Mitochondria, Statins and Parkinson-like Symptoms

by aiP / 2015

Table of Contents



The following research was conducted in 2015 on behalf of a gentleman diagnosed with Parkinsonisms in 2011.

The aim of this document was to promote a dialogue with his consultant, as his L-Dopa "treatment" had provided no perceived benefit and was likely the cause of his "freezing", a symptom not present prior to his taking Madopar (L-Dopa); and it was these regular freezing episodes that were causing the greatest distress.

In this document the man is referred to as Patient X.

Patient X had suffered a heart attack fourteen years prior to his diagnosis in 2011 and so by 2015 had been taking statin medication in conjunction with Ramapril for 18 years.

In 2011 Patient X had complained of "rapid ageing" as though he had aged 10 years in just a few months. A number of weeks later he was diagnosed with Parkinsonisms (Parkinson-like symptoms). Soon after that he was prescribed Madopar and in 2015 Madopar in conjunction with Stalevo.

The research is presented here in the hope that it may be of some benefit to:

  • those suffering with Parkinson's
  • doctors treating Parkinson's
  • family members caring for Parkinson's sufferers, and
  • anyone taking statins or other cholesterol lowering medication



The SNCA gene (gene family = PARK) provides instructions for making a small protein called alpha-synuclein. At least 18 mutations in the SNCA gene have been found to cause Parkinson disease 1.

  • Alpha-synuclein (a-Synuclein) is a small lipid binding protein which binds membranes.
  • In the brain, a-Synuclein is found mainly at the tips of neurons in structures called presynaptic terminals. 
  • Presynaptic terminals release neurotransmitters from compartments known as synaptic vesicles.
  • The release of neurotransmitters relays signals between neurons and is critical for normal brain function.
  • Aggregated a-Synuclein leads to the degeneration and death of dopaminergic neurons.

a-Synuclein is natively unfolded; it's not a structured protein and when it's not doing its job binding membranes it can form oligomeric species and fibrils which are toxic.

a-Synuclein toxicity has been linked to:

  • vesicle trafficking defects (it physically blocks donor to target membranes)
  • mitochondrial dysfunction
  • manganese homeostasis defects
  • iron and Ca++ homeostasis
  • mutations in ATP13A2/PARK9 


There are a number of genes that directly affect a-Synuclein toxicity (i.e. over-expression) such as mutations in ATP13A2, and there seems to be a vicious feedback loop: Something is causing the over-expression of a-Synuclein, and one of the effects of this over-expression is mutations in the ATP13A2 gene which is a suppressor of a-Synuclein toxicity.

Susan Lindquist points out in her talk, "New Clues to Parkinson's Disease From An Unlikely Source":
"We're using the same neurons we had when we were born. Maybe after a long time, the protein "quality control systems" of the cell start to deteriorate and breakdown".

Lindquist mirrored this 'process of overburdening' initially in yeast cells, by doubling the expression of a-Synuclein. "There's an extreme dosage sensitivity here. You can make one dose of this protein and the cells are perfectly fine; they make twice as much as they normally would and they die." 

This process is conserved in humans.

So, is it not possible that mitochondrial dysfunction (low ATP + production of reactive oxygen species), leads to said "quality control" issues in DNA synthesis / protein folding, which in turn causes mutations in one or more of these PARK genes? Thus, a-Synuclein gets over-expressed, which leads to dopaminergic neuronal degeneration and Parkinson-like symptoms.

If so, then whatever is causing mitochondrial dysfunction would be part of that causal chain (as least in the non-hereditary forms of Parkinson's / Parkinsonisms).

It's hard to identify the origin of non-hereditary Parkinson's. But it's not hard to imagine that mitochondrial dysfunction could have a detrimental impact in the DNA synthesis and protein folding realms, since mitochondria are so fundamental to these cellular processes.

Thus something which disrupts one of the key inputs for mitochondrial function must surely be taken very seriously. Indeed, anything that has a profoundly negative impact on the functioning of mitochondria must surely be regarded as harmful.

What I've outlined above is based (in the main 2, 3 ) on Susan Lindquist's work in her lab at the Whitehead Institute for Biomedical Research, MIT.

Lindquist tested 6000 genes in yeast and 1% affected a-Synuclein pathology. Several of those genes are now known to be involved in Parkinson's in humans. 


