When it comes to cholesterol, is lower really better?

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Very few of us will not have noticed that the last couple of decades have seen a concerted effort from health agencies and health professionals to persuade us that we should be driving our cholesterol levels to lower and lower levels. When I was at medical school the upper limit of cholesterol was 6.5 mmol/l (255 mg/l). But it’s come down steadily since then and now stands at 5.0 mmol/l (195 mg/l). My suspicion is that it will fall even lower over the years. Who knows, it may get so low that practically everyone will be classified as having a raised cholesterol, and be recommended to lower this with specialised food products and/or drugs.

However, seeing that cholesterol is a constituent in the walls of cells in the body as well as what are known as ‘steroid’ hormones, there is an argument for questioning whether lower really is better. Some have suggested that low levels of cholesterol may predispose to health issues including those that relate to brain function.

Last month saw the publication of a study in the journal Neurobiology of Aging in which Dutch researchers assessed the relationship between cholesterol levels and mental function in about 1200 individuals aged 65 or older. The participants in the study were assessed over a 6-year period. Lower cholesterol levels in this group were associated with a reduction in both general cognition and information processing speed. The authors of this study concluded that their results indicate that: �lower total cholesterol may be considered as a frailty marker, predictive of lower cognitive functioning in elderly.�

Of course with studies of this nature, it is impossible to know whether the low cholesterol is responsible for the associated poorer brain function. However, one way to assess this might be to attempt to lower cholesterol levels and see what it does to brain function. In one study, individuals treated with lovastatin (a cholesterol-reducing drug), compared to those taking a placebo, saw significant reductions in measures such as vigilance and general cognitive function [2]. This study, though, did also test the effect of another statin drug (pravastatin) which did not appear to have this same adverse effect on brain function.

Even if we take the apparent association between lovasatin and impaired brain function as face value, we do not know whether this was due to cholesterol lowering per se or, say, some side effect of the medication.

Another study, though, does add further evidence to support the notion that lower cholesterol levels may impair brain function. In it, a low fat diet was pitted against a standard diet over a 12-week period [3]. The performance of a task that required sustained attention was significantly worse in individuals who had reduced their cholesterol over the course of the trial. And the lower the cholesterol fell, the worse the performance in this test was.

Even if it turns out the cholesterol reduction is bad for the brain, I have no doubt that proponents of the cholesterol concept will point to other benefits of this endeavour. Though I do think it is worth bearing in mind that the evidence shows that in essentially healthy individuals, cholesterol reduction through drugs has not been shown to save lives. And dietary approaches do not appear to reduce funeral rates either, even in those with a history of cardiovascular disease.

And finally, there is at least some evidence that in later life, higher levels of cholesterol are actually associated with enhanced longevity [4-7]. There is mounting evidence, I think, which suggests that as far as cholesterol is concerned, lower is not necessarily better.

References:

1. van den Kommer TN, et al. Total cholesterol and oxysterols: Early markers for cognitive decline in elderly? Neurobiol Agin. 2007 Sep 19; [Epub ahead of print]

2. Roth T, et al. Comparative effects of pravastatin and lovastatin on nighttime sleep and daytime performance. Clinical Cardiology. 1992;15:426-432

3. Wardle J, et al. Randomized trial of the effects of cholesterol-lowering dietary treatment on psychological function. Am J Med 2000;108(7):547-553

4. Brescianini S, et al. Low total cholesterol and increased risk of dying: are low levels clinical warning signs in the elderly? Results from the Italian Longitudinal Study on Aging. Journal of the American Geriatrics Society 2003; 51(7):991-996

5. Forette B, et al. Cholesterol as risk factor for mortality in elderly women. Lancet, 1989; 1:868-870

6. Jonsson A, et al. Total cholesterol and mortality after age 80 years. Lancet, 1997;350:1778-1779

7. Weverling-Rijnsburger AW, et al. Total cholesterol and risk of mortality in the oldest old. Lancet, 1997;350:1119-1123

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