The OxLDL Replication Experiment – Findings – Part I

This experiment was conducted from August 30th to September 14th over three five day phases: a maintenance (weight stable calorie), hypocaloric (low calorie), and hypercaloric (high calorie).

See OxLDL Replication Experiment Design post for further information on setup.

Again, this experiment was executed with the intent replicate the prior OxLDL experiment in April of last year. As such, we have excellent comparison data as well.

But of special interest is the “OxPL-apoB” assay offered through Boston Heart Diagnostics. It was a key consideration given my interest in this metric long before it was even commercially available. (More on this in the next post)

General Observations

Overall, the experiment went very well. I was able to keep eating very close to schedule and exercise roughly equivalent as intended.

I did experience some calf and foot cramping in the late evenings and early mornings characteristic of electrolyte depletion. This took place two days into the Hypocaloric Phase and I responded by adding additional electrolyte supplements along with added salt dissolved in water (food log coming soon). These issues persisted until three days into the Hypercaloric Phase.

And sure enough, the bloodwork coming back after the experiment for both the hypo and hypercaloric phases showed below reference range for both Sodium and Chloride (see data).

Daily Metrics

Each morning within 20 minutes of having woken up I would test: Glucose (Keto Mojo), beta hydroxybutyrate [BHB -> ketones] (Keto Mojo), lipid panel of total/LDL/HDL/triglycerides (CardioChek), and body weight. A few days in I added Acetone (Biosense).

Note in all the graphs below that “v1” refers the first OxLDL experiment and “v2” refers to the replication experiment just completed.

Body weight will be very unsurprising, of course. In each experiment it generally maintained during baseline, dropped in hypocaloric, increased in hypercaloric.

Same with glucose…

LDL cholesterol levels were generally noisy, but did follow the inversion pattern overall, going higher in hypocaloric, lower in hypercaloric.

Now here is where it gets interesting. It’s entirely expected that ketones overall would rise as I went hypocaloric and would fall as I went hypercaloric. But note the largest spike wasn’t after the last full day of the low calorie phase — it was after the first full day of high calorie phase. (Remember these tests are taken the morning of the day listed)

We see this exact same surplus also reflected triglycerides. In fact, this is the most substantial change in all the data collected, and is demonstrated in both experiments, of course.

Lastly, I want to point out this becomes the corresponding nadir for HDL cholesterol.

These last three — BHB, triglycerides, and HDL cholesterol are extremely central to the Lipid Energy Model. In fact, if we didn’t see these change for our controlled setting (thus, removing competing confounders), this it would have provided strong evidence against it.

The important takeaway beyond the general phase-specific patterns is that brief period where we can actually observe what appears to be the “traffic jam” of fuel transport (as reflected in BHB/TG) and turnover (as potentially reflected in HDL-C). Moreover, we have a spike of fat-based energy sources coming in from Chylomicrons that I believe will directly compete with VLDL binding/uptake.

In our coming Lipid Energy Model paper, we will have more supporting studies in particular that are relevant to the triglyceride and HDL-C relationship as it pertains to VLDL triglyceride turnover, but I won’t be going into that here.

End of Phase Bloodwork

After completing each five day day phase I had blood taken that went to two labs, Labcorp and Boston Heart Diagnostics. Siobhan and I already have lots of experience working with Labcorp for the last several years and it’s our primary provider for OwnYourLabs.com. Boston Heart is new for us, but it has definitely been a very positive experience thus far – both in testing and customer service.

I’ve combined the calorie and diet macros, the Labcorp tests from both experiments, and the Boston Heart Diagnostic tests for this experiment into one spreadsheet which you can download here:

Raw Data for Labs (version 0.7)

PLEASE NOTE: As of this writing, the raw data spreadsheet isn’t fully cleaned up with regard to reference range artifacts, etc. We hope to have that done in another pass soon and will update this page (and its version) accordingly.

Not surprisingly, we see many other blood markers in support of the energy model here:

Up Next – Digging Deeper into the Bloodwork

This post was primarily focused on reporting the data coming back and how it related to the Lipid Energy Model.

Next week we’ll dive into the many, many other amazing aspects of this robust dataset and what it can tell us about these markers.

Our Work Discussed on The Joe Rogan Experience!

In the podcast dropped today by the prolific Joe Rogan, our work with the Lipid Energy Model, consideration of lipid risk in a metabolic context, and of course, the LMHR Study all got some decent airplay.

Mega thanks to Paul Saladino who brought all these concepts up about an hour and 49 minutes in. (The video link above is queued to that time)

Talking Cholesterol, Oxidation, Hyper-responders, and Risk with Paul Saladino

Had a great conversation with Paul. Not surprisingly, lots of topics came up with regard to the risk, my current oxLDL vs oxPL experiment, my recent research regarding FH receptors, etc.

I did mention tendon xanthomas and why it is that I’m looking very closely for it with hyper-responders in general, and LMHRs especially (as you’ll note from my many posts requesting this information)

And of course, I mention the LMHR study at several points, including my pointing to how I feel those skeptical of LMHR having high LDL should be the most proactive in helping us make this happen.

Presenting on Lipoprotein(a) For Low Carb Houston

As some of you may know, I got the opportunity to present on the topic of Lipoprotein(a) for Low Carb Houston 2019. Just this past week the video was released, and is now available to view!

