I am personally trying to take a broad approach to treating my Parkinson's disease. I am also trying to carefully choose a range of supplements to address known problems. I'm trying to get exercise and do qigong.
Conventional medications for PD do very little to slow the actual progression of the illness. Other approaches may have the potential to slow the degeneration and reduce the progressive increase in symptoms of PD. These include exercise, nutrition, and a set of candidate supplements.
But is there anything we can do to grow neurons back in the parts of the brain that have been affected? I know that there have been some attempts at stem cell therapy. But is it possible to induce the brain to regrow nerve cells on its own, without sticking needles into the brain?
I was looking into neurogenesis just a little bit today. Two decades ago, it was accepted that adults did not grow new neurons in the brain. In the past decade or so, neurogenesis was recognized in a few areas, such as the hippocampus.
Kempermann, Gerd. "Off the beaten track: new neurons in the adult human striatum." Cell 156.5 (2014): 870-871. [Accompanying editorial, also free, you can also click the PDF link]
So, what does this do for us? Is there potential for a person with Parkinson's disease to partially regrow the damaged nerve cells in their striatum? Is this a false hope? Or do we not know?
I honestly have only just begun to look at this. One thing I will note is that the neurogenesis that was reported by Ernst et al (2014) was "appears restricted to interneurons". Interneurons are the nerve cells that make connections.
This is what the author say:
“The finding that neurons are continuously added in the adult human striatum poses the question of whether this process can be utilized therapeutically in neurological disease. The presence of increased numbers of putative neuroblasts in the human striatum after stroke may indicate increased neurogenesis in this situation (Macas et al., 2006), similarly to what is seen in other mammals. It will be important to study whether such neuroblasts give rise to mature neurons. Increasing the generation or promoting the survival of new neurons is an interesting option in stroke. Moreover, studies in rodents have suggested that promoting cell proliferation in the subventricular zone can have a positive effect in models of Parkinson’s disease, likely mediated by the new cells having a neurotrophic effect on the nigro-striatal system (Androutsellis-Theotokis et al., 2009; Zachrisson et al., 2011). Investigating how striatal neurogenesis is potentially affected in pathological situations and identifying factors that promote the renewal of striatal neurons may facilitate the development of therapeutic strategies to improve functional recovery after injury or to tackle neurodegenerative disorders.”
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ElliotGreen
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I'm fortunate to have a background in biology. I studied biology at the top tier university along with all of the premed students, and I graduated with honors. My professional career since then has sometimes involved combing through complicated scientific literature and understanding the nuances.
I also have a history of saving my own ass through medical research. 16 years ago, I had a persistent infection after hernia surgery. My surgeon just kept prescribing me with more antibiotics, but it wasn't going away. I did my own research and discovered that some hernia patients had infected mesh implants, and that they needed to be removed. Moreover, until that happened, I was at risk of sepsis and toxic shock. WTF?
I didn't stop there, I kept digging. I discovered a brand of replacement mesh made of pig collagen (instead of plastic) which could be placed into infected fields. This meant I only need to have one further surgery, rather than two.
I may be a little bit compulsive sometimes with the research, but sometimes inquisitive research pays off.
The first of these citations says this: "Alterations in adult neurogenesis appear to be a common hallmark in different neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD)."
Here is a brave speculation: What if the problem with Parkinson's is less about the fact that the cells are dying, and more about the fact that they aren't being replaced with neurogenesis?!
I'm hoping that since the striatum nigra is close to the hippocampus, that factors which increase neurogenesis in the hippocampus also helped nerves grow in the striatum nigra.
I got some Ashwagandha today and have started taking out today on the basis of claims that it improves neurogenesis.
I had a consult with David Tomen of Nootropics Expert end of March. He sent me a list of some things that could help my husband (PWP). I settled on a couple, one being Lion's Mane Mushroom (nootropicsexpert.com/lions-.... I have to say this has made a huge difference in my husband's cognitive ability and I'm not so sure about his main PD symptom, tremors. Within a short time of starting the supplement (600 mg), he was reading and comprehending again, he started to do Sudoku in a printed book, he was able to re-engage with clients in our business. He continues in this manner as I write this. His tremors also lessened a bit and he's been able to use utensils better, which has made him more willing to eat out occasionally. I don't know what else to attribute this change to. I will post the brand he is using if people are interested. I get from Amazon - it had the best ratings.
