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May 11

Cholesterol Research Breakthrough

A few important caveats before getting started:

  • This is very preliminary. While it’s true I’ve both produced and reproduced these results, it’s still very early to draw significant conclusions, which I detail further below.
  • This does not constitute medical advice. I realize many may read this and act on it, but I urge you to consult with your doctor and/or trusted medical professional — particularly if you are diabetic or insulin resistant.

Going Low Carb / Keto

Before I started the ketogenic diet, my carb intake was probably north of 250g a day and my fat intake was likely around 75g. After going keto, I brought my carbs down to around 20g with my fat shooting up to around 220g. (My protein remained relatively constant at 25% of my calories.)

To illustrate this, I’ll be using this simple graphic to show a sliding scale from left to right as 100% carbs & 0% fat to 0% carbs & 100% fat.

carbs_to_fat_percent

So let’s overlay the quantities of my carbs and fat both before and during the diet.

carbs_to_fat_quanitites

Sure enough, after adopting this lifestyle, I felt better than I ever have before it.

But then I got my cholesterol scores seven months after starting which showed an extraordinary jump in both total (TC) and LDL cholesterol (LDL-C). And this is where I learned I was one of the fraction of those going low carb who see a dramatic rise in total and LDL cholesterol known as a hyper-responder.

cholesterol_before_vs_after

To be sure, my HDL going higher is presumed good and my triglycerides going lower is presumed good. But the doctors care much more about LDL-C and will insist my higher levels on a low carb diet should be of great concern.

The Assumed Solution

Up to this point I’ve given the same advice to fellow hyper-responders as I’ve read from doctors and researchers: If you want the one surefire method for reducing your cholesterol, you will likely have to give up being low carb.

Let’s look at that graphic again and apply this to myself:

carbs_to_fat_target

If we assume at least a rough linear relationship with fat and cholesterol, then I’d pretty much have to go almost entirely back to where I was before starting keto. By some basic calculations, I could estimate a total cholesterol of around 200, LDL of 140, HDL of 42, and TG of 130 if I get back to about a 50/50 mix of carbs and fat (as shown by the “Best Goal?” overlay above).

This makes perfect mechanistic sense, given how the lipid system works. If eating more fat means my body is trafficking more fatty acids for energy, then necessarily it must traffic more cholesterol in these same lipoproteins.

Weighing the Choice

Let me illustrate this another way to get across the relationship:

scale_even

As fat rises, so does Total, LDL and HDL, with Triglycerides falling. Total and LDL-C going up is supposedly bad (red), HDL going up and Triglycerides going down is supposedly good (green).

scale_fat

Reversed, we see Total, LDL and HDL drop with Triglycerides rising. Total and LDL-C going down is supposedly good (green), HDL going down and Triglycerides going up is supposedly bad (red).

scale_carbs

Three Clues

So given this assumption, I expected my own data would likewise reveal this as well. When taking my blood tests, I’ll always have some variations of carbs, even if they are generally low. Moreover, I’ve had some variation in the ratio of carbs-to-fat. Yet while these were tiny shifts, there wasn’t a linear relationship appearing.

I didn’t put too much thought into it until a series of recent experiments and what it revealed to me. Let’s revisit everything I’ve done to date, excluding only the “extreme” experiments (such as the Extreme Drop I did that spawned the protocol).

markers_to_date_positive

As usual, I’ll be flipping the left axis so you can better see the inverse relationship between three day dietary fat and LDL-C. Past this point, all graphs will have this same inversion with the left axis.

markers_to_date

Above, the darkened lines of orange and blue lines show where I did the distance running and thus lowered my LDL-C marginally. Just after that, I’m going to take the blue highlighted area at the far right and break it down further.

markers_zoomed_in

From here, I’ll highlight each of the experiments I did over this period of time. This is further detailed on my Experiments List page.

markers_with_notes

During first major experiment I had eaten only eggs and cheese for 10 days, changing the quantity in the middle. But unlike other experiments, I had moved it from a moderate quantity to a low quantity. This yielded a sustained gap like I hadn’t ever seen before in my series. I also felt general malaise; didn’t enjoy it much for the second half. But the big first clue came in the form of my fasting blood glucose being unusually correlative with my mood. Lower FBG = worse mood.

The second major experiment was with fasting, which I posted on recently. This too yielded a major clue given it coupled tightly as would otherwise be expected with LDL-C.

The third clue came from the two experiments to follow. In the first, I had one cup (250 ml) of whole milk with each meal, in the second it was a single slice of bread. What astonished me was how tightly the Inversion Pattern held even going up to 78g of carbs / day. This proved the biggest clue of all as I’d have expected the gap between between the three day average and LDL-C to have widened.

teaser_full

The Calculation

There’s a big part of this story I can’t fill in yet. It’s how each of these clues along with a theory I’ve been working on for a long time led me to the next major experiment. I’ll detail it in a future post once it has been tested against, which will take several more experiments to achieve.

I’ll just say that the theory + these clues led me to calculate a range of 90 to 130g of carbs needed to hit this mythical “Sweet Spot”.

The Shakes and Bread Experiment

With this calculation in hand, I wanted to devise an extremely controlled experiment. Indeed, this would be one of the most intensive I’ve ever done.

I wanted to:

  1. Have a keto ratio of food that was nutritionally complete, yet somehow very consistent and quantifiable
  2. Have a common carbohydrate food as the intervention variable, but likewise as simple as reasonably possible

I figured out I could achieve (1) by having a ketogenic meal replacement drink, and for (2) I would just have simple slices of bread. I managed to find one that was both 100 calories a slice and allowed me to get within the net carb range I was looking for at 5 slices a day.

I would do five days of the shakes alone, then five days replacing 500 calories of the shakes with 500 calories of the bread. The first five days I’d be at around 30g of net carbs, with the second five at around 95g. This way I could really hit that target range while being extremely controlled on exactly what I ate.

To further ensure control, I ate to a very specific schedule of 11am, 3pm, and 8am in all but the first two days.

swap_graphic

A Striking Result

Before getting to what happened, it’s worth noting the data advantage I enjoy coming into this experiment. If you’ve been following my work for a while, you are already aware. But if you’re just joining us, you should know I’ve done 63 blood draws in 18 months and effectively have my own Inversion Pattern mapped now. So unlike anyone else I’m aware of, I’ll know when one or more variables are having an impact on my lipid system given the anticipated coupling you see in my graphs. Even in the outliers, there is little significant deviation from the mean, and until this graph below, no repeating patterns of a gap.

Below I highlight the blood test I took following the 5 days of keto shakes, which couples as we’d expect to the Inversion Pattern. Then, a clear gap forms between the higher expected LDL-C and the actual resulting LDL-C.

shake_and_bread

In other words, swapping out 500 calories of the keto shake for 500 calories of the whole wheat bread resulted in a lower LDL cholesterol than we’d expect.

Best of Both Worlds?!?

Right about now you’re probably thinking, “Sure, but isn’t this what you took so much time to explain at the beginning? That increasing carbs will result in better cholesterol numbers?”

Actually, there’s a huge number of differences here between the assumption above and this outcome. Let’s start with a closer look at the other lipid numbers.

lab

Not only was my total and LDL cholesterol the lowest I’ve ever had while on keto at 220 and 140, respectively — but my triglycerides were an impressively low 46, and my HDL was an extremely high at 71. Which is to say, this is the best looking cholesterol lab I’ve ever had.

