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B Vitamins

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Title
High dose-B-vitamin treatment of hyperhomocysteinemia in dialysis
patients.
Author
Bostom AG; Shemin D; Lapane KL; Hume AL; Yoburn D; Nadeau MR; Bendich
A; Selhub J; Rosenberg IH
Address
USDA Human Nutrition Research Center on Aging' Tufts New England
Medical Center' Boston' Massachusetts' USA.
Source
Kidney Int, 49(1):147-52 1996 Jan
Abstract
Hyperhomocysteinemia' an arteriosclerotic risk factor' persists in 75%
of dialysis patients despite routine low dose supplementation with the
B-vitamin co-factors/substrates for homocysteine (Hcy) metabolism' and
normal or supernormal plasma status of these vitamins (Atherosclerosis
114:93' 1995). We conducted a placebo-controlled eight-week trial of
the effect on plasma homocysteine of adding supraphysiologic dose folic
acid (15 mg/day)' B-6 (100 mg/day)' and B-12 (1 mg/day) to the usual
daily dosing of 1 mg folic acid' 10 mg B-6' and 12 micrograms B-12' in
27 hyperhomocysteinemic dialysis patients. Total plasma homocysteine
was measured at baseline' and after four and eight weeks. Blinded
analyses revealed no evidence of toxicity in the group randomized to
supraphysiologic dose B-vitamin supplementation. Plasma homocysteine
was significantly reduced after both four weeks (-29.8% vs. -2.0%; P =
0.0024) and eight weeks (-25.8% vs. +0.6%; P = 0.0009) of active versus
placebo treatment. Also' 5 of 15 treated versus 0 of 12 placebo group
patients had their plasma Hcy reduced to within the normative range (<
15 mumol/liter). Supraphysiologic doses of B-vitamins may be required
to correct hyperhomocysteinemia in dialysis patients.

Title
Excess prevalence of fasting and postmethionine-loading
hyperhomocysteinemia in stable renal transplant recipients.
Author
Bostom AG; Gohh RY; Tsai MY; Hopkins-Garcia BJ; Nadeau MR; Bianchi LA;
Jacques PF; Rosenberg IH; Selhub J
Address
Jean Mayer USDA Human Nutrition Research Center, Tufts New England
Medical Center, Boston, Mass., USA.
Source
Arterioscler Thromb Vasc Biol, 17(10):1894-900 1997 Oct
Abstract
Hyperhomocysteinemia, either fasting or after methionine loading, may
contribute to the increased incidence of cardiovascular disease events
experienced by renal transplant recipients. Limited data are available
on fasting homocysteine (Hcy) levels, and none on
postmethionine-loading Hcy levels, in these patients. We assessed the
prevalence and potential determinants of fasting and
postmethionine-loading hyperhomocysteinemia in 29 stable renal
transplant recipients and 58 age- and sex-matched, population-based
controls free of renal disease with serum creatinine levels of 1.5
mg/dL or less. Total (t) plasma Hcy was determined fasting and 2 hours
after methionine loading, along with fasting determinations of the
B-vitamin cofactors/substrates for Hcy metabolism, ie, pyridoxal
5'-phosphate, B-12, and folate and serum creatinine. Geometric mean
fasting (18.1 versus 9.8 microM, P < .001) and postmethionine-loading
increase (22.0 versus 15.2, P = .001) in tHcy levels were significantly
greater in the renal transplant recipients, as were the prevalence odds
(with 95% confidence intervals) for fasting [14.8 (3.4-64.7) ,
postmethionine loading [6.9 (1.5-32.8) , combined fasting and
postmethionine-loading [18.0 (2.3-142.1) hyperhomocysteinemia, and
inadequate circulating folate [4.2 (1.1-16.5) or pyridoxal 5'-phosphate
[3.2 (0.9-11.0) status. Correlation analyses suggested important
potential relationships between creatinine and both fasting (+0.64, P <
.001) and postmethionine-load increase (+0.38, P = .045) in tHcy,
folate and fasting (-0.41, P = .025) tHcy, and pyridoxal 5'-phosphate
and postmethionine-loading increase (-0.33, P = .091) in tHcy. We
conclude that there is an excess prevalence of fasting and
postmethionine-loading hyperhomocysteinemia in stable renal transplant
recipients. Renal function is related to both fasting and
postmethionine loading-hyperhomocysteinemia, inadequate folate status
is associated with fasting hyperhomocysteinemia, and inadequate vitamin
B-6 status may be related to postmethionine-loading
hyperhomocysteinemia in this patient population.

