CDP-Choline Helps with Memory

CDP-Choline Can Help You Remember

CDP-Choline Helps with Memory
In which you see a certain kind of biomedical research through new eyes,
courtesy of … the Hand
By Will Block

ou’re puttering around the yard, minding your own business, when suddenly a gigantic hand reaches down from the sky, picks you up, and whisks you away to a strange place where there’s a huge, black, open-top water tank, about 60 feet in diameter. The hand plops you into the water and disappears. Although the water is nice and warm, you’re thinking, “What the … What was that? … Why me, Lord?” You like a nice swim as much as the next guy, but you’re freaked out by the thought of that hand, and your sole desire is to escape from the tank and run like hell.

Problem #1: The edge of the tank is far beyond your reach, and the water is deep, so you can’t touch bottom. The only way out is via the ladder.

Problem #2: There’s no ladder. In fact, the wall is perfectly smooth all around, with nothing to hold onto. You know this because you’ve just covered every inch of it.

Problem #3: You’re starting to panic, because you flunked water-treading in school. In fact, you’re now kind of hoping that the Hand will come back and snatch you out of there. You cry for help, but there’s no answer.

Then, while contemplating your predicament, you notice something protruding above the surface some distance away—some sort of curved object. Hallelujah! At this point, anything solid that you can hang onto spells L-I-F-E. You swim like crazy and reach for the object like a … well, like a drowning man grasping at a straw.

But this is no straw! To your surprise, it turns out to be the top of a big white ball attached to a Plexiglas platform that’s hidden just below the surface, where it’s invisible. With a sigh of relief, you climb aboard the ball and count your blessings. You still want out, of course, but at least now you have some time to think things through without fear of drowning.

You look around and notice a few objects—geometric shapes—that are visible around the edge of the tank: a circle, a square, a triangle, and a cross. You’re wondering who’s behind this and what it all means, when suddenly … Whoosh! The Hand appears and plucks you out. It gently deposits you back in your yard and disappears again.

Well, all right! You’re back where you belong—soaking wet but none the worse for wear—but you’re still annoyed and mystified by the whole thing. You’ve barely dried off and settled down with a stiff drink to try to figure it out when … back comes the Hand! Splash! You’re in the pool again! Rats! “This isn’t funny, whoever you are! Let me out!”

No answer. You’re treading water again—but of course, you remember the ball … but where is it? You look all around and realize, with horror, that it’s no longer there. OK, don’t panic. Think! Maybe the ball is gone, but what if the platform is still there? Don’t need no stinkin’ ball if the platform is there! But it’s hidden! Gotta try to remember where it was in this huge, round, featureless tank.

No, wait … it’s not entirely featureless. There were things around the edge—visual cues to your position—and they’re still there! Let’s see—the platform was sort of between the square and the circle (swim, swim), wasn’t it? No, apparently not. Wait, it must have been between the square and the triangle (swim, swim), right? Yes! Whew! Saved again! And sure enough, here comes the Hand … but what’s this—it’s holding a huge stopwatch. That’s odd …

Swimming for Science

OK, that’s enough! That was a 600-odd word introduction to what it must feel like to be a laboratory rat involved in a certain type of memory test: the water maze. In reality, the tank is about 6 feet across, not 60, but other than that, the description above is pretty accurate. You get the picture: you (as a rat) are supposed to learn how to find the hidden platform by using those visual cues, and the Hand will time you to see how well you remember what you learned a minute ago, or an hour ago, or a week ago …

Our little scenario was oversimplified, though. With real rats (you’re now a human again, OK?), there are many training sessions before the ball is removed, because rats are slower learners than people. And there are many variations on the basic theme, including moving the platform around or removing it altogether, to confuse the rats. (That’s mean! When rats are aggravated, perhaps they silently shout, “People!”)

The Hand Selects CDP-Choline for Memory Studies

But what’s the point of all this? It’s to see how rats learn, how well they remember what they’ve learned, and how their age affects these processes. Ah, finally this is starting to sound relevant, because we humans are concerned about things like age-related memory impairment. We’ve heard all about that, and we want to do whatever we can to hang on to our memory marbles for as long as possible.

