Folic acid supplements early in pregnancy may reduce child’s risk of autism by 40 percent

Large study in Norway finds early timing of supplements is critical:

JAMAPrenatal 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 mother’s intake of folate appears to be a critical factor. Her child’s 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 mother’s 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 mother’s 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 University’s 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.

 

Reference

Surén P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie KK, Lipkin WI, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Smith GD, Øyen AS, Susser E, Stoltenberg C. Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in Children. JAMA 2013; 309 (6): 570-577.

 

Prenatal folic acid supplementation associated with lower risk of autism

JAMAIn a study that included approximately 85,000 Norwegian children, maternal use of supplemental folic acid from 4 weeks before to 8 weeks after the start of pregnancy was associated with a lower risk of autistic disorder in children, according to a study appearing in the February 13 issue of JAMA.

“Supplementation with folic acid around the time of conception reduces the risk of neural tube defects in children. This protective effect has led to mandatory fortification of flour with folic acid in several countries, and it is generally recommended that women planning to become pregnant take a daily supplement of folic acid starting 1 month before conception,” according to background information in the article. It has not been determined whether prenatal folic acid supplements protect against other neurodevelopmental disorders.

Pal Surén, M.D., M.P.H., of the Norwegian Institute of Public Health, Oslo, and colleagues investigated the association between the use of maternal folic acid supplements before and in early pregnancy and the subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children. The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (average age, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Analyses were adjusted for maternal education level, year of birth, and parity (the number of live-born children a woman has delivered).

A total of 270 children (0.32 percent) in the study sample have been diagnosed with ASDs: 114 (0.13 percent) with autistic disorder, 56 (0.07 percent) with Asperger syndrome, and 100 (0.12 percent) with PDD-NOS. The researchers found that there was an inverse association between folic acid use and subsequent risk of autistic disorder. Autistic disorder was present in 0.10 percent (64/61,042) of children whose mothers took folic acid, compared with 0.21 percent (50/24,134) in children whose mothers did not take folic acid, representing a 39 percent lower odds of autistic disorder in children of folic acid users.

Characteristics of women who used folic acid within the exposure interval included being more likely to have college- or university-level education, to have planned the pregnancy, to be nonsmokers, to have a pre-pregnancy body mass index below 25, and to be first-time mothers.

“No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use,” the authors write.

The researchers note that the inverse association found for folic acid use in early pregnancy was absent for folic acid use in mid pregnancy.

“Our main finding was that maternal use of folic acid supplements around the time of conception was associated with a lower risk of autistic disorder. This finding does not establish a causal relation between folic acid use and autistic disorder but provides a rationale for replicating the analyses in other study samples and further investigating genetic factors and other biological mechanisms that may explain the inverse association,” the authors conclude.

 

Reference

Surén P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie KK, Lipkin WI, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Smith GD, Øyen AS, Susser E, Stoltenberg C. Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in Children. JAMA 2013; 309 (6): 570-577.

 

Nutraceuticals and Headache: The Biological Basis

Headaches are a common and debilitating ailment from which most people suffer at one time or another. Common types of headaches include tension headaches, migraines, cluster headaches and sinus headaches. Headaches can have many causes, but serious causes of headaches are rare. 

This review discusses the biological basis for non-conventional or non-mainstream approaches to the treatment of migraine. Dr. Frederick Taylor discuss in this context magnesium, riboflavin, coenzyme Q10, petasites, feverfew, marijuana/cannabis, and oxygen/ hyperbaric oxygen.  

