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LDL Particles, Lipoprotein A, and Thyroid Health

Published April 4 2016

When it comes to the lipid markers, most people, as well as doctors, pay attention to the total cholesterol, LDL, HDL, and triglycerides.  While it’s desirable to see these lipid markers within the lab reference range, there are other lipid markers that can be an even better indicator of one’s cardiovascular health.  In other words, someone can have a “normal” total cholesterol and LDL and still be at risk for cardiovascular disease.  Similarly, having a high total cholesterol and/or LDL level doesn’t necessarily mean that you are at an increased risk for developing cardiovascular disease.  That’s why you want to consider testing the LDL particles and lipoprotein A.

If you are interested in learning more about the “standard” lipid markers I mentioned in the opening paragraph, I would refer to an article I wrote entitled “How Does Thyroid Hormone Affect Cholesterol, LDL, and The Triglycerides? [1]“.  But in this article I am going to focus on the LDL particles and lipoprotein A.  And I will of course discuss how they relate to thyroid health.  I’ll also discuss a few other advanced markers.  But right now I’d like to go ahead and talk about the LDL particle number and lipoprotein A:

LDL Particles.  Having high numbers of LDL particles (LDL-P) can increase one’s cardiovascular risk.  You ideally want to see the LDL-P less than 1,000 nmol/L, and less than 700 nmol/L would be even better.  A value over 2,000 nmol/L is considered to be extremely high.  However, while you want to have a low number of LDL particles, you don’t want to have a small LDL particle size.  I know this might be somewhat confusing, but I would just remember that you want to have low numbers of LDL-P and a larger LDL particle size.  I’m going to focus more on the number of LDL particles in this article, rather than the LDL particle size.

It’s also important to understand that even if you have low LDL-cholesterol (LDL-C) levels you still can have elevated LDL particle numbers (1) [2].  Chris Kresser gives a pretty good analogy in this article [3] to help people better understand what an LDL particle is.  LDL particles travel through the bloodstream, and Chris compares the bloodstream to a highway, and he compares the lipoproteins to cars that carry the cholesterol and fats around your body.  He discusses how the main concern is when there are a lot of cars on the road (a large number of LDL particles).   I would definitely read this article for a better understanding of what an LDL particle is, and shortly I’ll discuss some factors which can help to decrease the numbers of LDL-P and/or increase LDL particle size.

Lipoprotein A.  Lipoproteins are molecules that consists of both fat and proteins.  They carry cholesterol and other substances through the blood.  So lipoprotein a, which is also known as Lp(a), is a type of lipoprotein, and it has been confirmed as a risk factor for coronary heart disease, atherosclerosis, thrombosis, and stroke (2) [4] (3) [5].  LP(a) levels less than 50 mg/dL (125 nmol/L) are considered to be normal.  Genetic factors are primarily responsible for elevated Lp(a) levels, and many sources suggest that lifestyle changes don’t have much of an impact on this marker, although I’ll discuss shortly how certain nutrients might be able to help lower this marker.

How Do These Markers Relate To Thyroid Health?

As I discussed in the previous article on lipids, both total cholesterol and LDL-C will usually increase in hypothyroid conditions.  And the same is true with LDL particles, as the research shows that these also increase as thyroid function decreases (4) [6] (5) [7] (6) [8].  So if testing determines that you have a large number of LDL particles, then one important step is to make sure that you don’t have low or depressed thyroid hormone levels.  And while this mostly relates to those people with hypothyroidism and Hashimoto’s Thyroiditis, those with hyperthyroidism and Graves’ Disease who take antithyroid medication might also experience an increase in LDL particle size that is resolved upon stopping the antithyroid medication.

You might wonder if Lp(a) is also affected by low or depressed thyroid hormone levels.  The evidence does show that hypothyroidism is associated with elevated levels of Lp(a), and thus can be decreased with thyroid hormone replacement (7) [9] (8) [10].

How To Decrease LDL-P and Lipoprotein A Naturally

It does appear that dietary factors can impact the LDL particles.  Just as a reminder, you ideally want to decrease the LDL particle number and increase the LDL particle size.  One study showed that a high-fat diet can cause a significant increase in LDL particle size, and a significant decrease in the proportion of small LDL particles (9) [11].  I came across a study which showed that subjects eating one fresh avocado per day over a period of five weeks had a significant decrease in the LDL particle number (10) [12].  Another study showed that alternate day fasting with a high fat diet is effective in improving LDL particle size and distribution (11) [13].  Some nutrients which might have a positive effect on LDL-P include extended-release niacin (12) [14] (13) [15] and fish oils (14) [16].

