timothytn

Mutat Res. 2001 Apr 18;475(1-2):57-67. Related Articles, Links


The role of folic acid and Vitamin B12 in genomic stability of human
cells.

Fenech M.

CSIRO Health Sciences and Nutrition, Adelaide, Australia.
michael.fenech@hsn.csiro.au

Folic acid plays a critical role in the prevention of chromosome
breakage and hypomethylation of DNA. This activity is compromised when
Vitamin B12 (B12) concentration is low because methionine synthase
activity is reduced, lowering the concentration of S-adenosyl
methionine (SAM) which in turn may diminish DNA methylation and cause
folate to become unavailable for the conversion of dUMP to dTMP. The
most plausible explanation for the chromosome-breaking effect of low
folate is excessive uracil misincorporation into DNA, a mutagenic
lesion that leads to strand breaks in DNA during repair. Both in vitro
and in vivo studies with human cells clearly show that folate
deficiency causes expression of chromosomal fragile sites, chromosome
breaks, excessive uracil in DNA, micronucleus formation and DNA
hypomethylation. In vivo studies show that Vitamin B12 deficiency and
elevated plasma homocysteine are significantly correlated with
increased micronucleus formation. In vitro experiments indicate that
genomic instability in human cells is minimised when folic acid
concentration in culture medium is >227nmol/l. Intervention studies in
humans show: (a) that DNA hypomethylation, chromosome breaks, uracil
misincorporation and micronucleus formation are minimised when red
cell folate concentration is >700nmol/l folate; and (b) micronucleus
formation is minimised when plasma concentration of Vitamin B12 is

concentrations are achievable at intake levels in excess of current
RDIs i.e. more than 200-400microgram folic acid per day and more than
2microgram Vitamin B12 per day. A placebo-controlled study with a
dose-response suggests that based on the micronucleus index in
lymphocytes, an RDI level of 700microgram/day for folic acid and
7microgram/day for Vitamin B12 would be appropriate for genomic
stability in young adults. Dietary intakes above the current RDI may
be particularly important in those with extreme defects in the
absorption and metabolism of these Vitamins, for which ageing is a
contributing factor.

Publication Types:
Review
Review, Tutorial

PMID: 11295154 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

timothytn

You do to some extent have to connect the dots. Some people miss the
forest for the trees. One may be dead before long term studies provide
definitive incontrovertible answers. I know what I would do and do.


1: Circulation. 2000 Nov 14;102(20):2479-83. Related Articles, Links


Improved vascular endothelial function after oral B vitamins: An
effect mediated through reduced concentrations of free plasma
homocysteine.

Chambers JC, Ueland PM, Obeid OA, Wrigley J, Refsum H, Kooner JS.

National Heart and Lung Institute, Imperial College School of
Medicine, Hammersmith Hospital, London, UK.

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for
coronary heart disease (CHD). Dietary supplementation with B vitamins
lowers plasma homocysteine by up to 30%. However, little is known
about the potential beneficial effects of homocysteine lowering on
vascular function in patients with CHD. METHODS AND RESULTS: We
investigated 89 men with CHD (aged 56 [range 39 to 67] years).
Brachial artery flow-mediated dilatation (endothelium dependent) and
nitroglycerin-induced dilatation (endothelium independent) were
measured before and 8 weeks after treatment with either (1) folic acid
(5 mg) and vitamin B(12) (1 mg) daily (n=59) or (2) placebo (n=30).
Total, protein-bound, and free plasma homocysteine, serum folate, and
vitamin B(12) were measured at baseline and at 8 weeks. Flow-mediated
dilatation improved after treatment with B vitamins (2.5+/-3.2% to
4.0+/-3.7%, P:=0.002) but not placebo (2.3+/-2.6% to 1.9+/-2.6%,
P:=0.5). Vitamin therapy lowered plasma concentrations of total
homocysteine (from 13.0+/-3.4 to 9.3+/-1.9 micromol/L, P:<0.001),
protein-bound homocysteine (from 8.7+/-2.8 to 6.2+/-1.4 micromol/L,
P:<0.001), and free homocysteine (from 4.3+/-1.2 to 3.0+/-0.6
micromol/L, P:<0.001) and raised concentrations of serum folate (from
10.3+/-4.3 to 31.2+/-10.8 ng/mL, P:<0.001) and vitamin B(12) (from
314+/-102 to 661+/-297 pg/mL, P:<0.001). In regression ****ysis,
improved flow-mediated dilatation correlated closely with the
reduction in free plasma homocysteine (r=-0.26, P:=0.001), independent
of changes in protein-bound homocysteine, folate, and vitamin B(12).
Nitroglycerin-induced dilatation was unchanged after both B vitamins
and placebo. CONCLUSIONS: Folic acid and vitamin B(12) supplementation
improves vascular endothelial function in patients with CHD, and this
effect is likely to be mediated through reduced concentrations of free
plasma homocysteine concentrations. Our data support the view that
lowering homocysteine, through B vitamin supplementation, may reduce
cardiovascular risk.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 11076820 [PubMed - indexed for MEDLINE]


Tim

william a. noyes

You shouldn't pound the table with your shoe about that just yet
about the CHD outcomes. The Australian null result study
had a very wide confidence interval. Moreover, it was just
the low levels derived from diet not enough to lower
homocysteine in those with a double dose of certain gene
variations nor did they test those homocysteine levels as
I recall.

The Dutch study was small and only covers period of two
years in patient with already established CAD. The dose
was 0.5 milligrams of supplement folic taken in isolation.
Even they admit that FA improves vascular endothelium
function....... which should serve to improve quality of life.
It would have made more sense to test it in angina sufferers
or even ED sufferers along with 10 grams of arginine.

Remember if you can that hyperhomocysteine levels
are a strong independent risk factor for both dementia
and AD according to an article in last years JAMA.

As a micronucleus index is more than mere cir***stantial
evidence. In radiobiology, they have are clear relationship
to genetic damage.

The three year old wine is perfect but the new wine
sweet and good...........William A. Noyes