Worsening Lipoproteins on a Low-Carb Diet: The National Lipid Association

Worsening Lipoproteins 1

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.

Here is the link to the issue from their site.

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.

Mechanism

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:

  1. Liver converts acetyl-CoA directly into cholesterol which is packaged into LDL
  2. Liver converts acetyl-CoA into ketone bodies, which then signal the liver to produce more cholesterol
  3. Hypersynthesis of cholesterol in the liver will signal the liver to decrease LDL-receptor expression.
    1. This decreases clearance of LDL-P from the blood stream
    2. 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.

FINAL THOUGHTS

Dr. Dayspring also presented a similar case as this author a few years ago that I wrote about:

Ketosis and High Cholesterol According to Dr. Dayspring

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:

Diving Deeper into Cholesterol: Sterol Testing with Dr. Dayspring

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…

15 Responses to Worsening Lipoproteins on a Low-Carb Diet: The National Lipid Association

  1. James says:

    Just curious, does the CIMT pose any long-term cancer risk or is it completely benign in that regard? If I’ve hit the right sites searching the web, this is ultrasound-based? Whereas Coronary artery calcium CT is a type of test using xrays?

    I’ve considered the Coronary artery calcium CT, but always question whether these radiation-based imaging tests do more long-term harm than good.

    The whole cholesterol risk on CVD seems so complex. Just when I think I am seeing good signs–increase in particle size–I see something like this. It’ll be interesting to see how the research pans out.

    Appreciate the post.

    • Eric says:

      CIMT is completely safe and cheap. Runs about $250 USD. It is an ultrasound so no radiation. The CT Calcium is low dose radiation and relatively safe. CIMT looks at the thickness of the intima media layer or the carotid artery and can also show plaque. Thickened intima media and plaque= really bad! Plaque alone=bad. Thickened intima media=not so good but not as bad. Normal intima media thickness and no plaque= you’re doing great. The study Dr. Hallberg is doing will follow those with elevated lipids on a lchf diet and attempt to see if the carotid intima media is getting thicker while eating fat. I can’t wait to see the results. Most of the obesity doctors that I know have been doing this test on their patients with rising lipids but improvements in all other markers. “The word on the street” is that their intima media is actually thinning not thickening on a lchf diet.

      • BJJ Caveman says:

        I prefer CIMT because I think you’ll see changes to intima thickness before coronary calcifications.

        I too am looking forward to Dr. Hallbergs results! Thanks for sharing the word on the street!

  2. willie haris says:

    Great job on keeping us up to date.

    I think it is fairly common from my research, from what I have read, that 25% of the folks on LCKD that their LDL-P and ApoB skyrocket. Mine did as well. So what I did was to take 3000 MG of niacin and the number popped down in 2 months. This also included reducing my fat intake, no more Dave Asprey stuff, and increase the protein. No change in carbs (<25 net). This included taking your advice on the Gut regiment you prescribed.

    BTW I was on statin for 11 years. Off now for 1 year.

    BTW – The article did state that you need to get a CAC scan. Hmmm, so it time to step up… 🙂

    BTW – The reference in the Article about kids and seizers are from 2003.
    JAMA. 2003;290(7):912-920. doi:10.1001/jama.290.7.912..

    BTW – The number one doctor in the World is out of Johns Hopkins who pioneered this treatment for kids and seizers was not included in the research reference. So I wonder if they picked a study to help their discussion. Hmmm. However, both of us had their LDL-P and ApoB go up.

    Thanks again for the post. Really appreciate it.

  3. Xn says:

    I just did a google search for “increase LDL-receptor expression” and came up with some papers. It looks like there are some polyphenols that occur in red grape juice and wine; some plant sterols; and exercise that affect ldl-receptor expression. I’m definitely going to research more.

    Question, do you have a PPAR-G mutation? See: http://www.snpedia.com/index.php/Rs1801282

    I’m sorting that one out now. If you do, check this out:
    http://www.pterostilbene.com/pterostilbene-a-natural-alternative-for-healthy-cholesterol-levels/
    (I understand that this site is biased, but you can start your own research from here. Rhonda Patrick, advises its use.)

