My requirement for levodopa is declining. I will address why later.
When diagnosed nearly 20 years ago, I was prescribed 300mg of levodopa. Within about 8 to 10 years, I had increased to around 800mg per day. I then started to take an interest in various supplements and treatments.
In the subsequent years, I was able to reduce my total daily levodopa to around 125 to 150mg.
Yesterday,at 8-00am I took just 50mg levodopa plus Mirapexin 0.7mg, trihexyphenidyl 2mg and azilect 1mg.Within 30 minutes I was on, and only switched off 4 hours later, at 12-00. I had lunch at 1-00pm. As soon as I started to eat, I switched on again, and the on lasted 1.5 hours. Yet there could be no contribution from the 8-00am dose of levodopa.
I have seen this effect before, that either swallowing or chewing switches me on. Since my last levodopa was 5 hours ago, and then only 50mg, and a half life of just over 2 hours, I must be generating some of my own dopamine. However, when on, I suffered dreadful diskinesia
What is going on?? Over the years I have tried all manner of supplements and treatments. Previously 50mg of levodopa was totally incapable of switching me on. Now 50mg lasts me 4 hours on, and this is after 20 years of progression of thre disease.
I can only assign the improvement to consistently taking at aleast 1,000mg of curcumin per day.for around 8 years. I use the type containing piperine (bioperine). All the other supplements were quick, flash in the pan type and had no short term improvement. Curcumin must have steadily reactivated or regenerated dopamineric neurons until I can last 1.5 hours hours on my own dopamine.
Do others see mealtimes acting as a spur to initiating an on period ? This information should give researchers a clue to what triggers being switched on, and starting to regenerate own dopamine production.
Ron

Ron,

This is fantastic news! It supports a hypothesis I just ran across last week that proposes not all of our neurons are dying, some are just impaired by alpha-synuclein. There are now indicators that alpha impedes signaling long before cell death. Further supporting this is a study of advanced PD through PET scans showing that twenty years post diagnosis we still have an endogenous dopamine reserve. I'd say that you provide even further proof. This is from the study on alpha-synuclein:

“Even people with advanced Parkinson’s still have a substantial number of dopamine-producing neurons that remain. Our prediction is that even the neurons that survive don’t work very well, due to functional impairment at synapses.”

You are so right! If they started treating us from a "glass half full" perspective, they would actually be doing something novel and beneficial instead of with the usual there's nothing to be done routine of pills and a pat on the back.

As for your food question. I have noticed that sometimes I have to eat in order to switch back "on"; however, it is usually in the later morning or early afternoon. I don't note that any particular food source (carb vs. protein) plays a role.

Laura

Ron-
I often find that a bite to eat will kick me on. I've always marked it off to glucose levels but I have no other sugar problems so that may be entirely wrong.

I do think that your loyalty to curcumin has paid off for you. A couple studies of note:


1. Acta Neuropathol. 2008 Apr;115(4):479-89. Epub 2008 Jan 10.

Curcumin inhibits aggregation of alpha-synuclein.

Pandey N, Strider J, Nolan WC, Yan SX, Galvin JE.

Department of Anatomy and Neurobiology, Washington University School of Medicine,
St Louis, MO 63110, USA.

Aggregation of amyloid-beta protein (Abeta) is a key pathogenic event in
Alzheimer's disease (AD). Curcumin, a constituent of the Indian spice Turmeric is
structurally similar to Congo Red and has been demonstrated to bind Abeta amyloid
and prevent further oligomerization of Abeta monomers onto growing amyloid
beta-sheets. Reasoning that oligomerization kinetics and mechanism of amyloid
formation are similar in Parkinson's disease (PD) and AD, we investigated the
effect of curcumin on alpha-synuclein (AS) protein aggregation. In vitro model of
AS aggregation was developed by treatment of purified AS protein (wild-type) with
1 mM Fe3+ (Fenton reaction). It was observed that the addition of curcumin
inhibited aggregation in a dose-dependent manner and increased AS solubility. The
aggregation-inhibiting effect of curcumin was next investigated in cell culture
utilizing catecholaminergic SH-SY5Y cell line. A model system was developed in
which the red fluorescent protein (DsRed2) was fused with A53T mutant of AS and
its aggregation examined under different concentrations of curcumin. To estimate
aggregation in an unbiased manner, a protocol was developed in which the images
were captured automatically through a high-throughput cell-based screening
microscope. The obtained images were processed automatically for aggregates
within a defined dimension of 1-6 microm. Greater than 32% decrease in mutant
alpha-synuclein aggregation was observed within 48 h subsequent to curcumin
addition. Our data suggest that curcumin inhibits AS oligomerization into higher
molecular weight aggregates and therefore should be further explored as a
potential therapeutic compound for PD and related disorders.


PMID: 18189141 [PubMed - indexed for MEDLINE]



1. BMC Neurosci. 2010 Apr 30;11:57.

Curcumin reduces alpha-synuclein induced cytotoxicity in Parkinson's disease cell
model.

