L-DOPA: Episode 1 of the our Ingredient Insights Series!

Just to inject a quick foreword here:
As promised I went well and deep into L-Dopa, and this might come across as quite heavy learning.

But hey, I'm sure you've got plenty of time on your hands locked up in your lockdown cubby-hole. And really, if you can take away even just a fraction of the learning from this deep dive they will certainly come in handy for the future.
Knowledge begets knowledge.

So believe in yourself, I believe in you - anyone can learn, you just have to be willing to try! And now I am proud to present, L-DOPA - Episode 1 of Ingredient Insights!(aka. Levodopa)(L-3,4-dihydroxyphenylalanine)


What is L-Dopa:

L-DOPA is a Large Neutral Amino Acid (LNAA) made from the hydroxylation of L-Tyrosine, and is a precursor of notable neurotransmitters dopamine, adrenaline and noradrenaline. L-DOPA is also an essential precursor of melanin (what we often know for its skin colouring property) which is present in plants and animals.

We can source L-Dopa from a great number of plants, most commonly Mucuna Pruriens and others of that family. That said, the majority of L-Dopa used in the medical community (mainly for Parkinsons) is directly synthesised in the lab rather than from plant extracts. The supplemental community tends to prefer plant extract forms, likely for regulatory reasons… but there is also some evidence to suggest plant derived L-Dopa advantages over synthetics. You will find L-dopa in a good number of high stimulation nootropics, as well as libido supplements.

Why its Supplemented/Prescribed:

The simple answer - supplementing with L-Dopa is useful as it can cross the Blood Brain Barrier (BBB) then act as a direct building block to our much loved neurotransmitter dopamine. Dopamine found its fame for its action in the Central Nervous System (CNS) (aka. Brain & Spinal cord) where it plays a major role in mood and reward-motivation pathways… it makes you feel good when you do certain tasks, encouraging repetition of that task. So for those that like to feel good, it can be nice to have a the required materials to do so on hand.

Dopamine also has a host of actions in both CNS and outside (and not necessarily actions we want). But a notably valuable contribution is its role in motor control pathways, such that for Parkinsons patients (who characteristically have lost/damaged dopamine secreting cells) it can be life changing to supplement with L-Dopa as a source of dopamine.

Metabolic Challenges:

While L-Dopa supplementation can reignite movement in those without, as with any input, there will always be tradeoffs. L-Dopa must be consumed orally in fairly large quantities, which is then transferred into the bloodstream before crossing the BBB. The challenge is that the enzyme Dopa decarboxylase (DDC) will metabolise L-Dopa to dopamine too fast, and dopamine cannot cross the BBB. When excessive dopamine is present outside of the brain, a number of nasty side effects can occur including vomiting and nausea.

So in steps Carbidopa! Carbidopa is an inhibitor of DDC, this allowing more L-Dopa to cross the BBB. But alas, another challenge arises, as this then upregulates the second main metabolic pathway of methylation to 3-O-Methyldopa via Catechol Methyltransferase (COMT). This brings with it a number of undesirables, including decreased dopamine uptake and increased cell oxidative damage and death. Newer understanding is linking 3-O-Methyldopa to a number of downstream side-effects of chronic use of L-Dopa. Concepts such as introducing a COMT inhibitor to the mix is also proposed, as well as the different effects plant sourced L-Dopa is demonstrating.

There's also the challenge of LNAA transporter systems. Some journals discuss the how that at the BBB can be easily saturable.

TLDR:

L-Dopa is a valuable supplement and medication for its function as a precursor to Dopamine. This can support better mood and reward motivated behaviour, as well as motor control for those previously deficient. Though necessary as in the case of Parkinsons, chronic use should be avoided if possible due to side effects of excessive dopamine and 3-O-Methyldopa. For maximum efficiency of conversion to dopamine within the CNS, Dopa decarboxylase and Catechol methyltransferase inhibitors can be considered.

All up - an interesting an complicated ingredient! I hope this has been helpful - and especially for those in the industry, would love to hear your feedback on any points I may have glossed over, mislead or straight up boggled up. This walk through hasn't been evaluated by a acreddited professional, just a dude who reads waaaay to much. #notadoctor #justlikereading

 

Extra Reading Resources:

If you're keen to do some extra reading on the topic, check out the resources linked below that I were particularly useful in establishing my knowledge. If you have any issues getting access to the full papers, let me know and I'll be happy to help. :)

  1. A. Levodopa: the story so far. Nature 466, S6–S7 (2010). 
  2. The role of L-DOPA in plants. Plant Signalling & Behavoir. (2014)
  3. Pharmacokinetics of L-dopa. Journal of Neurology. (2006).
  4. Levodopa in Mucuna pruriens and its degradation. Nature Research. (2014)
  5. The role of 3-O-methyldopa in the side effects of L-dopa. Neurachem Research. (2008)
  6. Mucuna pruriens in Parkinson’s disease: a double blind clinical and pharmacological study (2003). Journal of Neurology, Neurosurgery & Psychiatry.

There's also this excellent explainer video by 2-Minute Neuroscience:

If your still thirsting for more after all that, just shoot me an email at thomas@vitakea.co.nz and I'd be very happy to shoot over some more resources!

Where can I get L-Dopa in New Zealand?

First important to note, L-Dopa is a prescription substance in New Zealand. So if you do not have a prescription, then tough cookies mate. However Mucuna Pruriens is perfectly legal, and is available in a number of nootropic stacks we have here at VitaKea. So take a look around and see what you fancy! 


Any questions, thoughts, critique?

Key players in my current health regime include meditation, regular exercise (type depending on current fixation), early to bed, early to rise, packing in as many fungi leafy greens as possible. 
My 
supplementation varies as I test out new protocols. That considered, I prioritise anything that can be utilised for long-term benefits. Of course, for special cases I can definitely appreciate a good stimulant, or perspective modifier.


Sincerely,

Your KeaLad, Thomas.

 


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