WO2002049657A1

WO2002049657A1 - Methods and compositions for reducing or preventing onset of milk fever

Info

Publication number: WO2002049657A1
Application number: PCT/NZ2001/000296
Authority: WO
Inventors: Gavin Wilson
Original assignee: Massey University
Priority date: 2000-12-21
Filing date: 2001-12-21
Publication date: 2002-06-27
Also published as: AU2002228500A1

Abstract

A method of preventing or reducing the onset of hypocalcaemia and/or milk fever developing in mammals, in particular ruminant animals, including administering to the mammal a sufficient quantity of an agent capable of binding or complexing calciumin the food intake to stimulate calcium absorption in the gastrointestinal system while avoiding symptoms of hypocalcaemia. Compositios capable of use in such methods, are also included.

Description

METHODS AND COMPOSITIONS FOR REDUCING OR PREVENTING

ONSET OF MILK FEVER

Field of the Invention

This invention relates to a method of reducing or preventing the onset of milk fever in mammals. More specifically, it relates to such a method in pre-parturient ruminants, which stimulate and/or "prime" the calcium absorption capacity of ruminants, and thus reducing or preventing onset of milk fever and/or hypocalcaemia.

Background to the Invention

Milk fever is a complex metabolic disorder that occurs in mammals, in particular dairy cows, but may also occur in other animals, such as sheep and goats. If milk fever is not treated within an appropriate time, affected animals will die. Normally, calcium is administered as an immediate method of treatment, such as by intravenous infusion.

Worldwide, milk fever is probably one of the most significant diseases to affect dairy industries. The implications of the disease are wide ranging; having both economic and animal welfare related effects. For this reason the disease has been extensively researched over the last 100 years.

Milk fever stems from hypocalcaemia, or low calcium levels in the blood. This occurs in cows when the requirements for calcium, especially for the production of colostrum, temporarily exceed the available supply of calcium. Thus, hypocalcaemia is caused by a breakdown of calcium homeostasis. Hypocalcaemia can also be of commercial significance through reduced levels of milk production even if not resulting in milk fever. A mammal has three main mechanisms for maintaining and/or affecting calcium homeostasis. These include re-absorption of calcium from urine in the kidneys; mobilising calcium from bone reserves; and increasing the absorption of calcium in the gut. Although there is some debate surrounding the relative importance of each of these mechanisms in relation to milk fever, most research attention has focused on calcium reserves in bones and the rate at which calcium can be mobilised from these reserves.

A major problem with relying on the mammal's homeostatic systems to prevent milk fever and/or hypocalcaemia is that changes to the supply of calcium from the bones or the gut may take days, or even weeks to fully implement.

A number of regimens for reducing milk fever effects are presently available, and show varying degrees of success. The best known technique involves feeding a low calcium diet which may activate the cow's own calcium homeostatic systems. This is detailed in US patent No. 3,908,020. However, this technique is not particularly acceptable in countries in which cows are grazed (including New Zealand) instead of being fed grain and roughage foods. In addition, most commonly used fresh and conserved stored feeds contain high concentrations of calcium, so this technique is generally not practical.

International Publication No. WO 00/561 67 discloses another alternative. This is the inclusion of 'non-food' compounds, such as synthetic zeolites, in the diet. These compounds are thought to form indigestible complexes with dietary calcium, and stimulate 'natural homeostasis' to provide a cow with protection from hypocalcaemia and milk fever. Exactly what process(es) is/are involved in homeostasis is not identified in WO 00/561 67. However, it appears to be assumed that this compound acts in a similar manner to intravenous infusion of EDTA (Fredeen H.H. et al 1 990) and the oral administration of zinc salts in inducing marked hypocalcaemia, or bouts of hypocalcaemia.

It has long been recognised that the natural calcium regulating defence mechanism of a mammal is to increase the rate of calcium removal from bone, compensating for day-to-day variations in calcium intake (Ramberg et al. 1 975) . Hence, the use in WO 00/561 67 of a "time to recover" test which reflects mobilisation of calcium from bone, to judge ability to resist hypocalcaemia.

Limitations of the method disclosed in WO 00/561 67 may thus include increased risks associated with the onset of severe hypocalcaemia as a result of removal of calcium from the cow's diet completely for a period of time.

