Humans need to maintain an adequate dietary intake of folate during various stages of their lives.

Folate plays an essential role in cell division and DNA synthesis and is involved in human growth and development. Folate deficiency has far-reaching negative health consequences at all stages of life and has been implicated in the etiology of a variety of disorders including but not limited to neural tube defects (NTDs), anemia, various forms of cardiovascular diseases, Alzheimer's disease and osteoporosis, all which have become pervasive health issues around the world in the 20th century.

Folate deficiency symptoms

Folate deficiency may have the following symptoms:

• Weakness
• Irritability
• Lack of energy
• Loss of appetite
• Paleness
• Sore, red tongue
• Mild mental symptoms, such as forgetfulness and confusion
• Diarrhea

The demand for folate increases when human cell growth is very active, such as in pregnancy. Studies have found that low dietary intake of folate increases the risk of delivering a child with several types of birth defects, particularly neural tube defects (NTD) and possibly leading to poor growth in the fetus or placenta.

Periconceptional and the first period after conception are particularly important for folate supplementation especially because a woman often does not know she is pregnant.

It is recommended that for all women folate levels should be high for at least one month prior to possible conception and continued at that level for the first three months of pregnancy.

Quatrefolic® as a source of (6S)-5-methyltetrahydrofolate might be particularly useful to provide the nutritionally active form of folate during preconception, pregnancy and lactation.

Spina bifida and anencephaly are the most common neural tube defects (NTDs) and, in randomized controlled trials, folic acid supplementation before conception and during the first trimester has been shown to reduce the recurrence of NTDs by 72% in women with a previous NTD affected pregnancy.

Data from USA birth certificates indicate a 19% decline in the birth prevalence of NTDs and a 23% decline in the spina bifida prevalence among births conceived after mandatory folic acid fortification (October 1998 through December 1999) compared with the NTD prevalence before folic acid fortification (October 1995 through December 1996) (Honein).

Folate is a critical nutrient when human cell growth is very active and folate deficiency can slow overall growth rate. Infants, children and adolescents are in a critical phase of growth and the proper level of folate is recommended to prevent a variety of medical conditions such as anemia.

Recommended dietary intake of folate for males and females during the age of growth has been defined.

Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. National Academy Press. Washington, DC, 1998."

Quatrefolic® use levels will be the same as that of folate.

There are numerous physical and physiological changes which occur during the aging processes. Several studies have focused on understanding how these changes can influence adults and elderly nutritional requirements, and also how diet and nutrition may influence or modify these changing functions.

Ageing is associated with changes in gastrointestinal function that could possibly affect the absorption of different folate forms. Partly as a result of these changes, a higher incidence of vitamin B12, folate and iron deficiency occurs in older people. This deficiency may be important with respect to blood formation, neurologic function, and cardiovascular function.

Research findings indicate that we can further control heart disease by nutritional means. Recent research shows that the amino acid homocysteine, like blood cholesterol, is a factor that contributes to the risk of coronary disease. The blood level of homocysteine is controlled in humans to a large extent by vitamin B12, vitamin B6, and folic acid.

Epidemiological studies and case observations have suggested that low concentrations of folate in the blood are related to poor cognitive function, dementia and Alzheimer's disease. It has been hypothesized that the relationship between folate deficiency and poor cognitive function may be due to the role of folate in reducing homocysteine blood and its effects on the vascular system.

Concerns about folic acid supplementation

Folic acid intake by fortification should represent an answer to decrease folate deficiency associated with ageing, but some concerns about possible adverse effects in elderly people are present. If high levels of folic acid are consumed from fortified foods, this may mask the diagnosis of vitamin B12 deficiency leading to pernicious anaemia and peripheral nerve damage.

Quatrefolic® does not mask vitamin B12

Quatrefolic®, as (6S)-5-methyltetrahydrofolate, does not mask vitamin B12 deficiency and should represents the right way to decrease homocysteine blood concentration, diminishing the potential for masking.

Clinical studies point out that there could be an association between mental vitality, dementia, Alzheimer's disease and the folate status of the brain. In addition, there might be a direct link between cerebral folate status and depression.

Furthermore, the involvement of folate and homocysteine metabolism has been documented in male and female subfertility.

Plasma folate levels and risk of spontaneous abortion

It has been suggested that the rapidly developing cells in the embryo may suffer from a lack of adequate folate. Failure to produce sufficient DNA and to regulate DNA function could lead to spontaneous abortion.


Folate has a long history of use in conjunction with vitamin B12 for the treatment of macrocytic anemia. Depending on the clinical status of the patient, the dose of folic acid or 5-methyltetrahydrofolate required to reverse macrocytic anemia varies, but the therapeutic dose is usually 800-1,000 µg daily. The duration of therapy to reverse macrocytic anemia can be as short as 15 days after initiation of supplementation, or it may require prolonged supplementation.

Megaloblastic anemia is characterized by red blood cells that are larger than normal. The red blood cells are also deformed, and both their rate of production and their lifespan are diminished. Folate anemia occurs most often in infants, adolescents, pregnant and lactating females, alcoholics, the elderly, and in those with malignant or intestinal diseases.


Homocysteinemia is widely accepted as an independent risk factor for coronary, cerebral, and peripheral vascular diseases.

This has been observed even when presupplementation plasma folate concentrations were well within the range of values currently accepted as reflecting adequate status.

Molecular mechanisms of homocysteine-induced cellular dysfunction include increased inflammatory cytokine expression, altered nitric oxide bioavailability, induction of oxidative stress, activation of apoptosis and defective methylation.

Several randomised placebo-controlled trials are presently being conducted to establish whether folic acid supplementation reduces the risk of cardiovascular diseases by lowering homocysteine blood levels.

Generally, reducing elevated plasma homocysteine means lowering not only an independent risk factor for cardiovascular disease, neural tube defects, other birth defects and altered male and female fertility, but also, Alzheimer's disease, cognitive decline, osteoporosis, rheumatoid arthritis, kidney failure, and cancer.

Depression, Cognitive Impairment, Dementia & Alzheimer

Studies suggest that there is an association between mental vitality, dementia, Alzheimer's disease and the folate status of the brain. In addition, there might be a direct link between cerebral folate status and depression.

A decline in folate levels in the cerebral spinal fluid (CSF) with age has been recognized and there is evidence causally relating folate levels to mental function, especially depression and dementia. Folate deficiency can contribute to depressed mood, and therefore folate supplementation may be useful for some depressed patients.

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