Mucuna vs Sinemet : benefits of natural levodopa

There is growing evidence in support of mucuna extracts as a natural medicine for the treatment of Parkinson’s disease.

FIRST DESCRIPTIONS

In 1978, a publication by R.A. Vaidya in India stated that Parkinson’s disease could be treated with extracts of a plant, Mucuna pruriens, which contains natural levodopa and is tolerated better than the synthetic version¹.

In the West the scientific writings that described improvement in parkinsonian symptoms after eating mucuna or other beans appear between 1990 and 1994 and are authored by B.V. Manyam, J.M. Rabey and P.A.Kempster^{2 3 4}.

In the first edition (January 1997) of one of my popular medical books, The Strange Case of Dr. Parkinson⁵, I have previously commented on these findings.

In the chapter implicatively entitled Beans instead of pills, I emphasized that these legumes could replace some of the conventional medication.  I have also included some recipes from “Parkinsonian Cuisine” that are based on beans.  In some of my other books, I have references to further publications on the subject ⁶.

MUCUNA SEED POWDER

Scientific journals have begun publishing cases of improvement in patients after eating mucuna.  The  Parkinson’s Disease Study Group undertook a multi-center clinical study (in collaboration with several hospitals) with 60 patients, of which 26 took Sinemet before the test and the other 34 were “pharmacologically virgins” (they had never taken levodopa).

All were treated for 12 weeks with powder from mucuna seeds: an average of 6 bags, each containing 7.5 grams, equivalent to 250 mg of levodopa.  In other words, each sachet contained the same amount of levodopa as a Sinemet 25/250, but without the carbidopa.

Neurologists of four centers screened patients using the appropriate scales (UPDRS) and found considerable improvement that was statistically confirmed.⁷. Thus, Ayurveda medicinal recipes have demonstrated their clinical effectiveness.

ZANDOPA: A MEDICINE WITH MUCUNA

This legume seems to work.  Investigations gave evidence of this and mucuna seed powder (called HP-200) was marketed as a drug, under the brand name Zandopa.⁸.

It was first distributed in India, and has been available in the United Kingdom since 2008.  Now customers can buy it freely online without a prescription.  It is important to be careful, however, because the levodopa dose is relatively high (250 mg per sachet) when combined with carbidopa or other antiparkinsonian drugs (see the description of Zandopa below).

IMPROVEMENT IN MICE DOUBLES OR TRIPLES

We can experimentally induce parkinsonism (unilateral or bilateral) in rodents via certain toxic substances.  Used in these trials, levodopa from mucuna has no side effects and produces an improvement that is double or triple that of the synthetic version.⁹.

This also suggests that mucuna can contain components that enhance the action of levodopa (as when combined with carbidopa, entacapone or tolcapone).  There is another possibility: namely that mucuna itself, regardless of its levodopa content, relieves the parkinsonian symptoms.

In another experiment, animals ate extract of mucuna for a year.  They were then put down and  their neurotransmitters were measured in different areas of their brains.

Interestingly, no changes were seen in the nigrostriatal pathway, but dopamine was significantly increased in the cerebral cortex⁸. This has two possible explanations: that natural levodopa is more potent, or that mucuna contains other beneficial chemicals.

ENDORSED BY THE AMERICAN ACADEMY

This clinical study¹¹ complies with the strict requirements laid down by the most rigorous scientific methodology established by the Quality Committee of the American Academy of Neurology¹².

This was a randomized, double-blind, crossover, study which adhered to precise objectives and clearly defined protocols, and was carried out by several independent observers.

They studied 8 Parkinson’s patients at (on average) 62 years of age, 12 years after diagnosis with a stage of progression of 3.5 on the Hoehn & Yahr scale.  Prior to this test they were treated with levodopa (572 mg mean value). In addition, patients were taking others previous associated drugs (amantadine, pergolide, ropinirole, pramipexole or cabergoline) that remain unchanged.  All had a rapid response to levodopa (1.5 to 4 hours) along with very disabling motor fluctuations during the morning.

Each subject was hospitalized three times (one week apart) and went without any medication the night before the test.  The next morning, at the same time,  each received at random one of three combinations: one dose of 200 mg of levodopa with 50 mg of carbidopa (two tablets of Sinemet Plus), or two or four sachets of mucuna (15 or 30 grams) equivalent to 500 or 1000 mg  of natural levodopa (100 or 200 according to the conversion factors).

