5. What is Folic Acid?
Folate is the natural (complex) form
found in foods such as dark-green leafy
vegetables, broccoli, asparagus, lentils,
beans, peanuts, strawberries, kiwi,
orange juice, liver.
Folate in foods can be lost through
processing and cooking, reducing the
amount of available folate.
6. What is Folic Acid?
A diet rich in folate is important, however
the average daily intake of folate from
foods is about 200 micrograms.
Efficacy of folate absorption is estimated
at 50%.
So, of the 200 micrograms that are eaten,
only about 100 micrograms are actually
used by the body.
7. What is Folic Acid?
Folic acid is the synthetic (simple)
form of folate.
Used in nutritional supplements and
food fortification.
Only form that can be transported
across membranes.
Most oxidized and stable form of
folate.
8. What is Folic Acid?
The FDA ruled that starting January 1, 1998,
all cereal and grain products labeled
“enriched” must be fortified with folic acid.
140 mcg FA per 100 grams of flour.
This translates to about 10% of the
recommended daily value for a slice of
enriched bread or 25% of the recommended
daily value for a 1 cup serving of cooked
pasta.
Some cereals are fortified with 100% DV (400
mcg) folic acid per serving.
9. Bioavailability
The structural difference between folic acid
and food folate accounts for differences in
bioavailability, with folic acid being more
readily absorbed.
To take into account this difference in
bioavailability the Institute of Medicine
introduced the Dietary Folate Equivalent
(DFE).
10. Dietary Folate Equivalent
(DFE)
1 mcg of food folate provides 1 mcg of
DFE.
1 mcg of folic acid taken on an empty
stomach provides 2 mcg of DFE.
1 mcg of folic acid taken with food or as
fortified food provides 1.7 mcg of DFE.
11. Where can you get folic acid?
Good sources of folic acid include:
Multivitamins – Most sold in the US have
all the folic acid you need (400 mcg).
Folic acid supplements – These are a
smaller vitamin pills that contain only folic
acid.
Cereals with100% DV of folic acid per
serving.
12. Who needs folic acid?
Just about everyone can benefit from
taking folic acid!
It is an important vitamin that is
recommended for all men and women.
Folic acid is most important for any
female who could possibly become
pregnant.
13. Institute of Medicine
Recommends all women of reproductive age
(capable of becoming pregnant) consume
400 mcg/d of folic acid from supplements or
fortified foods, in addition to a diet rich in food
folate.
For women who have had a previous affected
pregnancy, folic acid supplementation of 4
mg/d is recommended (under physician
supervision).
14. What does folic acid do?
Although the underlying biologic
mechanism is unknown, researchers
have found strong evidence that the B-
vitamin, folic acid, can prevent 50-70%
of neural tube defects (NTD) like
anencephaly and spina bifida.
15. How common are NTD’s?
Estimated 4,000 affected pregnancies yearly.
About 2,500 babies born yearly.
1,500 babies born with spina bifida.
1,000 babies born with anencephaly.
About 1,500 fetuses are miscarried or
terminated after diagnosis.
16. What are Neural Tube
Defects?
Neural Tube Defects (NTDs) are birth
defects of the brain and the spinal cord.
They occur when the neural tube, which later
becomes the brain and the spine, fails to
close properly.
This happens very early in pregnancy,
between the 17th and the 28th day after
conception.
17. What does folic acid do?
Half of all pregnancies are unplanned,
so it is important for women (14 –45 yr)
to get in the habit of taking folic acid so
that their body has it when it is needed
most.
18. What are Neural Tube
Defects?
After the egg and the
sperm unite, cells
divide and multiply to
form an elongated
structure as seen in
day 22.
19. What are Neural Tube
Defects?
A “zippering” effect
closes the groove or
the tube beginning in
the center and going
both up and down as
seen in day 23.
20. What are Neural Tube
Defects?
A defect may occur in the upper or lower
portion of the neural tube.
If the tube fails to close properly on the upper
portion of the neural tube, a brain defect
called anencephaly or another called
encephalocele occurs.
If it fails to close properly along the lower
portion of the neural tube, a spinal defect
called spina bifida occurs.
23. Spina Bifida
The damage that occurs
may lead to muscle
weakness, paralysis, and
loss of bowel and
bladder control.
Hydrocephalus also
occurs frequently in
these babies.
24. China Folic Acid Community
Intervention
NTD/Folic acid support is corroborated
by the recently published results of an
interventional study conducted by the
CDC in two areas of China, one with
high prevalence and the other with low
prevalence of NTDs (N Engl J Med
341:1485-1490, 1999).
