Answer Day: What Causes High LDL on Low-Carb Paleo?

First, thank you to everyone who commented on the quiz. I enjoyed reading your thoughts.

Is High LDL Something to Worry About?

Perhaps this ought to be the first question. Jack Kronk says “I don’t believe that high LDL is necessarily a problem” and Poisonguy writes “Treat the symptoms, Larry, not the numbers.” Poisonguy’s comment assumes that the LDL number is not a symptom of trouble. Is it?

I think so. It helps to know a little about the biology of cholesterol and of blood vessels.

When cells in culture plates are separated from their neighbors and need to move, they make a lot of cholesterol and transport it to their membranes. When cells find good neighbors and settle down, they stop producing cholesterol.

The same thing happens in the body. Any time there is a wound or injury that needs to be healed, cholesterol production gets jacked up.

When people have widespread vascular injuries, cholesterol is produced in large quantities by cells lining blood vessels. Now, to repair injuries cells have to coordinate their functions. Endothelial cells are the coordinators of vascular repair: they direct other cell types, like smooth muscle cells and fibroblasts, in the healing of vascular injuries.

To heal vascular injuries, these cells not only need more cholesterol for movement; they also need to multiply. It turns out that LDL, which carries cholesterol, also causes vascular cells to reproduce (“mitogenesis”):

The best-characterized function of LDLs is to deliver cholesterol to cells. They may, however, have functions in addition to transporting cholesterol. For example, they seem to produce a mitogenic effect on endothelial cells, smooth muscle cells, and fibroblasts, and induce growth-factor production, chemotaxis, cell proliferation, and cytotoxicity (3). Moreover, an increase of LDL plasma concentration, which is observed during the development of atherosclerosis, can activate various mitogen-activated protein kinase (MAPK) pathways …

We also show … LDL-induced fibroblast spreading … [1]

If endothelial cells are the coordinators of vascular repair, and LDL particles their messengers to fibroblasts and smooth muscle cells, then ECs should be able to generate LDL particles locally. Guess what:  ECs make a lipase whose main effect is to decrease HDL levels but can also convert VLDL and IDL particles into LDL particles and remove fat from LDL particles to make them into small, dense LDL:

Endothelial lipase (EL) has recently been identified as a new member of the triglyceride lipase gene family. EL shares a relatively high degree of homology with lipoprotein lipase and hepatic lipase …

In vitro, EL has hydrolyzed phospholipids in chylomicrons, very low density lipoprotein (VLDL), intermediate density lipoprotein and LDL. [2]

Immune cells, of course, are essential for wound healing and they should be attracted to any site of vascular injury. It turns out that immune cells have LDL receptors and these receptors may help them congregate at sites of vascular injury. [3]

I don’t want to exaggerate the state of the literature here:  this is a surprisingly poorly investigated area. But I believe these things:

1.      Cholesterol and LDL particles are part of the vascular wound repair process.

2.      Very high LDL levels are a marker of widespread vascular injury.

Now this is not the “lipid hypothesis.” Compare the two views:

  • The lipid hypothesis:  LDL cholesterol causes vascular injury.
  • My view:  LDL cholesterol is the ambulance crew that arrives at the scene of the crime to help the victims. The lipid hypothesis is the view that ambulance drivers should be arrested for homicide because they are commonly found at murder scenes.

So, to Poisonguy, on my view high LDL numbers are a symptom of vascular injury and are a cause for concern.

Big-Picture View of the Cause of High LDL

So, on a micro-level, I think vascular damage causes high LDL. But what causes vascular damage?

Here I notice a striking difference in commenters’ perspectives and mine. I tend to take a big-picture, top-down view of biology. There are three basic causes of nearly all pathologies:

1.      Toxins, usually food toxins.

2.      Malnutrition.

3.      Pathogens.

The whole organization of our book is dictated by this view. It is organized in four Steps. Step One is about re-orienting people’s views of macronutrients away from high-grain, fat-phobic, vegetable-oil-rich diets toward diets rich in animal fats. The other steps are about removing the causes of disease:

1.      Step Two is “Eat Paleo, Not Toxic” – remove food toxins.

2.      Step Three is “Be Well Nourished” – eliminate malnutrition.

3.      Step Four is “Heal and Prevent Disease” – address pathogens by enhancing immunity and, where appropriate, taking advantage of antibiotic therapies.

So when someone offers a pathology, any pathology, my first question is: Which cause is behind this, and which step do they need to focus on?

In Larry’s case, he had been eating low-carb Paleo for years. So toxins were not a problem.

Pathogens might be a problem – after all, he’s 64, and everybody collects chronic infections which tend to grow increasingly severe with age – but Larry hadn’t reported any other symptoms. More to the point, low-carb Paleo diets typically enhance immunity, yet Larry had fine LDL numbers before adopting low-carb Paleo and then his LDL got worse. So it wouldn’t be infectious in origin unless his diet had suppressed immunity through malnutrition – in which case the first step would be to address the malnutrition.

