Assessing possible hazards of reducing serum cholesterol.

Objective: To assess whether low serum cholesterol concentration increases mortality from any cause.

Design: Systematic review of published data on mortality from causes other than ischaemic heart disease derived from the 10 largest cohort studies, two international studies, and 28 randomised trials, supplemented by unpublished data on causes of death obtained when necessary.

Main Outcome Measures: Excess cause specific mortality associated with low or lowered serum cholesterol concentration.

Results: The only cause of death attributable to low serum cholesterol concentration was haemorrhagic stroke. The excess risk was associated only with concentrations below about 5 mmol/l (relative risk 1.9, 95% confidence interval 1.4 to 2.5), affecting about 6% of people in Western populations. For noncirculatory causes of death there was a pronounced difference between cohort studies of employed men, likely to be healthy at recruitment, and cohort studies of subjects in community settings, necessarily including some with existing disease. The employed cohorts showed no excess mortality. The community cohorts showed associations between low cholesterol concentration and lung cancer, haemopoietic cancers, suicide, chronic bronchitis, and chronic liver and bowel disease; these were most satisfactorily explained by early disease or by factors that cause the disease lowering serum cholesterol concentration (depression causes suicide and lowers cholesterol concentration, for example). In the randomised trials nine deaths (from a total of 687 deaths not due to ischaemic heart disease in treated subjects) were attributed to known adverse effects of the specific treatments, but otherwise there was no evidence of an increased mortality from any cause arising from reduction in cholesterol concentration.

Conclusions: There is no evidence that low or reduced serum cholesterol concentration increases mortality from any cause other than haemorrhagic stroke. This risk affects only those people with a very low concentration and even in these will be outweighed by the benefits from the low risk of ischaemic heart disease.