I had not heard this in the past so I am wondering what does this all mean?
So maybe there is dopamine being made but the cells can't use it properly?
"Dopamine, epinephrine and norepinephrine are the main catecholamines (a label based on having part of the same molecular structure). These hormones are made by your adrenal gland, a small hat-shaped gland located on top of each of your kidneys."
~50% made in gut, most of the rest is made in substantia nigra & hypothalamus. This is in people who don't take levodopa. If you take levodopa orally then you probably make over 90% of your dopamine in your gut.
That is nonsense. If you take levadopa orally, whilst some is converted to dopamine in the gut, in most people, most of the levadopa is absorbed into the blood as levadopa via the gut and then transported by the blood to the brain, where it is converted into dopamine. So people taking levadopa with Carbidopa probably make over 50% of their dopamine in the brain
with respect to oral C/L leading to "levodopa resistance" due to gut colonization of bacteria that metabolizes levodopa in gut that prevents reaching the brain see:
That is why you aren't suppose to take C/L with a meal. e.g. a higher concentration to pass into your blood, less to compete with to pass to blood, especially less competition with protein, less presence of probiotics in your gut to convert levodopa to dopamine.
The carbidopa inhibits (hinders) the conversion, it does not stop it.
If you take C/L orally your gut changes over time such that your microbiome metabolizes more and more of the C/L in your gut, slowing motility AND reducing levodopa availability to the brain, just to name two of the complications. As time goes by the same dose of C/L has less of a response to the patient because less dopamine is made in the brain, due to reduction in available substrate, levodopa, meanwhile the increasing dose of carbidopa causes vitamin deficiencies. The patient gets in a negative feedback loop of increasing C/L dose for diminishing PD effectiveness while increasing constipation, malnutrition and vitamin deficiencies.
This feedback loop is totally unrelated to the protein competition problem, but that should be greatly reduced by the subcutaneous pump as well.
Dopamine decarboxylase inhibitors prevent the conversion of levodopa to dopamine in the periphery. ncbi.nlm.nih.gov/books/NBK4...
The blood-brain barrier (BBB) is an important physiological barrier that separates the central nervous system (CNS) from the peripheral circulation... (I question, if they meant the entire CNS.) pubmed.ncbi.nlm.nih.gov/333....
The sub_q pump may well be a game-changer. Your links didn't establish that 50% of dopamine is synthesised in the gut. And you said 90%... "if you take levadopa orally". Can you point out in your links, or anywhere else for that matter how you achieve that calculation? The CSF assays suggest nothing of the sort.
Yes I have heard this in the past so I found it surprising that the article said the dopamine was made in the adrenals and of course the carbidopa helps the levodopa in pills cross the blood brain barrier so I guess I was wondering if the adrenals somehow figure in to all this
Posting the same message on a forum almost daily for 10 years can be considered as spam. If you also make references to selling your books on Amazon, it can be seen as a disguised form of self-promotion and advertising for your books. Posting repeated messages with commercial intent on HU is considered inappropriate and can be regarded as spam behavior.
But it's not the right message. In your book, you write about your serious problems with stress, which you mentioned 10 years ago at HU. Now, it's only about fast walking, which helped you to get rid of your stress, the underlying problem. Again, I'm not making this up; it's mentioned alongside other valuable information that you never share with us, all in your book. Even about diet LynnP1974 😉 Your current spam message seems to be mainly focused on promoting the sales of your book and benefiting the multinational Amazon.
Why isn't your entire book available for free on a website, or are you still working on adapting your story for a new edition? 🤔
I have your book!❤️ My husband was diagnosed last year. He’s 52. What’s your opinion on including a lot more fatty red meat in your diet? It seems like patients on the medication don’t eat much protein because protein competes with the meds. He’s not taking any meds yet. He’s eating fatty red meat, going very low carb and trying to keep moving and exercising every other day or every third day depending on how he feels.
The body produces most of its dopamine and noradrenaline from the adrenal glands.
