In this unique and pictoral guide of the cell areas and pathways of damage in PD, you will better understand options for healing.
[See also the Testimonial (below the following guide) of the individual who completely reversed her Parkinson’s Disease with supplements addressing the underlying causes, as well as the tissue-targeted treatments employed by a Neurologist.]
Briefly, PD is a slowly progressive of neurodegenerative disorder of the production of the neurotransmitter dopamine. Dopamine is a chemical messenger that transmits signals between two regions of the brain. A deficiency in the dopamine in the Striatum leaves the person unable to control movements and develop symptoms of Parkinson’s.
Externally, one method of trying to control symptoms (but not treating the underlying causes):
Depending on the areas of damage, or symptoms, doctors can use something called “Deep Brain Stimulation” (DBS) to try to control symptoms. A good resource for DBS is www.mayfieldclinic.com–A group of doctors who specialize in this procedure. See PD: DBS
Our first clue, is that PD occurs from the death of Dopamine-secreting cells in the Substantia Nigra–The cells that are already some of the fastest dying brain cells during aging! Most researchers believe that one of the causes of this is that dopamine is highly reactive and can form a (potentially damaging) free radical itself!
Importantly, this is already an area PARTICULARY PRONE TO FREE RADICAL (INFLAMMATORY) DAMAGE or OXIDATIVE STRESS–It not only produces many free radicals, but also is poorly supplied with free radical defenses–So a vicious cycle of free radical damage occurs, hastening dopamine cell death.
Reference: Wang, X. & Michaelis, E. K. Selective neuronal vulnerability to oxidative stress in the brain. Frontiers in Aging Neuroscience 2, 12 (2010).
Since the free radical, vicious cycle of cell damage is now the cause receiving most of the research inquiry, let’s go over what you can do about this deterioration.
A. As a test of your degree of ongoing free radical damage, do a 20 minute Glutathione infusion: See Dr. Perlmutter, who is one of the first neurologist to use this as a major treatment option for PD patients. Generally, he will do an initial infusion, and then order a home health nurse to continue treatments as long as you improve. It would be great if we could just measure a level and supplement glutathione until we reach a “good” level, but see the complexities involved on my page http://www.newhealthoptions.org/?page_id=2117
1. If you are unable to do intravenous therapy, choose among the Glutathione supplements at http://www.newhealthoptions.org/?page_id=2117
B. Address the main areas of free radical excess in the mitochondria of PD: Complex I releases more free radicals, and we have potential beneficial natural supplements: Complex III releases fewer free radicals and we have no way to ameliorate these.
Complex I is the purple structure and Complex III is the yellow structure below in the Electron Transport Chain (ETC)–One of the centers of energy production in the mitochondria.
(Schapira et al., 1989, 1990)
1. Complex I dysfunction includes dysfunction of CoEnzyme Q10 (CoQ10) and NADH leading to the release of free radicals that create more vicious cycles of damage. You can see that iron (FeS) also has a role in handling free radicals.
2. Take CoEnzyme Q (CoQ10) in the ubiquinol form, 200 mg/day to improve CoQ10 function.
3. Try sublingual NADH, which supplies Complex I, and which is also found to be abnormal. Birkmayer described improvements of short-term memory and other cognitive functions in Parkinson’s patients treated with NADH.
4. Detoxify iron–See Appendix: Iron as a Contributing Factor in PD.
5. Detoxify pesticides, one of which, Rotenone, is a model for Complex 1 induced free radical damage and cell death.
6. Reduce the free radical vicious cycle caused by the creation of peroxynitrite ion ONOO-
C. Increase the inadequate free radical defenses in this brain area: Prevent further damage with supplements and lifestyle:
1. Green Tea, Curcumin, Resveratrol, Omega-3 Fatty Acids, Alpha Lipoic Acid, Vitamin C and E, Quercetin, and N-Acetyl-Cysteine
2. Acetyl-L-Carnitine or N-Acetyl-Carnitine
1.5 grams of Carnosine was given daily for 30 days in Parkinson’s patients treated with L-Dopa. The addition of carnosine to the treatment regimen significantly improved neurological symptoms, with a 36 percent improvement in symptoms compared to a 16 percent improvement in the control group. Clinical signs of Parkinson’s disease, including decreased bodily movements, and rigidity of extremities, were also significantly improved. This improvement in the “everyday activity” of Parkinson’s patients allows them more independence and better quality of life, leading the authors of the study to conclude that carnosine is a reasonable way of improving the treatment of Parkinson’s disease and decreasing the possible toxic effects of standard drug therapy.
4. Take supplements to try to stop the self-destructive signals in the cell in response to excessive oxidative stress.
a. Rutin and Quercetin and other flavonoids in fruits and vegetables (and available as supplements) reduce PARP-1 cell death signals.
b. Vitamin D: There is a dramatically decreased incidence of a degenerative disease like Parkinson’s (67% lower risk) in people with the highest level of vitamin D.
We now understand that vitamin D stimulates more than 900 genes in human physiology, most of which reside in the brain. These genes code for a variety of activities like reducing inflammation, strengthening nerve cells, and even helping the brain rid itself of viruses.
D. Test for genetic predispositions
a. Approximately 15 percent of people with Parkinson’s Disease have a family history of this disorder. Familial cases of PD can be caused by mutations in the LRRK2, PARK7, PINK1, PRKN, or SNCA gene, or by alterations in genes that have not been identified.
b. Other genetic tests can detect genes of detoxification, oxidative stress, and others–Which you can help . One such panel is a Methylation Cycle Panel to see if you have a genetic “SNP” that makes you prone to low glutathione levels or other oxidative stressors. See http://www.newhealthoptions.org/?page_id=2129
However, to switch gears, recent research suggests that there may be a prior cause that interferes with mitochondrial function and results in the free radical damage: A recent study with a mouse model of PD reported high Endoreticulum Stress (“ER Stress”–Where proteins are folded) as being the first cause, with the tethering of mitochondria (seen below) to the ER as the second cause, thereby preventing them from their mitophagy (or re-cycling), releasing free radicals, with the result that the cell–middle panel–dies.
ER Stress has been studied extensively for it’s relationship to oxidative stress, mitochondrial dysfunction and proteasomal dysfunction.
It’s damage results in the misfolding of proteins with the development of the most prominent microscopic change of PD –The “clumping” of alpha-synuclein protein aggregates in the cells.
So an important area to address is to decrease ER Stress and protein misfolding: Specifically, we want to stop the misfolding of alpha-snyuclein, as many researchers have been suggesting that this is one of the main causes of abnormal cell functioning in PD.
