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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:

LDL-C HDL-C TG
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.”

    https://www.ncbi.nlm.nih.gov/pubmed/27207551

    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

    https://www.ncbi.nlm.nih.gov/pubmed/1921253

    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

    https://www.ncbi.nlm.nih.gov/pubmed/8304441

    ” 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

        http://hopefulgeranium.blogspot.co.nz/2015/02/the-guinea-pig-model-of-atherosclerosis.html

        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

            Absolutely!

            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 ).

            http://high-fat-nutrition.blogspot.com/search/label/High%20fat%20diets%20make%20you%20fat%20and%20stupid%20%282%29

            http://high-fat-nutrition.blogspot.com/2009/12/when-is-high-fat-diet-high-fat-diet.html

            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)
    HDL168
    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. 🙂

      1. Wendy p

        Hello Dave,
        On my long journey to find answers to my high cholesterol readings I found your website and you have giving me some answers and some relief, I been Keto for over three years and never has a high cholesterol reading before even though I was obese and very unhealthy, I’m very lucky to have a doctor that is very understanding and knowledgeable about cholesterol and doesn’t think that my husband and I need medications and that we are very healthy but he wants to send us to a specialist since I told him I was a little concerned. I’m 43 years old, I have lost 90 pounds, I workout five days a week mostly heavy lifting and gaining a large amount of muscle for the last year, my body fat is 23%, my total cholesterol is 344, TG 41, HDL 105, LDL 231. Note that last year my LDL was lower but since I been lifting heavy weight it has gone up a little, we thought that because I been so active and so healthy it would go down but it went up My husband is on the same boat with me but he has T2D And his A1C have been normal range for over three years on Keto but his cholesterol also went up the only difference is that he has always had high cholesterol that runs on his family but not me. My doctor and I also concluded that my thyroid Free T3 was on the lower side of the range so we decided to treat it to race it and see if that helps to lower cholesterol and to help with hair loss that I’m experiencing also. Thank you for sharing your findings and helping others

        1. Dave

          Hi Wendy–

          Indeed, your profile fits the Lean Mass Hyper-responder markers mentioned in this article. You are also close to the end point margin for body fat (around 22-23%). And again, this makes mechanistic sense, particularly with your TG as low as it is. It means there’s more demand on a per-particle basis to deliver those fatty acids.

          I’m curious about a few things — if you don’t mind sharing for research value…

          – If you’ve been doing dexa scans, can you share how much of your fat is visceral vs subcutaneous?

          – Also, what would you say your general fat/protein/carbs quantities are per day?

    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.

      https://www.dropbox.com/s/glpf1xe75coi1jk/Healthy%20HALP.pdf?dl=0

      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.

    Tim.

    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.

    Sabine

    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

    http://jn.nutrition.org/content/129/11/2005.full

    “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.

      http://www.kuuroorddeschouw.nl/images/Publicaties/Onderzoek_obese.pdf

      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

    Dave,

    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

        Dave,

        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:

        http://bjjcaveman.com/2016/05/30/dr-hallberg-ldl-lchf-talk/#comments

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

        Tim

        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.

          1. Tim

            Dave

            Thought I would follow up with the latest test. As I mentioned I went back to keto and mostly ate red meat ala Shawn Baker and essentially no carbs. Results are as follows:

            TC – 636
            HDL – 139
            LDL- 484
            TG- 60

            Also performed the CAC test with a score of 0.

            Work out with weights and cardio 5X per week and have single digit body fat (est of 8-10%). Again feel great but cannot wrap my head around these new numbers.

  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)
          Cortisol
          C-Reactive Protein (High Sensitivity)
          Ferritin, Serum
          GGT
          Hemoglobin A1c
          Homocyst(E)Ine, Plasma
          Insulin
          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

    Hi
    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

    Dave,

    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
    LDL:178

    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
            Tim

  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

    Dave

    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
    HDL112
    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.

    Best,
    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)
      Cortisol
      C-Reactive Protein (High Sensitivity)
      Ferritin, Serum
      GGT
      Hemoglobin A1c
      Homocyst(E)Ine, Plasma
      Insulin
      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
            Sietske

          2. Sietske

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

        2. Annlee

          Sietske,

          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.

    Cholesterol-335,
    LDL-225, HDL-79, Triglycerides-154
    Non HDL-256

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

    Catherine

    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.

    http://atvb.ahajournals.org/content/17/12/3542.long

    Tim.

    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.

    Cheers.

    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

    Dave,
    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.

    Cheers.

    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
    http://journals.lww.com/cardiovascularpharm/Abstract/2008/10000/High_Glucose_Concentration_Increases_Macrophage.5.aspx

    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,
    Andrea

    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.

    Thanks,
    Angela

    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.

    http://imgur.com/XVWwzSG

    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.

        http://i.imgur.com/DbZfdzn.png

        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:

        http://i.imgur.com/xnsldOx.png

        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

    1. Dave

      Thanks, Pam. Your LDL isn’t actually that high relative to many on LCHF. But your TG and HDL appear to showcase your athleticism quite nicely. 🙂

  33. David Mitchell

    I’m borderline. I started LCHF 5/4/15 on Mark Hyman beta program for EFGT book. I have stuck with it to date – perhaps 40-50 g carb / day on average including seasonal and other cheats. Here is something for your database. Note LDL values are Friedwald, but I believe better formula for would be Iranian formula for LCHF (see http://www.docsopinion.com/2017/01/02/ldl-cholesterol-overestimated-low-carb-high-fat-lchf-diet/ or use LDL (mg/dL) = TC/1.19 + TG/1.9 – HDL/1.1 – 38 (146 for my latest 6/17 physical with Friedwald 170, TC 255, HDL 72, TG 66; 6/16 was Fried LDL 141, 217, 63, 66). I’m not concerned about my higher LDL, but am confused by my stubbornly high prediabetic status. Here’s my post to Gerber (no response yet):

    You mention A1c test, a frustrating subject for a few. I’m LCHF for 2 years with TG/HDL going to 66/72 from 220/52, small LDL-p @ 217 with LDL-p slightly >1500 and LDL-C 140-170, bmi to 22 from 27, Naiman’s Homo-IR = 0.55 – all good except no change A1c 5.8-5.9 for last 5 yrs unchanged.
    From 1st glucometer 3/17 and many readings for various meals and fpg/bedtime, my average pbg estimate under most conservative assumptions is 102, not the 130-133 via formula from a1c results. (My highest reading after 100+ g cheat meal is 145 @ 1 hr back to 96 90 min after 15 minutes tag exercise; usual after 10-15g g carb LCHF meals is 110-115; return to 95-100 is at 2 hr usually or maybe 3 hr if I eat pasta or some other significant delayed digestion mechanism; I don’t snack and usually skip breakfast (not hungry)). MY CONCLUSION: I am rare individual with very long extended life RBC and A1c does not accurately represent my average pbg.
    (I’ve not found many detailed discussions of inaccurate A1c except Jenny Ruhl’s Blood Sugar Solution 101 (she has similar directional issue to mine, but most people say they’ve never heard of this much difference!). I have heard that many docs don’t like to use A1c as it has high inaccuracy rates for combined too high or too low. Jenny Ruhl says to trust actual meter readings more than A1c readings (even though many studies use A1c as a statistical construct.)
    Should I be concerned about IGT levels of HbA1c, even though clearly I am IS per your Crofts criteria (10/16 OGTT 75g glucose drink insulin levels were 2.5, 24, 14, 23, 10 at 30 minute increments (post only 3 days carb upload after 1.5 yrs LCHF, meaningless glucose readings high at 95, 174, 195, 156, 103)? Symptomatically I am healthy in all ways doing 30 mile day hikes AT, 100 mile backpack/day hike combo in Glacier NP and climbing Mt Whitney. I’ve never been on any meds other than 15 years of 10mg lipitor wasted expense before abandoning statins forever 2012. At M 67 I am EBT Agatston score or volume of about 165 @9/16 with family history of CHD (father) and diabetes T2 (mother no insulin). Have you seen any patients with good everywhere except A1c? It appears to me there is nothing I can do to improve my A1c.

    1. Dave

      Hi David–

      I honestly don’t put a lot of stock into a1c myself. Note I hover between 5.4 and 5.8 myself, yet my fasting glucose is consistently 80s to low 90s. (Turned out my Precision Xtra reports wrong at 100-ish)

      I haven’t done a post on it yet, but I regularly take a1c in each of my blood tests for this very reason — that I won’t to know what the chances are that they can change from one test to the next. As it happens, in my Breakthrough post, I had a series of days where the first was 5.7, the one right after where I swapped in bread was 6.0, and the one following that was 5.6. You read that right, all three days were one after the other. Thus, there is some combination of error margin and actual variability for this delta anyway.

  34. Neville

    Hey Dave, Few questions…

    – We hear that its not the cholesterol but the particle count where the risk is. However in all probability if your cholesterol is high, isn’t it likely LDL-p will be high too? Have you come across a major discordance between LDL-p and cholesterol numbers, like someone having cholesterol of > 350 but a LDL-p of 1500?

    – So i recently had a CIMT done [Right=0.87mm, Left=0.92mm] which definitely seems fine. In any-case, even the technician agreed that calcium score trumps CIMT when it comes to heart disease risk. My calcium score did increase on a low carb diet!

    I have (briefly) been on statins and heard that they can lead to an increase in calcium score. Have you heard of the same?

    – For folks who get calcium scores of 0, any thoughts on maybe they being genetic predisposed towards minimal plaque build-up in the first place. I mean, don’t we expect some plaque build up in all individuals post 30. Also, if someone had a calcium score of 0 before (or shortly after) starting a diet maybe his previous diet was working too?

    – I was on a low fat whole foods plant based diet (~0-10g fat, 0g saturated fat) which resulted in probably one of the (conventionally regarded) best blood reports (LDL-p 1150, LDL-C 105, HDL-C 46, trigs – 37, Small LDL-p 159, H1ac 4.9, Insulin 3.9), (I must add here that i felt way better on a ketogenic/low-carb diet).

    Does the cholesterol experiment work only if you are ingesting a certain amount of fat? If not, I would imagine anyone who has no fat in his diet, his cholesterol would be highest (which doesn’t seem to be true in my case). Whats the trigger for the inversion pattern to take effect?

    – I believe above post “Are you a Lean Mass Hyper-responder?” implies that the ones who see a higher cholesterol are usually athletic and with a low fat %. Again, my example could be an outlier. I’ve had sky high cholesterol level despite not being super lean (maybe ~23% at my leanest) or doing a lot of workouts.

    Thanks

    1. Craig

      Neville,

      LDL-C and LDL-P sometimes are sometimes discordant, meaning one is high when the other is low. If you account for LDL-P, LDL-C has almost no value as a risk factor. Here’s a good article on the topic:
      http://eatingacademy.com/nutrition/the-straight-dope-on-cholesterol-part-vi

      I expect both nature and nurture factors would contribute to a calcium score in middle age. However, I would think that there are traditional lifestyles where most elderly individuals have 0 scores (just based on very low incidence of CVD in almost all pre-agricultural societies). Steady accumulation of plaque seems to be a modern affliction.

      Relating to diet changes, if you were on diet A for 40 years and diet B for 3 months, you’re calcium score will be more a reflection of diet A. This is exactly my case. It will only be a retest in a couple years that I’ll know if diet B is any better.

      The experiment tested the inversion pattern (using the Feldman protocol) for long-term LCHF individuals. Fat-adapted individuals use a higher percentage of fat for their energy, so their LDL may change more in response to short-term fat intake. For individuals who get very little of their energy from fat (e.g., those that eat a sugar snack every 2 hours for 18 hours each day), other factors may drive their LDL levels (fructose clearance, metabolic syndrome, etc.). We don’t have a much data and and there is a lot still to learn.

      Craig.

      1. Neville

        Thanks Craig

  35. Csilla

    Hi Dave,

    Thanks for your blog. I’m 39 years old woman, 49-50 kg, 162 cm. I go to gym 2-3 a week and I do yoga. I’m on keto since 2 years and I eat 8/16 or 6/18. 18-20% fat mass.

