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-tocopherol in Plasma Lipoproteins from Calves Fed Milk Replacer 1 ,2 ,3
4
*
Department of Animal Science, Iowa State University, Ames, IA 50011;
National Animal Disease Center, Agricultural Research Service-U.S. Department of Agriculture, Ames, IA 50010;
**
Department of Dairy Science, South Dakota State University, Brookings, SD 57007;
Department of Human Food Nutrition, California State University, College of Agriculture, Pomona, CA 91768; and
Stuart Products, Inc., Bedford, TX 76022
4To whom correspondence should be addressed.
 |
ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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-tocopherol and
RRR--tocopheryl acetate, 155 µmol daily) on plasma
RRR--tocopherol and RRR-
-tocopherol
and RRR--tocopherol associated with plasma
lipoproteins (Lp) from milk replacer-fed Holstein calves from birth
to 28 d of age. The VLDL, LDL, HDL and very high-density
lipoprotein (VHDL) fractions were separated by ultracentrifugal
flotation, and the amount of vitamin E associated with each fraction
was determined by normal-phase HPLC. The amount and distribution of
RRR--tocopherol in Lp fractions were unaffected by
the form of dietary vitamin E. Plasma and Lp
RRR--tocopherol concentrations increased with age
(P < 0.0001) and were maximal at 28 d of age.
Concentrations of RRR--tocopherol associated with Lp
were 25% (P < 0.01) to 39% (P
< 0.0001) lower in calves fed 35.6 and 71.2 µmol of vitamin A
daily than in control calves at 28 d of age. The
RRR--tocopherol concentrations were unaffected by
dietary vitamin A (P 
0.05). In conclusion,
dietary vitamin A modulated the amount and distribution of
RRR--tocopherol in the circulation of milk
replacer-fed neonatal calves. Because of the essential antioxidant
role of vitamin E, the health-related consequences associated with
the depression of the LP RRR--tocopherol
concentrations in calves fed vitamin A at 35.6 and 71.2 µmol need to
be investigated.
KEY WORDS: • calves • vitamin A • vitamin E • lipoprotein • milk replacer
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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, Van Saun et al. 1989
). Deficiencies of these vitamins at birth are overcome
by feeding the calf colostrum within hours after birth (Blum et al. 1997
, Rajaraman et al. 1997
, Tomkins and Jaster 1991
). On many farms, newborn calves are removed
from the cow shortly after birth. In the United States, almost 60% of
calves are raised using milk replacer (Tomkins and Jaster 1991
). The vitamin A requirement of growing large-breed
calves fed only milk replacer has been set at 1.78 to 2.2 µmol daily
(NRC 1989
).6
The amount of vitamin A added to the diet of calves has increased over
the years because of the essential role of vitamin A in assuring
optimal cellular differentiation, growth and immune function
(Cohen and Cohen 1973
, Dennert and Lotan 1978
, Goldfarb and Herberman 1981
,
Goldman 1984
, Lotan 1980
). The toxicity of
vitamin A for ruminants is considered low (NRC 1989
). In
an attempt to maximize the benefits of vitamin A to the neonatal calf,
milk replacers available in the United States typically contain vitamin
A at concentrations that exceed the current NRC requirement (1989) by
10- to 20-fold.
Supplementing milk replacer-fed calves with excess vitamin A has
raised concerns regarding the impact of this practice on the
bioavailability of dietary vitamin E. Vitamin E is an essential
lipid-soluble antioxidant in vivo. In this role it quenches free
radicals and acts as a terminator of lipid peroxidation
(Halliwell and Gutteridge 1984
, Slater 1984
). Dicks et al. (1959)
reported a significant decrease in
plasma concentrations of vitamin E in 2-mo-old calves fed high amounts
of vitamin A. Similarly, 6-mo-old beef calves supplemented with 11.52
µmol of retinol palmitate/kg diet dry matter daily had lower plasma
concentrations of vitamin E than did calves receiving the NRC
requirement for vitamin A (Zinn et al. 1996
). A strong
negative association between plasma retinol and
RRR--tocopherol concentrations in 1- to 7-wk-old calves
fed milk replacer has been reported (Nonnecke et al. 1999b
). Franklin et al. (1998)
also observed lower
RRR--tocopherol concentrations in plasma from
milk-fed calves supplemented for 6 wk with 15.71 or 31.41 µmol of
vitamin A daily. Studies using other animal species have demonstrated
comparable interactions between dietary vitamin A and the
bioavailability of vitamin E (Abawi and Sullivan 1989
,
Pudelkiewicz et al. 1964
, Sklan and Donoghue 1982a
). These observations indicate that dietary vitamin A
influences plasma concentrations of vitamin E.
