Ask the Mito Doc – October 2025 Q&A
All answers today are based on personal experience of the participants. As always, please consult your personal physician prior to taking any action.
Topic: Fact or Fiction: Separating Science from Speculation in Mitochondrial Disease
Clinicians:
- Eva Morava-Kozicz, MD, PhD, Icahn School of Medicine at Mount Sinai, New York
- Amy Goldstein, MD, Children’s Hospital of Philadelphia
- Tamas Kozicz, MD, PhD, Icahn School of Medicine at Mount Sinai, New York
- Ibrahim Elsharkawi, MD, Icahn School of Medicine at Mount Sinai, New York
Q: Do you need a specific diagnosis to create a care plan? I was diagnosed with complex I and III via muscle biopsy in 2004. I am looking for an updated treatment plan but doctors keep asking me if I have a specific diagnosis i.e.: MELAS, LHON or MNGIE. Thank you for all you do in the mitochondrial world.
A: Amy Goldstein, MD: Most of the clinical trials require a genetic diagnosis, and it can be difficult to determine why the complexes were deficient, but there can still be some guidelines and recommendations made based on this information (i.e. exercise, supplements, anesthesia precautions) in my opinion.
Q: Can you speak to the efficacy and safety on using medical marijuana in symptom management for mitochondrial disease? Where to find providers that have knowledge on the type of medical marijuana specific to symptoms and appropriate modes of delivery? Are there dangers of vaping medical marijuana?
A: Amy Goldstein, MD: Oral is better than vaping/smoking, otherwise it depends on your symptoms and what you are trying to manage in terms of pain, sleep, etc. The dispensary doctors have far more knowledge than any mito doc that I have met. Caution about elevated liver enzymes; as a child neurologist I have seen CBD/THC in various forms be extremely helpful for children with epilepsy. Would recommend thorough evaluation in a center and disclose the mito diagnosis but with careful symptom review.
Q: Local compounding pharmacies just pull vitamin bottles off the shelf, vs purchasing pharmaceuticals to ensure proper potency and dosing. What would it take to remedy the situation by making pharmaceutical grade vitamins available for patients to manage their mito cocktail?
A: Amy Goldstein, MD: My experience with compounding pharmacies is that they research and vet best vitamins to use, which is one reason I use them, rather than tell patients to use Amazon or shop on their own. I also like other sources such as epic4health.com and Jo-Mar labs (I receive no benefits in recommending them – I like their products!)
Q: Can you please address therapies for a person who may have developed mitochondrial issues due to COVID infection and that has had long COVID for approximately 6 years? Also have you found dietary changes to be helpful? I have felt much better after changing my diet for 5 months to mainly fish, no grains, and extra fruits. Could it be due to an increase in Omega 3s?
A: Amy Goldstein, MD: I have recommended long COVID clinics for people with these symptoms; many of us take care of patients with primary (genetic) mito disease and do not know much about secondary mito from COVID.
Q: Is Amino Acid treatment one of the methods you can talk about?
A: Amy Goldstein, MD: Many people heard about this PRIZM study, which is Zagociguat, run by the drug company Tisento . And that is a drug which is also working in the same pathway that these phosphodiesterase inhibitors work a little bit downstream from that. The mechanism of action is vasodilatation. So this is also the same kind of story that we have with these phosphodiesterase inhibitors, and that is in a clinical trial for the mitochondrial ARS disorders. And we have the exact same debate happening right now. There’s a worldwide effort to have a protocol and maybe a randomized controlled trial, or at least everyone following the same protocol in Europe and in the US but we also have other people are already on amino acids for some of those disorders- I’m talking about LARS2, DARS2, CARS2. There’s going to be a very big worldwide effort that if you have a patient on amino acid therapy to collect the same data as everybody else’s, because as Dr. Morava pointed out, we don’t want to miss the opportunity to prove that these therapies work, because otherwise we’re just going to have more added to the pile of not knowing if it works, and we as a community get a lot of flack from other physicians, including physicians in Europe, who say, why are you prescribing this mito cocktail? They don’t prescribe anything to their patients, including everything that we give here, and some of us more than others.
Q: Is there any downside to using the contents of the mito cocktail like unwanted or risky side effects for specific systems impacted by mito disorders (like kidneys or liver, for example)? Why do your colleagues in Europe not recommend it?
A: Amy Goldstein, MD: The vitamins in the mito cocktail are safe, except for too high dose of vitamin A or vitamin E.
Q: If cocktail is not used in Europe, what treatment is there for mito patients?
A: Amy Goldstein, MD: European patients use sometimes riboflavin or coenzyme Q. When carnitine levels are low, this can be also supplemented.
Q: What is the status of stem & gene therapy clinical trials in adults affected by MELAS?
