Folic Acid Deficiency Linked to Depression and Cardiovascular Disease

A New York Times article that appeared online January 2, 2010 calls micronutrients—including folic acid—“the world’s healthiest food.” Why? Because folic acid along with iron, zinc and iodine have a profound effect on developing fetuses and can prevent a slew of developmental problems.1

Folic acid, also known as vitamin B9 and folate (the naturally occurring form) is essential to numerous functions in the body including the synthesizing and repairing of DNA, and the breaking down of homocysteine. (Homocysteine is an amino acid in the blood. When elevated, it is a marker for heart disease, stroke and peripheral vascular disease.)

Folate is especially important during periods of rapid cell division and growth. Adults and children need folic acid to produce healthy red blood cells and to prevent anemia. Folic acid is important for functioning of the nervous system at all ages.

Folate deficiency may lead to glossitis (chronic inflammation of the tongue), diarrhea, depression, confusion, anemia, and fetal neural tube defects and brain defects (during pregnancy), in addition to cardiovascular disease.

Folic acid affects mood and cognitive function, especially in older people. Over the past 35 years numerous studies have shown a high incidence of folate deficiency correlated with depression and cognitive decline in people with epileptic, neurological and psychiatric problems.2

Recent studies in elderly people suggest a link between folic acid, homocysteine, depression, and dementia, including Alzheimer’s disease and vascular disease.3

Depression in the elderly

Depression is one of the most prevalent mental health conditions and can affect people of all ages, but it is becoming more common among the older population with increasing life expectancy. Observational studies have found poor micronutrient status (particularly folate and vitamin B12) to be associated with an increased risk of depression in older people. Supplementation with folic acid has been shown to enhance anti-depressant drug treatment and may help improve depressive symptoms in older patients.45

A 2009 study of 669 Chinese adults aged 55 and older found that low levels of serum folate and B12 were associated with greater risk of depression.6

How much should you take?

Oral doses of both folic acid (800 microg daily) and vitamin B12 (1 mg daily) have been shown to improve symptoms of depression.5

The role of folic acid in cardiovascular disease

An estimated 13,500 deaths occur annually due to folate deficiency’s effect on coronary artery disease, and the risk of ischemic heart disease and stroke has been reduced by 15% since folate fortification regulations were enforced.7

Since 1969, high levels of homocysteine have been implicated as an independent cardiovascular risk factor. B-vitamins, particularly folic acid, reduce homocysteine levels effectively, and it has been suggested that supplementation with these vitamins might decrease cardiovascular risk and reduce the risks associated with stroke, coronary heart disease and peripheral artery disease. 8

Additionally, a study published online November 26, 2009, (ahead of the print copy to appear in the International Journal of Food Science Nutrition), shows that high levels of homocysteine are also a predictor of cardiovascular disease and hypertension among children. The aim of the study was to examine the effects of oral folic acid on homocysteine and blood pressure. Five hundred and twenty children participated in the study, and 26 of them were found to have high homocysteine levels. Twenty of these children randomly received 5 mg of oral folic acid supplement while the other six children were the controls.

Serum homocysteine levels, as well as systolic and diastolic blood pressure were statistically significantly decreased in the intervention group compared with the controls, while folic acid levels were statistically significantly increased. The researchers concluded that folic acid might be a safe and effective supplement to reduce homocysteine and possibly blood pressure, which consequently may prevent cardiovascular disease in children in early life.9


  1. Kristof, Nicholas D., World’s Healthiest Food, New York Times online, January 2, 2010.
  2. Reynolds, EH. Folic acid, ageing, depression, and dementia. BMJ. 2002 June 22; 324(7352): 1512-1215.
  3. Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM, et al. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer’s disease. Arch Neurol. 1998;55:1449–1455.
  4. Williamson C. Dietary factors and depression in older people. Br J Community Nurs. 2009 Oct;14(10):422, 424-6
  5. Coppen A, Bolander-Gouaille C. Treatment of depression: time to consider folic acid and vitamin B12. J Psychopharmacol. 2005 Jan;19(1):59-65
  6. Ng TP, Feng L, Niti M, Kua EH, Yap KB. “Folate, vitamin B12, homocysteine, and depressive symptoms in a population sample of older Chinese adults.” J Am Geriatr Soc. 2009 May;57(5):871-6.
  7. Iowa State University Extension publication, Sept. 2004.
  8. Ntaios G, Savopoulos C, Grekas D, Hatzitolios A. The controversial role of B-vitamins in cardiovascular risk: An update. Arch Cardiovasc Dis. 2009 Dec;102(12):847-54.
  9. Papandreou D, Malindretos P, Arvanitidou M, Makedou A, Rousso I. Homocysteine lowering with folic acid supplements in children: Effects on blood pressure. Int J Food Sci Nutr. 2009 Nov 26. [Epub ahead of print]