1-Carboxy and GABA

[alwaysgaining]

to bad powerfull is not L-Dopa but PureDOPA an extract of Mucuna Pruriens wich induces an increase in endogenous (natural) LevaDopa production that vastly outperforms synthetic LevaDopa
dose synthetic LevaDopa have more sides?

Wrong.

lol i took this from the write up and its wrong? get yer facts straight
u just unloaded a bunch or crap in this thread the op askd about some supps and u tell him all the long term studys that he gana get huntintons or parkinsins????

Reading this thread, one may form the impression that Parkinsons were a simple disease state that could be provoked by supplemental 1-carboxy or natural L-Dopa. This is not the case. It is well known that Parkinsons can occur as a spontaneous and permanent mutation in genetic building blocks. This even can be the end-result of a short or long process characterized by a combination of genetic irregularities and environmental stressors. These manifest as a degenerative event in one of the brain's control centers called the substantia nigra. The causes of this cell apoptosis can include trauma, drug use, toxins (free radicals), and so on. Now, back to the substantia nigra. The nerve cells of this control center release dopamine, a neurotransmitter, to coordinate movement in the body. Part of the released dopamine also stimulates the corpus striatum, another part of the brain involved in coordination. A certain minimum amount of functioning substantia nigra cells are required for movement or muscular coordination. Without sufficient dopamine, however, coordination and movement cannot be properly executed.
The amino acid L-Dopa, as well as dopamine agonists, are actually used in the treatment of Parkinsons. By stimulating the secretion of dopamine, L-Dopa's mechanism of action includes receptor activation or stimulation on the surface of the corpus striatum. As an aside, L-Dopa therapy usually includes the use of compounds that inhibit enzymes that metabolize dopamine. These enzymes include the amino acid decarboxylase, catechol-O-methyltransferase (COMT), and monoamine oxidase-B.

If the above is accurate, I would like someone to point out to me where and how (mechanism of action, please) 1-carboxy can cause Parkinsons.

thank u for clearing all this garbage up

 

[nattydisaster]

Reading this thread, one may form the impression that Parkinsons were a simple disease state that could be provoked by supplemental 1-carboxy or natural L-Dopa. This is not the case. It is well known that Parkinsons can occur as a spontaneous and permanent mutation in genetic building blocks. This even can be the end-result of a short or long process characterized by a combination of genetic irregularities and environmental stressors. These manifest as a degenerative event in one of the brain's control centers called the substantia nigra. The causes of this cell apoptosis can include trauma, drug use, toxins (free radicals), and so on. Now, back to the substantia nigra. The nerve cells of this control center release dopamine, a neurotransmitter, to coordinate movement in the body. Part of the released dopamine also stimulates the corpus striatum, another part of the brain involved in coordination. A certain minimum amount of functioning substantia nigra cells are required for movement or muscular coordination. Without sufficient dopamine, however, coordination and movement cannot be properly executed.
The amino acid L-Dopa, as well as dopamine agonists, are actually used in the treatment of Parkinsons. By stimulating the secretion of dopamine, L-Dopa's mechanism of action includes receptor activation or stimulation on the surface of the corpus striatum. As an aside, L-Dopa therapy usually includes the use of compounds that inhibit enzymes that metabolize dopamine. These enzymes include the amino acid decarboxylase, catechol-O-methyltransferase (COMT), and monoamine oxidase-B.

If the above is accurate, I would like someone to point out to me where and how (mechanism of action, please) 1-carboxy can cause Parkinsons.

I said about 5 times now that the reason you don't want to take L-Dopa is because it is well known that a strong tolerance is built up. It's mentioned numerous times in all of my neurophysiology textbooks. Also, as I previously stated before, there is no study on if this tolerance ever subsides, and if so how fast. Therefore, users are making themselves tolerant to a drug that is helping a disease that 1.5 million Americans have. If they were to get this disease, Levodopa would not be as effective or effective at all for them.

Since no studies have been done on healthy patients, the effects of L-Dopa are unknown.

All to their own on what you put into your body. If taking a neurotransmitter with no research done on anyone without Parkinson's to help you sleep is what you need then go for it. Don't go crying to the companies selling it when you get Parkinson's and your doctor says your Levodopa isn't working and you will progress faster than all the people using Levodopa. I came here to simply inform and warn. I asked a Neurophysiologist at my university about the use of L-Dopa as a healthy male and she told me that I would indeed feel effects from it but there was no point in me taking and and no point in starting to develop a tolerance at such a young age to a treatment of such a common disease.

 

[nattydisaster]

Parkinson's Disease is very often resulted from a idiopathic etiology. This means it can more than likely develop/potentiate via multiple different pathways in the loss of pigmented dopamine-secreting (dopaminergic) cells. I'll definitely get back here to comment more when i have time, but there are good arguments for both sides. It's a horrible disease, and in the end, treatment modalities ultimately fail to deliver a long term better quality of life for the individual.

Took the words right out of my mouth.

 

[nattydisaster]

lol i took this from the write up and its wrong? get yer facts straight
u just unloaded a bunch or crap in this thread the op askd about some supps and u tell him all the long term studys that he gana get huntintons or parkinsins????



thank u for clearing all this garbage up

Yes. It is wrong. Get YOUR facts straight. Product descriptions are not facts.

Every USP lab rep himself will tell you that L-Dopa is the same thing as "PureDOPA". The only difference is L-Dopa is only about 20-50% of the contents in the M. Purines extract. So essentially it's worse than synthetic L-Dopa. Just because it's "natural" in a plan doesnt mean it's natural in our bodies. Your body takes 100mg Synthetic L-Dopa the same as 200mg 50% M. Purines extract. You're the only one in this thread who doesn't understand this.

 

[GoHardOrGoHme]

So to summarize what you're saying natty is that these products will cause an individual to grow tolerant to L-Dopa therapy.

You arent saying it will cause PD, you are only saying that it will render L-Dopa therapy (which is one form of therapy, there are several) not as effective as if you never took these supplements? correct?

