More re DOPAL, DOPAC, L-Dopa, ALDH from the researcher
 

What the researcher, Dr. Michael Panneton, has to say about DOPAL, DOPAC, L-Dopa, ALDH: Printed with his permission. (Note: Part of this was posted previously and removed. With this repost, new material has been added.)

I wrote to Dr. Panneton and posed the question:

"Does L-dopa also produce this toxic chemical [DOPAL] when it breaks down? As we alleviate symptoms, are we feeding the disease?"

He replied:

" I first must state that I am not a clinician but rather a basic science researcher who never sees patients. That said I will tell you what I know of L-DOPA.

In Parkinson disease a pathological finding is that the dopamine neurons in the substantia nigra part of the brain degenerate and die. There are many theories circulating as to why these neurons die, and we are the principal proponents of the 'catecholaldehyde hypothesis'. This idea is based on the natural breakdown of dopamine by the cells. As much as we appear the same most of the time, the chemicals of which we are made are constantly breaking down and being replaced. Dopamine is one such chemical. First, dopamine is made by a chemical conversion of L-DOPA. Dopamine is broken down by an enzyme called monoamine oxidase (MAO) which causes a chemical change of the molecule into a product called 3,4-
dihydroxyphenylacetaldehyde (DOPAL for short). Aldehydes, though relatively common in the body, are toxins which makes cells sick, so the body makes it a priority to eliminate them from cells. DOPAL is thus quickly broken down by yet another enzyme called aldehyde dehydrogenase (ALDH) into a non-toxic chemical we call DOPAC for short.

We and others have shown previously that DOPAL circulated among dopamine cells growing in dishes kills them; my recent paper documents that DOPAL injected into the substantia nigra of the rat also kills only the dopamine cells in living animals while sparing nearby non-dopaminergic cells. It recently has been shown by investigators at the NIH that analysis of 14 brains of people who died with Parkinson disease had 4.4 times more DOPAL than the brains of people without Parkinson disease. Thus there is basis for this theory.

So, where does L-DOPA enter in? Neurons are all interconnected and use chemicals called neurotransmitters to communicate with each other. Dopamine, a neurotransmitter, is decreased in an area of the brain called the striatum (this is important for controlling movements) when the dopamine producing cells in the substantia nigra die. The most widely used therapy by clinicians is an attempt to replace that lost dopamine by L-DOPA. Thus ingesting L-DOPA provides more substrate and makes more dopamine, ergo, many of the symptoms of Parkinson disease are alleviated at least for awhile. L-DOPA therapy however has problems. Indeed 50% of patients on L-DOPA therapy develop dyskinesias (abnormal voluntary movements) within 5-10 years and these dyskinesias can be very troubling.

Now back to brains of Parkinson victims. The enzyme which quickly breaks down DOPAL (eg., ALDH) is DEFICIENT in the brains of Parkinson patients. This implies that DOPAL would thus stay in the cell longer and since it is toxic, would continually make these cells sicker and sicker and eventually they would die. Thus if L-DOPA is given to patients to make more dopamine, more DOPAL would also be created, and since DOPAL is not being eliminated at a normal rate, more dopamine cells would be killed. IN THEORY, thus L-DOPA may exaggerate the disease with time. "

He added:

"The specific gene which we are targeting is the ALDH1A1 isoform which apparently has been cited to be selectively located only in brain dopamine neurons and the cornea. We are proposing to make a "knockout rat" which has a deficiency in this aldehyde dehydrogenase enzyme. If this works we may indeed have an animal model upon which numerous studies can be made. We hope that its deficiency will induce DOPAL to increase, thus killing the dopaminergic neurons, and inducing Parkinsonian symptoms. If a viable animal model is produced it can provide a substrate upon which innumerable studies can be done to stimulate this enzyme to work harder, eliminate the DOPAL and hopefully eradicate Parkinson disease. We now unfortunately are in a Catch 22 situation; the animals cost money to produce (which we are lacking in these tough financial times - the NIH budget is going to be reduced yet again says Congress) but we need the animals to start more work."

What this tell me:
 

IMHO, Dopamine replacement therapy AS PRACTICED NOW is doomed from the start because it increases the toxin DOPAC without having the ability (which healthy cell have) to neutralise it, hence accelerating cell death.
Until this problem is resolved, I would avoid dopamine replacement, trying to make most efficient use of available dopamine through reduced stress and natural diet/supplement to boost dopamine and reduce the effectiveness of acetocholin.
cheers
Imad

Mark, I tried to avoid Sinemet & other meds for the first 3 years after diagnosis, but then when tremor got too bad to bear went on Sinemet for a few months, got terrible dystonia from it, quit the Sinemet, dystonia then disappeared, but tremor & slowness, etc., got so bad I'm now starting Mirapex. Hope I don't regret it too much.

Also, Mark, what do you take for diet/supplements? Mine: creatine, COQ10, resveratrol, fish oil, Amlodipine (for HBP but also possibly PD), multivitamin, Vitamin D, ibuprofen, aspirin, estrogen patch (may be relevant for PD), plenty of nuts, vegetarian + fish (for Omega 3), dance, yoga, walking, biking, aquatics class, plenty of sleep & rest, avoid stressful situations, etc. Yet I do get worse, esp. severe tremor. Any other thoughts?

we are in same boat
 

Poney
We are all forced at some point to take offered medication hoping for immediate relief and overlooking long term bad side effects. This strategy is specially logical if you were at my age (67).
As regarding supplements I found low carbo diet with plenty of coconut oil is good to maintain high energy.
cheers
Imad