Recent evidence also suggests that the use of zeolite supplements, causes an abnormal decrease in the concentrations of phosphorus and magnesium in the blood of treated animals (Enemark et al 2001 ). Zeolites also have a detrimental effect on palatability and hence intake of food.

Cows have also been fed anionic salt supplements in an attempt to reduce milk fever conditions (eg, US 5,360,823). It is believed that by feeding anionic salts, mobilisation of calcium from bone reserves may be increased. Calcium absorption may or may not be increased by this technique. However, for the treatment to be successful, this technique often requires feeding the cow large quantities of anionic salts. Cows find these salts unpalatable, and their inclusion can limit feed intake.

Magnesium supplementation has also been used, as a prevention method. A deficiency of magnesium often accompanies calcium deficiency. It is believed that by correcting the magnesium deficiency, the mobilisation of calcium may be increased (Sansom et al. 1983). The use of prepartum injections of vitamin D, and vitamin D derivatives, to directly increase the absorption of calcium has also been trialled (eg US 4,428,946). Another approach has been to acidify the ration fed to the cow to increase calcium bioavailability.

The most commonly used technique however, centres on administering a calcium supplement following calving. However, the supplement is often administered too late to prevent the onset of milk fever.

It is an object of the present invention to provide an alternative method of treating ruminants to reduce incidence of hypocalcaemia and/or milk fever. Other objects of the invention may become apparent from the following description given with reference to specific examples.

Summary of the Invention

According to one aspect of the invention there is provided a method of preventing or reducing the onset of hypocalcaemia and/or milk fever developing in a mammal, including administering to the mammal a sufficient quantity of at least one active agent capable of binding and/or complexing with calcium in the food intake of the mammal which stimulates an increase in calcium absorption capacity in the gastrointestinal tract without inducing symptoms of hypocalcaemia.

Preferably the mammal is a ruminant animal.

Preferably the active agent is administered for at least 2 weeks, immediately prior to parturition.

Preferably the method includes administering the active agent, for 2 to 4 weeks prior to parturition.

Preferably the method includes administration of the agent at least once a day.

Preferably the active agent is a complexing agent capable of reversibly complexing with calcium.

Preferably the active agent is administered as a drench.

Preferably the active agent is included in a feed or administered with food.

In one preferred form the active agent is a vegetable oil, animal fat, sodium bentonite and/or sodium hexametaphosphate.

Preferably the active agent is soya bean oil, peanut oil and/or tallow.

Preferably the active agent constituent makes up about 3% to 5% of the ruminant animal's feed intake when the active agent is soya bean oil.

Preferably the active agent is tallow and it makes up about 1 % to 3% of the animal's feed intake, preferably when included with other active agents.

According to a further aspect of this invention there is provided a composition capable of preventing and/or substantially reducing the onset of hypocalcaemia and/or milk fever in a mammal, wherein said composition includes an effective amount of at least one active agent capable of complexing with calcium and stimulating the calcium absorption capacity of the mammal in the gastrointestinal tract, without substantially inducing symptoms of hypocalcaemia.

Preferably the mammal is a ruminant animal.

Preferably the composition is administered to the mammal for at least 2 weeks immediately prior to parturition.

Preferably the or each active agent is capable of reversibly complexing with calcium.

Preferably the or each active agent includes at least one fat and/or oil.

Preferably the active agent(s) includes vegetable oil, animal fat, sodium bentonite and/or sodium hexametaphosphate.

Preferably the active agent(s) includes at least one fat and/or vegetable oil.

Preferably the oil is soya bean oil and/or peanut oil.

Preferably the composition constitutes about 5% to 1 5% of the ruminant's daily dry matter intake.

Preferably the composition constitutes about 10% of the ruminants daily dry matter intake.

In one preferred form the composition includes about 1 2% tallow, about 1 5 % sodium bentonite, and about 1 % sodium hexametaphosphate.

In another preferred form the composition includes about 1 2% tallow, about 1 5 % sodium bentonite, and about 0.5% sodium hexametaphosphate.

Preferably the active agent is tallow which makes up about 1 % to 2% of the animal's total intake.

