WO1991019489A1 - METHOD FOR REGULATING RUMINAL pH - Google Patents

METHOD FOR REGULATING RUMINAL pH Download PDF

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Publication number
WO1991019489A1
WO1991019489A1 PCT/US1991/003730 US9103730W WO9119489A1 WO 1991019489 A1 WO1991019489 A1 WO 1991019489A1 US 9103730 W US9103730 W US 9103730W WO 9119489 A1 WO9119489 A1 WO 9119489A1
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use
succinate
salt
ph
whey
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PCT/US1991/003730
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French (fr)
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Marvin Lee Ogilvie
Walter Joseph Smolenski
Charles Peter Cornell
Joseph Arlen Robinson
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The Upjohn Company
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic, hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/105Aliphatic or alicyclic compounds
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/142Amino acids; Derivatives thereof
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; THEIR TREATMENT, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K50/00Feeding-stuffs specially adapted for particular animals
    • A23K50/10Feeding-stuffs specially adapted for particular animals for ruminants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic, hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group

Abstract

The present invention provides a method for regulating ruminal pH levels in ruminant animals by administering salts of succinic acid and certain other carboxylic acids. It thus provides a method for preventing or treating ruminal acidosis often encountered in ruminants fed high energy rations.

Description

METHOD FOR REGULAΗNG RUMINAL pH

BACKGROUND OF THE INVENTION

The present invention provides a method for regulating ruminal pH levels in ruminant animals by administering salts of succinic acid and certain other carboxylic acids. It thus provides a method for preventing or treating ruminal acidosis often encountered in ruminants fed high energy rations.

Ruminants, such as cattle have a specialized digestive system which is well adapted to low energy forage diets. In the forestomach, or rumen, large populations of anaerobic bacteria convert the feed to volatile fatty acids (VFA's) and microbial cells. The VFA's and cells then become the actual food that supports the ruminant. Growth on forage diets, however, leads to a low energy input to the animal, and hence less potential output (as meat or milk) for the producer. Current animal husbandry practices employ intensive methods to increase the ruminants energy uptake, thereby speeding the growth and/or increasing the yield. Intensive beef and dairy production involves feeding an energy dense, high concentrate diet to the animals. These concentrate diets contain a high percentage of corn, wheat, milo or other starchy components. When starter cattle are switched from forage to concentrate diets, indigestion frequently occurs. CJ. Elam, J. Anim. Sci., 43, pp. 898-901 (1976); T.L. Huber, J. Anim. Sci., 43, pp. 902-909 (1976); B.A. Uhart, and F.D. Carroll, J. Anim. Sci., 26, pp. 1195-1198 (1967). This tendency to indigestion is due to the rapid and unbalanced growth of some of the bacteria in the rumen, when a readily fermentable diet is presented. The production of organic acids from the fermentation can be so great that the balance between ruminal acid production and utilization and ruminal buffering capacity are disrupted. This condition is termed acidosis. Acute acidosis is characterized by a rapid drop in pH and a sharp increase in the level of lactic acid in the rumen and in the blood. CJ. Elam, (supra); L.L. Slyter, J. Anim. Sci., 43, pp. 910-929 (1976); B.A. Uhart, and F.D. Carroll, (supra). An additional physiological effect of acute acidosis is inappetence with the period of anorexia varying from 2-6 days. B.A. Uhart and F.D. Carroll, (supra). Subacute acidosis is characterized by similar but less severe increases in acid production, generally with a lower percentage of lactic acid than found in acute acidosis. As with acute acidosis, cattle experiencing chronic or subacute acidosis exhibit an "oof-feed" condition with reduced feed consumption, but the severity of the inappetence is less. W.R. Fulton, T.J. Klopfenstein, and R.A. Britton, J. Anim. Sci. 49, pp 785-789 (1979).

When sufficiently severe, the over-production of lactic acid and other acids can contribute to a decrease in ruminal pH such that the balance of species in the normal microbial flora is further upset. Often the result is that only a few bacterial species, which are tolerant of the acidic conditions, survive. N. Krogh, Acta Vet. Scand., 2, pp. 102-119 (1961); R.I. Mackie, and

F.M.C. Gilchrist, Appl. Environ. Microbiol., 38, pp. 422-430 (1979); S.O. Mann, J. Appl. Bacteriol., 33, pp. 403-409 (1970).