Step Three, malnutrition, was the only logical answer. The conversion to Paleo removes a lot of foods from the diet and could easily have removed the primary sources of some micronutrients.

So I was immediately convinced, just from the time-course of the pathology, that the cause was malnutrition.

Micronutrient Deficiencies are Very Common

In the book (Step Three) we explain why nearly everyone is deficient in micronutrients. The problems are most severe for minerals:  water treatment removes minerals from water, and mineral depletion of soil by industrial agriculture leads to mineral deficiencies in farmed plants and grain-fed animals.

This is why our “essential supplements” include a multimineral supplement plus additional quantities of five minerals – magnesium, copper, chromium, iodine, and selenium. Vitamins get a lot of attention, but minerals are where the big health gains are.

Copper Deficiency and LDL

Some micronutrient deficiencies are known to cause elevated LDL.

Readers of our book know that copper causes vascular disease; blog readers may be more familiar with an excellent post by Stephan, “Copper and Cardiovascular Disease”, discussing evidence that copper deficiency causes cardiovascular disease. As I’ve just argued that cardiovascular disease causes high LDL, it shouldn’t be a surprise that copper deficiency also causes hypercholesterolemia:

Copper and iron are essential nutrients in human physiology as their importance is linked to their role as cofactors of many redox enzymes involved in a wide range of biological processes, as well as in oxygen and electron transport. Mild dietary deficiencies of both metals … may cause long-term deleterious effects in cardiovascular system and alterations in lipid metabolism (3)….

Several studies showed a clear correlation among copper deficiency and dyslipidemia. The main alterations concern higher plasma CL and triglyceride (TG) concentrations, increased VLDL-LDL to HDL lipoproteins ratio, and the shape alteration of HDL lipoproteins.  [4]

The essentiality of copper (Cu) in humans is demonstrated by various clinical features associated with deficiency, such as anaemia, hypercholesterolaemia and bone malformations. [5]

Over the last couple of decades, dietary copper deficiency has been shown to cause a variety of metabolic changes, including hypercholesterolemia, hypertriglyceridemia, hypertension, and glucose intolerance. [6]

Copper deficiency is, I believe, the single most likely cause of elevated LDL on low-carb Paleo diets. The solution is to eat beef liver or supplement.

So, was my advice to Larry to supplement copper?  Yes, but that was not my only advice.

Other Micronutrient Deficiencies and Elevated LDL

Another common micronutrient deficiency that causes elevated LDL cholesterol is choline deficiency that is NOT accompanied by methionine deficiency. That is discussed in my post “Choline Deficiency and Plant Oil Induced Diabetes”:

Choline deficiency (CD) by itself induces metabolic syndrome (indicated by insulin resistance and elevated serum triglycerides and cholesterol) and obesity.

A combined methionine and choline deficiency (MCD) actually causes weight loss and reduces serum triglycerides and cholesterol …

I quote both these effects because it illustrates the complexity of nutrition. A deficiency of a micronutrient can present with totally different symptoms depending on the status of other micronutrients.

Julianne had a really nice comment, unfortunately caught in the spam filter for a while, with a number of links. She mentions vitamin C deficiency and, with other commenters, noted the link between hypothyroidism and elevated LDL. As one cause of hypothyroidism is iodine or selenium deficiency, this is another pathway by which mineral deficiencies can elevate LDL.

UPDATE: Mike Gruber reduced his LDL by 200 mg/dl by supplementing iodine. Clearly iodine can have big effects!

Other commenters brought up fish oil. They may be interested to know that fish oil not only balances omega-6 to modulate inflammatory pathways, it also suppresses endothelial lipase and thus moderates the LDL-raising and HDL-lowering effect of vascular damage:

On the other hand, physical exercise and fish oil (a rich source of eicosapentaenoic acid and docosahexaenoic acid) suppress the activity of EL and this, in turn, enhances the plasma concentrations of HDL cholesterol. [7]

Whether this effect is always desirable is a topic for another day.

My December Advice to Larry

So what was my December advice to Larry?

It was simple. In adopting a low-carb Paleo diet, he had implemented Steps One and Two of our book. My advice was to implement Step Three (“Be well nourished”) by taking our recommended supplements. Eating egg yolks and beef liver for copper and choline is a good idea too.

Just to cover all bases, I advised to include most of our “therapeutic supplements” as well as all the “essential supplements.”

Since December, Larry has been taking all the recommended supplements and eating 5 ounces per week of beef liver. As I noted yesterday, Larry’s LDL decreased from 295 mg/dl to 213 mg/dl, HDL rose from 74 mg/dl to 92 mg/dl, and triglycerides fell from 102 to 76 mg/dl since he started Step Three. This is all consistent with a healthier vasculature and reduced production of endothelial lipase.


Some people think there is something wrong with a diet if supplements are recommended. They believe that a well-designed diet should provide sufficient nutrition from food alone, and that if supplements are advised then the diet must be flawed.