 

[GoHardOrGoHme]

"finding of a neurorestorative benefit by Mucuna pruriens cotyledon powder on the degenerating dopaminergic neurons in the substantia nigra"

http://www3.interscience.wiley.com/journal/109674875/abstract?CRETRY=1&SRETRY=0

article that implies M. Pruriens have neuroprotective attributes...possibly implying preventative measures to PD(parkinsons disease)

still havent found anything negative...even in the area of building tolerance to the supplement and it possibly effecting future treatment

 

[nattydisaster]

"finding of a neurorestorative benefit by Mucuna pruriens cotyledon powder on the degenerating dopaminergic neurons in the substantia nigra"

http://www3.interscience.wiley.com/journal/109674875/abstract?CRETRY=1&SRETRY=0

article that implies M. Pruriens have neuroprotective attributes...possibly implying preventative measures to PD(parkinsons disease)

still havent found anything negative...even in the area of building tolerance to the supplement and it possibly effecting future treatment

EDIT: Nevermind...

 

[GotTest]

I honestly haven't found any negative research for Mucuna Pruriens.
Here's some research that shows an increase in sperm motility and increase in T, LH, dopamine, adrenaline, noradrenaline:
http://www.ncbi.nlm.nih.gov/pubmed/18973898

 

[GotTest]

I appreciate you sharing this info natty!
I take Mucuna during every Tren cycle, but will reconsider.

 

[strategicmove]

I said about 5 times now that the reason you don't want to take L-Dopa is because it is well known that a strong tolerance is built up. It's mentioned numerous times in all of my neurophysiology textbooks. Also, as I previously stated before, there is no study on if this tolerance ever subsides, and if so how fast. Therefore, users are making themselves tolerant to a drug that is helping a disease that 1.5 million Americans have. If they were to get this disease, Levodopa would not be as effective or effective at all for them.

Since no studies have been done on healthy patients, the effects of L-Dopa are unknown.

All to their own on what you put into your body. If taking a neurotransmitter with no research done on anyone without Parkinson's to help you sleep is what you need then go for it. Don't go crying to the companies selling it when you get Parkinson's and your doctor says your Levodopa isn't working and you will progress faster than all the people using Levodopa. I came here to simply inform and warn. I asked a Neurophysiologist at my university about the use of L-Dopa as a healthy male and she told me that I would indeed feel effects from it but there was no point in me taking and and no point in starting to develop a tolerance at such a young age to a treatment of such a common disease.

I struggle to see the relevance of your response to what I wrote. Just wonder why you quoted my contribution as the basis for your response.

In any case, let's talk about tolerance for a moment. Every supplement user knows that one builds a tolerance to most pharmacologically active compounds that we take, not just L-Dopa. Besides, assuming identical physiological starting points, tolerance will be a function not just of the amount of the compound we consume, but also of the duration of use.

Furthermore, as you know, L-Dopa is a tyrosine-derived neurotransmitter. Tyrosine not used up for energy production is converted into catecholamine neurotransmitters (dopamine, norepinephrine, and epinephrine). For those interested, catecholeamine synthesis occurs in neurons and the adrenal medullary cells. When tyrosine is transported into these neurons and cells, it is converted into DOPA (3,4-dihydrophenylalanine) via the enzymatic action of tyrosine hydroxylase and the co-factor tetrahydrobiopterin. An enzyme, DOPA decarboxylase then converts DOPA to dopamine within the substantia nigra and some other parts of the brain. Within the adrenal medulla, however, dopamine is converted to norepinephrine via the action of the enzyme, dopamine β-hydroxylase. Finally, another enzyme, phenylethanolamine N-methyltransferase, converts norepinephrine to epinephrine. Why is this tyrosine angle relevant? Simple! DOPA is a substrate for not just dopamine, but also for norepinephrine and epinephrine. Put differently, not all L-DOPA (or even tyrosine) we consume ends up as dopamine in the substantia nigra, so we should keep this in perspective when we talk of tolerance as if everyone that uses L-DOPA takes supraphysiological doses that blast the substantia nigra continuously.

Now to your Neurophysiologist. I hope she is aware that only a small fraction of the levodopa or L-Dopa taken orally ever reaches the brain, as blood enzymes such as amino acid decarboxylases (AADCs) metabolize most of the levodopa before it reaches the brain, unless it is taken with appropriate dopamine agonists, enzyme inhibitors or transport vehicles such as carbidopa that inhibit L-Dopa decarboxylation in the bloodstream or in tissues outside the brain, ensuring an increase in the amount of L-dopa that finally reaches the brain for enzymatic conversion to dopamine. Without these co-factors, only a fraction of the consumed levodopa ever survives decarboxylation. Besides, she should also know that dopamine has other important functions in the body besides the transmission of signals from the substantia nigra to the corpus striatum and enabling coordinated movement.

Just to be clear, I do not advocate the reckless use of L-DOPA or dopamine agonists. Dopamine has its place in bodybuilding, if used in a responsible fashion. Same applies to most of the compounds bodybuilders and health enthusiasts use.

 

[strategicmove]

Took the words right out of my mouth.

He certainly did not! Nothing in what he wrote provides unwavering support for your position. At best, his contribution was neutral (in terms of the side of the debate he supports).

 

[strategicmove]

Summary of this thread:

This is more like a summary of your position!

1) L-Dopa should be used with caution. Don't just put something in your body because it's available as a dietary supplement and the product description sounds cool.

This applies to any other compound. I am not sure why you keep referring to a product description!

2) If you have Parkinson's in your family, I would not take L-Dopa.

Justification? How about cholinergic agonists?

3) If you do not have Parkinson's in your family, I would still not take L-Dopa.

That is a personal preference, so one should respect it.

4) L-Dopa from M. Purines is still going to cause all the same negative side effects and synthetic levodopa.

This is certainly not true.

5) Do research on what you're putting into your body.

Fully agree without any exceptions.

There is a big difference when it comes to supplements like amino acids that are well known of their effects, and supplements that alter the neurotransmitters of your brain.

Is L-DOPA not an amino acid?

 

[DAdams91982]

Wow... lots of blind faith going on here.

So I guess Natural and Synthetic testosterone are worlds apart as well. Next thing you know people will start claiming there is no Santa Clause!

 

[Robbo]

I watch this thread with interest, and slight apprehension, as I'm three weeks into some IGF-2 with Green Tea extract and vitamin B6...

