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OCR for page 11
vitamin D
Vitamin D has been known since 1920 as a chemical
and nutritional entity. Not until after the late 1960s,
however, has the biochemical basis of its physiological
role been at least partially defined. Since then, research
in vitamin D metabolism has resulted in new and impor-
tant information regarding its role in calcium and phos-
phorus metabolism. Research has also given insights
into the value of vitamin D in clinical medicine related to
abnormal mineral metabolism, endocrinology, and nu-
trition. This information has been fostered by the devel-
opment of high specific activity, radiolabeled vitamin D,
and more precise isolation and identification methods to
study vitamin D metabolism in greater detail.
NUTRITIONAL ROLE
Vitamin D can be considered a vitamin only in the
sense that, under modern farming conditions, many ani-
mals are raised in total confinement with little or no
exposure to natural sunlight. Adequate sunlight results
in the production of sufficient vitamin D3 from
7-dehydrocholesterol in the skin. Hence, vitamin D3 is
not required in the diet if sufficient amounts of sunlight
are received.
Lack of adequate photoproduction of vitamin D3 or
inadequate dietary supplementation of vitamin D leads
to the failure of bones to calcify normally. This meta-
bolic disease is known as rickets in the young and os-
teomalacia in adults. Once this deficiency was
recognized, the dietary supplementation of vitamin D
became a commonly accepted nutritional practice. The
dietary requirements for most animal species are in the
range of 200 to 1,200 TU/kg of diet.
FORMS OF THE VITAMIN
The vitamin D sterols that are used in human and
veterinary medicine and their relative biologic poten
cies in mammals are listed in Table 4. Toxicity has been
reported with many of these. The most common occur-
rences result from the use of vitamin D2 or vitamin D3
(Figure 21. Vitamin D toxicity has also occurred with
ingestion of certain plants containing a water-soluble
glycoside of 1,25-(OH)2-D3 (Hughes et al., 1977b).
ABSORPTION AND METABOLISM
Many excellent reviews have been written on the me-
tabolism and function of vitamin D (Haussler and Mc-
Cain, 1977; Norman, 1979; Stern, 1980; Norman et al.,
1982; Horst and Reinhardt, 1983; DeLuca, 1984; Horst,
1986) and should be consulted for in-depth information.
The following discussion, therefore, is limited to some
of the key events leading to the in vivo activation of
vitamin D.
Because it is fat soluble, vitamin D is absorbed with
other neutral lipids via chylomicrons into the lymphatic
system of mammals or the portal circulation of birds and
fishes. The two major natural sources of vitamin D are
cholecalciferol (vitamin D3, which occurs in animals) or
ergocalciferol (vitamin D2, which occurs predominantly
in plants). Vitamin D (absence of a subscript implies
either vitamin D2 or vitamin D3) either ingested or pro-
duced in the skin is carried through the circulatory sys-
tem to the liver, where it is converted to 25-hydroxy-
vitamin D (25-OH-D). This metabolite is the major circu-
lating form under normal conditions and during vitamin
D excess (Horst and Littledike, 1982; Littledike and
Horst, 1982~. For some time, it was considered to be the
metabolically active form of vitamin D (DeLuca, 1971~.
It is now known to be the precursor to I,25-
dihydroxyvitamin D (1,25-(OH)2-D), the active metabo-
lite that is produced almost exclusively in the kidney.
