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  Providing resources and ideas for therapies and medical developments for Parkinson's disease:

 

Parkinson's Disease: Vitamins, Supplements and Diet:

Parkinson's does not have a single cause or an exact symptom for all patients and thus there is no single approach to treatment. Options are presented below that can be used to tailor an individual treatment. One of the most common symptoms of Parkinson's disease is constipation. Luckily constipation is easily treatable with laxatives or by adding more fiber to one's diet. Some vitamins and supplements target mental cognition (vitamin B6, B12), some support liver detox (Calcium D-Glucarate and Glycine) and toxic heavy metal detox (NAC and Glycine). Some help combat vascular Parkinson's disease such as omega-3, niacin and aspirin. There are also vitamins and supplements which research has shown to support the battle with Parkinson's such as Nicotinamide riboside, vitamin D and Magnesium.

Probiotics and changing eating intervals to induce autophagy can also be helpful for Parkinson's patients. Research has also shown that a ketogenic diet is helpful for both Parkinson's and Alzheimer's disease for non-motor symptoms. There are strong ties between the protein NLRP3, inflammation, alpha-synuclein and Parkinson's. There are supplements and foods that have inhibitory effects on this NLRP3 pathway. Research has also found various vitamins and supplements to be beneficial for Parkinson's patients as noted below.

Certifications and Quality:

Producers of dietary vitamins and supplements are known to be of higher quality and consistency if manufactured to third party verified standards.

  • CGMP: Current Good Manufacturing Practice regulations are enforced by the FDA to assure proper design, monitoring, and control of manufacturing processes and facilities. This includes establishing strong quality management systems, obtaining appropriate quality raw materials, establishing robust operating procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories to insure pharmaceutical quality.
    FDA: Facts About the Current Good Manufacturing Practices
  • ConsumerLab.com: comparative study of supplements and nutritional products
    ConsumerLab.com
  • NSF International: certifying and testing. Performs audits of a company’s production sites to confirm they are following Good Manufacturing Practices (GMPs). Certification NSF/ANSI 173 for content and labeling.
    NSF.org
  • UL: quality assurance solutions, regulatory compliance testing, and global market access programs, to meet consumer and regulatory demands for high-quality dietary supplements.
    UL.com
  • U.S. Pharmacopedia: provides support to manufacturers to help ensure the quality of dietary supplements.
    USP.org
Pills - creative commons

Constipation Remedies:

Parkinson's disease (PD) is known to affect the muscles and nerves which control the digestive process thus impacting gastrointestinal mobility defined medically as "gastroparesis". Gastro-intestinal dysfunctions characterized by constipation affect almost 80% of PD patients (ref). If one has fewer than three bowel movements per week, one should consider a treatment for constipation. This is also true if the stool does not pass easily or is not moist and soft. There should be no discomfort, pain or blood associated with a bowel movement. Consider the following steps to relieve constipation:

  • Drink more water: Dehydration can make you constipated or make the stool hard and dry resulting is discomfort.
    Also see Mild dehydration: a risk factor of constipation?
  • Exercise more: While the evidence is mixed, it is thought that exercise moves the body and colon allowing for improved stool movement.
  • Consume more fiber: Fiber allows the stool to hold more moisture and improves the consistency of excrement. This includes oat bran, barley, nuts, seeds, beans, lentils, peas and fruits (especially prunes).
  • Fiber Suplements: allow one to retain more water in the stool and act as a natural laxitive. Meta Mucil shown here contains Psyllium husk in a gelatin capsule. Other fiber materials include polycarbophil and methylcellulose.
  • Laxitives: if none of the above are effective, see a doctor about stronger or prescription laxitives.
    • Chloride Channel Activators: induces the intestines to secrete fluid to help the flow of the stool.
    • Guanylate cyclase-C (GC-C) Agonists: also induce the intestines to secrete fluid to help the flow of the stool.
    • Lubricants: allow the stool to pass through the intestines more easily. Example: mineral oil.
    • Osmotic and Hyperosmotic Laxatives: balance the water concentration in the bowel through osmosis.
    • Stimulant laxatives: accelerates the speed at which the stool moves through the colon.
    • Stool softeners: allow the stool to absorb more fiber. eg Docusate Sodium (Col-Rite, Colace, Correctol, Diocto, Doc-Q-Lace, Docusoft, DSS, Silace, Surfak)

If these remedies do not help, see your doctor. If you are experiencing a high degree of pain or any blood in your stool, also see your doctor. Other much more serious ailments are possible causes.

