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Apr 20

The Fasting Disaster

fasting_macros

Fasting has been all the rage lately. Jimmy Moore and Jason Fung released a book on it that quickly shot up the New York Times Best Sellers list. In fact, it has been so popular that they launched a podcast on it at the beginning of this year. Oh, I did I mention the episode featuring Jason Fung and fasting is still the most downloaded of the 2 Keto Dudes podcast?

Yet other high profile low carbers such as Dr. Stephen Phinney are not part of the fan club. My personal favorite article on the subject was Not So… Fast… (A Rant) from the prolific Amy Berger.

While on low carb myself, I’ve only ever intentionally fasted for 14 hours at a time, which was only done to meet the requirements of a blood draw. But while I don’t feel hungry when fasting, I don’t feel… right.

To be sure, I’ve wondered if I want to eat all the time so that I either maintain or gain weight, given I’m underweight right now. And therefore my feeling odd when not eating is perhaps entirely mental manifestation. Regardless, a fast of a few days probably wouldn’t be that bad anyway, right?

The Experiment

The plan was pretty simple:

  1. I’d take a blood draw in the morning at the beginning of the fast.
  2. Fast for three days while both supplementing and keeping electrolytes high, but otherwise drinking only water.
  3. Take a final blood draw for comparison on the morning 72 hours after the first blood draw. So in all, 86 hours will have passed since my last meal, making it a total of 3.5 days.

Execution

Day One: I was surprised to find I wasn’t hungry at all. This seemed to back up my theory that if I had already made the commitment to myself to forgo eating, my brain wouldn’t send me subconscious “shouldn’t we be eating?” signals.

As happens with me when I’ve lowered my total calories for an experiment (but while still being keto), I feel run down and puny. I have an overall feeling of lower energy. I also feel a little dispirited in this state, but its hard to tell how much of that is annoyance of that phase of the experiment vs it being an actual physical response.

However, that not-feeling-right sensation I mentioned above?… I was certainly getting that signal. But I had hoped I’d only feel it on the first day.

Day Two: I still wasn’t feeling hungry. And while I did continue to feel low in energy, it wasn’t notably better or worse.

However, the not-feeling-right sensation was definitely much, much higher. It was like nothing I’ve experienced before this point. In my imagination it was as though my body found a red phone line and called some special center of my brain to say, “ABORT! ABORT!” No physical pain, no odd changes in the senses, nothing other than a feeling… a feeling this was terribly wrong.

By the evening I decided to go ahead and cut the experiment short. I’d take my blood on the morning of Day Three as opposed to Day Four. Heck, at least it was a 2.5 day fast in the Data Can. I just knew I’d feel annoyed if my numbers had hardly changed. (Just writing that last sentence makes me laugh out loud now…)

General Bloodwork

In every blood draw now, I get a slate of general panels like a CMP and CBC. The latter is known as a Complete Blood Count and has 14 markers. These numbers always been in range… until this time.

 

Ref Range 3/21/17 3/23/17
RBC 4.10-5.70 5.02 5.85
Hemoglobin 13.0-17.0 15.3 18.1
Hematocrit 37.0-49.0 44.6 52

All of these markers have to do with red blood cells and their functionality, which I won’t cover here. What I really wanted to see is if I had fallen off on my electrolytes, which would explain both the run down feeling and my general sense of malaise.

 

Ref Range 3/21/17 3/23/17
Sodium, Serum 134-144 137 136
Potassium, Serum 3.5-5.2 5.1 5.8
Calcium, Serum 8.7-10.2 9.6 10.5

Interesting — instead of being under, I was over on K and Ca.

Cholesterol

Of course the big one is the lipid profile. And if you follow me, you already know what I’d predict after fasting for the very first time given the Inversion Pattern –> a record increase in LDL cholesterol.

So what happened? I hope you’re sitting down for this….

 

Ref Range 3/21/17 3/23/17 Difference
Cholesterol, Total 100-199 371 479 +108
HDL-C >39 72 70 -2
LDL-C 0-99 284 368 +84
LDL-P <1000 2068 3348 +1280
Small LDL-P <=527 <90 546 +546
Triglycerides 0-149 76 205 +129

Indeed it was a record!