I think this is quite mistaken. The reality is that Paleolithic man was often mildly malnourished, and modern man – due to the absence of minerals from treated water and agriculturally produced food, and the reduced diversity and higher caloric density of our foods – is severely malnourished compared to Paleolithic man.

We recommend eating a micronutrient-rich diet, including nourishing foods like egg yolks, liver, bone broth soups, seaweed, fermented vegetables, and so forth. But I think it’s only prudent to acknowledge and compensate for the widespread nutrient depletion that is so prevalent today. Even when nutrient-rich food is regularly eaten, micronutrient deficiencies are still possible.

Eating Paleo-style is not enough to guarantee perfect health. Luckily, supplementation of the key nutrients that we need for health and that are often missing from foods will often get us the rest of the way.


[1] Dobreva I et al. LDLs induce fibroblast spreading independently of the LDL receptor via activation of the p38 MAPK pathway. J Lipid Res. 2003 Dec;44(12):2382-90.

[2] Paradis ME, Lamarche B. Endothelial lipase: its role in cardiovascular disease. Can J Cardiol. 2006 Feb;22 Suppl B:31B-34B.

[3] Giulian D et al. The role of mononuclear phagocytes in wound healing after traumatic injury to adult mammalian brain. J Neurosci. 1989 Dec;9(12):4416-29.

[4] Tosco A et al. Molecular bases of copper and iron deficiency-associated dyslipidemia: a microarray analysis of the rat intestinal transcriptome. Genes Nutr. 2010 Mar;5(1):1-8.

[5] Harvey LJ, McArdle HJ. Biomarkers of copper status: a brief update. Br J Nutr. 2008 Jun;99 Suppl 3:S10-3.

[6] Aliabadi H. A deleterious interaction between copper deficiency and sugar ingestion may be the missing link in heart disease. Med Hypotheses. 2008;70(6):1163-6.

[7] Das UN. Long-chain polyunsaturated fatty acids, endothelial lipase and atherosclerosis. Prostaglandins Leukot Essent Fatty Acids. 2005 Mar;72(3):173-9.

Leave a comment ?


  1. Hi Garrett,

    In your view are the tests accurate?

    Copper status in particular seems to be very difficult to measure.

  2. Hi John,

    You’re right about the missing word!

    Very nice thoughts and links. Nice response on the Shai study too.

    Hi Alex,

    Yes, I do think mild atherosclerosis is widespread.

    Hi simona,

    I’m not saying that high LDL in the general populace is mainly due to copper deficiency – I think that’s mainly due to atherosclerosis and metabolic syndrome. But among low-carb Paleo dieters, I think micronutrient deficiencies generally are the likeliest cause of high LDL. Copper is a likely specific culprit.

    Hi Bob,

    I don’t think Larry’s current numbers are ideal, but they’re better than they were.

    I don’t really know what “perfect” would be. Optimal LDL is higher for people with infections, lower for people who are infection-free. I’d guess that for a typical person optimal might be near 100 mg/dl for both LDL and HDL. But the healthy range is probably pretty broad.

    I trust the body to adjust LDL levels to the optimum for your state of health. I think if you fix all micronutrient deficiencies, your LDL numbers will become very good for you, wherever they end up.

    Hi Raj,

    My LDL numbers didn’t go up when I adopted low-carb high-fat Paleo, so I don’t think you can say everyone’s go up.

    In fact if you use the Iranian equation to correct for my decline in trigs, my LDL went down.

  3. Hi Paul–

    What do you consider “very high” LDL. At what point is it considered high?

  4. Hi Ellen,

    Again, I don’t have a specific number. But once you’re multiple standard deviations above the rest of the population, I would consider your LDL high.

    I think higher LDLs have diagnostic value for infections or nutrient deficiencies. Higher numbers indicate more severe problems.

  5. You know, I’m thinking I should have gotten pretty close to 2mg of Cu from the lamb, potatoes and spinach every day. That may not be sufficient all told, but it seems like it would have afforded me some amount of protection from this if Cu were the cause of this.

  6. fascinating post and so many intriguing comments. I’m just wondering, could we not collect also some relevant data? Like there must be some people with CAC scores on relatively long term paleo, some with the configuration at issue (high LDL, but high HDL low TG etc.) At least anecdotally, do their scores tend to be worse? Anybody at all with this configuration and two measurements somewhat spaced in time?

  7. The excellent back and forth on this post only highlights how theoretical/speculative understanding plaque build up and arterial health still is.

    10 days ago, my family had an uncle, 67 years old, thin and health conscious get ‘stented’ during a routine cath. procedure after he was short of breath. He was 85% blocked where they could stent. The other problem areas were to small to open.

    Fortunately there was no heart attack, and his docs were very surprised, said he was extremely lucky based on how tight he was blocked…he told me really only a passage the size of a thick tread was working.

    We are talking about a smart man actively following advise and much concerned about his health who had been going to a younger “progressive” doctor and on a heart healthy plan. Fruits, vegetables, whole grains, etc.

