What Causes Elevated LDL Particle Number? | Chris Kresser
HCTP Banner

What Causes Elevated LDL Particle Number?

by

Last updated on

iStock.com/Jezperklauzen

To read more about heart disease and cholesterol, check out this eBook on the Diet–Heart Myth.

In the last article in this series, I explained that LDL particle number (LDL-P) is a much more accurate predictor of cardiovascular disease risk than either LDL or total cholesterol. In this article, I’m going to briefly outline the five primary causes of elevated LDL-P.

Conventional medicine is primarily focused on suppressing symptoms. If your blood pressure is high, you take a medication to lower it. If your blood sugar is high, you take a medication to lower it. If your cholesterol is high, you take a medication to lower it. In most cases there is rarely any investigation into why these markers are high in the first place, with the possible exception of some basic (but often incorrect) counseling on diet and exercise.

On the other hand, Functional Medicine—which is what I practice—focuses on treating the underlying cause of health problems instead of just suppressing symptoms. If your blood sugar, blood pressure or cholesterol are high, the first question a Functional Medicine practitioner will ask is “why?” If we can identify the root cause of the heart health problem, and address it at that level, medication is often unnecessary.

To use a simple analogy, if you have weeds in your garden, what happens if you just cut the weeds from the top? They grow right back—and sometimes faster than before! If you really want to get rid of them once and for all, you have to pull them up by their roots.

With this in mind, let’s look at some of the potential causes of elevated LDL particle number. If your LDL-P is high, it makes sense to test for and treat any of the conditions below (with the exception of the last, which is genetic and thus can’t be treated) before—or at least along with—taking pharmaceutical drugs.

5 common causes of elevated LDL particle number that can increase your risk of heart disease.Tweet This

Insulin Resistance and Metabolic Syndrome

LDL particles don’t just carry cholesterol; they also carry triglycerides, fat-soluble vitamins and antioxidants. You can think of LDL as a taxi service that delivers important nutrients to the cells and tissues of the body.

As you might expect, there’s a limit to how much “stuff” that each LDL particle can carry. Each LDL particle has a certain number of cholesterol molecules and a certain number of triglycerides. As the number of triglycerides increases, the amount of cholesterol it can carry decreases, and the liver will have to make more LDL particles to carry a given amount of cholesterol around the body. This person will end up with a higher number of LDL particles.

Consider two hypothetical people. Both have an LDL cholesterol level of 130 mg/dL, but one has high triglycerides and the other has low triglycerides. The one with the high triglyceride level will need more LDL particles to transport that same amount of cholesterol around the body than the one with a low triglyceride level.

Numerous studies have found an association between increased LDL particle number, and metabolic syndrome. One study measured ApoB, a marker for LDL particle number, in a group of 1,400 young Finns with no established disease. The participants with the highest LDL particle number were 2.8 times more likely to have metabolic syndrome than those with the lowest levels of LDL-P. (1) A much larger study of over 300,000 men also found a strong association between LDL-P and metabolic syndrome and its components (i.e. insulin resistance, abdominal obesity, high blood pressure, etc.). (2)

Poor Thyroid Function

Poor thyroid function is another potential cause of elevated particle number. Thyroid hormone has multiple effects on the regulation of lipid production, absorption, and metabolism. It stimulates the expression of HMG-CoA reductase, which is an enzyme in the liver involved in the production of cholesterol. (As a side note, one way that statins work is by inhibiting the HMG-CoA reductase enzyme.) Thyroid hormone also increases the expression of LDL receptors on the surface of cells in the liver and in other tissues. In hypothyroidism, the number of receptors for LDL on cells will be decreased. This leads to reduced clearance of LDL from the blood and thus higher LDL levels. Hypothyroidism may also lead to higher cholesterol by acting on Niemann-Pick C1-like 1 protein, which plays a critical role in the intestinal absorption of cholesterol. (3, 4)

Studies show that LDL particle number is higher even in subclinical hypothyroidism (high TSH with normal T4 and T3), and that LDL particle number will decrease after treatment with thyroid hormone. (5)

