My presentation at Low Carb Breck is finally up!
Transcription for Cholesterol is a Passenger, Not a Driver
Cholesterol is a Passenger, Not a Driver
Transcript of https://www.youtube.com/watch?v=0LuKwsz9Woc
Transcribed by Kerry Ireland from https://www.facebook.com/kerryscomms/
Published 12 May 2018
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Animation: Logo for Low Carb Down Under
[Slide: Low Carb Brek 2018]
[Slide: Cholesterol is a Passenger, Not a Driver]
Alright guys. I’ve got something really special for you today. So, buckle up. Because I have put a lot of work into putting all of the things I know into a single analogy.
First of all, conflicts of interests. None
But I will tell you about a great bunch of great individuals at the end of the talk.
I don’t really want to spend a lot of time on. I’m a software engineer. I’m obsessed with lipids, conducting crazy n=1 experiments. You could just google Dave Feldman and cholesterol. You’ll find plenty on me.
I like to call myself a cholesterol traveller now because I’ve move lipid numbers up and down several times through a series of experiments and I’ve brought my LDL as high as 368, down to 98, all since the last time I was here. But how am I doing this?
Well, I like to say that I’m working from a theory that seems to continue to keep on working. And what I’m happy about is that I managed to solve the two biggest problems. The two biggest problems are that I am talking to two audiences all the time.
[Slide: Two audiences, two problems]
Fortunately, for the experts, they prefer that I don’t simplify the language and to be fair, they’ve got a good point.
But I also can’t tell an entire audience of lay people all about lipidology very easily. I am still kind of learning about it myself.
So, I am excited, because this analogy will be a way for me to get you the abstraction that I see, the way that I see it. Because the most important message is the one I want to get across to you as to what cholesterol is a passenger in.
So, without further ado, I bring you a wonderful story.
[Slide: A tale of five problems.]
So, in a dystopian future, our country is hit with a massive flood. And the president turns to the secretary of engineering, that’s a future cabinet position, by the way.
He says, “Ok, well the houses are fine because it’s the future and everyone can work from their home. Its alright but we still need to be able to get food to them. How are we going to do that?”
The engineer says, “Actually, its fine. We have got a really large company on the shoreline that can get the food from outside the country and ship it inside. And that’s the Intestine Delivery Co. It has exclusive rights to get all of the food that’s gathered from the outside and it has special ships, these brown ships (I’m keeping it colour coded, so remember ‘brown’), to deliver that food around to all of these different houses.
Fantastic. Fantastic. But, after a little while they realise that it is still kind of uneven. Some of the houses are getting it sooner than others and unfortunately some of the houses aren’t ready to use the food at the time that they need it. So that brought us to the second problem—a lack of local storage.
The engineer says, “No problem. No problem. We are going to have these food banks that we’ll have all around these different neighbourhoods and then that way, as the ships come around, sure, they’ll feed food to the houses. On top of that they’ll re-up the adipose food banks.”
Now we come to the third and most serious problem. And, that is that we still have mis-distribution. These neighbourhoods aren’t able to talk to each other. The adipose food bank can sometimes have enough, sometimes it doesn’t, sometimes the ships have enough to carry and sometimes they don’t. And so, we have not got to deal with the hardest problem of all—balance distribution.
For this, the Secretary of Engineering worked with his whole team and he got a lot of work done and he says, “We just need one central player.”
I give you the Liver Delivery Company.
This one is great because, guess what, not only will all of the brown ships eventually make their way there but also all of the food that got lost and spilled out into the water and no-one could capture. That will all eventually make their way here as well. They have their own special purple boats and that too can deliver this food all around to the different neighbourhoods.
The President is like, “This is fantastic. So let me see if I got this straight. Food that is coming from outside the country, that’s coming into the Intestine [Delivery Co], well then that is actually going to be loaded onto the brown ships, that’s going to be distributed. And, then all of the stuff that is in the food banks that spills off or spills off from trying to deliver it to the different houses, that’s also going to make its way to the Liver [Delivery Co] and that, those purple boats are going to counter balance the amount that’s coming from the brown boats?”
“Yes.” The Engineer says, “That’s exactly right. In fact, when there’s more that’s coming in from the outside, then that actually means that there’ll be less that needs to get pulled from the food banks and, ultimately, delivered via the Liver [Delivery Co]. Likewise, it counterbalances in the other direction.”
