Folic acid supplement by
Ray Sahelian, M.D.
Folic Acid health benefit
Folic acid generally functions in cooperation with vitamin
B12 in many metabolic reactions, including the making of DNA. Folic acid helps reduce
levels of homocysteine
and functions as a methyl donor. Folic acid is
found in almost all foods and the recommended daily intake is about 400 micrograms
or 0.4 mg. A shortage of folic acid can
lead to anemia, where
not enough red blood cells are made.
Folic acid is a synthetic compound of folate, and,
for practical purposes the terms are often used interchangeably.
Basically, folate is the form found in foods, and folic acid is the form
available as a supplement.
FDA allows these two qualified health claims for
Folic Acid:
A. Healthful diets with adequate folic acid may reduce a woman's risk
of having a child with a brain or spinal cord defect. The Institute of
Medicine of the National Academy of Sciences recommends that women capable
of becoming pregnant consume 400 micrograms of folic aced daily from
supplements, fortified foods, or both, in addition to consuming food
folic acid from a varied diet."
B. 0.8 mg folic acid in a dietary supplement is more effective in reducing
the risk of neural tube defects than a lower amount in foods in common
form. FDA does not endorse this claim. Public health authorities recommend
that women consume 0.4 mg folic acid daily from fortified foods or dietary
supplements or both to reduce the risk of neural tube defects."
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Also consider folic acid supplement 400 mcg.
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Folic acid 400 mcg.
Folic acid benefit
Folic acid is a nutrient essential for the health and function of DNA. Relative
deficiency of folic acid may occur in pregnancy and hyperproliferative or
chronic inflammatory disorders. Folic acid supplementation could prevent neural
tube defects and in limiting side effects of methotrexate. Supplements of folic
acid may reduce the risk of colon cancer and perhaps reduce cognitive decline.
Folic acid
is one of the vitamins that lower blood levels of homocysteine, which in turn is
a thought to be a risk factor for cardiovascular diseases. Folic acid
supplementation may be helpful in those who have chronic inflammatory skin
diseases, such as moderate to severe psoriasis. For the time being, a daily
supplement of 400 micrograms appears to be sufficient.
Women who take folic acid supplements for at least one year before
they become pregnant reduce their risk of delivering prematurely.
Older individuals may benefit from folic acid supplements as a way
to reduce the risk of dementia.
Folic acid and food sources
You can get folic acid in beans and legumes; citrus fruits and juices;
wheat bran and other whole grains; dark green leafy vegetables; and poultry,
pork, shellfish, and liver.
Folic acid and hearing loss
Folic acid supplementation appears to slow the decline in hearing loss that
commonly occurs with age, at least in people with high blood levels of the amino acid homocysteine. Dr. Jane Durga, from the Nestle Research Center in Lausanne,
Switzerland, and colleagues assessed changes in hearing among 728 subjects,
between 50 and 70 years of age, who were randomized to receive folic acid 800
micrograms or inactive placebo daily for 3 years. Because there is evidence
that folic acid may improve hearing by lowering plasma homocysteine levels, the
researchers excluded subjects who had low homocysteine levels at the start of
the study. At 3 years, the threshold for low frequency hearing increased by 1.0
dB in the folic acid group, significantly less than the increase noted in the
control group. By contrast, high frequency auditory acuity worsened by a similar
extent in each group. Whether the current findings are
applicable to subjects in the US is unclear since at the time of the study,
folic acid fortification of foods was prohibited in the Netherlands and, as a
result, the subjects had baseline folic acid levels that were about half of
those typically seen in the US population. Archives of Internal Medicine January
2, 2007.