(As an aside, I’m extremely thankful I did three full tests inside this five day intervention period to help rule out a lab error. Indeed, had this been the only test I performed, I’d have had a hard time reconciling it.)

Reproduction Test

After getting this final lab test four days later on 4/21, I immediately had a blood draw and attempted to reproduce it. However, I ate my “normal” keto diet instead of the shakes, but while likewise adding the bread with each meal to target nearly the same macros as I had on the shake-based diet.

Sure enough, the reproduction appeared to work as well.

markers_all

LDL-P

I ended up getting the particle count data late from the lab. There’s some analysis I’d have covered here regarding 3/23 and 4/7, but I’ll have to save that for a future post.

Like LDL-C above, LDL-P clearly shows the same divergence on its own inversion pattern (three days, with a two day gap).

discovery_ldlp

Revisiting the Assumption

Let’s look to the relationship graphic we had above, but with the new results added.

sweet_spot

Clearly we can see only a small change in total dietary carbs got me the “Sweet Spot” I highlight above. But again — and this is important to emphasize — it didn’t appear until I passed a certain threshold. Remember, just before this experiment I had done another (“One Slice of Bread”) experiment where I averaged 78g of carbs with no diversion in the Inversion Pattern.

In other words, this strongly suggests there is a threshold, a tipping point, a drop off with regard to my lipid numbers. That’s the reason I wanted to illustrate this analog relationship as I do above, because this strongly suggests it may be wrong.

With this in mind, let’s revise the concept.cliff

Here I’m illustrating how the shape of this cholesterol relationship appears different. With a sudden drop off point, it implies I can get the best looking lipid numbers by getting to the other side of this threshold.

Again, this is still very preliminary, but the testing so far supports it.

Other Observations

Naturally there’s much more to share about what happened than my changing lipid numbers. These are just the highlight while at 95-97g of carbs:

  • No Ketosis (of course). Ketone levels (BHB) were around 0.1-0.2 throughout, including morning (Keto average 1.2)
  • Very high postprandial glucose often 110-150 MG/DL two hours following a meal
  • Higher fasting glucose at 102 MG/DL (Keto average 92)
  • Slightly more tired following meals
  • Insulin averaged 5 UIU/ML (Keto average 3.8)

None of these came as a surprise to me given the higher carbs save the fasting insulin, which I expected to be higher.

What This Means

This may be the start of a solution for hyper-responders who seek a better lipid profile, while still staying low carb.

Instead of adding back hundred of daily carbs, I was able to stay just under 100g even if I was giving up ketosis. But again, I have a more distinct advantage than most due to knowing my own lipid patterns so well, so I can more easily identify where this carb threshold is and isolate it.

As far as the theory that led me here, that will have to wait for a later post.

However, while I’m happy if this may ultimately provide hyper-responders like myself with a new choice, not much has changed for me personally with regard to the risk assessment. I don’t know for sure that this lipid profile is a lower risk for all cause mortality today anymore than I would have a month ago. In short, I’m more interested in what this means on a system-wide level for the body’s regulation and control than I am for its personal impact on my life… at least, for now.

Next Steps

  • I’ll be pausing for a little while as I ramp up some contract work to rebuild my research funds. Up to this point I’ve been paying for the last 18 months of blood, medical, and technology expenses from my savings — save a few generous contributions from individuals through my donate button on the site. Thanks for the support!
  • I’m currently back to my “normal” keto ratio and expect to do another blood test following the pause to confirm my numbers have returned to the original Inversion Pattern. If so, we’ll know these changes were indeed transient.
  • Following that, I plan to experiment with other sources of carbs (fructose, lactose again, etc) to determine if the ratios hold regardless of the type of sugar.
  • I’m also tempted to do more lopsided intake of carbs where the same general macros are hit, but with a single meal being carb-heavy where the others are generally keto.

75 comments

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  1. Michael Babcock

    This is fascinating stuff, however . . . The assumption here has to do with having a total cholesterol and a LDL-C that is lower is better and that the standard cholesterol lab result targets are a good thing. Do we know this? Given that pretty much every other marker improves on a ketogenic diet, just maybe that rising total cholesterol and rising LDL-C is actually an improvement as well. Is there actually any research that shows anything detrimental about higher cholesterol and LDL-C numbers? Can we say with authority that raised LDL-C is definitely bad? Back to the other question: is it possible that those raised LDL-C numbers while you were on keto are a good result?

    I’d have to ask “the best looking cholesterol lab” according to who? Conventional medicine? If it turns out raised LDL-C is actually good, they don’t look like such a good set of results.

    What are the small, dense LDL particles are doing?.If they go up with a keto diet, that would be a concern.

    I’m curious: why the effort to make your lipid profile fit western medicine’s ideal? Are you certain it is the best thing for your health and longevity?

    1. Dave

      Hi Michael-

      You must be new, as you’d find my opinion is nearly identical. This is why I was using language like “best appearing” to set the stage from a conventional perspective. But note in my What This Means where I say:

      “However, while I’m happy if this may ultimately provide hyper-responders like myself with a new choice, not much has changed for me personally with regard to the risk assessment. I don’t know for sure that this lipid profile is a lower risk for all cause mortality today anymore than I would have a month ago. In short, I’m more interested in what this means on a system-wide level for the body’s regulation and control than I am for its personal impact on my life… at least, for now.”

      So in many ways I’m more excited about what this means for my research in the overall lipid system than for personal risk until and/or if I develop markers that suggest otherwise.

  2. Sergi

    As another hiper-responder, this is really interesting. I will have to test this out (my latest numbers are 2400 LDL-p and 1100 small LDL-p).

    Have you consider fiber as one of the reasons why increasing carbs using 500 cal of whole wheat toast reduces LDL-P so drastically?

    1. Dave

      I’m actually very doubtful fiber played a significant role in this result. I’ve had many keto meals that were high in fiber, yet low in net carbs. And I haven’t seen much significant correlation.

  3. Bob Niland

    I only recently began following your blog, so might have missed some key details in the back traffic, but did do some searching.

    Overall, you appear to be rediscovering material that is known to the community of Dr. William Davis (cardiologist), and compiled in his former Track Your Plaque program (now named Cureality, and soon to be Undoctored).

    Knowing your ApoE status is part of the puzzle. Another couple of tests I don’t see discussed are Lp(a) status, and any calcium [Agatston] score (CT or EBT calcium scan; not a CT angiogram).

    Dr. Davis used to have specific advice for ApoE4 (and E2) clients, but it rather looks as if the diet and lifestyle program he now recommends for everyone brings things under control for all but the most intractable lipidemias: grain-free, very low net carb, ad-lib specific fats, remediate and maintain microbiome, 3 grams or more per day of Omega 3 DHA+EPA, no added Omega 6 Linoleic Acid, supplement Vitamin D and magnesium to titer target, plus some other strategies.

    In his program, TC is deprecated, LDL-C is a bad joke, TG target is below 60, HDL target is above 60. LDL Particle Number matters (600 to 800), and there are other markers to consider. You can get a sense of them at: https://www.cureality.com/forum/topics.aspx?ID=18881

    Disclosure: I’m a contributor on Dr. Davis’ Wheat Belly Blog (where the topic of lipidemias, curiously, seldom arises).

