Mucuna Info by Mullet! (non USP-Specific)

[Mulletsoldier]

I wrote this in response to a discussion on another site, so I thought I'd bring it here.

As has been stated thus far, L-DOPA supplementation is more or less useless without concurrent decarboxylase inhibitor administration (most commonly, carbidopa). Without concomitant administration of DCIs, L-DOPA will undergo enzymatic conversion in peripheral tissues, leading to unwanted and unfortunate side effects; for this reason, and due to Dopamine's inability to cross the BBB, concurrent DCI administration is necessary for sufficient dopaminergic expression in the Substantia Nigra.

Furthermore, and has also been mentioned, L-DOPA administration over long periods can have neuro-degradative effects, as well as prominent effects on motor function fluctuation (dyskenisia). One of the most prominent negative effects of L-DOPA administration is its degradation of dopaminergic ions, leading to a substantially decreased endogenous dopamine production over lengthy dosing periods; obviously, this is antithetical to the stated purpose of L-DOPA administration. This deregulation of Dopamine production is congruent with the tolerability and long-term efficacy concerns demonstrated by synthetic L-DOPA administration. This has led to necessary research into alternative treatments for Parkinson's models, some of this research is provided briefly below.

Given these detriments, Dopamine agonism would seem to be not only foolish, but dangerous to one's health, as has been mentioned here. However, most of the negative effects mentioned herein have been focused exclusively, whether purposively or by oversight, on synthetic L-DOPA; this, then, begs the question of what differences arise as it pertains to synthetic L-DOPA administration and administration of naturally occurring L-DOPA. This question seems pertinent to raise for reasons twofold; firstly, Mucuna as a whole and PowerFULL itself have been mentioned within this discussion; secondly, this is an L-DOPA discussion, and any relevant discourse on the complexities of neurotransmitters must contain a certain degree of nuance and specificity. Without raising the very valid question of natural vs., synthetic L-DOPA administration, this discussion lacks the mentioned characteristics.

As stated, a large amount of research is currently being conducted on this same issue at hand; while results, just as with any compound, have been neither characteristically "good" or "bad", one could say the majority of research on MP has been encouraging. This stems from a demonstrated superiority of MP over synthetic L-DOPA, even with concomitant Carbidopa administration, to induce dopaminergic expression. This superiority is not minute in anyway, and, as the sources demonstrate, has been up to twice that of LD/CD administration. This efficacy is not only demonstrated in higher short-term, baseline increases of L-DOPA in MP, but in terms of long-term administration tolerability and efficacy profiles. This increased ability for long-term administration and efficacy itself has been postulated to stem from many factors; firstly, a high expression of Dopamine in the Substantia Nigra with a concurrent lack of dopaminergic expression in peripheral tissues has been noted (herein being used in the context of any tissue unresponsive to the desired effects of Dopamine). This increases the tolerability due to a lack of increase in motor flucuation compared to its higher mean concentration and longer on time, as well as a lesser degree of cognitive function degradation; secondly, MP has been postulated to contain not only alkaloids which may enhance L-DOPA (DCIs), but constituents which may exert independent, beneficial anti-Parkinson's/Dopamine induction effects. In either respect, this leads to an ability of MP to exert increased Dopamine production over synthetic LD/CD preparations with, once again, a lower expression of unwanted side effects; lastly, MP has demonstrated the ability to be neuro-restorative. This has been expressed in not only an increase (as opposed to decrease in its synthetic counterpart) of endogenous L-DOPA and Dopamine production, but a regeneration of damaged Dopaminergic Ions in the Substantia Nigra (therein leading to a circular increase in its efficacy), increased mitochondrial expression of Complex-I as well as increasing Serotonin and Norepinephrine. Crude preparations of MP were also shown to contain COQ-10 and NADH (both neuro-protective in Parkinson's treatment).

I feel it is important to note at this point, a few things, some in favour of, and some in reflective caution about, the benefits of MP mentioned herein. The question will now invariably raised about relative dosing of crude MP vs., synthetic LD/CD administration in the studies used. To address that question, it is imperative to note that the seeds/leaves of MP which contain roughly 9-14% L-DOPA are used to make a crude, liquidized preparation of MP so named "HP-200". This preparation, even in its crude form, is considered a viable alternative for Parkinson's treatment at an L-DOPA concentration of 4%. Most commercial preparations of MP are standardized to contain anywhere from 50-98% L-DOPA; in the case of USP Labs, we begin with a 75% standardization, and end up with a 50% standardization. Obviously, this leads to a much lower necessary dose of commercially standardized Mucuna to achieve the effects of HP-200.

