Citicoline

Citicoline is a naturally occurring chemical in the body that appears to play a role in brain health. Citicoline is available as a supplement in some countries, while in others it is sold as a drug. It is used to improve mental abilities in people who suffer from circulatory problems in the brain.

What is citicoline?

Citicoline (cytidine-5-diphosphocholine or CDP-choline) is important for the production of phospholipids such as phosphatidylcholine. These molecules form the cell membrane and the protective sheathing of nerves in the body. Citicoline is a more complex molecule than choline or alpha-GPC, but it is identical to what the brain naturally produces. To avoid confusion, scientists have chosen to refer to citicoline when this substance is used for therapeutic purposes and to use the term CDP-choline when referring to the substance naturally produced by the body. When consumed, citicoline releases two compounds: cytidine and choline. After crossing the blood-brain barrier, neurons in the brain use these compounds to produce citicoline and other phospholipids. Choline increases the levels of acetylcholine and other neurotransmitters that keep the nervous system functioning. The body converts citicoline into a number of other beneficial compounds. For this reason, citicoline may have more benefits and a better side effect profile than regular citicoline (1, 2).

How does citicoline work?

Citicoline increases the production of neurotransmitters and cellular building blocks. In addition to increasing acetylcholine production, it also increases the production of norepinephrine and dopamine in the brain (1, 3). It also improves blood flow to the brain and stimulates the production of mitochondria to produce more energy (1, 2, 4). Sufficient levels of CDP-choline maintain phosphatidylcholine and sphingomyelin, which form the protective sheath around the nerves known as myelin. In addition, citicoline inhibits the pro-inflammatory enzyme phospholipase A2 and increases levels of the key antioxidant called glutathione (5, 6). All in all, citicoline works by promoting the balance of neurotransmitters and protecting the nervous system from oxidative and age-related damage (7, 8).

Possible health benefits of citicoline

1. citicoline may improve cognitive performance

Citicoline may counteract age-related decline in cognitive ability Choline levels tend to decline with age due to poorer blood flow to the brain and other causes. A review of 14 clinical studies concluded that CDP-choline may improve memory and behavior in people with mild to moderate impairments, including poor blood flow to the brain (7). According to data from over 2800 elderly patients, after treatment with citicoline, memory problems disappeared in 21% of cases and were alleviated in 45% of cases. However, this study lacked a control group (9). In 350 elderly patients with mild cognitive impairment, citicoline at a dosage of 900 mg per day over a period of 9 months had benefits as it (10):

strengthened the membranes of the nerves
increased the levels of noradrenaline and dopamine
prevented oxidative damage

In three studies of 210 patients with dementia and poor blood flow to the brain, citicoline improved memory, reaction time and behavior. Higher doses of citicoline (2000 mg) resulted in better outcomes (11, 12).

Citicoline may have nootropic effects

Many users use citicoline to sharpen their minds, improve their memory and prevent a decline in cognitive performance. In two clinical trials involving 135 healthy adults, citicoline (250 to 500 mg) improved focus and mental clarity (13, 14). In another study of 60 subjects, a drink containing citicoline and caffeine improved cognition and reaction time. Caffeine is known to be a stimulant and likely contributed to the results (15).

In 24 healthy adults, higher doses of citicoline (500 or 1000 mg) improved a number of cognitive markers - processing speed, working memory, verbal memory and execution speed - but only in subjects with poor cognitive performance (16). In the same study, supplementation had no effect on subjects with average mental performance, and even slightly impaired cognitive performance in subjects with high cognitive performance.

Marijuana abuse can impair cognition. In a study of chronic marijuana users, 2000 mg of citicoline over an 8-week period reduced impulsive reactions and improved cognition. All of the subjects wanted to quit smoking, and the researchers believed that the effects of citicoline may have helped guide the subjects in that direction (17, 18).

Summary: Preliminary research suggests that citicoline may improve focus and mental clarity, especially in people with low mental performance.