 

Frederick R. Taylor

Nutraceuticals and Headache: The Biological Basis

Headache 2011; 51 (3): 484-501

 

ABSTRACT

Nutrition must affect the structure and functioning of the brain. Since the brain has very high metabolic activity, what we consume throughout the day is likely to dramatically influence both its structure and moment to moment function. It follows that nutritional approaches to all neurological disorders are being researched and entering medical practice, while nutraceutical use is a mainstay of public habits. This review discusses the biological basis for non-conventional or non-mainstream approaches to the treatment of migraine. This requires at least limited discussion of current migraine pathophysiologic theory. How nutrients and other chemicals and approaches are mechanistically involved within migraine pathways is the focus of this article. The nutraceuticals reviewed in detail are: magnesium, riboflavin, coenzyme Q10, petasites, and feverfew with additional comments on marijuana and oxygen/hyperbaric oxygen. This article reviews the science when known related to the potential genetic susceptibility and sensitivity to these treatments. As we know, the basic science in this field is very preliminary, so whether to combine approaches and presumably mechanisms or use them alone or with or without conventional therapies is far from clear. Nonetheless, as more patients and providers participate in patient-centered approaches to care, knowledge of the science underpinning nutritional, nutraceutical, and complementary approaches to treatment for migraine will certainly benefit this interaction.

 

Researchers Strive To Increase Awareness Of Forgotten Essential Nutrient

A group of researchers at the University of Alberta in Canada hopes to draw attention to what has become a forgotten essential nutrient.

Choline, a nutrient found in foods such as egg yolks, liver and soybeans, does not appear to be high on anyone’s list of eating priorities.

And this is something researchers Jonathan Curtis, Catherine Field and René Jacobs say they want to change.

“It’s gone off the radar,” said Field, a researcher in nutrition and metabolism. “It’s not being taught in schools as being an important nutrient and so our dietitians and health professionals don’t think about it.”

Part of the reason choline has been overlooked is because it is produced naturally in the liver. But people can’t produce enough to reap the positive benefits the nutrient offers, Field said.

Though choline is not as heavily studied as other nutrients, the limited human and animal research published suggests adequate choline intake is important for fetal development, memory function and prevention of liver and muscle damage.

“Choline has many different biological functions related to healthy development and it plays a role in preventing various diseases,” said Jacobs, a biochemist who has studied choline metabolism for the past decade.

Despite its apparent health benefits, few Albertans seem to be getting enough choline in their diets.

“Our preliminary dietary studies clearly show an insufficient choline intake compared to the recommended levels,” said Curtis, an analytical chemist and project leader for ongoing choline research at the university.

According to the Institute of Medicine, women should consume 425 milligrams of choline per day — the equivalent of almost four whole eggs. This value is higher for men and pregnant women.

In an ongoing study looking at the nutrition of pregnant women in Edmonton and Calgary, few study participants are meeting the adequate intake for choline and only one of the first 600 women surveyed reported taking a supplement that contained the nutrient.

This statistic is surprising given that 97 per cent of women reported consuming at least one supplement.

“Nobody’s taking it,” Field said. “If there was information out there on choline, we’d see a lot more of it in this high social economic group we had.”

But even if people are aware of choline’s health benefits, they will have a hard time finding a supplement to help them meet the recommended adequate intakes.

It’s a lesson Field learned first-hand.

When she went searching for a supplement containing the type of choline found in eggs for study purposes, she couldn’t find one in any Canadian health food store or even on the Internet. She eventually had to ask Curtis and his lab group to make one.

And making choline supplements could be next on the agenda if research like that happening at the University of Alberta continues to point to the importance of choline for health.

In a continuing animal study, Field and her team are looking at the effects of choline during lactation — a critical period, but one not well studied.

“It’s the most nutritionally stressful period for a woman,” Field said. “Her nutritional needs are far greater than during pregnancy because she has to produce milk, an important source of choline, for this growing infant.”

New mother rats were fed diets with varying amounts of choline. The amount they consumed appeared to influence the health of their pups.

“The pups who were fed from the mums who didn’t have the choline in the diet survived, but they didn’t grow as well,” Field said. “If there’s a decrease in growth, or not a normal rate of growth, that has mega implications for later health.”

And those implications are now under the microscope as researchers examine the grown pups, looking at immune health and brain development.

Current funding for choline research projects will end in the spring of 2012. The research crew is applying for more grants this summer so they can establish appropriate choline intake levels and work towards making a choline supplement.

 

Roger Clemens, DrPH, speaks about choline- where it can be found and why the body needs it.

