Sunday, November 18, 2012

Troubleshooting High Cholesterol: Part 2

This blog post is for informational purposes only and is not meant to diagnose or treat any medical condition.

If you haven't already see Part 1

Possible Causes of High Cholesterol or LDL-P

If you have high LDL-C or LDL-P, and whether you said yes to any of the things on the list above or not, it’s important to find to why you have high LDL-C or LDL-P as it could suggest an underlying problem that should be fixed 

Losing Abdominal and/or Liver Fat 

If you got your cholesterol tested and it came back high shortly after you changed your diet/lifestyle it could be that active weight loss and/or clearance of liver fat is temporarily increasing your cholesterol or LDL-P levels [1]. 

  • Both active weight loss and clearance of liver fat will increase triglycerides as more of them enter the circulation
  • LDL-P may increase slightly as more LDL particles may be needed to transport the extra triglycerides
  • These LDL particles stay in the bloodstream for longer, which increases their exposure to cholesterol ester transfer protein (CETP).  CETP may then exchange the triglycerides from the triglyceride rich VLDL particles with cholesterol from HDL particles, resulting in higher LDL-C and lower HDL-C 

Simply wait until your weight has stabilised, and then wait another a month or so until your next test.  You could be clearing liver fat even if you haven’t lost weight (especially if you were insulin resistant, drinking a lot of alcohol or had IBS and are now eating more eggs/liver), once again wait a few months.

Hypothyroidism 

While thyroid hormone increases both cholesterol synthesis and cholesterol metabolism (increases LDL receptor activity), people with hypothyroidism tend to have higher LDL-C and LDL-P with minimal differences in triglycerides and HDL-C [2].  People with subclinical hypothyroidism (high TSH but in the reference range) also have higher TC, non-HDL-C and triglycerides, but and lower HDL-C [3] 

Key nutrient deficiencies (iodine, iron, selenium) can impair thyroid function, although the most common cause of hypothyroidism in developed countries is autoimmune attacks against the thyroid (like Hashimoto’s thyroiditis).  Likely common causes of subclinical hypothyroidism include calorie restriction, overtraining [4] and very low carb diets [5] [6] [7] 

Insulin Resistance 

Insulin resistance results in higher triglycerides and LDL-P, which in turn can result in smaller increases in LDL-C and decreases in HDL-C [8] probably via an increased activity of CETP.  See Stephan Guyenet’s seven part series on: What Causes Insulin Resistance? 

Elevated LPS 

One function of lipoproteins, particularly LDL, is to neutralise LPS in the bloodstream.  LPS-binding protein binds to LPS and transfers it to either lipoproteins or CD14 expressing monocytes/macrophages [9].  LPS increases LDL-C levels: 

  • Administration of LPS increases cholesterol synthesis, LDL-C and triglycerides, but lowers HDL-C [10]
  • People with periodontitis have higher LDL-C (1.0 mmol/l), lower HDL-C (0.3 mmol/l) and higher triglycerides (0.6 mmol/l) [11] 

Inflammation 

One of the functions of the cholesterol transport of LDL is to repair cells and tissues, specifically the vasculature* [12].  So a high cholesterol level could indicate vascular injury.  Besides LPS, other source of inflammation are associated with high cholesterol: 

  • Copper deficiency promotes CVD [13] and increases LDL-C [14]
  • Homocysteine is a risk factor for CVD.  In children with high homocysteine, folate supplementation decreased homocysteine and cholesterol levels (0.6 mmol/l) [15] 
  • Severe vitamin C deficiency increases LDL-C [16] 
  • Ferritin is associated with LDL-C [17] [18] [19] 

* This function was actually one of the main ideas behind the response to injury hypothesis, where vascular injury (desquamation of endothelial cells) increased cholesterol transport to that area and if there was prolonged injury then the cholesterol would build up and form plaques. 

Stress 

Stress seems to raise cholesterol: 

  • Mental stress (10 minutes of mental arithmetic with harassment) raised TC, HDL-C, LDL-C and triglycerides (by ~20%), which was partially due to a reduction in plasma volume [20] 
  • Cholesterol levels in male medical students were on average 11% higher during examination week [21] [22] and 16.5% higher during the winter quarter exams [22] 

* On the effect of plasma volume on cholesterol levels: there is a minor seasonal variation, where cholesterol levels are slightly lower during summer, probably due to an increase in plasma volume during summer [23].  Also, salt restriction causes a minor increase in TC, LDL-C and triglycerides [24], which may be related to a slightly lower plasma volume 

See Chris Kresser’s blog post on 9 Steps to Perfect Health – #6: Manage Your Stress 

Genetics 

Like many things, genes explain a fair bit of the individual variation in cholesterol levels.  Some genetic determinants of high cholesterol include: 

  • Familial hypercholesterolemia (FH) is a rare inherited disorder, often resulting from a defect in the LDL receptor.  Only 1 in 500 people have the milder form (heterozygous), which results in very total cholesterol levels (~8-10 mmol/l) and LDL-C.  People with FH will have had very high cholesterol for their whole lives 
  • ApoE is a protein on LDL particles.  The ApoE4 polymorphism has a frequency of 14.7% and results in higher LDL-C, particularly in the context of a high fat or high cholesterol diet [25], and a greater risk of other diseases such as Alzheimer’s disease

See Should I Take a Statin?

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