Preferably the composition is a drench or an animal feed supplement. According to a further aspect of this invention there is provided an animal feed that may prevent or substantially reduce hypocalcaemia and/or milk fever in a mammal, wherein the feed includes minerals and/or cereal grains and at least one active agent capable of complexing with calcium and stimulating the calcium absorption capacity of the mammal without substantially including symptoms of hypocalcaemia.

Preferably the or each active agent is capable of complexing with calcium reversibly.

Preferably the or each active agent includes at least one fat and/or oil.

Another aspect of the invention provides a method of reducing and/or preventing the incidence of milk fever and/or hypocalcaemia in a mammal, the method including the administration of an effective amount of at least one of a fat, oil, sodium bentonite, and/or sodium hexametaphosphate to the mammals prior to parturition.

Other aspects of the invention may become apparent from the following description, which is given by way of example only and with reference to Examples 1 to 3, and the accompanying figures and table.

Brief Description of the Figures

The invention will now be described by way of example only and with reference to the drawings in which:

Figure 1 : illustrates the susceptibility of ewes treated with the active agent (oil) to hypocalcaemia, following fasting; Figure 2: illustrates the relationship between estimated calcium absorption and fasting plasma calcium; Figure 3: illustrates the inverse relationship between calcium from bone mobilisation (hydroxyproline), and calcium absorption capacity; Figure 4: illustrates the effects of animal feed of the invention on

(post fasting)) plasma calcium concentrations in mature dairy cows; Figure 5: illustrates the changes in plasma calcium levels following fasting in the herd.

Description of the Invention

This invention relates to a method of preventing or substantially reducing the effect of milk fever and/or hypocalcaemia conditions in mammals, and in particular, ruminant livestock or animals.

It will be appreciated that milk fever is a result of hypocalcaemia, a severe deficiency of calcium in the blood. Increasing the supply of calcium from bone reserves or from the diet, in synchrony with increasing demands for calcium, has been shown to reduce the likelihood of milk fever developing.

However, calcium absorption (Ca (absorption)) is dependent upon the amount of calcium ingested (Ca (intake)), the extent to which dietary calcium is 'bound' (Ca,_bioavai|_abi|_itv) %), and the calcium absorption capacity of the cow

'Ca_(physi0|_0gica|₎ %).

The Cao_jj_oavaii_abiii_ty) % depends upon both the physical and chemical characteristics of the diet. Calcium absorption capacity (Ca,_physio,_ogi(._a]) %) is hormonally controlled and is part of the homeostatic processes. While it is most often quoted that calcium absorption occurs in the small intestines there is contrary evidence, and especially with pasture feeding, that the rumen or stomach is the major site of absorption (Grace et al, 1974b).

The present invention involves feeding selected feed ingredients, or active agents, to a mammal and in particular is a ruminant animal prior to parturition. The preferred time scale is for at least 2 weeks prior to parturition and preferably 2-4 weeks. Slightly longer or shorter times could be used and should not be seen to fall outside the scope of this invention. These active agents have specificity towards dietary calcium and complex with calcium in the rumen or stomach. This "primes" the ruminant's rumen or stomach system to absorb more calcium when challenged by a calcium deficit at calving. It is shown herein that administering these certain specific active agents to a ruminant substantially increases the ruminant's calcium absorption capacity without increasing the risk of inducing hypocalcaemia.

Without wanting to be bound to a specific hypothesis it is thought that the selected active agents that increase calcium absorption capacity, are certain types of binding and/or complexing agents which have the ability to prevent or substantially reduce calcium bioavailability in the rumen or stomach of the ruminant. Thus, when the active agents are fed to a ruminant, dietary calcium will be complexed in the ruminant's rumen or stomach, reducing dietary calcium absorption and/or bioavailability. After some delay, the reduction in calcium absorption stimulates the ruminant's calcium absorption capacity in the rumen/stomach area. By improving the calcium absorption capacity, the ruminant is "primed" to absorb more calcium in the stomach before a time of high calcium demand (parturition). Hence the improvement in calcium absorption capacity caused by the use of the active agents allows an increase in calcium absorption from the ruminant's stomach (compared with untreated ruminants), when intake is reduced as a consequence of the stress of parturition.

