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Folate, vitamin B12, homocysteine status and
chromosome damage rate in lymphocytes of older men.
Fenech MF Dreosti IE Rinaldi JR
Fenech MF, CSIRO, Div Human Nutr, POB 10041, Gouger St,
Adelaide, SA 5000, Australia
Carcinogenesis 1997 JUL;18(7):1329-1336
Deficient levels of folic acid and vitamin B12 are
associated with elevated chromosome damage rate and high
concentrations of homocysteine in the blood. We have therefore
performed a study to determine the prevalence of folate
deficiency, vitamin B12 deficiency and hyperhomocysteinemia in
64 healthy men aged between 50 and 70 years, and evaluate the
relationship of these micronutrient levels in the blood with
the micronucleus frequency in peripheral blood lymphocytes. We
also performed a placebo-controlled, double-blind intervention
study to determine whether supplementation of the diet with a
daily dose of 0.7 mg (as a supplement in cereal) or 2.0 mg (in
a tablet) over a period of 4 months resulted in a significant
alteration of folate status, homocysteine status and the
micronucleus index. Twenty-three per cent of the men were
serum folate deficient (6.8 nmol/l), 16% were red blood cell
folate deficient (317 nmol/l), 4.7% were vitamin B12 deficient
(150 pmol/l) and 37% has plasma homocysteine levels 10 mu
mol/l. In total, 56% of the men had one or more abnormal blood
values for folate, vitamin B12 or homocysteine. The
micronucleus index of these men (n = 34) in
cytokinesis-blocked binucleated cells (19.2 +/- 1.1) was
significantly elevated (P = 0.02) when compared to the
micronucleus index of the rest of the men who had normal
levels of folate, vitamin B12 and homocysteine (16.3 +/- 1.3,
n = 30). Interestingly, the micronucleus index in men with
normal folate and vitamin B12, but homocysteine levels >10
mu mol/l (19.4 +/- 1.7, n = 15) was also significantly higher
(P = 0.05) when compared to those with normal folate, vitamin
B12 and homocysteine. This novel result was also supported by
the observation that the micronucleus index and plasma
homocysteine were significantly (P = 0.0086) and positively
correlated (r(2) = 0.172) in those subjects who were not
deficient in folate or vitamin B12. The micronucleus index was
not significantly correlated with folate indices, but there
was a significant (P = 0.013) negative correlation with serum
vitamin B12 (r(2) = 0.099). Daily supplementation of the diet
with 0.7 mg free folic acid in cereal for 2 months followed by
2.0 mg free folic acid via a tablet produced a 4-fold increase
in plasma folate, a 2.6-fold increase in red blood cell folate
and a 11% reduction in plasma homocysteine; however, these
changes were not accompanied by a reduction in the
micronucleus index. In conclusion, it is apparent that
elevated homocysteine status, in the absence of vitamin
deficiency and low but not deficient, vitamin B12 status are
important risk factors for increased chromosome damage in
lymphocytes.
Relations of vitamin B-12, vitamin B-6, folate, and
homocysteine to cognitive performance in the Normative Aging
Study
Riggs K.M.; Spiro III A.; Tucker K.; Rush D.
Jean Mayer USDA, Human Nutrition Res. Center on Aging, Tufts
University, 711 Washington Street, Boston, MA 02111 USA
American Journal of Clinical Nutrition (USA), 1996, 63/3
(306-314)
We investigated the relations between plasma concentrations
of homocysteine and vitamins B-12 and B-6 and folate, and
scores from a battery of cognitive tests for 70 male subjects,
aged 54-81 y, in the Normative Aging Study. Lower
concentrations of vitamin B-12 (P = 0.04) and folate (P =
0.003) and higher concentrations of homocysteine (P = 0.0009)
were associated with poorer spatial copying skills. Plasma
homocysteine was a stronger predictor of spatial copying
performance than either vitamin B-12 or folate. The
association of homocysteine with spatial copying performance
was not explained by clinical diagnoses of vascular disease.
Higher concentrations of vitamin B-6 were related to better
performance on two measures of memory (P = 0.03 and P = 0.05).
The results suggest that vitamins (and homocysteine) may have
differential effects on cognitive abilities. Individual
vitamins and homocysteine should be explored further as
determinants of patterns of cognitive impairment.
Folate, vitamin B-12, and neuropsychiatric
disorders.
Bottiglieri T
Bottiglieri T, Baylor Univ, Med Ctr, Kimberly H Courtwright
& Joseph W Summers Inst Me, Dallas,TX 75246 USA
Nutr Rev 1996 Dec;54(12):382-390
Folate and vitamin B-12 are required both in the
methylation of homocysteine to methionine and in the synthesis
of S-adenosylmethionine. S-adenosylmethionine is involved in
numerous methylation reactions involving proteins,
phospholipids, DNA, and neurotransmitter metabolism. Both
folate and vitamin B-12 deficiency may cause similar
neurologic and psychiatric disturbances including depression,
dementia, and a demyelinating myelopathy. A current theory
proposes that a defect in methylation processes is central to
the biochemical basis of the neuropsychiatry of these vitamin
deficiencies. Folate deficiency may specifically affect
central monoamine metabolism and aggravate depressive
disorders. In addition, the neurotoxic effects of homocysteine
may also play a role in the neurologic and psychiatric
disturbances that are associated with folate and vitamin B- 12
deficiency.
Lipid peroxidation induced in vivo by
hyperhomocysteinaemia in pigs.
Young PB Kennedy S Molloy AM Scott JM Weir DG Kennedy
DG
Young PB, Dept Agr No Ireland, Dept Biochem, Vet Sci Div,
Stoney Rd, Belfast BT4 3SD, Antrim, North Ireland
Atherosclerosis 1997 Feb 28;129(1):67-71
Much attention has been focused recently on the
relationship between homocysteinaemia and the development of
premature atherosclerosis. Hyperhomocysteinaemia constitutes
as strong a risk factor for the development of the disease as
either hypercholesterolaemia or smoking. Although the
mechanism involved is unclear homocysteine exhibits
prooxidative activity in vitro. This finding suggests that it
may be involved in the oxidative modification of low density
lipoprotein (LDL). In the current study hyperhomocysteinaemia
was induced in eight domestic pigs by intermittent exposure to
nitrous oxide for 4 weeks. At necropsy, cardiac tissue was
removed and malondialdehyde (MDA) and the unsaturated fatty
acid content were measured and compared with values obtained
from air-breathing control animals. Nitrous oxide treated
animals had significantly higher tissue concentrations of MDA
than the controls. There was also a reduction in the
contribution of linoleic and linolenic acids to the total
fatty acid content of heart. The hyperhomocysteinaemic animals
also had a significantly higher iron concentration in the
heart than controls. Hyperhomocysteinaemia was associated with
elevations in tissue iron stores and increased in vivo lipid
peroxidation.
Reduction of plasma homocyst(e)ine levels by
breakfast cereal fortified with folic acid in patients with
coronary heart disease.
Malinow MR, Duell PB, Hess DL, Anderson PH, Kruger WD,
Phillipson BE, Gluckman RA, Block PC, Upson BM
Division of Pathobiology and Immunology, Oregon Regional
Primate R
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