|By Jonathan Roseland||Connect|
A Fish Oil and B Vitamin cofactor with some interesting animal studies. A promising (but yet unproven) agent to improve memory via RNA mechanisms, it's undergone just a single human study, in which a positive effect was demonstrated on Depression and Bipolar Disorder.
Those yo-yoing between rage and blind optimism may find Uridine transformational. The sole human study done on Uridine, conducted over 6 weeks on a small group of Adolescents, suggested it's actually a mitochondrial hack for a healthy psyche:
"The collective evidence for mitochondrial dysfunction in bipolar disorder suggests a potential role for uridine in the treatment armamentarium. This evidence includes the co-morbidity of mood disorders with mitochondrial disorders... Rational development of new treatments for bipolar disorder would include compounds designed to normalize the bioenergetic abnormalities associated with mitochondrial dysfunction..."
"In this pilot case series, uridine was efficacious and well tolerated by study participants. Rapid onset of action may be a distinguishing feature of uridine."
While the Children's Depression Rating Scale scores lowered (which is an improvement) over the course of 6 weeks in the human trial, the study's conclusion is quiet bearish:
"Uridine should not enter clinical practice as a primary treatment for depressed adolescents with bipolar disorder until randomized placebo-controlled trials have been performed to confirm its efficacy."
It has a synergistic antidepressant effect in combination with omega-3's. From an 2005 animal study:
"Uridine and [omega-3 fatty acids] each have antidepressant-like effects in rats. Less of each agent is required for effectiveness when the treatments are administered together."
A Dr. Douglas Kondo and Dr. Perry Renshaw of Salt Lake City, as reported on in 2010, used Uridine and Creatine to treat patients. To quote Dr. Renshaw:
"We're reducing depressive symptoms by at least 50 percent within a couple of weeks... The two things that are remarkable, is one: it's a very large effect; and two: it's happening very quickly."
A Synaptic Hack
Uridine is hypothesized, in a 2010 American paper (Nutritional modifiers of aging brain function: use of uridine and other phosphatide precursors to increase formation of brain synapses) to aid synaptic function by providing phosphatidylcholine; it's a promising building block of membranes and dendrites which aid synaptic function. The researchers concluded in the Abstract of the paper:
"If similar increases occur in human brain, administration of these compounds to patients with diseases that cause loss of brain synapses, such as Alzheimer's disease, could be beneficial."
Uridine's benefit to those suffering from or trying to prevent Alzheimer's disease is at this point mostly hypothetical. In the limited rat studies in regards to Alzheimer's, Uridine was just one of multiple dietary factors that had an overall helpful effect.
In a 2011 Israeli study 26 elderly human participants experienced after 12 weeks of supplementation...
"A significant improvement in memory abilities (recall, recognition, and spatial short term) was observed following 2 weeks of Cognitex treatment... Attention (sustained and focused), visual learning, and activities of daily living (executive functions and mental flexibility) were improved as well following this short supplementation period..."
"The results indicate that the nutritional supplement may improve cognitive performance in elderly with memory complaints..."
Another animal study (Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils) indicated Uridine's potential as memory enhancing agent in combination with DHA, from it's abstract:
"These findings demonstrate that a treatment that increases synaptic membrane content can enhance cognitive functions in normal animals."
This is exciting because most memory enhancing smart drugs are just demonstrated as aiding the failing memories of the elderly whereas this study is saying that Uridine improved the memories of healthy adults from baseline.
One self experimenter reported:
"I've personally noticed a gradual improvement in memory retention and flexibility of thinking, also mood stabilization and a certain degree of improvement in thinking skills. It's very subtle, however the gains are really remarkable when I look back over the time period from when I started to now. In a way of putting it, for the sake of verbosity, the long term memories formed over the period of this stack is more mentally accessible, especially with very detailed subjects."
Beer seems to be the best food source of Uridine with approximately 100 milligrams per liter, a Japanese study found that the alcohol content did not effect the absorption of Uridine. Breast milk and infant formula are also rich in Uridine.
However, you would have to drink a lot of beer (or breast milk!) to get the 500 - 1000 milligrams daily that's been demonstrated to have Nootropic effects. In supplemental form it's a little more expensive with a one month supply running around $30.
An MIT study demonstrated that Citicoline is a Uridine source:
"Plasma uridine was elevated significantly for 5-6 hr after all three [citicoline] doses, increasing by as much as 70-90% after the 500 mg dose, and by 100-120% after the 2000 mg dose."
Uridine supplementation itself is a relatively unproven biohacking tool, while in contrast Citicoline has over 50 human clinical trials and I see a whole lot more value in Citicoline than Uridine. Unless you are just an insatiable self experimenter, who needs to try every sexy new Nootropic molecule, I'd encourage you to go with Citicoline as your uridine source which in supplemental form starts at $15.
