Gut Bacterial Tyrosine Decarboxylases Restrict Levels Of Levodopa In The Treatment Of Parkinsons Disease
Interestingly, the paper highlights a phenomenon in which bacteria in our small intestines may produce, as by-products of their life cycles, very similar chemicals as those involved in the innate bio-chemical production of neurotransmitters. In particular, the researchers discovered how specific types of bacteria in the gut create chemicals called Tyrosine Decarboxylases . TD is actually the enzyme which catalyses the conversion of Tyrosine in to Tyramine, but it can also catalyses the conversion of L-Dopa into Dopamine.
The outcome of this is that the high levels of these bacteria in the gut, found in people with PD who rely on L-Dopa supplementation, can cause significant amounts of the L-Dopa to be converted directly to Dopamine in the small intestine, before it is absorbed into the blood stream and can get across the blood-brain-barrier. This results in not enough of the L-Dopa reaching the brain, requiring ever increasing dosages.
Another issue with excessive TD in the gut is then that Tyrosine will also be effectively converted to Tyramine more competitively with the conversion of Tyrsosine to naturally produced L-Dopa. This could be another way that the Tyrosine pathway to Dopamine is effectively cut off, and another reason why Tyrosine supplementation doesn’t appear to provide the same benefits as L-Dopa for some people with PD, because then the Tyrosine is preferentially feeding the production of Tyramine rather than that of L-Dopa.
Clinical Aspects Of Dopaminergic Therapy
The clinical benefit of levodopa has not been doubted since its description and is still the most effective symptomatic drug for PD . Current therapeutic approaches rely upon levodopa and dopamine agonists. Levodopa, the precursor of dopamine moves across the BBB and combines with the peripherally-acting decarboxylase inhibitors such as benserazid and carbidopa to ensure its bioavailability in the CNS and thereby its clinical effectiveness in patients . However, it does not relieve other disabling symptoms of PD possibly derived from alterations in other neurotransmitter systems, such as cholinergic, noradrenergic, and serotonergic systems . Furthermore, several classifications of PD subtypes were created with the need of an individual and/or combined strategy to pharmacotherapy during the course of the disease.
What Are The Most Common Medicines Used To Treat Pd
Sinemet®
Levodopa is the most commonly prescribed and most effective medicine for controlling the symptoms of PD, particularly bradykinesia and rigidity.
Levodopa is a chemical found naturally in our brains. When given as a medicine, it is transported to the nerve cells in the brain that produce dopamine. It is then converted into dopamine for the nerve cells to use as a neurotransmitter.
Sinemet is made up of levodopa and another drug called carbidopa. Levodopa enters the brain and is converted to dopamine while carbidopa prevents or lessens many of the side effects of levodopa, such as nausea, vomiting, and occasional heart rhythm disturbances. It is generally recommended that patients take Sinemet on an empty stomach, at least ½ hour before or one hour after meals.
There are two forms of Sinemet: controlled-release or immediate-release Sinemet. Controlled-release Sinemet and immediate-release Sinemet are equally effective in treating the symptoms of PD, but some people prefer the controlled release version. Ask your doctor which approach is best for you.
Dopamine agonists
Dopamine agonists are medicines that activate the dopamine receptor. They mimic or copy the function of dopamine in the brain.
Parlodel®, Requip®, and Mirapex® are all dopamine agonists. These medicines might be taken alone or in combination with Sinemet. Generally, dopamine agonists are prescribed first and levodopa is added if the patients symptoms cannot be controlled sufficiently.
Symmetrel®
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What Is Amino Acid Therapy For Parkinsons
As discussed earlier, many of the most prominent, motor function-related symptoms of Parkinson’s disease can be traced back to insufficient levels of a neurotransmitter called dopamine. However, other symptoms such as sleep issues, mood changes, and more, are not linked to dopamine levels. According to an article published in the European Journal of Neurology, those symptoms stem from the influence of “complex, interconnected neuronal systems regulated by a number of different neurotransmitters.” The authors go on to state that developing treatments that optimize levels of several neurotransmitters “could prove invaluable for the treatment of the disease.”
A study published in the journal PLOS One in January of 2018 evaluated the relationship between concentrations of various amino acids in the blood and the progression of Parkinson’s disease. The authors explained that amino acids are crucial to the central nervous system, serving as neurotransmitters, neuromodulators, and regulators of energy metabolism. Changes in blood concentrations of amino acids in Parkinson’s patients have been linked to the amount of damage to the nervous system. The researchers discovered significant differences in concentrations of four amino acids: alanine, arginine, phenylalanine, and threonine. This specific amino acid profile could serve as a biochemical marker of Parkinson’s progression, they concluded.
