Made in year: 2024-2025
Grade 1st attempt: 7.6
,Lecture 1 folic acid
Folic acid à B11
- Mainly present in vegetable foods.
- The RDI is 300 micrograms per day.
- For pregnant women it is recommended to take in 400 micrograms extra (via
supplementation) per day 4 weeks before until 8 weeks after conception.
- The upper limit is 1000 micrograms per day.
The intake of folate via an equivalent diet is 262 micrograms, which is not fully up to the
recommended intake.
Functions of folate
- AA metabolism
Proteins are broken down to methionine, homocysteine, and cysteine.
5-methylTHF can be converted to folate when homocysteine converts to methionine.
- DNA metabolism
Folate deficiency reduces DNA synthesis because it is important for the speed at
which this process happens.
This is especially for red blood cell division. Therefore, anaemia is one of the
symptoms of folate deficiency.
During embryo development, cell division is extremely rapid. The neural tube
develops from day 21-27 post conception. Here, inadequate folate reduces cell
division and thereby affects neural tube development.
Consequences of this are:
o Spina bifida – incomplete closing of the backbone and membranes around
the spinal cord.
, o Anencephaly – rostral head end of the neural tube fails to close.
The prevalence of this is 8.16/10000 births in Europe.
NTD history
All NTD’s have common etiology because of increased risk of reoccurrence.
Partly, there was a genetic part that could be seen by reoccurrence rate and twin
studies. However, there were also not constant cases over time, which increased the
thoughts of environmental effects.
Then research was performed by Hibbard (1964) where women with pregnancies
with NTD had higher urinary formiminoglutamic acid than the normal population.
Since folate is involved in the breakdown of this, there were first observations here.
Additionally, research was done with multivitamin pills. Here, NTD development was
higher in the not-supplemented group.
o Problems with this research
The multivitamin did not yet give specific information on folate.
The control group was depicted after the intervention. Which is not an ideal
selection and could also bring problems with ethics since the placebo group
was thought to have a lower health effect compared to the treatment group.
Another study by Laurence (1981) did an intervention with 4 mg/day of folic acid
compared to a placebo. The outcome was that there was no statistically difference
between the two groups.
o Problems with this research
The compliance with the intervention was low, which caused that these
people actually were part of the control group.
Then after this, the study was done again with compliance considered. Then the
rates were significantly higher, and the conclusion was that folic acid could prevent
NTD.
Another big study was performed with 4 groups (folic acid, folic acid and
multivitamin, multivitamin, placebo). Then the outcomes were that NTD were only
low in the folic acid groups.
, Recommendations are now
o 400-500 micrograms/day from 4 weeks before conception until 8 weeks
after.
o Additionally, for women with history of NTD-affected pregnancy, the intake is
even 4000-5000 micrograms per day.
Optimizing folate intake – strategies
- Diet
Increased intake of natural foods high in folate.
However, major dietary changes are needed to increase folate intake substantially.
- Supplements
However, not effective on population level. For instance, when a person is not
planning on becoming pregnant, then the intake cannot be regulated. Additionally,
the compliance with the intake of a supplement each day is very low.
- Fortification (verrijking)
This is done with adding the folate to food that is often eaten (e.g., bread).
E.g., this is done in Canada since 1998. Here, they put it in the grain (140 micrograms
per 100 grams of product).
o The problem with this is that the whole population is reached, and effects of
this are unknown – e.g., possible adverse effects.
o Additionally, B11 will mask the symptoms of B12 deficiency. Therefore, this
might cause that this deficiency is not seen in all people.
o Another problem is that the intake is still not at 400 micrograms per day
extra.
o Another problem is that it brings extra costs for which the effects are not
really known. Therefore, they want to know if there are other possible health
effects to see if this also brings positive effects (e.g., for CVD).
CVD relation with folic acid
Homocysteine is created when the protein methionine is broken down. When folate is
present, then homocysteine will be converted back to methionine (since it gives the 5
methyl group).
Homocysteine is a sulfur-containing amino acid produced from methionine, A high level is
associated with increased risk of CVD.