New research is increasingly identifying Choline as a key nutrient for the brain and liver. In the past research has shown that while the liver synthesizes choline, it may
not produce adequate amounts, at least from the food that some people in the
Meeting IOM's dietary-intake goals, however,
can be a hit-or-miss proposition since there is a dearth of data on how much
choline most foods contain. Steven H. Zeisel's laboratory at the
New studies show, too, that prenatal
nutrition may influence how much of the nutrient an individual requires.
Moreover, IOM's nutrition guidelines were developed to prevent liver damage,
whereas optimum health may require more choline.
Enriched diet
Meck, a neuroscientist, had been enriching
the diets of adult rats with choline in hopes that it might improve their
performance in certain memory tests. He knew that choline is a building block
of acetylcholine. A chemical that nerve cells use in signaling, it plays an important
role in memory.
Recalls
So, Meck and Williams launched a study in
which they gave pregnant female rats water laced with choline. This
supplementation roughly quadrupled the animals' normal choline intake. For a
few weeks after birth, the pups received injections of additional choline.
The scientists then tested these offspring
throughout their short lives on their recall of locations in a maze where the
researchers had hidden food. The experiment measured whether the rats could
remember and not revisit sites they had already emptied as they sought out the
remaining food during the day.
"We found that the prenatally
supplemented animals clearly outperformed the others," Williams says. With
repeated testing, scores improved for many of the animals in both the
supplemented group and an unsupplemented group that served as a control. Yet
even after 16 weeks of daily testing, she notes, the supplemented rats
continued to make fewer errors than the others did.
One aspect of the results was even more
startling, Williams notes. The more difficult the tests of memory and learning
became, the bigger the apparent benefit of that prenatal enrichment. The best
explanation is that the choline-supplemented offspring could "hold more
information," Williams told Science News. "We know of no other
treatment that increases memory size."
Her group and others have repeatedly
confirmed the findings. "What's so amazing," Williams contends, is
that the aptitude for learning in prenatally supplemented animals "is as
good in old age as it was when they were young. They show no decline." In
contrast, animals not supplemented prenatally with choline show signs of
senility in old age. It appears that with supplementation, "we're building
a better brain," she says.
Narrow window
Nuances
in choline action are showing up. By narrowing the window of prenatal
supplementation, Williams and others have identified only two small periods
during which extra choline boosts a rat's intelligence. The first is from days
12 to 17 in gestation. This correlates roughly with the second half of a human
pregnancy. The other window runs from 2 to 4 weeks after birth - a period that
corresponds loosely with human infancy and toddlerhood.
Recently, scientists have begun delving into
what underlies that first malleable period. It coincides with the formation of
a complex network of choline-sensitive nerve cells that sends information to a
region of the brain known as the hippocampus, Williams notes. This area is
active in learning and memory.
Five years ago or so, Williams and other
researchers asked Swartzwelder to look for signs that early choline exposure
somehow changes the brain. Dubious that a week of prenatal enrichment could
smarten animals, much less trigger detectable physiological changes, he
nonetheless agreed to a pilot study.
The results changed his perspective.
In a hippocampal neuron, certain patterns of
incoming chemical signals can trigger a response called long-term potentiation.
During this response, newly arriving signals are more effective than under
other conditions. The process helps cement memories by "promoting the encoding
and consolidation of new information. It's the first step in learning,"
Swartzwelder explains.
Compared with hippocampal tissue from
unsupplemented animals, brains primed with prenatal choline showed long-term
potentiation more readily, Swartzwelder found. When he then turned to brains
from animals whose mothers had been choline deficient, he found hippocampal
circuits unusually resistant to the effect.
It appeared that choline is "powerful
stuff," Swartzwelder recalls. But to make sure of his results, he repeated
the analyses, using rats reared and treated by a different group of
researchers. Again, he saw the same effect. Overall, the greater the prenatal
exposure to choline, the larger the effect on the brain.
That was 2 years ago. Now, Swartzwelder is
focusing on glutamate, a primary chemical messenger responsible for triggering
long-term potentiation. Brain cells have specialized protein complexes, called
NMDA receptors, that respond to glutamate. They don't promote long-term
potentiation unless they receive closely timed signals from other brain cells
(SN: 9/4/99, p. 149: http://www.sciencenews.org/sn_arc99/9_4_99/fob3.htm).
Swartzwelder's team has now shown that NMDA
receptors in the brains of animals that received prenatal choline enrichment
are unusually responsive to signals. This finding suggests that these animals
might make memories more readily than others do.
Protecting neurons
Prenatal supplementation with choline can also
protect the brain later in life. That finding, to be published soon in the Journal
of Neuroscience, is "the wildest thing of all," Swartzwelder
says.
His group and its collaborators find evidence
that choline can influence the effects of a toxic drug. Prenatal
supplementation protects neurons in the brains of adolescent rats from the cell
death ordinarily associated with high doses of a drug that blocks the NMDA
receptors.
