U.S. patent application number 10/946745 was filed with the patent office on 2005-03-17 for process for optimizing milk production.
This patent application is currently assigned to Novus International, Inc.. Invention is credited to Knight, Christopher D., Koenig, Karen M., Rode, Lyle M., Vandenberg, Michael J., Vazquez-Anon, Mercedes.
Application Number | 20050059739 10/946745 |
Document ID | / |
Family ID | 25412487 |
Filed Date | 2005-03-17 |
United States Patent
Application |
20050059739 |
Kind Code |
A1 |
Knight, Christopher D. ; et
al. |
March 17, 2005 |
Process for optimizing milk production
Abstract
A method of supplying a ruminant with its nutritional
requirements for methionine is provided wherein an ester of
2-hydroxy-4(methylthio)butanoi- c acid that is available for
absorption by a ruminant is administered to the ruminant.
Preferably, the ruminant is administered an ester of
2-hydroxy-4(methylthio)butanoic acid is selected from the group
consisting of methyl, ethyl, butyl, and 3-methylbutyl, and salts
thereof.
Inventors: |
Knight, Christopher D.; (St.
Louis, MO) ; Koenig, Karen M.; (Lethbridge, CA)
; Rode, Lyle M.; (Lethbridge, CA) ; Vandenberg,
Michael J.; (Somers, AU) ; Vazquez-Anon,
Mercedes; (Chesterfield, MO) |
Correspondence
Address: |
SENNIGER POWERS LEAVITT AND ROEDEL
ONE METROPOLITAN SQUARE
16TH FLOOR
ST LOUIS
MO
63102
US
|
Assignee: |
Novus International, Inc.
|
Family ID: |
25412487 |
Appl. No.: |
10/946745 |
Filed: |
September 22, 2004 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
10946745 |
Sep 22, 2004 |
|
|
|
09990677 |
Nov 16, 2001 |
|
|
|
6814988 |
|
|
|
|
10946745 |
Sep 22, 2004 |
|
|
|
09697235 |
Oct 26, 2000 |
|
|
|
6319525 |
|
|
|
|
09697235 |
Oct 26, 2000 |
|
|
|
09333095 |
Jun 15, 1999 |
|
|
|
6183786 |
|
|
|
|
09333095 |
Jun 15, 1999 |
|
|
|
08900414 |
Jul 25, 1997 |
|
|
|
6017563 |
|
|
|
|
Current U.S.
Class: |
514/550 ;
424/442 |
Current CPC
Class: |
A23K 20/142 20160501;
A23K 50/10 20160501; A23K 20/105 20160501; Y10S 426/807
20130101 |
Class at
Publication: |
514/550 ;
424/442 |
International
Class: |
A23K 001/165; A61K
031/22 |
Claims
What is claimed is:
1. A method of supplying a hydroxy analogue of methionine that is
available for absorption to a dairy cow, comprising administering
to the cow an ester of 2-hydroxy-4(methylthio)butanoic acid,
wherein the ester is selected from the group consisting of methyl,
ethyl, butyl, and 3-methylbutyl, and salts thereof.
2. The method of claim 1, wherein the ester of
2-hydroxy-4(methylthio)buta- noic acid comprises the methyl ester
of 2-hydroxy-4(methylthio)butanoic acid.
3. The method of claim 1, wherein the ester of
2-hydroxy-4(methylthio)buta- noic acid comprises the ethyl ester of
2-hydroxy-4(methylthio)butanoic acid.
4. The method of claim 1, wherein the ester of
2-hydroxy-4(methylthio)buta- noic acid comprises the butyl ester of
2-hydroxy-4(methylthio)butanoic acid.
5. The method of claim 1, wherein the ester of
2-hydroxy-4(methylthio)buta- noic acid comprises the 3-methylbutyl
ester of 2-hydroxy-4(methylthio)buta- noic acid.
6. The method of claim 1, wherein at least 20% of the ester of the
2-hydroxy-4(methylthio)butanoic acid is available for absorption by
the cow.
7. The method of claim 1, wherein at least 40% of the ester of the
2-hydroxy-4(methylthio)butanoic acid is available for absorption by
the cow.
8. The method of claim 1, wherein between about 40% and about 55%
of the ester of the 2-hydroxy-4(methylthio)butanoic acid is
available for absorption by the cow.
9. The method of claim 1, wherein the ester of
2-hydroxy-4(methylthio)buta- noic acid is administered to the cow
by feeding the cow a feed comprising the ester of
2-hydroxy-4(methylthio)butanoic acid.
10. The method of claim 9, wherein the feed is a ruminant feed
ration.
11. The method of claim 10, wherein the feed ration comprises a
grain portion.
12. The method of claim 10, wherein the feed ration comprises a
forage portion.
13. The method of claim 12, wherein the forage portion is selected
from haylage and silage.
