Utah State University
DigitalCommons@USU All Graduate Theses and Dissertations
Graduate Studies
1981
Vitamin A and Vitamin E Status of Persons on Hemodialysis Kathleen S. Johnson Utah State University
Follow this and additional works at: http://digitalcommons.usu.edu/etd Part of the Human and Clinical Nutrition Commons Recommended Citation Johnson, Kathleen S., "Vitamin A and Vitamin E Status of Persons on Hemodialysis" (1981). All Graduate Theses and Dissertations. 5296. http://digitalcommons.usu.edu/etd/5296
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Utah State University
DigitalCommons@USU All Graduate Theses and Dissertations
Graduate Studies
1981
Vitamin A and Vitamin E Status of Persons on Hemodialysis Kathleen S. Johnson
Follow this and additional works at: http://digitalcommons.usu.edu/etd Part of the Human and Clinical Nutrition Commons This Thesis is brought to you for free and open access by the Graduate Studies at DigitalCommons@USU. It has been accepted for inclusion in All Graduate Theses and Dissertations by an authorized administrator of DigitalCommons@USU. For more information, please contact
[email protected].
VITAMINA ANDVITAMINE STATUS OF PERSONSON HEMODIALYSIS by
Kathleen
S. Johnson
A thesis submitted in partial fulfillment of the requirements for the degree of
MASTER OF SCIENCE in Nutrition
and Food Sciences
UTAHSTATEUNIVERSITY Logan, Utah
1981
ii ACKNOWLEDGMENTS Special
thanks
Wyse for their I would also his
invaluable like
suggestions Special
operation
this
Salt
my appreciation
throughout
this
study.
to Dr. LeGrande Ellis
as a member of my supervisory
is given to the following,
for
connnittee.
without
M.D.; Edward Zawada, M.D.; Mary Spitzer,
Lake City,
Kidney Center I am grateful
Traineeship
and support
and Dr. Bonita
whose co-
study could not have been accomplished:
of the hemodialysis
Center, Valley
to express
appreciation
to Dr. Deloy Hendricks
assistance
and assistance
German Ramirez, staff
is extended
unit
of the Veterans
Administration
as well as the hemodialysis
and Utah Dialysis
for financial
support
R.D.;
Lab, Salt provided
staffs
and the Medical
of Central
Lake City. by Allied
Health
Program Grant number 5 A02 AH 00746-04 and 05. Kathleen
S. Johnson
iii
TABLEOF CONTENTS
Page
ACKNOWLEDGEMENTS
ii
LIST OF TABLES
iv
LIST OF FIGURES. ABSTRACT
v
vi
INTRODUCTION.
1
REVIEWOF THE LITERATURE.
6
METHODOLOGY.
23
RESULTS.
29
DISCUSSION.
42
REFERENCES
50
APPENDICES.
56
iv LIST OF TABLES Table
Page
1.
Subject
2.
Plasma vitamin A levels and controls ...•..
in dialysis
Plasma vitamin E levels and controls .•••••
in dialysis
3.
and control
description
4.
Pre and post
5.
Plasma carotene levels and controls ••••.•.••••••
6.
Plasma vitamin and controls.
7.
Vitamin
intake
and controls.
8.
Vitamin
levels
dialysis
.
••
............ patients
........... ......
30
plasma
A/carotene
levels
in dialysis
35 patients 35
in dialysis
patients
for dialysis in dialysate
39
patients
. . . . . . . . . . . . . . . . .
measured
29
patients
. . . . . . . . . . . . . . . . .
estimates
24
samples •.•
40
41
v
LIST OF FIGURES Figure
Page
....... patients. ..
1.
Vitamin
2.
Plasma vitamin
A vs.
3.
Plasma vitamin
A
vs.
dialysis
4.
Plasma vitamin
A
VS,
months of dialysis.
5.
Plasma vitamin patients
A vs.
6.
Plasma vitamin
E vs.
age of dialysis
7.
Plasma
vitamin
E vs.
months of dialysis.
Plasma vitamin
E vs.
vitamin
8. 9.
A absorption
...
patients
. . . .
Current
information
and transport age of dialysis
vitamin
hours/week
A
intake
on metabolism
32 33 34
patients.
E intake
31
of dialysis
....
. . . . . . . .
13
.
36 37
of dialysis . . . . .
of ~-tocopherol
38
46
vi ABSTRACT Vitamin
A and Vitamin
of Persons
E Status
on Hemodialysis by
Kathleen
S. Johnson,
Utah State
Master
of Science
University,
1981
Major Professor: Dr. Deloy G. Hendricks Department: Nutrition and Food Sciences The study status
was designed
of persons
from thirty matched
receiving
persons
controls,
tene using
A and E were estimated
elevated
studied. vitamin
in persons
assay
for
questioning.
when compared with
failure
controls.
Vitamin
and in plasma were higher
than expected.
plastic
ether
and the petroleum
in false
high values.
between
the two groups
and supplemental
intake
in the hypervitaminosis
Vitamin
reacted intakes
E measured
of vitamins
It
carotene
hemodialysis,
is possible
during
levels
in dialysate
the assay
samples
that
the
and resulted
were not significantly was considered.
A is most likely
A seen in renal
A and E, and a
showed significantly
maintenance
when supplementation of vitamin
E, and caro-
intakes
E, and decreased
receiving
as age and sex-
Samples of dialysate
of the investigation
A, normal vitamin
with renal
Dietary
E
Blood samples
A, vitamin
for vitamins
carotene.
via verbal
Results
as well
for vitamin
a spectrofluorometric
A and vitamin
hemodialysis.
hemodialysis,
were analyzed
assay
the vitamin
maintenance
receiving
spectrophotometric
were also
to assess
failure,
different Dietary
not of importance
as physiological
or
vii biochemical
roles
min A levels. lipase, synthesis clotting
appear
A role
unsaturated is possibly in persons
to be the underlying
of hypervitaminosis fatty
acid
receiving
vita-
phospho-
and therefore
prostaglandin
in altering
hemodialysis
of elevated
A in regulating
production,
a mechanism
cause
platelet
aggregation
and
treatment. (75 pages)
CHAPTERI I INTRODUCTION Elevated
plasma levels
been reported etiology
in persons
of these
of vitamin
undergoing
findings
elusive
regarding
this
questions;
of vitamin
group of hemodialysis
prescribed
patients
with vitamin
for patients.
is some indication exhibiting
hemodialysis.
