Hi @TomParkinson, have you looked at Ambroxol by any chance? I cannot find side effects or contraindications of this cheap OTC coughing medicine. It’s currently trialled (phase 3) as a disease-modifying treatment for Parkinson’s, after a successful phase 2 trial. See also the following papers:
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I also found this review interesting: Nutrients | Free Full-Text | Parkinson Symptom Severity and Use of Nutraceuticals
They asked 1,084 Parkinson’s patients which supplements they took and followed the progression of their symptoms. It’s purely self-reported and prone to a lot of confounders, but the conclusion is: “Nutraceuticals associated with improved outcomes were Ginkgo biloba (GB), NAD+ or its precursors, 5-methyltetrahydrofolate, glutathione, mucuna, CoQ10, low dose lithium, curcumin, homocysteine factors, DHEA, coconut oil, vitamin C, and omega-3 fatty acids (fish oil).”
Taurine, astaxanthin, and sulforaphane were not part of the survey (or maybe not used by the participants), but they may be worth exploring:
- Astaxanthin is neuroprotective in an aged mouse model of Parkinson’s disease - PMC
- Taurine protects dopaminergic neurons in a mouse Parkinson’s disease model through inhibition of microglial M1 polarization | Cell Death & Disease
- Neuroprotective effect of sulforaphane in 6-hydroxydopamine-lesioned mouse model of Parkinson’s disease
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Hello Lin,
thank you very much for the information.
I have also planned to take melatonin.
However, at the moment I am trying out other therapies and still need time for this. My condition is very stable with slight improvements. Therefore, I do not have very much pressure.
Many, many thanks for your help!
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Hello adssx,
thank you very much for the information.
I have already planned to take Ambroxol.
I also have Ambroxol at home. However, I am still waiting to see what the study results will bring.
However, at the moment I am trying out other therapies and still need time for this. My condition is very stable with slight improvements.
Therefore, I do not have very much pressure.
Many, many thanks for your help!
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Hello adssx,
I know the list with the nutritional supplements.
I already take some of them.
Thanks for the info!
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Glad to hear this!
What’s your current stack?
Some people also report improvements with red light therapy. This medical device is for instance approved for Parkinson’s: Parkinson's Treatment For Home Use - PDCare Laser | LED Light Therapy – SYMBYX Biome
There’s another thread on selegiline that may interest you: Anyone taking Selegiline / Deprenyl For Longevity?
Selegiline is a Parkinson’s drug at 10 mg/d (swallowed, equivalent to 1.25mg in oral dissolving tablets) but at low-dose (1mg/day swallowed) it may have life extension properties and may prevent or slow down Parkinson’s. It’s still unclear whether selegiline and rasagiline have disease-modifying properties for Parkinson’s because trials showed an inverted U shape relationship: low rasagiline doses seemed to slow down the progression while high doses did not. The FDA considered that the absence of a dose dependent relationship proved that it wasn’t a DMT but you would argue the opposite: it’s consistent with trials of selegiline on mice that showed an inverted U shape as well: no impact on longevity for super low doses, positive impact for low/medium doses and negative impact for high doses.
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Impressive: congrats!
This new paper may revolutionize the way we understand Parkinson’s disease: Parkinson's Onset Theory Challenged: Synaptic Dysfunction Before Neuron Death - Neuroscience News
“Contrary to the widely held belief that Parkinson’s disease originates from the degeneration of dopaminergic neurons, a new study suggests a precursor: synaptic dysfunction. […] Based on these findings, we hypothesize that targeting dysfunctional synapses before the neurons are degenerated may represent a better therapeutic strategy.”
If you ask ChatGPT how to enhance synaptic activity, you’ll get the usual suspects: Omega3, antioxidants, exercise, meditation, learning new things, reading and problem-solving, vitamins B and D, and cognitive behavioral therapy. But also nootropics, antidepressants, neurofeedback, deep brain stimulation (DBS), and transcranial magnetic stimulation (TMS).
