What are Vitamin B9 dietary sources?
Vitamin B9 is an essential dietary component due to its important role in metabolic functions. B9 is crucial for DNA synthesis, proliferation, and repair, as well as the metabolism, synthesis, and recycling of methionine, an amino acid important for protein synthesis.
Furthermore, it plays a part in several other biosynthetic and catabolic reactions in the body. Vitamin B9 is commonly referred to as folate, which is the generic name for a large number of compounds, and the synthetic form of B9 is folic acid.
Sources of Vitamin B9 include:
- Dark green vegetables
- Fortified cereals
- Orange juice
The current recommended daily intake is 200 mcg per day, which the National Diet and Nutrition Survey suggests is easily met by the UK population.
It is important to note that due to its chemically unstable structure, only approximately 50% of B9 is absorbed from food. Therefore, intake data that does not take this into account may not accurately represent B9 status in the body, as shown by the low blood folate levels observed in young women, despite intake appearing adequate.
Absorption is observed to increase at high pH levels such as in the presence of milk, due to increased stability of binding proteins, though it is also reduced by alcohol and conjugase (breakdown enzymes) inhibitors in food. The synthetic form however, is entirely absorbed, therefore those taking supplements do not need to be concerned that they are not receiving the full amount.
Who is at risk of deficiency?
The recommended daily intake of Vitamin B9 increases to 400 mcg per day during female reproductive years and pregnancy, which may not be being met by these groups. This is particularly important as Vitamin B9 is essential to prevent neural tube defects such as spina bifida in infants. These defects result in severe conditions as the neural tube is what eventually forms the brain and spinal cord. The association between a vitamin B9 deficiency and neural tube defects in babies has been unequivocally demonstrated, with randomised control trials observing that giving participants folic acid reduces the risk of neural tube defects in infants by more than 70%.
Vitamin B9 is absorbed in the small intestine after being cleaved by conjugate enzymes, hence why conjugase inhibitors in food reduce absorption. It is then converted and bound to albumin to be circulated and taken up into tissues. Excess B9 is either stored in the liver to meet requirements during deficiency, or excreted. Deficiency can occur due to inadequate intake over a prolonged period, or malabsorption as a result of disease, drugs, or flattening of micro villi in the gut as a consequence of alcoholism. Several studies have shown a link between excessive alcohol intake and a Vitamin B9 deficiency, and a case study discussing this can be found here.
Consequences of Deficiency
The consequences of a B9 deficiency are not limited to neural tube defects in infants. In the deficient individual it will also cause impaired cell division, megaloblastic anaemia (characterised by a reduced number of red blood cells that are a larger size than usual), abnormal gut mucosa, and neuropathy. The symptoms of deficiency include a sore tongue, fatigue, headaches, and palpitations. Furthermore, deficiency can cause hyperhomocysteine in the blood serum, which itself causes endothelial dysfunction, oxidative stress, thrombosis, and atherosclerosis.
There are a few different ways to measure an individual’s vitamin B9 or folate status. Serum folate provides an indication of their recent intake, whilst red cell folate indicates long term intake. FIGLY (Formiminoglutamic acid) excretion can also be measured, FIGLY is an intermediate in the conversion of the amino acid histidine to glutamic acid. As folic acid is key to the conversion of FIGLY to glutamic acid, in deficient individuals it builds up in excessive amounts and is excreted in urine. Plasma homocysteine can also be used as a biomarker, and typically more than one of these tests will be used to confirm a deficiency is present.
A Case for Mandatory Fortification?
Some countries, though not the UK, have implemented mandatory fortification of folic acid. Though there is some suggestion that increased intake can cause issues by masking vitamin B12 deficiency, this does not appear to occur in America, where fortification is mandatory. Other issues with fortification or increased intake are that an increased dosage of some anti-cancer medications may be required, and insulin resistance in offspring can also occur.
With regards to toxicity of vitamin B9, up to 15mg per day has been observed to be problematic, particularly in the elderly and epileptics, causing insomnia, irritability, and GI distress. To avoid toxicity, the upper intake limit is 1 mg per day. Considering these issues, it may be prudent to target high risk groups rather than employ mandatory fortification, however it is worth nothing that neural tube defects are more common in areas that don’t have mandatory fortification. A summary of the fortification debate developments can be found here.
Similarly, to vitamin B12, the evidence is increasingly pointing to detrimental effects of a sub optimal B9 status, with wide ranging effects including neural tube defects, cardiovascular disease, cancer, and neuropsychiatric disorders. All these outcomes are now thought to be of increased risk even in the absence of abnormal biomarkers or clinical symptoms. This was investigated using data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial, which recruited 101,700 participants.
The results of this data analysis provided evidence that higher intake of dietary folate and foods fortified with folic acid is associated with a decreasing risk of head and neck cancer in a dose-response manner, the full study can be found here. The debate regarding mandatory fortification is ongoing, and isolating and targeting groups at risk of sub optimal levels of both B9 and B12 is undeniably a difficult challenge. For those at risk or concerned about their B9 status, supplementation is a valid tool, especially given the reduced absorption from dietary folate.