Dr. Hallberg LDL on LCHF Talk

Hallberg LDL on LCHF 1

I first came across Dr. Sarah Hallberg’s name when I read Dr. Pokrywka’s guest editorial in Lipid Spin discussing the “Worsening Lipoproteins on a Low-Carb Diet.”

Dr. Pokrywka pointed out that Dr. Hallberg is in the midst of a large study investigating the effect of a ketogenic diet vs standard American Diabetes Association diet on type 2 diabetics and prediabetics.  In this study she’s examining NMR lipoprofiles, carotid intima media thickness, and other metabolic markers

In the course of her investigations she’s noticed a sub-population of patients that, like myself, develop elevated LDL-P and cholesterol numbers despite an improvement in everything else.

Her study seems to be the best we have currently of actually getting to the answer of: is this a bad thing?  Good thing?  Or a doesn’t matter thing?

Right now the consensus answer among the experts is, we don’t really know… but we’re worried because we know it’s a bad thing in non-low carb patients, and therefore would prefer you to have a lower LDL-P.

Since I’m one of the lucky few people who has this problem, I have a selfish reason to be interested in this topic… hence the deviation of the majority of my posts into the land of cholesterol… with less and less BJJ and Caveman sort of topics.

The beauty of having an online forum where I can publicly explore my thoughts and share my research is that many of you chime back and send me fantastic resources.

I want to thank Richard Arneson for sharing the link to Dr. Hallberg’s talk which I was eager to digest immediately.

Here is the video if you’re interested:

And, like I do with videos I really want to understand and process, I took notes.  Here they are:

My Notes

Dr. Hallberg is a board certified lipidologist that runs a low carb practice that also deals with metabolic health.

She only orders NMR Lipoprofiles, because like every other lipidologist, she believes that LDL-C doesn’t provide enough information.

What do we know about LDL on LCHF?

  • Saturated fats cause LDL-C and LDL-P to rise in SOME patients
  • Multiple studies show LCHF decreases small dense LDL (sdLDL)

What do we not know?

  • Exact percent of patients who have a rise in LDL?
  • Can we identify these patients ahead of time?
  • How much does LDL-C rise correlate with LDL-P?
  • Does rapid weight loss temporarily increase LDL-C?
  • How much of an improvement in sdLDL
  • Residence time of LDL particles
  • Does a rise in LDL-C/LDL-P represent increased risk?

When she reviewed LCHF research that included NMR panels, she found that overall, numbers improved, but there are sub-groups where the numbers worsen (hello!  that’s me!).

In her own practice she has patients that are insulin resistant, go low carb, and everything gets better EXCEPT for the elevated LDL.

She thinks this may be due to an insulin sensitivity problem.  (This is also what Dr. Dall thinks)

Hallberg LDL on LCHF 2

Dr. Hallberg does a good job going over the biochemistry of how cholesterol is affected after insulin binds to the receptor.

As you can see, the Akt step is the first major branch point in this pathway.

Akt does two things.

  1. Blocks FoxO1 which does two things:
    1.  Inhibits gluconeogenesis. (This makes sense because the presence of insulin indicates a glucose rich environment which means there wouldn’t be any need for gluconeogenesis)
    2. Decrease ApoB lipidation (essentially decreasing LDL-P)
  2. Stimulates mTORC1 which inhibits ApoB translation (also decreasing LDL-P)

For the purposes of this talk, ApoB = LDL-P

Basically, this slide shows that in normal physiology:

↑ Insulin ⇒ ↓ LDL-P (keep in mind that this doesn’t apply to  people who are insulin resistant or diabetic).

She then posits that in people who go low carb and subsequently develop low circulating insulin levels (LIKE ME – my fasting insulins have always been low), could this then explain why LDL-P goes up?

