High Cholesterol and Hypothyroidism - Connecting the Dots | Chris Kresser
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High Cholesterol? CVD Risk? It Might Be Your Thyroid

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Do you have high cholesterol? Are you concerned about your heart health? You might want to get your thyroid checked out. Thyroid hormones play a major role in lipid metabolism and are one of the major causes of high cholesterol. Read on to learn more.

Thyroid and cholesterol
Thyroid hormones are an important component to lipid metabolism and can contribute to high cholesterol. istockphoto.com/Srisakorn

I’ve written enough articles on thyroid disorders to fill an entire eBook: all about low T3 syndrome, five thyroid patterns that won’t show up on standard lab tests, the little-known cause of hypothyroidism, and the gut–thyroid connection.

Thyroid hormone regulates a great deal of metabolism, and virtually every cell in the body has a receptor for thyroid hormone. In a recent podcast, I mentioned poor thyroid function as one of the six underlying causes of high cholesterol. In this article, I’ll discuss exactly how your thyroid impacts lipid metabolism, cholesterol levels, and other risk factors for cardiovascular disease. First, though, a quick review of the major hormones involved.

A Quick Review of Thyroid Physiology and Lab Panels

The thyroid is a small butterfly-shaped gland that sits at the front of the neck. It receives a hormone signal from the pituitary and secretes other hormones into the bloodstream. You might be familiar with these hormones, which are included in a full thyroid panel:

Thyroid-stimulating hormone (TSH): This hormone is released by the pituitary gland and reflects the body’s need for thyroid hormone. This means that when TSH is high, not enough thyroid hormone is being produced (hypothyroidism). When TSH is low, there is more than enough thyroid hormone in the body (hyperthyroidism).

Do you have heart disease or high cholesterol? You might want to get your thyroid checked

Thyroxine (T4): The thyroid gland releases large amounts of this largely inactive form of thyroid hormone, which must be converted into the more active T3 by deiodinase enzymes. Low amounts of T4 may indicate hypothyroidism; high amounts may indicate hyperthyroidism.

Triiodothyronine (T3): This is the active form of thyroid hormone, secreted in small amounts by the thyroid gland and formed from the conversion of T4 to T3. T3 is the primary thyroid hormone that will act on cells all over the body to regulate metabolism. Low amounts of T3 may indicate hypothyroidism or low T3 syndrome; high amounts indicate hyperthyroidism.

If thyroid medication is given for hypothyroidism, it is usually in the form of T4, T3, or a combination of the two.

The Association between Thyroid Hormone Levels and Cholesterol

The association between thyroid function and cholesterol has been known for quite some time. As early as 1934, it was recognized that “the concentration of blood cholesterol is usually raised in hypothyroidism, and lowered slightly in hyperthyroidism” (1).

Today, a PubMed search for thyroid and cholesterol yields more than 3,000 articles—yet few people, and even few doctors, are aware of how various thyroid conditions can impact cholesterol levels.

Let’s review the four major types and how they impact basic cholesterol measurements:

Hypothyroidism: People with an underactive thyroid, or hypothyroidism, often have increased levels of total cholesterol and LDL cholesterol (2) and may have elevated triglyceride levels as well (3). Thyroid medication can significantly improve lipid profiles. A study in newly diagnosed hypothyroid patients found that total cholesterol and LDL cholesterol levels decreased after T4 treatment. Those with higher TSH levels (indicating a greater need for thyroid hormone and a greater degree of hypothyroidism) at baseline saw a more dramatic reduction in cholesterol levels with T4 therapy (4).

Subclinical hypothyroidism: Subclinical hypothyroidism (SH) is characterized by elevated serum TSH with normal levels of free T4 and free T3. Subclinical hypothyroidism is far more common than overt hypothyroidism and may affect up to 9 percent of the population (5). Studies are mixed on the effect of subclinical hypothyroidism on lipid profiles, but even within the normal range of values, increasing TSH is associated with an increase in total cholesterol and LDL cholesterol (6, 7). One systematic review found that T4 substitution therapy on average resulted in an eight mg/dL decrease in total cholesterol and a 10 mg/dL decrease in LDL cholesterol in people with subclinical hypothyroidism (8).

Thyroid autoimmunity: Autoimmunity is a major cause of hypothyroidism. An estimated 90 percent of people with underactive thyroid have autoimmune thyroiditis, also known as Hashimoto’s disease. People with high-normal TSH levels that have positive anti-thyroid antibodies are even more likely to have abnormal cholesterol levels. On the bright side, their cholesterol levels are more likely to respond to thyroid medication (9).

