Too much dopamine the problem?

[stocktiki]

Found another study showing too much dopamine as the issue. Is there something to this?onlinelibrary.wiley.com/doi...

[CuriousMe12]

Dr Sackner Bernstein latest postparkinsonsdisease.blog/7-2-...

[LAJ12345 in reply to CuriousMe12]

rightbrainbio.com

[Gymsack]

You will notice that this statement is not the result of any actual study or physical analysis of people with PD. It is a theory that contradicts many actual long expensive studies that showed the opposite and written as if it was somehow the undisputed truth.

[CaseyInsights in reply to Gymsack]

The paper cited by stocktiki is an actual study. It is much too short to draw definitive conclusions, but is quite interesting. My fist preliminary take 🌺

[JayPwP in reply to CaseyInsights]

It would be great if someone posts a solution...

[Antig in reply to Gymsack]

it is a theory that can only be proven or disproven by a clinical trial. But try getting funding from parties that can afford it, even if driven by an actual PD sufferer, and you run into a wall of silence. Why? Decades of long expensive studies have so far failed to find a cure! I suggest PD sufferers are only interested in a fix not who gets the Nobel prize.

[MarionP in reply to Antig]

Not by a single clinical trial, and not by one badly designed or insufficient, draw a consequences of not spending a great deal one way or another. There's a long way to go, a very long way to go. It's a very interesting theory and has merit as far as basic research might go, or a lot of clinical research might go... But nothing has been done yet. Needs to. Otherwise, offer it for free unless the people you're selling it to are desperate and have a lot of money, or const ground it for you, and then have at it because the world is sales after all and success is defined by selling well. So to say something works has to include the modifier "works for who?" If I convince you to give me a lot of money for something, then although maybe if it doesn't work for you, it's still works very well for me, and that's success... For one of us anyway. The fraud you made a hundred million dollars off of resveratrol by selling A phony concept with no evidence I put a very effective "sales" campaign, in which really he was just selling himself extremely convincingly, from his Harvard medical school laboratory, had great success. He had great success transferring more than 100 million dollars over his costs from the pockets of a lot of people to his own pocket. When they gave him all that money, and still do, he felt much better. So much better that now, 20 years later, he's trying it again.

[YOParky]

Having been taking the amino acid levodopa, doamine's precursor dopamine for 17 years this theory resonates with me very well. Ever since I've been put on C/L I've always have felt the opposite of what my doctors had told me what I'm lacking and what will help my symptom(tremor only). This entire time most of my doses my tremors begin 5-15 min after taking it. MDS and many neuros have not been able to give me an answer other than it's timing and I was late on taking my c/l. Which makes sense on a couple occasions but sure not 17 years of it! I've always have thought and felt that I've had too much dopamine but just have not said anything as it seemed too extreme.

[shaken-not-stirred in reply to YOParky]

Have you tried reducing your dosage a little at a time to see how you respond?

[YOParky in reply to shaken-not-stirred]

Yes, if my dose is under 1.5 pills it's as if I didn't take any.

[shaken-not-stirred in reply to YOParky]

Do you feel better? Are you taking it for tremors only?

[YOParky in reply to shaken-not-stirred]

No as that's when my full body tremors begin

[shaken-not-stirred in reply to YOParky]

Madopar has never stopped PWP having tremors - he has them on the right side - the only time they subside is if he he relaxed and not stressed at all. CBD Oil is the only thing that has made much difference as it relaxes you.

[LAJ12345 in reply to YOParky]

Is it the 50/12.5 or 100/25?

[YOParky in reply to LAJ12345]

100/25

[LAJ12345 in reply to YOParky]

Have you tried asking for the 50/12.5 tablets? Try cutting these in half and spreading throughout the day to see if that helps.

[YOParky in reply to LAJ12345]

I wasn't aware there was an option to get 50/+2.5! I will definitely ask. Thank you LAJ!

[LAJ12345 in reply to YOParky]

The one we have is madopar. I am not sure if it is available in all brands and countries.

[LAJ12345 in reply to YOParky]

”Finally, by modulating the dopaminergic pathway with MAO inhibitors (Goldstein et al., 2016) or ALDH inhibitors (Casida et al., 2014), the TH-HI mouse model may provide the unique opportunity to dissect the relative contribution of dopamine oxidation and DOPAL buildup to the pathogenesis of PD and help to identify pathological drivers in the dopamine dyshomeostasis paradigm.”

Anyone heard of a Aldh inhibitor?

[YOParky in reply to LAJ12345]

Interesting.Not sure if this relates at all but I've noticed if I hae a drink or few containing alcohol I can go without a couple of doses and I'm free of all symptoms and side effects.

[LAJ12345 in reply to YOParky]

Interesting. How long until they come back? And are they worse then ?

[YOParky in reply to LAJ12345]

I was able to fall asleep, slept about 5-6 hours (more than usual), but then of course woke up and needed c/l die to foot and shoulder dystonia

[Ghmac]

This is my very naive opinion. But in support of this theory, I have read on this feed several times about people who have been on dopamine for a long time, ease themselves off little by little. Just food for thought.