Up to 25% off Amino
Role Of Diet And Nutritional Supplements In Parkinsons Disease Progression
However, my experience and research points to a long term solution: seek to decrease the disruptive effect on digestion and the Enteric Nervous System due to over-activation of the Dorsal Vagus Nerve, by regulating and calming the Nervous System, and increase Ventral Vagal and Parasympathetic Nervous System tone. This includes learning to how relax, reconnecting body and mind and establishing healthy sleep cycles. The many other articles on this website document the practical steps I have been undertaking towards this goal. Interestingly, I am currently experiencing a phase in which the effectiveness of my L-Dopa supplementation is becoming more effective again, such that it is much more likely that a dose will actually switch my movement back on, with significantly more on time, and less severe side-effects, such as Dyskinesia, overall.
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How Should I Take L
When considering the use of herbal supplements, seek the advice of your doctor. You may also consider consulting a practitioner who is trained in the use of herbal/health supplements.
If you choose to use L-Tyrosine, use it as directed on the package or as directed by your doctor, pharmacist, or other healthcare provider. Do not use more of this product than is recommended on the label.
Your dose of L-Tyrosine will depend on the amount of protein you consume in your diet. Follow your doctors dosing instructions very carefully.
L-Tyrosine is only part of a complete program of treatment that may also include a special diet. Follow the diet plan created for you by your doctor or nutrition counselor. Get familiar with the list of foods you must eat or avoid to help control your condition.
Store at room temperature away from moisture and heat.
The Dorsal Vagus Nerve And Parkinsons Disease
a number of otherwise vital biochemical reactions in our brains and bodies can go awry. We may stop producing healthy levels of particular enzymes, peptides, hormones and neurotransmitters, or make too much of these, or else stop being able to remove toxic by-products, that are necessarily created as part of the chemical steps in the creation and degradation of these substances, fast enough.
For example, our bodies may become depleted of specific chemicals called co-factors, required for proper functioning of detoxification biochemistry, lacking now perhaps due to long years of overburden exposure to ingested or internally created personal poisons. We have already explored an example of this which arises as part of Dopamine biochemistry, whereby the metabolic steps in the breakdown of this neurotransmitter creates a toxic aldehyde called DOPAL.
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Tyrosine Increases Mental Performance
Students and professionals are often subjected to a mental performance requirement. It is in this context that tyrosine offers an interesting alternative to caffeine, but also and especially to chemical stimulants, which are not always healthy. L-Tyrosine, on the other hand, presents an entirely natural solution.
Dr. Lorenza Colzato of the Dutch University of Leiden and her team discovered that tyrosine can increase brain performance by promoting the production of dopamine with 32 subjects consuming orange juice with tyrosine added, and then in a later phase, pure orange juice.
Mental performance was significantly increased when tyrosine was administered.
Treatment With Efswt And Efstdc Bacteria
Rats were treated orally with 200mg/kg body weight Rifaximin for five consecutive days as previously shown. Subsequently, the rats were treated orally with 10101011 CFU wild type or tdc E. faecalis v583 cells for five other consecutive days. One day following the bacterial treatment, the rats were orally supplied with levodopa/carbidopa mixture as described above.
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Niacin Is A Protector With Metal Binding Properties
Vitamin B3, or niacin, also known as nicotinic acid, may alleviate certain types of early-onset PD symptoms . Niacin has been shown to attenuate neuroinflammation through an action on niacin receptor 1 , also known as GPR109A and may have a therapeutic potential toward PD . Although moderate amounts of niacin are found in a number of foods, including chicken, turkey, beef, peanut and mushrooms, the vitamin can be supplemented in therapeutic doses as tablets. In MPTP exposed rodents, the administration of nicotinamide gave a dose-dependent saving of striatal DA levels and SN neurons . Niacin, which is a precursor for nicotinamide adenine dinucleotide needed for DA production, may serve several purposes, i.e., reduce inflammation through NIARC1-related mechanisms, increase DA synthesis in the striatum through NADPH supply and increase NAD/NADH ratio to restore complex 1 functions in mitochondria. Niacin can also bind transition metal ions including Fe into stable complexes .