Yes. Read my response to ElliotGreen to see what he was already taking. As I said, there might have been a small improvement in energy from those things. It wasn't until I added the Lion's Mane Mushroom that he started to do some of his normal things. He wasn't even aware that was what he was taking as he really doesn't care. He just wants to feel better. That was the only thing I had consistently added in, so again, yes, I attribute his improvement to that.
I occasionally give him taurine as l-dopa depletes. I also tried some bacopa monieri and haven't done much with that. His functional med doc who follows the William Walsh protocol started him on P5P, B12 (not methyl or cyano but some other form), zind, selenium, vit C, quercetin and digestive enzymes last November. I do think these things helped in a small way. However, nothing really major happened until the lion's mane mushroom (brand - Real Mushrooms - from Amazon - he takes 2 600 mg a day now). He also takes a relatively low dose of B1 (300 mg once or twice a day but this addition has been more recent). Anyway, there is s limit to what he wants to swallow 3+ times a day.
I had posted about this supplement some time ago and its miraculous results. My husband was taking it but stopped it due to his recent surgery. I am reordering it from Amazon. Two more supplements are excellent for PwP: Ashwagandha and Bacopa Monnieri.
Husband did Ashwagandha sometime last year and stopped. He's done bacopa monnieri as well and stopped. Neither did much after a couple months trial. Within a month, we started to notice the changes with the addition of the LMM.
On a side note, hope your husband is recovering well. If I remember, you are in Nashville - we are in Louisville. Just up the road, so to speak.
No, we are not in Nashville. Our MDS is at Vanderbilt.
Yes, he is recovering very well, except the statins he is on now have taken their toll. . .he will stop them end of this month. Evil drugs which affect memory and muscle pains, to name a few side effects. . .
Thank you! He took his first walk tonight 11 days after his discharge. Almost 4,000 steps three weeks after his near fatal post op complications ain't bad!
I will look up your LMM supplement on Amazon. Don't remember what I was getting but it will be easy to find from my previous purchases list.
I am a bird watcher. 85% of field work is auditory. So basically I can follow birds with help from other birder friends who rotate me in the direction of a Canada Warbler high up a on a branch. So how do we wake up our aging brains and will our reliance on technology leave our kids' brains unable to perform simple math? Yes. Where is this done? Hippocampus. Many of you use meditation and exercise both = spatial memory. Exercise and Meditation improves recall of WE ARE AT THIS PRECISE MOMENT using visual and auditory clues and mapping our route without a GPS. MR O'Connor's new book Wayfinding explains why we need to rely on our hippocamus "Use it or Lose It". Please excuse errors written on the go with this Smartphone. DUMB. should I try pen and paper?
Except, we know from DaT scans that PD brains show significant loss of dopamine neurons. And though I know the current thinking is that there IS normally neurogenesis in the adult brain, how could there be enough in even a healthy person to make up for the continuing loss you normally see in PD?
My conclusion is still that PD is not about the inhibition of neurogenesis nearly as much as it is about neurodegeneration. That doesn't mean that stimulating neurogenesis wouldn't be helpful--it's just that I have trouble believing it's the root cause. It doesn't mean I'm right either--it just means it doesn't make sense to me right now.
My strategy is to do everything I can to protect the neurons I have, figuring that those same strategies will promote a brain environment favorable to grow "baby" neurons as well. So maybe it ends up being the same thing! But I am hugely into autophagy, and anti-oxidation.
One problem: there are a zillion products out there (ashwagandha only one of them) and you could go crazy! Also, supplements can interact with each other, so just popping a bunch of things might not be the best strategy. I focus on my (ketogenic/fasting/crazy) diet and take a few key supplements that have been through studies or have clear mechanisms of action...and I keep reading. Like you!
There are clearly different causes to Parkinson's. Loss of dopamine neurons is clearly involved in a part of the problem. For some people, it may be exposure to pesticides or other toxins like mold. For other people, they have a genetic predilection to producing too much alpha-synuclein, and this gums things up, stresses the mitochondria in the cell, and provokes inflammation and thereby programmed cell death.
