CA2183418A1 - Improving growth and lactation of ruminants - Google Patents

Abstract

Disclosed is a method for increasing the growth rate of ruminants which comprises administering orally to the ruminant an effect amount of carnitine. Also disclosed is a feed formulation for ruminants which comprises carnitine.

Description

W O 95/22259 2 1 a3 4 1 8 PCTrUS95/02211 Il\~PROVING GROVVTH AND LACTATION OF RUMINANTS

FIELD OF THE INVENTION
The present invention is in the general field of nutrition for r lmin~nt ~nim~l~, such as cattle and sheep. In a particular aspect, it relates to a method of feeding or infusing n)min~nt ~nim~l~ with a formulation which enh~nres the growth of the ~nim~l~
and/or improves the content of the milk produced by l~rt~ting ~nim~l~, as evidenced, for example, by an increase in the solid-not-fat (SNF) component of the milk. Rllrnin~nt animal diets or infusions of this invention include an amount of a carnitine, such as L-carnitine or a L-carnitine salt. The amount present in the diet or infusion is such that the growth of the animal is increased and/or the content of particular desirable components of the milk produced by l~rt~ting animals is improved over those ~nim~l~ not fed this diet or receiving the infusion.

BACKGROUND OF THE INVENTION
Recent studies on the function of carnitine in metabolism in lactating rl-min~nt~ have found that c~rnitin~ stiml-l~tes the ketogenesis of p~lmit~te in ovine hepatocytes (Faulkner et al. Comp Biochem Physiol [B] 98(2-3):283-6, 1991) and increased hepatic oxidation in bovine liver (Drackley et al. J Dairy Sci 74(9):3014-24, 1991). The presence of propionate blocked both of these effects. Both of these studies were done on a cellular level, and involved the addition of carnitine and propionate in vitro.
Carnitine has been used as a feed additive for starter pigs (Blum et al., U.S.
Patent No. 5,192,804), for fini~hing pigs in combination with lysine (Blum et al., U.S.
Patent No. 5,124,357), for poultry (Blum et al, U.S. Patent Application 08/049,258), for catfish (Blum et al., U.S. Patent No. 5,030,657) and for domesticated dogs and cats (Keene et al., U.S.

W0 95122259 ~ 1 8 3 4 1 8 PCTIUS95/02211 Patent No. 4,883,672). JP 0126420 teaches the addition of carnitine for ~nim~lc and hl-m~n.c~ a growth stimnl~tor. However, none of these feed are fonTlll~ted for the use of r lmin~nt ~nim~l~, nor is there any suggestion that rllmin~nt~ would display an increase in growth rate or an improvement in the content of milk or the components of the milk 5 or the digestability of the feed of l~t~ting rumin~nt~ with the feeding of carnitine.
Additionally, none of these report the infusion of c~".i~ P directly into the stomach of the animal.
Tables 1 and 2 sl-mm~rize a number of patents related to methods, generally feed additives, which increase growth rate and/or increase in lactation of rumi-10 nants. However, none of these methods involve the use of c~"~ P.

INCREASE GROWTH RATE

Patent-No.~ ~Date ~Inventor ~ Additive ~ irpose~
5,202,136 04/13/93Evans et al. saLulaled fat (at weight gain rate least 10C) 4,760,909 07/26l88Nissen et al. ketoisocaproate increase weight gain or wool 4,353,902 10/12/82Hedde et al. hi~t~minP H2 increase growth receptor agonist 4,258,031 03/24/81Fletcher et ronnel/monersin increase growth al.
4,211,775 07/08/80 Ioset rormel increase growth 4,186,212 01/29/80Howell HMW/aliphatic increase alcohols metabolic energy 4,087,554 05/02/78Haydock et iodonium salts increase growth al. rate/feed effciency 3,953,606 04l27l76Demkovich uroidotetralin increase growth et al. rate 3,210,194 10/05/65Burroug_s 2- promote mercaptoimi~1~701e/c growth/increase arotine feed ~ltili7.~tion 2,951,759 09/06/60DeZeiw et glucocorticoid growth stimulus al.
SUBSTITUTE SHEET (RULE 26J