And surprise, I’ve been talking about Lipids this whole time. This is why I don’t have a shining future as a magician.
[Slide: Lipid Analogy Legend]
Yes, the houses were cells.
The fatty acids were the boxes. And, of course, if you have three of those boxes, you have triglycerides.
That, of course, was energy being distributed everywhere. But the main thing that I wanted you to focus on, the reason I really wanted to drive this home, is all the way up to this point my story has been about only one thing—distributing food, which was actually just fat-based energy.
So, what were the means of delivering the food?
Well, on the brown line we’ve got Chylomicrons. Chylomicrons start with a whole bunch of fat-based energy. They eventually become Chylomicron remnants and where do they end up? They end up back at the Liver. The Liver has its own line, which has VLDLs and IDLs. Once they are emptied of all of their energy, they return back but there is something missing from this schematic of course.
But remember this is the energy-delivery portion. If you are watching this on a video, I would be fine if you paused it right now, pondered that for a day, and come back to this next part. Because the moment I bring up the “C” word everything is going to fall apart because it has too much attention associated with it.
So, now, let’s get to the FOURTH problem—support.
[Slide: 4th Problem: Support]
The President turns back to the Secretary of Engineering and says, “You’ve been doing such a great job but unfortunately the flood wiped out all of our emergency services. Do you think there is any way, you with your smarts, could figure out a way that we can still get that support around to the houses?”
He said, “Yeah. You know what we’ll do, since these purple boats are the most present of all the boats that are sitting around in our country, we are going to outfit them with the special care package. Now, granted, their first job will still be delivery. The first job is still delivery. The second job is support.”
Naturally what I’m talking about here is cholesterol.
So, I want to reemphasise this again because this may be the most important slide and you might not realise it.
First job is delivery. It doesn’t both deliver and support. It first delivers and then it supports.
That’s extremely relevant to the rest of this analogy.
[Slide: Analogy/Fat-based energy]
So, without question, as we’re watching in the first job, we’re seeing this counter balance between chylomicrons and VLDLs in delivering fat-based energy. And then, after the chylomicrons deliver their energy they have clocked out, they’re done. The VLDLs take about as much time to deliver the energy and they then have a second job. They hang out in the neighbourhood. They chase off pathogens. They get endocytosed into the cells for additional repair, right? They’ve got a second gig and they take that second gig pretty seriously.
So, now we can add the LDL to our schematic and the HDL to our schematic even though I haven’t talked about it yet you just need to know this, with this little dotted line I’m talking about two different sides. Energy delivery on one side. Support on the other side. Very relevant when you are looking at these cool graphs I get to make that you’ll see in other videos.
[Slide: Graph entitled, “Three-day average of dietary fat, with a two-day gap vs LDL-P cholesterol”]
This one, of course, I showed at the last Breckenridge talk, where I was pointing out that I was able to have dietary fat on a three-day average and isolated about right when I needed to do it in order to get resulting LDL-P. LDL-P the support boat, right?
Why was I able to do that, do I theorise? Well, now you are starting to get it. You are starting to get the abstraction. I had less dietary fat coming in from the Intestine Delivery Co, which resulted in my body needing to up-regulate VLDLs. What do VLDLs eventually clock out and become? LDL-P, that’s right.
Likewise, when my dietary fat was high, sure enough, my LDL-P was low.
So, don’t take my data for it.
Let’s talk about the emerging data in the Low Carb High Fat Community.
[Slide: Emerging Patters of LCHF Cholesterol]
Now, I use to lament that Doctors that I was meeting early on, low carb doctors, they had this great wealth of data from their own patients on cholesterol numbers. And, in the spirit of being careful what you wish for, I started this website and now I see, like, a dozen or more lipid profiles almost every single day. Like it has really ramped up to get to ridiculous levels. But the neat thing is that we can now see the patterns that I was looking for in the first place. You might be surprised to find this out but, metabolically healthy low carbers (the key is that they are metabolically healthy). You would think, as I certainly did, as you go from overweight to lean what would happen to your cholesterol? It would go down, right? It would go down.
But it doesn’t! It actually goes up.