Researchers
however,
The
in this
the answers
that
E have been reported
in Japan Eis
(Ito
not part
Further
of vitamin
A can be beneficial
et al.,
area
remain
in one small 1971),
of the current
investigation
supplementation
low serum values
serum vitamin
unclear.
symptoms have
abnormality.
Low plasma levels
supplementation
maintenance
remains
have posed many interesting
A and toxicity
however therapy
is needed since
with vitamin
E in animals
E with concomitant
in normalizing
there
elevated
both serum vitamin
levels.
Background of the Problem Elevated ly reported
levels
of plasma vitamin
in the 1930's
and 1940's
A in renal
disease
(Hedburg and Lindquist,
were initial1938;
Clausen and McCoord, 1938; Wendt, 1936; and Popper and Steigmann, but,
little
investigative
the 1970's. levels
Elevated
attention retinal
in the plasma of persons
was paid
binding
protein
with renal
by Smith and Goodman (1971) and Vahlquist researchers features
stated
that
with uremia,
vitamin
et al.
that
phenomenon until
(RBP) and vitamin
failure
A intoxication
it was concluded
to this
1943);
A
have been reported (1973).
shared
Although
many clinical
hypervitaminosis
A was
these
2
not specifically
incriminated
in the pathogenesis
of any part
of the
uremic syndrome. Sullivan,
as well as Kopple and Swendseid,
1974 discussing that
vitamin
very little
requirements
vitamin
vitamins
from plasma during
minimal,
they concluded
vitamins
A, E, or K.
In Greece, with varying
degrees
A, as well
chronic
renal
of renal as,
failure.
hypervitaminosis
liver
similarity
A in chronic
with discontinuation
1979).
continues
insome dialysis
1979).
investigation
with
between
against
patients
after
supplementa-
reviewing
the
A symptoms
was documented
containing
vitamin
A still
1979).
of the Problem
et al.,
1971) reported
on hemodia1ysis;
has been reported
advised
One case of reversing
(Shmunes,
Statement
E in six persons
A, in persons
A supplementation
units
(Ito
serum
and hypervitaminosis
The use of multivitamins
A group in Japan
A in persons
a relationship
hemodialysis
of vitamin
(Shmunes,
of vitamin
vitamin
strongly
of symptoms between uremia
(Shmunes, 1979 and Murray,
vitamin
of
osteodystrophy.
In 1979, two U. S. researchers of vitamin
to be
and found elevated
They suggested
A and renal
treat-
was no need to give supplements
function
elevated
of dialysis
would be expected
(1975) studied
et al.
in
Because the removal of fat-soluble
hemodialysis there
papers
They acknowledged
on the effect
status.
that
Yatzidis
vitamin
tion
and dialysis.
data were available
ment on fat-soluble
presented
low plasma levels
however,
in the literature.
no follow-up Elevated
levels
of
3
vitamin
A and RBP in persons
documented
in the literature;
and possible
abnormalities
An interrelationship
animal
chronic
however, in renal
Vitamin
to protect
with
elevated
the effect
of this
of vitamin
is
factor.
limited,
therefore
various
A.
If
this
vitamins
etiologies,
Age and sex-matched
failure
it
any one abnormality in chronic
in renal
renal as possible.
failure
is
would add to the knowledge
which may have a significant
involved
had been found,
of as many of the imbalances
investigation
of
concomitant
in renal
to attribute
goal of treatment
of fat-soluble further
low levels
E would have been evaluated.
complications
impossible
if
abnormality
interrelated
the normalization
study
A
1957 and
hemodialysis,
of the Study
The major
in the area
This
of vitamin
was to determine
with vitamin
and probably
Research
of a subject
documentation.
A (Cox et al.,
Significance With the multiple,
failure
further
E
A and E has been shown in
on maintenance
of supplementation
to a single
vitamin
of the Study
research
in persons
levels
is impractical
regarding
require
hypervitaminosis
Purpose
E occurred
information
have been well
1970),
Mccuaig and Motzok,
vitamin
failure
E given with high levels
against
The objective
renal
failure
between vitamins
studies.
appears
with
impact
Research
Design
30 persons
with
receiving
maintenance
"healthy"
persons
end-stage
on future
renal
hemodialysis
treatment.
disease treatment.
were used as controls.
of
4 Blood samples ment.
Post
dialysis
subjects.
in carotene,
vitamin
questioning
of all
from the subjects type of kidney artificial
E.
used,
types
samples
Blood samples
were analyzed from control
Subjects
from
length
of time on dialysis
length
of time per
medications.
Dialysate
obtained
therapy,
type of
other
samples
were collected
medical
from four hourly
and
A and E.
for this
Educational
of the
study.
however,
both groups.
Although
total
intake
Study old served
Twenty-seven
and economic
and controls;
levels
a variety
a food frequency
on a voluntary
of the thirty
were not matched of levels
questionnaire
subjects between
was obtained
in
was utilized,
was not evaluated. Limitations
Many of the foods as well
via verbal
the following:
treatment,
kidneys
and foods
Information
included
with a mean age of 48 years
as subjects
supplements
E was obtained
records
of artificial
for vitamins
in potassium
of the
by the researcher.
medical
and prescribed
dietary
from five
of vitamin
Delimitations
subjects
taken
plasma
A, and vitamin
and/or
kidney
were male.
treat-
in the same manner as samples
intake
subjects
disease,
representative
basis
a dialysis
subjects. regarding
analyzed
dialysis
were drawn and treated
before
were also
A, and vitamin
Information
problems,
samples
and post
vitamin
the research
high
blood
Predialysis
for carotene, subjects
were drawn from subjects
of the Study
on the food frequency
as in vitamin
A.