Refereneces:
Metamucil

Vitamin B3:

There are so many forms associated with this vitamin it can get confusing fast. There are three forms: niacin, nicotinamide, and nicotinamide riboside. Vitamin B3 is most often associated with niacin and can be often found in multi-vitamins and enriched flour and derived products. Nicotinamide, sometimes known as niacinamide, has a different molecular structure than niacin and avoids the flushing associated with niacin. Nicotinamide riboside is a precursor to the NAD+ vitamin and NAD-deficiency is a key-event in the pathogenesis of Parkinson's Disease as it leads to mitochondrial dysfunction leading to impaired neuronal metabolism. NAD+ also helps combat oxidative stress.

Clinical Trails:
  • NCT03808961 (2020)
    Niacin for Parkinsons Disease (NAPS) study to examine the blood, urine and spinal fluid of persons with Parkinson's to look for evidence of inflammation and whether vitamin B3 (niacin or niacinamide) supplementation may reduce the inflammation and/or improve Parkinson's Disease motor and non-motor symptoms.
    Institution: VA Office of Research and Development
  • NCT03462680 completed (2020)
    Study to examine the blood, urine and spinal fluid of persons with Parkinson's to look for evidence of inflammation and whether vitamin B3 supplementation may reduce the inflammation and/or improve symptoms.
    Institution: VA Office of Research and Development
  • NCT03568968 (2020)
    Nicotinamide Riboside (1000 mg dose) Supplementation in Early Parkinson's Disease (NOPARK)
    Institution: Haukeland University Hospital
  • NCT03816020 (2020)
    NAD-supplementation (Nicotinamide Riboside 500 mg dose) in Drug naive Parkinson's Disease (NAD-PARK)
    Institution: Haukeland University Hospital

Nicotinamide Riboside

Niagen: Nicotinamide Riboside

Vitamin B12:

Vitamin B12 is required by the body for red blood cell production, DNA formation, nerve function, and metabolism. Vitamin B12 has also been shown to have correlation to dementia for both Parkinson's and Alzheimer's diseases. The results of a study concluded that one's vitamin B12 blood levels aught to be more than 587 ng/L (nanograms per Liter) for only an 11% chance of developing dementia. Those with less than 587 ng/L vitamin B12 level had a 50% chance of having dementia within 5 years of a Parkinson's diagnosis. This is especially important for those on levodopa treatment which has been associated with lower levels of vitamin B12.

Vitamin B12 (along with vitamin B6 and folic acid) has been shown to improve cognition, lower oxidative stress and lower homocysteine levels, a known inflammation marker linked to Parkinson's disease and other movement disorders. Also see Inflammation and Parkinson's: homocysteine

The adult recommended daily intake (RDI) for vitamin B12 is 2.4 mcg (micrograms). Absorbption is typically 10 mcg per 500 mcg of supplement.

Warning: not to be used without professional medical supervision by those who have Leber disease, megaloblastic anemia, polycythemia vera, an alergy to cobalt or cobalamin or by those who have recently received a coronary stent (WebMD)

Reference: Possible Link Found Between Vitamin B12 Levels and Dementia in Parkinson's

Foods with high levels of vitamin B12 include:
FoodServing Size% Recommended Daily Intake
Liver and kidneys (lamb, beef, veal)100 g3,000+ %
Clams100 g4,000 %
Sardines150 g500 %
Beef100 g245 %
Fortified cereal50 g50+ %
Trout100 g300 %
Salmon175 g200 %
Milk240 ml46 %
One Egg50 g25 %

Thus four, 50 gram eggs, would be required to achieve the Recommended Daily Intake of vitamin B12.

The recommended daily intake of vitamin B12 is at least 6 mcg. Measured levels of vitamin B12 in blood are healthy when in the range of 587 to 1245 pg/mL.

Vitamin D:

Vitamin D deficiency has been found to be linked to an increased risk for Parkinsons disease and is based on a Finish study. Vitamin D potently induces Glial-cell-line Derived Neurotrophic Factor (GDNF) expression where GDNF has been investigated as a treatment for Parkinson's disease as the GDNF protein has been shown to support the survival of dopaminergic neurons. It is believed that a chronic inadequacy of vitamin D leads to the loss of dopaminergic neurons in the substantia nigra region to further Parkinson’s disease progression. Vitamin D is typically produced by the skin when exposed to sunlight (UV-b) but can be supplemented especially when one spends a lot of time indoors. Adequate levels as measured in blood serum are considered to be in the range of 30 to 60 ng/ml (or 75-150 nmol/L). Typically a dose of 1000 IU of vitamin D will raise the blood serum level 5 ng/ml.