    They might as well have been witch doctors jumping around scaring demons, they did him absolutely no good (harm really) with the diet advise and barely caught the problem before it killed him.

    I wonder why more studies aren’t done around cath procedures and 3d imaging…seems like alot of guessing is going on.

  8. Perry,
    Do you know or could you find out what your uncle’s history was as far as cholesterol levels?

  9. Jeff I don’t know but I’ll find out and post it here eventually…it may take a while though.

    He was on a statin I know.

  10. Why specifically Beef liver?

    How about Lamb’s liver?

  11. Hi Derek,

    Yes, lamb liver is equally good. The key is the liver needs to be from red meat animals – beef, sheep, goat.

  12. Links to sites that teach me how to properly prepare liver for eating?

  13. I woke up this morning (different time zone) thinking perhaps it’s not totally redundant to elaborate my previous comment. suppose there are people on relatively long term paleo with long term high LDL and high LDL/TG and healthy CAC: this would strongly support poisonguy’s attitude, in that even very high LDL may not matter. this by itself would not show of course that it is invariably irrelevant. however if bad CAC’s tend to be easily explainable by independent factors (like e.g. long time previous SAD) and particularly if well spaced consecutive CAC’s with such lipids never show deterioration (that is not easily attributable to independent causes) that would considerably strengthen his position. Conversely, deteriorating scores with this lipid configuration would tend to support Paul’s theory. info on this would be extremely helpful to many. it would not tell us about the mechanism, but surely would strongly constrain theorizing on that too. Is it really the case that we have absolutely no info on this?

  14. long term high LDL and high LDL/TG >>long term high LDL and high HDL/TG, of course, sorry

  15. Larry Eshelman

    One thing I haven’t made clear and which hadn’t occurred to me until after reflecting on some of the comments to Paul’s post is that my rising LDL parallels my decreasing consumption of nuts. During my first five years of low carbing, I was eating a cup to a cup and a half of nuts every day, including about a half a cup of walnuts which are very high in copper. (I was getting nearly the daily recommended amount of copper just from nuts.) Then, for various reasons, I started eating less nuts, which was coincidental to when I started to eat more saturated fat. This was when my LDL started to rise. As I read more paleo blogs I became concerned about the pufa content of nuts and by the end of 2009 had almost totally eliminated nuts from my diet. This was when my LDL peaked at about 300, almost three times higher than it had been a few years before. My LDL did not start to come down until after I started taking Paul’s recommended supplements, including consuming 5 oz of beef liver per week.

  16. Hi Larry,

    The PUFA in nuts can lower LDL. So skipping nuts could cause an increase.
    Basically, this was the main reason for blaming saturated fat to increase LDL: most studies used PUFA rich oil in the control group. This reduced LDL levels, but given that they were the control, it was assumed that saturated fats increased LDL, as their levels were relatively higher. When similar studies were done with a MUFA control group, there was no difference (but the idea that saturated fat raises LDL remained…).

    Stephan has a nice blog entry about this:


  17. When anyone wants to get a list of copper rich foods, you can use the Nutrient Search Tool at Nutrition Data.

    Calf/beef liver ranks highest with 15 mg per 100 g.


  18. ‘morning, y’all.

    RE: Shai et al. Don’t have access to my laptop, so I won’t quote any other papers, but I still believe Shai et al supports my points. Although the authors didn’t think LDL change was significant, their data doesn’t quite speak so decisively. They performed an intent to treat analysis, which tends to mask differences in the treatments, and that shows up in the results. From a population point of view, the mean values show little change in most lipid profiles, especially LDL. But if one wants to look at the response of the individuals, one has to look at the standard deviation of the mean. That’s more telling. And which lipid profile got affected the most at the individual level by very modest changes in dietary macronutrient? That would be LDL (taken from the graph). Imagine if they had brought there CHO ingestion down to below 40% of calories. Macronutrient ratios can affect sdLDL/puffy ratios, so why not quantity?

    In addition to what donat said, it would be interesting to know by what mechanism LDL is lowered in patients with Wilson’s disease. That might be telling.

    Not sure if Paul answered this, but why does he suspect copper deficiency in the paleo world? Wouldn’t the SAD slobs wolfing down phytic acid-rich foods be at greater risk of copper deficiency? Why don’t we see higher LDL in them?

    Also, you’d think the the paleo people have reduced the effect of oxLDL/oxLDL-IC on vascular damage (as involved in either cause of damage or pathogenesis of damage). You’d think their vasculature would be improved. So, I’m trying to figure out where all that suppose damage is coming from. It’s even difficult to get around the choline thing, since paleos likely get more of that than most.

    Still trying to understand how paleos, big liver eaters, get copper deficiency, and whether copper’s lowering of LDL is therapeutic or from a toxic mechanism.

    Nice chatting…gotta go.

  19. Hi Fibrous Cap,

    There are some liver recipes on this thread:

    Hi donat,

    Calcium scores are farther downstream in the atherosclerosis development process. You can have high LDL without calcification, and I suspect that’s a situation most of the Paleo folks may be in.

    Factors that contribute to moving from high LDL to calcification include low vitamin K, low magnesium, low vitamin D, high PUFA consumption, high sugar consumption, hyperglycemia, infection. Chris Masterjohn’s upcoming series may shed some light on this.

    Hi Poisonguy,

    I still think the effects of macronutrient changes would be small unless there was a micronutrient deficiency such that, e.g., a rise in PUFA led to excessive peroxidation due to lack of antioxidants.

    The fact that the effects of macronutrients appear not in the mean but in the standard deviation may reflect a dependence on micronutrient status.

    Since most people get copper from grains, beans, nuts, and seeds, and Paleo diets don’t always include these as Larry’s comment illustrates, I think it’s quite plausible that many Paleo dieters may be copper deficient. Not everybody eats liver. Also, some eat chicken liver or pork liver which are low in copper. It’s only ruminant livers that have the copper. Finally, copper is not a popular supplement.

    Best, Paul

  20. Larry Eshelman


    I agree that PUFA can lower LDL — somewhat. But in my case we are talking about LDL a little above 100 versus LDL close to 300. I’ve never seen any study that showed such a large effect from varying PUFA. Furthermore, I’m now consuming minimal PUFA, but getting more copper and my LDL is coming down. Of course, none of this proves that copper is the critical variable.


  21. Hi Travis,

    You wrote: “It seems that a diet high in PUFAs/n6 alone would lead to cell membranes that are improperly constructed and thus there would be a high demand for the proper materials as those cells degrade and are replaced.”

    This is somewhat similar to what Mary G. Enig wrote in her book Know Your Fats, but with a little twist. The idea there is that too much PUFA ends up in the cell membrane, which makes it too fluid. To counter this effect, extra cholesterol is added to the membrane. So on a high PUFA diet cholesterol levels in the blood go down, tissue levels go up.

    Just take a look at figure 10-11 in the section The Fluidity of a Lipid Bilayer Depends on Its Composition of the online edition of Molecular Biology of the Cell, 4th ed. In that image, there is only one cis-double bond in the fatty acid (MUFA), which creates a space between the two phospholipids. This space can/must be filled by cholesterol. In case the fatty acid would contain more cis-double bonds (PUFA), that space would become larger, leaving more room for cholesterol.

    So, let’s speculate: first you severely ‘pollute’ your membranes with PUFA by years of eating a diet high in PUFA, and the membrane gets stuffed with extra cholesterol. Then you switch to a low PUFA, high SaFA diet. In that case it might be that the PUFA in the membrane gradually gets replaced by SaFA (and probably MUFA). As the SaFA doesn’t need the extra ‘stabilizing’ cholesterol for membrane stability, it is released into the blood stream.
    End result: higher cholesterol.
    How long would cholesterol remain elevated due to this? Probably until most of the unnecessary membrane PUFA is replaced.
    Could you speed up this purely hypothetical process? I don’t know.


  22. Hi Paul,
    we’re not talking about the general populace eating the SAD here on this thread and I am, like most here, interested in helping my body repair itself. As Stephan pointed out in his posts on LDL, in general LDL doesn’t go up significantly on a high sat fat diet and if it does it comes down after a while. In general, that means in the general population. However, among low carb dieters (like myself since August 2008) there are a few who can show that their LDL particle count/apoB/calculated LDL has gone up, for some more than for others. Discussing the significance of this was the starting point for your two interesting and timely posts.
    Mine (lightcan) has gone down a tiny bit (from 10 to 9) on its own during last year. I’ve been taking T3 in the last month, reducing sat fat and continuing to take my supps. I’ll keep you posted.

  23. Excellent post, Paul. There’s a lot of debate about whether and when supplementing is necessary, and a surprising lack of conclusive research (well, not so surprising considering the low profit potential in nonpatentable compounds). Relying on informed evolutionary speculation is a good base but doesn’t go quite far enough.

    I’m interesting in hearing more about what you said above:

    Other commenters brought up fish oil. They may be interested to know that fish oil not only balances omega-6 to modulate inflammatory pathways, it also suppresses endothelial lipase and thus moderates the LDL-raising and HDL-lowering effect of vascular damage […]Whether this effect is always desirable is a topic for another day.

  24. Hi John,

    The idea is a good one but a couple of factors make it less important:

    1) Membrane fatty acid profile is highly regulated and the fatty acids in excess are preferentially removed and burned for energy. That’s why linoleic acid is the most likely dietary fat to be burned in Americans — much more likely than a saturated fat in the same meal.

    2) Cholesterol is also regulated. Moreover it doesn’t sit uniformly in the membrane, but gathers in “lipid rafts” to create alternating rigid patches on the membrane separated by fluid areas with little cholesterol.

    Overall I doubt this pathway is a major source of blood cholesterol.

    Hi simona,

    Yes, keep me posted! These experiences are very interesting.

    Hi Lacie,

    There will be some blog posts coming up on fish oil.

    Our advice is moderation: 1 lb salmon/sardines/other fatty cold-water marine fish per week, no supplements.

    Fish oil toxicity in high doses seems to be something not a lot of people are aware of, so it’s worth a blog post or two.

    Best, Paul

  25. Hi Paul,

    Thanks for the feedback. My feeling would also be that it probably is not a significant factor. But to be honest, I have no data whatsoever to back this up.
    Unfortunately, I cannot find a reference in Know Your Fats (at least not in the Dutch translation I have) to the PUFA-membrane-cholesterol findings Mary Enig mentions. That reference might provide some information about the amount of cholesterol reduction due to the membrane PUFA (and thus how much cholesterol could subsequently be released potentially).


  26. I waffle on the need for supplements, sometimes feeling certain they are a waste of money (Eat Real Food!) and sometimes feeling certain supplements are essential to make up for lost years or diet deficiencies.

    Thanks for getting me to think, and question what I think I know, as always.

  27. I just wanted to pop in and say that this has been the most pleasant, civil and informative discussion that I can recall.

    Enjoying this greatly, guys!

    And to think, this all might mean nothing or it might be of critical importance, yet we can’t say which one for sure. It’s great discussion.

  28. I am wondering if you could talk more about Simona’s original point regarding APOE-4 influencing a person’s response to increases in the fat content of diet; a significant minority of people have one copy of this gene isoform although very few are homozygous for it.

    I have had the pattern of slowly but steadily increasing cholesterol levels over the years since switching to a higher fat diet. I supplement virtually all of the things on your recommended list but continue to have the cholesterol increases over time. I consume a lot of raw cocoa which I understand is high in copper, my multivitamin has copper and so it is hard for me to believe this particular issue could be the problem in my case Most recent numbers are approximately
    TC=12.8 mmol

    About a year ago, the numbers were TC around 9 mmol, ldl around 6 and hdl around 3; trigs were around .9
    Several years ago my total cholesterol was 6.5, so it has always been a bit high, now it has literally doubled since then; my HDL was always good, and my LDL was always a bit high even before switching from SAD to high fat / low carb diet. my doctor wants to send me to a lipid specialist in another city because he finds my numbers so bizarre. Reading this post I was glad to see I’m not so unusual for a person who eats this way.

    I do worry a lot about APOE-4 however; my mother died of Alzheimer’s and had two strokes before that. At least three of her siblings developed Alzheimer’s and one of my cousins has it and he’s only 53 years old. Some research shows that if a person has both HSV infection (cold sores) and APOE-4 in combination their risk of getting dementia is extremely high. I don’t know my APOE genotype but I do get cold sores so I worry about this a lot. I know you have a lot of good posts you’re working on but could you at some point write a bit about your views on APOE-4 and whether having a copy of this gene changes what a person should be eating for a healthy diet

    Thanks so much,

  29. This is a comment for Larry Eshelman. Did you ask the farmer who you received the grass fed beef from about his soil and mineral supplementation program? It might be a good idea to let him know that his meat might be deficient in copper.

  30. Paul – thanks for the reply. I started adding safe starches a while ago but have not had my lipid panel done since. Pleased to hear that starches may have a positive effect on these in addition to the other benefits… Thanks for recommending this!

    Nonetheless, something about your “malnutrition” hypothesis does not seem right, at least in my case. You see, I went from eating healthy “crap” (grains, oatmeal, chicken, protein shakes, egg whites ONLY, olive oil) to now for almost 2 years eating strictly whole nutrient dense Paleo foods (eggs, liver, grass-fed meat, pork, yams, coconut oil) and I eat a LOT. Yet, as a result of this healthy dietary change my LDL has doubled? My ratios are excellent, and have improved so I am not worried about atherosclerosis… And while it may be possible that I am lacking in some nutrients, I find it unlikely that I am getting less Copper, Choline, etc. than I was on my healthy “crap” diet. Especially since my gut health and body composition is also significantly improved on this diet.

    I think I would side with a few of the comments in that LDL is really just a reflection of ones diet (in my case a diet much higher in lipids) instead of a sign of nutrient deficiency/malnutrition. Also, although my total LDL is higher I would expect that my oxLDL and vLDL numbers are much better now then they were when my trigs were over 100 even with twice as much LDL.

    So, the million dollar question(s): Should I be worried that my diet is causing my LDL to increase? Or, should I just continue to focus on improving the ratios (HDL keeps going up, Trigs stay low) — confirming my low vLDL and likely low oxLDL?

  31. Larry,

    Interesting that you mention your decrease in nut consumption correlating to an increase in LDL, since I am allergic to nuts and sit here with a TC of 391.

    I should have mentioned previously that I eat a couple pounds of wild crustaceans (shrimp/crab/lobster) every week, but I tend to avoid mollusks due to potential contamination by pollution. This should have supplied some Cu in addition to the other foods I eat.

    I have just started supplementing with 200 mcg Se and a supplement that has 2mg of Cu yesterday and have an order in for a couple pounds of grass-fed lamb liver. I think I’ll choke down half a pound a week for a month and then go down to a quarter pound. I’m sure I’ll come across a recipe that makes it marginally less disgusting. My only concern is the vitamin A in it, since I’m already getting quite a bit from spinach and sweet potatoes. I’m hoping that 5000IU of D3 should cancel it out a bit.

    Thanks for the post Paul and everyone else for chiming in.

    It occurs to me that we ought to poll those paleo people with very high LDL and see if any of them eat adequate amounts of liver every week.

  32. Hi karen,

    I’ll definitely put that in my queue for posts. Thanks for the request.

    Hi Henry,

    You haven’t told me whether you supplement with a multi or anything else. As we argue in the book, it’s very easy to be malnourished if you don’t supplement.

    Obviously your HDL is great at 97 and trigs are excellent. You’re not going to get atherosclerosis with those. The LDL is a bit high at 163 but within shouting distance of the optimal range. It suggests a mild nutritional deficiency, but it could be one of many things. Look at Mike Gruber’s success with iodine.

    If you supplement, I would expect the LDL to go back to 100.

    Either way, it’s hard to be too concerned with only one measurement. Transient factors could have influenced the number.

    Hi Travis,

    Sounds like a good plan. Let me know how things go.

    I agree, a diet survey would be very informative. Probably very few of the high LDL people eat beef liver.

    Best, Paul

  33. Larry Eshelman


    The grassfed beef liver that I am now eating is from the same farm as the other beef I have been eating, so I have no reason to believe that it is raised on soil that particularly low in copper.

    Earlier I forgot to point out that when I started Paul’s supplements they included a daily multi-vitamin which has 0.5 mg of copper. Earlier, when I moved from a low carb diet to a paleo diet, I stopped taking a multi-vitamin. So besides reducing, and eventually eliminating, my nut consumption (mainly almonds and walnuts), I also eliminated this source of copper.

    The 12 years prior to my low carb period, when I was eating a very low fat (and by default, a low PUFA) diet, I was eating a lot of lentils and other legumes, which are a fairly good source of copper, plus I was taking a multi-vitamin. So, although it may have not been a particularly healthy diet, it was not a copper deficient diet. (Evidence that it was not healthy: During my low fat period I developed rosacea, which started to clear up when I went low carb, and completely cleared up once I eliminated wheat, and severely restricted fructose and PUFA.)


  34. I, too have steadily – and alarmingly – increasing cholesterol since adopting a paleo/primal diet almost two years ago. Last bloodwork has total cholesterol at 12.25 mmol/L (478); LDL at 9.29; HDL 2.67; Triglycerides 0.63. I am a female with Hashimoto’s and wary of iodine supplementation. I take 200 mg Selenium almost daily. I’ve been eating calf liver every week or every two weeks for many months now. I understood, perhaps mistakenly, that zinc deficiency was more common in hypothyroid patients so am struggling with the copper deficiency concept.

  35. Good morning everyone, welcome back to the best discusssion of paleo and lipids on the internet!

    High LDL and HDL/TG on paleo, –let’s have a name for ease of reference: say the paleo-lipid syndrome, PALS.

    Paul’s hypothesis has a weak version that is clearly valid in general: whenever PALS is due to toxins/malnutrition/pathogens, that cause should be attended to. But the intended stronger and more interesting version of his hypothesis is that in a strong sense PALS is only apparently multifactorial, it is always in fact due to vascular damage (which itself may be due to multiple causes).

    This version clearly rejects the commonly employed policemen/ambulance-crew-on-the-roads-metaphor, in that it says that overabundance of policemen invariably indicates high crime rate (and not the government keeping too many of them for some other reason, –paranoid or not). Or to spin it out, perhaps all the police stations are being closed (say for renovation) and the police hang out in the open. etc. (Linking to some recent earlier comments,how about some subset of PALS people reacting to SaFats with having a stronger and non-transient LDL receptor downregulation?)

    Paul, –you say that LDL levels are tightly regulated. Assuming this is true generally, are there concrete reasons to reject the hypothesis that at least some PALS cases could be due to (perhaps tightly, but) inappropriately (wrt crime rate/vascular damage)regulated levels?

    (It would then be a further and distinct question whether it is a cause for concern in such crimeless circumstances to have too many policemen around. Perhaps that depends on how well they are trained…)

  36. Hi donat,

    From weak statement / high confidence to strong statement / low confidence:

    1) PALS is due to toxins/malnutrition/pathogens.
    2) PALS is due to malnutrition (my confidence is still high)
    3) PALS is a sign of vascular damage (I suspect this will be true in a majority of cases, and nearly all the slow-developing ones; liver issues will tend to be more dynamic)

    Re your police metaphor, I think our bodies are a lot smarter than the government! I think contemporary medicine greatly overestimates the frequency with which our bodies will spontaneously screw up our health. Ill health nearly always has an exogenous (toxin/pathogen/malnutrition) cause.