14. A method of improving milk, the method comprising administering
to a dairy cow an ester of 2-hydroxy-4(methylthio)butanoic acid,
wherein the ester is selected from the group consisting of methyl,
ethyl, butyl, and 3-methylbutyl, and salts thereof.
15. The method of claim 14, wherein the milk improvement comprises
increased milk protein content.
16. The method of claim 14, wherein the milk improvement comprises
increased milk fat content.
17. The method of claim 14, wherein the milk improvement comprises
increased milk volume.
18. The method of claim 14 wherein at least 20% of the ester of the
2-hydroxy-4(methylthio)butanoic acid is available for absorption by
the cow.
19. The method of claim 14 wherein at least 40% of the ester of the
2-hydroxy-4(methylthio)butanoic acid is available for absorption by
the cow.
20. The method of claim 14 wherein between about 40% and about 55%
of the ester of the 2-hydroxy-4(methylthio) butanoic acid is
available for absorption by the cow.
21. A ruminant feed ration comprising: a plurality of natural or
synthetic feed ingredients which comprises one or more grains; and
an ester of 2-hydroxy-4(methylthio)butanoic acid; wherein the ester
is selected from the group consisting of methyl, ethyl, butyl, and
3-methylbutyl, and salts thereof.
22. The ruminant feed ration of claim 21, wherein the feed
ingredients further comprise a forage portion.
23. The ruminant feed ration of claim 21, wherein the forage
portion is selected from haylage and silage.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a Ser. No. 09/990,677, filed Nov. 16,
2001, which is a continuation of U.S. application Ser. No.
09/697,235, filed Oct. 26, 2000, which is now U.S. Pat. No.
6,319,525, which is a continuation of U.S. application Ser. No.
09/033,095, filed Jun. 15, 1999, which is now U.S. Pat. No.
6,183,786, which is a continuation of U.S. application Ser. No.
08/900,414, filed Jul. 25, 1997, now U.S. Pat. No. 6,017,563, the
entire disclosure of which is incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] The present invention generally relates to a process for
satisfying the nutritional requirements of ruminants for
methionine, and more specifically, to a process for meeting those
nutritional requirements using the hydroxy analog of methionine
(2-hydroxy-4(methylthio)butanoic acid) and its salts, amides and
esters.
[0003] High producing dairy cows need methionine, lysine and other
key essential amino acids to reach their genetic potential for milk
production. While amino acids can be added directly to the diets of
monogastric animals to overcome nutritional deficiencies, free
amino acids are rapidly degraded by rumen bacteria and are of
little or no practical benefit in alleviating amino acid
deficiencies in ruminants.
[0004] Traditionally, undegradable intake protein ("UIP") such as
blood meal, fish meal, corn gluten meal and others have been used
to provide essential amino acids to ruminants. It is difficult,
however, to accurately deliver needed levels of methionine and
other essential amino acids without providing excess levels of
other non-essential amino acids and, any excess nitrogen which UIP
delivers to the rumen must be degraded and eliminated by the
animal. Consequently, formulating feeds which satisfy the
methionine requirements using UIP sources is not only expensive, it
can also affect cow health and productive status.
[0005] As an alternative to UIP, attempts have been made to modify
or protect methionine in a manner so that it is not susceptible, or
at least is less susceptible, to rumen degradation. Various
"coatings" for methionine have been proposed which, in theory,
enable the rumen protected methionine ("RPM") to clear or "bypass"
the rumen without significant destruction by rumen microflora and
deliver this key amino acid to the small intestine. Once in the
small intestine, the coating dissolves thereby freeing the
methionine which is absorbed from the intestine.
[0006] The practical application of rumen protected methionine,
however, has presented some challenges. For example, some products
have limited solubility. For others, pelleting, expander
conditioning, mixing, and other normal milling practices fracture
the protective coating, making the methionine molecule vulnerable
to rumen degradation. Some dairy producers have circumvented this
problem by top dressing the rumen protected methionine on final
rations. This labor intensive practice, however, does not allow the
ingredient to be uniformly distributed in the diet. As a result,
cows within a herd may consume different amounts of methionine.
[0007] It has been reported that the milk production of dairy cows
can be increased by supplementing the diets of the cows with the
hydroxy analog of methionine and its salts and esters. See, e.g.,
U.S. Pat. No. 4,388,327. Previous attempts to implement this
technology, however, were met with unpredictable milk production
responses.
[0008] More recently, the calcium salt and the free acid forms of
the hydroxy analog of methionine have been combined with bypass
fats in a dry product for use as an ingredient of a ruminant food
ration. As understood, the level of inclusion of the bypass
fat/hydroxy analog dry product has been determined using a computer
model which matches the nutritional requirements of the ruminant
with available feed ingredients. This approach, however, suffers
from several disadvantages. Because the two ingredients are
combined in a predetermined ratio, the product offers less
flexibility in formulating a ration which meets a least cost
objective and precludes the possibility of formulating a feed
ration which includes the hydroxy analog of methionine but not
bypass fat. In addition, the dry form of the product is susceptible
to the formation of undesirable dust and to non-uniform mixing with
other feed ration ingredients.