25. China Folic Acid Community
Intervention
The investigators found that among
women who took 400 mcg/d of folic
acid from the time of their premarital
examination until the end of the first
trimester of pregnancy, the risk of
NTDs was reduced by 85 % in the
region with high risk for NTDs and by
40 % in the low risk region.
26. Additional Birth Defects
Researchers are studying other
potential benefits of multivitamins
containing folic acid.
Heart Defects
Cleft Lip/Cleft Palate
Limb Defects
Urinary Defects
27. What else does folic
acid do?
Folic acid and other B vitamins are
needed to produce red blood cells.
Folic acid is also necessary for the
production and maintenance of DNA
and RNA, the building blocks of cells.
It may reduce your risk of heart disease,
stroke and certain cancers.
29. Metabolic Role
The roles of folic acid
1) nucleic acid metabolism
2) amino acid metabolism
Its role in nucleic acid metabolism
involves two pathways…
30. Metabolic Role
The first pathway involves purine and
pyrimidine synthesis which makes folic
acid essential for cell division and DNA and
RNA synthesis.
The second pathway includes synthesis of
the methyl donor S-adenosylmethionine
(SAM), used in hundreds of methylation
reactions, including methylation of DNA
(which plays a key role in gene
expression).
31. Metabolic Role
Amino acid metabolism
Folic acid derivatives are needed for the
conversion of the amino acid homocysteine
to methionine.
32. Cardiovascular Disease
Homocysteine is an amino acid in the blood,
too much of it is related to a higher risk of
coronary heart disease, stroke and peripheral
vascular disease.
Evidence suggests that homocysteine may
promote atherosclerosis by damaging the
inner lining of arteries and promoting blood
clots.
Folic acid and other B vitamins help break
down homocysteine in the body.
33. New Evidenced-Based Guidelines for
CVD Prevention in Women
(AHA 2004)
Last year recommendations were published
for CVD preventive care in all women age 20
years and older.
One of these is that folic acid
supplementation should be considered in
high risk women if a higher than normal level
of homocysteine has been detected.
34. Cardiovascular Disease
Several studies have found that higher
blood levels of folic acid and B vitamins
are related to lower concentrations of
homocysteine.
Other evidence shows that low blood
levels of folic acid are linked with a
higher risk of fatal CHD and stroke.
35. March 5, 2004
Researchers reported…
Folic acid fortification of enriched grain
products in the late 1990’s appears to have
resulted in a decline in stroke and ischemic
heart disease deaths.
There has been evidence of three-fold
acceleration in the decline of stroke related
mortality that has been temporarily related to
folic acid fortification.
36. Folic acid may prevent
hypertension
Researchers from Brigham and Women's
Hospital in Boston found that women who
consumed high levels of the B vitamin from
food and supplements significantly reduced
their risk of developing hypertension.
JAMA. 2005;293:320-329.
37. Folic acid may prevent
hypertension
Among younger women who consumed at
least 1,000 micrograms per day of folate from
dietary and supplemental sources, there was
a 46 percent reduction in risk of hypertension
compared to women whose folate intake was
less than 200 micrograms per day.
Older women had an 18 percent reduction in
risk of hypertension.
38. Cancer
Since folic acid is involved in the synthesis,
repair and functioning of DNA (our genetic
map), a deficiency may result in damage to
DNA that leads to cancer.
A relationship between folic acid and several
types of cancers has been observed in
several population-based studies but is most
clearly defined for colorectal cancer and
colorectal adenomas.
39. Colon Cancer
Nurses’ Health Study cohort
After 14 years of follow-up, women
consuming at least 400 mcg/d of total
folate had a 31% decreased risk of colon
cancer.
After 15 years of taking a vitamin
supplement with folic acid, relative risk
of colon cancer was decreased by 75%.
40. Colon Cancer
Nurse’s Health Study and Health
Professionals Follow-up Study.
A 30-40% decreased risk for colorectal
adenomas was found with total folate
intakes greater than 700 mcg/d.
41. Cancer
Epidemiologic studies provide support
for the hypothesis that decreased
methyl group availability may contribute
to cancer risk.
Risks were exacerbated by methyl
deplete diets: high alcohol, low folate,
low methionine.
42. Alzheimer’s Disease
Recent research suggests that folate
deficiency and a high homocysteine
level may increase the risk for
development of Alzheimer's disease
and vascular dementia.