Since
questionnaire
were high
low potassium
diets
are an
5
adjunct regarding vitamin
for
therapy
low potassium A containing
Vitamin type
and technique,
artificial problems,
instruction
to dietary
intake
of
samples
can be minimized
can be a concern by careful
in this
handling
but not avoided. which were accounted
on each subject
of kidney
the responses
in the blood
This problem
Limitations
type
diets,
have had intensive
foods may have been conservative.
instability
of study.
collected
and the subjects
disease,
kidney
used,
and medications
include
for and for which data
the following
variables:
length
of time on dialysis
length
of time per treatment,
prescribed.
therapy, other
were age,
sex,
type of medical
6 CHAPTERII REVIEWOF THE LITERATURE The objective
of this
ground information
necessary
min A and vitamin possibility persons
literature
to evaluate
E in persons
of modifying
search
with
the current
chronic
abnormalities
was to provide
renal
the back-
status
of vita-
failure.
in the vitamin
Also,
status
the
of these
was reviewed. Vitamin
Vitamin tenoids
that
A is a generic exhibit
term retinoid natural
out biological
term used for compounds other
biological
has been accepted
forms and synthetic activity
A
activity
similar
as a general
analogs
to retinal.
A, both with and with-
(Goodman, 1979).
sues,
vitamin
A is found in the form of long-chain
Plant
sources
of vitamin
sion
to vitamin
Conversion
A contain
8-carotene
The conversion
to Vitamin
of 8-carotene
tene-15,15'-dioxygenase
retinaldehyde
retinyl
tis-
esters.
which requires
conver-
A to vitamin
mucosa of the duodenum and jejunum
8-carotene
In animal
A.
of Carotene
15'-dioxygenase,
The
term for both the
of vitamin
of retinal
than caro-
at the central
and requires
and retinaldehyde
a soluble
A occurs
two enzymes:
reductase.
mucosa! enzyme, catalyzes double
(Goodman and Olson,
bond to yield 1969).
primarily
in the 8-caro-
8-carotene-15, the cleavage
two molecules
of
of
The enzyme has an absolute
7 requirement
for molecular
detergent, vitro
such as bile
activity
aldehyde tase,
salts,
non-specific
aldehydes
one molecule
in
of the retin-
retinaldehyde
reduc-
to be a relatively
short
or medium chain
of $-carotene
A, but actually
are at least
yields
ten carotene
S, and cryptoxantine
can yield
two
only one molecule
Conversion intestine,
precursor
of carotene
liver,
kidney,
is almost
(Baker
in depot
Transport
and Absorption being
ported
mainly
micron
remnants
In the liver, esters
fat
(Baker
of Vitamin
in association are cleared
are
of the
unconverted
concarotene
A retinyl
esters
lymph chylomicrons.
by the
liver
(Smith
and reesterification
stored,
in diseases
1968).
intestine,
with
The S form
In hypothyroidism,
Absorbed,
and Frank,
only
1968).
A is limited
blocked.
formed in the
hydrolysis
and Frank,
and in diabetics.
(Baker
known, however
in human nutrition.
to vitamin
completely
is stored
After
precursors
are useful
is the most important
hepatocytes
several
for
1968).
There
retinyl
for
for a
(Goodman, 1979).
of vitamin
version
The reduction
by the enzyme,
reductase
Stoichiometrically,
a,
1967).
requirement
such as lecithin,
NADHor NADPHand appears
aldehyde
and Frank,
and a lipid
is catalyzed
which requires
molecules
and a nonspecific
(Goodman et al.,
to retinal
aliphatic
oxygen
associated
with
trans-
The chylo-
and Goodman, 1979).
occur lipid
are
and the resulting
droplets,
within
(Goodman, 1979).
In the 1960's
it
was demonstrroted
that
circulating
vitamin
A is
8
transported
in plasma as the alcohol,
protein,
retinal-binding
protein
Smith and Goodman (1979) olism
that
liver
to the extrahepatic
available volves
cell
that
surface
suggests
on bovine 1975).
there
serum albumin, cells
retinal
the RBP delivers
sites
that
"recognize"
metabolism
and action.
Roles
of Vitamin The major
clearly
defined
dition,
it
tenance
of life.
of vitamin
rhodopsin.
cell
cells
of vitamin
of retinal
process
surface
was taken
receptors
for
and releases
retinal
RBP and the retinal
1976)
up without
and
uptake
bound to bovine
up by the pigment
From current
RBP
1977 and Heller,
nonspecifically
1977).
in-
has been reported
(Chen and Heller,
was not taken
Information
(Rask and Peterson,
retinal
A metab-
from the
the delivery
Evidence
cells
knowledge,
epithelial it
appears
at specific
cell
surface
then enters
the cell
for
A physiological
function
on a biochemical
Recent
research
A in the synthesis role
of vitamin
(visual
A that
is the role
for growth,
has been
in vision.
reproduction,
has been done which suggests
of glycoproteins A occurs
and hexosamine-containing Rhodopsin
of vitamin
basis
is known to be required
The visual a hexose
mucosa!