But what about if you go from sedentary to high energy, high energy demands? Anyone?
It goes up!
It goes up!
Now, I keep looking at this from the abstraction I just showed you and I keep thinking, wait a sec. If the triglycerides are still staying low but I’m seeing more of the purple boats, should I be concerned? I don’t know that I should.
So this is when the hypothesis was born. It’s the one I’ve been working on for quite a long time now. This is an overly brief version. Basically, high LDL cholesterol and particle count on a low carb high fat diet can be a reflection of higher VLDL secretion and use. The key is ‘and use’. These guys are actually needing to drop off these triglycerides at a higher rate and therefore becoming low density lipoproteins. Wouldn’t it be great if we had a profile that showcased this perfectly?
Some of you already know where I’m about to go.
We now have what we call the Lean Mass Hyper-responder.
A hyper responder if someone who goes on a low carb high fat diet and they see their cholesterol go up substantially. Lean mass hyper responder was something I identified back in July. I wrote an article about it and honestly it was kind of a ‘testing the waters’ thing. I wanted to write this article and I wanted to see what the response was. I half expected a lot of people to write in saying, “No. No. No. Actually I have an LDL of 200 or I have a triglycerides below 70. I am actually very sedentary. I have all of these other issues. Etc.”
No. On the contrary, I got inundated. This is the most commented on post of any of that I’ve had on the blog, thus far. There are people all around the world, and many of you medical professionals on low carb, you probably know a few, that are a lean mass hyper responders. They tend to be very lean. They tend to be very athletic.
[Slide: Tear Down this Hypothesis]
Now, this all sounds great.
What’s the first thing you want to do?
And this is why I’m so glad that Ivor took place before me. We are all about the root cause.
Do you want to know how you know an engineer … they are their own worst critic. They have to be because their fellow engineering friends are constantly challenging them. They need to challenge themselves first.
I love this quote:
[Slide: The great tragedy of science—the slaying of a beautiful hypothesis by an ugly fact. Thomas Huxley]
BRING ON THE UGLY FACTS
One of the advantages I have been able to have with the little bit of my name equity moving up is I’m actually nearing about 10,000 followers on Twitter. I get to actually get responses to the people that follow me and they’re not all fans of low carb high fat, let me tell yah.
So, I put this out.
Question for those in the know: Are there any studies that show high LDL with high CVD in spite of having low triglycerides?
And, in doing so, I managed to get one response from Dr T. Hats off to Dr T for this one. From our friends at Framingham. And, actually, I really liked this sample size. Because it was people that didn’t already have cardio vascular disease and after excluding users for lipid-lowering therapy. That’s a big deal to me. I don’t like gene or drug studies. That’s a talk I can do all by itself.
Well, sure enough. I get into the chart. And I’m like, ok, so their baseline here, they have it at an odds ratio zeroed out at triglycerides below 100, LDL below 100, Low HDL-C. Which by the way was below 40 for men, below 50 for women.
Naturally, as you would expect, if you have a high HDL-C, odds ratio being lower is better, you have the best version, if your triglycerides are below 100, your LDL is below 100 and you have high HDL. That’s like the ideal profile, right?
So, we would expect, if LDL got flipped and we started looking at 100 and above, the odds ratio would probably also flip, right? … go to like 1.3 and 1.4. No! Actually, it’s the next-best risk marker and its right next to it at 0.7.
Well, ok. Maybe this was including a lot of people that had an LDL of 105 and 110.
Fortunately, though, they also had a category for people who had an LDL of 130 and above. How many people get prescribed statins for 130 and above? That’s the high risk category, right?
Actually, its identical. It’s a 0.7.
As you can see on the confidence interval, on the right side, this isn’t a fantastically large study, but unfortunately I wasn’t able to find any fantastically large studies.
I got really ornery and I built this graphic.
I pushed it around on social media. I really, genuinely, and not in a trolly kind of way, truly, trying to ping all of the biggest pro lowering LDL experts that I know.
If you ever get bored you can look through my twitter feed you can see me doing this.
I said, “Look. Look. Look. You guys are saying we shouldn’t take comfort in having low triglycerides and high HDL Cholesterol when our LDL cholesterol is high. Can you bring me just one study? One study? The best study you can. So long as it’s not a drug or gene study. One that shows that we have higher rates of cardio-vascular disease.”