Relevant Papers:

  • Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase 4
  • Expression of mutant a-synuclein causes increased susceptibility to dopamine toxicity 5


1 Genetics Home Reference, NIH
2 Susan Lindquist Keynote Lecture at The International Society for Stem Cell Research in Vancouver, 2014
3 New Clues to Parkinson's Disease From An Unlikely Source, 2008
4 Nature Genetics - 38, 1184 - 1191 (2006)
5 Human Molecular Genetics, Volume 9, Issue 18, Pp. 2683-2689



Mitochondria, ATP and Protein Folding

Mitochondrial dysfunction results in low ATP and increased oxidative stress (production of free radicals). The link between Parkinson's and mitochondrial function is well established.

Low ATP affects key cellular process such as DNA synthesis and repair, protein synthesis and enzyme activation. Protein mis-folding is at the root of all neurodegenerative diseases 6.

Free radicals may be one of the important agents responsible for the destruction of substantia nigra neurons, leading to Parkinson's disease.

ATP is produced most efficiently by mitochondria using oxygen and Nicotinamide adenine dinucleotide (NADH, see Krebs cycle):

Krebs Cycle

Image Source: Shallenberger, Health, Aging, and Disease - It's all About Energy
Note: Mitochondrial function is inside the blue outline

If mitochondrial function is hampered due to a lack of any of the above inputs, oxidative stress occurs as large numbers of free radicals are produced, compounded by a reduction in anti-oxidants. This leads to cell death and tissue damage 7.


6 Dr. Susan Lindquist (Whitehead Institute for Biomedical Research and MIT) "New Clues to Parkinson's Disease From An Unlikely Source"
7 NAD+/NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences



Oxidative Stress & Parkinson's

In people with Parkinson's disease, nigral cells deteriorate and die at an accelerated rate, and the loss of these cells reduces the supply of dopamine to the striatum.

It appears that the substantia nigra cells may be particularly vulnerable to oxidation stress.

Oxidation stress occurs in the substantia nigra cells because the metabolism of dopamine requires oxidation and can lead to the formation of free radicals from hydrogen peroxide formation.

The hydrogen peroxide is normally detoxified by reduced glutathione in the reaction catalyzed by Glutathione peroxidase, thus an increased rate of dopamine turnover or a deficiency of glutathione could lead to oxidative stress.

Thus, it appears that free radicals may be one of the important agents responsible for destruction of substantia nigra neurons, leading to Parkinson's disease.



Glutathione (intra-cellular anti-oxidant)

Glutathione (or GSH) is a small protein molecule composed of 3 amino acids: cysteine, glutamate, and glycine called GSH precursors or building blocks.

GSH is the body's main intra-cellular anti-oxidant and aids the following:

  • Regulation of cell growth and division
  • DNA synthesis and repair
  • Protein synthesis
  • Amino acid transport
  • Enzyme catalysis
  • Enzyme activation
  • Metabolism of toxins
  • Metabolism of carcinogens
  • Enhancement of systemic immune function
  • Decreases free radical damage
  • Decreases oxyradical damage
  • Metabolizing of hydrogen peroxide (H2O2)
  • Recycling of other antioxidants (master antioxidant role)
  • Storage and transport of cysteine
  • Regulation of homocysteine
  • Participation in nutrient metabolism
  • and much more .....


Many studies have associated low glutathione levels and altered mitochondrial function with Parkinson's 8, 9. Unknown at present is whether it's causal or symptomatic. However, since glutathione is required for the regulation of cell growth and division, DNA synthesis and repair and protein synthesis and all neurodegenerative diseases are breakdowns in these very processes it's worth knowing Patient X's glutathione levels.


8 Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia
9 Altered mitochondrial function, iron metabolism and glutathione levels in Parkinson's disease



Parkinson's Medication and Glutathione

L-Dopa Parkinson drugs:

"A dilemma that has been noted in recent studies is that the administration of dopamine (singly or in the combined form of carbidopa and levodopa) results in an increase in the formation of free radicals and the continuation of the disease process. Thus, while the administration of levodopa offers amelioration of the symptoms of Parkinson's disease it does not change the underlying mechanisms of free radical formation, oxidation and loss of glutathione intracellular. After several years of use the effectiveness of carbidopa/levodopa decreases and patients need higher and more frequent doses to control their symptoms." 10

So the drugs Patient X is taking reduce his glutathione levels. Higher dopamine doses are required over time to get the same effect. This further reduces glutathione levels. And it's very possible that low glutathione levels either cause or exacerbate Parkinson-like symptoms in the first place.


