[Update 2020-08-14: After some issues over the second day (see social media discussion), I’m changing the design and restarting the experiment with lower overall dosage of both the EVOO and butter arms. The schedule is likewise pushed back exactly one week. All changes reflected below…]

The original version of this experiment was unfortunately paused due to some issues that I believe were electrolyte related. I’ve been looking to restart it under a new design but had a number of scheduling conflicts and some unusually low triglyceride readings for the last few weeks that have since normalized.
Experiment Design
This experiment will be a double crossover for five weeks. I will start with a neutral baseline diet, then begin alternating between each intervention for one-week phases. I will attempt to keep all other variables as equivalent as possible throughout: eating times, exercise times/duration, and sleep schedule.
For the extra virgin olive oil (EVOO) I’ll be using Kirkland, and for the butter, Kerrygold. Both will be combined with warm water by emulsion blender and then mixed with a meal replacement shake powder (Ketochow).
Schedule Outline
- August 13-19 – Baseline
- August 20-26 – EVOO
- August 27-September 2 – Butter
- September 3-9 – EVOO
- September 10-16 – Butter
Everyday Constants
All meals will consist of one lean beef burger patty from Metabolic Meals.
For the morning meal (~9am) I’ll be adding one or more foods with the intent of meeting close to a 50/50 ratio of saturated fat vs mono/polyunsaturated.
For the middle and late meals (~2pm and ~7pm), I will be consuming roughly 250 calories each (500 total) of either intervention for that week.
Omega 3 such as EPA and DHA will be provided via daily supplements from Zhou.
To prevent against the electrolyte issues from last time, I’ll be consuming 9 grams of pink salt dissolved in water each morning, along with electrolyte beverages ad libitum throughout the day.
Exercise will consist of two to three miles a day of walking with moderate, ad libitum upper body exercise (such as pushups).
Sleep will be ad libitum some time between 10pm and 8am.
Blood tests for mornings of August 20, 27, and September 2, 9
- Apolipoprotein A-1
- Apolipoprotein B
- C-Reactive Protein
- Complete Blood Count (CBC)
- Comprehensive Metabolic Panel (CMP)
- Cortisol
- Fatty Acids, Free (NEFA)
- Ferritin, Serum
- Fructosamine
- GGT
- Glucagon, Plasma
- GlycA
- Hemoglobin A1c
- IGF-1
- Insulin and C-Peptide
- Leptin
- Lipid Panel
- Lipoprotein(a)
- Lp-PLA2 Activity
- Nuclear Magnetic Resonance (NMR)
- Oxidized Low-density Lipoprotein (OxLDL)
- Reverse T3
- Testosterone, Serum
- Thyroid Panel
- Uric Acid, Serum
- Vitamin B12 and Folate
- Vitamin D, 25-Hydroxy
I’m also excited to announce I’ll be adding new tests from Boston Heart Diagnostics as well. These include:
- Adiponectin
- Cholesterol Balance
- Fatty Acid Balance
- HDL Map
- Interluekin-6
- Leptin (Redundant, but of high interest)
- Oxidized Phospholipids on apoB (OxPL)
Endpoints of Interest
As with my original design of this experiment I have outlined two categories of interest: lipid levels and inflammation markers. However, I’ll now be adding an additional test via Boston Heart that I’ve been waiting for — the Oxidized Phospholipids on apoB test (OxPL).
Something I’ve long speculated on is whether OxLDL would track tightly with OxPL. OxLDL is a pass/fail test — either the LDL particle has detectable levels of oxidation or it doesn’t. But the OxPL should show the degree of oxidation in those particles detected as an average for the total sampled. Thus, I think it will be an excellent test for risk and give us much more valuable information (but I do have some caveats, discussed below).
- Will EVOO interventions have lower relative total and LDL cholesterol levels (TC & LDL-C)?
- Will EVOO interventions have a greater oxidized LDL to total LDL particle count ratio (OxLDL/LDL-P)?