Anyone want to guess how many studies I got?
I am actually hoping, genuinely hoping, that this feed in this video will help inspire some people to bring more into comments. I’m sure there’s a chance that there’s some out there. But, I still haven’t seen it yet.
[Slide: Remnant Cholesterol]
What I am thankful for is that it brought me around to something that most people don’t know about even in the low carb community. It’s called ‘Remnant Cholesterol’.
[Slide: Remnant Cholesterol, from Wikipedia]
I think Wikipedia summarises this really well.
They say, look, remnant cholesterol, also known as remnant lipoprotein, is a very atherogenic lipoprotein composed primarily of very low-density lipoproteins, that’s these guys. And intermediate-density lipoproteins, that’s these guys.
“Stated another way, remnant cholesterol is all plasma cholesterol that is not LDL cholesterol or HDL cholesterol.”
This was a big moment for me because before I read any further studies, I said this is actually a perfect match, for what it is that I believe is ultimately the root cause of the disease.
Let’s go back to our analogy again. Right.
I’m not worried about this. What am I worried about? I’m worried about this. There’s not good engineering reason, and I state this all of the time, for a lot of energy to be parked in the blood.
I cannot think of one and I have not had anyone present one to me yet.
I have to emphasise, once again, when you think of things from a first job, second job, is it really that high levels of triglycerides are atherogenic or even, as the remnant cholesterol people are saying, that it’s a more atherogenic particle? I don’t think so. I think it is a failure of the VLDLs from being able to drop off energy, fat-based energy, version of triglycerides.
What do you suppose remnant cholesterol is highly correlated with?
Well, I’ll actually drive it home. I forgot I had this slide in here too. So I’ll have to fit this one in to really drive this point home.
VLDL to LDL lifecycle
How long do you think that VLDLs last in the blood in a normal lipidemic person?
An hour! Yes!
30 to 60 minutes
How long for IDL?
Less than 30 minutes.
Now, if it doesn’t get absorbed by the liver, how long do they stay in that support role as a low-density lipoprotein?
2 to 4 days.
In other words, 98-99% of the rest of their lifespan is for that long.
So, yes, where I was going was [inaudible], sure enough it correlates closely with insulin resistance.
[Slide: Plasma RLP-C in Secondary Dyslipidaemia—Insulin Resistance]
In fact, remnant cholesterol correlates much closer to insulin resistance than what I have seen with LDL, as Ivor brought up.
[Slide: Remnant cholesterol as a cause of ischemic heart disease]
Same thing with ischemic heart disease. Notice, by the way, as HDL is going down, remnant cholesterol is going up, even with LDL hardly moving at all.
[Slide: Premature myocardial infarction is strongly associated with increased levels of remnant cholesterol]
Myocardial infarction: Remnant cholesterol was the lipid fraction most associated with premature myocardial infarction.
[Slide: Extreme Non-fasting Remnant Cholesterol vs Extreme LDL Cholesterol as Contributors to Cardiovascular Disease and All-Cause Mortality …]
My favourite of all. All-cause mortality
Which graph do you think you would like to be in?
The LDL moving up or on the Remnant Cholesterol moving up?
[Slide: A Simple Comparison]
Here’s a simple comparison. Someone I’ve worked with a lot throughout this whole period. They had about 177 total cholesterol and an LDL-C of 121. HDL 40. HDL is a little bit low but triglycerides are 80.
That looks pretty good, right?
And now on low carb high fat, two and a half years later, they have a total cholesterol of 284, an LDL-C of 201, HDL-C of 71 and triglycerides of 58. This is actually at the cut points of a lean-mass hyper-responder.
Yet, on the left side, they have remnant cholesterol of 16 mg/dl. They actually have a lower remnant cholesterol on the right side even for as high as the cholesterol numbers are.
Well, let me give you a little bit more of a challenge. After I reveal who this person is. (Slide reveals it is Dave Feldman, the speaker)
[Slide: Craig Moffit, 40]
I want to talk about Craig Moffit who, by the way, contributes a lot to our website. Thank you, Craig.
He also will have some data that I will share with you in a second.
Would you guess that he is a lean-mass hyper-responder? Yeah. He is actually very thin and very athletic.
