folic acid use in prenatal and antenatal time,dose ,benifites,time of start consmption,folic acid difficiensy,metabolism and role of folic acid in cells,hemolytic disease,high dose folic acid side effect,role of it in preventing cancers,role of folic acid in preventing hypertention,recomend doses in

1. Folic acid disorder managment
DR parichehr pooransari
perinatalogist,shohaday tajrish hospital
This Photo by Unknown Author is licensed under CC BY-SA

2. Up to date:
• Folic acid is also called vitamin B9 and is the synthetic form of the
vitamin, whereas folate is the form found naturally in food. Folinic
acid (also called leucovorin) is a naturally occurring form of reduced
folate that is primarily used to prevent toxicities of methotrexate; it is
more expensive, and while it is effective for treating folate deficiency,
it not typically used for folate repletion in patients without a specific
indication.

3. Up to date:folic acid difficiency
Gastrointestinal disorders that prevent absorption of dietary
folates in the duodenum (eg, bariatric surgery)
● Severe malnutrition, restrictive diets, or reduced oral intake
● Chronic excessive alcohol use, which may be associated with
chronic malnutrition and increased metabolic needs
● Reduced intake of green leafy vegetables if residing in a
country where cereals and grains are not routinely
supplemented with folic acid

4. Up to date:
Chronic hemolytic anemia with increased red blood cell turnover
● Other conditions associated with high cellular turnover such as
severe eczema .
In these cases, oral folic acid at a dose of 1 mg daily is typically
sufficient to prevent deficiency from developing.
Antimetabolites such as methotrexate act by reducing intracellular
folates and cause a predictable megaloblastic anemia.

5. May 14, 2015
• Folic acid is the synthetic form of folate,
• a water-soluble B vitamin that takes part in several critical functions in the human
body.
• The active form of folate is tetrahydrofolic acid.
• It serves in one carbon reductions reactions.
• These reactions are involved in synthesis of nucleotides and amino acids1.
• The amino acids requiring folic acid for metabolism are methionine, cysteine,
serine, glycine, and histidine.
• Folic acid also serves as a coenzyme in conversion of methionine to homocysteine.

6. May 14, 2015
• Methionine conversion also requires vitamin B12 and B6.
• Thus, folate or B12 deficiency can result in an elevated homocysteine level.
• Methionine, as S-adenylmethionine (SAM), serves as the donor of one carbon
units to methylate sites within DNA, RNA, proteins, and phospholipids2.

7. May 14, 2015
• The enzyme responsible for conversion is dependent on riboflavin (B3).
• There are multiple level interactions among the B vitamins required for DNA
synthesis3.
• Folic acid is required for erythropoiesis, thus folic acid deficiency leads to
megaloblastic anemia.
• Adequate dietary intake of folic acid is critical for DNA repair and normal cell
growth.

8. • Adequate folate intake is vital for cell division and homeostasis
due to the essential role of folate coenzymes in nucleic acid
synthesis, methionine regeneration, and in the shuttling,
oxidation and reduction of one-carbon units required for normal
metabolism and regulation (Wagner 1995).

9. • When folic acid is deficient in the diet, oral supplementation is required. The
dosage for supplementation varies by age and underlying conditions.
• For the general population, supplementation for folic acid deficiency is
maintained at a dose of 0.4 mg/day.
• This dose can be increased to 0.8 mg/day for pregnant and lactating women.

10. Washington DC: National Academy Press; 1998:196-305.
• Recommended dietary allowance for folic acid is 400 µg/day for men and
women and 600 µg/day for pregnant woman.
• Lactating women should consume 500 µg/day of folic acid from their diet4.
• The dosages may have to be increased in alcoholics and patients on
anticonvulsant therapy.

11. Valera-Grand D ea. Folic acid supplements during pregnancy and child psychomotor development after the first year of life.
2014;168(11):e142611
• Excessive doses of folate supplementation are not encouraged in pregnant
females.
• Folic acid doses higher than 5000 µg in pregnant females have shown to be
associated with adverse affects including respiratory allergies, delayed
psychomotor development, and insulin resistance.

12. • Valproic acid, phenytoin, carbamazepine, primidone, and phenobarbital are
known to decrease folate levels.
• Dosage adjustments for folic acid supplementation may be necessary in
pregnant females who are taking anti-convulsants16.
• Battino D, Tomson, T. Management of epilepsy during pregnancy. 2007;67(2727-2746)

13. • Folic acid prevents neural tube defects like spina bifida, while its
ability to lower homocysteine suggests it might have a positive
influence on cardiovascular disease.