    Before ketogenic diet my results are:
    TC: 7,1 mmol/l (273 mg/dl)
    TG: 0,79 mmol/l
    HDL: 2,48 mmol/l
    LDL: 4,24 mmol/l
    Glucose: 5,1 mmol/l
    H1A1c: 5,5%
    TSH: 2,65 uIU/ml

    …and with keto:
    TC: 17-20 mmol/l (660-769 mg/dl)
    TG: 0,89 mmol/l
    HDL: 3,82 mmol/l
    LDL: 15,78 mmol/l
    Glucose: 3,8-4,4 mmol/l
    H1A1c: 4,8-5,0%
    TSH: 1,8 uIU/ml
    Apolipoprotein A1: 269,0 mg/dl (ref: 125,0-215,0)
    Apolipoprotein B: 304,0 mg/dl (ref: 55,0-140,0)
    Lp(a): <30 mg/L (ref: <300)

    My blood pressure from 90/60 to 100/70 and I haven't heart problem.
    My liver result are fine and my Doppler test on my neck was normal. The NMR measurement not available in Hungary.
    I'm ApoE3. I have alpha-1 antitrypsin deficiency (PiSZ phenotype).
    My husband is on keto too, we eat same food but his cholesterol levels are not so extreme like as my results.
    I would like to continue the low carb lifestyle and 2 weeks ago I started the zero carb diet. I' m curious about my new cholesterol level.

    Thanks,
    Csilla

    1. Dave

      Incredible numbers, Csilla! (cool name too!)

      You’re in excellent example of extraordinarily good numbers that a conventional doctor would balk at with regard to cholesterol.

      I’m likewise very interested in what happens with your ZC numbers, please come back and share! 🙂

  36. George Henderson (@puddleg)

    Hi Dave and Tim,

    I found this paper on high cholesterol in the diabetic (near zero insulin) rabbit.
    it says
    When cholesterol influx into arteries is reduced, in spite of high plasma chol levels, atherogenesis is prevented.
    http://www.jlr.org/content/29/11/1491.full.pdf

    They’ve used alloxan to drastically reduce beta cell function. The lack of insulin plus the high dietary cholesterol load results in large particles, and these aren’t being taken up.
    Now, these lipoproteins are full of TGs, and the rabbit has no CETP, so there are differences from our human models. But, in principle, LDL and other particles can be rejected by arteries when insulin is low, even when plasma cholesterol is high, and particle size is part of the equation.

    1. Justin

      Hi George
      Here are two more articles on diabetic rabbits with hypercholesterolemia:
      https://www.ncbi.nlm.nih.gov/pubmed/18129862
      https://www.ncbi.nlm.nih.gov/pubmed/13130788#
      And here is a one with a diabetic dog where insulin administration caused atherosclerosis:
      http://circres.ahajournals.org/content/9/1/39.long

      In response to your earlier question “so what if foam cells STOPPED consuming LDL in low inflammatory states? Would that make LDL pile up in serum?” – Here are two in vitro studies on the effect of insulin on the monocyte LDL receptor
      https://www.ncbi.nlm.nih.gov/pubmed/2843407
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407326/

      The LDL receptor seems “linked” with the insulin receptor as both a properly functioning insulin receptor as well as a small amount of insulin are needed for the LDL receptor to function:
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314476/
      https://www.ncbi.nlm.nih.gov/pubmed/22278734

      Additionally, insulin also affects the production of LDL receptor. Low insulin levels both decrease LDL receptor mRNA synthesis as well as decrease PSCK9, so there are less LDL receptor and less receptor degradation. Presumably, this has no net effect, but it would be interesting to test it.
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810413/
      Tim, what are your thoughts on this? It seems to against your idea that LDL catabolism and LDL receptor activity are high. Although, I do agree that the size of LDL will be as you stated.

      Low insulin levels can also cause an increase in ApoB secretion, but I could not find the numbers for the insulin levels so it may or may not be relevant physiologically
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810413/

      Dave I think you’re going to like this one if you haven’t already seen it, infusion of fatty acids caused differing effects on the liver based on whether or not they were bound to albumin. Specifically, the conclusions are “1) increased FA delivery to the liver in vivo increases secretion of apoB-lipoproteins via post-transcriptional mechanisms, 2) OA-induced apoB-lipoprotein secretion occurred at least in part via mechanisms other than by providing substrate for TG synthesis, and 3) the route of delivery of FA is important for its effects on apoB secretion.”
      http://www.jbc.org/content/279/18/19362.full

      Finally, this discussion is fascinating, but may also end up being irrelevant if cholesterol does not enter from the luminal side of the artery as this article would suggest: http://www.sciencedirect.com/science/article/pii/S1359644616301921

      1. George Henderson (@puddleg)

        ” A suppression of LDL-receptor activity resulting from deficiency of insulin and elevated plasma catecholamine concentrations in uncontrolled insulin-dependent diabetic patients may contribute to the increased levels of LDL cholesterol observed in these patients.”
        All good stuff and I think there is a shut-down of LDL-R simply due to less cholesterol being needed by all sorts of cells in the pseudo-unfed state, combined with a dumping of the excess cholesterol from shrinking cells like adipocytes and possibly reversing plaques.
        Looking at epidemiology, merely to create a narrative around this, I’ve found populations – Malmo is the best example – where cholesterol is associated with CHD mortality and yet a higher total fat % of the diet is protective against it (in men, who have most CVD deaths) and saturated fat is benignly neutral.
        http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2796.2000.00568.x/full
        http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2005.01520.x/pdf
        Presumably these protected cases also have higher LDL (i.e. compared with equally healthy people not eating high fat), but in any case it shows that the contribution of increased fat oxidation to raised cholesterol is not the cause of population associations, is instead protective, and neither is the effect of higher SFA.
        Something that raises LDL – probably genes – does increase CVD risk but it’s not the effect on LDL of eating more fat, which is probably protective.
        If we consider total mortality instead, higher LDL seems to be protective in high-fat, high-SFA populations, but not necessarily in low fat ones (but it’s not clear what total mortalty was in the Iran paper)
        https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750440/
        https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919865/

        1. Justin

          Those are good narratives. I particularly like the Denmark paper, although I wish they had stratified by statin usage instead of adjusting for it. I think aging to 50+ without developing diabetes or CVD likely means the participants are relatively normo-insulinemic, which explains the following: “However, we did exclude all those with a diagnosis of CVD or diabetes at baseline. These subjects could be the vulnerable subjects, leaving a population resistant to the harmful effects of high LDL-C or TC levels.”

          1. George Henderson (@puddleg)

            The Demark paper is consistent with healthy high LDL being a side-effect of HDL efficiency in a high-fat population, while unhealthy high LDL (or any LDL) will associate with poor HDL function.
            Many people are diagnosed with CVD or T2DM over the age of 50, probably most are, there’s a bit of discussion around this in the paper. And the lowest LDL category, <2.5 mmol/L, includes the healthy recommendation – it's not some freakishly low "occult disease" group.
            As the statin use was voluntary not randomised it's hard to say what effect it had.

          2. Dave

            You guys rock!

            When rolling through my comments, I find yours to be the ones I want to bookmark and come back to for the “deep reading”.

            And George, why do you have to have a blog too? I’m never going to get any rest with all that nutrition-rich content you churn out!

  37. Eran

    Hi Dave.
    This caught me at perfect timing! I was just sent by my doctor to a lipidologist because my LDL is too high.
    I am not LCHF, but a strict Paleo for years, and beacuse I’m very lean and active I live on around 150-200 gr of carbs daily, usually much more. My LDL and HDL rose significantly on this diet, while my trigs are very low.
    Can your protocol work on this type of diet?
    If so, can I up my calories intake by upping only the fat?
    What type of fat do you recommend (I understand not coconut oil)? Can it also be MUFAs or just SF?
    Can’t wait to test your theory! (to get the doc of my back)

    Thanks.

    1. Craig

      Eran,

      So far, we have had mostly LCHF’s do the protocol, so I’d be awesome to get some more data on other types of diets. At 150-200g of carbs, you might be closer to the carb-swap experiment that Dave did. Exercise also has an impact.

      The interaction between gut-based and liver-based delivery of fat energy is the most likely driver of the inversion pattern. All other things being equal, eating more fat in the 3-days prior to a test should drive down LDL. In the ketofest experiment, there was no guidance on type of fat, just proportions of macros. I would advise you to not increase your intake of carbs, though, especially sugar and alcohol.

      Craig.

  38. Anna

    Hi Dave, so I’m basically a 29-year-old female I weigh 150 lbs , and I’m 5’6 y’all. I started the keto genic diet about 3 1/2 weeks ago, and I felt 100% better on it and I’ve even lost 8 pounds . I went in for some bloodwork, and when my total cholesterol came back it came back at 393!! My doctor wanted to put me on a Statin. And do another blood test in a month.i’m afraid that I might be a hyper responder, and I’m afraid that I won’t be able to continue at this rate I don’t care myself. Is there something I can do to bring to my cholesterol down?? I really want to continue on keto. The rest of my results were triglycerides 88 mg/dl, HDL is 57 LDLC is at 318, any ideas or help would be really appreciated thank you!!

    1. Craig

      Anna,

      If you feel great and look great on keto, that’s 2 very strong reasons to KCKO (keep calm, keto on). If you are also happy with your lifting and HIIT performance, you’d need to hear a very strong argument to change back to your old diet. (although 3 1/2 weeks is barely enough time to become athletically fat-adapted) I’m not convinced high LDL-C alone is enough evidence for any change, either to add back the carbs or start taking a Statin.

      If you just want to lower LDL-C for your doctor, follow Dave’s protocol for 3 days before your next test.

      If you want to get a better risk assessment for your own peace of mind, you can instead ask to broaden the set of tests to do next time, e.g. do NMR Lipoprofile instead of just LDL-C. Dave has a whole list he gets to “debug” his metabolism that I’m looking to writeup sometime soon.

  39. Anna

    Hi Dave, so I’m basically a 29-year-old female I weigh 150 lbs , and I’m 5’6 y’all. I started the keto genic diet about 3 1/2 weeks ago, and I felt 100% better on it and I’ve even lost 8 pounds . I went in for some bloodwork, and when my total cholesterol came back it came back at 393!! My doctor wanted to put me on a Statin. And do another blood test in a month.i’m afraid that I might be a hyper responder, and I’m afraid that I won’t be able to continue at this rate I don’t care myself. Is there something I can do to bring to my cholesterol down?? I really want to continue on keto. The rest of my results were triglycerides 88 mg/dl, HDL is 57 LDLC is at 318, any ideas or help would be really appreciated thank you!! I also forgot to mention that I’m very active , I wait lift and do hit workouts

    1. Dave

      Hi Anna–

      Sorry to hear about your initial shock. Certainly, I relate as I was feeling quite depressed in November ’15 when I first got my hyper-responder numbers. In many respects, this blog was created as a net to catch others coming into that same place. 🙂

      As always, as a good scientist, I emphasize that I don’t claim to know with certainty that higher LDL-C/-P isn’t ultimately a greater risk for heart disease / stroke — only that the case for it is surprisingly weak.

      First, if you’re athletic, your hyper-responder status makes even more sense given how the lipid system is upregulating LDLp to meet energy demands. (Obviously I’d reference the very post this comment is in!)

      Second, if you don’t believe however good you feel you will reach a point where you’re comfortable with having higher LDL-C (a perfectly valid position), you may want to start swapping back in carbs for fat as I believe the change in your energy status will likely lower your LDL. But to be sure, this too I believe is for energy distribution reasons, not actual positive outcomes in mortality. While still preliminary, I show this with my carb-swap experiment here: http://cholesterolcode.com/cholesterol-research-breakthrough/

      If you want my personal opinion — given the context of your athleticism, your HDL of 57 and your TG of 88, I presume you’re metabolically healthy and actually in good shape. I’d want to get other blood markers to be sure (such as hsCRP, fasting insulin, CMP, Thyroid, etc). But I completely understand your hesitation and concern with these numbers given (like me) you’ve had a lifetime of hearing how bad cholesterol is.

      Hope this helps! 🙂

  40. Kevin Fansler

    I am a hyper-responder who is now 79 years old. My total cholesterol was around 200 with a healthy conventional diet 15 years ago. My triglycerides were nearing 400. My testosterone level was 289 ng/dL and I started taking testosterone supplements. My doctor later prescribed Lopid to lower the triglycerides. I decided to go on an LCHF diet instead. This approach brought my TG down near 100, but my TC went up to around 350. I was on this regime for around 12 years when I decided to go off my testosterone supplement. The resulting testosterone level was a perfectly normal result of almost 700, which is quite a bit higher than President Trump’s 4xx. What to make of these results? I think the LCHF diet was what I needed to improve my general metabolism, statins be-damned. By the way, I fired a GP who tried to bully me into taking statins and found a more compliant physician.

