Gotts1936: Perhaps you know far more than you realize.
Brian C: Thanks for the paper. I look forward to reading it.
Now here are some personal anecdotes.
I had actually stumbled upon the power of uridine while in synergy with other supplements. Any decent choline source should have the ability to raise uridine levels. I originally used Alpha GPC to increase cholinergic brain cells and the number of acetylcholine receptors. This was an attempt to increase brain function. Eventually I started using alpha-GPC as an effective way to raise bioavailability of various supplements requiring choline. It was at this moment fairly amazing things started to occur. I only fairly recently have figured out precisely what though.
By the way, another great source of choline would be CDP-choline, as the anabolic precursor of choline and cytidine. Alpha-GPC is considered the catabolic predigested product of choline, stripped of its fatty acids for easier assimilation - especially by neurons. It appears to me that Alpha GPC is not only cheaper but more effective, with much reduced sides. Although, alpha-GPC and CDP-choline should similarly raise blood uridine levels. Of course, another side benefit is an increase in blood dopamine and receptors, which also leads to increased levels of HGH.
There was a recent study showing that: DHA in combination with uridine and choline decreased symptoms of depression. Of course, who wouldn't be depressed with poor brain and mitochondrial function. Although uridine supplementation can do so much more in helping reversing autoimmune and neurodegenerative diseases.
Uridine also does many wonderful things besides just improve mitochondrial function. As an overall neuroprotective, uridine greatly decreases neurotoxicity to drugs and chemicals (such as statin drugs,) has anti-tumor affects, greatly increases BDNF or Brain-derived neurotrophic factor (directly related to nerve growth factor.) Acetylcholine itself is also necessary for activating REM sleep, and helps keep neural membranes healthy and complete -- instead of brittle and fractured. It would also help prevent an excess build-up of amyloid protein. This is similar to the promise of methylene blue, while perhaps being safer and more biologically plausible. I'm not completely certain yet. +Although, I received an email from a registered pharmacist stating 58mcg daily should be fine.+
Now for the good part.
Apparently there's a substance created by Repligen that has received orphan drug status called PN401 or triacetyluridine. This is basically triacetylated uridine through a patented process. My mom has been using this product for over two months. Triacetyluridine increases uridine biosynthesis 5-10x better than ordinary uridine, much better than any combination of substances. This is great for anyone tired of using many supplements in synergy for mitochondrial regeneration.
I had already been using a sometimes 2x daily combination of 600mg of alpha-GPC, 100mg of orotic acid, sometimes magnesium orotate, 500mg of DHA on my mom. It was very extremely effective in clearing any residual statin-induced symptoms. Up until recently, I had always felt we were only hitting the periphery of the recovery problem. I have pretty much tried every plausible theory within reason, some even documented on the forum. In my estimation, this is the first time we have truly hit the bulls-eye. Triacytleuridine intensified her regimen and allowed for a more remarkable transformation.
Speaking of orotic acid, also considered (by some) vitamin B13... orotic acid is another good way to increase uridine, being as its chemical makeup is almost identical to that of uracil. However, orotic acid alone would be inefficiently diffused into the cells. Yet orotic acid bound to another element would act as an efficient transporter along the pentose phosphate pathway. For instance a chemically charged orotate, such as magnesium orotate, would not only help a neutrally charged orotic acid better entrance into the cell, but uracil and the bound magnesium as well. This makes orotic acid itself a fairly exciting and effective mitochondrial pathway reviver and transporter.
For those suffering from mitochondrial diseases, the most uniform complaint seems to be about gastric intolerances, or polygenic and genetotropic diseases: such as IBS and GI dysmotility. These appear to be compounded in part due to improper mitochondrial lipid, protein, amino, sugar digestion. Uridine or triacyteluridine helps promote the very mitochondrial pathways needed to release energy from lipids and carbs. In my mom's case, I'm talking about an improvement upon a sometimes tri-weekly bout of annoying bloating, gas, and diarrhea or loose bowels. While her long-term memory problems have now subsided, per se, difficulties in learning new short-term tasks or information (especially under duress) remained. This has also now diminished greatly with triacytleuridine treatment. Her memory recall and response times have also greatly quickened to even the most mundane or ordinary questions. Shortness of breath under mild exertion or a shuffling gate under great physical exertion has also greatly reduced. Does this sound similar? How many of those in statin recovery still complain about all these symptoms?
I would be more excited at the discovery though, if not for being so exhausted. We're talking about the very heart of DNA synthesis. Uridine nucleotides are directly coupled to the respiratory chain. In a state of lactic acidosis, the mitochondria begin to use glucose instead of oxygen. Oxygen is obviously required for proper energy production.... with hypoxia being the main cause for cellular death (both apoptosis and necrosis,) cancers, or more importantly mutations in mtDNA. For instance, a slowing DNA synthesis creates large immature red blood cells incapable of carrying oxygen and dividing. Heme would also play a role here. Purine and pyrimidine metabolism is then greatly reduced along the pentose phosphate pathway. This would further limit ribose synthesis, or the energy needed for ATP production.