8 Health Risks of Low Cholesterol – by Dr. Christina Bjorndal and Lachlan Crawford

It’s commonly known that elevated cholesterol in the blood is a risk factor for developing heart problems. In fact, high cholesterol is recognized as a major contributor to cardiovascular disease, the #2 leading cause of death in Canada, second only to cancer¹. To combat this major public health concern, over 38 million prescriptions for statin pharmaceuticals to lower cholesterol were written in Canada in 2012². With so much effort to lower cholesterol, you might think it advantageous to get your levels as low as possible. Having too-low cholesterol, however, has its own risks, calling into question the trending practice of prescribing statins to anyone even at risk of elevated levels. New insight into the effects of low cholesterol are showing the importance of staying within a healthy optimal range and not falling into low levels – a state called hypocholesterolemia.

What is Cholesterol? The Good and the Bad

Cholesterol is a lipid (fat molecule) that is made by the body (mostly the liver) and also consumed in the diet. Our total blood level of cholesterol is a combination of what’s made ‘in-house’ and what’s picked up in our food. Cholesterol has a specific molecular structure consisting of four rings of atoms. This structure makes it a sterol (type of fat) that is the building block for many other physiological molecules, including our hormones.

There are two main types of cholesterol in the body, namely HDL cholesterol (commonly called “the good cholesterol”) and LDL cholesterol (commonly dubbed “the bad cholesterol”). HDL stands for high-density lipoprotein and is considered good because this is the form that is thought to play a protective role in our cardiovascular system. HDL is a bundle of molecules that includes cholesterol, and it moves cholesterol from the body’s vascular system to the liverwhere it can be processed and made into something else. If the cholesterol stays in the vascular system it can become oxidized which is damaging to blood vessels. This contributes to plaque formation in the vessels which causes heart disease. Therefore, when cholesterol is in the HDL bundle, it is good because it is moving away from where it can cause damage. Conversely, LDL (low-density lipoprotein) is a bundle of molecules that includes cholesterol and it moves cholesterol from the liver to the peripheral body and blood vessels, keeping it where it is more likely to be oxidized and cause damage. This is why the LDL-bundled-cholesterol has a bad reputation.

Why is Cholesterol Important for our Bodies?

Cholesterol is used in countless physiological processes, but here is a list of some of the major categories of its wide range of use:

1. First, cholesterol is an essential part of our cell membranes. Every single cell in your body requires cholesterol to keep its fluidity and integrity to function properly at body temperature. Having insufficient cholesterol can make cell walls rigid and lead to premature cell death.
2. Second, its sterol structure is the building block for many important hormones, including estrogen, testosterone, progesterone, cortisol and aldosterone, to name a few highly important examples³. With cholesterol dipping too low, the body can compensate for a time by making its own cholesterol, but at a point it cannot compensate for all the demands of cholesterol and some hormonal functions may be impacted.
3. Cholesterol is also the precursor to bile salts. Made by the liver and stored in the gall bladder before being released into the small intestine, bile salts are compounds used in the digestive tract that allows for the absorption of fats.
4. Finally, cholesterol is important for proper nerve function. Neurons in the central nervous system require cholesterol for the formation of synapses, the parts of neurons that facilitate neuronal communication⁴, the formation of myelin sheaths for neurons, as well as being essential for the synthesis of some neurotransmitters⁵. Therefore, having sufficient cholesterol is important to ensure smooth neurotransmitter flow in the brain and spinal cord.

After taking a look at its importance in the body, we might expect some adverse effects if our cholesterol level dips too low. But what should we look out for?

What Happens when Cholesterol is Too Low?

First off, frank hypocholesterolemia (where levels are below the 5^th percentile of the normal human population, or around 3.1mmol/L) is uncommon and usually seen only in patients with other severe conditions or infections, multiple physical traumas or just after surgery⁶. However, many studies have been done that show cholesterol levels at or slightly below the low end of the normal range may have adverse conditions. Many compare healthy controls to patients that are ill and find significant differences in cholesterol levels. Ideal total cholesterol is 5.2 mmol/L, a level below 4.7 mmol/L can be a problem for some, and total cholesterol below 3.1 mmol/L indicates a serious problem.

Part I: Cholesterol and the Brain

Depression, Suicidality

A number of studies have found a relationship between low serum cholesterol levels and mood disorders. Rafter et. al. found that those with low serum cholesterol levels scored significantly worse on depression assessments than those with normal cholesterol⁷. In patients diagnosed with depression, low blood cholesterol levels have been associated with suicidal ideation and suicide attempts, with some studies showing a direct correlation: the lower the cholesterol, the more likely a patient would be to have suicidal thoughts or to make an attempt⁵. The magnifying effect of low cholesterol on low mood has also been documented in people who suffer from seasonal affective disorder and post-partum depression⁵. However, still other studies have shown no correlation between mental health markers and cholesterol levels, showing the relationship is likely a partial one, or that cholesterol levels play a part in the mental health outcomes of only certain populations. So although it may not be a perfect predictor for all populations, it is nonetheless important to note cholesterol plays a role in significant mental health outcomes. If you are concerned about taking cholesterol-lowering drugs and their effect on your mental health, the research is still out. As with the data on depression, conflicting data show a correlation between anti-cholesterol drugs and psychiatric symptoms while other studies show no correlation⁵. More studies are being done to determine the nature of the relationship between cholesterol, pharmaceuticals and mental health.