Let’s unpack a few things:

  • Like the Extreme Drop Experiment from last year, this one had a heavy shift in dietary energy, as in a sudden drop off. And likewise this huge degree of change broke the Inversion Pattern with LDL-P, while still demonstrating its general direction (lower fat = higher cholesterol).
    • Given the pattern up to this point, we’d have expected LDL-P to land around 2200, but it instead landed much further upward at 3348. This is strikingly consistent with with the drop experiment that likewise overshot in the other direction (from 2597 to 1487 in three days!).
    • Yet LDL-C would be expected to land around 355 +/- 22 and sure enough it landed at 368.
  • While I don’t like doing these huge shift experiments, I am glad they continue to reinforce the general mechanics of the Inversion Pattern and further establish its nature.
  • Once again Small LDL-P pops up in a low dietary energy context.

Final Thoughts

  • While the experience wasn’t great, the data from this experiment was golden! As predicted, the Inversion Pattern kicked in and demonstrated just how fast cholesterol can rise while fasting, particularly for a hyper-responder like myself. I guess that last bit doesn’t actually sound like good news, but don’t worry, the blood test taken just 4 days later (not shown) had my Total and LDL cholesterol drop down near where they were on 3/21.
  • I already didn’t enjoy fasting for even a half day before this experiment… now I’m very sure I don’t want to fast for longer either. This might be something I’d consider if I weighed more, but probably not. The incredibly alarming feeling I experienced was something I’d prefer to leave in the past.

[UPDATE]

Hat tip to James DiNicolantonio who pointed out my Uric Acid likely had likely risen and I sure enough it proved to be true:

Ref Range 3/21/17 3/23/17
Uric Acid, Serum 3.7-8.6 5.8 8.2

I run a script that captures every marker outside its reference range and (unfortunately) mostly noticed those that did. Technically, Uric Acid was still inside, but obviously moving upward fast. Would it have gone above range had I been fasting another day? Alas, I’m now unwilling to find out anyway.

63 comments

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  1. Alejandro

    Very similar experience for me.
    1. Ketogenic diet for several month
    2. fasted for 4 days (96hs) before blood work
    3. blood work 14 days later (eating “normally” and not being in ketosis)

    Resutls
    Fasted 4 days ===>>> eating “normally” + not in ketosis
    Tot Col 434 ====>> 338
    Trig 109 =======>> 92
    LDL-C 337 ====>> 259
    HDL 75 ========>>61

    1. Dave

      Wow — yet one more datapoint to show the Inversion Pattern!

      Thanks for the addition!

  2. Theresa F.

    For some reason, I’m not concerned with my cholesterol going up while fasting, nor does the ‘hunger’ that lasts maybe a minute bother me. I feel it’s merely psychological since anyone burning fat has plenty to ‘eat’ in their fat stores. My energy is good, I feel fit and my HA1C went down from 6.7 to a steady 5.4. The effortless weight loss and almost total lack of carb cravings is a real relief, as well, but to each their own. 🙂

    1. Dave

      That’s great! Again, I only speak for my own experience and you’re exactly right that it might have been entirely mental. But that said, it wasn’t my favorite experience, that’s for sure.

      And once more, I have to emphasize that I personally know several dozen people who have been using fasting to great success for themselves.

  3. Nicole recine

    The electrolytes likely reflect dehydratation. I hope you rechecked them since. Those being abnormal can cause heart arrhythmias

    1. Dave

      Hi Nicole!

      Yes, I actually get an electrolyte panel with every blood draw. All markers were back within range four days later, save potassium (which was just a hair above range at 5.3, but was back to normal in the test after at 4.3).

  4. Bryn

    Do you think dehydration contributed to the changes? Particularly in light of the CBC changes?

    1. Dave

      I give it a very strong possibility. My doc thought it was primarily dehydration and recommended really upping my electrolytes after he saw my panels a few days later.

  5. Herbie

    Brilliant article

    1. Dave

      Thanks, Herbie.

  6. Charles

    Why is a TC of 371, DL-C of 284 and LDL-P >2000 GOOD??

    1. Dave

      Not sure I follow — I didn’t call those numbers “good”. I’m appreciative of the data revealed in how these numbers move, exposing more of the pattern. But I don’t believe I’ve ever said I feel my higher cholesterol numbers are good. After all, discovering both how they work and why is the reason I started my research (and this blog).

      1. Charles

        Do you think that your numbers are good? If nit have you ever considered cghanging your diet to lower them?

        Have you ever had a CT Scan and/or a carotid artery scan done?

        1. Dave

          – I don’t know if my numbers are good. I’m well aware the vast majority of doctors would insist they aren’t, but I’m working out the context of both how and why of how they got there from an engineering perspective.

          – Yes — I’ll likely change my diet if I see progressing signs of heightened inflammation, oxidative stress, and/or atherosclerosis. In short, while I feel better than I ever have while likewise having low levels of inflammation and (so far) stable signals for heart health, then I need more reason to change.

          – I’ve had 2 CIMT scans done (and am about to go in for a third) where the numbers are nearly a match. I had a CAC score of 0 from last year and will have another one soon as part of a more advanced CT scan that I’m getting in a couple weeks. Per my point above, I’m very, very actively capturing enormous data on my health and will likely catch one or more signs of declining vascular health early on (I say “likely” because it is still very challenging).

  7. Sj

    I’m wondering what this would look like on a non hyper responder Dave. Any hypothesis on whether it might have something to do with the results?

    1. Dave

      I currently believe this same Inversion Pattern applies to the vast majority of people were they on a low carb diet, and quite possibly if they weren’t. Obviously this would likely be altered if there were an underlying metabolic disease, energy/lipid modifying medication, or weight instability, for example. But absent things of this nature… I’m inclined to bet the pattern would hold.

      In other words, it may well be that anyone on any diet that stuck to the same composition of fat/carb/protein but dropping total quantity would likewise see a spike in their LDL cholesterol as the necessity to mobilize VLDLs (and the stored energy they carry) become higher.

  8. Joe

    I wonder if what you saw here was actually a good thing (if done in the short term, not chronically?!

    If in fact fasting stimulates autophagy, then perhaps we are seeing blood cell turnover where you made lots more and then the old ones get broken down.

    Similarly, since cholesterol is involved in so many repair and production processes such as hormone precursors.

    1. Dave

      There’s just a few of us that think the same thing as I do. That cholesterol is the red herring. That mostly, this is due to higher demand for fat-based energy coming from storage in the form of triglycerides being carried by VLDLs. The cholesterol being measured resides in those VLDL-originating LDL particles, which is why it’s quantity is inverted from the total amount of dietary fat I eat.

      More fat in my low carb diet? Less need for fat-based energy from storage, less VLDLs mobilized, less cholesterol riding along with it. Lower cholesterol score.

      Less fat in my low carb diet? More need for fat-based energy from storage, more VLDLs mobilized, more cholesterol ridding along with it. Higher cholesterol score.

  9. Julie Gregory

    Hi Dave,

    Another fascinating experiment! The folks at ApoE4.Info (www.apoe4.info) have been closely following your work with admiration. We applaud your citizen scientist approach to understanding the role of cholesterol. We’d like to invite you to speak with us at the LowCarb San Diego event in August. We’re especially eager to hear more about what you’ve learned about being a hyper-responder of dietary fat. I suspect your work may have implications for our population. Please contact me at: [hidden] for details. Thanks for your consideration.

    Best-
    Julie

    1. Dave

      Hi Julie —

      Thanks so much for the kind words. I’ve emailed you directly. 🙂

  10. Chris

    Dave,

    Fascinating as usual! I’ve asked you think on Twitter but to reiterate, what I really want to know is: based on lipid response to fasting, when is the ideal time to measure lipids to give the absolute *best” insight into future CHD risk? Is it best to do one in the middle of a normal day, one 12-14 hours fasting, and perhaps one just after a meal?

    -Chris

    1. Dave

      That’s difficult to answer with regard to risk, because risk itself is based on *not* knowing about the Inversion Pattern’s influence on cholesterol testing.

      So if the question is “how can I get my best median cholesterol number?” — I’d say try to eat at the median of your calories/composition for five days, then fast for 12 to 14 hours before. You want that fasting period so you can be sure you’ve cleared out the chylomicrons which would impact the score.

  11. Macro Four

    Interesting that you found fasting uncomfortable. I have done two three day fasts always breaking them for social reasons rather than for feeling unwell. The difference is I am chowing down mostly on my own on body fat as I am overweight. My understanding via the 2ketodudes protein episode is that there is an upper % limit to the body fat you can convert so It makes sense that if fasting when not overweight your body would signal discomfort at eating too much body protein.

    Thanks for putting up with your pain mistress called science!

    Macro Four

    1. Dave

      Funny you say that — I often joke with my wife that “science” is indeed my mistress.