 

[strategicmove]

Listen...

...That study is saying that there are neuroprotective attributes found in MP. Want to know why? Because it has L-Dopa in it.

Sounds to me like this is contrary to your original position. One got the impression from reading your earlier posts that L-DOPA were neuro-destructive!

Therefore, you should not be researching if MP makes you grow tolerant. You should be looking at L-Dopa. L-Dopa is L-Dopa. Whether it is from a lab, from a plant, or from a squirrels cum, it doesn't matter. You body will react to it the same if it is all L-Dopa.

See my comment on the natural and synthetic enantiomers of lipoic acid and their actions at binding sites.

The fact that Levodopa (100% L-Dopa) creates a tolerance in the body is FACT. It is KNOWN SCIENCE.

I agree it is a fact, but where is the science in it? L-DOPA is not the only agent that provokes a tolerance.

There are not only studies proving this, but 1 million patients a year proving this. There is an entire section in my neurophysiology book by McGraw Hill about it.

Forget your neurophysiology book for a second. Those one million patients are Parkinson's cases with compromised dopaminergic systems, and not healthy subjects. Besides, tolerance, even in those impaired or dead substantia nigra nerve cells takes up to five years to occur. We are talking about five solid years of daily supplementation with high doses of levodopa (or combined with dopamine agonists and enzyme inhibitors).

You can all continue taking it. I don't care. I was simply trying to inform and warn and I had to end up prove my point and proving other people wrong.

Fair enough. The objective of all this was not to prove anyone wrong! Just to present verifiable facts.

Next time you visit your physician tell him you have been taking Levodopa for sleep (because that's what you're doing). See his reaction....

Chances are he uses it himself!

Or you can continue to believe the brotelligence of the bodybuilding interweb.

I like that! rivateeye:

...But like T1 said, the Parkinson's is a lot more complex than everyone is making it out to be....

1) T1 certainly was not the first to state that.
2) If you agree it is that complex, why do you emphasize levodopa use, as if it were the sole causative agent?

And again I am not trying to bring down any company or supplement. I am just saying that L-Dopa shouldn't be used by anyone without PD.

Cheers.

---

 

[strategicmove]

I watch this thread with interest, and slight apprehension, as I'm three weeks into some IGF-2 with Green Tea extract and vitamin B6...

No cause for worry! That is a great stack!

 

[scoooter]

Summary from an observer's / follower's perspective of this thread.

First I was shocked and then quickly became paranoid since I'm using bulk 1-carboxy so I then became angry at myself for not researching enough but now I'm getting a little confused with all the technicalities.

Conclusion: I have ceased using the 1-carboxy and have chosen to NOT consider IGF-2 which I was planning to use after the 1-carboxy.

 

[GoHardOrGoHme]

i think strategic brought up some amazing points to really finish up this discussion

there seems to be a large misunderstanding on the actual science that goes into L-Dopa therapy. Strategic i believe really began to elaborate that supplementing with 1-carboxy and MP is world different from L-Dopa therapy.

Its almost like eating oats, broccoli, and tons of read meat to up your test vs. injecting the real deal(not an accurate example but im trying to get across a larger theme).

It seems like the only way to have MP or 1-carboxy cause L-Dopa tolerance you need to A)massive doses continuously for years B)take it with the proper chemical agents to insure the proper amounts cross the blood brain barrier and target the substantia nigra and C)disregard all proper instructions on how to use these supplements

The same argument can be made with just about any supplement if abused similarly.

Also considering MP extracts have been around for quite some time, some ancient cultures would use these plants for medicinal purposes(i believe).


Proper supplementation seems to lead to nothing put positive sides.

 

[bioman]

I view parkinson's and related disorders as a disregulation of glutamate production which is a essentially a free radical and neuro excitotoxin with a particular affinity to several regions in the brain. Other factors are, of course, equally relevant like exogenous excitotoxins and other free radicals.

I'm not sold on the "don't take L-Dopa" argument just yet. If you're taking it, downregulation will naturally occur and upregulation will commence upon cessation as part of your body's natural buffering capacity...ie the trend towards homeostasis. SO basically, unless there is solid evidence that a dopamine surge causes disregulation of glutamate levels, or other as yet unidentified excitiotoxins, I'm less concerned about that than I am overall lifestyle choices (like not taking up boxing or smoking).

The magnitude of the dopamine increase should also be taken into account. How much of a surge are we talking here...3x, 10x or 1000x the normal amount. Drugs like X we know elevate seratonin to extreme levels, but is L-Dopa's effect comparable. Also, if drugs like Marijuana elevate dopamine, why aren't we seeing millions of ageing potheads jerking around? Just things to consider because even though I view all of your collective textbook wisdom as amazing and an asset to this board, we also know from our guniea pigging around here that what's on paper doesn't always translate into reality due to the fact the body has so many compensatory mechanism that it's quite rare to give a definitive answer based on the observation of just 2-3 factors.

That and I love L-dopa for recovery after a heavy lifting day, lol.

 

[giantbrandon]

great thread, good points from both sides

 

[GotTest]

In any case, let's talk about tolerance for a moment. Every supplement user knows that one builds a tolerance to most pharmacologically active compounds that we take, not just L-Dopa. Besides, assuming identical physiological starting points, tolerance will be a function not just of the amount of the compound we consume, but also of the duration of use.

This is something I was racking my brain with for a few hours.
I just can't understand (or find any research/documentation) that shows L-Dopa causing MORE tolerance than any other drug, where even the cessation of the L-Dopa will not diminish tolerance for months, or even years.

I'm curious to know if there is some irreversible damage, that makes L-Dopa uneffective as oppose to a "super tolerance" :think:
They are finding this with HEAVY Ecstasy users now.

 

[silverSurfer]

I feel like I just went to L-Dopa school, thanks everyone.

 

[brk_nemesis]

hmmm.... Very interesting thread.

I feel like I just went to L-Dopa school

True that!

 

[strategicmove]

This is something I was racking my brain with for a few hours.
I just can't understand (or find any research/documentation) that shows L-Dopa causing MORE tolerance than any other drug, where even the cessation of the L-Dopa will not diminish tolerance for months, or even years.