The bioavailability of vitamin E to newborn calves also may be
influenced by the form of dietary vitamin E. Neonatal calves are fed
frequently milk replacers containing esterified vitamin E
(RRR--tocopheryl acetate) that is more stable and less
costly than is RRR--tocopherol. Some reports indicate
that greater plasma RRR--tocopherol concentrations are
achieved when newborn calves are fed RRR--tocopherol
rather than RRR--tocopheryl acetate (Eicher et al. 1997
, Hidiroglou et al. 1989
). Others
(Burton et al. 1988
, Cheesman et al. 1995
, Ochoa et al. 1992
), however, report that
the form of vitamin E has no effect on plasma
RRR--tocopherol concentrations in sheep, humans and rats.
Plasma vitamin E is transported in association with Lp in ruminants
(Al Senaidy 1996
), humans (Behrens et al. 1982
, McCormick et al. 1960
) and rats
(Bjørneboe et al. 1987
, Peake et al. 1972
). The
HDL are the major plasma Lp (>80% of total Lp) in neonatal calves
(Bauchart et al. 1989
, Forte et al. 1981
,
Jenkins et al. 1988
) and adult ruminants (Raphael et al. 1973
). There are no reports regarding the distribution
of vitamin E on plasma Lp of newborn calves and on the effects of
dietary vitamin A on this distribution.
A 4 x 2 factorial experiment was conducted to evaluate the
effects of feeding vitamin A at 20- to 40-fold the NRC requirement on
the distribution of vitamin E in Lp fractions of neonatal calves.
Newborn calves were fed a low vitamin A milk replacer supplemented with
0, 1.78 (NRC requirement, control), 35.6 and 71.2 µmol of vitamin A
daily from birth to 4 wk of age. Calves also were fed vitamin E (155
µmol daily) as RRR--tocopherol or
RRR--tocopheryl acetate.
|
MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Animals.
Male Holstein calves (n = 53) from two commercial
dairies were used to evaluate effects of amount of vitamin A and form
of vitamin E on tocopherol concentrations in plasma Lp fractions.
Calves (24) were evaluated between August 28 and December 5, 1996, and
29 calves between April 26 and July 30, 1997. Precolostral calves were
removed from their dams at birth and taken to the South Dakota State
University Dairy Research and Teaching Facility (Brookings, SD), where
they were housed for the duration of the study in individual calf
hutches. A 4 x 2 factorial experiment was conducted in six to
seven replicates. Calves received orally 0, 1.78 (NRC requirement,
control group), 35.6 or 71.2 µmol (0, 1,700, 34,000 and 68,000
IU) of vitamin A daily as a water dispersible retinyl
acetate (MicrovitTM A Prosol 500; Rhone Poulenc, CA).
Calves within each vitamin A group received orally either
RRR--tocopherol or RRR--tocopheryl
acetate at 155 µmol (100 IU) daily in milk replacer
(Stuart Products Inc., Bedford, TX). The amount of supplemental vitamin
E exceeded the NRC requirement (31 µmol daily) by five-fold and
was typical of the amount present in commercial calf-milk
replacers. Combinations of vitamin A and E were mixed with
double-distilled water and added to the milk replacer.
Calf-related procedures were approved by the Institutional Animal
Care and Use Committee of South Dakota State University (Brookings,
SD).