SUMMARY OF THE INVENTION
[0009] Among the objects of the invention, therefore, is the
provision of a process for satisfying the nutritional requirements
of ruminants for methionine, the provision of such a process in
which it is unnecessary to coat or otherwise protect the methionine
source from rumen microflora, the provision of such a process in
which a predictable milk response is obtained, the provision of
such a process which avoids providing excess levels of fats or
other non-essential amino acids to the ruminant in order to satisfy
the methionine needs, and the provision of such a process in which
some of the UIP in a balanced ration may be replaced with a lower
cost source of methionine to yield a cost improvement.
[0010] Briefly, therefore, the present invention is directed to a
process for formulating a ruminant food ration for a ruminant. In
this process, the methionine needs of the ruminant are determined.
A plurality of natural or synthetic feed ingredients and the
nutrient composition of each of said ingredients is identified
wherein one of said ingredients is 2-hydroxy-4-(methylthio)butanoic
acid or a salt, amide or ester thereof. From the identified feed
ingredients, a ration is formulated to meet the determined
methionine needs of the ruminant which comprises one or more
grains, a hydroxy analog of methionine, and optionally a bypass fat
wherein (i) the hydroxy analog of methionine is selected from the
group consisting of 2-hydroxy-4-(methylthio)butanoic acid and the
salts, amides and esters thereof, (ii) the hydroxy analog of
methionine is added separately from any bypass fat which is
included in the ration, and (iii) the ration is formulated on the
basis that at least 20% of the hydroxy analog of methionine is
assumed to be available for absorption by the ruminant.
[0011] Other objects and features of this invention will be in part
apparent and in part pointed out hereinafter.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] FIG. 1 is a graph of HMB (DL,
2-hydroxy-4-[methylthio]butanoic acid) versus time for the study of
Example 1.
[0013] FIG. 2 is a graph of HMB (DL,
2-hydroxy-4-[methylthio]butanoic acid) concentration in the
duodenum versus time for the study of Example 1.
[0014] FIG. 3 is a graph of chromium concentration in the rumen
versus time for the study of Example 1.
[0015] FIG. 4 is a graph of chromium concentration in the duodenum
versus time for the study of Example 1.
[0016] FIG. 5 is a graph showing rumen and duodenal HMB (DL,
2-hydroxy-4-[methylthio]butanoic acid) and serum methionine
response following oral dosing of 90 g HMB in lactating dairy cows
for the study of Example 1.
[0017] FIG. 6 is a graph showing milk production (kg/d) versus time
for the study of Example 2.
[0018] FIG. 7 is a graph showing fat percentage in milk versus time
for the study of Example 2.
[0019] FIG. 8 is a graph showing fat corrected milk yield (kg/d)
versus time for the study of Example 2.
[0020] FIG. 9 is a graph showing protein percentage in milk versus
time for the study of Example 2.
[0021] FIG. 10 is a graph showing milk production (lb./cow/day)
versus time for the study of Example 4.
[0022] FIG. 11 is a graph showing milk protein (lb./cow/day) versus
time for the study of Example 4.
[0023] FIG. 12 is a graph showing milk fat (lb./cow/day) versus
time for the study of Example 4.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0024] Optimizing milk production in ruminants requires matching
the nutritional requirements of the ruminant with least cost
sources from available feed ingredients. In recent years, several
computer models have been developed for this purpose; these models
enable a dairy nutritionist to predict the methionine and other
nutrient requirements for high milk producing dairy cows and to
formulate a feed ration using least cost sources. Two of the more
well known models are the Cornell Net Carbohydrate and Protein
System (CNCPS) and the University of Pennsylvania DAIRYLP program.
See, Fox, D. G., Using Computer Models in Extension to Develop More
Profitable Feeding Systems, The National Dairy Database, June 1992;
Galligan, D. T., J. D. Ferguson, C. F. Ramberg, Jr. and W. Chalupa.
1986. Dairy Ration Formulation and Evaluation Program for
Microcomputers. J.Dairy Sci. 69:1656; Galligan, D. T., C. F.
Ramberg, Jr., W. Chalupa and J. D. Ferguson. 1989. J.Dairy Sci.
72:suppl 1):445. In general, the computer models use input data
such as animal type, body weight, fat test, milk production level,
environmental conditions, nutrient composition of available feeds,
feed cost, and rumen bypass rates for degradable protein and amino
acid sources. From this information, the models formulate a least
cost feed ration which accurately meets the ruminant's nutritional
requirements to support the desired level of milk production from
available sources which typically will include corn, soy, alfalfa,
vitamins, minerals, molasses, fat sources, amino acid sources,
undegradable intake protein, and a variety of other feedstuffs.
