Fortifying cereal grains has been effective in increasing serum folate levels, reducing neural tube defects and other fetal malformations.1 2 3 An examination of the 1994 edition of the National Health and Nutrition Examination Survey (NHANES) shows mean serum folate concentrations for all women of childbearing age increased from 6.3ng/mL in the time prior to fortification to 16.2ng/mL after fortification (NHANES, 1999). Neural tube defects and other birth defects have decreased by 20% since fortification began in 1998.4 However, folate adequacy not only reduces birth defects, it also reduces pregnancy complications such as pre-eclampsia (the most common cause of maternal death in Westernized countries).5

Folate has many roles, but transfer of methyl groups to amino acids and DNA are critical. Homocysteine's methylation to methionine is impaired even without overt folate deficiency, so homocysteine levels rise in the bloodstream. It is a marker of heart disease risk on par with elevated cholesterol and also is linked with cancer, dementia and Alzheimer's disease.

Folate and Chronic Disease

Numerous studies show that those with the highest folate intakes had a 30%-60% reduction in risk of cardiovascular and related diseases, including stroke, when compared with those with the lowest intakes.6 7 8 9 10 Folate also reduced the risk of various cancers. Low folate intakes are associated with increased occurrence of colorectal cancer and precursors such as polyps, especially if alcohol intake is high.11 12 Low folate intakes were associated with increased risks of breast, lung (amongst former smokers), cervical, and mouth and throat cancers.13 14 15 16

Folate and Brain Function

Low folate levels are related to depression.17 Young adults with major or mild depression had lower folate levels than those with no depression.

Elevated homocysteine levels may render the brain vulnerable to age-related neurodegenerative disorders by subjecting cerebral vessels and neurons to damage caused by oxidative stress seen in Alzheimer's and some dementias.18 19 20 Folate helps to protect against these destructive oxidations, and higher intakes were associated with improved brain function in the free-living elderly.21 Unfortunately, existing dementia was not impacted by folate supplementation.22 Folate deficiency in experimental animals makes them more prone to Parkinson's disease.23


The health benefits of folate are exciting, as are the benefits derived from folate fortification.24 However, more research needs to be done because folate status at the time of conception is critical for preventing birth defects. Tragically, many young women and nearly 30% of the elderly are deficient in folate. Women of child-bearing age should be taught to ingest a variety of folic sources: broccoli, spinach, peas, Brussels sprouts, corn, beans, lentils, oranges, breads and folate-fortified cereals.

The preventative effects of folate in terms of chronic disease and dementia means that the entire population needs to be more folate-conscious in order to reap the B-vitamin's benefits. Further fortification of foods such as whole grains, as well as a general educational effort, also may be important industry steps.


1Refsum H, 2001. Folate, vitamin B12 and homocysteine in relation to birth defects and pregnancy outcome. Br J Nutr.; 85 Suppl 2:S109-13

2Wilson RD, et al., 2003. The use of folic acid for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can.; 25:959-73

3Moore LL, et al., 2003. Folate intake and the risk of neural tube defects: an estimation of dose-response. Epidemiology; 14:200-5

4Wald NJ, et al., 2001. Lancet; 358:2069-73

5Patrick TE, et al., 2004. Homocysteine and folic acid are inversely related in black women with pre-eclampsia. Hypertension; 43:1279-82

6Voutilainen S, et al., 2001. Low dietary folate intake is associated with an excess incidence of acute coronary events: The Kuopio Ischemic Heart Disease Risk Factor Study. Circulation; 103:2674-80

7Wilmink AB, et al., 2004. Dietary folate and vitamin B6 are independent predictors of peripheral arterial occlusive disease. J Vasc Surg.; 39:513-6

8Merchant AT, et al., 2003. The use of B vitamin supplements and peripheral arterial disease risk in men are inversely related. J Nutr.; 133:2863-7

9Wolters M, et al., 2004. Age-associated changes in the metabolism of vitamin B(12) and folic acid: prevalence, aetiopathogenesis and pathophysiological consequences. Z Gerontol Geriatr.; 37:109-35

10He K, et al., 2004. Folate, vitamin B6 and B12 intakes in relation to risk of stroke among men. Stroke; 35:169-74.

11Giovannucci E, et al., 2003. Methylenetetrahydrofolate reductase, alcohol dehydrogenase, diet, and risk of colorectal adenomas. Cancer Epidemiol Biomarkers Prev.; 12:970-9

12Martinez ME, et al., 2004. Folate and colorectal neoplasia: relation between plasma and dietary markers of folate and adenoma recurrence. Am J Clin Nutr.; 79:691-7

13Adzersen KH, et al., 2003. Raw and cooked vegetables, fruits, selected micronutrients, and breast cancer risk: a case-control study in Germany. Nutr Cancer.; 46:131-7

14Shen H, et al., 2003. Dietary folate intake and lung cancer risk in former smokers: a case-control analysis. Cancer Epidemiol Biomarkers Prev.; 12:980-6

15Hernandez BY, et al., 2003. Diet and pre-malignant lesions of the cervix: evidence of a protective role for folate, riboflavin, thiamin, and vitamin B12. Cancer Causes Control.; 14:859-70

16Pelucchi C, et al., 2003. Folate intake and risk of oral and pharyngeal cancer. Ann Oncol.; 14:1677-81

17Tucker KL, et al., 2004. Breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 increases vitamin concentrations and reduces homocysteine concentrations: a randomized trial. Am J Clin Nutr.; 79:805-11

18Shea TB and Rogers E., 2002. Folate quenches oxidative damage in brains of apolipoprotein E-deficient mice: augmentation by vitamin E. Brain Res Mol Brain Res.; 108:1-6

19Mattson MP, 2003. Will caloric restriction and folate protect against AD and PD? Neurology; 60:690-5

20Mattson MP, 2003. Gene-diet interactions in brain aging and neurodegenerative disorders. Ann Intern Med.; 139(5 Pt 2):441-4

21Requejo AM, et al., 2003. Influence of nutrition on cognitive function in a group of elderly, independently living people. Eur J Clin Nutr.; 57 Suppl 1:S54-7

22Malouf M, et al., 2003. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev.; CD004514

23Duan W, et al., 2002. Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson's disease. J Neurochem.; 80:101-10

24Morris MS, et al., 2003. Depression and folate status in the US Population. Psychother Psychosom; 72:80-7.