Hyperthyroidism: While not as common, hyperthyroidism is associated with low levels of total cholesterol, HDL cholesterol, and LDL cholesterol (10, 11). While this may seem like a good thing, low blood cholesterol has been associated with altered cell membrane function, depression, anxiety, memory loss, and increased mortality (12, 13, 14).

How the Thyroid Regulates Lipid Metabolism

Fair warning, this section contains the nitty gritty details of lipid metabolism. If you’re not in the mood for a physiology lesson, you can skip on to the next section!

Thyroid hormones regulate cholesterol synthesis

You may have heard that dietary cholesterol doesn’t have much impact on blood levels of cholesterol. This is because cholesterol is also synthesized by the liver. This process is tightly regulated by several hormones, including thyroid hormones. TSH increases the expression and activity of an enzyme called HMG CoA reductase, which controls the rate of cholesterol synthesis (15). This means that hypothyroidism increases the amount of cholesterol produced in the liver. This cholesterol is then packaged with triglycerides into VLDL particles, which are shipped out to the bloodstream.

Thyroid hormones affect lipoprotein lipase (LPL)

VLDL particles travel through the bloodstream until they reach the small blood vessel beds, where they encounter an enzyme called lipoprotein lipase (LPL). This enzyme breaks down the triglycerides in the VLDL particle into fatty acids, which are taken up by adipose, heart, and muscle cells. T3 stimulates LPL to increase this breakdown of triglyceride-rich VLDL (16). Eventually, the cholesterol content of the lipoprotein becomes higher than the triglyceride content, and these particles become LDL.

Thyroid hormones increase LDL particle uptake

LDL particles circulate around in the blood until they bind to LDL receptors. This binding triggers the capturing of LDL particles into the cell. There, the LDL particles are degraded and the contents used for cell membrane structure or converted to other steroid hormones. Through several mechanisms, T3 increases the expression of LDL receptors (17, 18). This reduces the amount of time that LDL particles spend circulating in the blood and the total number of LDL particles in the blood.

Thyroid hormones affect LDL particle oxidation

Excess LDL particles in the blood can cause some particles to “crash” into the blood vessel wall and be taken into the inner lining of the blood vessel. Once there, the LDL particles can become oxidized, which triggers inflammation and is thought to be the major event initiating the formation of arterial plaque. T3 acts as a free radical scavenger and may protect LDL from oxidation (19). However, high free T4 can also enhance LDL oxidation (20). Thus, both hypo- and hyperthyroidism can lead to LDL oxidation.

The Dangers of Statins in People with Thyroid Dysfunction

If you’ve been following my work for a while, you probably know my opinion of statin drugs. Here are just a few of the articles I’ve written on statins:

But it turns out that statin use is particularly concerning when the cause of high cholesterol is poor thyroid function. This is due to the effects of statins on creatine kinase levels.

Creatine kinase (CK) is an enzyme expressed in many different tissues throughout the body, though it’s probably most well-known for its action in muscle cells. CK is responsible for adding a phosphate to creatine to form phosphocreatine, which serves as an energy reservoir and allows for the quick release of energy in times of need.

Both statins and hypothyroidism result in CK release into the blood, and the cumulative effect is severe CK elevation (21, 22). This can potentially amplify the adverse side effects of statins.

Statins can cause a variety of skeletal muscle problems, including damage and inflammation to the muscle. Based on several case reports, researchers have speculated that the use of lipid-lowering agents in hypothyroid patients may severely increase the risk of myopathy and rhabdomyolysis (23, 24).

Yet, in reviewing the relevant medical records of 77 patients treated receiving statins in a hospital, a team of medical researchers discovered that only 23 percent of patients had received a thyroid panel before beginning statin treatment. Worse yet, 12 percent of patients with overt hypothyroidism received statins without receiving a thyroid panel or hypothyroid diagnosis (21).

The authors commented on their findings, emphasizing the need for routine thyroid screening in patients with lipid abnormalities:

We must not begin and continue to use these drugs without checking the possibility of hypothyroidism. (21).

Statin drug information in Japan and the UK now includes warnings that emphasize the need for careful use in patients with hypothyroidism. The same cannot be said for the United States or in other countries. Thus, it’s very important to exclude other diseases that cause high cholesterol, such as hypothyroidism, diabetes, and kidney dysfunction, before even considering taking a statin.