[0025] Depending upon the dose, location of administration and diet
or management factors, experimental evidence to date suggests that
the amount of methionine hydroxy analog which bypasses the rumen
and is available for absorption when the analog is fed to a
ruminant in the absence of a bypass fat is at least about 20% on a
molecular basis. Experimental bypass data and field work with dairy
cattle (based upon milk response) further suggests that the amount
which by-passes the rumen is at least about 40% on a molecular
basis. Additional experimental evidence suggests that about 8.8% of
the analog is absorbed by the omasum and should be available for
use. Still further experimental evidence suggests that a certain
percentage of methionine hydroxy analog which doesn't clear the
rumen is actually absorbed through the rumen's epithelial lining.
Everything considered, therefore, the amount of the hydroxy analog
of methionine which bypasses the rumen and is available for
absorption is between about 40% and about 55%.
[0026] In the process of the present invention, a conventional
computer model is used to determine the methionine and other
nutritional requirements of the ruminant and a least cost feed
ration which will meet these requirements is formulated.
Advantageously, the feed ration includes the hydroxy analog of
methionine and is formulated on the basis that at least 20% of the
hydroxy analog is assumed to be available for absorption by the
ruminant. Preferably, the ration is formulated on the basis that at
least about 40% of the hydroxy analog is assumed to be available
for absorption by the ruminant and more preferably on the basis
that between about 40% and about 55% of the hydroxy analog is
assumed to be available for absorption by the ruminant.
[0027] The hydroxy analog of methionine ("MHA") which may be used
in the process of the present invention include
2-hydroxy-4(methylthio)butanoic acid, its salts, esters, amides,
and oligomers. Representative salts of MHA include the ammonium
salt, the stoichiometric and hyperstoichiometric alkaline earth
metal salts (e.g., magnesium and calcium), the stoichiometric and
hyperstoichiometric alkali metal salts (e.g., lithium, sodium, and
potassium), and the stoichiometric and hyperstoichiometric zinc
salt. Representative esters of MHA include the methyl, ethyl,
2-propyl, butyl, and 3-methylbutyl esters of MHA. Representative
amides of MHA include methylamide, dimethylamide, ethylmethylamide,
butylamide, dibutylamide, and butylmethylamide. Representative
oligomers of MHA include its dimers, trimers, tetramers and
oligomers which include a greater number of repeating units.
[0028] In the dairy farm industry, dairy cows are fed as a ration,
commonly referred to as a total mixed ration (TMR), which consists
of a forage portion and a grain concentrate portion. The forage
portion is typically provided by the dairy farmer and generally
consists of haylage or silage, with the forage and grain
concentrate portions being mixed by the dairy farmer. The grain
concentrate portion is typically prepared by a commercial feed mill
and is generally prepared by mixing grains such as corn, soy, and
alfalfa with vitamins, minerals, molasses, fat sources, synthetic
amino acids and a variety of other feedstuffs. These ingredients
are blended in commercial feed mills using conventional milling
techniques which include augering, mixing, expanding, extruding,
and pelleting.
[0029] In accordance with the present invention, the hydroxy analog
of methionine is added separately and individually as an ingredient
in the grain concentrate portion of the ration; stated another way,
the amount of hydroxy analog added to the grain concentrate portion
of the ration is independent of the amount of bypass fat added (if
any) to the grain concentrate portion. Preferably, the hydroxy
analog of methionine is the free acid which is a liquid offering
several handling and mixing advantages. As a liquid, it is evenly
absorbed by the grains and does not settle out of the mixture
before consumption by the ruminant. Since its availability to the
ruminant is not derived by any protective coating, it can be mixed,
augered, exposed to high temperature steam conditioning, extruded,
expanded or pelleted with no loss of product activity. In addition,
once consumed by the ruminant, the hydroxy analog of methionine is
subject to no loss of activity resulting from mastication and cud
chewing, as are calcium soaps of fatty acids (common bypass fats),
amino acids and other nutrients that derived their activity in the
ruminant as a result of a protective coating.
[0030] In addition, the hydroxy analog of methionine which is
incorporated into the grain concentrate need not be coated with or
incorporated into a bypass fat in order to be available to the
ruminant. This provides added flexibility to allow the hydroxy
analog of methionine to be added at the level required given the
ration ingredients and the productivity of the cows receiving the
ration.
[0031] In general, a bypass fat is a fat which has been chemically
or physically altered or synthesized to remain insoluble (or inert)
as it passes through the rumen of the cow. Bypass fats typically
remain as a solid as they pass through the first parts of a
ruminant's digestive tract including the rumen. After passing
through the rumen, the fat is solubilized in the initial regions of
the small intestine and then becomes available to enzymatic
activity through well known mechanisms of fat absorption. Some
commercially available bypass fats are described, for example, in
U.S. Pat. Nos. 5,182,126; 5,250,307; 5,391,787; 5,425,963; and
5,456,927 which disclose C14-C22 fatty acids, their glycerides, or
their salts including, but not limited to, palmitic, oleic,
linoleic, stearic, and lauric compounds. As used herein, however,
the term bypass fat does not include fats of natural origin which
are normally present in the diet of a cow which include, but are
not limited to, animal fats such as poultry fat, animal tallow,
animal oil, or vegetable oils such as canola oil, coconut oil, corn
oil, cottonseed oil, palm oil, peanut oil, poultry fat, sunflower
oil, soybean oil, or safflower oil.