Infections

Another cause of high cholesterol profile is infection. Multiple studies have shown associations between bacterial infections like Chlamydia pneumoniae and H. pylori, which is the bacterium causes duodenal ulcers, and viral infections like herpes and cytomegalovirus and elevated lipids. (6) For example, H. pylori leads to elevated levels of total cholesterol, LDL cholesterol, lipoprotein (a), ApoB or LDL particle number, and triglyceride concentrations as well as decreased levels of HDL. (7)

Several mechanisms have been proposed to explain the association between infections and elevated blood lipids. Some evidence suggests that viral and bacterial infections directly alter the lipid metabolism of infected cells, and other evidence suggests that lipids increase as a result of the body’s attempt to fight off infection. Other evidence suggests that LDL has antimicrobial properties and is directly involved in inactivating microbial pathogens. This has been confirmed by studies showing that mice with defective LDL receptors—and thus very high levels of LDL—are protected against infection by gram-negative bacteria like H. pylori. (8)

Leaky Gut

One of the primary functions of the intestinal barrier is to make sure that stuff that belongs in the gut stays in the gut. When this barrier fails, endotoxins such as lipopolysaccharide (LPS) produced by certain species of gut bacteria can enter the bloodstream and provoke an immune response. Part of that immune response involves LDL particles, which as I mentioned above, have an anti-microbial effect. A protein called LPS-binding protein, which circulates with LDL particles, has been shown to reduce the toxic properties of LPS by directly binding to it and removing it from the circulation. (9) Studies have also shown significant increases in LPS-binding protein (and thus LDL particles) in cases of endotoxemia—a condition caused by large amounts of circulating endotoxins. (10)

Though more research is needed in this area, the studies above suggest that a leaky gut could increase the level of LPS and other endotoxins in the blood, and thus increase LDL particle number as a result. I have seen this in my practice. I recently had a patient with high LDL-P and no other risk factors. I tested his gut and discovered H. pylori and small intestine bacterial overgrowth (SIBO). After treating his gut, his LDL-P came down to normal levels.

Genetics

The final cause of elevated LDL-P is genetics. Familial hypercholesterolemia, or FH, involves a mutation of a gene that codes for the LDL receptor or the gene that codes for apolipoprotein B (ApoB). The LDL receptor sits on the outside of cells; the LDL particle has to attach to the LDL receptor in order to deliver the nutrients it’s carrying and be removed from the circulation. ApoB is the part of the LDL particle that binds to the receptor. If we use a door lock as an analogy, apolipoprotein B would be the key, and the LDL receptor is the lock. They both need to be working properly for LDL to deliver its cargo and to be removed from the bloodstream.

Homozygous carriers of FH have two copies of the mutated gene. This condition is very rare. It affects approximately 1 in a million people. And people that are homozygous for this mutation have extremely high total cholesterol levels, often as high as 1000 mg/dL. And unfortunately they usually die from severe atherosclerosis and heart disease before the age of 25.

Heterozygous carriers, however, only have a single copy of the mutated gene, and the other copy is functioning normally. This is much more common. The prevalence is between 1 in 300 to 1 in 500 people, depending on which study you look at. These heterozygous carriers of FH have total cholesterol levels that often range between 350 and 550 mg/dL, along with very high LDL particle number. They have about three times higher risk of death from heart disease than people without FH if it goes untreated.

It’s important to note that people with FH have primarily large, buoyant LDL particles, and yet are still at much higher risk for cardiovascular disease. While it’s true that small, dense, oxidized LDL particles are more likely to cause atherosclerosis, large, buoyant particles can also be harmful when their concentration is high enough. This is one reason why LDL particle number is a superior marker to LDL particle size.

In the next article in this series, I will debunk the myth that statins extend lifespan in healthy people with no pre-existing heart disease.

