OK, I'm a pillhead, a bulwark of the vast international pharmaceutical conspiracy, er, industry. You got the pill? I got the ill. I take 3 kinds of pills for my Parkinson's Disease. Two of these I take every few hours. I also take a multi-vitamin, and a vitamin D supplement, and, what the heck, throw in some salmon-oil gels while you're at it. Even my dog takes a tranquilizer before a trip to the vet. It would be depressing, but I'm on a pill for that as well.
Still, when my wise old internist announced a year ago that he wanted to put me on something for my high level of "bad" cholesterol, I balked. He gravely showed me the lab report numbers that said "HEART ATTACK COMING" But the thought of more pills, pills, pills was just too much. He reluctantly agreed to let me try to cope with the problem by modifying my diet.
A year passed. Leaves turned to gold and fluttered to the ground, snow fell only to be pierced by the green shoots of Spring. Birds returned with their raucous calls, as buds swelled and then burst into leafy glory etc... etc... and with the same majestic inevitability, my bad cholesterol numbers got worse.
So I went back to my wise old Internist. While waiting for him in the examining room, I dimly remembered some controversy about Parkinson's and statins, the commonly prescribed remedy for evil cholesterol. I whipped out my cell phone and googled "statins" and "Parkinson's Disease" and was rewarded by the following: Statins+PD=BAD. But, what's this? I also got Specific Statin+PD= good.
The first article, from Science Daily in January, 2007 warns
"Researchers are sufficiently worried by new study results that they are planning clinical trials involving thousands of people to examine the possible link between Parkinson's disease and statins, the world biggest selling drugs, reports Patrick Walter in Chemistry & Industry."
While the second, from a July 2007 edition of the same online publication, heralds one particular statin as a significant hindrance to both Alzheimer's Disease and Parkinson's!
ScienceDaily (July 19, 2007) — Researchers from Boston University School of Medicine (BUSM) have found that the statin, simvastatin, reduces the incidence of Alzheimer's disease and Parkinson's disease by almost 50 percent. This is the first study to suggest that statins might reduce the incidence of Parkinson's disease.
For a brief moment I became more concerned about schizophrenia in science than the question of whether or not I should begin statins. I informed my wise old Internist of my findings, and he asked me where I came down on the issue, and what I wanted to do. Really what I wanted was for him to stop treating me like an intelligent adult and tell me what I wanted to do. After all, he is the one with a medical degree, and all I have is a smart phone. But this is the day of the empowered patient, and my responsibility to be the master of my fate and the captain of my pills was clear.
I opted for the simvastatin. I don't know if it helps with PD. I'm just hoping that if it actually prevents heart attacks, I'll live long enough to find out.
Post script: Here with an unusually well-informed view on the above question is a reply that appeared as an anonymous response the comments section. I am posting it here for people who do not read the comments. Thanks, anonymous,
I would have a DNA profiling done prior to taking a statin to make certain I do not possess either of the 2 SNPs discovered in the SLCO1B1 gene which encodes a transport protein responsible for moving statins into the liver for detoxification for elimnation. Some individuals with these SNPs have been found to have greatly increased plasma statin levels, toxic levels, in my opinion. Incredibly high levels of a fat soluble statin does not make for a healthy individual. Imagine severely depleted coQ10 production; severely depressed production of selnoproteins and thus glutathione reductase; severely impaired glycoprotein function; depressed cholesterol levels-how will neuronal and myelin cholesterol levels be maintained; depleted dolichol within the melanin of the substantia nigra (and what is the significance of this event?).Mutations in this gene are not rare, though many individuals develop such severe myopathies or myalgias that they stop the drug. I think for those who do not suffer the muscle myopathy problems,neurodegeneration may occur. my 2 cents worth of personal opinion
11 comments:
I've also noticed the articles with very conflicting views -- I think it comes down to that age old thing of 'nobody knows anything.'
Unless you're a drug company - in which case, you know everything.
"Nobody knows" is such an unsatisfying answer it must be true. We just have to stumble forward. This is forward. Right? Oh.. and compliments on the Cinema Paradiso avatar. Nice.