    1. Kevin Fansler

      I am a hyper-responder who is now 79 years old. My total cholesterol was around 200 with a healthy conventional diet 15 years ago. My triglycerides were nearing 400. My testosterone level was 289 ng/dL and I started taking testosterone supplements. My doctor later prescribed Lopid to lower the triglycerides. I decided to go on an LCHF diet instead. This approach brought my TG down near 100, but my TC went up to around 350. I was on this regime for around 12 years when I decided to go off my testosterone supplement. The resulting testosterone level was a perfectly normal result of almost 700, which is quite a bit higher than President Trump’s 4xx. What to make of these results? I think the LCHF diet was what I needed to improve my general metabolism, statins be-damned. By the way, I fired a GP who tried to bully me into taking statins and found a more compliant physician.
      I wanted to clarify my too-brief remarks above. I did not explain why I stopped taking testosterone supplements. I found a research article concerned with the testosterone levels of men with metabolic syndrome. These men presented with lower than average levels of testosterone. I did not have all the symptoms of metabolic syndrome, but my three siblings all developed diabetes. Because I had become normalized with the LCHF diet, I thought that my testosterone levels would also have become normalized. I was proved right. Low testosterone levels are often a sign that something has adversely affected the metabolic processes. Taking testosterone supplements will most likely not improve your metabolic processes. Likewise, taking a statin will most likely not improve your metabolic processes, even though you may then attain the cholesterol levels of your youth.

      1. Craig

        Great story, Kevin. Sounds like you took control of your own health and got to a great place that wouldn’t have been possibly blindly following the advise you were given.

      2. Dave

        Very interesting stuff, Kevin. FWIW, I’ve talked to quite a few people in the last couple years who have claimed they too have seen an improvement in their testosterone levels on LCHF.

  41. Vijay Iyer

    My report after 3 month of keto

    BLOOD KETONE (D3HB) – 5.5 mg/dL

    Cholesterol Test

    TOTAL CHOLESTEROL > 500 mg/dl

    HDL CHOLESTEROL – 85 mg/dl

    LDL CHOLESTEROL – > 300 mg/dl

    TRIGLYCERIDES – 100 mg/dl

    TC/ HDL CHOLESTEROL RATIO – 5.9

    LDL / HDL RATIO – 3.5

    VLDL CHOLESTEROL – 20 mg/dl

    NON-HDL CHOLESTEROL – 414.8 mg/dl

    Diabetes Test

    Fasting INSULIN – 2.12

    HbA1c – 5.4

    FASTING BLOOD sugar – 92

    1. Craig

      Thanks for sharing, Vijay. Did you happen to have your pre-keto numbers to compare against? I assume you are feeling great, otherwise you’d have switched back.

  42. Mike

    I don’t quite fit.
    Here is my Nov. 14 2016 lab report:

    LDL-P 2943
    LDL-C 305
    HDL-C 61
    TG 76
    TC 381
    HDL-P 29.0
    Small LDL-P 692
    LDL Size 21.8

    An April 12, 2016 DEXA body scan had me at 17.8% fat.

    That seems not very lean yet for my age at the time of 60.4 years that put me in the 1st percentile. I.e., 99% of people my age had higher total body fat percentages.

    1. George Henderson (@puddleg)

      Hi Mike,

      I’m probably not super-lean either but I think leanness might be a genetic category here, with most people in it being lean, and same with activity, being a born fidget at any lean mass might be similar to being an athlete.
      Or another way of looking at this, the level of fat mass at which your metabolism decides you’re lean enough can vary.

      1. Dave

        Yes — not sure if you guys have heard of the “Personal Fat Threshold” talked about by Naiman and others regarding the adipose storage limit before cascading to severe IR, etc. But per George’s comment, I suspect there’s a likewise personal threshold with regard to this as well that will be somewhat different for each person.

  43. Mike

    Sorry for the second post but I just found an Oct. 24 2015 NMR. Feel free to combine this with my previous post.

    LDL-P 1831
    LDL-C 232
    HDL-C 72
    TG 70
    TC 317
    HDL-P 33.4
    Small LDL-P 213
    LDL Size 21.9

    From Cronometer, here are my macros for the five days preceding the blood draw:

    11/9/16-11/13/16 2415 kcal; 100 g PRO; 22 g CHO; 218 g fat

    10/19/15-10/23/15 3440 kcal; 96 g PRO; 24 g CHO; 335 g fat

    Basically an increase of 50% in fat brought LDL-P down more than 1,000 nmol/L, LDL down more than 70 mg/dl, and Small LDL-P more than 2/3.

    Living in NY or NJ makes getting testing hard. Requestatest recently called me up and cancelled an order. But I think I found a workaround so that I can test again next weekend.

    1. Craig

      Mike, thanks for sharing your data! Another solid example of the Inversion Pattern in action.

      You’re reminding me I should go eat some more to improve my numbers for tomorrow. It’ll be my first NMR Lipoprofile.

  44. George Henderson (@puddleg)

    Assuming that CETP is accelerated in the LMHR phenotype,

    Transfer of CE from HDL directly to LDL by CETP could also be antiatherogenic if the LDL is cleared by the liver LDL receptor. This role of RCT is especially important if the original source of cholesterol is from plaque (4). As this process is potentially antiatherogenic, inhibition could be disadvantageous.

    An additional concern is that excessive CETP inhibition increases HDL-C to supra physiological levels (>70 mg/dl), which appear to result in paradoxically high rates of cardiovascular disease (CVD), as shown in several epidemiological studies (13, 14) and in one CETP inhibitor interventional trial (15) but not in another (dal-OUTCOMES). The dal-OUTCOMES trial was terminated for lack of efficacy, and the details of this study were not available at the time of this review. Regarding the former study, increased CVD was attributed to hypertension, and an unusual number of patients had fatal sepsis; HDL is known to be crucial for innate immunity, e.g., lipopolysaccharide sequestration (16). High levels of circulating HDL-C may also be associated with dysfunctional HDL species in some studies (17). Finally, as CETP activity decreases in the general population, increased rates of CVD are observed (18). From the entire pro- and antiatherogenic concepts of CETP inhibition and clinical intervention trial results, no clear conclusions are apparent.

    From this review, it appears likely that CETP action is pro-atherogenic when TGs are high (when VLDL-1 and sdLDL are major players) and anti-atherogenic when they are low.

    http://www.jlr.org/content/53/8/1451.full

    1. Dave

      It’s funny, this one seems pretty straightforward to me early on.

      Basically, if VLDLs aren’t dropping off their cargo (TG) and not remodeling in a timely matter, it’s an obvious dysregulation as we see more and more backup. This is why a high level of VLDLs in a fasted state is so closely correlative to disease.

      Which is why the intentional inhibition of CETP (as with PCSK9) seems so extreme to me.

      1. George Henderson (@puddleg)

        Here’s a good line of thought consistent with that –
        we have previously reported that apoA-I and HDL directly affect HL-mediated triacylglycerol hydrolysis, and showed that the rate of triacylglycerol hydrolysis is regulated by the amount of HDL in plasma.

        http://www.jlr.org/content/44/4/733.long

        So – HDL2 and ApoA1, increased by high fat diets, directly by their effect on hepatic lipase, increase FFA release from VLDL. HDL can also shed via lipase the FFAs it got from non-HDL in CETP reciprocation.
        The point of CETP may be that HDL particles are smaller than non-HDL so better for delivering FFAs in capillaries.

        So we’re getting back to your glycogen compartment theory; high release of FFAs from all lipoproteins in the fat-burning state means higher fat oxidation, more cholesterol in non-HDL fraction, and more freedom for HDL to perform efficient cholesterol efflux and reverse cholesterol transport, in which non-HDL has become enlisted.

        However Jeff Volek says hepatic lipase goes down on keto.
        “A reduction in hepatic lipase (HL) prevents larger LDL-C from being delipidated to smaller, dense (atherogenic) LDL, resulting in a predominance of larger LDL particles.”
        But also that “A VLCD leads to lower glucose and insulin levels, which decrease LPL and increase hormone-sensitive lipase (HSL), promoting TAG hydrolysis and increasing fatty acid (FA) rate of appearance.”
        http://jn.nutrition.org/content/135/6/1339.full

        But the use of some of these TAGs to produce ketones instead of FFAs reduces FFA requirements, just as an equimolar amount of glucose would.

        1. Craig

          Very interesting George, great links, including the video!

          Let me repeat that theory to see if I got it:
          The driver of LMHR LDL-C is the HDL delivering more TG to cells. It’s getting that TG from VLDL/IDL/LDL, and it needs to swap 1-1 for a Chol. When the LDL are done with their TG delivery, they have more Chol and are thus larger and less dense in their end stage.

          As a LMHR who just got his fancy bloodwork, this lines up almost perfectly with my observed NMR Lipoprofile.

        2. Dave

          Yes, George — once again you bring such great research to this blog!

          Of course, there hasn’t been a lot I’ve come across on HDL delivery of TG, but it likewise makes perfect sense in the wider distribution chain.

          Taking it back to the 50k systemic view:

          1) Cells are getting fatty acids from all three players: LDL, HDL, and NEFAs.

          2) Technically, adipose tends to be greedier in picking up TG from LDLs relative to muscle tissue, who have a higher relative proportion of NEFAs instead. I don’t have a link to it, but look up “Fatty acid metabolism in adipose tissue, muscle and liver in health and disease” Keith N. Frayn*1, Peter Arner† and Hannele Yki-Järvinen‡. In it, they show adipose would pick up 45g TG and just 5g of NEFAs, where skeletal muscle would pick up 10g TG and 20g NEFAs. Which is why it is fair to say that adipose tissue is like a giant middle man between LDL and skeletal muscle — at least, in a proportional sense.

          And this makes PERFECT sense as adipose is like the grocery store taking big shipments, then releasing small bags of groceries over a more controlled non-fed period.

          3) When you take 1 and 2 into account, you can see how there’s such an effective system of bioavailability of fatty acids for tissues that is being passed along throughout the players.

          4) But wait — with this in mind, it likewise seems obvious why this changes with a LMHR. Now that “middle man” of adipose isn’t delivering on the same grocery schedule as it would in someone with a lot more stores in play. That’s why I suspect you’d find less NEFAs in a LMHR compared to a sedentary low carber, thus necessitating higher demand for LDLs to be available to make up the difference.

  45. David

    Hi, Dave.

    I’ve been reading through with interest.
    I’m T2 on LCHF with normal weight, normal BG but high lipids.

    I will post my numbers when I can dig them out, but I’m intrigued by your theory that lean athletic people eating low carb tend to run higher blood fat levels.

    A simple take on this could be that the body is learning that it is more efficient to store fat in the blood than in fat cells because the fat is always being burned off at a high rate.

    I would be interested in the mechanism the body uses to achieve this.
    Fat storage usually involves insulin so the usual suspects would be lower insulin production or insulin resistance in the fat cells.

    1. Dave

      I’m not sure I’d say “storing” fat in the blood per se. Rather, making more available in the blood to meet existing demand.

      Remember, *in spite* of having higher LDL particles in a fasted state, they have *much* lower overall TG. Thus there are more boats circulating, yet with less cargo overall — showing lots of usage.

  46. George Henderson (@puddleg)

    Here’s an idea;
    keto is a pseudofasting state. Fasting elevates LDL. So, does already being in a pseudofasting state predispose us to a more rapid effect of fasting itself, so that the short fast before a lipid test is enough to push up lipids?
    That is, does a lean, healthy, active ketogenic dieter experience a rapid transition to fasting state lipids?
    This would be consistent with your hypercaloric feeding experiments – the extra energy and insulin response to that slows the transition to the fasting state afterwards.
    Does anyone have non-fasting results? And wouldn’t these be bollixed anyway because chylomicrons can end up in the LDL fraction?

    1. Craig

      Funny enough, I actually got a blood lipid test in a non-fasted state by accident. I thought they would defer my test to the next day because of that, but they just said “they’ll adjust for it” (ha!).

      Test1 is 2 hours after a hearty bacon & eggs breakfast, but 36 hour fast before that breakfast. 2-months later, test2 is 3-day low-calorie, test3 is 3-day high-calorie.

      TC 342 360 367 333
      TRIG 176 80 68 51
      HDL 98 113 115 114
      LDL 209 232 238 209

      Just a few data points, but take it for what you will.

      UPDATE: Added test4. Average calorie keto, massive run 48 hours prior.

      1. George Henderson (@puddleg)

        This paper finds that even in the normal diet non-fasting lipid test has lower LDL and higher TGs, same HDL.
        https://www.ncbi.nlm.nih.gov/pubmed/18955664

        So it’s not a stretch that a pseudofasting diet can push this relationship further in the opposite direction

  47. George Henderson (@puddleg)

    So not as much difference between low and high calorie, as between fasting and non-fasting.
    And non-fasting really skews the TG/HDL ratio – but does lower LDL and total C. So the chylomicrons in your case seem to be in the TG fraction, and it’s likely that a better separation that removed chylomicron cholesterol from the equation would see LDL even lower.
    As far as we can tell from 3 tests anyway!

