Cancer Detect Prev. 2005;29(1):46-53. Epub 2004
Nov 11.
The role of folates in squamous cell carcinoma of the head and
neck.
Kane MA.
Division of Medical Oncology, University of Colorado Health Sciences
Center and the Denver Veterans Affairs Medical Center, Denver
VA Medical Center (111F), 1055 Clermont Street, Denver, CO 80220,
USA.
The primary objective of this review is to explore the hypothesis
that folate insufficiency may be important in the pathogenesis
of squamous cell carcinomas of the head and neck (SCCHN) and that
folate repletion may be an effective component of chemoprevention.
The main results are that folate insufficiency disrupts DNA global
and specific gene methylation patterns such that the activity
of certain tumor suppressor genes such as p16 and possibly p53
may be lost. Folate pool imbalance and impaired repair mechanisms
may contribute to DNA instability and strand breaks. Sensitive
methods exist for identification of individuals with folate insufficiency
in contrast to the relatively insensitive conventional serum or
red cell folate assays with broad "normal" ranges. The
impact of folate supplementation can thus be quantified. Folate
imbalance may result from alterations in folate cellular uptake
by the reduced folate carrier (RFC) and/or the folate receptor
(FR) and polymorphisms in enzymes important in folate retention
such as folylpolyglutamate synthetase and in folate modification
such as methylene tetrahydrofolate reductase (MTHFR). Known predisposing
factors for SCCHN such as alcohol and tobacco carcinogens may
influence folate balance. Folate supplementation may reduce primary
or secondary risk of cancer. Formal studies of folate sufficiency
in persons at risk for or diagnosed and treated for SCCHN are
needed to define the role of folate supplementation in the prevention
of these cancers.
Z Kardiol. 2004 Jun;93(6):439-53.
Clinical use and rational management of homocysteine, folic acid,
and B vitamins in cardiovascular and thrombotic diseases.
Stanger O, Herrmann W, Pietrzik K, Fowler B, Geisel J, Dierkes
J, Weger M.
Universitatsklinik fur Herzchirurgie, Private Medizinische Universitat
(PMU), Landeskliniken Salzburg, Mullner Hauptstrasse 48, 5020,
Salzburg, Austria.
About half of all deaths are due to cardiovascular disease and
its complications. The economic burden on society and the healthcare
system from cardiovascular disability, complications, and treatments
is huge and becoming larger in the rapidly aging populations of
developed countries. As conventional risk factors fail to account
for part of the cases, homocysteine, a "new" risk factor,
is being viewed with mounting interest.Homocysteine is a sulfur-containing
intermediate product in the normal metabolism of methionine, an
essential amino acid. Folic acid, vitamin B(12), and vitamin B(6)
deficiency and reduced enzyme activities inhibit the breakdown
of homocysteine, thus increasing the intracellular homocysteine
concentration. Numerous retrospective and prospective studies
have consistently found an independent relationship between mild
hyperhomocysteinemia and cardiovascular disease or all-cause mortality.
Starting at a plasma homocysteine concentration of approximately
10 micromol/l, the risk increase follows a linear dose-response
relationship with no specific threshold level. Hyperhomocysteinemia
as an independent risk factor for cardiovascular disease is thought
to be responsible for about 10 percent of total risk. Elevated
plasma homocysteine levels (> 12 micromol/l; moderate hyperhomocysteinemia)
are considered cytotoxic and are found in 5 to 10 percent of the
general population and in up to 40 percent of patients with vascular
disease. Additional risk factors (smoking, arterial hypertension,
diabetes, and hyperlipidemia) may additively or, by interacting
with homocysteine, synergistically (and hence overproportionally)
increase overall risk. Hyperhomocysteinemia is associated with
alterations in vascular morphology, loss of endothelial antithrombotic
function, and induction of a procoagulant environment. Most known
forms of damage or injury are due to homocysteine-mediated oxidative
stresses. Especially when acting as direct or indirect antagonists
of cofactors and enzyme activities, numerous agents, drugs, diseases,
and life style factors have an impact on homocysteine metabolism.
Folic acid deficiency is considered the most common cause of hyperhomocysteinemia.
An adequate intake of at least 400 microg of folate per day is
difficult to maintain even with a balanced diet, and high-risk
groups often find it impossible to meet these folate requirements.