W095/22259 ~ 1 8 3 4 1 8 PCT/US95/02211 INCREASE LACTATION

S Patent No. ~ ~Date ~ v~ r~ Additive ~ Purpose ~
5,141,922 01/29/80Krivi val'26 BGH enhance lactation 5,041,452 08/20/91White tli~mi~es increase feed util./lactation 4,978,682 12/18/90White ~litoth~nolamine increase feed triacetic acid util./lactation 4,966,917 10/30/90White tetramide increase feed util./lactation 4,895,951 08/20/91White heterocyclic increase feed ~i~mirles util./lactation 4,883,820 11/28/89White tetramide increase feed util./lactation 4,882,355 12/18/90White ~ieth~nolamine increase feed triacetic acid util./lactation tri~mi~les 4,801,618 11/28/89White ~ mino tetramides increase feed util./lactation 4,800,213 12/18/90White ~lifth~nolamine increase feed triacetic tri~mi~es util./lactation 4,783,524 11/08/88Kotts et al. bovine IGF-II increase (peptides) growth/lactation 4,704,276 11/03/87Kantor antibiotic LL- increase growth E19020 rate/feed util./lactation 4,534,969 08/13/85Phillips antibiotic increase lactation teichomycill 4,430,328 02/07/84Scheirmgel glycopeptide increase lactation antibiotics 4,336,250 06122182Scheifinger vhginI~lly~ll/elfa increase miLkmycin production SUBSTITUTE SHEET (RULE 26) woss/222ss 2 1 8 3 4 1 8 PCT/US95/02211 All of the patented methods involve the addition of compounds other than carnitine, many of which are expensive and may have other unwanted effects on the animal. Therefore, there remains a need in the art for a method of increasing growth rate of rl1min~nt~ and/or altering milk content of l~rt~ting r~lmin~nt~ or increasing digestability 5 of the feed which is inexpensive and does not affect other aspects of the ~ "i"~"l~' health.
Accordingly, one aspect of the present invention is a diet for r!-min~ntc which comprises an effective amount of c~, ,,ili,,~, where the desired effect is an increase growth rate and/or a desirable alteration in the content of milk produced by l~rt~ting rllmin~ntc .
A further aspect of the present invention is a method of increasing growth rate of l,l"~in~ which involves feeding the r~lmin~nt~ a standard diet which has been supplemented with an effective amount of callliLille. This method can also be achieved by infusion of the c~rnitin~ directly into the absom~llm of the animal.
A still further aspect of the present invention is a method of altering the 15 content of milk produced by l~rt~ting ~""i,-~"l~ which involves feeding the l~lnlil~"l~ a standard diet which has been supplemented with an effective amount of c~".i~i"~. As above, this method can also be achieved by infusion of the callli~ e directly into the absom~ llm of the animal.

It has now been discovered that by feeding carnitin~ to rllmin~nts, or infusing c~rnitin~ into the abom~nm~ there is an increase in growth rate of the animal.
Further, if the rllmin~nt is l~rt~ting, there is a desirable alteration in the content of the milk produced. This is achieved by feeding l~llllin~n~ a diet which comprises an effective 25 amount of c~ll~line. ~lle"~ively, the c~",ilin~ can be infused directly into the abomasum of the animal. Specifically, it has been discovered that calllilhle supplementation increases average daily gain, in~ir~ting an increase in growth rate. In l~rt~ting l"~"in~n~, c~l,lilillr supplementation has been found to increase SNF content, which is potential]y important with more markets moving to pricing milk on the basis of 30 SNF or protein. This treatment has also been shown to change in nitrogen retention and utilization which is important for improving production efficiency, and also will become increasingly important from the standpoint of decreasing nitrogen excretion into the enviro~ lcnt. Finally, an illlplovelllent in digestibilities of fatty acids, fiber, energy, and crude protein by dairy cows with c~ supplementation offers potential for increasing productive efficiency.
DETAILED DESCRIPTION OF THE INVENTION
All patent applications, patents, and lile.dlule l~felellces cited in this specification are hereby incorporated by l~fe.ence in their entirety.
The present invention relates to a diet or infusion for l~ AIII~ w_ich comprises c~..,il;l-~. The c~...i~i.-P is present in concentrations which make the diet or infusion suitable for use in the method of the present invention. The present method 10 increases growth rate, as in(lie~te~ by an increase in ADG and desirably alters the content of l~t~ting rllmin~nt~ treated by this metho~, as in~ te~l by increased SNF content of the milk produced. C~rnitin~ has also been shown to increase nitrogen retention and improve digestabilities of particular components of the cow diet. Rec~lse of the increase in SNF, it would be expecte~l that c~...il;..~ will increase miLk volume and/or l,~rcellLdge 15 of fat or protein in the milk.
Suitable l-llnill~ to be fed the diet of the present invention include but is not limited to beef cattle, dairy cattle, and sheep. Animals of all ages benefit from this treatm~nt method. For example, young ~nim~l~, which have undeveloped rumen, are expected to respond to a combination of carnitine and a "milk replacer" diet in a very 20 similar fashion to older ~nim~l.c which have the c~. ..ilil-~ infused into the abom~nm. The feeding of this diet should occur from birth to S months of age.
The c~.,-ili..~ can be any isomer of C~ , preferably L-c~...ili.-~, and can be ~yllLll~LiC, microbial produced, or naturally occurring. Also suitable for forrnulation of the diet or infusion of the present invention are salts of c~rnhin~, such as 25 acetyl calniLille. The c~ is present in an effective amount, where the desired effect is an increase in growth rate or a desirable alteration in the content of the milk produced.
Given the l~t~ile~ glli~nr~e of the present specification, it is believed within the level of one of ol.lil~ly skill to test a range of c~rnhin~ concentrations using a trial feed in order to optimize the collcellLl~tion for the particular species and breed being fed 30 or infused. Table 3 lists average feed intake for various sizes and types of l~llll;l-~llls, to be combined with the c~l ,-;1;,-~. The average daily feed intake figures are from "Clinical and Diagnostic V~Lelin~y Toxicology, 2nd ed., William B. Buck et al. Kenrl~ll/Hunt Publishing Co. Dubuque, Iowa. Generally, the effective c~rnitinP concentration is between about 125 mg per head per day to about 20 grams per head per day. The ~rcfcllcd amount is dependent on the particular animal being treated and the size of the animal. For specific rccullelll nutritional requirements, l~,felcnce is made to such 5 publications as the 1985 NRC Publication on Sheep, the 1984 Publication on Beef and the 1978 NRC Publication on Dairy Cattle (such references being incorporated by lef.,lcllce herein) and such similar publications as are well known in the art. In feeding or infusing dairy cattle, a preferred amount is approximately 5 grams per head per day. In feeding or infusing beef cattle, a plcfellcd amount is approximately 2 grams per head per day.