Currently, a stepwise adaptation to high concentrate diet are used to minimize the occurrence of acidosis. The adaptation procedure however, is labor and time intensive and decreases the potential efficiency of beef and dairy production. Thus, new methods for adapting ruminants to high concentrate diets so as to minimize the occurrence of acidosis and the accompanying adverse physiological effects, are needed.

INFORMATION DISCLOSURE

It is known to use succinate as a pH buffer. R.N. Costilow, "Biophysical Factors in Growth," in Manual of Methods for General Bacteriology, American Society for Microbiology, Washington, D.C., pp. 66-69 (1981).

The mechanism by which bacteria convert succinate in equimolar amounts to propionate is presumably accomplished by decarboxylation of succinate, which is an intermediate in rumen fermentations. R.L. Baldwin and M.J. Allison, "Rumen Metabolism," J. Anim. Sci. 57 (Suppl 2):461 (1985); T.H. Blackburn and R.E. Hungate, "Succinic Acid Turnover and Propionate Production in the Bovine Rumen," Appl. Microbiol. 11:132 (1963); MJ. Wolin, "The Rumen Fermentation: A Model for Microbial Interaction in Anaerobic Ecosystems," Adv. Microbial Ecology 3:49 (1979).

Bacterial decarboxylation of succinate is catalyzed by methylmalonyl-CoA decarboxylase, a biotin containing enzyme, which consumes protons [H+] and liberates CO2. P. Dimroth, "Biotin-Dependent Decarboxylases as Energy Transducing Systems," Annals of the New York

Acad. of Sciences 447:72 (1985); P. Dimroth and A. Thomer, "Subunit Composition of Oxaloacetate Decarboxylase and Characterization of the a Chain as Carboxyltransferase," Eur. J.

Biochem. 137: 107 (1983); W. Hilpert and P. Dimroth, "Purification and Characterization of a New

Sodium-Transport Decarboxylase: Methylmalonyl-CoA decarboxylas from Veillonella Alcalescens," Eur. J. Biochem. 132:579 (1983).

Other carboxylic acids, such as fumarate, aspartate, malate, oxaloacetate and pyruvate, have been shown to undergo decarboxylation by pure cultures of Propionegenium modestrum to form carbon dioxide, propionate or acetate. B. Schink and N. Pfenning, "Propionegenium modestum gen. nov. sp. nov. a New Strictly Anaerobic, Nonsporing Bacterium Growing on Succinate," Arch. Microbiol. 133:209 (1982).

The primary buffering system in the rumen is bicarbonate (CO2-HCO3.) G.H.M. Counotte and R.A. Prins, "Regulation of Rumen Lactate Metabolism and the Role of Lactic Acid in Nutritional Disorders of Ruminants," Vet. Sci. Comm. 2:277 (1978). R.E. Hungate, "The Rumen and Its Microbes," Academic Press, New York, (1966).

Data from in vitro incubations of ruminal contents suggest that a succinate containing whey by-product, when incubated in the presence of a polyether ionophore (monensin), may stimulate propionic acid production. J.G. Lumanta, M.G. Beconi, N. Samuelov, M. Jain and M.T Yokoyama, J. Anim. Sci. 67 (Supplement 1), p. 500 (1989).

U.S. Patents 3,988,483 and 4,232,046 disclose liquid starch-urea ruminant feed and method of preparing the same.

U.S. Patent 3,476,565 discloses animal nutrient blocks containing gum arabic.

Chem. Abstracts 122: 234298 m, (1990) discloses sodium succinate in fattening of swine for transportation.

SUMMARY OF THE INVENTION

The present invention particularly provides:

A method for regulating the pH of the rumen in ruminant animals which comprises administering an effective amount of a salt of a carboxylic acid wherein the acid is succinic, fumaric, aspartic, citric, malic, oxaloacetic, pyruvic, tricarballyic, α-ketoglutaric or maleic;

A method for preventing or treating acidosis in ruminant animals in need thereof which comprises administering to the ruminant an effective amount of a salt of a carboxylic acid wherein the acid is succinic, fumaric, aspartic, citric, malic, oxaloacetic, pyruvic, tricarballyic, α-ketoglutaric or maleic;

A method for increasing the efficiency of feed utilization or rate of weight gain of ruminant animals which comprises administering an effective amount of a salt of a carboxylic acid wherein the acid is succinic, fumaric, aspartic, citric, malic, oxaloacetic, pyruvic, tricarballyic, α-ketoglutaric or maleic; and

A method for increasing feed intake of ruminant animals which comprises administering an effective amount of a salt of a carboxylic acid wherein the acid is succinic, fumaric, aspartic, citric, malic, oxaloacetic, pyruvic, tricarballylic, α-ketoglutaric or maleic.

