
Elusive mitochondrial connection to inflammation uncovered - dtawfik1
https://www.nature.com/articles/d41586-018-05988-z
======
fasteo
Interesting post and comments, as usual. I wanted to give some pragmatic
information related to this.

I have a genetic condition that makes my mitochondria to malfunction. I was
diagnosed about 10 years ago. At first, I started taking supplements to
increase the production of ATP, but my "vitality" did not improve much. I
could workout normally, but my recovery ability was poor, and from time to
time I would just crash and burn for 2-3 days.

After much reading, I came to the conclusion that the problem was not a
shortage of ATP. Rather, it was the mess created by all the workarounds my
body was doing to maintain a level of ATP that could keep me alive. So, I
started taking the following pre-bed stack. It is meant to be a clean-up the
mess, anti-inflammatory:

\- 2g Vitamin C

\- 500 mg reduced glutathione

\- 500 mg curcumin (I prefer BCM-95)

\- 1-5 mg melatonin (depending on activity level)

\- 100 mg CoQ10

(I am also considering adding Ashwagandha to the stack)

As of today, I workout 4-5 times per week, with 2 sessions of boxing (like
punching in the face, not the aerobic variation), 1 heavy lifting session
(usually squats) and 1-2 metabolic circuit sessions.

Sure I feel tired at times, but it is not liked the deep, extreme fatigue I
felt before starting this stack.

Hope this helps.

~~~
Numberwang
I'd recommend turmeric instead of curicumin and to not take melatonin but I'm
happy you are feeling better, so whatever works for you.

~~~
fasteo
Thanks for the recommendation.

Could you elaborate a bit, specially about melatonin ?

~~~
mtgx
On the melatonin I would add that studies have shown negligible increase in
effectiveness over 0.3mg. Yes, most pharma stores offer only 3mg and above,
but that seems to be wrong.

Personally I've only taken melatonin when I most needed it, and then gave up
on it. You should try giving it up, too, unless you really can't do without
it.

You should check the vitamin D level, too, whenever you do your next blood
test.

As for curcumin, the Longvida formula seems to be most effective. I can't say
I've noticed any effects from it myself, but I haven't taken it daily, and
I've also read that you need to take curcumin for 2+ weeks to see the effects.

[https://www.turmericforhealth.com/curcumin-benefits-and-
dosa...](https://www.turmericforhealth.com/curcumin-benefits-and-
dosage/8-popular-curcumin-supplement-types-in-market-today-a-quick-review)

~~~
fasteo
On the melatonin, note that I do not take it to fall asleep, but for its
protective effects in the mitochondria. This [1] is a good review.

[1]
[https://onlinelibrary.wiley.com/doi/full/10.1111/j.1600-079X...](https://onlinelibrary.wiley.com/doi/full/10.1111/j.1600-079X.2004.00181.x)

~~~
Numberwang
Here is an interesting video re melatonin:

[https://www.youtube.com/watch?v=2q1ln6vaSE0](https://www.youtube.com/watch?v=2q1ln6vaSE0)

------
jonmc12
If you are interested in more information about Autophagic processes, this
video interview is great:
[https://www.reddit.com/r/fasting/comments/6qobj7/rhonda_patr...](https://www.reddit.com/r/fasting/comments/6qobj7/rhonda_patrick_brings_nerd_level_video_on/)

Rhonda Patrick interviews Dr Guido Kroemer, an expert in Autophagy. Its one of
the most accessible, well-referenced and thorough discussions on Autophagy
(including Mitophagy), that I've come across.

~~~
dpatrick86
Transcript and other resources available here.
[https://www.foundmyfitness.com/episodes/guido-
kroemer](https://www.foundmyfitness.com/episodes/guido-kroemer)

Thanks for sharing!

~~~
ra
Dr Rhonda Patrick's podcast, Found My Fitness, is excellent.

------
reasonattlm
Oxidative stress and inflammation go hand in hand. Aging has rising levels of
both.

Mitochondrially targeted antioxidants such as SkQ1 were first approved for use
against inflammatory eye conditions. They act to dampen the consequences /
amount of inflammation, and do this by cutting down on oxidizing molecules
produced within mitochondria. They were first developed out of an interest to
slow aging through this sort of modulation of mitochondrial oxidative stress
and damage. They do slow aging to some degree, but don't do anywhere near as
well as calorie restriction - say 10% in flies, something less than that in
mice, which isn't impressive.

The first earnest human trials for mitochondrially targeted antioxidants such
as MitoQ (which from the studies is actually less effective than SkQ1) suggest
it can reduce the impact of oxidative stress or inflammation on the smooth
muscle cells in blood vessel walls. Their dysfunction produces some fraction
of the stiffening of blood vessels with age. That stiffening causes raised
blood pressure, which in turn causes too many bad things to list here.

So these are not massive effects. You can probably do as well as MitoQ by
bumping up your exercise level to the next tier. But then you can always both
exercise and take a mitochondrially targeted antioxidant. The costs are not
high, so it may be worth it based on the preliminary data.

Not a cure for aging, and thus not worth spilling immense amounts of ink and
effort over it. Just something to think about doing and then get on with
better development projects with better expected outcomes.

~~~
SubiculumCode
Then melatonin supplementation might be the way to go....
[https://scholar.google.com/scholar?as_ylo=2018&q=melatonin+m...](https://scholar.google.com/scholar?as_ylo=2018&q=melatonin+mitochondrial+stress&hl=en&as_sdt=0,5&as_vis=1)

------
ArtWomb
One mental model which may help in visualizing "oxidative stress" in
mitochondrial networks is to liken it to a "first-order phase transition" in
solid-state physics. Gene expression regulates structure. And structure
determines function.

