If you’re a woman of childbearing age, you’ve heard—likely more than once—the message. Whether it’s from special interest groups like the Spina Bifida Association, whether it’s from the buzz surrounding “Folic Acid Awareness Week” every January, or whether it’s your own OBGYN handing you supplements, the message is ubiquitous: You need to be taking folic acid.
They’re (mostly) right. Folic acid, a b-vitamin essential in promoting cell growth, is crucial in preventing the occurrence of birth defects like anencephaly and spina bifida, which can be fatal. And not only should women be taking folic acid, doctors agree women aren’t getting enough as it is. In March, the Journal of the American Medical Association released a new study entitled, “Higher Folic Acid Intake Needed.” The study, which measured the occurrence of neural tube defects (NTDs) such as spina bifida and anencephaly across certain populations, concluded that because the number of NTDs hasn’t decreased in the last fifteen years, U.S. women have insufficient folic acid reserves. In order to prevent NTDs, the United States Department of Agriculture began fortifying grains with synthetic folate in 1998. A brief decline in NTDs was observed from 1999-2000, but as the JAMA study noted, rates have remained stable ever since.
What many don’t know—and what the JAMA study failed to mention—is that a significant part of the U.S. is unable to process folic acid at all.
There’s no solid consensus, but some reports state that anywhere from 10 to 15 percent of Caucasians and more than 25 percent of Hispanics are unable to metabolize folic acid. Called methylenetetrahydrofolate reductase, or MTHFR for short, this defect refers to the MTHFR gene, which produces the enzyme responsible for converting synthetic folic acid (what’s found in prenatal vitamins and fortified grains) to methylated folate (the metabolized nutrient that protects against NTDs).
Diane Keddy, a dietician and nutritionist based in Newport Beach, Calif., has specialized in MTHFR and other genetic defects throughout her 28-year career. MTHFR, she says, is a little-known but incredibly common defect that currently affects several million people in the U.S.
“I think we’re at the very beginning of being able to understand [MTHFR],” Keddy says. “A lot of physicians don’t know anything about it. It’s like where Celiac’s Disease was 10 years ago.”
The gist of MTHFR, according to Keddy, is this: A huge subset of the population has some sort of MTHFR defect, and the MTHFR gene can be defective in several different ways. The two most researched polymorphisms of the MTHFR gene are known as C677 and A1298. Although many people have MTHFR defects, not all defects will manifest in symptoms, says Keddy. People who show severe symptoms, such as recurrent and unexplained pregnancy loss, blood clots, or unexplained, early-onset heart disease, are likely homozygous for one or both mutations. Other symptoms include migraines, anxiety, depression, increased risk of birth defects, and even strokes and certain types of cancers. The more defects, typically the more severe the symptoms. A blood panel or a simple saliva test can determine whether someone has the gene.
April Butchee was diagnosed with an MTHFR defect in 2009 after suffering two miscarriages in close succession. During her third pregnancy, Butchee’s obstetrician ordered a recurrent pregnancy loss panel (RPL) to test for chromosomal problems that might have been causing her miscarriages. Days later, the results were in: Butchee tested positive for a homozygous A1298 mutation.
“I knew for years that something was wrong,” Butchee said. “I had migraines, depression, miscarriages.” After her diagnosis, Butchee rallied her family to get tested through a web site called 23andme.com, which provides low-cost DNA analysis. Billed as a genetic ancestry test, these tests can also pinpoint any genetic defects, including MTHFR. Most of Butchee’s family (her mother, father, and two brothers) tested positive for the heterozygous MTHFR mutation.
MTHFR defects are, in Keddy’s experience, more prevalent among women. “I’ve been specializing for a long time,” she says. “I’ve seen over one hundred women [with MTHFR] and maybe two men.” Keddy has two theories why MTHFR defects are more common among women. First, Keddy says, in her experience at least, men are less likely to see a doctor. Another theory is that women, due to childbearing, are more likely to be goaded into taking folic acid. When women with the MTHFR defect take synthetic folic acid that they’re unable to metabolize, the folic acid builds up in their body and can trigger the growth of pre-cancerous cells, and exacerbate MTHFR-related symptoms like migraines and blood clots. “It literally acts as a poison for some women,” Keddy says.
After her third pregnancy, Butchee moved out of state. Unsure as to how to best treat her MTHFR defect, Butchee saw a hematologist to address some of her blood-clotting issues. “Hematologists are more likely to know what MTHFR is,” says Butchee. “But he wasn’t knowledgeable and, back then, neither was I.” The hematologist, unfamiliar with MTHFR, prescribed her synthetic folic acid to help her clotting. Months later, Butchee was admitted to the hospital with shortness of breath and chest pains. The culprit? Multiple pulmonary embolisms—life-threatening blood clots that develop in the lungs. Pulmonary embolisms can be fatal in 15 percent of cases, and can be a lethal side effect of the MTHFR mutation.
MTHFR is commonly linked to clotting disorders, according to Keddy. “Folate is key in converting methionine to homocystine,” Keddy says. When folate reserves are low, homocystine levels can become elevated, leading to blood clots like Butchee suffered, or even heart attacks and strokes. “A lot of times you have young people with unexplained heart disease,” Keddy says. “And most of the time they test positive for a homozygous MTHFR mutation.”
The severity of her blood clots left Butchee with a slow and grueling recovery. During her recovery, Butchee began researching MTHFR in earnest. Butchee’s online research led her to some MTHFR support groups, where she got tips on how to change her diet. “At the advice of my doctor, I went completely dairy- and gluten-free two years ago,” she says. But even going completely gluten-free has its challenges. “Even the gluten-free noodles and cereals are ‘enriched’ with folic acid.” Gradually, Butchee’s symptoms have improved. She has been clot-free for nearly three years.
Diane Keddy recommends a similar approach for her clients with MTHFR. “The first things I tell them is to avoid folic acid. This means going completely gluten-free, because there’s synthetic folic acid in almost all breads and cereals.” Keddy also recommends clean eating and avoiding chemical exposure, since the amino acids involved in liver detoxification are usually impaired as well.
“I do a lifestyle program,” Keddy says. “I don’t sell anything. I just recommend products that I’ve tried or that I’ve seen be successful.”
As for supplementing foods with folic acid? Keddy isn’t so sure.
“I think it needs to be discontinued until proven safe for women with MTHFR,” she says. And to women who supplement with folic acid, she offers a word of caution: “Anyone who has a family history of infertility, heart disease, strokes, miscarriages, birth defects—they should get tested,” she says. “I think everyone would benefit from knowing their MTHFR status.”