Body Wei~ht % Feed Intake lbs. kg - Body Weight Beef Cattle 300 136 2.3 450 204 2.5 650 295 2.4 1000 454 2.1 T.~t~tin~ Cattle 770 350 1.4 1760 500 1.2 Non-T~rt~tin~ Dairy Cattle 770 350 1.8 1960 800 1.2 59 27 4.5 99 45 3.9 The animal feeds most generally used in colljul,clion with the method of this invention are composed of various grain m~xLul~cs and/or roughage feeds such as hay, W O 95/22259 2 1 8 3 4 1 ~ PCTtUS95tO2211 cottonseed hulls, rice hulls, silage or other high fiber feedctllffc used in various combinations commonly fed to meat, milk and/or wool-producing rllmin~nt~. Generally, the feed should contain from 40 to 60 percent by weight of high collcellLldtc diet, the balance of which may be roughage. A fifty-fifty Illi~lUlC iS l,lef~ cd. Such diets are - S known to shift the ruminal volatile fatty acid (VFA) profile in the direction of more propionate production and less acetate production. This may give increased lltili7~tion of enregy and therefore more milk volume.
The feed schPdlllP and feed rates can also be any standard s~llPdllle and rate used in the art, including feed restrictive programs.
Increase in growth rate can be dcle"llilled by an increase in daily average growth (ADG), increase in backfat or ribfat, increase in feed conversion, or any other art accepted way of measuring growth rate.
Milk content of crude protein and protein components, solid-not-fat, fat and fat components can be measured using standard methods well known in the art.
The following examples are ~c~ se~ e of the present invention but is not to be considered limiting to the scope of the invention.
Research was con~ cted to ~ e. .l.il-P effects of c~. ..ili"P supplementation of stocker heifer and steer diets con.cicting of good quality hay fed with a corn-soybean mal supplement on pasture. Rnmin~lly c~nmll~tçd steers were fed the diets to dætç~ ",inP
20 VFA, and ruminal fluid and plasma c~ . . ,i l i ,-P concentrations over 24-h intervals. Finally, a trial on dairy cows was con-hlctPd to d~Ptç" ~ P the effect of c~rnitinP of miL~ production and content, as well as the nutrition effects on the cows thpmcçlves.

Example 1: Heifer Trial Experimental Procedure:

Forty-two (42) beef heifers, approximately 9 months of age (473.4 lb average initial weight) were acsi~nP~ by breed and weight to six groups of seven heifers.
Two groups of heifers were then randomly ~signlq~l to each of three L-c~
tre~tm~ntc: A=No L-c~ ; B=0.6 g L-c~ P/hd daily; C=1.2 g L-calllil;l-P/hd daily (Table 4). The L-c~l "i~ premixes (Tledl-llellls B and C) were added at 1.0% (20 10 lb/ton) of final diet composed of 75 % ground corn and 25 % soybean meal (Table 5). The final diets were fed at 2.5 kg (5.5 lb)/heifer daily in feed troughs in pastures for 42 d.
Tifton 85 hay in 55-60 lb square bales was fed free-choice in hay racks. Hay refusals were weighed back periodically to accurately ~et~rmin~ hay intake.