Wang MS, Boddapati S, Emadi S, Sierks MR.

Department of Chemical Engineering, Arizona State University, Tempe, AZ
85287-6006, USA.

BACKGROUND: Overexpression and abnormal accumulation of aggregated
alpha-synuclein (alphaS) have been linked to Parkinson's disease (PD) and other
synucleinopathies. alphaS can misfold and adopt a variety of morphologies but
recent studies implicate oligomeric forms as the most cytotoxic species. Both
genetic mutations and chronic exposure to neurotoxins increase alphaS aggregation
and intracellular reactive oxygen species (ROS), leading to mitochondrial
dysfunction and oxidative damage in PD cell models. RESULTS: Here we show that
curcumin can alleviate alphaS-induced toxicity, reduce ROS levels and protect
cells against apoptosis. We also show that both intracellular overexpression of
alphaS and extracellular addition of oligomeric alphaS increase ROS which induces
apoptosis, suggesting that aggregated alphaS may induce similar toxic effects
whether it is generated intra- or extracellulary. CONCLUSIONS: Since curcumin is
a natural food pigment that can cross the blood brain barrier and has widespread
medicinal uses, it has potential therapeutic value for treating PD and other
neurodegenerative disorders.


PMCID: PMC2879277
PMID: 20433710 [PubMed - indexed for MEDLINE]

ie not dead. THis is something I have felt for a long time. For example, so many of us report being more mobile after a good nights sleep.
Laura, so much of the information you post above confirms we still have the ability to generate dopamine, if it can be awakened.
Rick, your refs fit in very well,

"Our data suggest that curcumin inhibits AS (alpha synuclein) oligomerization into higher
molecular weight aggregates and therefore should be further explored as a
potential therapeutic compound for PD and related disorders."

" RESULTS: Here we show that
curcumin can alleviate alphaS-induced toxicity, reduce ROS levels and protect
cells against apoptosis."

Curcumin is not an immediate overnight miracle, it seems to need regular doses over a long period to have an effect. It does seem to stop AS from polymerising into oligomers (polymers formed from 2, 3 or 4 monomers), which then block the dopamine neurons.
A quick search showed swallowing does have an effect on brain chemistry, but I have not found data yet to show dopamine production is enhanced.
Ron

My theory is that balance in everything, it is the key I think to something that initializes outside the brain and causes the consequent response dead or dormant cells in the substantia nigra.
I manage my medication well.At times I can take significantly less, Every person's body chemistry is different hence our symptoms differ as much as our medication regimes
We are test tubes and every one of us has a different mixture.Fluid balance also can make an incedible difference,the bodies transport system,easy to maintain but much neglected.
The cure or solution could be different fo each of us

I have at times noticed a boost[although not always] to my alertness and function with small amounts of protein,usually a resonse to a craving,not an addictive one. So are dopamine levels boosted naturally? or with meds? The effects usually kick in within 10-to-30 minutes.

Fact is Protein foods are broken down into their amino acid building blocks during digestion. One amino acid, called tyrosine, will increase the production of dopamine, nor epinephrine and epinephrine. These essential neurotransmitters are comple beyond understanding,but patterns emerge,that is perhaps what we should analise.We are complex and compromised more than we understand by diet emotion,living

Most of us eat a high carbohydrate breakfast as cereals have become the norm. I read an atrticle some time go by a bio-pharmacist and it was his opinion that breakfast is the time of day for eating a high protein meal.
Food for thought.Hippocraties was no oaf let thy medicine be thy food

Sometimes when my pills don't seem to be kicking in, I'll remember that I haven't eaten enough or soon enough. Once I eat, then the pills work. I've thought it was something to do with blood sugar, but I don't really know.

Ron, the curcumin I have right now is a "horse pill". I have to dissolve it and make a smoothie to get it down. Do you know of a source for a smaller one or a capsule I could open. I'm away from home right now, but I think it's Dr. Best and I know I ordered it with bioperine on your advice. I think it makes a difference and I'd probably be better off if I took it more regularly. Thanks for letting us know about it and your results.

Hi Wendy,
I buy from iHerb, and they are also horse pills.
However, I suck them for a minute, then as it breaks up I take a drink to wash the small particles down. It is quite easy to do.
Hope this helps.
Ron

Hi Ron,

What was your experience with the Longvida circumin? thx md

I have at times noticed a boost[although not always] to my alertness and function with small amounts of protein,usually a resonse to a craving,not an addictive one.


Food for thought.Hippocraties was no oaf let thy medicine be thy food[/QUOTE]


Swept,

Do you have type O blood?I do and also find protein is synergistic with sinemet.

md

Hi Moondaughter,
Sorry, I have not tried longvida curcumin. You could be right, it is a while since i looked into it, and then there was insufficirnt trials.
Good point, has anyone else tried it?
Ron