Folic acid: for the young and heart.
Those who survive will lack bowel and bladder control, and many will be paralyzed from the waist down or suffer from mental retardation. Another five pregnancies will be aborted when the defects are diagnosed prenatally.
"Our best estimate is that half of these tragedies could be prevented if women consumed more of the B-vitamin folic acid," says Godfrey Oakley, head of the Birth Defects section of the Centers for Disease Control in Atlanta.
Today - and every day - more than 1,500 Americans will die of heart disease. Folic acid might prevent somewhere between 50 and 100 of those deaths, estimates Shirley Beresford, an epidemiologist at the University of Washington.
What's more, three research trials are under way to see if folic acid can prevent colon cancer, the number-two cancer killer in the U.S. Are you getting too little folic acid? It's worth finding out. It's also worth finding out if you're getting too much.
Godfrey Oakley has spent all of his professional life trying to prevent birth defects like spina bifida. While some scientists argue that preventing an estimated 1,250 birth defects and 750 aborted pregnancies each year isn't much, the pediatrician disagrees. "No one says there are only 1,700 cases of pediatric AIDS a year," he says. "It's a shame."
Three years ago, a rock-solid study in Hungary showed without question that folic acid can prevent at least some children from being born with spina bifida, anencephaly, or other similar birth defects. "Folic acid is the Salk vaccine of the '90s," says Oakley.
The defects occur when the neural tube - which develops into the spinal cord - fails to close 18 to 26 days after sperm meets egg. If the error occurs at the top of the tube, the child is born with anencephaly (no brain) and dies soon after birth.
If the error occurs further down the spinal cord, the child is born with spina bifida (an open spine). It's the damage to the exposed spinal cord that usually keeps these children in wheelchairs or on crutches.
"They're great kids and great adults," says the University of Washington's Shirley Beresford, "but they'd be much better without spina bifida."
Researchers aren't sure exactly how folic acid prevents some defects in the neural tube. But it makes sense that the fetus needs folic acid (and its extended family of folates).
"Whenever there's rapid cell division, you need lots of folic acid to make DNA," says Oakley. (DNA is the carrier of genetic information.) And if cells are ever rapidly dividing, it's during the first few weeks of pregnancy.
It's not that some pregnant women are deficient in folic acid, but that they - or their fetuses - need more than others. The catch is: there's no way to know which fetuses those are.
"There are 60 million women who could get pregnant each year," says Oakley. "As far as we know, they're equally at risk for having a child with a neural tube defect."
And there's another catch: Because the defect occurs before most women even know that they're pregnant, and because roughly half of all pregnancies are unplanned, women have to take folic acid throughout their childbearing years.
How much? The U.S. Public Health Service says 400 micrograms (mcg) a day, either from food (see "Folate: Good Sources") or a supplement. But taking a supplement is a safer bet.
"Diet may provide adequate protection, but we don't know that," says Beresford. "If you want to be sure, you need to take a multivitamin math 400 micrograms." (Most multivitamins contain 400 mcg, which is the U.S. Recommended Daily Allowance.)
Because millions won't take supplements, says Oakley, "the most important public health measure would be to fortify foods." He's talking about adding folic acid to the "enriched" flour in foods like breads, cereals, and pasta.
The price tag for fortifying those foods - $100 to $250 million a year, depending on how much was added - would be dwarfed by savings from fewer birth defects, says Patrick Romano of the University of California School of Medicine at Davis.
And he didn't consider the possibility that folic acid might prevent heart disease in adults by lowering levels of an artery-damaging substance known as homocysteine. if he had, says Oakley, the benefit-to-cost ratio "would have gone through the roof."
HOMOCYSTEINE & THE HEART
"A man ahead of his time." That's how people refer to Kilmer McCully, now a pathologist at the Veterans Affairs Hospital in Providence, Rhode Island. More than 25 years ago, McCully came up with the idea that homocysteine could damage arteries. Homocysteine is an amino acid that's used to make protein.
