Informative article with links re PD and Gut microbiome

[Jandeb]

Gut-Brain Gateways to Parkinson's

Once it was thought that Parkinson’s disease (PD) was primarily a central nervous system condition that impinges upon motor function, but now we know that it entails critical inputs from the enteric nervous system (ENS), intestinal and brain barriers, exposome, enteric immune response, and microbiome. Deeper digging into the founding mechanisms of Parkinson’s suggests that it could actually originate in the intestines, employing immune dysregulation and the resulting inflammation as a chronic distress signal for recruiting the broader whole-body response; even the concept of the vagus nerve serving as a direct physical vector for conveying substances between the brain and gut is no longer revolutionary,

The relative and absolute makeup of gut microbe metabolites (fatty acids, neurotransmitters, peptides, hormones, etc.) affects immune cell metabolism and cytokine production, and the microbiome is, in turn, profoundly influenced by dietary inputs and environmental exposures. Consistent changes in relative abundance of several bacterial phyla has been noted in the PD microbiome, and may relate to inflammation and altered production of ghrelin (a hormonal factor in brain dopamine function), B vitamins, and short-chain fatty acids, especially butyrate (a crucial energy substrate for enteric health); some scientists feel that smoking and coffee drinking may impact PD through the microbiome. One well-known microbial candidate, Helicobacter pylori, may contribute to PD through multiple mechanisms, including altering gut microbiota composition, exacerbating inflammation, altering dopamine metabolism, worsening motor symptoms, and producing neurotoxic substances. Intestinal bacterial overgrowth is more common in those with PD, and PD patients with dysbiosis have shown greater symptomatology that improves with antimicrobial treatment. Animal models additionally present evidence for negative effects of microbiome transplants from PD patients on motor function.

Gastrointestinal difficulties like constipation and reduced motility characterize early Parkinson’s disease to some degree, and overexpression and aggregation of the distinctive Parkinson’s protein alpha-synuclein occurs in the intestines as well as the brain. The enteric nervous system (and particularly the inflammation-sensitive dopaminergic neurons in the intestinal musculature), which interacts in a profusely intimate fashion with the microbiome, appears to be a focal point in Parkinson’s pathology. Heightened intestinal permeability can additionally compromise the blood-brain and blood-cerebrospinal fluid barriers, introducing or aggravating neuroinflammatory processes, and the presence of pesticides in the individual exposome clearly contributes to PD risk.

[WinnieThePoo]

There is a lot of research in this area, and it begs the question - "why not try to do something about it"? See my "Parkinsons is poo" post. So far I have approached this in a fairly casual manner and, over a short timespan, with a population of ONE (and a half), and had promising results. It frustrates me that I haven't yet found a PD clinician who will assist with being a bit more scientific and technical. Interest at the moment seems to be "can we find a drug to affect the gut?" How about asking "How much could we affect the gut with diet, exercise, targetted probiotics, and possibly enemas or faecal transplants?" And "what effect will that have on PD progression and symptoms?"

[francis6]

I switched to a ketogenic diet in February and the effect on my overall health has been quite profound. Initially you feel like crap but, for me, it was worth the effort. The changes to my bowel habits were one of the many changes so I had a detailed gut biome analysis which showed very good results except for one bacteria that is involved with vitamin B1. So now I take a B1 supplement. I am now taking about 1/3 rd the level of Sinimet that I was prescribed last year and feel much better. From my experiences of the last couple of years I would say that sugar and near sugars (refined carbs) have been pretty toxic to me and this linkage of PD (and other conditions) to the gut biome makes absolute sense. Following a healthy diet, exercise and sleep regime makes far more sense than waiting for a magic pill. Just put that slice of cake in the bin.

[2bats in reply to francis6]

Hi Francis, I’ve been on Keto Diet since June and off 7years Ropinirole and Sinemet since 5th July - no meds, just supplements - with generally good results. However I still haven’t got my full strength back yet and still have strong but reducing tremor. Bowels working well, which I had put down to massive kale consumption - having watched Paul Mason on fibre I’m now not so sure!