1968).
of the vitamin.
that
specific
to the cells
(Chen and Heller,
that
of action
of cells,
When presented
the delivery
for RBP.
epithelial
In both kinds
in a review
suggests
are
intestine
pigment
of RBP.
sites
receptors
that
on monkey small
for
studies
bound to a specific
(RBP) (Kanai et al.,
reported
RBP is responsible
from animal
retinal,
protein,
purple)
(DeLuca et al.,
as it
combines
and maina role 1973).
with opsin,
to form the visual
is a combination
In ad-
pigment
of the protein
9 scotopsin
(opsin)
and the
carotenoid
and is present
in the rod cells
vitamin
of rhodopsin
moiety
pigment
retinene
of the retina.
is 11-cis
(11-cis
The active
retinene
(also
retinene)
form of the
called
retinal,
retinaldehyde). Rhodopsin the
cis
to the
scotopsin. signals
is decomposed trans
During are
to the cis night
form.
regeneration
process
the central requiring
Some of the vitamin results
prevent
night
process
as it
system.
retinene
molecule.
and
The pigment
is isomerized
back
in the process,
vitamin
and
A is available
Both retinal
but retinoic
from
away from the
the rods are excited
is degraded
when insufficient
blindness,
pulling
nervous that
changes
and retinalde-
acid
can not be converted
for
is not effective
in vivo
to either
selective
vitamin
or retinaldehyde.
Retinoic
Acid
Retinoic
acid,
activity,
should
and renal
failure.
a compound that
also
Kleiner-Bossaler excretion
product
retinol.
of vitamin
With loss
and thus
be mentioned
demonstrates in relation
to vitamin
and DeLuca (1971) described
them to the conclusion
acid
into
and the retinene gradually
splitting
of the rhodopsin
in the visual retinal
this
in the dark,
blindness
hyde will
configuration,
transmitted
is regenerated
by light
reduced
that
A derivatives. retinoic
of renal excretion
tissue,
acid
Their
studies
A metabolism
acid
as an
in rats
is formed in the kidney
decreased
of vitamin
retinoic
production
A derivatives
A
led from
of retinoic may occur.
10 Goodman (1979) retinaldehyde ported
oxidation
in plasma Fidge
described
retinoic
in the
acid
intestine.
(1968)
the portal
system
and does not accumulate
the liver
or other
excreted
Vitamin
is partially
is absorbed
is rapidly
producing
is trans-
1973).
in significant
reabsorbed
through
amounts
metabolized
in
and
metabolite, from the intestine
an enterohepatic
circu-
in vivo when the level
of
1967).
A toxicity
appears
to occur
A in the body is such that
unbound retinal
in plasma and thus becomes available to RBP.
acid
A Toxicity
Vitamin vitamin
acid
The major biliary
back to the liver,
(Olson,
it
formed from
(Smith et al.,
retinoic
Instead
and bile.
retinoyl-8-glucuronide,
lation
found that
tissues.
in the urine
and transported
Retinoic
bound to serum albumin
et al.
as being
The nonspecific, manner may lead
to vitamin
1979).
Data consistent
with
from studies
of vitamin
this
to circulate
to membranes in a form not bound
unregulated
in this
begins
delivery A toxicity
interpretation
A transport
of vitamin
A to tissues
(Smith and Goodman, has been reported
in humans (Smith and Goodman,
1976). Effects
of overdose
ing symptoms: ful
irritability,
bones and joints,
abnormal decreased (Kutsky,
1973a).
nerve
mucous cell
bone growth, clotting
with vitamin
loss
time,
A can include
lesions, formation
of hair, and elevated
jaundice,
fatigue,
any of the followinsomnia,
in keratinized itchy
serum alkaline
skin,
pain-
membranes, anorexia,
phosphatase
11 Vitamin A in Renal Failure Early
investigators
(Hedburg and Lindquist,
1938; Clausen
and
McCoord, 1938; Wendt, 1936; and Popper and Steigmann,
1943) reported
high plasma vitamin
types
disease,
whereas
A levels
others
reported
1938b) or even reduced Possible either
reduced
excretion
vitamin
A transport
chronic
renal
rise
(Yatzidis
serum vitamin
1975).
have been reported
of prealbumin
remains
normal
and Vahlquist
et al.,
1973).
suggesting
by the kidney
most,
In a recent stated
that
The normal
review
et al.,
the kidney
levels
the fact
that
and that
catabolism
is small
enough to be filtered
renal
metabolism
studies important
done by Vahlquist role
of
to be elevated,
while
that
four hour half-life with chronic
extent,
renal
failure,
(1973),
for RBP, RBP alone
however when Although
glomerular
it
reflect
site
disease.
glomeruli,
major ' catabolic
of the RBP-prealbumin
failure
the main catabolic
can not be filtered.
et al.
renal
Smith and Goodman (1979)
in chronic
its
of free
RBP in plasma is catabolized
by the renal
it
1971;
1973).
is normally
found to a great constitute
or
or RBP) in
of RBP seen in renal
is impaired
complexed with prealbumin, is not usually
free
of the subject,
the elevated
protein
protein,
in patients
if not all,
(Vahlquist
failure
(Smith and Goodman, 1971; Peterson,
10 to 15 fold
that
A in renal
Plasma concentrations
(retinol-binding
failure
RBP is increased
1938a and
in serum retinol-binding
et al.,
protein
(Catel,
of renal
1937).
for elevated
a previous
with various
normal values
ones (Grant,
mechanisms
include
in patients
filtration
route.
free
RBP
and
From turnover
can be interpreted
complex is the sparing
than an of RBP
12
from glomerular
filtration.
tion
A in renal
of vitamin
Figure
of impaired
failure
catabolism
are marked with an asterisk
the water-soluble
the fat-soluble
vitamins
vitamins
are more dialyzable
than
such as A and D which are protein
bound
(Smith and Goodman, 1971 and Haddad and Chuy, 1971). concerning there
the adequacy
was very
vitamins
little
of dialysis, published
A, D, E, and K.
necessary
to give
dialysis, vitamin
A in dialysis
need for vitamin
based
have many signs been reported Gotloib before
10% decrease in carotenoid justified
vitamin
of elevated
there
that
et al.
is not
levels
uremia
to be a
on reconnnenda-
patients,
and Yatzidis
of
et al.
the (1975) were
and vitamin
A toxicity
deficiency
has not
1977). (1978),
and after
in Israel,
measured
hours
of hemodialysis
eight
in plasma vitamin levels.
it
in hemo-
does not appear
and symptoms in connnon and that (Stone,
on
nutrition
in hemodialysis (1974)
concluded
of dialysis
In a 1977 report
supplementation
The author
that
A, E, or K.
reviewed
that
reported
was then made that
on reports
patients,
of Feldman and Singer
reviewed.
crease
(1975)
At a conference
(1974)
on the effect
of vitamins
A supplementation.
for vitamin
studies
data
supplements
and concluded,
Sullivan
The conclusion
Kopple and Swendseid
levels
in
A and Dialysis
In general,
tions
and excre-
1.