10 Patent Application: Liposome-encapsulated glutathione for oral administration, US 8252325 B2



Statins, Coenzyme Q10 and Glutathione

Coenzyme Q10 (CoQ10) is a substance similar to a vitamin. It is found in every cell of the body. Your body makes CoQ10, and your cells require it to produce the ATP (via the mitochondria) your body needs for cell growth and maintenance. It also functions as an antioxidant, which protects the body from damage caused by harmful molecules.11


CoQ10 Deficiencies

Your body produces less and less CoQ10 as you get older.

People with certain conditions, including diabetes, Parkinson’s disease, and heart problems tend to have low levels of CoQ10 in their bodies. Researchers don’t know if the disease causes the deficiency or if the deficiency appears first, causing cells to age faster and making disease more likely. 12

"Although the causes of Parkinson's disease are not all known, decreased activity of complex I of the mitochondrial electron transport chain and increased oxidative stress in a part of the brain called the substantia nigra are thought to play a role.

Coenzyme Q10 is the electron acceptor for complex I as well as an antioxidant, and decreased ratios of reduced to oxidized coenzyme Q10 have been found in platelets of individuals with Parkinson's disease. One study also found higher concentrations of oxidized coenzyme Q10 in the cerebrospinal fluid of patients with untreated Parkinson’s disease compared to healthy controls. Additionally, a study of coenzyme Q10 levels in postmortem Parkinson’s disease patients found lower levels of total coenzyme Q10 in the cortex region of the brain compared to age-matched controls, but no differences were seen in other brain areas, including the striatum, substantia nigra, and cerebellum " 13


What happens when you take Statins?

According to a number of studies (University of Maryland Medical Center, Columbia University and Kanazawa University etc.) statins lower your body’s levels of coenzyme Q10. As your CoQ10 levels go down so does mitochondrial ATP production, while free radical formation increases. Additionally the detrimental side effects of statins also increase (such as muscle breakdown, muscle pain etc). 14

"In contrast to the current belief that cholesterol reduction with statins decreases atherosclerosis, we present a perspective that statins may be causative in coronary artery calcification and can function as mitochondrial toxins that impair muscle function in the heart and blood vessels through the depletion of coenzyme Q10 and ‘heme A’, and thereby ATP generation. Statins inhibit the synthesis of vitamin K2, the cofactor for matrix Gla-protein activation, which in turn protects arteries from calcification. Statins inhibit the biosynthesis of selenium containing proteins, one of which is glutathione peroxidase serving to suppress peroxidative stress. An impairment of selenoprotein biosynthesis may be a factor in congestive heart failure, reminiscent of the dilated cardiomyopathies seen with selenium deficiency. Thus, the epidemic of heart failure and atherosclerosis that plagues the modern world may paradoxically be aggravated by the pervasive use of statin drugs. We propose that current statin treatment guidelines be critically reevaluated." 15, 16

Further, "it is well established that the mevalonate pathway is involved not only in the biosynthesis of cholesterol but also in the biosynthesis of the essential co-factor required for energy production, coenzyme Q10 (CoQ10, ubiquinone). As such, HMG CoA reductase inhibitors block the cellular production of cholesterol and of coenzyme Q10 (Rudney 1981, Goldstein 1990). 17

"Cholesterol is vitally important for brain function. While your brain represents about 2-3% of your total body weight, 25% of the cholesterol in your body is found in your brain, where it plays important roles in such things as membrane function, acts as an antioxidant, and serves as the raw material from which we are able to make progesterone, estrogen, cortisol, testosterone and even vitamin D". 18

The brain uses glial cells as factories for producing its own cholesterol on demand". Statins inhibit glial cells' ability to produce cholesterol. 19


11 What is coenzyme Q10?
12 Coenzyme Q10 and Statin-Induced Mitochondrial Dysfunction
13 OSU Micronutrient Information Center
14 Source 1, Source 2
15 March 2015, Vol. 8, No. 2 , Pages 189-199 (doi:10.1586/17512433.2015.1011125) Harumi Okuyama, Peter H Langsjoen, Tomohito Hamazaki, Yoichi Ogushi, Rokuro Hama, Tetsuyuki Kobayashi, and Hajime Uchino
16 How Statins Really Work Explains Why They Don't Really Work (Seneff, MIT)
17 The clinical use of HMG CoA-reductase inhibitors (statins) and the associated depletion of the essential co-factor coenzyme Qlo; a review of pertinent human and animal data. By Peter H. Langsjoen, M.D., F.A.c.c.
18 Your Brain Needs Cholesterol
19 Lipitor: The Common Drug that Destroys Your Memory



Parkinson's and the Gut

The Enteric Nervous System (ENS)

The gut's brain or the "enteric nervous system" (ENS) is located in the sheaths of tissue lining the esophagus, stomach, small intestine and colon. Considered a single entity, it is a network of neurons, neurotransmitters and proteins. The gut contains 100 million neurons - more than the spinal cord.