    1. Craig

      Now 4. 🙂 I think my body was eating up those LDL-C’s to rebuild my sore muscles.

      1. Dave

        Wouldn’t some degree of the lower LDL-C just be the friedewald equation being goosed from the higher TG inbound from the chylomicrons?

        So in theory, all things being equal, if I ate half a stick of butter an hour or two before the test to maximize chylomicron presence in the blood, I’d spike my TG, but lower my LDL-C (if “calculated”). This has been my presumption to this point, but I haven’t tested it directly yet.

  48. George Henderson (@puddleg)

    FYI, here’s an animation of the cholesterol transport system that has most of the working parts, including the role of the various lipase enzymes
    https://www.youtube.com/watch?v=97uiV4RiSAY

    1. Dave

      Oh yes — I actually watched that video at least five or six times when I was first starting out. It’s extremely well done and actually covers a lot in a very short time span.

  49. George Henderson (@puddleg)

    To support my “Reverse Cholesterol Transport on Steroids” model, this paper studying the kinetics of hypercholesterol feeding in the guinea pig model.
    Guinea pig is a good human-equivalent lipoprotein model, and Fernandez works with Jeff Volek now.

    Guinea pigs were fed
    15% (w/w) .fat diets (lard, olive oil, or corn oil) with cholesterol
    levels corresponding to absorbed intakes of 6 (basal), 50, 100, or
    200% endogenous cholesterol synthesis. Guinea pigs maintained
    stable plasma cholesterol levels until cholesterol intake
    equaled or exceeded endogenous synthesis (P corn oil, with olive oil being intermediate
    (P < 0.05). Hepatic membrane apoB/E receptor number (Bmu)
    decreased as dietary cholesterol increased (P < 0.001) without
    an independent effect of dietary fat saturation. B,,, values were
    significantly correlated with plasma LDL cholesterol levels
    (r = -0.632), and with hepatic free (7 = 0.527) and esterified
    cholesterol (Y = -0.512) concentrations, which were both increased
    with dietary cholesterol (P < 0.001). significant interactions
    between dietary fat type and cholesterol mediated the extent
    of hepatic free and esterified cholesterol accumulation.
    Dietary fat and cholesterol interactions also contributed to
    changes in LDL particle composition and peak density. a The
    results of these studies do not support the thesis that dietary
    cholesterol-mediated suppression of apoB/E receptor expression
    is ameliorated by intake of polyunsaturated fatty acids. Dietary
    fat type and cholesterol amount interactively affect hepatic
    cholesterol concentrations and LDL composition and size,
    which in part determine plasma LDL cholesterol levels.-
    Lin ECK, Fernandez ML, Tosca MA,
    McNamara DJ. Regulation of hepatic LDL metabolism in the
    guinea pig by dietary fat and cholesterol. J Lipid Res. 1994. 35:
    446-457.
    http://www.jlr.org/content/35/3/446.full.pdf

    If reverse cholesterol transport saturates the hepatic cholesterol pool LDL receptors will be downregulated.

    Evidence from the cholesterol-fed, hypercholesterolemic, guinea pig model (which produces huge elevations in LDL) that cholesterol accumulation in aorta is prevented by a 10% carb diet.

    Methods
    Twenty guinea pigs were fed either a LCD or a low-fat diet (LFD) in combination with high-cholesterol (0.25 g/100 g) for 12 weeks. The percentage energy of macronutrient distribution was 10:65:25 for carbohydrate:fat:protein for the LCD, and 55:20:25 for the LFD. Plasma lipids were measured using colorimetric assays. Plasma and aortic oxidized (oxLDL) were quantified using ELISA methods. Inflammatory cytokines were measured in aortic homogenates using an immunoassay. H&E stained sections of aortic sinus and Schultz stained sections of carotid arteries were examined.

    Results
    LDL cholesterol was lower in the LCD compared to the LFD group (71.9 ± 34.8 vs. 81.7 ± 26.9 mg/dL; p = 0.039). Aortic cholesterol was also lower in the LCD (4.98 ± 1.3 mg/g) compared to the LFD group (6.68 ± 2.0 mg/g); p < 0.05. The Schultz staining method confirmed less aortic cholesterol accumulation in the LCD group. Plasma oxLDL did not differ between groups, however, aortic oxLDL was 61% lower in the LCD compared to the LFD group (p = 0.045). There was a positive correlation (r = 0.63, p = 0.03) between oxLDL and cholesterol concentration in the aorta of LFD group, which was not observed in LCD group (r = −0.05, p = 0.96). Inflammatory markers were reduced in guinea pigs from the LCD group (p < 0.05) and they were correlated with the decreases in oxLDL in aorta.

    Conclusion
    These results suggest that LCD not only decreases lipid deposition, but also prevents the accumulation of oxLDL and reduces inflammatory cytokines within the arterial wall and may prevent atherosclerosis.

    http://moscow.sci-hub.bz/345843438787e3c7d7ac2312b6b5a667/10.1016%40j.atherosclerosis.2009.10.005.pdf

    We're not under as much stress as the cholesterol-fed guinea pig. Fernandez points out here that RCT is the protective feature of HDL and is actually unaffected or improved by HDL catabolism.
    https://www.ncbi.nlm.nih.gov/pubmed/20104929

    This all fits with LMHR being a side effect of increased RCT in people in whom it was already ideal, driven by increased fat oxidation and/or ketosis, i.e. the TAG breakdown driven by HDL.

    1. Dave

      That’s so awesome, George!

      And indeed if true for LMHRs, it would be the cruelest irony that they are being scared the most by the higher LDL scores alone.

  50. Joseph

    Hi Dave,
    Could you please give me your E-mail address for sending you my CIMT and Calcium Scan test reports? I have done them as you had suggested.
    Thanks.

    1. Dave

      Sure. 🙂

      1. Joseph

        Hi Dave, how to get your e-mail address? Are you posting it here? Thanks.

  51. George Henderson (@puddleg)

    Yes – NEFAs released by lipase from HDL or LDL should not last long in plasma, I don’t see a mention of albumin, so I’m not sure how accurately measureable they are – this should be a localised phenomenon.
    Brown and Goldstein estimated that 30-60% of LDL is removed by macrophages. Insulin increases macrophage oxLDL uptake by 80%. So in a low insulin, low glucose/fructose state – fasting or keto – this LDL is not being oxidised as much and even the oxLDL is now being taken up at nearly half the rate by a prime consumer.
    It can’t be avidly taken up by the liver as HDL is returning Chol to the liver so well that LDL receptors there are downregulated, so there’s a sluggish uptake there.
    That would explain why LDL is high but there’s no obvious signs of pathology. Not just for keto but for all the heart-healthy, insulin sensitive older people with high LDL out there.

    1. Dave

      Really excellent observation, George! (As usual)

  52. Andy

    Found this site after a very depressing and shocking visit to my internist. Before keto I had a “normal” cholesterol profile. After 5 months of strict keto:

    10-11% body fat (weight train 4 days/week)
    ApoE E3/E4

    *Chol 349
    *LDL 271
    HDL 89
    TG 60
    *LDL-P 1868
    *sdLDL-C 59
    hs-CRP 0.2
    *LpPLA2 279 (ref <180)
    MPO 198
    Fibrinogen 334
    A1c 5.2
    HOMA-IR 1.1 (optimal insulin resistance)
    Glucose 88
    *Total T3 0.7 (low)
    Free T3 2.5

    I'm now at a loss for what to do next. What are your thoughts on these numbers? Carry on since all the ratios are good and inflammatory markers are normal except for the LpPLA2? Reduce saturated fat and add carbs to stay just outside of ketosis? I feel great doing keto, but I don't want to chance a serious cardiovascular event on a gut feeling.

    1. Craig

      Andy,

      Your numbers are pretty close to mine! In my own case, after 1) a CAC scan and 2) bunch of research, I’m no longer worried about CVD from my LDL-C / P. I’d encourage you to do those 2 things and KCKO as long as you feel great and maintain low inflammation.

      Here’s a really good talk to get you started:
      https://www.youtube.com/watch?v=UZoQiDaWnuE

      Craig.

      1. Andy

        Watching the video now. Would a CAC scan be of any benefit to me if I’m only 37 yrs old? In other words, would a negative scan afford any reassurance given a lack of time for calcification to develop no matter my diet/cholesterol at my age?

        1. Tim

          Andy,

          The CAC is useful mainly in that it indicates progression or the lack of it so you need several scans. Your numbers look great so I wouldn’t bother. Your TG/HDL (.67) is way below the level of concern ~2 so again no point.

          If you do decide on a scan you will need to do another in 6 months, maybe 1 year to see the difference.

          I don’t do the CAC since it is expensive here ($700) and since my TG/HDL is also good, I don’t need it.

          Cheers.

        2. Dave

          Hi Andy–

          Your numbers look very solidly like the LMHR profile this comment is under, of course. The Lp-PLA2 I don’t put as much stock in — for reasons I won’t go into here as they are lengthy.

          I myself would want you to get a CAC score soon so you could know for sure what it was to “bookend” your keto diet. If you were to get it in 5 years but had a positive score, you’d be wondering what amount can be attributed to your lifestyle before LCHF and what amount after. Even if you were going on an entirely different diet, you’d probably still want to see the delta in isolation.

  53. Tim

    Hi Dave.

    Just got my bloodwork back.
    Hemoglobin A1C 5.1 (fasting glucose 365 day average is 5.0mmol/l (90.1))
    Cholesterol 9.27mmol/L (357.9)
    LDL Cholesterol 6.61mmol/L (255.2)
    HDL Cholesterol 2.20mmol/L (84.9)
    Chol/HDL (Risk Ratio)4.21
    Non HDL Cholesterol 7.07mmol/L
    Triglycerides 1.02mmol/l (90.27)
    Trigs/HDL Ratio 1.02/2.2 = 0.46 should be below .7 (from Jay Wortman)

    C Reactive Protein (High Sensitivity) 0.5 should be below 1 (Low risk: less than 1.0 mg/L Average risk: 1.0 to 3.0 mg/L

    High risk: above 3.0 mg/L1

    25-Hydroxyvitamin D 362 nmol/l

    Get a load of the vitamin D, range is 75-150 here and they think >200 is toxic (no symptoms though).
    This on a 8,000IU/d dose (recently bumped from 6,000IU/d), which is well within reasonable bounds, another mystery to solve. No wonder I don’t get sick. Getting it retested.

    Food macros are:
    Carbs 58g/d
    Protein 64.7g/d
    Cholesterol 559mg/d
    Sugar 19.28g/d
    Fat 124.76g/d
    Sat fat 77g/d
    Sat fat MCT 25.197g/d
    Sat fat LCT 56.669g/d
    Mono 49.6g/d

    Cholesterol continues in fh territory, extremely high but stable as is LDL. HDL very high (there is no risk at any level of LDL at this HDL) and the all important TG/HDL well into safe territory, not much inflammation. Cholesterol has been high since Jan 2014, that’s about 42 months, no sign of it coming down – now I think I know why.

    I get 16 hours aerobic exercise/week.
    Will be 70 in November.

    I am extremely lean (wife says I look like a concentration camp survivor) height 5-6 weight 126lbs.

    Getting back to the subject at hand.

    George’s “Reverse Cholesterol Transport on Steroids” argument is interesting and I like it a lot as it ties in several important threads.

    However I still think its a minor theme and I have another idea to offer to my previous effort that I believe further explains my own situation which is similar to Daniel’s. Whether it explains other LMHR is debatable, but I think there is a good chance it is relevant.

    LDL production rate I still believe is the single most important factor in LDL levels. This is influenced disproportionately by saturated fat, particularly 12:0 (Lauric – tropical oils, ie coconut) and 14:0 (Myristic – dairy products) acids. The influence, surprisingly, is modulated (gated) by Linoleic acid 18:2 n6. Linoleic acid is the only saturate capable of increasing LDLR activity when in adequate supply (greater than about 3% dietary energy to about 7% or above) below that the ability of 12:0, 14:0 and 16:0 to generate overproduction of LDL is remarkable and I believe is at least as important as LDLR effects, insulin or channeling. An inadequate supply of 18:2 opens the gate to very large increases in LDL, whereas an adequate supply >7% energy shuts off the ability of saturated fat, in any form to effect LDL levels to any great extent. This is a totally unexpected result (to me) but seems robust. Studies in humans are somewhat inconclusive since the gating function of 18:2 has not been well known or controlled for, however the effect has been extensively studied in primates. The effect is enhanced by cholesterol feeding. The mechanism is the concomitant suppression of LDLR activity by elevated hepatic cholesterol which blocks LDLR activity. Remarkably this combination of LDL production and LDLR suppression can elevate LDL levels by a factor of 10 in cynomolgus monkeys but is also present in rhesus, cebus and African Green monkeys. The effect derives in somewhat larger part from increases in production than decreases in catabolism, but both are present.

    http://sci-hub.bz/10.1016/s0952-3278(97)90420-8 (May have to supply Kaptcha).