This metabolite functions with the parathyroid hor
11
OCR for page 12
12 Vitamin Tolerance of Animals
TABLE 4 Vitamin D Sterols Used in Human and Animal Nutrition: Their
Relative Antirachitic Potencies and Duration of Effects Following Withdrawal in
Mammals
Name
Vitamin D
Synonym
Caleiferol
Relative
Poteneya
Duration
(weeks) Comments
6-18
Vitamin D3 Choleealeiferol 1
6-18
Vitamin D2 Ergoealeiferol 1 6-18
Either vitamin D2 or
vitamin D3
Animal form:
produced bar
irradiation of
7-dehydroeholesterol
Plant form: produced
by irradiation of
ergosterol
Dihydrotaehy- DHT 0.05-0.1 1-3 Sterolgenerated
sterol during irradiation of
ergosterol
25-OH-D3 Caleidiol 2-5 4-12 Liver metabolite of
vitamin D3
1,25-(OH)2-D3 Caleitriol
la-OH-D3
5-10
cx-Caleidiol 5-10
0.2-0.8 Kidney metabolite of
25-hydroxy
vitamin D3
0.3-1.0 Synthetic analogue
aAdapted from Parfitt (1980).
mone (PTH) to bring about blood calcium and phos-
phorus homeostasis. The PTH acts with 1,25-(OH)2-D
to regulate plasma calcium and phosphorus concentra-
tions. The hormone is also an important mediator of the
renal production of 1,25-(OH)2-D (that is, of the 25-OH-
D-Ic'-hydroxylase). Other factors, however, can influ-
ence the biosynthesis of I,25-(OH)2-D, some of which
are listed in Figure 3. Once formed, 1,25-(OH)2-D binds
to a specific receptor in the enterocyte nucleus and initi-
ates events leading to a stimulation in calcium and phos-
phorus absorption (Norman et al., 1982~. Also,
1,25-(OH)2-D acting with PTH mediates the resorption
of bone with the release of calcium and phosphorus (De-
Luca, 1984~. A series of new discoveries has made it
FIGURE 2 Chemical structures of vitamin
D3 and vitamin D2.
apparent that 1,25-(OH)2-D plays a much wider role in
biology than was thought. A variety of tissues not re-
garded to participate in mineral and skeletal homeosta-
sis have been found to possess specific receptors for
1,25-(OH)2-D (Norman et al., 1982~.
There are many metabolites of vitamin D that circu-
late in plasma other than 25-OH-D and 1,25-(OH)2-D.
Table 4 lists some of the vitamin D3 and vitamin D~
metabolites. One metabolite, 24,25-dihydroxyvitamin
D (24,25-(OH)2-D), has also been considered as a biologi-
cally active vitamin D metabolite. Although the physio-
logic significance of 24,25-(OH)2-D is not yet
understood, it has been proposed to have a role in the
formation of bone (Norman, 19801.
22 24 H
~3
~8
'CH2
4 10
Vitamin D3
(cholecalciferol)
HO:
CH3
CH3~<26CH3
~L~
'~CH2
nr
Vitamin D2
(ergocalciferol)
OCR for page 13
Vitamin D 13
7-Dehydrocholesterol
Ultraviolet light
25-OH -D
Phenobarbital
Hypovitaminosis D
Low plasma Ca
Low plasma P;
Parathyroid hormone
Estrogens
3
Prolactin +
1 ,25-(OH )2 -D -
High plasma Ca
HYPERVITAMINOSIS
Skin
Vitamin D3 ~Diet
Liver
-in -V3
I Kidney
1,25-(OH)2-D3 24,25-(OH)2-D3
Putscher noted vitamin D toxicity as early as 1929.
Toxicity has been described in many species, including
humans. Accidental toxicity has been reported in vari-
ous species of animals, including monkeys, dogs, cattle,
horses, pigs, and chinchillas.
Although its toxicity in humans has been known for
more than 40 years, the vitamin's significance in veteri-
nary medicine has drawn greater attention in connec-
tion with massive administration to prevent milk fever
in ~ airy cows.
Clinical signs
Many investigators have described the clinical signs
of hypervitaminosis D in mammals. Cole et al. (1957)
reported that cows receiving 30 million IU of vitamin D2
orally for 11 days developed anorexia, reduced rumina-
tion, depression, premature ventricular systoles, and
bradycardia. Kent et al. (1958) observed in monkeys
weight loss, anorexia, elevated blood urea nitrogen
(BUN), diarrhea, anemia, and upper respiratory infec-
tions. In pigs, Chineme et al. (1976) described anorexia,
stiffness, lameness, arching of the back, polyuria, and
aphonia.
