
Parkinson’s disease ‘may start in gut’ - sjcsjc
http://www.bbc.co.uk/news/health-38173287
======
apinstein
My Dad was recently diagnosed. Very early stage. This is very interesting
news.

My take is that Parkinson's is a little like cancer in that it likely has
multiple root causes that can injure the same part of the brain (substantia
niagra) and cause the disease.

My research for his case led me to vitamin k2 deficiency as a possible cause /
complicating factor. There are some genetic models and mouse trials that show
k2 as a modality. He had his gallbladder removed about a year before symptoms
started. He also has kidney stones. K2 is fat soluble, only acquired through
diet, and affects calcium regulation. Oddly connected to his history/symptoms.
So hard to help debug stuff like this.

He's on a supplement now. We don't have a great way to measure if it's
working. The symptoms have such natural variance day to day.

~~~
NPMaxwell
Would it help to record the tremor intensity while tracing a smoothly moving
dot with his finger on a cell phone screen? And/or record the tremor while
holding the phone and tracing along a line with a corner of the phone. I bet
you could get pretty good at-the-moment measurement of the tremor. Combine
that with graphing and a rolling average, and you might have a pretty clear
picture.

~~~
Declanomous
I bet you could homebrew an electromyograph pretty easily. It probably
wouldn't be particularly accurate, but you could probably achieve enough
precision to provide repeatability and measure day-to-day variance.

Edit: Hackaday had an article about a simple EMG recently

[https://hackaday.com/2016/11/20/emg-tutorial-lets-you-
listen...](https://hackaday.com/2016/11/20/emg-tutorial-lets-you-listen-to-
your-muscles/)

------
dtf
Last year, there was an interesting story about a woman who could smell a
certain odour that seemed to be given off by people with Parkinson's
(primarily her husband).

[http://www.bbc.co.uk/news/uk-scotland-34583642](http://www.bbc.co.uk/news/uk-
scotland-34583642)

~~~
trendia
If it's ketones, then it would be easy to train a dog to detect it.

~~~
NickM
I don't see any mention of ketones in the BBC article. What led you to that
hypothesis?

~~~
pizza
Not GP but ketones have a fairly distinct and strong aroma. That said, if it
were ketones, they'd probably be _too_ distinguishable for this story to be
uniquely news-worthy.. it's probably a less identifiable smell than ketones,
whatever it is..

------
ianai
I watched my great grandfather lose everything to Parkinson's. I really hope
this leads to a treatment that stops the progression of symptoms and fast.

~~~
simonh
My father suffered from the disease and passed away in October. Awful disease.
This is great news, but it looks like any treatment based on this will still
be quite some way off.

~~~
peteretep

        > but it looks like any treatment
        > based on this will still be
        > quite some way off
    

I came away with the opposite impression. Wouldn't you just need a targetted
antibiotic?

~~~
beef234
Fecal implant would be an obvious solution.

~~~
ianai
That's my bet too.

~~~
olva22
Now, if we can only get the FDA to allow it!

------
fibbra
There is need for research into what is happening in the gut, what the
microbiome looks like and how it is influenced by food and stress.

This research money can either come by government funding (ideal for basic
research) or by private funding (focused, to produce top medicines).

As it looks now, the private funding may not work because any remedy in the
form of a medicine, would be applied a couple of times and that's it. There
may not be enough money to make.

~~~
kmonad
And there is, tons of it. Though I do agree that private investments need to
find a niche beyond yoghurts.

[https://www.broadinstitute.org/hmp/human-microbiome-
project](https://www.broadinstitute.org/hmp/human-microbiome-project)
[https://www.mskcc.org/research-areas/topics/microbiome-
infla...](https://www.mskcc.org/research-areas/topics/microbiome-inflammation)
[http://humanfoodproject.com/americangut/](http://humanfoodproject.com/americangut/)

------
sushid
To those familiar with various skin conditions, this may not be a big surprise

Skin conditions such as seborrheic dermatitis disproportionately affect those
with HIV or Parkinson's and those skin conditions themselves have been liked
to gut health, although not widely received in the medical community.

Seeing as how many skin ailments are linked to those with early or long term
use to antibiotics (e.g. childhood ear infections, antibiotic use as infants),
and Parkinson's patients are disproportionately affected by them, this is an
even greater reminder that gut flora health is something not to be taken
lightly.

