CDP-Choline supplement review and research studies by Ray Sahelian, M.D. CDP Choline benefit and side effects, proper dosage

CDP-choline stands for cytidine 5-diphosphocholine, an intermediate in the biosynthesis of membrane phospholipids and brain acetylcholine. CDP-choline is approved in Europe and Japan for use in stroke, Parkinson’s disease and other neurological disorders and is sold by the brand name Citicoline. In a way, you could consider CDP-choline as a more potent form of choline. Studies show that CDP-choline helps make phosphatidylcholine in human brain cell membranes in older individuals; may increase acetylcholine synthesis; improves mental performance in patients with Alzheimer's disease; and even improves memory in elderly patients with memory deficits. A Belgian study has shown that CDP-choline administration to dogs improves their ability to learn and remember.

CDP-Choline, 250 mg, 60 Capsules

Stabilized CDP-Choline (cytidine 5'diphosphocholine) is a naturally occurring, water soluble biological compound that is an essential intermediate for the synthesis of phosphatidylcholine, a major constituent of the grey matter of brain tissue (30%).  CDP choline is metabolized to yield the free nucleotide cytidine and choline.  Scientific research demonstrates that CDP Choline consumption promotes brain metabolism by enhancing the synthesis of acetylcholine, restoring phospholipid content in the brain and regulation of neuronal membrane excitability and osmolarity (by its effect on the ATP-dependent sodium and potassium pumps).

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CDP-Choline Supplement Facts:
CDP Choline  250 mg (from stabilized cytidine 5'diphosphocholine)

Suggested Use: One cdp-choline capsules before breakfast or lunch.

CDP-choline Potential
The administration of oral CDP-choline may be of use in reversing age-related changes in the brain. CDP-choline helps to increase levels of phosphodiesters such as phosphatidylcholine and glycerophosphoethanolamine in the brain. These phosphodiesters form part of the cell membrane of brain cells and their levels are known to decline with age. Hence, CDP-choline supplements may help replace the declining levels of these important phosphodiesters.
   CDP-choline may be helpful in reducing damage after a stroke.
   CDP-choline may be helpful in Alzheimer's disease.

Dr. Vittorio Porciatti at the Institute of Neurophysiology in Pisa, Italy, tells me, "CDP-choline is commercially produced in Europe under several product names. Neurologists have found this nutrient useful in Parkinson’s disease, brain trauma, and aging in general. It may surprise you that I mention Parkinson’s disease. In addition to the understandable action on cell membranes, we have been somehow surprised that CDP-choline has dopamine-like effects. Interestingly, dopaminergic-like activity seems to be long lasting, possibly due to stabilization of the effects at membrane level."

CDP-choline availability
CDP-choline became available over the counter in the US in 1998. Most pills come in a 250 mg dose.

CDP-choline side effects
Toxicology studies show that CDP-choline is safe and produces no serious side effects in doses ranging from 250 mg to 500 mg a day. However, most of the studies lasted less than a few weeks. Long-term safety is not known.

CDP-Choline Research Update
CDP-choline in the treatment of chronic cerebrovasculopathies.
Arch Gerontol Geriatr. 1994 May-Jun;18(3):161-8.
Ninety-two patients affected by chronic cerebrovasculopathy were treated with cytidine diphosphate choline ( CDP-choline ) 1000 mg/day i.m. or with placebo, in a double-blind study. Two cycles of therapy of 4 weeks each were performed, with an interval of 1 week. There were 46 patients in each group with chronic cerebrovascular diseases, and the two groups were comparable as far as mental deterioration was concerned. The comparison between the two groups revealed significant improvements in the CDP-choline group compared with the placebo group in some of the attention capabilities. No side-effects were detected in the CDP-choline group.