I would have a DNA profiling done prior to taking a statin to make certain I do not possess either of the 2 SNPs discovered in the SLCO1B1 gene which encodes a transport protein responsible for moving statins into the liver for detoxification for elimnation. Some individuals with these SNPs have been found to have greatly increased plasma statin levels, toxic levels, in my opinion. Incredibly high levels of a fat soluble statin does not make for a healthy individual. Imagine severely depleted coQ10 production; severely depressed production of selnoproteins and thus glutathione reductase; severely impaired glycoprotein function; depressed cholesterol levels-how will neuronal and myelin cholesterol levels be maintained; depleted dolichol within the melanin of the substantia nigra (and what is the significance of this event?).Mutations in this gene are not rare, though many individuals develop such severe myopathies or myalgias that they stop the drug. I think for those who do not suffer the muscle myopathy problems,neurodegeneration may occur. my 2 cents worth of personal opinion
Wow! Great comment. I will put this up as part of the main post. Thanks.
Pete
So, did you start the statin? Dr. Lieberman, Florida,reported a very poorly designed study looking at 2 sets of PD patients--one group on statins and the other having never taken a statin. He followed
Dr. Lieberman did this small study looking at progression rates of 2 different groups of PD patients--one taking a statin, the other not on statins., His conclusion after following these 2 groups after a period of 2yrs) was that their rates of progression were "similar". Included in this study was a small paragraph noting that of the original group who were not taking a statin, 5 patients were started on a statin during the trial period. Importantly (to me anyway) was the fact that ALL FIVE PATIENTS EXPERIENCED AN INCREASE IN SEVERITY OF THEIR SYMPTOMS AFTER STARTING A STATIN. I know that is a small #, but that's 100% of all the patients who were started on a statin during the trial period. the statin was stopped for a "washing out" period and when the symptoms did not revert, the drug was re-started. Does not increasing severity of symptoms qualify as "progression of disease?
Consider also the following:
Cholesterol has recently been found to be ESSENTIAL to the neuronal synapses in the brain and
ApoE is the most abundant apolipolipid in the brain and delivers cholesterol to the neurons. (studies with statins and alzheimer's utilizing statins to decrease ApoE4 are Still underway. Problem with these studies is that initially one would expect some benefit from statins due to their anti inflammatory effects, but IF they ran long enough (ie >5 ys) any effects w/ depletion of cholesterol would be evident. Cholesterol is reported to be made de novo in the brain itself; cholesterol theoretically cannot cross the blood brain barrier, so the brain has its own mavelonate pathway to its production. and fortunately, brain cholesterol has a VERY LONG HALF LIFE--5 yrs. any studies that last <5yrs (almost ALL pharmaceutical studies) will not pick up the effects of lowered brain cholesterol and ApoE. Recently, Alzheimer's reserach has been shifting toward increases in tau phosphorylation as etiopathogenic in Alzheimer's--and statins increase tau phosphorylation. statins are studied in alzheimer's because they specifically decrease ApoE--the substance responsible for transporting cholesterol to the neurons for synaptic functions to occur. with the newest information that Apoe is essential for neuronal synapses, manipulating cholesterol and apoe for alzheimer's seems more than a questionable undertaking.
NEUROBIOLOGY:
Cholesterol--Making or Breaking the Synapse
Ben A. Barres and Stephen J. Smith
Synapses are regions where neurons meet and communicate. But how is their formation regulated in the developing and adult brain? As Smith and Barres explain in their Perspective, the answer could not be simpler. It turns out that, at least in the culture dish, a type of glial cell called an astrocyte produces the molecule cholesterol, which is taken up by neurons and then directs formation of synapses perhaps by regulating vital signaling pathways (Mauch et al.).
"Neurons need cholesterol secreted by glial cells to form and maintain functional synapses. And cholesterol is necessary for synaptogenesis and probably for production and transport of vesicles necessary for neurotransmission." If one accepts the concept of neuronal plasticity in the adult brain, then deliberately suppressing cholesterol metabolism in the brain seems questionable.
And yes, I am "anonymous" in the blog noting the major problems for those with SNPs in SLCO1B1,
Anonymous, thanks for sharing your amazing trove of knowledge. To start by answering your question, yes, I started simvostatin a year ago. Your post certainly left me unsettled. Could I sum up your statin fear by saying there is a possibility that in addition to known hazards, there is also possible degradation of brain function due to destruction of the brain cholesterol necessary for proper synaptic function?
If I have that right I would go on to ask:
1. Is it known whether statins cross the blood/brain barrier?
2. Is cholesterol level outside the brain correlated with cholesterol level within the brain?
3. I assume that cholesterol degradation the synapses would be a problem for everyone who takes Statins, not only people with Parkinson's Disease. Statins have been around for awhile in fairly widespread use, correct?. Has there been a correlation between statin use and cognitive or other brain dysfunction in the wider, non-PD suffering population?