~~~
mahyarm
So how do you go about actually fixing it? I've had that condition in a minor
form for pretty much my entire life, getting worse when I was a teenager. I've
gone to many derms and they all end up just giving me some form of
corticosteroids.

I've tried vegan diets, various supplements, probiotics, natrual paths, salt
baths, oatmeal baths and on and on, and it doesn't do much other than treat
symptoms. I haven't tried to fix it any further because it's just a minor
annoyance in my life, but I'm all ears if there is something that explains it
better and some measurement that I can use to help understand it.

~~~
sushid
I would say first and foremost, avoid all uses of topical steroids and topical
antifungals. And do not use antibiotics "just in case" (this is common for
routine dental surgeries, but unnecessary). I do know from enough anecdotal
evidence and reading published literature that those are only stopgaps and
will eventually make your symptoms worse.

Unfortunately, I'm not a doctor and I don't exactly know either. All I know is
that there are serious links to diseases like IBS, Crohn's, dementia,
Parkinson's, seb/atopic dermatitis, etc. that many have known to be associated
with gut that is being only proven in recent years.

Personally, I have reduced my intake of carbs (even "healthy" carbs) to a
minimum. I eat a small serving of carbs when I'm eating other food, but never
a small serving of carbs by itself. I rarely eat anything with yeast or sugar,
which is a dealbreaker for most people.

I drink kefir and kombucha in small amounts and I take copious servings of
probiotics. Right now I'm taking synthol and garden of life but I'll switch to
a different set in a few months.

I also consume a lot of natto, kimchi (you can make this at home), and organic
unfiltered apple cider vinegar.

I apply a very small amount of sea salt and water and keep it on everyday and
clean my face with ACV for a few minutes each morning and evening.

------
trendia
This is especially interesting, since coffee is moderately protective for
Parkinson's.

Does that mean the coffee may be working at the gut level rather than its
caffeine working in the brain? On second thought, coffee definitely works on
the gut in normal people, if you know what I mean.

~~~
PascLeRasc
I remember reading that study too but I think coffee was only shown to be
significantly protective for 8-10+ cups/day.

~~~
r00fus
Wondering if decaf would be as useful as caffeinated for this purpose?

------
gravelc
Mother in law has had it for about 15 years (so has lived longer than
expected). Currently has implanted electrodes in the brain, which fixes some
issues and leads to others.

Recovery is unlikely at this stage, but even preventing the disease from
progressing further would be quite something.

------
soundwave106
For those who want to explore deeper, I think this article is referencing a
paper published in Cell recently:
[http://www.cell.com/cell/fulltext/S0092-8674(16)31590-2](http://www.cell.com/cell/fulltext/S0092-8674\(16\)31590-2)

------
gus_massa
From the article:

> _The bacteria can break down fibre into short-chain fatty acids._

This doesn't make any sence. Fibre(fiber) is composed by carbohydrates bounded
in a different way of the sugar that is used to sweeten.

Perhaps bacteria can eat fibre and produce fatty acids, but fibre is not made
of fatty acids.

This is probably an error in the press article. Do someone with access to the
research paper to understand what this means?

~~~
alexholehouse
Short chain fatty acids can be things like acetic acid, propionic acid,
butyric acid. The fermentation process takes in fiber and puts out these guys,
so while fiber isn't an SCFA polymer, I don't think this statement is
inaccurate (i.e. I don't have the metabolic pathways off hand but these could
be direct breakdown products given the shortness of the carbon chains - acetic
acid almost certainly is.)

~~~
gus_massa
I mostly agree.

The main path for glucose involves splitting it in two 3 carbon molecules,
mainly pyruvate
[https://en.wikipedia.org/wiki/Glycolysis](https://en.wikipedia.org/wiki/Glycolysis)
From this it's easy to make acetic acid (2 carbons), like the acetic acid in
vinegar. And , I guess it's also not very difficult to make propionic acid (3
carbons).

I can accept that they say that fiber or glucose is "break down" to acetic
acid, propionic acid, but I think it's misleading. (And the usual definition
of fatty acid starts at 4 carbons
[https://en.wikipedia.org/wiki/Fatty_acid](https://en.wikipedia.org/wiki/Fatty_acid)
)

I had to search for the pathway to produce butyric acid (4 carbons). The main
path is apparently splitting the glucose in pyruvate and adding a carbon to
it, so it's not a direct break down. But there is an additional pathway, with
glutaric acid, that perhaps may qualify, but I'm not convinced.
[https://en.wikipedia.org/wiki/Butyric_acid](https://en.wikipedia.org/wiki/Butyric_acid)
[http://mbio.asm.org/content/5/2/e00889-14/F1.expansion.html](http://mbio.asm.org/content/5/2/e00889-14/F1.expansion.html)

