Health for life

Prenatal folic acid supplements appear to reduce the risk for autistic spectrum disorders, according to a study published today (February 13) in the Journal of the American Medical Association (JAMA).

The Centers for Disease Control and Prevention estimate that about 1 in 88 children in the U.S. have been identified with an Autism Spectrum Disorder (ASD). ASDs are amongst the most heritable of mental disorders, but little is known about how the disorder develops. Consequently, methods for diagnosis, prevention, and treatment are limited.

Folic acid (Vitamin B9) is required for DNA synthesis and repair in the human body, and its naturally occurring form—folate—is found in leafy vegetables, peas, lentils, beans, eggs, yeast, and liver. Taking folic acid supplements during early pregnancy is known to protect against spina bifida and other neural tube defects in children. In the United States, Canada, and Chile, folic acid is added to flour, so as to automatically provide these supplements to consumers. Norway does not enrich its flour, and since 1998, the Norwegian Directorate of Health has recommended that all women planning to become pregnant take a daily supplement of folic acid from one month before the start of pregnancy through the first trimester.

Despite this policy, studies from North America and Europe have shown that many pregnant women have a lower dietary intake of folate than what is necessary to prevent neural tube defects.

The report in JAMA emerged from the Norwegian Mother and Child Cohort Study (MoBa) and its sub-study of autism, the Autism Birth Cohort (ABC) Study. This international collaboration (see list of members below) comprises the largest prospective birth cohort devoted to the investigation of gene-environment interactions and biomarker discovery for neuropsychiatric disorders.

A total of 85,176 MoBa babies—born from 2002-2008—and their parents participated in the study. Prenatal dietary habits were recorded, and families were regularly surveyed for 3-10 years to measure the development of autism spectrum disorders. A total of 270 cases of autism spectrum disorders were identified in the study population (114 autistic disorder; 56 Asperger syndrome; 100 atypical or unspecified autism; i.e., pervasive developmental disorder not otherwise specified, PDD-NOS).

Mothers who took folic acid supplements in early pregnancy had a 40% reduced risk of having children with autistic disorder compared with mothers who did not take folic acid. The reduction in risk was observed in those who took folic acid during the time interval from 4 weeks before to 8 weeks after the start of pregnancy. Autistic disorder is the most severe form of autism spectrum disorders in children. No reduction in risk was observed for PDD-NOS. For Asperger syndrome, the number of children was too low to obtain sufficient statistical power in the analyses.

The use of folic acid in early pregnancy increased substantially from 2002 to 2008 among women who participated in MoBa. In 2002, 43% of mothers took folic acid supplements; by 2008, 85% of mothers did. However, many women began taking folic acid later than recommended, and only half started before the beginning of pregnancy.

The timing of a mothers intake of folate appears to be a critical factor. Her childs risk of autism was reduced only when the supplements were taken between 4 weeks before to 8 weeks after the start of pregnancy.

"We examined the rate of autism spectrum disorders in children born to mothers who did or did not take folic acid during pregnancy. There was a dramatic reduction in the risk of autistic disorder in children born to mothers who took folic acid supplements," says Pål Surén, first author and epidemiologist at the Norwegian Institute of Public Health (NIPH).

The researchers also analyzed whether the risk of autistic disorder was influenced by the use of other dietary supplements. They did not find any association between the mothers use of fish oil supplements (cod liver oil and omega-3 fatty acids) in early pregnancy and the risk of autistic disorder, and no association for the mothers use of other vitamins and minerals.

In recent years, researchers have started to investigate whether folic acid has other beneficial effects on the development of the fetus brain and spinal cord. A study of language development from MoBa, published in 2011, showed that children whose mothers took folic acid supplements in early pregnancy had only half the risk of severe language delay at age three years compared with other children. A separate 2011 study from the University of California, Davis, demonstrated a lower risk of autism spectrum disorders in children of mothers who had used prenatal vitamin supplements during pregnancy. Prenatal vitamin supplements contain folic acid in combination with other vitamins and minerals.

Joint senior author Ezra Susser, professor of Epidemiology at Columbia Universitys Mailman School of Public Health and professor of Psychiatry at the College of Physicians and Surgeons, stated, "Our findings extend earlier work on the significance of folate in brain development and raise the possibility of an important and inexpensive public health intervention for reducing the burden of autism spectrum disorders."

"This elegant work illustrates the power of the ABC cohort for not only chipping away at the riddle of what causes autism, but for developing new methods for early recognition, prevention and treatment," says W. Ian Lipkin, John Snow Professor of Epidemiology at the Mailman School of Public Health and principal investigator of the ABC cohort.

Taking enough omega-3 fatty acid supplements to change the balance of oils in the diet could slow a key biological process linked to aging, new research suggests.

The study showed that most overweight but healthy middle-aged and older adults who took omega-3 supplements for four months altered a ratio of their fatty acid consumption in a way that helped preserve tiny segments of DNA in their white blood cells.