    1. Dave

      Hi Bob-

      Interesting comment. Yes, I’ve read some of wheatbelly’s material.

      I’m an ApoE 3/4, my calcium score was actually assessed again last week at 0. My Lp(a) test last year was in normal range (don’t have that number handy).

      On Omega 3, I typically have 1 tsp of cod liver oil each day and salmon twice a week. (I’d have it 7 times a week if I weren’t concerned about mercury — can’t trust the origins necessarily)

      I’ll check into your link later, but you should know I’ve gotten very, very cozy with lipid numbers and the patterns they are exhibiting. For me, this is clearly an energy distribution system (see my breck presentation) and I’m not interested in lowering any lipid numbers (or raising them) without disentangling this part of the puzzle. Simplified, I believe there are good and/or bad reasons lipids are elevated, given they wear many hats. The *real* question is how you can distinguish between the two.

      1. Simon Hunter

        Eating fish further down the food chain can help with the mercury. So smaller the better. Thats why sardines are my preferred fish and I’d avoid things like tuna & swordfish. Also with the smaller fish its no problem to eat the bones as well because they are small so extra nutrients we rarely get there as well. Keep up the good work.

        1. Dave

          That’s great advice — I’ll be sure to try that out.

          And thanks!

      2. Bob Niland

        re: «Yes, I’ve read some of wheatbelly’s material.»

        The latest program summary would be the book Undoctored, just released this week. Davis, by the way, basically put himself out of the interventional cardiac business because his patient population simply stopped having events.

        re: «I’m an ApoE 3/4…»

        I saw that. Tip for your readers on that: the $99 23andMe Ancestry test provides the same Raw Data download as the full $200 test, and it’s easy to extract ApoE status from the two SNPs involved. Anyway, my understanding is that some E4s might need to fine tune fats, if the markers that matter aren’t brought into comfortable bounds by the basic Davis program.

        re: «…my calcium score was actually assessed again last week at 0.»

        Excellent. That’s generally considered to be a 5 year warranty of near-zero likelihood of events. A CT CAC can often be had pretty cheaply ($99 around here, no referral required), as hospitals use it as a loss-leader to recruit patients for the major procedure funnel. Anyone concerned about heart disease might consider getting a scan as a baseline. Take the number, but politely decline the advice.

        re: «My Lp(a) test last year was in normal range (don’t have that number handy).»

        Beware of proclamations of “normal” from consensus healthcare. Normal is not the same word as healthy, which itself is not the same word as optimal. On Lp(a), optimal might be zero.

        re: «…1 tsp of cod liver oil each day and salmon twice a week.»

        One tsp. might not get to this level, but getting 3-to-3.6 grams of DHA+EPA per day from CLO raises risk of excess Vitamin A in addition to the toxin uptake concerns.

        Whole fish is the ideal way to get ω3, if it’s a lower-food-chain fish (as another reader pointed out), and if (as you allude) you have some confidence that it’s truly wild-caught, and not off-shore-farmed, which are fed grain-based CAFO garbage that drives down ω3, raises ω6LA and adds new toxin hazards. Three cans of sardines a day would do the trick, but that product is a minefield, due to packing fluid concerns, packaging concerns, and my observation that a can often does not contain a dozen or more nearly complete little fishies, but 6 or less chunks of some larger critters.

        I personally use two Sam’s Club fish oil products, one of which is also my Vitamin D source.

        re: «…I’ve gotten very, very cozy with lipid numbers and the patterns they are exhibiting.»

        The standard lipid panel is 40 or 50% informative. An advanced lipoprotein panel is much more useful. Here’s Dr. Davis on Friedewald.

        re: «…I’m not interested in lowering any lipid numbers (or raising them) without disentangling this part of the puzzle.»

        Now if we could just the high priests of the Cleveland Clinic to grasp that concept. You’d think that with the failure of CETP Inhibitors, and what appears to be the looming failure of PCSK9 Inhibitors*, that they’d figure out that just shoving markers around has no necessary correlation with actual outcomes.

        * PCSK9s may have some real benefit for those with Lp(a), and who are taking otherwise optimized nutritional steps, but we may never learn the full picture on that, and these agents may be withdrawn from the market, because the number of people with matching net-beneficial indications may be too small.

        1. Dave

          – Thanks, I may check out the new book.

          – Yes, I likewise obtained my ApoE status from 23andMe SNPs. I’d further emphasize to the readers that there are MANY great benefits to 23andMe in mining personal health data.

          – Completely agree on the CAC. Or at least, the CAC score along with the context of its progression. Ivor Cummins covers this topic quite a bit.

          – Not sure on Lp(a), I plan to return to that topic soon after I get another test. I likewise don’t like “normal” ranges — but this applies in all directions (including advice from inside the LC community). For example, I’m less certain of smLDLp risk in a LCHF context given a number of factors.

          – Seafood hazards — Yeah, this is actually why I wish I lived on the coast. Getting prepared seafood in any manner carries the risks you detail.

          – CETP and PCSK9 make extremely obvious sense to my networking friends from a mechanistic standpoint. They are providing the most negatively impressive case of “scorecarding” medicine where you only care about modifying the number (LDL and HDL) rather than working within the system that governs it.

      3. Charles

        You do realize that, in the only paper Dr Davis has published, he used a low fat diet, and statins to drive LDL down to <60 in order to reverse arterial plaque

        http://sci-hub.bz/10.1097/MJT.0b013e31817a8f3c
        Effect of a Combined Therapeutic Approach of Intensive Lipid Management, Omega-3 Fatty Acid Supplementation, and Increased Serum 25 (OH) Vitamin D on Coronary Calcium Scores in
        Asymptomatic Adults

        The impact of intensive lipid management, omega-3 fatty acid, and vitamin D3 supplementation on atherosclerotic plaque was assessed through serial computed tomography coronary calcium scoring (CCS). Low-density lipoprotein cholesterol reduction with statin therapy has not been shown to reduce or slow progression of serial CCS in several recent studies, casting doubt on the usefulness of this approach for tracking atherosclerotic progression. In an open-label study, 45 male and female subjects with CCS of ≥ 50 without symptoms of heart disease were treated with statin therapy, niacin, and omega-3 fatty acid supplementation to achieve low-density lipoprotein cholesterol and triglycerides ≤60 mg/dL; high-density lipoprotein ≥60 mg/dL; and vitamin D3 supplementation to achieve serum levels of ≥50 ng/mL 25(OH) vitamin D, in addition to diet advice. Lipid profiles of subjects were significantly changed as follows: total cholesterol −24%, low-density lipoprotein −41%; triglycerides −42%, high-density lipoprotein +19%, and mean serum 25(OH) vitamin D levels +83%. After a mean of 18 months, 20 subjects experienced decrease in CCS with mean change of −14.5% (range 0% to −64%); 22 subjects experienced no change or slow annual rate of CCS increase of +12% (range 1%-29%). Only 3 subjects experienced annual CCS progression exceeding 29% (44%-71%). Despite wide variation in response, substantial reduction of CCS was achieved in 44% of subjects and slowed plaque growth in 49% of the subjects applying a broad treatment program.