As I mentioned earlier, numerous studies suggest that lifestyle factors may not affect Lp(a) levels.  Studies show little effect of moderate exercise on Lp(a) levels, although a possible exception may be elevated levels in adult endurance and power athletes who exercise intensely on a regular basis (15) [17].  One study looked to see if a gluten-free diet has an effect on Lp(a) levels.  It was a small study involving 17 patients with Celiac disease, and the results showed that the Lp(a) levels weren’t modified (16) [18].  Another small study actually showed that dairy can decrease Lp(a), while soy may increase it (17) [19].  The research does show that certain nutrients can lower Lp(a), and these include extended-release niacin (18) [20], omega 3 fatty acids (in non renal patients) (19) [21], flaxseed (20) [22] (21) [23], and CoQ10 (22) [24].

Other Cardiovascular Markers Worth Mentioning

Although the main focus of this article was to discuss LDL particles and lipoprotein a, I want to briefly mention a few other advanced markers:

Apolipoprotein B (ApoB).  The ApoB gene provides instructions for making two versions of the apolipoprotein B protein, a short version called apolipoprotein B-48, which is produced in the intestine, and a longer version known as apolipoprotein B-100, which is produced in the liver (23) [25].  Both of these are components of lipoproteins.  What’s important to understand is that high levels of ApoB are correlated with an increased risk of developing heart disease.  Apolipoprotein B is a key structural component of all the atherogenic lipoprotein particles, including LDL and VLDL (24) [2], and so if someone is unable to test for the LDL particles, they can still get valuable information by testing ApoB.  Most labs use a reference range between 40-125 mg/dL, although some sources suggest keeping it lower than 80 mg/dL.  Hypothyroidism can lead to an increase in ApoB (25) [26], and hyperthyroidism can cause a decrease in this marker (26) [27].  Some nutrients which might help to decrease ApoB include niacin (27) [28], omega 3 fatty acids (28) [28], Green tea catechins such as EGCG (29) [29], and berberine (30) [30].

Apolipoprotein A-1  (ApoA1).  This is another marker that can help to determine the risk of developing cardiovascular disease.  ApoA1 is a protein that plays a role in the metabolism of lipids, and it is the main protein component of HDL particles (31) [31].  Low levels of ApoA1 are associated with low levels of HDL and impaired clearance of excessive cholesterol from the body, and thus low levels of this marker are associated with an increased risk of cardiovascular disease.  With regards to thyroid health, one study I came across showed that hypothyroidism was associated with an increase in ApoA1, whereas hyperthyroidism was associated with a decrease in ApoA1 levels (32) [32].  In most cases I don’t think it’s necessary to order this test, although some like to look at the ratio of ApoA1 to ApoB, which has been shown to be an effective predictor of coronary heart disease risk in those who are overweight or obese (33) [33].  You ideally want ApoB/ApoA1 ratio to be <0.8.  There is evidence that extended-release niacin can help to increase apoA1 (34) [34] (35) [35].

Lipoprotein-associated Phospholipase A-2 (Lp-PLA2).  This is a marker of vascular inflammation, and it is associated with atherosclerosis.  This marker can determine if you have stable or unstable plaque.  A high Lp-PLA2 usually means that you have an unstable plaque that is prone to rupture, or has already done so.  A concentration <200 ng/mL is optimal, while a concentration between 200-235 ng/mL is associated with a moderate risk of cardiovascular disease and stroke, and a concentration >235 ng/mL is associated with a high risk of cardiovascular disease and stroke (36) [36].  Some research shows higher Lp-PLA2 levels in those with subclinical hypothyroidism (37) [6].  Some nutrients which can decreased Lp-PLA2 include niacin (38) [37] and omega 3 fatty acids (39) [38] (40) [39].

In summary, while a standard lipid panel can provide some valuable information, testing for other markers such as LDL particles and lipoprotein A can be a better indication of one’s risk of developing cardiovascular disease.  With both LDL-P and Lp(a), a lower value will decrease the risk of developing cardiovascular disease.  Low thyroid hormone levels can increase both of these markers, and dietary factors may play a greater role in affecting LDL-P than Lp(a), although I listed some nutrients that can impact both of these.  Some other cardiovascular markers you might want to consider testing for include Apolipoprotein B, Apolipoprotein A-1, and Lipoprotein-associated Phospholipase A-2.