L Dopa or Levodopa, how to increase brain chemical, dihydroxyphenylalanine
Feb 19 2014 by
Ray Sahelian, M.D.

 

L dopa, dihydroxyphenylalanine, is the most effective symptomatic agent in the treatment of Parkinson's disease and the "gold standard" against which new agents are compared. More than 30 years after its development, levodopa is still the most effective treatment for the symptomatic control of Parkinson's disease. Although a number of therapies have been developed in an attempt to improve Parkinson's disease management, such as dopaminergic agonists and inhibitors of COMT and MAO-B, most patients still depend on levodopa alone because of its superior ability to control PD symptoms. The issue of toxicity has been raised by in vitro studies suggesting that levodopa might be toxic to dopaminergic neurons, but this has not yet been proven. A more pressing concern regarding levodopa is its association with the development of motor complications after long-term use.

More than 50% of Parkinson's disease patients treated with L-dopa develop L-dopa-induced dyskinesias in the long term. Some patients exhibit severe dyskinesias soon after starting low doses of L-dopa, whereas other patients remain free of this disabling complication despite treatment with L-dopa. Avoiding or delaying the appearance of l dopa induced dyskinesia is one of the main objectives of the management of PD.

 

Formation of L Dopa
Phenylalanine amino acid > Tyrosine amino acid > L-Dopa > Dopamine > Norepinephrine > Epinephrine.

 

Natural Supplements with L Dopa
Mucuna pruriens is an herb that contains a small percentage of natural L Dopa. Mucuna pruriens is available without a prescription. For more information on mucuna pruriens and levodopa, click on the link provided.

 

I have mucuna extract 99 percent l dopa from a company I use here in the UK but can you please tell me something. I realise pure l dopa which I have can release hgh etc and good moods. but do I have to use mucuna powder for testosterone raising or will my pure l dopa raise testosterone as well? I'm really confused what is the benefit of mucuna extract 99 percent compared to just mucuna powder (seeds) untouched? And will I benefit from them both in the same way or dies 99 percent extract wipe out all the other mucuna ingredients?
    Much depends on how each company prepares their l dopa extract from the herb. There could be differences between companies, and there is no guarantee that the product would be 99 percent pure. As a general rule, it is quite likely that many of the other substances in the mucuna herb would be removed and they contribute to many of the health benefits of this herbal product. Rather than focusing on elevating testosterone levels, one has to evaluate what exactly do they wish to benefit from taking either the l dopa 99 percent product or mucuna. There are a number of other herbs and supplements that influence mood and sex drive.

 

Is the product "Mucuna Pruriens extract of 200 mg 15%" equal to 30 mg of L-Dopa? If so, I will go back to the website to purchase.
   It has 30 mg l dopa but this herb has many other substances in it that have various effects and benefits so it cannot be simply compared to L dopa medication.

 

Hawaii J Med Public Health. 2013. Case of levodopa toxicity from ingestion of Mucuna gigantea. Hawai'i is home to 1000 native species of flowering plants. Mucuna gigantea is one such Hawaiian species which has been studied as affordable sustenance and as a cover crop in developing countries. Mucuna gigantea and other Mucuna species (spp.) in general, are known to contain natural levodopa and its utility in the treatment of Parkinson's Disease has also been evaluated. Levodopa is converted in the periphery into dopamine which can then act on dopamine receptors to cause nausea, vomiting, arrhythmias, and hypotension. We describe a case in which a patient presents with abdominal pain, nausea, and vomiting after legume ingestion. The bean was ultimately identified as Mucuna gigantea and the patient was diagnosed with levodopa-induced gastrointestinal toxicity from consumption of the legume. A literature review was conducted using the database search engines, Biological Abstracts and PubMed, with a broad combination of keywords of which include "mucuna, "gigantean," "levodopa," "l-dopa," "toxicity," and the association between Mucuna gigantea ingestion and levodopa toxicity is discussed. These findings expand the differential diagnosis of abdominal pain associated with nausea and vomiting in the correct clinical context.

 

Antioxidants and L Dopa
It is possible that the use of certain antioxidants could slow the progression of Parkinson's disease, or mitigate the potential side effects from l dopa.

 

Side effects of levodopa
Chronic treatment is associated with motor complications that marred the clinical benefit of levodopa. These problems and experimental data in cell cultures indicating a neurotoxic effect of levodopa have led to the idea of delaying the introduction of levodopa treatment for as long as possible to avoid the side effects of L dopa.
      However, after an initial period of dramatic benefit, several limitations become apparent including, "dopa resistant" motor symptoms (postural abnormalities, freezing episodes, speech impairment), "dopa resistant" non-motor signs (autonomic dysfunction, mood and cognitive impairment, etc), and/or drug related side effects (especially psychosis, motor fluctuations, and dyskinesias).  They can be very disabling and difficult to treat. Though mechanisms underlying motor complications are only partially understood, recent work has revealed the importance of pulsatile stimulation of postsynaptic dopamine receptors and the disease severity. As a result of intermittent stimulation there occurs a cascade of changes in cell signalling leading to upregulation of the N-methyl-D-aspartate subtype of gamma-aminobutryric acid-ergic neurones. Modified preparations of levodopa (controlled release preparations, liquid levodopa), catecholamine-o-methyltransferase inhibitors, dopamine agonists, amantidine, and various neurosurgical approaches have been used in the prevention and/or treatment of motor complications.