Better Markers of Cardiovascular Risk

Wait, but I thought cholesterol tests were out—aren’t lipoprotein particle numbers what we really care about?

Yep. I’ve discussed in several articles and on my podcast why lipoprotein particle numbers are much better predictors of cardiovascular risk than cholesterol levels. However, there are few studies that have assessed the effects of thyroid hormones on lipoprotein particle number, compared to the number of studies that have assessed standard cholesterol measurements. Still, we see similar effects:

  • LDL particle number (LDL-P): Subclinical hypothyroidism has been associated with higher levels of ApoB-100, a surrogate marker for LDL particle number. T4 treatment significantly reduced ApoB-100 levels (25).
  • Oxidized LDL: Decreased thyroid function increases the number of LDL particles and promotes LDL “oxidizability” (26).

Thyroid health also impacts other cardiovascular risk factors:

  • Blood pressure: Underactive thyroid is strongly associated with hypertension. This is due to both sympathetic and adrenal activation (27). One study of 30 patients with both hypothyroidism and hypertension found that hypertension was reversed in 50 percent of patients after thyroid medication therapy (28).
  • C-reactive protein (CRP): CRP, a marker of inflammation, has been shown to be negatively correlated with levels of free T4 (29). Patients with subclinical hypothyroidism have also been found to have increased CRP (30).
  • Lipoprotein(a) (Lp(a)): Lp(a) is a measure of how many lipoprotein particles are carrying apolipoprotein A1. Apolipoprotein A1 has a high affinity for oxidized lipids and is thought to be largely based on genetics. Patients with overt hypothyroidism and subclinical hypothyroidism have increased Lp(a) (31, 32). Some studies of subclinical hypothyroidism patients suggest that thyroid medication can reduce Lp(a) (33), but others found no significant change (34).
  • Phospholipase A2 (Lp-PLA2): This is an enzyme that travels largely with LDL particles, is highly pro-inflammatory, and is involved in the development of atherosclerosis (35). Subclinical hypothyroidism subjects have been shown to have higher Lp-PLA2 (36).
  • Homocysteine: Hypothyroidism is associated with increased plasma homocysteine levels (37)
  • Insulin resistance and BMI: Insulin resistance and a high BMI are both positively correlated with low thyroid function (38, 39).

Conclusion

I hope I have convinced you that thyroid function plays a major role in lipid metabolism. I can’t tell you the number of patients I have seen in my clinic with lipid abnormalities that had undiagnosed thyroid conditions. Restoring thyroid health by correcting nutrient deficiencies, rebalancing the immune system, and making simple diet and lifestyle changes can often make a major difference in cholesterol levels and cardiovascular risk markers. In some cases, thyroid support in the form of medication may also be helpful and is much less harmful than statins.

Now I’d like to hear from you. Do you have cardiovascular risk factors? When was the last time you had a full thyroid panel? Did you know about the thyroid–cholesterol connection? Share your thoughts in the comments below.

  1. Karen, it started with my Arthritis doctor. She did a blood test and mention that my thyroid was a “little” high. I knew if I went to regular MD, i would get the standard one pill fits all and I wasn’t having it. I became interested in chelation and that is how I stumbled across this wonderful doctor. TSH was 6.89, now 3.39 T3 was 78, now 97. She also diagnosed me with Epstein Barr a/k/a Mono and everyone has it. You need to read a lot about it’s . This virus is very sneaky and stays with you.

  2. Chris, is there anyone in the Raleigh/Durham area that can offer the type of health care service that you provide in California?

  3. Chris, I can not find any practitioners in the Atlanta area that have gone through the Kresser Institute. Any recommendations would be appreciated. This article seems to explain some of my issues. My internal medicine doctor keeps telling me how healthy I am and that he has never seen a HDL level as high as mine —145. (LDL is high at 129 but VLDL is 9). Triglycerides at 45. High TSH and low free T3. I am very concerned about my low blood pressure, often coming in under 90/60. Most of these changes have occurred since I went on a Paleo diet a few years ago.

    • I had same issues. I have been seen holistic doctor she straighten all of this out. so thankful, I found her

      • Thanks Sharon. How did you find an “enlightened” doctor? If you don’t mind to share, what diagnosis? Curious since you have the same symptoms.

  4. Thank you Chris,
    I truly appreciate your articles. Sure wish someone could “fix” healthcare in this country. We need to stop “treating” symptoms and get to the root causes of illness.
    Keep fighting the good fight!