        1. Bob Niland

          Charles wrote: «You do realize that, in the only paper Dr Davis has published, he used a low fat diet, and statins to drive LDL down to <60 in order to reverse arterial plaque»

          My read of it is that he used fish oil and Vitamin D to accomplish the goal. The diet and meds were chosen to be SoC-compliant both to get IRB buy-in, and to minimize variables. I was given a copy of the paper some years ago by one of the authors, but didn’t keep any references for my interpretation of why they did what they did.

          In any event, Dr Davis’ current recommendations are clearly laid out in several books, web sites and blogs subsequent to that 2009 paper, most recently Undoctored, published just last week. All of it is based on actual results in his patient and subscriber populations. The diet is what I term enlightened ancestral: very low net carb, high specific fat, microbiome-attentive, specific micronutrient attentive (including D and fish oil) and thyroid optimizing. The fictional LDL-C is basically ignored now (actually measured small LDL particles are not).

    2. Charles

      http://www.cureality.com/blog/post/2006/11/06/the-track-your-plaque-rule-of-60.html

      The Track Your Plaque recommended targets for conventional lipids (i.e., LDL, HDL, triglycerides) are LDL 60 mg/dl, HDL 60 mg/dl, and triglycerides 60 mg/dl: 60-60-60.

      Not only is this set of values easy to remember—60-60-60—but is grounded in science and the results of clinical trials.

      LDL 60 mg/dl
      The LDL target is based on experiences such as that of the Reversal Trial, the PROVE-IT Trial, and the Asteroid Trial, all of which showed that LDL cholesterol values in the range of 60 mg/dl dramatically enhance the likelihood of stopping plaque growth or achieving regression, reducing risk of heart attack more than more lenient LDL targets.

      1. Dave

        You might be new to this site and unfamiliar with my research. If confirmed, it will be very relevant for all prior clinical trial data.

        But before discussing that, can I confirm you’re already familiar with the Inversion Pattern I’m tracking?

  4. Michael Babcock

    I had another thought after sending the previous post. I do see that your trig/HDL ratio is significantly better at your “sweet spot.” I’d love to see you discuss the balancing of different health markers. Yes, your “sweet spot” might improve the lipid markers but your insulin and glucose not so much. Which set of markers do you seek to optimize or how do you balance the various markers?

    1. Dave

      Ah ha! See, you’re doing it too — you’re seeing the “Sweet Spot” and assessing it is “significantly better” — we don’t actually know that. Maybe it *appears* better, without actually being so.

      This is why it was a bit annoying to write this post as I knew I’d need to add another 500 words of qualifiers to every mention of a marker to make it clear the difference between a positive appearance and just… a reported number.

      The journey I’ve had with these patterns keep making it clear that many foundational assumptions with lipids and the biological network that governs it are very wrong. Thus, I’m not inclined to assume much of anything.

      That said, there are many who are hyper-responders and don’t care about the particulars — they just want better *appearing* lipid numbers. And that’s a choice we should definitely respect. To that end, I hope I’ve helped make a small contribution to better understanding how we can get there while still being LCHF. 🙂

      1. Michael Babcock

        Dave, thanks for the replies. (Yes, I am new.)

        It’s fascinating stuff. After a year on LCHF my total cholesterol was 294 with LDL 201. (HDL 79, trigs 69). My doctor offered me statins and without even thinking I just asked her “Are you kidding?” (She wasn’t.) It just seems so evident (as in there is actual real evidence here) that statins are dangerous and a waste of time/money for primary prevention. At least she took some articles to read. Sigh.

        I can see one use of this info to improve lipid profiles prior to a test so that your doctor would be happier. Heck, I can up the carbs for 3 days if I want to go that route.

        1. Dave

          Many have done the protocol I wrote up a page where I detail how I did this. I think at last count I have had around 13 in the last eight months contact me to say they did it for this purpose.

          The carb increase from this last experiment is much newer and still very preliminary. And again, it only worked once past the threshold I was able to find. Thus, if this proved true to many, one could increase their carbs a certain amount and see no benefit because they hadn’t passed this threshold, to begin with. And again, this is all theoretical and speculative.

  5. eric25001

    P!ease read cell metabolism DEC 2014 Time RESTRICTED FEEDING

    What hours did you eat?
    Seems time is an important factor
    Eric

    1. Dave

      Per the graphic above (http://cholesterolcode.com/wp-content/uploads/2017/05/swap_graphic.png), I ate at 11am, 3pm and 8pm each day.

  6. Jorn Vikse

    You are doing a fantastic job with these experiments, and the documentation. I haven’t read all of your post, but I will. Have you discovered the reason for this «hyperesponder» fenomena. I understand that apoE is involved. But the fat you eat is shuttled in chylomicrons, and surely this is not measured in your lipid tests ?
    The standard answer to why ldl-c raises in respons to fat is downregulating of the receptors. Can this really account for these big differences you observe ?

    Thanks again for your work.

    1. Solomon

      Great Job Dave is doing. Jorn, the summary of Dave’s work is this: For the Keto adapted person, the Lipoproteins are in the main, energy distribution particles. The more fat you consume the less of it that you need. And the important factor is the body uses the sum of the last 3 day’s fat consumption to determine how much particles it should produce. For particle numbers, there is a two day delay for the three days used. More fat, less LDL is what the data is bearing out so far.

      This new insight says, you can still get ‘great lipid numbers’ for you Insurance Company by doing less fat and a little more carbs. Just that the Glucose starts coming up. Metformin?

    2. Dave

      Hi Jorn-

      Yes, Chylomicrons aren’t measured as I always fast about 14 hours before a blood test, thus they should be almost entirely cleared from the system.

      Solomon’s comment summarizing my work is good. If you’re referring to what determines the higher LDL-C/-P in the first place (becoming a hyper-responder), that is still yet to be determined.

  7. Eric

    Look at my circadian clock. Org
    Eating keto in a time restricted feeding seems the logical evidence based way.
    Salk institution has the data and evidence
    Eric

    1. Dave

      I may try testing that in isolation with regard to lipids at some point.

  8. Rob

    “This does not constitute medical advice. I realize many may read this and act on it, but I urge you to consult with your doctor and/or trusted medical professional — particularly if you are diabetic or insulin resistant.”

    I wonder if all nutritionists will have to put that caveat on their blogs from now on after the Noakes trial

    1. Dave

      Probably. We live in a heavily lawyered society now.

      But to be sure, I do encourage everyone to have a good relationship with their doctor. If you find you feel you know better than they do about nutrition and goals for your health, you should find another doctor rather than being compelled to lie or omit your lifestyle from them.

  9. Latife

    I appreciate your work and feel lucky having you, thanks a lot.
    I am hyper-responder too. But I was doing intermittent fasting, like 20/4, 22/2 and have done 46-8 hours fasting few times. I was fast when had test and my cholesterol was really high ( 10.6= about 429). I was on low carb, high fat diet at the that time. So intermittent fasting and HFLC!
    I should have another test without being fast and see how fasting effects on my cholesterol.
    I am not worried about having high cholesterol after reading and watching your work.
    I would like to know how much fasting shot my cholesterol. My understanding from you is, when we eat fat or our body fat is used for energy it is normal if we have high cholesterol and LDL.:)
    I have T2D.
    Thanks again.

    1. Dave

      I believe so — but to be sure, I’m a good scientist and can’t say I know for certain one way or another.

      The one thing my data and research are clearly illustrating is just how much the lipid system is about energy distribution and maintenance. That cholesterol is actually a red herring in that it is just a passenger in the process, not a driver.

