Introduction to Choline Supplements
Cognitive enhancers, best known as nootropics are a class of drugs that target the improvement of brain functions. Although international sales have soared since 2015 (over US $1 billion), the scientific research surrounding them remains at a preliminary stage.
In most cases, their mode of action is not well known. However, there seems to be a consensus that they improvecognitive functions by affecting the metabolism of the brain.
Two modes of actions are depicted, namely increasing the availability of neurochemicals to the brain, and neurogenesis (stimulation of neuronal growth) .
With such effects as increased memory, improvement in learning, stimulation of the mind, few side effects and low toxicity, nootropics are quickly becoming a very attractive choice for neuroenhancement in healthy adults.
If you are the type of consumer who jumps on any new bandwagon and likes to “try before think”, then I would recommend you stop reading just about now.
On the other hand, if you have a curious mind and you like to read articles and opinions before deciding on a new product, then maybe this article will interest you.
My goal is to help you formulate your own intelligent opinion on what you consider to be the best choline nootropic, how is that for cognitive enhancement!
Chemical Structures of Choline Supplements
So today’s article will discuss the general term “choline” and its related drugs available on the market of nootropics. As an intelligent consumer who is searching the internet for more information on the effects of choline, you may find yourself inundated with chemical terms and nomenclature that tend to confuse you (at best) or completely demotivate you (at worse!).
Hopefully, the few paragraphs below help to shed some light. The first important distinction to make is that choline (or choline salt, see structure below) is not a vitamin or a mineral. It is a nutrient involved in the biosynthesis of larger biomolecules essential for healthy organ functions.
Simply put, it can be considered as a small building block (precursor) used to make more complex biomolecules.
In brackets here you can see the choline cation (so the choline is positively charged) and the X- is what we call a counter ion, negatively charged.
Common counter ions are chlorine (Cl-), and also bitartrate as we will see below. Our body uses choline as a building block to make acetylcholine, shown below.
In the red circle we find the choline building block which has been “acetylated” as would say an organic chemist:
Importance of Acetylcholine
Now let’s get to the interesting part: acetylcholine belongs to a class of molecules called neurotransmitters. They essentially enable communication via nerve impulses across the junction between certain types of nerve cells ( p.374). The sketch below shows a neurotransmitter (o) released from the axon (nerve cell) making its way to the receptor of another cell.
It begs the question here, if we want to increase brain activity like focus, memory or alertness, why aren’t we making acetylcholine pills? Acetylcholine (because it has a positive charge next to the N atom) does not go through membrane cells easily and remains on the outside of cells.
It needs to take a different (sometimes bigger) form in order to increase its bioavailability, in other words, to make it easier for our body to transport acetylcholine where it is needed. Examples of forms of choline that have a higher bioavailability are alpha-GPC and CDP-choline. Let’s have a closer look at those two sources of choline.
Alpha-GPC as a Source of Choline
L-Alpha glycerylphosphorylcholine (alpha-GPC, choline alfoscerate) is a natural choline compound that is present in small amounts in the brain. Unlike other choline salts (choline citrate or choline bitartrate are some examples), Alpha-GPC crosses the blood-brain barrier easily, allowing rapid delivery of choline to the brain.
In addition, it is a biosynthetic precursor of acetylcholine . The blood-brain barrier can be compared to a selective filtration system then isolates the brain from the general blood circulation (, p.1168).
As a natural process, when the brain is low in acetylcholine, it breaks down components of cell membranes (phospholipids for example) to make alpha GPC, which is then used to produce the desired neurotransmitter acetylcholine. Below is the chemical structure of alpha-GPC within red our choline building block:
Bringing all those facts together, alpha-GPC seems to be an excellent choice for a cognitive enhancer: it is naturally occurring in the brain, it is a natural metabolite from membrane lipids and it is a precursor to acetylcholine. The benefits of alpha-GPC and more information can be found here .
CDP-Choline as a Source of Choline
Citicoline, also known as cytidine diphosphate-choline or cytidine 5′-diphosphocholine (CDP-choline) is also a naturally occurring choline compound. It is involved in the biosynthesis of phosphatidylcholine from our building block choline, which occurs in cell membranes.
Citicoline contains another interesting building block as far as the brain is concerned: cytidine. On the figure below, we show the structure of CDP-choline with again our choline block in red together with the cytidine block in blue.
Once in the body, cytidine is converted into uridine , and used by our brain to repair cell membranes and maintain our neurons healthy.
The benefits of CDP-choline can be seen as two-fold, namely, increase the amount of choline available to the brain, as well as providing building blocks involved in maintaining neuron integrity .
How Much Choline am I Getting?
As intelligent consumers who always thrive to get the best product, we may want to maximize the amount of effective ingredient we are getting with each choline supplement.
Let’s make a simple analogy here: If I buy one pound of boneless and skinless chicken breasts, I will get more chicken in the package compared to a one pound package of chicken breast bone-in with skin.
For nootropics, it turns out we can calculate easily the amount of choline since it simply depends on its molecular form.
For example, CDP-choline has a molecular weight of 489 units (g/mol). Choline bitartrate weighs in at 253 units (g/mol) for the same amount of molecules. And GPC-choline weighs 257 units so about the same as choline bitartrate.
Keeping in mind that the choline itself weighs 107 units, we can easily calculate that a given amount in grams of GPC-choline contains 41.6 % of choline by weight, whereas CDP choline only contains approximately 20% of choline. As a conclusion, not all choline nootropics are created equal as far as the amount of choline they contain.
Which Nootropic Source of Choline is Best for me?
Another question that we can ask as a consumer is how effective is the ingredient that I am purchasing? And ultimately, which nootropic is best for me?
This is definitely not something that can be answered easily without supporting research. However, there are a few general concepts we can use to evaluate the potency of a nootropic, like bioavailability as we have discussed earlier.
For our choline candidates here, we see that although both choline bitartrate and choline-GPC contain the same amount of choline (about 40% per weight), they do not exhibit the same bioavailability due to their different chemical structure. Choline-GPC will reach your brain much more efficiently than choline bitartrate so it is believed that the benefits will not be the same .
Now if we compare choline-GPC with choline-CDP, we know that both candidates do not contain the same amount of choline, however, choline-CDP has an added bonus of being a source of another chemical that is good for your brain: uridine. As a conclusion, not all choline nootropics are created equal as far as how efficient they deliver the choline to your brain, and what other benefits they provide.
I think by now you should be convinced that choline is essential for your brain, it is like food. You can get it from your diet and also from supplements as we have discussed.
As an intelligent consumer, getting informed is as essential to your brain’s health as nootropics themselves. On this note, happy reading and as would Frasier say: “Good night, Seattle and good mental health”!
 Voet & Voet, Biochemistry, John Wiley and Sons, 1990.
 Parnetti, Lucilla; et al. (2007). “Cholinergic precursors in the treatment of cognitive impairment of vascular origin: Ineffective approaches or need for re-evaluation?”. Journal of the Neurological Sciences. 257 (1–2): 264–9. doi:10.1016/j.jns.2007.01.043. PMID 17331541.
 Wurtman RJ, Regan M, Ulus I, Yu L (Oct 2000). “Effect of oral CDP-choline on plasma choline and uridine levels in humans”. Biochem. Pharmacol. 60 (7): 989–92. doi:10.1016/S0006-2952(00)00436-6. PMID 10974208.
Martine Monette holds a Ph. D in Physical Chemistry. She is an experienced scientist in the biotechnology industry. As a very enthusiastic lecturer, she always welcomes a stimulating scientific discussion.