CDP-choline increases plasma ACTH and potentiates the stimulated release of HGH, TSH and LH: the cholinergic involvement.
Fundam Clin Pharmacol. 2004 Oct;18(5):513-523.
Abstract In the present study, we investigated the effect of intracerebroventricular (i.c.v.) administration of cytidine-5'-diphosphate (CDP) choline on plasma adrenocorticotropin (ACTH), serum growth hormone (GH), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in conscious rats. The involvement of cholinergic mechanisms in these effects was also determined. In basal conditions, CDP-choline increased plasma ACTH levels dose- and time-dependently, but it did not affect the TSH, GH, FSH and LH levels. In stimulated conditions, i.c.v. administration of CDP-choline produced an increase in clonidine-stimulated GH, thyrotyropin-releasing hormone (TRH)-stimulated TSH, LH-releasing hormone (LHRH)-stimulated LH, but not FSH levels. Injection of equimolar dose of choline (1 μmol, i.c.v.) produced similar effects on hormone levels, but cytidine (1 μmol, i.c.v.) failed to alter plasma levels of these hormones. Pretreatment with hemicholinium-3, a neuronal high affinity choline uptake inhibitor, (20 μg, i.c.v.) completely blocked the observed hormone responses to CDP-choline. The increase in plasma ACTH levels induced by CDP-choline was abolished by pretreatment with mecamylamine, a nicotinic receptor antagonist, (but not atropine, a muscarinic receptor antagonist. The increase in stimulated levels of serum TSH by CDP-choline was blocked by atropine but not by mecamylamine pretreatment. However, CDP-choline induced increases in serum GH and LH levels were greatly attenuated by both atropine and mecamylamine pretreatments. The results show that CDP-choline can increase plasma ACTH and produce additional increases in serum levels of TSH, GH and LH stimulated by TRH, clonidine and LHRH, respectively. The activation of central cholinergic system, mainly through the presynaptic mechanisms, was involved in these effects. Central nicotinic receptors solely mediated the increase in plasma ACTH levels while the activation of central muscarinic receptors was involved in the increase in TSH levels. Both muscarinic and nicotinic receptor activations, separately, mediated the increases in serum GH and LH levels after CDP-choline.

Chronic treatment with a precursor of cellular phosphatidylcholine ameliorates morphological and behavioral effects of aging in the mouse [correction of rat] hippocampus.
Ann N Y Acad Sci. 2004 Jun;1019:41-3.
Normal aging is commonly associated with a decline in memory, mainly for that related with newly acquired information. The hippocampal formation (HF) is a brain region that has been implicated in this dysfunction. Within the HF there are several cellular types, such as pyramidal cells, granule neurons of the dentate gyrus, and astrocytes. CDP-choline is a well-known intermediate in the biosynthesis of phosphatidylcholine, a phospholipid essential for neuronal membrane preservation and function; thus, this compound would attenuate the process of neuronal aging. To test this, three groups of male mice were used in this study. An adult 12-month-old group, a 24-month-old, and an old experimental group (OEG) were administered orally a solution of CDP-choline (150 mg/kg per day) from 12 up to 24 months. Experimental observations suggest that CDP-choline has a positive effect on memory (reference errors were attenuated), and hippocampal morphology resembled that of younger animals.

Therapeutic applications of citicoline for stroke and cognitive dysfunction in the elderly: a review of the literature.
Conant R, Schauss AG.Technical and Regulatory Affairs, Life Sciences Division, American Institute for Biosocial and Medical Research, Inc. (AIBMR), Puyallup, WA 98373, USA.
Altern Med Rev. 2004 Mar;9(1):17-31.
Citicoline (CDP-choline; cytidine 5'-diphosphocholine), a form of the essential nutrient choline, shows promise of clinical efficacy in elderly patients with cognitive deficits, inefficient memory, and early-stage Alzheimer's disease. CDP-choline has also been investigated as a therapy in stroke patients, although the results of trials to date are inconclusive. Produced endogenously, CDP-choline serves as a choline donor in the metabolic pathways for biosynthesis of acetylcholine and neuronal membrane phospholipids, chiefly phosphatidylcholine. The principal components of CDP-choline, choline and cytidine, are readily absorbed in the GI tract and easily cross the blood-brain barrier. Exogenous CDP-choline, as the sodium salt, has been researched in animal experiments and human clinical trials that provide evidence of its cholinergic and neuroprotective actions. As a dietary supplement, CDP-choline appears useful for improving both the structural integrity and functionality of the neuronal membrane that may assist in membrane repair. This review, while not intended to be exhaustive, highlights the published, peer-reviewed research on CDP-choline with brief discussions on toxicology and safety, mechanisms of action, and pharmacokinetics.