A DNA Hack
...are also veritable sources of Urdine. However there's an absence of a good study that demonstrates Uridine in the blood plasma of human participants after consuming these dietary sources. The Uridine cheerleaders online are all reporting positive effects from consuming it in supplemental form. So this is one Nootropic you'll probably need to take in supplemental form if you want it's purported benefits.
For some it's quiet a sleep hack:
"Seems to (on an unpredictable basis) help me need less sleep. Oh, and if I am ever sleep deprived, uridine completely picks me up and helps me feel better."
While at least a handful of others report that it causes various degrees of tiredness:
"...I had to stop taking it after I almost fell asleep while driving."
From a Japanese review of Uridine:
"This review deals with the concept of sleep mechanism based on our uridine receptor theory. It is well established that uridine is one of the sleep-promoting substances... We propose here that the induction of sleep may be mediated by uridine through uridine receptor in the CNS, although the structure of uridine receptor is not yet elucidated."
Mechanism of Action
Uridine can pass the blood brain barrier and is uptaken via an equilibrative and a concentrative transporter.
A 2006 Swiss-German paper on the effects of a Uridine rich stack supplement on HIV infected patients has some useful passages in regards to it's mechanism:
"Exogenous uridine supplementation might prevent uridine depletion at the cellular level, as the key enzyme of endogenous pyrimidine synthesis is also encoded by mitochondrial DNA and therefore might be affected by mitochondrial DNA depletion."
UMP vs TAU
All Uridine is not created equal...
Uridine-5'-Monophosphate (UMP) is the most common supplemental form, it's water soluble (take it with just a glass of water) and can be taken sub-lingually. According to anecdotal reports it's the most effective form.
Triacetyluridine (TAU) is fat soluable so take it with a meal or fish oil capsules.
Even considering the lower bioavailability of UMP it's still a better value as a supplement than TAU. So unless you are just feigning for tri-acetyls UMP is clearly the best option.
The Uridine Stack
A Longecity moderator and originator of an epic discourse about Uridine, who goes by the handle Mr. Happy proposed stacking:
- 150-250 milligrams -5′-Monophosphate (UMP)
- >700 milligrams DHA + >300 milligrams EPA
- 150 milligrams Alpha GPC
The self experimenters on Reddit give mixed reports of the experiential effects of this stack; from very enthusiastic...
"I've completely cut caffeine from my diet. The "energy" and alertness this stuff gives is way better. It's a calm, stable, mental awakening. Nice mood lift and stabilization."
To completely underwhelmed...
"I became extremely drowsy and wanted to nap/sleep all day."
You can order it pre-stacked from PureNootropics.com for $55, a purveyor of pharmaceutical grade Nootropics. At it's low price point it seems worth trying to me
Conclusion and a Rant
A debate of the potential merits of Uridine produced a 93 page thread on Longecity while in stark contrast there is just the single human study conducted on it.
In a Nootriment article, they called Uridine
A must have Nootropic in your stack.
Which I thought was a little crazy, since when is a molecule with just a single human study a must have!? In the best selling Trust Me, I'm Lying, the author describes how something really undeserving will go a little viral and become popular on Reddit, social media or a forum and journalists or bloggers will pick up the story and promote it to wider audience on a more popular news site. I think we are seeing that somewhat in the Biohacking space online.
So I encourage you to practice some rationality while researching your Biohacking. To this point a 2011 Hungarian paper emphasized how little is known about Uridine:
"Information only starts to be accumulating on potential mechanisms of these uridine actions. Some data are available on the topographical distribution of pyrimidine receptors and binding sites in the brain, however, their exact role in neuronal functions is not established yet."
Don't trust me.
Definitely don't trust Nootriment which is a content farm site that just anonymously publishes a bunch of articles full of affiliate links.
I implore you to search Pubmed and make your decisions about what researchers are saying about a given Nootropic. Uridine is not a must have Nootropic, it's something to watch the science on as it comes out and maybe self experiment with if you have a higher risk tolerance and unquenchable pharmacological curiosity.
There seems to be a consensus that Uridine should be taken with DHA and EPA, in fact the presence of Uridine improves the utilization of DHA by the brain.
It has a similar effect on choline and phosphocholine utilization. From the abstract of a 2004 Harvard animal study:
"These results show that oral UMP, a uridine source, enhances the synthesis of CDP-choline, the immediate precursor of [phosphocholine]"
A Canadian paper and a 2006 patent application indicated a conflict with and treatment potential for the withdrawals of Nicotine, so while less proven than a lot of other options out there, it's worth considering if you are a frustrated smoker who's tried everything to quiet smoking.
Anecdotally, supplementing Uridine while consuming moderate to high levels of caffeine results in unpleasant irritability and anxiety attacks. At least a few users have reported on Reddit that combining caffeine with Uridine has a disastrous effect on sleep quality.