    I viewed a first cut of Sarah Hallberg’s presentation on LDL hyperesponders at Low Carb Vail and during the Q&A which didn’t make it to the final video a doctor commented that he routines advises cutting BPC to lower LDL cholesterol and the advice is present on many web sites where high LDL is discussed.

    It seems evident to me now (since I have been tracking it) that my elevated cholesterol is due to a large intake of saturated fat in the form of coconut oil, dairy and cholesterol combined with a very small intake of PUFA, especially 18:2 (I do track it). This may be a common characteristic of LMHR individuals.

    Cheers.

    1. George Henderson (@puddleg)

      Good stuff Tim.
      The relationship of chain length of SFAs to LDL output is matched pretty much exactly to their effect on HDL, and of course both correlate with the different half-lives of these SFAs. As only C14 and C16 are significant transcription factors, and their levels are modulated by dietary carbohydrate, this effect is unlikely to be mediated directly by SFA adducts acting on protein expression levels – it is instead an effect of fatty acid oxidation, either peroxisomal or via mitochondrial ROS signalling.
      This does not apply in the same way to unsaturated fats, but in evolutionary terms there is only really one of these, oleic acid, and it tracks alongside SFAs, and requires saturation before oxidation.
      I have a fairly high intake of LA as I don’t attempt to avoid it from whole foods (chicken, pork, nuts) or olive oil. When I tried to control my lipids by reducing dairy SFA, coffee, and cholesterol, and increasing MUFA, my lipids increased to their maximum, similar to yours.
      However I do not consume much coconut oil.

      With regard to lipids and CVD risk, it is important to note that CHANGES in LDL are not a subject of risk calculations (except for drops in LDL in the elderly). Framingham scores and the like are only predicated on steady state levels in populations eating within the normal dietary macronutrient intake range. As such they include at least a 50% genetic contribution to LDL risk (according to mendelian randomisation anyway), which would be unaffected by diet-driven changes. If lipids were not high before keto, this aspect does not apply. If they were, lower TG/HDL ratio predicts freedom from CVD at these LDL levels.
      https://www.ncbi.nlm.nih.gov/pubmed/22119890

      1. George Henderson (@puddleg)

        PS

        any model of LMHR has to explain fasting LMHR. The depot fats in this case would be roughly 30% SFA, 60% MUFA, 5% PUFA, 5% MC/SCFA.

      2. Dave

        Really interesting discussion, as usual, gents.

        I had done an 11 day high MUFA low SF diet last year in February, eating lots of avocados, avocado oils, etc. Overall, it didn’t appear to have too significant of an effect on my numbers.

        However, I intend to come back around to it again and do an even more controlled test, breaking it out to the specific subsets of fats as you describe above. Given how tightly I’ve mapped my own inversion pattern, I feel can isolate and observe these changes better than ever now.

  54. Tim

    High Dave.
    This is a long post on atherosclerosis, ie what actually causes it.
    Lots of people are concerned about the possibility of heart disease or atherosclerosis and take statins on doctors advice. This is an attempt to reassure those people that high LDL is not a major cause unless it is in the form of small/dense which is unlikely for LMHR individuals.

    If you think this is inappropriate or overlong please can it, but I thought it might be useful to share it here.

    FACEBOOK POST (UPDATED) ON ATHEROSCLEROSIS
    Atherosclerosis has a distinct presentation so any attempt to explain it must account for it in its entirety, this the the high LDL theory does not do. I think there is an explanation however but it is composed of several moving parts.

    First the presentation of atherosclerosis:
    There are several things characteristic of atherosclerosis which must be explained.

    Bizarre smooth muscle cells.
    The abundance of matrix vesicles.
    The abnormal and dystrophic basement membranes and their separation from smooth muscle cells and endothelium.
    The dystrophic collagen.
    The vascular fragility with intimal tears.
    Ulceration.
    Aneurysm.
    The localization and development of intimal thickening that precede
    lipid accumulation.

    From Stehbens (with my comments added after quotes and in brackets within quotes):

    https://static1.squarespace.com/static/52faa95ee4b0b0a74811f732/t/58eefbff15d5db893a62d6d5/1492057091240/20170413+DIET+CHOLESTEROL+AND+HEART+DISEASE+-+EPIDEMIOLOGICAL+ILLUSION+OR+DELUSION+Stehbens-1993-Stress_Medicine.pdf

    http://sci-hub.cc/http://www.sciencedirect.com/science/article/pii/S0033062005800349 (May have to supply Kaptcha).

    “1. Atherosclerosis occurs in arteries, the heart, and veins. It is more severe in the systemic arteries than in the pulmonary arteries, and is of least severity in low pressure veins. The distribution suggests that blood pressure is of importance and hypertension aggravates the disease in each of these systems, whereas systemic hypotension (low blood pressure) is associated with longevity.” Thus it manifests mostly in high pressure areas around the heart, the systemic arteries carrying blood to the main circulation system are more susceptible than the pulmonary arteries carrying blood back to the lungs, the higher the pressure the more atherosclerosis. Low blood pressure is associated with a lessening of the problem.

    “2. Within the systemic circulation there is variation in severity from vascular bed to vascular bed and within a single artery the disease may be of pronounced severity on one side while the intima on the opposite wall may appear unscathed. Such observations, difficult to explain on the basis of some circulating metabolite, can be explained more readily by hemodynamics (relating to the flow of blood).” Thus there is a pronounced variation within different vascular beds and even a pronounced difference in severity can be seen within adjacent areas of the same artery, some badly affected, others not at all affected.

    3. “The severity in any vascular bed is directly related to the caliber of the vessel and in the systemic circulation it is most pronounced in the aorta. This distribution is thought to be related to the mural tension (a measure of the stress placed upon the wall of the artery during filling and emptying) and the higher Reynolds number (used to predict the transition from laminar to turbulent flow) because the pressure differential is small. Blumenthai et al 8 documented a progressive increase in wall thickness of cerebral arteries with age, the increase being greatest in the larger vessels in which mural tension and atherosclerosis are greatest and least in smaller vessels. The thickening is due to progressive intimal proliferation that correlates with concomitant diminution in medial thickness.” The intimal thickening is due to progressive intimal proliferation that correlates with concomitant diminution in medial thickness, ie the intima expands but the media contracts. This precedes essentially from birth but progresses at disparate rates in individuals. It is also present in all animals.

    4. “The severity is more pronounced in the abdominal aorta and large vessels of the lower limb than in the proximal aorta, presumably because of augmented systolic and pulse pressures distally due to a summation effect of the reflected pulse waves.” Where it is evident that pressure gradients are increased due to mechanical pressure summation effects the severity is more pronounced.

    5. “In the anastomosed veins of therapeutic arteriovenous shunts for renal dialysis and in venous bypass grafts (locations where surgery has been used to provide grafts or shunts between arteries or viens), atherosclerosis develops at an accelerated rate as a result of the augmented stress for which the veins are not architecturally designed. They would have remained only mildly affected by the disease if left alone for the remainder of the individual’s life.” Atherosclerosis rates increase at the sites of surgically placed shunts and grafts because of the increased blood pressure.

    6. “The disease affects all of the coats of the vessel wall, the intima most severely and the adventitia least, suggesting that the intima has greater exposure than the media”. The intima is the layer (coat) nearest to the lumen (blood flow) the media is the outermost layer.

    7. “The disease has a predilection for arterial forks, junctions, curvatures, and fusiform (spindle shaped) dilatations, and appears to run an accelerated course in berry aneurysms”” (a small aneurysm that looks like a berry and classically occurs at the point at which a cerebral artery departs from the circular artery).

    8. “External support of an artery seems to afford the vessel some degree of protection.” If the artery is supported whereby the support takes at least some of the hemodynamic pressure then the artery is more protected and lasts longer.

    9. “The augmented flow in the iliac artery in children with only one umbilical artery accentuates the severity of atherosclerosis in that vessel.”

    10. “The consistent localization of intimal proliferation in infants and neonates suggests a strong hemodynamic influence. The accumulation of lipid occurs preferentially in the intima in spontaneous atherosclerosis of humans and other animals 12 and also in cholesterol-fed animals. 13 Therefore, the cause and nature of this intimal proliferation is crucial to the understanding of atherosclerosis. It is in this intimal thickening that overt atherosclerosis preferentially and insidiously develops without a sharp line of demarcation. The intimal proliferation and atherosclerosis are only phases of a continuous process and have a similar distribution. 2 Moreover, the development of the whole range of changes from the mild musculoelastic intimal proliferation to advanced atherosclerosis with its complications in experimental 14’15 and therapeutic arteriovenous fistulae I~ substantiates this view.”

    11. “In rabbits it has been determined an arteriovenous shunt on the afferent artery, in the absence of hypercholestemia, exhibited extensive tears and fragmentation of the internal elastic lamina of the elastic common carotid arteries, this was observed in all animals. Fragmentation and loss of elastic tissue as well as loss of muscle in the media accompanied progressive mural atrophy and tortuosity. Close to the fistula and in regions of tortuosity, fibromusculoelastic intimal proliferation was superimposed on the atrophic medial changes. The accumulation of matrix vesicles (cell debris), bizarre shaped smooth muscle cells, irregularly thickened multilaminated and reticulated basement membrane material beneath the endothelium and about smooth muscle cells, and abnormal shaped collagen fibrils were observed in the intima. Lipid was frequently found in the extracellular matrix and within smooth muscle cells while monocytes and lipid-laden macrophages were a feature of the more advanced intimal changes. These experiments confirm that in the absence of hypercholesterotemia the hydraulic stresses associated with an arteriovenous shunt cause severe mural atrophy and proliferative changes in the intima similar in nature to those of atherosclerosis.” Essentially, in rabbits, a condition very similar to atherosclerosis can be induced merely by placing a shunt in an artery, in the absence of high cholesterol.

    It is evident that most of the manifestations of atherosclerosis are pressure effects, not amenable to explanation by a circulating metabolite such as LDL. In fact these effects, including lipid deposition, can be induced in the presence of low/normal cholesterol.

    However returning to the high LDL theory for a moment there are other objections.
    One issue is how does the cholesterol get into the plaque. Previously I had read the entire Goldstein/Brown series but a definitive mechanism was still elusive. They insisted as does Dayspring that very elevated LDL is a prime mechanism, but how? Their treatment of familial hypercholesterolemia is, to me anyway, not convincing because you get fh patients who do not get heart disease even after a lifetime of extremely high levels and the comparison of those fh who get heart disease to those who don’t seems to implicate the well known mets candidates, ie very high LDL is involved but not proven culpable.

    Nature doesn’t do things casually and there has to be a well defined receptor or other transport mechanism and it seems to me the LDL has to be taken in purposefully. In addition the statistics of cardiac admits to hospital peak at low to normal LDL levels (but high small/dense in relation to normal LDL), low HDL and higher but not super high trigs. So the facts on the ground conflict with the GB hypothesis, yet Dayspring/Attia et al still think its relevant.

    The main route in some cases seems to be macrophages, or in the case of arterial damage structural entities like fibrin but the affinity for native undamaged LDL is small in both cases (unless delivered by LP(a) as part of the triage process. In addition it has been shown that the first cholesterol deposits occur at the media/intima boundary far from the lumen surface so there must be a coherent transport mechanism from either the lumen or the vasa vasorum to the boundary, where possibly it cannot be transported further.

    I had previously identified several, to me reasonable, connections.

    1. Hypovitaminosis C. I like Pauling/Rath’s explanation of ascorbic acid as a cofactor to collagen production so it seems to make sense that sub clinical scurvy would weaken arterial walls in two respects. First maintenance of established structure would be compromised, particularly the elastin layers that provide strength (like rebar in concrete) and second the construction of new structure would suffer, so there would be a deficiency of structural integrity to the arterial wall that would result in “bleeding out” like you see in the gums in outright scurvy. This may occur or be more likely if other insults like high BP, as detailed extensively above, or inflammation was involved. In this case the production of LP(a) would be encouraged and LP(a) has a well defined role in would healing and binds readily to structural components like fibrin. So it seems entirely likely that arterial wall damage would receive cholesterol as a result of the repair mechanism. This explanation doesn’t implicate damaged LDL directly and it seems the cholesterol deposition would start at the lumen/vasa vasorum surface rather than deep in the wall. So this explanation, while attractive, cannot explain a lot of cases. It is also worth noting as explained above that the changes associated with lack of vitamin C can be induced solely by hemodynamic pressures.

