X-Message-Number: 26664
Date: Tue, 19 Jul 2005 19:05:36 -0700 (PDT)
From: Doug Skrecky <>
Subject: optimal intake of folic acid is unknown

[Folic acid sounds great. It lowers blood pressure, cholesterol, as well
as IMT, which is a measure of atherosclerosis. The kicker is that is
may also increase the risk of dementia.]

Atherosclerosis. 2005 Jul;181(1):131-5. Epub 2005 Feb 16.
Decrease of carotid intima-media thickness in patients at risk to
cerebral ischemia after supplementation with folic acid, Vitamins
B6 and B12.
  OBJECTIVE:: Hyperhomocysteinemia is associated with
atherosclerotic risk. Although vitamins can lower homocysteine
(Hcy), information about effects on atherosclerosis is scarce.
METHODS:: We used carotid intima-media thickness (IMT) as an
accepted marker of atherosclerotic changes. Fifty patients
(60+/-8 years) with IMT>/=1mm were included. In a double blind,
randomized trial they received daily 2.5mg folic acid, 25mg
Vitamin B6, and 0.5mg Vitamin B12 or placebo for 1 year. RESULTS::
In the treatment group, Hcy decreased from 10.50+/-3.93 to
6.56+/-1.53mumol/l (P<0.0001), whereas it remained unchanged in
the placebo group (10.76+/-2.36 versus 10.45+/-3.30mumol/l). IMT
decreased from 1.50+/-0.44 to 1.42+/-0.48mm (P=0.034) in the
treatment group, whereas it increased from 1.47+/-0.57 to
1.54+/-0.71mm in the placebo group. The mean individual changes of
IMT between both groups differed significantly (-0.08+/-0.17
versus 0.07+/-0.25mm, P=0.019). Multiple regression analysis
revealed that the observed effect on IMT depended only on
medication. CONCLUSIONS:: Vitamin supplementation significantly
reduces IMT in patients at risk. This effect is independent of
Hcy concentration.

J Clin Endocrinol Metab. 2005 May 17; [Epub ahead of print]
L-FOLIC ACID SUPPLEMENTATION IN HEALTHY POSTMENOPAUSAL WOMEN:
EFFECT ON HOMOCYSTEINE AND GLYCO-LIPID METABOLISM.
  Context. Hyperhomocisteinemia as well as alterations of the
glycemic and lipidic metabolism are recognized as risk factors
for cardiovascular diseases. Objective. To study the effect of
L-folic acid supplementation on homocysteine (Hcy) and related
thiols such as cysteine (Cys) and cysteinil-glicine (Cys-Glyc)
pathways and their relationship with glucose, insulin and lipidic
metabolism in normoinsulinemic postmenopausal women. Design.
Randomized placebo not double blind trial. Setting. Accademic
research center. Patients or Other Partecopants. Twenty healthy
postmenopausal women were selected. No patient was taking drugs
known to affect the lipid or glucose metabolism. Intervention (s).
Patients underwent two hospitalizations before and after 8 weeks
of L-acid folic (7.5 mg/d) or placebo administration. The
glycemic metabolism was studied by an oral glucose tolerance
test (OGTT) and a hyperinsulinemic euglycemic clamp. The
homocysteine metabolism was studied by a standardized oral
methionine loading test. Main Outcome Measure (s). Homocysteine,
cysteine (Cys) and cysteinil-glicine (Cys-Glyc) basal and post
metionine loading test were measured. Basal insulin, glucose,
Pep-C levels as well as AUC-I, AUC -pep, FHIE, M were assayed.
The total Col, HDL LDL levels and the Cholesterol/HDL and LDL/HDL
ratio were also measured Results. Total basal homocysteine (tHcy)
concentration and plasma post-methionine loading Hcy values
significantly decreased (P < 0.01) in L-folic acid treated
patients whereas post methionine loading Cys-Glyc levels
markedly increased (P < 0.02). Furthermore L-folic acid intake
induced a significant improvement of the carbohydrate metabolism
through an increase of fractional hepatic insulin extraction
(P < 0.05) and peripheral insulin sensitivity (P < 0.02) in
normoinsulinemic women. HDL levels considerably increased
inducing an improvement of other atherosclerotic indexes such as
Cholesterol/HDL and LDL/HDL ratio (P < 0.03). Conclusions. These
results show that folic acid supplementation lowers plasma Hcy
levels and improves insulin and lipid metabolism reducing the
risk of cardiovascular disease.