I'm curious to know if there is some irreversible damage, that makes L-Dopa uneffective as oppose to a "super tolerance" :think:
....

These are valid questions, and the answers are complex. In particular, they involve the state of the individual's dopamine receptors before the onset of L-DOPA or levodopa treatment, whether or not dopamine agonists, dopa decarboxylase inhibitors, monoamine oxidase B inhibitors, catechol-o-methyltransferase, acetylcholine blockers, and neuroprotectants are used, in what concentrations and combinations, the duration of the treatment, and some extraneous factors.

To highlight some of the inherent complexity I alluded to earlier, consider dopamine receptors. Recall that dopamine is unable to cross the blood brain barrier, and in the cases of Parkinson's, dopamine is completely ineffective therapeutically if administered into peripheral circulation. The immediate metabolic precursor of dopamine, namely, (-)-3-(3,4-dihydroxyphenyl)-l-alanine, also known as levodopa, is transported to the brain by an amino acid transporter (LAT). Once reaching the brain, levodopa is decarboxylated to dopamine via dopa decarboxylase. Recall also that DOPA is the amono acid precursor of dopamine, epinephrine, norepinephrine, and epinephrine. Levodopa is the levorotatory sterioisomer of DOPA.

Now, there are five known dopamine receptors, D1, D2, D3, D4, and D5. These, however, fall into two categories, D1-type (D1 and D5), and D2-type (D2, D3, and D4). All dopamine receptors are metabotropic (G protein-coupled). In fact, most neurotransmitters bind to so-called ionotropic receptors. These are ligand-gated channels that are opened by the binding of neurotransmitters to the channel. Apart from binding to ligand-gated channels, most neurotransmitters also bind to metabotropic receptors (G protein-coupled receptors) that modulate voltage-gated channels. [Voltage-gated channels are those that react to changes in a cell's membrane potential]. The direct interaction of G proteins with the voltage-gated ion channel within the membranes of nerve cells usually targets calcium channels and potassium channels. The interaction of G proteins with calcium channels usually inhibits channel function when presynaptic metabotropic receptors are activated. In the case of post synaptic metabotropic receptors, however, potassium channels are activated. Furthermore, metabotropic receptors can induce effects outside the nerve cell membrane by activating second messengers such as cAMP.

As already stated, all dopamine receptors are metabotropic. Dopamine itself induces a slow inhibiting action on central nervous system neurons, such as dopamine-containing substantia nigra neurons. Here, activating D2-receptors leads to the opening of potassium channels via the Gi coupling protein.
On their part, D1-type dopamine receptors are located in the zona compacta of the substantia nigra. Presynaptically, they are located on striatal axons (both from cortical neurons and from dopaminergic cells in the substantia nigra). Postsynaptically, the D2-type dopamine receptors are located on striatal neurons and presynaptically on sustantia nigra axons emanating from neurons in the basal ganglia.

Most dopaminergic drugs for the treatment of Parkinson's act on D2 receptors, although D1 stimulation increases the overall efficacy of the treatment. On the other hand, dopamine blockers with selective D2 antagonism can cause Parkinson's.

This means that, ceteris paribus, the state of the dopamine receptors, especially the D2 receptos, plays an important role in L-DOPA/levodopa response. Decreasing responsiveness (increasing tolerance) to L-DOPA/levodopa treatment in parkinsonism can be due to the fact that the daily dose of levodopa must be reduced over time to avoid side effects; and it can also be due to some patients becoming less responsive to levodopa administration, such that previously effective doses fail to produce any therapeutic benefit.
Responsiveness to levodopa treatment may disappear completely and permanently in parkinsonian states because of the disappearance of dopaminergic nigrostriatal nerve terminals; or because of some pathologic processes directly involving the striatal dopamine receptors.

So, in parkinsonian states, the tolerance may be permanent, while this should be extremely unlikely in healthy individuals on controlled and cycled supplementation with dopamine agonists. Remember that in parkinsonism, dopaminergic function is impaired, and this impairment is degenerative (= gets worse over time). Considering that levodopa does not stop the progression of Parkinson's, degenerative dopaminergic impairment ultimately leads to complete loss of dopaminergic function. In such a state, levodopa/L-DOPA tolerance (non-responsiveness) will be permanent. In healthy individuals (with normal dopaminergic function), however, there is no evidence that tolerance should develop if mega-doses of L-DOPA/levodopa are not administered long-term. Besides, there is also no evidence that tolerance will remain permanent upon cessation of levodopa/L-DOPA or dopamine-agonist administration.

 

[strategicmove]

...
It seems like the only way to have MP or 1-carboxy cause L-Dopa tolerance you need to A)massive doses continuously for years B)take it with the proper chemical agents to insure the proper amounts cross the blood brain barrier and target the substantia nigra and C)disregard all proper instructions on how to use these supplements....

Great comment! To add to that, considering that Mucuna Pruriens or even 1-carboxy does not contain anything close to the amount of levodopa administered to Parkinson's patients, the issue of permanent tolerance here is overdone.

Let's concentrate on levodopa again for a second. Depending on the rate of gastric emptying and the pH of the gastric contents, levodopa is rapidly absorbed from the small intestine. It's appearance in plasma may be delayed by food ingestion. Furthermore, certain amino acids compete with levodopa for uptake from the gut and for transport to the brain from the blood. Nevertheless, plasma levodopa concentrations peak between 1 and 2 hours post oral dosing, and the plasma half-life lies between 1 and 3 hours. Within 7-8 hours of oral dosing, about two-thirds of the dose appears in the urine as metabolites! Ultimately, only about 1-3% of orally dosed levodopa usually enters the brain, with the rest being metabolized in extra-cerebral cells to dopamine via decarboxylation. As is well-known, dopamine cannot cross the blood brain barrier, so large doses of levodopa are required when it is administered alone (that is, without any dopamine agonists, dopa decarboxylase inhibitors, monoamine oxidase B inhibitors, catechol-o-methyltransferase (COMT) inhibitors, acetylcholine blockers, or neuroprotective agents).

The interested reader may want to consider the above, then think of the amount of L-DOPA one ultimately gets per dose or per cycle from 1-carboxy or from Mucuna Pruriens, and then reach his/her own conclusion.