2) Citicoline may aid recovery after a stroke

An interrupted blood supply to a specific area of the brain can destroy neurons and cause massive brain damage. Citicoline could help by strengthening the nerve membranes and blocking the production of free radicals (19, 20). According to a meta-analysis of 4 clinical trials with a total of 1300+ subjects, 2000 mg of citicoline within the first 24 hours after stroke could increase the chance of full recovery by 38% (8). Data from over 4000 stroke survivors showed that citicoline supports recovery. Higher doses (2000 to 4000 mg) were more effective. However, the lack of a control group does not allow any definitive conclusions to be drawn (21). Two other studies with over 3000 patients were unable to observe any significant benefits of citicoline in acute stroke (22, 23). Drugs that dissolve blood clots remain the first choice in the treatment of acute stroke. However, two comprehensive study reviews concluded that citicoline may provide additional benefits or help patients who cannot receive first-line treatment (24, 35).

Summary: Rapid administration of citicoline may improve recovery after stroke. However, drugs that dissolve blood clots remain the first choice.

3) Citicoline can help with vision problems

Just as it can protect the nerves in the brain and spinal cord, citicoline may have the same effects on the optic nerve. It could reverse damage to neurons in the retina and help with eye problems such as the following (26):

optic neuropathy
glaucoma
visual impairment

Glaucoma

Elevated intraocular pressure and other factors can damage the optic nerve and cause glaucoma, which can lead to total blindness. In two clinical trials involving 80 patients with glaucoma, long-term treatment with citicoline was able to repair optic nerve damage, improve vision and slow the progression of the disease (27, 28). Eye drops with citicoline showed the same effects in two further clinical studies with 68 patients (29, 30).

Amblyopia

Amblyopia, also known as visual impairment, occurs when the eye and brain do not communicate well with each other. This results in blurred vision in one eye. Oral citicoline improved the results of standard treatment in three clinical trials involving 190 children (31). Injections of CDP-choline (1000 mg per day) healed the optic nerve and improved vision in 10 adults with amblyopia. However, this study lacked a control group (32)

Optic neuropathy

Optic neuropathy is another form of optic nerve degeneration that can impair vision. In 26 patients with this condition, citicoline (1600 mg per day for 2 months) was able to improve vision by repairing the optic nerve (33).

4) Citicoline may be helpful for brain and nerve damage

Oxidative stress, autoimmune reactions and environmental toxins can cause serious cell damage in the brain. Citicoline may protect the brain and spinal cord from these stressors, maintain the myelin sheath of nerves and increase levels of important neurotransmitters.

5) Citicoline could help with Alzheimer's disease

In three clinical trials, citicoline (1000 mg per day over a period of 1 to 3 months) was able to alleviate the symptoms of Alzheimer's disease by (34, 35)

improving mental performance
improving blood flow to the brain
lowering the levels of pro-inflammatory molecules (histamines and IL1B)

However, two of these studies lacked a placebo group.

In the third study, patients with a genetic predisposition to Alzheimer's disease - carriers of the APOE-e4 gene - experienced greater benefits. This is an important fact, as carriers of this gene often respond differently (often worse) to different interventions (35, 36). Citicoline improved the effect of Alzheimer's treatment and slowed the progression of the disease in two observational studies involving 600 patients (37). In rats with Alzheimer's disease, citicoline protected the nerves from protein mutations and reduced blood flow. As a result, the rats suffered less cognitive impairment and their memory performance improved (38).

Parkinson's disease

The destruction of dopamine neurons in Parkinson's disease causes muscle stiffness, tremors and other symptoms.

In rats with Parkinson's, citicoline was able to relieve muscle stiffness by increasing dopamine levels in the brain. It also improved the effect of a standard treatment (39).

Multiple sclerosis

Inflammatory destruction of the myelin sheath of nerves can cause multiple sclerosis with severe physical and cognitive impairment. In animals with multiple sclerosis, scientists have observed the potential of citicoline to promote regeneration of the myelin sheath and improve coordination of movement (40).

6) Citicoline can help with mental disorders and drug addiction

Citicoline may be helpful for depression

The addition of citicoline to treatment with the antidepressant citalopram alleviated symptoms of depression and improved recovery in a study of 50 patients (41).

In rats, citicoline increased norepinephrine, dopamine and serotonin levels in the brain centers for memory, emotion and movement (42).