~~~
spangry
I think this is the crux of the issue. If one ascribed to the prion
hypothesis, than ketogenic metabolism would almost certainly have to be
related to higher probability of prion formation, and more survivable
conditions in vivo.

Another common way some AAs are metabolised is by hydrogenation is red blood
cells. So I think this eats up a hydrogen ion at the very least, leading to
greater intra-cellular oxidisation and a messed up blood plasma pH, increasing
the occurrence of abnormal enzymatic reactions. The metabolites you mentioned
are present in much larger quantities on low carbs, due to increased synthesis
and use of proteins for energy, including for the brain...

Oh and at least a few of those metabolites sometimes ultimately metabolise to
acetone, especially if normal metabolism disrupted by wonky pH balance.

Anion gap in soft tissue cells may also explain 'twitches': spontaneous
muscular activation due to soft tissue cell hyper-natremia (unbalanced towards
sodium).

Crazily, excess acetone restoration is one theory that explains spontaneous
human combustion (acetone is quite volatile and flammable)...

~~~
spangry
Damn auto-correct. That should be "acetone respiration".

------
fatdog
There is related work on dementia as well, wish I could find it. Something to
do with increasing dietary ketones (using oils) to make up for glucose
processing issues in people who were long term pre-diabetic.

It was a dinner conversation, where a guy was reasoning that some degenerative
and autoimmune diseases were related to tissue starvation as a result of
inhibited glucose processing, and he was using ketones (with some perceived
success) to treat symptoms of his own auto-immune disorder.

It's not evidence or confirmation in any way, but for any biohackers out there
it's something to play with.

~~~
spangry
Just to provide the counter-point: also possible that increased protein
metabolism and synthesis (the defining feature of ketogenic diets) increases
the likely hood of long -lived prions: proteins that fold abnormally, which
can be learned by other newly synthesised proteins leading to these "mutant
proteins" forming plaques on the brain (which is now burning protein for
energy due to depletion of glucose).

And there might be a runaway/tipping point somewhere here: some amino acids
have acidic metabolites and also need to capture hydrogen ions from red blood
cells to metabolise/synthesise protein. Some of these metabolites also cause
acetone build up in body, which starts to be expelled via lungs.

So combo of high rates of protein synthesis, abnormal blood plasma pH balance
and increases cell oxidisation and anion gap == greater rate of prion
formation and survival.

This is just a personal hypothesis, no real evidence to back it up. Just
suggesting caution should be exercised here. PD is a horrible disease, I
wouldn't wish it on my worst enemy.

~~~
fatdog
It's important to discuss. There is a lot of stuff out there that screams
snakeoil about MCT and coconut oil products, and it can have the effect of
both discouraging legit research and duping the dupable.

If there were only a way to test medical hypothesis like hacking on code.
Maybe a platform to crowdsource data for experiments then control for factors
and double blind it.

------
GeertVL
Too little to late for my dad. R.I.P.

~~~
feld
same, lost my father two weeks ago.

~~~
learned
Sorry for your loss.

------
laypersonjoe
By country. Does gut bacteria have differentiation by region/country/diet and
by extension can some diets be less causative?
[http://www.worldlifeexpectancy.com/cause-of-
death/parkinson-...](http://www.worldlifeexpectancy.com/cause-of-
death/parkinson-disease/by-country/)

~~~
zdean
I'm not sure if it has differentiation, but lifestyle factors could have an
impact. If, for example, in more developed countries there's a great emphasis
on (especially) childhood cleanliness, it may be affecting the development of
"good" bacteria:

[http://www.bbc.com/future/story/20151118-can-you-be-too-
clea...](http://www.bbc.com/future/story/20151118-can-you-be-too-clean)

Another lifestyle example could be the prevalence of C-section births in more
developed countries:

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110651/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110651/)

~~~
laypersonjoe
From the map I linked above, developed countries seem to have high rates.
Parkinson's doesn't seem to discriminate there, so is there any other thing
interesting by country? Spurious and sounds silly, but spicy foods, maybe?