 

[DAdams91982]

Great comment! To add to that, considering that Mucuna Pruriens or even 1-carboxy does not contain anything close to the amount of levodopa administered to Parkinson's patients, the issue of permanent tolerance here is overdone.

Let's concentrate on levodopa again for a second. Depending on the rate of gastric emptying and the pH of the gastric contents, levodopa is rapidly absorbed from the small intestine. It's appearance in plasma may be delayed by food ingestion. Furthermore, certain amino acids compete with levodopa for uptake from the gut and for transport to the brain from the blood. Nevertheless, plasma levodopa concentrations peak between 1 and 2 hours post oral dosing, and the plasma half-life lies between 1 and 3 hours. Within 7-8 hours of oral dosing, about two-thirds of the dose appears in the urine as metabolites! Ultimately, only about 1-3% of orally dosed levodopa usually enters the brain, with the rest being metabolized in extra-cerebral cells to dopamine via decarboxylation. As is well-known, dopamine cannot cross the blood brain barrier, so large doses of levodopa are required when it is administered alone (that is, without any dopamine agonists, dopa decarboxylase inhibitors, monoamine oxidase B inhibitors, catechol-o-methyltransferase (COMT) inhibitors, acetylcholine blockers, or neuroprotective agents).

The interested reader may want to consider the above, then think of the amount of L-DOPA one ultimately gets per dose or per cycle from 1-carboxy or from Mucuna Pruriens, and then reach his/her own conclusion.

You are making a sweeping statement about a group of people that do not hold back on their dosages. You of all people should know to do something like that. There are users around here utilizing grams of your 50% L-Dopa extract (And I pulled that directly from your bosses writings

I will just let people compare but the statement made that this was 1-carboxys better half was fabricated and based on assumption. I'm not sure his intentions but NP is still a store that makes money off other Vendors products so trashing a competitors product to boost it's individual sale is not great business.

We extract for 50% L-dopa and natural decarboxylase inhibitors within Mucuna.

Now how do you go to say people are not taking the doses necessary doses for tolerance, not to mention a nice little decarboxylase inhibitor added?

Now lets pull side effects, and read the VERY bottom:

Side Effects

The side effects of L-DOPA may include:

* Hypotension, especially if the dosage is too high
* Arrhythmias, although these are uncommon
* Nausea, which is often reduced by taking the drug with food, although protein interferes with drug absorption
* Gastrointestinal bleeding
* Disturbed respiration, which is not always harmful, and can actually benefit patients with upper airway obstruction
* Hair loss
* Disorientation and confusion
* Extreme emotional states, particularly anxiety, but also excessive libido
* Vivid dreams and/or insomnia
* Auditory and/or visual hallucinations
* Effects on learning; there is some evidence that it improves working memory, while impairing other complex functions
* Somnolence and narcolepsy
* A condition similar to stimulant psychosis

Although there are many adverse effects associated with L-DOPA, particularly psychiatric ones, it has fewer than other antiparkinsonian agents, such as anticholinergics and dopamine receptor agonists.

More serious are the effects of chronic levodopa administration, which include:

* End-of-dose deterioration of function
* On/off oscillations
* Freezing during movement
* Dose failure (drug resistance)
* Dyskinesia at peak dose
* Recent studies have demonstrated that use of L-DOPA without simultaneously giving proper levels of serotonin percursors depletes serotonin
* The long term use of L-DOPA in PD has been linked to the so called dopamine dysregulation syndrome.[3]

Clinicians will try to avoid these side effects by limiting L-DOPA doses as much as possible until absolutely necessary.

So physicians limit doses as much as possible, yet we have people using it as a sleep aide here, and we call it safe... why... because it is coming from MP? You want to protect your product, I understand that, but passing off neurotransmitters like is just another creatine is a bit misleading.

 

[strategicmove]

You are making a sweeping statement about a group of people that do not hold back on their dosages. You of all people should know to do something like that. There are users around here utilizing grams of your 50% L-Dopa extract (And I pulled that directly from your bosses writings

Feel free to verify the statement you branded sweeping!
Drop the emotion and re-read my earlier contributions in this thread. Not to sound defensive, as I do not see any need to, yet nowhere did I recommend unbridled consumption of L-DOPA or any other supplement for that matter.

Now how do you go to say people are not taking the doses necessary doses for tolerance, not to mention a nice little decarboxylase inhibitor added?

That was your interpretation. Now, define tolerance! How could you hypothesize about tolerance without knowing in what state the user's dopamine receptors are? In what sense is any discussion of tolerance even meaningful without reference to a dosage protocol or to a usage duration, or both? Where in my comments in this thread did I mention or recommend L-DOPA dosages? If you want to challenge someone's statements, focus on the content of his comments!

Now lets pull side effects, and read the VERY bottom:

So physicians limit doses as much as possible, yet we have people using it as a sleep aide here, and we call it safe... why... because it is coming from MP? You want to protect your product, I understand that, but passing off neurotransmitters like is just another creatine is a bit misleading.

Most supplements have side effects in healthy individuals, and these side effects are usually dose-dependent. L-DOPA is not an exception. Nor are acetylcholine, icariin, serotonin, melatonin, and so on. That is not the point! My thesis is that 1-carboxy or L-DOPA taken in recommended doses in a cycling protocol will not impair dopaminergic function like one of the earlier posters here maintained. Why is that so? A series of chemical reactions in the body ensure only a small amount of the consumed L-DOPA finally gets converted into dopamine. And depending on where this conversion occurs, some of the dopamine will end up as norepinephrine and epinephrine. So, it is not as if the dopamine receptors are constantly bombarded and destroyed from an L-DOPA or 1-carboxy cycle.
Users here that have had a cycle or more of 1-carboxy, PowerFULL, IGF-2, Somnidren-GH, and so on, at recommended doses should compare your list of side effects with what they experienced and make their judgments.

Now to Mucuna Pruriens. I saw your earlier insinuation and ignored it. The reason I mentioned Mucuna at all is because it contains a small amount of L-DOPA, and not because the L-DOPA from it were ineffective.