    Best, Paul

  37. What about scurvy as a contributor to vascular damage and elevated LDL?

  38. Paul – Thanks again. I am currently supplementing with:
    Vitamin D
    Digestive Enzymes – Super Enzymes
    Alpha Lipoic Acid
    CoQ10 – QH Absorb

    Based on your feedback I am going to add these into my mix right away:
    Iodine and Copper

    Still considering:
    Chromium, K2, Selenium, Vitamin C

    I will let you know how that goes. I’m still not convinced that my current whole foods diet is somehow deficient in ways my old diet was not; and that this in turn is the cause of my higher LDL vs. the more likely MUCH higher Cholesterol intake. However, adding these seems like a low risk n=1 way to find out. My insurance company will be eliminating my “healthy measures” discount with my LDL at this level… Otherwise, I would probably not be bothered to try.

    Best in health,


  39. Hi Michelle,

    Near-fatal scurvy raises LDL sharply in guinea pigs, Presumably this is also true in humans.

    However, in more typical vitamin C depletion/deficiency conditions, my sense is the main effect of vitamin C is to reduce the oxidation of LDL to oxLDL. Thus vitamin C deficiency leads first to oxLDL formation and progression of atherosclerosis; probably only later to higher LDL mass.

    So I think vitamin C deficiency is a possible cause of high LDL. We think everyone should supplement vitamin C regardless, but certainly everyone with high LDL should. But I wouldn’t expect C by itself to fix high LDL in most people. It’s a good prophylactic. Also, there may be indirect effects, as C helps maintain other antioxidants such as glutathione which also influences zinc-copper superoxide dismutase and therefore could help maintain copper status.

    Hi Henry,

    Well, I think it would help to take selenium, K2, and C also. However, you should do what you are comfortable with. Adding supplements one at a time will help you interpret any changes. Also, some nutrients — especially iodine! — need to be introduced gradually, starting from low doses and taking months to build up the dose.

    Since C, selenium, and zinc/copper are all antioxidants, taking them will improve your lipoic acid and CoQ10 status and might mean that you can drop those supplements. Something to consider.

    Best, Paul

  40. It seems to me that liver is such a concentrated source of Cu, Se and Cr that simply eating enough of it should make supplementation with any of those redundant (and perhaps excessive). I see in the PHD and here that liver is only listed as a way to avoid having to supplement Cu; ought that to extend to all 3?

  41. Hey Paul,
    What dosage of these supplements should one take? Does it depend on bodyweight? age? sex? I am 145 lbs male, 28 yrs old. How much copper, selenium, vit C, vit k2 and iodine should I get? low dose is sufficient? And also, can I get iodine from seaweed instead of supplementing?

    Thank much!

  42. The reason I asked about lambs liver, is that I like it and regularly consume it.
    About 4oz once a week, so in theory I should be getting plenty of copper.

    I recently had some lab result (first I’ve seen, so no earlier values to give trending):

    Values as mmol/l (converted to mg/dl)

    TC 12.0 (464.0)
    LDL 9.2 (355.8)
    HDL 2.4 ( 92.8)
    TG 0.9 ( 79.7)

    FBG 6.2 (111.6)

    [Note – I have no data for ‘particle size’]

    So, this could appear to be another example not fitting your above hypothosis.
    The liver I’ve been eating for about 20 months, which is when I decided to improve my diet.
    Said diet probably includes a lot of saturated fat, so maybe this lends weight to proposition that LDL is being driven by diet choices.

    I eat fish twice a week (once being mackerel) so that should cover ‘fish oil’ and possibly iodine.
    I imagine I also get a number of other micronutrients from food sources.

  43. Hi Travis,

    Here’s the nutritiondata page for beef liver:

    100 g beef liver provides 488% of the RDA of copper but only 57% of the RDA of selenium and less of other minerals. So 4 oz liver per week is only fulfilling 8% of the recommended allowance for selenium and less for other minerals. And the RDAs are too low. So I think liver replaces supplements only for copper.

    Hi Raj,

    Recommended doses are given on our supplement recommendations page:

    They don’t depend much on bodyweight. Yes, you can get iodine from seaweed, but for higher doses I would recommend supplements.

    Hi Derek,

    Your case wouldn’t seem to fit the copper deficiency hypothesis but I still think micronutrient deficiencies would be the logical explanation. Vitamin D, K2, C, selenium, and thyroid status might be things worth checking.

  44. Really appreciating this discussion. Does anyone know of any accurate home cholesterol monitoring devices? Those available, say, on Amazon seem accompanied by poor reviews that question their accuracy. Would love to be able to gauge lipids as I do blood sugar, experimenting with the ideas contained in this fine discussion.

  45. Derek, what does the rest of your diet look like typically?

  46. Would taking a combination copper/zinc supplement be a safer strategy for those with thyroid disease?

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