So again, I'm not saying that cell death isn't a problem.
My bold suggestion and hope however is that this doesn't have to necessarily be a one-way trip. Perhaps. At least for some people. Maybe. Given the evidence I have seen, I think it is entirely realistic to be at least open to this possibility.
What evidence do we have of this?
I don't want to spend all day on the Internet right now, so I can't get into everything I have in mind. But here are a few things that I know.
1) We know that some people can get stuck in a chronic state of brain inflammation. I posted about this not long ago. I had a reference.
2) Psychologically (and neurologically) people can also get stuck in a “Shutdown Mode”, a sort of trauma response of the autonomic nervous system. This brings together polyvagal theory (which has now enough solid evidence to be much more than merely a “theory”) and the writings of Dr. Janice Walton-Hadlock about Parkinson’s from a Chinese medicine point of view.
3) It is also possible to get unstuck from these modes. The brain can come out of chronic inflammation. The autonomic nervous system can come out of shutdown. The brain can get into a “gamma waves” state where the microglia are are helping activate cell repair (rather than inflammation and a scorched earth autoimmune attack of reactive oxidative species and programmed cell death).
4) Mice who were bred to exhibit the amyloid plaques of Alzheimer’s disease (which are similar to the alpha-synuclein Lewy bodies of Parkinson’s) were entrained into a gamma wave brain state with tones and flashing lights. After about a week, their amyloid plaques were reduced by about half. If I recall correctly. This may sound crazy, but it was published in Nature. The point is that some of the “bad stuff” that happens in neurodegenerative illness can be reversed – under the right circumstances. We now know that NORMALLY their is neurogenesis in the striatum. It seems this is reduced in PWP. Perhaps it can be rehabilitated or turned on again. More controversially, there are arguments and evidence for neurogenesis in the substantia nigra. It's speculative, and a big ask, but maybe there are ways of (re-)activating this, too. I genuinely believe it may be possible.
5) Based on the recent successes of a multi-pronged approach to reverse mild cognitive impairment and early Alzheimer’s disease, Dr. Laurie Mischley believes that it may be within our grasp to reverse Parkinson’s.
6) There are a few people who have evidently recovered from Parkinson's disease. One such person is Bianca Mollé. Another one was referenced in the recent post about Meditation.
I like your focus on inflammation, shutdown (or pause) mode, and neurogenesis and combining them seems like a great idea. If you find ways to stop the brain inflammation and/or kickstart those two brain areas, I volunteer to try it!
We actually don't know for certain that there is significant neurogenesis in a normal adult human brain, not yet. Yes, we have evidence for it, but I believe most of that evidence comes from rodents.
Despite what Laurie Mischley believes--I think the alzheimer's study she references had only 10 subjects and was not blinded. Sadly I'm too much of an old fashioned scientist to get very excited about that, and double-sadly nobody has found anything else.
I'm not sure I understand most of the rest of what you are saying, except I certainly agree that inflammation is a HUGE problem for our parkinson brains. We should do everything in our power to keep it at bay!
There is strong evidence of neurogenesis in areas of normal adult human brains. It is incorrect to say that most of the evidence for this comes from rodents. There is significant evidence from human studies, too. Some of that is included in the original study I cited at the top of this page. I also offer you this summary statement:
"In recent years, it has become accepted that adult neural stem cells located in the subventricular and subgranular zones have the ability to proliferate and differentiate in order to replace lost or damaged neural cells." (2016)
EDIT: Admittedly, neurogenesis in the substantia nigra is a bigger ask. Unlike the striatum, is outside the subventricular zone.
Nevertheless, there is also evidence of neurogenesis here, at least in mouse studies. This may happen either after injury at a faster rate, or at an ongoing slower rate (but fast enough to replace all of the cells over the course of a mouse's lifetime). This subject was reviewed in 2009 in a book chapter. I may try to delve into that more in another post at a later date.
Neurogenesis in Substantia Nigra of Parkinsonian Brains?
Lamm, Omri, et al. "Harnessing neurogenesis for the possible treatment of Parkinson's disease." Journal of Comparative Neurology 522.12 (2014): 2817-2830.
