QUATREFOLIC, the "active form" of folate is safer, more soluble, more stable and more bioavailable than regular folate.
Folate and Our Needs in the Modern World
Most folate consumption is coming from folic acid, the synthetic version in supplements which is also added to foods. Folic acid (like food folate) is inactive and must be metabolised to 5-methyltetrahydrofolate (5-MTHF) to become metabolically active. Today we know that this is a complex metabolic process.
Many people taking folic acid supplements may still be gravely folate deficient; this is because numerous genetic variations can impair the conversion of folic acid into the bioactive form in many people. Despite this folate intake is often poor in the diets of many people for various reasons. Natural folates are susceptible to oxidation and 90% can also be destroyed by cooking. Typical folates also have a low and incomplete bioavailability. [1,2]
The methyltetrahydrofolate reductase (MTHFR) is a polymorphic enzyme. Various genetic variations can occur which may impair MTHFR activity and the resulting conversion of folic acid into 5-MTHF. 57% of the population is estimated to have a MTHFR polymorphism and do not produce adequate or effective MTHFR.
The emerging field of nutrigenomics has now shed light on how MTHFR polymorphism’s are implicated in chronic disease states. Folate and dietary folate may contribute to supporting adequate methylation and overall health.
There are currently more than 50 identified MTHFR variants, the two prime variants are C677T and A1298C. The number identifies the location on the MTHFR gene and the letters to the amino acid position. The MTHFR gene is reported as either heterozygous or homozygous. 
Compared to a normal MTHFR enzyme, polymorphic variants may function at 55% to 70% efficiency. Homozygous implies two genes are affected which may mean an enzyme efficiency decrease to approximately 7% to 10% compared to normal. Also, more common in those predisposed to cancer, heart disease and autism. The mutation frequency can exceed 90% of these populations. 
MTHFR gene mutations may affect over 40% of the world population, which to date has been largely ignored.
Current population data shows gaps especially in some ethnic groups or large geographical areas: about 50% women in Caucasian (higher in the North American Caucasians, Italian and the Hispanics), Mexico (34.8%) and in the North part of China (around 20%) (6,7]
"UMFA", unmetabolised folic acid in the serum
Studies have now found an increase in the serum of unmetabolized folic acid (UMFA) levels with increased concern over potential risk of adverse effects. Evidence suggests that high intake (≥1 mg/d) of folic acid may worsen some pre-existing cancers or progression of precancerous lesions, such as in the colon and prostate. In older women, with high levels of UMFA, the natural killer cell activity has been reported to be decreased. Evidence also suggests that UMFA can mask vitamin B12 deficiency and potentially worsen neurological damage with prolonged B12 deficiency. [8,]
QUATREFOLIC, the "active form" of folate does not add to the build up of unmetabolised folic acid in the blood.
Increased need for folate
Dietary intake is inadequate
Pregnancy and lactation
Digestive system disorders
Preconception both males and females
Aging & Older People (Mild Cognitive Impairment)
Excessive alcohol intake
Medications compromising folate
Taking certain antacids, antibiotics, anticonvulsants, antidepressants, anti-inflammatory drugs, diuretics, pain killers, corticosteroids, oral contraceptives, HRT, medication for cholesterol, diabetes, hypertension, Parkinson’s & ulcers for extended periods may affect folate levels.
Considerations for supplements
Animal studies and human clinical trial confirm that Quatrefolic® has a superior bioavailability profile over (6S)-5-methyltetrahydrofolate calcium salt and folic acid. In a single dose, balanced, two sequences, two periods, two treatments randomized crossover study.