Diet.
All calves were fed colostrum at 5% of body weight within 6 h
after birth. Colostrum that had been collected, pooled and frozen for
each trial was thawed prior to feeding. Colostrum was given by
esophageal feeder to calves that would not suckle. Colostrum from each
pool was analyzed for vitamin A content. Within 12 h after being
fed colostrum, calves were fed custom-formulated low vitamin A milk
replacer (Table 1
) at 5% of body weight each feeding. Diets were reconstituted to a
solution of approximately one part milk replacer to eight parts water
immediately before feeding. Calves were fed at ~0630 and 1800 daily.
Calf starter was not offered during the study. Concentrations of
vitamin A in colostrum ranged from 7.37 to 9.02 µmol/L. Two batches
of milk replacer were fed during the experiment. The first batch
contained endogenously the equivalent of 0.53 µmol of vitamin A/kg of
milk replacer and batch two contained the equivalent of 2.48 µmol of
vitamin A/kg of milk replacer. The second batch was fed to only 25% of
the calves.
|
Blood from six adult nulliparous Holstein heifers was collected and similarly processed for comparison with calves. The average age of these heifers was 21 (± 5) mo.
Analytical methods
Lp separation.
All procedures were performed under yellow light to prevent degradation
of vitamin A. The method for separating Lp from bovine plasma was
essentially that of Havel et al. (1955)
. Plasma (9 mL) was overlaid
with 2.7 mL of a solution consisting of sodium chloride (0.15 mol/L).
The VLDL-chylomicrons were first removed from plasma by
ultracentrifugal flotation (138,000 x g, 18 h
at 18°C) by using a Beckman L-8M ultracentrifuge and type 50.2 TI
rotor (Beckman Instruments, Fullerton, CA) and stored at -80°C until
analyzed. The LDL, HDL and very high-density lipoprotein (VHDL)
fractions were separated by adjusting sample densities with solutions
containing sodium chloride and potassium bromide as described by Havel et al. (1955)
. Four Lp fractions were separated by using the following
density intervals recommended for ruminant animals (Jenkins et al. 1988
): VLDL and chylomicrons, <1.006 kg/L; LDL,
1.006–1.063 kg/L; HDL, 1.063–1.21 kg/L and VHDL, >1.21 kg/L. Samples
then were frozen at -80°C for later analyses. Because of the limited
amount of blood available on the day of birth, we did not separate Lp
from calves of this age.
Analysis of retinol, retinol palmitate,
RRR--tocopherol and
RRR--tocopherol.
All solvents, with the exception of hexane, were HPLC- or
spectrophotometric-grade (Burdick & Jackson,, Muskegon, MI). Plasma
retinol and concentrations of RRR--tocopherol and
RRR--tocopherol in Lp were determined by
reverse-phase HPLC by using a modified method of Kaplan et al. (1987)
. Ethanol (200 µL) containing 0.76 nmol of
all-trans-retinyl acetate (Eastman Kodak Company,
Rochester, NY) as an internal standard was combined with 200 µL of
plasma or Lp sample. Samples were vortexed, 1.5 mL of hexane were added
to extract the samples, and after 15 min at 20°C samples were
centrifuged (1,090 x g, 15 min at 4°C, J-6M
ultracentrifuge; Beckman Instruments, Fullerton, CA) to remove the
precipitated protein. After phase separation, the upper (hexane) phase
was removed. The hexane extraction then was repeated. Hexane
extractions were dried by using a vacuum centrifuge with a refrigerated
vapor trap (SAVANT Instruments, Farmingdale, NY). Residues were
dissolved in 30 µL of chloroform and allowed to sit for 5 min at
20°C. Samples then were diluted by the addition of 120 µL of
methanol/double-distilled water (75:5, v/v) and injected (150 µL)
into a 150 mm x 4.6 mm, 3-µm C-18 Alltech Econosphere column (Alltech
Associates, Deerfield, IL) of an HPLC. Samples were eluted by using a
75:20:5 (v/v/v) mixture of methanol/chloroform/double-distilled water
and a flow rate of 1.1 mL/min. The mobile phase for the chromatographic
analysis was degassed under a vacuum for 60 min before use. Retinol,
RRR--tocopherol and RRR--tocopherol
were detected by monitoring their absorbance at 280 nm using a fixed
wavelength detector (Waters 440 Absorbance Detector; Waters Associates,
Milford, MA). External standards consisted of
all-trans-retinol (0.87 to 2.62 nmol),
RRR--tocopherol (0.58 to 1.74 nmol; Eastman Kodak
Company, Rochester, NY) and RRR--tocopherol (0.60 to
1.80 nmol, Sigma, St. Louis, MO).