By "regulating the pH of the rumen" is meant controlling the pH such that if the pH of the rumen is acidic, the pH is raised closer to neutrality and/or is prevented from dropping to a lower pH. It also means controlling the pH so that if the pH of the rumen is close to neutrality, it is maintained at that level.

Under normal conditions, when succinate is fed to cattle, it is converted to propionate in the rumen of the cattle in equimolar amounts relative to the amount of succinate added. Most of the ruminants' carbohydrate requirements are met by synthesis from the ruminally produced VFA's. Propionate is accepted as a precursor of sugar, R.E. Hungate, "The Rumen and Its Microbes", Academic Press, New York (1966), and greater weight gains have been found in animals given a diet favoring propionate formation. W.L. Enset et al., J. Dairy Sci. 42:189 (1959).

According to the methods of the present invention, it has been found that certain known compounds may be used to regulate the pH of the rumen of ruminants. Surprisingly and unexpectedly, it has been found that by administering these compounds to ruminants, the pH of the rumen is maintained closer to neutrality, even though concentrations of total volatile fatty acids are increased. Thus, the present invention would be useful to prevent or treat detrimental increases in ruminal acidity which often occurs post-feeding of typical high energy rations consumed by ruminants, such as feedlot and/or lactating dairy cattle, which condition is termed acute or subacute acidosis.

A common physiological effect of acidosis in ruminants is inappetence. Thus, by preventing or treating acidosis, the present invention would prevent or treat inappetence caused by acidosis, resulting in increased feed utilization and/or increased rate of weight gain of such animals

The compounds useful in the methods of the present invention include the salts of succinic acid and certain other carboxylic acids. The salts of succinic acid include, but are not limited to, calcium, potassium, sodium, ammonium and magnesium. The salts of succinic acid are also contained in a whey-succinate by-product made by Michigan Biotechnology Institute, East Lansing, MI (MBI).

Whey, a by-product of the cheese manufacturing industry, is fed to food-producing animals as liquid whey, condensed whey, dried whey or as dried whey products, such as partially delactosed or ammoniated whey. D.J. Schingoethe, "Whey Utilization in Animal Feeding: A Summary and Evaluation," J. Dairy Sci. 59:556 (1975); CA. Reddy, et al., "Bacterial Fermentation of Cheese Whey for Production of a Ruminant Feed Supplement Rich in Crude Protein," Appl. Environ. Microbiol. 32:769 (1976).

In studies with beef cattle, addition of 1-4% dried whey or whey products to the diet increased weight gains 2-13% compared to controls and often slightly improved feed efficiency. D.J. Schingoethe, "Whey Utilization in Animal Feeding: A Summary and Evaluation," J. Dairy Sci. 59:556 (1975). However, the amount of whey which can be fed to feedlot cattle may be restricted due to the observation that many of the microbes in the rumen have a limited ability to ferment lactose. R.E. Hungate, "The Rumen and Its Microbes," Academic Press, New York (1966). If this is the case, partially delactosed whey or other modified whey products containing no lactose might have more utility in the ruminant. Such a by-product is available from Michigan Biotechnology Institute, East Lansing, MI(hereinafter MBI). It is produced via a fermentation process that converts the lactose in liquid whey to succinate. The spent culture medium is then dried to yield a powdery feed supplement, known as whey-succinate which contains succinate as the active ingredient. Data from in vitro incubations of ruminal contents suggest that this succinate containing whey by-product, when incubated in the presence of a polyether ionophore (monensin), may stimulate prop ionic acid production. I.G. Lumanta, M.G. Beconi, N. Samuelov, M. Jain and M.T. Yokoyama, J. Anim. Sci. 67 (Supplement 1), p. 500 (1989).

In addition to succinate salts, other carboxylic acid salts which are useful in the methods of the present invention are fumarate, aspartate, citrate, malate, oxaloacetate, pyruvate, tricarballylate, α-ketoglutarate, or maleate. These salts include, but are not limited to, calcium, potassium, sodium, ammonium and magnesium.