However, the choice of binding and/or complexing agents determines the stability of the calcium complexes formed. The active agents weakly bind calcium and may be broken down under the physiological conditions of the lower gut to subsequently release calcium for absorption by the mammal. Alternatively the complexes may be altered, modified and/or absorbed further along the gastro-intestinal tract. This results in a reduction of the risk of hypocalcaemia being brought about by the treatment itself, as calcium may be still absorbed by the animal, and is much safer and less aggressive than treatments currently in use.

Important properties of the active agent(s) are therefore that they decrease calcium absorption in the rumen or stomach of the mammal thus increasing the calcium absorption capacity later, and do not cause adverse side effects to the mammal as a result of calcium depletion.

The invention may also provide a method of preventing or reducing the incidence of hypocalcaemia and/or milk fever by administering to a ruminant animal an active agent capable of binding calcium and preventing absorption in the stomach or rumen. The calcium complexes formed with the active agent(s) do not substantially prevent and/or block calcium absorption further along the gastrointestinal tract.

The active agent(s) preferably include vegetable oils, such as soya bean oil and/or peanut oil; animal fat, such as tallow; sodium bentonite; and/or sodium hexametaphosphate. It is preferred that the active agents will be natural food ingredients as these are readily available, have beneficial nutritional effects and are less damaging to the animal. The amount of such agents will be in sufficient quantities to bind sufficient calcium from the animal's ration to stimulate calcium absorption capacity in the stomach or rumen. It will be appreciated that there may be a number of other feed ingredients, which can act as "active agents" such as oxalates, certain soils or certain plant species. For example bentonites other than sodium bentonite could be used. Fats and oils from a variety of sources, such as from copra and a variety of grains, can also be used. It is to be understood that other food ingredients with the ability to prime the gastrointestinal system without lowering the levels of calcium in the animal sufficiently to induce symptoms of hypocalcaemia may be used in this treatment regime without departing from the scope or spirit of this invention/

It is also within the scope of the invention that active agents may be chemically developed and/or synthesised to include the desired properties. Alternatively, natural feed ingredients herein disclosed may be chemically modified to optimise the desired properties.

In one form, the active agent(s) may be included with certain minerals and/or cereal grains, in the form of an animal feed. Alternatively it may be a supplement to be drenched or fed on its own, or with ruminant feeds. As a supplement the active agent(s) may be formulated as a solid, powder or liquid product.

The amount of active agent(s) required will depend on a variety of factors including the desired method of administration, the dry matter intake of the pregnant cow, plus the chemical and physical nature of the diet (for example, whether the animals are predominantly pasture fed or fed with feed concentrates) and the selection of active agent.

In a preferred form, where animals are predominantly pasture fed, and the need to provide any animal feed supplement is desirably kept to a minimum, then the inclusion of active agents in a proportion of 25% to 30% of an animal feed concentrate, fed at a rate of about 1 kg/day/cow, may be appropriate. In such circumstances the animal feed supplement may constitute between about 8% to 1 5%, preferably about 10%, of the daily dry matter intake.

Preferably when the active agent is a vegetable oil or tallow, it will form about 3% to 5% of the animal's total intake. However, when these agents are incorporated in the animal feed concentrate together with the other active agents, it is preferable that they form only 1 % to 3% of total intake.

An animal feed supplement to provide between about 8% and 1 5% of the animal's daily dry matter intake may include about:

- 10% to 1 5 % tallow; preferably about 1 2%; and/or

- 13% to 1 7% sodium bentonite; preferably about 1 5%; and/or

- 0.3% to 1 .5% sodium hexametaphosphate; preferably about 0.5% or 1 %.

It will be appreciated that the amounts may vary outside the preferred ranges listed above, these amounts being preferences only.

The feeding regimen should begin at least 2 weeks prepartum, but preferably about 3 to 4 weeks. The animal feed or feed supplement which includes the active agents should be administered daily substantially until calving for maximum benefit.

