CDP-Choline is an essential nutrient that is said to improve your cognitive performance by enhancing neurotransmitters, providing key components needed for neuron repair, and increasing brain energy.
CDP-Choline seems to offer a lot of potential as a nootropic, but is it as good as it claims to be?
What Is CDP-Choline?
Choline is an essential nutrient that was only recognized as such in 1998 by the Institute of Medicine. Choline seems to have a wide range of effects on metabolism, inducing changes to cell structure and neurotransmitter synthesis. There are also links between varied diseases and a lack of choline, with liver damage, atherosclerosis (build-up of plaque in arteries e.g. the heart), and some neurological diseases all possibly occurring due to a choline deficiency (1).
Choline is also essential in the production of phospholipids that are vital components of membrane, these phospholipids include phosphatidylcholine, lysophosphatidylcholine, choline plasmalogen, and sphingomyelin (2).
CDP-Choline is simply a naturally occurring source of choline, although it’s delivery method is anything but simple. CDP-Choline stands for cytidine-5-diphosphocholine and is made up of cytidine and choline which are linked through a diphosphate bridge. Once you digest CDP-Choline it actually splits into its two separate forms of cytidine and choline and then on delivery to the brain it reforms back into CDP-Choline. This reforming of CDP-Choline occurs through CTP-phosphocholine cytidylyltransferase (CCT) with cytidine triphosphate (CTP) and phosphocholine (3).
CDP-choline also works as “a choline donor in the biosynthesis of the neurotransmitter acetylcholine” (3). Acetylcholine (ACh) is the main transmitter used to communicate between nerve cells and other cells and is therefore very important for proper brain function. Choline is needed to create acetylcholine and it is often grabbed from cell membranes to help cell signaling processes.
It was thought that the damage caused to cell membranes from this grabbing of choline was fixed directly through CDP-Choline, but the process is slightly more complicated than that. Cytidine, one of the components of CDP-Choline, is left behind after choline is grabbed to be used in signaling processes. Cytidine can then be biosynthesized, or converted, by recombinant uridine-cytidine kinase and acetate kinase into uridine (4). Uridine is then thought to improve membrane health by synthesizing phosphatidylcholine, which is a major component of cell membranes (5).
Where To Find Choline?
Choline can be found in many foods, although most men, women, pregnant women, and children all show inadequate levels of choline. One of the richest and most easily available sources of choline in food is egg yolks, which provide 680 milligrams of choline per 100 grams of egg yolk (1).
Other concentrated sources of choline include liver and wheat germ and human breast milk has high concentrations of choline compounds. Spaghetti, quinoa, beets, and spinach all also contain related compounds of choline.
One study (6) found that women received the majority of their choline from animal products like milk, eggs, chicken, and beef. Even though eggs are higher in choline concentration than milk the research found that milk was actually a larger source of choline for the participants because more milk was consumed than eggs. To get an idea of the difference in concentration, you would need 3 ¼ cups of milk to provide you the same amount of choline as one egg would (1).
You often use CDP-Choline faster than your body can produce it because it is required for so many functions and as such CDP-Choline levels need to be supplemented. There are some recommendations for adequate choline level intake and the Institute of Medicine (7) recommends that adult women supplement with 425mg of choline a day, while adult men require 550mg a day. To put this in perspective, one egg, the largest concentration of food source choline contains 125 milligrams of choline, which is just over ¼ of the recommended daily amount of choline for adult men. However, it is thought that as much as 50% of people have genetic variations in their genetics which means that they need choline at even greater levels than this (1). One study showed that even when provided with the recommended amount of supplementary choline, some men still developed symptoms associated with a choline deficiency, highlighting the fact that appropriate choline levels will differ from person to person (8).
CDP-Choline Supplements
For those not wanting to increase their choline intake through food alone, CDP-choline supplements may provide a convenient solution. The supplements can be bought as capsules or powder and are easy to consumer and control dosage.
As previously stated the Institute of Medicine recommends supplementary choline levels of 425mg for adult women and 550mg for adult men a day. With these recommendations, it’s probably best to start supplement dosage at this level, although you are also able to start at a lower level if you wish.
Benefits Of CDP-Choline
CDP-Choline and its simpler form of choline are essential to a range of brain functions.
