A Forget-Me-Not Dietary Supplement?

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, Lisa 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 (SN: 11/3/01, p. 282: Brain Food). 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 (see Heard about Choline?). 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 Richard 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-choline–supplemented 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.