Low cholesterol levels associated with depression and other mental health issues

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I know that some doctors and scientists would have us believe that, where cholesterol is concerned, “lower is better”, but I have real difficulty mustering any enthusiasm for this stance. And one major reason for this is the fact that low levels of cholesterol are associated with enhanced risk of death, perhaps most notably from increased risk of cancer [1-4]

Some have suggested that low cholesterol is a marker for “frailty” in the elderly. However, this concept is contradicted by evidence which finds that the association between low cholesterol levels and enhanced risk of mortality occurs in younger people too [5].

It has also been suggested the relationship between low cholesterol and enhanced risk of mortality is the result of “reverse causality” i.e. that disease processes such as cancer can cause low cholesterol, even up to a decade before the underlying condition is diagnosed (sometimes referred to as “Iribarren’s hypothesis”). However, long-term studies provides evidence which counters this concept [6].

It should perhaps be borne in mind that cholesterol is a component in cell membranes, and an essential constituent of steroid hormones and vitamin D (which increasing evidence suggests has disease-protective properties, particularly with regard to cancer prevention).

The fact that cholesterol is a component in cell membranes might have significance to many biological processes, including neurological ones. It is possible, in theory at least, that low levels of cholesterol might somehow disturb the function of nerves in the brain. Could low levels of cholesterol, then, lead to mental health issues?

In a study published this month, the relationship between cholesterol levels and depression was assessed in a group of French men and women over the aged 65 or older [7]. The assessment continued for 7 years. This study found that:

1. In men, low levels of low density lipoprotein (LDL) cholesterol (supposedly “unhealthy” cholesterol) were associated with an increased risk of depression

2. In women, low levels of high density lipoprotein (HDL) cholesterol (supposedly “healthy” cholesterol) were associated with an increased risk of depression

Now, epidemiological studies of this nature cannot be used to determine that lower cholesterol studies cause depression. However, bearing in mind cholesterol’s role in brain cell health, the potential for a “causal” link does indeed exist.

This study, by the way, is not the only one to link low cholesterol levels with mental health issues. For example, last year a Spanish review [8] of the evidence concluded that: “It is shown that low cholesterol levels in serum are associated and related to different neuropsychiatric disorders. Lowered cholesterol levels seem likely to be linked to higher rates of early death, suicide, aggressive and violent behaviour, personality disorders, and possibly depression, dementia and penal confinement among young males.”

Now, some will claim that any problems with lower cholesterol need to be balanced with the “benefits” of this, in terms of reduced risk of heart disease. We do need to be slightly wary of this argument, though, because there is actually quite a lot of evidence that in the elderly, higher cholesterol levels are not necessarily associated with an enhanced risk of cardiovascular disease and/or overall risk of death [9-18].


1. Jacobs D, et al. Report of the conference on low blood cholesterol: mortality associations. Circulation 1992;86(3):1046-60

2. Alawi A, et al. Statins, Low-Density Lipoprotein Cholesterol, and Risk of Cancer. Journal of the American College of Cardiologists 2008;52(14):1141-7

3. Yang X, et al. Independent associations between low-density lipoprotein cholesterol and cancer among patients with type 2 diabetes mellitus. Canadian Medical Association Journal 2008;179(5):427-437

4. Schatzkin A, et al. Serum cholesterol and cancer in the NHANES I epidemiologic follow up study. National Health and Nutrition Examination Survey. Lancet 1987;2:298-301

5. Ulmer H, et al. Why Eve is not Adam: prospective follow-up in 149650 women and men of cholesterol and other risk factors related to cardiovascular and all-cause mortality. J Womens Health 2004;13(1):41-53

6. Schatz IJ, et al. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet 2001;358(9279):351-5

7. Ancelin ML, et al. Gender and genotype modulation of the association between lipid levels and depressive symptomatology in community-dwelling elderly (the ESPRIT study). Biol Psychiatry 2010;68(2):125-32

8. Martinez-Carpio PA, et al. Relation between cholesterol levels and neuropsychiatric disorders. Rev Neurol 2009;48(5):261-4

9. Scientific steering committee on behalf of the Simon Broome Register group. Risk of fatal coronary heart disease in familial hypercholesterolaemia. British Medical Journal 1991;303: 893-896

10. Forette F, et al. The prognostic significance of isolated systolic hypertension in the elderly. Results of a ten year longitudinal survey. Clinical and Experimental Hypertension. Part A, Theory and Practice 1982;4:1177-1191

11. Nissinen A, et al. Risk factors for cardiovascular disease among 55 to 74 year-old Finnish men: a 10-year follow-up. Annals of Medicine 1989;21:239-240

12. Krumholz HM, et al. Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. Journal of the American Medical Association 1994;272:1335-1340

13. Weijenberg MP, et al. Serum total cholesterol and systolic blood pressure as risk factors for mortality from ischemic heart disease among elderly men and women. Journal of Clinical Epidemiology 1994;47:197-205

14. Simons LA, et al. Cholesterol and other lipids predict coronary heart disease and ischaemic stroke in the elderly, but only in those below 70 years. Atherosclerosis 2001;159:201-208

15. Fried LP, et al. Risk factors for 5-year mortality in older adults: the Cardiovascular Health Study. Journal of the American Medical Association 1998;279:585-592

16. Chyou PH, et al. Serum cholesterol concentrations and all-cause mortality in older people. Age and Ageing 2000;29:69-74

17. Menotti A, et al. Cardiovascular risk factors and 10-year all-cause mortality in elderly European male populations; the FINE study. European Heart Journal 2001;22:573-579

18. Räihä I, et al. Effect of serum lipids, lipoproteins, and apolipoproteins on vascular and nonvascular mortality in the elderly. Arteriosclerosis Thrombosis and Vascular Biology 1997;17:1224-1232

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