All of these salts may be administered as a dietary supplement to ruminants. They may be in the form of natural feed stuffs, by-products or pure chemicals. An effective amount of the salts would comprise 1-10% of die dry matter intake of the ruminants per day. Preferably, it would comprise 2-5% of the dry matter intake of the ruminants per day. The duration of treatment with the salt depends on the purpose to be achieved and would be readily ascertainable to one of ordinary skill in the art of animal husbandry. For example, for adapting ruminants, such as feedlot cattle, the duration of treatment would be from seven to twenty-eight days; and for dairy cows, the duration of treatment would be from ten to one-hundred days of lactation.

When the salts described above are used according to the methods of the present invention, the expected beneficial effects to ruminants include more than just pH buffering. These additional benefits include the direct production of propionate (an extremely important carbon source for ruminant nutrition), as well as the possibility of enriching the rumen bacterial population with organisms that utilize the succinate decarboxylation pathway and may therefore indirectly increase the rate of propionate production from other substrates besides succinate, and direct the overall fermentation away from products such as lactate. In addition, the present invention involves the manipulation of the ruminal fermentation via the administration of naturally occurring substances, rather than a drug or synthetic chemical.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

EXAMPLE 1 Effects of sodium succinate and whey-succinate on in vitro ruminal pH, volatile fatty acid (VFA) patterns and gas production.

Rumen contents are taken via an esophageal tube from eight yearling, beef-type steers group fed a diet consisting (dry matter basis) of 30% corn silage, 60% cracked corn and 10% protein supplement. Each sample of fluid (~ 300 ml) is strained through two layers of cheesecloth into a flask flushed with CO2, and then cooled on ice.

Equal volumes of strained fluid from each animal are transferred to a clean flask to prepare a pooled sample. After mixing, an aliquot is diluted 10 fold (w/w) with IVI buffer, S.E. Lowe et al., "Growth of Anaerobic Rumen Fungi on a Semi-Defined Medium Lacking Rumen Fluid," J. Gen. Microbiol. 131:2225 (1985), and thoroughly mixed. Twenty-five ml of this rumen fluid-buffer mixture are dispensed into 100 ml glass serum bottles containing the appropriate amount of test material and 0.5 g feed substrate. The feed substrate is the same ration fed to the inoculum source animals, except it is dried to constant weight at 60°C and milled through a 1.0 mm Wiley mill screen. Amounts of sodium succinate incubated are 101 mg, 201 mg, 302 mg and 403 mg per bottle. Amounts of whey-succinate incubated are 128, 255, 383 and 510 mg per bottle. The succinate content of the sodium succinate and whey-succinate added to the serum bottle are equivalent.

The bottles are incubated at 39 °C in a gyratory shaker water bath set at 150 rpm. Total gas production is collected from each bottle using a water jacketed manometer-assembly and percent methane in the headspace gas is measured by gas chromatography. After 24 hours the pH of the bottle contents is measured and fermentation terminated by cooling the bottles in an ice bath. Volatile fatty acids are assayed using a gas chromatographic method. Supelco, Inc., "Separation of VFA C2-C5," Bulletin 749D (1975).

The results of this example indicated that succinate, contained in the sodium succinate and whey-succinate was metabolized to propionate during incubation with diluted rumen contents (Table 1). From the data presented in Table 1, it was seen that the propionate levels in the incubations were nearly 100% of theoretical; the average for the four different levels was 101 and 97%, respectively, for sodium succinate and whey-succinate.

Analysis of variance was used to test for differences between treatments at each level and for differences between each treatment and controls.

The least squares means for each of the variables for the negative control and the test materials are shown in Table 2. LSD's (least significant differences) are listed at the bottom of each column under the appropriate variable.

Significantly (P < .05) higher pH values occurred in the incubations to which sodium succinate or whey-succinate are added compared to controls. The increase in pH in response to sodium succinate was directly proportional to the mass of succinate added to the bottles. A leastsquares linear regression of pH against a level of added succinate yielded a slope and intercept of 0.0027 and 5.17, respectively, with an r2 of 0.997.

Total VFA production due to the addition of sodium succinate or whey-succinate was significantly greater (P < .05) than controls. Furthermore, total VFA increased as the level of each test material was increased.

