The Importance of Cholesterol for Mood and Brain Health

28 Sep The Importance of Cholesterol for Mood and Brain Health

Cholesterol is often viewed negatively due to its association with heart disease. However, this essential molecule plays a critical role in maintaining life, and is particularly critical in brain health and mood regulation. While elevated cholesterol can indeed present health risks, extremely low cholesterol levels can be life-threatening, leading to psychological and neurological issues, including an increased risk of depression and suicide.



In this blog post, we will explore the importance of cholesterol for brain health, hormone synthesis, and mood regulation, emphasizing the often-overlooked dangers of low cholesterol.

Cholesterol: Essential for Life

Cholesterol is an indispensable component of human physiology. It serves as a building block for cell membranes and is crucial in the synthesis of hormones, including cortisol, testosterone, estrogen, and progesterone. Numerous body processes, such as metabolism, stress response, and reproductive health, are regulated by these hormones. Hormone synthesis would be compromised in the absence of sufficient cholesterol, impacting mental and physical well-being.

Furthermore, cholesterol preserves the integrity and shape of cells by constituting the phospholipid bilayer of cell membranes. This is especially important in the brain, which is mostly made of fat (cholesterol) at a ratio of roughly 60%. Since the brain contains the highest concentration of cholesterol of any organ in the body, low cholesterol can impair brain function and cause mental health issues. 

Cholesterol and Brain Function

Cholesterol plays an essential role in the brain, facilitating neurotransmission and maintaining the balance of key chemicals that influence mood. Serotonin, sometimes known as the “feel-good” neurotransmitter, is one of the most important neurotransmitters impacted by cholesterol. Low levels of serotonin are associated with anxiety, sadness, and other mood disorders. Serotonin is one of the key neurotransmitters in mood regulation. 

Serotonin receptors need cholesterol to operate properly. Research has indicated that elevated brain cholesterol levels are associated with a commensurate upsurge in serotonin receptors. On the other hand, decreased membrane cholesterol leads to a decrease in serotonin receptors, which reduces the potency of serotonin. According to Engelberg (1992), this decrease in serotonin transmission may result in increased aggression or suicidal thoughts as well as poor mood control.

In fact, research has demonstrated a strong association between low cholesterol levels and an increased risk of depression, anxiety, and even suicidal behavior. A study published in The Journal of Psychiatric Research found that individuals with low total cholesterol (less than 165 mg/dL) were significantly more likely to die prematurely from unnatural causes such as suicide and accidents (Partonen et al., 1999). For instance, men with low total cholesterol levels were found to be seven times more likely to die from suicide or accidents (Mosaic, 2023). This underlines the crucial need for balanced cholesterol levels for mental health.

Low Cholesterol and Increased Risk of Mortality

With cholesterol, the “Goldilocks” principle applies. Too much can be bad, but too little can actually be worse. While high cholesterol has been associated with cardiovascular disease, low cholesterol levels pose equally significant risks.  Specifically, low cholesterol has been associated with a higher risk of mortality from all causes, which includes violence and suicide. Research looking at cholesterol-lowering therapies have found an unanticipated rise in violent or suicide deaths (Muldoon et al., 1992). We have learned this mostly due to the increased use of statins; often these medications are used to drive cholesterol very low. When this happens, there can be unintended consequences for the brain.

Research suggests that low cholesterol may impair serotonin regulation, leading to increased impulsivity and aggression. According to a study, those with low cholesterol had an increased risk of acting violently or taking their own life (Golomb, 1998). In a similar vein, it was discovered that patients who had previously attempted suicide had far lower cholesterol than those who had not (Jow et al., 2008).

This increased risk of suicide and violent behavior is not limited to men. Women with low cholesterol are also vulnerable to depressive symptoms and suicidal tendencies as well. A study of Swedish women found that those in the lowest cholesterol percentile had significantly higher rates of depressive symptoms. According to a study that was published in Acta Psychiatrica Scandinavica, depression symptoms in middle-aged and older Swedish women were significantly correlated with low cholesterol levels (Steegmans et al., 2000). These results imply that mood and mental health can be significantly impacted by low cholesterol levels, independent of gender. 