~~~
spangry
That would be an interesting data point. Highly acidic...

------
andy_ppp
What do we know so far?

\- Gut Bacteria are involved

\- Inflammation is involved

\- The brain works on glucose

\- The brain can also work on Ketones

\- Cinnamon seems to help in mice trials (and also has anti-inflammatory
properties).

\- Could diabetes be analogous to Parkinson's? Diabetics generally have lost
the ability to process carbs (usually by eating too many); could Parkinsons be
caused by people being very dopamine focused and wearing their brains out?

I wonder if diet can change the type of bacteria in the gut, the inflammation
in the body, have a neuroprotective effect on the brain?

Sounds like I'd try a ketogenic diet which has known neuroprotective effects,
changes the bateria in your gut and reduces inflammation.

~~~
pascalmemories
> Diabetics generally have lost the ability to process carbs (usually by
> eating too many)

That's an outrageous misrepresentation of diabetes ( _all_ types).

Diabetics process carbs exactly like everyone else. The body breaks them down
and throws the sugars into the bloodstream in the perfectly normal way.

The lack of insulin (generally Type 1) or the resistance to insulin present
(generally Type 2), means the cells struggle to process the glucose, leading
to uncontrolled rise in glucose levels to dangerous levels.

The body has a poor 'over-limit' response to glucose and tries rather
inefficiently to dump the excess in urine which has limited success. As a
consequence lots of short-term and long-term damage to the body results - some
of which is still being discovered.

Causes of diabetes have multiple possible elements, including none, one or
more of : genetics, environmental [e.g. infection] and lifestyle.

"eating too many [carbs]" is a myth and intended to be derisive and
offensively stereotype diabetics as being wholly responsible for their
condition - just dressed up as a more socially acceptable victim-blame than
saying they're receiving God's punishment for having sugar in their coffee.

Science has conclusively proven diabetes is not some simple response to over-
indulgence in carbohydrate.

Stop making offensive and untrue claims.

~~~
andy_ppp
I'm sorry for upsetting you but from my research eating high sugar/carb diets
(without exercise) causes insulin resistance in the majority of people. There
are some groups that are more susceptible to this of course.

I'm not blaming anyone or even thinking about that; I've just done a lot of
research and listened to a lot of interesting studies about the gut biome,
western diet, insulin resistance, weight training, HIIT, noticing how I feel
if I eat lots of sugar and carbs, and trying to eat a more health diet.

Maybe I'll be proved to be wrong, I'm just giving an opinion based on some
research I've done.

Also by process I've definitely used the wrong word there. I definitely mean
utilise.

~~~
paulcole
>Maybe I'll be proved to be wrong

That day has come

[http://goaskalice.columbia.edu/answered-questions/it-true-
ea...](http://goaskalice.columbia.edu/answered-questions/it-true-eating-too-
many-carbohydrates-can-cause-diabetes)

~~~
andy_ppp
That doesn't disprove anything I've said; it says diabetes is _probably_
caused by eating too much which spikes blood glucose which causes diabetes.
What you are saying with your pithy comment is really great but what I've said
is eating sugar and processed carbs spikes blood sugar, over time it leads to
resistance to the insulin your body produces. If you eat too much your body
(even some fats or protein) produce an insulin spike. If you spike your
insulin 20 times per day with soda you will almost certainly at some point
become diabetic. You simply won't be able to eat enough fat or protein let
alone veggies to do this so we are back to my original point...

~~~
paulcole
> If you spike you insulin 20 times per day with diet soda

"the evidence that connects artificial sweeteners to “insulin spiking” is
limited"

[http://www.goaskalice.columbia.edu/answered-
questions/diet-s...](http://www.goaskalice.columbia.edu/answered-
questions/diet-soda-and-insulin-spikes-0)

~~~
andy_ppp
Sorry I mistyped somehow (corrected) diet soda is a whole different
discussion...