Secondly, while every consumer is sick and tired of each company lauding their extraction and sourcing ability, and the effect on the end product therein, in the case of Mucuna, this is a tangible and necessary concern. Genotype, latitude, cultivation and preparation methods all exert an effect on the quality and concentration of L-DOPA in Mucuna seeds.

Thirdly, more research is necessary - that is clear. It has only been relatively recently that L-DOPA's role in Parkinson's has been elucidated, and thereby only very recently that a large body of legitimate research on Mucuna has been undertaken. Therefore, while the sources below demonstrate its vast superiority to synthetic LD/CD preparations, for various reasons, more research needs to be conducted on its long term efficacy and tolerability. However, I feel confident in refuting much of the cautionary evidence presented in this discussion on L-DOPA, at least as it pertains to natural preparations.

As a final note, I would like to agree that standard L-DOPA administration is unnecessary and potentially harmful, but espouse that the opposite is true in terms of MP preparations. Along with the effects on Dopamine mentioned herein, it is also objectively documented to raise Testosterone, Semen volume, as well as display potent Anti-Oxidant, Anti-Inflammatory, and Anti-Depression effects. In no way is MP useless, and I speak of MP in a general sense.

I would also like to apologize for the disorderly nature of my sources; this was not a pre-fabricated nor planned write-up, and I chose to include relevant text as well. However, the assertions made within are substantiated in full by the evidence.

Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study. Katzenschlager R, et al.

National Hospital for Neurology and Neurosurgery, London, UK.

RESULTS: Compared with standard LD/CD, the 30 g mucuna preparation led to a considerably faster onset of effect (34.6 v 68.5 min; p = 0.021), reflected in shorter latencies to peak L-dopa plasma concentrations. Mean on time was 21.9% (37 min) longer with 30 g mucuna than with LD/CD (p = 0.021); peak L-dopa plasma concentrations were 110% higher and the area under the plasma concentration v time curve (area under curve) was 165.3% larger (p = 0.012). No significant differences in dyskinesias or tolerability occurred. CONCLUSIONS: The rapid onset of action and longer on time without concomitant increase in dyskinesias on mucuna seed powder formulation suggest that this natural source of L-dopa might possess advantages over conventional L-dopa preparations in the long term management of PD. Assessment of long term efficacy and tolerability in a randomised, controlled study is warranted.

 

[Mulletsoldier]

More data:

Effect of antiparkinson drug HP-200 (Mucuna pruriens) on the central monoaminergic neurotransmitters. Bala V. Manyam et al.,

ABSTRACT
HP-200, which contains Mucuna pruriens endocarp, has been shown to be effective in the treatment of Parkinson's disease. Mucuna pruriens endocarp has also been shown to be more effective compared to synthetic levodopa in an animal model of Parkinson's disease. The present study was designed to elucidate the long-term effect of Mucuna pruriens endocarp in HP-200 on monoaminergic neurotransmitters and its metabolite in various regions of the rat brain. HP-200 at a dose of 2.5, 5.0 or 10.0 g/kg/day was mixed with rat chow and fed daily ad lib to Sprague-Dawley rats (n = 6 for each group) for 52 weeks. Controls (n = 6) received no drug. Random assignment was made for doses and control. The rats were sacrificed at the end of 52 weeks and the neurotransmitters were analyzed in the cortex, hippocampus, substantia nigra and striatum. Oral administration of Mucuna pruriens endocarp in the form of HP-200 had a significant effect on dopamine content in the cortex with no significant effect on levodopa, norepinephrine or dopamine, serotonin, and their metabolites- HVA, DOPAC and 5-HIAA in the nigrostriatal tract. The failure of Mucuna pruriens endocarp to significantly affect dopamine metabolism in the striatonigral tract along with its ability to improve Parkinsonian symptoms in the 6-hydorxydopamine animal model and humans may suggest that its antiparkinson effect may be due to components other than levodopa or that it has an levodopa enhancing effect.

Mucuna pruriens proves more effective than L-DOPA in Parkinson's disease animal model
Ghazala Hussian, Bala V. Manyam

Department of Neurology, Southern Illinois University School of Medicine, PO Box 19230, Springfield, Illinois, USA