Are your symptoms continuing to improve after 9mths on the Keto Diet?

Best regards, Phil 2bats

[WinnieThePoo in reply to 2bats]

Interesting. I have noted the ketogenic diet is popular in Parkinsons alternative treatments - deriving I think from David Perlmutter and his books. He also promotes gluten free. I have experimented with both a bit and am now low gluten and (on good days) low sugar. Pretty sure refined sugar is almost universally recognised as a sinner, and contributes to inflammation in PD, but I eat (by ketogenic standards) quite a lot of sugar from fresh fruit, yoghurt, and honey. I haven't noted any mainstream support for the ketogenic diet but there is tons about the microbiome. I wonder whether the ketogenic diet is a backdoor microbiome improver. Lower sugar is definitely going to help with starving the wrong bacteria, and my diet adds a lot of fibre too. But my focus is on changing the bacteria. If transplanting human PD patient bacteria into mice in a lab gives them PD symptoms, and giving them normal bacteria doesnt, then I want to change my PD bacteria for normal bacteria. Why should lab mice get all the best treatments?

[francis6 in reply to WinnieThePoo]

My feeling is that our high carbohydrate diet is at the root of the problem (although, clearly, there are other factors) but I have no qualifications in this field, just personal experience. We don't evolve much over a few thousand years and the amount of sugar/carbs that most people consume would not have been available - we simply are not designed for a modern diet. Obviously our diet has a big effect on our gut biome but how this affects neurons (possibly via the vagus nerve?) is anyone's guess.

I decided to try the ketogenic diet because a) my hospital (UCLH) have had early trial success on PD subjects with drugs (exenatide) developed for T2 diabetes, b) my wife is T2 diabetic and wanted to give it a go because the ketogenic diet has been shown to help with T2 diabetes. Some researchers have described PD as insulin resistance in the brain.

There have only been a couple of studies on PD and the ketogenic diet. The first was in the US and very small scale but showed measurable improvement, more recently (2018) there has been a larger scale trial in NZ that also showed some improvements.

It's a personal choice but i am happier to change my diet than wait for a fecal transplant (and would any benefits persist with a high carb/sugar diet?).

My wife has also cut her meds for T2 diabetes as keto works well to control blood glucose levels.

[jeeves19 in reply to WinnieThePoo]

I contacted two consultants in the UK who are at the forefront of experimenting with fecal transplants. They weren’t awfully helpful and declared that they only did these currently for colostrum dificile? There’s a clip on YTube about some guy trying his own homemade transplant. Dutchman if I remember rightly. Just type the required key words into the YT search and see if you can find it.😊

[WinnieThePoo in reply to jeeves19]

There is a clinic where i could get a faecal transplant but I am looking at £5000. Fine if it cures PD but that seems unlikely. Key questions at this stage are

1) Would changing the microbiome significantly change the disease?

2) Would the disease change the microbiome back again (or seek to)?

3) Are there other ways to change the microbiome enough that are less drastic (and costly) than a faecal transplant?

4) Are there other gut factors affecting disease pathology even when the microbiome is fixed?

Regarding No3 - I am working on diet and probiotics (with exercise) and may consider probiotic enemas. But if the scientific community would investigate this seriously it might be possible to develop targetted specific probiotic strains rather than just nice (but transient) bacteria which help shift the environment a bit. When I worked for a probiotic research company many years ago they developped species specific probiotics for calves and lambs as a treatment for scour (diahorrea) which avoided antibiotics in the food chain. With the resources and motivation it should be possible to develop both probiotic and targetted antibiotic treatments

Yoghurt, Kefir, Kombucha and my homemade sauerkraut with a good probiotic supplement mix, and a diet shift away from artificial sugar and gluten towards fresh fruit and vegetables and fibre seems to be doing ok for now. But its an amateurish, hit&miss approach (and a sample population of 1 over a short time span)

[jeeves19 in reply to WinnieThePoo]

My own problem is staying power over weeks and months. I do think your approach would change the biome but it’s not going to be a quick fix and there’s the rub: you’ve got to deny yourself ‘nice’ foods permanently after 40/50 years of ingesting them. This requires a Herculean effort and willpower which has - as yet - eluded me I’m sorry to say. Maybe I’m just not sick enough yet?