Based on the available evidence, there is an increasing call for
the diagnosis and treatment of elevated homocysteine levels in
high-risk individuals in general and patients with manifest vascular
disease in particular. Subjects of both populations should first
have a baseline homocysteine assay. Except where manifestations
are already present, intervention, if any, should be guided by
the severity of hyperhomocysteinemia. Consistent with other working
parties and consensus groups, we recommend a target plasma homocysteine
level of < 10 micromol/l. Based on various calculation models,
reduction of elevated plasma homocysteine concentrations may theoretically
prevent up to 25 percent of cardiovascular events. Supplementation
is inexpensive, potentially effective, and devoid of adverse effects
and, therefore, has an exceptionally favorable benefit/risk ratio.
The results of ongoing randomized controlled intervention trials
must be available before screening for and treatment of hyperhomocysteinemia
can be recommended for the apparently healthy general population.
Br J Biomed Sci. 2004;61(2):84-7.
Folate and homocysteine levels in pregnancy.
Megahed MA, Taher IM.
Department of Biochemistry, Medical Research Institute, Alexandria,
Egypt.
This study aims to determine serum folate and plasma homocysteine
levels in healthy pregnant women following a live birth and compare
them with healthy non-pregnant women. Fifty healthy gravid multiparous
women are included in the study and 25 normal non-pregnant female
subjects act as controls (group I). The pregnant women are divided
into two groups according to interpregnancy interval: group II
(six months or less); group III (18-24 months). Venous blood samples
are analysed for red blood cell folate and homocysteine, vitamin
B12, serum folate and albumin, and serum aminotransferases (ALT
and AST). There was a significant decrease in red cell folate
and serum folate in group II compared to the control group (P<0.001).
Serum vitamin B12 showed no significant difference. Plasma homocysteine
and serum albumin showed significant decreases in both groups
II and III compared to the control group. (P<0.001) There was
significant positive correlation between homocysteine and serum
albumin in the three studied groups. (r=0.42, P<0.001; r=0.45,
P<0.001; r=0.51, P<0.001, respectively). There was significant
negative correlation between red cell folate and homocysteine
in the three studied groups. (r=-0.48, P<0.001; r=-0.53, P<0.001;
r=-0.49, P<0.001, respectively). Two cases in group II showed
signs of intrauterine growth retardation. The results suggest
that pregnant females with short interpregnancy intervals are
more likely to develop folate deficiency. Educational strategies
are required to increase folate awareness among women to promote
the benefits of folic acid supplementation. Mandatory folate fortification
of foods should be defined and monitored.
Cancer Epidemiol Biomarkers Prev. 2004 Jul;13(7):1244-9.
Effect of folic Acid supplementation on the folate status of buccal
mucosa and lymphocytes.
Basten GP, Hill MH, Duthie SJ, Powers HJ.
Human Nutrition Unit, University of Sheffield, Coleridge House,
Northern General Hospital, United Kingdom.
Folate deficiency may be associated with an increased risk of
cancer at certain sites. There is a need to measure folate status
and putative biomarkers of cancer risk in the same target tissue,
or in surrogate tissues. A study was carried out to develop a
method for the rapid measurement of folate in human buccal mucosa
and lymphocytes and to evaluate the responsiveness of this measurement
in both tissues to folic acid supplementation in healthy subjects,
relative to conventional markers of folate status. Three hundred
and twenty-three adults, ages between 20 and 60 years, were screened
for RBC folate concentrations. Sixty-five subjects with red cell
folate between 200 and 650 nmol/L participated in a randomized,
double blind, placebo-controlled, folic acid (1.2 mg) intervention
trial, lasting 12 weeks. As anticipated, a significant baseline
correlation (r = 0.36, P < 0.01) was observed between red cell
folate and plasma 5-methyltetrahydrofolate (5-MeTHF). Lymphocyte
total folate was significantly associated with plasma 5-MeTHF
(r = 0.28, P < 0.05) and plasma total homocysteine concentration
(r = -0.34, P < 0.05). Buccal mucosa total folate showed no
correlation with either red cell folate or 5-MeTHF, but was significantly
associated with lymphocyte total folate (r = 0.35, P < 0.01).
Supplementation elicited a significant increase in lymphocyte
total folate (P < 0.01), and this was strongly associated with
the increase in RBC total folate (P < 0.01) and plasma 5-MeTHF
(P < 0.01). Buccal mucosa total folate was not influenced by
folate supplementation. Methods have been developed for the rapid
measurement of lymphocyte and buccal mucosal total folate. Lymphocyte
folate is sensitive to folate intake and is reflected by plasma
5-MeTHF.
Zentralbl Gynakol. 2004 Jun;126(3):112-8.
Women with epilepsy planning pregnancy.
Beyenburg S, Schmutzler AG.
Service de Neurologie, Departement des Neurosciences, Centre Hospitalier
de Luxembourg, Luxembourg.
There are many important health issues for women with epilepsy,
in particular for women of childbearing age. Recent surveys have
shown that only a minority of such patients received information
on important issues concerning pregnancy. Pre-pregnancy counselling
should include information on interactions of antiepileptic drugs
(AEDs) and oral contraceptives, risk of teratogenicity, use of
folic acid, the importance of monotherapy with the lowest effective
dosage of an AED, and the safety of breast feeding as well as
other special aspects of epilepsy and pregnancy. Planned pregnancy
and counselling before conception is crucial. With a multidisciplinary
approach the majority of pregnancies will have a favourable outcome.
The article addresses these issues and describes practical considerations
for the counselling of women with epilepsy who are planning pregnancy.
N Engl J Med. 2004 Jun 24;350(26):2673-81.
Folate therapy and in-stent restenosis after coronary stenting.
Lange H, Suryapranata H, De Luca G, Borner C, Dille J, Kallmayer
K, Pasalary MN, Scherer E, Dambrink JH.
Kardiologische Praxis, Klinikum Links der Weser, Heart Center,
Bremen, Germany.
BACKGROUND: Vitamin therapy to lower homocysteine levels has recently
been recommended for the prevention of restenosis after coronary
angioplasty. We tested the effect of a combination of folic acid,
vitamin B6, and vitamin B12 (referred to as folate therapy) on
the risk of angiographic restenosis after coronary-stent placement
in a double-blind, multicenter trial. METHODS: A total of 636
patients who had undergone successful coronary stenting were randomly
assigned to receive 1 mg of folic acid, 5 mg of vitamin B6, and
1 mg of vitamin B12 intravenously, followed by daily oral doses
of 1.2 mg of folic acid, 48 mg of vitamin B6, and 60 microg of
vitamin B12 for six months, or to receive placebo. The angiographic
end points (minimal luminal diameter, late loss, and restenosis
rate) were assessed at six months by means of quantitative coronary
angiography. RESULTS: At follow-up, the mean (+/-SD) minimal luminal
diameter was significantly smaller in the folate group than in
the placebo group (1.59+/-0.62 mm vs. 1.74+/-0.64 mm, P=0.008),
and the extent of late luminal loss was greater (0.90+/-0.55 mm
vs. 0.76+/-0.58 mm, P=0.004). The restenosis rate was higher in
the folate group than in the placebo group (34.5 percent vs. 26.5
percent, P=0.05), and a higher percentage of patients in the folate
group required repeated target-vessel revascularization (15.8
percent vs. 10.6 percent, P=0.05). Folate therapy had adverse
effects on the risk of restenosis in all subgroups except for
women, patients with diabetes, and patients with markedly elevated
homocysteine levels (15 micromol per liter or more) at baseline.
CONCLUSIONS: Contrary to previous findings, the administration
of folate, vitamin B6, and vitamin B12 after coronary stenting
may increase the risk of in-stent restenosis and the need for
target-vessel revascularization.
Nippon Hinyokika Gakkai Zasshi. 2003 Jul;94(5):551-9.
Folic acid reduces risks of having fetus affected with neural
tube defects: dietary food folate and plasma folate concentration.
Kondo A, Kimura K, Isobe Y, Kamihira O, Matsuura O, Gotoh M, Okai
I.
Department of Urology, Komaki Shimin Hospital.
OBJECTIVES: Risk of having fetus affected with neural tube defects
can be reduced by maternal periconceptional folic acid supplementation.
The purpose of the present study is to investigate how folate
is taken from diets and to measure plasma folate concentrations.
SUBJECTS AND METHODS: A total of 222 women comprising 5 groups,
i.e., healthy women, mothers of myelodysplastic patients, pregnant
women, myelodysplastic patients, nurse students, participated
in our study. Food frequency questionnaires kept 3 days were analyzed
based on the 5th standard table of food composition in Japan.
