Evidence: High Potential Benefits: High Safety: High
TABLE OF CONTENTS
What is CDP-choline?
CDP-choline, also known as citicoline, is a choline donor that contains about 18% of choline by dry weight. CDP-choline converts to phosphatidylcholine in the body so these two forms provide similar benefits. The upside of CDP-choline is that there is more research to support its benefits for brain health and cognition. On the other hand, the downside is that this form produces 3-4 times more TMAO than phosphatidylcholine. This supplement is most helpful if you are deficient in choline. If you already get enough choline from food, CDP-choline can still improve some aspects of health (mainly brain health and cognition) beyond the baseline. This article is about the main benefits of CDP-choline, its potential side effects, the best time to take it, and more.
Potential benefits
It is important to note that all of the potential benefits mentioned below are dose-dependent. Generally, the higher the dose, the more pronounced the effects are. However, they do reach a plateau at a certain point. We will discuss the best dosing protocol later in this article.
Many possible benefits fall under the umbrella of ‘correcting a deficiency’ and are therefore not mentioned in the article. If you are deficient, CDP-choline supplements can affect your cognition, performance, and overall health in a remarkably positive way.
Major benefits
Correcting or preventing a choline deficiency – Choline deficiency can be terrible for your health and overall quality of life. Fortunately, a severe deficit is relatively rare. A mild deficiency is much more common and can lead to many problems mentioned later in the article. If you are experiencing symptoms of deficiency or know that your choline levels are too low, correcting a deficiency is the main benefit of CDP-choline supplements.
Minor benefits
Reduced addiction rates – This effect was mainly studied in cocaine addicts where CDP-choline was able to lower addiction rates among those who wanted to quit using the substance. This effect almost certainly applies to most other cholinergic supplements, albeit to a lesser degree. While it has not yet been fully proven, cholinergics appear to be quite effective at helping people get through addictions to other substances and activities.
Reduced cognitive decline – This effect primarily applies to alpha-GPC and CDP-choline but other cholinergics, such as phosphatidylcholine, may also be beneficial in this regard. Cholinergics have been shown by multiple studies to have neuroprotective effects.
Reduced pain – Activation of choline receptors causes a release of opioid painkillers. Anecdotally, some people report that choline citrate is able to reduce nerve pain more than other choline donors.
Improved memory – Cholinergics (CDP-choline in particular) increase memory in older adults and probably young people as well. Studies don’t yet strongly support that these supplements improve memory in youngsters but animal studies do suggest there is an effect.
Reduced homocysteine – CDP-choline supplements can slightly reduce homocysteine levels. 3 grams of TMG (trimethylglycine) have been shown to decrease homocysteine levels in healthy individuals by about 10% and by 20-40% in people with elevated homocysteine. This effect is caused by TMG but is not exclusive to TMG supplements since choline from CDP-choline or other forms can convert into TMG. Some choline supplements are even more effective at increasing TMG levels than supplemental TMG itself. However, taking 3000 mg of these forms would not be as safe as taking 3000 mg of trimethylglycine.
Increased attention and reaction time – This effect was observed in people with acute stress when alpha-GPC was paired with caffeine and phosphatidylserine. It likely applies to other cholinergics but only to a smaller degree.
Reduced folate and vitamin B12 deficiency – Choline can replace folate and vitamin B12 in some of their functions related to methylation. While it is important to address both of these deficiencies, choline can help prevent the damage before you get to optimal levels of folate and B12. This is also why low MTHFR activity can increase your need for choline if you don’t get enough folate or B12. Low MTHFR activity increases your need for choline by 60-100%.
Improved attention – Cholinergics can notably improve attention span. Interestingly, a lower dose may be more effective in this regard. For example, 250 mg of CDP-choline seems to improve attention more than 500 mg.
Increased power output – Alpha-GPC increases power output by about 14%, which is more than caffeine does. This effect probably applies to other sources of choline but only to a lesser degree. Increased power output has also been shown in one study on TMG but has later been disproven so TMG is unreliable in this regard. The same can be said about phosphatidylcholine where no study has ever shown a benefit.
Increased training volume – One study found that taking TMG increases training volume by about 6.5%. This effect may also apply to alpha-GPC, CDP-choline, and a few other forms but choline bitartrate doesn’t seem to increase training volume.
Reduced liver fat – CDP-choline supplements can reduce liver fat and prevent fatty liver disease. Phosphatidylcholine is necessary to move fat out of our liver. It also helps digest fat in general. People with NAFLD (non-alcoholic fatty liver disease) will benefit the most.
Reduced liver damage – This effect mainly applies to TMG but again, choline supplements can increase TMG levels. People with NAFLD (non-alcoholic fatty liver disease) will benefit the most.
