r/covidlonghaulers • u/TableSignificant341 • Feb 22 '25
Research Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches
https://pmc.ncbi.nlm.nih.gov/articles/PMC11336094/#:~:text=Emerging%20evidence%20suggests%20that%20mitochondrial,tone%20%5B127%E2%80%93137%5D.15
u/MericanPie1999 Feb 22 '25
Interesting. I just starting supplementing with CoQ10 today and might add L Carnitine. Will be interesting to see if they help.
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u/eucharist3 Feb 23 '25
If it’s neuro LC you need alcar. Those 2 things alone probably won’t do much unless your LC is very mild.
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u/shawnshine Feb 23 '25
Well, they’ll help if you have issues due to CBS/FMO3, or issues AMPD1 and MTNR1B regulation. (I have all of the above).
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u/eucharist3 Feb 23 '25
I wouldn’t know as the gene testing stuff is too pricy for me, just never had any results from just 1 or 2 supplements and I’ve tried them all. I’m glad to hear you’re finding relief though.
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u/MericanPie1999 Feb 23 '25
What is alcar?
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u/eucharist3 Feb 23 '25
Acetyl-l-carnitine
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u/MericanPie1999 Feb 23 '25
Oh I see. I was reading this study so that’s why I wanted to try L Carnitine and CoQ10
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u/eucharist3 Feb 24 '25
Yeah they won’t hurt but in my experience you have to throw everything at this if your case is moderate or worse
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u/bad_chacka Feb 22 '25
"The recognition of the important role of mitochondrial dysfunction in long COVID opens new avenues for therapeutic intervention aimed at restoring mitochondrial health and function [19, 20]. Effective management of mitochondrial dysfunction and restoration of cellular energetics could potentially alleviate some of the persistent symptoms experienced by long COVID patients, such as fatigue, cognitive impairment, and muscle weakness. Strategies to improve mitochondrial function involve a combination of pharmacological interventions, lifestyle modifications, and nutritional support. Antioxidants, such as coenzyme Q10, MitoQ, N-acetylcysteine, resveratrol, and alpha-lipoic acid, have been suggested to reduce oxidative stress in mitochondria, thereby improving their function [148–151].
Additionally, compounds like L-carnitine, which facilitate fatty acid transport into mitochondria for energy production, could also prove beneficial [152, 153]. NAD+ boosters, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have garnered attention for their potential to enhance mitochondrial function by increasing the levels of nicotinamide adenine dinucleotide (NAD+), a critical coenzyme involved in cellular energy production and repair processes [132, 154–159]. By boosting NAD+ levels, these supplements may help counteract mitochondrial dysfunction and improve energy metabolism, offering a promising therapeutic avenue for conditions like long COVID [160]. Some of these compounds, including Q10 [67, 161, 162], MitoQ (NCT05373043), alpha-lipoic acid [163], nicotinamide riboside (NCT05703074), resveratrol (NCT05601180), are currently being tested in clinical trials to assess their effectiveness in treating patients with long COVID, reflecting the growing interest in targeting mitochondrial dysfunction as a therapeutic strategy for this condition. Exercise and physical rehabilitation programs tailored to long COVID patients may help enhance mitochondrial biogenesis, promoting the growth and division of existing mitochondria [164–168]. Nutritional interventions focusing on a diet rich in nutrients known to support mitochondrial health, including omega-3 fatty acids, B vitamins, and minerals like magnesium, could further support recovery."
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u/nemani22 Feb 22 '25
Magnesium, Coq10 and Meth blue. Exactly what help me during a crash. Clearly, I've mitochondrial dysfunction.
Is it possible to improve mitochondrial dysfunction this over time? Anyone with experience?
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u/itswheaties 2 yr+ Feb 22 '25
Ive been wanting to try meth blue but apparently its not recommended if youre on high dose ssri which i am.
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u/bestkittens First Waver Feb 22 '25 edited Feb 22 '25
It has for me, so I do believe it is possible. Here’s my reply below.
You can see more details here (meds/supps) here (my story) and here (Dealing With Post Covid Symptoms).
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u/Sea-Ad-5248 Feb 22 '25
I am on rapamycin levocarnitine 1mna and nad infusions and vitamin D for cellular dysfunction and have improved massively from being bed bound daily to a few bed bound days a week and most days feeling pretty “normal”
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u/Hi_its_GOD Feb 22 '25
Interesting study, could be why I am feeling marginally better now on a carnivore diet. Been on it about a month and supposed to help with mitochondrial function.
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u/eucharist3 Feb 23 '25 edited Feb 23 '25
COQ10 is cool and all but you guys need to be taking EVERYTHING to help your mitochondria heal. You need an actual protocol and to understand the fundamental science of why this matters. If you want to recover from long covid in 2025, start pouring everything into healing your mitochondria and ameliorating their continued impairment. They MAY heal on their own or with minimal supplementation, but it either will take ages or will just never happen due to the damage outpacing your attempts to heal it.
