we ever tested in this model,” says Flaumenhaft. Of particular note, rutin was shown to inhibit both platelet accumulation and fibrin generation during thrombus formation. “Clots occur in both arteries and in veins,” explains Flaumenhaft.

      “Clots in arteries are platelet-rich, while those in veins are fibrin-rich. This discovery suggests that a single agent can treat and prevent both types of clots.”
      Even with the use of existing anti-clotting therapies, such as aspirin, clopidogrel (Plavix) and warfarin (Coumadin), each year there are approximately 400,000 recurrent episodes among patients who previously experienced a stroke or heart attack, says Flaumenhaft.

      “A safe and inexpensive drug that could reduce recurrent clots could help save thousands of lives,” he adds. “These pre-clinical trials provide proof-of-principle that PDI is an important therapeutic target for anti-thrombotic therapy, and because the FDA has already established that rutin is safe, we are poised to expeditiously test this idea in a clinical trial, without the time and expense required to establish the safety of a new drug.”

    • Jeffrey of Troy  May 11, 2012

      @ Anthony

      how to tell which plant foods send the healing signal, and which don’t, and how to incorporate them into a LC diet:

      http://www.jeffreybrauer.blogspot.com/2012/03/signaling-nutrigenomics-made-easy.html

  43. Jennifer  May 7, 2012

    Peter,
    I’m so glad you are doing this series! I feel like you read my mind- I just received my lab work back from the doctor and my cholesterol is high. I have been working on eating a ketogenic diet, and so was confused if this was bad or not. My LDL is high, but HDL is even higher, so the doctor said I was safe. All this was so confusing and I was wanting to learn more about it, and suddenly… your blog post! Can’t wait for the next installments!

    (reply)
    • Peter Attia  May 7, 2012

      Part III should be ready tomorrow or Wednesday.

    • Debbie  May 9, 2012

      My HDL is high too – the highest my cardiologist has ever seen: 161. Yeah, HDL. They lab repeated it. My LDL is 151. He’s doing a more advanced cholesterol test, but also talking about statins.

  44. Dan  May 8, 2012

    Just wanted to say thanks for taking the time and effort to put these posts together and that I am now a regular reader of your blog! You do a great job at articulating some really tough concepts.

    (reply)
  45. Victoria  May 8, 2012

    I hope your posts include how to increase de novo cholesterol synthesis within cells. (I presume that’s mostly a good thing?) :)

    (reply)
  46. Anon  May 8, 2012

    Hi Dr. Attia,

    For the last 5-6 months, I switched over to a low carb (~50-75g/day) diet, mostly making up the calories with whey protein and lots of fats (olive oil, avocado, grass fed butter). I’m also supplementing with vitamin D and lifting weights 3x a week.

    While a lot of clear markers improved, my total cholesterol and LDL jumped quite a bit, to levels that I believe you’ve mentioned you feel are high. (I’m male and I think you mentioned 220 as a reasonable limit)

    What next tests or changes would you make if you were me?

    Total cholesterol: 204 –> 238 * scares me the most out of all thee numbers. Most say this should be below 220.
    HDL: 60 –> 70 * very nice improvement
    Triglyceride: 104 –> 84 * very nice improvement
    LDL: 123 –> 151 * big jump here. most docs hate to see this, but from what i’m reading LDL doesn’t mean very much – only particle size.
    Triglyceride/HDL ratio: 1.73 –> 1.2 * this is considered the best predictor of cardiovascular disease. Very nice change here

    Should I be worried about that 238 number?

    (reply)
  47. steve  May 9, 2012

    Hi Dr. Attia:
    Might be helpful for you to tell us what some of your mentors say about diet if cholesterol does not matter, or sat fats. This is what the Nat Lipid Assoc member dietician says in an online interview: fiber rich whole foods- fruit, vegs and whole grains! Substitute mono and poly fats for sat fat.
    http://www.reachmd.com/xmsegment.aspx?sid=6548

    (reply)
    • Peter Attia  May 9, 2012

      They agree these guidelines are based on dogma not rigorous science.

  48. John Dawson  May 9, 2012

    At the top of Cho II it says 112 comments, but scrolling down I cannot get beyond #48

    (reply)
    • Peter Attia  May 9, 2012

      The 112 includes all of the sub-comments.

  49. Mike N.  May 9, 2012

    Dr. Attia, three weeks after a carotid endarterectomy my LDL-C has spiked. Is an increase in LDL-C a normal healing response to such surgery?