Folic acid helpful for mental decline
Among older adults with elevated blood levels of homocysteine, three years of
folic acid supplementation improves
cognitive function to levels generally seen
in people several years younger. Dr. Jane Durga, currently with the Nestle
Research Centre in Lausanne, Switzerland, and her associates in the Netherlands
have been conducting the Folic Acid and Carotid Intima-media Thickness FACIT
trial. The FACIT trial included 818 subjects 50 to 70 years old who were likely
to benefit from folic acid homocysteine lowering effect. Subjects with low
blood levels of homocysteine and those with homocysteine levels caused by
factors other than low folic acid were excluded. The participants were randomly
assigned to folic acid at 800 micrograms per day or placebo. Blood folate levels
at the beginning of the study averaged 12 nanomoles per liter, but by 2004, had
risen to 76 nanomoles per liter, while in the placebo group, it
remained at 13 nanomoles per liter. The average total plasma homocysteine level
was 13 micromole per liter in the folic acid supplement group and 12.9
micromoles per liter in the placebo group. This declined to 10 micromoles per
liter in the folic acid group and rose to 13 in the placebo group. Compared with the placebo group, the folic
acid group had significantly less decline in sensorimotor speed,
information-processing speed, and complex speed. The folic acid group also
improved significantly more than their counterparts in memory and word fluency.
The researchers determined that patients who received folic acid supplements
performed the tests as well as people 5 years younger for memory, 2 years
younger for sensorimotor speed, 2 years younger for information processing
speed, and 1.5 years younger for global cognitive function.
Delayed memory was improved by folic acid to match the
performance of a person nearly 7 years younger. The Lancet, January 20, 2007.
Folic acid and dementia
Lack of folic acid, also called vitamin B-9, increases the risk of developing
dementia in old age. Researchers in South Korea measured naturally occurring
folic acid levels in 518 elderly persons, none of whom showed any signs of
dementia, and then tracked their development over the next few years. At the end
of the period, 45 of the patients had developed dementia, including 34 diagnosed
with Alzheimer's disease. When the researchers rechecked folic acid levels, they
uncovered a strong link with the dementia.
Folic acid and memory
Folate deficiency inhibits proliferation of adult hippocampal
progenitors.
Neuroreport. 2005 Jul 13;16(10):1055-9. Kruman II, Mouton PR, Emokpae R Jr,
Cutler RG, Mattson MP.
Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351
Neurogenesis in the adult hippocampus may play important roles in learning
and memory, and in recovery from injury. The perturbance of homocysteine / folate or one-carbon metabolism can adversely
affect both the developing and the adult brain, and increase the risk of neural
tube defects and Alzheimer's disease. Ddietary folic acid
deficiency dramatically increases blood homocysteine levels and significantly
reduces the number of proliferating cells in the dentate gyrus of the
hippocampus in adult mice. In vitro, the perturbance of one-carbon metabolism
represses proliferation of cultured embryonic multipotent neuroepithelial
progenitor cells and affects cell cycle distribution. Dietary folate deficiency inhibits proliferation of neuronal progenitor cells in
the adult brain and thereby affects neurogenesis.
Dr. Sahelian's comments: Folic acid could benefit those
with folic acid deficiency, but it is unlikely those with normal folic acid
levels would have a memory improvement by taking a folic acid supplement.
Benefits of folic acid
- homocysteine
Folic acid reduces plasma homocysteine levels and may be an important therapy
for preventing cardiovascular disease. A key mechanism in the benefit of folic
acid in heart disease may be the reduction of
arterial stiffness. Folic acid is a safe and effective supplement that targets large artery
stiffness and may prevent isolated systolic hypertension.
Folic acid and osteoporosis
Folic acid and other B vitamins seem even more of a wonder drug than anyone
suspected: Already known to prevent severe birth defects and heart attacks, they
may also reduce the risk of osteoporosis.
Folic acid and colon cancer
A suboptimal intake of folic
acid may play a role in the development of colorectal cancer, which points to a
possible role for folic acid supplementation in colorectal
cancer prevention. In
individuals with colorectal adenomas -- polyps that can be precursors to bowel
cancer -- folic acid supplementation reverses so-called DNA hypomethylation.
Effect of folic
acid supplementation on genomic DNA methylation in patients with colorectal
adenoma.