Vitamin D comes in two forms: D2 and D3, of which D3 is more effective at improving vitamin D levels in the body.
  • Vitamin D2 (ergocalciferol) typically plant sourced or found in fortified foods like fortified milk and fortified orange juice
  • Vitamin D3 (cholecalciferol) typically animal sourced: fish, liver, eggs and produced by your skin in sunlight (UV-b)

Warning: doses of over 4000 IU/day for the long term are not safe and may cause elevated calcium levels in the blood. Other effects of excessive use include weakness, fatigue, sleepiness, headache, loss of appetite, dry mouth, metallic taste, nausea and vomiting. Vitimin D can make atherosclerosis worse, can lead to kidney stones especially for those with kidney disease. (WebMD)

References:

Foods with high levels of vitamin D include:
FoodServing Size% Recommended Daily Intake
Salmon100 g84 %
Fortified milk16 oz32 %
Fortified yogurt100 g7 %
Pork chop100 g5 %
One Egglarge6 %

The recommended daily intake of vitamin D is 20 micrograms or 800 IU. Measured levels of vitamin D in blood are healthy when in the range of 30 to 100 ng/mL. The dosage to maintain a healthy blood level of vitamin D will depend on one's metabolism and size.

Multi-vitamin
Most daily multivitamins have an ample dose of vitamin A, B, C, D and D as well as essential minerals.

Calcium D-Glucarate:

The liver is the body's first line of defense against toxins. The liver filters and separates toxins from the blood stream and dumps it into the bile duct which feeds into the gastrointestinal (GI) tract for evacuation. Supplementation of calcium D-glucarate has been shown to help with liver detoxification properties attributed to its ability to excrete, through the biliary and urinary tracts, potentially toxic compounds. Calcium D-glucarate is also known to have anticarcinogenic properties as studied in various animal tumor models including colon, prostate, lung, liver, skin and breast cancer. This supplement is often taken with Glycine for maximum liver detox support. Calcium D-glucarate is a substance produced naturally in small amounts by mammals and is found in many fruits (eg oranges, apples, and grapefruit) and cruciferous vegetables (broccoli, cabbage, and Brussels sprouts). Calcium D-glucarate is also known to lower estrogen and estradiol hormone levels as well as LDL cholesterol in the blood.

This supplement may be of interest to those Parkinson's patients who belive that their's was induced by toxins and thus are in need of detoxification of their liver. The liver has three detox phases of which calcium D-glucarate plays an instrumental role in phase two.

Liver Detox Phases:
  1. enzymes (cytochrome P450s or CYPs) and oxygen convert fat soluble toxins into a water soluble and less toxic form to be eliminated.
  2. requires amino acids, minerals, vitamin C, bioflavonoids and B vitamins to process and clear toxins. Glutathione (GSH) transferase further processes toxins to be more water-soluble and less toxic to the body.
  3. transport phase. Byproducts of phase I and II reactions are transported out of the liver cells into the bile duct.

Also see toxins and Parkinson's.

References:

Glucuronidation:

Glucuronidation is the body's biological mechanism to process xenobiotic (foreign) substances (pesticides, idustrial compounds, pharmaceutical compounds, dyes, dioxins, etc) into water soluble moloecules for excretion from the body in bile or urine. Glucuronidation is also a primary pathway in the liver's phase 2 detoxification to make toxins hydrophobic (more water soluble) to enable their removal by the kidneys as urine or by the liver as bile through the gastrointestinal tract. Calcium D-Glucarate is a participant and enabler in the glucuronidation process. Calcium D-Glucarate, when ingested, is metabolised to D-glucaric acid (by HCL stomach acid), which can be further metabolised into D-glucaro-1,4-lactone or D-glucaro-6,3-lactone, all of which have important roles in detoxification. Calcium D-Glucarate also inhibits beta-glucuronidase, an enzyme which can disrupt phase 2 detoxification by allowing toxins to be released and reabsorbed rather than be excreted. Thus Calcium D-Glucarate helps the liver excrete toxins and inhibits reabsorbtion.

Also see:
Calcium D-Glucarate supplement

Precursors to Glutathione:

Glutathione (GSH) is the body's first line of defense against toxins and free radicals. GSH can be released by astrocytes, glial cells and by neurons themselves to help defend neurons and within neuron cells from oxidative stress and free radicals. Glutathione is produced within the cells and is used to expel toxins from within the cell. A glutathione oral supplement is not effective for mercury detoxification as it does not survive the digestion tract to be passed into your cells. Instead, supplements which are the precursor or raw ingredients that a cell can use to generate glutathione is preferred.