240 Comments

Join the conversation

  1. Very interesting comment thread. I have been in an experimentation phase with my diet over the past six months.

    I just got what looks like a bad lab test back (52 years old, 5 ft 10 in, 205 pounds, 25% body fat), and am trying to decipher. As a result of these numbers I am going for a coronary artery scan/calcium score next week:

    LDL-P 2432
    LCL-C 199
    Small LDL-P 817
    LDL Size 21.6
    Triglycerides 106 (vs 160 2 years earlier)
    Insulin Resistance Score <25

    So, the history here is I went on LCHF diet with some intermittent fasting last August, lost 15 pounds and 7 inches off my abdomen by November, down from 220 to 205, but then stalled through January (holidays!). In general, I have felt great on this diet – better than I can ever remember.

    I had a blood test in December, but didn't have particle size tests, but otherwise numbers were slightly better across the board in December vs. March, but close.

    What changed between Dec and March? I cut out all alcohol from my diet (10-15 drinks per week mostly red wine or low carb spirits) just to see if it helped with weight loss (goal weight is 190 and ~20% body fat).

    I actually GAINED 10 pounds back by early March after quitting alcohol, back up to 215 !! However, there were 2 other changes that might have had impact – I was doing less intermittent fasting, and I also entered a super-stressful phase at the same time related to work, where I wasn't sleeping well, etc. so the weight gain may have been tied to one of those factors I figure.

    I started feeling better in early March, sleeping again, but still no alcohol, and re-introduced IF and the weight started coming off going into the blood test when I got back to roughly the same weight I was at in November with the same body composition (I did hydrostatic weighing in Jan and March).

    Reading on this thread that losing weight can increase overall cholesterol might be an explanation for my high readings given my weight re-loss in past several weeks? I won't take statins. Ultimately, I'll see what the coronary scan has to say next week. No history of heart disease or heart attacks in my family, but I have a stressful life at times.

  2. Not only did I just find out I have a LDLp of 1827, sdLDLc of 35, small LDL-P of 895, total cholesterol of 203, LDLc of 127, triglycerides of 156, non-HDLC 139, but the kicker was an APOE genotype of 4/4. I didn’t know what any of this meant, but I’m freaking out about that 4/4, especially since no one in my very large family had/has Alzheimer’s. So I heard that eating lots of coconut oil is excellent to ward off dementia or Alzheimer’s, but isn’t that terrible for cholesterol? I feel like if I try to reduce chance of Alzheimer’s, I’m putting myself at further risk before cardiac disease. So I guess I’m asking what I can do… if there’s a diet that could help my heart AND my brain? There is so much conflicting info out there that I’m getting very confused as to what I should do. :(((

  3. My physician has wanted to put me on a statin for several years due to high cholesterol levels. I have resisted and still resist even with latest results. My NMR Lipoprofile is as follows: LDL-P=1869; LDL-C=190; HDL-C=100; Trigs=83; Total Cholesterol=307; HDL-P=42.9; Small LDL-P=<90; LDL size=21.7; LP-IR score<25. I've been considering a paleo diet. Would that be beneficial?

    • Not a doctor, but your numbers are very high. The benefits of statins probably outweigh and the risk of side effects and also the serious risk of heart disease you face. You should discuss the risks and benefits with your doctor.

      • what benefits are there to statins Joe? My dad has been on low dose statins for 20 years and developed parkinsons and dementia 8 years ago. He recently looked into the benefits of statins compared to the risks and decided to stop taking them and do a keto diet in hopes the progression of his ailments would slow. Oh wait, benefits to the drug companies, right? b/c 40 percent of women who take statins get diabetes? PPS i did keto diet & got optimal on natural thyroid and now my cholesterol numbers are perfect

    • Yes your LDL-P is certainly high should be somewhere around 1000-1200 mark for non-high-risk people. I think you should give statins a go. Yes, they would decrease your total cholesterol but they will initially decrease particles as well. Statins are not a long term solution anyway. I have read, some diabetes drugs like metformin also helps with lowering of LDL-P. But at the end of the day its the life style changes that would bring the maximum benefits.