Levodopa treatment
Levodopa remains the mainstay treatment for Parkinson's disease. There remain two areas of controversy: (1) whether levodopa is toxic, and (2) whether levodopa directly causes motor complications. Levodopa is toxic to cultured dopamine neurons, and this may be a problem in PD where there is evidence of oxidative stress in the nigra. However, there is little firm evidence to suggest that levodopa is toxic in vivo or in PD. Clinical trials have not clarified this situation. Levodopa is also associated with motor complications. Increasing evidence suggests that they are related, at least in part, to the short half-life of the drug (and its potential to induce pulsatile stimulation of dopamine receptors) rather than to specific properties of the molecule.

 

Mov Disord. 2013. The history of parkinsonism: descriptions in ancient Indian medical literature. The clinical syndrome of parkinsonism was identified in ancient India even before the period of Christ and was treated methodically. The earliest reference to bradykinesia dates to 600 bc. Evidences prove that as early as 300 bc, Charaka proposed a coherent picture of parkinsonism by describing tremor, rigidity, bradykinesia, and gait disturbances as its components. The scenario was further developed by Madhava, Vagbhata, and Dalhana all through history. The 15th-century classic "Bhasava rajyam" introduced the term kampavata, which may be regarded as an ayurvedic analogue of parkinsonism. The pathogenesis of kampavata centered on the concept of imbalance in the vata factor, which controls psychomotor activities. The essential element in therapy was the administration of powdered seed of Mucuna pruriens, or atmagupta, which as per reports, contains 4%-6% of levodopa.

 

Levodopa Addition Medication
Zelapar (selegiline HCl, Valeant) Orally Disintegrating Tablets, a monoamine oxidase-B (MAO-B) inhibitor, was approved in 2006 as a once-daily adjunct therapy for Parkinson's disease patients being treated with levodopa / carbidopa who exhibit deterioration in the quality of their response to this therapy.

 

Levodopa Carbidopa

Levodopa and carbidopa are used for the treatment of Parkinson's disease. Levodopa can be used alone, but adding carbidopa lowers the amount of levodopa that is required and may reduce some of the levodopa side effects such as nausea and vomiting. Carbidopa is a medication (called a decarboxylase inhibitor) that, when taken with levodopa, helps prevent the levodopa from converting to dopamine outside the brain. The combination of carbidopa and levodopa allows more levodopa to get to the brain. The levodopa carbidopa combination decreases side effects caused by increased dopamine levels outside the brain by reducing the supply of “free” dopamine outside the brain. Most people take levodopa and carbidopa together, rather than levodopa by itself.

L Dopa or Levodopa research
Proc Natl Acad Sci U S A. 2013. Single dose of L-dopa makes extinction memories context-independent and prevents the return of fear. Traumatic events can engender persistent excessive fear responses to trauma reminders that may return even after successful treatment. Extinction, the laboratory analog of behavior therapy, does not erase conditioned fear memories but generates competing, fear-inhibitory "extinction memories" that, however, are tied to the context in which extinction occurred. Accordingly, a dominance of fear over extinction memory expression--and, thus, return of fear--is often observed if extinguished fear stimuli are encountered outside the extinction (therapy) context. We show that postextinction administration of the dopamine precursor L-dopa makes extinction memories context-independent, thus strongly reducing the return of fear in both mice and humans. Reduced fear is accompanied by decreased amygdala and enhanced ventromedial prefrontal cortex activation in both species. In humans, ventromedial prefrontal cortex activity is predicted by enhanced resting-state functional coupling of the area with the dopaminergic midbrain during the postextinction consolidation phase. Our data suggest that dopamine-dependent boosting of extinction memory consolidation is a promising avenue to improving anxiety therapy.

 

A meta-analysis of the response to chronic L-dopa in patients with schizophrenia: therapeutic and heuristic implications.
Psychopharmacology. 2004. Jaskiw GE, Popli AP.
Psychiatry Service, Louis Stokes Cleveland VAMC, Brecksville, OH
While it is generally believed that administration of the dopamine precursor levodopa ( L-dopa ) exacerbates symptoms of schizophrenia, numerous reports suggest that adjunctive L-dopa may be beneficial. This body of literature has not been critically reviewed. On the basis of published studies, to determine whether L-dopa administered concomitantly with antipsychotic drugs provides a beneficial response in patients with schizophrenia. METHODS: This review examined 30 studies involving 716 patients. Due to wide methodological variability and limited statistical information, only five studies encompassing 160 patients could be included in a meta-analysis. The others were evaluated qualitatively. When L-dopa was added to antipsychotic drugs, the overall improvement was moderate and highly significant. There were 16 other studies in which L-dopa was added to antipsychotic drugs, but which did not meet criteria for inclusion in the meta-analysis. In these, worsening occurred in less than 20% of patients; the percentage of improved patients varied widely but had a central tendency around 50%. In patients already on antipsychotic drugs, the addition of L-dopa can be beneficial. Dopamine agonists merit further consideration as adjuncts to antipsychotic drugs in the treatment of schizophrenia.