+ Hypervitaminosis D
· ~Parathyroid hormone
1 ,25-(OH )2 -D
+ High plasma Ca
FIGURE 3 Factors regulating 1,25-dihy-
droxyvitamin D and 24,25-dihydroxyvitamin
D biosynthesis.
It is generally assumed that vitamin D2 and vitamin D3
are equally potent in most mammals. In certain animals,
however, it is quite clear that there are substantial dif-
ferences between the two sterols. In birds (Chen and
Bosmann, 1964) and in New World primates (Hunt et
al., 1967), vitamin D3 is substantially more active than
vitamin D2. It has generally been assumed that vitamins
D2 and D3 are equally active in Old World monkeys in
augmenting calcium absorption and preventing os-
teomalacia. However, when large and potentially toxic
doses were administered orally to rhesus monkeys
(Hunt et al., 1972), vitamin D3 was more toxic. Hyper-
calcemia, extensive soft tissue calcification, and death
occurred in many animals. By contrast, the administra-
tion of vitamin D2 produced hypercalcemia to a lesser
degree. Animals survived, and soft tissue calcification
was absent or only mild. Similarly, Harrington and Page
(1983) found vitamin D3 more hypercalcemic and
overtly toxic to horses than vitamin D2.
The development of methods to measure vitamin D
and its metabolites in plasma (Horst et al., 1981) has
provided insight into the possible mechanism of vitamin
D toxicity and also has provided information regarding
the metabolic bases of the differences in toxicity be-
tween vitamins D2 and D3.
As stated earlier, the predominant vitamin D form in
OCR for page 14
14 Vitamin Tolerance of Animals
plasma following vitamin D overdose is 25-OH-D. This
metabolite circulates normally at 30 to 50 ng/ml in most
species (Horst and Littledike, 19821. However, during
vitamin D intoxication, it increases from 200 to 400 ng/
ml (Littledike and Horst, 1982~. When circulating at
very high concentrations, 25-OH-D can compete effec-
tively with 1,25-(OH)2-D for receptors in the intestine
and bone. Therefore, during vitamin D toxicosis, 25-
OH-D can induce actions usually attributed to
1,25-(OH)2-D. Thus, 25-OH-D is believed to be the criti-
cal factor in vitamin D intoxication.
When equal amounts of vitamin D3 and vitamin D2 are
presented together in diets of mammals, the predomi-
nant circulating form of the vitamin is usually 25-OH-D3
rather than 25-OH-D2 (Horst et al., 1982~. Similarly, in
toxicity experiments where vitamin D2 was less toxic
than vitamin D3, the metabolite 25-OH-D2 was found to
be present at lower plasma concentrations than was
25-OH-D3 (Harrington and Page, 1983~. Therefore, the
difference in toxicity between these vitamins is proba-
bly attributable to the less efficient metabolism of vita-
min D2 to its more active metabolites, particularly
25-OH-D2. In most species, plasma concentrations of
1,25-tOH)2-D decrease during toxicosis (Hughes et al.,
1977a). However, there are differences between species
in this response. For example, bovine species show sub-
stantial increases in plasma 1,25-(OH)2-D following in-
tramuscular doses of vitamin D3 in massive amounts (15
FIGURE 4 Scheme for the pathogenesis of
vitamin toxicosis. The abbreviations and their
meanings are: Ca, calcium; GFR, glomerular
filtration rate; 25-OH-D, 25-hydroxyvitamin
D; P. phosphate; PTH, parathyroid hormone;
Tm, tubular maximum.
million IU) (Horst and Littledike, 1979~. Therefore, vi-
tamin D toxicity in ruminants may be partially a re-
sponse to elevated 1,25-(OH)2-D.