A: Amy Goldstein, MD: Gene therapy is still in research but making headway in terms of figuring out how to get CRISPR into the mitochondria! MitoTALENS and similar techniques getting closer; no clinical trials to my knowledge yet for gene therapy.
Q: What is heteroplasmy? How do I find out what my heteroplasmy is?
A: Amy Goldstein, MD: It is the percentage of abnormal mtDNA with the mutation compared to normal. Finding out requires testing, sometimes more than one tissue depending on the mutation: cheek swab, saliva, blood, urine, can also be done on muscle biopsy if needed.
Q: Are there any vitamins or treatments that help with movement disorders or muscle pain that causes sensations in pain associated with mitochondrial disorder? ARS genes, LARS2
A: Amy Goldstein, MD: Movement disorders can be difficult to treat and I recommend seeing a specialist for this (neurologist trained in movement disorders); muscle pain can be treated in many different ways – would ask neurologist and physical therapist, stretching can help, also host of over the counter and medications that may be helpful, need exam to determine what else may be needed.
Q: Talk about hyperbaric oxygen chambers. I was told years ago not to do since my oxygen levels are always high?
A: Ibrahim Elsharkawi, MD: Right now, hyperbaric chambers are not therapies/interventions we recommend for our patients under any circumstance.
A: Eva Morava-Kozicz, MD: I think that it has been shown, by the group led by Vamsi Mutha, in different animal models, cell models, that it actually works in primary mitochondrial disorders. I think the challenge here that what they did, they kept the animals continuously on hypobaric (low oxygen) condition. So they were on, 24 hours, seven days a week, I don’t think that this is something that could be done at this point. With the technological developments I think it’s very challenging to do it in a human, to keep somebody in a hypobaric oxygen kind of condition for a long time.
A: Amy Goldstein, MD: The opposite of hyperbaric is helpful (hypobaric). We had a flurry of people looking at hyperbaric oxygen maybe 15 years ago and it’s kind of come back. And I feel like there are places that have opened again and for some reason advertising to the community of children, people that have kids with autism and other special needs. And I’m not really sure why they are going for this population. I’m going to focus again on the mitochondrial community. And this is what we know for the majority of people who have mitochondrial disease, the problem is not getting oxygen into your life. There’s a time and a place for hyperbaric oxygen. If you have carbon monoxide poisoning, if you have the bends from going deep sea diving, you need high oxygen delivery this way. Having mitochondrial disease is not one of those times. In fact, when we put people on a mito cocktail, a lot of what that cocktail is antioxidant therapy. You’re on antioxidants to get rid of those reactive oxygen species. And so if you go to a hyperbaric oxygen chamber, you’re just creating more and more of those reactive oxygen molecules and you’re going to do more cell damage and there’s not going to be enough scavengers in the world, no matter how many antioxidants you take to try to get all of that up. So people are usually worse when they come out of that chamber.
Q: Have they done any trials yet with tadalafil or sildenafil including CPEO?
A: Amy Goldstein, MD: No trials, but individuals tried off label the lowest dose of Cialis in CPEO.
Q: Have they done any trials yet with tadalafil or sildenafil on ARS genes?
A: Amy Goldstein, MD: On one YARS2 patient.
Q: What about patients with MIDD? Any findings? I’m a mito patient with bilateral hearing loss and Diabetes. Both my kids have mito with different heteroplasmy percentages. I would like to know if there is any way I can help them or any route to go to prevent them developing?
A: Amy Goldstein, MD: A monogenic diabetes center in Chicago is deeply studying MIDD – Dr. Lou Phillipson in Endocrinology, big registry.
Q: Is Viagra standard therapy for heart failure in regular non-mito disease patients?
A: Amy Goldstein, MD: No. Viagra is only standard treatment for erection disorders. Heart failure meds are very different. But using Viagra is absolutely contraindicated in coronary disease, if someone uses the medication nitroglycerine.
Q: I thought oxygenation was not a problem in mito disease so curious how a drug like Viagra might be useful.
A: Amy Goldstein, MD: You are correct. We are not sure how Cialis and Viagra help some of the patients. We just know that they affect vascular circulation, but if this helps through better oxygen delivery is not yet clear.
Q: Did the drugs help mitigate MELAS strokes?
A: Ibrahim Elsharkawi, MD: We did not specifically measure that, and we did not look at this in a randomized controlled clinical trial, so we can’t say either way.
Q: Do these drugs or any other drugs help with the cognitive decline associated with mitochondrial disease?
A: Amy Goldstein, MD: It is reported that the PDE5 inhibitors as well as the Tisento drug mentioned currently in trials will help with the cognitive issues.
Q: It’s concerning to hear about therapies causing harm, are there things we should avoid? Is there a list somewhere?
A: Amy Goldstein, MD: There are published lists of medications to be avoided in mitochondrial disease. For new innovative therapies, some could help certain conditions but be harmful in others. You should have a trusted mito doctor to discuss these individually.