    (reply)
    • Peter Attia  May 9, 2012

      Good question. I do not know the answer.

  50. Roz  May 10, 2012

    Hello, again. I am curious to know your thoughts (if any), in a nutshell, about bulletproofexec.com? This site and the lifestyle it supports is quite Paleo in nature and also argues against high carbs/bad carbs. As always, thank you for sharing your knowledge, thoughts and inspiration!

    (reply)
    • Peter Attia  May 10, 2012

      I have not read it.

    • KevinF  May 12, 2012

      Any website that advocates adding a stick of butter to your coffee gets two thumbs up from me…

  51. Paul  May 15, 2012

    Peter – Interesting bit in the NYTimes today. Although they still don’t get it, there is some evidence in their model that points in the right direction, though they don’t seem to understand the cause/effect (e.g. insulin sensitivity/metabolic syndrome).

    http://www.nytimes.com/2012/05/15/science/a-mathematical-challenge-to-obesity.html?_r=1&hpw

    “That the conventional wisdom of 3,500 calories less is what it takes to lose a pound of weight is wrong. The body changes as you lose. Interestingly, we also found that the fatter you get, the easier it is to gain weight. An extra 10 calories a day puts more weight onto an obese person than on a thinner one.”

    (reply)
    • KevinF  May 15, 2012

      That IS interesting, although I don’t believe for one second they’ve succeeded in creating a “single equation” that can accurately predict anyone’s weight response. Starting with the flaw that their prized simulator overestimates the daily caloric intake that makes me weight-stable by about 1000 calories! (I wish…)

    • lorraine  May 16, 2012

      I think the statement “an extra 10 calories a day puts more weight onto an obese person than on a thinner one” is of the kind that makes Gary Taubes nuts.

  52. lorraine  May 16, 2012

    Getting ready for Part IV by re-reading the series (and also took an initial stab at Dr. Dayspring’s cholesterol synthesis slides at Lecturepad).

    A question which has bugged me from Part I and is related to this post as well is: why is cholesterol which is excreted via the biliary pathway reabsorbed? Is this just a product feedback thing, or does this only happen pathologically?

    Ready for Part IV: Hit me!

    (reply)
    • Peter Attia  May 17, 2012

      Reabsorption is 100% necessary and normal. Only when out of balance is it a problem. Part IV coming soon…

  53. Nina  May 28, 2012

    Thank you for all you do, Peter. You’ve opened up a whole new area of interest & study for me – it’s absolutely fascinating. Also love Lecture Pad & the Lipid Center sites.

    I have a question about point #4 in your information below the figure depicting the various sizes of lipoproteins. Should not the ratios of VLDL’s say (5:1) 5 times more TG to CE & LDL’s (4:1) 4 times more TG to CE, rather than saying CE to TG? I’ve just read something by Dr. Dayspring that said VLDL’s have 5 times more TG than CE.

    (reply)
    • Peter Attia  May 28, 2012

      In a VLDL particle TG is > CE; In an LDL particle, this is reversed. See the table in part II of this series. Let me know if I’ve misrepresented this fact somewhere.

  54. Sarah  June 1, 2012

    I’d like to add additional information about cholesterol and you will find it here – http://articles.mercola.com/sites/articles/archive/2010/08/10/making-sense-of-your-cholesterol-numbers.aspx

    (reply)
  55. Jay Booth  June 28, 2012

    I studied as a Medical Technologist and we were never taught any of this in Clinical Chemistry, which would have been very interesting to me. And I have to agree with the statement about doctors;I worked at JHH, and we taught alot of the doctors( residents).They are bombarded with so much information at once that it’s very hard for them to learn in a “crash course”. Being on both sides, as a transplant patient and a Med Tech, I have become more aware of my health.
    Thank you, Dr. Attia.

    (reply)
    • Peter Attia  June 28, 2012

      Jay, I wonder if we ever overlapped when I was at Hopkins? I was there 2001 to 2006. Did lots of stuff on transplant with some great folks.

  56. Jay Booth  June 29, 2012

    Maybe Peter, I was there 2000-2005, and worked in the Microbiology Lab; it’s a big place but possible. I met many great folks there as well.

    I have a question. From your experience, would it be possible to have an effect on my lipid levels while being on the various meds for transplant? Just curious if might have a general idea.
    Thanks, Jay.

