Mitochondria may hold keys to anxiety and mental health
quantamagazine.org
quantamagazine.org
That's accepted as scientific orthodoxy now, but it wasn't always. In the 1960's, evolutionary biologist Lyn Margulis proposed the theory that cell organelles such as mitochondria and chloroplasts were once independent bacteria, which combined through symbiotic mergers of bacteria to evolve into eukaryotic cells. Ernst Mayr called this "perhaps the most important and dramatic event in the history of life".
Throughout her career, Margulis' work could arouse intense objection. One grant application elicited the response, "Your research is crap, do not bother to apply again", and her formative paper, "On the Origin of Mitosing Cells", appeared in 1967 after being rejected by about fifteen journals.
In 2002, Discover magazine recognized Margulis as one of the 50 most important women in science.
In 1995, Richard Dawkins said, "I greatly admire Lynn Margulis's sheer courage and stamina in sticking by the endosymbiosis theory, and carrying it through from being an unorthodoxy to an orthodoxy. I'm referring to the theory that the eukaryotic cell is a symbiotic union of primitive prokaryotic cells. This is one of the great achievements of twentieth-century evolutionary biology, and I greatly admire her for it."
> Margulis said that "the set of symptoms, or syndrome, presented by syphilitics overlaps completely with another syndrome: AIDS," and also noted that Kary Mullis[a] said that "he went looking for a reference substantiating that HIV causes AIDS and discovered, 'There is no such document.' "
> This provoked a widespread supposition that Margulis had been an "AIDS denialist." Notably Jerry Coyne reacted on his Why Evolution is True blog against his interpretation that Margulis believed "that AIDS is really syphilis, not viral in origin at all."[50] Seth Kalichman, a social psychologist who studies behavioral and social aspects of AIDS, cited her 2009 paper as an example of AIDS denialism "flourishing",[51] and asserted that her "endorsement of HIV/AIDS denialism defies understanding."[52]
Also: 9/11 crankery!
> Margulis argued that the September 11 attacks were a "false-flag operation, which has been used to justify the wars in Afghanistan and Iraq as well as unprecedented assaults on ... civil liberties." She claimed that there was "overwhelming evidence that the three buildings [of the World Trade Center] collapsed by controlled demolition."[5]
This fascinating discussion will make your jaw drop https://www.discovermagazine.com/the-sciences/discover-inter...
She's not esteemed in the field of what causes AIDS. She's esteemed in a different sub-field. In terms of AIDS, the actual experts have come to the conclusion she's wrong, and one thing we should all have learned by now is that our ignorance is not equal to the knowledge of experts.
> This fascinating discussion will make your jaw drop
Not for the reasons you think it would, though.
The history of science also told us by now that experts are stubborn, and sometimes they have to first die, for the next generation to accept another theory.
It has also taught us that important new discoveries more often than not come not from established experts in a field, but by people from another sub-field or another field all together...
It has also taught us that scientists should continue challenging prevailing hypotheses all the time, because that's part and parcel of doing science...
It tells us too that cranks will be cranks regardless of the evidence against them, and that cranks are more common than true revolutionaries.
Expertise is the result of successful scientific seeking.
So I knew this was mitochondrial but it was revealed when I received my genome. We have issues with our electron transport chain; Complex I (ND1 and ND4) and Complex III (MT-CYB).
So diet and lifestyle was crucial in getting me off all of my meds, and I was on a lot. High dose riboflavin was a huge help.
Getting complex I to work well helps with the heart since it increases NAD. Also getting enough ubiquinone from diet helps. I get it mostly from seafood like Salmon and Liver. I might try and take a CoQ10 supplement soon. But the fact that we make it endogenously makes me think it is not needed. Statins will stop the production of CoQ10 by lowering FPPP production which is why they fail to help people with Heart Disease.
Balancing the flow and the oxidative stress from the mitochondrial electron transport chain is crucial.
That sounds awfully familiar. Would you be so kind to provide any starting point to begin research into this, including the supplement stuff you mentioned afterwards?
The supplements came after I saw my genetics and from past anecdotal experiments. But maybe start by understanding the electron Transport chain. When I saw all the oxidative stress created there I began looking at the several pathways for the flow of O2- and H2O2. To me, mood disorders have their root in this flow being unobstructed.
Riboflavin ended up being big for me for several reasons.
Keep in mind, mood disorders are polygenic, may causes, so for you it might be something with Monoamines or what ever.
I wish doctors would get serious about testing for these deficiencies in people wit mood disorders...
I checked https://www.snpedia.com/index.php/Depression but maybe you know better which SNPs are most important?
I got my genome and checked it using promethease, but 'sadly' I didnt get any major 'depression' hit; only minor SNPs which were correlated with 1.5x more probability to get depression
And I got no advice on which diet could help me :)
The ortate I took as an experiment wen I was more recently depressed and it made me hypomanic. This makes sense if you know Lithium inhibits IMPase and IPPase. And on the other side GSK-3.
It is only at high doses that you get the NMDA and GABA effects. Which is too high IMHO. I still rely on Klonopin now and then when I mess up. (No, I do not take it everyday and I take the lowest dose possible, so don't bother telling me how dangerous it is.)