14. • Neural tube defects (NTD) due to folic acid deficiency have been established
with numerous randomized controlled trials. Supplementation, when begun
preconception, has been shown to decrease the risk of first incidence of
NTDs.
• It is important to note that NTDs associated with folic acid deficiency are
isolated and not associated with syndromes involving NTDs18.
• Prevention of the first occurance of neural-tube defects by periconceptional vitamin supplementation. Dec 24 1992;327:1832-
1835

15. • In addition to NTDs, studies have shown that folic acid supplementation also
decreases the likelihood for having a small for gestational age infant19.
Congenital heart defects (CHD) are also associated with folic acid deficiency.
Studies have shown a reduced risk of CHDs in mothers with adequate
multivitamin and folic supplementation20.
• Protective effect of periconceptional folic acid supplements on the risk of congenital heart defects: a registry-based case -control study in
the northern Netherlands. 2010;31(4):464-471

16. The American Journal of Clinical Nutrition, Volume 87, Issue 3, March
2008, Pages 517–533, https://doi.org/10.1093/ajcn/87.3.517
• In humans, increased folic acid intake leads to elevated blood
concentrations of naturally occurring folates and of
unmetabolized folic acid.
• High blood concentrations of folic acid may be related to
decreased natural killer cell cytotoxicity, and high folate status
may reduce the response to antifolate drugs used against
malaria, rheumatoid arthritis, psoriasis, and cancer.

17. The American Journal of Clinical Nutrition, Volume 87, Issue 3, March
2008, Pages 517–533, https://doi.org/10.1093/ajcn/87.3.517
• In the elderly, a combination of high folate levels and low
vitamin B-12 status may be associated with an increased risk of
cognitive impairment and anemia
• and, in pregnant women, with an increased risk of insulin
resistance and obesity in their children.

18. • Folate deficiency may contribute to aberrant DNA synthesis and
carcinogenesis by decreasing methionine availability and interfering
with normal DNA methylation.
• Biologic and observational evidence suggest that sufficient folate
intake might prevent cancers in certain populations at risk.

19. The American Journal of Clinical Nutrition, Volume 87, Issue 3, March
2008, Pages 517–533, https://doi.org/10.1093/ajcn/87.3.517
• Folate has a dual effect on cancer, protecting against cancer
initiation but facilitating progression and growth of preneoplastic
cells and subclinical cancers, which are common in the
population. Thus, a high folic acid intake may be harmful for
some people.

20. High folate intake may reduce the risk of hypertension.
[ There is insufficient evidence to recommend folic acid
supplementation to reduce the risk of hypertension.
●
It is unclear whether folate intake is associated with hearing loss. There
is conflicting observational evidence about whether increased serum
folate levels are associated with a decreased risk of age-related hearing
loss .

21. • Excess folate intake (approximately twice the recommended dose)
has been associated with peripheral neuropathy, despite normal
serum levels of vitamin B12, in older individuals who have a common
polymorphism in the transcobalamin vitamin B-12 transporter gene

22. • Elevated homocysteine levels have been associated with osteoporosis
and dementia. It is not known whether these associations are causal
and whether lowering homocysteine levels with folic acid
supplementation would affect risk.

23. • In one randomized trial of folic acid supplementation (800 mcg daily
for three years) versus placebo in adults age 50 to 70 years with
elevated homocysteine, those randomly assigned to folic acid had a
slightly slower decline in low-frequency hearing than those receiving
placebo . No such difference was seen for decline in hearing in the
high frequencies.

24. Up to date:how longs is it
• For those with a reversible cause of deficiency, therapy is generally
given for one to four months or until there is laboratory evidence of
hematologic recovery.
• For those with a chronic cause of folate deficiency, therapy may be
given indefinitely. Intravenous folic acid may be appropriate in certain
settings, such as individuals who are unable to take an oral
medication (eg, due to vomiting or obtundation) or those who have
• severe or symptomatic anemia due to folate deficiency and hence
have a more urgent need for rapid correction.

25. • It is important to be aware that administration of folic acid can
partially reverse some of the hematologic abnormalities associated
with vitamin B12 deficiency; however, the
• neurologic manifestations of vitamin B12 deficiency are not treated
by folic acid. Thus, administration of folic acid to an individual with
vitamin B12 deficiency can potentially mask
• untreated vitamin B12 deficiency or even worsen the neurologic
complications (the latter for reasons that are not entirely clear)

26. • Test for vitamin B12 deficiency in individuals with suspected folate
deficiency, those with folate deficiency whose anemia and/or
macrocytosis does not resolve with folic acid treatment, and/or those
who develop new neurologic symptoms upon treatment with folic
acid.

27. Up to date
• Administer vitamin B12 to individuals with megaloblastic anemia who
are being treated with folic acid before results of vitamin B12 testing
are available.
• Administer vitamin B12 to individuals with folate deficiency who
develop neurologic symptoms after treatment with folic acid. Ideally,
testing for vitamin B12 deficiency is also sent, but administration of
vitamin B12 should not be delayed while awaiting the results.

28. Up to date
• Methylenetetrahydrofolate reductase plays a central role in folate and
homocysteine metabolism by catalyzing the conversion of 5,10-
methylenetetrahydrofolate to 5-methyltetrahydrofolate, the primary
circulatory form of folate which is utilized in homocysteine
remethylation to methionine.

29. Up to date
• eople have two MTHFR genes, inheriting one from each of their
parents. Mutations can affect one (heterozygous) or both
(homozygous) of these genes.
• There are two common types, or variants, of MTHFR mutation:
C677T and A1298C.

30. Up to date
• Methylenetetrahydrofolate reductase, or MTHFR, is an enzyme
that breaks down the amino acid homocysteine. The MTHFR
gene that codes for this enzyme has the potential to mutate,
which can either interfere with the enzyme’s ability to function
normally or completely inactivate it.