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Uridine Supplement Stacks Help Repair Dopamine Receptors
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Daryl
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DHA
29 January 2014
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For many people, the neurotransmitter dopamine is a key factor in success when optimizing mental function. Having steady levels of dopamine in the right areas of the brain is important for maintaining motivation, attention span and supporting the ability to learn.
The Problem of Dopamine Imbalance
A localized deficiency in dopamine is believed to cause problems such as attention deficit hyperactivity disorder, unipolar depression and even persistent anxiety. On the other hand, an excess of dopamine can lead to severe mood disturbances such as bipolar disorder.
Many pharmaceutical drugs exist to treat disorders caused by dopamine imbalance, including the common brands Adderall (amphetamine salts) and Ritalin (Methylphenidate). Standard medications can be beneficial in the short term, but they introduce side effects such as increased blood pressure, over-stimulation and withdrawal upon cessation. Plus, these drugs mainly serve to mask the symptoms of the disorders and are not designed to correct the underlying source of the problem.
A Proposed Treatment Using Uridine and DHA Supplements
Thankfully, recent studies into a common group of organic substances have revealed a method of correcting dopamine imbalance in the long term. All of this research has led to the creation of a nootropic stack with the important genetic factor uridine at its core. The members of the stack are necessary but interchangeable, meaning many different supplements could be used for a particular role in synergy.
The basic requirements for this officially unnamed stack (I call it the uridine stack) are as follows:
- Uridine in a bioavailable form (the various forms are covered later)
- DHA or decosahexaenoic acid, an omega-3 fatty acid
- A choline source
- Highly absorbable B vitamins, especially B12 (cobalamin) and B9 (folate)
The choline and B vitamins (3, 4) are highly recommended but not absolutely required, as they may increase effectiveness in some individuals but not all. Another possible add-on to the stack is magnesium, which can aid with anxiety and memory function.
As mentioned, all four of the base components can be satisfied according to personal preferences.
Much of the information contained in this article regarding ingredients and dosing comes from a major thread on Longecity.org, the same place in which the famous CILTEP stack originated.
Components of the Uridine Stack
Uridine
Uridine is a major component of RNA and a promoter of DNA repair and cell growth. When combined with other members of its eponymous stack, uridine can stabilize dopamine activity at the receptor level as well as encourage healthy levels of nerve growth activity.
By itself, uridine cannot be taken as a supplement. It must be ingested as one of two compounded forms in order to cross over into the bloodstream in high enough amounts.
The first form is uridine monophosphate (or UMP), which is generally less expensive and can be taken either orally or sublingually. UMP taken sublingually is seven to ten times more potent than taken orally, although some users report a slight burning sensation when taking it in this manner. The standard oral dosage is 250mg.
The second form of bioavailable uridine is triacetyluridine (or TAU), which is approximately four to seven times more potent than UMP taken orally. TAU is lipid-soluble, meaning it can only be administered orally and not under the tongue. However, the benefit to this is that TAU absorbs without a problem with food in the stomach, as opposed to UMP where this is questionable. The standard dosage is between 25-50mg.
Both forms of uridine can be bought online in the form of powder and sometimes in pre-filled into capsules. A few websites where they can be found are smartpowders.com, superiornutraceuticals.com and of course amazon.com. Jarrow formulas also make capsuled UMP, which can be found in supplement stores outside the web.
DHA (docosahexaenoic acid)
Those taking fish oil may be familiar with DHA because it is one of two major omega-3 fatty acids, which are the desired parts of the oil. DHA is needed in order to create and maintain myelin sheaths on nerve cells, which greatly help in propagating impulses efficiently.
Because of this, supplementing DHA can greatly aid in the creation of new nerve connections and ensure that existing ones stay healthy.
Getting DHA as a supplement is rather easy, as fish oil typically suffices for this purpose. However, it is generally recommended to get a formulation with a higher ratio of DHA to EPA, as high as 4:1. This is because DHA is more important than EPA for nerve maintenance, yet you don’t want to take unnecessary amounts of fish oil and waste money.
Fish oil is available in almost all grocery stores and on the internet, and is perhaps the most popular supplement taken. A general recommendation for dosage is between 500mg and a gram of DHA.
Vegetarians can opt for flaxseed oil as a source of DHA/omega-3 if needed.
Choline
Choline is a nutrient that is required to build cell membranes and produce the neurotransmitter acetylcholine. In the uridine stack, choline supplementation helps in the maintenance of nerve cells, similar to what the DHA does. Additionally, choline is thought to have a balancing effect on dopamine systems of the brain, as it counteracts high levels of the neurotransmitter.
There are many forms of choline available on the market, all with their own pros and cons. Users on the main uridine Longecity thread mention alpha-gpc at the start, but any type will do. Interestingly, CDP-choline (or citicoline) has an additional effect relevant to the purpose of the stack. In the process of breakdown, one of the metabolites is in fact uridine! This is perhaps one of the reasons why CDP-choline is such an effective supplement, as noted by our recent take on it.
A quick breakdown of available choline sources for the stack, from least to most potent: Soy Lecithin, Choline Bitartrate, Choline Citrate, Alpha GPC, and CDP-Choline.
Another possible additive is Acetyl L-Carnitine (or ALCAR), which aids in acetylcholine production and could serve as an alternative to other choline supplements for those who are sensitive to the typical options.
