Written by: Kevin Cann
More often than not when we are addressing problems related to cholesterol we are referring to its affects on heart health. Cholesterol, for one, is important for maintaining the structure of our cells. It is also the precursor for our steroid hormones, serves as a major role in our inflammatory response, and allows us to convert sunlight into vitamin D. One role of cholesterol that is often overlooked is its affect on our mental health.
Approximately 25% of the cholesterol in our body is made in our brain. The blood-brain barrier even has a protection mechanism to stop this locally produced cholesterol from being exchanged with the lipoproteins in the blood (Bjorkhem, 2004). The cholesterol is actually used to help build the myelin sheath that surrounds the axon of our neurons. Statin drugs and cholesterol lowering diets are widely prescribed to people, is this coming at a cost to our mental health?
Morgan and colleagues attempted to understand the mechanisms that were causing increased suicide attempts and violent deaths in clinical interventions attempting to lower plasma cholesterol. Their study concluded by saying that men aged 70 years and older with low serum cholesterol, were 3 times more likely to develop depressive disorders (Morgan, 1993).
Steegmans and colleagues showed the same results in middle-aged men. Men between 40 and 70 years old with cholesterol below 4.5 mmol/liter had a significantly higher risk of depression than men with cholesterol levels between 6 and 7 mmol/liter (Steegmans, 2000). Women are also at danger of low cholesterol levels causing depression. In another study, 300 women between the ages of 31 and 65 were checked for cholesterol levels and depressive symptoms. The researchers found that women with total cholesterol below 4.7 mmol/liter had significantly higher risk of depression (Horsten, 1997). So how does low serum cholesterol make us depressed?
Cholesterol is an important factor in the receptor sites of the cells binding with the appropriate neurotransmitter, in particular acetylcholine and serotonin. Research has suggested that cholesterol is the facilitator of the attachment between the neurotransmitter and the cell membrane, as well as their delivery to specific protein receptors (Fantini, 2009). Another study goes a step further and hypothesizes that this mechanism actually causes inhibition of neurotransmitter release due to the low levels of cholesterol (Shin, 2009).
Researchers at the University of Penn showed that cholesterol is actually located in the protein portion of the receptor site. They demonstrated that cholesterol actually served to stabilize the protein’s structure. According to Grace Brannigan “Our model takes cholesterol out of the background role in the protein’s structure and function and places it at center stage” (Reese, 2008). Lowering cholesterol can have profound effects on the structure and function of these receptor sites.
Long term use of statins showed significant changes in the structure and function of serotonin cell receptors (Shrivastava, 2010). Serotonin is responsible for fighting off depression and anxiety. Having improper structure and function at these sites will lead to depression in a high number of cases. This is most certainly a topic that should be discussed with your doctor before being placed on a statin drug.
Condemning cholesterol has had a profound effect on our well being. Statin drugs are widely prescribed, and may come at a great emotional cost. Cholesterol causing heart disease has been refuted by solid science throughout the last few decades, and I recommend everyone look at Chris Masterjohn’s site, www.cholesterol-and-health.com, and Chris Kresser’s High Cholesterol Action Plan, http://highcholesterolplan.chriskresser.com/ for more information. There is no need to fear cholesterol as it is important for a number of reasons in our body and may be the missing link to you getting out of a depressed hole.
References
Horsten, Myriam (1997). Depressive Symptoms, Social Support, and Lipid Profile in Healthy Middle-Aged Women. http://www.psychosomaticmedicine.org/content/59/5/521.long
Steegmans, Paul (2000). Higher prevalence of depressive symptoms in middle-aged men with low serum cholesterol levels. http://www.psychosomaticmedicine.org/content/62/2/205.full.pdf+html
Morgan, R.E. (1993). Plasma cholesterol and depressive symptoms in older men. http://www.sciencedirect.com/science/article/pii/0140673693925569.
Bjorkhem, Ingemar (2004). Brain cholesterol: Long secret life behind a barrier. http://atvb.ahajournals.org/content/24/5/806.short
Shrivastava, Sandeep (2004). Chronic Cholesterol Depletion Using Statin Impairs the Function and Dynamics of Human Serotonin 1A Receptors. http://pubs.acs.org/doi/abs/10.1021/bi100276b.
Reese, Jordan (2008). Penn Biophysicists Create New Model for Protein Cholesterol Interactions in Brain and Muscle Tissue. http://www.upenn.edu/pennnews/news/penn-biophysicists-create-new-model-protein-cholesterol-interactions-brain-and-muscle-tissue.