A summary of the major pathogenic factors involved
in vitamin D toxicity is shown in Figure 4. Treatment
with excess vitamin D or 25-OH-D stimulates intestinal
absorption of calcium and, to a lesser degree, augments
intestinal phosphate transport. Bone resorption of cal-
cium is increased. The overall effect is an increase in
serum calcium and reduction in PTH. With modest hy-
percalcemia, glomerular filtration rate (GFR) may re-
main stable, and hypercalciuria may be substantial
because of the increased filtered load of calcium and the
reduction of tubular reabsorption of calcium as a result
of reduced PTH secretion. When GFR is maintained,
serum calcium may only be modestly elevated by 10 to
20 percent. There is an increased risk of nephrolithiasis
because of the hypercalciuria, however. With further
increases in serum calcium level, the GFR decreases.
This decrease is due to the potentiating action of cal-
cium on angiotensin [I-mediated vasoconstriction of re-
nal afferent arterioles. A further, rapid increase in
serum calcium might then occur due to the clecrease in
filtered calcium and the subsequent fall in urinary cal-
cium. Polyuria, along with vomiting (in nonruminants),
may cause the extracellular fluid volume to be reduced,
which would further contribute to reduced renal func-
tion. Thus, reduced renal function is the major event
Vitamin D excess
t25-OH-D
1
/ 1 \
TP absorption ~ Bone resorption
/ I
~ /
tCa absorption
"Dietary Ca
TSerum P Alkalosis / tPTH
\ \ / ~ \
\ \ Hypercalcemia ITm Ca
~T \
IConcentrating Soft tissue f Filtered load
ability by kidney calcification of Ca
~\1 ~ ~
Polyuria Decreased Hypercalciuria
GFR ~
Nephrolithiasis
OCR for page 15
Vitamin D 15
that leads to the total loss of control of calcium homeo-
stasis and to the severity of hypercalcemia during vita-
min D intoxication.
Soft Tissue Changes
Postmortem examination of vitamin D-intoxicated
animals generally reveals extensive cardiovascular and
kidney mineralization. In cows and sheep given toxic
doses of vitamin D3, the collecting tubules of the me-
dulla are the major mineralization sites. The cortex is a
minor mineralization site (Capen et al., 1966; Simesen et
al., 19781. However, the cortex and papillae are major
mineralization sites in lx-OH-D (a precursor to 1,25-
(OH)2-D3) toxicity in sheep (Simesen et al., 1978~. Car-
diovascular lesions are primarily located in the aorta,
stomach arteries, aortic valves, aortic arch, large arte-
rial bifurcations, and area around the openings of small
vessels.
Mineralization within the respiratory tract is also one
of the most frequent lesions. Kent et al. (1958) described
calcification of the basement membrane of small bron-
chi, alveolar ducts, and bronchial cartilage in monkeys.
Chineme et al. (1976) described calcification of the alve-
olar septa, bronchial submucosa, and walls of arterioles
. .
in pigs.
Kent et al. (1958) also showed that after kidney le-
sions, calcification of the salivary glands (calcification
occurs twice as often in the submaxillary gland as in the
parotidd) was the next earliest and most frequent lesion.
Chineme et al. (1976) have described calcification in the
mucosa and muscularis mucosae of the stomach of the
pig's stomach.