Enhancing Neurotransmitters
As discussed earlier, choline can increase levels of neurotransmitters like acetylcholine to improve communication from neural cells and lead to a range of effects.
One study found that 100mg/kg of CDP-Choline, the naturally occurring intermediate of choline, taken once a day for seven days resulted in an increase of noradrenaline in the cerebral cortex and hypothalamus regions of the brain, an increase of dopamine in the striatum region of the brain, and an increase of serotonin in the cerebral cortex, hypothalamus, and striatum (9).
Dopamine: Dopamine is critical to the modulation of a range of cognitive abilities like learning, motivation, memory, and attention. You might be familiar with dopamine as creating feelings of pleasure.
Research has shown that a reduction in dopamine in the basal ganglia region of the brain leads to learning impairments, indicating that dopamine is critical in controlling learning (10).
Other research further tells us that dopamine may be involved in feelings of motivation, reward, and cognition and dysfunction in dopamine production is associated with disorders including (11):
- Schizophrenia
- Autism
- Attention deficit hyperactivity disorder (ADHD)
It, therefore, stands to reason that a lack of choline could result in reduced levels of dopamine and disruptions to motivation, learning, and cognition as well as potentially contributing to disorders like schizophrenia or ADHD.
Serotonin: Serotonin is a nerve cell chemical that plays a crucial role in cognitive health as it helps to stabilize emotions and mood. Studies have shown that drugs that lower serotonin levels can result in reduced neurocognitive performance, impaired memory, and negative effects of mood and sleep (12).
Other studies involving modulation of serotonin levels show us that serotonin plays a crucial role in higher-order brain function and that low serotonin levels in the brain can lead to poor memory and a depressed state (13).
It is reasonable to conclude that if reduced levels of choline occurr you might expect to see lower levels of serotonin production which could result in reduced mood, poor memory, and an overall reduced cognitive performance.
Improved Brain Energy
Brain energy refers to the sugars that the brain uses to fuel its cellular activities. Neurons have the highest energy demand of all cells and require a constant delivery of energy such as glucose to fire. Regulation of energy levels in the brain is therefore very important for maintaining healthy brain physiology. To put into perspective the energy demands of the brain, the brain only makes up 2% of your entire body weight, but yet it requires around 20% of all glucose energy (14).
CDP-Choline, the intermediate of choline, was shown in one study to significantly increase the high-energy phosphate metabolites required for membrane synthesis in the frontal lobe area of the brain. Citicoline was taken orally for 6 weeks and participants saw significant increases to phosphocreatine and beta-nucleoside triphosphates. This study indicates that choline may be able to improve bioenergetics in the frontal lobe of the brain, increasing energy reserves, and energy utilization. A lack of energy reserves in the brain is linked to cognitive disorders that are associated with aging (15).
Uridine can be converted from cytidine, one of the components of CDP-Choline. Uridine may then impact brain energy levels because it can be converted into uridine diphosphate glucose (UDP-glucose), which is responsible for the production of glycogen in the brain. Glycogen is a storage form of glucose which is used for energy in the brain. Uridine can further be helpful as an inducer of brain energy as it is a precursor to the sugar cytidine triphosphate (CDP) which is essential for the production of membrane phospholipids (16).
Successful brain function relies on energy sources such as glucose, and disruption to the brain’s energy sources could result in cognitive disorders. Neurons are typically intolerant to low energy supplies and so any disruption to appropriate energy levels can be disastrous.
One disorder that can be caused by persistent hypoglycemia (low levels of blood sugar) is neuroglycopenia. Neuroglycopenia is a developmental disorder of the brain that can result in “mental retardation or developmental delay, anomalous coordination and muscle time, and well as thalamocortical hypometabolism” (14). Neuroglycopenia is particularly debilitating and sufferers of it may experience cognitive symptoms such as drug-resistant seizures in children, developmental retardation, and microcephaly. Microcephaly is a condition where the head is a smaller size than usual and is associated with intellectual disability and speech delay.
Other neurodegenerative disorders like Alzheimer’s disease may also be associated with low energy levels in the brain. In fact, research tells us that “one of the earliest signs of Alzheimer’s disease is a reduction in cerebral glucose metabolism” (14), and both human studies and animal models suggest that disturbed glucose metabolism is associated with Alzheimer’s disease progression. Treatments that involve increased energy metabolism have been effective in fighting cognitive dysfunction in early studies (17).