The Role of Cholesterol in Hormone Synthesis and Cellular Health

Cholesterol is vital for the synthesis of all steroid hormones, including those that regulate stress, metabolism, and mood. If cholesterol levels are too low, the body cannot make enough pregnenolone, progesterone and cortisol, these hormones are essential for stress tolerance and mood. Low pregnenolone and cortisol imbalance can effect focus, and it can present as anxiety, mood swings and low frustration tolerance.

Cholesterol is literally incorporated into every cell in our bodies. It is essential for preserving the structural integrity of cell membranes. Cholesterol is necessary for the phospholipid bilayer, which constitutes the outer layer of cells. This membrane needs to remain fluid and permeable; this is possible due to cholesterol. This is especially crucial for neurons since cholesterol makes it easier for brain cells to communicate effectively with one another.

The quantity (and QUALITY) of cholesterol in cell membranes directly affects neurons’ capacity for efficient communication. Low cholesterol can interfere with this communication/neurotransmission, making it difficult to think clearly and control one’s emotions. Thus, maintaining healthy cholesterol levels is essential for maintaining mood stability and cognitive function.

Low Cholesterol, Depression, and Suicide

Numerous studies have highlighted the link between low cholesterol and mental health disorders, particularly depression and suicide. A 2001 study found that patients hospitalized for depression had lower cholesterol levels than healthy controls (Steegmans et al., 2001). Similarly, a 2008 study examining individuals who had attempted suicide discovered that those who used violent methods had significantly lower cholesterol levels than those who used non-violent methods (Jow et al., 2008).

Low cholesterol may affect the intensity the symptoms of depression, increases the risk for developing depression, and seems to increase the risk of not only suicidal ideation. but actual suicide attempt.

Conclusion

Cholesterol has been unfairly demonized due to the potential cardiovascular effects of hyperlipidemia. In this demonization, they have forgotten that cholesterol is vital for life. Adequate cholesterol is especially crucial for brain function, hormone synthesis and mood control. Reduced cholesterol has been associated with higher risks of suicide, depression, and death from all causes. Maintaining the integrity of cell membranes, promoting neurotransmission, and generating essential hormones that control mood all depend on cholesterol. 

Bottom line, it is important to know your levels. 

Ideally, we can make 80% of the necessary cholesterol and we get 20% from our diet. Depending on your genetics (APOE status etc..), you may be good at making cholesterol or you may be challenged in this area. One diet does not fit all. For those who do have high cholesterol, a predominately plant based diet may be good, or if you are APOE4 positive, it is recommended. For other people, with different genetics, this can be disastrous.

Each person is an N of one. There are no two alike. Each person will have different history, genetics, chemistry, predispositions etc. In my practice there is not a boiler plate approach. Each person I see will have a slightly different plan / recommendations. With every person, I look at all the possible known factors and, as a team, the patient/family and I determine individualized treatment plans that will work for each person. 

References

Engelberg, H. (1992). Low serum cholesterol and suicide. The Lancet, 339(8795), 727-729.

Golomb, B. A. (1998). Cholesterol and violence: Is there a connection? Annals of Internal 

Jow, G. M., Yang, Y. M., & Chen, C. C. (2008). Leptin and cholesterol levels are low in major depressive disorder, but are associated with violent suicide attempts: Psychiatry Research, 158(3), 277-280.

Mosaic. (2023). The implications of low cholesterol in depression and suicide. Mosaic Diagnostics.

Muldoon, M. F., Manuck, S. B., & Matthews, K. A. (1992). Lowering cholesterol concentrations and mortality: A quantitative review of primary prevention trials. British Medical Journal, 304(6824), 1254-1257.

Partonen, T., Haukka, J., Virtamo, J., Taylor, P. R., & Lönnqvist, J. (1999). Association of low serum total cholesterol with major depression and suicide. The Journal of Psychiatric Research, 33(3), 231-239.