EXPERIMENTAL PADDOCKS AND DESIGN OF ~ K AND STEER TRIALS

L-Carnitirle, g/hd daily Item o 0.6 1.2 Heifer trial No. pastures (0.81 ha) 2 2 2 No. heifers 14 14 14 Initial wt. Ib. 472 475 474 Steer trial No. pastures (0.81 ha) 2 2 2 No. steers 14 14 14 Initial wt. Ib. 508 510 510 SUBSTITUTE SHEET (RULE 26) W09S/22259 2 1 ~ 3 4 1 ~i PCT/US95/02211 _ PREMIX AND FINAL DIET COMPOSITION

Premi~ forrnnl~ion Item Premix A'Premix B Premix C
Ground corn, kg(lb) 0 35.409 (78.077) 34.537 (76.154) L-~ nitin~, kg(lb) 0 .872 (1.923) 1.744 (3.846) g/lb 0 10.9 21.8 Total 80.0 80.0 L-C~mitinP g/hd/dayb Final ~ lt~llelll D~ (A) O (b)0.6 (C) 1.2 Corn 1500 1480 1480 Soybean meal 500 500 500 Premix (A, B, or C), lb 0 20 20 a No premix A was formnl~t~ O c~..,il;i-~.
b Treatment supplennPnt~ co.l~ premix A, B, or C fed at 5.5 Ib (2.5 kg) per heifer 20 (38.5 lb/day for each pen of 7 heifers) to deliver 0, .6 or 1.2 g ca~ e/hd daily. Hay fed free- choice.

All heifers were weighed on two consecutive days at the initiation and 25 tç~nin~tion of the trial, and the mean of these respective weights were used as initial and final weights. Heifers were weighed at 21-d intervals, providing two weight periods. On d 21, heifers were rotated on replicate pastures within tre~tm~nt.~ to remove any pasture effects. On d 1 of the trial, all heifers were injected with Vitamins A and D, injected with Discovery 4L5~ (IBR, PI3, pneumonia, lep~ospilosis vaccine) and injected with 30 Tramisol~. A free-choice trace mineral and vitamin supplement (Vh~min-le~D) was available at all times with free access to water.
The two-acre (.81 ha) pastures used in the trial (Table 4) were composed of dormant bermn(l~grass stubble during the November to January time frame for the experiments. Thc..,fo~, the majority, if not all, of the nutrients for the cattle in each trial 35 were supplied by supplen ~nt~l grain and hay. The heifers had been weaned in early September, therefore they had ample time to recover from ~ g stresses and to adapt to grain/hay diets which were provided from weaning time until trials were inhi~te(l All SUBSTITUTE SHEET (RULE 26) W095/22259 21 a34l 8 PCT/US95/02211 heifers were born and weaned on University of Georgia Research Farms, therefore they had received similar p~c~a~ g and postweaning management. All cattle were a~alelllly healthy when the trial was initi:ltf'Cl The hay utilized as the basic roughage in the heifer trial was from the same 5 hay cutting of well-fertilized Tifton 85 bermn(l~grass forage. The hay averaged 13.91%
crude protein and 90.16% dry material (DM), and had a fresh hay odor and bright green color. Hay DM col~ull,plion averaged 56.5% of total dry matter intake (DMI) in the Heifer Trial (Table 6).

PERFORMANCE OF WEANED HEIFERS FED L-CARNITINE AND HAY IETS
Item Control _0.6g L- _1.2g L- _ SE
XfC~rnitin~ XC~rni~inP X
R, R~ Rl R2 Rl R2 No. 7 7 7 7 7 7 In. wt. Ib 473 471472 476 473 475 472 475 474 12.

Day 21 wt483 474 479 507 496 501 489 495 492 12.

