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Accurate Education – Citicoline

Citicoline

Citicoline is a brain nutrient that supports mental energy, focus, attention, and overall cognitive health. It is sometimes referred to as choline or coline (see below).

 

See also:

 

CAM Alternatives for Cognitive Impairment:

   Acetyl-L-carnitine (ALC)

   Alpha-Lipoic Acid

Bacopa

 

 

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Citicoline (CDP-choline)

Citicoline and CDP-choline have the same molecular structure. CDP-choline refers to the endogenous form that is present in every cell of the human body. Citicoline refers to the form that is taken exogenously. Citicoline is available in 2 forms: (1) citicoline sodium which is a prescription medication used to treat neurological disorders in numerous countries and (2) citicoline free-base which is a dietary supplement in the United States.

 

The biomolecule Citicoline (CDP-choline or cytidine-5 ́-diphosphocholine) is an essential precursor for the neurotransmitter acetylcholine in the central nervous system and also for the synthesis of membrane phospholipids. Phospholipids create the structural integrity of all cell membranes and are essential to cellular growth and repair. In the brain, phospholipids are also essential for the synaptic function of communication among all brain cells. The primary phospholipid in the brain—phosphatidylcholine—makes up 30% of the gray matter.

 

Despite the importance of CDP-choline in phospholipid synthesis, however, the brain preferentially uses CDP-choline for production of acetylcholine. If availability of CDP-choline is low, phospholipids are stolen from neuronal membranes for acetylcholine production and phospholipid synthesis slows down, compromising membrane integrity and function. Thus it is important to maintain adequate levels of citicoline.

 

A human study conducted at Harvard Medical School evaluated brain changes after citicoline supplementation in healthy older adults. The researchers detected brain MRI changes indicating increased phosphatidylcholine synthesis after 6 weeks of supplementation with 500 mg of citicoline per day.

Supplementation with citicoline is thought to improve cognitive dysfunction and neurological recovery in various conditions including traumatic brain injuries, stroke, vascular dementia, Parkinson’s disease, and aging. However, the research to support citicoline benefits remains lacking and definitive recommendations for supplementing with citicoline cannot be made.

 

That being said, citicoline is well documented to be safe and there is growing evidence of its benefits for improving cognition, nerve function and possibly helping in addiction recovery.

 

Pharmacology and mechanism of action

Dietary Choline

Citicoline is manufactured in the body from choline. However, the National Health and Nutrition Examination Survey (NHANES) revealed that only 8% of US adults consume the recommended amount of choline on a daily basis. Low dietary choline intake may be related to deficit performance on neuropsychological tests. In one study of a population of non-demented individuals, high dietary choline intake was related to better cognitive performance but the effects persisted only in association with continued high intake. Research findings show that early higher choline intake at midlife may be neuroprotective. Further study is necessary to determine whether an adequate dietary intake of choline is related to improved cognitive function throughout the life span and to determine the role it plays regarding the preservation of brain health.

 

Even if dietary choline consumption is sufficient, there are additional benefits to consuming sources of CDP-choline (citicoline) itself. CDP-choline is required for the rate-limiting step of phospholipid synthesis, making choline insufficient to support cell membrane integrity on its own. Citicoline is synthesized from choline which is found in foods like liver, meat, beans, eggs, and cruciferous vegetables (broccoli, cauliflower), while only liver, brain, and organ meats provide appreciable amounts of CDP-choline (citicoline).

 

Both choline and citicoline support phospholipid metabolism, acetylcholine production, and cell signaling. But citicoline is also a source of cytidine. It is the cytidine component that gives supplementing with citicoline an advantage over choline. The cytidine component of citicoline converts to uridine before crossing the blood-brain barrier. The uridine component is required for the rate-limiting step of phosphatidylcholine production and that uridine also promotes neuronal growth. Uridine is the molecule responsible for increasing brain levels of norepinephrine and dopamine, improving mitochondrial function, and boosting energy production in the brain.

 

Supplementation with citicoline offers a way to boost endogenous levels of CDP-choline in a way that cannot be achieved by other means. The oral bioavailability of citicoline exceeds 90%, its metabolites cross the blood- brain barrier, and citicoline is resynthesized in the brain after oral consumption.

 

In healthy adults it has been shown that an oral dose of citicoline is rapidly absorbed with greater than 90 percent bioavailability. Citicoline is metabolized by hydrolysis into choline and cytidine in the gut wall and these two products (choline and cytidine) are distributed throughout the body and utilized in various biosynthetic pathways. They also cross the blood-brain barrier to re-synthesize into citicoline in the brain.

 

Dosing of Citicoline

It is estimated that the daily dietary allowance of choline is 550 mg/day for men and 425 mg/day for women.

 

Oral, intravenous and intramuscular doses for citicoline typically range from 500-2,000 mg/daily. Most clinical trials evaluating citicoline —particularly those involving healthy adults and teens—have utilized dosages of 250 mg or 500 mg per day. Both of these dosages have produced beneficial effects.

 

Dosages as high as 2,000 mg per day have shown benefit in patients with addictive disorders, and dosages of 2,000-4,000 mg per day for 6-12 weeks produced more significant improvements than lower dosages in patients recovering from a stroke. Researchers who conducted the Italian VITA and IDEALE studies, propose that citicoline administration of at least 6 months is required to observe its greatest neuroprotective effects.

 

The safety profile and tolerance of citicoline is excellent and no serious adverse events have been reported in clinical trials of citicoline at dosages ranging from 250 mg to 4,000 mg per day. Side effects are mild (never severe) and rare, mainly consisting of gastrointestinal discomfort, irritability, uneasiness and restlessness. Citicoline has also undergone several toxicological studies and has been proven safe.

 

Therapeutic Targets of Citicholine

 

Addiction

Citicoline affects acetylcholine, dopamine, and glutamate neurotransmitter systems; serves as an intermediate in phospholipid metabolism; and enhances the integrity of nerve membranes. Interest has grown in citicoline as a treatment for addiction since it may have beneficial effects on craving, withdrawal symptoms, and cognitive functioning, as well as the ability to attenuate the neurotoxic effects of drugs of abuse.

 

One mechanism proposed for citicoline’s benefit for addiction is that it increases dopamine levels in the corpus striatum by enhancing tyrosine hydroxylase activity and inhibiting dopamine reuptake. This indicates citicoline’s potential enhancement of the condition of Reward Deficiency Syndrome, the underlying basis of addiction associated with depletion of dopamine in the reward centers of the brain.

See: Reward Deficiency Syndrome

 

Most addiction research has evaluated citicoline for cocaine and methamphetamine use although it is suggested that citicoline may also hold promise for other addictions including alcohol, cannabis dependence and binge eating. Although not well studied in opioid addiction, the benefit of citicoline is also suggested.  Citicoline appears to decrease craving and is associated with a reduction in cocaine use, especially in patients with both bipolar disorder and cocaine addiction.

See: Reward Deficiency Syndrome & Addiction

 

Learning and Memory

Experimental studies in both animals and humans have suggested that citicoline has ability to promote learning ability and memory. In a double blind, crossover trial, it was showed that citicoline improved the ability to recall words and objects.