[WinnieThePoo in reply to jeeves19]

Yup. My Dad who has parkinsons wants someone to invent a yellow pill to cure him. My father in law, who also has it, wants someone else to take the pill on his behalf. One of my objections to the ketogenic diet (usually seems also to be gluten free) is just the one you mention. If I have to give up beer and bread then the disease wins - albeit that victory might be better than a zimmer-frame victory. (The other objection I have is the "diet of our ancestors" myth. Dairy cream, grass fed or otherwise, was not the staple of our forebears. We were hunter gatherers and need fruit in our diet - well we need to ingest vitamin C. I accept our forebears did not live on a diet of burgers, fries and donuts). So my diet is not that restrictive. Nor do I believe a very restrictive diet is necessary to change the microbiome. I have just bought a "flute" (big baguette) for lunch today. Mostly, in addition to a few supplements, I have adopted a Mediterranean diet. We eat a lot of salads and vegetables and grilled meat and fish. This is made a bit easier by the fact that 2 years ago we relocated to the mediterranean. To precis - I saw a lot about the keto diet, I am pretty sure those doing it and reporting success are genuine, but it is maybe more restrictive and less focussed than is necessary if the microbiome is the key to the whole gut/brain thing. There is plenty of recent research, increasing exponentially it seems, that the microbiome premis is solid.

[francis6 in reply to 2bats]

The change after the first few weeks was significant (particularly the loosening of previously stiff muscles). Since then I feel there have improved further but at a slow rate. You notice the difference over months rather than weeks. I feel my walking is better (longer strides, more coordination) but also still need to build up muscle strength.

I walk and exercise daily (stretching and strength building) guided by my physiotherapist. I am positive about the future and feel that, at the very least, I am no worse than I was several years ago.

Apart from diet and exercise I also ensure I get plenty of sleep (typically 8 to 9 hours) which may be a challenge for some.

It also helps to have supportive doctors -my new GP (whom I met today) is involved in research on the keto diet and does not dismiss my experience unlike my neurologist who just thinks more Sinimet is the answer.

[2bats in reply to francis6]

What excellent fortune to get a GP who’s interested in Keto Diet!.... I track my fitness by riding my bike and recording the ride on STRAVA - there’s no self delusion because as the saying goes “if it’s not on STRAVA, itt didn’t happen”. Playing Squash solo with a racket in each hand, every day if possible, keeps me motivated and fit and evidences improvements in coordination and timing. I take Creatine after the bike/squash/bike activity as this is supposed to help with Parkinson’s Disease as well as re-build the muscles.

[PDGal4 in reply to 2bats]

How much creatine do you take? In what ways do you find it helpful? I aim to walk outside or on the treadmill every morning and find some days that vigorous exercise badly and suddenly depletes any dopamine C/L may have supplied.

[2bats in reply to PDGal4]

I started on 10g a day for a couple of weeks but am now going with maintenance dose of 5g (one small scoop) as soon after exercise as possible. Good supplier on amazon - bodybuildingwarehouse £12.95 per kg.

A large study sugggests no benefit - medscape.org/viewarticle/84..., but I like the theory behind the treatment and I am on a Keto Diet taking no PD Meds and very keen to maintain muscle mass. I’d point out that I’ve never been able to build muscle in the absence of creatine before Diagnosis, so it’ll be interesting to see if I succeed with it! All the studies concur that it’ll do no harm...

Best regards, Phil 2bats

[PDGal4 in reply to 2bats]

Thanks. I will check it out. I am taking CoQ10, 800 mg a day. Studies also are mixed on this, with the last study also suggesting no benefit, but my neuro said go ahead and I have reduced my meds since taking it. I do believe it is helpful. I also take C, D3, Magnesium Taurate, a probiotic, E, and B12.

[jeeves19 in reply to francis6]

Francis. The only thing that puzzles me is why so many eat cake sugar etc and don’t get Parkinsons.