Gain (42-d), lba 50 40 45 57 56 56 55 55 55 3.5 ADG Ib Day 21b 0.48 0.19 0.34 1.401.07 1.270.82 0.94 0.88 0.1 Day 42c 1.19 0.96 1.07 1.361.34 1.351.30 1.31 1.30 4 Feed intake, Ib Supplement 5.5 5.5 5.5 5.5 5.5 5.5 5.5 5.5 5.5 Suppl. DMC 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 Hay, as-fed 7.6 7.0 7.3 7.0 7.5 7.2 7.4 6.9 7.1 Hay DMId 6.8 6.3 6.6 6.3 6.7 6.5 6.7 6.2 6.4 Total DMI 11.8 11.3 11.6 11.311.7 11.511.711.2 11.4 DMI 42d 496 475 487 475 491 483 491 470 479 Feed/gain (DM)' 9.9 11.9 10.98.3 8.8 8.6 8.9 8.5 8.7 0.6 Treatment means differ (P< C.06).
b Treatment mean differ (P < 0.01).
c Supplements fed at 5.5 lbthd (38.5 lb/pen daily); Est. DM=90.0%.
30 d Hay samples (6 samples from 5 bales; 3 sites/bale) had 90.16% DM and 12.91% CP.
' Tre~trl ~nt means differ (P < 0.12).
f Treatment mean SUBSTITUTE SHEET (RULE 26) W095/22259 2 1 ,334 1 8 PCT/US95/02211 In the Heifer Trial (Table 6), the average daily gain (ADG) was variable between replicators and tre~tm~nt~, however 21-d ADG was higher (P < 0.01) for L-c~rnitinr supplem~nt~cl tre~tmrntc (26% and 21% higher for 0.6 and 1.2 g treatments) con,l)aled with controls. The 42-d ADG and 42-d gain/heifer were higher (P < 0.06) for 5 L-c~rnhinr supplem~nt~d heifers colll~aled with controls. The 42-d ADG was very similar for each replication within each L-carnitin~ treatment, and 42-d ADG was not improved by feeding 1.2 9/hd daily compared with 0.6 g/hd daily. Although hay was provided free-choice, there were only slight dirre~llces in col~uu~plion betweentre~tm~nt~. Hay was chPr~ l for col~u~--pLion daily, and fresh hay was supplied in 10 amounts estim~tr~ to be con~llm~l in 24 h each day. Hay DMI tended to be lower (P >
0.10) for increasing level of L-ca~ ine supplem~nt~tion. With increased gain on L-c~rnitinr treatmrnt~ and similar DMI intake for all tre~tmPnt~, feed conversion efficiency was improved (P < 0.12) by 26.7% and 25.3%, ~s~ecli~ely, for 0.6 g and 1.2 g L-c~ iLin~ tre~tmpnt~ compared with controls.
Example 2: Steer Trial A 42-d stocker steer trial was con~ cted using the same diets, experimental design and treatment ~Signmrnt procedures, L-c~ tre~tm~nt~, hay and grain supplements and pastures as described above. The steers were 10 months of age when the 20 trial began and averaged 509.3 lb initially. All of the preliminary injections and treatments described above were ~tlmini.ctrred to the steers on d 1 of the trial. Initial and final weights were means of two consecutive daily full weights. On d 42 of the steer trial, backfat of each steer was ~l~trrmin~d by using a Renco~ electronic backfat meter.
As above, the steers have been weaned in early September. All steers were 25 born and weaned on University of Georgia Research Farm. All were ap~a~e..lly healthy when the trial was initi~ted. The same cutting of hay was used as above. Hay DM
co.~ul~lion averaged 65.2% of the total DMI in the Steer Trial.
In this trial (Table 7), the control steers actually gained slightly more than LCalll;L;~r treatment steers at both d 21 and for the entire 42-d trial. There were no 30 signifir~nt dirr~lel~ces (P < 0.10) for any LreaL~llelll~ in this experiment. The replication 2 steers in each of the L-c~l,lilil-~ tre~tm~nt~ tended to have lower gains than replication wossl222ss 2 1 ~34 1 8 PCT/US95/02211 1 steers and control steers. Reasons for those differences in performance are not ~;u~ ly known.

Item Control _ 0.6 g L- _1.2 g L- _ SE
X' C~nitin~ XC~-nitint~ X
R, R2 R, R2 R, R2 No. 7 7 7 7 7 7 Steer wt. lb.
Initial 586 508 508 511 509 510 511 510 509 8.4 Day 21 550 552 551 555 544 550 559 541 550 9.2 Day 42 572 577 575 579 556 548 576 564 570 8.7 Gain (42-d), 64.0 68.7 66.468.747.0 58.165.554.4 60.0 4.7 lb.
ADG lb Day 21 2.00 2.10 2.062.141.67 1.902.291.50 1.89 .19 Day 42- 1.52 1.64 1.581.641.13 1.381.561.30 1.43 .11 Feed intake, Ib SU~ 5.5 5.5 5.5 5.5 5.5 5.5 5.5 5.5 5.5 Suppl. DM 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 Hay, as-fed 10.0 10.3 10.210.510.1 10.310.210.8 10.5 Hay DMI 9.1 9.2 9.2 9.4 9.1 9.3 9.2 9.7 9.5 Total DMI 14.0 14.2 14.114.414.1 14.314.214.7 14.5 DMI 42d 592 596 594 605 592 598 596 617 607 Feed/gain 9.25 8.68 8.948.8112.6 10.29.1011.3 10.11 1.3 (DM) 0 4 Backfat, mm D 1 10.9 10.6 10.710.611.1 10.911.112.0 11.6 0.5 D 42 12.1 12.3 12.213.112.4 13.913.411.9 12.6 0.7 Change 1.2 1.7 1.5 2.5 1.3 1.9 2.3 -0.1 1.1 0.7 Treatment mean~
The hay intake was higher for steers than for heifers (Tables 6 and 7), primarily because of colder weather later in the season during the Steer trial, and because the BW was greater initially for the steers. Dirrelences in hay colL~,u"l~Lion (Table 7) 35 among tre~tm~nt~ were minim~l . Food/gain ratios were lowest for controls, and 15.1 %

-and 13.1% higher (P < 0.20), respectively, for 0.6 g and 1.2 g L-c~.,.il;lle treatments colllp&l.,d with controls.
Individual steer backfat depth at the initiation of the trial (d 1) and at d 42 (Table 7) were measured. Treatment means inrlic~te~ that all steers increased backfat 5 depth during the 42-d trial. Steers fed 0.6 g of L-c&~ e a~&le.lLly had the highest increase in level of bar~ t~ followed by control steers, with the high-level L-c~",il;,~e steers (1.2 g/hd daily) posting the smallest amount of change. Variation was quite high for backfat measurements, consequently there were no tre~tmPnt dirrelellces (P > 0.20).
It should be noted that one replication of the 1.2 g L-c~".ilinP tre~tment had a 2.3 mm 10 increase in backfat colllpal.,d with a 0.1 mm decline in backfat for the other replication.
The highest numerical changes in backfat depth were measured for steers on the two L-c~,.-;l;,-P treatments.