J Am Coll Cardiol. 2005 May 17;45(10):1580-4. Epub 2005 Apr 26
High-dose folic acid acutely improves coronary vasodilator
function in patients with coronary artery disease.
  OBJECTIVES: We investigated the acute effect of orally
administered high-dose folic acid on coronary dilator function in
humans. BACKGROUND: Folic acid and its active metabolite,
5-methyltetrahydrofolate, increase endothelium-dependent
vasodilation in human peripheral circulation. However, the acute
effect on coronary circulation is not known. METHODS: Fourteen
patients with ischemic heart disease, age 62 +/- 12 years
(mean +/- SD), were enrolled in a double-blind, placebo-controlled
crossover trial. Basal and adenosine-stimulated myocardial blood
flow (MBF) were determined by positron emission tomography, and
myocardial flow reserve was calculated. Each patient was studied
after ingestion of placebo and after ingestion of 30 mg folic acid.
Myocardial zones were prospectively defined physiologically as
"normal" versus "abnormal" on the basis of MBF response to
adenosine 140 microg/kg/min (normal = MBF >1.65 ml/min/g). Abnormal
and normal zones were analyzed separately in a patient-based
analysis. RESULTS: Folate was associated with a reduction in mean
arterial pressure (100 +/- 12 mm Hg vs. 96 +/- 11 mm Hg, placebo
vs. folate, p < 0.03). Despite the fall in mean arterial pressure,
folic acid significantly increased the MBF dose response to
adenosine (p < 0.001 using analysis of variance) in abnormal zones,
whereas MBF in normal zones did not change. In abnormal segments,
folic acid increased peak MBF by 49% (1.45 +/- 0.59 ml/min/g vs.
2.16 +/- 1.01 ml/min/g, p < 0.02). Furthermore, folate increased
dilator reserve by 83% in abnormal segments (0.77 +/- 0.59 vs.
ml/min/g 1.41 +/- 1.08 ml/min/g, placebo vs. folate, p < 0.05),
whereas dilator reserve in normal segments remained unchanged
(2.00 +/- 0.61 ml/min/g vs. 2.12 +/- 0.69 ml/min/g, placebo vs.
folate, p = NS). CONCLUSIONS: The data demonstrate that high-dose
oral folate acutely lowers blood pressure and enhances coronary
dilation in patients with coronary artery disease.

Arch Neurol. 2005 Apr;62(4):641-5.
Dietary folate and vitamin B12 intake and cognitive decline among
community-dwelling older persons.
  BACKGROUND: Deficiencies in folate and vitamin B12 have been
associated with neurodegenerative disease. OBJECTIVE: To examine
the association between rates of age-related cognitive change and
dietary intakes of folate and vitamin B12. DESIGN: Prospective
study performed from 1993 to 2002. SETTING: Geographically defined
biracial community in Chicago, Ill. PARTICIPANTS: A total of 3718
residents, 65 years and older, who completed 2 to 3 cognitive
assessments and a food frequency questionnaire. MAIN OUTCOME
MEASURE: Change in cognitive function measured at baseline and
3-year and 6-year follow-ups, using the average z score of 4 tests:
the East Boston Tests of immediate and delayed recall, the
Mini-Mental State Examination, and the Symbol Digit Modalities Test.
RESULTS: High folate intake was associated with a faster rate of
cognitive decline in mixed models adjusted for multiple risk factors.
The rate of cognitive decline among persons in the top fifth of
total folate intake (median, 742 microg/d) was more than twice that
of those in the lowest fifth of intake (median, 186 microg/d), a
statistically significant difference of 0.02 standardized unit per
year (P = .002). A faster rate of cognitive decline was also
associated with high folate intake from food (P for trend = .04) and
with folate vitamin supplementation of more than 400 microg/d
compared with nonusers (beta = -.03, P<.001). High total B12 intake
was associated with slower cognitive decline only among the oldest
participants. CONCLUSIONS: High intake of folate may be associated
with cognitive decline in older persons. These unexpected findings
call for further study of the cognitive implications of high levels
of dietary folate in older populations.

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