Lesions That Are Not Associated with Hypercalcemia
The possibility that long-term treatment with high
levels of vitamin D or an active sterol may cause tissue
damage, particularly to the kidney, in the absence of
hypercalcemia has been the subject of considerable
speculation. While the bulk of information suggests that
hypercalcemia is the sine qua non to manifestation of
vitamin D intoxication, there are studies in experimen-
tal animals suggesting that mild ultrastructural abnor-
malities occur before the appearance of hypercalcemia
or the deposition of calcium in tissues (Manston and
Payne, 1964~. Also, there have been reports of the de-
velopment of nephrocalcinosis and hypercalciuria in hu-
mans without known hypercalcemia treated with
vitamin D or dihydrotachysterol (Dinkel,1966~. A retro-
spective evaluation of 27 patients with hypoparathy
roidism treated with pharmacologic doses of vitamin D
or dihydrotachysterol has suggested that renal function
did decrease in certain patients in the absence of hyper
calcemia (Parfitt, 1977~. In 5 patients, the development
of nephrocalcinosis correlated with the frequency and
severity of documented hypercalcemia. Nephrocalcino-
sis developed in 3 other patients, however, in whom
there was no correlation with the frequency or severity
of hypercalcemia nor tendency toward hyperphosphate-
m~a.
Factors Affecting Toxicity
The severity of the effects and pathogenic lesions in
vitamin D intoxication depend upon such factors as the
type of vitamin D (vitamin D2 versus vitamin D3), the
dose, the functional state of the kidneys, and the compo-
sition of the diet. Vitamin D toxicity is enhanced by a
rich dietary supply of calcium and phosphorus, and is
reduced when the diet is low in calcium (Hines et al.,
1985~. Toxicity is also reduced when the vitamin is ac-
companied by high intakes of vitamin A or by thyroxin
injections (Payne and Manston, 1967~. The route of ad-
ministration also influences toxicity. Parenteral admin-
istration of 15 million IU of vitamin D3 in a single dose
caused toxicity and death in many pregnant dairy cows
(Littledike and Horst, 1982~. On the other hand, oral
administration of 20 to 30 million IU of vitamin D2 daily
for 7 days resulted in little or no toxicity in pregnant
dairy cows (Hibbs and Pounden, 1955~. Napoli et al.
(1983) have shown that rumen microbes are capable of
metabolizing vitamin D to the inactive 10 keto-19-nor
vitamin D. Parenteral administration would circumvent
the deactivation of vitamin D by rumen microbes and
may partially explain the difference in toxicity between
oral and parenteral vitamin D.
Various measures have been used in human medicine
for treatment of vitamin D toxicity. These measures are
mainly concerned with hypercalcemia management. Vi-
tamin D withdrawal is obviously indicated. It is usually
not immediately successful, however, due to the long
plasma half-life of vitamin D (5 to 7 days) and 25-OH-D
(20 to 30 days). This is in contrast to the short plasma
half-life of lor-OH-D3 (1 to 2 days) and 1,25-(OH)2-D3 (4
to 8 hours). Because intestinal absorption of calcium
contributes to hypercalcemia, a prompt reduction in di-
etary calcium is indicated. Sodium phytate, an agent
that reduces intestinal calcium absorption, has also
been used successfully in vitamin D toxicity manage-
ment in monogastrics (Reeker et al., 1979~. This treat-
ment would be of little benefit to ruminants due to the
presence of rumen microbial phytases. There have also
been reports that calcitonin (West et al., 1971), glucagon
(Ulbrych- Jablonska, 1972), and glucocorticoid therapy
(Streck et al., 1979) reduce serum calcium levels result-
ing from vitamin D intoxication.
OCR for page 16
16 Vitamin Tolerance of Animals
Concentrations in Milk and Liver
Hollis et al. (1981), Reeve et al. (1983), Kunz et al.
(1984), and McDermott et al. (1985) have reported the
distribution of vitamin D and vitamin D metabolites in
milk and colostrum of normal dairy cows. Estimates
have also been made following administration of phar-
macologic amounts of vitamin D or vitamin D metabo-
lites to dairy cows. Colostrum from cows receiving
normal dietary amounts (10,000 to 50,000 IU/day) of
vitamin D had 200 to 300 IU of vitamin D activity/liter.