[0032] To derive benefit from addition of the hydroxy analog of
methionine, one needs only verify that the ration fed at expected
levels of consumption, is limiting in its content of available
methionine. This is achieved through the use of computer models
such as the CNCPS and DAIRYLP in conjunction with the
supplementation of the appropriate level of the hydroxy analog of
methionine, based on its availability in the ruminant.
[0033] As described in greater detail in the examples presented
herein, research has confirmed that the hydroxy analog of
methionine is readily available as a methionine source for ruminant
animals. This work has confirmed the rumen survivability of the
hydroxy analog of methionine and its absorption, conversion,
appearance in blood plasma as 1-methionine and utilization for milk
or muscle tissue. In particular, field trials have demonstrated
that the hydroxy analog of methionine statistically increased milk
output versus control groups that were verified to be methionine
deficient through the use of computer models. In addition, when
compared to other sources of rumen protected methionine, or
methionine provided via various sources of undegradable intake
protein, the hydroxy analog of methionine can be one of the most
economical means to provided needed methionine to the ruminant.
Formulating a feed ration with the flexibility of being able to
identify the specific methionine needs of high producing cows from
the methionine hydroxy analog instead of from UIP thus provides
cost, herd health, and production advantages to the dairy farm
industry.
[0034] The following examples will illustrate the invention.
EXAMPLE 1
[0035] Objective:
[0036] To determine the rumen bypass and gastrointestinal
availability of HMB (DL, 2-hydroxy-4-[methylthio]butanoic acid) and
the response of serum methionine to HMB supplementation in
lactating dairy cows.
[0037] Experimental Procedures
[0038] The absorption and metabolism of
2-hydroxy-4-[methylthio]butanoic acid sold by Novus International
(St. Louis, Mo. under the Alimet.RTM. was measured in four
lactating dairy cows fitted with rumen and duodenal T-type cannulae
(10 cm distal to the pylorus). The cows were offered a basal diet
of barley-based concentrate (Table I) and alfalfa hay. The
concentrate was fed at a level of 1 kg for every 2.5 kg of milk
produced (Table I) and access to alfalfa hay was ad libitum. In
addition, cows received 30 g HMB mixed with 2 kg ground corn grain
per day for six days to allow for adaptation of the rumen
microflora. Cows were then fed 90 g HMB mixed with the ground corn
and were administered 600 ml chromium-EDTA (3 g Cr) (Binnerts et
al., "Soluble chromium indicator measured by atomic absorption in
digestion experiments" Vet. Rec. (1968) page 470) into the rumen
via the rumen cannula. The HMB meal was offered to the cows for 20
minutes prior to the morning feeding and any of the remaining meal
was placed in the rumen via the rumen cannula.
[0039] Blood, rumen and duodenal samples were collected at 0, 1, 3,
6, 9, 12 and 24 hours post-HMB-feeding. Blood was collected by
jugular veni-puncture into 2.times.10 ml sterile tubes (Vacutainer
Brand SST tubes for serum separation, Bectin Dickenson, Rutherford,
N.J.), allowed to stand for 30 minutes in an ice bath and
centrifuged at 3000.times.g to separate the serum from cells. Serum
was divided into two fractions. The first fraction was
deproteinized by adding an equal volume of acetonitrile and then
centrifuging to obtain the supernatant. The deproteinized serum was
then frozen (-70.degree. C.) until analysis. A second fraction was
not deproteinized but directly frozen (-70.degree. C.). Rumen fluid
(100 ml) collected from several sites within the rumen was strained
through four layers of cheesecloth and subsampled. The subsample
(30 ml) was acidified with 6 M HCl (0.5 ml) and frozen (-40.degree.
C.). Duodenal samples collected (100 ml) were also stored frozen
(-40.degree. C.). Rumen and duodenal samples were later thawed and
centrifuged at 23 000.times.g, 4.degree. C., for 20 minutes to
obtain the clarified supernatant. The clarified rumen and the
duodenal samples were then frozen until analysis. Serum was
analyzed for methionine and rumen and duodenal samples for HMB.
Chromium was measured by atomic absorption spectrophotometry in
rumen and duodenal samples that were diluted with an equal volume
of a calcium chloride solution to yield samples with approximately
400 ppm Ca.sup.2+ (Williams et al., "The determination of chromic
oxide in faeces samples by atomic absorption spectrophotometry" J.
Agric. Sci., Vol. 59 (1962) pp. 381-385).