Vitamin
are
Sites
A levels
however,
as the levels
A and carotene
and observed
(p < .01) with
They did not believe,
supplementation,
vitamin
little that
a
change this
of plasma vitamin
deA
13 S-carotene S-carotene 15,15 1 -dioxygenase (oxygen, bile salt, lipid)
Retinyl
Esters
(preformed)
l
2 Retinaldehyde (small amount oxidized ret· to retinoic acid in red J.naJ.deJlntestine) Ov-4.D~c tase de Of
N
'-4.Dpl!J
Retinol
l l
Absorbed Reesterified Lymphatic
into
mucosal
with LCFA (mainly circul~ion
l
/
Tissue triglyceride)
saturated)
(chylomicrons)
*Blood (retinol-RBP Extrahepatic (chylomicron
cell
complex)
~Liver
(chylomicron retinyl esters stored in hepatocytes)
l
Retinol-RBP-Prealbumin
t
Peripheral
l
l
Retinoic
Liver ------------
Portal
~dney
l
Bile (retinoyl-8-glucuronide) (Adapted Figure
1.
from Goodman, 1979) Vitamin
A absorption
and transport,
sites
Complex of action
Acid (complexed to serum albumin) System
(metabolized)
Urine
14 were elevated
(5.88
IU/ml or 176.4 µg/dl)
in patients
on maintenance
hemodialysis. Werb et al. dialysis
(1978) from Canada,
frequency,
tration
length
termined vitamin
a single
A level,
patients.
dialysis
but that
with continuation
dialysis.
did have higher
results,
has no effect
the serum vitamin
of regular
min A supplementation
From their
treatment
A per
it was deon the serum
A level
does rise
The patients
receiving
levels
than those
steadily vita-
who were un-
supplemented. A French persons
study by Taquet
with chronic
renal
failure.
showed the following
means:
2.29 µg/dl);
renal
liter
chronic
(114.27
(141.77
± 15.75
± 11.74
0.74 µmole/I
µg/dl);
(87.35
of retinal
hemodialyzed serum vitamin
µg/dl);
µg/dl).
the role
of retinal
2.03 ± 0.08 µmole/I
without
chronic
and chronic
in Japan,
patients.
hemodialysis peritoneal
values (58.14
±
4.95 ± 0.41 µmole/I
dialysis,
The results
of
3.99 ± 0.55 µmole/
dialysis
of hemodialysis
studied
3.05 ±
shown here would itself
± 50.1
various
of dialysis.
in males with hepatic µg/dl).
parameters
He found no significant
A and duration
were lowest
or 119.73
The results
groups
in the elevation
levels.
Ueno (1978),
levels
(1978) compared three
normals, failure
± 21.19
cause one to question
et al.
Males without
in 72 regularly
correlation
between
Mean serum vitamin damage (399.1 hepatic
of
program and adminis-
5,000 IU (1720 µg) vitamin
containing
hemodialysis
that
a study of the effects
of time in the dialysis
of a multivitamin
day on regular
reported
± 167.0
A IU/dl
damage had a mean of
15 494.0 ± 209.1 IU/dl hepatic
(148.2 ± 62.73 µg/dl)
damage had the highest
177.39 ± 49.59 µg/dl). ported
between
crit,
serum vitamin
which Ueno suggested
crit
through
seen between Ellis
Significant
stopping
after
vitamin
patients revealed
strongly
dialysis Because
patients
with vitamin
known to be deficient tinues for
diets
of supplementing
fear
of depleting
supplementation
them.
contain
In recent
studies
a similar
for normalization
on 50
study
and nonchanges
(1976) it
appears
of serum
transplant.
there
was documentation
supplementation
in the liter-
of chronic
hemo-
1979 and Murray,
1979),
for persons
on dialysis
are
however,
a tendency
con-
vitamins, on chronic
maintenance
Many of the preparations
vitamin
(1376-3440 µg) (Shmunes,
of 5,000 IU (1720 µg)
et al.
prescribed
patients
and twelve
and found no difference
A (Shmunes,
in certain
were
work.
significant
renal
on hernato-
correlations
no statistically
against
the restricted
effects
supplemented
1979 that
advising
or hernato-
into
is required
a successful
It was not until ature
divided
From work by Yatzidis
two years
A after
patients
were re-
A before,
A supplementation
Werb (1978) conducted
groups
at least
serum vitamin
hemodialysis
hemodialysis
six months.
that
A and PTH from Ueno's
vitamin
in mean serum levels.
supplemented
end point
damage to RBC membrane.
per day in 14 chronic
chronic
A and hemolytic
(1978) measured
or
correlations
deteriorating
et al.
months after
positive
may exert
serum vitamin
without
(591.3 ± 165.3 IU/dl
values
Significant
and females
hemodialysis used for
this
A in amounts of 4,000 to 10,000
1979) and no vitamin
of hemodialysis
patients,
E. elevated
plasma
IU
16 levels
of vitamin
202.2 ± 30.3
µg/dl
1971; Yatzidis
patients
levels
levels
of plasma vitamin
may have some effect
therapy. renal ing,
skin
pheral
paresthesias,
1975).