Finally, your conclusion about protecting my product is completely wrong! Someone earlier expressed concern about IGF-2 and I responded that he had nothing to worry about. Last time I checked, IGF-2 was not part of what you would label my product. My interest in this thread is just to correct certain impressions I thought were inaccurate. Feel free to counter-check everything I have written. Whether people buy 1-carboxy, PowerFULL, IGF-2, Somnidren-GH, and so on or not is completely irrelevant here, and it is their decision. They should have the accurate information to make informed decisions. That is all!

 

[DAdams91982]

Great comment! To add to that, considering that Mucuna Pruriens or even 1-carboxy does not contain anything close to the amount of levodopa administered to Parkinson's patients, the issue of permanent tolerance here is overdone.

1-Carboxy DOES contain the amounts in the pharma grade... especially if people are utilizing powders.

There is no emotion here strat... not emotional, just irritated that people are pushing drugs like this. As for you comment about tolerance, do you really need anyone here to pull study after study about the built tolerance? That is well documented, and I am sure you know that. Now to redirect your own question to yourself, how do you know what state someones receptors are in?

You are harping on said unknowns about healthy individuals, but only provide hypothesis instead of fact why you believe it will not be a problem. I am taking factual study information about built tolerance, but that isn't good enough for this environment? Why?

As for the piece about your product, I say that because this has been focused around 1-carboxy, hence your entrance in to the thread. Not knocking you for that.

 

[strategicmove]

1-Carboxy DOES contain the amounts in the pharma grade... especially if people are utilizing powders.

There is no emotion here strat... not emotional, just irritated that people are pushing drugs like this. As for you comment about tolerance, do you really need anyone here to pull study after study about the built tolerance? That is well documented, and I am sure you know that. Now to redirect your own question to yourself, how do you know what state someones receptors are in?

You are harping on said unknowns about healthy individuals, but only provide hypothesis instead of fact why you believe it will not be a problem. I am taking factual study information about built tolerance, but that isn't good enough for this environment? Why?

As for the piece about your product, I say that because this has been focused around 1-carboxy, hence your entrance in to the thread. Not knocking you for that.

If you seriously think there are no facts in what I have written so far, only hypotheses, then that is up to you. I do not see any further basis to continue this pseudo-discussion, as we have long left the realm of science, and are deeply entrenched in speculations. I invite any interested objective readers to go through this thread, verify my facts (or from your point of view, hypotheses) and form their opinions.

 

[DAdams91982]

If you seriously think there are no facts in what I have written so far, only hypotheses, then that is up to you. I do not see any further basis to continue this pseudo-discussion, as we have long left the realm of science, and are deeply entrenched in speculations. I invite any interested objective readers to go through this thread, verify my facts (or from your point of view, hypotheses) and form their opinions.

Agreed, I will leave you with just one more fact while you are on you way out.

Toxic effects of L-DOPA on mesencephalic cell cultures: protection with antioxidants
B. Pardoa, M.A. Mena , a, M.J. Casarejosa, C.L. Paínoa and J.G. De Yébenesb
aDepartamento de Investigación, Hospital Ramón y Cajal, Madrid ,Spain
bServicio de Neurología, Fundación Jiménez Díaz, Madrid ,Spain

Accepted 28 February 1995.
Available online 6 April 2000.

Abstract
The toxicity of L-3,4-dihydroxyphenylalanine (L-DOPA) was studied in neuronal cultures from rat mesencephalon. The survival and function of DA neurons were assessed by the number of tyrosine hydroxylase-positive (TH+) cells and3H-DA uptake and those non-DA neurons by the exclusion of Trypan blue and the high-affinity3H-GABA uptake. L-DOPA was toxic for both DA and non-DA neurons. DA neurons were more severely affected than non-DA neurons after short periods of treatment and with exposure to a low dose of L-DOPA (25 vs. 100 μM) and less selectively affected after 1 or 2 days of treatment. After incubation with L-DOPA, a disruption of the neuritic network and an overall deterioration were observed, more evident for TH+ cells in the whole culture. Auto-oxidation to quinones is responsible in part for L-DOPA toxicity in non-DA neurons since the levels of quinones correlated well with the severity of cell death in the cultures. The damage of DA neurons took place before the rising of quinones, suggesting that quinones are not essential in L-DOPA toxicity for DA neurons. Antioxidants, such as ascorbic acid and sodium metabisulfite, completely prevented L-DOPA-induced quinone formation as well as the death of non-DA neurons. In contrast, they could only partially prevent the damage produced by L-DOPA in DA neurons. Mazindol, a selective inhibitor of DA uptake, protected TH+ cells from L-DOPA.

Keywords: L-DOPA; Parkinson's disease; Dopamine neuron; Neurotoxicity; Rat mesencephalic cell culture; Ascorbic acid

 

[GoHardOrGoHme]

man and here i was about to open a canal to my mesencephalon to directly inject my purified L-Dopa extract to really get some gains....

I feel that study is showing how L-Dopa in high concentrations in one specific area of the brain can cause damage...but if L-Dopa were to naturally cause such a siginigicant amount of damaged then your own bodies production would render this area of the brain useless in a matter of years. Remember that there are natural means to raise L-Dopa by means of diet and levels fluctuate naturally throughout the day. Times in your life were L-Dopa is the highest (youth) is also associated with the most neuronal development(connections between hemispheres continued to develop till around 25)...so it seems that your are taking that study out of context to prove a point that i feel has no sure footing.

Heaven forbid an individual has a high protein diet giving them an abundant amount of tyrosine to convert into L-Dopa and so on. Also in that abstract it doesnt mention the specific kind of DA receptors within that area, as strat mentioned there are 5 kinds of receptors...specifically D1 and D2 are the emphasis on PD research, and I know for a fact there are many D3 receptors within the mesencephalon(heavily studied for the treatment of schizophrenia).....as well as d4 and d5...so which are the ones dying and in what region of the mesencephalon seeing as you may well know there are many.

