Samenvatting van alle lessen, powerpoint en literatuur van het vak Public Health Nutrition
Summary of all the lectures, powerpoint and literature of the course Public Health Nutrition
LECTURE 1: HEALTH EFFECTS OF FOLATE: CURRENT EVIDENCE
Learning goals
• Student knows about the current evidence in the field of health effects of folate.
• Student can discuss the arguments supporting and opposing folic acid fortification.
• Student knows potential strategies to optimize nutrient intake with their strengths and
limitations.
Folate, folic acid, and adverse pregnancy outcomes.
Folate and folic acid
Folate is present in food:
• Main food sources: vegetables, fruits, grains.
• Recommended daily intake:
o 300 µg/day
o 400 µg/day for women who want to become pregnant or are pregnant.
§ 4 weeks before and 8 weeks after conception
• Upper limit: 1000 µg/day
• Intake folate equivalents diet in NL: 258 µg/day (men: 284 µg/day, women 231
µg/day)
Functions of folate
There are two functions:
• DNA metabolism
• Amino acid metabolism
Folate metabolism
We have the DNA synthesis side and the protein side of the metabolism.
Protein side of the metabolism.
• The methionine cycle is a metabolic pathway that involves the conversion of
homocysteine to methionine.
• In this cycle folate, specifically as 5-methyltetrahydrofolate (5-MTHF), provides a
methyl group that is added to homocysteine to form methionine.
• This reaction is catalyzed by an enzyme called methionine synthase, which requires
vitamin B12 as a cofactor.
• In addition to its role in the methionine cycle, folate metabolism is also connected to
the synthesis of cysteine, another amino acid.
• Cysteine is formed from homocysteine through a process that requires vitamin B6 as
a cofactor.
• This highlights the importance of both vitamin B12 and vitamin B6 in amino acid
metabolism.
,DNA synthesis side of the metabolism.
Folate metabolism, through the conversion of 5,10-methylene THF to 5-methyl THF by the
MTHFR enzyme, provides the necessary methyl groups for DNA synthesis and DNA
methylation reactions. This active form of folate is essential for the growth and regulation of
the DNA molecule.
If you miss one of the B-vitamins or it is limited the whole system breaks down.
Folate and DNA synthesis
• Folate deficiency reduces DNA synthesis.
• The result is that the cell division disturbed.
o Red blood cells – megaloblastic anemia. The first sign of folate deficiency is
anemia.
o If you give folate it will disappear.
Folate and neural tube defects (NTD)
Neural Tube Defects (NTD’s)
• During embryo development and growth cell division is extremely rapid.
• Neural tube develops from 21-27 weeks post conception.
• Inadequate folate à cell division goes down à neural tube development goes down.
Especially in the beginning of the pregnancy a higher dose of folate is important.
Main NTD forms
• Spina bifida: incomplete closing of the backbone and membranes around the spinal
cord.
• Anencephaly: rostral (head) end of the neural tube fails to close.
Prevalence Europe: 8,16/10,000 births
o Live births: 2,22
o Fetal deaths/stillbirths: 0.37.
o Termination of pregnancy following prenatal diagnosis: 5,57.
Consequences of NTD
• Anencephaly: children generally die during or shortly after birth.
• Spina bifida: children are affected with life-long morbidity and disability and have a
10-fold higher risk of mortality.
• Estimated lifetime expenditures:
o Total lifetime direct costs of care of the child born with spina bifida.
o Emotional costs
o In the US, 3000 pregnancies are affected by neural tube defect every year.
,NTD – History
• All NTD’s have common etiology because it happens in certain groups (you look in all
this groups if there is a link):
o Genetic
§ Recurrence rate
§ Ethnic groups
§ Twin studies
o Environmental
§ NTD rate is not constant over time à Q: what is the role of nutrition?
• In the 1964 Hibbard found that women with pregnancies with NTD had higher urinary
formiminoglutamic acid than the normal population. He found that folate is involved in
the breakdown of formiminogluctamic acid.
Folate/folic acid research
NTD and folate – interventions
Smithells (1980)
• Intervention: multivitamin (n=178)
• Control: not supplemented women were not recruited for the trial (n=260). This was
done because the ethical commissions did not approve to put women in the control
group without supplements.
o NTD rates:
§ 1 child in intervention group (0.6%).
§ 13 children in not supplemented women (5%).
à this was not a good study, so the evidence was not good enough.
Laurance (1981)
• Intervention 4 mg/day folic acid (n=60)
• Control: placebo (n=51)
o NTD rates:
§ 2 rates in intervention group
§ 4 in control group
This study was on the recurrence of NTD. You should check levels of folate acids in the
blood to see if the participant really took the pills, but they did not do that in the study. When
they removed two women from the study because they did not take the folic acid pills, you
see whole other results:
• NTD rates:
o 0 children in mothers who took supplement.
o 6 children in mothers who did not receive/take supplement.
Conclusion: folic acid may prevent NTD.
NTD and folate – MRC study
• Multicenter
• 1.817 women with previous NTD-affected pregnancy
o Folic acid group (4 mg/d)
o Folic acid group + multivitamin
o Multivitamin
o Placebo
• 1195 had a completed pregnancy.
o 6 children had NTD in folic acid groups.
o 21 children had NTD in other groups.
o RR: 0.28.
, Folate and NTD – Conclusion
• Folic acid supplementation prevents NTD.
• Advice to take folic acid supplements periconceptionally.
o Normally: 400-500 µg/day folic acid from 4 weeks before conception until 8
weeks after.
o For women with history of NTD-affected pregnancy: 4000-5000 µg/day.
Optimizing folate intake – strategies
Strategies to optimize folate status.
Q: What can you do to stimulate people to higher their folate intake?
• Diet: increased intake of natural foods high in folate (liver, vegetables)
o Limitations:
§ Major dietary changes needed to increase folate intake substantially.
§ Bioavailability à the bioavailability from a diet is low and from
supplements high.
• Supplements: easy and effective
o Limitations: non effective on population level (compliance/unplanned
pregnancies)
• Fortification?
Fortification
• Folic acid fortification of grain foods
• Mandatory in US & Canada since 1998
o 140 µg/100g product
à mean additional intake about 100 µg/d.
• Whole target population is reached (women at childbearing ages)
• Limitations: some women still don’t get the folate because they have a different diet.
Effect of folic acid fortification of population level?
• Possible other health effects?
o Cardiovascular disease
• Safety issue for?
o Women not at childbearing age.
o Men, children.
o Older adults – masking of B12 deficiency. The signs of a B12 deficiency is
giving the same clinical signs as folate deficiency.
Exploration of the evidence on folic acid, homocysteine,
and cardiovascular disease
Folate metabolism role in amino acid metabolism –
homocysteine
• Homocysteine is a sulfur-containing amino acid
produced from methionine.
• A high homocysteine is thought to be related to
cardiovascular disease.
• To get rid of the homocysteine you can make
cysteine, but homocysteine can also go back in the
cycle.
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