Example 3: Rllmin~l C~nn~ t~P(I Steer Trial Three mature ruminally c~nn~ tPd steers (avg. BW 1100 lb) were fed 14.5 lb of the same hay and 11.0 lb of the same L-c~lllilii-P treatment supplements described above (control, 0.6 g, or 1.2 g of L-c~.,lil;llP/hd daily). The average metabolic size of the three r~lmin~lly c~nnlll~tecl steers was approximately two times the average of the steers and heifers used in the trials described above, therefore we ~sllmP~ rumen volume 20 would be approximately twice as large for these steers as for the stocker heifers and steers. Consequently, daily grain/~rotei~l supplement and hay were doubled, and held constant, for these steers, reslllting in L-c~ e intake of 0, 1.2 or 2.4 g/steer daily.
The steers were fed applopliale L-c~lllil;l-P Ire~l",r,-l.~i in a 3 x 3 latin square experiment, allowing each of the three steers to be on each of the L-c~ l ,.il i ~P- diets.
25 Steers were randomly a~signP~ to tre~tmPnt~ initially, and followed a st~ti~tirally designed format for tre~tmPnt rotation. Each steer was fed the ~pl~liate diet for 10 d in each of three periods, with sample collection over a 24-h period beginning on the morning of the last day of each period. All steers were treated for internal parasite prevention (Tramisol~), a res~ to~ infection prevention (Discovery 4L5~9), and injected with 30 vi~ills A and D two days before the ~elill,ent began.
On d 10 of each period, samples were collected beginning at 0700 h, and steers were then immPfli~tely fed daily grain/L-c~rnitinP supplemPntc and hay Jugular acNI ~r-Aerox l~lec p~r /u~u 4-,~U-~D ~ lrM ~ 0~ ' lU~ JU~ l `~ 2 i ~334 1 8 14 57 Rec'd PCT/PTO 2 5 MAR 1996 blood . nd ruminal fluid ~ampl~ were cit~ "r~ at 0 h behre feeting aQd at 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 podr~ ~. Puminsl fluid wa~ ai~d thSouE~}~ 6 layer~ of c~ t~ d pH wa~ n~;d Blood sampl~ ~ere proceg90d ~lding pl~sma for p~a urea n,l,og~, pl~ma chnl~s~ , plasma tnglycende and pla~ma 5 ~L, ";~;".~ 9,f~ySe~, p~min~l fluid ~9mrl- - were treated with perchlor~c acid rl S ml/dl of wholo ruminal fluit) to ~t~ O~ y, and then ~l~.Jh;rug~l (10,000 RPM) to .ro l~r~er ~ before fre~i~g. Pvmln~l fluid ~ample8 werc ~ubjcct~i to analyse~
to ~h,....,Le V~A and c~...it: -~ c~ r~ nr ~r~ ~ ~Y~s w~ ~-- f~ on data from each of the 10 three tri~ ~ coopention with our st4ff r~-iCti~9l con~ultant in thc De~artment of t~o~ -v~ ~ nd Sta~tical Se.~, CPl~S, Tifton.
m;n~1ly cannulatod ~tccrs were fed L~ A~ at 0, 1.2 or 2.4 g/~d c39,ily u~lized th~ samo hay ~ource with gr~ p~tdn ~upplement and hay intsl~ wasadjusted to p~ovide tho ~ame p~po,lio~ of hay ant gra~ a~ consumed in Bxample~ 1 and lS ~. This ~ wa~ A~t~ d to account for ~ in rumsnal 6ize and BW of n~minally r9r~ml~ co-~ wl~ ~ .g~ wea~ teers ant heifers utili~d abo~ro. ~ i8 t~ wa~ ot to ~,u.it~ infotmation o~ N.nins1 ~r~ ~ for I~nitin~, effech of L~ upplementation on ~ 19l V~7A pro.1uc~ion whlch affec~ cn~ m h ,., ~ , and to ol.s~ n~ n pla~ma r~ levds 20 o~rer time w~ ~latlvdy high lovd~ of dietary L~ -- were inge~ted.
Pla~ma urea r;~ ) plaana choltorol and pla~ma h~l~ite o~ averaged a-rer 11 ~A~p~ mes withi~ 2~ h ~ shown ~n Table 8 fos t~t~ qVith supp~ wer~ no dilr~.~Ac~ (P ~
0.20) for dietuy L-c~ ments for PUN, cholo~terol or triglyce~ide~, ~.._.~, 25 PUN c3r~ n~ wete ditl~l ~P c 0.01) o~,rer time. Cho1e~st~ml and tnglyceride C4nC~ nc wore t l~rr~r~i (P > 0.10) by o~ p~ g timo. The da~ show a glatual ease 1~ P~ c~ t.d1;on~ after fPAding fo~ all ~ ,tietary ~Atm~tc, followed by a ~ratual teclillo after 12 h with 24 h Cf~ A~ irn~ n~ to those ob.~ ui a 0 h, Woro fe~ding. These re~ suggest that L~ suE~ mPntAtin~ at high l~vels on 30 a ~la~ve y high ~ gh-Avo diet has very little, if any effect on ~u~ uptake from the mmon.