------
ccvannorman
I found a related article that lists specific bacteria for anyone interested:
[http://www.parkinson.org/find-help/blogs/whats-
hot/january-2...](http://www.parkinson.org/find-help/blogs/whats-
hot/january-2015)

------
codeulike
Tldr: they showed certain gut bacteria are necessary for Parkinson's to
progress (but not the sole cause) using an experiment with genetically
identical mice.

~~~
dekhn
More importantly, our understanding of parkinson's wasn't "Transformed", so
much as, somebody ran a highly specific experiment on a substrain of mice that
is not representative of humans, and tried to generalize their results.

------
varchar1
My friend is a good Ayurvedic doctor. As per Ayurvedic diagnosis and treatment
- root cause of most disorders point to improper digestion and accumulation of
'ama' (no English translation although some people say toxins for lack of
better word). Practically all Ayurvedic treatments have diet guidelines to be
followed with treatment.

I've seen some remarkable healing and recovery in people. But diagnosis and
treatment is a specialized skill. Many modern Ayurvedic doctors also use
allopathic diagnosis and reports in conjunction with pulse and other Ayurvedic
diagnosis.

------
nonbel
Has anyone noticed how quickly a new research direction gets connected to all
the big diseases? It has only been a few years since microbiome research
really became a thing. It is disconcertingly fad-like. From pubmed:

    
    
      pubmed - human microbiome	
      year	count
      2017	27
      2016	5464
      2015	5544
      2014	4283
      2013	2993
      2012	2064
      2011	1405
      2010	910
      2009	679
      2008	520
      2007	392
      2006	290
      2005	245
      2004	160
      2003	135
      2002	118
      2001	74
      2000	78
      1999	57
      1998	57
      1997	54
      1996	35
      1995	30
      1994	17
      1993	18
      1992	23
      1991	24
      1990	24
      1989	25
      1988	27
      1987	14
      1986	11
      1985	20
      1984	10
      1983	10
      1982	8
      1981	9
      1980	10
      1979	13
      1978	11
      1977	7
      1976	10
      1975	3
      1974	2
      1972	1
      1971	3
      1970	2
      1969	2
      1968	2
      1967	2
      1966	3
      1965	2
      1964	2
      1963	3
      1961	2
      1958	1
      1956	1

~~~
Benjamin_Dobell
I know _nothing_ about microbiome research. However, I don't think _" fad-
like"_ is a logical conclusion just because the amount of research is
continuing to increase. This just seems more like typical human advancement
and dissemination of knowledge.

For instance, I'm sure you'd find a similar trend with "computer", "solar
energy" and "global warming". Someone discovers something and it takes a while
for everyone to catch on. However, if the concept has legs, more and more
research will take place until we understand the concept enough for it to
become a part of every day life.

~~~
nonbel
>"I don't think "fad-like" is a logical conclusion just because the amount of
research is continuing to increase. This just seems more like typical human
advancement and dissemination of knowledge."

I mean that the direction things are going it will eventually be discovered
that "everything is correlated with everything else"... in hundreds of years.
Why not just assume that to begin with? Take it as a first principle. Instead
what we care about is measuring the quantitative relationships (what
functional form, etc) between various factors.

Also, I just now looked at the paper. I cannot believe neuroscientists are
still getting away with this. There is not a single scatter plot. Let's look
at the highlights:

    
    
      - Gut microbes promote a-synuclein-mediated motor deficits and brain pathology
      - Depletion of gut bacteria reduces microglia activation
      - SCFAs modulate microglia and enhance PD pathophysiology
      - Human gut microbiota from PD patients induce enhanced motor dysfunction in mice
    

So I expect to see scatter plots of:

    
    
      "# of gut microbes" (or "% pathogenic microbes") vs "motor deficits"
      "a-synuclein levels" vs "motor deficits"
    
      "# of Gut microbes" (or "% pathogenic microbes") vs "brain pathology"
      "a-synuclein levels" vs "brain pathology"
    
      "Gut bacteria levels" vs "microglia activation"
    
      "SCFA levels" vs "microglia activity"
      "SCFA levels" vs "PD pathophysiology"
    
      "# of human PD microbes" (or "% human PD microbes") vs "motor dysfunction"
    

You can see the entire project was designed around _seeing if there is a
correlation_ , which we should already assume is true. Instead we should be
looking at those scatter plots, so we can achieve the useful goal of
_discerning the relationship between various biological phenomena_.