[0040] Results and Discussion
[0041] The cows refused to consume the 90 g HMB meal and,
therefore, the meal was placed in the rumen. The concentrations of
Cr (liquid marker) and HMB in rumen and duodenal fluid for each of
the four cows at various times after intraruminal dosing is
presented in Table II and FIGS. 1-4. When the data was plotted on a
semilogarithmic scale (natural logarithm), it followed a straight
line (data not shown). The slope of the line from the
semilogarithmic plot is equal to the fractional rate constant (K).
The rate constants were calculated by linear regression of the
natural logarithm of Cr and HMB concentration verses time (Table
III). Regression analysis of rumen Cr concentration was performed
with data for 1 to 24 hours (excluding data for 0 hour). The rumen
concentration of HMB declined to levels below the detection limit
of the analytical technique (<10 ug/ml) by 24 hours and,
therefore, regression analysis was performed with data for 1 to 12
hours (excluding data for 0 and 24 hours).
[0042] Regression analysis for duodenal Cr and HMB concentration
included the data for 3 to 24 hours and 3 to 12 hours,
respectively. Excluding the data for 1 hour simplified the analysis
by omitting the delay for the translocation of digesta from the
rumen to the duodenum. The mathematical equations describing the
decline of Cr and HMB in the rumen (R.sup.2, 0.9855 and 0.9738,
respectively) and duodenum (R.sup.2, 0.9744 and 0.9674,
respectively) were well fitted to the data.
[0043] Assuming that the decline in rumen HMB concentration is due
to the passage of HMB from the rumen and microbial degradation of
HMB within the rumen, then the fractional rate constant for HMB
(-0.3269; Table III) in the rumen will equal the sum of the rate
constants for the passage and degradation of HMB.
K.sub.[HMB-rumen]=K.sub.[passage]+K.sub.[degradation]
[0044] The HMB is soluble, and therefore, the rate at which HMB
passes from the rumen will be equivalent to the rate of passage for
Cr, the liquid marker (-0.1307). Thus, the rate constant for
microbial degradation within the rumen is -0.1962
(K.sub.[HMB-rumen]-K.sub.[passage- ]=K.sub.[degradation]). The
rumen degradation of HMB was determined based on the ratio of the
rate of degradation of HMB to the total rate of decline of HMB
(-0.1962/-0.3269). Thus, 60% percent of the HMB dose disappeared in
the rumen with 40% of the dose bypassing the rumen
fermentation.
[0045] The fractional rate constant for the decline in HMB
concentration at the proximal duodenum (-0.3380; Table III) is
equal to the sum of the rate constants for passage and
disappearance of HMB.
K.sub.[HMB-duodenum]K.sub.[passage]+K.sub.[disappearance]
[0046] The rate constant for passage of HMB (K.sub.[passage]) to
the duodenum was determined by calculating the rate constant for
the passage of the Cr marker (-0.1053; Table III). Thus, 31.2% of
the HMB fed to the cows passed to the small intestine
(-0.1053/-0.3380.times.100) and 68.8% disappeared
[(-0.3380-(-0.1053))/-0.3380.times.100). The K for disappearance at
the duodenum includes the K for degradation in the rumen and the K
for absorption postruminally but pre-intestinally (presumably the
omasum).
K.sub.[disappearance]=K.sub.[rumen degradation]+K.sub.[omasal
absorption]
[0047] It was determined from the rumen decline in HMB, that 60% of
the HMB disappeared in the rumen. Therefore, the remaining 8.8% of
HMB disappearance was due to omasal absorption. Of the original
dose of HMB fed to the dairy cows, 60% was degraded in the rumen,
8.8% was absorbed in the omasum and 31.2% passed to the small
intestine for absorption. While we have defined ruminal
disappearance as degradation, the substantial quantity of omasal
absorption of HMB indicates that it is likely that some fraction of
the 60% ruminal disappearance may have occurred via absorption
through the rumen wall. As HMB is absorbed via passive diffusion in
other species, it is reasonable to expect this phenomenon to occur
in rumen epithelium as well. Therefore, the bioavailability of 40%
for HMB, as a methionine source for ruminants, is likely a
conservative underestimate.
[0048] Peak concentrations for ruminal and duodenal HMB occurred at
1 and 3 hours, respectively. Peak serum methionine concentration
occurred at 6 hours. By 12 hours, all values had returned to
pre-dose levels (FIG. 5). The absorption of HMB from the omasum and
small intestine and its subsequent metabolism to methionine
produced an increase in serum methionine of 200% above pre-dose
levels at the peak concentration.
