Copper deficiency: The other approach.
By: Wilbert Frieling and Piet van Geest.
The Fair Isle Shetland Sheep in Holland has suffered from the loss of some Shetland Sheep due to
what eventually turned out to be copper deficiency.
There was not very much information available on the subject and we wanted to get to the bottom of
things. Well, losing four sheep on a total of a few hundred may be considered a normal loss, but losing
four out of fifteen is alarming. Laboratory tests showed rates of 16 Mg/Kg in the liver and 26Mg/Kg in
the kidneys. Especially the liver being very low.
Copper deficiency shows in a clinical and a non-clinical or hidden form. The incurable clinical form
showing symptoms like swayback. The hidden form causing reduced fertility, poorer wool quality with
a shorter staple length and reduced growth rates. Lambs with low copper levels are also less
protected against infections.
In times the ewe is under a lot of stress e.g. immediately after lambing the hidden form can change
into the clinical form, affecting the brainstem, certainly causing death. If the disease is passed on to
the lamb there is no cure also. The only treatment is prevention.
Some bloodlines or individual animals show a higher susceptibility then others. The breeder has to
inspect all his animals regularly for possible symptoms in order to recognise the hidden form in an
early stage. First of all the sheep look a bit apathetic. The best information, however, comes from the
wool. The wool of a sheep with low copper levels has heavily felted tips, a great loss of crimp and
significant de-pigmentation. Moreover the wool becomes more and more tender.
At first we thought that feeding more copper was the answer (using cow concentrates). But on the
contrary laboratory tests proved even lower copper rates in liver and kidneys, ranging from 7 Mg/Kg in
the liver to 12 Mg/Kg in the kidneys.
An unwanted side effect was the growth of pounds of internal fat. So this was not the right solution for
our problems.
The other approach.
In our search for a solution a letter from Ms. Roswitha Norton in England led us to Dr Stewart B. Telfer
from Leeds University in the UK. We decided to have some blood samples tested in Leeds in the
U.K., not being any similar facilities available in the Netherlands.
In Dr. Telfer’s view copper deficiency is in fact molybdenum toxicity. Research has shown that
molybdenum can form a toxic compound with sulphur known as thiomolybdate in the rumen of the
animal. Copper can bind to this thiomolydate and therefore prevent absorption in the blood. In case of
high thiomolydate levels in the rumen much of the copper is used for detoxification and therefor is no
longer available to the animal. This can lead to low copper levels and in the end also to the
appearance of free thiomolybdate in the blood. According to Dr. Telfer this thiomolydate is causing the
clinical problems of copper deficiency.
The other approach is not to supply extra copper, but to remove the thiomolybdate.
Iron can also obstruct the intake of copper in the body by forming a complex with sulphur and copper.
From the above it is clear that there can be different causes of the clinical appearance of copper
deficiency. Reaching from sufficient copper in the feed (in combination with high molybdenum and iron
levels) to poor copper levels in the feed. Molybdenum and iron can be found in the soil and industrial
pollution may have its contribution also. Administering copper intravenously or feeding cow
concentrates are not really the cure. Laboratory tests should give the exact cause of the clinical
problems.
Dr. Telfer developed a medication called CoSeCure. It is not only about copper, but also about
Selenium and Cobalt. The function of selenium is part of the body’s mechanism for dealing with the
toxic metabolites that the use of oxygen invariably generates. Cobalt is very important to the growing
animal. Deficiency manifests itself in poor growth and performance, known as “pine”.
CoSeCure is a soluble glass bolus administrated orally into the rumen, that is to say into the second
stomach at the bottom of the rumen. The bolus prevents the uptake of the thiomolybdates in the blood
and makes copper available to the body again.
Within a short period of time the wool improves and the sheep is far livelier. The best time to
administer the boluses is just before tupping. Lamb boluses can be given at ten weeks of age. The
boluses can be regurgitated though, especially when the sheep are turned on their back. It is very
important to administer the boluses at the right temperature, that is room temperature. In Holland we
have boluses for other purposes with a kind of umbrella on them opening after administration to
prevent regurgitation. We discussed this with Dr. Telfer, but he was against it because of the risk of
choking.
The first blood samples were drawn in November 1997 before using CoSeCure.
The results are given followed by Dr. Telfer’s slightly adapted and abbreviated comments.
Date of sampling: 11/97
Sample
Num.
1.
2.
3.
4.
5.
6.
7.
8.