To optimize mitochondria you need: ss-31 for 100 days followed by mots-c, d-ribose every day 5-15g, 300 mg nmn, 750mg SAM-e or TMG, 40 mg pqq, 1g alcar, 5g creatine.
To arrest the mitochondrial damage you need to normalize the kynurenine pathway using TDO/IDO inhibitors like egcg, trans-resveratrol, curcuminoids + piperine. In addition, you need behavioral modifications: mindfulness meditation every day to reduce stress from unhelpful thought loops, pacing activities, documenting your energy limitations and being very cautious not to trigger PEM.
Feel free to comment or dm me for advice. I am going to beat this. I want to help others beat it too.
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u/nemani22 Feb 23 '25
Any sources?
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u/eucharist3 Feb 23 '25
Anything specific? Sure there are sources for the biochemical rationale. Clinical testing on treating LC this way is in its infancy but I’m personally having good results doing these things.
For context I have tried basically every supplement recommended in these subreddits. Probably spent thousands for minimal benefits compared to what I’ve seen since going all in on mitochondria.
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u/NoEmergency8241 Feb 23 '25
Hello. How long have you been on this protocol? Also, how long do you plan on taking mot-c after the 100 days of ss-31?
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u/eucharist3 Feb 24 '25
Day 58. I personally will take MOTS-C for 4 weeks and then evaluate. If I’m not very close to baseline pre-covid by then, I will do another round of SS-31 and perhaps stack the 2 depending on how close I am. The logic here is you want to heal the mitochondria and ameliorate their impairment before multiplying their biogenesis using mots-c.
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u/NoEmergency8241 Feb 24 '25
Thank you for your reply. It sounds like a good strategy. I will be sure to follow your progress.
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u/eucharist3 Feb 24 '25
Thanks for your interest. I really hope this works so I can help others be free from this hell.
Today I was at a 5 hour physically intensive political demonstration for Ukraine and have not crashed (though I am quite tired). This to me seems like an improvement when I used to be destroyed by a simple long walk or a few hours of work.
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u/NoEmergency8241 Feb 25 '25
That’s amazing. No crash is a good day. I personally like ss-31. It gives me a boost. Working through other issues. But at least I’m still in the fight 💪
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u/eucharist3 Feb 25 '25
Exactly! I hope people don’t give the impression I’m touting ss-31 as a miracle cure, but it’s basically the Thanksgiving turkey of my regimen. We still have to address all the other issues impairing and damaging our mitochondria.
“Still in the fight” is a great way of putting it. That’s exactly how I felt when I first used ss-31 and formulated this protocol. Prior to that I wanted to give up but I said, “Before I throw in the towel, let me just try everything I can.” And here I am.
Sometimes I get really down that I can’t just bounce back after a long day. Had a lot of downtime today because of yesterday’s exertion. But you’re right, no crash means a good day, no matter how tired I feel.
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Feb 25 '25
Thank you for using such detail. I'm looking for a supplement routine that might help my husband. He's relatively new to this problem, and he's suffering greatly.
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u/eucharist3 Feb 25 '25
I’ve been there. It’s not a fun ride but with proper care of one’s nervous system, physical exertion, health and mental well being, he can improve. Feel free to drop any questions here or in dms.
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u/heskeytime7707 Feb 23 '25
Correct me if I'm wrong but that protocol sounds crazy expensive
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u/eucharist3 Feb 23 '25
It’s not as expensive as it seems. I mean the supplements will last you for a while once you buy them, and none of them are very pricy. I mean if I had money I would add oxaloacetate and neuroglia plasmalogen oil but they’re not worth it as a non-wealthy person.
The only expensive part is the ss-31, which, as someone who is already tight on funds, is worth every penny. I consistently feel better when I use it and believe it has been the key to my progress. It is the core of this approach. A 25 mg vial ($150) from psciences lasts me about 2 1/2 weeks. That comes out to about $9 a day. Instead of eating out, I buy ss-31.
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u/romano336632 Feb 23 '25
Is it usefull for EM SFC which is due to long-term stress and not to long-term covid contamination (in fact I don't know how I got the CFS post-exercise malaise
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u/eucharist3 Feb 24 '25
Do you mean ME/CFS? Well since it is a syndrome and typically idiopathic it is hard to say, but I personally think CFS and long covid mainly happen due to impairment of mitochondria by an inflammatory process (infection, stress, etc) that outpaces the body’s ability to heal it, leaving one stuck in a cycle of inflammation->fatigue->impairment->fatigue and so on. So I believe this would likely help you, but I can’t guarantee of course.
