Dietary Supplement Background Page (Pro)

Folic Acid
In 1998, the FDA implemented the fortification of folic acid in
the refined grain food supply in an effort to decrease the
occurrence of neural tub defects in newborn children. Over 40
countries worldwide have adopted the fortification of folic
acid, and yet this remains a controversial topic.
This fact sheet describes the specific reasoning for the
promotion of folic acid supplementation, as well as addresses
the issues of concern by opposing proponents.
SUPPLEMENT BACKGROUND
Folic acid is the highly absorbable synthetic form of folate, a
water-soluble B vitamin essential for DNA replication and
enzymatic reactions involved in amino acid synthesis. It is
required for the conversion of homocysteine to methionine in
the synthesis of S-adenosyl-methionine, an essential methyl
donor.
Inadequate maternal folate status associated with neural tube
defects (NTD), low infant birth weight, preterm delivery, fetal
growth retardation. Current recommendations for women are
for recurrence 4 mg/day and for occurrence 0.4 mg/day. The
tolerable upper limit for folic acid is
1000 mcg.
Population groups at risk of folate
deficiency:

Women of child bearing years

Non-Hispanic black women

Pregnant women

Alcoholics

People with malabsorptive disorders

Population groups at risk of folate toxicity:

Aged >50 years (5% exceed UL)

Children
EVIDENCE SUPPORTING FORTIFICATION
Neural Tube Defects
Folic acid fortification was followed by a 25-30%
reduction in NTD frequency in the US4.
Periconceptual folic acid supplementation may reduce
NTDs by 50-60%4.

50% of pregnancies are unplanned, therefore FNB

advises intake of 400 g for women of childbearing
age6.
Australian study examined the cost-effectiveness of
mandatory folic acid fortification of foods to reduce
NTDs2.
Authors found the mandatory fortification to be costeffective in the categories of quality-adjusted life-years,
life-years gained, avoided NTD cases and severe
neuropathy cases2.
Dementia and Cognitive Dysfunction
Folic acid supplementation over a 3-year period
significantly improved domains of cognitive function
related to information processing, reaction speed and
overall thinking.
Cardiovascular Disease and Stroke
Supplementation reduced homocysteine levels and risk
of stroke5.
Depression
Low folate has been linked to depression and poor
response to antidepressants
Supplementation may be helpful to support treatment
EVIDENCE AGAINST FORTIFICATION
Neurological Impacts
Doses >400 ug/d increase risk of cognitive decline9.
Masks vitamin B-12 deficiency
Irreversible neurological impacts
Prevalent in elderly
Tumor Progression
May promote progression of existing (pre)neoplastic
lesions7.
Altered Synaptic Transmission
Excessive supplementation during
pregnancy may alter synaptic
transmission and seizure susceptibility
in offspring8.
CONCLUSION

References
1. Honein MA, Paulozzi LJ, Mathews TJ, Erickson JD and Wong LC. Impact of Folic Acid Fortification of the US Food Supply on
the Occurrence of Neural Tube Defects. JAMA. 2001;285:2981-2986.
2. Rabovskaja V, Parkinson B and Goodall S. The Cost-Effectiveness of Mandatory Folic Acid Fortification in Australia. J Nutr.
2013;143(1):59-66.
3. Nilsson K, Gustafson L and Hultberg B. Improvement of cognitive functions after cobalamin/folate supplementation in elderly
patients with dementia and elevated plasma homocysteine. Int J Geriatr Psychiatry. 2001;16(6):609-14.
4. Pitkin RM. Folate and neural tube defects. Am J Clin Nutr. 2007;85(1):285S-288S.
5. Clarke R, Halsey J, Lewington S, et al. Effects of Lowering Homocysteine Levels With B Vitamins on Cardiovascular Disease,
Cancer, and Cause-Specific Mortality: Meta-analysis of 8 Randomized Trials Involving 37 485 Individuals. Arch Intern Med.
2010;170(18):1622-1631.
6. http://ods.od.nih.gov/factsheets/Folate-HealthProfessional/
7. Manshadi SK, Ishiguro L, Sohn K-J, Medline A, Renlund R, et al. Folic acid supplementation promotes mammary tumor
progression in rat model.
8. Girotto F, Scott L, Avchalumov Y, Harris J, Iannattone S, et al. High dose folic acid supplementation of rats alters synaptic
transmission and seizure susceptibility in offspring.
9. Morris MC, Evans DA, Bienias JL, et al. Dietary folate and vitamin B12 intake and cognitive decline among communitydwelling older persons. Arch Neruol. 2005;62:641-645.