  4. I was diagnosed with Dyslipidemia in 2010. I have since lost weight and started taking Niacin 1000MG (with flush) once a day. I take them at bedtime with 50mg of Benadryl. On Nov 2nd and again today I broke out all over in hives at about 10am- what appears and feels like the flush from the Niacin. Why would this happen 12 hrs after I took the medicine?

  5. Actually I’m suffering from skin disease (hairfall, itching, excessive dandruff, scales etc. ). I had consulted from a dermatologist in vivekanand hospital Lucknow and undertook her treatment for 2 months but still I got no relief then she prescribed me a test known as lipid profile test. Next day I got the test report according to which my cholesterol level was high (Total cholesterol-228 and LDL cholesterol-171).
    After going through my test report she (dermatologist) reffered me to homeopathy. 
    Now the question arises that why she prescribed me lipid profile test because this test is all about cholesterol and how cholesterol is related to skin disease and second question is that why she referred me to homeopathy. 

  6. Hi please help explain these numbers. LDL-P 3039, LDL-C 194,
    HDL-C 60, TRIGLICERIDES 135, CHOL TOTAL 281, HDL-P 38.0,
    SMALL LDL-P 833 LDL size 22.0. Hemoglobin A1c 5.7 I have hashimotos and take synthroid 50 MCG, I also have tested positive for a viral infection and was treated for another one. My father died of heart disease 60, open heart surgery 42, diabetes runs in family and cancer. I do not smoke or drink and I am 67. I am a bit over weight 32# 5’1″. What should I do? Please help as the Doctors do not help only suggest statins and do not explain results or what I can do. There is very conflicting information and theories on the web. Please help.

    • I can tell you that my cholesterol to LDL ratio went down drastically which is a fair indicator of lowering ldl-P by lowering carbs- Recently we’ve gone keto all the way. As a side effect my a1c reduced from 5.7 to 4.9 since last year. Wondering if you tried lowering carbs?

    • A normal total cholesterol is 100-150mg/dL. A normal LDL cholesterol is 50-70 mg/dL. LDL-p should be well below 1000. According to your sky high numbers, your LDL-p(3039), cholesterol(281), and LDL(194), your chances of diying from heart disease are ultra high. You need to get these numbers in check. Eliminate meat, eggs, dairy, oils, sugars and refined floors. All your numbers will fall quickly. If you do not believe me, try for two weeks you will see. Make a blood sample before and after your experiment. May health be with you again.

  7. I was diagnosed with a high LDL particle number (2185) 2.5 years ago. I’ve been on a very LCHF diet for that amount of time. My number has gone down as low as 1517, but started creeping back up again, and is now higher than it was pre-LCHF. It’s now 2250. I keep reading not to do a statin, and I don’t plan to. But not sure what else to try. For the last 3 months I’ve taken 1000 mg of niacin per day, but that didn’t help at all… 1989 pre-niacin, and 2250 now. REALLY don’t know what to do and super frustrated and emotional. Seems like it’s just going to go higher and higher…

    • Don’t you think you could be a hyper absorber of cholesterol?
      That would make the most sense, thus statin/ zetia would definitely fix your problem, or cut way back on SF’s. Drop the ketosis too. Just a thought.

    • It is your ultra high fat and cholesterol laden diet that are likely
      the cause of these numbers. LDL-p should be under 1000.

      Here a trial for you : Eliminate industrial foods, floors, meat, eggs, dairy, oils, sugars and refined floors for two weeks. All your numbers will fall quickly. Make a blood sample before and after your experiment.

  8. Hello,

    So can one infer from
    High LDL-P and
    Normal LDL-C and
    High Number of Small and Medium LDL

    that reducing Triglycerides would be beneficial in reducing the count of LDL-P since each LDL particle can now carry more cholesterol and hence the number of LDL particles decrease (of course assuming that LDL-C remains constant).

    Thanks,

  9. So, am I to understand that there are only 5 reasons for High LDL Particle Number?

    In the first four cases, Chris has mentioned the treatment process. However, what should one do if it is none of the four cases i.e. genetics? Statin? Or something else?

[if lte IE 8]
[if lte IE 8]