Dr. Dayspring tweeted a link to Lipid Spin journal highlighting this article, and when I saw the title I knew I had to read it forthwith.
Lipid Spin is the official publication of the National Lipid Association and is, in my mind, a legit resource.
In case the link ever breaks (which I’ve discovered happens pretty frequently), I’ve taken the liberty of uploading it to my site, HERE.
While there isn’t anything groundbreaking, he does do a wonderful job of summarizing where we are currently.
He illustrates a typical case where a 55 year old female has normal lipids, goes low carb/Paleo, loses 30 lbs in three months and then develops an alarming lipid panel, akin to mine.
He posits the same question that I did:
Is this presumed increase in atherogenic lipoproteins (no baseline lipoprotein values other than that inferred by unremarkable non-HDL-C) dangerous?
Then he notes
The most consistent and predictable lipid change on LCKD is a decrease in triglycerides. Changes in other lipid parameters have been variable, but an increase in LDL-C often has been noted (anecdotally, about 30 percent of the time) in clinical practice…
Yup, in line with everything I’ve read thus far. But then things get interesting. He cites this study:
A six-month study in children placed on a ketogenic diet for epilepsy showed a significant and persistent increase in Apolipoprotein B.
Hmmm…. I’d never heard this before. I didn’t realize they looked at this in the pediatric population.
Why does this happen?
The next part is great and I think I’ll just quote it here. At this rate I’m pretty much just quoting the whole friggin article.
What is the etiology of the increase in LDL-C/ApoB/LDL-P in our patient?
The expected drop in triglycerides in such a diet would obviously change the composition of LDL lipoproteins, causing an increase in their size and cholesterol composition and a shift from small dense “pattern B” to lage and buoyant “pattern A….”
Ok… this part didn’t really help me too much, especially since Dr. Dall said we should focus more on the number of LDL particles rather than their size. In fact she even told me that the pattern A vs pattern B thinking is already becoming obsolete.
What about saturated fat?
Most LCKD followers also increase their dietary saturated fat intake, which is a recognized cause for an increase in LDL-C levels.
In my case, despite cutting back on my saturated fat intake my LDL-P remained high. I don’t think this plays as big a role as people think.
This next part gets very interesting:
The explanation for the ApoB/LDL-P increase from carbohydrate restriction is more complex.
When dietary carbohydrate restriction occurs, the body switches to fatty acid (FA) catabolism for energy.
Intracellularly, these FA are activated to form acyl-CoA, and then acetyl-CoA, which eventually is utilized for fuel production via the Krebs cycle.
Acetyl-CoA may be converted into ketone bodies…
Two acetyl-CoA may combine to form acetoacetyl-CoA, which can be utilized to form mevalonic acid and, ultimately, increase cholesterol synthesis through the 3-hydroxy-3-methyl-glutaryl- CoA reductase (HMG-CoA) pathway.
Also, when ketone bodies are in excess, there is an increased production of HMG-CoA, again driving the cholesterol synthetic pathway.
Anecdotally, it has been observed that many on LCKD with increased LDL-C/ ApoB/ LDL-P have increased desmosterol levels, a marker for increased cholesterol synthesis.
Diabetic ketoacidosis and anorexia nervosa patients have elevated LDL-C/ApoB/LDL-P, in part via similar mechanisms.
Excessive hepatic cholesterol synthesis will drive the formation of more ApoB particles, and the increased synthesis in the liver will decrease the expression of the LDL-receptor (modulated through the nuclear transcription factor “sterol toxicity sensor” Liver X Receptor [LXR]), prolonging LDL clearance, and adding to the increased LDL-P concentration in circulation.
What he’s essentially saying is when we go on a low carb diet and shift our metabolism to burning fats which are broken down into the molecule acetyl-CoA, a few things can happen to cause our livers to hypersynthesize cholesterol:
- Liver converts acetyl-CoA directly into cholesterol which is packaged into LDL
- Liver converts acetyl-CoA into ketone bodies, which then signal the liver to produce more cholesterol
- Hypersynthesis of cholesterol in the liver will signal the liver to decrease LDL-receptor expression.
- This decreases clearance of LDL-P from the blood stream
- Which increases the concentration of LDL-P in the bloodstream
So what does all of this mean?
He knows as much as I do right now… which is not much:
No one knows what the CVD [cardiovascular disease] risk of increased LDL-C/ApoB/ LDL-P is in LCKD states, and the evidence for the long-term safety of this dietary approach is lacking.
BUT, there’s hope
At this very moment people are actively looking into this question in patients with prediabetes or type 2 diabetes:
Sarah Hallberg, DO, of Indiana University is the principal investigator for a large study comparing patients with type 2 diabetes or prediabetes who are being treated with a ketogenic diet vs. patients being treated using the standard American Diabetes Association (ADA) dietary guidelines, looking at NMR LDL-P, metabolic markers, and carotid intima-media thickness (cIMT) over two years.
She said, “Atherogenic dyslipidemia so dramatically improves and diabetes resolution occurs so frequently that we have to be asking, even in the patients who have a rise in LDL-C, are we not still improving their health? For those patients with a rise, is there a perfect blend with statin therapy?”
What does the author recommend right now for low carb folks with high LDL?
Step 1: Test with NMR Lipoprofile or ApoB
Step 2: Image with CIMT or Coronary artery calcium CT. He provides a caveat that this is optional for “primary prevention” patients which means no prior history of heart disease (I fall into this group).
Step 3: Decrease saturated fat, increase protein, increase carb intake, and retest. (I’ve definitely been down this road)
Step 4: If persistently high LDL-P/ApoB, treat with statins.
Dr. Dayspring also presented a similar case as this author a few years ago that I wrote about:
If you want to learn a little more about cholesterol synthesis and absorption since I reference the term hypersynthesis above, check out these notes I took from Dr. Daysprings Lectures:
If you have the time, you should watch the lectures in their entirety!
It was interesting to see the author refer to the data showing similar findings in anorexics, which is something I came across as I as preparing to see my lipidologist.
Regarding the steps recommended by this author. I’ve definitely done Step 1. Testing and retesting. Testing and retesting. If you’ve been following this site at all, you’ll know what I’m talking about (here is my latest test).
I’ve been on the fence regarding Step 2. When I brought this up with Dr. Dall, we both agreed that no matter what the results came back as, it wouldn’t really change our plan of action. Despite this, I may just get a CIMT done just for the heck of it. Now to find a place…
Step 3… Decrease saturated fat, check. Increase protein, check. Increase carbs, check. Retest, check. One thing I can explore is really upping the carbs for a month or so… maybe into the 200-300 gm range. One thing I suspect is that eating in the 100-150 gm range of carbs might still be too low for me given my activity level. Sigh… and yet another experiment to add onto the list.
Step 4… before jumping to statins I wanted to explore some alternative remedies, and as readers here know, I discovered a combination that actually worked! Only now I’m in the process of figuring how much, if any, effect each of those components had.
I have a lot more experimenting to do before I consider taking statins…