Citicoline (cytidine diphosphate choline, or CDP-choline) is not just a source of choline, the main building block of the neurotransmitter acetylcholine. Instead, Citicoline is a brain phospholipid booster. The most popular and well-known brain phospholipid supplement is phosphatidylserine (PS). But brain function relies on a wide spectrum of phospholipids, and not just PS. Of course, PS supplements contain small amounts of some of the other key brain phospholipids, such as (phosphatidylcholine [PC] and phosphatidylinositol [PI]). But they don't contain these nutrients, in the same proportions as are found in a healthy, functioning brain. Taking individual phospholipids, such as PS, forces more of the specific phospholipid that you're taking into the membranes of nerve and other cells. But it cannot restore the youthful balance of all brain phospholipids.
By contrast, Citicoline works by enhancing the brain's ability to synthesize its own phospholipids. Citicoline's real "business end" is its cytidine group. Taking Citicoline delivers cytidine to the brain, where it is transformed into cytidine diphosphate (CDP). CDP plays a key role in the body's production of the brain's phospholipids. Studies show that cytidine itself, or cytidine delivered as Citicoline, boosts brain and neural PS by 37.2%, PC by 22-30%, PI by 16%, and PE by 11-13%. By supporting the brain's ability to make its own phospholipids, Citicoline increases levels of all phospholipids in neural membranes - yet the healthy, youthful proportions of the various phospholipids are not altered.
At the same time, new research suggests that Citicoline allows the body to make better use of phospholipids derived directly from the diet or supplements. When you take phospholipid supplements, the fatty acid "tails" have to be modified as they are taken from the blood, then brought into the cell's outer membrane, so that they meet the specific needs of the local tissue. Studies in isolated neuron precursor cells show that Citicoline selectively enhances the ability of phospholipids to incorporate a variety of fatty acids into their "tails," facilitating this "customization" process. As well, Citicoline increases the manufacture or release of key neurotransmitters, including acetylcholine, norepinephrine, dopamine, and serotonin.
Controlled human studies prove that Citicoline provides effective nutritional support in a wide range of cognitive disorders - a broader range than other phospholipids-based nutritional supplements such as PS. Trials have documented the powerful support provided by Citicoline supplementation in Alzheimer's disease, stroke, dementia associated with Parkinson's disease, and head trauma, and that it improves the odds of a good outcome after high-risk brain surgery.
Most importantly for most healthy people looking to maintain, protect, boost, or restore healthy brain function, double-blind, placebo-controlled trials have also shown that Citicoline significantly improves memory function in persons with "normal" age-associated memory impairment (AAMI).
In one such trial, older subjects who were experiencing problems with their memory, but who were not suffering dementia, were tested on a battery of memory tests, and found to perform more poorly than young controls. Then the subjects were given each of four treatments, for four weeks each, at different times. All volunteers underwent three periods with different Citicoline regimens (a high (1000 mg) or moderate (500 mg) dose of Citicoline, or a lower (300 mg) dose combined with nimodipine (a blood pressure drug also used to treat some neurological deficits)). Subjects also underwent a dummy-pill phase. The results showed that Citicoline significantly improves performance on several memory tasks, including the free recall of word lists and the ability to remember a set of objects (either immediately after seeing them or later on). All Citicoline groups showed some improvement over the course of the trial. The only side effects were a decrease in blood pressure, and immunomodulatory effects shown as minor changes in the populations of white blood cells.
Citicoline was also tested in AAMI in a randomized, double-blind, placebo-controlled trial run by MIT in conjunction with US Army Research Institute of Environmental Medicine. In the first phase, ninety-five older volunteers with no active psychiatric or neurological disorders, and who were within the normal range on tests of mental status, were randomly assigned to take either a dummy pill or Citicoline for three months. The subjects with poorer memory at baseline showed improvements in recall (remembering details of a story heard one half hour previously). Subjects who began the study with poorer memories were then used in an additional study, in which they received one of two high doses of Citicoline for two months each. The higher dosage of Citicoline was "clearly associated with improved immediate and delayed logical memory." And while some side effects were reported, the incidence of side effects was actually higher in the placebo group than in people taking Citicoline!
A team of researchers at McLean Hospital in Belmont recently tested the effects of a six week supplementation of Citicoline. Volunteers were given an MRI at the beginning and end of the six week period to observe any changes. They found that supplies of brain energy were increased in critical regions of the brain.
Does "PS" Even Work?
All of the original trials documenting the benefits of "PS" supplements used a phosphatidylserine concentrate derived from cow brains. This product nearly vanished from the marketplace a decade ago when BSE ("mad cow disease" swept through Britain and threatened to create an epidemic across Europe. It was replaced by a form of "PS" derived from soy - a supplement fundamentally different in its biochemical structure from the original, mammalian brain-derived material. Until recently, there were only two small, nonrandomized, low-power, uncontrolled studies available to tell us about what this vegetal PS might do for a person.
Now, the first proper, double-blind, placebo-controlled trial using soy-derived PS has been performed. The results clearly show that unlike the original brain-derived PS supplements, the soy-based "PS" you can buy in capsules or softgels at health food stores today actually doesn't work any better than dummy pills at supporting memory or other aspects of brain function.
Neurons Beyond the Brain
Of course, the proper functioning of neurons is required for a lot more than just the workings of the brain. The final word isn't in, but preliminary evidence suggests that Citicoline is helpful with many non-brain conditions grounded in neurological dysfunction. Glaucoma, for instance, is most commonly the result of a buildup of pressure from the fluid in the eye (intraocular pressure), which literally squeezes the nerves that leave the eyeball, causing them to lose their supply of nutrients and slowly starve. In an open trial, 36 patients with glaucoma were given one gram of Citicoline daily for ten days. While the study was too short to assess any improvement in symptoms, the researchers did find that Citicoline "acts positively on the glaucomatous optic nerve damage" and led to "favorable neurotrophic [nerve-nourishing] effects."
Likewise, amblyopia, or "lazy eye," is ultimately a neurological disorder, although always associated with some other problem with visual function (such as a misalignment of the focus of the two eyes). Amblyopia develops when the nerve cells, which connect one eye to the brain are literally turned off, because the sensory messages the poorer eye is sending don't match up with those being sent by the dominant eye. After years of being deactivated, the nerves leading to the amblyopic eye can ultimately cause that eye to go fully blind.
Again, Citicoline may offer hope. Italian researchers have performed several trials in patients with amblyopia, which have confirmed that Citicoline significantly improves both symptoms and neurological function, and can be used to increase the effectiveness of occlusion (the standard therapy for "lazy eye").
With ongoing research, we may expect the fulfillment of some present promises, and the discovery of new applications for this remarkable nutrient.
Bring the Balance Back
Our minds are what make us who we are. Memories are our connection to our history, and the foundation of who we are today. The workings of the mind reflect the structure of the brain, and phospholipids play a vital part in that structure. Citicoline restores more youthful levels and balance of brain phospholipids, carrying us from our past into a clear future.
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