    2. Another attractive proposition is the metabolic channeling of lipoproteins. This is driven by trig levels so you get the “chanelling” of VLDL and LDL/HDL into essentially two states, one atherogenic (small dense, LDL III/IV/V, large VLDL) and one not atherogenic (LDL I/II, small VLDL). The atherogenic LDL pool is driven primarily by CETP (cholesterol ester transfer protein, enhanced by rising trig levels) which cholesterol depletes LDL and HDL in exchange for lipid. Plasma normally has little to no esterase activity and this is provided by triglyceride enhanced production of CETP. Subsequently the particles are processed by lipases to produce small/dense LDL and small HDL which is much easier to clear from circulation. This “explains” the low/normal LDL (but predominantly small/dense) and the low HDL at the higher trig levels. The higher trigs are explainable by high carb input so this explanation seemed reasonable. It is again worth noting that lipid deposition can also be induced solely by hemodynamic pressures in the presence of normal cholesterol levels.

    3. The affinity of small/dense LDL for fructose now adds another dimension to this situation (from a Luc Tappy paper via Gary Kettke).

    4. Calcium deposition may occur through the changed morphology of the damaged arterial wall. In this case the most used structural entity is sphingomyelin which has an affinity for calcium since the sphingomyelin head protrudes into the lumen and is oppositely charged to the plasma resident calcium ions so calcium gets deposited. Kummerow has a series of papers on this which is also attractive.

    5. Hemodynamic pressure as detailed above.

    It seems that because small/dense LDL is dangerous and must be processed you need to take it in via the scavenger receptors in macrophages (from Seneff) (which are in far greater abundance than receptors for normal LDL) so the artery wall to a large degree takes over LDL recycling from the liver (small dense LDL has much higher plasma residence time so liver recycling declines) and this process may become overwhelmed if the supply outpaces demand. Fructose seems to tip the balance so is a valuable addition to the story.

    In essence I believe atherosclerosis is a hemodynamic pressure story with hypovitaminosis C as a cofactor.

    Seperately I believe hyperlipidemia produces a triad of low/normal LDL, low HDL and higher trigs which supplies additional pressure by forcing the arterial wall to supplement the liver in detoxifying damaged LDL, this is the result of a bad diet. These two streams converge to provide most of the story. The process is augmented by inflammation, insulin resistance, both a dietary story, opportunistic infection through bacterial and viral vectors which seperately damage the arterial wall so there is a multifactorial pressure manifested against the wall and it fails most quickly where these pressures peak in combination. This explanation I believe covers all the points raised by Stehbens.

    In summary circulating LDL has almost no connection except where LDL is corrupted through hyperlipidemia, oxidative damage, acetylation or glycation, all or mostly dietary factors, and then it is damaged LDL rather than native that bears responsibility.

    Cheers.

    1. George Henderson (@puddleg)

      To support the vitamin C hypothesis, the peak years of the CHD epidemic (1950-1970) were the peak years of food refining without vitamin C fortification or preservation; as vitamin C has become a common preservative and supplement and fruit juice a common form of sugar, CVD mortality has declined.
      This also applies to other vitamins and minerals with plausible roles in atherosclerosis, including vitamin E and folic acid.

    2. Dave

      Awesome, Tim — thank you for posting.

      I was only able to read a little of the beginning as I’m just now rolling through a lot of comments and responding to them in a batch. You and George are always my Knowledge Landmine Comments where I find I’m continually pulled in for some deep and engaging reading. Jerks! 😀

      I may actually link to this comment directly in an upcoming variety post that I’ll be doing in the next week or two.

    3. Justin

      I think it is quite plausible that pressure/flow/sheer stress cause atherosclerosis. Particularly because disrupted flow activates the MAPK pathway in endothelial cells (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718045/). This would result in cellular growth that is consistent with histological analysis (http://www.sciencedirect.com/science/article/pii/S1359644616301921). Similarly, anything that activates this pathway (MAPK), may also contribute to atherosclerosis in my opinion.

      For example, hyperinsulinemia/insulin resistance causes increased endothelial growth via the MAPK pathway and decreased nitric oxide (with possibly decreased oxygenation) via the PI3K pathway (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380736/). This may be compounded by dysfunctional adipocyte signaling, omega 6 fatty acids, or possibly other mechanisms. Decreased FOXO activity may also play a role as FOXO activity is associated with longevity

      1. Tim

        Thanks Justin, I was unaware of these references.
        Will check.

        Cheers.

        1. George Henderson (@puddleg)

          Shear stress reminds me of Klaus Schwartz’s (of selenium fame) silicon hypothesis.
          Proteoglycans are the shock absorbers in the arteries and joints. Their resilience depends on their ability to hold water, which depends on silicon cross-linking.
          Water in Finland was very – like as in VERY – low in silicates, and dietary changes there included plenty of grain fibre, the best dietary source of silicate. French wine and mineral waters are also good sources, as are bean pods.
          Schwartz noticed that every food and fibre type that seemed to prevent atherosclerosis in animals in the 60’s and 70’s happened to be a good source of silicate.
          Essentiality of silicon, which Schwartz proposed but could not show (due to silicon contamination of all lab equipment and refined diets, which Schwartz was diligent enough to record and publish) before his death in 1977, has been proven recently by discovery of mammalian silicon transporters in kidney.

  55. George Henderson (@puddleg)

    Good stuff Tim.
    The relationship of chain length of SFAs to LDL output is matched pretty much exactly to their effect on HDL, and of course both correlate with the different half-lives of these SFAs. As only C14 and C16 are significant transcription factors, and their levels are modulated by dietary carbohydrate, this effect is unlikely to be mediated directly by SFA adducts acting on protein expression levels – it is instead an effect of fatty acid oxidation, either peroxisomal or via mitochondrial ROS signalling.
    This does not apply in the same way to unsaturated fats, but in evolutionary terms there is only really one of these, oleic acid, and it tracks alongside SFAs, and requires saturation before oxidation.
    I have a fairly high intake of LA as I don’t attempt to avoid it from whole foods (chicken, pork, nuts) or olive oil. When I tried to control my lipids by reducing dairy SFA, coffee, and cholesterol, and increasing MUFA, my lipids increased to their maximum, similar to yours.
    However I do not consume much coconut oil.

    With regard to lipids and CVD risk, it is important to note that CHANGES in LDL are not a subject of risk calculations (except for drops in LDL in the elderly). Framingham scores and the like are only predicated on steady state levels in populations eating within the normal dietary macronutrient intake range. As such they include at least a 50% genetic contribution to LDL risk (according to mendelian randomisation anyway), which would be unaffected by diet-driven changes. If lipids were not high before keto, this aspect does not apply. If they were, lower TG/HDL ratio predicts freedom from CVD at these LDL levels.
    https://www.ncbi.nlm.nih.gov/pubmed/22119890

  56. Dom hills

    My cholesterol comes at around 5.6mmol/L

    Ldl is usually between 3-4mmol/L
    Hdl around 1.2mmol/L
    Triglycerides around 1mmol/L

    I used a lower carb diet and my cholesterol went to 8.2mmol at one point and cholesterol around 6mmol.

    Drop down to moderate carb and fat and it is back to my first my first numbers.

    Ideas?

    1. Dave

      Pretty straightforward — you’re now deriving more of your energy from carbs (glucose) necessitating less circulation of LDLp to deliver your energy from fat (TGs). http://cholesterolcode.com/cholesterol-research-breakthrough/

      1. Dom hills

        So is it best to go lower fat for me if my cholesterol spikes up high?

        1. Craig

          One of my big takeaways from this work is LDL-C is usually not relevant for judging your health, especially when looking at low-carb diets.

          With those numbers, I’d choose the diet where you feel better.

          If you feel better on low-carb, but are still concerned about LDL-C, there are another set of blood tests that better give the complete picture. We’ll have an article about that out soon.

          1. Dom hills

            I feel best with moderate fat and carbs. Low carb I felt drained and low fat dropped my testosterone which wasn’t good and left me grumpy.

      2. Dom hills

        Hey Dave

        So in regards to this is it bad if I go low carb and high fat and my LDL cholesterol goes back up?

        1. Dave

          I try to be a good scientist and insist I don’t know for sure whether it is a net good or bad. That said, I think the case for LDL-C/-P being causally atherogenic is surprisingly weak. So as with myself, so long as my other markers show low inflammation, I’m comfortable with having higher LDL given it makes mechanistic sense on a LCHF diet. (See http://cholesterolcode.com/a-simple-guide-to-cholesterol-on-low-carb/)

  57. Tim

    Hi George.

    Yes the Rath hypothesis is interesting. They have produced an ascorbate knockout mouse that duplicates the train wreck seen in atherosclerosis, particularly in the elastin layers, but pretty much everything is deranged. That’s the only difference between a normal mouse and the atherosclerotic one.

    I keep coming back to this idea. What intrigues me is that almost all other animals produce ascorbic acid endogenously so its incredibly important and it looks like a freak of climate caused us to lose our ability (40 million years ago when ascorbate must have been plentiful in the diet, otherwise it could not have happened) and we may have paid a high price since, particularly when we migrated north. Our endogenous production if maintained has been estimated by Pauling at somewhere around 2-5 grams/day. That’s a lot. LP(a) appears to have taken some of the slack in triage, especially arteries, but this comes at a big price.

    So I think the combination of C deficiency and hemodynamic pressure explains a lot.

    Cheers.

  58. Tim

    Hi Justin.

    Sorry for the tardy response to your interesting question on LDL pool size and catabolic rate WRT triglycerides and insulin, where the efffects seem to be opposite.

    The observation on acceleration of catabolic rates at low trigs comes from Shepherd et al,

    “A, LDL cholesterol levels (□, dotted line) change dramatically as a function of plasma triglyceride (note log scale). This is due first to a fall-off in the FCR for LDL apoB as plasma triglyceride rises from 0.5 to ≈1.8 mmol/L and then an increase in the FCR above this value (▴, dashed line). The lines are quadratic fits to data taken from References 77, 112, and 113, and unpublished work. B, The ratio of urine radioactivity excreted compared with the mean plasma radioactivity (U/P) following injection of a tracer of radioiodinated LDL is a daily measure of the catabolic rate of the lipoprotein. If the protein under study is kinetically homogeneous, it should be a constant value over the whole period of the turnover. The fall-off in U/P ratio in a subject with a low normal (▪) or an average (▴) plasma triglyceride indicates metabolic heterogeneity, with the early loss of a rapidly removed species (pool α) and an increasing proportion of slowly cleared (pool β) LDL remaining.”

    http://atvb.ahajournals.org/content/17/12/3542.long#sec-6 (Check figure 5).

    I agree the reference you quote shows insulin works at cross purposes. Unfortunately neither study references the other or controls for the other variable so we are left with two opposing effects.

    I chased down several of the references in both studies but I cannot find a direct comparison if you do, let me know.

    Cheers.

  59. Bruce

    So I did the protocol for my recent blood test. I am concerned about my triglycerides going up. I am not sure what to think to be honest. I feel like I am not a hyper responder, but I’m still in “bad” territory? I’m converting everything from mmol/L here…

    (Feb 2017- Aug 2017)
    ~~~~~~~~~~~~~~~
    A1C = (7.0 – 4.8)
    *Trig = (72 – 97)
    LDL = (162 – 131)
    HDL = (42 – 51)
    C-HDL Ratio = (6 – 4)

    I don’t have my before total cholesterol but it’s now 225.

    My goal was to remove diabetes, and I think I’ve done that having the last two A1C’s come back below 5. I do a LOT of extended fasting, so the protocol was a bit harder for me as I don’t eat much at all. I managed to get in at least 4000 calories a day.

    I am most likely going to get the “Statin talk” on my next visit.

    I wonder if my extended fasts might make my trigs be higher? I eat keto when I am not fasting, but I did fast for 6 days before the protocol.

    1. Dave

      Hi Bruce–

      In find trigs to be the “noisiest” of the markers I track. If it goes up or down by 20 or 30 per test, it doesn’t even register on my radar. (You can actually see how much my own TG *does not* track as tightly as the other markers on my recent LC USA presentation here: https://youtu.be/V8nltu2awvE?t=1775)

      I would hope you wouldn’t get the “statin talk” with those numbers given your LDL was at 131. But then I know they like to prescribe it at even 100 mg/dl.

