Keen Cuisine: The Queen B

The privations of war, all too often, provide important if inadvertent lessons in nutrition. Such is the case with the B vitamin folate. Toward the end of World War II, Nazis blockaded the western Netherlands, limiting access to food for over 4 million people, thus killing more than 20,000. The six months of starvation that have come to be known as the Hunger Winter also gave scientists a rare opportunity to study the biological consequences of nutrient deficiency, particularly during pregnancy. Babies conceived during the famine were twice as likely as children conceived before or after it to have had neural-tissue defects like spina bifida or to have developed schizophrenia. Such outcomes, first noted in the 1970s, gave rise to the idea that nutrients play a crucial role in early brain and nervous system development. Folate may be among the most important.

"The nervous system needs folate to carry out a number of absolutely fundamental metabolic processes," says Joanne Berger-Sweeney, a neuroscientist at Tufts University. Like Dutch women pregnant during the Hunger Winter, expectant mothers today who don't consume enough folate are at an increased risk of giving birth to children with nervous system defects. Their children are also more likely to develop schizophrenia, autism, attention problems, and language delays.

What, exactly, does folate do? "Believe it or not, we still don't fully know why and how it works," says Rebecca Schmidt, a public health scientist who studies folate at the University of California at Davis. One of the vitamin's most important jobs is orchestrating the way DNA is read. Folate delivers molecular tags known as methyl groups to genes, thereby regulating the amount of protein the body makes from them. "What makes your ear your ear and your nose your nose—even though they have the exact same genetic code—is DNA methylation," Schmidt explains.

Scientists are still working to solve many of folate's molecular mysteries, but here are some insights gleaned from recent studies.

Stamp of Starvation

If nutrient deficiency in utero affects the way DNA is methylated, then people conceived during the Dutch Hunger Winter should have abnormal DNA methylation patterns even as adults. Studying 60 people who were conceived during the Hunger Winter and 60 of their same-sex siblings who were not, researchers analyzed methylation patterns of an oft-methylated gene, insulin-like growth factor 2 (IGF2), which regulates growth. Methylation of the gene indeed averaged 5.2 percent lower among those conceived during the famine.

Minding Methylation

Do people suffering from mental illness have DNA methylation abnormalities? UK and Danish researchers compared DNA methylation patterns in 22 sets of identical twins, one of whom had schizophrenia or bipolar disorder. They found significant differences between the healthy twins and those with mental problems. Affected sibs had lower methylation levels in certain genetic regions than healthy sibs. Since folate abets methylation, the findings suggest that prenatal folate deficiency may affect brain development by impairing gene regulation.

Autism Protection

Over 85,000 Norwegian women who took folic acid supplements from four weeks before conception through the first eight weeks of pregnancy were 40 percent less likely to have autistic children than mothers not taking folate. A U.S. study finds that the autism link is strongest among mothers or babies who have common variations in genes that impair folate metabolism. It may be extra important for the nearly 50 percent of women said to have genetic variations in folate metabolism to consume adequate amounts of the vitamin during pregnancy.

Brain Boost

Autism has been tied to low prenatal folate exposure, but it also may result from the presence of antibodies that keep folate from doing its job. U.S. researchers recently analyzed the blood of 93 autistic children and found that three-quarters of them had antibodies in their blood blocking folate from crossing the blood-brain barrier and entering brain cells. When the researchers treated the children with a chemical form of folate that the so-called "auto-antibodies" spare, folate could enter the brain cells and autism symptoms diminished.

Depression Cure

Depressed adults often have low folate blood levels. But is folate deficiency causing their symptoms? A group of depressed adults who were not responding to treatment with a selective serotonin reuptake inhibitor (SSRI) were additionally given 15 mg a day of L-methylfolate, an active form of the nutrient. A similar group was given a placebo. Those who took the folate were more than twice as likely to report improvements in symptoms. Researchers speculate that folate alleviates depression by boosting a chemical precursor of serotonin and dopamine.

Appetite Link

Rodents exposed to low levels of folate in the womb are more likely to become obese later in life. For yet-unknown reasons, the folate-deficient animals consume more fat. The low-folate, high-fat mix does a double whammy on animals' brains. It lowers levels of DNA-repair enzymes. Folate-deficient rats also suffer more oxidative damage to the brain, which can destroy tissue and set the stage for DNA mutations. The findings suggest that a low-folate diet predisposes animals to poor dietary decisions that ultimately put their brains at multiple risk.

Getting Your Folate Fix

In addition to its contribution to brain function, folate acts as an antioxidant, helping the body eliminate the dangerous byproducts of metabolism known as free radicals, which damage body tissues and degrade DNA, setting the stage for new mutations and disease. The vitamin also helps to synthesize DNA and repair genetic damage, which could reverse disease-causing mutations that arise in the womb.

Adults should aim to consume 400 micrograms of folate every day, but pregnant or breastfeeding women should consume slightly more (600 micrograms and 500 micrograms daily, respectively). So where, exactly, can you get your folate fix?

Dark leafy greens like spinach, collard and turnip greens, brussels sprouts and broccoli are rich with the vitamin—spinach contains a whopping 263 micrograms of folate per cup and asparagus is close behind—because the vitamin is essential for plants' growth and metabolism, just as it's important for our own. (But unlike humans, plants can make their own folate.) There's good reason to eat a folate-rich diet even if you're not pregnant: Some research suggests that the vitamin reduces cancer risk by facilitating DNA repair.

Beans—garbanzo, black-eyed, pinto, black, and navy—are also packed with folate; beans are plant seeds, where nutrients tend to be concentrated. Doctors frequently recommend beans as a way to boost heart health, and folate could have something to do with their benefits: A 2012 meta-analysis of 14 studies found that for every 200 extra micrograms of folate consumed per day—a cup's worth of cooked beans—a person's risk of developing heart disease drops by 12 percent.

On the sweeter side, some fruits—specifically, oranges, papayas, bananas, and cantaloupes—also contain moderate amounts of folate. When European researchers compared the blood levels of folate in more than 5,500 adults with what they ate, they found that those who consumed the most fruit had folate levels twice as high as those who consumed the least.

Since 1996, flour and grains have been fortified with folate. Bran flakes typically provide more than 600 micrograms per cup. Long-grain white rice delivers 716 micrograms per cup.