Folic Acid Deficiency – Causes and Health Consequences

Folic acid (folate) deficiency is an established risk factor for the development of certain types of cancer, cardiovascular disease, developmental defects (e.g. neural tube defects), and neurological or psychiatric disorders. Folic acid’s health benefits make it a key nutrient for optimising health.

Folic acid (folate) is involved in homocysteine metabolism and inadequate folic acid has been characterized as a major cause of hyperhomocysteinaemia (higl levels of homocystein).

Although most of the adverse effects of low folate (folic acid) levels is explained through its interplay with homocysteine levels, there is evidence suggesting direct health-beneficial effects of folic acid (folate), including its favourable effects on vascular endothelial function.

Endothelial cells line the entire circulatory system, from the heart to the smallest capillary. Endothelial cells are involved in many aspects of vascular biology, including:

    Vasoconstriction and vasodilation, and hence the control of blood pressure
    Blood clotting (thrombosis & fibrinolysis)
    Formation of new blood vessels (angiogenesis)
    Inflammation and swelling (oedema)
    Endothelial cells also control the passage of materials — and the transit of white blood cells — into and out of the bloodstream.

High homocystein levels is a well-established risk factor for atherothrombotic disease, Alzheimer’s disease and other neuropsychiatric disorders, osteoporosis and hip fractures.

Researchers in Ireland found an inverse relationship between tobacco consumption and serum (blood) folate concentrations. Smokers had significantly lower blood folate levels than non-smokers, and folate concentrations decreased by increasing consumption of cigarettes.

A negative association between smoking and folate levels has been reported in other studies, and is generally attributed to the different nutritional status of smokers. More specifically, smokers tend to consume lower amounts of several vitamins, fruits and vegetables, resulting in decreased intake of dietary folic acid.

It should be noted, however, that smoking may have more direct anti folic acid effects, producing local vitamin deficiency in individual tissues as shown in a 1992 study. (Int J Cancer 1992, 52:566-569).

Th researchers in Ireland also found that blood folate concentrations were inversely related to coffee consumption.

Those with higher intakes of potatoes, legumes, fruits and/or vegetables – all foods considered major sources of folic acid (folate) – had a significantly decreased risk for low blood folate, compared to those with no consumption.

On the other hand, higher intakes of cereals and meat products were related to decreased blood folate (folic acid) concentrations.

It should be noted however, that the lower intakes of cereals and meat among the study subjects with lower blood folate levels might be simply due to substitution by other foods, namely fruits, vegetables, and legumes.

Finally, an alternative explanation for the associations between blood folate levels and nutrients and foods, might be that serum folate serves as an overall nutritional biomarker and indicator of diet and health quality.

Christos M Hatzis, George K Bertsias, Manolis Linardakis, John M Scott and Anthony G Kafatos. Dietary and other lifestyle correlates of serum folate concentrations in a healthy adult population in Crete, Greece: a cross-sectional study. Nutrition Journal 2006, 5:5 doi:10.1186/1475-2891-5-5. © 2006 Hatzis et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (

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