Major neurotransmitters like serotonin, dopamine, glutamate, norephinephrine and nitric oxide are in the gut.

Victims of Alzheimer's and Parkinson's diseases suffer from constipation. The nerves in their gut are as sick as the nerve cells in their brains. 20

Many neurologists are turning their attention toward the ENS to better understand what is happening in the brain.

"In Parkinson’s disease, for example, the problems with movement and muscle control are caused by a loss of dopamine-producing cells in the brain. However, Heiko Braak at the University of Frankfurt, Germany, has found that the protein clumps that do the damage, called Lewy bodies, also show up in dopamine-producing neurons in the gut. In fact, judging by the distribution of Lewy bodies in people who died of Parkinson’s, Braak thinks it actually starts in the gut, as the result of an environmental trigger such as a virus, and then spreads to the brain via the vagus nerve.

Likewise, the characteristic plaques or tangles found in the brains of people with Alzheimer’s are present in neurons in their guts too. And people with autism are prone to gastrointestinal problems, which are thought to be caused by the same genetic mutation that affects neurons in the brain." 21

Approximately 50% of Dopamine is produced in the gut (Enteric Nervous System)

Considerable urinary excretion of dopamine metabolites indicates that large amounts of dopamine are produced in unknown locations of the body. This study assessed the contribution of mesenteric organs (gastrointestinal tract, spleen, and pancreas) to the total body production of dopamine in humans and examined the presence of the rate-limiting enzyme for dopamine synthesis, tyrosine hydroxylase, in gastrointestinal tissues. [...] The results show that mesenteric organs produce close to half of the dopamine formed in the body, most of which is unlikely to be derived from sympathetic nerves but may reflect production in a novel nonneuronal dopaminergic system. 22

A recent study examined the microflora of patients suffering from Parkinson’s disease.

It was observed that Parkinson’s patients have a different balance of bacteria in their guts, as compared to healthy controls. The most noticeable differences reported were that they appear to have much less intestinal bacteria from the Prevotellaceae family, and much more from the Enterobacteriacaea family. [...] Symptom severity seems to correspond directly with levels of Enterobacteriacaea. The higher the levels of this bacteria the more severe the Parkinson's symptoms. 23

Perhaps another area of attack may be to source pro-biotics that increase intestinal bacteria from the Prevotellaceae family, and investigate ways to reduce the Enterobacteriacaea.


Constipation: Early symptom or possible cause?

Is it possible that this bacterial imbalance is due to constipation increasing the duration of toxic waste products as they move through the gut?

In some cases, constipation may precede the onset of motor symptoms in Parkinson's patients. Data from the Honolulu-Asia Aging Study showed that men who reported less frequent bowel movements had an increased risk of Parkinson's disease during a 24-year follow-up period. 24

Other reports from the Honolulu study described an association between constipation and incidental Lewy body disease and a reduced neuronal density in the substantia nigra. 25

Although the data supported the biologic plausibility of constipation as an early non-motor manifestation of Parkinson's disease, the authors offered several alternative explanations:

  • Constipation and Parkinson's disease could be independent manifestations of an unknown risk factor
  • The association might reflect a genetic susceptibility
  • Constipation might have an indirect, but causal, role in Parkinson's disease, such as increased intestinal absorption of substances toxic to the substantia nigra 26.



20 The Enteric Nervous System: The Brain in the Gut
21 Emma Young, New Scientist
22 Substantial production of dopamine in the human gastrointestinal tract. Eisenhofer G1, Aneman A, Friberg P, Hooper D, Fåndriks L, Lonroth H, Hunyady B, Mezey E.
23 Helsinki University Central Hospital (HUCH) and University of Helsinki also related
24 Neurology 2001; 57: 456-62, J Neurol 2003; 250(suppl 3): III30-39.
25 Mov Disord 2007; 22: 1581-86, Mov Disord 2009; 24: 371-76.
26 Constipation May Be Early Clue to Parkinson's Disease




