Experiments That Changed Nutritional Thinking - TUUM EST

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SUPPLEMENT
TABLE 1
pairs liver copper storage. Pertinent data from two experiments
are presented in Table 2. All sheep consumed approximately
Liver copper and blood molybdenum concentrations of sheep 10 mg of copper and some were supplemented with 10 mg of
fed different sources of forage supplemented with 10 mg molybdenum per day. When the animals consumed oat hay,
each of copper and molybdenum per day for 6 mo1 the addition of molybdenum had no effect on liver copper
storage, but when they consumed alfalfa it markedly decreased
Dietary forage Increase in Blood Mo copper storage. When the oat hay diet was supplemented with
(chaffed hay) liver Cu2 conc.3 2.2 or 4.4 g of sulfate per day as well as with molybdenum,
copper storage was reduced to the same degree as in sheep fed
mg mcg/100 mL alfalfa supplemented with molybdenum. The lower level of
sulfate (2.2 g) was just as effective as the higher level in de-
Lucerne 9 48
creasing liver copper in sheep consuming oat or alfalfa hay.
Lucerne 3:oat 1 19 96
Lucerne 1:oat 1 35 180 These experiments clearly established the existence of a three-
Lucerne 1:oat 3 70 378 way interaction among copper, molybdenum and sulfate as
Oat 113 447 regards liver copper storage.
In spite of the decrease in liver copper storage observed
1 Adapted from Dick (1952); n Å 6 animals per group. when the diet was supplemented with both molybdenum and
2 The increase in total liver copper is the difference between the sulfate, the concentration of blood copper was increased, as
estimated initial content and that at slaughter; the initial value was
shown by the data summarized in Table 3. The blood copper
approximately 27 mg.
3 The values are the means of weekly blood samples taken over the concentrations rose with increasing levels of both molybdeperiod.
num and sulfate, and there appeared to be an interaction.
Even though the blood copper concentration increased, the
effect as the hay itself. The results summarized in Figure 1
copper was not available for biological function. Sheep fed
show that the administration of potassium sulfate lowered
high levels of molybdenum and sulfate and a nominally ade-
blood molybdenum in a sheep fed oat hay supplemented with
quate level of copper developed signs of copper deficiency even
10 mg of molybdenum per day. The lower blood molybdenum
with blood copper concentrations that were normal or greater
resulted from increased excretion of molybdenum via the kidliver
copper concentration. Clearly, under these conditions of
than normal. There was loss of crimp in the wool and decreased
ney, an effect that was independent of urine volume. This and
related experiments established the Mo-S interaction.
high molybdenum and sulfate intake, blood copper was not a
Subsequently, Dick (1953b) showed that sulfate is also the
valid measure of copper status because there was evidence of
factor in alfalfa that, in combination with molybdenum, imconcentrations.
copper deficiency in spite of normal or elevated blood copper
An explanation of the Cu-Mo-S interaction must account
for the fact that S renders both copper and molybdenum biologically
unavailable and that molybdenum lowers copper
availability only in the presence of dietary S. Suttle (1974)
pointed out that the formation of cupric tetrathiomolybdate,
a highly insoluble complex, could occur in the sulfide-rich
environment of the rumen. This would account for low copper
absorption but not for the high blood copper concentration.
Normally all of the copper in blood is solubilized by trichloroacetic
acid (TCA), but this was not true in cases of high
molybdenum intake. To explain this phenomenon, Dick et al.
(1975) prepared di, tri- and tetrathiomolybdates and observed
that their addition to blood in vitro resulted in a TCA-insoluble
fraction that contained most of the copper. When tetrathiomolybdate
was administered to sheep intravenously, there
was an immediate rise in the TCA-insoluble copper in the
blood. Thus, formation of copper thiomolybdates, particularly
CuMoS 4 , in the rumen accounts for the poor absorption of
copper when the intake of molybdenum is high. The absorption
of thiomolybdate and subsequent formation of CuMoS 4
in the blood accounts for the high concentration of blood
copper that is not bioavailable.
The experiments described here revealed a three-way interaction
of copper, molybdenum and sulfate in ruminant animals,
in which bacterial fermentation plays a major role in
digestion. The interaction in monogastric animals is much less
dramatic, because there is less sulfide available to form the
thiomolybdate complexes. Ruminal microflora normally play
FIGURE 1 Effect of a single oral dose of potassium sulfate on
a major role in this three-way interaction, but the interaction
the blood concentration (mcg/100 mL) and urinary excretion (mg/d) of
molybdenum. The sheep was fed oat hay and drenched daily with 10 can be demonstrated in monogastric animals by administration
mg of Mo as ammonium molybdate. Collections were made over 7 d; of thiomolybdates. Interestingly, tetrathiomolybdate has been
the time of sulfate administration is indicated by arrow. Figure 4 from used to treat Wilson’s disease in human patients (Brewer et
Dick (1953a).
al. 1994). This genetic disease results in accumulation of cop-
/ 4p09$$0062 04-07-97 14:02:12 nutras LP: J Nut May Suppl
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