Title
Vitamins and cancer.
Author
van Poppel G; van den Berg H
Address
TNO Nutrition and Food Research Institute' Zeist' The Netherlands.
Source
Cancer Lett, 114(1-2):195-202 1997 Mar 19
Abstract
The prospect that high intake of certain vitamins may confer protection
against cancer has drawn substantial attention during the last decades.
This paper gives a concise update of the role of a number of promising
vitamins in prevention of cancer. Vitamin A and its analogues have an
important role in cellular processes related to carcinogenesis.
However' blood vitamin A levels are under strict control and a high
intake of preformed vitamin A does not seem to be relevant for cancer
prevention. The antioxidant vitamins C and E and beta-carotene may also
have other biological activities than free radical trapping that relate
to their cancer preventive properties. Mechanisms include immune
stimulation' inhibition of nitrosamine formation' enhancement of cell
communication and an influence on metabolic activation of carcinogens.
Epidemiological data for the antioxidant vitamins are promising' but
cannot rule out that another factor or combination of factors in fruits
and vegetables might be responsible for a protective effect. The B
vitamin folic acid is one of these potential factors that is currently
thought to have an influence on DNA methylation and thus on
proto-oncogene expression. Folic acid seems to be promising and
deserves further study. Vitamin D might be relevant in colon cancer
development due to its close links with calcium metabolism that might
influence cell proliferation. Overall' results are promising' but the
first human intervention trials on (antioxidant) vitamins and human
cancer have yielded somewhat disappointing results. At this moment the
data seem insufficient to make recommendations for vitamin
supplementation to prevent cancer. The results are certainly in line
with the advice that a diet rich in fruits and vegetables will help
reduce cancer risk.

Title
Environmental and physical stress and nutrient requirements.
Author
Askew EW
Address
Division of Foods and Nutrition' University of Utah' Salt Lake City.
Source
Am J Clin Nutr, 61(3 Suppl):631S-637S 1995 Mar
Abstract
When faced with hot' cold' or high-altitude environments' humans can
either modify the microenvironment to fit human physiology' adapt their
physiology to fit the environment' or use a combination of these two
tactics. Metabolic adaptations to heat' cold' and high-altitude
exposure may' in some instances' be accompanied by changes in nutrient
requirements. Energy expenditure is increased in all three
environments. B-vitamin cofactor requirements increase in proportion to
energy expenditure (oxidation of fat and carbohydrate). Increased
B-vitamin nutrient requirements are usually adequately met by an
increased consumption of the diet to meet energy requirements. Other
nutrients such as iron may be required in greater amounts to meet the
altitude-induced hematopoietic response in females. Additional
quantities of vitamins and minerals with antioxidant properties may be
beneficial to reduce the increased oxidative stress associated with
work in heat' cold' or high-altitude outdoor environments.

Title
Lipid peroxidation in mitochondrial inner membranes. I. An integrative
kinetic model.
Author
Antunes F; Salvador A; Marinho HS; Alves R; Pinto RE
Address
Grupo de Bioqu]imica e Biologia Te]oricas' Instituto de Investiga,c~ao
Cient]ifica' Bento da Rocha Cabral' Lisboa' Portugal.
Source
Free Radic Biol Med, 21(7):917-43 1996
Abstract
An integrative mathematical model was developed to obtain an overall
picture of lipid hydroperoxide metabolism in the mitochondrial inner
membrane and surrounding matrix environment. The model explicitly
considers an aqueous and a membrane phase' integrates a wide set of
experimental data' and unsupported assumptions were minimized. The
following biochemical processes were considered: the classic reactional
scheme of lipid peroxidation; antioxidant and pro-oxidant effects of
vitamin E; pro-oxidant effects of iron; action of phospholipase A2'
glutathione-dependent peroxidases' glutathione reductase and superoxide
dismutase; production of superoxide radicals by the mitochondrial
respiratory chain; oxidative damage to proteins and DNA. Steady-state
fluxes and concentrations as well as half-lives and mean displacements
for the main metabolites were calculated. A picture of lipid
hydroperoxide physiological metabolism in mitochondria in vivo showing
the main pathways is presented. The main results are: (a) perhydroxyl
radical is the main initiation agent of lipid peroxidation (with a flux
of 10(-7)MS-1); (b) vitamin E efficiently inhibits lipid peroxidation
keeping the amplification (kinetic chain length) of lipid peroxidation
at low values (approximately equal to 10); (c) only a very minor
fraction of lipid hydroperoxides escapes reduction via
glutathione-dependent peroxidases; (d) oxidized glutathione is produced
mainly from the reduction of hydrogen peroxide and not from the
reduction of lipid hydroperoxides.