Only in recent years have researchers taken McCully's work seriously. They tested people who've had heart attacks, strokes, clogged arteries in their necks or legs, you name it. All were more likely to have high levels of homocysteine in their blood than their healthy counterparts.
"The results from more than 20 studies are remarkably consistent," says Meir Stampfer, an epidemiologist at Harvard Medical School. In the Physicians' Health Study, for example, men who started out with high homocysteine were three times more likely to have a heart attack over the next five years.
"We really don't know the mechanism," says Jacob Selhub of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston.
But, thanks to Selhub and others, we do know that nearly one out of three residents of Framingham, Massachusetts, aged 67 or older has high homocysteine. And we know why, says Selhub. "In this older population, two-thirds of the cases of high homocysteine could be attributed to inadequate vitamin intakes."
FOLATE IN FRAMINGHAM
In Framingham, homocysteine is high in people who get too little folic acid or vitamins B-6 or B-12. Why?
The body needs all three vitamins to convert homocysteine to other things. When the vitamins are too scarce to keep the assembly line moving, the homocysteine "backs up."
But when researchers in South Africa tested each of the three vitamins on a group of 100 men with high homocysteine, B-12 lowered their levels by only 15 percent and B-6 didn't work at all. Folic acid cut their homocysteine by 42 percent.
B-12 might have played a larger role had they studied older people. Nevertheless, says Selhub, "folic acid is by far the most effective means of reducing the kind of elevated homocysteine levels we've seen in Framingham."
Researchers think that some people are born with an inefficient form of the enzyme that gets folate ready to interact with homocysteine. And that means homocysteine builds up. "But that's correctable if they consume enough folate," says Harvard's Stampfer.
The next step, say researchers, is to see whether folic acid-with or without B-6 and B-12 - can keep arteries from clogging or strokes and heart attacks from occurring. But that will take years.
In the meantime, says Stampfer, "I recommend that people get at least 400 micrograms of folic acid a day from food or a supplement."
Fewer birth defects. Less heart disease. "What's nice is that they both get fixed by folic acid," says the CDC's Godfrey Oakley.
But others fear that too much folic acid - whether it comes from a supplement or fortified foods-poses a risk, especially to older people.
The problem is that folic acid can cover up, or mask, a vitamin B-12 deficiency. it fixes the anemia (too few red blood cells) caused by too little B-12, while another symptom - nerve damage-gets worse.
"If you take folic acid and have an uncorrected B-12 deficiency, it's possible that you'll delay the anemia but that the neurological damage will progress," says Sally Stabler, who researches B-12 at the Colorado Health Sciences Center in Denver.
One answer, says John Lindenbaum, a B-12 expert at Columbia University, is to "educate physicians to recognize the early signs of neurological damage due to B-12 deficiency."
That's important because, with or without folic acid, says Stabler, "about a third of people with B-12 deficiencies never get anemia."
Instead, they get "an unpleasant feeling, tingling, or burning pain in their hands or feet," she explains. "Then it goes up the legs. After months, they get numbness and a loss of sensation below the knees." Once they lose muscle strength, they seldom go back to normal.
In a younger person, those symptoms are easier to diagnose, she adds. But "in an older person who may already be unsteady because of osteoarthritis, who may have diabetic feet, or who is already going to the doctor for 20 things, it's difficult to tell what's making their feet hurt."
Other seniors with a B-12 deficiency get dementia that could be confused with irreversible conditions like Alzheimer's disease.
Yet all the physician needs to do is a blood test for B-12. If it's at or below the lower end of the normal range (less than 300 pg/ml), a blood test for methylmalonic acid and homocysteine can nail the diagnosis of a B-12 deficiency.
A BLAST OF B-12
Should fear of permanent nerve damage keep you from taking folic acid? Hardly.
Among older residents of Framingham, 12 to 20 percent had early signs of B-12 deficiency. "But only a small fraction will develop the neurological damage, because it takes decades to deplete the body's stores of B-12," says Lindenbaum. "A lot of elderly are going to die of other things before that happens."