The procedure for extracting retinol palmitate from plasma was the same as for retinol and tocopherols. Hexane extracted (twice) and vacuum dried samples were resuspended in a 60:40 (v/v) mixture of hexane/chloroform and injected (150 µL) into a 150 mm x 4.6 mm Econosphere silica 3-µm column (Alltech Associates) with a flow rate of 2.5 mL/min (normal-phase HPLC). The mobile phase consisted of 60:40 (v/v) hexane/chloroform. The first 2.5-min elutions were collected and dried by using a vacuum centrifuge with refrigerated vapor trap (SAVANT Instruments). These samples were dissolved in 30 µL of chloroform, allowed to sit for 5 min at 20°C and then were diluted by addition of 120 µL of methanol/double-distilled water (75:5, v/v) and injected (150 µL) into a 150 mm x 4.6 mm, 3-µm C-18 Alltech Econosphere column (Alltech Associates). Samples were eluted by using a 75:20:5 (v/v/v) mixture of methanol/chloroform/double-distilled water and a flow rate of 1.1 mL/min (reverse-phase HPLC). Retinyl palmitate was detected by monitoring its absorbance at 340 nm [(Waters 440 Absorbance detector) Waters Associates]. Internal and external standards consisted of all-trans-retinyl acetate (0.305 nmol) and all-trans-retinyl palmitate (0.024–0.095 nmol; Eastman Kodak Company, Rochester, NY), respectively.
Statistical analysis. Data were assessed for normality of distributions using the univariate procedure of SAS and when warranted were log10-transformed prior to statistical analyses. Data were analyzed as a split-plot with repeated measures ANOVA using the general linear models of SAS (SAS/STAT Version 6; SAS Institute, Cary, NC). Dietary treatments and their interactions constituted the main plot, and the age of the calves was the repeated measure or split plot. Statistical significance of differences between means was declared at P < 0.05. When main effects or interactions were significant, indicated significant differences were taken from the matrices of the Student’s two sample t test that accompanied the least square means from the ANOVA. Least-square means were converted back to original units of measurement for the purpose of data presentation. Values are presented as arithmetic means ± SEM.
Pearson’s product-moment correlations were computed between plasma
retinol and plasma RRR--tocopherol and
RRR--tocopherol associated with Lp fractions by using
the correlation procedure of SAS (SAS/STAT Version 6; SAS Institute).
Correlations were judged to be significant at P < 0.05. Plasma RRR--tocopherol and
RRR--tocopherol associated with Lp fractions of adult
nulliparous heifers were compared against those of calves by using the
ANOVA procedure of SAS (SAS/STAT Version 6; SAS Institute).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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-tocopherol and
RRR--tocopherol.
The concentrations of retinol in plasma reflected vitamin A intakes
(Table 2
). Plasma levels of retinol were not different (P > 0.05) among calves at birth. At 28 d of age, plasma retinol
concentrations in calves fed 35.6 and 71.2 mmol of vitamin A daily
exceeded by 47% (P < 0.001) and 66% (P
< 0.0001) concentrations in control calves fed 1.78 µmol of
vitamin A daily. Unsupplemented calves had lower concentrations of
retinol compared with calves fed 35.6 (P < 0.05) and
71.2 (P < 0.0001) µmol of vitamin A daily by d 28.
|
).
|
-tocopherol in plasma were not
different (P > 0.05) among calves at birth (Table 2)
.
