Hubby has been having a bad patch lately with symptoms deteriorating so we decided to try increasing his madopar from 3 1/2 x 50/12.5 tablets to 5 but he couldn’t tolerate the extra (usual extra rigidity and suicidal thinking) so reduced back to 4 1/2. PD nurse still thinks it isn’t enough. Maybe with move his movement would be improved he just doesn’t tolerate it.
My guess is it’s because of his dopamine beta hydroxylase running fast, (genetic testing picked this up) breaking down the dopamine too fast so it runs out too quickly and causes rigidity and anxiety.
I looked up dopamine beta hydroxylase how to slow it down naturally and apparent st johns wort does this. So I’m trying him on a cup of this a day at the start and he seems a bit calmer but I will keep you posted over whether it is effective.
“SummaryExtracts from the herb “St. John’s wort” (Hypericum perforatum L.) are used for the treatment of mental depression, nervousness, sleeplessness and for their wound healing, diuretic and antirheumatic properties. As one biochemical mechanism for depression lack of catecholamine neurotransmitters has been discussed. The results of this investigation show that alcoholic extracts from Hypericum perforatum L. on the basis of total hypericin content inhibit dopamine - β - hydroxylase with an IC50of 0.1 µmol/l; pure commercial hypericin inhibits with an IC50 of 21 µmol/l. Enzymes involved in the synthesis of dopamine from tyrosine, namely tyrosinase and tyrosine decarboxylase, are not influenced by hypericin at concentrations from 1 up to 10 µmol/l.”
” It has been recently reported that alcoholic extracts from Hypericum perforatum inhibit dopamine-beta-hydroxylase (D-beta-H) with an I50 of 0.1 mumol/l on the basis of total hypericin content and with an I50 of 21 mumol/l with pure commercial hypericin.”
“recent studies report antidepressive, antineoplastic, antitumor and antiviral (human immunodeficiency and hepatitis C virus) activities of hypericin; intriguing information even if confirmation of data is incomplete and mechanisms of these activities still remain largely unexplained. In other contemporary studies, screening hypericin for inhibitory effects on various pharmaceutically important enzymes such as MAO (monoaminoxidase), PKC (protein kinase C), dopamine-beta-hydroxylase, reverse transcriptase, telomerase and CYP (cytochrome P450), has yielded results supporting therapeutic potential. Research of hypericin and its effect on GABA-activated (gamma amino butyric acid) currents and NMDA (N-methyl-D-aspartat) receptors also indicate the therapeutic potential of this substance whereby new insights in stroke research (apoplexy) are expected”
His genes analysis report is attached. Note St. John’s wort can interfere with meds so check interactions and proceed with caution
For anyone who is interested you can get test from a natural practitioner from opus23. You need to do saliva tests and get file from ancestry.com and 23&me then the practitioner gets the test analysed and talks you through it. I would be very interested in comparing genetics of anybody who wants to and can afford to have the test done so we can see if similar symptoms and reactions to drugs occur in people with the same gene defects. Is there anyone keen to try ?
Sorry to hear that you and your husband been through all these.
Have you checked MAO A and MAO B and COMT enzymes activities in your husband genetic testing?
If MAO A is fast which I think in most of Pwpd is and dopamine and seretonin get oxidised rather too quickly. In this case low dose SSRIs can be helful (under health professionals supervision) but should not be mixed with any drugs, supplements and herbs with similar effects including St. John’s wort as mixing them can create severe reaction including seretonin syndrome.
they don’t mention COMT as a problem although the diagram has it shaded.
Definitely maoa and maob are brought up as an issue. They recommend excess of b2 which he has every day, vitamin d he also has. Berberine and quercetin he has had in the past but he isn’t taking now. I might try him on those again.
He has most foods on their list regularly adzuki beans,almonds,liver, dark chocolate oat bran, black beans. Lamb and milk a little.
He cannot tolerate SSRI as they make him extremely agitated and suicidal before long.