So before you try and state a study that L-Dopa is killing dopamine neurons for the sake of those who are studying this thread(myself includied) it will be very helpful to set up:

1)parameters of the study- this study was done in isolate rat cultures
2)applicable nature of those parameters- not an in vivo test subject
3)specifics of the findings that apply to the topic at hand- what kind of receptors at play and are dying


That seems like a specific example of a very useful precursor isolated in a situation that would not occur in vivo...shown to be damaging. Kind of like showing that saying....hey did you know that if you put put a lipase, protease, and a piece of muscle in a in vitro culture, the enzymes will break down the muscle...so dont take extra digestive enzymes with your meal cause you will break down muscles. Something easily takin out of context but hold a grain of truth.

 

[GoHardOrGoHme]

strategic your posts are amazingly dense with a lot of info that will answer about 99.9% of questions on this thread. The best part it was like reading a study guide to last 2 years of college (a total of 64+ neuroscience credits) when it comes to the basics of dopamine neurons.

I really dont see this thread as "drug pushing" MP has been around for a long time and been used in the velvet bean form for a long time. And the L-Dopa increasing aspect of it was true even then...it also increases testosterone, lowers blood sugar, increases urination, etc( the bean when eaten part of a daily diet). Now Parkinsons is a relatively new disease in the span of human history...and there are societies where this bean is eatin throught the year, on a daily basis in high volume(grown as a food crop in guatemala to this day)....and im pretty sure they arent ridden with parkinsons, schizophrenia, and huntigintons. Heck in central america it was even used as a coffee substitute!

So...mucuna...when done right...very good for you!

 

[scoooter]

I'm no bio-scientist but its pretty common info that experimental results in mice & rats sometimes do not directly correlate to the same effect in humans so we must rely on the loggers of products to be our lab rats who self medicate and post the effect here in on-line forums.

 

[GoHardOrGoHme]

its not direct but they are used as models for a reason.

There are a lot of correlations that can be found within drug interactions between mice/rats and humans...but as we all know many things dont directly carry over, but its used as a sound first step in researching. Many, many of the breakthroughs in research started with rats, moved to higher primate testing, and then hit humans and of course was tweaked along the way to account for the vast differences between species.

But good point scooter

 

[DAdams91982]

man and here i was about to open a canal to my mesencephalon to directly inject my purified L-Dopa extract to really get some gains....

I feel that study is showing how L-Dopa in high concentrations in one specific area of the brain can cause damage...but if L-Dopa were to naturally cause such a siginigicant amount of damaged then your own bodies production would render this area of the brain useless in a matter of years. Remember that there are natural means to raise L-Dopa by means of diet and levels fluctuate naturally throughout the day. Times in your life were L-Dopa is the highest (youth) is also associated with the most neuronal development(connections between hemispheres continued to develop till around 25)...so it seems that your are taking that study out of context to prove a point that i feel has no sure footing.

Heaven forbid an individual has a high protein diet giving them an abundant amount of tyrosine to convert into L-Dopa and so on. Also in that abstract it doesnt mention the specific kind of DA receptors within that area, as strat mentioned there are 5 kinds of receptors...specifically D1 and D2 are the emphasis on PD research, and I know for a fact there are many D3 receptors within the mesencephalon(heavily studied for the treatment of schizophrenia).....as well as d4 and d5...so which are the ones dying and in what region of the mesencephalon seeing as you may well know there are many.

So before you try and state a study that L-Dopa is killing dopamine neurons for the sake of those who are studying this thread(myself includied) it will be very helpful to set up:

1)parameters of the study- this study was done in isolate rat cultures
2)applicable nature of those parameters- not an in vivo test subject
3)specifics of the findings that apply to the topic at hand- what kind of receptors at play and are dying


That seems like a specific example of a very useful precursor isolated in a situation that would not occur in vivo...shown to be damaging. Kind of like showing that saying....hey did you know that if you put put a lipase, protease, and a piece of muscle in a in vitro culture, the enzymes will break down the muscle...so dont take extra digestive enzymes with your meal cause you will break down muscles. Something easily takin out of context but hold a grain of truth.

Seriously... so which ones are dying? Honestly, is it okay for any of them to die? You are still separating L-DOPA and Mucuna... 1-carboxy is 50% L-DOPA... thats not some magical l-dopa that is void of the negatives.. it is real L-Dopa.

I feel like I am talking at a rock.. when the study doesn't suit your side of the argument, you want to ineffectively refute it, without showing the evidence to the contrary.

By all means, keep playing with neurotransmitters to help you sleep... might as well go slam your head into a wall while you are at it.

So effectively slamming your head into the wall is very good for you!

 

[Urban Monk]

A good thread to refer back to:

http://anabolicminds.com/forum/nutraplanet/66763-1-carboxy-2-a.html

 

[bigmoe65]

I think the fact of the matter is not any real spectacular gains are going to be achieved from taking MP. So why even bother.

 

[GotTest]

Now, this all being said would it be BETTER/EFEECTIVE/SAFER to raise dopamine levels by using a dopamine agonist like Caber?

 

[GoHardOrGoHme]

now adams i am doing no such thing...i only slam my head into walls on special occasions

understand the only reason why i refute is when i find holes and understand your article is effectively not proving ur point. And yes it matter wat receptor are dying in what parts of the mescencephalon. And remember those neurons died in culture when L-Dopa was directly injected into rat cells...you dont see how that is different from supplementing some MP via diet?

And understand we have shown evidence, we present facts and u say dispute their validity. What have I or strategic said that doesnt stand true? Have you not fully read my posts? or strategic posts? I mean thoroughly read and comprehended what we are trying to get across?

I can understand these posts can be long winded but i believe they hold some good info to answer ur questions.

What your getting at is the risk of abusing a supplement...im saying proper supplementation can lead to benefits...look up the benefits of velvet beans where mucuna is extracted from. Also look up the benefits of mucuna and its history of use in different civilizations. Now compare that to present day PROPER supplementation.

 

[GoHardOrGoHme]

i dont know anythign about caber or dopamine agonist supplementation... the most ive used is Lipotrohin PM with mucuna and powerfull with 1 carboxy. Both are excellent supps.


When u say spectacular what are u comparing it to? I think my gains on powerful were spectacular...but yet im a very meat and potatoes athlete that the smallest extra is huge for me

 

[scoooter]

So I bumped into this little tid bit which finds another "natural" compound, not MP, can be used to derive L-dopa.

