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:
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)
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.
- Blocks FoxO1 which does two things:
- 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)
- Decrease ApoB lipidation (essentially decreasing LDL-P)
- 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
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 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.
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