The pattern of VFA produced was affected by addition of succinate. Compared to the controls, there were significantly lower molar percentages of acetate produced by the test materials at all levels, except for whey-succinate at the two lower levels. The molar percentages of propionate were significantly (P < .05) higher in the incubations containing the test materials at all levels relative to the controls. The sodium succinate incubations contained the highest molar percentages (Table 2) of propionate. The acetate/propionate ratio was significantly (P < .05) reduced by all levels of the test materials. The largest reduction in this ratio was observed for incubations to which sodium succinate was added (Table 2).

Compared to the controls, molar percentages of butyrate were significantly (P < .05) less in incubations containing sodium succinate and whey-succinate (except at the lowest level). Molar percentages of isovalerate were less for all test materials at all levels relative to controls (Table 2). Molar percentages of valerate were less for sodium succinate and whey-succinate (except at the lowest level) compared to the controls (Table 2). No detectable differences were observed in molar percentages of butyrate, isovalerate or valerate between incubations containing whey-succinate and those containing sodium succinate.

Total gas production was significantly (P < .05) increased by all levels of the test materials relative to controls (Table 2). This observation is consistent with the increase in total VFA production and is indicative of increased fermentative activity. Compared to the controls, there was significantly (P < .05) more methane produced in the sodium succinate and wheysuccinate incubations.

EXAMPLE 2 Effects of sodium succinate and whey-succinate on in vitro ruminal pH.

In Example 1, the maintenance of pH after 24 hours of fermentation in die presence of increased concentrations of total VFA was an unexpected observation. This increase in pH relative to the controls in these fermentations prompted conducting Example 2. Example 2 is a continuation of Example 1 in which only pH was measured. Collection of rumen contents, amounts of substrates utilized, preparation and incubation of samples were the same as in Example 1, except initial (0 Hour) and 24 hours pH measurements were made.

Consistent with the results of Example 1, pH was higher in the incubations to which sodium succinate or whey-succinate were added and pH was elevated in proportion to the level of sodium succinate or whey-succinate added (Table 3). The initial (0 hour) pH values were almost equal in the control and were only slightly elevated (.04-.10 pH units) in the bottles containing sodium succinate or whey-succinate. Thus, the data from Example 2 show that the elevated 24 hour pH values observed in the sodium succinate and whey-succinate fermentations are not due to differences in pH prior to incubation.

The results of Examples 1 and 2 of these in vitro experiments are consistent with the hypothesis that succinate, whether added as reagent-grade sodium succinate or as whey-succinate, a fermented whey by-product, is converted in equimolar amounts to propionate by 10-fold diluted, mixed populations of rumen bacteria. Compared to dried whey and feed substrate, sodium succinate and whey-succinate produced higher concentrations of total VFA and altered other responses that are indicative of increased fermentative activity. Fermentations to which sodium succinate or whey-succinate were added had nearly equal pH values after 24 hours incubation and these values were higher than the controls. This effect on pH is hypothesized to occur as a result of decarboxylation of succinate to form propionate during which CO2 is liberated and protons are consumed. EXAMPLE 3 Effect of sodium succinate addition on the in vitro rate of pH decline and the final pH at 24 hours in batch incubations of undiluted rumen fluid.

Rumen contents are collected from six beef-type steers via an esophageal tube, filtered through two layers of cheese cloth under an atmosphere of anaerobic grade CO2, and transported back to the laboratory on ice. A composite sample containing equal volumes of fluid from each steer is prepared, and 75 ml aliquot are transferred to 100 ml serum bottles containing 1.5 g of ground feed substrate. Treatments include: control (feed only), and succinate (feed + 1.209 g sodium succinate hexahydrate), with two bottles per treatment. The bottles are incubated at 39°C and 150 RPM in a gyratory shaker water bath. To determine pH, a 3 ml sample is removed from each bottle by syringe at 30 minute intervals for 6 hours, and then again at 24 hours. The pH of the sample is then measured with a pH meter. This experiment was replicated 3 times.

Two summary variables were chosen to compare the difference between the controls and treatments: 1) the rate of pH decline (slope) is determined from linear regression of the variables, time vs pH (for the first 4 hours); 2) the final pH at 24 hours. The results of Example 3 are presented in Table 4. The data was analyzed as a balanced two-way mixed model with treatment

(control vs succinate) as a fixed effect and block as a random effect.