See the below recent exciting pre-clinical results of a study that prevented neurologic deterioration by inhibiting iron-mediated aggregation of proteins seen in PD– such as alpha-synuclein.
PBT434 (designed to inhibit oxidative stress and iron-mediated aggregation of Parkinson’s associated proteins like alpha synuclein.) prevented neuronal loss, motor function and cognitive impairment in preclinical models of movement disorders by modulation of intracellular iron’, was presented by Associate Professor David Finkelstein, of the Florey Institute of Neuroscience and Mental Health (Melbourne, Australia).
E. Decrease ER Stress and other causes of alpha-synuclein aggregation:
1. Caloric restriction reduces ER Stress
2. Detoxify “acrolein,” a cause of protein misfolding and protein aggregation
a. Use Carnosine to detoxify acrolein.
3. Reduce excessive “lipid peroxidation” which adds to ER Stress.
a. Decrease lipid peroxidation with Nrf2 stimulation.
c. Reduce ER Stress: Dispose the aggregated alpha-synucleins by stimulating autophagy–the cell’s garbage disposal systems–including chaperone-mediated autophagy (CMA) or macro-autophagy.
It has been proposed that dysfunction of these degradation pathways may be a contributing factor to Parkinson’s Disease.
d. Use Proteasome protectors to reduce ER Sress
α-synuclein can also be turned over by the proteasome (Webb et al. 2003), and proteasome impairments are linked to the formation of inclusions in neurodegenerative disorders, including PD.
1. Nrf2 stimulators
2. PARP stimulators, and
3. Oral antioxidants.
4. Finally, protect the proteasome by reducing the mitochondria complex I dysfunction.
Complex I dysfunction causes increased free radicals, with Oxidation of Acrolein (direct adduction to 20S Proteasome) and Proteins (binding of aggregated oxidized proteins to the catalytic site of Proteasome 20S) with resulting dysfunction. (Shamato-Nagai et al 2003)
e. Reduce ER Stress by stimulating “Heat Shock Proteins (HSPs) which act to provide proper protein folding and reduce aggregation by increasing HSPs– especially HSP90, but also HSP70 in PD.
1. Sauna to heat your core temperature raises HSP production
Hsp90 is an abundant molecular chaperone that prevents protein aggregation and increases Hsp expression. Although several studies suggest Hsp70 plays a mechanistic role in alpha-synucleinopathies, Hsp90 has been demonstrated to be the dominant HSP involved in regulating alpha-synucleinopathies.
Finally, and potentially most importantly, see the picture below to understand the importance of what your blood vessels present to your Dopamine-secreting cell, but also a supporting cell, the Glial cell.
This is an illustration of how nutrients flow from your blood vessels to the supporting “Glial” cells and the Dopamine cell. (labeled “Neuron”)
Depending on what you eat, if you exercise, and what you are exposed to, your glial cells may or may not produce GDNF, which is a growth factor that helps protect the dopamine cell. And of course any blood-borne nutrients, allergens directly affect whether “growth” or “cell death” signals enter glial and dopamine cells.
The most pronounced “cell death” and “cell growth” signals is the collection of “cytokines,” or immune signals that shower the cells as the immune cells migrate and cluster to the glial and dopamine cells as below:
“We and other investigators found increased levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6, and decreased levels of neurotrophins such as brain-derived neurotrophic factor (BDNF) in the nigrostriatal region of postmortem brains and/or in the ventricular or lumbar cerebrospinal fluid (CSF) from patients with sporadic PD. These changes in cytokine and neurotrophin levels may be initiated by activated microglia, which may then promote apoptotic cell death of dopamine neurons.”
Ultimately, microglial cells directly harm or benefit these vital dopamine-secreting cells, by producing cytokines or neurotrophins (Nerve Growth Factors) depending on the state of the inflammatory process of PD.”
So it is extremely important to target the ongoing inflammation in PD by identifying and removing possible toxicities, identifying food allergens, and identifying environmental allergens and treating as needed.
A. Protect the glial cell, and both stimulated it to produce GDNF, and reduce “microglial,” or “glial” activation–or inflammation.
2. Get your Vitamin D3 level and maximize it to increase glial cell GDNF. See “PD: GDNF” for the research efforts to increase GDNF’s protective actions on the dopamine cell.
Returning to identify what you might be exposed to from the capillary to the glial cell and dopamine cell, it includes:
A. Damaging inflammatory foods (allergies). As an example, for some people, gluten and/or casein are extremely inflammatory.
1. Get a food allergy panel, and practice an elimination diet or rotation diet and obtain antigens, as needed.
B. Natural environmental allergens such as molds, pollens, grasses and others.
1. Get an allergy panel and use preventative antigens, as needed.
C. Pesticides: With less than one percent of PD caused by genetics, researchers have been looking into many possible environmental contributors. The epidemiological and toxicological evidence is repeatedly identifying exposure to pesticides, as well as specific gene-pesticide interactions, as significant adverse risk factors that contribute to PD.
1. For protection, see my section on pesticides which is listed on the left panel.
D. Heavy metals: Reference:
Toxicology. 1995 Mar 31;97(1-3):3-9. Heavy metals and the etiology of Parkinson’s disease and other movement disorders. Montgomery EB Jr
Heavy metals, such as iron and manganese, are involved in neurologic disease. Most often these diseases are associated with abnormal environmental exposures or abnormal accumulations of heavy metals in the body. There is increasing recognition that heavy metals normally present in the body also may play a role in disease pathogenesis through free radical formation. When a part of the brain known as the basal ganglia is affected, movements become disordered. Parkinson’s disease is one of the most common movement disorders and is related to destruction of neurons in the substantia nigra pars compacta (SNpc) of the basal ganglia. The combination of high concentration of iron and the neurotransmitter, dopamine, may contribute to the selective vulnerability of the SNpc. Dopamine can auto-oxidize to produce free radicals particularly in the presence of iron and other heavy metals.
Many are unaware that heavy metals are absorbed, not only from water and food (fish has been the most publicized), but also through air. It is found on tiny bits of floating particulate matter–one of which is called PD50. Studies have demonstrated the presence of these in the air of big cities, heavily industrialized areas, inside and outside your car in congested traffic, and even in your indoor air.
1. Get an air filter–At least for your bedroom.
2. Filter your water.
3. Choose fish with the least mercury using easily accessible lists on search engines.
Before we go into the treatments for this vicious cycle, I will review the tentative position of dopamine itself in this problem with oxidative stress as dopamine itself can be destroyed by “auto-oxidation.”