Gut. 2005 May;54(5):648-53. Pufulete M, Al-Ghnaniem R, Khushal A, Appleby P,
Harris N, Gout S, Emery PW, Sanders TA. Nitritional Sciences Research Division,
Department of Nutrition and Dietetics, King's College London, Franklin Wilkins
Building, London SE1 9NH, UK
A low dietary folate intake can cause genomic DNA hypomethylation and may
increase the risk of colorectal neoplasia. The hypothesis that folic acid
supplementation increases DNA methylation in leucocytes and colorectal mucosa
was tested in 31 patients with histologically confirmed colorectal adenoma using
a randomised, double blind, placebo controlled, parallel design.
Subjects were randomised to receive either 400 microg a day folic acid supplement
or placebo for 10 weeks. Genomic DNA methylation, serum and
erythrocyte folate, and plasma homocysteine concentrations were measured at
baseline and post intervention. Folic acid supplementation increased
serum and erythrocyte folate concentrations and decreased plasma homocysteine concentration. Folic acid supplementation resulted in increases in
DNA methylation in leucocytes and in colonic mucosa. These
results suggest that DNA hypomethylation can be reversed by physiological
intakes of folic acid.
Chemopreventive
role of folic acid in colorectal cancer.
Front Biosci. 2004 Sep 1;9:2725-32. Majumdar AP, Kodali U, Jaszewski R.
Veterans Affairs Medical Center, Karmanos Cancer Institute, Department of
Internal Medicine, Wayne State University, Detroit, Michigan
Accumulating evidence suggests that folic acid, a water soluble
vitamin, could be an effective chemopreventive agent for colorectal cancer.
Results from several studies have demonstrated that a diet deficient in folic
acid may be associated with an increased risk of colonic neoplasia, whereas
dietary supplementation of this nutrient may be chemopreventive. Although the
mechanisms by which folic acid exerts its chemopreventive role in colorectal
carcinogenesis remain to be fully elucidated, supplemental folic acid has been
shown to arrest the loss of heterozygosity of the tumor suppressor gene DCC (deleted in colorectal cancer) and to stabilize its protein in normal
appearing rectal mucosa of patients with colorectal adenomas. Data from in vitro
studies utilizing colon cancer cell lines suggest that supplemental folic acid
or its metabolite 5-methyltetrahydrofolate (5-MTF) attenuates the expression and
activation of EGF-receptor (EGFR) as well as proliferation of cells. The folic
acid mediated reduction of EGFR function could partly be the result of
suppression of EGFR gene through increased methylation of CpG sequences within
its promoter.
Folic acid and rheumatoid arthritis
Folic acid may be helpful in
rheumatoid arthritis patients on methotrexate.
Folic acid and stroke
After folic acid fortification of enriched grain products was fully
implemented in 1998, deaths due to strokes dropped rapidly in the US and Canada.
The main reason for folic acid fortification was to reduce the number of babies
born with neural tube defects such as spina bifida. There is "accumulating,
controversial evidence" that homocysteine -- an amino acid in the blood -- is a
risk factor for stroke and heart disease, Dr. Quanhe Yang, from the Centers for
Disease Control and Prevention in Atlanta, said in a statement. Folate decreases
homocysteine levels, which may help explain the drop in stroke deaths. Yang's
team compared stroke mortality trends between 1990 and 2002 in the US and Canada
with those in England and Wales, where folate fortification is not required.
Stroke mortality was already falling in the US and Canada from 1990 to 1997, but
in 1998 a precipitous drop began, the report indicates. In the US, the annual
decrease in mortality during the earlier period was 0.3 percent, whereas
starting in 1998 the reduction was 2.9 percent. Similar results were seen in
Canada. By contrast, stroke mortality rates did not decline significantly in
England and Wales between 1990 and 2002. Source: Circulation, March 14, 2006.
Folic acid appears to lower the risk of hemorrhagic strokes,
strokes caused by bleeding in the brain.
Benefit of folic acid in depression
Reduced plasma, serum, or red blood cell folic acid is commonly found in major
depressive illnesses. Supplementing antidepressant medication with folic acid
enhances the therapeutic effect. Although more work is required to confirm these
beneficial results, it is suggested that, meanwhile, 0.4 to 0.8 mg of folic acid
be given during the acute, continuation, and maintenance treatment of
depression.