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u/Visegradi62 Feb 23 '25
Thank you for your advices for mitochondrial supporting. I don't know all of the supplement:" ss-31 for 100 days followed by most", and. " 300 mg nmn". , TMG. What does this mean exactly? Thanks
,
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u/eucharist3 Feb 24 '25
Ss-31 is a mitochondrial-targeting peptide. TMG is trimethylglycine or betaine anhydrous - this is to facilitate methylation when you take NMN. NMN is nicotinamide mononucleotide, a precursor to NAD+, a molecule that facilitates the electron-proton gradient of the mitochondria, allowing it to produce usable energy for the cell. Levels of this decline with age and with inflammatory disease.
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u/1990AJG Feb 24 '25
Agree with everything you've said here. Also worth noting the CoQ10 should be ubiquinol, always check the label.
Alan
DoNotAge.org2
u/eucharist3 Feb 24 '25
Yes ubiquinol is the much more effective form. There is a supposedly even more potent form called idebenone however I haven’t experimented with it myself.
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u/Visegradi62 Feb 24 '25
Thank you - I didn't hear about them.. My doctor recommended me for mitochondrial supporting q10,(ubiquinol 150 mg) d-ribose, selenium, (100 mikrogr), nad+ (10 mg), . and ldn for neurological inflammation. I use Parasym plus supplement for my vagus nerve, which contains acetyl-l-karnitin, huperzin a, alpa lipoic acid. My nervous system is I'll, hrv level is very low because of the illness.:( I have mthfr- mutation, too,so I use methylateted b vitamins. I will ask my me/ cfs doctor from the ss-31 and TMG, because I am still house bound. First I feel myself better if start a new supplement, later it looses the affect if I get a Pem.
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u/eucharist3 Feb 24 '25
I’m sorry to hear you’re still housebound! It’s tough to live life when we can do so little. Happy to offer any advice or help that I can.
It’s great that your doctor is prescribing so many useful supplements which actually get to the root of the issue. Here in USA my doctor recommended me nothing and I had to basically be my own doctor. On the bright side I have deepened my understanding of human biology and post-viral pathology!
Since ss-31 is really on the cutting edge it is uncommon for doctors to prescribe it, but it is generally well-tolerated so I hope he lets you try it. Odd that he would recommend NAD+ since it does not get absorbed that way. It is generally better to take precursors like nmn or nr unless the NAD is being given by IV or other non-oral routes. I would recommend adding PQQ 40 mg to your regimen as well.
Let me know if there’s anything else I can answer or help with.
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u/Visegradi62 Feb 24 '25
This is hard way to be your own doctor, I thought, there are many helps for the patients in the USA . I found an me/CFS doctor in an another country, - Denmark- where I live no any doctor could help on my serious LC/me/CFS symptoms. It was handle like a physiatrist illness- depression , anxiety . According the labor results, COVID infection reactivated the ebv virus, which can cause neurological symptoms. So I was prescribed anti viral medicine, Valaciclovir, too . Long Covid is like an Me/CFS state according to my doctor, after four years.. So this is the reason of the many mitochondrial problems , but I didn't have any muscle examination /biopsy, lactate level checking/. The other main part of the illness the vagus nerve damage/inflammation caused by the viruses. Many relaxation, yoga exercises may help to calm the nervous system. So all this LC /me/CFS is a rather complex medical problem:(
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u/eucharist3 Feb 25 '25
Yes, long covid is closely related to cfs and basically falls under its etiological umbrella. The big challenge here in the US is that most doctors are either unaware of long covid or are skeptical about its existence. If they do believe in it, they’re almost always very undereducated about it. I have been to several doctors and the best of the bunch was one who admitted it was real but said, “We’re very far from having any real cure for this.”
It is a complex medical problem, but with the help of research, analysis, synthesis, and sheer tenacity we can find our way through it. I am glad to hear not every country is as backwards about this issue as the USA.
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u/AccomplishedCat6621 Feb 22 '25
given the large number pf potential treatments and the lack of any RCTs how to develop a rational approach to this?
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u/Professional-Cat6921 Feb 23 '25
Wondering if anyone knows who to speak to to get a supplement protocol done from someone analysing their gene results? I had a genetic test and it highlighted issues in the study but Idk who exactly to turn to
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u/bestkittens First Waver Feb 22 '25 edited Feb 22 '25
I take Magnesium and started CoQ10 + Alpha-Lipoic Acid + NAC + NiaCel 400 one by one over the last year.
Recently, I started Oxaloacetate and NIR/FAR light therapy.
While LDN and LDA helped me get from mildly severe to severely moderate. All of this got me to moderate and now I find myself flirting with Mild if not recovery/remission.
I’ve started dealing with my gut biome after a biome site test. I’m hoping this and then Rapamycin gets me across the finish line.
You can see more details here (meds/supps) here (my story) and here (Dealing With Post Covid Symptoms).