Neuronal Death Of Dopaminergic Neurons
Neuronal cell death is a phenomenon accompanying age. Adult neuronal cells do not divide anymore and are thus exposed for life to the milieu inside the brain, which will change over time. In case of TH-positive neurons, remarkable length of axons bridges the cell bodies in the substantia nigra to the target regions in caudate and putamen. Causes of death thus may even be mechanic stress during osmotic changes or shrinkage in the brain. Dopaminergic neurons as well depend on their oxygen supply. A considerable part of PD cases according to Udagedara et al. is considered to be caused by cerebrovascular changes. A wide body of studies claimed environmental toxins such as herbicides, pesticides and natural toxins to be potentially responsible for neuronal cell death .
Studies on a drug related to heroin, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , have gained wide attention. MPTP is a neurotoxin, which causes symptoms of PD in humans and animals. Metabolized by monoamine oxidase the product 1-Methyl-4-phenylpyridinium inhibits the mitochondrial respiratory chain and destroys dopaminergic cells in the substantia nigra .
Excitotoxic death by glutamate is as well discussed for midbrain dopaminergic neurons. Timely clearance of glutamate from synaptic clefts is necessary to prevent high levels of extracellular glutamate resulting in excitotoxicity and neuroinflammation .
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Levodopa In The Treatment Of Parkinsons Disease: Current Status And New Developments
Article type: Review Article
Authors: Salat, David | Tolosa, Eduardo
Affiliations: Universitat Autònoma de Barcelona, Barcelona, Spain | Parkinsons Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic, University of Barcelona Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas Barcelona, Spain
Note: Correspondence to: Eduardo Tolosa MD, FRCP, Neurology Service, Hospital Clinic, University of Barcelona, Villarroel 170, Barcelona 080036, Spain. Tel.: +34 93 227 57 85 Fax: +34 93 227 57 83 E-mail:
Keywords: Levodopa/carbidopa, Parkinsons disease, wearing-off, dyskinesia, entacapone
DOI: 10.3233/JPD-130186
Journal: Journal of Parkinsons Disease, vol. 3, no. 3, pp. 255-269, 2013
Abstract
It May Improve Mental Performance In Stressful Situations
Stress is something that everyone experiences.
This stress can negatively affect your reasoning, memory, attention and knowledge by decreasing neurotransmitters .
For example, rodents who were exposed to cold had impaired memory due to a decline in neurotransmitters .
However, when these rodents were given a tyrosine supplement, the decline in neurotransmitters was reversed and their memory was restored.
While rodent data does not necessarily translate to humans, human studies have found similar results.
In one study in 22 women, tyrosine significantly improved working memory during a mentally demanding task, compared to a placebo. Working memory plays an important role in concentration and following instructions .
In a similar study, 22 participants were given either a tyrosine supplement or placebo before completing a test used to measure cognitive flexibility. Compared to the placebo, tyrosine was found to improve cognitive flexibility .
Cognitive flexibility is the ability to switch between tasks or thoughts. The quicker a person can switch tasks, the greater their cognitive flexibility.
Additionally, supplementing with tyrosine has been shown to benefit those who are sleep deprived. A single dose of it helped people who lost a nights sleep stay alert for three hours longer than they otherwise would .
And while tyrosine may provide cognitive benefits, no evidence has suggested that it enhances physical performance in humans .
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Special Precautions & Warnings
Pregnancy and breast-feeding
Overactive thyroid or Graves disease: The body uses tyrosine to make thyroxine, a thyroid hormone. Taking extra tyrosine might increase thyroxine levels too much, making hyperthyroidism and Graves disease worse. If you have one of these conditions, dont take tyrosine supplements.
Dopamine Aldehyde Poisoning And Parkinson’s Disease
The cofactor in this case is molybdenum, which is required for an enzyme to be able to break down the poisonous DOPAL fast enough. If molybdenum is depleted or exhausted in our system, Dopamine production and degradation becomes self-poisoning, and our systems response can be inherently wise: to stop producing Dopamine.