Folic acid and pregnancy
Pregnant women
with low levels of folic acid in their blood are more likely to have a baby with
a low birth weight, Folate is essential for fetal growth and gene expression,
helping produce and maintain new cells. Women are already advised to take folic
acid supplements, a synthetic compound of folate, before conceiving and during
the early months of pregnancy, to reduce the risk of defects such as spina
bifida, a defect of the spinal column. Researchers from the University of
Newcastle upon Tyne examined folate levels in red blood cells for nearly 1,000
pregnant women and looked at lifestyle data. They found higher folate levels in
women were associated with increased birth weight for their babies -- a marker
for good health in infancy and later in life.
Folic acid and neural tube defects
Researchers who reviewed birth-defect data from 21 states before and after the
FDA mandated the fortification of grain products with folic acid have found that
spina bifida and anencephaly decreased by about one third. However, since
current fortification levels do not guarantee that pregnant women will consume
the recommended amount of 400 micrograms a day, supplementation is still
appropriate for women likely to get pregnant.
Folic acid in the diet not only helps prevent birth
defects but also improves the one-year survival rate of children who are born
with defects.
Folic acid fortification in Canada
In 1998,
folic acid fortification of a large variety of cereal products became mandatory
in Canada, a country where the prevalence of neural-tube defects was
historically higher in the eastern provinces than in the western provinces. A
review of the benefits completed in 2007 indicates food fortification with folic
acid was associated with a significant reduction in the rate of neural-tube
defects in Canada. The decrease was greatest in areas in which the baseline rate
was high.
Folic acid and cleft lip prevention
Women who take a folic acid supplement in early pregnancy can reduce the risk of
cleft lip in their baby. Folic acid has been recommended to prevent neural tube
disorders such as spina bifida. But its impact on cleft clip has been less
clear. "Folic acid supplements during early pregnancy seem to reduce the risk of
isolated cleft lip (with or without cleft palate) by about a third," according
to Allen Wilcox of the National Institute of Environmental Health Sciences in
Durham, North Carolina.
Biochemistry of
folic acid
Folic acid is a water-soluble B vitamin and enzymatic cofactor that is
necessary for the synthesis of purine and thymidine nucleotides and for the
synthesis of methionine from homocysteine. Impairment of folic acid -mediated
one-carbon metabolic pathways can result from B-vitamin deficiencies and/or
single nucleotide polymorphisms, and increases risk for pathologies, including
cancer and cardiovascular disease, and developmental anomalies including neural
tube defects. The coenzyme form of folate is called tetrahydrofolate.
Folic acid intake and minorities
Racial and ethnic differences in blood levels of folate persist despite
the fortification of food with folic acid in the US. Even after the US cereals
and grains were fortified with folic acid in 1998, women in racial and ethnic
minority groups have lower serum folate levels than women who are non-Hispanic
whites, Latina, black or Pacific Islander women, as well as women who are
overweight and obese, may be particularly at risk of having lower folate levels.
In one study, folate levels were the highest among women who consistently used
vitamins and were progressively lower among women who had just started taking
vitamins, were former vitamin users or did not take vitamins. Women who were
underweight or normal weight had the highest average folate levels, the
researchers note, and values were lower for overweight women and lowest for
obese women. Folate deficiency is linked to an increased risk of having a baby
with a neural tube defect like spina bifida.
Folic acid supplement questions
Q. What is the ideal dose of folic acid supplement to lower homocysteine
levels?
A. Each person has a different requirement and dietary
intake, but it appears from most studies that 400 mcg of folic acid, or 0.4 mg,
to be adequate. Because of lower baseline homocysteine values due to consumption
of folic acid fortified food, the degree of the homocysteine lowering response
to supplemental folic acid would be expected to be less in North American
countries than in countries without folic acid food fortification.
This folic acid
page was last updated in Feb 2008.
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