Plasma folate concentrations were measured by means of chemiluminescent
immunoassay method. Changes in plasma folate concentrations and
possible adverse effects following the folic acid supplementation
for 16 weeks were also investigated. RESULTS: The dietary intake
of folate, plasma folate concentration and energy intake averaged
293 micrograms/day, 8.1 ng/ml and 1,857 Kcal, respectively, among
the subjects. Pregnant women took the largest amount of folate
from diets and demonstrated the highest plasma folate concentration
among the groups. The dietary folate in myelodysplastic patients
and nurse students was significantly lower compared to that of
healthy women. The Recommended Dietary Allowance of folate was
not fulfilled in 22% of non-pregnant adult women and 72% of pregnant
women. The dietary folate was mainly taken from the 3rd food group
but the 4th group of food was consumed most. Mean folate intake
was significantly correlated with circulating concentrations of
serum folate (p = 0.012 r = 0.186). The consecutive administration
of 400 micrograms supplements for 16 weeks increased a baseline
plasma value of 8.7 ng/ml to 32.6 but fell down rapidly to 17.3
24 hours later without any adverse effects. CONCLUSIONS: The dietary
folate and serum folate concentrations averaged 293 micrograms/day
and 8.1 ng/ml, respectively. The former is the first report based
on the 5th standard table of food composition in Japan. Majority
of pregnant women took less dietary folate than what recommended
by the government. Those who are capable of becoming pregnant
are recommended to consume much of the 3rd food group and those
who are planning to become pregnant are recommended to take 400
micrograms of folic acid supplements from 4 weeks before to 12
weeks after conception.
J Am Coll Cardiol. 2003 Jun 18;41(12):2105-13.
Secondary prevention with folic acid: effects on clinical outcomes.
Liem A, Reynierse-Buitenwerf GH, Zwinderman AH, Jukema JW, van
Veldhuisen DJ.
Department of Cardiology, Oosterschelde Ziekenhuizen, Goes, The
Netherlands.
OBJECTIVES: We sought to conduct a randomized trial with folic
acid 0.5 mg/day in a patient population with stable coronary artery
disease (CAD). BACKGROUND: Folic acid has favorable effects on
vascular endothelium and lowers plasma homocysteine levels. In
addition, homocysteine appears to be an independent risk factor
for atherosclerotic disease. However, the value of folic acid
in secondary prevention had seldom been tested. METHODS: In this
open-label study, 593 patients were included; 300 were randomized
to folic acid and 293 served as controls. Mean follow-up time
was 24 months. At baseline all patients had been on statin therapy
for a mean of 3.2 years. RESULTS: In patients treated with folic
acid, plasma homocysteine levels decreased by 18%, from 12.0 +/-
4.8 to 9.4 +/- 3.5 micromol/l, whereas these levels remained unaffected
in the control group (p < 0.001 between groups). The primary
end point (all-cause mortality and a composite of vascular events)
was encountered in 31 (10.3%) patients in the folic acid group
and in 28 (9.6%) patients in the control group (relative risk
1.05; 95% confidence interval: 0.63 to 1.75). In a multifactorial
survival model with adjustments for clinical factors, the most
predictive laboratory parameters were, in order of significance,
levels of creatinine clearance, plasma fibrinogen, and homocysteine.
CONCLUSIONS: Within two years, folic acid does not seem to reduce
clinical end points in patients with stable coronary artery disease
(CAD) while on statin treatment. Homocysteine might therefore
merely be a modifiable marker of disease. Thus, low-dose folic
acid supplementation should be treated with reservation, until
more trial outcomes become available.
Epilepsia. 2003;44 Suppl 3:33-40.
Clinical care of pregnant women with epilepsy: neural tube defects
and folic acid supplementation.
Yerby MS.
North Pacific Epilepsy Research, Portland, Oregon 97210, USA.
Women with epilepsy (WWE) have a risk of bearing children with
congenital malformations that is approximately twice that of the
general population. Most antiepileptic drugs (AEDs) have been
associated with such risk. Valproate and carbamazepine have been
associated specifically with the development of neural tube defects
(NTDs), especially spina bifida. Other factors may contribute
to the risk, including concomitant diseases such as diabetes mellitus,
occupational exposure to teratogens, excessive prepregnancy weight,
and various nutrient deficiencies. In the general population,
maternal folate deficiency, in particular, has been linked with
the development of NTDs, and periconceptional folate supplementation
with a reduction of risk. It is unclear whether folate supplementation
has a comparable protective effect for WWE. Data concerning the
risk for congenital malformations associated with the newer AEDs
(gabapentin, felbamate, lamotrigine, levetiracetam, oxcarbazepine,
tiagabine, topiramate, and zonisamide) are still limited. Several
pregnancy registries for women taking AEDs have been established.