Citicoline could help with meth and cocaine addiction

Citicoline at a dosage of 2000 mg per day for 2 months reduced depression in 60 methamphetamine addicts, but did not interfere with drug abuse. In another study of 31 meth addicts, citicoline protected the brain and reduced drug abuse (43, 44). In over 130 cocaine addicts with bipolar disorder, citicoline at a dosage of 500 to 2000 mg per day over a period of 3 months did not alter mood, but did reduce drug abuse. However, it showed no effect in another study of 20 severe cocaine addicts (45, 46). A review of 9 studies concluded that citicoline has mild benefits in medication or drug dependence, while emphasizing the need for further studies (47).

Citicoline may be helpful in schizophrenia

Citicoline improved the effects of standard treatment in a study of 66 patients with schizophrenia. It improved negative symptoms such as dampened emotions, poor communication and rigidity. These symptoms are difficult to treat with conventional methods (48). In 24 healthy adults, citicoline improved cognition by stimulating acetylcholine receptors, which are often underactive in schizophrenia (16).

What is citicoline used for?

Some people take citicoline for memory loss and other problems with declining mental abilities that can occur with aging. Some scientific research supports such use. Studies have found that citicoline supplements can help improve memory in older people. There is also some evidence that citicoline may help with recovery after a stroke. A recent study was able to show that citicoline does not help with memory recovery after head injury. Other studies suggest that citicoline supplements may help with Alzheimer's disease, glaucoma and some symptoms of Parkinson's disease. However, more research is needed to be sure.

Recommended intake

There is no generally accepted dosage recommendation for citicoline for the treatment of specific conditions. Some studies have used dosages of 1000 to 2000 mg per day.

Can citicoline be taken naturally with food?

The body produces citicoline from cytidine and choline. The best way to increase dietary citicoline levels is to consume adequate amounts of foods that provide both.

Foods rich in choline include

offal
eggs
poultry
fish
Whole grain products
Beans

Cytidine, an RNA nucleoside, is found in meat (especially offal) in the highest doses. It is also found in colostrum.

Risks and side effects

Many clinical studies with citicoline have confirmed its safety. In rare cases it can cause mild digestive and nervous problems. In a safety study with rats, citicoline caused no significant side effects even at very high doses (2000 mg per kilogram of body weight). Long-term use of high doses increased creatinine levels and kidney mineralization, probably due to the phosphorus content (49)

In another study with rats, citicoline increased ACTH blood levels, which stimulates the production of the stress hormone cortisol. However, the scientists injected citicoline directly into the brain and it is not clear whether oral consumption has the same effects (50).

Children and pregnant or breastfeeding women should not use citicoline, as not enough is known about its safety in these groups of people.

Interactions: If you are taking medication, you should discuss the use of citicoline supplements with your doctor to rule out any unwanted interactions.

Citicoline dosage

The following Citicoline dosages have been shown to be useful in scientific studies

Improvement of cognition and memory: 250 to 1000 mg per day
Age-related decline in cognitive abilities: 1000 to 2000 mg per day for 4 or more weeks
Alzheimer's disease: 1000 mg per day for 1 to 3 months

Higher doses in the range of 2000 to 2500 mg per day for 6 or more weeks were effective for the following indications:

Depression
drug addiction
Recovery after a stroke

Most eye diseases responded to 800 to 1600 mg citicoline and treatment lasted 2 to 4 months. For glaucoma, 3 eye drops per day were effective for 4 months.

Summary

Citicoline (CDP-choline) protects nerves by strengthening their membranes and increasing levels of important neurotransmitters. It may have nootropic effects in healthy people, prevent a decline in cognitive function in the elderly and aid recovery after a stroke.

Oral supplements or eye drops could also help with eye diseases such as glaucoma. The building blocks for citicoline can be obtained from food, particularly from meat. However, the dosages used in clinical studies (1000 to 2000 mg per day) can only be achieved with the help of supplements.

Citicoline is safe and well tolerated. Mild side effects such as digestive problems and headaches are possible. Children, pregnant women and people who are allergic to foods containing choline should avoid citicoline.