 

Questions
Q. A while back you presented an article concerning Mucuna Pruriens as a potential natural source of L-dopa (precursor to dopamine). In order for L-dopa to efficiently cross the blood brain barrier however, measures must be taken so that it doesn’t get absorbed into the periphery (gut). The traditional way to do this is to administer the L-dopa along with a peripheral DDC (dopamine decarboxylase) inhibitor such as carbidopa as well as with a COMT (Catechol-O-methyl transferase) inhibitor. I have read that green tea extract can act as a natural COMT inhibitor but have never heard of any natural substances that can act as a DDC inhibitor. Are there any natural substances that can improve the efficiency of the Mucuna Pruriens by increasing the amount of L-dopa that crosses the blood brain barrier?
   A. You ask a good question regarding L Dopa and decarboxylase inhibitor, but we have not come across such research yet, but we will keep our eyes open.
 

Q. What do you think of Coq10 supplement taken the same day as L dopa.
   A. I have not seen any studies combining the two, There could be overstimulation.
 

Q. On the subject of: Parkinson' s Disease- Natural Treatment Options and Parkinson's Disease Information, I read on your website that "Perhaps levodopa acts as an oxidant, damaging nerve cells" and also that Mucuna may work as an antioxidant. Since Mucuna Pruriens contains levodopa which is an oxidant, then Mucuna is also an oxidant, Right? How do we know whether a herb or a drug is an antioxidant or not?
   A. Only a small percent of mucuna pruriens is L dopa, the rest are other substances that have antioxidant protection whereas L dopa, the pharmaceutical drug, is 100 percent L dopa. Each herb has to be individually studied to determine whether it has antioxidant properties.
 

Q. I love your site and the information you provide, and have purchased some very helpful supplements from Physician Formulas. I know that those suffering from Parkinson's who take Dopamine find that it works well at first, but begins to be less effective over time. Is it possible this could happen with L-Dopa from mucuna pruriens, or does the fact it comes from a natural source that the body converts to Dopamine reduce the chance of loss of effectiveness over time? As an "aging" male of 56, soon to be 57 (though I'm pretty healthy and fit & certainly don't feel "old"!), I'm aware that my hormone levels are probably declining, and decided to try L-Dopa to boost natural levels of testosterone to aid in muscle-building, but now I've become concerned whether long-term use could actually leave me WORSE off - is that possible? Thank you for your time, and keep up the great work you do to help all of us out here get a handle on our own health - I'm a firm believer in "natural" cures & that we shouldn't just leave it all to our family doctors and prescription drugs.
   A. This is a good question. Unfortunately we are not aware of long term human studies with mucuna pruriens to determine what kind of effect it has on dopamine receptors in the brain or other influences on brain tissue. We suspect that mucuna pruriens does not have a similar effect as does L dopa. But, to be sure, we often suggest taking breaks from the use of supplements, which could be a day or two off a week, a few days off each month, and a week or two off every 3 months.

 

Q.  I have Friedreich's ataxia, i was wondering if the doctor thinks L-dopa might be beneficial?
   A. I have not studied the role of L dopa in Friedreich's ataxia.

 

Q. I am from Greece. I checked myself in an ELECTRO INTERSTITIAL SCAN STATUS REPORT and the results was that my brain dopamine and my catecholamines was very low. Will the mucuna pruriens with 15% l dopa be helpful? Also i m an Olympic athlete and i want to know if this is OK with DOPING CONTROL!!! Do you know something else that can improve my dopamine to the normal levels?
   A. I am not familiar with the Electro Interstitial Scan status report test. I doubt mucuna pruriens is tested for doping control. Rather than focusing on a particular brain chemical in the brain, as a doctor I prefer treating the whole person not just a lab number. But, mucuna prurines has l dopa and it is an interesting herb that can increase energy and sexuality although it can also increase body temperature which may not be very good for athletic pursuits.

 

I would like to tell you that I think your web-site is great. I have a question concerning L-Dopa. I am considering taking a supplement containing L-Dopa. While researching L-Dopa, I saw that one of the side effects could be hair loss. I recently had been taking a low dosage (10 mg daily) of DHEA capsules for about 6 weeks. I noticed that I was starting to lose some of the hair on my scalp, so I stopped taking it. I am worried that if I start with the L-Dopa I might have the same experience. But then, I was not sure if the side effect of hair loss was limited to pharmaceutical L-Dopa and not the natural L-Dopa from Mucuna Pruriens. Do you have any ideas on this?
    I am not aware of any research or feedback from users that hair loss occurs from the use of mucuna pruriens herb.