Absolutely fascinating deep dive into mitochondrial’s many functions. Mitome looks to be a very personalized tool in understanding our own unique physiology. I’ve been an elite athlete for most of my 68 years and have used bio impedance testing on myself and with clients. Always found it hilarious that these tests repeatedly identified my “mitochondrial age” to be TWELVE when I was chronologically 65! I’m still an extremely lean, muscular lady requiring an enormous amount of calories. Mitome may provide some answers. 🤷🏼♀️ Thank you!
Hi Chris! Thank you for the deep dive into serotonine! I am very much interested in perioheral actions if serotonine, which seems to be very complex. In the study https://pmc.ncbi.nlm.nih.gov/articles/PMC11380450/ serotonine in the context of chronic stress disrupts intestinal barrier function via 5HT7 and AMPK PGC1alpha signaling, causing mitochondrial biogenesis problems.
Do you think extra stimulation of 5-HT2A receptors (=>mitobiogenesis) could also explain why psilocybin and LSD are now both reported to increase lifespan?
The cardiac hypertrophy study is mentioned. Mitochondrial function is the determinant of electrolyte handling which is the determinant of heart rhythm. Almost all arrhythmia is either a dietary deficiency or sweat/urine -induced electrolyte deficiency or a deficiency of energy to handle electrolytes properly.
Chris prior to me taking an ssri and benzo I had no heart issues, once I went on them 3 months into it and on 2 years and slowly tapered off I developed heart arrhythmias and heart block. Off 11 years and still get the arrhythmias. So I’m thinking the drugs caused damage to the electrical system of the heart?
I reached out to you here on Substack at the end of last year regarding picking up with the $999.99 USD value consultation I had left over in the package I purchased from you. You sent me a link to book in on your calendar but I was unable to do this promptly as I had a series of medical emergencies through Christmas and start of the year that required emergency treatment. I emailed in February and May of this year but have not had any reply. The link you sent me doesn't show any available dates for consultation. Please can you advise me what to do?
There’s no getting around the fact that some oxidizing agent has to be finally consumed and depleted in large quantities for respiration to continue. What keeps oxidizing the melatonin to the cation radical? Or are you just proposing that melatonin is acting as a “shuttle” between oxygen-rich tissues and hypoxic tissues? It doesn’t seem like the cation radical would be stable enough to fulfill this purpose. Perhaps melatonin is just serving as a signaling molecule to indicate that 1) there is not much oxygen but 2) there still is SOME oxygen.
There was a Science paper a few years ago showing that fumarate can function as a terminal electron acceptor in mammalian ETC. The idea is that a buildup of ubiquinol in hypoxic tissues can produce succinate by driving succinate dehydrogenase in reverse, and then the succinate can be exported to more oxygen-rich tissues which oxidize it to malate and send it back. Incoming malate can then keep the TCA cycle and ETC going in the hypotoxic cells. Perhaps serotonin/melatonin help coordinate that type of thing.
Is there evidence that ketone bodies like beta-hydroxybutyrate (BHB) are produced from glucose? That would be a very different kind of “ketosis” - a hypoxic-induced one rather than a hypoglycemic one - but it fits what you'd want cells to be doing under hypoxia. Metabolizing glucose to BHB (and then exporting it) produces 9.5 ATP/Glc, so not the 32 ATP/Glc for full TCA cycle but still much better than a pithy 2 ATP/Glc for lactate. (Plus not as acidifying: only 1 H+ exported per 9.5 ATP vs 1 H+ per 1 ATP for lactate.) But Glc—>BHB actually utilizes oxygen even better than full glycolysis-TCA (6.33 ATP/O2 vs 5.33 ATP/O2). Of course fat metabolism is the worst for O2 utilization - a palmitic acid only gives 4.6 ATP per O2. So if you had tissues that are low on oxygen you might want a “midway” solution which prioritizes sugar over fat utilization and oxidizes pyruvate to acetyl-CoA but doesn't go all the way through TCA cycle and instead exports ketone bodies. Then other tissues which are getting a better supply of oxygen could catabolize fats and BHB (or ketones could just be urinated out or partially decomposed to acetone and exhaled). Again, not sure what the role would be for melatonin, other than as a signaling molecule to coordinate that.
Hi Chris, it would be interesting to know if, given the speem producing cells are using serotonin, whether frequent ejaculation could cause serotonin insufficiency elsewhere in the body.