Calves fed the greatest amount of vitamin A had the lowest
concentrations of RRR--tocopherol in plasma. Calves
supplemented with 35.6 and 71.2 µmol of vitamin A daily had 26 and
39% (P < 0.01, P < 0.0001,
respectively) lower RRR--tocopherol concentrations
compared with control animals by d 28. Concentrations of
RRR--tocopherol in control calves were 23% lower
(P < 0.001) than calves fed no vitamin A by d 28.
Concentrations of RRR--tocopherol increased in all calves
with increasing age (P < 0.001).
Plasma concentrations of RRR--tocopherol are shown in
Table 2
. Calves were born with undetectable amounts of this isomer of
vitamin E. Calves supplemented with 35.6 and 71.2 µmol of vitamin A
daily had greater (P < 0.05) concentrations of
RRR--tocopherol by d 8 compared with control calves.
RRR--Tocopherol concentrations were not different among
treatment groups by the end of the experiment (P > 0.05).
Concentrations of RRR--tocopherol in plasma Lp.
Concentrations of RRR--tocopherol associated with Lp
fractions (HDL, LDL, VHDL and VLDL) were not different among calves by
d 2 (Fig. 2a
, b
, c
, d
). Calves supplemented with the greatest amount of dietary vitamin A
had the lowest concentrations of RRR--tocopherol
associated with HDL (P < 0.001), LDL (P
< 0.01), VHDL (P < 0.01) and VLDL (P
< 0.01) fractions, by d 14. At 28 d, calves supplemented
with 35.6 and 71.2 µmol of vitamin A daily had 21 (P
< 0.1) and 39% (P < 0.001) lower
RRR--tocopherol associated with HDL when compared with
control calves. Control calves had 25% lower (P < 0.01) RRR--tocopherol associated with HDL when compared
with calves fed no vitamin A. Changes in RRR--tocopherol
concentrations in LDL, VHDL and VLDL fractions followed those observed
in HDL. The amount of RRR--tocopherol associated with
HDL, LDL, VHDL and VLDL increased (P < 0.0001) in all
calves with age.
|
-tocopherol and RRR--tocopherol
associated with Lp fractions (HDL, LDL, VHDL and VLDL) are presented in
Table 3
. No relationships were found among these variables at d 2. There were
significant positive correlations (P-values and
r-values given in Table 3
) between plasma retinol and plasma
RRR--tocopherol and RRR--tocopherol
associated with Lp fractions by d 8. In contrast, inverse relationships
were observed among plasma retinol and RRR--tocopherol in
plasma and all four Lp fractions by d 14 and 28.
|
-tocopherol in plasma Lp.
Distribution of RRR--tocopherol (in percentage to total
Lp RRR--tocopherol) in each Lp fraction was not affected
by vitamin A intake. Dosage of dietary vitamin A did not affect
distribution of RRR--tocopherol among the different Lp
fractions (P > 0.05) (Fig. 3
). Concentrations of RRR--tocopherol in Lp across all
treatments and all periods averaged 5.41, 1.42, 0.70 and 0.41 µmol/L
for HDL, LDL, VHDL and VLDL, respectively. The HDL, LDL, VHDL and VLDL
fractions accounted for ~59.3, 14.4, 22.2 and 3.9% of the total
RRR--tocopherol in Lp (Fig. 2)
. Distribution of Lp
RRR--tocopherol averaged 31.9, 21, 31.2 and 15.5% for
HDL, LDL, VHDL and VLDL, respectively, at the day of birth. The amount
of RRR--tocopherol associated with HDL increased
(P < 0.05) from 32% at birth to 66% by d 8 and to
71% by the end of the study (d 28). In contrast, the amount of
RRR--tocopherol associated with VHDL, LDL and VLDL
decreased (P < 0.05) from birth values of 31, 21 and
15.5% to 6, 17 and 4%, respectively, by d 28.
|
-tocopherol concentrations in Lp between
newborn and adult animals.
