Which is better – CDP-Choline or Alpha-GPC?
Every complete natural nootropic stack should contain some form of cholinergic compound; be it Centrophenoxine, choline bitartrate, DMAE, CDP-Choline or Alpha-GPC. While choline supplements alone do not make a nootropic stack, the absence of cholinergics is a serious flaw in any modern brain supplement.
But which choline ‘pro-drug’ is best?
An awful lots of debate surrounds that question. Many people swear by DMAE, while others eschew taking any form of cholinergic at all.
Despite the many disparate opinions that circulate on the internet, there seems to be a tentative consensus on which choline supplements work best. It is generally accepted that the best way to supplement choline is to take either CDP-Choline of Alpha-GPC.
People cite a whole host of reasons for why their favourite is the ‘best’, and many of those benefits apply equally to both compounds.
So what should you do? Which is best for you?
The only intelligent thing to do is to learn all you can about the two nootropic substances and make up your own mind. That is what this article is here to help you do.
What are cholinergics?
Cholinergic quite simply refers to any substance that has a positive effect on acetylcholine levels. Hereafter, cholinergic will refer to any substance that increases acetylcholine concentrations as a result of oral supplementation.
The most basic cholinergic is choline itself (usually bought as choline bitartrate), but it is merely one example of many, and it is regarded as one of the least efficient supplements to take for boosting acetylcholine levels. This mirrors the paradoxical effects of many supplements (taking certain types of fat to burn more fat, for instance).
Cholinergic can actually be applied to different types of nootropic compounds.
There are those, such as Alpha-GPC, which actually contain choline and confer it to the body after supplementation.
Then there are others, such as Huperzine A, which work the “other end” of the equation. These substances inhibit the production of acetylcholinesterase; the enzyme responsible for the breakdown of acetylcholine.
One type of substance is therefore directly effective, while the other is indirectly effective. In either case, the end result is more acetylcholine being available in the brain.
Why are they important nootropic stack ingredients?
Acetylcholine is a neurotransmitter associated with both the peripheral and central nervous systems. In the brain, it is closely associated with short term memory, motivation, mood, and attention. These are by no means its only functions, but as far as nootropic supplementation goes, they are the most interesting.
Maximising acetylcholine availability is key for any supplement that aims to get your brain firing on all cylinders.
To put it in a less accurate but easily understandable way: you can give your brain all the energy you want, but unless it has sufficient neurotransmitter levels to get the job done, the extra energy isn’t going to be put to proper use.
If the goal of a supplement is to optimise cognitive performance, then cholinergics are a must.
So, which cholinergic is right for you? CDP-Choline or Alpha-GPC?
Alpha-GPC (or Alpha-glycerophosphocholine to give it its proper name) has been shown in numerous studies to be a reliable method of increasing acetylcholine production in the brain. It is typically 40% choline by weight.
In terms of where it fits into the choline ‘cycle’, Alpha-GPC is a by-product of phosphatidylcholine. This means that it is much closer to the form of choline used by cells than other analogues.
The glycerophosphate part of the compound is thought to contribute to healthy cell membranes. It therefore appears to contribute to optimal brain health and cell maintenance. More study is needed on this, but there is good reason to believe that Alpha GPC provides this additional neurological benefit.
When bough in bulk, it is often shown as ‘Alpha-GPC 50%’, the other 50% usually being made up of an inert bulking agent which helps with the capsuling process.
It is without doubt one of the most effective ways of boosting acetylcholine availability. It is able to positively effect both systemic and brain concentrations of choline.
Alpha-GPC is found naturally in the human diet, and is particularly concentrated in oats, wheat, and milk. However, it is not found in large enough amounts for these foods to have a significant, appreciable effect on cognition. Supplementation is therefore necessary to derive real cognitive benefits.
The benefits of Alpha-GPC
The main reason people use Alpha-GPC as a cholinergic is because of its efficiency relative to other compounds.
Alpha-GPC appears to be the best currently known cholinergic in increasing plasma and brain choline levels, as it has better transportation into the brain than does choline (somewhat similar to CDP-choline) but since it is a greater percentage choline by weight (relative to CDP-choline) taking X dose of either drug gives more choline when using Alpha-GPC
It is simply more efficient to take Alpha-GPC than CDP-Choline if you want to directly increase brain choline levels.