His total cholesterol is 457 mg/dl
His LDL-C is 335 mg/dl
His HDL-C is 109
Triglycerides are 67
He is the picture of a far-end lean-mass hyper-responder so you would at least expect remnant cholesterol to probably go to scale, right? Like it’s probably a bit higher, anyway? You could probably do the math right now.
Actually, 13 mg/dl. It’s actually just one pip higher than mine on my last test.
[Slide: How do you calculate remnant cholesterol?]
How do you calculate remnant cholesterol?
There is a caveat to that, which I’ll say in a second.
Yes, you just take your total cholesterol, you subtract your LDL, you subtract your HDL.
You can be forgiven if you thought that actually this whole time total cholesterol was those two added together. No. That reminder is those VLDL boats, those IDL boats and specifically the cargo of cholesterol that is inside them.
The caveat that I want to fit in, a lot of you already know this. LDL is typically a calculated number from the Friedewald equation. So that is a little bit of a confounder, but all of the studies are built on the Friedewald equation. In that sense, there’s a little bit of fuzziness. Generally speaking, I tend to find this looks pretty good.
This is what’s neat.
[Slide: CholesterolCode Data for Remnant Cholesterol]
I literally calculated this, just morning.
CholesterolCode Data from our site, for remnant cholesterol, we have a whole bunch of submitted labs that people have and I created the criteria of an LDL cholesterol of 200 mg/dl or above, right. That, by the way is well into range of familial hypercholesterolemia. Which means your doctor will give you two medications before you can leave the office. Right? There’s probably statin police around the corner. He just calls them in, or something.
With triglycerides of at least 10mg/dl or below. What’s neat is we now have a lot of entries, just on the site, of 456 (total). Of that, I found 138 that met this criteria. How many of those hyper-responders who were typically on a high fat low carb diet for the highest, medium highest and medium risk categories combined: we found 9. For the Medium low risk category: 44. For the lowest quintile of remnant cholesterol: 84.
So over 90% of those who have submitted in concern to our site about their high levels of LDL cholesterol, and in particular I am picking them out for those that have over 200 and above. Over 90% of them have very low remnant cholesterol.
Now, I do have some caveats.
This presentation doesn’t discuss the influence of glucose and glycogen and so forth. And if you follow my work, you know, and my whole phase 2, is based on being able to manipulate that as well.
Also, I do believe there are bad reasons for higher LDL cholesterol, however, they are typically related to still having higher triglycerides and, for that matter, also with HDL, you do want to keep an eye on low HDL. That’s actually genetically influenced.
So, how am I doing on time?
Ten Minutes!!! Yesssss!!!!!!
OK, I’m excited about that. That analogy I worked on for a long time.
This is great. We can actually look back at the inversion pattern that I had from the prior talk
[Slide: The Inversion Pattern Revisited]
and you guys probably remember this for those who have already seen it. For those that haven’t, real quick.
[Slide: Dietary Fat Inversion]
The inversion pattern as I’ve found in my data. I’ve shown this over and over again with the large number. I’ve had a total of 88 blood draws at this point. Insane engineer.
As it turns out, if I were to take my cholesterol this morning, then I would look back to the three days of dietary fat and I would find that they had the greatest influence on what my LDL-C would be and likewise, it’s also a three-day window for LDL-P but there’s a two-day gap.
Craig Moffit, I didn’t get a chance to include it, he actually replicated this experiment entirely with four different data points. You can look it up on the CholesterolCode.com site where he also talks through. I don’t have the slides for it but he basically did exactly the same thing and proved the same inversion pattern for both LDL-C and LDL-P.
What’s neat is, in the summer of last year, we got a bunch of people together for the KetoFest cholesterol experiment, which by the way just opened its kick starter, small plug.
[Slide: Ketofest Cholesterol Experiment—July 11–17, 2017]
July 11-17, we managed to get a bunch of people to eat a very low-calorie but still ketogenic for three days and everybody did a water fast. Then we all took a blood test. One blood test. Then gorged out on fat for three days and took a second blood test.
What do you suppose happened?
First, I posted the hypothesis before the experiment began.
I said I suspected that it would get much lower.
I’m thankful for PTS diagnostics who helped pay for all of the bloodwork.