_.............. AMF~D~Q Sl IEET , ~CI~I I O T ~ r ~ i tl C C p ~ ~: l / U ~ U ~ r lll L I L I .~ L ~
- ~ 1 834 1 8 ~ T~6~ 9 5 1 2 2 1 1 15 ~ ~3~ j ?~Ti~TO 2 ~ MAR 1996 T~R~-~ 8 PI4~S~IA UR~A NlTRt~n ~. Pr o~ ~ ~nT ~ OT
~9~ TRlGLYt~ RTn~ ~T ~7.c Pn S ~ T~ T_r-T ~ IBVE~L_ OVE~R T.

Ibm Atdo~ diot~y T - ' (gtt) O l.Zg 2.~,g S~
No.~ 33 33 33 ~UN, mg/ldl 19.6 - 19.2 19.6 0.6 0 ~ ol, mg/dl 96.S 99.2 102.0 1.0 .;to mgldl 22.1 22.1 22.8 0.6 Mean of da~ CnllPrt~ at 11 T'~ime8 durlng a Z4 h perlod ~n a 3 x 3 laffn ~quare udng 3 n~ninally c7~nvl~t~d ~teers.

Tablo 9 show~ m~al fluid V~A in molar ~ gra a~ d over 6 e imes in a 24 h periot. Key ~w.~ ~e~ of 0, 2, 4, 9, 16 ant 24 h wore do~o. ~vious ~r~ withLc~ P~ tionbat~hown~otr~e~teffocts 20 whon L-c ...it~ wa~ fed to foeLot ca~tle on high Cl;w~ A~ did:s. ~ V~A ma~
(T~ble 8) ~ere emar'~ably ~imilar ~P ~ 0.10) for oach Indl~ld~ A at~ayed. p~lm7n~1 fluidpH~eal~twe~ (P~ O.lO)by~ suppl~ ,hu..~.u,pH
was ~rl;~ ~' tP C 0.06) bg s~ ino timc, with slig'~t ~ ~t~S OC~ g at 1 h and 6 h postf~ng. ptlminq1 fluid pH ~anged from 6.3 to 6.6 thmughr~ut the s~dy, ~vell wit'nin 25 ae~pt~ ange~ for the ~cind of diet bdng fed.

AMENDED SHEEr S~NT ~V:Xerox Telecopier 7020 ; 4-30-9~ ; 3:00~M ; ~ u~ JU~ 4i~ ~
2la34ls PCTflJS~5/02211 57 Rec'd PCT/P-O 2 5 MAR t996 T~T.~ g RUI~A~ rn~.~.~rR ~rlY AaDS ~7 ~T AV~ .~n O ~ 11~
, mE3Rs p~n T~T~ .11-~ T-~ OF I~CARNIIINE

Itcm Addod dictuy I~ Wd) No. ~ 18 ¦ 18 ¦18 ~J~, m~l/100 1 ` 10 ~o~o 67.0 67.2 67.S .32 ~` 'r 11.2 17.5 17.0 .8 1.6 1.~ 1.6 . 1 l~u~ric 11.0 10.'~ 10.8 .5 T . ' 2.1 . 2.0 2.0 .03 15 V-l~dc 1.1 1.1 1.1 .01 3.9 3.9 4.0 .2 Tot~ itcr 93.1 92.6 94.~ 1.2 Rllm~l *-ld p~ 6.41 6.41 6.38 .04 20 ' Moans b~et upon six ~rl~a o~rcr 24 h interval~ at 3 peri~ ~ a 3 x 3 latin ~quar~
c~ using 3 ~um~nally CD~
_ ~ Mcan~ fcr pH ba~ed upon 33 Co~pl~ per stocr over 11 ~nmrling ffmc~ in thr~o 24 h period~ ~ the 3 x 3 ~ati~ ~uare e~ i~ ut~ng tbrec r-- r7in~11y csnn~7l~hd ~teers.
~5 Ille dah oP~n~ show the followmg chulgeJ in V~7A cn~ --s with time ant ..