1TABLE I Composition of Concentrate Item Ingredient, % (as-fed
basis) Barley grain (medium roll) 51 Rolled corn 10 Beet pulp 8.5
Blood meal 11.5 Soybean meal 4.2 Canola meal 4 Canola oil 3.5
Liquid molasses 2 Mineral premix.sup.1 2 Sodium bicarbonate 1.5
Dicalcium phosphate 1 Perma-Pell 0.8 Vitamin ADE.sup.2 0.025
Flavor.sup.3 0.017 .sup.1Supplies per kg of concentrate: Na, 0.7%;
S, 0.2%; K, 0.02%; Mg. 0.01%; Zn, 154 mg/kg; Mn, 147 mg/kg; Cu, 40
mg/kg; 1, 2 mg/kg; Se, 0.8 mg/kg; and Co, 0.6 mg/kg. .sup.2Supplies
per kg of concentrate: vitamin A, 2500 IU; vitamin D, 250 IU; and
vitamin E 2.5 IU. .sup.3ACS Cattle feeding flavor, Alltech,
Inc.
[0049]
2TABLE II Chromium and HMB Concentration in Rumen and Duodenal
Fluid Chromium Concentration Time (ug/ml) HMB Concentration (ug/ml)
(h) 124 131 133 138 124 131 133 138 Rumen 0 0.04 0.07 0.01 0.02
<10 <10 <10 <10 1 31.83 36.27 40.44 45.51 538.6 615.1
766.6 875.8 3 23.77 29.11 34.52 37.05 326.7 401.1 539.1 656.3 6
19.29 18.09 16.62 27.94 209.9 170.3 173.4 342.0 9 12.93 8.89 10.79
13.89 78.6 50.8 59.3 94.0 12 9.16 5.04 7.86 8.28 22.1 13.2 22.8
19.7 24 3.62 1.07 2.08 1.97 <10 <10 <10 <10 Duodenum 0
1.36 0.05 0.05 0.02 <10 <10 <10 <10 1 11.69 23.80 12.14
17.98 159.3 370.6 189.2 336.8 3 18.30 24.55 25.41 27.23 245.5 324.5
367.5 477.8 6 11.99 17.86 18.42 23.24 81.7 146.2 169.8 276.3 9
11.00 12.16 16.36 19.26 40.6 47.1 70.3 142.7 12 7.89 6.39 7.89 8.39
11.6 13 15.1 25.4 24 3.88 2.06 2.29 2.85 <10 <10 <10
<10
[0050]
3TABLE III Linear Regression Analysis of the Natural Logarithm of
Cr and HMB Concentration in Rumen and Duodenal Fluid Verses Time
Chromium HMB Cow Constant K R.sup.2 Constant K R.sup.2 Rumen 1 to
24 hours 1 to 12 hours 24 3.4702 -.0940 .9883 6.7179 -.2809 .9654
131 2.7330 -.1576 .9878 6.9865 -.3506 .9835 133 3.7310 -.1302 .9781
7.1155 -.3317 .9940 138 3.9905 -.1411 .9877 7.4596 -.3444 .9524
Mean 3.7312 -.1307 .9855 7.0699 -.3269 .9738 SD 0.2124 .0270 .0049
.3081 .0317 .0185 Fitted Y = 41.7292e.sup.-.1307t Y =
1176.0304e.sup.-.3269t Equation Duodenum 3 to 24 hours 3 to 12
hours 124 3.0038 -.0705 .9747 6.4793 -.3285 .9895 131 3.5284 -.1201
.9823 6.9923 -.3595 .9895 133 3.6342 -.1173 .9796 7.1167 -.3486
.9713 138 3.7419 -.1135 .9608 7.3626 -.3155 .9194 Mean 3.4771
-.1053 .9744 6.9877 -.3380 .9674 SD .3273 .0234 .0096 .3722 .0198
.0331
EXAMPLE 2
[0051] In a lactation study, the effects of providing Alimet.RTM.
(2-hydroxy-4-[methylthio]butanoic acid sold by Novus International
(St. Louis, Mo.)) feed supplement in the close-up pre-lactation dry
period and in early lactation diets was evaluated. The diets (Table
IV) were formulated to include Alimet.RTM. to meet the methionine
requirements as determined using existing computer modeling
technology (CNCPS and DAIRYLP). The diets were balanced to meet
amino acid requirements and included standard feed ingredients used
in dairy rations. In the absence of added Alimet.RTM., the control
diet was predicted to be first limiting in methionine. The
estimated need for methionine was approximately 9 grams per day.
Alimet.RTM. was added assuming an availability to the ruminant of
20%.
[0052] This study included 10 multiparous and five primiparous cows
per treatment, supplemented with Alimet.RTM. for two weeks before
calving and for 12 weeks of lactation. The Alimet.RTM. treatment
group produced more milk (33.9 vs 31.3 kg/d; FIG. 6) with a higher
fat content (4.01% vs 3.71%; FIG. 7) than unsupplemented cows. This
resulted in more fat-corrected content (FCM) production for the
Alimet-fed cows (33.4 vs 29.2 kg/d; FIG. 8) but not milk protein
content (FIG. 9). At peak milk yield, Alimet-fed multiparous cows
produced 7.9 kg/d more FCM than unsupplemented cows (42.0 vs 34.1
kg/d). The benefits of supplying post ruminal amino acid would
appear to be greatest during the close-up dry period and early
lactation.