 

 

High Folate Intake Linked to Better Grades in Swedish Teens

Swedish teenagers who are deficient in folate have poorer grades than teens who have a high folate intake, according to new research published online July 11 in Pediatrics.

Nilsson TK, Yngve A, Böttiger AK, Hurtig-Wennlöf A, Sjöström M.High Folate Intake Is Related to Better Academic Achievement in Swedish Adolescents.  Pediatrics. 2011 Jul 11. [Epub ahead of print].

 

ABSTRACT

Background: Adolescents are vulnerable to increased plasma total homocysteine (tHcy) and to insufficient folate status. Folate status and Hcy metabolism are linked to cognitive functions, but academic achievement by adolescents has not been studied in this respect.

Objective: To assess a possible link between academic achievement in adolescents and tHcy and its determinants, dietary folate intake, MTHFR 677 TT homozygosity, and socioeconomic status (SES).

Subjects and Methods: A study of 386 Swedish adolescents aged 15 years in whom plasma tHcy and MTHFR 677C →T genotype were assayed. The sum of school grades in 10 core subjects obtained in the final semester of compulsory 9 years of schooling was used as outcome measure of academic achievement. Lifestyle and SES data were obtained from questionnaires.

Results: Academic achievement was strongly correlated to tertiles of tHcy (negatively; P = .023) and to tertiles of folate intake (positively; P < .001). Other significant predictors were gender, smoking, and SES (proxied by school, mother’s education, and father’s income). When these were controlled for, tertiles of folate intake (P < .002) but not tertiles of tHcy (P = .523) or MTHFRgenotype remained significantly related to academic achievement.

Conclusion: Folate intake had a positive association with academic achievement in the 15-year-olds, which was not attenuated by SES or MTHFR677 TT homozygosity. These results provide new information that points to the importance of keeping a closer watch on folate status in childhood and adolescence. They may also have direct implications for school meal provisions, school teaching programs, and information to parents.

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Folate Intake May Reduce Colorectal Cancer Risk

A new study finds high folate intake is associated with a reduced risk of colorectal cancer, a finding consistent with the findings of most previous epidemiologic studies. The study is reassuring, as previous recent evidence has suggested that consumption of very high levels of folate through supplements and from folate-fortified diet may increase risk of some cancers. Nonetheless, the potential importance of folate in colorectal cancer prevention remains in question because at least one other study found folate supplementation had no effect on recurrence of colorectal adenomas, precursors to colorectal cancer.

The study appears in Gastroenterology, and is the first to look at the association of folate with colorectal cancer risk with follow-up entirely after the mandatory fortification of the U.S. diet with folate. It also is the first to distinguish between the forms of folate found naturally in forms and folic acid, the form used for fortification and in supplements.

A research team led by Victoria Stevens, Ph.D., strategic director of laboratory services at the American Cancer Society, investigated the association between folate intake and colorectal cancer among 99,523 participants in the Cancer Prevention Study II Nutrition Cohort. A total of 1,023 participants were diagnosed with colorectal cancer between 1999 and 2007, a period entirely after folate fortification began. Neither higher nor lower risk was observed during the first two years of follow-up (1999 to 2001), but during 2002 to 2007, high folate intake was associated with a reduced risk of colorectal cancer.

“While folate fortification has been a public health success in reducing the risk of neural tube defects, the potential for an increase risk of cancer has been legitimate,” said Dr. Stevens. “Our study population included many participants who consumed these very high levels of folate and we found no increased risk of colorectal cancer in these individuals. Nonetheless, one randomized clinical trial failed to show folate supplementation reduced the risk of adenomas, the non-cancerous colon polyps that can become cancerous, so we need to continue to investigate the influence of folate on cancer development in high risk populations as well as potential differences in the action of natural and synthetic form of this vitamin.”

Reference
Stevens VL, McCullough ML, Sun J, Jacobs EJ, Campbell PT, Gapstur SM. High levels of folate from supplements and fortification are not associated with increased risk of colorectal cancer. Gastroenterology 2011; 141 (1): 98-105.e1.