Let’s understand the problem with dopamine in PD. In PD, it is the lowering of dopamine levels from damage to, and death of, dopamine cells which is why the first line of treatment from a neurologist is aimed at increasing the dopamine in your brain–either directly with “L-Dopa” (which allows the cells to make more dopamine) and a drug to help L-Dopa to cross into the brain, or indirectly with “Dopamine Agonists” (drugs that stimulate the cell’s production of dopamine in different ways).
In an exciting research trial by a company named Voyager, researchers used gene therapy to increase an enzyme (making dopamine) that normally drops during the deterioration of Parkinson’s Disease. Their trials are in the early phases, however, so it will be years before this could become available.
But as you can imagine, if the oxidation of dopamine is part of the problem, one must use great caution when increasing dopamine levels–It requires a careful balance between “healthy” and “unhealthy” levels of dopamine.
Too much dopamine can worsen oxidative stress both inside the cell and out in the synapse (the area where the cell dumps its dopamine.) In the picture below, I show the life-cycle of dopamine in and out of the “synapse,” or area between the dopamine cell and whatever cell it is communicating to:
A. First, the dopamine is manufactured and extruded into the synapse.
B. The dopamine (orange star-like structure) then moves across the synapse and attaches to a receptor on the next cell–signaling it.
C. The dopamine then disengages from that receptor and moves back across the synapse, and it attaches to a receptor that takes it back into the original cell to break it down.
If there is too much dopamine in this synapse, auto-oxidation can occur, damaging the structures in the synapse. In a different pathway, excess dopamine in the cell can undergo auto-oxidation as well–damaging cellular tissues.
Obviously, this teaches you that you need to communicate to your practitioner the drugs, supplements, or herbs that you are consuming that affect dopamine levels.
Next, the picture below shows the dopamine cell as it begins to be injured. The arrows point to the “branches” of the cell that are partially damaged: The fact that many cells are only partially damaged is great news–You may be able to rescue these partially damaged cells and regain their function.
1. Restore the brain’s protective antioxidants with intravenous, subcutaneous, and/or oral approaches. Dr. Perlmutter has been a pioneer of the use of intravenous glutathione, a powerful antioxidant, for his patients with Parkinson’s Disease and also has produced “Brain Sustain,” a nutritional product to support brain cell health. Maximize the blood’s free radical defences–For instance, increasing your Uric Acid to the high normal level. (Uric Acid has been reported to be able to neutralize up to 60% of blood free radicals,.)
2. Identify and reduce the excessive free radicals, or *inflammation.” Avoid circumstances that produce large number of free radicals in the body. Avoid unnecessary x-radiation and exposure to microwaves. If your doctor recommends a cat scan, make sure it is really necessary. And if you do have to have a cat scan, fluoroscopy or other intensive X-ray procedure, load up on antioxidants before and after the event. Absolutely do not smoke and avoid breathing second-hand smoke. Do not use tanning booths. Avoid exposure to heavy metals and toxic chemicals. Do not consume liquids that are in plastic bottles that have been frozen or overheated, such as water bottles baked in a car in the summer sun. Avoid situations likely to lead to infections. Wash your hands frequently; many infections are communicated by touch. Avoid unnecessary stress, be it physical, circumstantial or emotional. Too vigorous exercise can be harmful.
Learn how to avoid exposure to beta-carbolines and isoquinolones, from food as well as from Candida infections. Check for “silent” food allergies and allergies of any other kind. You can use Hydroxy-B12 to bind excessive superoxide free radicals. (Use after heavy meals.)
Reducing free radicals reduces NF-kappaB, and that allows your nerve cells to grow. Research has shown that the following promote neurogenesis: DHEA, pregnenalone, resveratrol, curcumin, Ginkgo bilboa and EPA fish oil
Consider a “ketogenic diet.”
Ketones are a special type can stimulate the pathways that enhance the growth of new neural networks in the brain. A ketogenic diet is one that is high in fats, and this diet has been a tool of researchers for years, used notably in a 2005 study on Parkinson’s patients which found an improvement in symptoms after just 28 days. The improvements were on par with those made possible via medication and brain surgery. Ketones do more than just that though. They increase glutathione, a powerful, brain-protective antioxidant, levels in the hippocampus. Ketones facilitate the production of mitochondria, one of the most important actors in the coordinated production that is the human body.of fat that
– See more at\\on YouTube video lectures on a ketogenic diet.
7. Use dietary patterns with the awareness of the cellular natural circadian rhythms to maximize lysosomal and macroautophagy disposal of alpha-synuclein.
8. Go over the risks and benefits of replacing dopamine to compensate for the decreased levels from the cell damage in the Substantia Nigra. A gentle way is to take the amino acid L-Tyrosine, the building block for dopamine. An extremely complex area is the use of L-Dopa for greater increases in cell dopamine. The “Life Extension” website has an extremely thorough review of considerations on taking L-Dopa for Parkinson’s Disease.
8. Consider the use of some of Annetta Freeman’s tools outlined below
Appendix: Endoplasmic Reticulum Stress: (ER Stress): Could it be a first step in causing PD?
How to reduce ER Stress
This includes reducing activation of the
1. JNK pathway
2. NFkB, and
3. Cytokine production.
And reducing acrolein levels. Reference: Toxicology and Applied Pharmacology Volume 234, Issue 1, 1 Jan 2009, Pages 14-24 Role of endoplasmic reticulum stress in acrolein-induced endothelial activation Petra Haberzettla, Elena Vladykovskayaa, Sanjay Srivastavaa and Aruni Bhatnag aInstitute of Molecular Cardiology U of Louisville
“Acrolein is a ubiquitous environmental pollutant and an endogenous product of lipid peroxidation. It is also generated during the metabolism of several drugs and amino acids…. Acrolein-induced increase in (changes of ER Stress) were prevented by treating the cells wth the chemical chaperone — phenylbutyric acid (PBA). Treatment with acrolein increased the JNK pathwauy, NF-κB nuclear trannlocation, and an increase in cytokine productioon. Increased JNK pathway, expression of cytokine genes and NF-κB activation were not observed in cells treated with PBA. These findings suggest that exposure to acrolein induces ER stress and triggers the unfolded protein response and that NF-κB activation and stimulation of cytokine production by acrolein could be attributed, in part, to ER stress. Chemical chaperones of protein-folding may be useful in treating (ER Stress) associated with excessive acrolein exposure or production.”
ER Stress study in mice suggests it is the first cause of PD Appendix: Iron as a cause of PD:
The neurodegeneration that occurs in Parkinson’s disease is a result of stress on the endoplasmic reticulum in the cell rather than failure of the mitochondria as previously thought, according to a study in fruit flies. It was found that the death of neurons associated with the disease was prevented when chemicals that block the effects of endoplasmic reticulum stress were used.