This is partly because the former confers more choline after oral supplementation by weight than the latter, and partly because it is a by-product of and not a precursor to phosphatidylcholine.
Here is a good diagram illustrating the biosynthetic pathway of acetylcholine:
As you can see, Alpha-GPC is just a short ‘step’ away from acetylcholine.
That is, however, just one reason why nootropics users include Alpha-GPC in their stacks. Another major reason is its proven effectiveness.
For instance, this study found that participants with Alzheimer’s exhibited “cognitive improvement” after supplementing with Alpha-GPC for 180 days. Moreover, the link was thought to be fairly robust, the researchers concluding that: “The results of this study suggest the clinical usefulness and tolerability of CA in the treatment of the cognitive symptoms of dementia disorders of the Alzheimer type.”
Another study found that Alpha-GPC was able to assuage the symptoms of dementia in some patients to a degree not seen when said patients were supplementing with phosphatidylcholine.
How does that help people without Alzheimer’s?
For one thing, the best way to treat any condition is always going to be prevention, if prevention is possible of course.
For another, I think the mechanisms by which Alpha-GPC works to help those people living with Alzheimer’s can just as easily benefit people with relatively healthy memories. In theory, the mental performance of healthy adults can be just as hampered by acetylcholine depletion as older people experiencing cognitive decline; in my opinion, the difference is in degree and duration.
By making sure you have adequate acetylcholine levels in the brain, you can be sure that your brain isn’t underperforming as a result of acetylcholine depletion.
This can happen due to acute stress, which you may experience as mental “burnout”. It is certainly not something solely experienced by the elderly, although chronically low acetylcholine levels may be.
More generally, studies on rats have found that Alpha-GPC supplementation is able to improve learning and short-term memory function, as judged by performance in behavioural pain avoidance tasks.
Rats are not humans, but they do tend to give us a fairly good idea of how a drug will act in humans.
Something often overlooked when examining Alpha-GPC’s potency as a nootropic substance is the presence of glycerophosphate.
Alpha-GPC is essentially a choline-containing phospholipid composed of glycerophosphate and choline.
Phospholipids are the fundamental building blocks of our membranes. It doesn’t take a great mental effort to understand that, in order to properly maintain optimal brain function, you need to ensure that it has all of the building blocks it needs at its disposal.
Therefore, by supplementing with phospholipids, you can support the synthesis and maintenance of brain cell membranes, ensuring an optimally performing, healthy brain.
You can actually see from the diagram above how Alpha-GPC can be used to form both acetylcholine and phosphatidylserine. One process is simply a bit more convoluted than the other.
Supplementing with Alpha-GPC is to supplement for both acetylcholine availability and cellular membrane integrity. This means it is supplementing for both improved cognitive function and enhanced brain regeneration. As such, it is undoubtedly a holistic nootropic substance.
The drawbacks of Alpha-GPC
As with all supplements, Alpha-GPC is not uniformly effective, and it has its critics.
In my opinion, the most serious issue that arises from supplementing with Alpha-GPC seems to be the unpredictability of results, even in the same person on different occasions.
Take the testimony of this LongeCity user for example:
As you can see, this user got very mixed results from taking Alpha-GPC. These bad experiences were apparently not correlated to any particular dosage.
They may be associated with the user taking in too much choline from dietary sources without realising, but we can’t rely on that assumption. Particularly as other users say the same thing:
Here’s another user who experienced milder but still less than ideal effects from Alpha GPC:
These side effects are clearly mild, but they are still a concern fro anyone looking for something to take as part of their daily supplementation routine.
Unpredictability is not really what we want when we’re looking for something to include in our daily nootropic stack. We want something that will be almost boring in its uniformity. We want consistent, subtle, gradual improvement.
It might seem then that Alpha-GPC isn’t a good candidate for a nootropic stack. However, I believe that it is a brilliant stack ingredient regardless of the negative reports of some users.
Nootropics are far from an exact science, and the variability between people is enormous.
Some people react terribly to even trace amounts of caffeine, while others take many hundreds of milligrams daily.
Some people get stomach cramps and nausea from taking Bacopa monnieri for just a few weeks. Others take it for months without a single problem.