Last year, prenatal choline supplementation
in another study prevented memory defects following drug-triggered brain
lesions. The researchers used a drug that induces convulsive epileptic seizures
in rodents. Epileptic seizures not only damage the brain, but they also tend to
impair memory and learning.
Gregory L. Holmes of Harvard Medical School's
Center for Research in Pediatric Epilepsy in Boston and his colleagues
administered the neurotoxic drug to rodents?some of which had received prenatal
choline supplementation?and then monitored the animals' learning skills.
Using a standard test of spatial memory, the
researchers daily released each rat into a pool of milky water and waited for
the animal to find a stationary platform just beneath the surface. Animals that
had not experienced seizures oriented themselves more quickly every day. This
learning showed up in rats whether or not they had received prenatal choline
supplementation.
After the experienced rats developed
epilepsy, however, the pattern changed. When tested a week after seizures,
prenatally supplemented animals remembered where the platform was and in
succeeding days continued to improve their performance. But rats that had
received no prenatal choline supplementation acted as if they had no memory of
where the platform had been and showed less improvement in finding it during
the following days.
If studies of people confirm an effect of
prenatal choline on the brain's response to assaults after birth, Holmes' team
wrote in the Nov. 15, 2000 Journal of Neuroscience, these findings
"could lead to nutrition-based preventive strategies." The authors
liken the possibility to the use of folate vitamins now routinely prescribed to
pregnant women to prevent neural tube defects in the fetus.
Jan Krzysztof Blusztajn of
Three years ago, he showed that extra choline
available during hippocampal development permanently modifies that area's
efficiency in using the nutrient. When choline concentrations in the womb are
low, the brain becomes "very frugal" with this nutrient, Blusztajn
says, whereas the choline metabolism of animals that encounter an abundance in
the womb "becomes quite wasteful." Prenatal conditions probably determine
how much choline an adult requires.
His studies indicate that an overly frugal
hippocampus may lead to problems. Its parsimony may leave little choline free
to perform mentally demanding activities.
With a low stockpile of choline, production
of the neurotransmitter acetylcholine may prove insufficient to carry out
sustained, high-throughput communications between memory neurons. They just
poop out and learning slows. However, Blusztajn reports that prenatally
supplemented rats "have some sort of cognitive reserve?which is probably
also a biochemical reserve. It lets them sustain longer [choline-fueled]
neurotransmission."
Improving memory
Evidence is emerging that choline
supplementation in adulthood, too, may sometimes improve memory. This result
comes from a study of people who, because of gastrointestinal problems, receive
virtually all of their nutrition intravenously. Manufacturers don't regularly
fortify with choline most nourishment that's administered intravenously.
"We now know that between 20 and 50
percent of patients receiving [intravenous] nutrition long-term develop liver
disease," notes Alan L. Buchman of
The researchers also administered IQ and
other tests to 11 participants. They initially scored below normal on verbal
memory and visual memory tests. In the January-February Journal of
Parenteral and Enteral Nutrition, the scientists reported that those scores
improved "significantly" in the men and women receiving supplemental
choline. This suggests, they said, that severe choline deficiency in adulthood
may impair memory reversibly.
Zeisel is beginning several more human
trials. In one, resembling the animal experiments, 80 pregnant women will be
given specially prepared waffles and asked to eat one with each meal from about
15 weeks into their pregnancy until a month after their baby is born. Some of
the women will get normal waffles, the rest will get ones fortified with either
one egg or its choline equivalent in the form of soy lecithin.
When the women's babies are 10 and 12 months
old, psychologists will test the infants' visual memory?the child's recall of
where Mom's picture last appeared.
Minimum requirements
Zeisel has also just launched the first
detailed analysis of how much choline people need for basic health. Eighty
volunteers will be held "captive, " Zeisel says, for 71 days in a
university metabolic ward. Everything they eat and excrete will be measured.
The food"resembling heavily fortified milk shakes" will initially carry a
normal range of recommended nutrients. Then, all the participants will be
switched to a cholinefree version.
They'll remain on that diet until enzymes indicative
of liver damage begin appearing in their blood. At that point, Zeisel says,
"we'll begin adding back increasing amounts of choline until we discover
how much it takes to return each to normal."
Because the test will include men and women,
blacks and whites, and premenopausal and postmenopausal women, it should
determine whether particular groups differ in their needs.
Today, few people exhibit overt choline
deficiency. Zeisel suspects, however, that at least some teeter on the brink of
insufficiency. Because the best-known choline-rich foods tend to be animal
products, especially ones high in fat, he worries that vegans and those who
have successfully pared most fat from their diet may be vulnerable.
Don't be afraid of eating eggs despite their
cholesterol, he chides. Their yolks are among the richest known natural sources
of choline. A tall glass of skim milk offers as much choline as an egg does.
And coming soon, predicts Gregory Paul, director of nutrition for Central Soya
of Ft. Wayne, Ind., will be a host of foods?orange juice, baked goods, and
pasta?fortified with choline-rich soy lecithin.
So, keep an eye out for those new choline
labels, Williams says; they'll help identify "what we call food for
thought."