  10. DrDan

    Insulin represses the expression of the orexigenic peptides NPY and AGrP. By going into ketosis, I guess that the arcuate nucleus no longer gets the message via insulin that you’ve just eaten. You’d therefore produce more NPY than expected … and NPY increases VLDL-TG secretion by the liver. Taking some CHO would increase insulin, reduce NPY and reduce increases VLDL-TG secretion.

    1. Dave

      Interesting theory on the mechanism, DrDan. I’ll have to look into that. 🙂

  11. eric25001

    Not what 9 hour period during the 5 to 10 day window but do you eat in 9 hour windows now?
    Does 3000 calories mean 1000 excess? What about maintenance?
    135 grams of protein? Too much for me to maintain be and ketone levels.

    What about six months or more? Years?

    My day average is 180 fat and protein is 3 days of 66.25 grams and one of 12.5 grams along with 3 days of 30 grams carbs and one day of 50 grams.

    Two eating styles that might be interesting to compare all meat diet for years and or every other day eating.
    What are the blood results after years? Better worse same? How?
    Eric

    1. Dave

      – I believe I eat more in a 11-12 hour period normally.

      – Yes, I believe 2800-3000 calories while ketogenic to be my maintenance for weight stability.

      – re: protein — I genuinely crave fatty meats (particularly red meat) and have allowed for this as a major staple of my diet. Lots of steaks, burgers, etc.

      – Ketone levels aren’t as relevant to me as they are for most on a keto diet.

      – I plan to do a ZC (all meat) diet experiment at some point soon (summer or fall). I too am very interested in what the numbers will show.

  12. Alberto

    Why not forget entirely about cholesterol and focus on your Calcium (CAC) Score, that is scientifically proven to have a much more accurate correlation with cardiovascular disease? I’m a hiper responder who chose to go all in in keto, without looking back. CAC score: zero!

    1. Kanel

      Because this research is not only important for Dave, but for all of us. Finding out the truth about the lipid system and its connection (or lack of connection) to heart health is vital if we want to see a change in the current dietary advice and health care.

      1. Dave

        Yes, Kanel — it’s certainly a major driving force for me personally! I hope to make a small contribution in the understanding of this system, particularly as it seems so much clearer from an engineer’s point of view. Indeed, it really does have so many things in common with a network that make it easy to test against.

    2. Dave

      Hi Alberto-

      I focus on my CAC as well and likewise agree it is probably a far better predictor. Note throughout my article I use words like “presumably better” and “appears” rather than “is” for lipid test results. I’m emphasizing how the test scores look by conventional standards as opposed to whether or not they are indeed *actually* better. Which is why I emphasize in the What This Means section at the end that little has changed for me with regard to assessing risk.

  13. Peter

    Have you measured your CIMT Carotid Intima Media Thickness?

    Also, have you measured your sterol absorption? http://www.bostonheartdiagnostics.com/science_portfolio_cholesterol_balance_test.php
    Sitosterolemia was one possible diagnosis given for high plant sterol absorption leading to very high cholesterol numbers.

    1. Dave

      – Yes on the CIMT and I’ll be presenting on this next week. (Spoiler alert: it hasn’t gone *up*)

      – No on the sterol absorption, but I intend to get that tested as well.

  14. Lary Beck

    Thank you, Dave for being there to curtail the stress of a newly discovered hyper-responder, although the data is clouded by quitting atorvastatin after 15 years at the same time. (I wonder about a rebound effect.)
    Been in ketosis for 3 months with average noon blood ketones at 2.0
    Numbers :
    TC from 147 to 407 and LDL(C) from 73 to 317. I am also intermittent fasting in order to lose weight. I have not read all the blogs, but combined with your Breckenridge video, I have a basic understanding of the interactions. Btw, 13 years ago at age 57 I had a CAC score of zero and last month it was at 55 which puts me in the 14th percentile, so with a family history of atherosclerosis, I feel I am not doing too bad.
    Next up, I will be looking to get an NMR lipids test.

    1. Dave

      Hi Lary-

      I’m very glad you got your CAC score early into the ketogenic diet so you can chart progression. Congrats on keeping it so low for your age. Although a statin proponent would likely say this was the result of your being on atorvastatin this entire time and that it would have been worse if you hadn’t been. So like me, you are potentially heading into unknown territory to see if dropping off the statin results in a different outcome. As I always say, *please* share back the data whether good or bad!

      That said, you may already know there are many studies now that confirm all cause mortality is *lower* with higher cholesterol in the elderly population. Which is why I’m genuinely glad my dad’s cholesterol rose slightly on keto.

  15. Karl Schmidt

    Several points –

    1 – I don’t think that the arrow of causation has been proven for LDL — Could be that damaged arteries alert the immune system and one of the responses to injury is cholesterol recruitment – via LDL. The LDL=bad narrative is failing – several drugs that lower LDL fail to improve CAD-mortality nor all-cause-mortality. Statins provide a very small benefit – and lowering LDL may only be a side effect. NNT for statins is 83 after taking for 5 years – no benefit if you don’t have CAD. http://www.thennt.com/nnt/statins-for-heart-disease-prevention-with-known-heart-disease/

    2 -There is no study that has shown that LDL is an independent risk factor if oxLDL is held constant.

    3 – There are several forms of LDL – often classified as dense vs fluffy – the only way we know to change the type to the assumed more healthy form is to eat less carbs.

    4- People losing weight will have higher LDL (transport out of adipose tissue). So having high LDL on low carb may only be temporary and represent a ‘good thing’.

    5- The latest Repatha paper showed lower LDL – yet increases in heart deaths and all-cause mortality. http://www.nejm.org/doi/full/10.1056/NEJMoa1615664

    https://xtronics.com/wiki/Cardiac_Disease_Carbohydrates_and_Weight_Loss.html

    1. Dave

      1 – Agreed! In fact, the Response to Injury model continues to make the most sense to me with regard to existing evidence. Not that it is the *only* possible pathway to atherogenesis, but I’m inclined to believe it is the most predominant.

      2 – Also agreed! I bring this up regularly in fact. I even believe it might have been on Twitter this week where I debated with someone and asked for any study that controlled for oxidative stress, inflammation, and endothelial damage. (The last one is obviously extremely hard to measure, but still highly relevant given you can induce atherosclerosis by denuding it)

      3 – This one is a little more complicated. I’m actually less certain that small LDL-P is independently atherogenic relative to larger lipoproteins because I think it more often reflects a diseased state in rare circumstances. I’m finding much more highly active keto athletes with smLDLp which makes sense given higher TG depletion due to greater energy demands. So mechanistically, this makes sense as a different reason leading to the same result.

      In other words, I believe where it associated some margin of detriment in the previous studies was due to a higher likelihood of disease state in subjects (bad reason for it). But in a new paradigm with keto athletes needing the TG for fuel and thus higher depletion from LDLp means smaller size makes for a good reason. Again, all that matters is whether it is, in fact, a *causal* agent. (And I’m guessing you, like me, are hard pressed to believe that without more substantial evidence).

      4 – Agreed. Although given my research so far, it looks like that amount of weight drop has to be pretty high to yield a sizable margin.

      5 – Yes — I’ve actually seen that one. Thanks for the link.