Finally, this seems to be a sort of damned-if-you-do-damned-if you don't problem. If i were to stop the statins, and suffered a heart attack, it would certainly be an adverse event for my health and for my ability to maintain that health. Having failed at attempts to lower my cholesterol without the statin, it seems I must weigh the speculative but certainly tangible likelihood of a heart attack against speculative and much less (at this stage) tangible possibility of brain damage.
Oops, one more thing. Suppose I were able to lower my "bad" blood cholesterol through some other means, say the massive consumption of oatmeal and tart cherries. Would the outcome for my brain cholesterol be different from doing this with simvostatin?
Thanks again for your provocative and learned posts and for the obvious amount of time you put into them.
Pete
I am a 55-year-old veteran who was treated with simvastatin by the VA for over three years. The VA rarely checked my liver enzymes other than once a year (except the first time), did not connect the depression that almost immediately followed the start of the statin. I also suffered from increased levels of anger and hostility, brain fog, and major memory problems. I also started having increased problems with my carpal tunnel, hand tremors (towards the end), and severe nasal congestion, among others. My cholesterol did not go down significantly on the statins (stayed in the low to mid-200s), even at 80 mg, except for the period when my car broke down and I had to walk everywhere because I could not afford repairs/replacement for several months. I got off of the statins about 15 months ago and will never use them again. While I am much improved, my memory has not returned in full yet, plus my vitamin D levels have gotten rather low (17). I would rather live a shorter life with a healthier, sharper brain than a longer life that is spent in a mental fog.
will attempt to answer to best of my ability"
1. all fat soluble statins cross BBB and therefore can affect production of brain cholesterol
: Locatelli S et al
Ataherosclerosis 2000 151 43.
report shows concentration of 24S hydroxycholesterol
indicating that (statins) penetrate blood-brain barrier and
inhibit synthesis within the CNS.
2. turnover rate for cholesterol in CNS 1/20 th what it is in rest of body, half life of CNS cholesterol reported to be 5 1/2 years,
3. cognitive dysfunction is now listed as a potential side effect for statins thus far this is not widely reported. who knows. perhaps compensatory mechanism kicks in or some people are or it may have no clinical significance for some
article in mainstream press:http://www.businessweek.com/magazine/content/04_47/b3909127_mz018.htm
a now dated reference:
Canadian Adverse Reaction Newsletter, Volume 15, No. 4
(statins) may cross the blood-brain barrier
and decrease the amount of central nervous system (CNS) cholesterol
necessary for the formation of myelin.2,3 Inadequate myelin production
may result in demyelination of nerve fibres in the CNS and thus lead to
memory loss.2 Memory impairment is listed in the product monograph for
Pravachol.5
Given these findings, changes in cognitive status temporally associated
with statin therapy should be monitored.2
4. serum cholesterol theoretically does not affect CNS cholesterol. brain cholesterol made by brain cells themselves. lowering plasma cholesterol by other means should not affect brain cholesterol levels. obviously many many statin users,promoters,believers think statins work wonderously. statins interrupt the mavelonate pathway 9 enzymatic steps prior to the step that makes cholesterol. do you supplement with coq10? You could google the mavelonate pathway
5. google the 2 researchers noted in the mainstream media article who address the cognitive issues,that may be of help.
6. I would never tell anyone else what to do about meds; i am no physician nor pharmacist. I am an amateur resarcher with a science background. On a personal note, for my husband we regret every day that he took a statin. we regret not knowing about the genetic mutation in the SLCO1B1 gene which probably resulted in toxic levels of statins for him. is there some other mutation that predisposed him to parkinson's in the mix? we do not know and neither does anyone else at this juncture. His is one case study that I am sharing.
7. best of luck to you. I did not post to cause anxiety. I was truly interested in the course of Parkinson's for those who take a statin.
8. as ad add on thought: one of the mutations in the SLCO1B1 gene which my husband possesses is theorized to cause inherently increased serum cholesterol levels. This transport protein the gene encodes is responsible for moving about 10% of total bile salts into the liver to enter into the feedback loop telling the liver how much cholesterol to make. without the transport protein, the regulatory bile salts do not get into the liver and the liver thinks it needs to make more cholesterol--thus the inherently higher cholesterol in thes individuals. Again is this of any clinicaal significance? I have no idea.
You deemed.my answer not post worthy?@
Au contraire, I haven't had the time to devote to a proper response. Will try to do right by your post as soon as possible. Hurridly,
Peter
My anonymous friend, did you delete your last reply? It seems to have gone missing.
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