From the Guidelines
Methylfolic acid deficiency is a significant health concern that can lead to a range of serious health implications, including elevated homocysteine levels, neurological symptoms, and increased risk of birth defects and cancer. Methylfolate deficiency occurs when the body lacks sufficient active folate (vitamin B9) in its methylated form, which is essential for numerous biological processes. This deficiency can result from genetic mutations (particularly in the MTHFR gene), poor diet, certain medications, or malabsorption issues, as noted in the context of nutritional deficiencies post-bariatric surgery 1. The health implications are wide-ranging because methylfolate is crucial for DNA synthesis, repair, methylation processes, neurotransmitter production, and homocysteine metabolism. Some key points to consider about methylfolate deficiency include:
- Genetic mutations, such as those in the MTHFR gene, can impair the body's ability to convert folic acid into its active, methylated form
- Poor dietary intake, malabsorption, and certain drug interactions can also contribute to deficiency, as seen in cases of noncompliance with multivitamin administration after bariatric surgery 1
- Deficiency can lead to elevated homocysteine levels, increasing cardiovascular risk, as well as neurological symptoms like depression, anxiety, and cognitive issues
- Birth defects, such as neural tube defects during pregnancy, anemia, compromised immune function, and increased cancer risk are also potential consequences of methylfolate deficiency Treatment typically involves supplementation with L-methylfolate, rather than regular folic acid, to bypass potential conversion issues, with doses ranging from 400-1000 mcg daily for general health, and higher doses for specific conditions. Dietary sources rich in natural folate, including leafy greens, legumes, and liver, can also help mitigate deficiency. Blood tests measuring homocysteine levels and folate status can aid in diagnosis, and for those with MTHFR mutations, genetic testing may be necessary to determine the best supplementation approach.
From the FDA Drug Label
L-METHYLFOLATE CALCIUM Tablets is a medical food for use under medical supervision and direction Folate therapy alone is inadequate for the treatment of a B12 deficiency. A major depressive episode may be the initial presentation of bipolar disorder 5-MTHF has been shown to enhance antidepressant effects of known antidepressants. Antiepileptic drugs (AED): The AED class including, but not limited to, phenytoin, carbamazepine, primidone, valproic acid, phenobarbital and lamotrigine have been shown to impair folate absorption and increase the metabolism of circulating folate
Methylfolic acid (Methylfolate) deficiency is not directly addressed in the provided drug labels. However, it can be inferred that a deficiency in folate, which includes methylfolate, can have significant implications for health, including:
- Masking vitamin B12 deficiency: Folate therapy alone is inadequate for the treatment of a B12 deficiency, and may even mask its detection 2.
- Depression and bipolar disorder: Methylfolate may enhance antidepressant effects, but caution is recommended in patients with a history of bipolar illness 2.
- Interactions with other medications: Folate, including methylfolate, may interact with various medications, such as antiepileptic drugs, capecitabine, and others, which can impair folate absorption or increase its metabolism 2.
The implications of a methylfolic acid deficiency can be significant, and may include:
- Increased risk of depression and bipolar disorder
- Interference with medication efficacy
- Masking of underlying vitamin B12 deficiency However, the provided drug labels do not directly address the question of methylfolic acid deficiency and its implications for health.
From the Research
Methylfolic Acid Deficiency
Methylfolic acid, also known as 5-methyltetrahydrofolate (5-MTHF), is a crucial form of folate that plays a significant role in various bodily functions, including DNA synthesis, cell division, and homocysteine metabolism 3, 4. A deficiency in methylfolic acid can have severe implications for health, particularly in pregnant women, as it can increase the risk of neural tube defects, cardiovascular disease, and cognitive dysfunction 3, 5.
Causes of Methylfolic Acid Deficiency
Methylfolic acid deficiency can be caused by various factors, including:
- Low dietary intake of folate-rich foods
- Poor absorption of ingested folate
- Genetic defects, such as polymorphisms in the MTHFR gene, which can affect the conversion of folic acid to 5-MTHF 6
- Drug interactions that alter folate metabolism
- Vitamin B12 deficiency, which can lead to a buildup of methylfolate and a deficiency in other forms of folate 7
Implications of Methylfolic Acid Deficiency
The implications of methylfolic acid deficiency can be severe and far-reaching, including:
- Increased risk of neural tube defects in pregnant women 4, 5
- Cardiovascular disease and stroke due to elevated homocysteine levels 3
- Cognitive dysfunction and impaired cognitive development in children 3
- Megaloblastic anemia, which can be masked by folic acid supplementation but not by 5-MTHF supplementation 3, 7
Supplementation with 5-MTHF
Supplementation with 5-MTHF can be an effective way to prevent methylfolic acid deficiency, particularly in individuals with genetic defects or those who are pregnant or planning to become pregnant 4, 6, 5. 5-MTHF has several advantages over folic acid, including: