Jul 03

Are you a Lean Mass Hyper-responder?

One of the benefits of establishing this niche in Low Carb Cholesterol Research is that I get people sending me their labs constantly. Naturally, I obsess over possible patterns with hyper-responders.There’s one pattern that is clearly emerging that I’m calling a Lean Mass Hyper-responder. (LMHR)

General Hyper-responder vs Lean Mass Hyper-responder

I consider a hyper-responder (like myself) as anyone who sees a dramatic rise in their LDL cholesterol after adopting a low carb diet. Usually, this is 50% or more. As is typical for a low carb diet, most people see their HDL go up and their triglycerides go down.

However, a Lean Mass Hyper-responder takes this to a new level. I consider the cut points as follows:

  • LDL-C 200 mg/dl (5.2 mmol/l) or higher
  • HDL-C 80 mg/dl (2.1 mmol/l) or higher
  • Triglycerides 70 mg/dl (0.79 mmol/l) or lower

Note these are just the starting ranges. Typically I see both LDL-C and HDL-C hit levels no one else has, while likewise having very low Triglycerides. Here are some examples:

431 147 46
226 98 52
342 110 61
263 89 55
277 102 67

This is only the first five I found to plug into this post. I suspect I probably have at least another half dozen or more that I’ve responded to on Twitter, email, or comments here at the site.

In fact, the very first LMHR I encountered was Nicole Recine here on the comments of a blog post. I’ve since collaborated with her quite a bit and consider her a damn awesome resource for low carb. (See her site at NicoleRecine.com) She’s sub-10% fat mass, very energetic/althletic, and much more comfortable standing than sitting. She holds at an extremely high LDL-C of 558 with an HDL-C of 140 (Total Cholesterol of 721). Yet, like me, she gets frequent checkups such as the CIMT that continue to show normal results.

Characteristics of a Lean Mass Hyper-responder

As the name suggests, LMHRs tend to be on a very low carb diet while also lean and/or athletic. Some are ultra-athletes and have taken strongly to the low carb way of life with great appreciation. And of course, all of them are shocked to see their cholesterol scores at these levels. Yet there’s clearly a mechanistic reason for this…

A Simple Theory

For me, this certainly has an Occam’s Razor-level explanation. Before reading below, be sure you at least know your basics with my Simple Guide to Cholesterol on Low Carb series.

Lean and/or athletic low carbers have three things in common:

  1. Lower adipose stores (less body fat energy) relative to the average peer.
  2. Lower glycogen stores (less incoming dietary carbs) relative to a carb-centric diet.
  3. Higher energy demands.

Our body seeks to keep our glycogen stores in our liver and muscles reasonably stocked, even on a low carb diet. But obviously, this is more of a challenge when you are both lowering dietary carbs and burning through it at a faster rate than most. Per Volek and Phinney, the body gets better at sparring (and I have my own data that confirms this), but the demands are still relevant for available fuel.

So think about it — (1) lower adipose fuel tank, (2) lower glycogen fuel tank, yet (3) higher energy demands. It makes perfect sense for the body to want to mobilize more fat-based energy to meet the need. And yes, that will ultimately mean more LDL particles (LDL-P) delivering more triglycerides to the cells. Likewise, this means more of the cholesterol in those boats (LDL-C) being circulated along with them.

This explains why both LDL-P and LDL-C would be higher, while TGs would be remarkably low, relatively. The TGs are getting depleted from use, yet there’s no denying that more “boats” (LDL-P) are needed to provide them.

Likelihood for Children on a Low Carb Diet

This needs to get talked about as soon as possible. If this mechanism is indeed true, I’d hypothesize many children going on a low carb diet would likewise exhibit signs of a LMHR given higher metabolic rates relative to adults. Indeed, there have been three cases I’ve been made aware of in the last couple months. One privately shared via email, one in the comments of this site, and one on the forums of another. In all three cases, the child fits the pattern of an LMHR.

Naturally, this means many children could be incorrectly diagnosed as having Familial Hypercholesterolemia. Again, FH is, in fact, a genetic disease. That it often gets diagnosed on cholesterol scores alone is a modern tragedy. My fear is that this will happen more often as low carb diets become more popular and GPs don’t know enough about cholesterol and the lipid system to understand what is happening in this context.


Final Thoughts

All things considered, I hope the theory proves true given it makes a lot of sense. Before this particular pattern emerged from having lots of labs to compare to each other, I often speculated a higher mobilization of LDL-P could be used by the body as an “alternative glycogen store”. This profile adds some weight to this possibility.


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  1. George Henderson (@puddleg)

    This makes sense to me.
    It’s been theorised that SGLT2 inhibitors, used in the treatment of diabetes, increase LDL by increasing fat trafficking. They don’t cause an increase in MIs and do reduce deaths from heart failure and kidney disease significantly.
    “These data suggest that empagliflozin, by switching energy metabolism from carbohydrate to lipid utilization, moderately increases ketone production and LDL cholesterol levels.”


    These drugs are keto diet mimics across a range of effects, including natriuresis. It’s also possible natriuresis itself contributes to LDL elevation, as low salt diets increase LDL


    Interestingly cholesterol synthesis itself is via HMG-CoA reductase which is induced. by insulin and suppressed by glucagon. Hence the increase in HDL – reverse cholesterol transport may be increased to supply cholesterol for the VLDL transport of TGs. VLDL will be less TG-rich.
    Low insulin can increase LDL in some because ApoCIII clearance is insulin-dependent, as is ApoB recycling in hepatocytes. FFAs elevate insulin, so there’s a neat feedback loop between adipose stores via insulin controlling LDL levels, even in low carb states, consistent with your hypothesis.

    1. Dave

      Very interesting comments, George–

      I like the feedback loop as you describe regarding insulin’s role (the usual suspect) with regard to HMGCR and particularly ApoCIII (your Apo-fu is strong!).

      While I’ve not worked out all the details regarding the pathways. I can say that I think it is not entirely supply-driven, such as a lipolysis and glycerolneogenesis combination influencing at the liver to higher VLDL synthesis/recirculation. Rather, there seems to be a systemic, demand-driven process, which better explains my own data and it’s tight homeostasis.

  2. Thein

    I am 43 yrs old, in low carb for one yr. But more liberal LCHF. I am 175cm, weight fluctuate 59kg to 61kg. (was 65kg before LCHF).
    Last year Nov, blood test:
    HDL 76 mg/dl
    LDL 220 mg/dl
    Tri. 54 mg/dl.

    1. Dave

      Hi Thein-

      Very interesting. You are at the edge of the ranges, like myself.

  3. tigris

    Very interesting. It appears I’m a LMHR, too.

    The best theories are those that simply explain the observations, are falsifiable, and make testable predictions. I was thinking about what some those tests might be.

    If we have a LMHR, removing any one of the of the three pillars should decrease LDL-P

    LDL-P should be decreased by:
    1. Gaining 10 pounds of body fat (then readapting to LCHF). Might be possible to test with someone who’s weight fluctuates with cycles of feasting / fasting or strict LCHF / normal diet.
    2. Filling the glycogen stores of the liver by carb loading. You’re N=1 experiments are consistent with this. Others appear eager to replicate to produce “ideal” lipid scores.
    3. Eliminating exercise and switching to a sedentary routine. Seems unlikely many elite athletes would willingly atrophy their muscles, but injuries happen, and could be studied retrospectively.

    Another prediction. Someone who is overweight and gradually losing weight should hit a tipping point as their %BF declined where LDL-P jumps up (provided they are at least moderately active). It would be extremely interesting to plot LDL-P against %BF from say 30% down to 10%.

    1. Dave

      Hi Tigris–

      Excellent points. I likewise would say a theory must be falsifiable, which is why I get frustrated with a lot of pop science.

      Per your points:

      1. Weight gain — I actually joked about this on a recent podcast. I don’t know that it could be as little as 10lb, it might take more. But I likewise believe this would help determine if this was a factor, either way.

      2. Glycogen stores — yes, certainly my Breakthrough post address this directly. I’m more inclined to believe it is glycogen stores over the actual carb combination itself given the sheer degree of change in the lipids. (For only a 1/6th swap in dietary energy, we end up with a far higher proportion change in LDL)

      3. Exercising or sedentary. This one is a bit trickier. Some amount of LDLp/c will be impacted by exercise for different roles beyond energy supply, such as non-hepatic endocytosis for muscle repair. I also think if the lipid system is behaving like a network as I suspect, then it won’t likely be very analog in this regard. It may have threshold points where it operates more like a state machine (sorry — some software dev talk here…)

      — Yes, per my above point, I likewise believe the prediction you state as a distinct likelihood. Which is part of why I’m annoyed I didn’t manage to get all this data on my way down in weight at the very beginning of the diet.

  4. George Henderson (@puddleg)

    Also have a look at this


    ” Two days of fasting caused a reduction in body weight with an approximately 40% decrease in the epididymal fat depot and fat cell size. No changes in serum cholesterol were noted, but serum triglycerides fell approximately 55% with fasting. LDL receptors detected by immunoblotting decreased progressively with fasting to levels that were 95% below controls in adipocytes isolated from epididymal fat pads by 2-3 days. In contrast, hepatic LDL receptor expression was unaltered by fasting. After 2 days of fasting, the rate of synthesis of LDL receptors in isolated adipose cells was decreased approximately 35%, whereas levels of LDL receptor mRNA were diminished approximately 55%. It is concluded that the expression of LDL receptors in rat adipocytes is markedly downregulated during fasting through transcriptional and posttranscriptional mechanisms. Furthermore, LDL receptor expression is differentially regulated in adipose tissue and liver during fasting in the rat.”

    So, are adipose LDL receptors downregulated by the fasting mimicking ketogenic diet?

    1. Dave

      Incredible find, George!

      I was particularly struck by the fact they noticed no serum cholesterol differences in the fasting state. This is certainly very different from the research and data is collected thus far regarding humans. In fact, since my fasting disaster post, I’ve had a massive number of people send in labs suggesting likewise outcomes.

      Now I’m going to be haunted for a while wondering if the Inversion Pattern does *not* apply to our little mammal cousins. If so — this would have ***massive*** implications.

      Damn it… I need to get my own lab…

      1. George Henderson (@puddleg)

        I reckon rat studies are sound human analogies for basic metabolism pathways, and HMG-CoAR and LDL-R are necessary for shifting energy around in all mammals – but they’re much less reliable for lipid levels because of various differences (no CETP means very high HDL, low LDL) and other factors – see the chart here


        So the model we’d want is the guinea pig, but on these low carb diets LDL goes down. So far.

        1. Dave

          I did not know about the missing CETP with rats and rabbits. That has huge implications in the overall lipid management, clearly. In fact, I’m a little annoyed I didn’t know it up to this point. Rat lipid models are so commonly treated as though congruent to their human counterparts.

          George — you’re an excellent lipid resource — bravo!

          1. nicole recine

            You need to look into this, dave! In all of my research on LCHF, keto, etc. EVERY TIME i come across a study with negative outcomes from a ketogentic diet, the subjects are rats or mice.
            It reminds me of the cholesterol-heart hypothesis resulting from feeding rabbits cholesterol back in the day.

          2. Dave


            There’s already too large of a gap between animal statin trial outcomes and humans to begin with.

          3. xtronics

            @nicole recine

            Actually, that is because a lot of the rodent high-fat diets didn’t even have fat in them. If you dig into the supplementary material, look up the actual test-diet product they used, most often the so-called high-fat diet is a combination of sugar and hydrogenated vegetable oils.. (Pedro over on hyperlipid has written about this as well ).



            All the rodent high-fat diets that don’t contain fat should be retracted – but this is not going to happen..

            The other bit – to do the real experimental phase of science, there needs to be a single variable. This means the addition or subtraction of a single type of fatty-acid or carbohydrate. Back in the Apollo program they did some of this – they found that fructose spikes trygly – no one in medicine apparently noticed.

            You can find some links to the synthetic diet research here

  5. James

    Is the LDL conversion you give correct? I think 200 mg/dl is 5.2 mM (mmol/l).
    I cycle 100 km or 200 km (up to 10 hour ride) at least once a week on an empty stomach. I closely follow a very low carb diet for two years. Anyway, my results are broadly in keeping but I’m not so lean (bmi 24).
    Trig: 0.8 mM
    HDL: 1.5 mM
    LDL: 6.3 mM

    1. Dave

      Hi James–

      – You’re right on the conversion! I made the correction…

      – Interesting on your numbers. By chance, do you know your body fat %?

      1. James

        Hi Dave, I’m 22% fat, 77.5 kg, 1.78 m tall.
        All I know for sure is I do frequent regular endurance exercise on virtually zero carbs. So I figure there be a high level of fat flux and distribution, otherwise I couldn’t do it, right? On week days I fast 16 hours a day. Occasionally I also fast for two or three days before doing a 100 km ride, and I’ll push hard and go quick on challenging (hill climbing) courses.
        Anyway, I really do want to thank you for doing your amazing research. I think you’re findings are way ahead of much of the big funded research, certainly of the consensus. From a philosophy of science perspective it’s incredibly interesting. I have a PhD in evolutionary biology so I’ve never really worried about my lipid numbers anyway and just accepted them as an adaptation without concerning myself about the mechanisms. You worried about your results, and had the intelligence and ability to actually investigate it, and to discover something important. I do expect big pharmas, researchers and s are watching your blog carefully. There will be more details to be discovered but you’ve made a serious breakthrough. Well done!

        1. Dave

          Thank you, James.

          The biggest irony for me isn’t just the reveal of this data. It’s that I find it so difficult to bring this to the doctors and researchers of lipidology itself. When you don’t have big pharma money and/or a dozen letters after your name, the strength of your data is nearly irrelevant.

  6. Bill

    I have your top HDL beat. None of my docs has ever seen anyone even close. Latest lipids (roughly consistent over many years):

    LDL 199 (calculated)
    TG 38
    Fasting insulin 2 (“normal” lab range 2–14)

    I eat moderate low carb, intermittent fast (no breakfast), and do very brief but extremely high intensity strength training 2x/week. Otherwise no athlete, though resting heart rate at 59 is 45. I am lean though certainly not ripped, maybe 10% body fat.

    I have resisted the temptation to get an advanced lipid panel since I really don’t know what I could reasonably do with the information. And I’m unconvinced that LDL-P or anything else on such a panel has a demonstrated causal role in CVD at this time.

    Another data point for you…thanks for your incredible research and thinking about all this.

    1. Dave

      Hi Bill–

      – That is indeed a remarkable HDL!

      – While it is still theoretical, I’ve suspected for some time that resistance training will ultimately lead to lower LDL-C/-P due to a higher degree of endocytosis for tissue repair, thus removing lots of LDL particles from the bloodstream. This was anecdotally supported in my marathon training/running when I saw the biggest gaps in the expected trend lines at the two times I was the sorest (cold open 7 miles with no conditioning, and the marathon at the end). http://cholesterolcode.com/impact-of-endurance-running-on-cholesterol/

      In other words, I suspect if you are tearing more muscle and inducing repair, this will ultimately lower your LDL-C/-P *relative* to what it would be without it. So most likely, you’d have a higher LDL-C/-P as a runner than you would as a bodybuilder with the same diet.

      – And yes, thanks for the added data point. All this info I’m gathering from others helps me to recognize these patterns to hopefully benefit us all. 🙂

    2. George Henderson (@puddleg)

      Hi Bill, you can have high HDL for genetic reasons, such as a CETP defect – and whether this is good or bad for you depends on your insulin level.
      So, you are doing fine.


      1. Bill

        Thanks, George. I should have mentioned that, indeed, high HDL (and my lipid profile in general) does seem to run in my family even though none of them eat or exercise like I do. However, their pattern is far less exaggerated than mine. So I’d guess that, as you suggest, some of my profile is genetic, the rest resulting from some combination of low carb/intermittent fasting/high intensity strength training. I’m still not convinced anyone really knows what it all means for CVD risk (aside from various modest correlations of unknown causal significance and possibly highly context dependent). Luckily my doc knows better than to suggest a statin :-). Thanks again.

  7. OobLaDee

    I’m so glad to have found you, Dave!

    I’m a 74 year old male, but I do still fit the lean, athletic, LMHR profile.

    My recent NMR results: HDL- 82, LDL- 202, Trig’s- 59, aligning about perfectly with your cut points.

    I assumed my body had good reason for the out of whack numbers, but I’m relieved, thanks to you, to find they’re not uncommon.
    I eliminated all grains and sugars 2 years ago, and for months now I’m all out keto.

    I abused my body for 45 years with a heavily grain based vegetarian diet and ended up with a CAC score of 2300.
    Got any idea’s on how I might get that number down?

    1. Dave

      Hi OobLaDee–

      – No — your numbers are not uncommon at all. In fact, in just the 24 hours since writing this article, I’ve had at least two dozen who have commented on Twitter, Facebook, and here that this fits their profile.

      – I’m sorry to hear about your CAC score. BUT I’ve seen plenty of compelling evidence that it isn’t the total that matters nearly as much as the *progression*. I’m sure you’ve seen a lot of Ivor Cummins work — if not, check into everything he has on the subject.

  8. Tim

    Hi Dave.

    Been following your work with interest.
    This last post is especially germane.

    I almost fit the profile, (LDL extremely high, HDL a little lower than your cut and trigs a little higher, intensive exercise). I am almost 70. When I get tested I will send my results for your database.

    Logic makes a lot of sense and answers questions I have had for years.
    Keep up the good work.


    1. Dave

      Hi Tim-

      – Glad to hear it.

      – And yes, please feel free to return and share your data.

  9. Sabine

    Hi Dave,
    44-year old athletic female coming out of the woodworks 🙂 Your hypothesis makes a lot of sense to me. I lift weights, do pilates, barre, and a lot of body weight training, and kick and punch the crap out of bags. I have been low carb for a while, but recently I have been leaning toward the very low carb end of things. With 132 lbs at 5’7″ I am lean.
    Had the lipid NMR done a couple of times. The last one definitely puts me in the lean mass hyper responder category (from memory):
    LDL 200
    HDL 115
    Trigs 68
    Small, dense LDL particles were below the detection limit of the NMR in both tests. I am happy to dig up and share my data with you via email.


    1. Dave

      Wow — yet another right in line with the pattern. Thank you for sharing, Sabine. I’ll add yours to the spreadsheet.

      1. Sabine

        Hi Dave,

        Ok, I dug up the exactl numbers of a couple of NMR data sets for your spread sheet. The first one is a lipid NMR from July 2016, me doing my normal thing being keto, but with what I believe was a 16-h fast before the draw:
        TC: 308
        HDL-C: 100
        TG: 65
        LDL-C: 195
        LDL-P: 1835
        small LDL-P: < 90 (that seems to be this lab's detection limit)
        Fasting insulin: 1.6 uU/mL

        Then, fast forward to Feb 2017, when I thought I'd try your method and utterly failed because I just plain could not eat that much though I tried. This one had a 13-h fast before the draw.
        TC: 345
        HDL-C: 115
        TG: 68
        LDL-C: 216
        LDL-P: 1956
        small LDL-P: < 90 again
        Fasting insulin: 3.8 uU/mL

        Suffice to say that some of these raised some flags 🙂 But I have never felt so good as I do now. My seasonal allergies are gone, for the first time ever. So yay!

  10. George Henderson (@puddleg)

    More evidence – huge increases in LDL cholesterol after a 7-day fast


    “Fasting increased total serum cholesterol from 4.90 ± 0.23 to 6.73 ± 0.41 mmol/L (37.3 ± 5.0%; P < 0.0001) and LDL cholesterol from 2.95 ± 0.21 to 4.90 ± 0.36 mmol/L (66.1 ± 6.6%; P < 0.0001). Serum apolipoprotein B (apo B) increased from 0.84 ± 0.06 to 1.37 ± 0.11 g/L (65.0 ± 9.2%; P < 0.0001). The increases in serum cholesterol, LDL and apo B were associated with weight loss. Fasting did not affect serum concentrations of triacylglycerol and HDL cholesterol."

    Even though fasting downregulates HMGCR; so the downregulation of adipocyte LDL-R might indeed be the deciding factor.
    We're just not eating enough, Dave (and when you do, your LDL drops).

    1. George Henderson (@puddleg)

      And here we go – the same length fast in obese subjects lowered LDL.
      So there is definitely a “lean high LDL” phenotype for some reason when burning fat.


      1. Dave

        Right! While I speculate it may ultimately be in response to lower glycogen and adipose stores jointly, we’d need to do muscle biopsies to be sure, of course.

        Once again, thanks for bringing more studies that demonstrate this. I’m much less adept at perusing pubmed than most others in the industry.

  11. Tim


    Great information. I am a 54 yr old male. Went low carb and had the following lipid results:

    LDL 304
    HDL 91
    TG 78

    This occurred when I was initially losing weight 206 lbs to 190 lbs over an 2 month period. I am also fairly lean and Weight train ~5x week during this time which I have been doing for many years.

    Become very concerned and Cut back on sat fats and added small amounts of carbs. Lipid profile change as follows two months later:

    LDL 135
    HDL 95
    TG 59

    Did not feel as good so reduce the carbs again after some research and will have a blood test later this year. Eating more red meat also.

    1. Dave

      Hi Tim–

      That’s funny, your pattern matches a Lean Mass Hyper-responder first, then you happen to do something that sounds similar to my carb swap experiment. http://cholesterolcode.com/cholesterol-research-breakthrough/

      But likewise, you didn’t feel as good as you did previously while very low carb.

      I’ll be interested in your new lipid scores — although I’d guess they’d return to the LMHR level if your diet is much the same.

      1. Tim


        Just as a reference, the following lipid test was before going LCHF and before my ldl skyrocketed. I was mostly following a lower fat diet with a decent amount of carbs and protein. Not sure if this reference data is useful for you.

        TC 214
        LDL 116
        HDL 81
        TG 84

        Also, you may be familiar with Dr. Sarah Hallberg who was also trying to understand hyper responders that she has seen during her practice. See the following link for her video:


        Cannot find out any information whether she has gained any further understanding.


        1. Dave

          Yes, Sarah is great. I actually chat with her now and then (she’s crazy busy). I was fortunate to see the presentation you linked above at the LC Vail conference live.

  12. Joseph

    I am on zero carb meat only diet since 5 months. Age 60, height 166 cm, weight stable at 55 kg. On completing 45 days (03-04-2017) on the diet my lipids were as follows.
    TC: 446
    TG: 205
    HDL: 61
    LDL: 344
    On completing 90 days (17-05-2017) on the diet as follows.
    TC: 673
    TG: 69
    HDL: 104
    LDL: 555
    Any comments please!
    Thank you.

    1. Dave

      Hi Joesph–

      Yes, it appears you are well into the cutpoints for LMHR.

      No doubt your LDL-C scores would shock your doctor — they are close to those of Nicole Recine. Yet your TG is 69, implying high energy usage of fat by contrast. It is certainly possible you have Familial Hypercholesterolemia if your cholesterol numbers have *always* been high (not just on a zero/low carb diet).

      But whether any of this is a problem is a much bigger, longer subject. That said, if the numbers concern you and you’d like to lower your LDL, you can check into my references on the FAQ (in the menu above) or possibly try adding back carbs (see my “breakthrough” post from a few months ago… http://cholesterolcode.com/cholesterol-research-breakthrough/)

      Out of curiosity — are you likewise lean and/or athletic?

      1. Joseph

        Hi Dave,

        Before starting “zero carb meat only diet” I was on LCHF diet for reversing diabetes and obesity for more than a year. I successfully reversed diabetes and obesity. While on LCHF diet my TC and LDL never went above 270 and 150 respectively. When I was on standard LFHC diet TC and LDL were not above 210 and 150 respectively but TG was always higher than normal. Hence I am confident that I do not have FH. I believe if I just go back to LCHF diet, my lipids will come down. When I was on LCHF I was using Coconut Milk and Coconut Oil. Now on zero carb meat only diet, I am not taking anything that originates from plants, hence use only Animal Fats instead of plant based fats like coconut products. I feel very healthy, happy and extremely comfortable with Zero Carb High Fat diet. Actually, the fact is, I do not know if I should be concerned about my high lipid numbers since I feel extremely healthy and happy. In around 40 days, I will be completing six months on zero carb meat only diet. On completion of six months, I intend to do all the tests necedsary to ensure if I am in good heath or not. I kindly request you to suggest appropriate tests I should undergo.

        I am not an athletic but always active, stay always busy doing something. Walk on bare foot more than an hour every day, most of the time under the sun and also do weight lifting (20kg) and dumbbells (10kg) infrequently.

        I highly appreciate your work, thank you.

        1. Dave

          Your story is pretty cool!

          I enjoy getting lipid panels from ZCers as their lipids can be quite different. As a scientist, I try not to render an opinion of knowing for sure whether something is good or bad — but I *do* put a lot of stock in how one feels and if there are any genuine markers of concern.

          Indeed, I’d want you to get a lot of blood tests now if mainly just to have “baselines” to observe progression if important. I’ll repost the list I have from a comment below for favorite blood tests to do at least once… (I’ll put this into a blog post soon)

          Apolipoprotein A-1
          Apolipoprotein B
          Apolipoprotein Lp (a)
          Cbc With Differential
          Comp. Metabolic Panel (14)
          C-Reactive Protein (High Sensitivity)
          Ferritin, Serum
          Hemoglobin A1c
          Homocyst(E)Ine, Plasma
          Iron And Tibc-Iron Bind.Cap.(Tibc)
          Nmr Lipoprofile (nuclear magnetic resonance)
          Thyroid Panel
          Uric Acid, Serum
          Vitamin B12 And Folate
          Vitamin D, 25-Hydroxy

          And of course, I highly recommend getting a CAC and CIMT as soon as you can. Note that each of these may reflect activity taken place long before your diet/lifestyle change too. But again, you want to observer their progress with later tests.

  13. Mike Broadley

    58yr old male.
    Weight 83.5 kg – was 95kg 3 years ago. Very active 6/7 days per week. Weights and HITT.
    LCHF 3years
    16:8 Fast on daily basis
    Blood draw done fasted.
    VLCHF 6months
    Cholesterol 10.1
    Trig 0.8
    HDL 2.5
    LDL 7.2
    TC:HDL 4

    Never felt better

    1. Dave

      Hi Mike–

      That’s awesome!

      I so often have hyper-responders approach me with, “I don’t get these numbers… I mean, I feel better than ever.”

  14. Carlos Lacayo


    Last November (before Keto) I found out I had High Cholesterol and Doctor put me on Atorvastatin. Please see Bloodwork 1.

    Choleterol: 280
    Tryglycerides: 64
    HDL: 89
    VLDL: 13

    February got checked again (still before Keto) see Bloodwork 2

    Cholesterol: 252
    Triglycerides: 54
    HDL 83
    VLDL: 11
    LDL: 158

    At the beginning of May I discovered Keto because I had trouble loosing body fat for years. Keep in mind that I am a very active person (for the last 10 years) with weights, and cardio 4-5 a week. 2 months in Keto have changed my everyday lifestyle. My focus, my well being, my workouts have all gotten so much better. My body fat% went from 27% to 19% in just a little over 2 months and love my results. I also do Crossfit 2 times a week now because of my new discovered energy source. Also as soon as I started Keto I stopped taking the statin because I hated the way it made me feel and heard from many Keto was suppose to help me. Now Bloodwork 3 came in last week .
    Bloodwork 3

    Cholesterol: 360
    Triglycerides: 64
    HDL: 101
    VLDL: 13
    LDL: 246

    I freaked out because all this hard work I put in has been for nothing. My doctor now wants to put me on a drug called Crestor and I want to refuse it. Can you offer some advise on what steps I cant take to lower this number? I am thinking about trying the increased in Saturated Fats like you did or possibly just cut them out and increase my carbs to about 70g a day. My macros has been consistent with 5c/25p/70f. Please let me know what you think.

    1. Carlos Lacayo

      I also want add that after being fat adapted for a month (beginning of June) I applied intermittent fasting 16/8. Fasting really kicked my Keto into gear especially at the gym.

      Thank you for all that you’ve done and I think it’s amazing how you are helping people discover this mystery. I will definitely be donating to you buddy.

    2. Dave

      Hi Carlos–

      Your activity and diet make perfect sense for the LMHR profile.

      However, if you are still concerned, you may consider bringing up your carbs as I did in a recent set of experiments (http://cholesterolcode.com/cholesterol-research-breakthrough/), but whether that is a net benefit is another story.

      1. Carlos Lacayo

        Ok thanks Dave. I am going to cut my Sat Fats by as much as possible and take in a bit more Carbs for a month. I will also begin testing my Keytone levels to ensure I don’t get out of Ketosis. I’m curious to find out where my “fence” is as you mentioned in your Biohackers Lab interview. I will post my blood results again in a month and see what changes took place.

        Thanks again buddy.

        1. Dave

          That’s great, Carlos!

          I look forward to seeing how it goes. Be sure to come back and share the data! 🙂

  15. Tim Newton

    Hi Dave

    Here’s another from the UK from a 66 year old marathon runner (10th fastest in UK this year!), 2 yr 6 months LCHF. I’m frequently in ketosis: 3.1 after a recent long run. Numbers in mmol:

    TC: 8.05
    Trig: 0.71
    HDL: 2.94
    LDL: 4.78
    TC/HDL 2.74
    Weight 9st 1lb (127 pounds)
    BMI around 18/19

    I had the blood test recently as part of the 5 yearly NHS healthcheck for us oldies. The GP called me in when he saw the figures and immediately opened the question of statins! I quickly disabused him, as politely as I could (not very), of the notion that I would ever contemplate that, and I would do without extra 3 days of life, thank you very much. It brought home to me with thump the grip the pharma industry has on our sacred health service. He realised I knew my stuff and backed off, saying it was fine, but I didn’t think he was convinced. I’m now thinking about finding a more sympathetic and knowledgeable GP.

    Keep up the good work!

    1. Dave

      Hi Tim–

      Fantastic story! I may share it in one of my upcoming presentations! 🙂

      1. Tim Newton

        Please do, Dave. I’d be hono(u)red! By the way my TC 5 years ago, before I went LCHF, was 4, but I don’t know the other numbers. If it would be helpful, I could try to find out while I’m still registered with the practice. A couple of further details: I lost 1 1/2 st (21 pounds) in the first 3 months of LCHF and have stayed very stable ever since; my marathon time before LCHF was 3:43. 18 months later I ran 3:20 in Berlin. Still hoping to drop a few minutes more before Father Time finally catches up with me. My age-graded times now are far better than when I ran my first marathons in my 30’s.

        1. Dave

          Holyfreeholies!!! You’re 66 and running marathons in 3:20??? Are you an X-Man mutant?!

          Yes, if you come across those prior lipid numbers, I’d definitely be interested.

          1. Tim Newton

            Hi Dave, I now have my results from 2012, which I have set alongside the 2017 figures: (in mmol/L again)

            2012 2017
            TC: 3.91 8.05
            Trig: 0.70 0.71
            HDL: 1.50 2.94
            LDL: 2.09 4.78
            TC/HDL 2.74 2.61
            Weight 148 lb 127 lb
            Height 5ft 9in

            Hope you find this interesting! I started LCHF in December 2014. TAll the best with the research, which I follow with great interest.
            Best wishes

  16. Matt Remine

    Hi Dave,

    47M/5’5″/137lbs 14%BF Zero Carb for 3 months at time of test. 18hr daily fasts. High output daily workouts/cardio/labor in trades.

    TC 471
    HDL 80
    Trig 88
    LDL 373

    Hope that helps. Thank you for all of your work.

    1. Dave

      Hi Matt–

      Thanks for adding more numbers for us!

      It’s incredible just how many LMHRs are showing up in just the last 48 hours since I posted this.

  17. Yas


    I am a 50 years old full marathon and an ultra marathon runner.
    LCHF 7~8years. Height 162 cm, weight 53~54 kg.(before LCHF weight 73kg)

    LDL 261
    TC 420
    TG 31
    Fasting insulin 2.7

    Your work is very very interesting.
    I also want to know what is happening?

    Keep up the good work!

    1. Dave

      Another great data point, Yas — thanks!

  18. Sietske

    Hi Dave,

    I’d like to add a datapoint for you. It’s my husband, they diagnosed his as FH last year purely based on his lipid profile and told him he could come back for a staton prescription or not at all. No option for further testing. Not even genetics! He didn’t go back for statins, no way he’ll ever take them! FH or CVD doesn’t run in his family at all, but unfortunately we have no tests from before our LowCarb lifestyle. We suspect he’s a LMHR but we cannot be for sure. Your work is very interesting and reassuring, because it’s hard to be comfortable with these numbers and turning down professional medical help.

    Height: 178 cm
    Weight: 75 kg
    Waist to height ratio: 0,45
    Body fat: probably below 10%
    Activity: callisthenics exercises 2-3 times a week, desk job but stand desk, little walk every day
    Diet: VLCHF since 2009, no IF at the time of testing
    TG: 502
    TG: 124
    HDL: 62
    LDL: 418

    Hope this helps. TG little high for your LMHR profile? What could that mean? We plan on asking te retest since it’s been 2 years now. Of course we’ll happily share those numbers, also if he gets the chance for a second test. The. Hell do the Extreme Drop protocol.

    Sietske (Sweden)

    1. Sietske

      Last sentence scrambled up! Should be “… second test, then he’ll do the ED protocol.” Oh, and forgot to mention; 42 years old male. And its now two years ago that we got those numbers and diagnosis, not last year. Time flies!

    2. Dave

      Hi Sietske–

      Your husband’s profile appears pretty common for a hyper-responder (but probably not a LMHR given the HDL and TG).

      It’s true there’s a chance he has genetic FH — but the fact your doctor *refused* testing for it is a testament to the state of modern medicine. I don’t give individual medical advice here, but you can guess what I’d do if someone said, “come back for a statin, or not at all.”

      If you’re concerned about the higher cholesterol, as I mention above here, you can try adding back in more carbs as I did in a recent experiment. http://cholesterolcode.com/cholesterol-research-breakthrough/

      If you’re wanting to learn more for now and remain cautiously optimistic, I recommend learning further information with:
      1) A CAC scan (be sure to check out Ivor Cummins talks on this if you haven’t already)
      2) A CIMT (a little less useful, but still helpful)
      — note with both the CAC and CIMT, you may get back scores that partially or mostly reflect his lifestyle/diet before going keto, which is why it is worth doing this as soon as possible. You’ll want to watch these numbers to determine progression on later tests.

      3) Bloodwork I recommend everyone take at least once — (I need to do a full post on this soon)

      Apolipoprotein A-1
      Apolipoprotein B
      Apolipoprotein Lp (a)
      Cbc With Differential
      Comp. Metabolic Panel (14)
      C-Reactive Protein (High Sensitivity)
      Ferritin, Serum
      Hemoglobin A1c
      Homocyst(E)Ine, Plasma
      Iron And Tibc-Iron Bind.Cap.(Tibc)
      Nmr Lipoprofile (nuclear magnetic resonance)
      Thyroid Panel
      Uric Acid, Serum
      Vitamin B12 And Folate
      Vitamin D, 25-Hydroxy

      1. Sietske

        Hi Dave,

        Thanks for your elaborate answer. Problem is, here in Sweden you don’t just go and order tests… Not even when you’re willing to pay for it. It’s your doctor who orders your tests and as said above, ours is not very open minded. Might find another one more open minded when you live in Stockholm or something, but not on the countryside up north where we live. You see why two years have gone by since those numbers and diagnosis came in? It’s kind of frustrating when you want to know more! We really hit a wall with the doctors here. Don’t see it happening that we can ever get all those numbers done that you mention… and if we could, who would explain what the outcomes mean?

        Luckily we’re not really prone to worry about it, especially after reading a lot we can find about cholesterol (including everything here on CholesterolCode) an about statins. It’s just not comfortable saying no to your doc, who is used to being treated like an authority. We’re convinced though that statins don’t hold any value (Zoe Harcombe is very clear on this for instance, but there’s a lot more!). Lowering the numbers would be interesting, but my husband doesn’t feel as well when on more carbs. It wouldn’t be a permanent solution, nor do we believe it would be beneficial for his health. Which is quite excellent by the way, especially since lowcarbing since 2009. But it would be interesting to confirm the inversion pattern with 3 days of more fat and also your “breakthrough pattern”! For now we just wanted to share his numbers for your data collection.

        A CAC is first on our wishlist indeed, as well as genetics for FH. Would you think a CAC would reflect damage from years ago? Since we’re already 8 years on this lifestyle? How does that work? Doesn’t the damage get repaired or lessened over time? Just to brace ourselves for the result, if we get the doc to order a CAC… my husband has been vegetarian until 2009 and also smoked for a while even longer ago. Would that still impact his CAC score now I wonder? Of course I realize you don’t give medical advice, nor do we ask for it. Just you knowledge based opinion

        1. Dave

          I try to keep from getting too ranty — but your story both saddens and angers me in equal helpings. It’s a sad state of medicine that seeks to turn away information and prevent a deeper diagnosis.

          Thank you for sharing his data. If you get a chance to travel here to the states, we have plenty of labs you could privately pay for. 🙂

          Given the prior lifestyle and particularly the smoking, you shouldn’t be surprised if the CAC comes back with a score. But even if it does, you want to watch for *progression* more than anything. I’d rather have a 300 with a 2% progression than a 50 with a 100% progression. I want to tell you this in advance so you don’t overreact if you see this score being anything other than 0.

          1. Sietske

            We feel the same, pal! The anger maybe a little more than the sadness. Thanks for your kind words though. We might do a trip to the US once in the future and we’ll certainly add a “medical” note to it then!

            So, if we can convince our doc to do a CAC, the result might freak him out even more! It’s good to know, we can brace ourselves for that Thanks for everything you do Dave, keep going, it is all very interesting!!!