We got people like this guy who helped to contribute and people like these people to eat a bunch of the fat. They were all a part of it.
[Slide: “Broken Ladder” Graph]
We ended up with what I like to call the ‘broken ladder’.
You see on the left side, the Friday, of all of the tests that were drawn. You see on the right side the Monday of the second of all of the tests that were drawn and all that fat that was eaten in between.
What do you see most of those lines doing? Going up? Down? Sideways?
Actually, about 19 had a decrease of between 5 to 38% of their LDL cholesterol. Only 3 had an increase. It was only 1 or 2%.
Now, you look across the board, if you take them all across the board …
[Slide: Average change in LDL-C]
… there’s a drop of 16% of their LDL-C in three days for a total [drop] of 25.7 mg/dl.
[Slide: The Feldman Protocol one year later]
So, let’s look at that protocol for the last time I’d done this at Breckenridge, that part on the left is actually what I had shown from before. We had had a 100% success rate, so far, and that was when we had a lot less people. Now it is approximately 85% of a success rate.
There are some caveats that we found that I think I also have a slide here for, but at that time nine had tried out of curiosity, 10 had used it to get their doctor off their back.
Well, between Comments on twitter, Facebook, CholesterolCode, Reddit, blogs, we have somewhere over 100 people who have tried it. We’ve lost count. But it’s absolutely amazing that it is still holding to that 85% success rate given how many people have done this.
Last time, at least 4 people had used this to improve their life insurance rate. At my last count, I found 13. All low carbers. Again, I kind of blame Jeffrey Gerber. He was the first to tweet out about that.
[Slide: Possible Protocol Pitfalls]
So, look, here’s the possible protocol pitfalls if you are considering doing the Feldman protocol.
Anecdotally, these anecdotes these elements have been the most common.
Use of MCT or coconut oil, we kind of discourage because that seems to be a confounder.
This is also a new one. Use of coffee. Sorry. It seems like coffee does in fact have some different effects on the lipids and has had impacts for our protocol results.
Also, some with hypothyroidism appear to have some unexpected results and that’s also worth pointing out.
So, in summary, more VLDLs may be trafficked on a low carb high fat diet for fuel.
I know I haven’t talked about ketones. I know I haven’t talked about glucose. But I’m telling you it’s a big elephant in the room that nobody talks about. You get a lot of direct delivery of fatty acids via VLDLs. And, this may result in a higher presence of its later stage as an LDL particle, resulting in, of course, in what it carries, the passenger—LDL cholesterol, right. This may not only be appropriate but may be mechanistically necessary. This all relates back to why there’s so much overlap with remnant cholesterol, even though they are coming to very different conclusions than I am. I don’t believe VLDL and IDL … let me just put it this way. I don’t believe any lipoprotein is atherogenic. I believe broken systems are atherogenic.
So, remnant cholesterol is a far stronger indicator of risk of both heart disease and all-cause mortality than LDL-C.
Finally, remnant cholesterol typically drops on a low carb diet.
I think the reason that there hasn’t been a lot of attention on remnant cholesterol is because there’s not a drug for it yet.
It’s just my opinion.
[Slide: Thank you, Patrons!]
I wanted to thank my Patrons because I don’t accept any money from any business entity. I have made that a rule up front because I didn’t want to compromise the integrity of the data.
I am honoured to have 109 people who directly pull money out of their pockets, small amounts, that actually allow for this research to happen. So, please, if you could thank them for me.
[Slide: Thank you for watching]
Thank you so much. I hope you enjoyed this.
A Quick Update on Remnant Cholesterol
I wanted to give a reminder that I’m still very early on in my research of Remnant Cholesterol. We’re working through a lot of studies to find what is most applicable.
Many have asked me for what range I consider best, and I continue to point out that my opinion is still very new on this and subject to change.
So take it with a grain of salt for now, but I’d speculate the following:
- Below 20 mg/dL (0.49 mmol/L) is generally optimal
- Around 20-30 mg/dL (0.49-0.78 mmol/L) is generally medium risk
- Above 30 mg/dL (.78 mmol/L) is higher risk
I will have a follow-up article on Remnant Cholesterol soon that will be much more in-depth and probably likely to refine the cut points above.