Animal
No
0006
092*
097*
0007*
303*
095*
132+
133+
Hb
(g/l)
126
122
118
111
131
103
145
99
Hc
(%)
41
38
39
35
44
36
46
34
CP
(mg/dl)
22.4
29.9
18.1
10.2
10.5
3.2
1.4
4.3
Pl-Cu
(µM)
13.6
12.2
9.4
7.1
7.9
N.D.
N.D.
0.4
TCA-Cu
(µM)
14.3
11.8
9.6
6.9
7.9
2.5
2.3
2.7
SOD
(U/l)
3318
3686
2973
3692
3593
3444
2424
3750
GSHpx
(U/ml)
141
140
159
170
218
135
50
121
CP/PL-Cu
1.6
2.4
1.9
1.4
1.3
1.3#
0.6#
1.6#
Hb - Haemoglobin Hc - Haematocrit CP - Serum/Caeruloplasmin
PL-Cu - Plasma Copper
TCA-Cu Trichloroacetic Acid Soluble Copper SOD - Erythrocyte Super Oxide Dismutase GSHpx Erythrocyte Glutathione Peroxidase
+ no minerals or cow concentrates
* being fed or had cow concentrates
# ratio based on TCA Copper
Normal values:
Pl-Cu: > 12 µM
CP: > 15 mg/dl
TCA-Cu/Pl-Cu: 1
CP/Pl-Cu: > 2: normal
: 1.5 – 1.9 questionable
: < 1.5 very low
Copper: Plasma copper concentrations range from non-detectable to 13.6 µM/l. There are five animals
with concentrations that are lower than 8 and are regarded as being in the deficient category of which
three have very little copper in their blood at all. A further one is in the marginal category (8-12) and
this leaves two animals in what is regarded as the normal range (>12). The TCA copper
concentrations range from 2.3 to 14.3 µM/l These values agree well with the plasma copper values,
indicating that there is no significant quantity of copper thiomolybdate present in the blood of these
animals. The caeruloplasmin activities range from 1.4 to 29.9 Mg/dl with there being five animals with
activities that are deficient (<15), whilst the rest are in the normal range (>15). The
caeruloplasmin/plasma copper ratios range from 1.3 to 2.4 and on this basis there are two animals
with normal ratios of 1.9 or more, one animal with a marginal ratio of 1.6. Two animals with ratios less
than 1.5 that are indicative of a significant presence of free thiomolybdate in their blood. There are,
however, three further sheep (095, 132 and 133) where the ratios are difficult to determine, but it is
almost certainly the case there is free thiomolybdate present. The TCA copper values of 2.5, 2.3 and
2.7 could be used and this would give ratios respectively of 1.3, 0.6 and 1.6 which are all indicative of
the presence of free thiomolybdate in the blood. The superoxide dismutase activities ranges from 2400
to 3750 µ/gm Hb and these are all in the normal range (>2000).
Selenium: gluthatione peroxidase activities range from 50 to 218 units/ml PCV and these are all the
normal range (>40) although one animal is at the bottom end (number 132) whilst the rest are all
towards the top end of the normal range.
Hb/Hc: these values are normal.
Overall: animal samples numbers 1-6 have all been fed cow concentrates and still obtaining cow
concentrates. This may be having an effect on the plasma copper, but there is a strange mixture of
values from animal number 095 that is very low in the blood to animals 6 en 92 that are reasonable in
terms of blood. Nevertheless the significant variable is the caeruloplasmin /plasma copper ratio that is
indicating that the majority of these sheep have severe problems in respect of the presence of free
thiomolybdate. The animals that have virtually no detectable copper in their plasma, but have 2µM as
far as TCA is concerned, along with animals numbers 7 en 303, are a group that is particularly
severely affected and this is likely to result in clinical signs. Wool samples clearly show a depigmentation of the wool and a change in the structure of the wool indicative of one of the clinical
signs that is called copper deficiency, but that has been caused by the presence of some free
thiomolybdate. The differences between the sheep I would expect to be due to some differential intake
of the free access feed. The selenium status looks very good in the majority of the sheep with only one
animal having glutathione peroxidase activities that are significantly different from the rest of them.
The overall conclusion is that these sheep are certainly suffering from the presence of free
thiomolybdate that will cause clinical problems such as swayback that you have seen as well as the
fleece changes. I would be quite happy to use CoSeCure in these sheep. The cow concentrates are to
be removed. I note that the selenium state is quite high. The extra selenium from CoSeCure will not be
detrimental to the sheep. My one concern is the difference between the sheep from virtually
undetectable copper in the blood to three animals that have normal copper intakes. This must indicate
that there is a variable copper intake and/or a variable iron intake in these animals. The net result is
that some of the animals are in receipt of significant quantities of copper which can be absorbed,
whilst the others are not. It would be comforting to have an explanation for these differences as they
do not fit into the groupings of animals number 1-6 and then 7-8 located elsewhere.
