Sarah

I first became aware of Sarah Hallberg from watching her amazing talk at my very first low carb conference in 2016, Low Carb Vail. The talk was LDL on LCHF and thus she instantly became someone I needed to talk to about my quirky ideas about diet-induced cholesterol levels on low carb. In spite of my being completely unknown to everyone, Sarah followed up with me by phone after the conference to discuss my crazy ideas.

Ever since, she has connected me with many important people inside the world of lipidology and I can’t imagine having gotten this far without her help.

Odds are, you may have first heard of her from the extraordinarily viral TED talk, Reversing Type 2 Diabetes starts with ignoring the guidelines. I quite literally interviewed people during the shooting of our documentary who recounted how that was their first real introduction to low carb.

Yet one of the most daunting accomplishments was her drive as Medical Director at Virta Health to amass a truly unique and powerful dataset on treatment of patients with severe type 2 diabetes using a low carb diet. These ongoing studies have been immensely powerful to clinicians around the world who are considering this advice for their patients.

Somehow she managed to achieve all these milestones while actively raising a family with three children.

Today I read an article in the Tampa Bay Times where she provides her thoughts on the challenges we’re facing with COVID-19 and how it is affecting her personally.

I have advanced cancer. Stage 4 lung cancer, to be exact, even though I have never smoked, and I am only 48 years old. Cancer is scary enough, but now I am in a real unknown, with so many others like me: dealing with advanced cancer in a pandemic.

In spite of the shock so many of us are feeling in her sharing this news for the first time, it’s really an opening to her very pragmatic advice throughout the rest of the article on the urgency to act.

We need to prepare for that second wave. That’s why, right now, physicians must begin urging those who need medical treatment to receive the care they need, whether virtually or in-person. I understand how this delay of care can be as deadly as COVID-19 itself. In addition to being a cancer patient, I am also a practicing physician. Even before COVID-19, I treated my patients virtually. That made a huge difference when the pandemic hit. My patients all have diabetes or prediabetes, conditions that put them at a high risk of COVID-19 complications — just like me. Connecting with them virtually meant that their care was never delayed.

She’s correctly pointing to our need to look ahead to many different downstream consequences of this pandemic to care, and importantly, how that will affect further diagnoses (including those with cancer). This article could have been written without sharing her very personal news. But including it certainly helps drive the point home.

I realize this stage of cancer is very serious and time may be limited. To say I’m very saddened by this news would be a profound understatement. That said, for as long as I’ve known her she has been the greatest of patient advocates and taught us not to see the disease before the person. Rather, seeing all someone has done and is still doing should always be in view — and let’s face it, that’s easy to do with her many accomplishments to date.

She has never stopped working to help others, and today is no exception.

Extra Virgin Olive Oil vs Butter Experiment – Design

As I often say, I believe looking at LDL cholesterol levels alone is like reading the last chapter in a long book… you need to know all the elements in the story before that point to get an idea of how it ended up there.

Certainly I’ve been focused on the energy model and how being “powered by fat” is very relevant to resulting lipid levels. But I’m also aware of many other factors that impact cholesterol levels as well:

  • Fiber
  • Exercise
  • Medication
  • Genetics

Yet one of the most common suggestions in lowering cholesterol (both total and LDL) is “replace saturated fat with mono and polyunsaturated fat”. This advice appears to have lots of evidence behind it. I’ve both read many studies and heard many stories that back up this advice, although individual results can vary.

In particular, I regularly hear one should “replace butter with extra virgin olive oil” where they can. Given the enormous popularity of both these sources of fat, I decided to set up an experiment to test each in isolation — and it’s going to be a bit ambitious.

Experiment Design

This experiment will be a double crossover for four weeks, meaning I will be alternating between two interventions each twice, resulting in a total of four 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). In addition to the shakes

Schedule Outline

  1. June 30-July 6 – EVOO
  2. July 7-13 – Butter
  3. July 14-July 20 – EVOO
  4. July 21-27 – Butter

Everyday Constants

Water and electrolyte beverages will be consumed ad libitum

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 between 12am and 8am.

Blood tests for mornings of June 30, and July 7, 14, 21, and 28:

  • 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

Endpoints of Interest

There are two categories of interest to me for this experiment: lipid levels and inflammation markers. But more specifically, I’m interested in what will happen with LDL-C/LDL-P/ApoB vs Oxidized LDL (oxLDL).

  • I posit the EVOO interventions will have lower relative total and LDL cholesterol levels
  • I posit the EVOO interventions will have a greater proportion of oxidized LDL relative to total LDL particle count (oxLDL/LDL-P)

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.

Regardless, I suspect we’ll have lots of other data from the many other blood markers I’m capturing that may prove quite useful.

Philippa’s Hypothesis – Thyroid Dysfunction May Explain LMHR Phenotype

In this interview, Dave talks to Philippa about her hypothesis that the Lean Mass Hyper-responder phenotype may be described by an underlying thyroid dysfunction. They deep dive into the idea to discuss the relevant research, and compare it to Dave’s lipid energy model.

0:00 Intro and brief overview of Lean Mass Hyper-responders

Site mentioned: Lean Mass Hyper-responders facebook group

1:30 How does Philippa’s view on Lean Mass Hyper-responders differ from Dave’s?