Across all blocks, the rate at which the pH declined was significantly slower in bottles treated with succinate (P = 0.0003). Also, the final pH at 24 hours was higher in bottles treated with succinate (P = 0.0044). These results indicate that succinate, when added to rumen fluid, has a highly significant effect on the pH of the system. Also, since this study used undiluted rumen fluid as opposed to ten-fold diluted rumen fluid used in Examples 1 and 2, it comes closer to mimicking the pH effect in vivo.

EXAMPLE 4 Testing of Additional Salts.

The sodium salts of certain carboxylic acids including citric, tricarballyic, fumaric, α-ketoglutaric, malic, maleic and succinic, and the potassium salt of aspartic acid, which have similar effects to that of succinate on pH in batch incubations of undiluted rumen fluid, were tested using the methods of Example 3.

The results are listed in Table 5. The initial rate of pH decline, except for α-ketogluterate, was reduced (P < .01) and the final 24 hour pH was higher (P < .10) compared to the controls.

EXAMPLE 5 In Vivo Cattle Study

The effect of sodium succinate on ruminal pH was evaluated in vivo using an animal model for subacute acidosis. The protocol for this animal model was as follows: Fistulated cattle are maintained on a 50% concentrate ration, containing 60% corn silage, for a period of not less than two weeks. The daily meal is split into two portions: one is offered mid-morning while the other is offered mid-afternoon. Beginning two days prior to induction of subacute acidosis, the afternoon meal is offered at 11 p.m. to 12 midnight. The following morning, initial ruminal pH values for all test cattle are measured. Then a 95% concentrate ration (containing rolled wheat) is mixed with twice the mass of water and dumped through the fistulas of the cattle directly into the rumen, in order to induce acidosis. The amount of the challenge ration varies between 1.5 to 1.9% on a body weight basis. The ruminal pH is measured at the following times after induction: 4, 6, 8, 10, 12, 14 and 24 hours. Samples of ruminal contents are also taken at these times for later measurement of lactate (D- and L+) and VFA concentrations. The above model is designed to give an average ruminal pH of about 5.3 (CV= 10% or less) with a total lactate concentration of less than 5 mM.

In this example, ruminal pH was elevated in the above model by including succinate in the challenge ration at a level equivalent to 1 g/kg body weight. Three Hereford x Angus cattle were used in an initial test of the effects of sodium succinate on the development of subacute acidosis. An additional three fistulated Hereford x Angus cattle served as controls. The average ruminal pH for the control animals declined from 6.4 to 5.3 within 8 hours while the ruminal pH for the treated group dropped from a mean of 6.5 to a minimum of only 6.0 at 4 hours. (Table 6).

Thus the results of Example 5 indicate that 0.1% succinate (on a body weight basis) prevents the development of subacute acidosis in vivo.

EXAMPLE 6 Feed Intake Study

The objective of this study was to test the effect of sodium succinate on voluntary feed intake and ruminal pH when administered to cattle as a dietary supplement. Twenty-four rumen fistulated crossbred steers averaging 293 kg were restrained in individual tie stalls and offered hay ad libitum followed by diets containing increasing concentrate levels. This was a randomized complete block experiment with four treatment combinations involving two diets containing different levels of wheat, with and without added sodium succinate. The concentrate portion of each diet contained rolled corn, rolled whet, soybean oil meal, mineral and vitamins. A step-up program was used to adapt the cattle to final ration containing 90% concentrate: 3 rations consisting of 50:50, 70:30 or 90: 10 concentrate:hay were fed ad libitum during days 1-7, 8-14 and

15-28, respectively. Sodium succinate was mixed into the concentrate portion of the ration so that me 50:50, 70:30 and 90: 10 concentrate:hay rations contained 2.5, 3.25 and 5.0% sodium succinate hexahydrate, respectively, on a total dry matter basis. The concentrate portion of each concentrate:hay ration contained 35 or 75% rolled wheat. Dry matter intake (DMI) in kg and the pH of ruminal contents taken at 6, 12 and 24 hours after feeding from each steer were recorded daily. Weekly averages of daily DMI and daily pH (averaged across time) were analyzed statistically for effects of diet (% wheat) and sodium succinate (presence and absence). Treatment effects due to diet were nonsignificant; thus, the response variable means were combined across diets.