↓ Insulin ⇒ ↑ LDL-P

It’s possible…

When carbs are low and glucose is low, fat is oxidized for energy.  Fat is oxidized into Acetyl-CoA, which is the precursor for both ketone bodies AND cholesterol.  Individual variation can explain why in some people more of it is shunted into cholesterol rather than ketone bodies.

LDL Residence Time

Dr. Hallberg thinks that this could be a protective mechanism in people with high LDL-Ps, because maybe they’re residence times are LOW.

Therefore, while the LDL-P is high, this simply reflects a high turnover, and they’re simply not around long enough to suffer oxidative damage.

She also points out that previous studies linking high fat diets to decreased LDL receptor activity (therefore causing more LDL-P to hang around) were also high carb diets… they were both high fat and high carb, which really muddies the waters.

PCSK9

PCSK9 inhibitor drugs are currently being rolled out which makes her nervous because of the potential for unintended consequences down the line…

Inhibiting PCSK9 ⇒ More LDL Receptors ⇒ Decreased LDL residence time and decreased LDL-P

Insulin however stimulates PCSK9 which therefore leads to the opposite ⇒ Less LDL Receptors ⇒ Increased LDL residence time and Increased LDL-P

Therefore… if we can DECREASE insulin, we can INCREASE LDL receptors, and subsequently DECREASE LDL-P.

This is why those studies that were both high fat AND high carb may not be applicable to people who are carb restricted.

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Effect of Rapid Weight Loss

Anecdotally, she’s seen that this DOES effect LDL.

Are people over absorbing cholesterol in their diet?

She says NO…. (but my markers say I’m both a hyper-ABSORBER AND a hyper-SYNTHESIZER).

What she’s looking at now…

Took a group of 500 insulin resistant patients.  Put 100 of them in the control group eating the standard American Diabetes Assocation diet and the remaining 400 on a ketogenic diet.

She’s measuring body weight, metabolic syndrome criteria, type 2 diabetes status, carotid intima media thickness, NMR lipoprofiles, and full body DEXAs.

Questions she wants to answer

  • Does the rise in LDL-P in a minority of patients on a LCHF diet represent an increased risk of vascular disease?
  • Does LDL-P residence time go down thereby making a high particle number less relevant?
  • Can we predict who will have a rise in LDL-P?
  • Do all patients have a decrease in sdLDL who follow a LCHF diet?
  • How long after dietary changes should we be checking lipids or should we wait for weight stability?
  • Is insulin a double edged sword for some?

I personally can’t wait to see the results of her studies

Other posts you may find interesting if you liked this:

Worsening Lipoproteins on a Low-Carb Diet: The National Lipid Association
Reviewing the Labs My Lipidologist Ordered
Diving Deeper into Cholesterol: Sterol Testing with Dr. Dayspring
Chris Kresser and Chris Masterjohn On Cholesterol: Part 1
Chris Kresser and Chris Masterjohn On Cholesterol: Part 2
Chris Kresser and Chris Masterjohn On Cholesterol: Part 3
Ivor Cummins and the Cholesterol Conundrum
Apo-E, Alcohol, and LDL Cholesterol – The Framingham Offspring Study
Ketosis And High Cholesterol According to Dr. Thomas Dayspring
Great Article on Ketogenic Diet and Increased Cholesterol

6 Responses to Dr. Hallberg LDL on LCHF Talk

  1. Greg says:

    I just found your site recently and see that we are on a similar journey. My LDL-P went through the roof on a paleo diet. Over the last year, I have made a lot of progress on figuring out why. To do so, I have taken many, many blood tests, tracked everything I have eaten, and experimented with various supplements.

    I, too, am an APOE3/4, and I think this may be an important factor driving high LDL-C and LDL-P. My first clue came last fall when I experimented with removing cheese, butter, and yogurt (not paleo but I love it) from my diet. My LDL numbers dropped significantly. Then, I started removing meat from my diet and replacing it with vegetables. My numbers further improved. Finally, I admitted to myself that maybe the paleo diet wasn’t the best choice for me. I switched to a whole food plant based (vegan) diet earlier this year and my numbers continue to improve.