Title
Net uptake of plasma homocysteine by the rat kidney in vivo.
Author
Bostom A; Brosnan JT; Hall B; Nadeau MR; Selhub J
Address
Framingham Heart Study' MA 01701' USA.
Source
Atherosclerosis, 116(1):59-62 1995 Jul
Abstract
Hyperhomocysteinemia is a common finding in dialysis-dependent
end-stage renal disease (ESRD) patients' but its etiology and
refractoriness to standard homocysteine-lowering B-vitamin therapy are
poorly understood. In the absence of actual in vivo data' it has been
hypothesized that loss of normal renal parenchymal uptake and
metabolism of homocysteine is an important determinant of
hyperhomocysteinemia in ESRD' given that urinary homocysteine excretion
by healthy kidneys is trivial. We assessed net renal uptake and
metabolism of homocysteine using an established rat model for measuring
arteriovenous amino acid differences across the rat kidney' along with
simultaneous determination of renal plasma flow' urine flow' and
urinary homocysteine concentration. Substantial homocysteine uptake and
metabolism by normal rat kidneys was demonstrated' and we also
confirmed that urinary homocysteine excretion is minimal. These data
suggest that loss of the sizable homocysteine metabolizing capacity of
the intact kidneys may be an important determinant of the refractory'
potentially atherothrombotic hyperhomocysteinemia frequently observed
in ESRD.

Title
Folate metabolism and neural tube defects: a review.
Author
Steegers-Theunissen RP
Address
Department of Epidemiology' University Hospital NiJmegen' The
Netherlands.
Source
Eur J Obstet Gynecol Reprod Biol, 61(1):39-48 1995 Jul
Abstract
The importance of folate in normal fetal development and wellbeing has
been recognized only during the past three decades and knowledge
concerned is still far from complete. In man' folate acts as a
substrate in the transfer of one-carbon moieties and thereby' plays an
essential role in the synthesis of several amino acids such as
methionine and nucleic acids. Consequently' folate requirements are
related to the amount of tissue growth. Epidemiological' clinical and
teratological research showed that this B-vitamin is particularly
involved in the prevention and pathogenesis of neural tube defects.
Therefore' in this review the metabolism of folate has been outlined.
Furthermore' the characteristics of the various genically determined
folate `deficiencies` as well as a possible biochemical explanation of
the relationship between folate and neural tube defects are being
discussed. Finally' the new recommendations launched in November 1993
by the Dutch Health Council as well as the Food and Nutrition Council
with regard to folate supplementation in the prevention of neural tube
defects are presented.

Title
Effect of factor B on vitamin B12 status and propionate metabolism in
sheep.
Author
Rickard TR; Elliot JM
Source
J Anim Sci, 55(1):168-73 1982 Jul
Abstract
Growing lambs fed diets containing two concentrations of Co (basal and
basal plus 1 ppm) were inJected with Factor B (cobinamide) or saline
during an 8-wk trial conducted to determine the effects of Factor B on
liver B12 levels and on propionate metabolism. At the end of the trial'
lambs given Factor B had lower (P less than .05) liver vitamin B12
concentrations and higher (P less than .05) Factor B concentrations
than controls fed the high Co diet. The high Co diet did not enhance
liver B12 levels in the lambs treated with Factor B. Feed intake and
body weight gain were not significantly affected by treatment. Plasma
propionate increased (P less than .05) with time on experiment' and
concentrations during the final period were negatively correlated (r =
-.45; P less than .05) with liver B12 levels. When the lambs were
loaded with propionate' a similar correlation (r = -.59; P less than
.05) was observed between log plasma level at t = 20 and liver B12
levels. Liver B12 levels (.2 to 1.1 micrograms/g) were all within what
is usually considered a normal range. .No significant relationship
between plasma propionate and liver Factor B levels were observed.

