The occurrence of neural tube defects (NTDs), a major and common birth defect, is directly linked to insufficient folate levels during preconception and early pregnancy. Early observational studies which were later supplemented by intervention studies provide evidence that folate supplementation can reduce the risk of the recurrence and occurrence of NTDs.
Health authorities throughout the world encourage women of childbearing age to take folate supplements, as there is a direct link between folate levels of a mother-to-be and the health of the unborn child. Studies conducted with Metafolin® have shown benefits of the naturally-occurring predominant form of folate.
Despite having introduced mandatory fortification of grain products with folic acid in 1998, red blood cell folate concentrations in more than 75% of non-pregnant women aged between 15 and 44 in the U.S., are considered too low to safely prevent NTDs in their offspring.
The Essential Role of Folate
Sufficient folate levels are critical throughout our entire life. Less than optimal folate intake has been implicated in the etiology of a variety of disorders including anemia, neural tube defects (NTDs), various forms of cardiovascular diseases (CVD), depression, Alzheimer’s disease and osteoporosis. However, despite the importance of folates, a large part of the population has an insufficient intake of folate from food sources alone.
Folate is the generic term comprising all the folate forms and the synthetic provitamin folic acid. They play a key role in a variety of biochemical reactions and are required, for example, for normal cell division and repair. Natural folates, consisting predominantly of L-methylfolate (such as Metafolin® and Arcofolin®), are found in green leafy vegetables in particular, which also gave this class of substances its name (folium is Latin for leaf).
Unfortunately, it can be challenging to consume the amount of food or beverage necessary to achieve the recommended daily level of folate. For example:
- One liter of orange juice
- One kilogram of vegetables
- ½ kilogram of liver
- Four liters of beer
Preconception and Pregnancy
Infants, Kids, and Adolescents
Sufficient folate levels are critical in life phases of growth, cell division and repair, as folates are needed for the production of DNA building blocks and cell integrity.
Adults and Elderly
Sufficient folate levels are critical in adult and the elderly, as less than optimal folate nutrition has been implicated in the etiology of a variety of disorders including cardiovascular diseases. The homocysteine-lowering effect of folate is said to play an important role in prevention of some of these disorders. The elderly population in particular does not reach the recommended daily intake (RDI). In most European countries, folate intake in the elderly (>64 years) is below current recommendation (D-A-CH 2013, NNR 2012).
Heart Health
An increased homocysteine blood level is regarded as a risk factor for cardiovascular diseases and stroke. L-5-Methyltetrahydrofolate is positively involved in this process by increasing folate blood levels and by decreasing homocysteine blood levels. Evidence from a recent meta-analysis suggests that lowering homocysteine with folate may have a beneficial effect on the prevention of cardiovascular diseases and stroke, especially in populations without mandatory folic acid fortification.
Cognitive Impairment, Dementia, and Alzheimer’s
There is a highly significant decline of folate level in the cerebral spinal fluid (CSF) with age and there is evidence causally relating folate status to mental function, especially depression and dementia. Epidemiological studies and case observations suggest that low concentrations of folate in the blood are related to poor cognitive function, dementia and Alzheimer’s disease.
DNA Synthesis and Repair
Folate deficiency is assumed to reduce a cell’s capacity for DNA synthesis and repair. Impaired DNA synthesis would become most obvious in those cells undergoing rapid division. L-methylfolate supplies methyl groups for the synthesis of S-adenosylmethionine (SAM), which is a methyl donor for many methyltransferase enzymes. These enzymes transfer the methyl group to a wide range of substrates as diverse as proteins, lipids, hormones, DNA, etc. The methylation cycle is involved in many important biochemical reactions.