  12. ReneeAnn

    I’m not interested in fasting at all, but am always about 14 or 15 hours fasted when I have my cholesterol checked and I have high total (around 300), high HDL, low trigs, high LDL and high particle count. I wonder if I tried getting tested after breakfast if I would have a better reading? I have not heard of a hyper responder to fasting before.

    1. Dave

      Hi ReneeAnn-

      I suspect you’d have higher trigs and LDL cholesterol if you ate before your lipid test given it would have newly introduced Chylomicrons from your meal being picked up in the measurement.

    2. Nadir

      you should get it checked normally like you do after a 14 hour fast but eat high fat for the three days before like Dave Feldman has done. That will work better.

  13. Rob

    Is it known if the ratio of cholesterol to other “passengers” in LDL and VLDL stays constant? Or could it be that when the body needs more fat due to e.g. Fasting, the relative amount of cholesterol in LDL and VLDL goes down.

    So you see a rise in VLDL and LDL but there might not be a change in the bodies’ total circulating cholesterol?

    1. Dave

      I’m very doubtful the composition of cholesterol on a per particle basis is being up and down regulated. Mainly this is due to how they traffic in the bloodstream in their readiness of circulation.

      1. Rob

        … so the body increases cholesterol production, just because it needs to deliver more fat for energy when in a fasted state

        1. Dave

          Close–

          The body needs to pull more fat-based energy (fatty acids) from storage to fuel cells, which necessitates more LDLp (Low Density Lipoprotein particles) to carry them (as triglycerides), which likewise carry cholesterol. Hence, LDL cholesterol blood tests actually becomes a useful proxy to see what the stored energy is doing, since they are only picking up the cholesterol from storage-based LDL particles (VLDLs).

  14. Charles

    Incredible short term changes, what do you think the long term effects would have been, for people doing 10+ day fasts? Gene changes would kick in?

    1. Dave

      Not sure what would happen with regard to myself, but my friend Tom Seest did a version of my protocol that was fasting only and it showed that past 3 days he noticed LDL-C and LDL-P began to head back down.

  15. Emmanuel

    (Minor typo with small LDL-P: +564 -> +546)

    1. Dave

      Corrected. Nice catch!

  16. Manu

    I see exactly the same effect in my tests. So the implication is to stop fasting because it drives LDL to unhealthy levels?

    1. Leigh Yaxley

      Why assume that the LDL levels are unhealthy? That’s just the old paradigm with which we have all been brainwashed.
      Some people in this world are short and some people are very tall. Is it dangerous for them to be so different to the average height of the human population.
      I think the same applies to cholesterol.

    2. Dave

      Per my discussions on the Inversion Pattern, in this context I’m doubtful the higher cholesterol test score is that relevant for overall “health”. And I emphasize “test score” because if my higher levels of cholesterol were indeed unhealthy, then I believe they were nearly as unhealthy before the fast as I was circulating more cholesterol in chylomicrons in the fed state.

      It helps to know what I mean by this if you’re already familiar with my research and the concept behind the Inversion Pattern.

      1. Leigh Yaxley

        Dave,
        re my twitter comment I have some data to share with you if you are interested.
        Leigh

  17. Fleur Brown

    How about repeating the experiment but trying a 16/8 fast for a few weeks by skipping breakfast….you may lose some weight though.
    Dr Mark Hyman who says he needs to keep his weight up as he is very slim, eats some starches like sweet potato to ensure he doesn’t lose weight so when you eat after the 16 hour fast you may need to add in some low GI starchy carbs perhaps.if you start losing weight.
    Dr Terence Kealey has written a very illuminating and interesting book on skipping breakfast ” Breakfast Is A Dangerous Meal “….

    1. Dave

      Thanks — I’ll check out their work on 16/8. But I’ll concede fasting is now a bit lower on my list now given the new set of experiments.

  18. Philip

    Just got lab results today which flabbergasted me. I have been on the extreme LCHF version of my diet needed to actually lose weight (I shoot for 500-1000 cal, 90% from fat and most of that saturated fat).

    BTW, doing LCHF for over 5 yrs.

    Cholesterol numbers are through the roof for me:
    LDL-P 2260
    LDL-C 227

    HDL-C went down from my usual range and is at 53.

    What interests me about my results are the high Triglycerides (168) and high glucose for me (104). Any speculation about what would drive these numbers up due to my near-fasting? If I need to get myself up to speed science-wise here, any resources to understand this mechansim?