Neurodegenerative Disorders

Epidemiological studies show cholesterol levels also have a correlation with neurodegenerative diseases of the aging brain. Many investigators are working to determine if these relationships are simply a correlation or are causative, in other words if low cholesterol contributes as a risk for developing dementia or Alzheimer’s. Mostly this work is leaving conflicting evidence. When looking at studies in which cholesterol level was assessed in middle age and follow-up for neurodegenerative outcomes was 20 to 30 years, a positive association with Alzheimer’s and high cholesterol was found⁸. Based on these studies, statins were given to those in mid-life with high cholesterol and resulted in less cognitive decline in later life⁹. The relationship between high cholesterol and Alzheimers is due to cholesterols role in the development of amyloid plaques.²⁵ On the other hand, when cholesterol levels are measured later in life, Alzheimer’s and dementia is associated with low cholesterol. For example, Dimopolous et. al. showed significantly lower cholesterol levels in elderly patients with dementia¹⁰, and Kuussisto et. al. found a correlation with Alzheimer’s disease¹¹– both studies measuring cholesterol in late life. Discussions around these results gave rise to a hypothesis that low cholesterol may be a secondary effect of neurodegeneration and not its cause. A 2008 literature review on the relationship between cholesterol and neurodegeneration presents this topic as conflicting and needing more evidence to report sound conclusions⁸.

Parkinson’s Disease

Previously, the research around Parkinson’s disease and cholesterol was also inconclusive, but new evidence is sparking interesting and important new discussion. In recent years the prevailing theory was that high cholesterol was the very culprit for developing Parkinson’s. This has led to clinical studies to test a statin drug as direct treatment for Parkinson’s, such as the four-year clinical trial from The Plymouth University Peninsula Schools of Medicine and Dentistry in the UK that is in its final year, pending results in 2017. Systematic reviews of evidence for this theory, however, have uncovered confounding reasons why this may not hold truth¹². Correcting for these confounding factors, a large prospective study published in 2015 followed patients in the USA for 10 years and found that statin use may be associated with a higher risk of Parkinson’s disease, whereas higher total cholesterol levels is actually associated with lower risk¹³.

Autistic Spectrum Disorder

New studies have highlighted a particular group of children with Autistic spectrum disorder (ASD) as having very low cholesterol. Specifically, children with the condition SLOS (Smith-Lemli-Opitz syndrome), that have an inability to make cholesterol, are much more likely to develop ASD than children with regular cholesterol synthesis¹⁴. Although SLOS is only present in a small percentage of children with ASD, it provides important insight into the role of cholesterol metabolism in the development of ASD in the rest of the population, and future possibilities of treatment¹⁵. Children with ASD and SLOS treated with cholesterol management therapies show improvement of symptoms, giving hope that this may help others with ASD.

Part II: Cholesterol and the Body

Hormone health and Fertility

This is one of the major categories where cholesterol dysregulation has an affect on the body and its functions. Because cholesterol is a precursor to all steroid hormones, it is understandable that hormone levels are directly affected by cholesterol. Many studies show decreasing levels of estrogen, progesterone, testosterone, cortisol, aldosterone and other hormones with low levels of cholesterol^16,3. Having low steroidal hormones can affect female fertility by not preparing the ovaries or uterus properly for implantation or fetal growth. A startling result from a study looking at the effect of statins on embryo development after fertilization showed marked embryotoxicity caused by the cholesterol-lowering drugs leading to failure of a fertilized embryo to implant for growth¹⁷. Low cholesterol also affects male fertility – low synthesis of total testosterone from low cholesterol stores leads to lower sperm counts and can decrease libido as well¹⁸. A 2009 literature review calls for more research while acknowledging the possible blunting of the adrenal and/or sex hormone function in both males and females¹⁹.

Immune health

Cholesterol also affects the immune system in a significant way. People with low cholesterol also have lower-than-normal counts of immune cells that are necessary to fight off even the most basic infections²⁰. The downstream effects on the immune system also predispose a patient with low cholesterol to more severe inflammation from bacterial invasion. Studies have shown that having low cholesterol before a surgery makes it more likely to have post-operative complications including sepsis²¹. Epidemiologic studies have also identified a relationship between hypocholesterolemia and increased mortality from all causes²². Overall, low cholesterol is associated with a higher rate of mortality in all hospitalized patients, in comparison to those with normal or high cholesterol levels. Though these findings may mislead some to think that cholesterol should be raised indiscriminately, it is instead shown here to illustrate the pitfalls of lowering it too far, below what is necessary to upkeep important cellular and metabolic functions.