Alopecia
vitamin
containing
reported tion
levels Levels
tance
of vitamin of vitamin
vitamin
the lipocytes regular
Three
the elevated
of persons
muscle
patient
taking
A and having with
on dialysis
nausea,
fasciculation,
vomitperi-
(Yatzidis
et al.,
only a routine
elevated
cessation
chronic
multi-
serum vitamin
of the vitamin
A was
A supplementa-
A A in the liver
of the vitamin
have been considered
A status
A is found in the liver (Bronfenmajer
and number variable
generally
that
of hypervita-
1979).
in evaluation
stored
remains
and bone changes
in a dialysis vitamin
levels
A such as anorexia,
pruritis,
bleeding,
to have reversed
(Shmunes,
Liver
headache,
1979).
A seen in chronic
of symptoms between
and hypervitaminosis
dryness,
(Shmunes,
toxic
on the morbidity
There are many similarities failure
1978; and Shmunes, 1979).
of 20-80 µg/dl
the possibility
(n=lOO) to
(Smith and Goodman,
et al.,
are below the usual
A in most cases,
µg/dl
the range
the elevated
hemodialysis
tent
1975; Gotloib
are within
Although
± 20.49
from 85.37
(n=lO) have been reported
et al.,
Normal values
minosis
A ranging
used to estimate separate
and distribution
groups
et al.,
in a special
1966),
(Wake, 1974). total
reserves
have recently
in human livers
of humans.
of impor-
Most of the
group of cells,
whose distribution Single,
small
(McLaren et al., investigated
from autopsies.
is ir-
samples
are
1979).
the retinol
con-
17 Huque and Truswell (retinol)
content
usually
µg/g.
considered
age.
creasing
(20-29
age.
years)
the vitamin
in 281 subjects
at autopsy.
of 100-300
or how large
stores
specify
Although
did vary
gradually
increased
of
no
significantto a peak in
gradually
which section
a sample was analyzed,
A
to be in what is
µg/g.
and then declined
did not
with
in-
of the liver
both factors
which
to be of importance. (1979)
vitamin
A in 143 post-mortem
finding
distinctly
lobe.
than
1.4% of total
liver
In the United
States,
is stored
of vitamin
the caudal
pattern
central,
medial,
than
of vitamin
A is due in part cells
volume
(McLaren et al.,
lobes
whole specimens that
than
A gradient
to the fact
the left.
studied
the distribu-
of human liver.
samples
reported than
they examined,
was noted. differed
They
of vitamin
They also
concentrations
lobes
not more
1979).
the concentration
had lower
Among the 26 major
and peripheral
(1979)
the left
the same liver.
which comprise
Olson et al.
A in autopsied
of vitamin
lobe
of
and reported
were found within
lobe was greater
lobes.
of human liver
fold
in parasinusoidal
and central
the distribution
on the right
as had McLaren et al.,
in the right
and left
values
distribution
it
studied
samples
up to twenty
that
reported,
in Scotland
greater
Differences
The irregular
tent
range
in infancy
The report
McLaren et al.
tion
determined
subjects
median retinol
Low levels
was sampled,
tissue
50% of their
the normal
was found,
young adulthood
appear
of human liver
They reported
sex difference ly with
in England,
was 242 µg/g with a median of 181 µg/g and a range
The mean value 6-1201
(1979),
A that
the right
no consis-
Even in a given significantly
lobe, in 50%
18 of the specimens.
Concentrations
and ventral
samples
the values
of samples
lobe agreed that
within
a single
stores
Liver
taken
sampling
of Vitamin levels
mean.
five
(Yatzidis
et al.,
an increase
A in renal
times greater 1975).
in human livers
adequate
review
study,
concluded
indicator
failure
of vitamin
A
1932, Breusch and
1938; and Kerpola,
workers
suggested
A in chronic
of the retinol that
1931)
that
content
taken
there
is
patients.
and distribution
would not be within
would be of value
were carefully
patients
hemodialysis
such analysis
as the results
number of samples
have been reported
1938; Wolff,
These latter
it was decided
the scope of this
The authors
than normal in two hemodialysis
body vitamin
From the previous
of the right
A in Renal Failure
of vitamin
of total
that
technique.
1934; Moore, 1937; Lindquist,
to values
portion
as a useful
from very low (Hedburg and Lindquist, Scalabrino,
internal,
It was reported
from the midcentral
sample can serve
with proper
A in dorsal,
showed a gradient.
15% of the overall
liver
Liver Levels
rarely
of vitamin
only if an
from the same location
in the livers. Vitamin According
to Bieri
human nutrition Although sight
into
was described
the results possible
to go in contrast
(1976),
to animal
only a short as a "vitamin
of recent functions
E
human research of vitamin
research.
time ago vitamin in search
of a disease."
have provided
E, there
E in
is still
some ina long way
19 Being a fat-soluble body in a similar the intestinal
reach
a maximum four
is uniform to nine
sites
Four isomers
and Bro'Wll, levels
(Institute
of Food
with
alpha,
prevent
tissue
and
daily
is ex-
in frozen
oxidative
for approximately
of the natural
to 1 IU,
source,
acetate
The acetate
storage
gamma, and 80% of
of Food Technology,
dl- a -tocopheryl
equal
beta,
accounts
oxygen under most conditions do occur
adipose
E ingested
E (Institute
instability
1 mg being
losses
completely
of vitamin
preparation
to atmospheric
E include
Alpha tocopherol
of the
the synthetic
muscle,
1973b).
of vitamin
activity
Because
erol
ingestion
the
from
the body and blood
after
E include
(Kutsky,
tocopherol.
dard,
within occurs
the lymph (Pike
60-70% of the vitamin
in the feces
the total
E absorption
throughout
hours
of vitamin
Approximately
delta
via
transported
1977).
Storage
creted
Eis
Vitamin
lumen and excretion
Distribution
liver.
vitamin
manner to fats.
1975).
Technology,
vitamin,
1977).
d- a -tocopherol,
has become the ester
(Horwitt,
is very 1976).