Title
B-vitamin supplementation of diets for feedlot calves.
Author
Zinn RA; Owens FN; Stuart RL; Dunbar JR; Norman BB
Source
J Anim Sci, 65(1):267-77 1987 Jul
Abstract
B-vitamin supplementation of diets for 144 shipping-stressed crossbred
calves (116 kg) at levels up to 10 times that recommended for growing
pigs did not influence (P greater than .20) weight gain or feed
conversion during a 56-d receiving trial. However, vitamin
supplementation tended (P less than .10) to reduce morbidity. In a
second trial, supplemental B-vitamins had no effect (P greater than
.20) on efficiency of microbial growth or site and extent of digestion
of organic matter, acid detergent fiber and N. Supplemental dietary
riboflavin, niacin, folic acid, B12 and ascorbic acid were largely
metabolized [degraded and (or) absorbed] anterior to the small
intestine, with escape values of 1, 3, 10 and 0% of added vitamins,
respectively, while dietary B6 and biotin largely escaped the rumen.
Thiamine and pantothenic acid were intermediate in ruminal escape (52
and 22%, respectively). Small intestinal absorption of thiamine,
niacin, riboflavin, B6 and B12 averaged 75, 79, 25, 79 and 48%,
respectively. Coefficients for ruminal escape and microbial synthesis
for each B-vitamin were calculated using the slope-ratio technique.
Measured flows for thiamine, riboflavin and B12 in a third experiment
were similar to flows predicted from escape and synthesis equations,
though flow of niacin and B6 were under-predicted by 37 and 44%,
respectively. Results are interpreted to indicate that intestinal
B-vitamin supply can be predicted based on dietary composition and
intake.

Title
Vitamin supplementation and physical exercise performance.
Author
van der Beek EJ
Address
Department of Human Nutrition' TNO Toxicology and Nutrition Institute'
Zeist' The Netherlands.
Source
J Sports Sci, 9 Spec No():77-90 1991 Summer
Abstract
Vitamins' Just as minerals and trace elements' meet with great interest
in the world of sports because of their supposed role in enhancing
physical performance. Of the 13 compounds now considered as vitamins'
most water-soluble vitamins and vitamin E are involved in mitochondrial
energy metabolism. The influence of vitamin supplementation on
mitochondrial metabolism is largely unknown. The principal argument for
vitamin supplementation is the assumed increased vitamin requirement of
athletes. Theoretically' an increased requirement can be caused by
decreased absorption by the gastrointestinal tract' increased excretion
in sweat' urine and faeces' increased turnover' as well as biochemical
adaptation to training. Of course' a marginal low vitamin status can
simply be the consequence of a long-term inadequate intake. However'
considering the RDAs there are no indications that long-term vitamin
intake among athletes is insufficient. Neither are there indications
that vitamin excretion or turnover is increased in athletes. However'
it is very likely that the (apparently) increased requirement is the
consequence of biochemical adaptation to training and does not indicate
a decreased intake. Although a marginal vitamin status' induced by
inadequate vitamin intake' may have a negative effect on performance'
there is no evidence to support the view that this occurs in trained
athletes. Moreover' vitamin supplementation in athletes with an
adequate vitamin status has no effect on physical working capacity.
Possibly' exceptions have to be made for the use of vitamin E at high
altitudes and for the use of vitamin C and multiple B-vitamin
supplements in hot climates.