The thing they seem most concerned about is the dopamine beta hydroxylase running fast. The say it is bad outcome. And I don’t think there are Parkinson’s drugs for that. Just disulfiram for alcoholics.
The antialcoholism drug disulfiram has shown recent promise as a pharmacotherapy for treating cocaine dependence, probably via inhibition of dopamine beta-hydroxylase (DBH), the enzyme that catalyzes the conversion of dopamine (DA) to norepinephrine (NE).
He doesn’t take much else drug wise. A tiny dose of procyclidine and clonazapam in a dose doctors think should have no effect. And the tiny amount of levodopa he can barely tolerate.
They have prescribed entacapone now which is a COMT inhibitor but I’m not sure that is the right thing. 😬
I will see how St. John’s wort does first as it seems it is at least targeting the right thing
In my opinion vitamin B2 in this circumstance is adding fuel to the fire. B2 causes MAO A works even faster. Plus it also causes drooling. I have the fastest version of MAO A snips. I can’t take more than 20mg of b2 every few days. For people with fast MAO A, 3 meals a day that consist of protein, carbs and fats recommended as well as foods containing tryptophan.
PS: You will need to establish whether your husband’s MAO A is fast or slow. If slow then B2 is helpful.
I read that as it is running too slow, hence the need for b2? So an inhibitor would make it worse?
You are completely right. B2 in case of slow MAO A is helpful as well as avoiding too much tryptophan.
how do you read the maob one? It doesn’t say if his is fast or slow does it? Comment seems general? But it does recommend the b2 as well so I’m guessing slow.
Can one be too fast and the other too slow? Can they balance each other?
I’m thinking that once upon a time his genes all balanced reasonably well for him to function so there must be pluses and minuses in areas that cancel each other out? He was always very low mood low emotion for as long as I have known him 22 years. His mother said as a little kid he refused to be hugged or show any affection. I start to wonder if he has always been a bit on the autism spectrum as he does have a lot of the manefestations when he is not feeling well. He can’t handle stimulation or noise or people etc.
As far as I can see from the images MAO A is slow( first line of the report indicates). It doesn’t say anything about slowness of fastness of MAO B (perhaps their SNPs database not sufficient to compare MAO B against it).
yes. It does say to take b2 though so implies it’s slow? Or can they offset each other?
Not necessarily. They have recommended a routine remedy for MAO B while they are not sure about its tendencies.
“Does exercise increase MAO?Those activities during and after the physical exercise have different tendency in each other enzyme. MAO-A activity was sharply decreased with stress by physical activities compared to the normal group, whereas MAO-B activity was increased for 60 minutes after exercise.”
Whaaat? Does that mean exercise can be bad?
fo r general reference
“Tryptophan Tryptophan is an amino acid needed for normal growth in infants and for the production and maintenance of the body's proteins, muscles, enzymes, and neurotransmitters. It is an essential amino acid. This means your body cannot produce it, so you must get it from your diet.FunctionThe body uses tryptophan to help make melatonin and serotonin. Melatonin helps regulate the sleep-wake cycle, and serotonin is thought to help regulate appetite, sleep, mood, and pain.The liver can also use tryptophan to produce niacin (vitamin B3), which is needed for energy metabolism and DNA production. In order for tryptophan in the diet to be changed into niacin, the body needs to have enough:Iron Riboflavin Vitamin B6”
”Tryptophan can be found in:Cheese.Chicken.Egg whites.Fish.Milk.Sunflower seeds.Peanuts.Pumpkin seeds.”
that’s interesting. Maybe what the other person yesterday needs for his drooling?
I would double check St . Johns wort with his health practitioner as it also slowing down the MAO A activity.
I asked PD nurse and she said fine, see if it helps, but to honest I have no faith in anything coming from that lots as they just want to try scattergun approach. They have prescribed entacapone which is COMT inhibitor for a trial. Will see if St. John’s wort works first as that seems more targeted at the dopamine beta hydroxylase . As far as I can see COMT is ok