These segments, called telomeres, are known to shorten over time in many types of cells as a consequence of aging. In the study, lengthening of telomeres in immune system cells was more prevalent in people who substantially improved the ratio of omega-3s to other fatty acids in their diet.

Omega-3 supplementation also reduced oxidative stress, caused by excessive free radicals in the blood, by about 15 percent compared to effects seen in the placebo group.

“The telomere finding is provocative in that it suggests the possibility that a nutritional supplement might actually make a difference in aging,” said Jan Kiecolt-Glaser, professor of psychiatry and psychology at Ohio State and lead author of the study.

In another recent publication from this study, Kiecolt-Glaser and colleagues reported that omega-3 fatty acid supplements lowered inflammation in this same group of adults.

“Inflammation in particular is at the heart of so many health problems. Anything that reduces inflammation has a lot of potentially good spinoffs among older adults,” she said.

Study participants took either 2.5 grams or 1.25 grams of active omega-3 polyunsaturated fatty acids, which are considered “good fats” that, when consumed in proper quantities, are associated with a variety of health benefits. Participants on the placebo took pills containing a mix of oils representing a typical American’s daily intake.

The researchers say this combination of effects suggests that omega-3 supplements could represent a rare single nutritional intervention that has potential to lower the risk for a host of diseases associated with aging, such as coronary heart disease, Type 2 diabetes, arthritis and Alzheimer’s disease.

The study is published online and scheduled for later print publication in the journal Brain, Behavior, and Immunity.

Participants received either the placebo or one of the two different doses of omega-3 fatty acids. The supplements were calibrated to contain a ratio of the two cold-water fish oil fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), of seven to one. Previous research has suggested that EPA has more anti-inflammatory properties than DHA.

In the case of fatty acids, omega-3 supplementation alone doesn’t tell the whole story of how this dietary change can affect health, explained Martha Belury, professor of human nutrition at Ohio State and a co-author of the study. Also important is the ratio of omega-6 fatty acids to omega-3 fatty acids that are present in a person’s blood.

Omega-6 fatty acids come from vegetable oils, and since the 1960s, research has suggested that these oils, too, can help protect the cardiovascular system. However, the typical American diet tends to be heavy on omega-6 fatty acids and comparatively low in omega-3s that are naturally found in cold-water fish such as salmon and tuna. While the ratio of omega-6 to omega-3 fatty acids averages about 15-to-1, researchers tend to agree that for maximum benefit, this ratio should be lowered to 4-to-1, or even 2-to-1.

The long chains – or bigger molecules – that make up EPA and DHA fatty acids are believed to be the secret to their effectiveness, Belury said.

Both groups of participants who took omega-3 supplements showed, on average, lengthening of telomeres compared to overall telomere effects in the placebo group, but the relationship could have been attributed to chance. However, when the researchers analyzed the participants’ omega-6 to omega-3 ratio in relationship to telomere lengthening, a lower ratio was clearly associated with lengthened telomeres.

“The idea we were looking at with the ratio of omega-6 to omega-3 fatty acids was an increase in the denominator to make the ratio smaller. In the United States, we need to focus on the omega-3 part because we don’t get enough of those,” Belury said.

The researchers also measured levels of compounds called F2-isoprostanes to determine levels of oxidative stress, which is linked to a number of conditions that include heart disease and neurodegenerative disorders. Both omega-3 groups together showed an average overall 15 percent reduction in oxidative stress compared to effects seen in the placebo group.

When the scientists revisited their earlier inflammation findings, they also found that decreases in an inflammatory marker in the blood called interleukin-6 (IL-6) were associated with telomere lengthening. In their earlier paper on omega-3s and inflammation, they reported that omega-3 supplements lowered IL-6 by 10 to 12 percent, depending on the dose. By comparison, those taking a placebo saw an overall 36 percent increase in IL-6 by the end of the study.

“This finding strongly suggests that inflammation is what’s driving the changes in the telomeres,” Kiecolt-Glaser said.

Telomeres are a hot topic in science, and their tendency to shorten is associated with such age-related problems as heart disease and early mortality. These short fragments of DNA act as caps at the end of chromosomes, and can be likened to the protective plastic at the end of a shoelace.

“Anything that reduces inflammation has a lot of potentially good spinoffs among older adults.”

“If that plastic comes off, the shoelace unravels and it doesn’t work anymore,” said study co-author Ron Glaser, professor of molecular virology, immunology and medical genetics and director of the Institute for Behavioral Medicine Research (IBMR) at Ohio State. “In the same way, every time a cell divides, it loses a little bit of its DNA at the ends, and over time, that can cause significant problems.”

Kiecolt-Glaser noted that this population was disease-free and reported very little stress. The study included 106 adults, average age 51 years, who were either overweight or obese and lived sedentary lives. The researchers excluded people taking medications to control mood, cholesterol and blood pressure as well as vegetarians, patients with diabetes, smokers, those routinely taking fish oil, people who got more than two hours of vigorous exercise each week and those whose body mass index was either below 22.5 or above 40.

“People who are less healthy than this group, and especially those who experience chronic stress, may gain even more benefits from omega-3 supplementation,” she said.