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Jun 22

Cholesterol Code – Part III : The Divergence

In Part I, I shared the data of my first 15 cholesterol blood tests and how closely it correlates with dietary fat. To recap:

  1. My cholesterol baseline jumped after starting a ketogenic diet, which led me to do close blood testing against a theory I had on the lipid system appearing as a network (more on that theory later)
  2. If the theory had merit, there would be two tenants to assume:
    1. The cholesterol transporting lipid system would prove to be agile – much more so than is typically believed (this appears to be accurate).
    2. Discrete patterns should emerge between the diet and serum cholesterol now that disruptive inflammation is lower (this certainly appeared to be the case).
  3. After the testing, my bloodwork showed the following:
    1. The more fat I ate, the lower my Total Cholesterol. (87% inverted correlation)
    2. The more fat I ate, the lower my LDL-C. (90% inverted correlation)
    3. The more fat I ate, the lower my Triglycerides. (61% inverted correlation)
    4. The more fat I ate, the higher my HDL-C. (74% correlation)

 

In Part II, we moved beyond LDL-C into total and small LDL-P and their differences in the findings.

  1. LDL-P and small LDL-P appeared to have a correlation with a three day average of dietary fat as like LDL-C, but with a key exception of adding a two day gap between the dietary period and the blood test.
  2. Small LDL-P appeared to correlate closely with LDL-P but at a higher gain to loss ratio.
  3. Both LDL-P and small LDL-P proved to be extremely agile and easily ramped up or cleared when observing via daily blood tests (data points 9-14). In fact, shifts in the hundreds of particles per day were easily achieved in either direction.

 

The Ratio Problem

If I were playing devil’s advocate to my own research up to this point, I could make the case that we can’t be completely certain my LDL cholesterol was inverting with fat, since the same could be said for protein. After all, my protein intake ran very proportional to my fat intake, even if at a smaller fraction. When running Three Day Average Protein against the LDL-C, I also got a significantly close correlation at -0.789

protein3_vs_ldlc_positive

Inverted…

protein3_vs_ldlc

Thus, we need to have at least one experiment to have a lopsided ratio of one against the other relative to the ketogenic ratios.

The Intended Divergence

Me being me, I decided to do two tests: one with a Super High Fat (SHF) ratio 95% fat / 4% protein / 1% net carbs for three days, and one with a Super High Protein (SHP) ratio 50% fat / 45% protein / 3% net carbs for three days. And finally, I added a third test in the following four days at closer to my usual ketogenic ratio with 75% fat / 21% protein / 4% net carbs  to see if my numbers snapped back into the original correlation.

 

 fat_sprint  protein_sprint  snap_back

To meet the requirements for the Super High Fat sprint, I averaged 293g fat, 31g protein, and 4g net carbs.

Here’s a sampling of the food I was eating over those three days:

fat_foods

Here are the results:

three_fat_vs_ldlc_16

Inverted…

three_fat_vs_ldlc_16_r

Sure enough, at a preposterously high ratio of fat to protein, my inversion correlation appears to still follow the fat, not the protein. My blood ketone levels (BHB) over these days were 2.1, 2.1, and 1.4 respectively.

Then I switched to Super High Protein. Over these three days I averaged 119g fat, 233g protein, 13g net carbs.

I was actually looking forward to this part of the experiment given I’ve always been a big fan of meat. In fact, I wondered if I wouldn’t get hooked on the higher protein ratio due to how much more meat I was allowed to consume.

Here’s a sampling of the food I ate:

protein_foods

But then something unexpected happened…

notes

In addition to all this biometric data I collect, I also keep regular notes on any unusual aches, nausea, or pretty much anything I feel that seems out of the ordinary. As I was getting to the end of the Super High Protein sprint, it was the only time I felt gastrointestinal distress that I associate with my days before the diet. It was a familiar feeling, but certainly not one I was missing.

I likewise felt heavier and less energetic, taking a nap on two of the three days. While I knew I was generating a higher glucose load via Gluconeogenesis due to all the protein, I actually rechecked all my food labels to make sure I didn’t accidentally eat something high in carbs.

Here are the results:

three_pro_vs_ldlc_17

Inverted with overlays…

three_pro_vs_ldlc_17_r

No question – we have a clear divergence where LDL-C does not follow dietary protein for the last two data points, Very High Fat (VHF) and and Very High Protein (VHP). Note it didn’t follow the dietary fat for this period either:

three_fat_vs_ldlc_17_r

It’s worth taking a moment to point out two very important observations.

First, if my only goal was to reduce my “bad cholesterol,” this would appear as good news. Assuming this trend held, having higher protein and less fat would result in lower LDL-C. As you can see from the graph above, were the inverse correlation holding, the lower 119g of fat would likely push up the LDL-C to around 323 rather than the 263 we see instead.

However, the energy level and GI issues I was experiencing were certainly a drawback. It also seemed to fall in line with the second tenet of my theory if it was causing inflammation.

See, here’s where the dark side of my theory comes in. What if there are steps I can take which lower my LDL cholesterol but only because it increases inflammation and/or oxidative stress? I might interpret this as a good outcome when it’s happening because, as everyone well knows, lowering dangerous cholesterol is all that matters.

Yet what if my body is sending me the correct signals in the first place? High Carb = feel slower, with occasional GI issues.  Low Carb, High Fat = feel great with little to no issues. High Protein, Moderate Fat = same as High Carb.

I decided to do my final data point to follow the VHF and VHP, which did snap back to the correlation envelope. I then went on the Low Carb Cruise and connected with a few more doctors to discuss the data. After getting back, I did my 19th and 20th NMR with the intent to bring all my data to this blog by the end of May.