I would like to know more about this. I've been on a statin for several years and feel like my energy has dropped through the floor in that time. I also feel like I have a 'statin hangover' when I wake up in the morning (I usually take it with my supper). This could all be correlation, and aside from cholesterol levels I haven't been diagnosed with heart disease. But I would like to know more, because I hate taking this stuff and really don't like the idea of being on it the rest of my life.
https://ubiquinol.org/sites/default/files/statins.gif
The thinking on cholesterol and heart disease is changing rapidly and there really is no strong evidence high cholesterol before a heart attack leads to any bad outcomes. After a heart attack, statins are ok.
But like we see, side effects. My doc wanted me on them but they gave my mother horrible myopathy so I passed. My HDL was really low until I took out all plant oils and eat fats pretty much only from fish and olive oil. Now my HDL in mid range normal. This is becasue the omega 3 helps with reverse cholesterol transport.
But again, this is me and my genetics. We have Saami (Inuit) heritage which is why I think i need this diet.
Nobody is going to deny that a badly functioning component in your body can affect your mental health, and some of the mechanisms sound interesting, but not enough to call mitochondria the "key to anxiety and mental health". It's more like: an easily overlooked factor that can contribute.
"Mitochondrial Mg2+ homeostasis decides cellular energy metabolism and vulnerability to stress"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960558/
Anecdotally, I've been taking Magnesium l-threonate and it's probably the least anxious I've ever been in my entire life (I'm 42).
The only thing comparable was Lexapro, but I always had a love/hate relationship because of the side effects.
I take one scoop, 2-3 a day. Depends on how stressed I am. Always once in the morning. Sometimes in the afternoon (it seems to help my concentration stamina). Once close to bed.
Ruminations have diminished. Anxiety greatly lowered.
I still get sad, angry, etc. But those feelings seem to dissipate much quicker. Mentally I get exhausted less. N=1, of course.
*I also take a calcium/vitamin d/zinc combo as well.
I'm open to this being placebo effect.
In the morning especially, my anxiety always seemed to be at its highest. If I took the mg l-threonate before bed, those feelings in the morning just weren't there.
Have several crippling conditions. Magnesium has brought drastic relief.
Muscle aches, migraines, cognitive issues.
Al much improved.
Haven't tried msg l threonate, will order some thing week.
Full disclosure: studied nutritional medicine in a formal capacity.
https://www.vitaminshoppe.com/p/one-daily-men-multivitamin-1...
Check back here later, or contact me as per details in my profile.
But if you are sensitive to magnesium's laxative effects you may want to look for another formulation.
> protected mice vulnerable to behaviors associated with depression in humans
Which I'm curious about as well.
Anectdotally also, I take Magnesium Bisglycinate from Thorne occasionally and it helps me relax and feel less anxious. My muscles stay pretty rigid normally and after taking the magnesium supplement I can feel everything loosen up. Helps with sleep too.
I experienced some reduction in anxiety with the glycinate. It also seems to be the best form for sleep support.
But the l-threonate was on the level of an SSRI for me. The anti-anxiety effect was really pronounced.
The authors findings demonstrate low brain free [Mg2+] in our patients and indicate that it resulted from failure of the respiratory chain.
I interpret that as saying that the more Magnesium you have in your body, the less energy you have. Also, the less energy you have, the less anxiety you feel. That sounds wrong to me, although I can't explain why.
Am I confused? What am I missing?
This is how I understand the anxiolytic effect of mg works:
>It acts as the gatekeeper for the N-methyl-D-aspartate (NMDA) receptors, which are found on your nerve cells and aid brain development, memory and learning.
>In healthy adults, magnesium sits inside the NMDA receptors, preventing them from being triggered by weak signals that may stimulate your nerve cells unnecessarily.
>When your magnesium levels are low, fewer NMDA receptors are blocked. This means they are prone to being stimulated more often than necessary.
Maybe this is why I experience more rumination without magnesium?
https://www.healthline.com/nutrition/what-does-magnesium-do#...
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960558/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997778/
In case you are wondering, Suramin[1] is the drug
> It is also interesting to note in the context of stress regulation that all steroid hormones, including glucocorticoids and sex hormones, are synthesized in a process that is regulated by, and occurs in mitochondria, further linking mitochondrial biology to stress signaling.
Stress in this sense refers to all biological stressors such as physical exertion. Mitochondria, therefore, are not only central to energy production but also to stress response. This is simply how the system works.
That being said, there were recently some breakthroughs in this area: https://www.nature.com/articles/d41586-020-02094-x
We’ve known TALENs can edit for a while, but that breakthrough made it a lot more efficient.