The animal feed supplement and/or active agents can utilise natural feed ingredients, which also provides the ruminant with essential nutrients, or buffering capacity. The active agents are palatable, and have no substantial adverse side effects on the ruminant. Therefore, this new approach to reducing hypocalcaemia and/or milk fever is practical as it can be readily incorporated into many different ruminant feeding systems without the need for substantial procedural changes. There are also significant economic benefits that may arise from this regimen. A high benefit to cost ratio is achieved in a relatively short period of time. As the effects of hypocalcaemia may be avoided by the regimen herein described, the ruminant's health, milk production and reproduction are all likely to be significantly improved.

While the invention has particular application to ruminant animals, similar effect will be seen on other mammals (eg humans). The methods and compositions can also have applicability in treatment of other mammals should hypocalcaemia/milk fever be considered a problem.

The invention will now be described by examples, and with reference to the Figures.

Example 1

An initial experiment was conducted with 28 twin-pregnant ewes grazing on pasture. A group of 14 pregnant ewes were each drenched twice daily, over a 3-week period commencing about 5 to 6 weeks prior to parturition, with (25 ml) soya bean oil (active agent). A control group of 14 twin-pregnant ewes were not drenched. It will be appreciated that the soya bean oil is the active agent in this experiment. The drench was administered so that the active agent made up about 3% to 5% of the ruminant's total intake.

At the commencement of the experiment, and after the 8 and 21 days of treatment, blood samples were taken and the plasma calcium concentrations were determined for each ewe respectively.

The feeding of oil did not cause marked hypocalcaemia symptoms as is illustrated by data on plasma calcium levels (Table 1 ). Table 1 : Plasma calcium levels (mM) taken after 8 and 21 days of treatment.

A further sample was obtained following a 20-24 hour period of fasting. The fasting period simulates what happens on the day of parturition. Figure 1 shows the measured concentrations of plasma calcium in the 28 twin-pregnant ewes after the fasting period. A low calcium level, especially below 2 mM, is indicative of hypocalcaemia. The treated group is shown as solid black bars, while the control group is shown as unfilled bars. A significant proportion of the treated group showed higher levels of calcium in the blood following fasting, than the control group. Therefore, the treated group were less susceptible to severe hypocalcaemia.

This study provided strong evidence to support the view that certain active agents can increase the efficiency of the homeostatic system for calcium.

The results from this study were further evaluated by the use of a technique which indirectly measures the calcium absorption capacity of the ewes from the rumen and/or stomach. The technique includes administering an oral dose of strontium chloride and measuring blood strontium after just 90 minutes. The strontium ion is known to mimic the absorption properties of the calcium ion (Wasserman, 1 998). In this study, the strontium chloride was administered at the end of the 3-week treatment period. Figure 2 illustrates the calcium absorption capacity of the ewes (as determined by the strontium tracer technique), with respect to the plasma calcium levels (shown in Figure 1 ). The treated group is represented by diamonds, while the control group is represented by squares. Clearly, the treated group showed a significant increase, both in calcium plasma concentrations, and in calcium absorption capacity.

The analyses of the plasma samples for hydroxyproline concentrations confirmed that the higher blood calcium levels observed in the treated group, were not primarily due to a greater mobilisation of bone calcium reserves. Hydroxyproline has been widely used as a marker for calcium derived from bone, as it is a breakdown product of bone collagen (Kent, 1 995) . In the treated group, the plasma concentration of hydroxyproline was only marginally higher than for the control group. The treated group shared an average hydroxyproline concentration of 1 .1 1 μg/ml, whilst the control group shared a concentration of 1 .03 μg/ml (p value 0.74).

In the control ewes, there was also a significant inverse relationship (correlation coefficient 0.76) measured between the hydroxyproline concentrations in the plasma and their calcium absorption capacities (see Figure 3), which strongly suggests that when either bone mobilisation, or absorption, is stimulated the other will probably decline. This also means that some feeding strategies of the prior art, that may prevent milk fever, work through bone mobilisation. The present invention, however, appears to target absorption capacity.

The results from this study suggest that administering the active agents increase both blood calcium levels and calcium absorption capacity, thus reducing the likelihood of the ruminant developing hypocalcaemia when subject to a short-term deficit of calcium.

Example 2

A group of 1 1 mature cows, 2 to 4 weeks prior to calving, were fed an animal feed, as well as a diet of grazed pasture. The animal feed was fed in a pellet form and included, cereal grains, minerals, and active agents. In this particular case, the animal feed included the active agents tallow (1 2%), sodium bentonite (1 5%) and sodium hexametaphosphate ( 1 %).