Most of these chemicals are produced as precursor molecules which then get converted in different areas. There is fine tuning at the tissue level that determines what turns into the other. That is why you cannot directly measure dopamine or noradrenalin levels in blood to meaningfully interpret the significance
In fact thyroxine, dopamine, noradr etc all have the same precursor. That
Eg adrenaline is formed from noradrenaline within vascular tissue to act on blood vessels , heart etc and lungs
Thyroxine is made by the thyroid glands using the precursor and adding other parts to it to chnage it and then stores it.
Science as we know it has tried to reproduce these chemical structures to create the synthetic versions and related chemicals that mimic the version of the type found in relevant tissue
Synthetic intravenously used dopamine is similar to brain dopaine that works D2 receptors in the brain. These D2 receptors are also found in gut (duodenum) and kidneys etc
Levo dopa is a short form of a levorotatory crystalline salt of dopamine that is probably more stable than a dextrorotatory salt version for packaging as a pill . For that matter levo thyroxine is used as tablet supplement for thyroxine deficiency.
The brains version of dopamine is less widely known , but we do know that there are atleast 6 identified dopamine receptors with different distribution in various parts of the brain.
Levo Dopa clearly shares many of the characteristics of the "parent compound " in that it does replace the function of many or most of the Parkinsonian function lost when there is identified loss of neurons in some of the areas associated with neuron loss in Parkinsons (usually having a high density of D2 and D3 receptors - substantia nigra, putamen etc)
I may have more information once I get hold of the detailed chemical composition of the Produodopa used in the new subcutaneous pumps) although I have no time now (it may take a while)
Regular intravenous dopamine is cheap as chips (we splashed it around when I was an internal medicine resident equivalent even in 1990s India but the monthly cost of the Produodopa is estimated as a few thousand British £££ per person so there must be a difference ????
Any so called foods that boost dopamine production are just a list of foods that have good levels of the essential aminoacids required for the precursor molecules.
Essential because they need to be in your diet as the body cannot make them from carboon, hydrogen and nitrogen.
pearlette . I am sure that you have given the cliffs notes version of the dopamine saga and I probably have to go deeper into biology in order to fully grasp the intricacies of the mechanics involved.
This just tells me that the Levodopa "experiment" if you will is just that. An experiment. Perhaps there's more to learn about the science behind Parkinson's than we give credit for? Maybe we still have hope? For new science and new treatments to come?
I had a suspicious feeling when I was more an internist that there was more to this disease. Then I became a critical care physician and waved so much of dopamine and norad syringes around that I thought I had understood these "drugs".
When I suspected that I had Parkinsons over 8 years ago , I read up about the science expecting that while people talked of all the fancy stuff about genes therapy and stem cells, someone would have looked at the basic sciences too.
I still feel that there is a simpler and more natural way of getting this beast under control. I have accepted that every ray of hope can be crushed as easily as it sprouts by the harshness around but I try and learn from the small wins and from the failed ones too.
And everyday I thank myself for reading Norman Doige's original book
"The Brain that changes itself " about 6 months after I was diagnosed. I was able to accept the promises of neuroplasticity so much more emotionally. In my past life I would have been more cynical of his upbeat rendition of outcomes !
“The Function determines the Structure” , if this axiom is true, maintaining the body in a very functional state it will repair the structure of the damaged organ that , in our case, is the brain.
This is why it is important for the Soul, that drives body , stay in excellent condition and does not fall in apathy, so to be able to push the entire organism through the bad condition determined by the disease.
This is how function imposes itself on structure. Easy to say but not to do.
Perhaps an old Indian proverb is valid for this purpose, it goes more or less like this: "Force yourself to smile and rejoice and soon you will feel like this, more cheerful and joyful", and I would add even more vital.
This is a good causal point to start from, that is, to exploit the ability to cause our own positive emotions rather than having them determined by the environment. Maybe.🤔
Make your life beautiful and interesting like a work of art.🤗.
Greetings from Italy.
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P.S. Definition of Function:
noun
1.an activity that is natural to or the purpose of a person or thing.
"bridges perform the function of providing access across water"
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Etymology of art:
The word art derives from the Latin ars which has as its first meaning any activity aimed at designing or building something in a suitable and harmonious way. The Latin word comes from the Sanskrit root *arche which expresses "going towards" and in a translated sense, "adapting", "doing", "producing".
…as you can see, we like definitions based on "how to do it" rather than descriptive ones.😊
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