Citicoline

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms

  • CDP, Cebrolux®, Cebroton, Cognizin®, cytidine diphosphate choline, cytidine-5′-diphosphocholine, cytidinediphosphocholine, diphosphocholine, Neuroton®, somazina.

  • Note: The terms citicoline, citicholine, and CDP-choline are used interchangeably throughout the literature. “Citicoline” will be used throughout this monograph.

Background

  • Citicoline was first used to treat stroke. Citicoline may help treat diseases of the nerves and brain. Citicoline may help prevent the release of harmful chemicals in the body after decreased blood flow to the brain.

  • Citicoline has been studied as a treatment for disorders associated with aging, including memory loss, glaucoma (increased eye pressure), and problems with nerve function.

  • Citicoline is used in Europe and Japan for stroke, head injury, and other nerve diseases.

Scientific Evidence

Uses

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Stroke

Citicoline was first used by Ferrer International for the treatment of stroke. It is used in Europe and Japan for stroke. Research suggests that citicoline may protect the brain and nerves. Additional research is needed in this area.

Aging (brain)

Research suggests that citicoline may help treat people with mild-to-moderate brain aging. Additional research is needed in this area.

Alzheimer’s disease

Research suggests that citicoline may help people with Alzheimer’s disease. It may improve thinking and increase blood flow to the brain. Additional research is needed in this area.

Bipolar disorder (added to conventional treatment)

Research suggests that citicoline lack an effect on depression symptoms. Additional research is needed in this area.

Brain damage

Research suggests that citicoline may help people with brain damage. Additional research is needed in this area.

Cerebral insufficiency (decreased blood flow to the brain)

Research suggests that use of citicoline may help people with disorders of the blood vessels in the brain. Additional research is needed in this area.

Cocaine dependence

Research suggests a lack of effect of citicoline on cocaine dependence. Additional research is needed in this area.

Delirium

Research suggests citicoline has a small effect on delirium. Additional research is needed in this area.

Dementia

Research suggests citicoline may benefit people with dementia. Additional research is needed in this area.

Depression

Research suggests citicoline may help people with depression. Additional research is needed in this area.

Eye disorders

Research suggests that citicoline may help treat amblyopia (“lazy eye”). Additional research is needed in this area.

Glaucoma (increased eye pressure)

Research suggests that citicoline may help treat glaucoma. Additional research is needed in this area.

Hemorrhage (bleeding)

Research suggests citicoline may help treat people with bleeding in the brain. Additional research is needed in this area.

Memory loss

Research suggests that citicoline may help improve memory in the elderly and in people with brain injury due to trauma. Additional research is needed in this area.

Muscle strength

Research suggests that citicoline may increase muscle strength in people with cerebral hemorrhage (bleeding in the brain) that is not caused by trauma. Additional research is needed in this area.

Neuropathy

Research suggests that use of citicoline in people with nonarteritic ischemic optic neuropathy (NION), a type of nerve damage in the eye, improved vision. Additional research is needed in this area.

Parkinson’s disease

Research shows mixed results of citicoline in people with Parkinson’s disease. It has been given with the normal levodopa treatment. Additional research is needed in this area.

Tardive dyskinesia

There is a lack of well-designed research to support the use of citicoline for the movement disorder tardive dyskinesia. Additional research is needed in this area.

*Key to grades:

Tradition

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

  • Alcoholism, cardiac arrhythmia (irregular heartbeat), encephalitis (brain inflammation), head injury, high cholesterol, Huntington’s disease, immunomodulation (affects the immune system), lung disease, neuroprotection (nerve protection), pain, poisoning (carbon monoxide).

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

  • For aging, 1,000 milligrams has been taken by mouth daily for 21 days.

  • For Alzheimer’s disease, 1,000 milligrams has been used by mouth daily for 12 weeks.

  • For bipolar disorder, added to regular treatment, 500 milligrams of citicoline daily, with a gradual increase to 2,000 milligrams daily has been used by mouth for 12 weeks.

  • For bleeding in the brain, 1,000 milligrams has been injected into a vein every 12 hours for two weeks. Also, 1,000 milligrams has been taken by mouth every 12 hours for two weeks.

  • For brain damage, 1,000 milligrams has been injected into a vein daily for four weeks.

  • For cocaine dependence, 1,000 milligrams has been used by mouth daily for four days. Also, 500 milligrams has been used by mouth twice daily for an unknown length of time.

  • For delirium, 1,200 milligrams has been used by mouth daily 24 hours prior to hip surgery and during the four days after surgery.

  • For decreased blood flow to the brain, 1,000 milligrams has been injected into the muscle daily for 28 days. Also, 1,000 milligrams of citicoline has been used by mouth daily for 28 days.

  • For dementia, 200 milligrams has been injected into the muscle every eight hours for the first 10 days, followed by an additional 200 milligrams every 12 hours for the next 10 days, and 200 milligrams every 24 hours for the last 10 days. Also, 500 milligrams has been used by mouth twice daily for an unknown length of time.

  • For depression, 500 milligrams has been used by mouth daily. The dose was separated into 300 milligrams at 8 a.m. and 200 milligrams at 5 p.m. for at least 21 days.

  • For eye disorders, 1,000 milligrams has been injected into the muscle daily for 15 days.

  • For glaucoma (increased eye pressure), 1,600 milligrams of Cebrolux® has been taken by mouth daily for 60 days. Also, 500 milligrams of citicoline has been taken by mouth twice daily for 14 days. In addition, 1,000 milligrams of Neuroton® or Cebroton has been injected into the muscle daily for 60-120 days.