The results were clearly better in those who take two sachets of mucuna extract: improvement in their symptoms occurred faster, their plasma levodopa levels were higher, and clinical efficacy was more durable.  In addition, their dyskinesia was not worsened.  The details follow.

“CITIUS, ALTIUS, FORTIUS ET DURABILIUS”

The Olympic motto “faster, higher, stronger” can be applied to mucuna, because, in comparison to Sinemet, it acts more rapidly (34 minutes instead of 68), produces a greater elevation of the plasma level of levodopa (110% higher), and appears to be stronger (the effectiveness of natural levodopa is double or triple that of the synthetic version).

In addition, the improvement achieved is more durable (with mucuna the “on” phase is prolonged 37 minutes longer than with Sinemet).  Therefore, it can be described as Citius, altius, fortius… durabilius.

TWICE AS EFFECTIVE

We have seen that the mucuna seed extract naturally contains levodopa.  If we quantify and compare it to the same dose of synthetic levodopa contained in tablets of Sinemet (or Madopar) we find that levodopa from mucuna is approximately twice as powerful in controlling parkinsonian symptoms. ¹³.

The efficacy of synthetic levodopa (without carbidopa) has been compared to that of natural levodopa (mucuna) using rats with experimentally induced parkinsonism.  The natural levodopa proved to be two times as effective at improving symptoms¹⁴. This test maintained the following proportions: 125 and 250 milligrams of synthetic levodopa were compared with the equivalent dose of natural levodopa (respectively, 2.5 and 5 grams of mucuna powder 5%).

This means that in addition to levodopa, mucuna provides other substances (with carbidopa-like or other properties) that increase its effectiveness.

Then the test was repeated, this time adding 50 mg of carbidopa to the two types of levodopa.  Again, mucuna proved to be more efficient.

THE PROBLEM OF VOLUME

Mucuna is more effective, more rapid and durable, however… to achieve a dose that will offer the same relief as Sinemet or Madopar, it would be necessary to prescribe large amounts of seed powder dissolved in liquid^{15 16}.

The need to consume seed powder several times a day would soon overwhelm the patient and the treatment would be abandoned as too cumbersome.

The solution to the problem can be found in concentrated extracts.  This allows for the presentation of mucuna in tablets or capsules, facilitating the application of different doses of the product and making it easy to manage daily consumption of mucuna in the amounts deemed necessary.

There is another choice that requires the cooperation of the neurologist: mucuna could be used in association with carbidopa to achieve greater efficiency with less seed powder.

We will see more on this further ahead.

MUCUNA WITH CARBIDOPA

The first trials that compared the effects of Sinemet with mucuna required six or seven daily sachets of powdered seeds.  This can be maintained for a few days, but becomes quite cumbersome with time.

Actually those studies were done to compare natural levodopa (mucuna) to a synthetic combination of levodopa and carbidopa (i.e. the contents of Sinemet).

The solution seems simple: add carbidopa to mucuna. This increases the efficiency of the natural levodopa contained therein and therefore eliminates the need to take large amounts of seed powder.

We must be careful when capsules of concentrated extracts are used because the dose can be excessive when you consider that mucuna is more effective than synthetic levodopa¹¹.

There are published trials in which mucuna is administered in combination with carbidopa and is compared to Sinemet.

Rats with experimentally induced hemi-parkinsonism were treated with powdered mucuna seeds (2.5 and 5 g) associated with carbidopa (50 mg) and in contrast to other groups wherein the equivalent synthetic levodopa dose (125 and 250 mg) was also associated with carbidopa.

Mucuna-carbidopa proved to be more than twice as effective as Sinemet and this was found by measuring the rotation contralateral (on the injured side) of the animals in each group¹⁴.

We know that the carbidopa in Sinemet prevents the peripheral side effects of levodopa (nausea, rapid heart rate) and enhances mobility.  It appears that, the carbi-dopa in mucuna is even more effective: it decreases mild side effects and doubles or triples patients’ strength¹¹.

MUCUNA DOES NOT PRODUCE DYSKINESIA

A different study, this time in monkeys (with unilateral parkinsonism induced experimentally), produced very interesting results on the possibility of dyskinesias.

One group was treated with Sinemet (levodopa and carbidopa), another with mucuna plus carbidopa, and the third only with mucuna.  All the animals experienced an improvement in their symptoms.