3:11 How Philippa found the Lean Mass Hyper-responders facebook group

6:39 Philippa’s history with Hashimotos and perspective on thyroid function in LMHRs

Producer note: Hashimotos Thyroiditis is an autoimmune condition affecting the thyroid often resulting in an underactive thyroid

7:52 Does Philippa feel Lean Mass Hyper-responders have a thyroid dysfunction?

11:05 In accordance with the lipid energy model, wouldn’t you need lower T3 in order for higher levels of lipolysis to take place?

13:43 Does higher relative delivery of Free Fatty Acids to the liver result in higher production of VLDL? Does it depend on context?

17:31 What is futile cycling of fatty acids? Does it make sense?

21:18 The distributed object network model of energy potential trafficking, and how VLDL and fat tissue repletion, may play a key role.

26:58 Is it possible for someone who has never had hypothyroidism symptoms who went on a low carb diet and developed a Lean Mass Hyper-responder profile to completely erase the profile with medication?

30:35 Example of a Lean Mass Hyper-responder reversing the profile from diet

Producer note: To provide a little additional information, having been in close communication with the LMHR in question, the drop of LDL to 140 mg/dL from 800 mg/dL+ was after increasing weight by ten pounds, increasing meal frequency from one meal a day to two meals a day, decreasing exercise intensity and frequency and including “carb ups”. So macronutrients did change as did multiple other factors. As Philippa said, these are consistent with the lipid energy model, and her thyroid/anabolic signaling model.

33:06 Is the loss of a menstrual cycle in female Lean Mass Hyper-responders a red flag, and/or common?

36:37 Review of triglyceride and fatty acid metabolism in adipose, skeletal muscle, and liver and how it relates to the lipid energy model.

Original table from Fatty acid metabolism in adipose tissue, muscle and liver in health and disease. Additional graphic overlay from Dave.
Energy potential trafficking.
Energy potential trafficking.

Study mentioned: Fatty acid metabolism in adipose tissue, muscle and liver in health and disease – Keith N. Frayn, Peter Arner and Hannele Yki-Järvinen 2006

44:13 What are the commonalities and differences between lipid profiles in people with hypothyroidism and Lean Mass Hyper-responders?

Study mentioned: The effects of thyroid dysfunction on lipid profile C.V. Rizos, M.S. Elisaf, and E.N. Liberopoulos 2011

47:50 Common reasons for high triglycerides in Lean Mass Hyper-responders, and generally for those on a low carb/carnivore diets.

Post mentioned: High triglycerides on low carb and what to do about it.

Producer note: Going by submitted data on CholesterolCode, triglyceride levels of 200+ are not that uncommon from coffee sensitivity. Although a pull of the data we have would be necessary to see exactly how frequent it is, anywhere between 150-250 is what I most commonly see, from memory.

51:05 HDL and triglyceride inverse correlation and relation to Lean Mass Hyper-responders and the thyroid dysfunction hypothesis

53:11 Are there other things to look out for that may help suggest a non-favorable situation relating to the Lean Mass Hyper-responder profile?

55:40 Dave’s data on IGF-1 and LDL-C compared to predicted correlation

Dave’s IGF-1 compared to LDL-C
Dave’s IGF-1 compared to LDL-C

58:27 Overview of thyroid markers, their structure, and function

1:02:33 Does Philippa have any additional thoughts to share before wrapping up?

Blood marker changes of interest in Lean Mass Hyper-responders mentioned: MCV (Mean Corpuscular Volume) in 90s-100s, RBC (Red Blood Cell count) decreasing slightly, RDW (Red Blood Cell Distribution Width) increasing slightly

1:05:05 Context of blood markers being studied and how correlation with pathological contexts may be relevant

1:07:29 Leptin levels in the context of low carb, the thyroid dysfunction hypothesis, and the lipid energy model

1:12:50 Will Lean Mass Hyper-responders show signs of insufficient anabolic signaling, such as low bone density, over time?

1:17:37 Dave’s thoughts on investigating potential downsides to the Lean Mass Hyper-responder profile.

Link Mentioned: Philippa’s google doc on the thyroid dysfunction hypothesis

1:23:08 Outro

Presenting the Lipid Energy Model to Stanford University

I was incredibly honored to be invited by Annelise E. Barron, Associate Professor, Dept. of Bioengineering, to present my research to her class and discuss the Lipid Energy Model in depth. Originally, I was going to be flying to the campus to give the talk directly, but with the current Covid-19 crisis all speakers were presenting via Zoom.

This proved to be an excellent opportunity provide an overview for general (not low carb) audience. Overall, the presentation was well received, maintained strong retention, and there was quite a bit of discussion afterward. (Discussion not included in the video)

Videos on Current Crisis to be Archived

I’ve been provided an analysis by a friend in the tech industry who has a firm that performs advanced analytics on social media and particularly YouTube .

This analysis has led me to the very reluctant decision to archive all videos related to SARS-CoV-2 / COVID-19. While the videos themselves are not inflammatory in nature, I’m now convinced the topic itself may have enormous volatility regarding the algorithms YT makes use of (at least at this time).

I can’t discuss him or his firm’s methodology beyond this (and had him sign off on this language before posting).

Comments are turned off for the video announcing this because they can also impact these variables, but you can comment here at this blog post.