      1. Karl Schmidt

        Re: Small dense LDL — trying to save the LDL=bad narrative by looking at different type os LDL also helped sell more expensive LDL tests…

        I’ve had similar doubts.

        The new narrative – that the initial damage is due to growth factors – likely insulin – brings us to insulin resistance being the bad thing – and that may well be caused by the consumption of LA(Linoleic Acid)

        See https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2011-1957#sthash.ZiwZ2AyH.dpuf
        The Lipid Peroxidation By-Product 4-Hydroxy-2-Nonenal (4-HNE) Induces Insulin Resistance in Skeletal Muscle through Both Carbonyl and Oxidative Stress

        https://www.researchgate.net/profile/William_Lands/publication/26756981_Measuring_blood_fatty_acids_as_a_surrogate_indicator_for_coronary_heart_disease_risk_in_population_studies/links/546ac6ba0cf20dedafd38e72.pdf
        Measuring Blood Fatty Acids as a Surrogate Indicator for Coronary Heart Disease Risk in Population Studies

        and https://xtronics.com/wiki/images/HUFA_6-A.JPG

        1. Dave

          Great links, Karl — thanks.

          To be sure, I try to be a good scientist and keep open-minded about possible alternate explanations at all times. But as always, the burden is on the one who asserts the argument (this includes me) for a theory. Yet I find in modern medicine there are a number of “givens” that seem to be presumed true, putting the burden of proof on the skeptic of this assumption. This certainly applies to the area of cholesterol.

          1. Leigh Yaxley

            OK , here is an alternate explanation to test your open-mindedness:

            Prior to these latest tests you did your fasting experiment 21 -23 March.

            Fasting is known to increase serum total cholesterol and LDL and the cause is most likely the increased lipolysis that occurs during fasting.

            After you stopped fasting lipolysis would have slowed down, especially once you increased your food intake to 3000 kcals per day.

            No surprise therefore that your LDL dropped.

          2. Dave

            Hi Leigh-

            – First, ALWAYS test my open-mindedness. I welcome all counter views here, especially if they are in stark contradiction to my own. I proactively watch/read vegans, other dieter commentary, and yes, even mainstream medicine counters to LCHF for this very reason.

            – Second, I think we were already on the same page. My theory behind the Inversion Pattern has always been mobilizing of energy via VLDLs in the absence of available incoming energy from the gut (Chylomicrons). And since the cholesterol in a blood test is picking up almost entirely VLDL-originating particles (Apo100), it will seem to go down when eating a lot and up when not eating a lot (and in this case, WAY up when not eating anything at all, as I predicted).

  16. Peter H

    Great post. An experiment eating ‘gluten free’ would be very interesting. I am high fat low carb without gluten. My LDL was 190 at the last count. I have cut down to one egg for breakfast instead of two. And using less meat fat. To try and bring this down. Though 190 doesn’t look too bad, compared with your 270. I should add that I am 65, nearly 6foot tall and weigh only 70.2 kilos. I am HFLC without gluten to keep my brain working.

    1. Dave

      Thanks, Peter – great comment. 🙂

      1. Karl Schmidt

        You might want to start by looking at :

        https://www.google.com/#q=site:http://high-fat-nutrition.blogspot.com/+gluten

  17. Richard Nikoley

    Very, very interesting. I’ll be citing it in a post soon.

    1. Dave

      Cool, I look forward to reading it. 🙂

  18. Neville

    Hey Dave, Just wanted to post my test results on a whole foods plant based diet (HCLF). Again, i haven’t been as precise as you’ve been in weighing/measuring food but here’s what my diet (kinda) looked like.

    – Breakfast: fruit bowl consisting of chia seeds, 4 spoons hemp protein, 1/2 banana, two handfuls of berries, 1/4th cup of granola

    – Lunch/Dinner Option 1: Salad Bowl consisting of ~ 80 gms spinach, 1 mango, 3-4 spoons hemp protein, 2 hand-full’s of berries, 1/2 cup granola.

    – Lunch/Dinner Option 2: Rice 3/4th cup rice, 2 servings of vegetable stew made up of cauliflower+potatoes

    LDL-P 1150 nmol/L
    LDL-C 105 mg/dL
    HDL-C 46 mg/dL
    Trigs 37 mg/dL
    Total C 158 mg/dL
    HDL-P (total) 27.1 umol/L
    Small LDL-P 159 nmol/L
    LDL Size 21.3 nm
    H1Ac 4.9 %
    Insulin 3.9 uIU/mL

    This report looks quite good to me(apart from the low HDL). I am surprised to see this (low) value for trigs! I’d also like to add that i think i have lost some muscle mass in the last month. So in that sense, preserving muscle while losing fat and general overall well being, i would put the ketogenic diet as superior to what i am doing right now. However, unfortunately my cholesterol seriously go for a toss on HighFatLowCarb.

    Going forward i might try adding fat gradually and see where these numbers go. Since, i am at the other side of the spectrum right now (HCLF) i’ll probably start adding fat gradually while lowering carbs. I did briefly go through your latest post on adding carbs (will read it in more detail soon). I must say, i had tried adding some carbs (maybe around 50gms) while i was doing LCHF but that didn’t seem to bring down the numbers. Maybe adding more carbs would have helped!

    1. Dave

      Hi Neville-

      Bravo — I rarely see an HDL-C at 46 for a HCLF diet. Plus your H1Ac and insulin look great. To be sure, your sample diet from above appears to be extremely nutrition dense and non-factory-ized. 🙂

      If you’re trying to boost your HDL-C while staying plant-based, I’d recommend shooting for coconut oil. There are several salad dressings you can make with it and it’s pretty easy to use in many cooking recipes. Of course, I’m not a nutritionist, but HDL-C is one of those that I watch very closely and it definitely seems to be impacted quite a bit by my saturated fat intake.

      1. Neville

        “I rarely see an HDL-C at 46 for a HCLF diet”
        Assuming you mean its on the higher side for HCLF

        “If you’re trying to boost your HDL-C while staying plant-based, I’d recommend shooting for coconut oil.”
        Thanks for the recommendation. Like in your case, i too have noticed HDL-C most impacted by saturated fat.

        To be honest, its going to be hard for me to stay vegetarian long term. I’m going to try to add fish to the mix and maybe evolve this into some kind of Mediterranean diet. In any-case, at every step i’ll keep testing to check if theres anything thats making my numbers shoot up radically!

        1. Dave

          – Yes, your HDL-C is high relative to a HFLC diet. 🙂

          – I’m curious — why do you feel it would be hard to remain vegetarian long term? I ask because I occasionally have vegetarians/vegans ask about going LCHF and would like to learn more about the challenges/benefits.

          1. Neville

            I think that was overall to do with how i feel currently. Primary reason I started the ketogenic diet was to improve body composition and even though the lipids have improved, that aspect seems to have worsened drastically. Also, being vegan i find it hard to intake sufficient protein (there’s a limit to how much hemp protein one can have :)). Given this situation i am pretty sure i might give some variation of an LC another shot.

            I can understand vegetarian attempting LC but would believe LC on vegan would be hard. Curious to see how someone would pull it off without even the use of dairy products!