Comprehensive postmarketing surveillance, regionally or nationally,
might be the ideal method of monitoring medication safety, but
government support for such an undertaking has for the most part
been lacking. Despite uncertainty about the efficacy of periconceptional
folate supplementation in WWE, these women should receive such
supplementation at dosage levels recommended for the general population
of women of childbearing age. Seizure control must not be neglected
in a pregnant woman with epilepsy since seizures are associated
with harm to the fetus as well as the mother. Risk may be minimized
by using a single AED at the lowest effective dosage.
Stroke. 2003 Jun;34(6):e51-4. Epub 2003 May 08.
Low vitamin B6 but not homocyst(e)ine is associated with increased
risk of stroke and transient ischemic attack in the era of folic
acid grain fortification.
Kelly PJ, Shih VE, Kistler JP, Barron M, Lee H, Mandell R, Furie
KL.
Stroke Service, Department of Neurology, VBK 802, Massachusetts
General Hospital, Fruit St, Boston, MA 02114, USA.
BACKGROUND AND PURPOSE: The introduction of cereal grain folic
acid fortification in 1998 has reduced homocyst(e)ine (tHcy) concentrations
in the US population. We performed a case-control study to determine
the risk of stroke and transient ischemic attack (TIA) associated
with tHcy and low vitamin status in a postfortification US sample.
METHODS: Consecutive cases with new ischemic stroke/TIA were compared
with matched controls. Fasting tHcy, folate, pyridoxal 5'-phosphate
(PLP), B12, and MTHFR 677C-->T genotype were measured. RESULTS:
Mean PLP was significantly lower in cases than controls (39.97
versus 84.1 nmol/L, P<0.0001). After stroke risk factors were
controlled for, a strong independent association was present between
stroke/TIA and low PLP (adjusted odds ratio [OR], 4.6; 95% CI,
1.4 to 15.1; P<0.001) but not elevated tHcy (OR, 0.92; 95%
CI, 0.4 to 2.1). CONCLUSIONS: Low B6 but not tHcy was strongly
associated with cerebrovascular disease in this postfortification,
folate-replete sample.
Chin Med J (Engl). 2003 Jan;116(1):15-9.
The effect of folic acid on the development of stomach and other
gastrointestinal cancers.
Zhu S, Mason J, Shi Y, Hu Y, Li R, Wahg M, Zhou Y, Jin G, Xie
Y, Wu G, Xia D, Qian Z, Sohg H, Zhang L, Russell R, Xiao S.
Department of Gastroenterology, The Ninth People's Hospital, Shanghai
Second Medical University, Shanghai 200011, China.
OBJECTIVE: To evaluate the roles of folic acid and beta-carotene
in the chemoprevention of gastric and other gastrointestinal (GI)
cancers. METHODS: In a randomized, double-blind, placebo-controlled
trial, a total of 216 patients with atrophic gastritis were randomly
assigned to one of the four groups: (1) folate (FA, 20 mg per
day plus vitamin B(12) 1 mg, intramuscularly, per month for one
year, then 20 mg two times a week plus 1 mg per three months for
the next year); (2) natural beta-carotene (N-betaC, 30 mg per
day for first year, then 30 mg two times a week for the next);
(3) synthetic beta-carotene (S-betaC, administered as in N-betaC);
and (4) placebo. Follow-ups continued from 1994 to 2001. RESULTS:
A total of 7 new cases of gastrointestinal cancers were diagnosed
with 3 stomach, 1 colon and 1 esophageal cancers occurring in
the placebo group; 1 stomach cancer in both of the N-betaC and
S-betaC groups, and no cancer occurring in FA group. In terms
of GI cancers, there was a significant reduction in the FA group,
compared with the placebo group (P = 0.04). A similar trend was
observed in both N-betaC and S-betaC groups (P = 0.07 - 0.08).
Taken together, the three intervention groups displayed a highly
significant decrease in occurrence (P = 0.004, vs placebo), and
a lower risk for GI cancers (OR = 0.12; 95% confidence interval,
0.03 - 0.51). For development of gastric cancer, any one of the
three active-treated groups did not reach statistically significant
reduction. The FA group showed obvious improvement of the gastric
mucosal lesions with more patients displaying lesions reversed
or stable atrophy and inflammation (P = 0.04), reversed intestinal
metaplasia (P = 0.06) at the end of follow-up, and reversed displasia
(P = 0.017) at 12 months. Two cases of false jaundice were found
in beta-carotene groups with no influence on administration, and
no side-effects were reported in FA group. CONCLUSIONS: This trial
revealed the interventional effect of folic acid on the development
of GI cancers, a similar effect of beta-carotene was also detected.