Q: HBOT, methylene blue, red light therapy, stem cell applications – can you touch on things like this that do not require a prescription, but some families have had success using?
A: Amy Goldstein, MD: HBOT is dangerous for mito – creates oxygen free radicals and damages the cell. Red light therapy is interesting, and Joanna Poulton is studying this in the UK for mito, she said this looks promising for mitochondria and going to do more research on it.
A: Eva Morava Kozicz, MD: Methylene blue is a dye, it’s a surgical dye. Initially it was used by the surgeons to inject people during surgery. For example, if somebody had breast cancer and they wanted to see where are the lymph nodes which are involved, then they injected in the tissue, and the dye went through the lymph system and you could see where the lymph nodes they have to surgically remove. There is a rare disease, a rare anemia, which is called methemoglobinemia. There are indications of using methylene blue when the methemoglobinemia is very severe and not a continuous use, you can recurrently use a very low dose and very careful. There are also certain conditions when somebody is dying and they cannot bring up the blood pressure that methylene blue can also increase systemic vascular resistance. But it’s a very old-fashioned treatment and we don’t use it anymore. Where we still have space to use this methylene blue therapy is in carbon monoxide poisoning. So maybe you heard about this, that sometimes somebody gets stuck in a burning house and they still use methylene blue to help to reduce the blood cells from the abnormal carbon monoxide molecules. So, this is a treatment which we usually use in very acute and severe conditions. And it’s an infusion therapy, for example for an adult it would be 50 milligram or 60 milligram IV and it’s like a half an hour infusion because the extreme side effects we know of. One is the so-called serotonin storm or serotonin syndrome when you give high doses, and if somebody is on a SSRI, antidepressant medication or opioid drugs, it if they get methylene blue they (can) get life threatening complications, they get headache and they can be psychotic. These are all signs of autonomic hyperactivity. The pupils change, the blood pressure changes, the heart races, and their neuromuscular system is also under attack. They start to have muscle twitches and muscle spasms.
A: Ibrahim Elsharkawi, MD: Red light therapy is not something we recommend in clinical practice.
Q: Can you also address Urolithin and C15?
A: Amy Goldstein, MD: C15 is an odd chain fatty acid. Some of the odd chain fatty acids could bring in extra energy to the mitochondria. Traditionally our community uses the C:7 (triheptanoin) more than C:15 for mid chain fatty acid treatment to improve energy intake from fat.
Q: Overall, the “health trend” media attention to mito health is annoying. Can the hype have a silver lining in the form of more attention from the people who fund research and trials?
A: Ibrahim Elsharkawi, MD: I think that’s a glass half full way to look at it for sure. It also might make mito supplements more readily available/produced more, since there’s a larger market.
Q: Any other companies doing drug research & trials beside Saol Therapeutics in Roswell, GA? How other people are navigating daily food Intake with mild PDHD1 deficiency when using 40 GM of carb intake?
A: Amy Goldstein, MD: Saol is going to keep going and work with the FDA; you can keep track of other possible trials with the UMDF and clinicaltrials.gov website and the PDH support group. Some people do well on full keto, others on the modified Atkins diet, you can work with a nutritionist.
Q: Adults over age 75 – any advice? Late onset (age 40) POLG
A: Amy Goldstein, MD: Any symptom in particular? Adults this age typically have ptosis, ophthalmoplegia, neuropathy, ataxia; you need a good ophthalmologist and neurologist, and physical therapy.
Q: I’m a 75-year-old who has had mitochondrial myopathy symptoms since age 10. It has caused weakness in my muscles and lungs. I wear AFOs as result of leg weakness and walk with a walker and back brace as a result of trunk and upper lumbar back weaknesses. Recently after spending a few days with my 7-year-old grandson I’ve concluded that he has issues in his legs that are similar to what I grew up with. Walking on toes, foot slap and lifting knees high to walk. No one noticed my symptoms until later in life. I have not been diagnosed with mitochondria disease but my muscle biopsy at 60 showed ragged red fibers and I did not fit into specific category. What does the medical community suggest for children this young? Growing up with these issues I feel he doesn’t need to know something is the matter until he notices it and his physical disabilities are making him different. Then he should definitely be made aware of the reason for it. The psychological effects of me not knowing about my condition had such a profound effect on my confidence, worth and ego. I really believe that L-carnitine is my magic drug but don’t know if it is appropriate for children that young. Just want him to have a few more years feeling he is just a normal kid.
A: Amy Goldstein, MD: You sound a little torn about this, but an evaluation now may alleviate your concerns; it may also provide help for your grandson sooner so I would be in favor for mentioning this to your child (their parent) to see if they agree to have them seen – but – is the parent (your child) also affected? Mito does not “skip a generation” but some family members can be more affected than others – trust your gut with this one.