    • BJJ Caveman says:

      I’m not sure about the PPAR mutation and haven’t looked into ptersostilbene before. Perhaps I’ll take a look into it. thanks!

      • Xn says:

        Essentially, that PPAR mutation interferes with saturated fats signaling reverse cholesterol transport(cholesterol clearance). There are studies where PUFA/MUFA to SFA ratios of 3 to 1 or greater normalize the transport. Trans-pterostilbene is a PPARG and PPARA agonist which ostensibly would increase that signal and possibly allow for narrower ratios.

        Here’s an article on herbs that are agonists. http://www.sciencedirect.com/science/article/pii/S0006295214004249

        I went down this path, because I saw this on D’agostino’s site:

        “In one particularly interesting case, a patient in self-prescribed nutritional ketosis presented to me with an LDL-P of more than 3500 nmol/L (i.e., more particles than could be measured by the NMR machine so the report simply said “>3,500 nmol/L”) despite feeling, performing, and looking great. Based on his through-the-roof desmosterol and cholanstanol levels, and a curb-side consult from the Godfather I mean Dr. Tom Dayspring, I decided to try an experiment. You see, the logical thing to do in this setting would have been to start two drugs immediately (a potent statin to address the hypersynthesis and ezetimibe to address the hyperabsorption) or tell him to abandon ketosis altogether. But this patient was adamant about staying in ketosis given the other benefits, though obviously worried about the long-term coronary implications. So, we agreed that for a 3 month trial period he would reduce SFA to an average of 25 g/day (vs. about 75 to 100 g/day) and make up the difference with monounsaturated fat (MUFA). Parenthetically, we also reduced his omega-3 PUFA given very high RBC EPA and DHA levels.

        So, on balance, he consumed about the same number of calories and even total quantity of fat, but his distribution of fat intake changed and he heavily swapped out SFA for MUFA.

        The result?

        His LDL-P fell from >3,500 nmol/L to about 1,300 nmol/L (about 55th percentile), and his CRP fell from 2.9 mg/L to <0.3 mg/L (and for the lipoprotein cognoscenti, both desmosterol and cholanstanol fell)."
        http://eatingacademy.com/cholesterol-2/random-finding-plus-pi

        …And I wanted to know why this could work. I'm in a similar position. I just started taking the pterostilbene, red clover and magnolia extracts and am going back into ketosis. I'm hoping to be able to stay in ketosis and keep my ldl-p < 1000.

  4. Richard B Arnesen says:

    You should check out Dr. Hallberg’s recent talk on this subject:

    https://youtu.be/w8jUmCe3zDs

    • BJJ Caveman says:

      Thanks for sharing this video. I think I’ll type up a summary of it as a separate post!

  5. Charles Grashow says:

    After a consult with the head of cardiology we agreed that, based on my 10 year risk average, to discontinue taking 20 mgs Atorvastatin EOD starting 10/21/15.

    Got a new blood test on 4/7/16

    TC – 169 mg/dl
    HDL – 56 mg/dl
    LDL (Calculated) – 103 mg/dL
    Triglycerides – 49 mg/dl
    Non-HDL Cholesterol – 113 mg/dl
    Cholesterol/HDL Ratio 3.0

    Apo B – 79 mg/dL Reference Range 52-109

    Cardio IQ hsCRP – 0.4 mg/L

    Cardio IQ LDL Particle Number – 1515 nmol/L
    Small LDL – 244 nmol/l
    Medium LDL – 253 nmol/l
    Large LDL – 1018 nmol/l

    HDL Large 6168 nmol/l

    LDL Pattern – A

    LP-PLA2 220 ng/dl

    Liproprotein A <10 nmol/l

    SO – I shall continue to not take a statin and continue to take my cholesterol lowering supplements

    • BJJ Caveman says:

      Thats fantastic news! congratulations Charles.

