Vitamin B9 — collectively referred to as "folate" — encompasses a family of chemically related compounds essential for DNA synthesis, DNA repair, and methylation reactions throughout the body. The two most relevant forms in human nutrition are folic acid (the synthetic, fully oxidised form used in supplements and fortified foods) and natural folate (found in food as a mixture of reduced forms, primarily tetrahydrofolate and its derivatives). A third form, methylfolate (specifically 5-methyltetrahydrofolate, or 5-MTHF), is the predominant circulating form of folate in the bloodstream and the active form delivered to cells.
The metabolic pathway
Folic acid from supplements or fortified food is biologically inert — it must be converted through a multi-step enzymatic pathway to become the active 5-MTHF. The critical enzyme in this conversion is MTHFR (methylenetetrahydrofolate reductase). MTHFR converts 5,10-methylenetetrahydrofolate to 5-MTHF, which is then used to remethylate homocysteine to methionine — a reaction that also requires vitamin B12 (as methylcobalamin).
MTHFR gene variants
The MTHFR gene has two common variants (single nucleotide polymorphisms) that affect enzyme function:
- C677T: The most studied variant. Homozygous individuals (TT genotype) have only about 30% of normal MTHFR enzyme activity. Heterozygous individuals (CT genotype) have approximately 65% of normal activity. Homozygous C677T is associated with elevated homocysteine levels.
- A1298C: A second variant, generally associated with less severe reductions in enzyme activity.
These variants are common — approximately 10–15% of most populations are homozygous for C677T. For individuals with reduced MTHFR activity, supplementing with pre-methylated 5-MTHF (methylfolate) bypasses the conversion step and may be more effective than folic acid at raising active folate levels.
Neural tube defects and pregnancy
The most robustly established role of folate supplementation is the prevention of neural tube defects (NTDs) — congenital abnormalities of the brain and spinal cord (spina bifida and anencephaly) that occur during neural tube closure in the first 28 days after conception. Large randomised trials and population studies established that women who had adequate folate intake before conception and in early pregnancy had significantly lower rates of NTDs. This evidence led to mandatory folic acid fortification of grain products in the US (1998) and dozens of other countries, and to global recommendations that women of childbearing age supplement with 400–800 mcg of folate daily.
Folate and homocysteine
One biochemical consequence of insufficient folate is elevated homocysteine — an amino acid intermediate that accumulates when the methylation cycle is impaired. Elevated homocysteine is associated with increased cardiovascular risk in observational studies, though randomised trials of B-vitamin supplementation (folate + B6 + B12) to lower homocysteine have produced mixed results for actual cardiovascular events, suggesting homocysteine may be a marker rather than a causal factor.
Folic acid and folate in Lebanon
Supplements & More carries folic acid and methylfolate supplements from US brands, available with cash on delivery across Lebanon.