    1. Dave

      Both the LDL-C and LDL-P are comparable to mine (avg 270 and 2400, respectively), suggesting you are a low carb hyperresponder as well. But the HDL-C of 53 and Triglycerides of 168 are unusual. That said, they aren’t necessarily worrisome depending on the context.

      If you’ve been reading my blog, you should know your diet and activity in the 3 day window of time before your blood test has a massive impact on your -C scores (with the 3 day window + 2 day gap for your -P scores). Did you eat an unusually lower amount of fat and/or calories in the days leading up to your test?

      1. Philip

        I went off half-cocked in my post. Frankly, I was panicked by the test results and came by your blog that way. Apologies. I have now read the whole blog, understand the science and your project.

        I have been doing something akin to what Atkins called the fat fast, except I restrict calories even more than he suggests (sometimes as low as 250-300 cal/day). I need to do this to get any weight loss. I even hold steady weight-wise at 1000 cal/day.

        I can’t imagine how much weight I’d gain at 5000 cal per day, even in 3 days. Did you and your sister see large weight gains? I have to scrupulously watch protein intake as well as carb.

        Planning to go back to maintenance once I reach weight goal. I will re-test at that level (90% fat).

        1. Dave

          I actually don’t have much data on fat fasting with regard to lipids as neither myself nor anyone who has reached out to me was doing this (that I know of). But in theory, I’d certainly expect lipid numbers to look “bad” relative to your being on a maintenance ratio.

          Again, if you’ve been following the inversion pattern, you know that your “bad” markers (LDL-C/-P and Trigs) will rise while the “good” (HDL-C/-P) will fall given you are trafficking more from storage. This is why I fully expected my markers would do exactly this for the fast I did from above.

          Please don’t feel you need to do the protocol if you are only looking to know what your numbers are for your median diet. Take the test when you are back around to it and you’ll have a better sense of what your average numbers are.

  19. Marie

    I wonder if the rise in your numbers with fasting is a type of stress response. I am a hyper responder and recently noticed a huge rise with acute stress – in a nutshell, I was admitted to hospital and very worried, cholesterol on admission 250, then sent home next day thinking all was ok, relaxed, then 3 days later got the results I wasn’t ok and spent the next 4 days in hyper stressed mode worrying myself sick. Cholesterol was 350 at next appointment! 10 days later in reduced state of stress, cholesterol was 227. This was all psychological stress not physical. So, do you think raised cholesterol is a response to cortisol – hard to do an experiment on this though!?

    1. Dave

      I absolutely believe hormones can play a roll, and especially those activated by stress like cortisol. But that said, I now firmly believe nothing trumps energy. I now have far too many data points to feel otherwise.

      Indeed, in a stressed state (particularly with modifiers like adrenaline in play), the body can require energy to be used at a far faster rate to meet the needs of readiness and intensive focus (both big metabolic burners).

      Possibly: Higher Stress => More Idle Energy Burned => More Energy Needed from Stores => Higher Cholesterol via VLDLs

  20. stephane

    Hi dave

    Thanks for providing such a useful information. I’m an hype-responder too and never tried longer than 14 hours fasts. Maybe one day I’ll try it with your experiment in mind to see if I can stand it.

    Apart from that, I’m wondering why Lipid tests don’t include NEFAS (Non Esterified Fatty Acids). If I’m not mistaken they take some part in the Lipid trafficking in the blood stream the difference being that they don’t come bundled in Lipoproteins but are bound to Albumin. Isn’t this a missing data point in any study about Lipid levels ? To my knowledge, they can be elevated in a series of conditions like Insulin resistance, uncontrolled Type 1 Diabetes and prolonged fasting.

    Thanks

    1. Dave

      Actually you’re right inside my wheelhouse with NEFAs as it is something I’m actively studying and trying to tease out myself. It is also a strong explanation as to why many who are lean and/or athletic (like myself) are disproportionately hyperresponders. But this is a medium correlation, not a strong one, so there’s still more studying to do.

      I actually have some papers on this in my reading short list that I need to get back to here soon. But without question, they are certainly a key factor in the overall Fatty Acid Cycle.

      1. stephane

        Ah ah the Typo “Hype-Responder”. Damned, I’m unmasked !

        Anyway thanks for the reply. Good to know that I’m not alone wondering about those molecules.

  21. Nils Hoernle, MD

    Hi Dave; These are curious results (speaking as a doctor who looks at lab results all day every day). The high potassium is surprising, and could be from hemolysis during the blood draw (the needle tip not being exactly in the vein slices the passing red cells open, releasing potassium). Or from the electrolytes?

