What role does folate play in young children, and what are the consequences of CFDS?

Vitamin B9, also known as folate, is an important water-soluble vitamin. It plays several crucial roles in overall health and has some very specific and important implications is brain function.

Some of the critical functions that folate is involved with in the brain include:

• Neurotransmitter Synthesis: Folate is involved in the synthesis of neurotransmitters such as serotonin, dopamine, and norepinephrine. These neurotransmitters are essential for regulating mood, behavior, and cognitive function. Folate plays a large role in the synthesis of neurotransmitters involved in mood regulation, such as serotonin and dopamine. Low levels of folate have been associated with an increased risk of depression and other mood disorders.
• Cognitive Function: Folate deficiency has been associated with cognitive impairment, including deficits in memory, attention, and executive function. Maintaining sufficient folate levels may help support optimal cognitive function throughout life.
• Methylation Reactions: Folate is necessary for methylation reactions, which are vital for regulating gene expression and maintaining the integrity of DNA. Methylation also plays a role in neurotransmitter metabolism and the production of myelin, the protective sheath surrounding nerve fibers.
• Homocysteine Metabolism: Folate is involved in the conversion of homocysteine, an amino acid, into methionine. Elevated levels of homocysteine have been associated with an increased risk of cognitive decline, dementia, and Alzheimer’s disease. Folate helps to lower homocysteine levels, thereby reducing the risk of these conditions.

Overall, adequate intake of vitamin B9, whether through diet or supplementation, is essential for supporting brain health and function.

Intake recommendations for folate are provided in the Dietary Reference Intakes (DRIs) developed by an expert committee of the Food and Nutrition Board (FNB) at the National Academies of Sciences, Engineering, and Medicine. DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and sex, include the following:

• Recommended Dietary Allowance (RDA): Average daily level of intake sufficient to meet the nutrient requirements of all healthy individuals; often used to plan nutritionally adequate diets for individuals.
• Adequate Intake (AI): Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA.
• Estimated Average Requirement (EAR): Average daily level of intake estimated to meet the requirements of 50% of healthy individuals.
• Tolerable Upper Intake Level (UL): Maximum daily intake unlikely to cause adverse health effects.

With respect to folate, current RDAs as marked as mcg of dietary folate equivalents (DFEs). The Food and Nutrition Board developed specific DFEs to reflect the higher bioavailability of folic acid than that of food folate. At least 85% of folic acid is estimated to be bioavailable when taken with food, whereas only about 50% of folate naturally present in food is bioavailable. Remember that our current food supply has been fortified with folic acid since 1998 as an initiative to prevent neural tube defects.

In January of 1998, the U.S. Food and Drug Administration (FDA) began requiring manufacturers to add 140 mcg folic acid/100 g to enriched breads, cereals, flours, corn meals, pastas, rice, and other grain products] to reduce the risk of neural tube defects. Because cereals and grains are widely consumed in the United States, these products have become important contributors of folic acid to the American diet. The fortification program increased mean folic acid intakes in the United States by about 190 mcg/day.

Based on these values, the FNB defined DFE as follows:

• 1 mcg DFE = 1 mcg food folate
• 1 mcg DFE = 0.6 mcg folic acid from fortified foods or dietary supplements consumed with foods
• 1 mcg DFE = 0.5 mcg folic acid from dietary supplements taken on an empty stomach

The following table lists the RDA for folate in the United States.

Table 1: Recommended Dietary Allowances (RDAs) for Folate [2]

Folate can be found naturally in many different foods, including green leafy vegetables, fruits and fruit juices, nuts, beans, peas, seafood, eggs, dairy products, meat, poultry, and grains. Folic acid is available in multivitamins and prenatal vitamins, supplements containing other B-complex vitamins, and supplements containing only folic acid.

About 85% of supplemental folic acid, when taken with food, is bioavailable. When consumed without food, nearly 100% of supplemental folic acid is bioavailable.

According to data from the National Health and Nutrition Examination Survey (NHANES), most people in the United States consume adequate amounts of folate. Mean dietary intakes of folate from foods range from 417 to 547 mcg DFE per day for children age 2–19.

About 35% of adults and 28% of children aged 1 to 13 years in the United States use supplements containing folic acid. A large percentage of children aged 1 to 13 years who take folic acid-containing supplements have intakes of folic acid from both fortified food and dietary supplements exceeding the UL of 300–600 mcg per day. Almost all children aged 1 to 8 years who consume at least 200 mcg/day folic acid from dietary supplements have total intakes that exceed the UL. Little is known about the long-term effects of high folic acid doses in children.

Certainly, there seems to be an abundance of folate and folic acid, therefore folate deficiency is relatively uncommon. With this in mind, young children in general should be getting enough folate through their diet.

There are instances, however, where this folate may not be properly transported into the brain. Recently, a particular set of autoantibodies (blocking/binding folate receptor autoantibodies) were discovered, whose presence indicates that the transport of folate into the brain and choroid plexus is hindered. In these cases, several cognitive and neurological symptoms may occur. Interestingly, a large percentage of children who have been diagnosed with autism spectrum disorder have tested positive for these autoantibodies.

It is thought that in these particular cases, the folate receptor autoantibodies affect the function of folate receptor alpha, which is one of the main transports of folate into the brain. The autoantibodies attack this receptor and render it dysfunctional, thereby not allowing folate to pass into the brain. This can create a condition known as cerebral folate deficiency and consequently wreak havoc in the brain.

Most interestingly, in these cases, folate levels may be quite adequate in the blood, indicating that there is no real folate deficiency. The folate receptor autoantibodies, however, prevent folate from getting into the cerebral spinal fluid, thereby creating a folate deficiency in the brain and cerebrospinal fluid. These autoantibodies may be detected through the use of a test known as FRAT^®. Once detected, physicians have found a specific treatment using another reduced folate known as folinic acid. Children that have these autoantibodies and have used folinic acid have shown some promising improvements in their ASD symptoms.

If you suspect any neurological or neuropsychiatric symptoms in your child, it may be a good time to speak to your physician about folate, folate receptor autoantibodies and FRAT^®.