ABSTRACT
Seeds of the Mucuna pruriens plant, now known to contain L-DOPA, have long been used for the treatment of Parkinson's disease patients in ancient Eastern Indian ethnotherapeutics. Following validation of the intrastraital 6-OHDA injection with amphetamine in the parkinsonian rat model, the animals were fed synthetic L-DOPA (125 or 250 mg/kg) or Mucuna pruriens endocarp (MPE, 2.5 or 5.0 g/kg) mixed with rat chow (n =6, for each dose and drug). Controls received no drug. An additional dose of L-DOPA or MPE in the same doses plus carbidopa (50 mg/kg) were administered via gavage (controls received only carbidopa 50 mg/kg) 1 h prior to testing with rotometer. Contralateral rotation (to the side of the 6-OHDA lesion) (CLR) was recorded for 240 min as a measure of antiparkinsonian activity. Results indicated that dose for dose, MPE showed twice the antiparkinsonian activity compared with synthetic L-DOPA in inducing CLR in the parkinsonian animal model. This study suggests that MPE may contain unidentified antiparkinsonian compounds in addition to L-DOPA, or it may have adjuvants that enhance the efficacy of L-DOPA.

Beans (Mucuna Pruriens) For Parkinsons Disease:
An Herbal Alternative

Bala V. Manyam, M.D.,
NPF Center of Excellence Plummer Movement Disorders Center Department of Neurology

Glenn R. Cryer, Scientific Publications and Biomedical Communications
Scott & White Clinic and Texas A&M University Health Science System College of Medicine


.....To establish how Mucuna would compare to synthetic L-DOPA, experiments were undertaken in animal models of Parkinson?s disease. Two different doses of synthetic L-DOPA and two different doses of Mucuna were administered making sure that the amount of L-DOPA present is the same in Mucuna as was the doses of synthetic L-DOPA. The effects of the drugs were tested using a specially designed instrument called "Rotometer." Dose for dose, Mucuna was two to three times more effective than equivalent amounts of synthetic L-DOPA. This suggests that Mucuna may contain compounds that make L-DOPA function better such as carbidopa, tolcapone (Tasmar), or entacapone (COMTan). It may also suggest that Mucuna independently improve symptoms of Parkinsons disease. Although quite encouraging, more research is needed to confirm these findings. This work was done at the time when the United States Congress established the Office of Alternative Medicine in the National Institute of Health and the work was one of the first to receive funding for alternative medicine....

Neuroprotective effects of the antiparkinson drug Mucuna pruriens. Manywam et al.,

Department of Neurology, Health Science Center College of Medicine, Temple, TX 76508, USA.

Mucuna pruriens possesses significantly higher antiparkinson activity compared with levodopa in the 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease. The present study evaluated the neurorestorative effect of Mucuna pruriens cotyledon powder on the nigrostriatal tract of 6-OHDA lesioned rats. Mucuna pruriens cotyledon powder significantly increased the brain mitochondrial complex-I activity but did not affect the total monoamine oxidase activity (in vitro). Unlike synthetic levodopa treatment, Mucuna pruriens cotyledon powder treatment significantly restored the endogenous levodopa, dopamine, norepinephrine and serotonin content in the substantia nigra. Nicotine adenine dinucleotide (NADH) and coenzyme Q-10, that are shown to have a therapeutic benefit in Parkinson's disease, were present in the Mucuna pruriens cotyledon powder. Earlier studies showed that Mucuna pruriens treatment controls the symptoms of Parkinson's disease. This additional finding of a neurorestorative benefit by Mucuna pruriens cotyledon powder on the degenerating dopaminergic neurons in the substantia nigra may be due to increased complex-I activity and the presence of NADH and coenzyme Q-10. Copyright

Bioavailability of L-DOPA from HP-200 - a Formulation of Seed Powder of Mucuna pruriens (Bak): a Pharmacokinetic and Pharmacodynamic Study. S.Mahajani et al.,

Department of Neurology, Southern Illinois University School of Medicine, Springfield, IL 62794-1316, USA

ABSTRACT
HP-200, a formulation made from the seed powder of Mucuna pruriens, contains among other constituents, about 4% L-DOPA. After five normal human volunteers were each given a single oral dose of 30 g of HP-200, plasma samples were obtained at 0, 20, 40, 60, 90, 120, 180, 240 and 360 min for assay of L-DOPA by HPLC technique using electrochemical detection. The supine systolic and diastolic blood pressures were recorded at each sampling time. The results indicate that on oral administration, L-DOPA was absorbed from HP-200 with plasma peak levels (Cmax=1.56?0.163 g/mL) achieved at Tmax=83?16.09 min. The plasma half life was 102?2 min and the auc was determined as 6.508?0.421 g/h/mL. The pharmacokinetic profile of HP-200 exhibited characteristics similar to formulations of synthetic L-DOPA, except for the lack of a sharp peak. HP-200, a new herbal formulation, appears to be suitable for the treatment of Parkinson's disease.