    Also, it’s unusual to see a true bump in Hct from one day to the next unless it’s from vascular volume loss (so the increase is relative to the decrease in blood serum). Fasting, we know, causes insulin to drop and Glucagon to rise, thus mobilizing our fat stores for fuel. But because Insulin causes sodium retention, it raises intravascular volume, and by fasting and thus dropping Insulin, there is a diuretic effect as sodium is dumped via the kidneys, and water follows it. (Hence the quick wt loss seen w a ketogenic diet, and the drop in BP). So you are probably not “dehydrated” as such, and probably don’t need to take electrolytes for such a short fast.

    A couple more points;
    – it’s hard to draw real conclusions from an “n of 1”, so please, please, repeat this and see if you get the same results (I’m guessing not)!
    – a lot of us (and likely you as well) are starting to conclude that chol and lipids made by the body naturally are normal healthy components of energy distribution, and their quantity (as opposed to quality) does not directly cause atherosclerosis. Plaque seems more the result of corruption of the particles from things like oxidation (smoking, artificial Trans and Oxidized fat (polyunsaturated seed oils), HTN (vessel wall stress), inflammation (immune response to damage from AGE’s from excess sugar, processed foods, additives, toxins, allergens, invaders, etc), calcium buildup from under-carboxylated Matrix GLA Protein due to Vit K2 (menaquinone-7) deficiency, and direct negative effects of Insulin on the endothelium (DM2 and Insulin-resistant DM1’s).
    – I have been reviewing CAC scores for my patients for almost a year now, (n=40), and have found no relation between high LDL and high calcium scores. There is a strong relationship between the Trig/HDL ratio, however (marker of Insulin resistance), as well as the ALT and AST (marker of hepatic inflammation and cell death, over about 20), cardiac CRP over 2 (inflammation of vessels), fasting Insulin over about 10, and A1c over 5.5 (3 mo avg blood sugar).

    PS – I love your inquisitiveness, and your inversion theory of cholesterol, and hope you keep pushing the envelope!! Below is a link to a really great article on Intermittent Fasting and it’s benefits. (I fast 16 – 23 hrs a day, and absolutely LOVE the way it makes me feel! My brain is sharper and more focused, and by exercising while fasting I have built much more muscle mass (and skiing agility) from the elevated Growth Hormone and BDNF (Brain-Derived Neurotrophic Factor). Note that it does take most folks about 2-3 weeks to switch to this form of metabolism)

    authoritynutrition.com/10-health-benefits-of-intermittent-fasting/

    1. Dave

      Hi Nils-

      Great comment!

      – The high potassium may have been due to my using Morton’s Lite Salt mixed in water as was advised by a friend who does frequent fasting. It was his favorite way to supplement potassium, but I might have overdone it. (I think I averaged 1 tsp / day)

      – Another possible confounder with the electrolytes was the amount of water I’ve been drinking heading into the blood test. I would usually average between 2 to 2.5 liters in the 2 hours before the test out of advice I had long ago from a doctor to help with the blood draw for my hard-to-reach veins. I had asked him at the time if it would have any impact on the tests to which he said, “almost none” — but I now believe otherwise. Unfortunately, I’m locked into it for now as I don’t want to change a variable that is present with all prior blood tests until I can do a comparison experiment to control for it.

      – Not sure I’ll be repeating this test, or at least, that I’ll be doing it soon. I have something very big on my plate now, but I might come back to it again later.

      – I agree with just about everything you said regarding cholesterol. While I can’t say I know for sure that I can rule either way just yet, it is always comforting to hear from other doctors who actually have a practice and see patients on a regular basis what the patterns are. Certainly I’m much more concerned about inflammation and oxidative stress for CVD health overall.

      – On that note, my one concern that I’ve mentioned here and in other places is my mysteriously high ferritin levels (generally in the 600s). I’ve done a few iron panels that come in normal range and it doesn’t appear genetically likely as hemochromatosis [ given rs1799945(C;G) rs1800562(G;G) ]. Thus I am concerned it is a possible indicator of oxidative stress. (The scientist in me is more annoyed at it being a research distraction from my normal lipid focus.)

