Patients who take statins in order to lower their blood cholesterol
levels often complain about muscle problems, typically muscle pain. But
why this occurs is still largely unresolved. In a recent study, the
pharmaceutical scientists Professor Alexandra K. Kiemer und Jessica
Hoppstädter from Saarland University have identified a potential causal
relationship. According to the results of their work, statins cause
enhanced production of a protein called ‘GILZ’ that impairs muscle cell
function.
The study has been published in
The FASEB Journal under the title “The Glucocorticoid-Induced Leucine Zipper Mediates Statin-Induced Muscle Damage.”
Cholesterol-lowering drugs, which are commonly referred to as
statins, are some of the most frequently prescribed drugs around the
world. Generally speaking, statins are well tolerated by patients.
However, it is not uncommon for patients on statins to complain of
muscle pain or muscle weakness. “According to figures from
observational studies, muscle problems have been found to occur in 5% to 29% of cases. Older patients and
female patients
appear to be at greater risk of developing these symptoms, but so too
are patients that are very physically active,” explains Alexandra K.
Kiemer, Professor of Pharmaceutical Biology at Saarland University. In
2018, more than 6 million patients in Germany were treated with statins.
This would suggest that muscle problems may be affecting several
hundreds of thousands of patients, potentially as many as 1.8 million,
in Germany alone. The precise nature of the bodily processes that induce
symptoms of muscle impairment has not yet been fully characterized.
Alexandra K. Kiemer and her research group may now have identified the actual cause of the
muscle pain
affecting patients receiving statins. They believe that a protein known
as GILZ is responsible. “The acronym GILZ stands for
glucocorticoid-induced leucine zipper,” explains Professor Kiemer. Over
the years, her research group has conducted numerous experimental
studies into this particular protein. “The main function of GILZ is
actually to suppress inflammatory processes in the body. Statins prevent
cardiovascular disease not only by lowering blood cholesterol levels,
but also by reducing vascular inflammation. That’s why we thought there
might be a connection between statins and GILZ. Our data indicate that
the presence of GILZ in the body can have both positive and
negative effects,”
says Kiemer. Building on this initial conjecture that there might be a
link between the protein GILZ and statins and their side effects, the
pharmaceutical researchers began analysing numerous datasets drawn from
research databases available around the world.
They assessed the data in terms of whether statins influenced the
production of GILZ in the body. After confirming their original
suspicions, the researchers were able to corroborate their hypothesis by
carrying out a series of experiments on living cells. “Statins cause an
increase in the cellular production of the GILZ protein. This, however,
leads to impaired muscle function, because increased GILZ production
results in an increased rate of muscle cell death. In addition, the
formation of muscle fibres is inhibited,” says Alexandra K. Kiemer. The
research team then tried switching off the GILZ protein in living cells
and observing what effect the statins then had. “When we look at what
happens when statins are administered to muscle cells or entire
muscle
fibres in which GILZ has been genetically deactivated, the damage that
was previously observed is now almost completely absent,” says Kiemer.
There also seem to be indications that people who engage in a significant amount of physical activity suffer from
muscle problems
when prescribed statins. Furthermore, the statins appear to impair the
success of physical training programmes. The pharmaceutical researchers
led by Alexandra K. Kiemer are therefore planning a new study to be
conducted in collaboration with the sports medicine physician Anne
Hecksteden from the research group headed by Professor Tim Meyer at
Saarland University. “We have some evidence that there is a link between
statins, physical activity and the GILZ protein, and our plan is to
shed more light on how these factors interact with each other,” says
Professor Kiemer.
More information: Jessica Hoppstädter et al, The glucocorticoid‐induced leucine zipper mediates statin‐induced muscle damage,
The FASEB Journal (2020).
DOI: 10.1096/fj.201902557RRR
