@John_Hemming Thanks for posting. There is quite a lot in here. I could not get my arms around the exactly what was being patented. The gist I understood from you before was to consume more citrate. I already take magnesium citrate because of your recommendation for more citrate. I’m also now considering calcium citrate for oxylate binding.
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Its quite complicated because ordinarily there is a level of citrate in blood serum. Hence when you take citrate initially the level in blood goes up. There is, however, a high intensity citrate transport expressed in liver cells that drags citrate out of blood and it is then metabolised in the liver cells. There is a half life of about 30 minutes.
Hence whilst citrate levels are higher than normal a limited amount of citrate gets into cells with a lower level of citrate.
Cells have citrate from the mitochondria and the problem arises when the mitochondria don’t provide enough citrate to the cytoplasm at times because the citrate carrier is underexpressed (a Nuclear Factor Kappa B issue).
Hence how much you take and when you take it matters. The balance between cations also matters.
When I am running a high citrate level I take some every 30 mins to an hour (although some times I miss it out for various ordinary life reasons where I am doing something else).
An additional complication is that cytosolic citrate inhibits glycolysis.
In the end, however, you can simply take a mix of citrate at certain times during the day.
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So, when sedentary, take some form of citrate every hour or so, basically? Maybe mix it up to get other benefits, such as from magnesium (citrate), calcium (citrate), phytonutrients in citric fruits (citric acid)?
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I read this and thought of you. Ketone esters.
“We showed for the first time that oral KE (ketone esters) led to an increase of acetyl-CoA and citric cycle intermediates in the brain of non-fasted mice.”
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Thank you for this. I am currently engaging in an acetate precursor. ACCS2 converts acetate to acetyl-coa
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There is an aging journal club that meets every weekend (at varying times on sunday and saturday). This saturday at 6pm UTC I am presenting my hypothesis on aging Launch Meeting - Zoom
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here is the presentation/discussion
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Thanks @John_Hemming . This was interesting. I’m also enjoying your video on sleep. I never heard of aspirin to get back to sleep. I’m going to try that the next time it happens.
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The problem with Aspiriin is that it lasts for more than one day so it will adversly affect sleep the next day after you take it.
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The mechanisms of sleep disruption after NSAID administration may relate to direct and indirect consequences of inhibiting prostaglandin synthesis, including decreases in prostaglandin D2, suppression of nighttime melatonin levels, and changes in body temperature.
@John_Hemming Okay. Thanks. This is new info for me. NSAIDs negatively impact sleep.
But why does aspirin help me go back to sleep? Does it suppress cortisol or adrenaline acutely?
Asprin reduces cortisol. I am not quite sure how. However, it is a cox-1 inhibitor
Personally I avoid cyclooxegenase-1 inhibitors. The trick in getting back to sleep substantially is to recognise you will probably be awake for one sleep cycle and to take melatonin to time with the next sleep cycle (about 90 mins).
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@John_Hemming Thank you. I think I will keep the aspirin handy but avoid using for sleep support. Now I need to think about aspirin in general which I take for longevity purposes.
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I would not be surprised if the reason why Aspirin has possibly some longevity benefits is a reduction in cortisol. Reducing cortisol is a good idea, but don’t think knockingout the prostaglandins is the best way to do it.
I use breathing exercises to reduce cortisol. It takes more effort than a pill, but I am happier with the outcome.
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I am surprised to hear that. I have taken aspirin daily for most of my life and have not detected any effects on my sleep.
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We have another aging presentation from me today at 4pm UTC (Noon US Eastern summer time)
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That paper seems to say that citrate supplementation can lead to both one thing and its opposite and apparently it’s all context dependent. This makes citrate supplementation seem pretty intriguing but also a double edged sword. How can you be sure you’re landing on the right side of what it can do short of continuously checking blood markers?
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I do check my blood markers quite frequently. I don’t think the people who wrote that paper got the mechanism right. I think it is all about gene expression.
I am still working on the dosing and dosing strategies, however.
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Following yesterday’s discussion, which will be uploaded at some stage, I have searched for some more recent papers on the use of variations in the partial pressure of Oxygen and updated my blog post about this:
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Thanks John
I am interested in how hypoxia affects mitochondrial health and efficiency. In particular I’m looking for the effects of breath holds and other tools for training co2 tolerance to improve oxygen exchange efficiency. Any thoughts?
Also, this description seems out of date.
“ Where there is not enough Oxygen cells can use Anaerobic glycolysis. This produces a lot less energy than Oxidative phosphorylation (2 ATP molecules per Glucose rather than 38). You will be used to this happening when your muscles tire out. That is because the cells are switching to Anaerobic Glycolysis which ends up with Lactic Acid.”
As I understand it, we almost never have a shortage of oxygen even though it feels like it in the moment. The use of anaerobic glycolysis is driven by the need for faster ATP production than can be accomplished by mitochondria. The resulting lactate is used as a fuel in aerobic ATP production in other muscle fibers or other organs. Once the lactate and related hydrogen ions cannot be used as a fuel (supply exceeds demand), the hydrogen accumulates and reduces the pH. This accumulation reduces the muscle cell’s ability to function. And a person can feel a “burn”. It’s not lactic acid.