I mean for this post to serve as a transparent and prospective article of scientific intent, not a contract or final document. I will express the aim, describe the design, pose my hypothesis and provide considerations.
Aim: To assess the impact of Oreo supplementation versus statin therapy on LDL-C levels in a lean-mass hyper-responder (LMHR) as an n = 1 crossover trial.
Design: The protocol is based on a two-arm crossover design. The participant (me) will assume a baseline ketogenic diet for 2 weeks prior to baseline lipid testing. Next, I will consume the baseline diet supplemented with 12 Oreo cookies per day for 2 weeks, along with exogenous ketone supplementation dosed in order to maintain ketosis throughout the protocol (rationale below). Lipid tests will be collected weekly. After a washout period, sufficient to return to baseline weight, I will be treated with 20 mg rosuvastatin for 6 weeks.
Hypothesis: If the LMHR phenotype emerges in the context of carbohydrate restriction and tends to reverse with carbohydrate reintroduction, supplementation with Oreos may have a similar (or stronger) effect than statin therapy in lowering LDL-C.
Disclaimer This is NOT a health intervention. Please do NOT try this at home.
More details and thoughts:
We’ve observed repeatedly that the lean mass hyper-responder (LMHR) phenotype is induced by carbohydrate restriction and can be reversed by carbohydrate reintroduction. (For interesting background, see Table 4 of the first LMHR paper; and for historic context, see Dave Feldman’s white bread experiment).
Another – and the conventional – option for lowering LDL-C/ApoB levels is pharmacotherapy, with statins being first-line standard of care.
So, an obvious and important clinical question arises: Which is more effective at lowering LDL-C/ApoB in LMHR carbs or statins? Of course, results will vary by individual, and dose matters.
Nevertheless, I desire to run a randomized crossover trial with LMHR trying to assess that very question. Resource scarcity (time and, more so, money $) make that project infeasible at this time – but that doesn’t mean I can’t pilot the concept on myself… with flare!
Disclaimer – AGAIN – for emphasis: DO NOT try this at home! This will be a scientific demonstration and is not meant to serve as any form of health advice. You can see I’m really trying to hammer home this point, so please take it seriously.
I will perform a rigorously controlled n = 1 crossover comparing Oreo supplementation to statin therapy for lowering LDL-C in an LMHR (myself). The design at present will be as follows:
- I will follow a standardized baseline ketogenic diet for 2 weeks as a run-in phase, followed by a baseline lipid panel.
- I will then begin Oreo supplementation for 2 weeks, during which time I will add 12 cookies / day to my diet, which amounts to ~100 g carbs and 640 kCal from Oreos.
Of note, this will be a dietary addition, i.e. baseline diet will remain the same. I deem this design decision preferable over controlling for calories as addition of Oreos would require reductions in fat or protein. If the Oreo addition (without other dietary subtraction) does indeed lower my LDL-C, then saturated fat intake cannot be the driver of the LDL-C.
I have also decided to remain in ketosis throughout the Oreo phase via supplementation with pure D-BHB exogenous ketone. The rationale here is to change as few metabolic variables as possible: remaining in ketosis through all phases will isolate increased Oreo (carbs) intake as a variable versus increasing carbs and knocking myself out of ketosis.
Why? There has been speculation the state of ketosis reduces LDL receptor expression to drive up LDL-C [for more see 1:21:52 in the below-linked YouTube]. I think it’s more likely the carbs are repleting liver glycogen, reducing the trigger for VLDL synthesis and export (and subsequent turnover) via the Lipid Energy Model. Remaining in ketosis with Oreos will better test the former versus the latter.
To be as rigorous as possible, I’ll aim to dose the exogenous D-BHB four times daily, targeting levels of ~1.2 – 2.0 mM, similar levels to my baseline diet for the study.
- Lipid tests will be collected weekly, while 12 – 16 hours water fasted.
- After the Oreo phase, I will undergo a washout. The time for this isn’t set but will be determined by how long it takes me to reduce my weight to baseline (prior to Oreo arm) and stabilize for at least 1 week. To compare apples to apples, I want to start the Oreo and statin arms at a similar body composition and LDL-C level, and my body fat will very likely influence my LDL-C.
- The statin arm will last 6 weeks. Yes, this arm will be longer than the Oreo arm. While I think 2 weeks will be enough of the Oreo effect (and, honestly, Oreo hyperphagy for more than a half a month sounds impractical and/or too unpleasant and/or unsafe for me), 6 weeks is considered a “fair” medication trial for statins given the medications half-life and time to reach steady state. I’ve consulted a cardiologist and a lipidologist on this matter. Rosuvastatin will be dosed at 20 mg.
For more, I appeared on PlantChompers (episode released 8/15/23: https://youtu.be/4KYsa7zG9TE) to discuss LMHR and this crossover experiment.
Concluding comment: Why Oreos?
I chose Oreos for this study because they are near universally recognized and accepted junk food. I could have used cereal, banana, pasta or Coke. Any carb should work. But the Oreos provide “flare” and – yes – I want attention on this one. I don’t want attention for my own sake, but in order to gather interest and financial resources for a larger study that will have implications on mechanism and clinical management of LMHR. Speaking candidly, it’s a challenge to draw attention to this topic. Demonstrations like this – if (or because!) they are apparently crazy – will do the trick. And, depending on what the data show, we might be challenged with the uncomfortable question: If Oreo hyperphagy lowers LDL-C in this context, is it a desirable outcome compared to no intervention at all? I like uncomfortable questions… of the right sort…