It seems that smoking increases synaptic dopamine, which may explain why smokers tend to be protected from Parkinson’s disease? Tobacco smoking and dopaminergic function in humans: a meta-analysis of molecular imaging studies | Psychopharmacology
According to this Japanese team, selegiline may recover synaptic plasticity in rodent models of Parkinson’s and depression:
- Selegiline Recovers Synaptic Plasticity in the Medial Prefrontal Cortex and Improves Corresponding Depression-Like Behavior in a Mouse Model of Parkinson’s Disease 2019
- Selegiline ameliorates depression-like behaviors in rodents and modulates hippocampal dopaminergic transmission and synaptic plasticity 2019
Same for red light therapy according to this 2023 Korean paper: Photobiomodulation improves the synapses and cognitive function and ameliorates epileptic seizure by inhibiting downregulation of Nlgn3
I’d love to see a detailed review of all potential synaptic enhancing interventions, ranked by certainty / potency / cost.
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Not an expert, but Jay Lombard is
I have recently been implementing cold showers and sauna. These are reputed to have positive impact. Good luck!
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@TomParkinson: do you have any positive experience with altitude?
Many Parkinson’s patients report that they improve when taking a plane or going to the mountains. See, for instance: Finding a talisman – The Science of Parkinson's
Altitude is HYPObaric, so people assume that the reason is because of the hypoxic environment, which could activate autophagy (same as intense exercise?).
There’s an ongoing clinical trial: TALISMAN-1: Parkinsonsymptomen beïnvloeden door een verblijf op hoogte - ParkinsonNEXT
If true, the extreme option would be to move to a place in altitude (another positive point: less pollution), but I wonder if regular trips to the mountain for holidays can also have a positive impact.
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The interplay between autophagy and ROS is very complex. I
" 5. Conclusion and Perspective
Plenty of studies have repeatedly shown that ROS accumulation displays detrimental implications for the basic function and survival of neurons. ROS or oxidative stress can provoke autophagy, and autophagy can take part in the removal and repair of ROS-induced oxidative lesions through a variety of signaling pathways. But autophagic neuronal death will still result if cumulative ROS go beyond the scavenging activity of autophagy. At present, it appears to be contradictory that autophagy serves as a cellular self-purification mechanism, but hyperactivity or hypoactivity of autophagy is unfavorable for the normal functionality of neurons [162, 163]. After all, the predetermined threshold level of perfect autophagy is often blurred, particularly under a variety of disease courses"
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Regarding ROS and autophagy, SGLT2 inhibitors seem super interesting, and especially in the context of PD, see:
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Jeesh. Do you feel better right away, or just generally think it slows progression? It just looks so painful.
I get in the hot tub most nights and try to get my pulse up to at least 110, then jump in the “cold” pool after, but to me, “cold” can’t be anything under about 72 degrees F.
Maybe you say it somewhere, but if you don’t mind, would you tell me what other drugs/supplements you take? Thanks!
I saw this post on twitter a few weeks ago, but have not had a chance to dig deeply into it. Christine is a local and very active Longevity Biotech startup person here in San Francisco, and founder of Longevity Global and NeuroAge Therapeutics, a company focused on therapies to treat Alz. in new ways. Related article on her company: NeuroAge Therapeutics: A New Approach to the War on Neurological Disease - Spannr
Christine’s bio is here: Christin Glorioso, MD PHD - Berkeley SkyDeck | LinkedIn
Perhaps someone here with deep knowledge of Mitochondria complex 1 can comment on her points here?
The paper referenced: Mechanistic Investigations of the Mitochondrial Complex I Inhibitor Rotenone in the Context of Pharmacological and Safety Evaluation | Scientific Reports
Another paper referenced:
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Shouldn’t a signal have emerged for metformin and alzheimers disease already if there was any link? Or rather aren’t there any clinical trials looking at alzheimers patients and metformin use?
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I think that the signal might be very hard to identify given the historically ill nature (typically obesity, diabetes, etc. for long periods of time) of the patient population, it would be hard to tease out of the data. If you have diabetes you are already at much higher risk of Alz.
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So, if you have diabetes, you get Alzheimers. If you take Metformin, you treat the diabetes but you still get Alzheimers. Damned if you do. Damned if you don’t.
I’ll go with the no diabetes and take my Metformin. It also prevents fatty liver.
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