Start Here (Pinned)

Welcome to CholesterolCode.com. This site serves as an information and research hub for emerging data on cholesterol. particularly in the context of a low carbohydrate lifestyle.

If you know little to nothing about cholesterol ->

If you’re wanting to learn more about why cholesterol could be higher, particularly on a low carb diet, we present the Lipid Energy Model (LEM) ->

If you’re looking to better understand the risk associated with high cholesterol on a low carb diet->

  • While several articles on this site present a more “cautiously optimistic” perspective on cholesterol in the context of fat adaptation, we strongly encourage everyone to consider the conventional view as well. Consider reading The Case for Lower LDL on Low Carb by our colleague and co-investigator, Spencer Nadolsky.

If looking to understand the “Lean Mass Hyper-responder” profile ->

If you’d like to understand possible relevance of cholesterol and the immune system, you can read Siobhan’s overview article on the topic here or watch her presentation here

If you’d like to learn more about lipoprotein(a), you can watch Siobhan’s presentation on it here

Lastly — you can always just ask us anything our Questions Page. (Just be aware our site does not constitute medical advice and we always recommend consulting with your doctor.)

Undeniable Hope

On November 27th, 2015, a number on a piece of paper changed my life forever. The massive increase I saw in my LDL cholesterol after adopting a low carb diet would ultimately send me into an entirely different life path, one I’d chronicle in real time on this blog. Now, eight and a half years later, I find myself completely entrenched spearheading research to unravel this mystery and whether it will demonstrate risk for folks like me.

But I have a confession… I’ve had many low points throughout this journey. Obstacles large and small have emerged to slow me down or even outright stop this research.

However, I’ve also seen just how far folks will go to support this effort. Beyond letters and DMs, many have contributed directly to our charity, the Citizen Science Foundation, or have networked us with the right researchers and personnel

https://twitter.com/realDaveFeldman/status/1744368194381291863?s=20

Yet nothing compares to what just happened. We decided to take a chance and hold a charity event – the Collaborative Science Conference – or as we call it, “CoSci”. It was over March 15 and 16th and… well… it was amazing. People from all over the world came to donate, with that donation being their ticket to the event.

https://twitter.com/MurseDarius/status/1769163840087007596?s=20

We had a mix of both featured speakers that were very popular, and citizen science speakers, many of which had never spoken at any conference before this one. And in spite of how short notice we were in announcing it just two and a half months ago, we had over 300 people come and join us.

The part I can’t express in words is how much our event had heart. It felt as though the “spirit of citizen science” was truly in the air. An optimism for what could be possible and how attendees were helping to make it real, just like the rest of us.

Given both the staggering generosity in donations and the considerably positive feedback, we will likely hold another CoSci next year as well. But more importantly, I’m thankful for the level of optimism this inspires for me. We’re proving this model of crowdfunded, self-directed science is quite real and can be well supported with events like these.

For everyone who donated and came to enjoy our event – thank you. You aren’t just helping us fund the next study, you’re reinforcing the drive for us to keep pressing forward.

Special Event: Live Reaction to Lipid Video by Nutrition by Science

A few days ago, Mario Kratz, released a video around lipids and ASCVD that also featured our work with Lean Mass Hyper-Responders and the Lipid Energy Model.

To be sure, while I did got a chance to listen to it at 2x speed on a drive between two meetings, it was more of a skimming, in a sense. But today I’m going to listen live with members & patrons at 7am PST (see companion post to this one – and if not a member, you can register here).

I’ve give my live reactions, but as always, I want to keep it both respectful and productive. I can say in advance my interest in this video is in large part due to my existing respect for Mario and his diligent work on his content. But moreover, he and I are already of comparable opinions with regard to metabolic health and its enormous importance in reducing risk.

I’ll then hand off my video to Mario directly, and if he feels it is helpful in advancing the conversation, I may release an edited version of the video for my channel.

Dr Budoff to Present Matched Cohort Analysis at WCIRDCD Conference

Original article via CitizenScienceFoundation.org

We’re excited to announce our Principal Investigator, Dr. Matthew Budoff, will be presenting preliminary data of our Lean Mass Hyper-Responder study (Keto-CTA) on the weekend of December 7-9th at the World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease conference in Los Angeles, California.

This is the first prospective study of CT Angiography on a keto diet population with extremely high LDL cholesterol levels, yet low cardiovascular risk factors and confirmed absence of monogenetic FH.

Dr. Budoff will be presenting a new CTA comparison analysis on this cohort against a matched control from the Miami Heart Study (MiHeart). The MiHeart cohort has been closely matched for demographics and risk factors, save LDL cholesterol levels, which average less than half of the Keto-CTA cohort.

Oreos versus Statins: An LMHR cholesterol drop N = 1

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.

Overview:

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…

One Year Since Publication of the Lipid Energy Model

On this day last year, May 20th, 2022, we published the Lipid Energy Model in Metabolites.

To say this was a milestone in my unlikely journey into research would be an understatement. The Lipid Energy Model (LEM) started as a simple idea around why I suspected my LDL cholesterol (LDL-C) would rise substantially on a low carb, ketogenic diet. I kept doing self experiments (N=1) and writing about it here, back when this was just a simple blog.

Over half a decade later, we have a rapidly evolving, published model that proposes core concepts surrounding this phenomenon and likewise makes bold, testable predictions. If you haven’t yet, I strongly recommend giving it a read. But if you’re pressed for time, I also put in quite a bit of work on its video abstract here (below).

Dream Team of Authors

A big game changer that made this all possible was our slate of coauthors who each had uniquely valuable contributions, Adrian Soto-Mota, Bob Kaplan, David S. Ludwig, and Matthew Budoff. I was incredibly humbled to have the great Anatol Kontush co-senior authoring it with me given his prior work was foundational to LEM. But I want to give an extra large shoutout to my good friend and LEM collaborator, Nick Norwitz. I’m certain we wouldn’t have gotten as far as we have without his considerable talent and drive.

Overall Reception

The paper has performed surprisingly well in spite of its specific niche.

Our overall Altmetric score is currently a whopping 339. (Over 20 alone is exceptional)

The paper also performed “higher than 99% of its contemporaries” in all four categories: All Research Outputs, Outputs from Metabolites, Outputs of a Similar Age, and Outputs of a Similar Age from Metabolites.

Challenges to the LEM?

Both Nick and I were quite certain our inboxes would be filled with challenges to the LEM once it had gotten published. However, to date the publisher hasn’t received a single Letter to the Editor. Moreover, we’ve actively corresponded with many senior lipidologists and cardiologists seeking critical feedback wherever possible.

The only challenge generally proposed via social media was the suggestion the LMHR phenotype can be mostly explained by the consumption of saturated fat. However, we’ve now published on this phenomenon extensively in papers prior to, and following, the LEM publication. Nick even wrote an extensive guest post on the topic here. (We also have some very powerful data on this topic dropping very soon.)

Coming LMHR Studies on Risk

Naturally, there is a degree of skepticism about whether this phenomenon is both physiological and poses minimal risk, underlining the significance of our direct investigation via the LMHR Study conducted at Lundquist at UCLA. We are pleased to share that participant recruitment concluded in February, followed by a brief presentation of an initial overview at Low Carb Denver. The findings thus far have been quite compelling, and we anticipate publishing them soon.

Moreover, these initial data have sparked further discussion for a companion study that we’re currently working on. I should have more updates on this in coming posts here and at CitizenScienceFoundation.org.

Click to enlarge