Some inherited forms of early-onset Parkinson’s disease have typically been blamed on poorly functioning mitochondria, the powerhouses of cells. Without reliable sources of energy, neurons wither and die. This may not be the complete picture of what is happening within cells affected by Parkinson’s. Researchers from the MRC Toxicology Unit at the University of Leicester used a common fruit fly to investigate this further; fruit flies were used because they provide a good genetic model for humans.
Studies on human subjects are of limited use for elucidating the signaling pathways and cellular processes underlying the neurodegenerative process. This is because both ethical and technical constraints limit the extent to which genetic analysis can be performed in humans.
Flies are a well-established model animal to understand the molecular mechanisms of human diseases. This is because about 75% of human disease-causing genes are found in the fly in a similar form. Also, they are easy to work with, breed quickly and many tools are available to manipulate any genes in the fly. In flies, potential therapeutic drugs can be mixed with food and readily tested.
It was found that the bulk of the damage to neurons with damaged mitochondria stems from a related but different source — the neighbouring maze-like endoplasmic reticulum (ER).
The ER has the important job of folding proteins so that they can do the vast majority of work within cells. Misfolded proteins are recognized by the cell as being dangerous. Cells halt protein production if there are too many of these harmful proteins present. While this system is protective, it also stalls the manufacture of vital proteins, and this eventually results in the death of neurons.
To find out if ER stress might be at play in Parkinson’s, a team led by Dr Miguel Martins analyzed fruit flies with mutant forms of the pink1 or parkin genes. Mutant forms of pink1 and parkin are already known to starve neurons from energy by preventing the disposal of defective mitochondria. These genes are also mutated in humans and result in hereditary versions of the disease. Much like Parkinson’s patients, flies with either mutation move more slowly and have weakened muscles. The insects struggle to fly and they lose dopaminergic neurons in their brains — a classic feature of Parkinson’s.
Compared to normal flies, Miguel’s team found that the mutants experienced large amounts of ER stress. The mutant flies did not manufacture proteins as quickly as the non-mutants. They also had elevated levels of the protein-folding molecule BiP, a telltale sign of stress.
One function of pink1 and parkin genes is to help degrade mitofusin — a protein that tethers the endoplasmic reticulum to mitochondria. Mutant flies have an abundance of this protein. It was found that the mutants had more of their mitochondria attached to the ER than normal flies. For this reason, the researchers suggest that ER stress is related to extra tethering of mitochondria, thereby preventing the removal of defective versions of the organelle.
Mutant flies, which have more of these tethers, have fewer dopaminergic neurons, which can have an adverse effect on the brain. By reducing the number of these tethers it is possible to prevent the loss of the neurons. When the researchers experimentally lowered the amount of mitofusin in the mutants, the number of tethers fell and the neuron number increased again. The flies’ muscles also remained healthy despite the mitochondria themselves still being defective.
These results suggest that the neurodegeneration seen in Parkinson’s is a result of ER stress rather than a general failure of the mitochondria. The scientists were able to prevent neurodegeneration in mutant flies not only by reducing mitofusin, but also with chemicals that block the effects of ER stress.
Dr Miguel Martins said: “This research challenges the current held belief the Parkinson’s disease is a result of malfunctioning mitochondria. By identifying and preventing ER stress in a model of the disease it was possible for us to prevent neurodegeneration. Lab experiments, like this, allow us to see what effect ER stress has on Parkinson’s disease. While the finding so far only applies to fruit flies, we believe further research could find that a similar intervention in people might help treat certain forms of Parkinson’s.”
Materials provided by University of Leicester. Note: Content may be edited for style and length.
- I Celardo, A C Costa, S Lehmann, C Jones, N Wood, N E Mencacci, G R Mallucci, S H Y Loh and L M Martins. Mitofusin-mediated ER stress triggers neurodegeneration in pink1/parkin models of Parkinson’s disease. Cell Death and Disease, June 2016 DOI: 10.1038/cddis.2016.173
Appendix: Iron as a Contributing Factor in PD.
Iron is a chemical element (symbol Fe). It has the atomic number 26 and by mass it is the most common element on Earth (it makes up much of Earth’s outer and inner core). It is absolutely essential for cellular life on this planet as it is involved with the interactions between proteins and enzymes, critical in the transport of oxygen, and required for the regulation of cell growth and differentiation.
So why then – as Rosalind asked in Shakespeare’s As You Like It – “can one desire too much of a good thing?”
Well, if you think back to high school chemistry class you may recall that there are these things called electrons. And if you have a really good memory, you will recall that the chemical hydrogen has one electron, while iron has 26 (hence the atomic number 26).
The electrons of iron and hydrogen. Source: Hypertonicblog
Iron has a really interesting property: it has the ability to either donate or take electrons. And this ability to mediate electron transfer is one of the reasons why iron is so important in the body.
Iron’s ability to donate and accept electrons means that when there is a lot of iron present it can inadvertently cause the production of free radicals. We have previously discussed free radicals (Click here for that post), but basically a free radical is an unstable molecule – unstable because they are missing electrons.
How free radicals and antioxidants work. Source: h2miraclewater
In an unstable format, free radicals bounce all over the place, reacting quickly with other molecules, trying to capture the much needed electron to re-gain stability. Free radicals will literally attack the nearest stable molecule, to steal an electron. This leads to the “attacked” molecule becoming a free radical itself, and thus a chain reaction is started. Inside a living cell this can cause terrible damage, ultimately killing the cell.
Antioxidants can help try and restore the balance, but in the case of iron overload iron doctors will prescribe chelator treatment to deal with the situation more efficiently. By soaking up excess iron, we can limit the amount of damage caused by the surplus of iron.
So what research has been done regarding iron content and the Parkinsonian brain?
Actually, quite a lot.
In 1968, Dr Kenneth Earle used an X-ray based technique to examine the amount of iron in the substantia nigra of people with Parkinson’s disease (Source). The substantial nigra is one of the regions in the brain most badly damaged by the condition – it is where most of the brain’s dopamine neurones resided.
The dark pigmented dopamine neurons in the substantia nigra are reduced in the Parkinson’s disease brain (right). Source:Memorangapp
Earle examined 11 samples and compared them to unknown number of control samples and his results were a little startling:
The concentration of iron in Parkinsonian samples was two times higher than that of the control samples.