Increased iron absorption – Choline supplements (primarily Alpha-GPC) may increase iron absorption. This particularly applies to nonheme iron from plant-based sources. Unfortunately, the evidence to support this effect is not very strong.
Lower blood pressure – This effect was observed in older adults who took CDP-choline but likely applies to other cholinergics as well.
Possible side effects
These side effects are dose-dependent. The risk for them increases (often linearly but sometimes exponentially) as you increase the dose. Some of the side effects only apply to very high doses.
Excess acetylcholine – Too much acetylcholine can suppress the effects of other neurotransmitters, including dopamine, serotonin, and noradrenaline. This can lead to many symptoms, including irritability, anger, depression, lack of focus, fatigue, ruminating, and more. It is important to note that choline supplements can also increase dopaminergic and serotoninergic neurotransmissions.
Low blood pressure – Very high doses (7-10 grams) can cause low blood pressure.
Body odor – 7-10 grams may also cause a fishy body odor.
Sweating and salivation – These side effects have also been associated with doses of multiple grams and are a means for the body to get rid of the excess choline.
Heart disease – Excessive choline intake leads to the production of TMA, which gets converted to TMAO in the liver. There is a concern that TMAO may increase the risk for heart disease. There are some ways to prevent or lower TMAO production, such as choosing the right type of choline supplements and spreading the dose throughout the day.
Contamination – Contaminated supplements are uncommon in the USA and other well-regulated countries. However, if you wish to buy products from China, India, or other countries without strict regulations, beware that the supplements may be contaminated. Either way, you need to choose the brand you order from wisely. It is highly recommended to check the certificates or read through some reviews for the specific product before you buy it. The FDA (Food and Drug Administration) has the power to regulate dietary supplements but can only do so after they have been on the market for a while. That’s because supplement companies are not obligated to announce to the FDA when releasing a new product on the market. The FDA has to discover the product and test it for potential impurities, which can take a lot of time. During that time, the supplement can be sold on the market even if it’s impure. Also, the supplement companies can change their manufacturers at any time without announcing it to the FDA.
Who should not take CDP-choline?
You should probably avoid taking the supplement if you:
already consume enough choline from food
experience a severe adverse reaction after taking the supplement
Who will benefit the most?
You should consider taking the supplement if you:
experience symptoms of deficiency, or you know you are deficient based on blood tests
don’t get enough choline from food (the easiest way to find out how much of this nutrient you are getting in your diet is to track your food intake for a while with Cronometer.com)
are on a plant-based diet (not eating eggs makes it harder to get enough of the nutrient)
take other nootropics (many of them are unlikely to work well if you don’t get enough choline; some nootropics, such as racetams, significantly increase your need for choline)
have low MTHFR activity (low MTHFR activity increases your need for folate and vitamin B12 but choline can replace folate and vitamin B12 in some of their functions related to methylation; people with low MTHFR activity usually need 60-100% more choline, assuming they also don’t get enough riboflavin)
often engage in cognitively demanding tasks
are deficient in folate or vitamin B12 (while it is important to address both of these deficiencies, choline can partially help by replacing folate or B12 in some functions)
Other forms of choline supplements
The main forms of choline supplements include:
Phosphatidylcholine – This is the main form of choline found in food. It is especially good at supporting liver health and fat digestion. If you chose this form, beware that only around 15% of phosphatidylcholine gets absorbed as choline. This means you’d need to take 1000 mg of phosphatidylcholine to get 150 mg of choline.
Choline bitartrate – This is the cheapest form but also the worst one to take. This form isn’t nearly as effective at producing acetylcholine as most other forms. It also isn’t as beneficial in most other areas. Around 40% of choline bitartrate is choline (by weight). The main concern with this form is that it produces 3-4 times more TMAO than most other forms.
Choline citrate – This form is less popular but also cheap. Around 50% of choline citrate is choline. Since we don’t know as much about this form as about the other ones, it is probably better to choose one of the other choline supplements instead. One benefit of this form is that it is better for muscle pain.
Alpha-GPC – This form is up to 10 times better at producing acetylcholine than the other forms. Around 40% of Alpha-GPC is available as choline and it crosses the blood-brain barrier much more easily than the other forms. It is by far the best form to take for improving brain function and power output.
CDP-Choline – This form, also known as citicoline, contains about 18% of choline by dry weight. Just like the bitartrate form, CDP-choline produces 3-4 times more TMAO than phosphatidylcholine. In the body, this form is converted into phosphatidylcholine so it doesn’t seem to have notable additional benefits. One reason to include CDP-choline in your supplement stack is that it synergizes well with some other nootropics.