            Warm wishes

          2. Sietske

            By the way, I typed his height wrong, should be 185cm

        2. Annlee


          Check with the team at Diet Doctor – he’s Swedish.

          http://www.kostdoktorn.se/kolesterol original site

          http://dietdoctor.com/about English site

  19. Ryley

    Hi Dave,

    Total cholesterol 6.4mmol/L
    Ldl 4.53
    HDL 1.74
    Tri 0.38
    Body fat around 8%
    Waist size 28″
    I’m 23 5’7 143lbs and would say I’m very active
    Warehouse job + working out and sports
    Been LCHF for 7 months with a weekly cheat day

    1. Dave

      Hi Ryley–

      Thanks for adding another N.

      There really appears to be inverse correlation with level of activity vs body-fat thus far. Now with so many contributing their data, I’m able to get a much larger aggregate.

  20. Shaq

    Adding to your list:

    54 years old
    6′ 7″, 210 pounds
    Desk job, daily fast of 10+ hours (although some heavy cream in coffee – not sure if that ruins the fast).
    Mostly lift weights, some walking. Read about myocardial fibrosis in endurance athletes and dropped running.
    I’m not a perfect fit for your definition, but:
    Total Cholesterol: 254
    Direct LDL Cholesterol: 176
    HDL: 83
    Triglycerides: 41
    Happy to provide other data if helpful.

    1. Dave

      Hi Shaq —

      While I haven’t talked about it in detail yet, I suspect those who do resistance training and muscle building would likely have lower LDL-C/-P due to repair. Cells can remove LDL-Ps from circulation via endocytosis (engulfing entire particle) to use for its many component parts. This is why I believe my biggest gaps in these scores happened to be (1) on the cold open run of my training for marathons last year and (2) on the final race — the marathon itself.

      In other words, I think you might have a higher LDL-C if you weren’t lifting weights and running instead.

  21. catherine

    Hi! I wanted to offer my stats as well. I was referred to you by the Ketogenic Diet Open Discussion site on Facebook. I’ve been following a keto diet for the past year and had blood work done with these resulting numbers.

    I am 52, weight is 135, height is 5’6″. I don’t consider myself a lean endurance athlete by any means, but I hike at least once a week and do HIIT on average about 3X per week. My job varies in terms of physical activity from sedentary to potentially walking several miles a day. But I would say it falls more on the less active side.

    LDL-225, HDL-79, Triglycerides-154
    Non HDL-256

    My Triglycerides seem to be higher to qualify as a hyper-responder.


    1. Dave

      Thanks, Catherine!

      Yes, the trigs are a little higher than usual. I find when the other patterns are consistent, this is usually a sign of higher combined fat+carbs together. Another possibility is that you weren’t fully fasted at the point you got your blood draw. But it can definitely be other things, these are just the two most common.

  22. George Henderson (@puddleg)

    I’ll give a little n=1 anecdote here; my chol was always a bit high, as far as I remember, despite having Hep C geno 3, which was a good thing at that time.
    Clearing HCV and being low carb, it is now significantly higher, within the pattern you describe.
    I’m naturally lean, exercise a bit but not intensely, practice IF to some extent.
    After a very high lipid test, I decided to replace butter with olive oil, cheese with avocado, as far as possible for a month or two.
    Next test, my total C and LDL were the highest they’ve ever been.
    Went back to ghee and coconut oil and they went down again by the next test, at least to the point where the ratios weren’t high risk.
    My conclusions?
    1) high LDL in my case is probably caused by high fat/low carb intake and low insulin, not high SFA%
    2) I may be a hyper-responder to plant sterols in this context.
    Put this on twitter and 3 or 4 other people said they fitted type and had same reaction to high MUFA oils replacing SFA.

    1. Dave

      That’s really interesting, George.

      To date, I don’t know that anyone has come back with having done a MUFA/PUFA replacing SFA story that resulted in an increase with the change, and a corresponding decrease when coming back. Myself, I’m skeptical as to how much impact the fatty acid types have on actual LDL-C overall. In my own experiment from last year, the effect was negligible.

  23. Tim

    Hi Dave.

    There is a mechanism involving triglycerides and apoB protein release and catabolism in liver that may partly explain your LMHR group.

    Trigs are the prime control factor in apoB metabolic channeling. They essentially divide LDL into an atherogenic and non atherogenic pool, with a switching mechanism dependent of the trig level.

    There is a U shaped curve in LDL production and catabolic rates. As trigs rise from low levels the scheme switches from non atherogenic to atherogenic LDL, with a plateau in the middle and higher values on both the lower and higher arms.

    At low trigs LDL production and catabolism can be very high, this would not apply to everyone but possibly to a small group, hyperresponders may be among this group.

    At the same time VLDL production can be scaled back as the liver can release a fairly broad spectrum of apoB particles directly into plasma, these would include IDL and LDL, possibly as much as 50%.

    The net result could be a large presence of LDL, high production and catabolism but subdued VLDL. This would presumably be a healthy state, in spite of the high LDL since it would be group a.

    Here’s the ref, check figure 5.



    1. George Henderson (@puddleg)

      Hi Tim,

      I’ve been thinking along similar lines but hit a speed bump. On LCHF no TR-VLDL, less VLDL, more IDL and LDL released directly; this is also in Krauss studies.
      But IDL has less TG, LDL has next to none, so how are these lipoproteins contributing to increased fat oxidation? Where does this fit in the energy demand model?

      I see another aspect like this – when you don’t eat carbs you don’t need so much cholesterol. Synthesis has decreased, adipocytes are rejecting it, HDL has risen to collect it from cells, and it’s being transferred to IDL for transport to the liver for increased excretion (I suspect), making more LDL.
      Also, foam cells consume 33-66% of LDL normally, according to Brown and Goldstein, with LPS attraction and oxidation as the triggers, so what if foam cells STOPPED consuming LDL in low inflammatory states? Would that make LDL pile up in serum?
      All of these mechanisms would surely be temporary and at some point whole-body cholesterol stores would get low enough that LDL would start to come down, at least I think so this model predicts.

  24. Tim

    Hi George.

    I think I agree but come at it from another angle.

    My take is that in healthy individuals at extremely low trigs LDL levels tend to be very low but production and catabolism very high so the hepatic LDLR activity is high. Here after a low carb/high fat meal LDLRs are available for catabolism of chylomicron remnants but tissue, adipose and muscle is fat replete and properly sized so the small amount of remnant fat gets recycled rapidly into IDL/LDL but catabolized very quickly so levels of LDL remain low but particles are large (with large lipid and cholesterol loads), and consist almost exclusively of LDL I/II, ie non atherogenic, VLDL is almost all VLDL2 so small and again non atherogenic. There is little to no cholesterol esterase going on so not much lipidation of VLDL, the action is mainly in LDL. The system buffers the high fat meal in muscle and adipose and meters it out later from adipose. I”m not sure how you can get high cholesterol in such a system except as a mismatch between production/catabolism, but even a small mismatch could see outsize levels as the rates are high, I suspect this would be rare.

    As trigs rise CETP (cholesterol ester transfer protein) gets turned on and cholesterol transfer from LDL/HDL to VLDL starts. This shifts part of the cholesterol load to VLDL from LDL/HDL and lipid is given in exchange. Subsequently HL and LPL delipidate both LDL and HDL so you are left with small/dense LDL and small HDL. The HDL particle is unable to retain the apoA1 protein and sheds it and it is cleared from circulation. In this system you would have higher but not necessarily super high trigs, low/normal LDL and low HDL. The LDL would be small and dense and reside in circulation much longer because the LDLR has less affinity for it. LDL, being in circulation longer has more oxidation and accumulates more sugar labels. As trigs rise further the situation would get progressively, but slowly worse. Your foam cells would start to accumulate as inflammation/oxidation would rise.