Since that first study, approximately 30 investigations have been made into levels of iron in the Parkinsonian brain. Eleven of those studies have replicated the Earle study by looking at postmortem tissue. They have used different techniques and the results have varied somewhat:
- Sofic et al. (1988) 1.8x increase in iron levels
- Dexter et al. (1989) 1.3x increase in iron levels
- Uitti et al. (1989) 1.1x increase in iron levels
- Riederer et al 1989 1.3x increase in iron levels
- Griffiths and Crossman (1993) 2.0x increase in iron levels
- Mann et al. (1994) 1.6x increase in iron levels
- Loeffler et al. (1995) 0.9 (lower)
- Galazka-Friedman et al., 1996 1.0 (no difference)
- Wypijewska et al. (2010) 1.0 (no difference)
- Visanji et al, 2013 1.7x increase in iron levels
Overall, however, there does appear to be a trend in the direction of higher levels of iron in the Parkinsonian brains. A recent meta-analysis of all this data confirmed this assessment as well as noting an increase in the caudate putamen (the region of the brain where the dopamine neuron branches release their dopamine – Click here for that study).
Brain imaging of iron (using transcranial sonography and magnetic resonance imaging (MRI)) has also demonstrated a strong correlation between iron levels in the substantia nigra region and Parkinson’s disease severity/duration (Click hereand here to read more on this).
Thus, there appears to be an increase of iron in the regions most affected by Parkinson’s disease and this finding has lead researchers to ask whether reducing this increase in iron may help in the treatment of Parkinson’s disease.
How could iron overload be bad in Parkinson’s disease?
Well in addition to causing the production of free radicals, there are many possible ways in which iron accumulation could be aggravating cell loss in Parkinson’s disease.
Possible causes and consequences of iron overload in Parkinson’s disease. Source: Hindawi
High levels of iron can cause the oxidation of dopamine, which results in the production of hydrogen peroxide (H2O2 – a reactive oxygen species – the stuff that is used to bleach hair and is also used as a propellant in rocketry!). This reaction can cause further oxidative stress that can then lead to a range of consequences including protein misfolding, lipid peroxidation (which can cause the accumulation of the Parkinson’s associated protein alpha synuclein), mitochondrial dysfunction, and activation of immune cells in the brain.
And this is just a taster of the consequences.
Appendix: Medications for PD
There have been many remarkable changes in treatments for Parkinson’s disease in recent years. Scientists have developed new drugs, and they have a better understanding of how to use older treatments. That has made a big difference in everyday life for people with the disease.
Most people can get relief from their Parkinson’s symptoms with medicines. But some may need surgery if their medications stop working well enough.
The medicines you take early on have a strong impact on how your condition will unfold over time. So it’s important to work with a neurologist or other Parkinson’s specialist who can guide you through those treatment decisions.
Common Drugs for Parkinson’s Disease
Levodopa and carbidopa (Sinemet). Levodopa (also called L-dopa) is the most commonly prescribed medicine for Parkinson’s. It’s also the best at controlling the symptoms of the condition, particularly slow movements and stiff, rigid body parts.
Levodopa works when your brain cells change it into dopamine. That’s a chemical the brain uses to send signals that help you move your body. People with Parkinson’s don’t have enough dopamine in their brains to control their movements.
Sinemet is a mix of levodopa and another drug called carbidopa. Carbidopa makes the levodopa work better, so you can take less of it. That prevents many common side effects of levodopa, such as nausea, vomiting, and irregular heart rhythms.
Sinemet has the fewest short-term side effects, compared with other Parkinson’s medications. But it does raise your odds for some long-term problems, such as involuntary movements (dyskinesia’s).
Adamas Pharmacy is bringing to market it’s lead product GOCOVRI which is indicated for treatment of dyskinesia’s (involuntary and non-rhythmic movements that interfere with daily living) in patients with Parkinson’s disease receiving levodopa-based therapy. Neurocrine is also bringing Ongentys (opicapone) to market for dyskinesia’s and Teva Pharmaceutical’s offers AZILECT (rasagiline tablets) as monotherapy, adjunct to levodopa (LD) or adjunct to dopamine agonists (DAs) for either dyskinesia’s or as monotherapy.
People who take levodopa for 3-5 years may eventually have restlessness, confusion, or unusual movements within a few hours of taking the medicine. Changes in the amount or timing of your dose will usually prevent these side effects.
You can take one of these drugs on its own or along with Sinemet. Most doctors prescribe dopamine agonists first and then add levodopa if your symptoms still aren’t under control.
Dopamine agonists don’t have the same risks of long-term problems as levodopa therapy. So they are often the first choice of treatment for Parkinson’s disease.
It works by raising the amount of dopamine that your brain cells can use, which helps you have fewer Parkinson’s symptoms. Recent studies have found that Symmetrel may help ease the involuntary movements that can happen with levodopa therapy. But it may cause side effects, such as confusion and memory problems.
Trihexyphenidyl (Artane ) and benztropine ( Cogentin). These drugs restore the balance between two brain chemicals, dopamine and acetylcholine. That eases tremors and muscle stiffness in people with Parkinson’s. But these medications can harm memory and thinking, especially in older people. Because of that, doctors rarely prescribe them today.
Tolcapone and entacapone. When you take levodopa, a chemical in your body called COMT makes part of the drug useless. The drugs tolcapone (Tasmar) and entacapone (Comtan) block COMT, so the brain can use levodopa more effectively, which eases Parkinson’s symptoms.
Addendum 2: Testimonial supporting a non-medication routine that reversed Annetta Preeman’s PD
An Improved Parkinson’s Therapy
by Steven Wm. Fowkes
For years, we have been discussing the use of deprenyl in the treatment of Parkinson’s disease and the use of antioxidants for the treatment of free-radical pathologies and aging. Now, Annetta Freeman, a 58-year-old housewife from Beverly Hills, California has put the two together with phenomenal results. In 1992, she was almost completely disabled by Parkinson’s disease, today she is largely recovered. She says “When I walk into a room today, no one would guess that I had Parkinson’s disease.”
Annetta Freeman’s Personal Regimen for Parkinson’s Disease
Compare this regimen to her updated regimen three years later.