Test results of the same sheep after administrating CoSeCure
Date of Sampling: 24/01/98
Sample
Number
1.
2.
3.
4.
5.
6.
7.
8.
Animal
No
0006
092
097
0007
303
095
132
133
Mean
Means
of
Sample
d
Nos. 18
Previousl
y
Ewes
Hb
(g/l)
111
125
112
109
126
110
146
145
Hc
(%)
33
35
33
33
Haem
33
40
43
CP
(mg/dl)
27.4
23.5
41.7
33.2
36.7
20.8
24.6
22.3
Pl-Cu
(µM)
12.8
12.8
17.3
13.4
11.0
13.1
13.1
12.5
28.8
12.5
TCA-Cu
(µM)
13.3
13.3
17.3
13.1
11.5
13.4
12.7
12.3
SOD
(U/l)
3293
3456
3103
3541
3246
3927
2288
2351
GSHpx
(U/ml)
172
205
198
172
302
238
160
141
Vit B12
(pg/ml)
1054
1407
1368
1043
950
1386
1177
1596
13.3
3100
199
2.2
7.2
3000
142
1.5
(Novemb
er)
Hb - Haemoglobin Hc - Haematocrit CP - Serum/Caeruloplasmin
PL-Cu - Plasma Copper
TCA-Cu Trichloroacetic Acid Soluble Copper SOD - Erythrocyte Super Oxide Dismutase GSHpx Erythrocyte Glutathione Peroxidase
Comments
Copper: Plasma copper concentrations range from 11 to 17.3 µM/l with there being one animal that is
marginal whilst the rest are in the normal category (>12). The TCA copper concentrations range from
11.5 to 17.3 µM/l and these values agree well with the plasma coppers indicating that there is no
CP/PL-Cu
2.1
1.8
2.4
2.5
3.3
1.6
1.9
1.8
significant quantity of copper thiomolybdate present in the blood of these animals. The caeruloplasmin
activities range from 20.8 to 41.7 mg/dl and these are all in the normal range (>15). The
caeruloplasmin/plasma copper ratios range from 1.6 to 3.3 with there being five animals with normal
ratios of 1.9 or more and three animals with marginal ratios of 1.6 to 1.8 which indicate the presence of
some free thiomolybdate in their blood. The superoxide dismutase activities range from 2200 to 3500
u/gm Hb and these are all in the normal range (>2000) although some of the activities are lower than
might have been expected if the plasma copper concentrations that have been measured had been
maintained in the five to six weeks prior to sampling.
Selenium: glutathione peroxidase activities range from 141 to 302 units/ml and these are all in the
normal range (>40) with the bulk of them being at the top end of this normal category.
Cobalt: the vitamin B12 concentrations range from 950 to 1590 and these are all well into the normal
range.
Hb/Hc: these values are all normal.
Overall: a comparison of these results with the previous sampling taken at the beginning of
November 1997 shows that there has been a significant improvement in the copper status of these
sheep. The plasma coppers are significantly higher than seen in November, but, more importantly, the
caeruloplasmin activities are much improved. This is reflected in the much better
caeruloplasmin/plasma copper ratios where there is now a clear indication of the thiomolybdate being
removed from the sheep’s system, although there are still three animals with marginal ratios with
number 095 being the worst affected. I would expect the superoxide dismutase activities to correct
themselves in due course as the boluses begin to take effect. But, given that they have only had a
month to six weeks in order to be effective and that superoxide dismutase turns over in a five to six
week period, then these values are satisfactory. I think we are seeing a significant improvement in
these sheep compared to previous samplings.
In October 1998 we had new laboratory tests performed here in Holland. They showed results within
the normal range: 36 Mg/Kg in the liver and 17 Mg/Kg in the kidneys.
Still taking some individual variations into account we think we are on right track with this other
approach. If there are any similar medications on the market we don’t know. Our objective opinion on
CoSeCure is that it does what it pretends. Almost everyone of the seventeen Shetland Sheep
breeder in Holland uses it. And all of them to their satisfaction.
We have better wool quality, livelier sheep and there were no clinical problems during and after 1998
lambing season.
December 1998