The animal feed was administered so that the active agent(s) made up 1 % to 3% of the total intake.

The animal feed was fed at approximately 1 kg per cow daily. A control group of cows, of a similar size and stage of gestation, were not fed the animal feed. All animals were fasted for 20 hours approximately a week prior to calving. Blood samples were taken following this period and the plasma calcium concentration for the individual cows was measured. Figure 4 illustrates the results from this study. The individuals from the control group, are shown as the unfilled bars, whilst the individuals of the treated group, are shown as filled bars.

The treated group had a higher plasma calcium concentration, than the control group. Thus, the treated group had a reduced risk of developing hypocalcaemia, than the control group.

Blood samples were also taken directly before the fasting period. Figure 5 expresses the difference in plasma calcium concentrations before and after the fasting period. The control group illustrated that many cows had difficulty maintaining their plasma calcium levels over the fasting period (negative values). However, in the treated group the calcium levels, substantially increased during the fasting period. The animal feed fed prepartum therefore substantially reduces the likelihood of severe hypocalcaemia.

Example 3

The animal feed and treatment regimen (as in Example 2) was also tested on a number of herds. The study was conducted using 7 herds, situated in a range of locations (Table 2). Table 2: Milk fevers in herds fed the animal feed.

The cows were fed on various proportions of pasture, hay and silages. The proportions of pasture in the total ration varied from 20% to 90%. The animal feed was mixed with silage on three farms (farms 3, 4, 5 in Table 2). On the remaining farms (farms 1 , 2, 6 and 7), the animal feed was fed from troughs, rows and/or piles placed in the pastures.

Within each herd, substantially half the herd were fed the animal feed containing the active agents, whilst the remaining half were not fed the animal feed (providing the control). The treated group were fed the animal feed substantially once daily, for 2 to 4 weeks prepartum.

It will be appreciated that the size of the herds, and the range of locations in which the herds were situated, provided sufficiently detailed data, such that the incidence of milk fever in the herds could be accurately assessed.

Table 2 illustrates that the incidence of milk fever is reduced, when the animal feed is provided in the prepartum diet of mature cows. It also shows that the invention is effective under a wide range of environmental conditions. The animal feed is also believed to have beneficial effects on other aspects of health, milk production, and reproduction.

A dietary regimen, as herein described with reference to the examples 1 to 3, has been shown to improve the resistance of ruminants to hypocalcaemia and milk fever. It has also be found that treatment regimen reduces the risk of hypocalcaemia being brought about by the treatment itself. This advantage is apparently mediated mainly through an improved capacity in the cows to absorb calcium.

It will be appreciated that although this invention has been described with reference to ruminants, it may have broader application to any animal that suffers from milk fever-type conditions, or to hypocalcaemia in general.

Where in the foregoing description there has been made reference to specific components or integers of the invention having known equivalents then such equivalence are herein incorporated as if individually set forth.

Although this invention has been described by way of example and with reference to possible embodiments thereof it is to be understood that modifications or improvements may be made without departing from the scope or spirit of the invention as defined in the appended claims.

References

Enemark et al (2001 ) Proc. Abildgaard Symposium: Hypcalcaemia, acidosis and calcium homeostasis, Royal Veterinary and Agricultural University, Copenhagen, Denmark 1 51 .

Fredeen H.H., and Van Kessel J.S. ( 1 990) Sudden loss of calcium from exchangeable pool stimulates bone calcium resorption in mature sheep. Canadian Journal of Animal Science 70: 887-894.

Grace N.D., Ulyatt M.J. and Macrae J.C. (1 974b) Quantitative digestion of fresh herbage by sheep 1 1 1 . The movement of Mg, Ca, P, K and Na in the digestive tract Journal Agricultural Science, (Camb.) 82:321 -330.

Kent G.N. ( 1 995) Markers of bone resorption and their application in metabolic bone disease. The Clinical Biochemist Reviews 1 6:4-10.