But I was in for one more twist. The biggest yet, in fact.

The Unintended Divergence

Here are all 18 NMRs where I was on the normal ketogenic diet (removing the SHF and SHP data points) with inversion:

three_fat_vs_ldlc_18b_r

Spot anything unusual?

Yes, data point 18 at the far right shows the largest single divergence in the correlation of any other coupling in this graph. Was it a lab error with my blood? Was it something I ate or drank differently?

The only major change I made was cutting out diet soda the week before (primarily Coke Zero). So I first kept to no diet soda for another week and did one more test just to be sure it wasn’t a lab error. The divergence appeared to hold (see below with 19).

After that, I went to town with Coke Zero for three days to see if it would spike the correlation to the other side. It seemed outlandish to think aspartame could have kept my cholesterol artificially high, but I had to be sure. Again, the divergence held (see below with 20).

three_fat_vs_ldlc_20_r_callout

This new data suggests my LDL-C has been dropping all on its own (and by extension, Total Cholesterol).

But data points 17-20 did not significantly change the correlations of HDL-C, LDL-P, or small LDL-P. In fact, it improved them slightly.

Other Markers Improve Correlation

HDL-C had a -0.733 before, now it is -0.761.

fat3_vs_hdl

LDL-P had a -0.812 before, now it is -0.845.

Inverted…

fat3-2_vs_ldlp

LDL-P had a -0.726 before, now it is -0.781.

Inverted…

fat3-2_vs_smldlp

Next Steps

Will data points 1-16 represent a temporary “phase” of my diet with regard to LDL-C, proving 17-20 as the New Normal? Or is it the other way around? Your guess is as good as mine given the 6/9/16 test was the last one I took as of this posting.

The next blood test I’m taking is this week and it will be a very large combo pack of CMP, CRP, A1C, and other goodies in addition to the NMR. I’ll need to as I’ll be making some large changes to my exercise schedule. Starting next weekend I’ll be training for half marathons in the coming months. Will it start to impact my numbers? Stay tuned…

Coming soon – The Lipid Network Theory (Or “What Led Me Down This Rabbit Hole in the First Place”)

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Prediction Contest » Cholesterol CodeDaveAnnie Q: SusanChayNYC Recent comment authors

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raphaels7
Guest

great analysis.

You hit the protein ceiling pretty hard it seems. Back in cave man days we were happy to give our lean kill to our domesticated wolves & keep the fattier cuts for ourselves.

Timothy K Foxon
Guest
Timothy K Foxon

Thanks for this Dave, lots to think about, really useful.

Regards.

Nicole
Guest
Nicole

I was referred to your blog by peter defty. I thought Id share my NMR results after 8 months of keto
TC: 687
TRIG: 88
HDL:152
LDL: 515
LDL-p: 3203
HDL-P: 31.8
small LDL-P <90
LDL size 23.0nm
Insulin fasting: 1.3
HS-CRP <0.2

I am very lean as far as body fat goes. I have been weight stable since starting keto. . I am also very well versed in reading these numbers, so I am not too concerned. but I have yet to come across numbers this high. I wanted to share my data. I test about every three months. So far i have seen an increase in LDL-P and a decrease in trigs.

Tom
Guest
Tom

My NMR results

TC: 346
TRIG: 41
HDL:74
LDL-C: 264
LDL-P:2412
HDL-P: 28.7
Small LDL-P:374
LDL size: 21.6

ChayNYC
Guest

I’m a hyper-responder.
Also a journo, so I prefer to provide my data to you via email.
Please contact me via coelicarr(dot)com
I initially connected with you via Twitter about my high numbers.
You referred me to your content at CholesterolCode, which I was glad to read.
Thanks,
C.

: Susan
Guest
: Susan

Hi Dave
Really interesting.

I am only able to get a standard lipid panel test. But have been low carb for many years. My numbers are
Total Cholesterol: 475
LDL-c: 321
Trigs: 319
HDL: 46
Dr wants me on statins of course.

I fluctuate my intake over 7-10 days. Carbs between 30-75 grams, Fat 150-175 gm Protein 75-90 gms
Depends on how I feel, and how much exercise I do. Every now and again I do super high fat for a few days.

My high trigs and low HDL are a bit of a concern, but not sure how worried I should be as fit, healthy, and stable weight: 60 kg: 132 lb.

I am keen to do your testing protocol and will report back on the results. I haven’t had the genetic testing done but might look into that as well. My kids all have similar numbers so obviously want the best management for them.

Thanks for the work you do.
Susan

Annie Q
Guest
Annie Q

I seem to be a hyper responder. Here are my stats FWIW.

I went on LCHF beginning in May 2017. I lost 28 pounds between then and the end of October 2017. Now I am in maintenance. My macros currently are approximately 71g protein/30g carbs/84g fat, but the fat changes depending on my exercise for the day. I do 40 minutes of vigorous aerobics twice a week, 30 minutes of resistance twice a week, and 30 minutes of brisk walking one day per week.

TC: 365
TRIG: 77
HDL:87
LDL-C: 263
LDL-P: 2364
HDL-P: 30.4
Small LDL-P: <90
LDL size: 22.1
LP-IR <25
CRP 1.38

The LDL-P number does cause me some anxiety but I cannot find anything empiric that addresses the risks of CVD when LDL-P is high but the particles are large. And of course there is some empiric data showing that LDL-P may be actually be protective when the particles are large — so it will be another cause for anxiety if my LDL-P goes down after my weight has been stable for awhile! Mostly I plan to ignore the whole thing because I feel SO GREAT on the keto diet — I would be miserable if I gave it up.

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