The three precursors to glutathione are:
  • N-Acetyl Cysteine (NAC) (amino acid Cysteine with an acetyl group attached to it) Can cross the blood-brain barrier. Not well absorbed oraly.
  • Glutamate (found in meat, eggs, dairy and soy sauce) also a neurotransmitter which can induce neuron excitotoxicity
  • Glycine (found in high protein foods such as meat and dairy products) also helps form water-soluble compounds which can be excreted more easily (conjugation reaction)

Details of Glutathione synthesis.

Glutathione is known to help the body handle neurotoxins which may be at the root cause of Parkinson's disease and other neurodegenerative conditions. Insufficient levels of glutathione are often found in Parkinson’s disease patients. Glutathione contains sulfur components that to bind mercury in a form that the body can dispose of via bile. When glutathione binds with toxic metals or compounds, it prevents them from binding to cellular proteins and causing damage to both enzymes and tissue. Glutathione also helps prevent mercury from entering cells and causing intracellular damage by binding into a glutathione-mercury complex.

Thomas Jefferson University is conducting a trial using intravenous and oral NAC for its potential to counteract intracellular damage that leads to dopaminergic neuron death and the potential to reduce oxidative damage in Parkinson's Patients. See trial NCT02445651.

Also see Environmental toxins and Parkinson's and Mercury and Parkinson's.

References: Counter arguments for chelation of mercury using glutathione include Dr. Andy Cutler who stated the following in reference to glutathione IV treatments:
"Many health practitioners incorrectly advise chlorella, cysteine, NAC and glutathione for chelation, which are not true chelators in the chemical sense, as they do not contain two or more binding groups (dithiol groups). Instead, they contain only one thiol group making them ineffectual chelators, with the capacity to simply move metals around, and cause more problems. These compounds can make matters worse by redistributing stored metals i.e. mobilizing them from their storage sites, but failing to bind and excrete them. This is like stirring up a hornets nest."

Reference: Oral Chelation for Mercury: The Andy Cutler protocol

Note that he prefers his own chelation protocol: ACC

Andy Cutler also states:
"If you have elevated cysteine and you want to convert some to glutathione, take a 2:1 weight ratio of glutamine and glycine (e.g. 2,500 mg caps of glutamine with one 500 mg capsule of glycine) and your body will do the rest."

These supplements can be taken on and off rounds, often twice a day suffices. It will be problematic if one is thiol sensitive and consuming thiols. The ACC protocol book, "The Mercury Detoxification Guide", has a section dedicated to thiol food sensitivity. This is the dose Andy stated, but everyone needs to find their own dose.

Glutathione is a thiol with one binder while chelators like DMSA, DMPS and ALA have two and are known as dithiols and cling to mercury more forcefully. Note that DMSA and DMPS act extracellularly (outside the cell) without the ability to pass through the cell membrane to grab mercury from within the cell but can work with glutathione as an intracellular (inside the cell) agent to procure intracellular toxins.

Glycine supplement NAC supplement

Magnesium:

A lack of magnesium can cause leg cramps, insomnia and fatigue and is also associated with Parkinson's disease. A study published in "Neuropsychiatric Disease and Treatment" found that the supplement Magnesium-L-Thorate elevates the magnesium level in the cerebrospinal fluid, attenuates motor deficits and dopamine neuron loss in a mouse model of Parkinson's disease. The type of magnesium supplement is also important as Magnesium sulfate failed to increase magnesium levels in the cerebrospinal fluid (CSF) and had no effect on neurodegeneration. The magnesium-L-threonate supplement also inhibited inducible nitric oxide synthase (iNOS)-mediated inflammation and oxidative stress.

Foods rich in magnesium include Almonds, avocados, bananas, lima beans, black beans, cashews, Edamame, kidney beans, pumpkin seeds, spinach, Swiss chard, yogurt and peanuts.

The recommended daily intake of magnesium is at least 432 mg. Measured levels of magnesium in blood are healthy when in the range of 1.5 to 2.5 mg/dL.

Warning: doses greater than 350 mg/day may lead to irregular heartbeat, low blood pressure, confusion, and may build up in the body causing coma and death (WebMD)

References:
Magnesium-L-threonate

Omega-3:

Study suggests that dietary intake exerts neuroprotective actions in an animal model of Parkinsonism. Omega-3 also potentially thwarts Arteriosclerosis and the potential for Arteriosclerotic Parkinsonism caused by micro-strokes. Omega-3 fatty acid, DHA, also has been found to reduce levodopa induced dyskinesia.