A Mind Booster Helpful After Strokes
Findings presented at the American Stroke Association's 27th International Stroke Conference indicate that CDP-choline may be helpful in reducing damage after a stroke. The most common cause of a stroke is blockage of a blood vessel within the brain, which leaves a portion of the organ starved for blood and oxygen. Bleeding within the brain can also lead to stroke. Much of the brain damage is caused by a cascade of harmful chemicals released by dying cells.
     Researchers at the National Institute of Neurological Disorders in Bethesda, Maryland, reported data on two trials of the supplement citicoline, sold in some health food stores or on the internet as CDP-choline. This nutrient is related to choline. One of the studies involved 41 patients who received 500 milligrams of cdp-choline daily for 6 weeks after having a stroke. In the other, 62 stroke patients took 2,000 mg of the drug every day for 6 weeks. The trials also included 111 patients who received an inactive placebo. The researchers gauged the CDP-choline’s effectiveness by measuring the size of the infarct, or area of dead tissue. They scanned patients' brains within 24 hours of the stroke and again 12 weeks later. At the end of the study period, the investigators found that infarct size measured by MRI scans had increased by 85% in patients on placebo, by 34% in patients receiving the 500 mg dose of cdp-choline and by only 2% in patients receiving 2,000 mg cdp-choline.
   Dr. Sahelian says: CDP-choline is a more powerful form of choline, and most users without a stroke notice an enhancement of mental focus, along with clarity of vision and thinking with as little as 200 mg.

Long-term citicoline (cdp-choline) use in patients with vascular dementia: neuroimaging and neuropsychological outcomes.
Department of Psychiatry and Human Behavior, Brown Medical School, Providence, R.I.
Cerebrovasc Dis. 2003;16(3):199-204.
Cytidine diphosphate choline (citicoline or cdp-choline) has been previously shown to have efficacy in reducing the functional impairments associated with acute stroke. Citicoline is thought to have neuroprotective benefits and has been used for the treatment of chronic cerebrovascular disorders, though its effectiveness has not been fully tested. This randomized, double-blind clinical trial was conducted to determine whether daily citicoline treatment improves neurocognitive and neuroimaging outcome over 12 months among patients diagnosed with vascular dementia (VaD). METHODS: 30 patients diagnosed with vascular dementia, were randomized and treated with either 500 mg of citicoline or placebo twice per day. RESULTS: The cdp-choline and placebo treatment groups did not differ in their neuropsychological performance at baseline and the 12-month follow-up. Significant declines in neuropsychological performance were noted, as well as significantly increased SH and reduced total brain volumes on MRI for both groups at the 12-month follow-up. CONCLUSIONS: The efficacy of long-term citicoline treatment for cognitive impairment and neuropathological decline in those patients already meeting criteria for VaD does not appear to be substantiated by the current study.