Liquid deprenyl citrate (1 mg/drop)
10 drops (3 morning, 2 noon, 3 early afternoon, 2 late afternoon)
DHEA (50 mg)
1 every other morning
Vitamin E (1000 IU)
1 each morning, noon and evening
Vitamin C (L-ascorbic acid powder)
approx. 1500 mg each morning and evening
Cell Guard (antioxidant enzyme)
5 tablets each morning for two weeks
3 tablets each morning thereafter
Vitamin A/D (25000 IU/1500 mg)
1 tablet each morning
Sun Chlorella A
5 tablets each morning, noon and evening
Coenzyme Q10 (30 mg)
1 each morning and evening
Viobin Prometabs (5 g octacosanol)
1 each morning and evening
L-Glutathione (50 mg)
1 each morning
Pycnogenol (50 mg)
4 each morning and evening
For My General Health:
GLA-125 (600 mg) [gamma linolenic acid]
1 each morning and evening
Ginkgo biloba (40 mg)
1 each morning and evening
MaxEPA (1000 mg omega-3 EPA) [eicosapentaenoic acid]
1 each morning and evening
1 each noon (don’t take if you take Sinemet!)
Potasium and Magnesium
1 each morning and evening
1 each morning
Maxi L-carnitine (500 mg)
1 each morning
Chromium picolinate (200 mg)
1 each morning
Cayenne Power Caps Hot
1 each morning and evening
(1 tbsp in 4 tbsp cottage cheese)
Melatonin (9 mg)
UPDATED REGIMEN 3 years later
Discovery-brand Liquid Deprenyl Citrate†
3 mg morning, 2 mg noon, 3 mg early afternoon, 2 mg late afternoon (adjust timing for smoothest effect, avoid taking with NADH).
50 mg (every other morning).
1000 IU (with breakfast, lunch and dinner).
Vitamin C (L-ascorbic acid)†
1500 mg in morning, same in evening (OK to take with or without food).
2 tbsp in morning (a barley green product, replaces Cell Guard).
Vitamins A and D†
25,000 IU A and 1500 mg D (with breakfast).
Sun Chlorella A†
5 tablets with breakfast, 5 with lunch and 5 with dinner (a broken-cell-wall green algae, not a blue-green algae product).
Four 30 mg caps, 2 with breakfast, 2 with dinner (mitochondrial energy enhancer).
Viobin Prometabs† (5 mg octacosanol)
One tablet with breakfast and dinner (a grain concentrate, special order from health food stores).
50 mg in the morning (an important cellular antioxidant).
Four 50 mg capsules in morning & evening (less expensive grape seed extract contains similar antioxidants).
Enada (NADH, coenzyme 1)†
Two 5 mg tablets first thing in the morning (some people take it before bed).
50 mg in morning, same in evening (mitochondrial enhancer, new to program, decreases morning stiffness).
One 500 mg tablet each morning (mitochondrial energy enhancer, new to program, replaces L-carnitine).
One with lunch (do not take if you take Sinemet!).
Once weekly (now with folic acid).
At least 8 glasses per day (take a full glass when taking supplements).
GLA-125 (gamma-linolenic acid)§
One with breakfast and dinner.
MaxEPA§ (1000 mg)
One capsule with breakfast & dinner (omega-3-rich cold-water fish oil).
One tbsp in 4 tbsp cottage cheese.
One tablet with breakfast.
Potassium and magnesium
One tablet each morning and evening (300 mg magnesium, 90 mg potassium).
200 mcg in morning (blood sugar stabilizer).
Cayenne Power Caps (Hot)
One each morning and evening.
Three 3 mg tablets before bed (dosage must be individually adjusted).
1 gram with one aspirin before bed (minimizes twitching and pain, reduces shaking the next morning and helps me sleep “like a baby” all night).
Gingko biloba (40 mg)
One tablet each morning and evening.
With meals, as needed (increases stomach acidity, aids digestion, improves nutrient absorption).
2-30 minutes after eating (Golden Health Products 217-696-2378).
1/3 to 1/2 glass with cranberry juice (takes more when eating allergenic foods).
Mild silver protein
1/4 tsp (a general prophylactic against illness).
Notes and Comments
† I consider these items most important for Parkinson’s, non-daggered items are for my general health.
‡ Steven Fowkes thinks that 100 mgs of each B vitamin is a faulty formulation (B-3 and B-5 doses need to be more; B-1, B-2 and B-6 can be much less). Because B-complex nutrients are water-soluble and have short half-lives, he suggests taking them in divided doses with each meal instead of once at lunch.
§ Polyunsaturated fatty acids can go rancid quite easily. Even the vegetable oils added to vitamin E pearls can rancidify easily. These products should be taste tested once a week to make sure they are still fresh. Rancidity produces a bitter and acrid taste/flavor in the back center of the tongue. It may also produce a gaging reflex.
Many of these medications try to lessen inflammation and oxidation of the cell, and instead provide antioxidants and other substances that might restore the health of the dopamine and glial cells.
Dr. Tipi Siddique from Northwestern University had written an article about a gene that he had discovered that was faulty in ALS and Parkinson patients. It was a gene that produces antioxidants.
Which did you try and which ones do you consider were most helpful?
I don’t think that there’s one product I can single out. The Pycnogenol has been a godsend and I cannot lower my dose, even today. Also, the Cell Guard must be considered a mainstay of the program.
I’ve had various doctors suggest that I try to eliminate one or more antioxidants and see the result. I’ve tried that and I did not do well. So I think the benefits I am getting are from the combination of the ones that I’m taking. I think the most important ones are vitamin C, vitamin E, the Cell Guard (which increases the SOD level in the body), the Pycnogenol (which magnifies the C and E), the glutathione (which everybody tells me can’t do a thing but it does), and a product that I never thought could help, Sun Chlorella.
How Can I Test For My Antioxidant Stress?
Measuring lipid peroxides could prove to be a very helpful marker in Parkinson’s. This is done with a sample of urine taken first thing in the morning. Unfortunately, there are several kinds of oxidative stress and insufficient clinical testing for each of these.
As you recall, inflammation from foods (allergies, imbalanced fats, oxidized cholesterol, etc), microbes in your body, chemicals, heavy metals and other sources produce Free Radicals: There are also dysfunctional–possibly injured or genetically impaired–parts of the mitochondria that may be addressed with treatments.
The relatively new awareness in the research community on the central role of free radicals in Parkinson’s Disease is obvious by the huge volume of recent research papers on this subject.
In PD, there may be other intracellular structures which release too many free radicals, damaging the inside of the cells. (Complex III releases too many free radicals and the increased NADH/NAD+ ratio causes the alpha KGDH enzyme to release too many free radicals.) Finally, the excessive free radicals may damage the mitochondrial DNA–activating calcium cascades that injure the cells.
Sophisticated Science for those interested…
A free radical is an atom which had an odd number of electrons in its outer ring so that one of the electrons is unpaired, unstable and “unhappy.” Below you can both see the “free radicals,” but also how they attack the cell and the cell membranes.