    (reply)
    • Peter Attia  June 29, 2012

      I would suspect transplant meds can likely have an impact on lipid and lipoprotein levels, though I can’t confirm that off the top of my head.

  57. Tina  July 27, 2012

    Hi Peter,

    Loving this series but I’m confused about statement 4 under the figure of different lipoproteins:
    Each specific lipoprotein has a different core make up – meaning the variable ratio of TG to cholesterol ester changes. A particle of VLDL has 5 times more CE than TG whereas a particle of LDL typically has 4 or more times more CE than TG (i.e., ratio > 4:1), and an HDL has 90-95% CE and < 10% TG in its core.

    Don't the ratios stated above mean that VLDL is 83% CE and 17% TG, and LDL would be 80% CE and 20% TG? Why would VLDL have more CE, if cholesterol concentration increases as the size of lipoprotein molecule decreases?

    (reply)
    • Peter Attia  July 28, 2012

      Great catch, Tina! Thank you. VLDL has 5 times more TG than CE. Corrected.

  58. Charles Spencer  August 19, 2012

    Peter,
    Thank you so much for this series. It’s going to take many many re-reads to begin to comprehend all this even though you have a gift for making the complex comprehensible. I look forward to understanding this on a deeper level as fat and cholesterol have played a key part of my recovery from the damaging effects of celiac disease as well as the secondary complications of severe rheumatoid arthritis. I eat high fat and on most days eat upwards of at least two dozen raw eggs as a crucial part of my recovery. I am not a biochemist nor am I trained in the medical sciences and so I sometimes go off on poorly informed goose chase tangents of speculation. I wondered aloud to myself as others were trying to figure out the mechanism of cholesterol plaque deposition on artery walls if there might be some sort of similar mechanism to the phenomenon of leaky gut. I cannot even begin to propose a mechanism for why this might be. I do know that lectin content in food was contributing to my leaky gut syndrome allowing all sorts of things into my circulation when my gut damage was severe and my systemic inflammation was so out of control . Would there be some inflammatory response in the arterial walls that would mimic the loosening of junctions in the gut wall thus making arterial walls more susceptible to deposition of cholesterol plaques, perhaps even regardless of particle size (although I do suppose there would be a prevalence of small particles just by mechanical limitations?) I know that when systemic inflammation was widespread, I was experiencing what I was told was permanent joint damage and that by eating lots of eggs and coconut oil while being very low carb I have actually reversed the joint damage and my last dexa scan numbers were much better than baseline three years ago and follow up two years ago. The only thing that has my doctor worries is my LDL number.. which I am not at all concerned about. Funny, he kept on congratulating me for making such incredible progress in all markers (including being an inch taller at my last dexa scan) having great numbers all around and looking better and being able to do things like walk again.. but when he looked at the LDL number immediately went the statin route. I politely told him I was not at all interested since they keep arbitrarily moving the numbers lower and that I am just fine. He had no response other than to tell me to keep up the good work. Sorry to be long winded but I will try to study harder and come up with a hypothesis for the leaky arterial wall theory over time. Thanks again for your incredible contribution.

    (reply)
    • JohnK  January 13, 2013

      Hi Charles –

      Just a thought, based on years of personal experience, that your celiac disease, “arthritis” and leaky gut may be related to chronic Lyme disease. I thought I had celiac disease, but when I got successfully treated for Lyme disease, it went away. I now live virtually carb-free at this point, but that’s a different story.

      My two sons also had chronic Lyme for many years. Fortunately it appears to be in remission for the time being. If you do look into this, trust me when I tell you that the medical community’s approach to this devastating disease is no better than the convention wisdom regarding diet, blood lipids and heart disease. You have to do a lot of research to home in on the truth.

      Good luck.

  59. Joseph  September 25, 2012

    There is an error in your page’s code on line 336 column 1128. There quotation mark is on the wrong side of the semi-colon. For quick reference it is in the link that is prefaced with the words “you’ll need to subscribe — for free — to”. The error causes a full paragraph of the article to be hidden from the viewer.

    Came here via Mark’s Daily Apple. I am liking this version much better than the summary on his site. When reading it on his I could tell that things were being cut short to make it fit into 2 posts, and the added information here is filling out the gaps that i perceived quite nicely. Thanks for this fantastic write-up.

    (reply)
    • Peter Attia  September 26, 2012

      Nice catch, Joseph! Thank you. Should be fixed now.