TMG – Trimethylglycine (TMG) is another word for betaine (or betaine anhydrous). TMG can provide up to 50% of your choline needs by replacing it in processes related to methylation. Therefore, if you are taking 275 mg o more of TMG, you should only need around a half of choline. On top of this, TMG has many other functions in the body.
Betaine HCl – Betaine hydrochloride can also provide betaine for methylation but it is much less beneficial or safe than TMG or other choline supplements. This form is not recommended unless you have a great reason to take it.
Lecithin – One tablespoon provides over 100 mg of choline in form of phosphatidylcholine. Lecithin also contains other beneficial compounds, such as phosphatidylserine.
All of these forms have their unique properties and all of them are worth consideration (except choline bitartrate and betaine hydrochloride, which are rarely better than the other forms). If cognition and brain function is your priority, a combination of alpha-GPC and CDP-choline is a way to go. If you are only willing to take one of these, alpha-GPC seems to be a better choice.
TMG deserves special attention since it has many benefits that go beyond replacing choline in methylation-related processes.
Symptoms of choline deficiency
The most common signs of deficiency include:
low energy
forgetting and poor memory
difficulty concentrating
learning disabilities
muscle aches
mood swings
nerve pain
Keep in mind that these signs are just indications of a deficiency. If you experience some or even most of them, it does not necessarily mean you need more choline. On the other hand, some people may be deficient even though they are completely asymptomatic.
With that said, if you experience many or most of these symptoms, there is a high chance that you are not getting enough choline. The more of these symptoms you have and the more severe they are, the more likely you are to have a deficiency.
How much CDP-choline should you take?
The AI (adequate intake) for this nutrient is 550 mg a day for men and 425 mg for women. The AI for pregnant women is 450 mg daily and for lactating women, it is 550 mg daily.
This should be enough to avoid symptoms of deficiency. However, it’s safer to shoot for 275 mg for every 1000 calories. Also, there is a case to be made that women don’t need less choline and may actually need more of it since high estrogen levels increase your need for the nutrient.
The main benefit of CDP-choline is correcting a choline deficiency so if you choose this form, you don’t need nor want to cross the RDA unless you have a great reason to do so. You want to get just enough choline.
CDP-choline is around 18% choline by weight, meaning that you’d need to take around 3050 mg to get enough choline. However, you’re also getting at least some amount of choline and betaine from food so taking 3050 mg would be unnecessary. Doses of 500-1000 mg should get the job done for most people.
You can also get around half of the choline requirements from betaine (also known as trimethylglycine or TMG). Betaine can mostly replace choline in the methylation process but not in other processes, such as making acetylcholine.
If you wish to get 550 mg of choline, you should only need 275 mg of choline if you get 275 mg of betaine. If you eat or supplement with more than 275 mg of betaine, you will still need the 275 or so mg of choline.
Beware that some things increase your need for choline. For example, low MTHFR activity increases your need for this nutrient by 60-100%. Certain nootropics, such as racetams, also increase the amount you need.
For nootropic effects, a reasonable dose can be anywhere from 300-2000 mg. Sticking to a lower end of the spectrum is safer and higher doses only make sense if you have a good reason to take them.
The upper safety limit for choline is set at 3500 mg for most adults. Higher doses may cause problems if you take the supplement for a prolonged period. Do not take more than this amount unless you have a great reason to do so.
The higher the dose you take, the higher the risk for side effects. Taking more than 2000 mg of choline donors daily should not be necessary and is not recommended unless you have a great reason to do so.
Food sources of choline
The richest food sources of choline are egg yolks and liver. As little as 4 eggs or 200-300 grams of liver should provide enough choline.
Nuts, seeds, vegetables, legumes, and some grains are also great sources of this nutrient.
You can also get around half of the choline requirements from betaine (also known as trimethylglycine or TMG). Betaine can mostly replace choline in the methylation process but not in other processes, such as making acetylcholine.
If you wish to get 550 mg of choline from food, you should only need 275 mg of choline if you get 275 mg of betaine. If you eat or supplement with more than 275 mg of betaine, you will still need the 275 or so mg of choline.
100 grams of fresh beetroot, frozen spinach, and some other leafy greens provide around 140 mg of betaine. Wheat germ is also a fantastic source. As little as 70 grams can provide most of your choline needs (by supplying both choline and betaine).
The easiest way to find out how much choline you are getting in your diet is with Cronometer.com – this free app allows you to track all vitamins, minerals, and more.
Best time to take CDP-choline
CDP-choline is water-soluble, which means you don’t have to take it with food to absorb it well. Taking the supplement with food is better if it causes stomach upset when you take it on an empty stomach.
For best results, take the supplement in the morning before breakfast. If you are taking other nootropics, such as racetams or acetyl-L-carnitine, take CDP-choline at the same time.