      – Thanks for your kind words on the PS. It really has been an unexpected journey in so many ways. 🙂

  22. Leigh Yaxley

    Dave,
    I have a simple explanation to offer. Here goes:
    1) Since you are well adapted to LCHF your metabolism is primarily utilizing fat for energy.
    2) During the 3-days of low fat consumption (and especially low fat + calorie deficit – the extreme drop) you are effectively ‘starving’ your metabolism and it will compensate by cranking up lipolysis of adipose tissue and greatly increasing your level of circulating free fatty acids (FFA) – akin to fasting.
    3) Most people think of adipose tissue as just ‘fat storage’, i.e triglyceride (TG) storage but it is also a large reservoir of stored cholesterol.
    4) The size of the cholesterol reservoir is proportional to the TG content, which suggests that homeostasis of cholesterol within adipose tissue might well be tightly coupled to TG metabolism. If so, any cranking up of TG lipolysis will likely be accompanied by an increased efflux of cholesterol out of adipose tissue along with the FFA.
    5) During fasting/semi starvation the rate of fatty acid cycling is much greater than actual oxidative demands – probably by a factor of two to three times. Therefore if cholesterol and TG metabolism from adipose tissue are indeed coupled there is a good chance it will get manifested as an increase in serum cholesterol.
    6) I will avoid trying to theorise a detailed mechanism for how the different lipoproteins participate in all of this except to say that it probably begins with an increase of HDL in order to reverse transport the increased cholesterol efflux and increased HDL is one of your observations.
    7) Now during the 3-days of high fat (and hypercaloric) re-feeding I think the opposite of the above happens. Adipose tissue lipolysis is cranked down and probably stops as chylomicrons and FFA flood in. Again if the ‘coupling’ assumption is correct the cholesterol efflux from adipose will also be cranked down and get manifested as a decrease in serum cholesterol.

    1. Dave

      1) Yes
      2) Yes
      3) Yes – mostly
      4) Yes – mostly
      5) Here’s where it gets a bit trickier. Yes the fatty acid cycle is in play and to the degree that the components found inside LDL particles (TGs and cholesterol) are more readily available is certainly a key component. (See more with NEFAs, of course)
      6) That’s actually a very large subject that takes much more unpacking.
      7) (See below)

      The mechanism as you are describing it is a supply-driven process, rather than a demand-driven one, which is where my headspace started out. And this is likewise where most doctors and researchers believe it to be.

      It’s actually the data itself that started me questioning it otherwise. The more tightly I saw the inverse correlation between dietary fat and LDL cholesterol (as well as LDL particle count), the more I realized it had to be a regulatory mechanism. This isn’t to say there is a single operator (such as the liver) that is orchestrating the the entire process, but there *does* appear to be a target configuration while on a specific macro-energy breakdown (keto diet). And many different players have the regulation instructions baked into it in order to meet that target.

      I come back to it again and again as the data is telling this to me — it’s all about the energy. The body clearly wants to keep both long term and short term (readily available) energy in place and this is shown to be more of a demand-driven process than a supply-driven one.

      In short, we can theorize the different pathways involving insulin, NEFAs, gut vs liver production of LDLp, etc. But for all these disparate elements to *coincidentally* land in the same high correlation distribution over and over again doesn’t fit Occam’s razor. Rather, it is the reverse — that something is influencing their pathways in a staging-and-pacing manner that resembles more of a cloud network that I see all the time in my line of work with load balancing (which would be consistent with many other operations of the human body).

      1. Leigh Yaxley

        I don’t follow why you say I am describing a supply-driven process.
        The process I have suggested is demand driven because it is trying to maintain the body’s fatty acid futile cycle in the face of semi-starvation. This is precisely an energy demand, for which reason the body releases stored TG in the form of NEFA’s.
        The futile cycle circulates these NEFAs at a rate, which is about 2 to 3 times higher than the actual metabolic oxidative requirements and the liver acts as a buffer for some of the excess circulating NEFAs by churning out more VLDLs.
        I am suggesting that your periods of low fat intake are akin to semi-starvation because your primary (maybe even 100%) source of energy is fat for direct oxidation and for ketone production.
        Your observation of increased LDL-P (albeit with a lag) following low fat intake/semi-starvation would be consistent with the liver increasing its VLDL output, which ultimately has to mean more LDL-P as the VLDL degrade.