  • For memory loss, 1,000 milligrams has been used by mouth daily for an unknown length of time. Also, 500-2,000 milligrams has been used daily for 4-8 weeks. In addition, 250-500 milligrams has been injected into the muscle daily for 14-20 days.

  • For muscle strength after stroke, 250 milligrams of citicoline has been injected into a vein twice daily for 14 days.

  • For nerve disease of the eye, 1,600 milligrams of Cebrolux® has been used by mouth daily for 60 days.

  • For Parkinson’s disease, 500-1,200 milligrams has been used by mouth daily for one month in addition to levodopa treatment. Also, 1,000 milligrams has been injected into the muscle daily for 15 days added to levodopa treatment

  • For stroke, 500-2,000 milligrams has been used by mouth once or twice daily for six weeks. Also, 500 milligrams of citicoline has been injected into a vein daily for seven days.

  • For tardive dyskinesia (movement disorder), 500-1,200 milligrams has been used by mouth daily for four weeks.

Children (under 18 years old)

  • There is no proven safe or effective dose for citicoline in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid in people with a known allergy or sensitivity to citicoline.

Side Effects and Warnings

  • Use cautiously in people taking growth hormone or agents that affect dopamine (a chemical in the brain). Use cautiously in people with disease of the heart or blood vessels, or frequent headaches.

  • Citicoline may cause back pain, changes in heart rate, constipation, diarrhea, difficulty sleeping, headache, low blood pressure, nausea, skin rash, stomach pain, swelling in the limbs, and vomiting.

Pregnancy and Breastfeeding

  • There is a lack of scientific evidence on the use of citicoline during pregnancy or breastfeeding.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

  • Citicoline may cause low blood pressure. Caution is advised in people taking agents that lower blood pressure.

  • Citicoline may interact with agents that affect dopamine, agents that affect heart rate, agents used to treat acute stroke, agents used to treat asthma, agents used to treat Parkinson’s disease, Alzheimer’s agents, anti-aging agents, cholesterol-lowering agents, growth hormone, and pain relief agents.

Interactions with Herbs and Dietary Supplements

  • Citicoline may cause low blood pressure. Caution is advised in people taking herbs and supplements that lower blood pressure.

  • Citicoline may interact with herbs and supplements that affect dopamine, herbs and supplements that affect heart rate, herbs and supplements that lower cholesterol, herbs and supplements that treat Alzheimer’s disease, herbs and supplements that treat asthma, herbs and supplements that treat Parkinson’s disease, herbs and supplements used for pain relief, herbs and supplements used to treat acute stroke, and antiaging herbs and supplements.

Author Information

  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Brown ES, Gorman A R, Hynan LS. A randomized, placebo-controlled trial of citicholine add-on therapy in outpatients with bipolar disorder and cocaine dependence. J Clin Psychopharmacol 2007;27(5):498-502. View Abstract
  2. Conant R, Schauss A. G. Therapeutic applications of citicoline for stroke and cognitive dysfunction in the elderly: a review of the literature. Altern Med Rev 2004;9(1):17-31. View Abstract
  3. Clark WM, Wechsler LR, Sabounjian LA, et al. A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients. Neurology 11-13-2001;57(9):1595-1602. View Abstract
  4. Clark WM, Williams BJ, Selzer KA, et al. A randomized efficacy trial of citicoline in patients with acute ischemic stroke. Stroke. 1999;30(12):2592-2597. View Abstract
  5. Diaz V, Rodriguez J, Barrientos P, et al. Use of procholinergics in the prevention of postoperative delirium in hip fracture surgery in the elderly. A randomized controlled trial]. Rev Neurol 10-16-2001;33(8):716-719. View Abstract
  6. Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Cochrane Database Syst Rev 2004;(2):CD000269. View Abstract
  7. Iranmanesh F, Vakilian A. Efficiency of citicoline in increasing muscular strength of patients with nontraumatic cerebral hemorrhage: a double-blind randomized clinical trial. J Stroke Cerebrovasc Dis 2008;17(3):153-155. View Abstract
  8. Jambou R, El-Assaad F, Combes, V, et al. Citicoline (CDP-choline): What role in the treatment of complications of infectious diseases. Int J Biochem Cell Biol 2009;41(7):1467-1470. View Abstract
  9. Kalisvaart KJ, de Jonghe JF, Bogaards MJ, et al. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc 2005;53(10):1658-1666. View Abstract
  10. Kidd PM. Integrated brain restoration after ischemic stroke–medical management, risk factors, nutrients, and other interventions for managing inflammation and enhancing brain plasticity. Altern Med Rev 2009;14(1):14-35. View Abstract
  11. Marcantonio ER, Flacker JM, Wright RJ, et al. Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc 2001;49(5):516-522. View Abstract
  12. Parisi V, Coppola G, Centofanti M. Evidence of the neuroprotective role of citicoline in glaucoma patients. Prog Brain Res 2008;173:541-554. View Abstract
  13. Saver JL. Citicoline: update on a promising and widely available agent for neuroprotection and neurorepair. Rev.Neurol.Dis. 2008;5(4):167-177. View Abstract
  14. Secades JJ, Lorenzo J. L. Citicoline: pharmacological and clinical review, 2006 update. Methods.Find Exp Clin Pharmacol 2006;28 Suppl B:1-56. View Abstract
  15. Secades JJ, Alvarez-Sabin J, Rubio F, et al. Cerebrovasc Dis 2006;21(5-6):380-385. View Abstract
  16. Virno M, Pecori-Giraldi J, Liguori A, et al. The protective effect of citicoline on the progression of the perimetric defects in glaucomatous patients (perimetric study with a 10-year follow-up). Acta Ophthalmol.Scand.Suppl 2000;(232):56-57. View Abstract

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.