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As has been mentioned, L-DOPA administration over long periods can have neuro-degradative effects (to be explained below), 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, primarily in the substantia nigra, leading to substantially decreased endogenous dopamine production over lengthy dosing periods – obviously, an effect completely antithetical to the stated purpose of L-DOPA administration. This dysregulation of Dopamine production is congruent with the tolerability and long-term efficacy concerns demonstrated by synthetic L-DOPA administration, and its presence has led to necessary research into alternative treatments in PDS modalities.
Given these detriments, Dopamine agonism would seem not only foolish, but also 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 two reasons. (1) Firstly, Mucuna as a whole and PowerFULL itself have been mentioned within this discussion. (2) 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; and while results, just as with any compound, have been neither characteristically "good" nor "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, and, as the literature 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.
Given these detriments, Dopamine agonism would seem not only foolish, but also 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 two reasons. (1) Firstly, Mucuna as a whole and PowerFULL itself have been mentioned within this discussion. (2) 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; and while results, just as with any compound, have been neither characteristically "good" nor "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, and, as the literature 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.