  60. KevinF  January 12, 2013

    Semi-irrelevant question, but it bugs me and I’m hoping someone can answer. This whole lipoprotein thing is necessary because fat is insoluble in water. But — how do you explain milk? Cream in coffee? I pour whipping cream into my coffee, and it seems to blend in nicely to make a smooth, consistent light brown liquid. Yet if I’d poured olive oil into water I’d get these unsightly globules floating around like a lava lamp. What’s the deal with fat in milk?

    (reply)
    • Peter Attia  January 12, 2013

      The fat is protein bound. So the proteins, like albumin, act like the lipoproteins and proteins in our plasma.

  61. Caitlin  July 25, 2013

    “Sugar and salt will easily dissolve in water. They are, therefore, hydrophilic. Oil does not dissolve in water. It is, therefore, hydrophobic. By extension, a molecule of glucose (sugar) or sodium and chloride ions (salt), because of their chemical properties which I won’t detail here, will travel through plasma without assistance. A lipid will not.”

    I’m on board with the whole fat and cholesterol are good for you in the absence of sugar and glucose, but what about salt? Based on your example above, it has the same (or similar) absorption properties as sugar where it could cause artery plaque (which jives with the conventional wisdom that a diet high in sodium is linked to heart disease). Since a lot of fatty foods are high in sodium I’m curious if you avoid those? It doesn’t seem like you do based on the sodium supplement you detail in your post on what you actually eat. Would love to know the “why” on that.

    (reply)
    • Peter Attia  July 26, 2013

      Evidence implicating sodium in hypertension is pretty weak, but may be context dependent. In other words, other dietary factors, such as fructose, may exacerbate impact of sodium on BP, if such an effect is present. Most recent report by Institute of Medicine says data implicating sodium in HTN is very poor, and low levels of sodium are probably harmful. Ketosis is a unique state that does required supplemental sodium beyond what most people get in their diet.

  62. Caitlin  August 1, 2013

    After thinking about this (the whole sodium thing) a little more, I came up with a perhaps oversimplified hypothesis: a sugar molecule is “stickier” than a salt molecule. If you think not of dissolving salt and sugar in a cup of water, but instead a cup of sugar and a cup of salt each with a few drops of water. The sugar becomes sticky where it interacts with water whereas the salt is still corse. This is the same idea as you mentioned, the effects of sodium may be magnified by the presence of fructose. Just a thought.

    (reply)
  63. danny  August 19, 2013

    Hey Peter. I know I’m pretty late to this party but I think I have a good question. I watched a bunch of Mr Daysprings lectures (awesome…but quite dense!) and I’m struggling to tell the functional differences between HDL and LDL cholesterol. Here’s what I’ve picked up
    1.They both seem to pick up and drop off cholesterol at various places, including each other.
    2. It seems like LDL’s are born of VLDL’s after the VLDL’s reduce TG content at adipocytes (may be right off the mark here)
    3. LDL’s dump cargo on artery walls.
    4. LDL’s are wrapped in APoB HDL’s are wraped in APoA

    Of course there are many more specifics may these are the key players that I could ascertain.

    Is it as simple as lipid density attracting either APoA or ApoB? What am I missing? Or am I trying to imagine a functional reason because HDL is the hero and LDL is the villian?

    Any help would be great. Big fan of your work. Cheers

    (reply)
    • Peter Attia  August 20, 2013

      All of our statements are more or less correct, less a few nuances, though I’m not sure I understand your specific question. Both LDL and HDL particles remove cholesterol from the subendothelial space. Their difference is that only LDL particles get retained there, and that most likely has to do with the structure of the apoB lipoprotein.

  64. Kevin  September 16, 2013

    Hi Peter,

    I am taking biochemistry in medical school and ran across this great series while we are studying cholesterol, lipid transport etc. In our lecture slides it states that HDL is the only carrier of cholesterol back to the liver in reverse cholesterol transport (the lecturepad link doesn’t seem to work anymore) which you state is not the case. I did a few quick Google searches for “indirect reverse cholesterol transport” and didn’t come up with much, do you happen to have a source that I may question (or grill) my professor about?

    Thanks

    (reply)
    • Peter Attia  September 16, 2013

      Just responded to your other question. LecturePad is place to go.

  65. Kevin  September 16, 2013

    I’m not sure if my last comment posted, but I am a medical student going through biochemistry and was wondering if you had a source, or article explaining indirect reverse cholesterol transport that I could show my professor. Our lecture slides seem to indicate that HDL is the only one that carries cholesterol back to the liver by using reverse cholesterol transport (the lecturepad link on this is sadly broken in the blog post).