You can see what’s coming next, can’t you: the Hand wants to know how various nutritional supplements might affect the rats’ performance in the water maze, because it knows that if it gets good results with something, it will be written about (scribble, scribble) in Life Enhancement—and what could be better for a Hand than that?

Today’s Hand—in the guise of a pair of researchers named Lisa Teather and Richard Wurtman, from MIT’s Department of Brain and Cognitive Sciences—used the water maze to test the memory of rats that had been ingesting CDP-choline daily for 2 to 3 months before the testing began. In two separate studies, they tested the effect of this brain nutrient on: (1) the learning and memory capacity of normal young rats vs. that of normal older rats,1 and (2) the learning and memory capacity of young rats raised in environmentally enriched conditions (lots of toys and other stimulation) vs. that of young rats raised in environmentally impoverished conditions (just a bare cage).2 We’ll get to the results shortly.

CDP-Choline Is an Important Precursor Molecule

CDP-choline is shorthand for cytidine-5'-diphosphocholine (it’s also known as citicoline). A naturally occurring molecule found in most life forms, it’s a chemical intermediate in the biosynthesis of two compounds that are very important to your brain: phosphatidylcholine and acetylcholine. As their names imply, these compounds are derived from the choline part of the CDP-choline molecule—the cytidine part plays no role in these processes. (To trace the convoluted path that CDP-choline takes to get to your brain, see the sidebar.)

What Happens to CDP-Choline When You Take It?

We tend to think that when a supplement is ingested, the nutrient in question is absorbed from the digestive tract into the bloodstream and finds its way, intact, to that part of the body (heart, brain, eyes, joints, etc.) where it will fulfill the role expected of it. Surprise—it’s rarely that simple. For one thing, the liver, in its role as the body’s nutritional “gatekeeper,” gets first crack at everything.

Nutrients that pass through the intestinal wall enter the portal vein, which goes straight to the liver. The liver “decides,” in a chemical sense, whether to leave a given nutrient alone and pass it along into the general circulation unchanged, or to decompose it into its constituent parts, or to add something to it to make a derivative of the original compound.

Once in the general circulation, the nutrient (in whatever form the liver has left it) will travel throughout most of the body, whether most of the body wants it or not. Some parts of the body may, however, selectively absorb it from the blood, and those are the places where it will have the greatest effect.

But why does it reach only most of the body? Why not all the body? Because there’s one part of the body that is uniquely protected from exposure to many different substances: the brain. Perhaps you’ve heard of the blood-brain barrier (BBB), which admits some compounds to the inner sanctum and excludes others. The system is effective, though not perfect. In any case, the BBB is not some kind of physical membrane that surrounds the brain, keeping the bad guys at bay. It’s not even a single entity of any kind. Rather, it’s the sum total of all the endothelial cells lining the microscopic blood vessels that nourish the brain’s 100 billion cells. Cumulatively, those endothelial cells are the BBB.

Now let’s see what happens when you take CDP-choline.1 After passing through the stomach into the small intestine, most of it is decomposed into cytidine, choline, and phosphate. To varying degrees, these constituent molecules pass through the intestinal wall (the portions that don’t pass through get excreted) and enter the portal vein. In the liver, some of the cytidine enters what’s called the cytidine nucleotide pool and may be incorporated into nucleic acids. Some of the choline enters metabolic pathways that result in the biosynthesis of various substances, including CDP-choline (back to square one!), betaine, and phosphatidylcholine.

The rest of the cytidine and choline (along with the reconstituted CDP-choline) are released into the general circulation and are absorbed by various tissues of the body, where they undergo further metabolism. When they reach the blood-brain barrier, CDP-choline is largely shut out: the brain absorbs very little of it. Cytidine and choline molecules are welcome, however, and once they’re inside the brain’s cells, some of them are again reconstituted to CDP-choline (phosphate is always available as a necessary participant). Finally, the CDP-choline serves as an intermediate in the synthesis of the vital brain molecules phosphatidylcholine and acetylcholine.