Also, folic acid may be of use to treat atrophic gastritis by
preventing or reversing the precancerous lesions.
Ageing Res Rev. 2002 Feb;1(1):95-111.
Folic acid and homocysteine in age-related disease.
Mattson MP, Kruman II, Duan W.
Laboratory of Neurosciences, Gerontology Research Center, National
Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224,
USA
It has been known for decades that babies born to women that have
a dietary deficiency in folic acid (folate) are at increased risk
for birth defects, and that the nervous system is particularly
susceptible to such defects. Folate deficiency in adults can increase
risk of coronary artery disease, stroke, several types of cancer,
and possibly Alzheimer's and Parkinson's diseases. Recent findings
have begun to reveal the cellular and molecular mechanisms whereby
folate counteracts age-related disease. An increase in homocysteine
levels is a major consequence of folate deficiency that may have
adverse effects on multiple organ systems during aging. Humans
with inherited defects in enzymes involved in homocysteine metabolism,
including cystathionine beta-synthase and 5,10-methylenetetrahydrofolate
reductase, exhibit features of accelerated aging and a marked
propensity for several age-related diseases. Homocysteine enhances
accumulation of DNA damage by inducing a methyl donor deficiency
state and impairing DNA repair. In mitotic cells such DNA damage
can lead to cancer, while in postmitotic cells such as neurons
it promotes cell death. The emerging data strongly suggest that
elevated homocysteine levels increase the risk of multiple age-related
diseases, and point to dietary supplementation with folate as
a primary means of normalizing homocysteine levels and increasing
healthspan.
Nutr Clin Care. 2002 May-Jun;5(3):124-32.
Folate, homocysteine, and neurological function.
Morris MS.
Nutritional Epidemiology Program, Jean Mayer USDA Human Nutrition
Research Center on Aging, Tufts University, 711 Washington Street,
9th Floor, Boston, MA 02111, USA.
The study of different neurological problems, including stroke,
Alzheimer's disease (AD), and depression, has propelled a greater
interest in interrelationships among folate, homocysteine, and
neurological function. Specifically, low folate status is a suspected
risk factor for depression that also results in an increase in
circulating levels of the sulfur amino acid homocysteine. Homocysteine
has emerged as an independent risk factor for stroke, and recent
studies suggest that vascular disease affecting the brain and
Alzheimer's disease may result together in senile dementia. The
relationship between stroke and AD was at first interpreted as
coincidence, given the pathologic distinctions between the two
diseases. However, the connection is now hypothesized to reflect
some common pathogenic factors involving folate, homocysteine,
or both. It remains unclear whether there is a causal relationship
between neurological dysfunction in either condition with folate
or homocysteine. Nevertheless, since improvement of folate status
lowers homocysteine levels, the hypothesis that folate supplementation
may lower the risk of several important health consequences of
aging, including various forms of neuropsychiatric dysfunction,
is worthy of current intensive exploration.
S D J Med. 2002 Sep;55(9):389-91.
Preventing birth defects with folic acid.
Stein Q, Keppen L, Watson WJ.
There a few birth defects known to be preventable, but neural
tube defects (NTDs) are one group of congenital anomalies that
can potentially be prevented. When 400 micrograms of maternal
periconceptional folic acid is taken daily, it can prevent many
neural tube-related birth defects and thus reduce morbidity and
mortality due to these birth defects. Health care providers should
encourage every woman of reproductive age to consume 400 micrograms
of synthetic folic acid daily, not just those who are planning
a pregnancy. Supplementation needs to be started prior to conception
for optimal effectiveness.
J Surg Res. 2002 Aug;106(2):342-5.
Oral folic acid improves endothelial dysfunction in cigarette
smokers.
OGrady HL, Leahy A, McCormick PH, Fitzgerald P, Kelly CK, Bouchier-Hayes
DJ.
Department of Surgery, Beaumont Hospital, Royal College of Surgeons
in Ireland, Dublin, 9, Ireland.
INTRODUCTION: Endothelial dysfunction is an early manifestation
of the atheromatous process and is evident without overt clinical
signs or symptoms of the disease. Cigarette smoking has been shown
to be associated with endothelial dysfunction in otherwise healthy
adults. Although cessation of smoking is the ideal objective,
it is not always attainable, and therefore any strategy to prevent
early endothelial dysfunction is desirable. Folic acid is currently
under review as a rational therapeutic agent in hyperhomocysteinemia.
