THE 4TH GENERATION FOLATE

Quatrefolic® is the fourth generation folate derivatives, a new generation of folate derivative made up of (6S)-5-methyltetra-hydrofolate and glucosamine salt which is able to overcome the existing calcium salt form limitations related to stability, poor solubility and bioavailability. This new source of folate has four key critical factors that make it a successful product: bioavailability, safety, stability and formulation flexibility.

Actually there are differences in the forms:

1st generation – Food folate

2nd generation – Folic acid

Folic acid lacks coenzyme activity and must be reduced to the metabolically active form within the cell, through a series of biochemical steps before it can be used by the body’s cells in vital metabolic pathways such as DNA production, cell reproduction and homocysteine metabolism.

3rd generation – (6S)-5-methyltetrahydrofolate calcium salt

The calcium salt of 5-methyltetrahydrofolate is available commercially and represents the third generation of folate. Until now, 5-methyltetrahydrofolate calcium salt was the only folic acid derivative available on the market, and able to penetrate the body cells without the need of further metabolism process.

The 4th generation: Quatrefolic®

Quatrefolic® represents the fourth generation folate endowed with long lasting stability as well as a peculiarly high water solubility, improved bioavailability and well established safety.

Solubility

QUATREFOLIC® is 100 times more soluble in water than calcium salt. Quatrefolic® demonstrates a surprisingly high solubility in water greater than 1 g/ml – compared with the slight solubility of the reference compound, (6S)-5-methyltetrahydrofolate calcium salt (1.1 g/100 ml).

Bioavailability

The pre-clinical study was a direct bioavailability comparison between Quatrefolic®, the (6S)-5-methyltetrahydrofolic calcium salt and folic acid. After single oral dosing in rats, Quatrefolic® showed plasma levels about 20% higher than those reached after a corresponding dose of the calcium salt.

Stability

Quatrefolic® shows an extraordinary long lasting chemical stability guaranteeing a quite unaltered purity even after several months, and an assay reduction in 18 months less than 1%, allowing easy handling and storage.

Safety

Quatrefolic®, as glucosamine salt of (6S)-5-methyltetrahydrofolate has been the subject of an extensive and relevant number of biological and toxicological studies in order to prove the safety and tolerability of this revolutionary folate.

Quatrefolic® supplementation allows 5 methyltetrahydrofolate to be immediately bioavailable for its biological action without being metabolized in the body

Quatrefolic® is the first choice in the folate supplementation because it maximizes the benefit of folate supplementation, protecting naturally all women and babies.

Women with MTHFR polymorphism could have a major risk to deliver a child with neural-tube defects, the development of common Congenital Heart Defects (CHD) in infants and children, spontaneous abortion and malformation including Down Syndrome and Autism. MTHFR mutations is implicated in homocysteine levels, a risk factor for recurrent embryo losses in early pregnancy. Maternal MTHFR deficiency resulted also in short-term memory impairment in offspring. The MTHFR also was associated with greater depressed mood during pregnancy and poor mood.( Q-Pregn)

Quatrefolic® as a source of (6S)-5-methyltetrahydrofolate is particularly useful to provide the nutritionally active form of folate to all women, including those with MTHFR polymorphism and to guarantee safe and healthy pregnancy.

Even today in Europe and United States half of pregnancies are unplanned and expose these women to a serious risk since defects of the brain and spine (Neural Tube Defects) develop in the first 28 days of pregnancy – before many women even know that they are pregnant.
Clinical evidence suggests that supplementation of the natural form, 5-MTHF, is a better alternative to supplementation of folic acid, and that can effectively improve folate biomarkers in young women in early pregnancy in order to prevent NTDs.

Spontaneous Abortion
Rapidly developing cells in the embryo may suffer by lack of adequate folate. Failure to produce sufficient DNA and to regulate DNA function could lead to spontaneous abortion.

Down Syndrome
Several studies have investigated maternal enzyme polymorphism in the metabolization of folate as a risk factor for Down Syndrome.

Lactation
Breast milk folate concentrations are maintained at the expense of maternal folate reserves. A lactating woman would require 128 μg/day of additional folate in order to restore her losses.
5-MTHF appeared to be as effective as, and perhaps more effective than, folic acid in preserving RBC folate concentrations during lactation.

Neural tube defects prevalence changes before and after folic acid fortification