  5. So about a year and a half ago the Dr. told me that I have an ‘under active thyroid’. I don’t remember what my numbers were, but I started taking levothyroxine 25 MCG tablets about a year ago. I was going to skip taking it altogether but I was feeling down a lot. So my mother advised me to take them because she had the same issue in the past and believed the meds worked for her.
    About 6 months ago I had blood work done and the Dr. said my cholesterol is “elevated”. Here are the numbers:

    Tests: (3) Lipid Panel
    Cholesterol, Total 221mg
    Triglycerides 59
    HDL Cholesterol 82
    VLDL Cholesterol Cal 12
    LDL Cholesterol Calc 127

    According to the paper, Cholesterol and LDL Cholesterol show as High. I don’t understand why because I’ve been paleo/primal for about 7 years. I also exercise. Is it my thyroid?

    My thyroid numbers:
    Thyroid Panel
    Thyroxine (T4) 8.2
    T3 Uptake 31%
    Free Thyroxine Index 2.5
    Test TSH
    TSH 3.670

    Those don’t seem out of wack. Does that mean the meds are working?

    I’m 35 years old, with 2 children. I have weight to lose(not sure how much because I don’t weigh myself), but the weight actually hasn’t budged for a few years. Strange.

    Can some one please tell me what my problem is?

    Thanks in advance!

  6. Great article, thanks Chris! The ‘nitty gritty’ on lipid metabolism was excellent…will be saving article for reference. 🙂

  7. Hi,

    I lost my thyroid 6 months ago and have been completely fine with my substitution medicine.

    However, lately, my lab results show high TSH and borderline high T4.

    I’ll make sure I check my cholesterol the next time. Wasn’t aware of the connection.

    Also, when you say T3 or T4, do you actually refer to the fT3 and fT4 or the general amount?

  8. Good article and thank you for the links. One problem I have with these medical articles: abbreviations! Some of us have no CLUE what things like CVD or VLDL or other such acronyms are! Help us, please by giving the full word at least once in the article so we know what is being talked about! Thank you!

  9. Hi Chris, you wrote: “Patients with SH have also been found to have increased CRP”. An you please define “SH” in this context? Couldn’t find it anywhere.

  10. Man everything you said, sounds just like me. TSH just a little high T3 just a little low. I started seeing a holistic doctor and she straighten me out, my thyroid number have come back normal and my cholesterol has dropped. She put me on this amazing supplement Thytropin PMG with a little Iodine. She watches my Iodine serum level very closely. When my thyroid numbers came back to normal, burst out crying because I was so happy. She got to the ROOT of the problem unlike others.

    • Thanks for sharing this information, I just got blood work done a couple of weeks ago during my annual well woman appointment and I actually had to ask the doctor to check my thyroid because I’ve been dealing on and off with all the symptoms that match those caused by an under active thyroid for more than 10 years now but every time I go to an Obgy I am told that everything is within the normal range that I’m just getting old! Mind you I’m 44 and this has been going on for over ten years during which I’ve been treated with birth control pills to level the hormones up because I started having acne brake outs in my 30s which didn’t make sense in the first place since I was told all the levels were within normal range, I even had a testosterone little thingy implanted in my hip because according to my Obgy this was a miracle cure for most premenopausal women who were experiencing low energy, poor sleep, weigh gain etc, well it wasn’t so good for me, it made my acne worst and didn’t do anything for my lack of energy or poor sleep…………..I would really like to find a doctor of alternative or holistic medicine that I could go to and get the right diagnosis and treatment. This time my exam results came back with the reverse T3 “altered” and so my doctor wants me to start taking Cytomel but I’m terrified to take anything else prescribed by a mainstream doctor, I’ve seen members of my family as well as closed friends struggled with hypothyroidism for most of their lives and just gotten worst following their doctors advised 🙁 so I’m desperate to find a good doctor who’s qulified and experienced with thyroid issues and not so quick to put me on any of the synthetic stuff out there without assesing what’s really the cause of my abnormal reversed T3 and all the symptoms I’m dealing with. Sharon you mentioned you went to a holistic doctor, would you please share her/his name with me?

  11. Very intersting. I suppose it could be kind of chicken and the egg. What caused the thyroid problem in the first place? Also, what about LDL particle size? Very good correlation to CVD. I agree that low trigs is good so less tranport of VLDL. A keto diet takes care of a lot of this. Nothing memtioned about not needing as much T4. Right on with inflammation though – it is the real troublemaker!

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