Double-blind placebo-controlled study with citicoline (cdp-choline) in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion.
Methods Find Exp Clin Pharmacol. 1999 Nov;21(9):633-44.
Cytidine 5'-diphosphocholine (cdp-choline) is a an endogenous intermediate in the biosynthesis of structural membrane phospholipids and brain acetylcholine. CDP-choline has been extensively used for the treatment of neurodegenerative disorders associated with head trauma, stroke, brain aging, cerebrovascular pathology and Alzheimer's disease. In this study we have investigated the efficacy and safety of the treatment with cdp-choline versus placebo in patients with Alzheimer disease. Thirty patients with mild to moderate senile dementia of the Alzheimer type were included in a double-blind, randomized and placebo-controlled clinical trial. After a 2-week period of drug washout, patients were treated with i) placebo or ii) 1,000 mg/day of CDP-choline for 12 weeks (84 days). Examinations were done at baseline (T0) and after the 12 weeks of treatment (T12). As compared to placebo, cdp-choline improved cognitive performance in Alzheimer's disease patients with APOE E4. CDP-choline also increased cerebral blood flow velocities in comparison with placebo when transcranial Doppler recordings from both hemispheres were considered together, as well as diastolic velocity in the left middle cerebral artery. Patients treated with cdp-choline showed an increase in the percentage of brain bioelectrical activity of alpha (occipital electrodes) and theta type (left side electrodes), accompanied by a decrease in relative delta activity particularly marked in the left temporal lobe. Treatment with cdp-choline tended to reduce serum IL-1 beta levels, mainly after 4 weeks of administration, with no modified blood histamine content. In addition, neither adverse side effects nor alterations in biological and hematological parameters were induced by cdp-choline. The present data indicate that cdp-choline (1,000 mg/day) is well tolerated and improves cognitive performance, cerebral blood perfusion and the brain bioelectrical activity pattern in AD patients. According to our results, it seems that cdp-choline might be a useful treatment in Alzheimer's disease, and that the efficacy of this compound is greater in patients with mild mental deterioration and/or bearing the epsilon 4 allele of the APOE.

Review of CDP-choline finds this nutrient to help memory
Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly.  University of Rome "La Sapienza", P.le A. Moro, 5, Rome, Italy, 00185.
In spite of uncertainties about its efficacy, CDP-choline is a frequently prescribed drug for cognitive impairment in several European countries, especially when the clinical picture is predominantly one of cerebrovascular disease, hence the need for this review. The objective is to assess the efficacy of CDP-choline (cytidinediphosphocholine) in the treatment of cognitive, emotional, and behavioural deficits associated with chronic cerebral disorders of the elderly.   All relevant, non-animal, unconfounded, double-blind, placebo-controlled, randomised trials of CDP-choline in cognitive impairment due to chronic cerebral disorders will be considered for inclusion in the review. Seven of the included cdp-choline studies observed the subjects for a period between 20 to 30 days, one study was of 6 weeks duration, 2 studies used cycles extending over 2 and 3 months and one study observed continuous administration over 3 months. The cdp-choline studies were heterogeneous in dose, inclusion criteria for subjects, and outcome measures. Results are reported for the domains of attention, memory testing, behavioral rating scales, global clinical impression and tolerability. There was no significant evidence of a beneficial effect of CDP-choline on attention. There were modest, but significant, beneficial effects of CDP-choline on memory function and behavior. CDP-choline was well tolerated. CONCLUSIONS: There is some evidence that CDP-Choline has a positive effect on memory and behavior in at least the short term. The evidence of benefit from global impression is stronger, but is still limited by the duration of the studies. There is evidence that the effect of CDP-choline treatment is more homogeneous for patients with cognitive impairment secondary to cerebrovascular disorder.

Babb, SM, et al. Chronic cdp-choline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study. Psychopharmacology (Berl). 2002 May;161(3):248-54. Epub 2002 Mar 22.  

CDP-Choline emails
Q. Dear Dr Sahelian, I noticed your Mind Power RX formula does not contain CDP Choline. Does this suggest that CDP choline should not be taken with choline, or is it safe to do so simultaneously?
     A. There are countless supplements and herbs that have an influence on the mind, and we had to limit the number we could place in Mind Power Rx. CDP-choline is an excellent mind nutrient, and it can be taken with choline, just that the dose of CDP-choline and choline need to be reduced in order not to get overstimulated.