"There is strong evidence that neurogenesis is impaired in PD, which has been related to the nonmotor symptoms of the disease. Recent evidence supports that this impairment in neurogenesis is partially caused by the lack of dopamine in one of the adult neurogenic niches, the SVZ. Thus, restoring the dopaminergic pathway in PD patients may have implications not only for motor function improvement, but for other cognitive and autonomic symptoms. "
Han, Myung-Hoon, Eun-Hye Lee, and Seong-Ho Koh. "Current opinion on the role of neurogenesis in the therapeutic strategies for Alzheimer disease, Parkinson disease, and ischemic stroke; considering neuronal voiding function." International neurourology journal 20.4 (2016): 276.
"In recent years, it has become accepted that adult neural stem cells located in the subventricular and subgranular zones have the ability to proliferate and differentiate in order to replace lost or damaged neural cells. There have been many limitations in the clinical application of both endogenous and exogenous neurogenesis for neurological disorders. However, many studies have investigated novel mechanisms in neurogenesis and have shown that these limitations can potentially be overcome with appropriate stimulation and various approaches. We will review concepts related to possible therapeutic strategies focused on the perspective of neurogenesis for the treatment of patients diagnosed with Alzheimer disease, Parkinson disease, and ischemic stroke based on current reports."
This is a very interesting thread that I missed due to holidays.
Neurogenesis is certainly a good line of investigation, but before we start thinking of growing new neurons, shouldn't we make sure we stop damaging the existing ones.
In a previous post by ElliotGreen on oxidative stress, I made the point that there must be intermediate states between 100% healthy and 100% dead neurons, just like any other cells. I admit that I am a complete novice in this area and I haven't yet had time to research this, so I'd be happy if anyone can support or refute this idea.
If this is true we should be focusing on nursing the damaged neurons back to health. Dr Mischely's paper on diet gives us some clues on what we should be looking for. Only the best conditions for existing neurons can be right to grow new ones. We may still need an extra condition or supplements to give the stimulus for neurogenesis, but supplements will not work if the conditions that caused cell death for years are still present.
I'm not saying it's true, but I think it makes sense and it's worth exploring. Are there post-mortem studies that show damaged, but still viable, neurons that can be nursed back to health?
Furthermore we can be pro-active and take the diet well beyond the terms of Dr Mischely's survey concentrating on the extremes of dietary components that have a strong positive or negative effect on PD progression.
"I'm beginning to build up a vague picture in my mind that the cause of PD and it's progression could be initiated by oxidative stress, aggravated by inflammation, followed by death of dopamine-producing neurons.
If this is the case, at any stage of the disease, I would imagine that impacted neurons could be classified into at least 3 groups:
1) fairly healthy or healthy neurons that are doing the hard work in helping us to function and don't need much externally sourced dopamine.
2) moderately damaged neurons, not yet condemned, producing some dopamine, but also capable of using dopamine available via medication
3) severely damaged or dying neurons that produce very little or no dopamine and are so damaged as to be largely incapable of taking up and using dopamine available through medication.
If this situation is caused by oxidative stress, and this stress was aggravated by diet over many years and is still continuing since we have not changed our habits (yes, that's a lot of ifs), then we should explore a strategy that covers:
a) damage limitation,
b) damage control,
c) damage reversal.
Damage limitation means not eating significant quantities of food that are reported to create oxidative stress or inflammation. These include carbohydrates, sugar, processed foods, dairy products, ice cream, canned fruit, fried foods, red meat (contains too much iron), etc.
Damage control means eating lots of foods containing antioxidants to combat the oxidants that arise naturally through various metabolic pathways. These foods include lots of fresh, and preferably raw, fruit and vegs, especially red fruit, berries, tomatoes, green leafy vegs, cabbage, broccoli, peppers, celery, avocados, nuts and fish.
The aim here is to protect stage 1 and stage 2 neurons from further damage.
Damage reversal means providing the means whereby stage 2 neurons can recover and reach a more healthy state resembling stage 1.
Damage reversal may be more difficult but it can only considered once damage limitation and damage control have been achieved.
I see damage reversal being helped by supplements or drugs, that help the recovery of brain cells damaged by any cause, not just PD : injury, drugs, stroke etc. high dose omega3 fish oils could be a possibility.
The recent article by Dr Laurie Mischley on diet related progression of PD made me think about this idea."
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