More clinical trials are needed.
43. Folic Acid Deficiency
Folic acid deficiency can lead to
impairment of cell division,
accumulation of possibly toxic
metabolites such as homocysteine, and
impairment of methylation reactions
involved in the regulation of gene
expression.
44. Folic Acid Status
May be affected by:
Genetics
Interactions with medications
Inadequate intake or absorption
45. Genetic Variation
The MTHFR enzyme is important for hemical
reactions involving folate.
A common polymorphism is found in the gene
for the enzyme MTHFR (methylene
tetrahydrofolate reductase), known as C677T
MTHFR.
Approximately 10% of the US population possess the
homozygous polymorphism.
Without the enzyme, homocysteine cannot be
converted to methionine.
As a result, homocysteine builds up in the bloodstream
and methionine is depleted.
46. MTHFR
The C677T variant has been associated with an
increased risk of cardiovascular disease
including coronary heart disease and stroke
in adults.
Research suggests that the variant may be a
risk factor for birth defects that occur during
the development of the brain and spinal cord
(neural tube defects).
47. Auto-Antibodies to Folate Receptor in
Maternal Serum Samples-Case Mothers
Women produce auto antibodies against the
folate receptors preventing the binding and
transport of folic acid to cellular components
during critical periods of embryonic
development. Supplemental folic acid
competes with the auto antibodies and
restores cellular folate concentrations.
Rothenberg et al., N. Engl. J. Med. 350:134-142, 2004
50. Summary of Rothenberg
Study
9 out of 12 (75%) mothers who previously
had a child with an NTD had auto-antibodies
to the folate receptor.
2 out of 20 (10%) mothers who previously
gave birth to non-affected infants had auto-
antibodies to the folate receptor.
51. Malabsorption syndromes, including
Crohn’s disease, tropical sprue, and
gluten sensitive enteropathy can result
in deficiency secondary to inadequate
absorption.
Alcoholism leads to impaired absorption
and poor diet.
Inadequate
Intake or Absorption
52. Drugs that interfere
with Folic Acid
Phenobarbital, phenytoin (Dilantin®), carbamazapine (Tegretol®) and
primidone (Mysoline®) are used to primarily prevent seizures.
Antibiotic combination of trimethoprim and a sulfonamide (Bactrim®,
Septra®) are commonly used for urinary tract infections.
Triamterene (Dyrenium®) is a diuretic used for high blood pressure.
Sulfasalazine (Azulfidine®) is used for ulcerative colitis and other
inflammatory conditions.
Anticonvulsant valproic acid (Depakene®)
Cimetidine (Tagamet®) is used to treat heartburn and reflux.
Beta-blockers and calcium-channel blockers are used for high blood
pressure and certain heart disorders.
Cholestyramine (Locholest®, Questran®) is used to lower cholesterol
levels.
54. Folic Acid Knowledge
2003 Folic Acid Knowledge (All women 18-45y)
79%
21%
10%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
Aware of folic acid Know it prevents birth
defects
Know to take it before
pregnancy
March of Dimes Folic Acid Survey conducted by The Gallup Organization, August 2003
55. Folic Acid Behavior
Daily Use of Vitamin Containing Folic Acid
(Non-Pregnant Women 18-45y)
30%
29%
32%
27%
31%
30%
24%
25%
26%
27%
28%
29%
30%
31%
32%
33%
1997 1998 2000 2001 2002 2003
Daily Use of Vitamin Containing Folic Acid
(Non-Pregnant Women 18-45y)
30%
29%
32%
27%
31%
30%
24%
25%
26%
27%
28%
29%
30%
31%
32%
33%
1997 1998 2000 2001 2002 2003
March of Dimes Folic Acid Survey conducted by The Gallup Organization, August 2003
56. Healthy People 2010
To increase at least by 80%, the
proportion of women of childbearing age
who take a vitamin with the
recommended 400 mcg per day.
57. Health Care Implications
The majority (89%) of women surveyed,
who do not currently take a vitamin
supplement on a daily basis, say they
would be likely to take one if advised to
do so by their physician or other health
care provider.
March of Dimes Folic Acid Survey conducted by The Gallup Organization, August 2003
58. Health Care Implications
Your patients listen to what you tell them.
Regardless of whether or not patients
planning a pregnancy, discuss the importance
of folic acid with all women of childbearing
age.
Make folic acid a routine and standard part of
the delivery of preventative healthcare
services.
