So I have been spending the last few months looking at the comparison of synthetic vs natural or food sourced vitamins and also bio-availability. This has turned out to be such a vast area to talk about that it just cannot be summarised into 1 newsletter. So I will gently spoon feed my findings and would greatly appreciate any feedback or comments. I will start with one B vitamin we all have probably heard of Folate – which is also known further down its conversion route as L-Methylfolate.
What is L-Methylfolate (5-MTHF)?
L-methylfolate is the biologically active form of vitamin B9 or Folate
That means it is the form the human body can actually use in circulation.
L-Methylfolate vs Folic Acid v Folate
The other forms of vitamin B9 you should know are folic acid and folate. These are the forms we eat, although L-methylfolate is also found naturally in some high-folate food too. Folate is often called the natural form of vitamin B9, but it actually refers to a family of different compound that occur naturally in some vegetables. Folic acid is the supplemental or “synthetic” form of vitamin B9 and is typically the first line of treatment for folate deficiency and related health conditions, such as high homocysteine and Neural Tube Defects. Recommended to take before and in the first few months of pregnancy in the UK. In fact, it has been so beneficial for the general population that the addition (fortification) of folic acid to wheat flour is now mandatory in Australia, USA, Canada and several other countries.
But note that folic acid is also found naturally in foods, as it is just another compound of folate.
Any folic acid we ingest must be metabolised (converted) into Dihydrofolate (DHF), Tetrahydrofolate (THF), and then finally into L-methylfolate (5-MTHF) to be used in the body. Once in this form it can be transported into cells, tissues and even across the blood-brain barrier. This is when questions may arise on bio availability. Issues can arise during metabolism for those with an enzyme issue, such as an MTHFR mutation. These individuals cannot complete the final metabolic step that converts folic acid to the active form L-methylfolate (5-MTHF.) Which can cause problems and deficiency of this vitamin.
Benefits of L-Methylfolate (5-MTHF)
Supplementing with L-methylfolate bypasses the entire folic acid metabolism cycle, which is good news if you have an MTHFR mutation. Studies show that L-Methyfolate supplementation is equally (if not more) effective than folic acid for increasing circulating folate in those with an MTHFR mutation. It is also highly effective at reducing homocysteine levels in healthy people.
It is also better absorbed and interacts with fewer medications than folic acid.
Methylfolate provides the methyl group for the re-methylation of homocysteine to methionine in the methylation (or methionine) cycle. The purpose of this cycle is to generate S-adenosyl methionine (SAM) the universal methyl donor and homocysteine is regenerated to methionine in the process. As homocysteine is such an inflammatory radical, if elevated levels are unresolved this will start a cascade of inflammatory responses in an individual. Homocysteine is now known to be an independent risk factor for heart disease and Alzheimer’s disease. Homocysteine levels can be increased when insufficient levels of ‘methyl group’ foods are consumed. Or as discussed above if we have a genetic mutations (eg MTHFR) mean that insufficient folate (from food or folic acid supplements) is converted to the active form.
There are several important factors to consider before starting L-methylfolate (5-MTHF).
• Supplementing L-methylfolate bypasses the body’s natural checkpoints for preventing over-methylation. So we must be incredibly cautious with the dosage, as unnatural levels of folate is linked with several issues including cancer risk.
• As with almost any supplement, this is not something you should take forever. Nor even everyday in most cases, but rather as a complementary medicine prescribed by your doctor. L-methylfolate also exists naturally in foods, so that should be your preferred source.
• Your vitamin B levels – particularly vitamin B12 (cobalamin) – must be adequate before taking L-methylfolate. Otherwise homocysteine cannot be broken down and transformed, even with adequate folate.
• Minimise intake of folic acid. That means shop-bought bread and anything else made with fortified wheat flour when taking a supplement.
• L-methylfolate (or any other form of vitamin B9 supplementation) can interact with numerous drugs and medications, so be sure to speak with your doctor first.
• If you have been diagnosed with depression, you must first be screened for risk of bipolar disorder. Folate can enhance antidepressant effects of known antidepressant drugs, and is believed (although not clinically proven) to potentially trigger mixed/manic episodes in those with bipolar.
Recommended L-Methylfolate Dosage and Product
L-methylfolate (5-MTHF) can be obtained with or without prescription, but for non-prescribed supplements ensure the label specifies the amount of active L-methylfolate. Prescription folate is available in 7 mg and 15 mg dosages which is very high. Unless recommended by your doctor, starting at less than 1 mg (1000 mcg) and then re-assessing is much more sensible if you are using because of an MTHFR mutation. 500 mcg (0.5 mg) or less appears to be the safest starting point, but always check with your doctor before taking any new supplements.