Obviously, then, people react differently to the same substances.
In order to make intelligent choices, you need to look at how people react to natural nootropic substances generally, and how the substances mechanism for action is likely to affect you as an individual, based on your own experiences with similar substances.
For the vast majority of people who take Alpha-GPC in sensible dosages on a regular basis, side effects seem to be negligible.
In my opinion, the testimonies that talk about the down sides of Alpha-GPC supplementation are exceptions rather than the rule.
They do not come close to equalling the number of people who take natural nootropic stacks containing Alpha-GPC on a regular basis and experience no side effects at all.
Some people already consume massive amounts of choline on a daily basis from their regular diet. Supplementing with more is likely to elicit some side effects in these people. But this is true of every substance; too much is too much.
You can mitigate the risk of side effects by thinking about your current intake and deciding whether supplementation is really necessary.
Everyone is different, and it is crucial that you think about how a drug works, how you respond to similar substances, and your current diet before you try anything new.
More importantly, if you have any doubts whatsoever about a substance, you should seek the advice of a practicising doctor before trying it on yourself.
- Product of the breakdown of phosphatidylcholine
- Closer to acetylcholine in the ‘synthesis chain’ than CDP-Choline
- Has been clinically proven to be beneficial for people living with Alzheimer’s and other memory-related illnesses
- Arguably the most efficient cholinergic by weight and speed of action
- Used to form both acetylcholine and vital phospholipids, contributing to cell membrane health and integrity
- Seems to be ineffective for some users, but these are obviously outliers
- Broadly well-tolerated and produces few to no side effects in most users
CDP-Choline, or cytidine diphosphate choline, is a fascinating cholinergic compound. It is an immensely effective nootropic supplement, and many people find it to be significantly more beneficial than Alpha-GPC, or any other choline pro-drug for that matter.
For starters, let’s look at CDP-Choline’s structure, and the effect it has on acetylcholine synthesis.
CDP-Choline is broken down in the body into cytidine and choline.
The choline portion of the compound is metabolised in the body into phosphatidylcholine. It is, in fact, an essential step on the biosynthetic pathway to the production of phosphatidylcholine, and as such, it is an integral part of brain cell membrane formation and maintenance.
Phosphatidylcholine is also a precursor in the biosynthetic pathway of acetylcholine.
The cytidine portion of the compound is thought to increase uridine synthesis. Uridine is a fairly complicated substance, requiring an entire article of its own.
Benefits of CDP-Choline
The benefits of CDP-Choline are as diverse as they are impressive. They also have robust clinical backing.
Like Alpha-GPC, it seems to be able to effectively cross the blood-brain barrier, contributing to elevated brain choline levels in a fairly short space of time.
The resulting proliferation of choline can then support healthy acetylcholine and phosphatidylcholine synthesis. The end result is better brain health, enhanced short term memory and focus, and an optimised brain.
Much like Alpha-GPC again, CDP-Choline seems to be incredibly effective at slowing down the onset of age-related mental decline, and in some cases it seems to be a highly beneficial treatment for those people already living with memory-related illness.
The manner in which it does this seems to be by preventing neural cell death (apoptosis) – the fundamental process of neurodegeneration. To quote the aforementioned study: “citicoline (CDP-Choline) exerts antiapoptotic, neuroprotective and antiamnesic effects in conditions of neurodegeneration”.
Once again, one might ask how this benefits health adults. I think the answer to that is simple: the best method of treating mental decline is prevention.
Degrading memory is not the sole preserve of the elderly, and anyone can benefit from optimising the function of their brain cells, as well as their neurotransmitter synthesis.
But, to make the point clear, some studies have been done on healthy adults. To take just one as an example, CDP-Choline was found to “improve attentional performance in middle-aged women”.
On top of that, we have strong clinical evidence which suggests that cytidine is able to promote brain phosphatide synthesis without interfering with acetylcholine synthesis. Great stuff.
As mentioned above, choline is just one part of CDP-Choline.
The cytidine content of the compound is far from just an inert molecular add-on. It is a vital part of the RNA formation process, and it is thought to be converted to uridine in the body. This has some pretty profound nootropic implications.
Perhaps the most impressive effect of uridine supplementation is synapse proliferation.
The often quoted study showing a relationship between synapse formation and uridine supplementation has its limitations.
For one thing, uridine was supplemented with DHA; the fatty acid constituent of fish oil that is already known to be a fundamental building block of neural tissue.
Yet there does seem to be a significantly more pronounced benefit in terms of synapse growth when DHA is supplemented alongside uridine.
The main reason for this is because uridine is also known to promote phosphatidylcholine synthesis.
Much like Alpha-GPC, then, the entire CDP-Choline molecule seems to work to promote brain health, memory function, and cognition.
Importantly, cytidine seems to further support the role of choline in delivering the benefits of CDP-Choline. By promoting phosphatidylcholine levels, cytidine frees more of the choline in CDP-Choline to go towards acetylcholine synthesis.
The benefits of uridine (and by extension, cytidine) go beyond that of course.
It is also linked with the production of neurotransmitters of the catecholamine variety – namely, dopamine and norepinephrine.
Many people do not realise how low neurotransmitter production can be the result of a poor diet. Yet neurotransmitters require raw materials for their production. Letting your catecholamine levels sink too low can have serious consequences.
Having low dopamine levels can cause mood swings, chronic fatigue, a complete lack of motivation, and short term memory loss. These effects will probably get worse over time if dopamine production is not brought up to speed.
It is therefore much to the credit of a nootropic stack if it can help maintain healthy dopamine output.
CDP-Choline supplementation seems to be a very reliable way to do this.
I would like to see more study done in this area,but thus far, the link between dopamine output and uridine seems well founded.
CDP-Choline as a Stimulant?
CDP-Choline is thought to have some mild stimulatory properties.
For instance, it is thought that it can increase heart rate, and enhance the perception of mental energy. This may be the result of increased dopamine release. I am not certain of this, but I can see no mechanism by which CDP-Choline would act as an actual stimulant.
It therefore makes sense to assume that enhanced dopamine and norepinephrine output is merely reducing the perception of fatigue and boosting motivation. The effect of this would feel like boosted mental energy.
CDP-Choline or Alpha-GPC: Comparison
Both CDP-Choline and Alpha-GPC are part of the choline ‘cycle’. One is a precursor to phosphatidylcholine, while the other is a by-product. They both have direct influence over choline availability in the brain.
Unfortunately, few studies have been done to compare the two compounds directly.
The clinical studies that have been done have used intravenous injections rather than oral ingestion. Although this might make a difference, one study I found stated that: “Absorption by the oral route is virtually complete, and bioavailability by the oral route is therefore approximately the same as by the intravenous route.”
These studies are unequivocal in their conclusion that Alpha-GPC is the more effective supplement for increasing brain choline levels.
One study that compares the two concludes: “After the administration of CTC, plasma choline levels showed a similar time course but were considerably lower than those observed after the administration of alpha-GPC.”
Other studies, available online, have found that Alpha-GPC is more efficient at increasing free choline levels in the blood.
But a handful of studies are not really sufficient to prove that one compound is ‘better’ than the other. Clearly, much more research is needed in this area before we can make a definitive decision either way.
That said, raising choline availability is not the only way to improve cognitive function. Both Alpha-GPC and CDP-Choline have peripheral benefits beyond conferring choline that make the choice between them even more difficult. And when we look at these benefits, it seems that CDP-Choline might have the edge.
Both Alpha-GPC and CDP-Choline are degraded into choline and another substance in the body.
In both instances, these substances contribute to higher levels of phospholipids, thereby ensuring healthy dendrite (nerve cell) growth and maintenance.
This is an incredibly important benefit of a nootropic supplement. Increasing neurotransmitter availability is certainly vital, but ensuring that your brain has a plentiful supply of phospholipids to rebuild itself is something very fundamental that you want to get right.
Alpha-GPC does this via conversion straight into phosphatidylserine, while CDP-Choline does this by first converting into phosphatidylcholine. But the important thing is that they both do it.
Where I think CDP-Choline may have the edge is down to the very exciting potential benefits of uridine supplementation.
Uridine has the potential to be one of those incredibly potent, holistic and lasting nootropic substances that eventually finds its way onto the ingredient list of every reputable stack on the market.