Title
Role of the B vitamins in the immune response.
Author
Axelrod AE
Source
Adv Exp Med Biol, 135():93-106 1981
Abstract
Studies conducted in our laboratory relating to the development of
immune processes in B vitamin deficiency states of experimental animals
have been reviewed. 1. The significant participation of certain of
these nutritional factors in the production of circulating antibodies
to a variety of antigens and the manifestation of delayed
hypersensitivity reactions' including the reJection of tissue
transplants' have been described. 2. Investigations on the mode of
action of pyridoxine and pantothenic acid have demonstrated a marked
reduction in the production of antibody-forming cells following
antigenic stimulation in both deficiency states. The metabolism of
antigen appeared to be normal. However' these two vitamins seem to
function at different loci in the development of the immune process.
Whereas pyridoxine appears to be necessary for the production of "C1
units from serine which are required for the biosynthesis of nucleic
acids' it seems likely that pantothenic acid is involved in the
secretion of newly-synthesized proteins into the extracellular
compartment.

Title
Vitamin deficiencies in rice-eating populations. Effects of B-vitamin
supplements.
Author
BamJi MS
Source
Experientia Suppl, 44():245-63 1983
Abstract
Rice is the staple food in many countries of Asia. Recent nutrition
surveys in eight states' conducted by the National Nutrition Monitoring
Bureau of India' show that though the average energy intake is
adequate' more than 50% of the households surveyed consumed less than
the Recommended Dietary Allowance (RDA) of energy. These households
generally had per capita incomes of less than Rupees 2/- (US+ 0.25) per
day. The average intake of vitamin A was only 42% of the RDA and that
of riboflavin' 70% of the RDA. The average intake of other nutrients
such as thiamin' niacin' ascorbic acid' iron and calcium was adequate'
although thiamin deficiency was present in populations where rice was
the main cereal' but not in populations where rice was the main cereal'
but not in populations that consumed mixed cereal or cereal-millet
diets. The magnitude of the riboflavin deficiency (after correction or
energy) was also more marked in the former. Vitamin A intake was not
related to the type of cereal' but had some relationship to the
quantity of vegetables consumed. Nutrition surveys from Japan also
reveal deficiencies in intake of energy' vitamin A' thiamin and
riboflavin. The Japanese diet tends to be deficient by 20% in vitamin A
and riboflavin' but not thiamin. Thus' vitamin A' riboflavin and energy
(in that order) are the maJor nutritional constraints in rice-eating
populations. Clear-cut correlations between the magnitude of dietary
deficiency and the prevalence of signs and symptoms of vitamin
deficiency were not apparent in the comparisons between populations'
suggesting that as well as dietary deficiency other environmental
factors play a role in the development of clinical deficiency. Attempts
to correlate clinical deficiency with the magnitude of biochemical
deficiency have also failed. Recent studies aimed at examining the
effects of food supplements (rural Gambian women) or vitamin
supplements (rural Indian boys) on vitamin status suggest that in some
communities' vitamin intakes close to the RDA fail to saturate the
tissues' as Judged by biochemical tests. In the Indian boys' there was
a marked rise in urinary excretion of riboflavin during winter when the
incidence of respiratory infections was high. Metabolic losses of
vitamins due to infections may preclude tissue saturation despite
adequate dietary intake. Administration for 1 year of B-vitamins at
levels close to the RDA failed to reduce the prevalence of clinical
deficiency signs' but did produce some improvement in hand steadiness -
a psychomotor test.(Abstract TRUNCATED AT 400 WORDS)

Title
Influence of norethindrone on drug-metabolizing enzymes of female rat
liver in various B-vitamin deficiency states.
Author
Wade AE; Evans JS
Source
Pharmacology, 15(4):289-301 1977
Abstract
Ingestion of high levels of thiamin significantly decreased the
activity of cytochrome P-450, NADPH cytochrome c reductase, and the
metabolism of aniline and ethylmorphine. Apparent VmaxS for
ethylmorphine N-demethylase and aniline hydroxylase were decreased by
high levels of riboflavin even though NADPH cytochrome c reductase was
elevated. High levels of dietary pyridoxine significantly decreased
only the Vmax for aniline hydroxylase. Generally, norethindrone
produces either no change or slight depression of cytochrome P-450
regardless or diet, whereas the administration of norethindrone
produced no change or an increase in activity of c reductase and
ethylmorphine N-demethylase. Norethindrone induces aniline hydroxylase
in animals fed all diets except those deficient in thiamin and
riboflavin. The activities of the four parameters of the drug
metabolizing system measured in these studies as well as the effects of
norethindrone are clearly affected by the dietary status of the animal.