Normal milk had 40 to 50 IU/liter. Colostrum from cows
receiving 30 million IU of vitamin D2 before parturition
contained 13,000 IU/liter. Normal milk taken 6 days
following parturition contained 2,400 IU/liter (Hibbs
and Pounden,1955~. Daily feeding of 162,000 IU of vita-
min D3 from cod liver oil led to an 11-fold increase in
vitamin D activity in milk (Krause and Bethke, 1937~.
Hollis et al. (1983) published one of the first reports
regarding the concentration of vitamin D and vitamin D
metabolites in milk from dairy cows and humans receiv-
ing large parenteral or enteral doses of vitamin D. In
cows that received 125 mg (15 million IU) of vitamin D3,
vitamin D3 and 25-OH-D3 concentrations in plasma in-
creased significantly 20 days before parturition. This
increase was reflected by similar increases in colostrum
and milk concentrations of these sterols (Figures 5 and
6~. Similarly, in mothers given supplementations of
CONTROL
0~0 TREATED
35.0 r
30.0
-
E 25.0
-
z
in
At:
CL
20.0
15.0
10.0
5.0 _
n _
'A
CONTROL
_ TR KATE D
4.o
12.0
_ 10.0
_ 8.0
t hi ~ ~ 4.0 As>
_ =
0 2 4 6 8 10 12
DAYS
2.0
O
FIGURE 5 Relationship between plasma and milk levels of
vitamin D in the cow. Treated animals were injected intramus-
cularly with 5 million IU of vitamin D3 approximately 20 days
before parturition. Control animals were maintained on a diet
containing 4,000 IU of vitamin D3/day (Hollis et al., 1983~.
CONTROL
0~0 TR EATED
Inn
- 70.0
-
C]
1
I
o
UD
at:
CL
60.0
50.0
4o.
30.0
20.0
0 - CONTROL
_ _ TR EATED
13.5
to ~
,
0 2 4
1 1 1 1
6 8 10 12
DAYS
3.0
2.5 _
E
2.0 `3
I
O
1.5 ~
Y
J
1.0
0.5
O
FIGURE 6 Relationship between plasma and milk levels of
25-OH-D in the cow. Treatments were the same as those de-
scribed in Figure 5 (Hollis et al., 19831.
2,000 IU of vitamin D2 during late gestation and early
lactation, the milk concentrations of vitamin D and
25-OH-D were significantly elevated from those ob-
served in milk from mothers given normal supplementa-
tions (400 IU/day). In both cases, the concentrations of
24,25-(OH)2-D and 1,25 (0H)2-D3 were not elevated.
When normal cows were treated with 400 ,ug of 1,25-
(OH)2-D3 parenterally, 1,25-dihydroxyvitamin D3 was
elevated in milk, however (Hollis et al., 1983~.
Vitamin D activity was also elevated in cows' livers
following dietary supplementation with 250,000 IU/day
for 2 to 3 weeks (Quarterman et al., 1964~. At the time of
sacrifice, the vitamin D activity had increased to 2,700
IU/100 g of tissue compared to 21 IU/100 g of tissue in
the control group. Following withdrawal of the vitamin
D, the activity in the liver had decreased to normal levels
within 2 to 3 weeks.
PRESUMED UPPER SAFE LEVELS
Existing data for several of the domestic species do
not allow precise estimates to be made for maximum
vitamin D tolerance levels. Rather, most of the experi-
ments to date reviewed (Table 5) have addressed the
clinical consequences of vitamin D toxicosis.
Several factors, such as the chemical form (vitamin D2
or vitamin D3), species, dietary intake of calcium and
phosphorus, route of administration, and duration of
treatment, can influence the maximum tolerable levels
OCR for page 17
17
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OCR for page 20
20 Vitamin Tolerance of Animals
of vitamin D in the diet. Table 6 attempts to establish
some reasonable estimates regarding safe dietary in-
takes of vitamin D3 as a function of dietary exposure
time for various species. In several of the species listed
in Table 6 (the horse, chicken, turkey, and probably the
Japanese quail), experiments have established that vita-
min D3 is 10 to 20 times more toxic than vitamin D2.