(Institute
stable
Tocoph-
where the temperatures
destruction
stan-
do not
of Food Technol-
ogy, 1977). The tocopherol 1975). cytes al.,
In vitro oxidize
studies
against Vitamin
Tocopherol
E deficiency
vitamin
(Tudhope and Hopkins,
are more susceptible
oxidative
is found in the membrane (Chow,
have shown that
more readily
1956) and also
Deamer, 1977). brane
in the erythrocyte
apparently
stress
in adult
al.,
erythro-
1975 and Horwitt
to potassium stabilizes
(Natta·et
E deficient
loss
et
(Harm and
the erythrocyte
mem-
1980).
man has been difficult
to produce
20 because sary
of considerable
tissue
for depletion.
feeding
Bunnell
in blood levels
weakness
or other
Clinical limited
possibly
evidence
ble roles
of vitamin
E contents
(Horwitt,
of vitamin
sion
of cyanocobalamin
steps
vitamin
to its
1% after
de-
deficiency et al.
Beneficial
conducted
also
(Haeger,
1974).
a variety
of possi-
with vitamin
E deficient
for the conver-
5'-deoxyadenosylcobalamin,
to clarify
the mechanism and Reviews,
1979).
treating
sickle
were promising, red cells
cell
as the percentage from 25 + 3%
decreased
of 450 IU (mg) of vitamin increased
have
in malabsorption
E may be required
(1980) involved
administration
~ith
effects
claudication
(Nutrition
sickled
completely
fed formulas
E treatment
coenzyme,
E. The results
levels
is almost
infants
1976).
are needed
irreversibly
Plasma tocopherol
E per day.
significantly.
E in Dialysis
Plasma levels studied
extensively
altered
in renal
min Eis
that
of this
anemia with vitamin
±
(Bieri,
In a study
in animals
The work of Natta
of circulating
of
however no muscular
have begun investigating
E.
it was suggested
enzymatic
E deficiency
with vitamin
researchers
studies
the effect
of one year,
1976) and intermittent
rats,
Further
neces-
and showed a significant
anemia in premature
vitamin
Current
E diet
period
symptoms were reported.
been produced
syndromes
and an extended
(1975) studied
over a period
to hemolytic
inadequate
Vitamin
et al.
PUFA with a low vitamin
crease
to 11
storage
thought
of vitamin
E in hemodialysis
to determine failure
if
the metabolism
(Feldman and Singer,
to not be dialyzed,
patients
of vitamin
1974).
most authors
have not been Eis
Because vita-
have stated
that
21 there
does not appear
patients
to be a need for
(Kopple and Swendseid,
Ito vitamin
et al.
(1971),
E (1.22
± 0.91
1975 and Stone,
in Japan, mg/dl)
no follow-up
patients
was reported
meeting
(1980).
the results tients. lipid
vitamin
and erythrocyte
E status
of 20 persons
age and sex-matched Values
for
lipid
ratio
total ference appear
between
conclusions persons
serum total
subjects
quirements
University,
reported
of hemodialysis
vitamin
E/serum
hemodialysis
pa-
total
with healthy,
E and serum total
normal
limits
and controls.
indirect because
derived
treated
Foundation
was used to compare the
receiving
vitamin
were within
probably
E in hemodialysis
controls.
to be a valid
patients,
hemolysis
how-
~idney
E status
E, serum total
patients
in the literature.
vitamin
State
of
± 0.73 mg/dl);
at the National
of her work on the vitamin
ratio,
vitamin
recently
levels
hemodialysis
(2.13
involving
Brown, from Michigan
Serum total
plasma
has been reported
known study
in dialysis
1977).
lower
controls
investigation
The only other
reported
in maintenance
(n=6) when compared with normal ever,
supplementation
study
with hemodialysis
can be met by usual
is normal dietary
did not
toxins.
the vitamin and that
intakes
dif-
E in hemodialysis
from uremic
were that
E/serum
was little hemolysis
of vitamin
of interference
from this
and there
Erythrocyte
assessment
vitamin
without
The
E status
vitamin
of
Ere-
the use of
supplements. Vitamin An interrelationship animal
studies.
Vitamin
A - Vitamin between
E Interactions
vitamins
E given with high
A and E has been shown in levels
of vitamin
A has
22 been shown to protect (1970)
found that
3,250,000 after
feeding
10,000
0% mortality.
The high
which was largely results
Chickens
IU (mg) vitamin
were found in rat Arthur
by excess
and excessive retinol
et al.
tocopherol amounts
deposits.
ous presence level
(1980)
by the
synthesis.
In a 1978 investigation reported
a possible
children
with vitamin
relation
between
and suggested mechanism
possibly
findings
that
of vitamin
Elevated could
plasma
levels
further
A and vitamin
E interaction
be reversed
with vitamin hold
true
A synthe$-carotene
the simultane-
at the intestinal
and Reddy in India,
are needed
of vitamin
studies
Similar
vitamins
they
A and E in
They found no significant
plasma levels
in animal
that
of the two vitamins
studies
E.
and then measured
$-carotene
between
A deficiency.
had
growth
of vitamin
acetate
by Jagadeesan
cor-
in their
to determine
study, the
in man.
A and low levels E supplementation
in persons
A
1957).
it was suggested
interrelationship
depressed
They administered
tocopheryl
with
acetate)
of vitamin
on inhibition
in young rats.
retinol
the same high vitamin
markedly
inclusion
reported
tocopheryl
A of
in 78% mortality
(Cox et al.,
From the data
inhibits
receiving
studies
of excess
vitamin
resulted
A intake
of dl-a-
Mccuaig and Motzok
E (as dl-a-tocopheryl
vitamin
restored
A.
excessive
µg) per kg diet
IU (1,118,000
plus
hypervitaminosis
chickens
32 days of feeding.
diet
sis
against
of vitamin if
on hemodialysis·
the
E
23 CHAPTERIII METHODOLOGY This
study
involved
dietary
intake,
persons
receiving
Thirty
a controlled
and vitamin
supplementation
maintenance
volunteer
subjects
any specific
group of subjects.
to participate
consent
forms
(Appendices
from various
which was probably
was made to select
The only consideration stable,
able
All subjects
controls
were obtained
University
for selection
to communicte, signed
and
informed
educational
not significantly
from employees
and local
was made to match educational
individuals
outpatient
2-5).
members at Utah State
no attempt
levels,
A and E in
from three
No attempt
in the study.