  60. ASMcClain

    Hi Dave – thanks for all your great and pioneering work on this. I suspect I am a hyper responder (and like other commenters have noted, I am also ApoE 3/4 – assuming it is related somehow.) 50-year old female, 5’7, 135 lbs. I am pretty lean and do strength training and HIIT. Since eating a ketogenic diet for one year (was relatively low-carb before) I have lost 15 lbs and my numbers have changed as follows:

    A1C = 5.3 –> 4.8
    Trig = 103 –> 53
    TC = 230 —>330
    LDL = 109 –> 217
    HDL = 107 –> 87

    As an Apoe4 carrier, my main concern is AD, followed by CVD. Feeling like I am on the right track, but always looking for reassurance! Also, I don’t get why HDL has gone down – that’s more worrying to me than LDL going up. Thanks for any thoughts.

  61. Jon

    Hi Dave,
    Have just finished watching your discussion on ZDoggMD for the nth time, great stuff and really interesting. I’d like to add my numbers to your dataset.
    I’m a 43 yo male, 1.88m, 85kg, highly active (CrossFit 6 times a week) and have been LCHF for about 10 years. Reasonably clued up on cholesterol, inflammation, etc. Have always been a hard gainer and think I may fall into your Lean Mass Hyper responder group.
    My total cholesterol has been high since going LCHF, typically around 7.5 (290), much to the chagrin of whichever doctor I discussed it with, even with a 10 year risk factor of 1-2%. Ratios have been good and trigs low, typically around 0.4 (35).
    Last week I had my first cholesterol check in about 18 months for reasons I’ll go into later as it’s a long story, and the results were.

    TC: 9.3 (360)
    HDL: 1.8 (70)
    LDL: 7.2 (278)
    Trig: 0.7 (62)

    This was non-fasted; of course my doctor was immediately concerned and despite the 10 year risk factor of 2.6% with all other things considered (no smoking, weight, etc) said it’s one of the highest readings she’s seen. FCH and statins were also mentioned. I wasn’t particularly worried, more intrigued with the bump compared to my usual readings.
    I had another, fasted, blood test on Friday, so I’ll post the results here when I have them, along with historical results for comparison. Would be grateful to hear your thoughts when you have time.

    1. Dave

      Hi Jon —

      – Indeed, your numbers are very close to a LMHR which certainly fits your profile too.

      – And yes, please share back your new numbers as well. 🙂

      1. Jon

        Hi Dave,
        A little later than planned but as promised, fasted results and some older readings.
        12h fasted results 1 week after the previous bloods were taken:

        TC: 9.3 (360)
        HDL: 1.9 (73)
        LDL: 7.1 (275)
        Trig: 0.6 (53)

        Older readings; thought I’d had one around 18 months ago but must be mistaken as I couldn’t find that in my records:

        Aug 2010
        TC: 6.4 (247)
        HDL: 2.1 (81)
        LDL: 5.0 (193) Friedewald – 3.74 (145) Iranian
        Trig: 0.4 (35)

        Feb 2014
        TC: 7.3 (282)
        HDL: 2.1 (81)
        LDL: 5.0 (193) Friedewald – 3.74 (145) Iranian
        Trig: 0.4 (35)

        July 2014
        TC: 7.2 (278)
        HDL: 2.4 (93)
        LDL: 4.6 (178) Friedewald – 3.38 (131) Iranian
        Trig: 0.4 (35)

        My diet is pretty much the same every day, I consume slightly less at the weekend but a typical day looks something like this:

        Total calories: ~4,000
        Protein: 240g (23%)
        Carbs: 100g (10%)
        Fat: 300g (67%)

        Eat as clean as I can, cook with lots of coconut oil, supplement with high quality Omega 3, Vitamin D3, Vitamin K2, Zinc and Magnesium I can give you a more comprehensive breakdown if that’d be useful.

        The reason I had the recent tests is because I’ve just finished a 6 month course of Warfarin in response to multiple PEs at the start of this year, and wanted to see what negative effects that has had.
        I’ve dug into the literature on Warfarin induced calcification (http://amjmed.org/warfarin-and-vascular-calcification/) and Vitamin K2 over the last few years as I’ve seen the damage it can do long term, in a family member who’s been on it for ~20 years.
        The usual scans (Leiden, Protein C) were unremarkable in my case and I’m fairly certain the PEs were caused by Effort Induced Thrombosis. Pain I had in my right elbow and arm during training the week previous to being admitted correlate strongly with typical symptoms.
        As the dose of Warfarin I was on was quite high, I had a CAC a couple of weeks ago to see if it had caused any calcification, and was surprised to receive a score of zero.

        My GP isn’t pushing hard for statins any more after a couple of lengthy discussions, but still thinks I need to change my diet. Am tempted to arrange an appointment with the dietician just to see what they recommend.
        If there’s any more info I can give you that’d be useful let me know anyway, can post it here or email it over.

  62. Jim Ingram

    48 y.o 5′ 6″ 155 pound runner, 11.7% body fat. Running 20 – 25 miles per week. LCHF diet, sometimes Ketogenic.

    TC 385
    HDL 80
    LDL 292
    TG 66

    Apo a 183
    Apo B 177

    Hs Crp 0.23

    LDP P 1851
    Small LDL P <90
    LDL particle size 22.4
    LP IR 24
    Glu 91

    Coronary Calcium Score 0.7
    CIMT – 0

    Mesa score ~ 4% risk of event

    Previously measured body fat as high as 26%, had multiple aches and pains and fatigue. After adopting LCHF, losing weight, and getting in shape feel incredibly better. Looking at multiple indicators of CV risk can be very confusing but continuing current path!

    Jim

    1. Dave

      Jim — you definitely fit the profile.

      Your LDL-P of 1851 is actually a little bit lower than I’d expect given your LDL-C of 292. Typically, with that score, it’s closer to 2500ish, but I suspect that depends somewhat on muscle repair at the time of the blood draw.

      1. Jim Ingram

        Interesting comment about muscle repair. Are you saying the LDL-P might be lower if there is active muscle repair going on? These labs were drawn when I was actively lifting weights. I’ve been running exclusively lately because of an elbow injury. I was considering rechecking the NMR. I’ll repost if I do.

  63. Kristian

    HI Dave I am 26 and have been on Ketones/low carb for a good 5 months now. I am a fairly active person who exercises 5-6 days a week(mostly resistance training with some endurance as well. Aporx 136lb, 8-10%BF,I had a blood test about 3.5 months(In April 2017) into being kept and my results were :
    Total Chol – 305
    HDL – 110
    LDL – 179
    Trigly – 80
    Apo B – 126
    HS CRP – 0.2
    LDL pattern A , Angstrom

    I just recently repeated a blood test just toes how things were(August 2017). The only real difference between my diet and lifestyle between this time frame was that I incorporated a lot more intermittent fasting(on average of about 16hrs/day +/- 2 hrs). And these were my most recent results:

    Total Chol- 379
    HDL – 108
    Trigly – 89
    LDL – 250
    Apo B – 163
    HS CRP – 0.2
    LDL pattern A, Angstrom

    On both occasions my blood glucose was below 90 as well. My question is, do think the fasting could of caused a change in the cholesterol numbers? Also Is it common to have a low HS CRP with high cholesterol, and could that be considered “good”? Are there any other markers that I should be keeping out for while on a ketogenic diet since cholesterol levels don’t seem to be a reliable source for some? Thank You

    Kristian

    1. Dave

      Hi Kristian-

      – It’s hard to say how much of the change was specific to IF and how much was a progressive change of your baseline numbers.

      – Yes, it’s VERY common for a healthy, lean low carber to have a very low hsCRP and high LDLs. And yes, I consider that good. (Important note: hsCRP can be elevated following intensive workouts/runs as I’ve seen in my own numbers taken 24 hours after half/full marathons)

      – For other testing, check out Craig’s new article up here: http://cholesterolcode.com/lab-testing/

  64. Dom hills

    Like Andy I worry with my numbers of cardiovascular disease risk.

    I am on a moderate carb and fat diet. Somewhere around 150-200g carbs and around 80-100g fats. Protein around 180-200g. Weight train 4-5 times a week and a personal trainer.

    Cholesterol results come in at:

    Total Cholesterol – 5.6mmol/L
    HDL – 5.6mmol/L
    LDL – Between 3.2-4mmol/L
    Triglycerides – 1mmol/L

    When I tried a lower carb higher fat the LDL went up so I reduced down but still worried I am eating too much fat etc which is causing the LDL to be high? Is it a problem where it is?

  65. Kaitlyn P.

    Interestingly, hypercholesterolemia is a common in anorexia nervosa patients but is described as a paradox as they usually eat very little fat or cholesterol. Usually LDL and HDL are elevated and are lowered upon refeeding. There is an entertaining range of proposed explanations for this phenomenon, none of which touch upon the idea of lipids being an energy mobilization strategy. The closest that they get is “cholesterol metabolism is accelerated.” At least it is not standard of care to start statins!

  66. Jim Ingram

    48 y.o 5′ 6″ 155 pound runner, 11.7% body fat. Running 25 miles per week. LCHF diet, sometimes Ketogenic.

    Just got my NMR results:
    LDL Particle number 1748
    Small LDL Particle number 194
    Large VLDL particle number 3.2
    HDL Particle number 31.8
    Large HDL Particle number 6.8
    LDL Particle Size 22.5
    VLDL particle size 45.5
    HDL Particle size 9.1

    Total Cholesterol 351
    TG 129
    HDL Cholesterol 69
    LDL Cholesterol 256

    Lipoprotein(a) 7

    Apo a 183
    Apo B 177

    Hs Crp 0.23

    Coronary Calcium Score 0.7
    CIMT – 0

    CV Risk assessment is like reading tea leaves, all markers every good except LDL and LDL particle number. All other markers are good or very good, which I think supports your theory that LDL is all about energy transport.

    As a Family Physician myself, it’s hard to see LDL that high, but knowing I’m not insulin resistant (by HOMA-IR), the LDL size is excellent as well as the Small LDL particle number, HDL is incredible and I feel better than I have in 30 years, it’s hard to take a statin with NNT of 120+ and NNH of ~ 60, with no mortality benefit.

    I’m waiting on my life insurance physical rating. Labs done same day as above. Hopefully they are aware of the Lean Mass Hyper-responder pattern and can see past the LDL and acknowledge other excellent markers.

    Thanks again for all of your work! I’m hoping this may push medicine into a better understanding of CV risk predictions and treatment. Unfortunately the Cholesterol hypothesis persists in spite of very poor trial evidence for any overall mortality reduction and weak if any primary prevention power.

  67. Jason Stevens

    Hi Dave,

    These are my results from the start of the month.

    Cholesterol H 10.88 mmol/L ( 3.90 – 5.50 )
    VLDL H 1.00 mmol/L ( 0.16 – 0.67 )

    IDL
    Mid C H 1.06 mmol/L ( 0.23 – 0.62 )
    Mid B H 0.68 mmol/L ( 0.13 – 0.44 )
    Mid A H 0.94 mmol/L ( 0.16 – 0.67 )

    LDL
    LDL 1 H 1.93 mmol/L ( 0.00 – 1.48 )
    LDL 2 H 2.36 mmol/L ( 0.00 – 0.78 )

    Small Dense LDL
    LDL 3 H 1.21 mmol/L ( 0.00 – 0.15 )
    LDL 4 H 0.14 mmol/L ( 1.00)
    S LDL-CHOL 7.9 H mmol/L (<3.5)
    S LDLC/HDLC 4.5 H (<4.0)
    S Chol/HDLC 6.1 H (<4.5)
    S IRON 14 umol/L (5-30)
    S TRF 2.1 g/L (2.0-3.2)
    S TRF SAT. 27 % (10-45)
    S FERRITIN 148 ng/mL (30-500)
    S GLU(FAST) 4.1

    As you can see my HDL is super low and my triglycerides are high. Also I my small dense LDL is very high. I am currently around 15% body fat and weight train 4 times per week and run about 15k.

  68. Sven

    Hi Dave,

    I would like to point out one thing from your latest presentation that is incorrect, although it doesn’t change the overall story.

    Please have a look at this article: http://www.jlr.org/content/15/5/491.full.pdf http://www.jlr.org/content/25/2/97.full.pdf
    It explains how in an energy deficient state, the adipocytes push out their fatstores, triglycerides, and how the LDL-p pick up this triglyceride from the adipocytes. From your presentation (https://www.youtube.com/watch?v=tf55H-_aEns) I understood that it is the liver which is producing this high number of LDL count but that would not be correct according to the article. The liver binds it to the VLDL-p to make it water soluble but how would the triglycerides get to the liver in the first place when released from the adipocytes? In order to get the triglycerides from the adipocytes, (as good as) empty LDL-p passes by and picks it.