Optimization Of The Brain
CDP-Choline can optimize brain function through a range of mechanisms.
Enhances Cognition
A 2012 study looked into the effects of CDP-Choline on cognitive function in healthy adult women aged 40-60. With 60 participants, the study provided a daily dose of either 250mg or 500mg of CDP-Choline for 28 days. The results showed that the 250mg group made fewer cognitive errors than the placebo group, while the 500mg group also made fewer cognitive errors than the control group and seemed to make fewer cognitive errors overall. The researchers concluded that CDP-Choline is likely able to reduce cognitive inhibition and that CDP-Choline treatment could possibly reduce cognitive deficits associated with central nervous system disorders (18).
Another study looked into choline’s ability to improve motor neuron communication and its ability to therefore potentially affect coordination. The 28 participants of the study were given two grams of choline over two separate sessions and then had to undergo a visuomotor aiming task where they had to try and hit the center of targets as fast as they could. The results of the study showed that those who had been given the choline supplement hit the center of the targets with more accuracy than participants in the control group. Pupil size is a biomarker related to cognition, and those who were given the choline supplement had reduced pupil size which was appropriate to the distance from the targets (19).
Current research, therefore, seems to indicate a connection between high choline levels and improved cognition.
Improves Memory
One study looked at the effect that CDP-Choline might have on the verbal memory of older patients. Participants were either given 1000mg of CDP-Choline a day for three months or a placebo. The 95 participants were aged between 50 and 85 years old and were screened for memory or neurological disorders before the study. The results showed that participants in the CDP-Choline treatment group had less delay when recalling memory passages in the tests. The study concluded that CDP improved the verbal memory skills of participants and that it shows promise as a treatment from the age-related cognitive decline that could possibly be an early indicator of dementia (20).
The effects of CDP-Choline were tested on rodents in one study to see if their memory was affected. CDP-Choline was given orally to the rodents at a dose of 10-500mg/kg either once or twice a day for up to seven days. The rodents were then trained an hour after the last dose of CDP-Choline, the training involved techniques such as passive and active avoidance of objects with punishment reinforcement. The rodents underwent activities like going through a maze, shuttle box, and stepping down and up. After this training, the rodents were then given different retention tests 3 hours, 24 hours, 7 days, and 10 days later to determine if they had remembered the training. The results showed that the CDP improved the memory of the rodents and the authors of the study concluded that CDP-choline is capable of improving cognitive levels (21).
Loss of choline neurons is thought to be a precursor of memory loss associated with Alzheimer’s disease. One study gave brain MRIs and neuropsychological evaluations to 1,391 dementia-free patients to determine the impact of choline on verbal and visual memory. Those with higher choline levels performed better in the verbal and visual memory tests, demonstrating a possible link between high choline levels and improved memory (22).
Side Effects
Studies involving CDP-Choline have shown that even at high doses there don’t seem to be any serious side effects and toxicology tests have shown that supplementary CDP-Choline has no serious negative effects on the cholinergic system (23).
Some mild side effects may include headaches, diarrhea, indigestion, and trouble sleeping. If you experience any of these you should stop taking CDP-Choline supplements to seek advice from a doctor before continuing.
Summary
CDP-Choline is a precursor to choline that delivers essential nutrients effectively and conveniently in supplement form. Choline is highly important to brain function and cognition as it acts on neurotransmission, energy levels, and other neurological processes to provide a range of positive cognitive effects. Choline may be able to provide you with improved memory and cognition, and well as improved brain energy levels and protection from some neurodegenerative disorders like Alzheimer’s disease and dementia. Choline may also be able to provide protection from cognitive disorders like neuroglycopenia, ADHD, depression and mood change, memory loss, and microcephaly.
CDP-Choline seems to be a safe and effective treatment for the large amounts of people with low choline levels. Receiving appropriate levels of choline from your diet requires planning and probably the consumption of a large amount of food, while CDP-Choline supplements are convenient and easy to dose.
If you’re suffering from reduced brain function or any of the symptoms listed, CDP-Choline could be the answer for you!
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