- 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->
- You can also check out or Frequently Asked Questions (FAQ) here
- You can watch Dave’s recent presentation for Stanford University on the Lipid Energy Model.
- You can also check out the Lipid Energy Model poster here
- If you’re looking to better understand the risk associated with high cholesterol on a low carb diet->
- Watch Dave’s Deep Dive on Cholesterol and Risk presentation
- If you’d like to understand possible benefits of cholesterol and the immune system, you can read Siobhan’s overview article on the topic here or watch her presentation 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.)
If you’ve followed me on social media for long, you’ll note I’m very proactive about engaging in conversations with people of opposing views.
(Note this has a companion Twitter thread here)
I consider this one of the most important tools for learning in my toolbox.
This isn’t because a single response tweet or comment can tell you everything you need to know all at once, but it can’t often give you a critical clue you needed that you were off course. But there’s a problem… especially these days.
Often people associate their opinions with their identity. I won’t be the first to observe this is a common, tribal instinct. And indeed, there are many, many studies on this. We enjoy a sense of belonging and togetherness.
Unfortunately, this can likewise manifest opposition and contempt toward other groups who associate around a different set of opinions that they draw collective identity from. An obvious example of this are political parties. But we now also see this commonly with nutrition.
And herein is the problem.
Crossing Party Lines
Imagine you (as an individual) want to have an intellectual conversation with someone from a different “tribe” to better understand where they (as an individual) are coming from. You have two major things working against you…
For one, they may already be hostile toward you given you inadvertently represent the last several people before you from your “tribe” that were hostile toward them. Their defenses are up.
For two, many simply won’t trust in your sincerity to have a fruitful conversation.
Changing one’s opinions on the above two can take a lot of work, but I think the cost/benefit has netted a positive for me overall. Sure, many people simply aren’t interested in strictly rational and non-personal conversation no matter how much you try to make it happen.
But for what it’s worth, I think you’d be surprised how many people will engage in such conversations if you can build trust and rapport with them.
I now have many, many good friends with opinions very different than mine, but for whom each of us has influenced each other.
I think the key is to continue being courteous well past the initial barbs thrown your way and, as they say, “kill them with kindness”.
Let me be blunt, doing this is very challenging. We aren’t built that way. We want to defend ourselves and fight back.
Economics of Self-control
While defensiveness can be appropriate in many cases, one of the biggest life lessons I’ve learned is that much of the time it is simply unproductive. It typically just keeps conflict alive or escalates it to new levels. Often showing persistent generosity deescalates.
One of the most common comments I get from friends in DMs: “Why are you talking/debating with ______??? They are a _______ and not worth a moment of your time!” In some cases this will prove true, in others false — but I don’t always know until a later point.
In business there’s a term called “cost of sale”. For example, if 100 spam mailers go out and only one person responds — but the margin on that one response exceeds the cost of all those mailers, then the “cost of 1 sale” was 100 mailers. Sorry, that’s how spam works, of course.
Thus, the key question is whether the gain of insight from 1 person with differing views and many successive, productive conversations is worth, say, 5 attempts with others that ultimately failed to do likewise? Right now, I’d say yes, it seems to be the case.
But more than that, I think it’s about maintaining the constant, unrelenting habit of challenging core beliefs. Some of my strongest held opinions came from failing to defend an opposing opinion I had at the time. I had to relent and adopt the view that made greater sense.
Sticking to the Arguments
With all that said, it’s important to keep one simple rule in mind and continually affirm with every conversation:
-> Where expressing an opposing opinion – one should strive to be attacking the argument they disagree with, not the person presenting it.
I do my best to practice this every day in every conversation, tweet, and blog post — particularly where addressing people directly. (As an aside, I’m definitely not saying I have 100% success rate by any means. I always feel I can do better.)
And for what it is worth, I often find people can follow my lead and do likewise when I’m chatting with them in this manner. Again, we’re social creatures. So in a way, you’re starting an instant “tribe” of rational discussion you both can feel belonging with in the moment.
However, sometimes it doesn’t work in the beginning or even develops problems later on. But having that compass built in at all times helps keep me aware as to how much these conversations are guided by analysis of the assertions over judgements of the person making them.
At a certain point you have to recognize there is much more of a problem in trying to overcome this perception than is worth engaging in. And by the way, this applies to *all* the people in your life: work colleagues, long time friends, romantic relationships, etc.
Which is why it’s easy to test by simply asking if each person can get through a conversation without ridicule, personal attacks, biting sarcasm, and any number of other expressions of negative judgement of the other person. If it seems persistent- probably need to let go.
This may seem like a lot of work. It is. It takes a lot of energy to push back from those deeper instincts.
But I can vouch it has been paying very big dividends in my journey thus far and I can’t imagine it any other way.
EVOOvsButter Experiment Paused
The Extra Virgin Olive Oil vs Butter Experiment had to be aborted. I was feeling a number of symptoms I assume to be related to electrolyte issues on Day 2 and some further issues on Day 4 and 5 that may or may not be electrolyte related. I may detail the symptoms more in a later write up (members can hear me discuss it on the MMM from this last Monday).
Regardless, I’ll still be doing the experiment, but likely with a new design. I haven’t fully decided on what that will be, but should have that determined soon.
LMHR Study Update
I’m happy to announce Tommy Wood, Spencer Nadolsky, and myself are ramping up work for the IRB submission that we hope to have ready soon. While the pandemic has certainly impacted all our lives substantially, we’re very much dedicated to getting this study underway as soon as we can.
Energy Model Paper Update
Like many a “labor of love”, the energy model paper is probably getting a bit more time applied to it than it should for a first draft. I’ll admit to occasionally falling victim to “perfectionism paralysis” — this is probably one of those times. That said, I’ve gotten some excellent guidance lately on techniques to move this endeavor further along and get it out the door. As the saying goes, “A work is never completed, but merely abandoned.”
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.
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:
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.
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
- June 30-July 6 – EVOO
- July 7-13 – Butter
- July 14-July 20 – EVOO
- July 21-27 – Butter
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)
- Fatty Acids, Free (NEFA)
- Ferritin, Serum
- Glucagon, Plasma
- Hemoglobin A1c
- Insulin and C-Peptide
- Lipid Panel
- 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)
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.
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.
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
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