    The dynamic action as this system progresses is in the LDL pool size and character as trigs move up. LDL pool size increases as catabolism rates decline and the spread between high and low increases so you can get high LDL at moderate but still relatively low trigs. The non atherogenic pool starts to decrease and the atherogenic (small/dense) starts to increase and HDL starts to drop. Later as trigs rise further you get increasing catabolic rates again and LDL pool size starts to drop but the character has changed to atherogenic. This I think is why cardiac admits have low/normal LDL.

    So highest LDL is seen when trigs are somewhat higher but still on the low/normal side. Also you see the biggest spread between low/high. I think this is where the hyperresponders fit. If you look at the chart (Figure 5) the densest cluster of high LDL is in this area.

    So how does this make sense in energy transport? Good question. On LCHF you eat less and lose weight at least initially so some of the LDL will be coming from adipose, as adipose distributes lipid and shrinks it cannot at some point hold onto the stored cholesterol so it comes into plasma. You could also, be getting additional from ectopic storage via reverse transfer from higher HDL and with lower inflammation perhaps foam cell discharge (this pool size could be large). This discharge could be quite large and sustained. I believe that cholesterol does eventually normalize for most individuals on LCHF but this can be a long time. If you were getting substantial flow from storage AND trigs were at the right levels the two streams (anabolic and catabolic) would add so you could in theory get very high LDL, perhaps this is the explanation as you say.

    Don’t know. I think you’re right, that cholesterol levels would eventually return to sanity and the mechanisms involved seem plausible so maybe. If this is right then the base levels of LDL may fit and Dave’s results would be a shorter term modulation of them.


    1. Dave

      Very interesting thoughts, guys. I keep coming to these three comments in the gaps between everything I’m doing and find I need to pause and come back again.

      I’ll be having another update soon on where my most recent blood tests landed, I think you both will have much more to talk about. 😀

  25. JohnD

    Some more data.
    First, I’m not 100% “LC”,
    Mornings are MCT and heavy cream coffee.

    Lunch Salad with some sort of protein (sardines, salmon, beef jerky…)
    Diet Coke, almonds and some 70% dark chocolate.

    Dinner is as LC as I can make it. (I eat with the family and don’t want to rock the boat).
    ice cream later at night

    Started in in Jan-2017 and dropped from 172 to 164 ish
    Run 4 miles 4 times a week (8:45 min miles)
    OR bike to work (30 to 45 miles total) 16->18 MPH average
    I consider myself reasonably athletic (compared to the general population)

    6’2″ (188cm)
    164 lbs (74.4kg)

    Blood work from last year (June 2016) when I wasn’t low carb:
    Total Chol: 204
    Trigs: 74
    VLDL 14
    LDL 126
    HDL 63

    Last month (June 2017) on the quirky low carb:
    Total Chol: 241 (up 37)
    Trigs: 61 (Down 13)
    VLDL 12 (down 2)
    LDL 149 (up 23)
    HDL 80 (up 17)
    A1c 5.5 (I don’t have a number from last year)

    I’lll get a physical in Sept and see what the Dr. has to say about these numbers.
    BTW, the 2017 data was from Walk In Labs, it was a $46 test, seems reasonable to me.

    I feel like I’m hovering around ketosis. On mornings with it’s a 35 miles ride in, I feel fine. However the 15 mile ride home is sluggish on the border of bonking. Then sometimes it’s another slice of seedy bread w/ PB. Eventually would like to go full keto and see if that goes away or gets different. I’m impressed by people that do sub 4 hour marathons in ketosis. Is it genetics, the ketosis or something else?

    One last bit, if you forget to enter the CAPTCHA code the post text gets deleted : (

    1. Dave

      I like those lipid numbers. You’re hovering close to a Lean Mass Hyper-responder, of course with the high HDL and low TG given all your exercise. http://cholesterolcode.com/are-you-a-lean-mass-hyper-responder/

      It sounds like you’re in a kinda-there, kinda-not zone. Trust me on this, you should set a period of time like a month or two, announce this to your family and friends in advance and then do it. When you (and they) know it’s for a fixed amount of time, they are more likely to keep that “boat” steady and you can see how much it does or does not matter for yourself.

  26. Tim

    Hi George/Dave.

    Further thoughts on the mobilization of cholesterol to/from plaque and fatty streaks and ectopic locations, this is a minor wrinkle on circulating LDL levels but may be important in some cases..

    The major holder of cholesterol in plaque is macrophages that aggregate into foam cells. Cholesterol entering these structures is damaged or altered in some form, ie it is not the native cholesterol from pool a. The mechanism of entry is receptor mediated endocytosis, ie receptors are concentrated in coated pits and bind lipoproteins like damaged LDL by invaginating and passing the contained material to lysosomes to seperate the cholesterol and other constituents for degredation. This is because macrophages do not have many receptors for native LDL but have numerous receptors for chemically altered LDL, so macrophages scavenge this damaged LDL as a way of reducing its presence in plasma. Once in the cholesterol is esterified in droplets but enters a futile esterification cycle where it is repeatedly re-esterified and returned to free cholesterol and is essentially trapped as the plaque builds. For exit from the vascular wall the membrane macrophage must find a cholesterol acceptor since free cholesterol is aquaphobic. Once there is a minimum of acceptors the interior foam cells can pass cholesterol to the membrane macrophages as there is an exit from the esterification cycle where free cholesterol can pass out of the cell.

    The main acceptor candidate is HDL although there are other known acceptors HDL seems to be the prime one.
    Once in HDL, cholesterol can be delivered to the liver, or if CETP is active it can be transferred to VLDL.

    To sum up the above several comments there seem to be the following things happening.

    1. At low trigs native LDL is predominant so there is little LDL traffic into the vascular wall and consequently not much out apart from that required for cholesterol homeostasis with the cell constituents of the wall itself, which is not that much compared to the deranged accumulation seen in atherosclerosis.

    2. At higher trigs poolb becomes dominant this pool contains far more damaged LDL so macrophage accumulation of cholesterol becomes important. This is compounded by lower levels of HDL accompanying the CETP activation.

    3. With LCHF the increase in HDL becomes important as does the drop in inflammation and the large drop in triglycerides. This seems to accomplish several things. The increase in HDL increases the cholesterol acceptor capability at the vascular wall which starts the plaque mobilization of cholesterol into plasma. This in itself may or may not be sufficient to stop plaque accumulation but for sure it will at least slow it down. The drop in triglycerides moves the system from accumulating small/dense LDL towards a more balanced structure with poola being restored somewhat and poolb degraded by less addition and continued, albeit somewhat slower catabolism and somewhat larger LDL total pool size, so balance gets restored to some degree between the atherogenic and non atherogenic pools. I suspect the combination does indeed stop further plaque build but the reversal and diminution of the plaque may be very slow, I suspect that it is. One reason may be that in parts of the plaque the cholesterol becomes crystalized and harder to mobilize.

    4. This stream of cholesterol may or may not be important compared to issue from adipose depending on circumstances and I have no idea what magnitude it may compose of circulating LDL cholesterol.

    5. Hyperresponders may be largely immune from plaque build because trigs are low enough to ensure predominance of poola relative to atherogenic poolb.

    6. Hyperresponders are a small group of LCHF, somewhere between 5-20% or so according to Sarah Hallberg and others so it seems a combination of circumstances may be required to produce one.

    Still puzzled.


    1. Dave

      Awesome comment, Tim. Lots to unpack:

      – We should weigh in with George on what studies he’s seen that address the atherogenetic association is with VLDL-specific particles relative to the other, more commonly used markers like LDL-C and LDL-P. Naturally I’d assume there is a stronger association as large amounts of VLDLs still being in circulation for a fasting blood test certainly suggest metabolic backup. But I’d be curious just how close that association is relative to others.