B Vitamins
Because one of the main effects of uridine involves DNA repair, the B vitamin folic acid or folate is used up more quickly since it is required for the process. If you don't get enough folate in your everyday diet, supplementation may be needed in order to see the full benefits of the uridine stack.
Vitamin B12 (cobalamin) is also involved in DNA maintenance and may require supplementation. If you choose to take vitamins, it’s best to go with forms that are more bioavailable, so you can rest assured that the nutrients are absorbed properly.
Methylfolate and methylcobalamin are the active forms of folate and B12, which are superior to “inactive form” supplements that are far more common. They are not common supplements in stores, although the online sellers Jarrow Formulas and Swanson Vitamins carry these high potency methylated nutrients.
How the Uridine Stack Works
The uridine stack works through two main mechanisms to provide therapeutic and nootropic effects.
- The chemical uridine promotes the creation of new dopamine receptors in the brain, an effect which is more pronounced in brains with fewer dopamine receptors. This is done by activating the D1 and D2 receptor signaling cascade, which stabilizes spikes of dopamine activity that would normally “burn out” receptors and reduce their effective number. Modulation also increases the rate of new receptor formation in areas where they are less dense, effectively increasing the number and density of dopamine receptors. Choline - particularly CDP-choline - also has the potential to increase dopamine receptor density.
- The stack as a whole supports growth of neural tissue and the protective phospholipid material around it. Having a well-connected and healthy set of dendritic pathways in the brain can improve both mood and cognition, because functionality is optimized or restored.
Some of the details surrounding the mechanisms of the stack come from clinical trials and animal research, which show positive feedback for the combination in a variety of applications.
Dopamine Balance
In a study done at Rutgers University, researchers measured rats’ performance on behavioral tests after being given cocaine or amphetamines. In an experimental group that was also given uridine, the rats reacted much more sensitively to the illicit dopamine-stimulating drugs, demonstrating that the population of dopamine receptors was denser. Another observation with the uridine group was that amphetamines did not raise striatal dopamine levels as much as with the placebo group, because of the balancing effect provided by modulation.
A study done in France provided further evidence for uridine’s benefit for dopamine levels. Scientists found that rats given uridine monophosphate had a higher rate of potassium-mediated dopamine release, as well as an increased rate of neurite growth.
Treating Mood Disorders
The co-administration of uridine and omega-3 fatty acids may be useful in treating depression, as confirmed by research done on rats given a forced-swim test. Either uridine or omega-3s improved the rats’ rate of mobility (showing their want to live), and giving them both substances reduced the dose size of each, displaying a synergistic effect.
Triacetyluridine can be used to treat both depression and bipolar disorder, according to results of a clinical study. Over the course of six weeks, patients of both disorders showed improvements on behavioral tests, meaning TAU could yield both stabilizing and motivating effects.
Improving Memory Function
A nootropic formula developed at the Massachusetts Institute of Technology was recently tested in several European countries. The concoction - dubbed “souvenaid” - contains uridine, DHA, and choline. Souvenaid was given to early-stage Alzheimer’s disease patients to test its ability to improve memory function (ie, avoid age-related memory loss).
From a large sample size of 259 people, researchers found that patients taking souvenaid performed better on memory related tests, while those in the placebo group worsened. According to MIT professor Richard Wurtman, the mixture works by stimulating the formation of new synaptic pathways in the brain.
You want to improve the numbers of synapses, not by slowing their degradation — though of course you’d love to do that too — but rather by increasing the formation of the synapses. (Wurtman, MIT)
Treating AnemiaUridine's benefits don't stop at memory enhancement. A Brazilian study showed that uridine, when combined with vitamin B12 and the additive cytidine, was effective for treating symptoms of anemia. The experimental group’s scores on psychological tests improved significantly after a course of treatment with the drug combination.
Other Benefits Reported By Users
Besides results unveiled by clinical trials, uridine stacking has several other benefits reported by users.
The big and dandy uridine thread on Longecity has many users reporting an increase in general motivation and a feeling of meeting their potential. The original poster (Mr. Happy) had the following to say after using the stack for six weeks:
The overall 'effect' is that you feel like yourself, but unimpeded - existing cognitive or emotional issues disappear over a week or so and you start feeling and being awesome. Your capacity to learn and retain information is noticably better. (Mr. Happy, Longecity)]
The online community at socialanxietysupport.com reports that the stack, or even uridine by itself, helps improve levels of anxiety.
Even the highly popular social forum Reddit touted uridine's benefits in a recent thread regarding the uridine stack, with a large user base reporting their findings.
Side Effects
The uridine stack behaves like a true nootropic combination in that there seem to be zero negative side effects. Compared to the massive list of side effects of most dopaminergic substances, this truly seems miraculous. However, a few individuals have reported emotional blunting when taking larger doses.
This can be attributed to higher levels of dopamine being released, overwhelming effects of other neurotransmitters such as serotonin. Some people can be sensitive to higher doses of choline as well, often generating a similar emotional drain when taking too much.
A good idea is experimenting with the dosing (carefully and observantly) in order to find the correct balance for you.
Conclusion
The combination of uridine with DHA, choline and B-vitamins is a stack that is both highly customizable and effective. It can heal the dopamine systems of the brain and provide the precious raw materials needed to develop new nervous connections. Plus, the ingredients are accessible and affordable and side effects are a non-issue. Join the growing movement of nootropics enthusiasts who enjoy the benefits of the uridine stack.