      Would you be interested in writing a guest post detailing your experience? What’s worked for you in the past, what didn’t? And what you’re currently doing?

      I know a lot of folks would be interested.

      • charles grashow says:

        Drop me an e-mail and we’ll see what happens. I’ll need help with the edit though. Not as good a writer as you are.

  6. Saelina says:

    Hi Bjj,

    We last spoke about a year and a half ago. At that time I was doing a net zero low carb diet and my cholesterol had skyrocketted 100 points to 319. They sent me to the cardiologist insisted I go on statins immediately stating it was genetic and all of that. I refused and told them I would lower it myself through diet. I went off the low carb completely, gained a good amount of weight back but dropped my cholesterol back down to 218 at my last visit. Cardiologist couldn’t understand how I was gaining weight but lowering my cholesterol.

    During that time I was doing a lot of reading and thought maybe you might find it worth checking into or considering. My thought process was maybe it falls down to vitamin/minerals that allow some people to do exceptionally well on the low carb diets while others of us are thrown into a high cholesterol state. I did the following to see if it would bring it down regardless of food choices and it worked.

    1. Probiotics, I think I wiped out my gut flora when I did almost zero carb. I added in probiotics that specifically had the strains that have be shown to reduce cholesterol. There are a number of studies out now referencing the probiotic effects of certain strains with cholesterol management, such as Lactobacillus acidophilus, Reuteri and Rhamanos. Im including a couple now.
    http://newsroom.heart.org/news/daily-doses-of-a-new-probiotic-239562
    http://www.medscape.com/viewarticle/775157_2

    2.) High Choleserol is linked to a copper deficiency. http://jn.nutrition.org/content/116/9/1735.extract#
    I added in food sources and supplements to provide an ample supply of copper molecules. Seafood, whole food vitamin C (innate response tablets – 800g a day), perfect desicatted liver capsules (undefatted). I realized my protein choices during my low carb did not include much protein outside of eggs, beef and chicken.

    3) Silica Deficiency – my vegetable choices were limited and basic, broccoli, cauliflower and asparagus. Low fiber diets in general create a silica deficiency. Silica which helps bind cholesterol and protect your arteries, also enchances copper metabolism. I started eating green beans, oatmeal, raisins, this is when I saw the biggest drop in my cholesterol.
    http://www.ncbi.nlm.nih.gov/pubmed/15539241
    http://www.dcnutrition.com/Minerals/detail.cfm?RecordNumber=45
    http://www.lifeextension.com/magazine/2003/4/report_silicon/Page-01

    4) Magensium – required in over 3,000 processes in the body. Deficiency in it brings all sorts of metabolic disfunction. In regards to cholesterol, deficiency is also linked to high cholesterol. I added in 5mg per lb of body weight in supplement form, A combination of Magnesium Malate, glyncinate, and oxid. A lot of info available, a few sample articles.
    http://www.ncbi.nlm.nih.gov/pubmed/19205579
    http://www.dailyherald.com/article/20150207/entlife/150209666/

    What are your thoughts on the cholesterol metabolism being directly affected by the other metabolic processes relying on various minerals or resulting deficiencies due to food choices, rather than simply fat intake?

    I sent you this on mfp as well.

    • BJJ Caveman says:

      Thanks for this extensive post. Looks like you’re going down the same rabbit hole as me!

      1. Probiotics – definitely plays a role. Was part of my regimen that helped me lower my cholesterol… although now that I’ve been trying them individually, I haven’t seen much if any of an effect.

      2. Copper deficiency – I went down this path too… loaded up on a bunch of copper supplements and noticed zero effect. I know there’s a relationship there… but it just wasn’t a significant one in my case.

      3. Silica – This is the first I’ve seen about this, so I can’t really comment on this.

      4. Mag – I’ve supplemented with tons of mag and haven’t noticed any effects in my cholesterol.

      I do think that there are cases where deficiencies in these minerals and alterations in probiotics can cause elevations in LDL… but at least in my case, they’re not the major factors.

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