And there's another way to make sure you don't run short of B-12: take a huge dose.
Older people typically have low B-12 levels not because they don't eat enough B-12-rich foods - meat, fish, poultry, eggs, or dairy products - but because they produce too little stomach acid to free the B-12 from their food.
But taking 500 mcg a day (the U.S. Recommended Daily Allowance for B-12 is only six mcg) floods the stomach with enough B-12 to reach anyone's bloodstream, says Lindenbaum. "A large dose would even treat patients with pernicious anemia," who lack the "intrinsic factor" that ordinarily ferries B-12 into the bloodstream, he adds.
Most doctors treat pernicious anemia with B-12 injections, but they don't need to. In fact, an editorial in the Journal of the American Medical Association recently suggested that using high-dose B-12 pills instead - as they do in Sweden - is "medicine's best kept secret."
The CDC's Oakley wants the FDA to require companies to add folic acid to "enriched" flour (which already has to contain three other B-vitamins). But researchers like Selhub and Lindenbaum don't want to rush into fortification.
"Who would have thought 30 or 40 years ago that giving estrogen - a natural hormone - to pregnant women who were in danger of losing their pregnancies would have led to cancer in their offspring years later?" asks Lindenbaum.
Still, he agrees that because we know that folic acid can prevent birth defects, we shouldn't wait years to find out whether it might pose some unknown risk. But he'd feel more comfortable if we at least knew more about the known risks and potential benefits.
"We could find out within two or three years whether folic acid is useful in preventing heart disease and strokes and how many cases of B-12 deficiency it will mask," says Lindenbaum.
That would be fine ... except that each day means another few coffins, another few wheelchairs.
"We don't need to wait for more studies," says Oakley. "There are so ma birth defects we can't do a thing about. And we're not even preventing the ones that we know how to prevent."
Food Folate (1/2 cup, unless specified) (mcg)
Product 19 cereal (1 cup) 400 Total cereal (3/4 cup) 400 Brewer's yeast (1 Tbs.) 313 Lentils(*) 179 Pinto beans(*) or chickpeas(*) 145 Spinach(*) 131 Red kidney beans(*) 115 Asparagus(*) (5 spears) 110 Orange juice, from frozen concentrate (1 cup) 109 Spinach, raw (1 cup) 109 Most breakfast cereals (1 cup) 100 Wheat germ, toasted (1/4 cup) 100 Romaine lettuce, shredded (1 cup) 76 Split peas(*) 64 Brussels sprouts(*) or peas(*) 47 Beets(*) 45 Orange juice, not from concentrate 45 Broccoli(*) 39
Source: USDA Handbook 8 and manufacturers.
THE BOTTOM LINE
* To get a good dose of folate - and reduce your risk of cancer - eat five to nine servings of fruits and vegetables every day.
* If you want extra insurance, take a multivitamin with 400 mcg of folic acid to possibly reduce your risk of heart disease and colon cancer.
* If you could become pregnant, take a daily multivitamin that has 400 mcg of folic acid (that's 100% of the USRDA). Fortified cereals like Product 19 or Total are good alternatives if you don't like pills.
* If you're 65 or older and you take a multivitamin that contains folic acid, make sure you also take 500 mcg of vitamin B-12 every day.
 New England Journal of Medicine 327: 1832, 1875, 1992.
 American Journal of Public Health 85: 667, 1995.
 American Journal of Pathology 56: 11, 1969.
 Journal of the American Medical Association 268: 877, 1992.
 Journal of the American Medical Association 270: 2693, 2726, 1993.
 Journal of Nutrition 124: 1927, 1994.
 American Journal of Clinical Nutrition 60: 2, 1994.
 Journal of the American Association 265: 94, 1991.
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|Title Annotation:||fetus development helped and adult hearts: includes a chart of foods rich in folic acid|
|Publication:||Nutrition Action Healthletter|
|Article Type:||Cover Story|
|Date:||Sep 1, 1995|
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