Title
Biochemical assessment of vitamins and trace metals.
Author
Jacob RA; Milne DB
Address
Western Human Nutrition Research Center' United States Department of
Agriculture' Presidio of San Francisco' California.
Source
Clin Lab Med, 13(2):371-85 1993 Jun
Abstract
The choice of nutritional assessment tests must be made with care' as
the available tests may reflect recent dietary intakes or body tissue
stores to different degrees. The interpretation of nutritional
assessment tests is complicated by the dynamic nature and broad range
of nutrient intake and metabolism and by a relative lack of age- and
sex-specific reference ranges. The latter problem can be minimized by
the use of function-based methods' such as the measurement of
vitamin-dependent red cell enzyme activities to assess B vitamin
status; however' few suitable function-based methods are now available'
and more research in this area is needed. Because calibration standards
and quality control materials may not be readily available' laboratory
analysts planning nutritional assessment testing must be especially
careful in establishing the credibility of assays and the quality
control program. Recent advances in analytic methodology include the
specificity offered by HPLC techniques and methodologies that provide
simultaneous determination of more than one nutrient (or form of
nutrient) in a single procedure. Examples of the latter include HPLC
methods that provide B vitamin or fat-soluble vitamin profiles' and
emission spectrometry techniques that provide trace metal profiles.
Further work in providing useful nutritional assessment profiles and
convenient automated methods is needed.

Title
Environmental and physical stress and nutrient requirements.
Author
Askew EW
Address
Division of Foods and Nutrition' University of Utah' Salt Lake City.
Source
Am J Clin Nutr, 61(3 Suppl):631S-637S 1995 Mar
Abstract
When faced with hot' cold' or high-altitude environments' humans can
either modify the microenvironment to fit human physiology' adapt their
physiology to fit the environment' or use a combination of these two
tactics. Metabolic adaptations to heat' cold' and high-altitude
exposure may' in some instances' be accompanied by changes in nutrient
requirements. Energy expenditure is increased in all three
environments. B-vitamin cofactor requirements increase in proportion to
energy expenditure (oxidation of fat and carbohydrate). Increased
B-vitamin nutrient requirements are usually adequately met by an
increased consumption of the diet to meet energy requirements. Other
nutrients such as iron may be required in greater amounts to meet the
altitude-induced hematopoietic response in females. Additional
quantities of vitamins and minerals with antioxidant properties may be
beneficial to reduce the increased oxidative stress associated with
work in heat' cold' or high-altitude outdoor environments.

Title
The effects of dietary niacin and riboflavin on voluntary intake and
metabolism of ethanol in rats.
Author
Pekkanen L; Rusi M
Source
Pharmacol Biochem Behav, 11(5):575-9 1979 Nov
Abstract
The effects of dietary deficiency and excess of niacin and riboflavin
on voluntary drinking of 10% (v/v) ethanol were studied in male rats.
The effectiveness of dietary deficiency and excess of both niacin and
riboflavin on tissue levels of these vitamins was demonstrated by
measurements of urinary N1-methylnicotinamide and blood glutathione
reductase (EC 1.6.4.2) activity. A high-niacin diet containing 75 mg
niacin/kg food decreased ethanol intake by about 36% compared to the
control diet containing 15 mgniacin/kg. Niacin or riboflavin deficiency
and a high-riboflavin diet containing 40 mg rtary levels of niacin or
riboflavin did not influence on ethanol elimination rate or levels of
blood acetaldehyde during ethanol oxidation. Therefore, blood
acetaldehyde was not responsible for the decreased ethanol intake of
rats fed with a high-niacin diet. It was concluded that the increased
ethanol intake caused by dietary deprivation of B-vitamin complex found
in earlier studies is not a result of deficiency of niacin or
riboflavin but niacin may be involved in the decrease in ethanol
drinking, which follows dietary B-vitamin complex supplementation.

 

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