Age and sex-matched staff
Lake City.
who were medically
willing
of vitamins
were recruited
units
patients
in Salt
of plasma
hemodialysis.
hemodialysis
included
investigation
residents.
and economic
and economic different
and Although
levels,
levels
were included
from the subjects
in
the study. All subjects searcher
utilizing
regarding
intake
were asked, nineteen
and controls
were verbally
pre-printed
questionnaires
of prescribed
and brand
food items
read
by the researcher.
ther
questioning
name was included.
in carotene, If
regarding Intake
by the re-
(Appendix
and non-prescribed
names included
high
questioned
6).
vitamin
whenever
possible.
vitamin
A and/or
the foods were eaten
was also
supplements A list
vitamin
by the subject,
the amoun~, type of preparation, of medications
Questions
queried.
of E was fur-
and brand
24 Table
Subject
1.
and control
description.
Controls
Subjects Sex Males Females Age 70 years Diabetics Non-diabetics
Average values
were not specific,
carrots
when both
types
of fats
Since
to 0.3 R.E.
all
duration
dietary
average
information
value
for
raw and cooked
Where subjects
the arbitrary
such as "only
value
where
did not estimate
of 3 tablespoons or "small
a little"
and oil,
per
amount."
values
for
were used.
analyses
for vitamin
were converted (µg retinal)
A are
to retinal
given
in international
equivalents
or 0.344 R.E.
using
(µg) for vitamin
1 IU equal
A acetate
supplements).
The following medical
i.e.,
consumed,
products
totals
(vitamin
1 4 4 4 10 6 1 1 29
names were not known for margarine
soybean-based
units,
1 4 4 5 9 6 1 7 23
were consumed.
week was used for answers Where brand
27 3
were used for all
answers
a quantity
27 3
record,
information
as possible:
of each dialysis
mented medical
problems,
was gathered length
treatment, and prescribed
from the subject
of time on dialysis artificial
kidney
medications.
or the
therapy, used,
docu-
25 Blood samples into
heparinized
predialysis, jects
and also
shifts,
post
dialysis
whenever
from five
possible.
or factors
with
two hours. plasma
foil
removed with
flushed
covered
disposable
with nitrogen,
with
foil,
into
sealed
plastic
with
flushed
with nitrogen,
covered
with
foil,
levels
covered
modified
to those
light.
and the were
of parafilrn,
artificial at hourly
kidneys intervals
were from
Tubes were immediately of parafilm,
capped,
Assays
from that
for vitamin
described
were calculated
of direct
layers
tubes
with a layer
Methods
laboratory
by Hansen and Warwick E analyses, for
by Baker and Frank
from absorbance All
reported
A and vitamin
SF-330 spectrofluorometer.
spectrophotometer.
minutes
and frozen.
(1977) was followed
were similar
three
machine.
Laboratory
the Varian
five
within
Plasma samples
different
test
tube of the dialysis
A micromethod
for
not
of blood were
and processed
pipettes.
from four
disposable
the drainage
glass
diabetes,
and frozen.
Samples of dialysate collected
were centrifuged
Sub-
of the time of some
The tubes
refrigerated,
was drawn
of the subjects.
Because
state.
and controls
subjects
such as insulin-dependent
immediately,
Blood samples
subjects
Blood from all
tubes.
blood was drawn in the fasting
covered
then
vacutainer
were fasting
dialysis all
of 7 ml were drawn from all
values
read
work was carried
utilizing
carotene
analysis
(1968).
carotene
on a Bausch and Lomb out in the
absence
26 Vitamin
A and Vitamin
Vitamin acetate,
E
A standard
was prepared
1 ml 95% ethanol,
hydroxide.
E standard
which was diluted tions:
0.0224, Quinine
0.0448,
sulfate
0.112,
samples
into
tic
on an automatic
15 ml glass,
with saran
alpha-tocopherol
to the
following
was dissolved
were thawed,
mixed,
screw-topped
tubes
Automatic
30 seconds,
5 ml of low boiling
point
petroleum
each tube.
All tubes
were again
and then centrifuged into
a cuvette
A, fluorescence
wavelengths
for
using
was read at 320 emission
Slit
widths
Vitamin
were set
mixer
fluorescence
equations
readings
(average
were utilized of duplicates)
for
for
on a vortex
glass
top portion pipette.
and 480 excitaE was read
at
at 10 nm excitation
and 20 nm emission. The following
plas-
was added to
The clear,
a disposable
on the spectrofluorometer~
290 and 320 respectively.
ether
minutes.
0.2 ml was
Tubes were
on a vortex
mixed for one minute five
standard.
were then used
and 1 ml of 95% ethanol.
water
acid
disposable
pipettors
mixing
tion
concentra-
and then using
After
For vitamin
acetate
in 0.1 N sulfuric
and capped.
was then pipetted
to the following
and 0.224 mg/dl.
pipettor.
to add 1 ml of distilled
mixer
ether
of 1.0 µg/ml and was used as a secondary
pipetted
covered
with
ether
dihydrate
Frozen plasma
A
and 0.5 g potassium
in petroleum
was prepared
with petroleum
to a concentration
tips
was diluted
water
of vitamin
301, and 603 µg/dl.
121,
Vitamin
2500 USP units
1.2 ml distilled
The standard
concentrations:
with
conversion to standard
of the units:
27 C F
concentration fluorescence blank standard plasma
B
s P
25(F - .179)(120.5 4.20
A
(F - .179)
µg/dl) - .002
E
=
717.6036
µg/dl
.112 mg/dl 5 • 19 )
