Chemistry Reference
In-Depth Information
intake, as folate status has to be in an optimal range already 4-6 weeks before
conception, a fact that cannot always be planned. Women with an NTD
anamnesis should take up 4000 mgday
-1
, which is the tenfold of the normal
dose. An actual meta-analysis described that folic acid combined with a multi-
vitamin supplementation was as effective at NTD reduction as folic acid alone
but additionally reduced a number of other congenital anomalies (Goh et al.,
2006). Anyhow, the exact mechanisms by which sufficient folate levels prevent
NTDs are still unclear; an actual ''methylation hypothesis'' suggests that folic
acid stimulates cellular methylation reactions (Blom et al., 2006).
A number of epidemiological and clinical studies showed an inverse corre-
lation of folate status/intake and coronary heart disease, based on the observa-
tion that (1) elevated plasma homocysteine levels are a strong and independent
risk factor for the development of atherosclerosis and (2) homocysteine plasma
levels increase during folate deficiency. As for riboflavin, the uptake of selected
nutrients (e.g. cereals, milk, yogurt and those containing riboflavin and folate)
was inversely related to serum homocysteine level (Ganji and Kafai, 2004). In
addition, high plasma homocysteine levels are linked to cognitive dysfunction
anddementiainconnectionwithreducedfolate,butalsovitaminB12levels;the
exact mechanisms are still unclear andhavetobeelucidatedfurther.
A long-term folate-free diet (4 months) leads to a change in the ery-
throcyte population, i.e. the total number decreases with a parallel increase of
oversized,
haemoglobin-rich
erythrocytes
(macrocytic
hyperchromatic
anaemia).
An overdosage of folate must be mentioned, especially concerning the
synthetic vitamin folic acid, as natural sources are regarded as safe over a wide
range. The safe upper intake level has been set to 1 mg day
-1
by the US Food and
Nutritional Board. Overdosage can lead to epileptogenic and neurotoxic effects
(in animals); in humans there is a risk of masking an unrecognized vitamin B12
deficiency (pernicious anaemia). However, the numerous tests for vitamin status
available strongly reduce the risk of such undiagnosed B12 deficiencies. There
seems to be evidence that supplementation with folate (
>
or = 400 mgday
-1
)
increases the risk of developing breast cancer by 20-30% (Kim, 2006).
13.9.
Cobalamin (Vitamin B12)
The terms vitamin B12 or cobalamin represent a group of several cobalt-
containing corroids. A corrin ring with four reduced pyrrole rings and cobalt
as central atom, a nucleotide-like compound and an additional variable
compound are their common features (Figure 13.13). B12 is the only vitamin
containing a metallic ion. In biological systems, hydroxo-, aquo-, methyl- and
5
0
-deoxyadenosylcobalamin occur, while cyanocobalamin is a decomposition