Ramberg C.F., Kronfeld D.F. and Wilson G.D.A. Regulation of Calcium metabolism in cattle during the growth, lactating and change in diet. In: Digestion and metabolism in the ruminant. McDonald I.W. and Warner A.C.I, (eds). Proceedings of the IV International Symposium on Ruminant Physiology. Pp231 -42. The University of New England Publishing Unit, Armidale, 1 975.

Sansom B.F., R. Manston and M.J. Vagg ( 1 983) Magnesium and milk fever. Veterinary Record 1 1 2:447-449.

Wasserman R.H. (1998) Strontium as a tracer for calcium in biological and clinical research. Clinical Chemistry 44:437-439.

Claims

What We Claim Is

1 . A method of preventing or reducing the onset of hypocalcaemia and/or milk fever developing in a mammal, including administering to the mammal a sufficient quantity of at least one active agent capable of binding and/or complexing with calcium in the food intake of the mammal which stimulates an increase in calcium absorption capacity in the gastrointestinal tract without inducing symptoms of hypocalcaemia.

2. The method according to claim 1 wherein the mammal is a ruminant animal.

3. The method according to claim 1 or claim 2 wherein the active agent is administered at least 2 weeks immediately prior to parturition.

4. The method according to any one of the preceding claims wherein the active agent is a complexing agent capable of reversibly complexing with calcium.

5. The method according to any one of the preceding claims wherein the active agent is administered as a drench or as a food supplement or additive.

6. The method according to any one of the preceding claims wherein the active agent is a vegetable oil, animal fat, sodium bentonite and/or sodium hexametaphosphate.

7. The method according to claim 7 wherein the active agent is soya bean oil, peanut oil and/or tallow.

8. The method according to claim 6 or 7 wherein the active agent constituent makes up about 3% to 5% of the ruminant animal's feed intake when the active agent is soya bean oil.

9. The method according to claim 7 wherein the active agent is tallow and it makes up about 1 % to 3% of the animal's feed intake.

10. A composition capable of preventing and/or substantially reducing the onset of hypocalcaemia and/or milk fever in a mammal, wherein said composition includes an effective amount of at least one active agent capable of complexing with calcium and stimulating the calcium absorption capacity of the mammal in the gastrointestinal tract, without substantially inducing symptoms of hypocalcaemia.

1 1 . The composition according to claim 10 wherein the mammal is a ruminant animal.

1 2. The composition according to claim 10 or 1 1 wherein the or each active agent is capable of reversibly complexing with calcium.

1 3. The composition according to claim 1 1 , 1 2 or 13 wherein the active agent(s) includes vegetable oil, animal fat, sodium bentonite and/or sodium hexametaphosphate.

14. The composition according to claim 13 wherein the oil is soya bean oil and/or peanut oil.

15. The composition according to any one of claims 1 1 to 14 wherein the composition constitutes about 5 % to 10% of the ruminant's daily dry matter intake.

1 6. The composition according to claim 1 3 wherein the composition includes about 1 2% tallow, about 1 5 % sodium bentonite, and about 1 % sodium hexametaphosphate.

1 7. The composition according to claim 1 3 wherein the composition includes about 1 2% tallow, about 1 5 % sodium bentonite, and about 0.5 % sodium hexametaphosphate.

18. The composition according to claim 1 1 wherein the active agent is tallow and is in an amount to make up about 1 % to 2% of the animal's total intake.

1 9. The composition according to any one of claims 1 1 to 1 8 wherein the composition is a drench or an animal feed supplement.

20. An animal feed to prevent or substantially reduce hypocalcaemia and/or milk fever in a mammal, wherein the feed includes minerals and/or cereal grains and at least one active agent capable of complexing with calcium and stimulating the calcium absorption capacity of the mammal without substantially including symptoms of hypocalcaemia.

21 . The feed according to claim 20 wherein the or each active agent is capable of complexing with calcium reversibly.

22. The feed according to claim 20 or 21 wherein the active agent(s) includes vegetable oil, animal fat, sodium bentonite and/or sodium hexametaphosphate.

3. A method of reducing or preventing the incidence of milk fever and/or hypocalcaemia in a mammal, the method including the administration of an effective amount of fat, oil, sodium bentonite, and/or sodium hexametaphosphate to the mammals prior to parturition.