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Implications of low cholesterol

I just had a patient come back with a cholesterol of 135 mg/dl. He thought it was great! I'm not so sure. Any thoughts on why his cholesterol would be so low?

We are assuming that level is total cholesterol… so then our first question would be, is the person on statin drugs? Statin drugs inhibit the endogenous production of cholesterol and it is possible to drive cholesterol down to dangerous levels. Ideally, total cholesterol should not be below 160 mg/dL (4.14 mmol/L).

Low levels of cholesterol are associated with malnutrition, neurodegenerative disease, cognitive and mood dysfunction, and mortality.

Cholesterol is produced in the body and is required for the synthesis of cell membranes, vitamin D, bile acids, steroid hormones (pregnenolone, progesterone, estrogen, testosterone, DHEA), aldosterone, and cortisol.

Craig, Micah, et al. “Biochemistry, Cholesterol.” StatPearls, StatPearls Publishing, 28 August 2020.

Huff, Trevor, et al. “Physiology, Cholesterol.” StatPearls, StatPearls Publishing, 2 March 2021.

Murugan, Subathra et al. “The neurosteroid pregnenolone promotes degradation of key proteins in the innate immune signaling to suppress inflammation.” The Journal of biological chemistry vol. 294,12 (2019): 4596-4607.

The brain contains and requires a significant amount of cholesterol, which is considered to be neuroprotective. Research suggests that serum cholesterol below 180 mg/dL (4.66 mmol/L) may be detrimental in neurodegenerative diseases such as Parkinson’s and ALS.

Orth, Matthias, and Stefano Bellosta. “Cholesterol: its regulation and role in central nervous system disorders.” Cholesterol vol. 2012 (2012): 292598.

Huang, Xuemei et al. “Serum cholesterol and the progression of Parkinson's disease: results from DATATOP.” PloS one vol. 6,8 (2011): e22854. 

Low total cholesterol is associated with mortality and is significantly associated with malnutrition especially at levels below 160 mg/dL (4.14 mmol/L).

Gavran, Larisa et al. “Evaluation of biochemical markers effectiveness in elderly malnutrition assessment.” Medicinski glasnik : official publication of the Medical Association of Zenica-Doboj Canton, Bosnia and Herzegovina, vol. 16,2 10.17392/1039-19. 1 Aug. 2019.

Zhang, Zhiying et al. “Evaluation of Blood Biomarkers Associated with Risk of Malnutrition in Older Adults: A Systematic Review and Meta-Analysis.” Nutrients vol. 9,8 829. 3 Aug. 2017.

Keller, Ulrich. “Nutritional Laboratory Markers in Malnutrition.” Journal of clinical medicine vol. 8,6 775. 31 May. 2019,.

Iwakami, Naotsugu et al. “Prognostic value of malnutrition assessed by Controlling Nutritional Status score for long-term mortality in patients with acute heart failure.” International journal of cardiology vol. 230 (2017): 529-536.

An inverse relationship between total cholesterol levels and cancer was observed in the analysis of cohort studies following 140,000 individuals.

Ravnskov, Uffe et al. “Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review.” BMJ open vol. 6,6 e010401. 12 Jun. 2016.

A meta-analysis of 12 prospective studies (more than 1.9 million subjects) concluded that higher total cholesterol correlated significantly with lower cancer risk. Total cholesterol le­­vels were categorized as 116 mg/dL (3 mmol/L), 193 mg/dL (5 mmol/L), and 270 mg/dL (7 mmol/L).

Wu, Bing et al. “Dose-response relation between serum total cholesterol levels and overall cancer risk: evidence from 12 prospective studies involving 1,926,275 participants.” International journal of food sciences and nutrition vol. 70,4 (2019): 432-441.

Research on serum cholesterol and mortality in the elderly revealed that the lowest cholesterol quartile of 149 mg/dL (3.85 mmol/L) was significantly associated with mortality compared to higher quartiles of 178 mg/dL (4.61 mmol/L), 199 mg/dL (5.15 mmol/L), and 231 mg/dL (5.99 mmol/L

Schatz, I J et al. “Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study.” Lancet (London, England) vol. 358,9279 (2001): 351-5.

Total cholesterol levels were evaluated in a study of 12.8 million Korean adults in which the association of total cholesterol with mortality followed a U-shaped curve.

Researchers concluded that the lowest rates of mortality, in general, were associated with a total cholesterol level of 210-249 mg/dL (5.4-6.5 mmol/L) for those without ischemic heart disease.

Exceptions to this observation were 18-34-year-old males who had the lowest mortality at total cholesterol levels of 180-219 mg/dL (4.7-5.7 mmol/L).

In women, lowest mortality rates were associated with a total cholesterol of 160-199 mg/dL (4.5-5.2 mmol/L) in ages 18-34 years; and 180-219 mg/dL (4.7-5.7 mmol/L) in ages 34-44 years.

Yi, Sang-Wook et al. “Total cholesterol and all-cause mortality by sex and age: a prospective cohort study among 12.8 million adults.” Scientific reports vol. 9,1 1596. 7 Feb. 2019.

Low cholesterol levels are associated with major depressive disorder. In depressed patients, total cholesterol was significantly lower in suicidal individuals who had levels of 134 mg/dL (3.47 mmol/L) vs 160 mg/dL (4.15 mmol/L) in those who were not suicidal.

Messaoud, A et al. “Is low total cholesterol levels associated with suicide attempt in depressive patients?.” Annals of general psychiatry vol. 16 20. 17 Apr. 2017.

Lower total cholesterol was associated with increased aggression, violence, and antisocial behavior, as well as a suicide risk. Low levels of total cholesterol in schizophrenic patients were associated with increased suicidal ideation and impulsivity. The average total cholesterol in this group was 130 mg/dL (3.4 mmol/L), significantly lower than healthy controls. Total cholesterol below 145 mg/dL (3.78 mmol/L) was found in 80% of patients who had recently attempted suicide.

Tomson-Johanson K, Harro J. Low cholesterol, impulsivity, and violence revisited. Curr Opin Endocrinol Diabetes Obes. 2018;25(2):103-107.