Adult nulliparous heifers had 62% greater
RRR--tocopherol associated with all Lp fractions than did
calves at d 2 (Table 4
). Calves at d 2 had less (P < 0.001)
RRR--tocopherol associated with HDL (31.9%) than did
adult nulliparous heifers (68.5%). In contrast, the amount of
RRR--tocopherol associated with VHDL and VLDL was greater
at d 2 (31.2 and 15.5%, respectively) compared with those of adult
animals (4.16 and 6.13%, respectively). Concentrations of
RRR--tocopherol associated with LDL in calves (21.4%)
and cows (21.2%) were not different (P 0.05). The
distribution profile of RRR--tocopherol among Lp in 8-d
or older calves was comparable to profile in adult cattle.
|
|
DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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-tocopherol
concentrations when compared to concentrations in control calves
supplemented with 1.8 µmol of vitamin A daily. Previous studies in
calves (Dicks et al. 1959
, Franklin et al. 1998
, Nonnecke et al. 1999b
, Zinn et al.
1996
) have shown that feeding calves high amounts of vitamin A
is associated with a reduction in plasma RRR--tocopherol
concentrations. We observed an inverse relationship between plasma
retinol and plasma RRR--tocopherol and
RRR--tocopherol associated with Lp fractions starting at
14 d of age (Table 3)
. This relationship suggests that vitamin A,
by yet unknown mechanism, suppresses circulating levels of vitamin E in
calves starting by 14 d of age. These findings confirm our
previous observation of a negative association between plasma retinol
and RRR--tocopherol in neonatal calves (Nonnecke et al. 1999b
). Feeding calves high amounts of vitamin A had no
effect on plasma RRR--tocopherol at 28 d of age,
which suggests that vitamin A affects specifically plasma
RRR--tocopherol, but not RRR--tocopherol,
in neonatal calves.
-Tocopherol transfer protein (-TTP), a liver protein,
specifically and predominantly binds and supplements nascent VLDL with
RRR--tocopherol at the expense of other isomers of
vitamin E (Traber et al. 1992
). The main function of
-TTP is to maintain sufficient plasma concentrations of vitamin E
(i.e., RRR--tocopherol). Conceivably, retinoic acids may
suppress production of -TTP, reducing the incorporation of
RRR--tocopherol into VLDL. If so, plasma concentrations
of RRR--tocopherol would be affected. In support of this
hypothesis are observations from this study, indicating that
concentrations of several retinoic acid isomers (9-cis-,
13-cis- and 9,13-di-cis-retinoic acid) in plasma
of calves fed excess vitamin A daily were elevated markedly when
compared with concentrations in calves fed 0 or 1.78 µmol of vitamin
A daily (Nonnecke et al. 1999a
). Recent reports indicate
that retinoic acid suppresses gene expression of other liver proteins
like apolipoprotein A-I, the major protein constituent of HDL
(Berthou et al. 1998
; Zolfaghari and Ross 1994
, 1995
). Similarly, rats fed retinoic acid
have several-fold lower RRR--tocopherol
concentrations in plasma and liver when compared to rats fed retinol
(Bieri et al. 1981
).
Plasma concentrations of RRR--tocopherol in groups of
calves fed 36.5 and 71.2 µmol of vitamin A daily were lower than in
control calves, but remained within the normal limits (>4.64 µmol/L)
for 28-d-old dairy calves. Calves fed 36.5 or 71.2 µmol of
vitamin A daily did not manifest symptoms of vitamin E deficiency.
