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Folate supplementation reduced the
risk for stroke by 18%, a
significant benefit compared with
placebo. There were some interesting
caveats to the positive results
associated with folate therapy. An
analysis of study characteristics
suggested that only trials lasting
over 36 months demonstrated a
significant benefit for folate
therapy. In addition, folate was
effective only in areas without
grain enrichment and among patients
without a previous history of
stroke.

A deficiency of folate, vitamin B12 or vitamin B6 may increase
blood levels of homocysteine, and folate supplementation has been
shown to decrease homocysteine levels and to improve endothelial
function . At least one study has linked low dietary folate intake
with an increased risk of coronary events. The folic acid
fortification program in the U. S. has decreased the prevalence of
low levels of folate and high levels of homocysteine in the blood in
middle-aged and older adults . Daily consumption of folic-acid
fortified breakfast cereal and the use of folic acid supplements has
been shown to be an effective strategy for reducing homocysteine
concentrations .
Evidence supports a role for supplemental folic acid for lowering
homocysteine levels, however this does not mean that folic acid
supplements will decrease the risk of cardiovascular disease.
Clinical intervention trials are underway to determine whether
supplementation with folic acid, vitamin B12, and vitamin B6 can
lower risk of coronary heart disease. It is premature to recommend
folic acid supplementation for the prevention of heart disease until
results of ongoing randomized, controlled clinical trials positively
link increased folic acid intake with decreased homocysteine levels
AND decreased risk of cardiovascular disease.

Folic Acid and Cancer
Some evidence associates low blood levels of folate with a greater
risk of cancer . Folate is involved in the synthesis, repair, and
function of DNA, our genetic map, and there is some evidence that a
deficiency of folate can cause damage to DNA that may lead to cancer
. Several studies have associated diets low in folate with increased
risk of breast, pancreatic, and colon cancer. Over 88,000 women
enrolled in the Nurses' Health Study who were free of cancer in 1980
were followed from 1980 through 1994. Researchers found that women
ages 55 to 69 years in this study who took multivitamins containing
folic acid for more than 15 years had a markedly lower risk of
developing colon cancer. Findings from over 14,000 subjects followed
for 20 years suggest that men who do not consume alcohol and whose
diets provide the recommended intake of folate are less likely to
develop colon cancer . However, associations between diet and
disease do not indicate a direct cause. Researchers are continuing
to investigate whether enhanced folate intake from foods or folic
acid supplements may reduce the risk of cancer. Until results from
such clinical trials are available, folic acid supplements should
not be recommended to reduce the risk of cancer.
Folic Acid and Methotrexate for Cancer
Folate is important for cells and tissues that rapidly divide .
Cancer cells divide rapidly, and drugs that interfere with folate
metabolism are used to treat cancer. Methotrexate is a drug often
used to treat cancer because it limits the activity of enzymes that
need folate.
Unfortunately, methotrexate can be toxic, producing side effects
such as inflammation in the digestive tract that may make it
difficult to eat normally . Leucovorin is a form of folate that can
help "rescue" or reverse the toxic effects of methotrexate . There
are many studies underway to determine if folic acid supplements can
help control the side effects of methotrexate without decreasing its
effectiveness in chemotherapy. It is important for anyone receiving
methotrexate to follow a medical doctor's advice on the use of folic
acid supplements.
Folic Acid and Methotrexate for Non-Cancerous Diseases
Low dose methotrexate is used to treat a wide variety of
non-cancerous diseases such as rheumatoid arthritis, lupus,
psoriasis, asthma, sarcoidoisis, primary biliary cirrhosis, and
inflammatory bowel disease . Low doses of methotrexate can deplete
folate stores and cause side effects that are similar to folate
deficiency. Both high folate diets and supplemental folic acid may
help reduce the toxic side effects of low dose methotrexate without
decreasing its effectiveness. Anyone taking low dose methotrexate
for the health problems listed above should consult with a physician
about the need for a folic acid supplement.
Caution About Folic Acid Supplements
Beware of the interaction between vitamin B12
and folic acid
Intake of supplemental folic acid should not exceed 1,000 micrograms
(μg) per day to prevent folic acid from triggering symptoms of
vitamin B12 deficiency . Folic acid supplements can correct the
anemia associated with vitamin B12 deficiency. Unfortunately, folic
acid will not correct changes in the nervous system that result from
vitamin B12 deficiency. Permanent nerve damage can occur if vitamin
B12 deficiency is not treated.
It is very important for older adults to be aware of the
relationship between folic acid and vitamin B12 because they are at
greater risk of having a vitamin B12 deficiency. If you are 50 years
of age or older, ask your physician to check your B12 status before
you take a supplement that contains folic acid. If you are taking a
supplement containing folic acid, read the label to make sure it
also contains B12 or speak with a physician about the need for a B12
supplement.
What is the health risk of too much folic acid?
Folate intake from food is not associated with any health risk. The
risk of toxicity from folic acid intake from supplements and/or
fortified foods is also low. It is a water soluble vitamin, so any
excess intake is usually excreted in urine. There is some evidence
that high levels of folic acid can provoke seizures in patients
taking anti-convulsant medications . Anyone taking such medications
should consult with a medical doctor before taking a folic acid
supplement.
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