Intended for healthcare professionals

Analysis And Comment Controversy

Should we lower cholesterol as much as possible?

BMJ 2006; 332 doi: (Published 01 June 2006) Cite this as: BMJ 2006;332:1330

Surely some mistake?

Ravnskov et al., state that 'all statins inhibit the synthesis of
hydroxymethylglutaryl coenzyme A (HMG CoA) reductase, an enzyme involved
in synthesis of the precursor of cholesterol'. This is incorrect. Statins
act as inhibitors of hydroxymethylglutaryl coenzyme A reductase and reduce
synthesis of mevalonate from HMG CoA. The consequent reduction in
cholesterol synthesis leads to upregulation of receptors for low density
lipoprotein (LDL) and a resultant increase in uptake of this lipoprotein
(largely by the liver) and reduced circulating LDL. In fact use of statins
is associated with increased amounts of HMG CoA reductase as a result of
reduced negative feedback on synthesis (1).

1. Brown MS, Goldstein JL. Multivalent feedback regulation of HMG CoA
reductase, a control mechanism coordinating isoprenoid synthesis and cell
growth. J Lipid Res. 1980;21:505-17.

Competing interests:
None declared

Competing interests: No competing interests

12 June 2006
Alun D Hughes
Professor of Clinical Pharmacology
Michael Schachter
NHLI Division, Faculty of Medicine, Imperial College London, UK