Therefore, the values in Table 6 should be adjusted ac-
cordingly for cases in which vitamin D2 is the sole di-
etary source of vitamin D.
Very little information exists regarding the maximum
safe dietary level of vitamin D3 for a long (more than 60-
day) exposure time. Horst and Littledike (1982) re-
ported plasma vitamin D and vitamin D metabolite
concentrations in several animal species that consumed
experimental diets for several months. A retrospective
analysis of dietary ingredients indicated that all of the
diets consumed by the different species contained 4- to
10-fold the required level of vitamin D3 (National Re-
search Council, 1975, 1978a, 1979, 1984~. Also, in these
experiments, plasma 25-OH-D3 concentrations, a sensi-
tive indicator of vitamin D excess, were found to be
within the normal range (20 to 80 ng/ml) for all of the
different species included in the analysis. In sheep fed
diets containing 10 times the level of required vitamin D
according to the Agricultural Research Council, similar
results have been obtained (Smith et al., 1985~. The
same workers, observed, however, that when dietary
vitamin D3 was 20-fold the sheep's nutritional require-
ment, plasma 25-OH-D3 concentrations increased sig-
nificantly. Most animal species appear to be able to
tolerate 10 times the level of vitamin D that they require
TABLE 6 Estimation of Safe Upper Dietary Levels of
Vitamin D3 for Animals
Dietary Exposure Time
Species Requirementa
~ 60db ~ 60d
IU/kgritamin D3 diets
Birds
Chicken200
Japanese1,200
quail
Turkey900
Cow300
Fish
Catfish
Rainbow
trout
Horse
Sheep
Swine
1,000
1,800
400
275
220
40,000
20,000
90,000
25,000
25,000
33,000
aFrom the National Research Council (1975, 1978a, 1978b, 1979,
1981,1983,1984).
bThe safe upper level of vitamin D3 for an exposure time of less than
60 days is undetermined for the horse, catfish, and rainbow trout.
COne IU = 0.025 fig of vitamin D3.
for long periods of time. Catfish and rainbow trout, on
the other hand, can tolerate as much as 20 and 500 times
their requirements, respectively (Andrews et al., 1980;
Hilton and Ferguson, 19821.
Under short-term feeding conditions (less than 60
days), most of the species listed in Table 6 can tolerate
up to 100 times their apparent requirements for vitamin
D. Experiments supporting this conclusion are, for the
most part, extracted from Table 5.
Although most animals can tolerate excess vitamin D
for extended periods, there has been no credible data
suggesting that exceeding dietary requirements by sev-
eral times improves performance. Therefore, other
than to compensate for oxidative losses, there is no justi-
fication for feeding excessive dietary vitamin D.
CONCLUSION
More research is needed to further clarify the vitamin
D mechanism that causes toxic effects in different spe-
cies. Whether the tissue calcinosis is purely a result of
hypercalcemia or due to some other factor is a question
of prime importance. Also, there is little information
regarding the quantity and distribution of vitamin D and
vitamin D metabolites in affected tissues.
2,800
4,700
3,500
2,200
20,000
1,000,000
1. Vitamin D is essential for normal bone formation in
animals. It is required in the diets of animals raised with
insufficient exposure to sunlight.
2. Studies indicate that vitamin D3 is 10 to 20 times
more toxic than vitamin D2.
3. For most species the presumed maximal safe level
of vitamin D3 for long-term feeding conditions (more
than 60 days) is 4 to 10 times the recognized dietary
requirement. Under short-term feeding conditions (less
than 60 days), most species can tolerate as much as 100
times their apparent dietary requirements.
4. There is no known benefit to feeding vitamin D to
animals in excess of the recognized dietary requirement
levels.
2,200
2,200
2,200 Andrews, J. W., T. Mural,
~· r ~
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Representative terms from entire chapter:
milk fever
