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.
- Eat baseline diet for five days, wide spectrum test + oxLDL
- Eat 1/2 baseline diet for five days, wide spectrum test + oxLDL
- 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.
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.
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:
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.
Wow- thanks for going through all of this – and for sharing it! Your educational generosity arms us with practical, decision-making ammo.
oxLDL / LDP-P * 100
Is the ratio more important than the count?
ie, if the ratio was more like 20% oxLDL, that would be a real risk factor, almost regardless of the actual LDL-P, itself?
Interesting but not yet sure how to use this info
Hello, I just got my lipid profile results
Total Cholesterol is 481
With such high LDL, Is this to be of concern?
Note: I am on a zero carb diet, although I cheat a little here an there. My blood pressure is 92 sys, 58 dia, and my pulse is 64.
You may want to check out this post. Considering the high HDL, two questions:
1) Were you 12-14 hours water only fasted?
2) Do you drink coffee?
Thanks for this experiment Dave – fascinating!
I have taken the liberty of plugging your numbers into your remnant cholesterol report form. See the attached graphic.
Obviously the various markers show the same degree of variability as do your basic lipids.
Has this experiment given you any thoughts about the validity of remnant cholesterol numbers versus actual inflammatory risk?
For example, it seems from the numbers that doing caloric reduction after your baseline diet significantly changes (in an undesirable direction) your number for “Atherogenic Index of Plasma”…. (actually the other widely used ratios aee also changed similarly.)
It seems to me that a *really* useful additional biometric in this situation would be, for example, high-sensitivity CRP…. (i.e. one or more biometrics that track actual inflammatory response)
Next time check your insulin/C-peptide. Your massive intake of 235g of protein drove up insulin which drives ApoB down and LDLR up, which then drives LDL down. Inverse that for the 17. April where your insulin was probably almost unmeasurable.
Hi, He did check his insulin during this experiment, it’s just not in the post likely for brevity. The drop in LDL is actually consistent with the inversion pattern – we can see similar and consistent drops in other versions of the protocol used, including my experiment. In my case insulin was essentially the same from baseline to intervention (7.6 to 7.8), and protein was actually lower during intervention but I still saw a large drop in LDL-C.
It is possible that in Dave’s case insulin impacted the results – but regardless of the mechanism the main point (the extremely tight correlation of oxLDL with LDL-P) remains rather relevant. 🙂
I am a 47 year old female and I do not drink coffee. I fasted (both food and water for ~15-16 hrs before blood draw).
Just received my bloodwork and I am nervous. I did Keto for 6 months and now Carnivore/Zerocarb for 6 months.
I am probably most concerned with my LDL-P– can you give me some insight? I am not lean/fit.
Here are my NMR Lipid results:
* . Optimal 189 . LDL-C is inaccurate if patient is non-fasting.
* Low 2000
* ———————————————————- ** INTERPRETATIVE INFORMATION** PARTICLE CONCENTRATION AND SIZE LDL AND HDL PARTICLES Percentile in Reference Population HDL-P (total) High 75th 50th 25th Low >34.9 34.9 30.5 26.7 <26.7 . Small LDL-P Low 25th 50th 75th High 839 . LDL Size 23.0 20.6 20.5 19.0 ———————————————————- Small LDL-P and LDL Size are associated with CVD risk, but not after LDL-P is taken into account. . These assays were developed and their performance characteristics determined by LipoScience. These assays have not been cleared by the US Food and Drug Administration. The clinical utility of these laboratory values have not been fully established.
Hi Gina – LDL-P tends to be LDL-C x10 +/- 15% in metabolically healthy individuals from what we’ve seen so far, so it is no surprise your LDL-P is high, if your LDL-C is high.
I’ve put your results through our new report tool, which gives a couple different risk reports:
–===== CholesterolCode.com/Report v0.9.5.15 =====–
• Female • 47 • Coffee:
• 6 on months on Carnivore/Zero Carb/Meat Only •
• 15h water fasted • Cholesterol Rx: false •
Total Cholesterol: 446 mg/dL 11.53 mmol/L
LDL Cholesterol: 336 mg/dL 8.69mmol/L
HDL Cholesterol: 68 mg/dL 1.76mmol/L
TG Cholesterol: 58 mg/dL 0.65mmol/L
Atherogenic Index of Plasma: -0.433 mg/dL >>> Lowest Risk Third
—-> Go to https://tinyurl.com/ycccmmnx for more on AIP
Framingham Offspring: 0.7 Odds Ratio >>> Low Risk
—-> Go to https://tinyurl.com/y5fc5adl for more on this Framingham study
Jeppesen: >>> Lowest Risk Third
—-> Go to https://tinyurl.com/y63xp7lj for more on the Jeppesen study
——CONVENTIONAL MARKERS AND RATIOS——
Friedewald LDL-C: 366 | Iranian LDL-C: 305
TC/HDL Ratio in mg/dL: 6.56
TG/HDL Ratio in mg/dL: 0.85 | TG/HDL Ratio in mmol/L: 0.37
**This does not constitute medical advice**
• Your triglycerides of 58 mg/dL are typically considered optimal.
• We would consider your HDL of 68 mg/dL as strong.
• We’d consider your LDL cholesterol as in range for what we’d call a “Standard Hyper-responder”. This is common for many going on a low carb diet. For more on hyper-responders, visit cholesterolcode.com/hyper-responder-faq. For a deeper explanation on our proposed mechanisms for this when powered by fat, see CholesterolCode.com/model.
Thank you so much for replying. So, I understand that the particle numbers make sense based on the total LDL-C. But, my true question is- is this something to be concerned about? Do I adjust my carnivore diet in anyway or just keep keeping on? There are a lot of difference in opinions when it comes to cholesterol. I’ve read ( Cholesterol Myth by Stephen Sinatra, M.D.) where the Trig/HDL is important (mine is 0.85) and I should only worry if I have pattern B particles (mine are less than 90). But, then I hear elsewhere (Dr. Attia and Dr. Sara Hallberg) that the LDL particle count matters and now I am all confused. Your insight and expertise in this area is greatly appreciated. Thanks!
Hi – I think part of the reason you are hearing conflicting opinions, is simply because we do not 100% know yet. I am personally cautiously optimistic that those with high LDL (LDL-C and LDL-P), plus high HDL, and low triglycerides may be in a context that does not lend to higher risk in itself as also discussed here, but others are what you may say cautiously pessimistic like Dr. Nadolsky.
I think at this point, the most any of us can do is read the research ourselves and decide what we are most comfortable with and make changes (or keep things the same) to ensure we are comfortable with where we’re at until we have more solid information on this.
Sorry not to give a solid answer, but I don’t think we have solid answers yet for this group. 🙂
What is the difference between oxLDL and sdLDL?
small LDL only refers to an LDL of a certain size, oxLDL refers to LDL that has been oxidized. You can have oxLDL that isn’t small, and small LDL that isn’t oxidized. Although there’s some research suggesting small dense LDL (sdLDL) may be more easily oxidized and/or LDL that has been oxidized and removed the damaged parts.
Hopefully that clarifies things a bit!