From an engineer’s perspective, mitochondria are kinda the equivalent to virtual machines running on normal computers, as little “virtual cells” within cells. Their genomes are so stripped down that you can do some wild things with them.
https://en.wikipedia.org/wiki/Lentiviral_vector_in_gene_ther...
https://en.wikipedia.org/wiki/CRISPR
These next two do the same thing as CRISPR, only they are older technologies that take you longer to generate the probes in the lab to target your spot in the genome. The real advantage of CRISPR isn't what it does, that was already out there, it's that it's cheap and fast (comparatively) and an undergrad can do the whole experiment.
https://en.wikipedia.org/wiki/Zinc_finger_nuclease
https://en.wikipedia.org/wiki/Transcription_activator-like_e...
But IIRC weren’t mitochondria subsumed by another cell for ATP output forever ago in our evolutionary development?
Note that 99% of the proteins contained in mitochondria are [coded] in the nucleus, only 1% is [coded] in the mitochondrial chromosome. It's extremely small, only containing 37 genes of which most are related to translation (but of course translation requires far more, e.g. elongation factors).
[1] https://en.wikipedia.org/wiki/Von_Neumann_universal_construc...
Perhaps with the right anti-depressant cocktail, I wouldn't bother.
George Bernard Shaw
0. https://twitter.com/buss_patriarchy/status/12890769568734658...
Sure, if social conditions are the primary factor in a person's mental health problems then "blaming" and attempting to address the issue at a neurochemical basis with medication may not be warranted. But to paint the entire illness with that brush is to overlook the complexity of the problem.
You have no safety living on the street. None of your possessions are safe if you leave them alone. You have no money, no resources at all because any step forward to lift yourself out of this requires putting money down up front. People treat you less than human based on your appearance alone, which grows more haggard the longer you are living out there with few pairs of clothes and limited ways to wash them or yourself.
It's absolutely awful how we treat our mentally ill in this country, and the lack of any will to do anything about it from all levels of government.
That's the "lack of any will to do anything about it from all levels of government" we should be worried about.
Also understanding does not automatically lead to fixing. We understand a lot of things that we haven't been able to change. And what if the understanding we gain shows us that the causes of our anxiety and mental health issues are things in the world around us?
In theory at least, with perfect mental health I will be able to confidently relate my feelings to the external world and be able to reason about changing the external world to deal with real anxieties rooted in perceptions of real danger.
I think for people who suffer from mental illness related to anxiety, or at least for me, the goal is not to completely eliminate anxiety but to be able to know that the anxiety I feel is reasonable and appropriate. (Similarly for my chronic depression)
Of course the line between reasonable and unreasonable anxiety is not always clear. The far points are clear, being anxious about some stranger approaching you with a gun, that's reasonable, being unable to get out of bed because you are certain everything is going to go wrong no matter what, that is unreasonable. But should you be anxious about this person because you did that thing but you have a history with this person and... that sort of thing is fuzzy.
Or the power of hackneyed sayings and satire :P
> “They’re the chief executive organelle of the cell.”
Which IMO sounds odd, given that Mitochondria are seldom described as having much "decision making" power.
TIL that evolution is a GAN.
Apparently, there is a whole economy for transporting microchondria within dendrites. More mitochondria in an area of the dendrites allows for faster growth and responsiveness to input.
(There is another time-lapse video I've seen before of mitochondrial transport, but I'm frustrated that my own browsing history isn't making it easier to find. Are there tools that help make ones own browsing history more useful/accessible?)
NR is a precursor to NAD+, which has been shown to improve mitochondrial function especially under stress.
NAD+ is one of those molecules used in a ton of metabolic processes and over a lifespan NAD+ avalability declines. This decline is linked to numerous age-related diseases. There's a bit of research showing NAD+ supplementation contributes to anti-aging effects.
NR is easy to take, well-tolerated, and a cheap precursor for NAD+. There are IV clinics that have NAD+ infusions, but they cost like $500. On the other hand, you can get a month's supply of NR for around $50 (Thorne's ResveraCel).
"Mitochondria and the Future of Medicine: The Key to Understanding Disease, Chronic Illness, Aging, and Life Itself"
-- by Lee Know
At least he's honest about his lack of medical expertise and conflict of interest.
>Do you think the medical industry is forward-thinking or adverse to new ways of thinking in general?
Both. It's so vast that sweeping generalizations don't really apply.
>... but there are many cases of people outside or peripheral to a domain without qualifications that make a huge impact on a particular area and lead the way for more research ...
Sure, but an ND with ties to the supplement industry ain't that.
>... and we are all aware of the medical establishment's lack of proper training when it comes to nutrition.
You could even argue the medically-recommended low-fat diet craze was one of the largest health disasters in modern history. Unfortunately it doesn't make this guy any more correct or rigorous in his opinions.
Please understand this isn't a personal attack. I take supplements and aggressively fast every day precisely because I largely believe in the mitochondrial theory of aging. For all I know, everything in the book could be factually correct and not misconstrued. It doesn't change the fact the author is presenting themselves as a medical expert.
It's a variant of Betteridge's law, if you will.
> Carmen Sandi recalls the skepticism she faced at first. A behavioral neuroscientist at the Swiss Federal Institute of Technology in Lausanne, she had followed a hunch
I feel like people use “radical ideas” like this to justify whatever their bullshit of the day is, and generally ignore the fact that they almost always come from experts in their respective fields.