4TABLE IV Basal Ration* Barley 27% Cottonseed 11% Soy bean meal
6.3% Corn distillers grain 8.0% Blood meal 2.0% Megalac (bypass
fat) 2.0% Alfalfa haylage 24% Alfalfa hay 17% *Standard basal diet
without Alimet .RTM.
EXAMPLE 3
[0053] In a field trial, Alimet.RTM.
(2-hydroxy-4-[methylthio]butanoic acid sold by Novus International
(St. Louis, Mo.) at a 40% bypass estimate) was fed to 75 high
producing early lactation cows as part of their diet. The Cornell
Net Carbohydrate Net Protein Model was used to evaluate the diet
(corn grain based diet) being fed to these cattle. The ration being
fed was balanced for 90 pounds of 3.7% butterfat milk per cow per
day. In the absence of added Alimet.RTM., the diet was predicted to
be first limiting in methionine.
[0054] Seventy five multiparous cows were used in each group. The
cows were housed in either side of a modern, well ventilated free
stall barn. Cattle were allocated to treatment by calving date. As
cows calved they were alternately placed in the Alimet.RTM. group
or a group fed the same commercial TMR without Alimet.RTM.. This
commercial TMR represents the standard TMR fed in the field at
commercial dairies at that time. Milk production of each cow was
measured at every milking until 75 cows had been on Alimet.RTM. for
approximately 90 days and 75 cows had been on the control TMR for
about 90 days.
[0055] The statistical model used was for a completely randomized
design. This design is established by assigning treatments at
random to a previously selected set of experimental units. In this
case, the treatments were Alimet.RTM. or no Alimet.RTM., and the
experimental units were cows that were freshening. Assignment to
treatment was completely randomized since it was based on calving
order. As previously mentioned, cows were placed alternately into
the Alimet.RTM. group or treatment group as they calved. The data
were analyzed with a one way Analysis of Variance procedure, using
the F test to determine statistical differences.
[0056] The data indicate that the cows receiving Alimet.RTM.
produced over 5 pounds more milk per cow per day during the period
of the trial. This production response was significant at the
P<0.04 level (Table V). One cow was excluded from the control
group due to extremely low milk production, therefore only 74 cows
were used for statistical analysis. The last cow to complete the 90
days of Alimet.RTM. feeding was not used in order to balance cow
numbers across treatments. This cow averaged 90 pounds of milk per
day. There was no significant difference in days in milk of cows in
either group when the trial was concluded.
[0057] In conclusion, this data set shows that Alimet.RTM. provides
an acceptable source of bypass methionine in high producing, early
lactation cows, when fed from the beginning of lactation onward, to
cows consuming a corn silage based diet.
5TABLE V ANOVA Source of Variation SS df MS F P-value F crit
Between Groups 935.5762848 1 935.5763 4.312277 0.039591 3.905939
Within Groups 31675.6377 146 216.9564 Total 32611.21399 147
[0058] Conclusion:
[0059] Trial compared two groups of early lactation cows. One group
was fed Alimet.RTM. and the other was not. The diets were
isonitrogenous; the Alimet.RTM. diet crude protein level was
adjusted to account for the nitrogen provided by the treatment.
Both diets were fed as Total Mixed Rations on an ad libitum
basis.
[0060] The data indicate that the feeding of Alimet.RTM. resulted
in an increase of 5.03 pounds of milk per cow per day. This result
is statistically significant at the P 0.0396 level.
EXAMPLE 4
[0061] In a field trial, Alimet.RTM.
(2-hydroxy-4-[methylthio]butanoic acid sold by Novus International
(St. Louis, Mo.) at a 40% bypass estimate) was fed to 600 cows of a
1900 cow commercial dairy as part of their standard, commercial
ration. Computer models were used to determine methionine
deficiency and to balance the ration for Alimet.RTM. inclusion. The
six hundred cows consumed an average of 3.8 grams of Alimet.RTM.
per head per day over a 102 day feeding period. In the absence of
added Alimet.RTM., the control diet was predicted to be first
limiting in methionine. The Alimet.RTM. supplemented cows produced
an average of 2.67 lb. (1.21 kg) more milk per cow daily. Milk
protein yield averaged 0.22 lb. (99.8 g) more per cow daily. Milk
fat yield averaged 0.26 lb. (118 g) more per cow daily.
[0062] FIGS. 10-12 summarize the data. It should be noted that the
supplement began on the sixth day of month 1 and ended on the
fifteenth day of month 4.
[0063] In the view of the above, it will be seen that the several
objects of the invention are achieved.
[0064] As various changes could be made in the above compositions
and processes without departing from the scope of the invention, it
is intended that all matter contained in the above description be
interpreted as illustrative and not in a limiting sense.
* * * * *