However, there are many other important biochemical steps which can get severely disrupted when we are stuck in freeze or the Fear Paraylsis Reflex for long times. This is because immobilization is mediated by Dorsal Vagus Nerve activation in the gut. This stress signal causes the digestive system to shut down, and breaks the communication between gut and brain. The Enteric Nervous System is put into a state of shock or into survival mode, from the ongoing threat signals coming from the Dorsal Vagus activation. In this emergency state, healthy digestive chemistry goes offline and the gut stops producing some enzymes, peptides, hormones and neurotransmitters, stops absorbing some nutrients from food, and may even stop being an environment in which good microbiota can survive. .A large portion of our biochemicals are synthesised in the gut: 50% for Dopamine, and 95% for Serotonin, for example. The digestive system also directly affects the biochemistry of the brain, which we now know relies on gut signalling to the brain or healthy functioning too.
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Side Effects And Adverse Reactions
The side effects of
- A condition similar to stimulant psychosis
Although many adverse effects are associated with l-DOPA, in particular psychiatric ones, it has fewer than other antiparkinsonian agents, such as anticholinergics and dopamine receptor agonists.
More serious are the effects of chronic l-DOPA administration in the treatment of Parkinsons disease, which include:
- End-of-dose deterioration of function
- Dyskinesia at peak dose
- Possible dopamine dysregulation: The long-term use of l-DOPA in Parkinsons disease has been linked to the so-called dopamine dysregulation syndrome.
Clinicians try to avoid these side effects and adverse reactions by limiting l-DOPA doses as much as possible until absolutely necessary.
Quantification Of Bacterial Tdc
To identify bacterial species carrying the tdc gene, a broad range of tdc genes from various bacterial genera were targeted as previously described . Quantitative PCR of tdc genes was performed on DNA extracted from each fecal sample of Parkinsons patients and rats jejunal content using primers targeting a 350bp region of the tdc gene. Primers targeting 16S rRNA gene for all bacteria were used as an internal control . All qPCR experiments were performed in a Bio-Rad CFX96 RT-PCR system with iQ SYBR Green Supermix in triplicate on 20ng DNA in 10µL reactions using the manufacturers protocol. qPCR was performed using the following parameters: 3min at 95°C 15sec at 95°C, 1min at 58°C, 40 cycles. A melting curve was determined at the end of each run to verify the specificity of the PCR amplicons. Data analysis was performed using the BioRad software. Ct values were corrected with the internal control and linearized using 2^- based on the 2^-Ct method.
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Dopamine Aldehyde Poisoning And Parkinsons Disease
The cofactor in this case is molybdenum, which is required for an enzyme to be able to break down the poisonous DOPAL fast enough. If molybdenum is depleted or exhausted in our system, Dopamine production and degradation becomes self-poisoning, and our systems response can be inherently wise: to stop producing Dopamine.
However, there are many other important biochemical steps which can get severely disrupted when we are stuck in freeze or the Fear Paraylsis Reflex for long times. This is because immobilization is mediated by Dorsal Vagus Nerve activation in the gut. This stress signal causes the digestive system to shut down, and breaks the communication between gut and brain. The Enteric Nervous System is put into a state of shock or into survival mode, from the ongoing threat signals coming from the Dorsal Vagus activation. In this emergency state, healthy digestive chemistry goes offline and the gut stops producing some enzymes, peptides, hormones and neurotransmitters, stops absorbing some nutrients from food, and may even stop being an environment in which good microbiota can survive. .A large portion of our biochemicals are synthesised in the gut: 50% for Dopamine, and 95% for Serotonin, for example. The digestive system also directly affects the biochemistry of the brain, which we now know relies on gut signalling to the brain or healthy functioning too.
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What Is Tyrosine And What Does It Do
Tyrosine is an amino acid that is naturally produced in the body from another amino acid called phenylalanine.
Its found in many foods, especially in cheese, where it was first discovered. In fact, tyros means cheese in Greek (
Tyrosine helps make several important substances, including :
- Dopamine: Dopamine regulates your reward and pleasure centers. This important brain chemical is also important for memory and motor skills .
- Adrenaline and noradrenaline: These hormones are responsible for the fight-or-flight response to stressful situations. They prepare the body to fight or flee from a perceived attack or harm (
- Melanin: This pigment gives your skin, hair and eyes their color. Dark-skinned people have more melanin in their skin than light-skinned people .
Its also available as a dietary supplement. You can purchase it alone or blended with other ingredients, such as in a pre-workout supplement.
Supplementing with tyrosine is thought to increase levels of the neurotransmitters dopamine, adrenaline and norepinephrine.
Summary Tyrosine is an amino acid that the body produces from phenylalanine. Supplementing with it is thought to increase important brain chemicals, which affect your mood and stress response.
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