http://www.phcogrev.com/issue1/19.pdf

Agrobotanical, nutritional and bioactive potential of unconventional legume - Mucuna. K R Sridhar and Rajeev Bhat
Microbiology and Biotechnology, Department of Biosciences, Mangalore University, Mangalagangotri 574 199, Karnataka, India




Effect of genotype and environment on L-Dopa concentration in Mucuna seeds. Capo-chichi, L. J. A., et al.,

Department of Agronomy and Soils, Auburn University, AL 36849, USA.
Tropical and Subtropical Agroecosystems, 2002 (Vol. 1) (No. 2/3) 319-328

Abstract:
High L-Dopa content in Mucuna seeds is most likely the greatest impediment to increasing their utilization as a food and feed. Breeding Mucuna to lower the L-Dopa content of the seeds would be one way to increase the utility of this cover crop as a food and feed. Breeding efforts would be aided by the evaluation of the natural range of genetic variability in L-Dopa content and its relationship to the growing environment. Our objective was to determine whether genotype ? environment (G ? E) interactions are present for L-Dopa in very different sites and with different management across a range of latitudes and, if so, to interpret the nature of the interactions as well as to determine their implications for a Mucuna breeding programme. Several accessions (four in 2000-2001 and eight in 2001-2002) were grown in numerous sites (four and six, respectively) in latitudes ranging from 18?S to 30?N. The relative magnitude of the G ? E interaction components, namely genotype ? site (G ? S), genotype ? years (G ? Y), and genotype ? site ? years (G ? S ? Y), was studied using variance component analysis. A standard multi-factor analysis of variance (ANOVA) test revealed that all first order interactions (G ? S, G ? Y, S ? Y) as well as second order interactions (G ? S ? Y) were either absent or not highly significant and accounted for a minimal amount of the variance, indicating that genotype performance was not dependent upon sites or years. Genotypes performance for L-Dopa synthesis fluctuated across sites inconsistently. As latitude increased, Mucuna L-Dopa fluctuations in seeds were more pronounced in some accessions than others. However, this response was not consistent for all accessions, indicating the need to test genotypes or clones at multi-environments over longer periods of time. At all sites, the early-maturing accession Rajada had the lowest L-Dopa content in seeds and its values ranged from 2.4% to 4.4% of seed dry weight (DW), averaging 3.5%. This was followed by Ghana, another early-maturing accession, for which L-Dopa content ranged from 3.1% to 5.6% (average 4.6%, all DW). The highest L-Dopa content was observed for the late-maturing accessions Cochinchinensis, Deeringiana, Preta, and Utilis, respectively averaging 5.4%, 5.4% 5.5%, and 5.2% DW. Thus, maturity time may be tested as a physiological trait for predicting the level of L-Dopa in seeds. For all accessions, the regression of seed L-Dopa content on latitude was not significant. Thus, the relationship between L-Dopa concentration and the environment may be more complex than a simple linear correlation to latitude

Standardization of cultivation and harvesting stage of velvet bean (Mucuna pruriens var. utilis) for optimum yield and quality. Krishnamurthy, R., et al.,
Zandu Foundation for Health Care, Ambach, Pardi, Valsad, Gujarat 396 145, India.
Indian Journal of Agricultural Sciences, 2003 (Vol. 73) (No. 11) 585-589

Abstract:
A field experiment was conducted in Gujarat, India during 2 crop cycles in 2000-01 to standardize the cultivation and postharvest drying of velvet bean (M. pruriens var. utilis) for commercial production. The crop was raised during the start of the monsoon rain in June and irrigated (surface) at 15-day intervals during the dry season of October-January. The crop gave the highest seed yield of 1.995 t/ha at a closer spacing of 1.0 m ? 1.0 m (10 000 plants/ha) with individual plant supporting system. The trial conducted with wider spacing (1.0 m ? 1.5 m, 8 000 plants/ha) and individual plant supporting (with bamboo stakes) with 12 rates of N, P2O5 and K2O/ha fertilizer resulted in higher number of pods/9 m2 (252-295) and seed yield with 75, 100 and 0 (1.196 t/ha); 150, 50 and 0 (1.476 t/ha); 150, 100 and 0 (1.496 t/ha); 225, 50 and 0 (1.504 t/ha); and 225, 100 and 0 (1.531 t/ha) applications. K was not applied as the farm soil contained high K2O (240 kg/ha). The pods picked at semi-dry maturity stage gave optimum seed yield (110.40 g/20 pods), L-Dopa (4.680%) and superior quality of seed (white colour, bold and without wrinkles and cracks) used in drug manufacturing industry.

 

[Mach .78]

So, What is the maximum dosage of 98% L-Dopa daily? I read several places saying that it was 500 mg. Does that sound right?