I was poking around Dr. Tara Dall’s website one day and came across this case study that surpisingly reminded me of my own case (I’ve uploaded a copy here just in case her link breaks).
Dr. Dall is the lipidologist I visited to help me review my cholesterol situation. Here are links to the posts documenting my consultation with her:
- What a Doctor Asks His Lipidologist
- Consultation with the Lipidologist
- Reviewing the Labs My Lipidologist Ordered
In fact, it was through my meeting with her that I learned that I am both a cholesterol hyper-synthesizer AND a hyper-absorber, and that I have an ApoE 3/4 genotype. I believe these are the main factors contributing to my persistently high cholesterol.
In my case, Dr. Dall hypothesized that the one of the primary reasons behind my persistently elevated LDL particle count is underlying insulin resistance, which she based on my elevated HbA1c’s of 5.7-5.9% and my LP-IR scores from my previous NMR Lipoprofiles which measured in the 45-50 range (normal is </= 45).
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Because of this, she recommended that I either try Metformin or Berberine, which she said had a lot of similarities to Metformin and could help address my cholesterol hyper-synthesis.
I found a paper from Expert Opinions on Investigational Drugs from 2005 showing that
Berberine upregulates the LDL receptor (LDLR) by a mechanism distinct from that of the statins…
…reduced LDL-cholesterol (from 3.2 to 2.4 mmol/l) without any effect on high-density lipoprotein-cholesterol.
This is why I started experimenting with Berberine which has had some level of success:
- Cholesterol Update with Berberine, January 2017
- Cholesterol Update after Increasing the Dose of Berberine, February 2017
- Cholesterol Update with Berberine AND Bergamot, April 2017
While I was finally able lay my HbA1c issues to rest by showing that the reason it always bounced between 5.7-5.9% is actually because my red blood cells live longer than normal, I suspect that I still DO have some degree of insulin resistance given my history of easy weight gain with carbs, and the fact that Berberine actually helps my LDL-P.
It’s with this background that I found this case study so interesting.
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Enter: A healthy woman with high cholesterol
The patient is a “healthy 45 year old woman who is on a low-glycemic diet and exercises 150 minutes a week [who] comes in for an evaluation of abnormal lipids despite her excellent lifestyle efforts.”
Sounds familiar doesn’t it? My diet for the past few years has either been ketogenic or low glycemic as with Tim Ferriss slow carb or paleo/primal or Whole 30, and my LDL-P has stubbornly remained elevated. On top of that, I exercise anywhere from 3-6 hours a week!
Ok, moving on. Here are the labs she presented with:
These labs are both very similar and very different. Our Total cholesterol, LDL-C, HDL-C, HbA1c, and LDL-P are nearly identical.
Where our labs diverge are that the highest my Small LDL-P has ever gotten is 1260, my triglycerides rarely creep above 100, my CRP generally stays below 1.0, and my LP-IR (Lipoprotein Insulin Resistance Index) has never gotten above 50.
These numbers seem to indicate that this patient is more insulin resistant than I am, but let’s see what Dr. Dall says:
Her LDL-P of 2,552 is considered very high risk and places her in the >95th percentile of the population based on both Framingham and MESA data (Table 1). If there were any hesitation to treat her dyslipidemia, one would be more inclined to treat with this additional information and elevated highly sensitive C reactive protein (hsCRP). She is currently preventing future childbearing, so a statin would be the first choice of therapy. If she is open to pregnancy, then alternatives to statin could include niacin, fibrate or bile acid sequestrant. A bile acid sequestrant would help lower LDL-P but should not be the first choice, because it has the potential to raise triglycerides further.
This definitely gives you a window as to how she likes to approach pharmacologic treatment of high cholesterol.
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Asking Why
When I met her, the thing that I immediately liked about her was that she was interested in understanding WHY my cholesterol was high. I didn’t want a physician that was going to shoot from the hip, fire off a prescription for a statin, and then send me on my way. Dr. Dall was exactly what I was looking for and she approached my case like she did in in this case.
She wanted to ‘rule out secondary causes of dyslipidemia’ before starting her drugs. She checked the patients thyroid levels to make sure there wasn’t any hypothyroidism pushing the lipids up. She made sure the patient wasn’t on any other medications or supplements that could elevate cholesterol. Dr. Dall also checked the patient’s HbA1c to assess the patient’s risk of diabetes and insulin resistance which can also contribute to high cholesterol.
It’s with the HbA1c of 5.7% which places the patient in the category of ‘prediabetes’ along with the pattern of LDL particles that suggested to Dr. Dall that insulin resistance was the source of this patients cholesterol issues:
This patient also has predominantly small dense LDL, which encompasses more than 50% of her total LDL-P, suggesting insulin resistance is contributing to high LDL-P.
Insulin resistance is a common secondary cause of dyslipidemia characterized by high triglycerides and low HDL-C. The metabolic changes induced by or accompanying insulin resistance produce even greater and more extensive abnormalities in lipoprotein subclass levels and particle size distributions, which are detected by advanced lipoprotein testing.
Specifically, large very-low-density lipoprotein (VLDL) and small LDL subclass particle concentrations are higher and large HDL subclass levels are lower in insulin-resistant individuals. NMR-measured VLDL LDL, and HDL particle sizes also reflect insulin-resistance status.
VLDL size tends to be greater and LDL and HDL sizes smaller when a patient is insulin resistant. This unique lipoprotein “window” into insulin resistance gives us an opportunity to identify, by nature of the lipoprotein status, a patient who may be a candidate for more aggressive lifestyle efforts or pharmacologic therapy.
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Treatment
In our patient case, metformin ER 1500 mg was initiated at the first visit because of the abnormal HbA1C, family history of diabetes and lipoprotein parameters suggestive of insulin resistance. After two months of metformin use, her lipoprotein and lipid values improved. LDL-P dropped from 2,552 to 1,440 without a significant change in LDL-C.
Metformin, as expected, caused triglycerides to improve, and she had a five-pound weight loss without any further change in her diet and exercise regimen.
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Advanced lipid testing provides information beyond just LDL-P and Apo B. This information may allow us to better diagnose a secondary cause of dyslipidemia, namely insulin resistance.
Metformin ER, an effective therapy for insulin resistance, is available as an inexpensive generic medication. Metformin also causes weight loss, improves lipids and is pregnancy category B, a safe option in women of childbearing age. The main contraindications for metformin are renal disease and/or elevated creatinine>1.4. As monotherapy, there should be minimal risk for hypoglycemia.
I wonder what would happen if I took Metformin. It might be something to seriously explore, especially since Metformin is thought to increase the lifespan in mice and its anti-aging properties are currently being investigated in human trials.
If you enjoyed this post and want to learn more about cholesterol here are some similar posts that you might find helpful:
- Ketosis And High Cholesterol According to Dr. Thomas Dayspring
- 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
- Low Carb and High Cholesterol from Around the Web
- Dr. Hallberg LDL on LCHF Talk
Nice post. Too bad she moved to Virginia, I could have seen her in WI. I can’t remember if you have discussed this but are you APOE4 positive and if so, did she discuss this with you?
Yes. She did discuss my apoe status with me. I have to watch my saturated fat intake!