Fantini, Jacques (2009). Sphingolipid/cholesterol regulation of neurotransmitter receptor conformation and function. http://www.sciencedirect.com/science/article/pii/S0005273609002971
Shin, Yeon-Kyun (2009). Cholesterol, Statins, and Brain Function: A Hypothesis from a Molecular Perspective. http://www.ibc7.org/article/journal_v.php?sid=31.
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Saw this in a Yahoo news article this morning:
“When you lower your refined-carb intake, it changes how your body metabolizes fat,” says Roussell. And with the emphasis on fruits and vegetables, you’re getting more phytonutrients, vitamins, and minerals on a paleo plan than you would eating a typical American diet (and probably enough calcium, if you consume plenty of leafy greens and add a supplement). ***Also, “when you reduce your consumption of starchy carbs, saturated fats [like those in red meat] have less of an impact on risk factors for heart disease than they do when you’re eating a higher-carb diet,” notes Roussell.***
Sounds like the mainstream is starting to wake up a little bit!
Not to mention, cholesterol is a precursor to testosterone. And there’s no better kick than a “T” buzz 😛
Mr. Cann,
This is a fascinating post since it is true as you say that the role of cholesterol in mental function is often overlooked. As an undergraduate student with interests in both the nutritional/exercise sciences and psychology, I was happy to find a post on this blog that focused on the intersection of the two. Many people are unaware that there is more than one variety of cholesterol, let alone that some of them are good to have in higher levels than others. Most people only think of cholesterol as a thing to avoid in one’s diet despite the fact that ingested cholesterol does not profoundly affect the blood serum levels in most people. Even worse, the role of cholesterol in mental function rarely enters the public discourse. It was interesting to see the correlation between low cholesterol levels and the development of depressive disorders; however, this post seems to take for granted that the studies conducted accounted for all other possible causes for the development of those disorders. Depression is a complex neurological disorder and despite cholesterol’s central role in the neuronal structure, is it not possible that the depression could have been brought on by a combination of factors, none of which might be low cholesterol levels?
Also you mention a study in which men with levels below 4.5 mmol/L have a greater risk of developing depression than men with levels between 6 mmol/L and 7 mmol/L (which is considered high by main stream standards). This is interesting because it suggests that there might be consequences to having cholesterol levels that are too low, but it does not seem to follow that having levels considered too high by most medical practitioners is patently better than having levels that could arguably be called too low. And if there is a happy-medium between levels that are too low and levels that are too high, would there not be a place for intelligent statin use? You later say that recent research has refuted the connection between heart disease and high cholesterol but there also seems to be a lot of evidence to the contrary. How would you explain the conflict? Ultimately I agree with you that blindly condemning cholesterol is problematic and that statins could be over-prescribed and not properly monitored as to their negative side effects, but I am still not entirely convinced that high cholesterol might not come with its own set of negative consequences—which is not to say I am inconvincible. I look forward to hearing back from you.
Here is a good link that explains cholesterol’s role in heart disease, http://www.cholesterol-and-health.com/Does-Cholesterol-Cause-Heart-Disease-Myth.html. The studies I mentioned were observational data and only show correlation and not causation. That is why I included the mechanisms of how cholesterol is involved in the structure and function of cells. When I look at this data as a whole I see that low cholesterol levels in the brain can have negative consequences on mood.
In terms of statins I do think there are cases that they should be used. I often feel they are over prescribed and a major side effect is neurodegeneration. There is a sliding scale of heart disease risk that includes a number of factors. Even if cholesterol were shown to cause heart disease it is a small part. High cholesterol is a symptom of something else going wrong whether it be low thyroid or an infection. I myself have “high” cholesterol. I do not have other heart disease risk factors. My inflammation is fine, my blood pressure is good, I am active, my total cholesterol to HDL ratio is good, etc. I feel I can mitigate the risks that may be associated with high cholesterol with proper lifestyle choices that do not come with side effects. Where my total cholesterol to HDL ratio is good I do not even feel there is a risk as this is a good predictor of heart disease in the literature.
I could get an LDL particle number test to see my risk for the potential damage to the epithelial lining, but personally it would not change how I manage my care. If someone does not want to make lifestyle changes maybe a statin is warranted and it has been shown effective in the literature for people who have had previous heart attacks. In the end everyone needs to educate themselves on these matters and make individualized choices as to what means to manage their health.
My previously healthy and ongoing 15 year old daughter began having panic attacks in class last year. We later found her total cholesterol at 70, LDL at 7. She is otherwise healthy, normal thyroid and vitamin levels, but has an anxiety/depression problem that is causing her to resort to online only classes, etc… She is even eating meat now (was a vegetarian). Her test this month had a total cholesterol at 62, HDL 38 and LDL of 0, how is this possible, and do you have any recommendations of places to treat this. Pediatric Hematology and Endocrinology at Children’s Hospital are now referring us to a Lipid Clinic.