        Now digressing back to cholesterol and considering just total serum cholesterol I observe the following:
        From your ‘identical diet experiment’ the consecutive swings in total serum cholesterol concentration from one 3-day period to the next range from about -60 to +70 mg/dL for yourself and about -30 to +55 md/dL for Darla (as best as I can read the data from your charts).
        However, the two of you must have very different blood serum volumes, probably around 3 liters for yourself and 2 liters for Darla. This means that although the changes in cholesterol concentration may look similar the consecutive swings in absolute serum cholesterol are rather more different, viz
        Dave: -1800 to 2100 mg Darla: -600 to +1100 mg

        I am postulating that these transient swings in serum cholesterol arise from the energy demand driven changes in adipose fat storage on the assumption that cholesterol has to be expelled along with TG during lipid droplet lipolysis and taken-in again when the metabolism switches back to fat storing mode.
        I think (but it needs checking) that the average cholesterol content of adipocytes is about 5 mg per g of stored TG, in which case the observed cholesterol swings would correspond to the following range of consecutive fat storage changes:
        Dave: -360 to +420g Darla: -120 to +220 g
        or since these occur over 3-day periods the corresponding average daily change estimates are:
        Dave: -120 to +140g/d Darla: -40 to +70 g/d
        The two of you ate identical diets but your energy demands are quite different. (78.5 kg male versus 64.4 kg female). Hence I would expect that your fat ‘turnover needs’ under the experimental conditions should be greater than Darla’s – as indeed the data suggest.

  23. Bert mellinger

    Occums Razer. Dave what if you redrew your charts with the following formula: Fat= Calories burned – dietary carb – dietary protein. So fat is 100% while fasting. And while in a calorie deficit, fat is dietary fat plus deficit fat burned.
    This would explain the continued increase in ldl p while fasting.

    1. Dave

      Interesting theory, Bert. When I next make a pass at my spreadsheet, I might play with that equation.

  24. beags

    Hi Dave – are all your blood tests done, fasted (e.g. overnight if not ‘fasting’) and at the same time?

    I’ve been in and out of keto for a few years and generally just supplement carb for intensive cycle rides. I’ve stopped counting macros but my last (overnight fasted) bloods where not so ‘good’:

    HDL 82
    LDL 432
    TRIG 122
    TC: ??!!

    1. Dave

      Yes — before *every* blood test I aim for around 14 hours of total water fasting to stay consistent. This experiment was the *only* time I went for longer than those 14 hours by design.

      Your profile falls right in line with an athletic hyper-responder. Indeed, I need to do a post on this at some point given how frequently I see it now. Mechanistically, the higher LDL makes sense given you need to traffic more total trigs to feed your cells meeting your energy demands (given you have lower adipose energy stores from being lean and lower relative glycogen stores from being low carb).

      In fact, I don’t think I’ve yet seen a single lab where trigs were < 150, HDL > 60, and LDL > 300 that wasn’t a lean and/or athletic low carber.

      1. beags

        Thanks for responding, Dave. These results have me questioning EVERYTHING! Going to now knock off Saturates for a couple of months and see if that turns the tide – I just don’t remember how I used to eat pre-LCHF!?!

        Read about perhaps upping fibre to help but If I start down the oats or grains route I find that’s a slippery slope back into all out carbdom.

        I am near my leanest (64kg/5’10″/14%bf),due to cycling occurring at this time of year but I wouldn’t say I’m super lean.

        Thanks again for your time. Do you do consultations?!

        1. Dave

          I’m happy to chat with people via Skype here and there, but I never charge. While I might someday have a patreon account to show the “sausage making” of my experiments, I plan to always have my data and analysis free to the public.

        2. Nadir

          Dave, this is Nadir – the cardiologist. I am interested in this data if you have. I am also a die hard cyclist and have several team members who are in the LCHF camp. They have not checked their numbers but I am interested in any information you have on athletic hyper-responders who are cyclist. I guess, what you are saying is that if they start out a ride in a fasted state, they will have no chylomicrons and thus will make a lot of VLDL to provide energy. Thus cyclist doing this repeatedly several times a week are burning fat and sparing the glycogen. Thus in order to for the muscles to get the Trigs to burn, the liver churns out more VLDL. I wish someone would do a mechanistic study on the cyclist following the LCHF vs the high carb diet.

          1. Dave

            Hi Nadir–

            Just to update anyone following this thread, you and I spoke over skype between the comment you made above and my response here.

            But for posterity, I’ll answer here as well — yes, the lipolysis in the fasted state would ultimately lead to production and recirculation of more VLDL-originating lipoproteins. This would likewise appear as though their “cholesterol went up” on a blood test, given a blood test is picking up almost entire VLDL-originating LDL cholesterol.

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