Stroke

A low level of total cholesterol is associated with an increased risk of intracerebral hemorrhage (a type of stroke) for people over the age of 65²³. While the mechanism for this is unclear, it is thought that low levels of cholesterol may decrease blood platelet activation, which is needed to stop bleeding if it were to occur. Decreasing platelet activity makes a person more prone to bleeding, in this case perhaps even leading to a stroke²⁴.

Cancer

Cholesterol deficiency also is being investigated as a risk factor for colorectal cancer. Because of the role it plays in the production of bile salts for the absorption of fats, it is observed that low cholesterol leads to improper fat absorption. This leaves more lipids in the digestive tract, which can then be oxidized in the colon, leading to cell damage in the colon wall. A large Japanese study also found very low cholesterol levels to be a risk for developing liver malignancies²⁰. Beyond being a risk factor for developing cancer, low cholesterol levels predict lower survival rates for any blood or solid organ malignancy²⁰.

Part III: What You Can Do

The most important thing is to be aware that cholesterol is an important molecule for proper functioning of our bodies and minds. This is meant to help you be your own health advocate by giving you valuable information about your body’s chemistry. Do not stop taking statin medication if you are currently taking it. Have a conversation with your health care provider about your concerns and to have your cholesterol checked. If you find it’s on the lower side and want to take some action to raise it into a healthier range, you can do it naturally. Here are some tips to help you achieve optimal cholesterol:

• Eggs: Very simply, include more organic eggs with their yolk in your diet. Egg yolk is one of the best sources of cholesterol- one large hard-boiled egg provides 71% of your recommended daily intake
• Olive oil: Just 2 tbsp of uncooked olive oil a day is effective at raising HDL cholesterol and improving total cholesterol levels. It’s as easy as one homemade salad dressing
• Fish Oil: Supplementing with this oil not only gives you a source of cholesterol, but helps with omega-3 and -6 balance of fats for an excellent overall lipid profile and protection against many mental health concerns and degenerative and chronic diseases
• Animal products: Include organic chicken, beef and pork in your diet to ensure you’re getting the proper fat profiles on a daily basis. Include real, unsalted, organic butter too.
• Control insulin spikes: Eat a diet that has a low glycemic index and low glycemic load. This means your insulin levels will be more level, your blood glucose control will be better and your cholesterol and lipid profiles will improve
• Vitamin D: This vitamin is actually synthesized from a molecule in the cholesterol family, 7-dehydrocholesterol. Supplementing with vitamin D will free up cholesterol precursors for other uses or for cell membranes
• Supplement cholesterol: New Beginnings Nutritionals makes a purified cholesterol supplement that will effectively raise levels. Be sure to talk with your health care provider as this product requires their referral
• Supplements containing beet concentrate and taurine thins bile allowing easier flow out of the gallbladder to help our bodies absorb fat
• Gall Bladder Support: Your cholesterol could be low because your gall bladder is not releasing bile into the digestive tract, meaning you have a hard time absorbing fats. Consult with a Naturopathic Doctor who address gall bladder health. There are herbs that facilitate proper bile flow and fat absorption, effectively helping your body regulate its cholesterol and fat levels on its own

Sources:

1. Anderson, Robert N., and Betty L. Smith. “Deaths: leading causes for 2001.” (2003). http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/hlth36a-eng.htm
2. Statistics Canada (2012) Health Facts Sheet: percentage of Canadians with unhealthy cholesterol. http://www.statcan.gc.ca/pub/82-625-x/2012001/article/c-g/desc/11732-01-desc-eng.htm
3. Berg, J. M., Tymoczko, J. L., & Stryer, L. (2002). Important Derivatives of Cholesterol Include Bile Salts and Steroid Hormones. http://www.ncbi.nlm.nih.gov/books/NBK22339/
4. Pfrieger, F. W. (2003). Role of cholesterol in synapse formation and function. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1610(2), 271-280. http://www.ncbi.nlm.nih.gov/pubmed/12648780
5. Sansone, R. A. (2008). Cholesterol quandaries: Relationship to depression and the suicidal experience. Psychiatry (Edgmont), 5(3), 22. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2710104/
6. Mouzouri, E. (2011). Hypocholesterolemia. Curr Vasc Pharmacol. Mar;9(2):200-12.
7. Rafter, D. (2001). Biochemical markers of anxiety and depression. Psychiatry research, 103(1), 93-96. http://www.ncbi.nlm.nih.gov/pubmed/11472794
8. Duron, E., & Hanon, O. (2008). Vascular risk factors, cognitve decline, and dementia. Vascular Health and Risk Management, 4(2), 363. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2496986/
9. Sjögren, M., & Blennow, K. (2005). The link between cholesterol and Alzheimer’s disease. The World Journal of Biological Psychiatry, 6(2), 85-97. http://www.ncbi.nlm.nih.gov/pubmed/16156481
10. Dimopoulos, N., Piperi, C., Salonicioti, A., Psarra, V., Mitsonis, C., Liappas, I., … & Kalofoutis, A. (2007). Characterization of the lipid profile in dementia and depression in the elderly. Journal of geriatric psychiatry and neurology, 20(3), 138-144. http://www.ncbi.nlm.nih.gov/pubmed/17712096/
11. Kuusisto, J., Koivisto, K., Mykkänen, L., Helkala, E. L., Vanhanen, M., Hänninen, T., … & Laakso, M. (1997). Association between features of the insulin resistance syndrome and Alzheimer’s disease independently of apolipoprotein E4 phenotype: cross sectional population based study. Bmj,315(7115), 1045-1049. http://www.ncbi.nlm.nih.gov/pubmed/9366728
12. Bykov, K., Yoshida, K., Weisskopf, M. G., & Gagne, J. J. (2016). Confounding of the association between statins and Parkinson disease: systematic review and meta‐Pharmacoepidemiology and Drug Safety. http://www.ncbi.nlm.nih.gov/pubmed/27527987
13. Huang, X., Alonso, A., Guo, X., Umbach, D. M., Lichtenstein, M. L., Ballantyne, C. M., … & Chen, H. (2015). Statins, plasma cholesterol, and risk of Parkinson’s disease: a prospective study.Movement Disorders, 30(4), 552-559. http://www.ncbi.nlm.nih.gov/pubmed/25639598
14. Tierney, E., Bukelis, I., Thompson, R. E., Ahmed, K., Aneja, A., Kratz, L., & Kelley, R. I. (2006). Abnormalities of cholesterol metabolism in autism spectrum disorders. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics,141(6), 666-668. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2553243/
15. Aneja, A., & Tierney, E. (2008). Autism: the role of cholesterol in treatment. International Review of Psychiatry, 20(2), 165-170. http://www.ncbi.nlm.nih.gov/pubmed/18386207
16. Kische, H., Gross, S., Wallaschofski, H., Völzke, H., Dörr, M., Nauck, M., & Haring, R. (2016). Clinical correlates of sex hormones in women: the Study of Health in Pomerania. Metabolism. http://www.ncbi.nlm.nih.gov/pubmed/27506736
17. Alarcon, V. B., & Marikawa, Y. (2016). Statins inhibit blastocyst formation by preventing geranylgeranylation.Molecular human reproduction, gaw011. http://www.ncbi.nlm.nih.gov/pubmed/26908642
18. Vangeepuram Satakopan, Cholesterol Levels May Influence Male Fertility. Sexual Health. https://sexual-health.knoji.com/cholesterol-levels-may-influence-male-fertility/
19. Hulisz, D. (2009). Do Statins Reduce a Patient’s Hormone Levels? Medscape Multispecialty. http://www.medscape.com/viewarticle/709320
20. Elmehdawi, R. R. (2008). Hypolipidemia: a word of caution. The Libyan journal of medicine, 3(2), 84. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074286/
21. Leardi, S., Altilia, F., Delmonaco, S., Cianca, G., Pietroletti, R., & Simi, M. (1999). [Blood levels of cholesterol and postoperative septic complications]. Annali italiani di chirurgia, 71(2), 233-237. http://www.ncbi.nlm.nih.gov/pubmed/10920496/
22. Shores, J., Peterson, J., VanderJagt, D., & Glew, R. H. (2003). Reduced cholesterol levels in African-American adults with sickle cell disease.Journal of the National Medical Association, 95(9), 813. http://www.ncbi.nlm.nih.gov/pubmed/14527048
23. Iribarren, C., Jacobs, D. R., Sadler, M., Claxton, A. J., & Sidney, S. (1996). Low total serum cholesterol and intracerebral hemorrhagic stroke: is the association confined to elderly men? The Kaiser Permanente Medical Care Program. Stroke,27(11), 1993-1998. http://www.ncbi.nlm.nih.gov/pubmed/8898804
24. Aviram, M., Davidai, G., & Brook, G. J. (1991). [Platelet hypoactivity in hypocholesterolemia].Harefuah, 120(4), 177-179. http://www.ncbi.nlm.nih.gov/pubmed/2066015/
25. Sjogren, M., Blennow K. (2005). The link between cholesterol and Alzheimer’s disease. World J Biol Psychiatry 2005;6(2):85-97. http://www.ncbi.nlm.nih.gov/pubmed/16156481