Dyskinesia was then assessed by the study of spontaneous activity in the substantia nigra.  Larger dyskinesia appeared in the Sinemet group.  In those treated with the combination of mucuna and carbidopa dyskinesia seemed more moderate.  Interestingly, in those who had only taken mucuna no dyskinesia was found.

LONG-TERM MUCUNA WITHOUT DYSKINESIA

A similar experiment was performed, but this time mucuna treatment was continuous, extending for a year.  It was done in rodents and compared mucuna with Madopar.

One group was treated with Madopar (levodopa and benserazide), another with mucuna plus benserazide, and the third only with mucuna.

All were controlled for a year.  The symptoms were alleviated in all groups, but the improvement was significantly higher in those who were treated with mucuna plus benserazide.

To highlight the results of long-term use: after one year, major dyskinesia appeared in rats that had taken Madopar.  Rodents treated with mucuna plus benserazide had some minor dyskinesia.  Animals that took only mucuna … none at all²⁰.

This suggests that the mucuna contains unknown ingredients that produce effects similar to those of benserazide (or carbidopa), or which, for some reason, reduce the need for this association in order to improve parkinsonian symptoms.

MUCUNA IMPROVES HALOPERIDOL-INDUCED DYSKINESIA

As previously mentioned, mucuna extracts do not produce dyskinesia after long-term treatment, but it seems that there is another advantage.

In an experiment with different dyskinesia (those produced by neuroleptics like haloperidol) these re-petitive movements improved when mucuna was administered²¹.

MUCUNA IS NEUROPROTECTIVE

Most clinicians believe that levodopa (the synthetic version thus far used) is harmful due to a possible association with increased free radical formation.

Some authorized opinions disagree and express doubts about the myth of “toxic levodopa” in cases where low doses are used.

Well, it seems that natural levodopa from mucuna (or the whole of the components in this legume) is non-toxic, and even neuroprotective ²².

This has been demonstrated in mice (with experimentally induced parkinsonism) which were given synthetic levodopa or mucuna.

Those treated with mucuna experienced an improvement in most of the symptoms.  Also, when they were slaughtered one year later for brain analysis it was found that the endogenous contents of levodopa, dopamine, norepinephrine, and serotonin in the substantia nigra was significantly restored²³.

These results have been attributed to other ingredients in mucuna known to protect against Parkinson’s disease: NADH (nicotinamide adenine dinucleotide) and coenzyme Q-10.

CHELATING AND ANTIOXIDANT PROPERTIES

In other studies with rodents, researchers agree that the extract of mucuna clearly is neuroprotective compared to synthetic levodopa²⁴ or estrogen²⁵.

They believe that this is due to its antioxidant and chelating activity (processing of iron), and because it avoids mutagenic effects in DNA^{26 27}.

MUCUNA IMPROVES BRAIN FUNCTION IN RATS

Antioxidant and neuroprotective properties of mucuna has also been shown in rodents that were previously damaged experimentally by nerve toxins such as Paraquat.

The results also highlighted the improvement in habits and cognitive functions of these animals²⁸.

DOSAGE DOES NOT INCREASE OVER TIME!

It sounds too good to be true: treatment with mucuna does not produce dyskinesia; and it also improves secondary abnormal movements which occur with chronic synthetic levodopa therapy.

One more thing: with mucuna it would be not necessary to gradually increase the dose as time goes on, as is the case with those taking synthetic drugs.

Below, I transcribe literally the benefits of mucuna extracts as reflected in the scientific foundations of the patent carried out by Van der Giessen, Olanow, Lees and Wagner²⁹, we are going to discuss this more broadly in the following post:

“Conventional L-Dopa therapy requires a gradual increase of the effective dose over time resulting of progression of disease and/or the neurotoxic effects of L-Dopa or dopamine with an increase of toxic reactions and, over time, the appearance of dyskinesia, increasing in severity with dose. In clinical experiences with Mucuna prurience seed preparations these negative phenomena have not been observed in that for the effective treatment of Parkinson’s, the dose of Mucuna pruriens derived L-Dopa remained relatively stable over longer periods of time, and in that dyskinesia, even in patients with pre-existing dyskinesia following long term therapy with conventional L-Dopa preparations, appeared to be less in occurrence and severity…”²⁹.

After reading this, it seems strange that mucuna is not yet dispensed in all pharmacies as a revolutionary drug.