This can basically be thought of as an improved, fleshed out update of my Big Deal About Lipoprotein(a) post, so if you’re curious about my thoughts on lipoprotein(a) I’d recommend giving it a watch!

I also provide some data from some of my own experiments, including my pork versus beef experiment, and experiments showing lipoprotein(a) following LDL-C e.g. during the protocol.

As always, discussion is welcome especially as this is a topic that’s far from closed – there’s still plenty to learn and I look forward to doing so as more work is done to understand – the still quite mysterious – lipoprotein(a).

Long Term Fasting Experiment – Design and Predictions

Lately I’ve been experiencing an urge to fast for longer than the 36 hours per week I’ve been doing over the last month or so, thus I decided to fast for as long as I can (safely and comfortably). Of course, I couldn’t possibly do this without gathering at least a little data, so it will be a bit of a loose experiment as it stands.

Experiment Design

The experiment will have multiple stages, that – except for the beginning and end phase – are not at a set length. They are as follows:

  1. Baseline
  2. Water fasting
  3. Fat fasting
  4. Re-feeding

Baseline

During the baseline, from September 1st to September 7th I’ll be consuming an ad libitum diet of 73/27 burgers (pre-formed), butter, and commercial pemmican. Beverages will include tea, herbal tea, and flavored sparkling water (no sweeteners). Supplements will include my normal fare of a methylated B vitamin complex, and vitamin D. Electrolytes will be consumed as needed.

1 mile of walking will be done every morning as is my usual.

Water Fasting

During water fasting, no calorie containing beverages or food will be consumed. Supplements, electrolytes, and beverages will be consumed as outlined in the baseline, and exercise will also continue as normal.

This phase will continue as long as I can comfortably maintain it, I suspect around one or two weeks.

Fat Fasting

If I reach a point where water fasting becomes uncomfortable I’ll be adding fat (via homemade broth made from marrow bones, and fat [e.g. cocoa butter and/or butter] added to hot beverages, according to hunger. I’ll continue this phase as long as I can comfortably do so.

Exercise, supplements, and beverages will continue as previously outlined.

Re-feeding

After I can no longer comfortably fast, or fat fast, I’ll return to eating by slowly breaking my fast and then returning to the baseline diet. After a week of re-feeding I’ll conclude the experiment. Exercise, supplements, and beverages will all follow the baseline, as well.

Data capture

I’ll be recording the following over all phases of the experiment:

  • Glucose (daily, morning)
  • Ketones/BHB (daily, morning)
  • Acetone (daily, morning)
  • Weight (daily, morning)
  • Measurements (waist, hip, thigh, arm; after baseline, weekly during fasting phases, after one week re-feed)
  • Blood testing (after baseline, weekly during fasting phases, after one week re-feed)
  • Food/Beverages/Supplements consumed (picture logging; constant throughout all phases).
  • Fasting time (via free fasting app, delineated between water and fat fasting)

I’ll be getting 12 tests total during each blood draw. This is pared down from what I’d usually get, but covers many metabolic markers.

  • Comprehensive Metabolic Panel (14)
  • Insulin and C-Peptide, Serum
  • Ferritin, Serum
  • Fatty Acids, Free (Nonester)
  • Complete Blood Count (CBC) With Differential
  • Glucagon, Plasma
  • Uric Acid, Serum
  • NMR LipoProfile
    • HDL-C
    • HDL-P
    • Total Cholesterol
    • LDL-C
    • Triglycerides
    • LDL-P
    • Small LDL
  • Lipoprotein(a)
  • GlycA
  • Oxidized Low-density Lipoprotein (OxLDL)
  • Leptin, Serum

Over the course of the fasting portions I expect the bolded items to decrease and the italicized items to increase. Non-marked items are unknown, or contain multiple tests.

As a side note, I don’t expect GlycA to significantly change over the course of the fast. I expect triglycerides to initially increase and then fall back to normal over the course of the fast. I expect ketones to increase and glucose to decrease over the course of the fasting periods, and weight and measurements will decline. By one week post re-feed I expect blood markers to return closer to baseline levels, with some (although not total) regain in weight and inches.

Safety

I’ll be checking in frequently with Dave on how I feel throughout the fast, and in contact with my primary care doctor. If I ever feel unwell, especially any nausea or abdominal cramping, I’ll immediately abandon the experiment and eat. If I ever feel “off” or feel like I should call off the experiment due to any health/safety concerns I will do so without hesitation.

Conclusions

Overall I am very curious to see how things will change over a longer term fast. I’ve previously done a 7 day water fast, outlined here, but this will (hopefully!) extend even beyond that. Adaptions to longer term fasting is definitely something I’m interested in, especially given some studies I’ve been reading recently, and as I’m currently “overweight” I feel I can comfortably take it on. I’m also curious to see what changes may occur comparing water fasting to fat fasting especially in regards to weight, and blood markers.

Given the longer fasting time I’ll definitely be overly cautious about safety and being sure I call off the experiment if I feel it’s necessary for my own health. Other than that, I feel pretty confident overall, especially given I have access to a doctor who has other patients who fast regularly, and am looking forward to sharing back the data.