CAM Alternatives for Cognitive Impairment:
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The biomolecule Citicoline (CDP-choline or cytidine-5 ́-diphosphocholine) is thought to improve the neurological recovery in various conditions including traumatic brain injuries, stroke, vascular dementia, Parkinson’s disease, and aging. It is administered to improve cognitive dysfunction in these conditions. 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 and improving nerve function and possibly in addiction recovery.
Pharmacology and mechanism of action
Citicoline is synthesized from choline and found in foods like liver, meat, beans, eggs, and cruciferous vegetables (broccoli, cauliflower etc. 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.
In healthy adults citicoline has been shown that 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.
Citicoline is the precursor to acetylcholine, a neurotransmitter, and also the precursor to sphingomyelin and phosphatidylcholine—structural components of cell membranes. The neurotransmitter acetylcholine is also intimately connected with nerve networks associated with memory. Cognitive impairments that precede the onset of Alzheimer’s disease have been related to alterations in brain neurotransmission systems, mainly acetylcholine deficits. The causes of the nerve structural changes, which lead to cognitive deterioration and are associated with this disease, are unknown. It has been proposed that citicoline may reverse these age-dependent changes in brain cells.
When oxidized, choline forms the methyl donor betaine for the conversion of homocysteine to methionine. High homocysteine concentrations have been shown to be related to both cognitive impairment and an increased risk of Alzheimer’s disease.
Several other potential neuroprotective mechanisms of citicoline have been described including reinforcement of the intracellular glutathione antioxidative system, stabilization of cell membranes, restoration of Na+/K+- ATPase activity and prevention of glutamate mediated neurotoxicity. Animal studies suggest that citicoline may increase density of the dopamine D2 receptors and acetylcholine receptors in areas of the brain associated with Reward Deficiency Syndrome (RDS) and addiction. This collection of proposed mechanisms for the actions of citocoline suggest potential benefits for the management of addiction and other manifestations of RDS.
Dosing of Citicoline
It is estimated that the daily dietary allowance of choline is 550 mg/day for men and 425 mgay for women Oral, intravenous and intramuscular doses for citicoline ranges from 500-2,000 mg/daily. The safety profile and tolerance of citicoline is excellent and the side effects are rare (never severe) and mainly consist of gastrointestinal discomfort and restlessness. Citicoline has also undergone several toxicological studies and has been proven safe.
Therapeutic Targets of Citicholine
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.
Most addiction research has evaluated citicoline for cocaine 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.
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.
The causes of memory impairment in the elderly include decreased neurotransmitter formation, inadequate circulation (vascular dementia), or Alzheimer’s disease.
Citicoline has neuroprotective and neuronal membrane-stabilizing effects and because of these properties it is expected that citicoline may be beneficial for individuals with Parkinson’s disease. In addition, citicoline has an ability to increase dopamine synthesis so may allow for the reduction of levodopa dosage. In the results from one study it was shown that citicoline improved speech, gait, posture, tremor, agility, and slowness of movements in Parkinson’s disease.
Citicoline supplementation has been found to improve blood flow to the brain in elderly individuals with senile dementia and improve mental function in patients with Alzheimer’s disease (particularly in early-onset Alzheimer’s patients). This benefit may also be due citicoline’s cholinergic effects and influence on cytokine production. It is also proposed that citicoline reduces excessive histamine that has been implicated in the cause of dementia associated with Alzheimer’s disease.
Traumatic brain injury
Citicoline’s neuroprotective benefits have been shown to be an effective with traumatic brain injury, improving motor, cognitive, and mental symptoms. Citicoline has also been shown to reduce post-concussion symptoms including improvements in recognition memory, and decreased incidence of headaches, dizziness, and tinnitus.
Because citicoline has been shown to be quite safe and lacking significant side effects, there has been a growing interest for neuroprotection and neuronal repair with citicoline. Results of many studies seems to show benefits of citicoline on several cognitive functions however there is a need for further studies to confirm citicolins effectiveness for neuro-protection and nerve repair.
Citicoline – Overviews
- Citicoline Affects Appetite and Cortico-Limbic Responses to Images of High Calorie Foods – 2010
- Neuroprotective properties of citicoline – facts, doubts and unresolved issues – 2014
- An overview of clinical and therapeutic implications of citicoline – 2014
- Cognizin Citicoline—The Ultimate Brain Nutrient | Brain Health | Articles | Magazine
Citicoline – Addiction
- Citicoline in Addictive Disorders – A Review of the Literature – 2014
- Citicoline Treatment Improves Measures of Impulsivity and Task Performance in Chronic Marijuana Smokers – 2015
- Cholinergic modulation of mesolimbic dopamine function and reward. – 2011
- The role of acetylcholine in cocaine addiction – 2008
- A randomized, double-blind, placebo-controlled trial of citicoline for bipolar and unipolar depression and methamphetamine dependence. – PubMed – NCBI
- Neurochemical alterations in methamphetamine-dependent patients treated with cytidine-5′-diphosphate choline – 2010
- Short-term treatment with citicoline (CDP-choline) attenuates some measures of craving in cocaine-dependent subjects: a preliminary report. – PubMed – NCBI
- Effects of daily treatment with citicoline – A double-blind, placebo-controlled study in cocaine-dependent volunteers – 2011
- Effects of short-term citicoline treatment on acute cocaine intoxication and cardiovascular effects. – PubMed – NCBI
- Changes in brain striatum dopamine and acetylcholine receptors induced by chronic CDP-choline treatment of aging mice. – 1991
Citicoline – Dietary
- Citicoline – A Food That May Improve Memory -2015
- The relation of dietary choline to cognitive performance and white-matter hyperintensity – 2011
- Nutritional Cognitive Neuroscience – Innovations for Healthy Brain Aging – 2016
Citicoline – Memory
- Citicoline – A Food That May Improve Memory -2015
- Improvements in Concentration, Working Memory, and Sustained Attention Following Consumption of a Natural Citicoline-Caffeine Beverage – 2014
- Citicoline Improves Memory Performance in Elderly Subjects
- Citicoline Improves Verbal Memory in Aging
Citicoline – Cognitive Dysfunction
- Citicoline (Cognizin) in the treatment of cognitive impairment – 2006
- The role of citicoline in cognitive impairment – pharmacological characteristics, possible advantages, and doubts for an old drug with new perspectives – 2015
- Therapeutic Applications of Citicoline for Stroke and Cognitive Dysfunction in the Elderly – A Review of the Literature – 2004
- CITICOLINE EFFICIENCY ON COGNITIVE FUNCTION – A SYSTEMATIC REVIEW – 2015
- Long-term citicoline (cytidine diphosphate choline) use in patients with vascular dementia: neuroimaging and neuropsychological outcomes. – PubMed – NCBI
Emphasis on Education
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