The Oxidized LDL Experiment

For quite a while I’ve been wanting to test a theory I’ve had regarding the blood test for oxidized LDL (oxLDL). The test has some research behind it suggesting a correlation with heart disease, which makes sense given this association of oxLDL in the artery walls and atherogenesis.

There’s an assumption that oxLDL will track with oxidative stress in the body. But I’ve long had the hypothesis oxLDL will track with LDL particle count (LDL-P) as well — and perhaps to a greater degree. For example:

I’ve already been a bit skeptical of oxLDL as a marker given it doesn’t distinguish total oxidized phospholipids on a per-particle basis, and thus I’m hypothesizing it will track more with total LDL particle count given the same level of oxidative stress…

— Dave Feldman (@DaveKeto) February 5, 2019

Deeper Mechanistic Reasons

In a previous draft of this blog post I go into my lengthy reasons for why this makes sense to me, but I think I’ll save that for later as some of it is a bit controversial.

But I’ll tease part of the answer can be suggested by this tweet:

… To simplify a bit, would you rather have 1000 LDLp with 1 oxidized phospholipid on their hull, or 100 LDLp with 10 oxidized phospholipids on their hull? If an oxLDL doesn’t pick up quantitative differences per-particle, then it seems the 1000 LDLp *appears* worse.

— Dave Feldman (@DaveKeto) August 23, 2018

Designing the Experiment

So is there a way to increase LDL-P while keeping oxidative stress roughly the same or even lower? Why yes, we use the Inversion Pattern.

1. Eat baseline diet for five days, wide spectrum test + oxLDL
2. Eat 1/2 baseline diet for five days, wide spectrum test + oxLDL
3. Eat 2X baseline diet for five days, wide spectrum test + oxLDL

The hypothesis: oxLDL will track with LDL-P. It will go up with LDL-P goes up and drop when LDL-P drops. If oxLDL has little to no movement or tracks inversely, this would be clear evidence against it.

In other words, if LDL-P increases from phase 1 to 2, and drops from phase 2 to 3, we should see similar movements with oxLDL.

Unexpected Amendment at Phase 3

While I did caveat in advance I might not be able to hit the Phase 3 goal of doing twice my baseline diet, I quickly found out my fear was met. Pretty quickly I realized I couldn’t consume that much food that quickly.

See my video on this as it happened here:

Thus, I compensated the difference with some Keto Chow shakes which allowed me to move up my levels a lot faster. (Full disclosure, Keto Chow provides us product support for experiments, but we draw no financial compensation from the company or have an agreement with it of any kind)

There were also additional circumstantial stressors in that last phase unrelated to the experiment, so I made note of this too and how it may be a confounder as well.

Process Woes

As an aside, getting this testing was both expensive and extra cumbersome. The lab I was getting by regular tests through didn’t allow for Boston Heart blood to be taken, so I had to make other arrangements to get the blood drawn and spun separately on that test. Then I had to pack it in ice myself and take it to FedEx to ship immediately afterward.

As experiments go, this one has a lot of planning and footwork to pull off by comparison.

The Thrill of Anticipation

The first test rolled in and these results would now serve as baseline.

Okay, 88 it is.

While waiting for the second test, I happened to be in the area of the clinic I was getting these labs through and dropped by. “Hey, any chance you got that second oxLDL test?”

“Actually, we got the email notification this morning. We’ll print it out.” Said the administrative assistant.

“Great!” I felt a wave of excitement hit me. “Before I see it,” I began, staring at the printer, “I predict the number will be higher than the test on the 12th before it.”

The sheet finally popped out and the assistant handed it to me. “YES!” I shouted, and then suddenly dialed it back, self-consciously remembering I’m in a doctor’s office. “Sorry.”

Certainly 128 was an incredible change for a five day difference. The effect size was more than I could have hoped for to test the hypothesis.

I was already out of town at the moment the last test came in. When I let the admin know I wanted her to send it over via email, she said, “Awww, we were hoping you’d see it in person here for the reaction.” We both chuckled.

Wow! 75 at the low. And again, this is just five days from the prior phase endpoint at 128.

Now again, I have to be intellectually honest. That last phase could have been confounded by the unexpected stressors and my having to add on Keto Chow to reach the caloric surplus. It could be posited one or both of these further impacted the outcome. Probably a stretch, but worth the mention.

Findings

Unsurprisingly, this is the tightest regression line I’ve ever posted.

To be sure, there were many runner ups that had less correlation, yet still in the 90s. Here’s the big rundown of both the diet and blood markers:

Final Thoughts

Needless to say, I was quite happy to finally have this experiment completed and ecstatic at the outcome data. While the correlation with LDL-P was something I’ve predicted for some time, I’ll concede it was far tighter than I was imagining.

I have many other thoughts on oxLDL which I’ll save for another time. But the biggest takeaway is how clearly dynamic this marker is, along with just about every other lipid that is central to the research of this site.