Q.  I have been taking CDP-Choline for about 3 - 4 weeks. I began taking it after reading Dr. Sahelian's publication on Natural Sex Boosters. My results with CDP Choline have been fabulous. Sensation and enjoyment have returned. My question is; should I take a break every so often, or will CDP-Choline just continue to be effective if taken continuously?
     A.  Thank you for your email and feedback. It's great that cdp-choline worked for you. It's an interesting supplement. Although we can't give specific advice, my philosophy regarding supplements is to take breaks from their use. As to the extent of breaks and their frequency, that is an individual matter and decision.

Q. What are the differences between CDP-Choline and GPC-choline? 2. I've had a chronic problem with stiff neck and DMAE made it worse. What's probability that either of these 2 versions of choline would do the same?
     A. We have come across GPC-choline but have not really looked into it in any detail since we can't find any revealing human trials with it. DMAE can make neck tenseness worse in higher dosages. We are not aware that CDP-choline would do the same. But to assure this, we recommend less than a full dose.

Q. I recently became aware that dogs can and do suffer from cognitive dysfunction. A popular holistic vet prescribes a supplement called Cholodin to every dog over 8. While my dog did not exhibit the usual symptoms (losing bladder control in the house, getting "stuck" in corners, etc., etc.) he does have some lethargy (his bloodwork is perfect) and he IS almost 13. He started acting sometimes like he didn't know where my voice was coming from, and was not as
responsive to stimuli. So I decided to try CPD choline with him. I tried 1/2 a 250 mg pill but I noticed the best results with an entire 250 mg capsule before breakfast. It certainly does make a difference!!
     I am thinking of rotating the brain supplements with him, OR better yet, finding one that might even perform better and give him also better physical energy. I looked carefully at your site and looked at both Choline and CDP choline
and especially Acetyl-carnitine with ALA. Without giving me medical advice and I know I am going to have to experiment with my dog BUT...what brain nutrient do YOU PERSONALLY find gives you both the best mental and physical motivation and energy out of the 3 mentioned? If plain choline works I might go with that because of the cost factor but I also want to know the one you are most impressed with.
     A. Interesting about your dog responding to DCP-choline. Thanks for the info. I personally rotate the use of my herbs and supplements since I like the effects of different ones. I like acetyl-carnitine since I notice the effects within an hour with more mental focus and clarity and I also like the fact that it is an antioxidant. CDP-choline is also excellent, and is one of my favorites. Choline is good, but I don't think it is as good as CDP-choline. Other options are DMAE and for a mood lift I like SAM-e.

Q.  wrote to you a a month ago about the dramatic results my 13 year old dog with minor Canine Dysfunction had with CDP choline. I was giving him 250 mg capsule on empty stomach (he is large). Even with minor CD, the results were very impressive. He had increased energy levels and much better attention span and reaction to stimuli. Since our conversation, I decided to try him on ALCAR with R-LA. Especially since there have been rat studies on how dramatically it affected them. I started him on approx. 500 mg ALCAR (Acetyl L-Carnitine) and 30 mg R-LA on empty stomach. I tried it for a week without the CDP choline. I was surprised at the lack of response to ALCAR. So I added back in the CDP choline along with ALCAR-no increased results, in fact it seems he has lost his edge also with CDP-choline. I have since gone to Alpha GPC and alternated with CPD choline and even have upped the ALCAR to 2 doses a day. No adverse responses but he is not back to what he was, that month he was on CDP choline. He still shows some signs of cognitive enhancement, just not like the reaction he did for that first month, like years have peeled away. I still continue to give him Alpha GPC and ALCAR because I believe in their benefits for him.

Q. I am interested in taking CDP Choline, and am going to discuss this with my neurologist. I was wondering if you had any knowledge about it's safety for people with Idiopathic Intracranial Hypertension, also called Pseudo Tumor Cerebri. I have this condition, and currently take Diamox and Lasix. I've tried to search and see if there are any contraindications for using it with this condition, but haven't found anything.
   A. I have not seen research with these conditions and the use of cdp-choline.