Because of the limited availability of liver samples in the present
study, hepatic concentrations of vitamin E were not quantified. A 38%
reduction in liver RRR--tocopherol content occurs in rats
fed vitamin A exceeding the NRC requirement by 10-fold (Blakely 1991
). In the present study, the amount of supplemental vitamin
E exceeded the NRC requirement by five-fold and the duration of the
study was limited to 4 wk. Conceivably, feeding 20- to 40-fold the NRC
amount of vitamin A and the NRC requirement of vitamin E to neonatal
calves for longer period would deplete body stores of vitamin E,
ultimately producing symptoms of vitamin E deficiency. Calves in which
experimental vitamin E deficiencies are produced show essentially the
same clinical signs as calves with dystrophic muscle disease that
develops under field conditions (NRC 1989
).
RRR--Tocopherol concentrations in plasma from newborn
calves were several-fold lower than concentrations in adult cattle.
The concentration of RRR--tocopherol in the plasma of
adult nulliparous heifers was 12.9 µmol/L, within the normal range
for adult dairy cattle (NRC 1989
). Plasma concentrations
of < 3.5 mmol/L are indicative of vitamin E deficiency in adult
cattle (NRC 1989
). The lower vitamin E levels in newborn
animals may be due to reduced placental transfer of
RRR--tocopherol (Van Saun et al. 1989
),
caused by a transient deficiency of prebeta Lp (Desai et al. 1984
) and very low -TTP mRNA concentrations at birth
(Tamai et al. 1998
). Recent research indicates that
-TTP in neonatal rats increases by feeding vitamin E and, with age,
achieving adult levels by d 28 of age (Fechner et al. 1998
, Kim et al. 1996
, Tamai et al. 1998
). In the present study, plasma concentrations of
RRR--tocopherol increased with age and by d 28 exceeded
adult levels, suggesting that 155 µmol (fivefold NRC requirement) of
vitamin E daily is a sufficient level of supplementation.
The main plasma carrier of RRR--tocopherol in neonatal
calves was HDL (68%), whereas LDL, VHDL and VLDL carried 18, 9 and 5%
of the total plasma RRR--tocopherol, respectively. This
report is the first to describe RRR--tocopherol Lp
associations in neonatal calves. In 3- to 4-mo-old calves, most
RRR--tocopherol is carried by HDL (62%), whereas LDL
carried 17% of total RRR--tocopherol (Chew et al. 1993
). The increase in plasma concentrations of
RRR--tocopherol content from d 2 to d 28 was greater with
HDL (19-fold) than with LDL (sevenfold), VHDL (fivefold) and VLDL
(twofold). The HDL in neonatal calves may function in the distribution
of vitamin E to peripheral tissues or in its excretion.
Newborn calves in this study had more RRR--tocopherol
associated with VHDL and VLDL and lower RRR--tocopherol
associated with HDL than did adult cattle. The distribution profile of
RRR--tocopherol among Lp fractions in 8-d-old calves was
comparable to that of adult animals. The physiological importance of
these changes is unknown. Data regarding the distribution of
RRR--tocopherol among Lp fractions in adult animals are
in contrast with those indicating that RRR--tocopherol is
distributed equally between HDL and LDL fractions (Al Senaidy 1996
), but they are in line with the finding that the major Lp
fraction in calves and adult ruminant animals is HDL (>80% of total
LP), whereas LDL constitutes <10% of total Lp (Forte et al. 1981
).
Our results agree with previous reports (Burton et al. 1988
, Cheesman et al. 1995
, Mathias et al. 1981
, Ochoa et al. 1992
), indicating that
the form of vitamin E (RRR--tocopherol or
RRR--tocopheryl acetate) has no effect on plasma
RRR--tocopherol concentrations. These authors reported
similar in vivo absorption of RRR--tocopherol and
RRR--tocopheryl acetate in sheep, humans and rats.
Mathias et al. (1981)
found that the esterified vitamin E is hydrolyzed
by a brush border esterase, both forms enter circulation as
RRR--tocopherol, and hydrolysis to tocopherol does not
affect absorption of RRR--tocopherol acetate when
compared with tocopherol. Other reports have demonstrated higher plasma
concentrations of RRR--tocopherol when calves are
supplemented with RRR--tocopherol compared with the ester
form (Eicher et al. 1997
, Hidiroglou et al. 1989
). The higher tocopherol levels reported by Hidiroglou et al. (1989)
might be explained by supplementation of vitamin E on an
equal-weight basis rather than on an equal-activity basis
(Ochoa et al. 1992
).