Interactions with other supplements
Vitamin B5 Vitamin B5 is needed to make coenzyme A (CoA), which along with choline can be used to create the neurotransmitter acetylcholine.
ALCAR and NAC Acetyl-L-Carnitine and N-Acetyl Cysteine both provide the acetyl group that can be used for the synthesis of acetylcholine. In other words, taking one of these makes it easier to produce acetylcholine when paired with choline donors.
Riboflavin Riboflavin can reduce the fishy smell that occurs mainly in people with a mutation in the FMO3 gene when they take choline supplements.
Piracetam Piracetam potentiates the flow and increases the effects of acetylcholine.
Aniracetam Aniracetam leads to higher releases of acetylcholine, increasing your need for this neurotransmitter.
Coluracetam and Pramiracetam These two racetams increase the conversion of choline to acetylcholine through the high-affinity choline uptake process (HACU).
Oxiracetam Oxiracetam increases choline acetyltransferase (ChAT), which is used to synthesize acetylcholine
Phenylpiracetam Phenylpiracetam increases the density of acetylcholine receptors.
Where to buy CDP-choline
Amazon seems to be the best option for ordering CDP-choline supplements in most countries. They offer some very affordable products backed by many positive reviews. Also, you can choose from a wide range of brands without having to search through other markets on the internet.
Beware some brands display the dosage per serving instead of per pill or capsule. Therefore, you may accidentally buy something less potent than you intended. Do not fall for this marketing trick.
FAQ
You can take the supplement daily and do not need to cycle it. However, it is certainly not a problem if you don’t take it daily. Not taking the supplement every once in a while could lead to better absorption, but no studies have proven this yet.
All of these options are fine. The two most important things to consider are the price and dosing. Powders are almost always the cheapest form. However, to dose them correctly, you may need a highly accurate scale (preferably 0.001g). You can get one for as little as $20 from Amazon. Dosing the powders also takes some time that can add up over months or years. The disadvantage of capsules is that they are sometimes made of unethical ingredients, such as bovine gelatine.
While it’s not a big problem to take the supplement at night, it is mildly stimulating and could negatively impact your sleep. For best results, take the supplement in the morning before breakfast.
CDP-choline supplements rarely go bad, but they can lose potency over time.
Keep the supplement in a cold, dark, and dry place, and they will remain just as potent for many months or even years.
The supplement doesn’t directly reduce acne, unfortunately.
While toxicity is rare, too much CDP-choline in the system can cause some problems, such as a fishy odor, excess sweating, and increased TMAO levels that may increase your risk for cardiovascular diseases. To stay on the safe side, it is best to stay below 2000 mg a day to prevent these side effects.
All of the supplemental forms have their unique properties and all of them are worth consideration (except choline bitartrate and betaine hydrochloride, which are rarely better than the other forms). If cognition and brain function is your priority, a combination of alpha-GPC and CDP-choline is a way to go. If you are only willing to take one of these, alpha-GPC seems to be a better choice.
TMG deserves special attention since it has many benefits that go beyond replacing choline in methylation-related processes.
The most common reason people become deficient is that they don’t get enough of this nutrient from their diet. However, many things can hurt your choline status and increase your need for this nutrient. These include low MTHFR activity and taking other nootropics, such as racetams.
You may need more of the nutrient if you: – experience signs of deficiency, or know that you are deficient from blood tests – don’t get enough choline from food (the easiest way to find out how much of the nutrient you are getting in your diet is to track your food intake for a while with Cronometer.com) – have low MTHFR activity (low MTHFR activity increases your need for folate and vitamin B12 but choline can replace folate and vitamin B12 in some of their functions related to methylation; people with low MTHFR activity usually need 60-100% more choline, assuming they also don’t get enough riboflavin) – are deficient in folate or vitamin B12 (while it is important to address both of these deficiencies, choline can partially help by replacing folate or B12 in some functions) – often engage in cognitively demanding tasks – take other nootropics (many of them are unlikely to work well if you don’t get enough choline; some nootropics, such as racetams, significantly increase your need for choline) – are on a plant-based diet (not eating eggs makes it harder to get enough of the nutrient)
In the long-term, it typically takes about a month after you start taking the supplement to start noticing the benefits.
The majority of CDP-choline supplements on the market are vegan-friendly but always check the label to be sure.
CDP-choline is water-soluble, which means you don’t have to take it with food to absorb it well.
No, it doesn’t. The supplement does not interfere with fasting in any significant way.
References
Most of the information provided in this guide is supported by scientific research that can be found and verified in the PubMed medical library. We highly encourage you to use the library to verify anything said in this article. We excluded from consideration studies that are either confounded or have a high conflict of interest.