- Will EVOO interventions have a greater oxidized phospholipid to oxidized LDL particle ratio (OxPL/OxLDL)
Discussion
As mentioned above, there are many factors that can influence cholesterol levels, particularly LDL. There is one effect that is rarely discussed in the literature but is of particular interest to me — how much we see particular types of dietary fat result in higher or lower oxidation per LDL particle.
In other words, are we seeing lower levels of LDL cholesterol because LDL particles are getting oxidized and cleared by scavenger receptors at a higher rate? There are many limitations to the experiment in how well it can provide evidence to this answer, but it might open the door.
We can’t easily know the true rate of clearance for OxLDL in vivo, or how much this is impacted by the degree of oxidation per particle. However, oxidized LDL particles are commonly understood to be cleared at a higher rate than unmodified LDL. So it will be meaningful data if we find a higher OxPL to OxLDL ratio in one intervention over the other.
Regardless, there will be quite a bit more data from all the other blood markers to provide comparisons that go well beyond lipids.
I think the ideal would be to use clarified butter to compare it with olive oil.
I wanted to go with two popular, yet considered “high quality” versions of each intervention. Kerrygold is a big favorite on the butter end, of course.
Why? Clarified butter/ghee just removes the water and protein. It changes nothing about the lipids.
Wow, great panel you’ve set up, Dave.
As always, looking forward to the results and your review.
Best,
Paul
Note: your first two or three questions have an extra “will” in the question.
Thanks!
And thanks for the note to edit…
While this will probably be instructive, a better comparison would be a high quality olive oil with high levels of polyphenols and oleocanthal. With Kirkland, you’ll be really comparing the different kinds of triglycerides, but not the true possible effects of a high quality, recent harvest olive oil, like Italians get on a daily basis. There IS a huge difference.
Definitely possible. I was trying to strike a balance between quality and wide availability/mainstream.
I lived in Italy lot of years, the EVOOs you buy in the local supermarkets are pretty much the same, with olives not from Italy and mixed with low quality oils, the only way to find decent quality was to buy directly from producers from Fara Sabina.
Glad to see the experiment back again. The previous version must have been difficult with only isolated oil. If I ate nothing but oil, my stomach would turn
And that might have been a factor, can’t say for sure.
Only one subject? Results might be applicable to that individual. What is this, a Russian vaccine test?
Keith touched on this… but, how can you be sure Kirkland EVOO is what it says it is? This could be a primarily soybean oil vs butter experiment.. ? I guess, still useful information could be gleaned if that was the case.
I doing my homework, I found multiple sources that suggested Kirkland to be a solid choice
ie https://www.businessinsider.com/costco-olive-oil-experts-top-budget-pick-2019-3
Kirkland EVOO is part of a more general approach at Costco: https://napkinmath.substack.com/p/how-costco-convinces-brands-to-cannibalize
Thank you. I will follow progress with interest
One thing to mention, the butter must come from a grass fed and grass finished version. Then it is going to be a great experiment
Dairy cattle are not “finished.” You are thinking beef.
Kerrygold butter is as close to being grass/hay fed as anything I’m aware of. It’s certainly more yellow than any other butter I’ve used. In fact, just a few days ago a daughter commented on how yellow it is. Higher betacarotene and I would guess a whole lot of other beneficial components.
Yes, of course any area that has a significant amount of snow means the cows can’t be 100% grass fed, because they’d need to supplement in the winter (with hay, etc). But as far as I’ve heard kerrygold is both 1) common and 2) pretty good quality.
Any update on this? Would love to see the status.
Hi, it was called off due to Dave feeling unwell, even after multiple iterations. Our first rule is always safety first, so if there’s sufficient malaise we always try to stop and reformulate the experiment to prevent it. There’s a chance he’ll retry with some differences to help with that goal but for now he’s putting it in hibernation for a bit and doing a replication of the OXLDL experiment with OxPL from boston heart labs instead. The summary of that experiment is here.