[stocktiki]

I'm trying to ease up. Prescribed 1 CL 3x daily, and did for four years. Taken down to 1, 0.5 and 0.5 daily and movement has slowed.

[amykp]

This is interesting, and upsetting, in the sense that, try even MENTIONING the possibility of a theory like this to your neurologist. She or he will look at you like you are completely stupid, and shame you even more intensely into taking C/L (or more than you already are).

Unless you have a better-- or at least more open-minded--neurologist than I do? Sigh.

[stocktiki in reply to amykp]

True this. My MDS gets actually mad when I mention this and says it's a debunked theory. My idea is that if you haven't cured PD, modesty and curiosity is in order.

[MarionP in reply to stocktiki]

Well if it's debunked, then there will be scientific evidence of the debunking and that can be cited, read, analyzed and competently consumed by people who know research and understand design and consumption of research. And if it is really well debunked, it will be pretty obvious to all the rest of us too without much difficulty. It is a lot harder to prove something than to disprove it.

[YOParky in reply to amykp]

I honestly don't think it's possible for any neuro or MDS to have an open mind to think this way. The out of the box thinking is not allowed.

[amykp in reply to YOParky]

Bwahahaha

[LAJ12345]

Defnitely too much makes hubby much worse, pretty much completely disabled.

On the ER madopar he was completely rigid half the time and confused and suicidal in the night.

The doctors just wanted him to take more.

He went back to the low dose 50/12.5 tablet and felt so much better. But he has to take it frequently. He has 1 every 3 hours with 1/2 a tablet in between so he is getting some every 90 minutes. That has worked well for a few years but lately he seems to be feeling worse again.

[MarionP in reply to LAJ12345]

Well the disease does progress, Plus his own neurological responsiveness changes in response to the steady long-term dose and schedule you are using, whether up or down. But you're showing that a flexible approach does make a (sometimes even considerable) difference. At least has for you in the past and recently. But the disease does move and so does your husband's neurological response over time to the amount of dopamine... Because his system does adjust and adapt itself (The number and responsiveness of his dopamine receptors... after a while, his nerves gradually become "used" to the changed dopamine levels and so you have to start adjusting again to once more pursue a change) to the long-term dose/schedule, his own body becomes a moving target. I'm not telling you something you don't know, it's more for other people who might not yet realize it. It's a very widespread thing in nature.

[LAJ12345]

this is interesting

onlinelibrary.wiley.com/doi...

I asked chatgpt

What diet or supplements can be used to slow down the the oxidation of dopamine to daq

ChatGPT

Preventing the oxidation of dopamine to dopamine quinone (DAQ) in humans involves both dietary considerations and the potential use of specific supplements. Here are some approaches:

Dietary Antioxidants

Fruits and Vegetables: Rich in vitamins and antioxidants, particularly:

Berries: Blueberries, strawberries, and raspberries.

Citrus Fruits: Oranges, lemons, and grapefruits.

Leafy Greens: Spinach, kale, and broccoli.

Nuts and Seeds: Especially those high in Vitamin E, such as almonds and sunflower seeds.

Whole Grains: Oats, brown rice, and quinoa provide a good source of antioxidants.

Legumes: Beans, lentils, and chickpeas.

Specific Antioxidants

Vitamin C: Found in high amounts in citrus fruits, strawberries, bell peppers, and broccoli.

Vitamin E: Present in nuts, seeds, and green leafy vegetables.

Polyphenols: Found in tea, coffee, red wine, and certain fruits like apples and grapes.

Flavonoids: Present in fruits, vegetables, and beverages like tea and wine.

Supplements

N-Acetylcysteine (NAC): A precursor to glutathione, a powerful antioxidant in the body.

Coenzyme Q10 (CoQ10): Supports mitochondrial function and has antioxidant properties.

Alpha-Lipoic Acid: Known for its ability to regenerate other antioxidants.

Omega-3 Fatty Acids: Found in fish oil and flaxseed oil, which have anti-inflammatory and antioxidant properties.

Resveratrol: Found in red wine and available as a supplement, known for its antioxidant properties.

Curcumin: The active ingredient in turmeric, known for its potent antioxidant and anti-inflammatory effects.

Lifestyle Factors

Regular Exercise: Promotes overall health and can boost antioxidant defenses.

Adequate Sleep: Essential for maintaining overall health and oxidative balance.

Stress Management: Chronic stress can increase oxidative stress, so practices like meditation, yoga, and mindfulness can be beneficial.

Avoidance of Oxidative Stress

Reduce Exposure to Toxins: Avoiding excessive alcohol, smoking, and environmental pollutants.

Balanced Diet: Ensuring a diet rich in a variety of nutrients to support overall antioxidant capacity.

Before starting any new supplement regimen, it is advisable to consult with a healthcare provider to ensure it is safe and appropriate for your individual health needs.