References:
Omega-3

Blood Testing for Vitamins and Minerals:

These services often require a doctor's order for a test.

Testing Requisitions:

These services provide a doctor's order for a test.

Ketogenic Diet:

The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet which forces the body to burn fats rather than carbohydrates and its glucose derivative. Normally brain function is fueled by consumption of glucose. During a ketogenic diet, fats are converted to keytones and replace glucose as an energy source for the brain. When the body enters this state, it is said to be in a state of ketosis. While of primary benefit for those wanting to lose weight or suffering from epilepsy, it has been found to be helpful in non-motor functions for people suffering from neurological disorders such as Alzheimer's, ALS and Parkinson's disease. A ketogenic diet may actually lead to an "intermittent exacerbation of the PD tremor and/or rigidity". Unfortunately the study was on a small sample size.

References:

Also see intermittent fasting and autophagy.

NLRP3 Inflammation Pathway Inhibitors:

NLRP3 is a component of macrophage immune cells (white blood cells which engulf and consume foreign substances) which react to stress and generate "inflammasome" which in turn contains a receptor protein (ASC) that encourages activities (autoinflammatory and autoimmune conditions) which lead to pyroptosis (cell death) and the flood of inflammation factors. Alpha-synuclein aggregates have been shown to promote inflammasome activation in brain microglia (brain immune macrophage cells, main form of immune defense in the central nervous system). Foods which inhibit this pathway, inhibit the progression of Parkinson's.

Also see:

Melatonin has been shown to be an important antioxidant and also an anti-inflammatory molecule which work against the activation of the inflammasomes and, in particular, of the NLRP3 inflammasome. While many of the current anti-inflammatory drugs have significant side effects, melatonin is an uncommonly safe molecule when taken as a supplement.

Warning: Melatonin can make depression, diabetes, blood pressure and seizure disorders worse. May also interfere with immunosuppressive therapies (WebMD)

References:

Foods which inhibit NLRP3:

Inhibition of NLRP3 is not only good for limiting the facilitation and instigation of Parkinson's disease progression but also that of Alzheimer's disease.

Melatonin
Melatonin: an NLRP3 inflamation inhibitor

Restore Gold:

This supplement contains vitamins and compounds claimed to have neuroprotective and restorative characteristics to help Parkinson's patients. They claim to acheive this by combating oxidative stress which causes mitochondrial dysfunction, support for mitophagy to supress Lewy body formation and free radical resistance to supress neural inflammation.

Restore Gold contains the following:
  • Acetyl-L-Carnitine (100 mg): brain energy management and mitochondrial function
  • Alpha Lipoic Acid (100 mg): contributes to xenobiotic detoxification and antioxidant protection
  • Grape Seed Extract (60 mg): alleviate neurodegeneration in Parkinson’s via enhancement of mitochondrial function and may inhibit toxic alpha-synuclein aggregation
  • Green Tea Extract (100 mg): neuroprotectant
  • L-Tyrosine (400 mg): increase dopamine turnover in patients
  • N-Acetyl-Cysteine (NAC) (400 mg): precursor in the cellular production of glutathione, the body's natural antioxidant and detoxification agent
  • Tauroursodeoxycholic acid (TUDCA) (300 mg): restore mitochondrial function

Note that this product contains a substantial dose of ALA, a known chelator of mercury. The Dr. Andy Cutler Chelation (ACC) protocol would consider it unwise to use this product if one has mercury amalgam dental fillings. If one experiences an uncomfortable brain fog or the effects of mercury toxcicity, it might be wise to chelate to lower the body burden of mercury prior to using this product. For more on mercury, chelation, dental amalgam removal and ALA see Parkinson's and mercury.

Also see:
Restore Gold

Restore Gold


Pros:
  • No negative side effects to adding fiber to one's diet unless one has a food sensitivity or allergy to the dietary changes. Some vitamins and supplements have been shown to be a positive treatment for Parkinson's especially if one is deficient.

Cons:
  • While fiber supplements are effective at relieving constipation and are assuredly an improvement of Parkinson's symptoms, they are not likely to effect the progression of Parkinson's. While shown to be healthy, the ketogenic diet is unlikely to have a profound effect on Parkinson's symptoms as it was only found to be helpful for non-motor symptoms and perhaps an "intermittent exacerbation of the PD tremor and/or rigidity" (ref).
Pro-con statements reference the content above.