In the present study, calves were born with comparatively low
concentrations of plasma retinol (0.19 µmol/L). In adult dairy
cattle, concentrations of retinol that are <0.69 µmol/L are
indicative of a vitamin A deficiency (NRC 1989
). Plasma
concentrations of retinol that are <0.69 µmol/L, however are not
abnormal for neonatal calves (Franklin et al. 1998
,
Hibbs and Krauss 1947
, Nonnecke et al. 1999b
). Calves fed 35.6 and 71.2 µmol of vitamin A daily had
1.7- to 1.9-fold greater plasma concentrations of retinol,
respectively, than control calves by d 28. Donoghue et al. (1983)
observed enhancement of plasma retinol in lambs with intake of vitamin
A, whereas Franklin et al. (1998)
reported no differences in retinol
concentrations in calves supplemented with 0, 15.71 and 31.41 µmol of
vitamin A daily in whole milk.
In calves fed 35.6 and 71.2 µmol of vitamin A daily, retinyl
palmitate was found at concentrations reaching 0.66% of total
plasma vitamin A vs. 0 and 0.2% in calves fed no vitamin A or 1.78
µmol of vitamin A daily, respectively. With normal vitamin A intake,
<5% of circulating vitamin A is esterified in humans (Smith and Goodman 1976
). Excess vitamin A elevates plasma
concentrations of retinol esters in sheep (Donoghue et al. 1983
), horses (Sklan and Donoghue 1982b
), humans
(Smith and Goodman 1976
) and rats (Mallia et al. 1975
). Donoghue et al. (1983)
observed that with high vitamin A
intake the absorption of esterified retinol is increased, whereas
clearance is unchanged, resulting in elevated concentrations of retinol
ester. Interestingly, Zimmerman et al. (1998)
found no increase in
plasma concentrations of retinyl palmitate in dairy cows supplemented
with 262 µmol of vitamin A (as retinyl palmitate) daily. Neonatal
calves fed milk exclusively, however, are functionally monogastric
animals (Hoppe et al. 1996
, Poor et al. 1992
). In the present study, the increase in plasma retinol and
retinyl palmitate associated with excess dietary vitamin A suggests
high dietary concentrations of vitamin A alter mechanisms controlling
steady-concentrations of vitamin A in neonatal, preruminant calves.
In conclusion, dietary vitamin A exceeding current NRC recommendations
by 10- to 20-fold was associated with a reduction in the concentration
of RRR--tocopherol in Lp fractions in plasma of
neonatal calves. The amount of Lp RRR--tocopherol was
lowest in calves fed 35.6 and 71.2 µmol of vitamin A daily (20- to
40-fold the NRC requirement) when compared with calves fed 1.78 µmol
daily (NRC requirement). Because of the critical antioxidant role of
vitamin E, the health-related consequences associated with the
depression of Lp RRR--tocopherol in the neonatal calf
fed high levels of vitamin A warrants further investigation. These
results also indicate that the more stable and less costly form,
RRR--tocopheryl acetate, be used as a dietary
supplement in calves since the form of vitamin E fed did not influence
circulating concentrations of RRR--tocopherol.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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2 Journal paper No. 3131 of the South Dakota State Experiment Station.
3 Journal paper No. 18440 of the Iowa Agriculture and Home Economics Experiment Station, Ames, IA, Project No.
5 Present address: Department of Animal Science, University of Kentucky, Lexington, KY 40546-0215.
6 Abbreviations used: Lp, lipoprotein; NRC, National Research Council; VHDL, very high-density lipoprotein; TTP, tocopherol transfer protein.
Manuscript received August 16, 1999. Initial review completed September 30, 1999. Revision accepted November 8, 1999.
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