  1. Statins inhibit the production of CoQ10 which is required for mitochondria to make ATP.
    Mitochondrial dysfunction leads to:
    a) poor DNA synthesis and repair, protein misfolding and poor enzyme activation.
    b) increased free radical production and associated oxidative stress.
  2. Statins inhibit Glutathione production, already likely low in people with Parkinsonisms, further reducing the body's ability to prevent free radical damage to substantia nigra neurons (and elsewhere).
  3. Statins reduce cholesterol production which is essential for brain function (and other mammalian functions like moving).
  4. Statins cause muscle weakness, muscle pain and likely atrophy, making it hard to determine the root cause of motor symptoms.
  5. In addition ACE Inhibitors such a Ramipril (which Patient X takes) may also deplete CoQ10 as well as depleting magnesium (essential for all brain activity, smooth muscle contraction, skeletal muscle contraction - more Parkinson like symptoms).
  6. The gut produces 50% of Dopamine (and incidentally > 90% of Serotonin). Yet as far as I'm aware we are yet to investigate Patient X's gut health or diet.
  7. Constipation is certainly a symptom of poor gut health, it's common among people with Parkinson's and may be causal. Poor hydration will make constipation worse and increase the toxicity of the Enteric Nervous System.
  8. Parkinson's sufferers have insufficient bacteria from the Prevotellaceae family, and too much from the Enterobacteriacaea family. Again, it's unknown whether this is symptomatic or causal.


Possible Deficiencies

These inputs are either required for mitochondrial function or indicate dysfunction*:

  • Vitamin B complex (B2, B3, B6, B12)
  • Folic Acid
  • Coenzyme Q10  (currently supplementing)
  • Cortisol
  • Thyroid (T3)
  • Lactate* (high levels of Lactate might indicate the production of ATP outside the mitochondria)


Additionally, the following deficiencies could be tested for to rule out symptoms that may complicate the further diagnosis and monitoring of Patient X's "condition".

  • Glutathione
  • Serotonin
  • Prevotellaceae bacteria
  • Magnesium (not blood serum)
  • Zinc
  • Sulphur
  • Vitamin D
  • Vitamin K2
  • Hydration: Additionally Patient X drinks approximately 750 ml of water (all forms, tea, coffee, wine, juices etc) per day and has done for years and years - can we attempt to determine if he is chronically dehydrated?

Should deficiencies be identified we'd like to discuss the efficacy of a possible supplementation regimen to compliment his existing medication (an example follows below).

Many of Patient X's symptoms pre-Parkinsonism diagnosis could possibly have been due to a long list of deficiencies some self-induced (Vitamin D, hydration, lack of exercise and poor posture) and some medication induced (low Coenzyme Q10, Glutathione, magnesium?). The list of symptoms from deficiencies of just some of those listed above would possibly fill a medical textbook and could just as easily be called "mitochondrial disease". 27

"Despite the fact that mitochondrial diseases can be so variable and affect so many organ systems, a few symptoms are common to many of these disorders. These include muscle weakness, muscle cramps, extreme fatigue, gastrointestinal problems (constipation, acid reflux), droopy eyelids (ptosis), [...]  seizures, ataxia (loss of balance and coordination) and learning delays".



Possible Supplementation (for discussion)

Mitochondrial support / anti-oxidant supplements:

  • Glutathione (Parkinson's = likely deficiency -- intracellular Anti-Oxidant)
  • N Acetyl L Cysteine (a Glutathione precursor -- intracellular Anti-Oxidant)
  • CoEnzymeQ10 (Krebs Cycle Input -- Mitochondrial function / Anti-Oxidant)
  • Alpha Lipoic Acid (Krebs Cycle Input -- Mitochondrial function / Anti-Oxidant)
  • Vitamin B complex (Krebs Cycle Input -- Mitochondrial function)
  • L-Carnitine (Mitochondrial function / Anti-Oxidant)

Restore muscle damage:

  • D-Ribose  (Muscle rebuild -- undo Statin damage)

Additional supplementation / dietary inputs:

  • Water - to prevent ongoing and possibly chronic dehydration
    PD medications can raise the risk for dehydration. Many people with PD don’t realize how important water is for health. Dehydration can lead to confusion, weakness, balance problems, respiratory failure, kidney failure, and death. 28  
  • Vitamin D3 - Sunlight exposure produces Cholesterol Sulphate, given sufficient sulphur, thus reducing LDL production via the liver.
  • Vitamin K2 - Vitamin K2 stimulates 2 enzymes one in the bones and one in the blood vessels that work in tandem to usher calcium away from the arteries and over to the bone where the other enzyme makes sure the calcium stays in the bone
  • Zinc   (possible)
  • Magnesium   (likely) 29


27 Sharon Hesterlee - Mitochondrial disease in perspective: symptoms, diagnosis and hope for the future
28 Parkinson’s Disease: Nutrition Matters
29 Immune Health