Derived from the Red Velvet Bean (no synthetic drugs are found in
this product), L-Dopa is a nutrient which causes a flood of positive fitness,
health promoting and anti-aging effects due to its ability to increase natural
human growth hormone. In 2002, a U.S. Patent was filed on the use of Red
Velvet Bean to stimulate the release of human growth hormone. Research
cited that the L-dopa precursor is converted to dopamine and stimulates
release of growth hormone via the pituitary. By naturally coaxing the body
to make more of it's own biologically perfect HGH, we avoid the side effects
(and huge expense) of synthetic alternatives.

 

[GoHardOrGoHme]

yep as i said in early posts the velvet bean is used to extract Mucuna P.

Basically you get all the goodies non of the badies....which is the purpose of supping Mucuna....or u can just eat **** tons of velvet bean and get the same benefits

From personal research i deduced PureDopa or 1-carboxy is extracted from Dolichos Pruriens L. (stated on the back of the bottle) and if i am not mistaken that is just another version of mucuna derived from similar if not the same plants.....so in essence what sets powerfull apart is that it is still the same safe ingredients but the extraction is different in order to improve efficacy.

 

[strategicmove]

So I bumped into this little tid bit which finds another "natural" compound, not MP, can be used to derive L-dopa.

Derived from the Red Velvet Bean (no synthetic drugs are found in
this product), L-Dopa is a nutrient which causes a flood of positive fitness,
health promoting and anti-aging effects due to its ability to increase natural
human growth hormone. In 2002, a U.S. Patent was filed on the use of Red
Velvet Bean to stimulate the release of human growth hormone. Research
cited that the L-dopa precursor is converted to dopamine and stimulates
release of growth hormone via the pituitary. By naturally coaxing the body
to make more of it's own biologically perfect HGH, we avoid the side effects
(and huge expense) of synthetic alternatives.

Mucuna Pruriens (L) is sometimes referred to as Velvet Bean, Cowitch, Cowhage, Kapikachu, and so on.

 

[scoooter]

yep as i said in early posts the velvet bean is used to extract Mucuna P.

Basically you get all the goodies non of the badies....which is the purpose of supping Mucuna....or u can just eat **** tons of velvet bean and get the same benefits

From personal research i deduced PureDopa or 1-carboxy is extracted from Dolichos Pruriens L. (stated on the back of the bottle) and if i am not mistaken that is just another version of mucuna derived from similar if not the same plants.....so in essence what sets powerfull apart is that it is still the same safe ingredients but the extraction is different in order to improve efficacy.

I agree, what sets products and/or companies apart that use the same compound is their extraction technique. Know of any links that explain (in laymans terms please) how these processes are performed ?

 

[matthias7]

Quite an interesting thread.

A very interesting thread.

If you are at risk of Parkinson's better not take Powerful 'cause of tolerence. Whether Powerful could cause Parkinson's ... I think that really serious dopamine antagonists (illegal drugs) would get there first.

I understand from a neurologists point of view this stuff is for therapy not lifestyle, but it demonstrates that this stuff does work.

I'd cycle them BTW - thats what I'm doing. 8 weeks PowerFull + ZMA 8 weeks GABA, threanine, ZMA + other, 4 weeks off.

 

[GoHardOrGoHme]

Considering L-Dopa enhancing herbs/foods have been around before Parkinsons and individuals who consume there herbs and foods on a daily basis have yet to show a tolerance to L-Dopa treatment...ive yet to see any evidence that CORRECTLY cycling powerfull will cause tolerance (can you tell i have still be researching this topic haha)

I think a normal 8-10 weeks on/12 weeks off cycle of powerfull will ensure that no tolerance will be aquired.

Or maybe ill just down 5 lbs of velvet beans a day

 

[DAdams91982]

Considering L-Dopa enhancing herbs/foods have been around before Parkinsons and individuals who consume there herbs and foods on a daily basis have yet to show a tolerance to L-Dopa treatment...ive yet to see any evidence that CORRECTLY cycling powerfull will cause tolerance (can you tell i have still be researching this topic haha)

I think a normal 8-10 weeks on/12 weeks off cycle of powerfull will ensure that no tolerance will be aquired.

Or maybe ill just down 5 lbs of velvet beans a day

Holy hell man... please prove it wrong. The tolerance is WELL documented. There is nothing stating the otherwise.

 

[GoHardOrGoHme]

so you are telling me that if i eat velvet beans i will develop a tolerance to L-Dopa?

I know L-Dopa therapy causes tolerance. Do you know what L-Dopa therapy implies?

 

[GoHardOrGoHme]

Also Mucuna extracts are more then L-Dopa...they actually contain additional substances that protect against L-Dopa toxicity and is neuroprotective.

Also there are studies of infertile men taking mucuna ( yes it increased seminal count and also was noted had a relaxing effect on the men) and they noted no negative side effects

Remember im not saying that is you consume levadopa for along duration and in high quantities you wont develop a tolerance. What im saying is i cant find that mucuna extracts cause a tolerance to L-Dopa therapy....do you understand the difference in what im saying?

 

[GoHardOrGoHme]

Let me quote this from a long term study using Mucuna in the treatment of parkinson's

"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."

Effect of antiparkinson drug HP-200 (Mucuna pruriens) on the central monoaminergic neurotransmitters
Bala V. Manyam 1 *, Muralikrishnan Dhanasekaran 1, Theodore A. Hare 2


So tell me how are you going to develop a tolerance to L-Dopa therapy if it doesnt increase the concentration of L-Dopa in the area you are concerned with developing a tolerance to?

YES L-DOPA CAN CAUSE TOLERANCE WHEN HABITUALLY SUPPLEMENTED IN A L-DOPA THERAPY FOR THE TREATMENT OF PARKINSON'S <- put in caps so you understand that i know this(not because im mad)

But it seems like your fears of tolerance to L-Dopa therapy (which is targeting the nigrostriatal pathway) is more based on fear then on meticulous knowledge of the subject. It is abundantly clear you know a lot of information on how L-Dopa interacts with the substantia nigra and hardcore supplementation can cause tolerance, but if mucuna supplementation does not increase endogenous concentrations...wouldnt you agree it is highly highly improbably for it to cause a tolerance to future treatment which is directed to that are?