However, thus far, we have just handful of proven benefits. Of those, one strikes me as being both thoroughly supported by clinical investigation, and enormously important for nootropics users: the interaction between uridine and DHA.
Uridine seems to work synergistically with DHA, making its effects more pronounced and, potentially, longer-lasting. The experiment in question clearly concludes that: “Hence it is possible that giving uridine plus DHA triggers a neuronal program that, by accelerating phosphatide and synaptic protein synthesis, controls synaptogenesis.”
To put it more simply, although DHA is believed to contribute to maintenance of neural tissue, stacking it with Uridine turns this support into a fully-blown program of reconstruction.
Obviously, we only have one study attesting to this phenomenon thus far, but what an exciting proposition it represents!
Another peripheral benefit not (to my knowledge) shared by Alpha GPC is dopamine modulation. CDP-Choline seems better placed to ensure healthy dopamine and norepinephrine than Alpha-GPC.
Optimising dopamine levels can have a profound effect on mood, motivation, and concentration. These are all huge nootropic benefits, and CDP-Choline seems uniquely placed to deliver them.
So, does that mean that CDP-Choline is the better of the two cholinergics?
Well, unfortunately, I can’t give you the answer to that question – it’s up to you to decide which of these two compounds you need in your stack.
As I have said again and again on this site, nootropics are very person-dependent. While we can extrapolate general rules based on the mechanism of different substances and anecdotal evidence, what is right for one person may not necessarily be right for another.
CDP-Choline and Alpha-GPC operate in very similar ways when ingested orally. They are both involved in the biosynthesis of acetylcholine and cell membrane forming phospholipids. However, the tiny differences between them mean that one may be more suitable to your needs than another.
As with all nootropic substances, you really need to pin down your own personal needs before deciding on the right stack for you. This is particularly true if you are designing your own stack from bulk bought powders.
Don’t just choose the ingredients that people say are “the best”, because there is no “best”! There is only “best for you”.
If you need something that is going to give you the biggest influx of choline in the shortest possible space of time, then Alpha-GPC is probably the cholinergic for you.
If you want something that isn’t as fast acting, but that has very similar results, and with arguably more potent peripheral benefits, then CDP-Choline might be the way to go.
Basically, it all comes down to what you want, and how you react to each substance.
The side effects often associated with Alpha-GPC are not, to my knowledge, usually associated with sensible CDP-supplementation. Not only that, but CDP-Choline is usually cheaper than Alpha-GPC (although this will only make a difference if you’re buying it in bulk for your own use).
That said, you might not experience any side effects from Alpha-GPC, like the vast majority of users out there.
As usual, it all comes down to trial and error.
- Precursor to phosphatidylcholine
- Effective at increasing brain choline levels
- Supports cell membrane structures and enhances the nootropic effects of DHA
- Widely used and well tolerated
- Delivers cytidine which has the potential to aid dopamine modulation
CDP-Choline or Alpha-GPC: Final Verdict
- Both CDP-Choline and Alpha-GPC are involved in the biosynthesis of acetylcholine, a key neurotransmitter, and phospholipids that constitute brain cell membranes
- Alpha-GPC seems to be more efficient (by weight) than CDP-Choline, and faster acting in terms of increasing brain choline levels
- Alpha-GPC is a ‘step closer’ to acetylcholine than CDP-Choline, whereas CDP-Choline is more closely associated with phosphatidylcholine synthesis
- CDP-Choline has been proven to be effective at preventing age-related cognitive decline, as well as assuaging the symptoms of memory loss related with neurodegeneration
- CDP-Choline delivers cytidine, which in turn elevates uridine levels in the body. This has the potential to promote real synapse proliferation and neural cell growth
- Some people report side effects of taking Alpha-GPC. Reports of side effects of taking CDP-Choline are, by comparison, few and far between
- CDP-Choline is associated with incredibly ‘peripheral’ benefits, including dopamine modulation, and enhancing the effects of DHA
- CDP-Choline is known to act as a stimulant. However, I think this might actually be the product of a reduction in the perception of fatigue and boosted motivation – a consequence of greater dopamine output
Clearly, each compound has its merits. While their action is broadly the same, small differences in their composition give them slightly different effects.
Which one you incorporate into your stack will very much depend on what you want to get out of your nootropic supplementation.