NADH plays a pivotal role in the function of complex I of the respiratory chain. Enzyme function of NADH ubiquinone reductase in the platelets of Parkinson’s disease patients is noted to be 30-60% lower than that of aged match controls. This activity increases following administration of NADH.
Birkmayer has demonstrated improvements of short-term memory and other cognitive functions in Parkinson’s patients treated with NADH. This report is not accepted by some, who doubt oral NADH can significantly increase the NADH needed in the injured cells of the brain. It is sold in sublingual form to bypass the digestive system to attempt to raise levels.
During excessive free radical production, it is important to lessen the energy crisis in the cell (dysfunctional mitochondria’s) to help save the dopamine cells so you can function better. NADH, Niacinamide and others may be able to help with the energy crisis. See my tab on the homepage on increasing mitochondrial function and cell energy.
The other free radicals sources include NAD(P)H and the cytochrome activity during the night and:
1) Inhibition of Complex I via DHBT-1 from the cell breaking down “used” dopamine.
2) Dopamine breakdown product: 5-S-CyS-DA to DHBT-1: DHBT-1 inhibits Complex I, (but not Complex II) and aKGDH Complex
Oxidative metabolites of 5-S-cysteinyldopamine inhibit the α-ketoglutarate dehydrogenase complex : possible relevance to the pathogenesis of Parkinson’s disease Journal of neural transmission SHEN X.-M. et al. 2000, vol. 107, no8-9, pp. 959-978 Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, A characteristic change in the substantia nigra of Parkinson’s disease patients is an apparent accelerated rate of dopamine oxidation as evidenced by an increased 5-S-cysteinyldopamine (5-S-CyS-DA) to dopamine ratio. However, 5-S-CyS-DA is more easily oxidized than dopamine to give 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (DHBT-1). Previous studies have demonstrated that DHBT-1 can accumulate by intact rat brain mitochondria and inhibits complex I but not complex II respiration.
In this study, it is shown that DHBT-1 also inhibits the α-ketoglutarate dehydrogenase complex (a-KGDH) but not cytochrome c oxidase (complex IV). The inhibition of α-KGDH is dependent on the oxidation of DHBT-1, catalyzed by an unknown constituent of the inner mitochondrial membrane, to an electrophilic o-quinone imine that covalently modifies active site sulfhydryl residues. The latter conclusion is based on the ability of ≥ equimolar glutathione to block the inhibition of α-KGDH by DHBT-1, without altering its rate of mitochondrial membrane-catalyzed oxidation, by scavenging the electrophilic o-quinone intermediate forming glutathionyl conjugates which have been isolated and spectroscopically characterized. Activities of mitochondrial α-KGDH and complex I, but not other respiratory complexes, are decreased in the Parkinsonian Substantia Nigra.
Such changes together with evidence for accelerated dopamine oxidation, increased formation of 5-S-CyS-DA and the ease of oxidation of this conjugate to DHBT-1 which inhibits α-KGDH and complex I, without affecting other respiratory enzyme complexes, suggests that the latter putative metabolite might be an endotoxin that contributes to the α-KGDH and complex I defects in Parkinson’s disease.
3) Chemicals (which can be related to certain foods and Candidiasis) such as Isoquinolones (IQs) and Beta Carbolines are neurotoxins which have been found in the brain of PD (Nagatsu, 1997)
Catecholamines (DA, NE, E) are converted by MAO, and the aldehydes may undergo a Pictet-Spengler type of condensation to yield 1,2,3,4-tetrahydroisolquinolines (TIQs), such as tetrahydropapaveroline (norlaudanosoline) [Davis and Walsh, 1970; Cohen and Collins, 1970; Zarrang and Ordonez, 1981] TIQs are present in cheese, banana, broiled sardine and beef, flour, yolk and white of egg, milk, beer and whiskey.
Here is a picture of how free radicals (red) disrupt the brain cell membranes–“kinking” them:
Hydroxyl radicals (OH•) damage membrane lipids and proteins by removing H atoms from the lipid chains and from protein sulfhydryl groups (SH). The structure of both lipids and proteins is disturbed.
Some neurons in the brain are more susceptible to oxidative damage than others. Those neurons that contain dopamine and other oxidizable neurotransmitters, such as serotonin, are quite vulnerable.
Oxidative damage (caused by any means) in different parts of the brain can produce different neurological effects. For example, dopamine neurons are found in pathways that control voluntary movement. Oxidative damage to dopamine neurons in these pathways can cause movement problems. Similarly, movement disorders are associated with Parkinson’s disease, in which dopamine neurons degenerate within an area of the brain called the basal ganglia. The basal ganglia are important in maintaining voluntary movement; degeneration within these structures results in tremors and tics.
Older vs Newer Treatments: “Shotgun approach” versus the Tissue-Targeted Approach ANTIOXIDANTS
Free radicals are the result of oxidative damage or oxidative stress, and are believed to play a leading role in certain diseases and age-related changes. Although the body also produces antioxidants, over time, production declines. Free radical destruction is thought to be a contributing factor to the decline in memory and motor performance seen in aging.
Brain cells are at particular risk of being damaged by free radicals because the brain has a high oxygen turnover, and CNS neuronal membranes are rich in polyunsaturated fatty acids, which are potential targets for lipid peroxidation. (Endocrinology, 1997 Vol 138, No. 1 p101-106) In addition, the brain is relatively deficient in antioxidants.
Free radicals and oxidative stress-induced neuronal cell death have been implicated in various neurological disorders, such as Parkinson’’ disease and Alzheimer’s Disease.
The well documented fact that one major change in the CNS that is associated with aging is free radical-induced oxidative damage.
Ames BN 1993 Oxidants, antioxidants, and the degenerative diseases of aging. (Proc Natl Acad ) 90:7915-7922
Vegetables are key sources of antioxidants.
(The Journal of Neuroscience October 1998;18.)
A diet rich in vegetables may help prevent age-related mental decline. Investigator’s results show that vegetables, particularly spinach, may be beneficial in retarding age-related central nervous system and cognitive behavioral deficits
Supplements that work as antioxidants.