[WinnieThePoo in reply to jeeves19]

Lies, damn lies and statistics. I keep telling my wife that neither removing my appendix nor drinking an extra cup of coffee a day to get me up to 3 will fix my Parkinsons. That doesn't dispute that there is a statistically significant lower incidence of Parkinsons in individuals with appendectomies, or who drink between 3 and 6 cups of coffee a day

[francis6 in reply to jeeves19]

Because life isn't that simple (if it were, I would hope that researchers would have discovered that by now) and there must be other factors in play (other environmental or a genetic disposition). Most smokers don't ever get lung cancer either but stopping smoking helps the odds.

There was some (very) recent research on patients with and without PD whom they gave a glucose drink and then measured their insulin response. In those without PD, insulin increased to deal with the glucose spike whereas there was little insulin response from many of those with PD so blood glucose levels spiked higher and for longer. High blood glucose levels are known to damage vital organs. Maybe those with PD were never designed to cope with carbohydrate rich diets.

[JAS9 in reply to francis6]

I've been checking my serum glucose levels since I heard about this 2 months ago, and it's just refined carbs that are the problem, which I avoid anyway. I eat a lot of fruit and whole grains and starchy stuff like sweet potatoes and beans and it's all fine. But, of course, I can't speak for anyone but me.

[Maxkas in reply to francis6]

I have been sugar & gluten free for over 2 yrs

Have lowered my PD meds

No shaking anymore

No constipation

Yep keel that cake in the bin 🦋

[francis6 in reply to Maxkas]

Well done. Apart from beer there is very little that I miss and my previous level of Sinimet was causing me increasing anxiety and other side effects. I am now much lighter, blood pressure lower, much better sleep and anxiety has melted away. I wouldn't trade all that for a slice of cake.

[HeartSong in reply to francis6]

Francis6, I have only elementary understanding of the keto diet. But from what I understand, with keto you have to:

1) Eat quite a lot of protein. How much protein do you eat and does it not interfere with your sinemet?

2) Eat abundant fats. How much fat do you eat and what kinds?

3) Limit starchy foods. Do you eat any whole grains, starchy veggies (like potatoes) or beans?

Thanks.

[francis6 in reply to HeartSong]

There's plenty of info about the keto diet if you are interested. It is not quite as you think:-

1) Protein. You should not eat too much protein, What is described as "a moderate" amount. I eat roughly the same amount as I always did, a certain amount is important to maintain muscle etc.

2) Fats. I eat fatty meats and fish, cheeses, cream, coconut oil, olive oil, butter. Fairly generous amounts. This is your main source of energy if you follow a ketogenic diet.

3) Carbs/starchy foods. I eat small amounts of sweet potatoes and beans/legumes. I also eat green leafy veg (lettuce, Kale, cabbage etc.) and some berries. I cut out all sugary foods a couple of years ago and bread, pasta, rice, potatoes etc. when I started the keto diet.

As far as Sinimet is concerned I have cut the amount I take significantly since being on the keto diet. Sometimes I forget to take it altogether and have not noticed any difference. Am toying with stopping altogether.

I still have some symptoms of Parkinson's but feel as good as I have for several years. I also make sure I exercise every day and get plenty of sleep.

[HeartSong in reply to francis6]

Thanks for your response, francis6. I hope you won't mind a couple more questions.

1) Is the protein that you eat plant or animal based?

2) What was your diet like just before you moved to the keto diet?

[francis6 in reply to HeartSong]

No problem.

1) Mainly animal based (eggs, cheese, meat, fish) but I also eat peanut butter. There are vegetarian keto recipes but they rely a lot on cheese and eggs for protein.

2) My diet was pretty standard (for UK). I did not eat much junk at all but probably ate quite a lot of bread, pasta, potatoes. In the last year before my diet I started to crave more sugary foods (something I had never had before) which may have been a sign of things going wrong.

[francis6 in reply to HeartSong]

I should add that, initially, I maintained the prescribed level of Sinimet when I first started and developed some unpleasant side effects (anxiety, palpitations) as a consequence. When it became apparent to me that this was linked to Sinimet I cut the amount I took and these effects cleared up almost straight away.