Comment · Thu, February 10, 2022 · Nootropics Depot & Natrium Health
Why nobody should use Uridine, in my opinion
Original post in this thread
sirsadalot · 42 points
Uridine is a form of nucleosides sold as either Uridine Monophosphate or Triacetyluridine. Many people use it to "upregulate dopamine" (like with Mr. Happy Stack) as it was shown to treat disorders frequently associated with malfunctioning dopamine networks. But we can all agree those are two vastly different contexts.
# Uridine and cancer
The carcinogenic action of Uridine is more potent in higher doses, sure, but it is a myth that Uridine isn't a carcinogen at all doses. Instead of worsening cancer by inducing proliferation, it directly causes DNA damage: https://pubmed.ncbi.nlm.nih.gov/26801745/
These data suggest that uridine homeostatic disorder leads to uracil DNA damage and that pharmacological uridine may be carcinogenic.
Others suggest that this may be due to B vitamin depletion, however I have seen no solid evidence that this is the sole mechanism behind uridine's carcinogenicity.
# Uridine and dopamine
Uridine's proposed dopamine receptor upregulation can actually be attributed to it inhibiting dopamine release, making it a hormetic response. The conclusion is drawn from the following paper where this effect was…
What they were answering
jimmythegreek1 · 10 points
thoughts u/MisterYouAreSoDumb ? Was just going to buy your new TAU supp.
u/MisterYouAreSoDumb · Nootropics Depot & Natrium Health
The issue is that many people talk about things with a level of certainly that I don't think is appropriate, given the available scientific data. Uridine is certainly involved in cancer, and plays a role in tumorigenesis. That's true. The same can be said of many things like nerve growth factor, which also has positive cognitive and mood effects. Just because something might be involved in cancer doesn't mean we should avoid it. It's much more complex than that. Interestingly enough, uridine can actually be administered alongside chemotherapy to prevent some of the toxicity. The direct DNA damage thing is really only seen at high levels. We consume a bunch of uridine every day, and it is an important endogenous compound. A few hundred milligrams extra most assuredly is NOT going to break your DNA at a high enough rate that you will get cancer.
The other thing to consider is that the study linked above is not looking at uridine supplementation. It's looking at disrupted uridine metabolism. They are specifically looking at disrupted uridine phosphorylase (UPase) activity. This is one of the enzymes that breaks down uridine, so if it is not functioning properly, then uridine builds up and DNA damage is possible. However, this would be like saying taking 5-HTP is the same exact thing as taking an SSRI, as both are leading to increases in serotonin levels. They most assuredly are not the same, though. SSRIs are going to cause much higher localized increases in serotonin, just like disrupted UPase enzyme activity is going to lead to much different amounts of uridine in specific areas than supplementing it would. These enzymes are inside of cells, and obviously disrupted UPase activity could cause massive localized increases in uridine concentrations in areas where this can be problematic. This absolutely does NOT mean that taking reasonable doses of supplemental uridine will lead to the same effects that disrupting UPase activity will, especially in humans vs. mice.
That being said, uridine signals through various different P2 receptors, all of which also have a link to cancer. The main one here is P2Y2. This is actually where uridine produces a lot of its cognitive benefits through. It's a fascinating receptor. Unfortunately, high levels of activation at P2Y2 can also be carcinogenic. Due to this, there is a case to be made for uridine to have carcinogenic potential. However, even things like ATP activate P2Y2 receptors, so it would seem odd that a little bit of extra P2Y2 activity would instantly give you cancer. If we start going down that path, we should also walk around in a UV protective full body suit, because UV light is insanely carcinogenic if you were to shine straight UVB rays onto isolated cells harvested from animals that are genetically pre-disposed to cancer, which is basically what this study is doing with uridine. However, we clearly need some level of UV exposure otherwise we start running into all sorts of issues. So this brings up that old adage "the dose makes the poison" because we run into issues with uridine deficiencies but we also seem to run into issues when we consume very large amounts of uridine. It's about balance.
All in all, it's very good to be aware of this sort of stuff but we also need to put it into perspective. While uridine is not the most amazing nootropic on the planet, it has its place and helps a lot of people. More importantly, it is an endogenous compound, and something we need a good amount of everyday, so there is no way around uridine anyways. Now that being said, taking multiple grams of the stuff everyday probably isn't the best idea and if you know that you have disrupted UPase activity, high doses of uridine could be extra tricky. More generally speaking, it's a little outlandish to claim that uridine is extremely carcinogenic and should be avoided at all costs. It's like saying we should try to diminish ATP levels because ATP can be carcinogenic, which it literally can be! So should we avoid creatine? Let's lower our ATP to prevent cancer!
Then you have this little tidbit of info...
https://academic.oup.com/cdn/article/2/5/nzy013/4931709
Dietary uridine, which is teratogenic in mice, decreases intestinal tumor formation in the ApcMin/+ mouse model. Dietary uridine mimics the effect of the common methylene tetrahydrofolate reductase (MTHFR) C677T variant in protecting against colorectal cancer, while contributing to the risk of NTDs.
So uridine supplementation, which is what we are actually talking about here, actually LOWERED tumor incidents in this mouse study. Far from a compound that we should avoid because it causes cancer. Also, the idea that uridine is just lowering dopamine, and simply causing a hormetic compensatory up-regulation because of that, is silly. It is much more complex than that. It has a lot of positive effects on the body and brain.