However, folic acid may modify endothelial function independent
of its effect on homocysteine. We therefore investigated the effect
of folic acid on endothelial function in young otherwise healthy
cigarette smokers. METHODS: Volunteer cigarette smokers (n = 10)
and control lifelong nonsmokers were enrolled in the study. Baseline
folate, vitamin B12, homocysteine, and cholesterol levels were
analyzed. Flow-mediated dilatation, an endothelial-dependent phenomenon,
was assessed using ultrasonography. This scan was performed at
baseline and following 4 weeks of folic acid supplementation (5
mg/day). RESULTS: There were no significant differences in the
baseline hematological investigations between the groups. Homocysteine
levels were within normal limits in both groups and did not change
following folic acid supplementation. Cigarette smokers demonstrated
significant endothelial dysfunction compared to controls (P <
0.005). This difference was significantly attenuated by folic
acid supplementation (P < 0.005). CONCLUSION: Folic acid significantly
improves endothelial function in otherwise healthy cigarette smokers.
This provides a potential therapeutic tool in attenuating the
atheromatous process in this group.
Int J Cancer. 2002 Feb 20;97(6):864-7.
Dietary intake of folic acid and colorectal cancer risk in a cohort
of women.
Terry P, Jain M, Miller AB, Howe GR, Rohan TE.
Department of Epidemiology and Social Medicine, Albert Einstein
College of Medicine, Bronx, NY, USA.
Folate is crucial for normal DNA methylation, synthesis and repair,
and deficiency of this nutrient is hypothesized to lead to cancer
through disruption of these processes. There is some evidence
to suggest that relatively high dietary folate intake might be
associated with reduced colorectal cancer risk, especially among
individuals with low methionine intake. A case-cohort analysis
was undertaken within the cohort of 56,837 women who were enrolled
in the Canadian National Breast Screening Study and who completed
a self-administered dietary questionnaire. During follow-up to
the end of 1993, a total of 389 women were diagnosed with colorectal
cancer, identified by linkage to the Canadian Cancer Database.
For comparative purposes, a subcohort of 5,681 women was randomly
selected from the full dietary cohort at baseline. After exclusions
for various reasons, the analyses were based on 295 cases and
5,334 non-cases. Folate intake was inversely associated with colorectal
cancer risk (IRR = 0.6, 95% CI = 0.4-1.1, p for trend = 0.25).
The inverse association was essentially similar among individuals
with low and high methionine intake, and was similar for colon
and rectal cancers when those endpoints were analyzed separately.
Among individuals with low methionine intake, folate intake did
not appear to lower the risk of rectal cancer, a finding that
may be due, in part, to the low number of cases in the subgroup
analysis. Overall, our data lend some support to the hypothesis
that high folate intake is associated with a reduced risk of colorectal
cancer.
Nutrition. 2000 Feb;16(2):107-10.
Effects of supplementation with folic acid and antioxidant vitamins
on homocysteine levels and LDL oxidation in coronary patients.
Bunout D, Garrido A, Suazo M, Kauffman R, Venegas P, de la Maza
P, Petermann M, Hirsch S.
Faculty of Medicine, University of Chile, Santiago, Chile.
Hyperhomocysteinemia is an important cardiovascular risk factor.
Serum homocysteine levels are specially dependent on folate nutritional
status. In addition, the oxidative modification of low-density
lipoproteins (LDLs) in the endothelial microenvironment is a damaging
factor that can be modified with fat-soluble antioxidant vitamins.
The present study was done to assess the effect of a supplementation
of folic acid and antioxidant vitamins on homocysteine levels
and in vitro LDL oxidation in patients with coronary artery disease.
Twenty-three patients with angiographically proven coronary artery
disease were given supplements for 15 d consisting of one capsule
twice a day of a multivitamin preparation containing 0.65 mg folic
acid, 150 mg alpha-tocopherol, 150 mg ascorbic acid, 12.5 mg beta-carotene,
and 0.4 microgram vitamin B12. Serum lipids, vitamin and homocysteine
levels, and in vitro LDL oxidation were measured before and after
the supplementation period. During the supplementation period,
serum folate levels increased from 5.0 +/- 1.5 to 10.8 +/- 3.8
ng/mL (P < 0.001), vitamin B12 increased from 317.4 +/- 130.4
to 334.5 +/- 123.8 pg/mL (P < 0.05), and alpha-tocopherol increased
from 8.2 +/- 5.1 to 13.7 +/- 7.9 mg/L (P < 0.001). Serum homocysteine
levels decreased from 8.7 +/- 4.3 to 6.3 +/- 2.2 mumol/L (P <
0.001). In vitro LDL oxidation decreased from 2.6 +/- 1.1 to 1.6
+/- 1.1 nmol malondialdehyde/mg protein (P < 0.001). In comparing
patients with healthy controls, basal levels of folate were lower
in the patients, whereas vitamin B12, alpha-tocopherol, and homocysteine
levels were similar. No changes in serum lipid levels or body
weight were observed. In conclusion, a short-term supplementation
with folic acid and antioxidant vitamins can reduce serum homocysteine
levels and in vitro LDL oxidation in patients with coronary artery
disease.
