Cholesterol Lowering Drugs May Lessen Brain Function

A guest post by Dr. David Cahill 

The researcher in question is Yeon-Kyun Shin, a biophysics professor in the department of biochemistry, biophysics and molecular biology. Shin was interviewed for an article in Science Daily and he says that the results of his study show that drugs that inhibit the liver from making cholesterol may also keep the brain from making cholesterol, which is vital to efficient brain function.

Says Shin: “If you deprive cholesterol from the brain, then you directly affect the machinery that triggers the release of neurotransmitters.” “Neurotransmitters affect the data-processing and memory functions. In other words – how smart you are and how well you remember things.”(1)

“Our study shows there is a direct link between cholesterol and the neurotransmitter release,” said Shin. “And we know exactly the molecular mechanics of what happens in the cells. Cholesterol changes the shape of the protein to stimulate thinking and memory.”

A recent book by Andrew Koob (2) discusses the glial cells – the cells which co-exist with neurons in the brain. Until fairly recently, the glial cells, even though they make up 90% of the number of cells in the brain, have been considered relatively unimportant compared with the neurons, or nerve cells. Koob turns this on its head with his synopsis of recent research. It appears now that the astrocytes (a type of glial cell) are where our thoughts and memory reside. Hardly unimportant! The astrocyte also seems to be responsible for synaptogenesis – the process whereby new connections are made between the neurons – basically the way new knowledge is learned and stored in the brain.

Research published back in 2001 by Mauch et al, isolated the molecule responsible for synaptogenesis – cholesterol (3). They demonstrated that it is the astrocytes that have the ability to synthesize cholesterol and release it from their cell bodies.

Thus, it has been shown for some time that synaptogenesis is facilitated by cholesterol, which is made in the astrocytes. And herein lies a potentially huge problem with cholesterol-lowering drugs – they have the effect of reducing cholesterol production in the liver, yet they also reduce cholesterol production in the brain.

In the October 2009 Journal of Lipid Research the following was stated:

the long-term effects of statin therapy could lead to transient or permanent cognitive impairment in patients who already have low levels of brain cholesterol. This is primarily an issue in the elderly because brain cholesterol synthesis and levels tend to be reduced in people with advanced age, and cholesterol as well as phospholipid levels are particularly reduced in patients with AD (Alzheimer’s Disease).”(4)

Disturbingly, it also appears very likely that the benefits of taking these drugs have been overstated. They have certainly been shown to reduce measurable blood cholesterol levels, but any benefit of doing that is appearing to be less than profound. A 2010 meta-analysis of the clinical trials that have been performed on statins, looked at all-cause mortality. That is, looked at whether taking the drugs actually lead to greater longevity, and it turns out that they DON’T, unless you are already suffering from coronary heart disease. For all others, who may simply have a cholesterol level labelled as high, their conclusion is quite clear and stated thus:

      This literature-based meta-analysis did not find evidence for the benefit of statin therapy on all-cause mortality in a high-risk primary prevention set-up.”(5)

I suggest that if you are taking cholesterol-lowering drugs (statins), at the very least discuss this research with your medical practitioner.

References:

  1. (The full research article by Shin was published  in March 09 in the “Proceedings of the National Academy of Sciences” journal. “A scissors mechanism for stimulation of SNARE-mediated lipid mixing by cholesterol” Jiansong Tonga, Peter P. Borbatb, Jack H. Freedb and Yeon-Kyun Shin.  PNAS March 31, 2009 vol. 106 no. 13 5141-5146. )
  2. Koob, A. The Root of Thought: Unlocking Glia–the Brain Cell That Will Help Us Sharpen Our Wits, Heal Injury, and Treat Brain Disease. FT Press 2009
  3. Mauch et al. CNS Synaptogenesis Promoted by Glia-Derived Cholesterol. Science, 2001 Nov 9; 294: 1354-1357
  4. Weijiang Dong et al. Differential effects of simvastatin and pravastatin on expression of Alzheimer’s disease-related genes in human astrocytes and neuronal cells. Journal of Lipid Research. 2009 Oct; 50: 2095-2102.
  5. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. Arch Intern Med. 2010 Jun 28;170(12):1024-31