Choline, memory, and aging

[Guest guest]

A Forget-Me-Not Dietary Supplement?

Janet Raloff, Science News 164:21 (22 Nov 2003)

By the time most people reach their 40s, the mind

has lost some of its youthful nimbleness. They

learn a little more slowly. They forget more

frequently. Sometimes, they don't remember where

they put the car keys or the name of that popular

actor.

Although minor memory lapses are no big deal, they

might hint at a vulnerability to serious aging-

related memory impairments somewhere down the

line.

But there may be hope for people with middle-age

forgetfulness yet. Last week, researchers at the

Massachusetts Institute of Technology reported

tantalizing animal data suggesting that a dietary

supplement can substantially preserve an aging

brain's dexterity. The substance, an experimental

formulation of choline known as cytidine (5')-

diphosphocholine (CDP-choline), won't make us

smarter, Teather explained at the Society for

Neuroscience annual meeting in New Orleans. It

might, however, limit the subtle onset of mental

fuzziness, she said. At least, that's what it did

for rats.

Choline plus

Found in every cell, choline plays an integral

role in the development of membranes, cholesterol

transport, and brain signaling. Although the liver

makes choline, most people don't eat optimal

quantities of the foods offering it. Among foods

naturally rich in choline are beef liver, eggs,

and peanut butter.

Two years ago, the Food and Drug Administration

authorized new food labeling that would not only

list a food's choline content, but also a claim

that the product represents a good or excellent

source of the nutrient. The idea was to help

consumers find foods that would boost their

choline intake. To date, food manufacturers

haven't rushed to extol their products' choline

content--and consumers still tend to eat choline-

light diets.

That could hurt the brain, says Teather's

colleague J. Wurtman. He notes that the

limiting ingredients for making the fatty

materials known as phospholipids, which play an

integral role in the consolidation of memories,

are in CDP-choline. Phospholipids are also

important building blocks of all membranes,

including the contact points through which signals

flow between nerve cells. These contacts, or

synapses, " get smaller and you have fewer of them "

as people age, Wurtman notes.

In the past, his group showed that daily intake of

CDP-choline could increase the membrane content of

a rat's brain by at least 15 percent.

In the new study, Wurtman and Teather decided to

probe the functional significance of this membrane

increase. So they fed a healthy diet to 3-month-

old and 15-month-old rats, representing young-

adult and middle-age rodents. Half the animals in

both age groups also received the supplement--

about a half-gram per kilogram of body weight per

day--for 2 months. Afterwards, the researchers

tested the animals' ability to memorize the

placement of an underwater platform in a water

maze.

The rats were given four tries to find on a

slightly submerged platform on each of four

consecutive days. On each day, the young and old

animals learned to find the platform, where they

could rest, Teather says. The effect of age

emerged in what the animals remembered 24 hours

later.

Among rats not getting CDP-choline, the older

animals seemed to forget much of the previous

day's learning, Teather says, while the young ones

didn't. By the end of 4 days of testing, she

notes, the difference between these groups " was

really huge, " suggesting that the older ones had

trouble forming long-term memories. However, she

notes, among CDP-choline­supplemented rats,

middle-aged animals " mastered the [maze learning]

as readily as the young animals did. " Her group is

now in the process of evaluating the impact of

CDP-choline on memory development in the rodent

equivalent of senior citizens.

No quick fix

" The interesting thing, " observes Teather, " is

that if you feed the [rats the supplemented] diet

for 1 month, you can't rescue memories. " The

animals had to get CDP-choline for at least 2

months to receive some memory protection. And

that, she says, points to a mechanism for what the

nutritional supplement is doing.

Normally, when the brain gets a dietary boost of

choline, the first thing the organ does is make a

signal-transmitting molecule known as

acetylcholine. And in the supplemented rats, brain

concentrations of acetylcholine rose within the

first month. However, at that point, maze-learning

in middle-age rats showed no improvement over

unsupplemented animals. This suggests, Teather

says, that acetylcholine deficiency isn't the

primary cause of fuzzy memories.

It turns out that once acetylcholine

concentrations become bountiful, the brain begins

shunting extra choline into the production of

membrane phospholipids. Only when these membrane

constituents built up--after about 2 months of

CDP-choline supplementation--did memory benefits

begin to emerge in the rats.

To maintain that benefit, taking a CDP-choline

supplement might have to be permanent. It's an

issue that Teather and Wurtman will be probing.

However, " the beautiful part of this is that it's

not a drug with side effects. It's a nutrient

that's very well tolerated " even in very high

doses, Teather says. Moreover, because the human

body doesn't clear the breakdown products of CDP-

choline as fast as the rodent body does, people

probably need no more than a half-gram of the

supplement per day to achieve beneficial brain

concentrations.

For now, CDP-choline is not on the U.S. market,

though health-food stores sell choline-enriched

products. However, Teather notes, CDP-choline's

integral ingredients can be derived from diets

rich in eggs, whole grains, and animal products.

Teather recently moved from the Massachusetts

Institute of Technology (MIT) to Wilfrid Laurier

University in Waterloo, Ontario, where she will be

organizing a laboratory to continue research on

CDP-choline. In conjunction with her colleagues at

MIT, her research will soon include tests of the

supplement in people.

" We received word that we're going to be funded by

the National Institutes of Health " for a host of

studies, including at least one involving people,

Wurtman notes. He says his team will give people

choline and uridine--the breakdown products of

CDP-choline-- " to see if they also positively

affect symptoms of minimal cognitive impairment, "

like those minor but common memory lapses that

plague the senior set.

" We're very excited, " he told Science News Online.

The supplement " worked so nicely in rats; we'll

now see if it also works in people. "

Teather is so buoyed by her team's findings that

she's got her whole family eating eggs and taking

choline supplements. " Even the dog's on it, " she

says.