DMI was numerically increased 8.8 to 24.6% in comparison to the control group when sodium succinate was added to the diet (Table 7). In addition, the pH of the ruminal contents was maintained (week 2) or was significantly greater (weeks 1, 3 and 4) when sodium succinate was included in the diet. During week 1 when the cattle were switched from hay to the 50:50 concentrate:hay ration, sodium succinate treated cattle consumed 8.8% more DM and ruminal pH was significantly higher (P < .05) mat for the controls. When the concentrate portion of the ration was increased to 70% (week 2), sodium succinate fed cattle consumed nearly 25% (P< .01) more DM and ruminal pH was maintained at the same level as the controls. During weeks 3 and 4 when a 90% concentrate diet was fed, sodium succinate treated steers consumed 10-12% more feed and had significantly higher (P< .01) ruminal pH values compared to the control group.

Data presented in Example 6 indicate that addition of sodium succinate hexahydrate at the rate of 2.5 to 5.0% of the dry mater content of the daily ration will result in an increase in DMI of steers during a step-up program to a final diet containing 90% concentrate. In addition, ruminal pH in sodium succinate treated animals is maintained or is significantly greater even though DMI is increased.

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Claims

Claims
1. A use of a salt of a carboxylic acid wherein the acid is succinic, fumaric, aspartic, citric, malic, oxaloacetic, pyruvic, tricarballylic, α-ketoglutaric or maleic to prepare a medicament for regulating the pH of the rumen in ruminant animals.
2. The use of claim 1 wherein the salt is calcium, potassium, sodium, ammonium or magnesium,
3. The use of claim 2 wherein the carboxylic acid salt is sodium succinate.
4. The use of claim 2 wherein the salts of succinic acid are contained in whey-succinate by-product.
5. The use of claim I wherein the pH of the rumen is maintained close to neutrality.
6. The use of claim 1 wherein the ruminant animals are goats, cattle, or sheep.
7. The use of claim 1 wherein the effective amount is 1-10% of dry matter intake of the ruminants per day.
8. A use of a salt of a carboxylic acid wherein the acid is succinic, fumaric, aspartic, citric, malic, oxaloacetic, pyruvic, tricarballylic, α-ketoglutaric or maleic to prepare a medicament for preventing or treating acidosis in ruminant animals in need thereof.
9. The use of claim 8 wherein the salt is calcium, potassium, sodium, ammonium or magnesium.
10. The use of claim 9 wherein the carboxylic acid salt is sodium succinate.
11. The use of claim 9 wherein the salts of succinic acid are contained in whey-succinate by-product.
12. The use of claim 8 wherein inappetence caused by acidosis is prevented or treated.
13. The use of claim 8 wherein the ruminant animals are goats, cattle or sheep.
14. The use of claim 8 wherein the effective amount is 1-10% of dry matter intake of the ruminants per day.
15. A use of a salt of a carboxylic acid wherein the acid is succinic, fumaric, aspartic, citric, malic, oxaloacetic, pyruvic, tricarballylic, α-ketoglutaric or maleic to prepare a medicament for increasing the efficiency of feed utilization or rate of weight gain of ruminant animals.
16. The use of claim 15 wherin the salt is calcium, potassium, sodium, ammonium or magnesium.
17. The use of claim 16 wherein the carboxylic acid salt is sodium succinate.
18. The use of claim 16 wherein the salts of succinic acid are contained in whey-succinate by- product.
19. The use of claim 15 wherein the ruminant animals are goats, cattle or sheep.
20. The use of claim 15 wherein the effective amount is 1-10% of dry matter intake of the ruminants per day.
21. A use of a salt of a carboxylic acid wherein the acid is succinic, fumaric, aspartic, citric, malic, oxaloacetic, pyruvic, tricarballylic, α-ketoglutaric or maleic to prepare a medicament for increasing feed intake of ruminant animals,
22. The use of claim 21 wherin the salt is calcium, potassium, sodium, ammonium or magnesium.
23. The use of claim 22 wherein the carboxylic acid salt is sodium succinate.
24. The use of claim 22 wherein the salts of succinic acid are contained in whey-succinate by-product.
25. The use of claim 21 wherein the ruminant animals are goats, cattle or sheep.
26. The use of claim 21 wherein the effective amount is 1-10% of dry matter intake of the ruminants per day.
PCT/US1991/003730 1990-06-08 1991-06-04 METHOD FOR REGULATING RUMINAL pH WO1991019489A1 (en)

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