  19. Tim Steele

    Hi Dave – New here, but great blog (Thanks, Allan!). Your inversion factor is interesting. I’d love to see similar labwork on people who follow other dietary patterns, SAD, WAPF, Med, etc. I recently did an Indiegogo project to raise money to test resistant starches and I had enough left over to get more people involved in an n=10 blood glucose experiment (see at potato hack.com). Maybe you could raise funds the same way…very easy to do.

    My only quibble with some of your experiments is that the gut flora of a keto-adapted dieter vs a carb/fiber eater would be quite different, and a couple days of eating bread would not change the gut flora significantly. Perhaps a future experiment would involve a high-fiber arm with a timeline that allows changes in gut flora, ie. 6-8 weeks on higher carb/fiber.

    There’s a long history of studies showing large and lasting reductions in LDL-C without reducing HDL-C or increasing triglycerides over long treatment periods.

    If nothing else, your recent experiments show the meaningless-ness of a single blood draw. I’m always disheartened to see doctors who prescribe (statins, bp lowering meds, diabetes meds…) based on just one or two lab results.

    1. Dave

      Hi Tim-

      – Your website and project look great — good work!

      – Sure, I’m hopeful I can crowdfund the study I’d like to do. But I know it will be a challenge as most successful CF campaigns provide a product or event. And of course, my product is data… it’s a little tougher sell, but I’m still optimistic.

      – Oh yes, I’d love to see comparisons with gut flora and I likewise agree it would take a decent stretch of time. Part of my problem is how serious I am about controlling for variables. Thus far I’ve not had any experiment exceed two weeks, so I’d want to be sure I could carry it through all traveling, engagements, etc.

      – Yes — my research/data should really discourage *anyone* from overreacting to a single test.

  20. Kanel

    Thanks Dave! Awesome work!

    Have you seen this talk by Sarah? https://youtu.be/w8jUmCe3zDs (around 15 minutes in)
    She explains how low insulin level can cause elevated LDL in some people so it could help explain how you hit your “sweet spot” by increasing the insulin a little.

    One thought that bothers me about all this is – basically every single marker of metabolic disease improves when going on a ketogenic diet so then why would the body decide to put you at higher risk of heart disease in the process? It does not make any sense to me.

    1. Dave

      Oh yes — in fact I was physically there to watch Sarah’s presentation and it was the first time we met and discussed my research. I’m still in regular contact with her and we’re discussing some exciting new possibilities ahead.

      – Yes, your bothersome thought is mine as well, of course. Mostly, as an engineer who marvels at the genius of the human body in its many overlapping, regulatory systems, I’m still perplexed as to why the assumption falls on it commonly making the very thing that would poisons it.

  21. Manu

    Love your approach, Dave. I also re-added some carbs after hitting a TC of 400 with regular fasts and keto-like carb intake. Some insulin seems to lower LDL. Discoveded it via Chris Masterjohn, who wrote a lot on this topic.

    .. in an insulin-sensitive person, carbohydrate stimulation of insulin has a powerful beneficial effect on LDL receptor activity.

    This doesnt answer the question if it’s an issue of course.

    1. Neville

      Hey Manu, curious to know how much have you been able to reduce TC by adding carbs.

      1. Manu

        About 20%, but I only did it for a short time by now.

  22. Leigh Yaxley

    “Second, I think we were already on the same page. My theory behind the Inversion Pattern has always been mobilizing of energy via VLDLs in the absence of available incoming energy from the gut (Chylomicrons)”

    Dave,
    Maybe we are on the same page but I’m not sure because your theory doesn’t explain where the increased cholesterol has come from or where it goes to when the serum cholesterol decreases.

    My own hypothesis does explain this and it is nothing so very surprising. It is simply an effect of cholesterol exchange with adipose tissue, which has been amplified by changing patterns of food intake that have been switching lipolysis on and off, i.e. increasing fat consumption down regulates lipolysis or switches it off whereas decreasing fat consumption or fasting up-regulates or switches it back on. Furthermore I would expect this phenomenon to be further amplified in someone who is LCHF adapted due to their heightened metabolic flexibility.

    The connection with lipolysis comes about because adipose tissue is a reservoir of cholesterol as well as fat. The cholesterol is part of the fat cell structure and must get expelled along with free fatty acids during lipolysis.

    Your data in the period 21-23 March show serum LDL-C increasing at an average rate of 58mg/dL per day and during the period 23 March to 17April it is decreasing at an average rate of 34 mg/dL per day.

    It is instructive to derive corresponding cholesterol fluxes: At 79 kg and 1.9 meters your total blood volume must be around 5.7 liters and serum volume around 3.1 liters = 31 dL. Multiplying the observed rates of change of serum LDL-C concentration by the serum volume gives an estimate of the mass flux of cholesterol in and out of the serum, i.e.

    Fasting/low fat intake period: + 1798 mg/d ~ + 1.8 g/d
    Re-feeding/high fat intake period: – 1054 mg/d ~ – 1.1 g/d

    (Whilst the above is based on LDL-C measurements previous data from your twin diet experiment shows a very tight correlation between total cholesterol and LDL-C (R^2 = 0.991) so the rate of change of LDL-C can be used as a proxy for rates of change of total cholesterol).

    My hypothesis is that the ‘fasting’ rate of + 1.8 g/d is a net rate at which cholesterol is being released from adipose storage and that the ‘re-feeding’ rate of -1.1 g/d is a net rate at which cholesterol is transferred back to adipose storage. Note that the ratio of the magnitude of these rates is 1.6, i.e. transfer to storage is slower than release from storage.

    These estimates are consistent with measurements of total cholesterol turnover rates that were made around 40 years ago in 54 subjects – see references [1] and [2]. Forward rates (release from storage) can reach 4.0 g/d and reverse rates (return to storage) can reach 2.5 g/d – interestingly the ratio of these rates is 1.6.

    There are 5 primary components of cholesterol metabolism, viz
    • Dietary intake (typically 0.2 to 0.6 g/d)
    • Bile metabolism (~ 0.6 g/d)
    • Liver synthesis (~ 1.0 g/d)
    • Excretion (~ 0.6 g/d)
    • Extra-vascular tissue exchange (up to 4.0 g/d)

    With so many components in play it is not really surprising to see serum cholesterol responding dynamically but extra-vascular tissue exchange is the only component that might account for both the direction and magnitude of the dynamic changes, which your data reveal.

    [1] Three-pool model of the long-term turnover of plasma cholesterol in man DeWitt S. Goodman, Robert P. Noble, and Ralph B. Dell, Journal of Lipid Research Volume 14, 1973 http://www.jlr.org/content/14/2/178.full.pdf

    [2] Prediction of the parameters of whole body cholesterol metabolism in humans DeWitt S. Goodman, Frank Rees Journal of Lipid Research Volume 2 1, 1980 http://www.jlr.org/content/21/6/699.full.pdf

    1. Dave

      Really fantastic numbers, Leigh. I’m a bit swamped this week so I can only give a quick comment, but I assure you I’ll be returning to this one as I’m intrigued by many of the elements you’ve broken out.

      You’re correct in that I’ve focused less on the origins of the cholesterol before being packaged into the VLDLs at the liver. But ultimately this is because I see the liver as a key staging-and-pacing regulator. In other words, I don’t think the liver is turning around the components of a VLDL just as quickly as it can process it, I think there’s process in place that determines the release — likely to meet target amounts of concentration in the bloodstream.