(Int J Biochem Cell Biol 2001 May;33(5):475-82)
Vitamin E, beta-carotene and N-acetylcysteine protect the brain from oxidative stress induced by lipopolysaccharide (LPS, endotoxin). Administration of the aforementioned antioxidants prior to LPS injection ameliorated the oxidative stress by reducing levels of MDA, restoring GSH content and normalizing the mitochondrial/cytosolic hexokinase ratio in the brain in addition to lowering levels of plasma corticosterone and glucose
Dr. Perlmutter’s Supplements
Vitamin E Of the various types of chemicals found within the body, fat is the most susceptible to being damaged by free radicals. This explains why the brain, having such a high content of fat, is at such an increased risk for free radical damage. Vitamin E is a “fat soluble” antioxidant meaning that its protective effect is most realized in tissues with a high fat content–like the brain. This explains why vitamin E has been so extensively studied in such brain disorders as Parkinson’s disease and Alzheimer’s disease. It is vitamin E’s profound ability to limit the damaging action of free radicals in the brain that likely explains why it outperformed a so called “Alzheimer’s drug” in a clinical trial of Alzheimer’s patients in a 1997 report in the New England Journal of Medicine.1 Indeed, diets rich in natural sources of vitamin E are associated with a reduction in the risk of Parkinson’s disease by an incredible 61%.2 In individuals already given the diagnosis, the progression of Parkinson’s disease has been dramatically slowed with vitamin E and C supplementation.3
Gingko biloba Like vitamin E, Gingko biloba, has potent antioxidant activity. It also directly improves brain metabolism and increases brain blood flow. Gingko biloba is clearly one of the most extensively studied nutritional supplements, especially in neurodegenerative conditions. In a placebo-controlled, double-blind randomized trial published in the Journal of the American Medical Association, not only did Gingko biloba stabilize Alzheimer’s disease, but in many of the subjects there was an actual improvement noted in various standardized psychological tests.4
Coenzyme Q-10 Coenzyme Q-10 plays an important role in the critical process of cellular energy and is found in every living cell of every living being. In addition, it serves an important role as a brain antioxidant. When administered orally it is readily absorbed and measurably increases the efficiency of cellular energy production as demonstrated in studies performed at the Massachusetts General Hospital.5 This explains why Coenzyme Q-10 is being vigorously evaluated at major institutions around the world as a therapeutic aid in brain disorders. Interestingly, Parkinson’s disease patients demonstrate dramatically lowered levels Coenzyme Q-10 which may in part explain why these patients experience higher levels of brain damaging free radical activity.6
Alpha Lipoic Acid This powerful antioxidant is the subject of intensive worldwide study in neurodegenerative diseases because of its powerful antioxidant activity as well as its ability to regenerate other important brain antioxidants including vitamins E, C, and glutathione. Unlike other antioxidants, alpha lipoic acid is both fat soluble and water soluble. This greatly enhances its ability to be absorbed from the gut and permits increased penetration into the brain.7
N-Acetyl-L-Cysteine (NAC) While glutathione represents one of the most important of the brain’s antioxidant’s defenses, it is generally considered useless when given orally. NAC is readily absorbed from the gut and dramatically increases the body’s production of brain protecting glutathione. The ability of NAC to increase brain glutathione is enhanced in the presence of adequate amounts of vitamin C and E. In addition to enhancing glutathione production, NAC itself is a potent antioxidant and has been demonstrated to reduce the formation of the free radical nitric oxide which has been implicated as having a causative role in Parkinson’s disease, Alzheimer’s disease, and several other neurodegenerative disorders.8
Acetyl-L-Carnitine Damaged brain neurons are characterized by a decreased ability to produce energy. Like coenzyme Q-10, acetyl-L-carnitine enhances neuronal energy production by functioning as a shuttle–transporting fuel sources into mitochondria, the energy producing machinery of the neuron. It also assists in removing toxic by products of brain metabolism and acts as a potent antioxidant. Acetyl-L-carnitine has been demonstrated to protect laboratory animals from developing full-blown parkinsonism when exposed to specific chemicals know to induce the disease.9 It has been extensively studied in Alzheimer’s disease and, as reported in a recent issue of the journal Neurology, acetyl-L-carnitine can profoundly reduce the rate of progression of Alzheimer’s disease in younger patients.10
Phosphatidylserine Research carried out at Stanford University evaluating 149 patients suffering from dementia demonstrated that orally administered phosphatidylserine produced a marked improvement on performance tests related to memory and learning in demented patients.11 Like acetyl-L-carnitine and coenzyme Q-10, phosphatidylserine plays an important role in maintaining the ability of brain neurons to produce energy. Phosphatidylserine is a fundamental component of the fatty membranes surrounding the mitochondria where energy production occurs. In addition, it also serves as a critical component of the membrane surrounding neurons and thus plays a fundamental role in the process by which brain cells both receive and transmit chemical messages.
Vitamin D Deficiencies of vitamin D have been found in Parkinson’s disease, multiple sclerosis, and Alzheimer’s disease. It is only in the past several years that vitamin D has been recognized as having far more important role in human health than simply aiding bone formation. Vitamin D is now recognized as a potent fat-soluble antioxidant. Several studies have indicated that vitamin D’s ability to quench free radicals is even more powerful than vitamin E.12
Vitamin B12 (Cyanocobalamin) Deficiency of vitamin B12 has been associated with mental slowness, confusion, depression, memory difficulties, abnormalities of nerve function, Alzheimer’s disease, and multiple sclerosis. Not only is vitamin B12 critical for the maintenance of myelin, the protective insulating coat surrounding each neuron, but it also helps reduce the level of a particular amino acid, homocysteine, which has been associated with increased risk for Alzheimer’s disease, stroke, and myocardial infarction.
Magnesium This important mineral is critical in a program designed to preserve and enhance brain function for several important reasons. First, adequate amounts of magnesium are necessary for the electrical depolarization of the neuronal membrane. This is the process by which chemical messages are transmitted from one neuron to the next. Next, magnesium enhances the function of various brain antioxidants thus helping to protect the brain against free radical damage. Finally, magnesium helps to prevent the production of specific chemicals within the body which increase inflammation. In Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, inflammation represents a fundamental mechanism enhancing the formation of brain damaging free radicals.
Folic Acid A large number of studies have confirmed a direct relationship between folic acid status and various neurological problems including dementia, memory loss, and even depression. Like vitamin B12, the importance of folic acid in preserving normal brain function likely stems from its role in reducing homocysteine. Homocysteine is a toxic amino acid, elevation of which is associated with more rapid deterioration in some forms of dementia as well as a dramatic increase in stroke risk.
Pyridoxine Pyridoxine is a B vitamin critical for maintenance of adequate cellular metabolism. Its role in preserving brain function has been demonstrated in several studies showing a direct relationship between low levels of pyridoxine and severity of dementia. Like folic acid and B12, pyridoxine helps reduce homocysteine.
Niacin (as niacinamide) Like pyridoxine, niacin is a B vitamin and a key cofactor in the fundamental process of brain cell energy production. Deficiencies of niacin can profoundly affect brain cell metabolism resulting in dementia.