    Thanks

    (reply)
    • Peter Attia  September 16, 2013

      Is it broken, or not giving you access? One needs to sign up (for free) to access LecturePad. Go there and sign up first, then try the link.

    • Irina  November 23, 2013

      Hey Kevin,

      Curious to hear an update: What were your findings with your professor re LDL transporting cholesterol back into the liver?

      Cheers.
      Irina

  66. GerryC  October 20, 2013

    Peter:

    I Have a question regarding the role lipoproteins play in fat transport. I understand that lipoproteins transport trigs from the liver to fat cells and muscle cells, but what about when fat cells release trigs as fatty acids to be used as fuel? Are these fatty acids rebundled (if you will) as trigs on lipoproteins to be carried to muscle cells or can they be transported directly in the bloodstream as fatty acids?

    I understand that lipoproteins transport trigs from the gut and liver, but am confused as to whether they also transport between fat cells and muscle cells.

    Thanks,
    Gerry

    (reply)
    • Peter Attia  October 21, 2013

      They are typically transported by albumin. Also, chylomicrons transport TG from the gut, so TG and FFA transport is kind of complicated.

    • James  April 4, 2014

      Peter. I’m having problems connecting your theories with practical application to the general population. Have you actually looked into Taubes books and what he says about carbohydrates and cholesterol? I think his efforts are rather deceiving and bias.

  67. Eren  January 9, 2014

    Hi Peter,

    First of all, thanks for this great resource on cholesterol. I am trying to learn as much as possible.

    this link, http://www.mendeley.com/research/dietary-cholesterol-and-coronary-artery-disease-a-systematic-review/ , from last weeks take away messages is broken. Can you provide a good one?

    Thanks

    (reply)
  68. James Quarello  February 1, 2014

    Hi Peter,
    I have been following a low carb diet for about 4 months now. I am not overweight and exercise 5 days a week. I have high BP which I am treating with meds. It was a year ago I discovered my high BP at my annual physical. The blood work at that time showed I had “high” cholesterol. I just came from the doctors office now a year later. My trigs are low (50) and have not changed. What has changed is my total cholesterol. It has risen 84 points. My total is now over 300! My HDL went up 30, my LDL 54. Needless to say my doctor is not pleased. When he used a risk factor calculator of some kind, I am still okay according the the math. My ratio (TC/HDL) is 3.2, which is “good”. Trig ratio is fantastic .5. Yet I can not help but be concerned at these numbers.

    I had been following a more conventional diet up until 4 months ago, high carbs, low fat. I had a blood test in October and my HDL had went up 14 points while my LDL did not move. That gave me my best TC/HDL ratio of 3.0. As I said that is when I began following a low carb diet.

    Right now I am having serious doubts about the wisdom of the low carb, high fat diet. Believe me I strictly follow the parameters. I can’t help but think this diet and my substantially elevated cholesterol is not the right answer.

    Thanks for putting up such a great site, you do provide lots of great insight into healthy eating.

    (reply)
  69. Mark Lewis  March 28, 2014

    The link to supporting research in point #7 in Section 2 (eating cholesterol) is broken – darn! and Rock on! Thank you for the tremendous gift of your time and expertise.

    (reply)
  70. Mike  April 5, 2014

    When scientist feed Aluminum salts in water to Wistar mice the alum levels were found to deposit into the hepatic area, liver. It makes since to follow your diet in order to avoid alum salts in food from being absorbed into the liver. In one of your lectures you also showed fat under skin and a place where aluminum salt could store. I do not find many people addressing alum salts issues in diet. Would you be interested in these published works. Thanks

    (reply)
  71. Gaston  October 31, 2014

    I still can’t understand what’s the point of making a particle to transport cholesterol through blood when every cell is capable of make it, just to return it back to the liver once the TG were delivered…. Maybe particle stabilization?

    (reply)
    • Peter Attia  November 1, 2014

      Not every cell. Paradoxically, two types of cells that need a lot of cholesterol are not capable of making any.

Add a Comment

Disclaimer: This blog is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this blog or materials linked from this blog is at the users own risk. The content of this blog is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard, or delay in obtaining, medical advice for any medical condition they may have, and should seek the assistance of their health care professionals for any such conditions.

Connect with Facebook