Cholesterol in Parkinson’s: Do Statins Alter the Yin and Yang Balance in the Brain?

“You cannot separate passion from pathology any more than you can separate a person’s spirit from his body.” Richard Selzer

What is cholesterol?
Cholesterol is a lipid (that is, a fat) that exists naturally in all parts of the body, including the brain. Your body needs cholesterol to function properly. You probably already know that if you have excess amounts of cholesterol in your blood, it can be deposited in the walls of your arteries. These abnormal lesions accumulate over time in arteries, and are termed plaque. Plaque can narrow your arteries or even block them, and this can eventually cause much sickness and death.

Cholesterol in the brain: Cholesterol helps to organize cell membranes (the outer surface of all cells).  Cholesterol is required by mammals to make steroid hormones and bile acids. Cholesterol is involved in special areas of cell membranes called lipid rafts.  Lipid rafts are thought to be involved in several aspects of brain function, including: relaying messages from outside of the cell to inside (signal transduction) and nervous system relays and conduction (axon guidance and synaptic transmission). Based on these functions alone, you could speculate that either a deficiency or excess of cholesterol in the brain might have severe consequences in brain function. Thus, the yin and yang balance in the brain is altered as cholesterol levels change (for a nice overview of yin/yang theory in medicine, go here: http://health.howstuffworks.com/wellness/natural-medicine/chinese/yin-and-yang.htm). The role of cholesterol in Parkinson’s is not well understood, but from a PubMed literature search, several excellent research groups are pursuing this topic area.

Statins and cholesterol: If you’ve watched TV or read newspapers in the past decade, then you have heard of the drugs called statins.  They are powerful agents at lowering cholesterol in arteries, and their impact in reducing cardiovascular-related illness/death have been profound. However, the use of statins remains controversial and now this controversy exists in Parkinson’s.

Statins and Parkinson’s: The simple goal of science is to ask a relevant question (the hypothesis) and then design studies to answer the question (testing the hypothesis). You gather the results, publish them and the true test is having some other research group verify your data.  Then you expand your studies, and sometimes the picture gets murky.  Such is now the case of statins and Parkinson’s. Previous studies showed that people taking statins may offer protective benefits against Parkinson’s. Some public health (epidemiology) studies agreed with this observation, while other studies did not find this association. Such is human-science research, and it seems to occur in Parkinson’s-related studies.

Dr. Huang (Penn State College of Medicine) previously showed that HIGHER blood cholesterol levels were linked to a LOWER incidence of Parkinson’s. To bolster these results, a new study was just published “Statins, plasma cholesterol, and risk of Parkinson’s disease: A prospective study” (the paper is here: http://onlinelibrary.wiley.com/doi/10.1002/mds.26152/abstract).  This was a large study of patient samples/history using ARIC (Atherosclerosis Risk in Communities study) and they looked at the relationship of Parkinson’s symptoms with cholesterol levels and medication history (i.e., statin use). This paper had 3 main results: (1) they confirmed their previous results that high cholesterol (LDL-C) levels showed a lower risk of Parkinson’s; (2) use of statins to lower cholesterol did not appear to protect from Parkinson’s; and (3) they found an increased risk of Parkinson’s for those using statins. What does this paper mean to many people taking statins and who have Parkinson’s?  First, we need more studies on cholesterol and Parkinson’s.  Second, seek the advice of your team of physicians (Internist/Family Med and Neurologist), they’re your experts.

I close with a song:  As a biochemist by training, in graduate school we studied/learned a lot of metabolism and pathways.  Yes, I memorized the pathway our body uses to synthesize cholesterol.  The lyrics below gets you on the way to making cholesterol (the key topic of this blog today), enjoy!

The Cholesterol Biosynthesis Song [lyrics by David Kritchevsky (to the tune of “Jingle Bells”)]

Take an acetate,

Condense it with a mate,

Pretty soon you’ll have

Acetoacetate.

Let ’em have a ball,

You get geraniol.

Add another isoprene

And you’ve got farnesol.

Farnesol, farnesol, good old farnesol,

First it goes to squalene, then you get cholesterol.

Farnesol, farnesol, good old farnesol.

First it goes to squalene, then you get cholesterol.

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