      This is where I tend to veer away from biochem thinkers who get focused on the lower level pathways as I’m eyeing the larger networking patterns. The tight correlation of the Inversion Pattern makes me skeptical that lipolysis activated by broad endocrine signaling just happens to keep providing that target concentration I see across the -C and -P markers with the liver as simply a throughput. Rather, I think the liver is very much a key regulator, and even more interesting, I think it relies on the network of lipoproteins for information feedback as well as distribution.

      Hopefully this helps to provide some context on where my thinking is at this point. Again, absolutely fantastic posts, Leigh. I’ll be returning to this one soon. 🙂

  23. HN Pandey

    Dave, this is wonderful!!
    I have some data to share and understand your perspective. In keto, my Trigs aren’t coming down. How can I share my excel with you?

    Thanks
    Pandey

    1. Dave

      I’ll reach out to you privately, Pandey. 🙂

  24. ginny51

    Thank you, Dave!
    I’m particularly appreciative of what you’ve done and are proving, as surely many others are, particularly as “Jill’s Story” hits close to home for so many women. Being a woman is singled out in statistics as a “risk factor”, eg. CHADS VASC score for prescribing anticoagulation therapy.
    I was prescribed statins just recently, with LDL 223, “prediabetic numbers” and heart problems. If I change my “numbers” I’m in an entirely different position to listen to whatever else the docs want to get me to do. This is one big, huge, understatement, the real change in the patient/doc relationship with a real drop in those “numbers” is awesome. (Statins interfere with insulin production, etc., and are known to push you over the edge into diabetes, clinching the score for mandatory anticoagulation therapy, for example.)
    I’m aware you need experimental data, but you might be interested in the pattern appearing even with rough data.
    I’ve logged my food daily in Cronometer since August 2016, steadily, though not even close to your standards, to try out low carb for prediabetes.
    A pattern appears along the lines of what you’ve decided to prove.
    Nov 5, 6, 7 2016 – Avg Fat 145 grs.
    Blood Test Nov 8: Total Cholesterol 325 / LDL 246
    Jan 30, 31, Feb 1 – Avg Fat 210 grs.
    Blood Test Feb 2: Total C: 218 / LDL 136
    Apr 2,3,4 Avg Fat 151 grs.
    Blood Test Apr 5 Total C: 319 / LDL 223
    This pattern (that thanks to your work I now see) actually happened by chance as I started that second period after Nov 8 trying for lowish Net carbs (60-70 grs) and low cholesterol (max 300 mg) but as I’m way too thin and tall and started to lose weight, about half way through I just decided to ditch the low cholesterol attempt and continued on to my next blood test, eating all the fat I wanted.
    Dear Dave, I am at a loss for words as to the marvellous Pandora’s Box you’ve pried open.
    Would data from Cronometer and a future Blood Test mid-June be of any use to you?
    In the meantime, my sincerest appreciation for what you’ve accomplished.
    ginny51

    1. Dave

      Hi Ginny-

      Thank you so much for the kind words!

      I may be following up with you regarding your data. I’ve gotten so swamped on so many fronts that my research with regard to other people’s labs/data has been a bit inhibited. But I’m hoping to open up more time this summer.

      Again, thanks so much! 🙂

  25. eric25001

    Take a look at toomy web site link from diet doctor
    Eat low low carb high fat web site
    He reports eight years of labs from eating once a day
    Hdl is above trig levels
    Hmm
    Looks like one time a day has potential
    Eric

  26. eric25001

    Dave
    Looking at the labs reported by tommy on his one meal a day and your 3 to 5 day switch on lipid blood levels then it seems reasonable to test five to ten days of one ketogenic meal a day.

    I am not willing to do the same for junk food once a day or vegan or anything but my keto but what an insight if a switch to one meal per day for 5 days can switch the blood results! Eric

    1. Dave

      Indeed… it could yield some interesting results.

      At some point I might try doing a single meal a day myself as an experiment.

  27. Leigh Yaxley

    Dave,
    I’ve dug up a few more clues from the literature – see references [1] and [2] below.

    Your combination of keto shake, bread and fat were probably a close emulation of the ‘casein + oligosaccharides + fatty meal’ experiment of reference [2].

    Any idea what type of protein was in your Keto shake?

    Key takeaways from these papers:

    • “Insulin acutely inhibits VLDL production via its ability to suppress free fatty acid [FFA] mobilisation from peripheral tissues” [i.e. it suppresses lipolysis in adipose tissue]

    • “Elevation of plasma FFA levels acutely stimulates VLDL production”

    • “The addition of oligosaccharides [i.e. carbohydrate] to a fatty meal suppresses the concentration of FFA due to increase of insulin but in addition chylomicrons and VLDL are delayed by effects of glucose and insulin on gastric emptying.

    • Casein [i.e. protein] added to an oligosaccharide-containing fatty meal reduces the chylomicron response. Casein also markedly suppresses FFAs in the presence and absence of oligosaccharides in the fatty meal.

    • Because FFAs fuel hepatic triacylglycerol production, a lowering of VLDL may be a long-term consequence when fat-rich meals are regularly combined with arginine-rich proteins such as casein.”

    [1] Interaction between Free Fatty Acids and Insulin in the Acute Control of Very Low Density Lipoprotein Production in Humans
    Gary F. Lewis, Kristine D. Uffelman, Linda W. Szeto, Barbara Weller, and George Steiner https://www.ncbi.nlm.nih.gov/pmc/articles/PMC295395/pdf/jcinvest00023-0176.pdf

    [2] Postprandial Lipid and Carbohydrate Responses after the Ingestion of a Casein-enriched Mixed meal
    Sabine Westphal, Stephanie Kästner, Elina Taneva, Andreas Leodolter, Jutta Dierkes, and Claus Luley
    http://ajcn.nutrition.org/content/80/2/284.full

    1. Dave

      – The product was Ketolent (chocolate flavor) – here’s a link to the nutrition label page: https://www.ketolent.com/pages/nutrition

      • “Insulin acutely inhibits VLDL production via its ability to suppress free fatty acid [FFA] mobilisation from peripheral tissues” [i.e. it suppresses lipolysis in adipose tissue]
      • “Elevation of plasma FFA levels acutely stimulates VLDL production”
      • “The addition of oligosaccharides [i.e. carbohydrate] to a fatty meal suppresses the concentration of FFA due to increase of insulin but in addition chylomicrons and VLDL are delayed by effects of glucose and insulin on gastric emptying.

      – Agreed — this is why disentangling the insulin response from the actual glucose load and glycogen store is so relevant (yet difficult to achieve without injecting it directly). In fact, it’s arguable that insulin’s role is MORE about inhibiting lipolysis than it is shuttling glucose into cells. (As talked about in Naiman’s 2016 Hyperinsulinemia presentation)

      • Casein [i.e. protein] added to an oligosaccharide-containing fatty meal reduces the chylomicron response. Casein also markedly suppresses FFAs in the presence and absence of oligosaccharides in the fatty meal.

      • Because FFAs fuel hepatic triacylglycerol production, a lowering of VLDL may be a long-term consequence when fat-rich meals are regularly combined with arginine-rich proteins such as casein.”

      – Casein was part of my previous experiment with whole milk, but not so much this one with the intervention being bread. To whatever degree it would be present in the shake, it would have been so in the control period as well (which landed inside the inversion pattern).

      Again, great comments and insights, Leigh. 😀

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