And what lifestyle factors would increase the oxidation rate?

Several lifestyle factors can increase the oxidation of dopamine to dopamine quinone (DAQ), contributing to oxidative stress and potential neurotoxicity. Here are key factors to consider:

Stress

Chronic Psychological Stress: Persistent stress can elevate cortisol levels, leading to increased oxidative stress and inflammation in the brain.

Lack of Stress Management: Inadequate coping mechanisms for stress can exacerbate its negative effects on the body.

Poor Diet

High Intake of Processed Foods: Foods high in sugar, unhealthy fats, and additives can contribute to oxidative stress.

Low Antioxidant Intake: Diets lacking in fruits, vegetables, and other antioxidant-rich foods can reduce the body's ability to combat oxidative stress.

Excessive Alcohol Consumption: Alcohol metabolism generates free radicals, which can contribute to oxidative stress and damage dopamine-producing neurons.

Environmental Toxins

Exposure to Pollutants: Air pollution, pesticides, and heavy metals can increase oxidative stress in the body.

Smoking: Tobacco smoke contains numerous oxidants and free radicals that can promote oxidative damage.

Lack of Physical Activity

Sedentary Lifestyle: Physical inactivity can lead to a reduction in antioxidant defenses and an increase in oxidative stress.

Overtraining: Excessive and intense exercise without adequate recovery can also increase oxidative stress.

Sleep Deprivation

Chronic Sleep Loss: Lack of adequate sleep can impair the body's ability to manage oxidative stress and maintain neuronal health.

Irregular Sleep Patterns: Disruption in sleep-wake cycles can negatively impact overall health and increase oxidative stress.

Substance Abuse

Drug Abuse: Certain drugs, especially stimulants like methamphetamine and cocaine, can increase dopamine release and oxidative stress.

Caffeine Overuse: Excessive caffeine consumption can contribute to increased oxidative stress and disrupt sleep patterns.

Mental Health

Depression and Anxiety: These conditions are often associated with increased oxidative stress and inflammation in the brain.

Neglecting Mental Health: Failing to address mental health issues can exacerbate their impact on oxidative stress.

Poor Health Management

Ignoring Chronic Conditions: Conditions such as diabetes, hypertension, and metabolic syndrome can increase oxidative stress if not properly managed.

Inadequate Medical Care: Lack of regular health check-ups and preventive care can lead to the unchecked progression of diseases that contribute to oxidative stress.

By addressing these lifestyle factors, individuals can help reduce the risk of increased oxidation of dopamine to DAQ and promote overall brain health.

[LAJ12345 in reply to LAJ12345]

And what is the effect of taking medications containing dopamine

Taking dopamine medications can have complex effects on the brain and overall health, potentially influencing the oxidation of dopamine to dopamine quinone (DAQ). Here are some considerations:

Potential Negative Effects

Increased Dopamine Levels: Dopamine medications, such as those used in the treatment of Parkinson's disease (e.g., Levodopa), increase the levels of dopamine in the brain. Elevated dopamine levels can lead to increased oxidation and the formation of DAQ.

Oxidative Stress: The metabolism of dopamine itself produces reactive oxygen species (ROS), which can contribute to oxidative stress. Higher dopamine levels from medication can amplify this effect.

Neurotoxicity: Excessive oxidation of dopamine to DAQ can lead to neurotoxicity, potentially damaging dopamine-producing neurons and exacerbating conditions like Parkinson's disease.

Potential Benefits

Symptom Management: For individuals with dopamine deficiency disorders, such as Parkinson's disease, dopamine medications are crucial for managing symptoms and improving quality of life.

Neuroprotection: Some dopamine agonists (e.g., pramipexole, ropinirole) may have antioxidant properties that could help counteract oxidative stress.

Mitigation Strategies

Adjunctive Antioxidant Therapy: Combining dopamine medications with antioxidants like Vitamin C, Vitamin E, N-Acetylcysteine (NAC), or Coenzyme Q10 (CoQ10) might help reduce oxidative stress.

Monitoring and Adjustments: Regular monitoring of the patient's condition and adjusting the medication dosage as needed can help balance symptom management and minimize oxidative stress.

Diet and Lifestyle: Maintaining a diet rich in antioxidants, regular physical activity, adequate sleep, and stress management can support overall brain health and reduce oxidative stress.

Consult with Healthcare Providers

Personalized Treatment Plan: A healthcare provider can tailor a treatment plan that considers the risks and benefits of dopamine medication, along with strategies to mitigate potential negative effects.

Regular Monitoring: Ongoing assessment and monitoring can help manage the balance between effective symptom control and minimizing oxidative stress.

While dopamine medications can increase the risk of oxidative stress and DAQ formation, their benefits in managing conditions like Parkinson's disease often outweigh these risks. Combining medication with antioxidant strategies and lifestyle modifications can help mitigate potential negative effects. Always consult with a healthcare provider before making any changes to medication or treatment plans.

[JayPwP]

The references section is interesting in the paper posted in the main post