N Engl J Med. 1998 Apr 9;338(15):1009-15.
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
Research Center, Beaverton 97006-3448, USA.
BACKGROUND: The Food and Drug Administration (FDA) has recommended
that cereal-grain products be fortified with folic acid to prevent
congenital neural-tube defects. Since folic acid supplementation
reduces levels of plasma homocyst(e)ine, or plasma total homocysteine,
which are frequently elevated in arterial occlusive disease, we
hypothesized that folic acid fortification might reduce plasma
homocyst(e)ine levels. METHODS: To test this hypothesis, we assessed
the effects of breakfast cereals fortified with three levels of
folic acid, and also containing the recommended dietary allowances
of vitamins B6 and B12, in a randomized, double-blind, placebo-controlled,
crossover trial in 75 men and women with coronary artery disease.
RESULTS: Plasma folic acid increased and plasma homocyst(e)ine
decreased proportionately with the folic acid content of the breakfast
cereal. Cereal providing 127 microg of folic acid daily, approximating
the increased daily intake that may result from the FDA's enrichment
policy, increased plasma folic acid by 31 percent (P=0.045) but
decreased plasma homocyst(e)ine by only 3.7 percent (P= 0.24).
However, cereals providing 499 and 665 microg of folic acid daily
increased plasma folic acid by 64.8 percent (P<0.001) and 105.7
percent (P=0.001), respectively, and decreased plasma homocyst(e)ine
by 11.0 percent (P<0.001) and 14.0 percent (P=0.001), respectively.
CONCLUSIONS: Cereal fortified with folic acid has the potential
to increase plasma folic acid levels and reduce plasma homocyst(e)ine
levels. Further clinical trials are required to determine whether
folic acid fortification may prevent vascular disease. Until then,
our results suggest that folic acid fortification at levels higher
than that recommended by the FDA may be warranted.
Med Hypotheses. 1995 Sep;45(3):297-303.
Folic acid as a cancer-preventing agent.
Jennings E.
Higher intakes of folic acid-rich foods such as vegetables, legumes,
and whole grains are associated with lower incidence of carcinomas
in international comparisons and case-control studies. Deficiency
of folic acid in experimental studies causes DNA damage that resembles
the DNA damage seen in cancer cells. The requirement for folic
acid in DNA synthesis and DNA methylation provides a plausible
mechanism for a mutagenic effect of a low-folate diet. It is suggested
that cancer can be initiated by DNA damage that results from folic
acid deficiency. The relatively low level of folic acid in North
American diets might be the underlying reason for high rates of
many cancers in North America.
Cas Lek Cesk. 1991 Jan 18;130(3):84-7.
Vitamin B12 and folic acid in chronic kidney failure and after
kidney transplantation.
Mydlik M, Machanova I, Derzsiova K, Pribylincova V, Reznicek J.
IV. Interna klinika fakultna nemocnica s poliklinikou, Kosice.
Vitamin B12 in plasma, folic acid in plasma and erythrocytes were
examined in 11 patients in the polyuric stage of chronic renal
failure without dialyzation treatment, in 38 patients included
in a long-term dialyzation programme before and after 3 months'
oral administration of folic acid--(2 X 5 mg week)--and in 23
patients after transplantation of the kidneys. In none of the
examined groups vitamin B12) and folic acid deficiency in plasma
was detected. A reduced folic acid level in erythrocytes, but
still in the reference range, was found in patients in the long-term
dialyzation programme without supplementation. Supplementation
with folic acid increased its concentration in plasma 4.5 times
and in red cells 5.5 times. Haemodialysis did not influence the
concentration of the examined indicators in plasma and red cells.
According to the recorded results it is not necessary to supplement
patients in long-term dialyzation programme and after renal transplantation
with vitamin B12 and folic acid, if their dietary protein intake
is not restricted.