    My own stats as hyper responder:

    Total Cholesterol 391 mg/dL
    LDL Cholesterol 282 mg/dL
    HDL Cholesterol 102 mg/dL
    TG 61 mg/dL

    ApoA1 2,17 g/L
    ApoB 1,96 g/L

    at the time of measurement
    body fat ~9%
    weight lifting 3x per week
    2 to 3 per week commuting to office 44km total on commuting days (not at a slow pace)
    avoid carbs completely except for a handful of nuts and vegetables all I can eat, still avoiding those high in carbs.

    I do wonder why this would not happen in anyone who is just loosing weight and is not very active. The same release of fats must be happening but it seems that the LDL-p count does not increase? Also important to note is that on a low carb (keto in my case), the storage of fat in the muscle fiber increases. Could it be that this hyper response is just linked to a great energy deficit?

    Cheers

  69. Belle Martin

    Just received some scary results – I’m a 54 yr old woman, weight around 100lb.
    I was low carb paleo for around 3 years before going keto about 4 months ago.
    Exercise 4-5 times a week, walking HIIT sprints & light-ish weights
    IF several times per week usually 20:4 hrs
    I’ve always had high cholesterol, and always managed to dodge taking statins. Last year I had genetic screening for FH which came back negative. I also had a 0% score on a CAC heart scan, so thought all was ok.
    Recent results have shocked me and prompted panic in my Dr. I’m being referred to a lipid clinic.
    Here are the results, any comments would be welcome
    (They were taken in the uk in mmol, I’ve done conversions so will post both. I’m also not sure if each test has the same name UK/US?)

    Serum chol level (total?) 16.01 mmol (619.10mg)
    Serum HDL level – 3.22 mmol (124.5 mg)
    Serum LDL level – 12.4 mmol (479mg)
    Serum trigs – 0.95 mmol (84.1 mg)
    Serum chol/HDL – 5 mmol
    HDL/Trig this wasn’t calculated, bit I’ve done it using nos above not sure if I’m right – 0.60 mmol (0.7 mg – I think)
    Non-high density lipoprotein chol 12.8 mmol

    So I guess I get to join your club.

    1. Dave

      Hi Belle–

      Yes, you are no doubt very concerned given these numbers. But you are by no means alone as I have about a half dozen people who fit these levels, all of whom are:
      1) Women
      2) Lean
      3) Athletic
      4) Feel GREAT!

      Per the article above, there are strong mechanistic explanations for this, and there are even more on the geekier side which I haven’t had a chance to do a post on just yet (centered around distribution coverage and NEFAs, but I digress).

      As always, this is a deeply personal decision and one I recommend you researching many sides on. I’ll have some new videos out soon that will go into risk and my research in more depth in the near future.

  70. Belle Martin

    Thanks for your response Dave – I have been researching as much as my non-scientific brain can cope with – there are so many conflicting studies and theories! Whilst I am loving being in ketosis, I am thinking maybe I should just abandon it and return to a more paleo WOE? I don’t know – it’s all very well people saying “oh the scientists have got it all wrong for years” but in the back of your mind is that nagging fear that maybe they were right about some things. I don’t know – I feel very confused and despondent, and in the meantime what do I say to the cardiologist!! Anyway hurry up and do all your research and let us know what to do!! By the way getting past your captcha is ridiculously hard!!

    1. Dave

      Hi Belle–

      I often say I was a 9 on a 10 scale of concern when I first got my cholesterol results two years ago, now I’m more like a 5 — but I’m *not* a 0.

      Like you, I don’t want to put all my stock in one “side” of the debate. I’m acutely aware that the vast majority of doctors in the world would assume my higher cholesterol is likely to end my life sooner. Moreover, I’ve grown up my whole life hearing a million times over how higher cholesterol = higher mortality.

      However, I also know how axioms happen — I see them all the time in engineering. A large group of very smart people have a core assumption they are invested in. One of the telltale signs of this is a dismissiveness toward compelling evidence that challenges this worldview — not theory, *evidence*. For me, I have observed this more than enough now in the area of cholesterol specifically.

      Ironically, I’m just now taking the blood draw from this morning on a very non-LCHF experiment. It was a success in that it brought down my lipid numbers, both LDL and HDL, as expected. But this was only for a demonstration, not a WOE. As with before, my experiments keep proving how this is related back to dietary energy and energy status of the body in a healthy body. Of course, my insulin when up, my glucose went up, I’ve been a lot more tired post-meal, my sleep schedule is erratic, and worst of all… it’s impacted my distance run training.

      In short, if not for my research gathering, I’d likely have remained keto this entire time. I now know far too many people who have been low carb (some for decades) and with high cholesterol that, like Tim, have no calcification, inflammation, oxidative stress or the mother of them all, hyperinsulinemia. All of which have *more* of a correlation than LDL to CVD and mortality as a whole. This doesn’t mean I’ve concluded the high LDLc/p is meaningless or that the Lipid Hypothesis is false — rather, that there’s enough evidence for me to question the axiom and gather more research/evidence.

  71. Tim

    Not all women, one male….myself. Belle Martin’s data mirrors my latest data including age, activity level, cac score. My latest reply to my July 5th post has the data and is reposted here so no need to score back. The July 5th post also shows how my lipids can significantly change by changing diet:

    “Dave

    Thought I would follow up with the latest test. As I mentioned I went back to keto and mostly ate red meat ala Shawn Baker and essentially no carbs. Results are as follows:

    TC – 636
    HDL – 139
    LDL- 484
    TG- 60

    Also performed the CAC test with a score of 0.

    Work out with weights and cardio 5X per week and have single digit body fat (est of 8-10%). Again feel great but cannot wrap my head around these new numbers.”

    Tim

    1. Dave

      Oh — right — my bad, Tim!

      Thanks for sharing your data as well! Have you gotten a CIMT, by chance?

      1. Tim

        Dave, I have not had the CIMT test but I did have a stress test and several EKGs…all of which were normal. The imaging center where I had my cac only has the Doppler test, but I may still try to find some other facility nearby if the test is reasonably priced. With the cac it would provide another baseline test for any future comparison/progress. My overall plan is posted in my reply to belle Martin which I am trying to play with diet.

  72. Belle Martin

    Hey Tim – glad to know I’m not alone. Is your doctor FREAKING out? What are you going to do – anything? nothing? I’m so reluctant to give up keto because I LOVE it and feel fantastic, but I’m uncomfortable with my numbers being as high as they are. I know I’ll be pushed towards taking statins which I have always previously refused – but am I harming my chances of living a long & healthy life? Aargh – I hate being in this situation!
    (If this is posted twice it’s because of my inability to get thru the captcha!!)

    1. Tim

      One other point I forgot to make relative to statins. If Dave is correct in that the lipid system is primarily an energy distribution system, and as a LMHR high levels of LDL are essentially delivering that energy in the form of TGs to the needed body parts, I would think that taking statins would significantly interfere with the process and reduce the body’s ability to distribute energy as needed. I wonder whether this would result in fatigue and negate all the good benefits of going low carb in the first place such as increased energy levels, mood, etc.

  73. Tim

    Belle, my doctor’s response was “your numbers are impressive” and he had never seen an LDL number that high. He also mentioned that he is thinking about discussing this at his next medical conference. However, he did not put me on statins. He said he usually prescribes statins if LDL number is >190 mg/dl, but he also considers ratios and that my ratios were not excessively bad (I.e., TC/HDL, LDL/HDL, TG/HDL). He does want me to try to lower the number and agreed to work with me.

    My plan is to first significantly lower my saturated fats and retest. My initial high lipid values included low carb and somewhat high saturated fats. These numbers returned to normal when saturated fats were cut along with an increased amount of carbs. I did not feel as good and decided to go all meat mostly eating red meat with essentially no carbs and had the latest highest numbers similar to yours (see my july 5th post above for all my various numbers). For me, I am not sure whether sat fats or low carbs (or both) is the main factor. I believe Dave had mentioned that he tried to switch from saturated fats to mono saturated fats and his numbers did not change much. If this does not work, then I will increase my carbs and try to find the minimum amount to improve my numbers. This increase in carbs to find the “sweet spot” in discussed on Dave’s site. Then I will need to reassess based on how I feel. With low carb I feel so much better both physically and mentally almost feeling like I am in high school. With the higher carbs I feel….well like a 54 year old, including stiffness, joint aches. This would be hard to give up. Based on what I have read, I am convinced that the medical community does not know what actually causes CVD or whether high LDL is the cause, and yes this makes it very confusing. Wouldn’t it be ironic if LMHR increased numbers are actually a good thing and provides protection for all cause mortality? Finally, if you have not seen dave’s interview on YouTube with “zDog”, it is very informative and entertaining.

    1. Dave

      >>> Wouldn’t it be ironic if LMHR increased numbers are actually a good thing and provides protection for all cause mortality?

      As you know, I try to be as objective as possible. But honestly, I think there’s a very strong case to be made for this. I think LMHR might actually be a superior profile — not because the numbers drive the good outcomes, but because the numbers *indicate* the good outcome (if you know what I’m saying).

      Which would make this whole era we’re in pretty sad if this proves true. And thus, it’s a big part of my drive right now. I certainly wouldn’t be going through all this out of general curiosity!

  74. Belle Martin

    Interesting Tim, thanks for your comments. You are lucky that your doctor is so calm about your data. I too am so reluctant to give up my LCHF regime – I feel so well and fit, with great energy and brain-clarity. I am trying to increase my carbs too but whilst keeping in ketosis. I am also reducing BPC (was on 2 per day – now only one). Also considering trying the 3 day carb load protocol prior to my next set of tests to try to hack results. I shall try to argue my case at my next appt, citing the other impressive results – great trig/HDL ratio, low insulin & fasting blood glucose etc. I fear though that the usual dogma regarding high LDL will be their response. Unfortunately I also have high blood pressure and take medication to control it. Being fit and LCHF has not reduced it – it will be seen as another problem, and further support their recommendation for statins. I’m interested to hear how being ZC affected you. And yes I did watch the ZDogg interview which was great. Think I’ll watch it again in fact!
    Regards
    Belle

    1. Dave

      Belle — very important — I definitely DO NOT recommend *adding* carbs. All my experiments with bringing in carbs were isocaloric, as in, I would “swap” out the same amount of calories of fat for calories of carbs.

      I’ve now had three people who have simply “added” carbs and it resulted in super high trigs and/or fasting glucose. This outcome makes perfect sense as my general theory is all about energy input and status. Bringing in a surplus of glucose simply emulates the SAD diet with energy overage.

      I’ve been able to change my numbers quite a bit with only a little-added carbs because (I speculate) I’ve topped off my glycogen stores and the body feels less need to upregulate TG availability in response. But again, this is all still very preliminary and it isn’t easily determined where these thresholds are.

  75. Anne

    Hi Dave,

    I don’t know if you read my post on Dr Eades’ blog. You had responded to me on Dr Eades’ blog back in July as I am very lean, eat low carb/high fat Paleo for the past ten years, and my cholesterol/lipid levels have been rising ever since going low carb/high fat. Anyway, I had my regular six monthly cholesterol/lipid profile test at the beginning of September. I increased my fat intake, which was already high, during the week before the test. The result ? It works ! It works !! My total cholesterol came down from 8.7 (336) to 5.5 (212), my HDL remained exactly the same at 3.5 (135), my triglycerides lowered from 0.5 (44) to 0.3 (26), and my LDL lowered from 5 (193) to 1.8 (69) !

    Anne

    1. Dave

      That’s awesome, Anne! Thanks for adding your data to our pool!

      You know, no matter how many times I read these — I’m still in a little bit of disbelief myself. It’s incredible how long modern medicine has gone without realizing how much this lipid system is tied to energy distribution, and of course, how cholesterol is along for the ride.

  1. Lab Tests – Measuring your Metabolic Health » Cholesterol Code

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    […] had his presentation the day before mine and I was ecstatic he even had a slide regarding Lean Mass Hyper-responders in particular. He likewise brought lots of attention to the importance of seeing the lipid system […]

  3. Energy Status Experiment » Cholesterol Code

    […] While theoretical, I’ve contended for some time that this makes sense on the part of the body when lacking “energy in the tank” of glycogen and adipose stores. If you’re lean and on a low carb diet, the less body fat (adipose) and lower carbs (less relative glycogen stores) may mean the body has reason to mobilize more fat-based energy on hand (LDLp). That appears to get further confirmed by the Lean Mass Hyper-responder pattern. […]

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