  1. PDR for Nutritional Supplements, p. 81. Medical Economics Co., Montvale, NJ, 2001.

Phosphatidylcholine (a lipid, or fatty compound) is the primary component of our cell membranes, upon whose structural integrity the healthy functioning of our cells depends. It is thus an integral part of all of our cells and is crucial for sustaining life. Acetylcholine is one of the brain’s (and body’s) primary neurotransmitters. It is the defining feature of the cholinergic system of neurons, which plays a central role in learning and memory.

Among the hallmarks of brain aging are alterations in cell membranes and dysfunction of the cholinergic system. That’s why the MIT researchers decided to have a close look at CDP-choline—that and the fact that previous research had suggested that supplemental CDP-choline can enhance memory function in elderly humans, especially those with memory impairment or outright dementia, such as Alzheimer’s disease. Despite some uncertainties about its efficacy, the compound has long been used in Europe to treat cognitive, emotional, and behavioral deficits associated with chronic cerebral disorders in the elderly.

CDP-Choline Improves Memory in Elderly Patients

The authors of a meta-analysis of the literature on human clinical trials with CDP-choline analyzed 13 randomized, double-blind, placebo-controlled trials that involved elderly patients suffering from cerebrovascular disorders, senile dementia (including Alzheimer’s disease), or normal or abnormal cognitive impairment associated with aging.3 They concluded that there were modest but significant beneficial effects of CDP-choline on memory function and behavior in these patients, at least in the short-to-medium-term duration (3 months or less) of the studies in question.

The dosage of CDP-choline used in 11 of those studies was 1000 mg/day, and in the other two it was 600 mg/day. By comparison, the daily dosage used in the MIT rat studies was enormous: about 500 mg per kg of body weight. For a 75-kg (165-lb) person, this is equivalent to about 37,500 mg (37.5 g). Another significant difference was that the rats took their CDP-choline orally (with their feed), whereas the humans took it orally in only three of the 13 studies; in the other 10, they received it via intravenous or intramuscular injection.

CDP-Choline Improves Memory in Older and Impoverished Rats

Thus, it’s nearly impossible to make meaningful comparisons between the rat studies and the human studies. Nonetheless, let’s see what the former revealed. In a nutshell, CDP-choline improved the declining memories of the older rats (described as “early-aged” rats, i.e., getting on in months, but not yet old), compared with control rats of the same age that received no CDP-choline.1 The supplement had no effect on the young rats. The protective effect of CDP-choline in the older rats was attributed primarily to a presumed increased in phosphatidylcholine synthesis in the brain; the authors explained in detail why they believed that increased acetylcholine synthesis was only a minor factor at best.

The same types of cognitive deficits seen in normal old rats are also seen in young rats that have been exposed to environmentally impoverished conditions (no toys) since the time they were weaned. The MIT researchers therefore used the same experimental technique for their second study (which was defined above). The data showed that the impoverished control rats were memory-impaired in comparison to the impoverished rats that had been given CDP-choline for 3 months (which is long-term for rats), and they were also memory-impaired compared with all of the enriched rats, whether the latter had been given CDP-choline or not.2 The supplement had no effect on any of the enriched rats. As in the previous study, the authors concluded that the protective effect of CDP-choline in the impoverished rats was due primarily to the synthesis of phosphatidylcholine, not acetylcholine.

The similarity of results in these two studies led the authors to an intriguing speculation:2

While the physiological bases for the memory impairments caused by aging and impoverishment have not yet been identified, the fact that supplemental CDP-choline benefits both impaired populations suggests that aging and impoverishment may have similar cellular and molecular alterations. Thus, this brings up the possibility that impoverished-condition rats could serve as a useful model for studying the physiological basis of aging.

A New Handle on Aging?

That’s cool! Although the experiments described above were very simple in concept and execution, their interpretation by researchers with a deep knowledge of neuroscience has told us something useful not just about CDP-choline but also, perhaps, about the nature of aging, with a new handle on studying it further. Let’s give that Hand a hand!

References

  1. Teather LA, Wurtman RJ. Dietary cytidine (5')-diphosphocholine supplementation protects against development of memory deficits in aging rats. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:711-7.
  2. Teather LA, Wurtman RJ. Dietary CDP-choline supplementation prevents memory impairment caused by impoverished environmental conditions in rats. Learn Mem 2005 (online preprint).
  3. Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. John Wiley & Sons, Chichester, UK.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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