    I continue to experiment with optimal levels of plant based fats, how much whole grains such as brown rice I can tolerate, etc. My understanding is that APOE3/4 and 4/4 folks do best on low fat but I am curious as to how much fat I can get away with.

    One thing that I am still confused about is that my insulin level dropped from 3.1 on paleo to 2.1 on the new vegan diet. This seems very low but I have not seen any ill effects. My LDL-P also decreased as well (2566 to 1096).

    Thanks for a great post! Very interesting to me for sure.

  2. TM says:

    I too just recently found this site and appreciate the video link from Dr. Hallberg. After going on the ketogenic diet from several months, my recent lipid test (last week) showed a very large increase (~2X) in TC and LDC-C. As you have noted, this seems to occur in a subset of the population with no actual explanation being known. As far as the limited research I have done, while on a ketogenic diet, increased levels of acetyl-CoA are noted to be produced. When the body goes into ketosis, and the fatty acids are broken down, the levels of acetyl-CoA increase in excess to ultimately produce ketones for fuel (http://biochemproj.blogspot.com/p/dieting-and-ketosis_08.html). The subsequent step in this process also produces HMG-CoA. So while in ketosis, there would be increased levels of both acetyl-CoA and possibly HMG-CoA.

    Now for cholesterol – the pathway for cholesterol synthesis is based on having both acetyl-CoA and HMG-CoA (https://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/cholesterol.htm). In fact, the statin drugs are inhibitors to HMG-CoA reductase which is derived from HMG-CoA.

    So is it possible that if acetyl-CoA and/or HMG-CoA are increased due to ketosis, cholesterol levels could also increase in some individuals? Is there something in these affected individuals that preferentially favors the cholesterol pathway in lieu of ketones? I do not know and it may be something totally different as to the cause. The metabolic pathways following these “precursors” are quite involved and any change in the steps could have an impact. At a minimum, it would seem that the “raw materials” for either path are the same.

    From my experience, the significant increase in my TC and LDL-C is unlikely due to my increased SFA or dietary cholesterol since the majority of the blood cholesterol is made in the liver and this would not explain my drastic jump. Reducing my SFA intake and dietary cholesterol while maintaining ketosis would most likely not cause my lipid levels to return to normal. Therefore, I believe that a fundamental change in my metabolism/hormones has occurred when in ketosis. I would conclude that adding enough carbs in my diet to transition out of ketosis should reduce my lipid levels. This seems to be similar to your experience when you added additional carbs. I am somewhat disappointed since dietary ketosis was easy for me to maintain and I felt great. However, the high lipid levels are too alarming for me to continue without knowing whether this is a concern for the long term.

  3. Ryan smith says:

    Thanks so much for all your work. I have been following your cholesterol journey for awhile now. I have very similar cholesterol issues and have learned a lot from your posts. I know they’re side effects that come with taking a statin and would love to figure out another way. But given all of your tribulations and high risk of heart dieses, is there any circumstance where you consider taking a statin? Curious to hear your prospective on statins. I have had a doctor tell me that if I didn’t get my issue under control he would gaurantee a heart attack. Thanks

    • BJJ Caveman says:

      Hmmmm, that’s a good question.

      Two situations.

      1. If I have documented familial hypercholesterolemia… then I would for sure take the statin.

      2. If I have high cholesterol that just will not change with any of the supplements or changes in diet or changes in exercise, AND I have documented worsening vascular disease with Coronary CT and/or Carotid Intima Media Thickness, then I would.

      When your doctor tells you he can guarantee a heart attack… he is full of $hit… unless of course you’ve had a previous heart attack… or fall into the above two categories.

      Of course I don’t know your other history so take my statements with a grain of salt (ie diabetes and smoking also greatly increase risk, so statins might be appropriate in that setting).

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