But whereas a typical sample of inorganic material may possess a handful of
stable states under room temperature conditions. Nuclear genomics in mammals
express 1000s of proteins.

MIT's Broad Institute has begun compiling a reference atlas:

MitoCarta 2.0: An Inventory Of Mammalian Mitochodrial Genes

[https://www.broadinstitute.org/scientific-
community/science/...](https://www.broadinstitute.org/scientific-
community/science/programs/metabolic-disease-
program/publications/mitocarta/mitocarta-in-0)

~~~
narrator
If you could acurately simulate biological systems with a computer model, you
could do drug development in the cloud without the need for clinical trials.
Unfortunately, protein folding and even predicting whether a molecule will be
an agonist at a particular receptor site are very slow algorithms.

~~~
JunkDNA
Accurately simulating biological systems in the cloud to run a virtual
clinical trial is like trying to predict the exact weather for Washington DC
at a specific date and time hundreds of years from now using weather forecast
models. It’s pretty much impossible with current biomedical knowledge.

To simulate humans well enough to eliminate a clinical trial, you would have
to simulate every single cell, organ, and organ system as well as the
substantial population of bacterial and fungal microorganisms that live on and
inside humans (as well as all their unique biology too). Building such a
simulation would require a level of knowledge of biology that the human race
currently does not possess.

~~~
snaky
That is and will stay impossible no matter how many resources for simulation
you have, actually.

> This technique, when applied to the real world, is sometimes useful, but can
> sometimes also lead to self-deception. This technique is called modelling.
> When constructing a model, the following idealization is made: certain facts
> which are only known with a certain degree of probability or with a certain
> degree of accuracy, are considered to be “absolutely” correct and are
> accepted as “axioms”. The sense of this “absoluteness” lies precisely in the
> fact that we allow ourselves to operate with these “facts” according to the
> rules of formal logic, in the process declaring as “theorems” all that we
> can derive from them.

> It is obvious that in any real-life activity it is impossible to place total
> reliance on such deductions, if only because the parameters of the phenomena
> studied are never known absolutely exactly and a small change in parameters
> (for example, in the initial conditions of a process) can totally change the
> result. It is for this reason that a reliable long-term weather forecast is
> impossible and will remain impossible, no matter how much we develop
> computers and devices which record initial conditions.

[https://dsweb.siam.org/The-Magazine/All-Issues/vi-arnold-
on-...](https://dsweb.siam.org/The-Magazine/All-Issues/vi-arnold-on-teaching-
mathematics)

------
fsnarskiy
This is actually very interesting.

Low-grade inflammation is often linked to aging and cancer developments, it is
however often unclear whether its cause/effect or correlation -
[https://academic.oup.com/biomedgerontology/article/69/Suppl_...](https://academic.oup.com/biomedgerontology/article/69/Suppl_1/S4/587037)

But mechanisms of inflammation are many and still pretty illusive, this is a
great step towards understanding aging mechanisms in general.

------
wolco
This is highly interesting. After taking ciprofloxan 10 months ago I'm still
trying to get my damaged mitochondria back in order.

~~~
delbel
Wow thanks for your post. I had to look up and I was surprised that
antibiotics can damage your mitochondria. But it makes sense because I was
told, back in biology, the mitochondria were actually a bacteria and
"swallowed up" by mammal cells. (forgive me, that's a extremely trivial recall
of my memories and I am not an expert in this field)

If you are interested (and very brave, there are risks here), apparently there
is a SARM that can help your mitochondria grow back. It's called Stenabolic
SR9009. I have never tried it (because I have no need), but I'd be interested
in what you think about it. You can find information on it online, I don't
want to post anything because I am not qualified to vet the information --
information is all over the web however.

~~~
wolco
For me the experience has made me less risky in general (this was a standard
10 day treatment for sinus infection). Fasting / exercise for now. My biggest
issue is the gut and repopulating bacteria. Once that's in order I may try
something like the Stenabolic.

------
king_panic
2012:
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536340/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536340/)

------
baccheion
Vitamin D3 (+ K; 10 IU D3 : 2 mcg+ MK-4) + chelated/TRAACS magnesium.
Magnesium is released by the body to clear inflammation. Vitamin D induces
autophagy, and counters inflammation and oxidation.

Riboflavin (selenium, vitamin E, etc) is involved in the recycling of
glutathione. MSM + silicon (monomethylsilanetriol) + vitamin C. 4g:1g MSM:C.

------
MarkThief
So this could be what is causing all these nearly undiagnosable cases of
autoimmune disease?

------
twodave
There are about half a dozen solid rock band names in this headline:

Hello [City], we are [Choose one below]! Duh nuh nuh nuh nuh, Duh nuh, Duh nuh
nayayayayay

\- Inflammation Uncovered \- Mitochondrial Connection \- Elusive Mitchondria
\- Elusive Inflammation \- Mitochondria Uncovered ...

------
0x8BADF00D
I wonder why we developed the STING protein in the first place. Was it perhaps
an early form of immunity, or a precursor to an immune response?

~~~
maxander
The name stands for STimulator of INterferon Genes, where interferons are
essentially message-carrying molecules involved with the immune system. STING
protein, I believe, is essentially a detector which gets triggered when a cell
is invaded by a virus or encounters a parasite. For that, it still serves an
important purpose.

------
jgalvez
Ray Peat anyone? :)

~~~
asdfasdfdavid
Absolutely, nobody knows better how to take care of our mitochondria than Ray
Peat.