      – Given the patterns I’m seeing, particularly with Lean Mass Hyper-responders, I’m now more of the mind hyper-responders *generally* have a particular profile that comprises key elements. If you are already hypercholesterolemic while obese and lose weight, but do not end up as LMHR (which very few would), then it is very possible you could see a net drop in your cholesterol *relative* to the previous state. As with the LMHR article, I believe a lot of this is dependent on your adipose and glycogen store status. In other words, there may be many more than 5-20% who are would-be hyper-responders, but their adipose and/or glycogen top off is preventing the body from mobilizing more TG for energy, and thus mobilizing more LDLp and LDLc along with it.

      – Your breakdown of plaque and RCT with the players matches closely with how I understand much of it, but I’m still learning more with regard to oxLDLp and what I can trust and not trust. By this I mean there is a lot of speculative literature that frames itself as a series of “givens” where you have to unwind where the assumptions come from to be sure.

  27. George Henderson (@puddleg)

    Hi Tim,

    Sarah Hallberg’s experience is with weight loss and I’d expect the lowest rate of hyper-responders in that population based on the fasting studies (and my own impressions based on feedback for the What The Fat diet book).
    I’m thinking if there was a large reduction in whole-body cholesterol as we’re discussing, this would take time because I don’t think fecal cholesterol reabsorption/excretion can be regulated by the LDL pool.
    In low insulin states foam cells make cholesterol directly from glucose and don’t take in LDL, insulin switches this off. This is the opposite of liver, where insulin stimulates HMG-CoAR

    1. Dave

      Ah — I just got done commenting on this! Yes, I likewise agree that there would be less hyper-responders from a weight loss group from a relative standpoint. (And again, I think they are less likely to result in lean, athletic outcomes such as LMHR)

      I didn’t know that about the foam cell cholesterol production, George. Very intriguing information…

  28. Andrea

    Hi Dave,

    Thanks for your passion in studying this topic!
    I feel a bit puzzled because I almost fit your profile (lean,very active,with LDL going way up on low carb),however in my case hdl goes down and trigs up on low carb+intermittent fasting (never went full keto).Here are my values (all in mg/dl):

    On low carb:
    ldl 250
    hdl 54
    trigs 105

    After 3 weeks of higher carb and lower fat:
    ldl 141
    hdl 60
    trigs 41

    I wonder if you have any insights into what might be the mechanism behind this pattern…

    Thank you,

    1. Dave

      Hi Andrea–

      To be sure, this wouldn’t be too far off from my Breakthrough outcome, which I could describe as “higher” carb, though still LCHF (95g net). http://cholesterolcode.com/cholesterol-research-breakthrough/

      But even with that in consideration, you’d want to be sure your total energy intake (carb v fat) was nearly the same on the 3 days prior for each test for an apples to apples comparison. Did you track everything you ate up to the tests?

      1. Andrea

        Hi Dave,

        Thanks for your response.I did not track my food intake systematically as I just eyballed portions.If anything my higher carb diet was lower in total calories as I cut down my fat intake quite a bit and I did lose some weight during those three weeks.I shall do another test in the coming weeks and I’ll carefully register my food intake.I plan to skip breakfast,eat a protein-rich lunch with some fats and maybe a bit of carbs and a carb-rich dinner with some fat and maybe some proteins for a total caloric intake of about 2500 kcals.I am especially curious to see if my hdl actually pushes above the 60 mg/dl ceiling.I am expecting my ldl and trigs to be roughly unchanged compared to the previous test (maybe ldl a bit lower).

  29. Angela

    Hi Dave,

    I conducted the Ketofest experiment at home in Florida (I’m saving my photo food logs for your Google Drive folder) and received my Friday morning lab results a few minutes ago (I fasted TWR except for supplements, coffee with HWC, water, salt). Here are some of the results:

    LDL-P: 2083
    LDL-C: 185
    HDL-C: 52
    TG: 71
    Total Cholesterol: 251
    HDL-P: 24
    Small LDL-P: 544
    LDL Size: 21.5
    C-Reactive Protein: 3.43

    I’m a 52-year-old woman and I’ve lost about 30 pounds so far in 2017–currently 172–on a ketogenic diet with some fasting. I weight-train approximately four days/week (including last week WRF while fasting).

    I really appreciate all your analysis. Had my second round of blood work this morning after three days of feasting. Looking forward to those results, too.


    1. Dave

      Hi Angela!

      Thanks for taking the time to do this in solidarity!

      I look forward to looking at your data when it comes in! 🙂

  30. Daniel

    Hi Dave,

    We’ve talked before on the apoe4.info forum. Very interesting stuff here! Here’s my lab numbers as I progressed from a 50% carb diet to ketosis. I am 72 yrs, 10% body fat, moderately active, apoE: e3/e4. Although you can’t see it here because I keep my SFA down, thanks to my e4, I am a hyper responder to SFA.


    Although I don’t take pictures, I’ve weighed and recorded my food intake for years as well as tracking other variables.

    – Dan

    1. Dave

      Hi Dan–

      First — super strong data set, sir. I salute you!

      – You might be surprised to know that I don’t actually consider you a hyper-responder, you’re at the very cusp at best. Your LDL went from 109 to 151, which — while a rise — wasn’t a *dramatic rise* as I’d describe it (50%). Moreover, you haven’t crossed into >190 territory, which I likewise consider extremely common for HRs (especially Lean Mass Hyper-responders).

      – Your lipid numbers are otherwise very strong at >60 and TG <100 very consistently.

      1. Daniel

        You don’t have my entire set of 36 lab numbers. Back in Jan 2012, I discovered that SFA was not for me. In experimenting, I let my SFA go to ave 26g / day and was shocked to get

        TC: 320
        HDL 101
        LDL 207

        No longer shocking to me now because I know it would be unusual for an apoE4 to not be a hyper-responder to SFA, because the e4 apoE has affinity for LDL and VLDL which impedes it’s binding to the receptors that would clear them when they became TG depleted.

        After that, I dropped my daily SFA intake to under 10% of calories. These last three test cycles, I allowed it to rise a little above 10%en, hoping being in ketosis would render them irrelevant (as claimed by Phinney & Volek), but, as you can see, sadly, that is not what happened.

        1. Dave

          Cool. So you’re a legit test case on SFA intake appearing to modulate your LDLc/HDLc. I haven’t had too many of those (including myself) as the impact seems small or non-existent with the change.

      2. Daniel

        Also interesting (to me at least), here’s my last 16 labs (chosen because my weight and thyroid function was stable during this period), LDL-C vs SFA intake with various averaging periods, 3, 9, or 30.


        Although individual data points varied quite a bit, the trendlines were essentially the same. I choose 3 because you use that, 30 because I was using that, and 9 because it give the best fit to the lab results:


        1. Dave

          Very, very interesting Daniel.

          The 3-day average was the one that followed most closely when I intentionally altered meal plans to create peaks and valleys. However, I don’t discount that there could be larger windows, particularly if steady for a longer period.

          What I’m especially interested in is the possibility the Inversion Pattern window could actually change under certain circumstances, but that might be a stretch.

  31. Lewis

    Any data on long lived people with healthy arteries & also have the LMHR profile?

    1. Dave

      Only anecdotal. I’ve certainly asked a number of doctors in the LC community that fit the bill, like Ted Naiman. All of whom appear to be doing excellent.

      That said, the sample size is relatively small and could be convenience-selected. So I don’t put a lot of stock into it just yet.

  32. pam

    Another person with results for you. I’m a 48 yo female, keto diet for a 3 months–fairly active with swimming,
    rowing, and yoga. Recent labs: Triglyceride 56, Total cholesterol 215,
    LDL 132, HDL 72, Vldl 11, Chol/Hdl ratio 3

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