From the Guidelines
Citicoline cannot be definitively recommended as a nootropic agent due to the lack of conclusive evidence supporting its efficacy in improving cognitive function in healthy individuals or those with cognitive impairment, as the largest and most recent trial, the International Citicoline Trial on Acute Stroke (ICTUS), was stopped prematurely due to futility 1.
Overview of Citicoline
Citicoline, also known as CDP-choline, is a compound that plays a role in the synthesis of phosphatidylcholine, a key component of cell membranes. It has been studied for its potential neuroprotective effects and as a nootropic agent.
Mechanism of Action
Citicoline is thought to work by increasing levels of neurotransmitters such as acetylcholine and dopamine in the brain, supporting cellular membrane integrity, and potentially enhancing mitochondrial function 1.
Clinical Evidence
While some studies suggest that citicoline may have a net benefit in reducing disability when started within 24 hours of onset of symptoms in patients with moderate to severe stroke, the evidence is not strong enough to support its use as a nootropic agent in healthy individuals or those with cognitive impairment 1.
Dosage and Side Effects
Typical doses of citicoline range from 250-1000 mg daily, divided into two doses. However, due to the lack of conclusive evidence supporting its efficacy, it is not possible to recommend a specific dosage for nootropic purposes. Citicoline is generally well-tolerated, with minimal side effects, which may include digestive discomfort, headache, or insomnia at higher doses 1.
Conclusion on Efficacy
In summary, while citicoline may have some potential benefits in certain contexts, such as in the treatment of acute ischemic stroke, the current evidence does not support its use as a nootropic agent, and its effects on cognitive function in healthy individuals or those with cognitive impairment are not well established 1.
From the Research
Mechanism of Action
- Citicoline, also known as Cytidine Diphosphate-Choline, is an essential intermediate in the biosynthetic pathway of structural phospholipids in cell membranes, particularly phosphatidylcholine 2, 3.
- It releases its two main components, cytidine and choline, after administration by both oral and parenteral routes, and is widely distributed throughout the body, crossing the blood-brain barrier and reaching the central nervous system (CNS) 2, 3.
- Citicoline activates the biosynthesis of structural phospholipids in neuronal membranes, increases brain metabolism, and acts on the levels of different neurotransmitters, such as norepinephrine and dopamine 2, 3.
Nootropic Effects
- Citicoline has been experimentally shown to improve learning and memory performance in animal models of brain aging 2, 3.
- It has also been shown to have a neuroprotective effect in hypoxic and ischemic conditions, decreasing the volume of ischemic lesion 2, 4.
- Citicoline may have therapeutic potential to reduce hypoglycaemia-induced neuronal death, as it reduces neuronal injury in animal models with cerebral ischemia and in clinical trials of stroke patients 5.
Clinical Applications
- Citicoline has been used to treat cerebral vascular disease, head trauma of varying severity, and cognitive disorders of diverse etiology 2, 3.
- It has also been used to treat senile cognitive impairment, secondary to degenerative diseases such as Alzheimer's disease, and to chronic cerebral vascular disease 2, 3.
- Citicoline has been shown to be effective in Parkinson's disease, drug addictions, and alcoholism, as well as in amblyopia and glaucoma 2.
Safety and Efficacy
- Citicoline is considered a safe drug, with no significant systemic cholinergic effects and is well tolerated 2, 3.
- It has been shown to be effective in several clinical trials, with excellent safety and possibly efficacy found in several trials 4.
- A meta-analysis of four randomized US clinical citicoline trials concluded that treatment with oral citicoline within the first 24 h after a moderate to severe stroke is safe and increases the probability of complete recovery at 3 months 4.