I would really like to know if people heal once off. And what is required. Thank you for this discussion on ssris. This all makes sense to me
Good stuff Chris
Absolutely fascinating deep dive into mitochondrial’s many functions. Mitome looks to be a very personalized tool in understanding our own unique physiology. I’ve been an elite athlete for most of my 68 years and have used bio impedance testing on myself and with clients. Always found it hilarious that these tests repeatedly identified my “mitochondrial age” to be TWELVE when I was chronologically 65! I’m still an extremely lean, muscular lady requiring an enormous amount of calories. Mitome may provide some answers. 🤷🏼♀️ Thank you!
Hi Chris! Thank you for the deep dive into serotonine! I am very much interested in perioheral actions if serotonine, which seems to be very complex. In the study https://pmc.ncbi.nlm.nih.gov/articles/PMC11380450/ serotonine in the context of chronic stress disrupts intestinal barrier function via 5HT7 and AMPK PGC1alpha signaling, causing mitochondrial biogenesis problems.
Do you think extra stimulation of 5-HT2A receptors (=>mitobiogenesis) could also explain why psilocybin and LSD are now both reported to increase lifespan?
How does this affect the heart muscle? And how does if cause arrythmias?
The cardiac hypertrophy study is mentioned. Mitochondrial function is the determinant of electrolyte handling which is the determinant of heart rhythm. Almost all arrhythmia is either a dietary deficiency or sweat/urine -induced electrolyte deficiency or a deficiency of energy to handle electrolytes properly.
Chris prior to me taking an ssri and benzo I had no heart issues, once I went on them 3 months into it and on 2 years and slowly tapered off I developed heart arrhythmias and heart block. Off 11 years and still get the arrhythmias. So I’m thinking the drugs caused damage to the electrical system of the heart?
How does one heal the deficiency of energy to handle electrolytes properly
so how does Motegrity work on the gut, especially colon , when there is constipation related to poor efficiency of peristalsis.
Since serotonin is produced with sunlight exposure, does this mean sunlight exposure leads to increased ATP production?
Hi Chris,
I reached out to you here on Substack at the end of last year regarding picking up with the $999.99 USD value consultation I had left over in the package I purchased from you. You sent me a link to book in on your calendar but I was unable to do this promptly as I had a series of medical emergencies through Christmas and start of the year that required emergency treatment. I emailed in February and May of this year but have not had any reply. The link you sent me doesn't show any available dates for consultation. Please can you advise me what to do?
Best wishes,
Sam
There’s no getting around the fact that some oxidizing agent has to be finally consumed and depleted in large quantities for respiration to continue. What keeps oxidizing the melatonin to the cation radical? Or are you just proposing that melatonin is acting as a “shuttle” between oxygen-rich tissues and hypoxic tissues? It doesn’t seem like the cation radical would be stable enough to fulfill this purpose. Perhaps melatonin is just serving as a signaling molecule to indicate that 1) there is not much oxygen but 2) there still is SOME oxygen.
There was a Science paper a few years ago showing that fumarate can function as a terminal electron acceptor in mammalian ETC. The idea is that a buildup of ubiquinol in hypoxic tissues can produce succinate by driving succinate dehydrogenase in reverse, and then the succinate can be exported to more oxygen-rich tissues which oxidize it to malate and send it back. Incoming malate can then keep the TCA cycle and ETC going in the hypotoxic cells. Perhaps serotonin/melatonin help coordinate that type of thing.
Is there evidence that ketone bodies like beta-hydroxybutyrate (BHB) are produced from glucose? That would be a very different kind of “ketosis” - a hypoxic-induced one rather than a hypoglycemic one - but it fits what you'd want cells to be doing under hypoxia. Metabolizing glucose to BHB (and then exporting it) produces 9.5 ATP/Glc, so not the 32 ATP/Glc for full TCA cycle but still much better than a pithy 2 ATP/Glc for lactate. (Plus not as acidifying: only 1 H+ exported per 9.5 ATP vs 1 H+ per 1 ATP for lactate.) But Glc—>BHB actually utilizes oxygen even better than full glycolysis-TCA (6.33 ATP/O2 vs 5.33 ATP/O2). Of course fat metabolism is the worst for O2 utilization - a palmitic acid only gives 4.6 ATP per O2. So if you had tissues that are low on oxygen you might want a “midway” solution which prioritizes sugar over fat utilization and oxidizes pyruvate to acetyl-CoA but doesn't go all the way through TCA cycle and instead exports ketone bodies. Then other tissues which are getting a better supply of oxygen could catabolize fats and BHB (or ketones could just be urinated out or partially decomposed to acetone and exhaled). Again, not sure what the role would be for melatonin, other than as a signaling molecule to coordinate that.
Hi Chris,
Thank you for a very informative article. I am interested in the Mitome Test. Do you have any discount codes available?
Hi Chris, it would be interesting to know if, given the speem producing cells are using serotonin, whether frequent ejaculation could cause serotonin insufficiency elsewhere in the body.