4. Thu~ ~ve~e no t~eatmo~t ~ffects for acctato ant prop~onate over a 24 h puiod Clable 9), but acet~ t propi~nqtA ~nt~ ~ Arr,~hA (P C 0.05) by ~me of 30 ' cnn~rling. The r~m~nal acetate tended to d~.~i se ~t~ 2 h and 16 h po~lÇ~ , with a sha~ clwe ~ 16 b a~t 24 h. Corresponding increa~e~ in p~"'~t~A~Ç
~;o~ n~ were obser~ed when acetate co~ tf~ti~n~ ~1in~. and pmpionate rl~r,lin~ sl~ghtly after 16 h when acçt~ d Ihese t~ends in acetate and praFion~
ro~ t~J~n~ may be e~ n~d by digestion of g~a~ portion of ~e diet turing th~
35 intervd from 2 h to 16 hr, which probably c~ntrihut~ to the clas~ic ~hift~ in acdate and p~ io~.. t~ cnn~ t. ~;OrlS ~l~h~ hnot stad9tica~ t&~ ';r~ ,plOpiGL~itCCQ~ t;~

r~At:rl~ Ccplt~ r~ LIL~ L,~ ,L.,,~, ,, 2i83418 PGrlUS q5102211 17 57 Rec'd PCT!PTO 2 5 I~AR 1996 were lowor on the L-c~ 't~ from 4 h to 16 h po~ K co~p&~d wilh the control~. ~o acc~t~.~ oplonate ~o~ were ~rf~c~ n ~ o.os) by tune, but tho ~oan~
over thB 24 h ~d were not ~rF~ 1 by treatment CIabb 9).
- I~b,~ te was ~ rr ~ bg time or ~atment. Butyra~
S wcro sr~ P C 0.01) by tu~o, but not by t~oatment (P ~ 0.10). 1 r~ t:ons for all l~ .r.~ ton~ed to ~n~c after fecding ~t 0 h, and f~
dightly ol~ated u~l 16 h postfic~di~, wheD. ~11 t~a~ents ~ A to &l~rlO~ ct~ 19 the ~ame CO~ n- at ~4 h a~ the ~tial ~)~ h~t;n~`- at O h. ~ fi~s~re of the~o ch~ng~ wh~.~, ~pecially since pla~a hl~~;dcJ ~vere ~fft~ by timc or 0 tr~tm~lt Table 9 ~ow~ t ~-U of b~<h~ ehai~ A isov~le~ato and valerate, wbieh a~ o~n conci~l~d minor Y}7~ for ~ of . ~..lnA~ ovalerate conr~'"~t ~ flll~hl4-e~ with timo, ~ ltit -~ a ~me effeet (P ~ O.OS), and a tre~t (P
~ 0.10) fortepresJod i~ovale~te c~n~ a~ e~ d uith co~ h ~ u~ tho 15 24 h ~. ValeIa~ c~n. ~ tlnn5 in~od (P ~ 0.01) o~ me from O h ~ 4 h, and gIadually ~ f~m 4 h to 16 h, and tbon ~ table through 24 h, ~ E to . IEvd~ ob~;vet at O h. Ihc ~cal aua~y~ ~n~ t~d ~ P ~ (P ~ 0.01) for ~ale~.
= ,~; .

20 ~; ~ y Cows ~rT~;

Thi~ tr~ w~s a repl;.catot~ 3 x 3 ladn u~e tesig~ u~ing 6 Im~lt~
Holstei~ cto~v5 that t-~_fabO;i Sl day~ ct~r~n at tho ~ of the ~ T~.r..-t .f~L~,, ~e wc~ 6 Obu,.~atiol~ per I ~n~nt for all v-D~ hlPs Pcri~d~ were 21 day~ long, wi~ tho first 14 days for -d~pt9tj~ and the l~t 7 for data coU.~:tinn-Tte~tmrnt~ were 1) control (no c~ ), 2) L~-~A;~n~ dosod into the mmen, _nt 3) L,CDrn;tin~ ~nfused c~n~inno~ y into the ~hnm90~In. Mu~.cAts of '1igl--tih~ -s and~-Inn~ of onorgy ant l--h~g~ wo~ made by total cr1II~t~n of fcc~ a~d urine.
Cowc w~re fed a total mixed diet The ifig.~ .t, of thit dliet aro s~ Table10andcl~- --r~1compositioni~s~ iinTabLc11. L~rDrritin~
wa~ r~mi~irt~,r~ at a mea~ of 5.96 g/d, wbich is thc oqui~alent to 227 ppm in diet dry mattcr, b~ed on acbual dry matter int~e~.
AMEN~ED S)IEET

WO95122259 2 1 8 ~ 4 1 ~i ~CT/US95/02211 INGREDIENT COMPOSITION OF TOTAL MIXED DIET
L~ % of DM
Alfalfa haylage 30.00 Corn silage 20.00 Soyhulls, pelleted4.00 Soybean meal 14.00 Corn, ground shelled 25.90 Energy Booster 3.00 Sodium l~;C.~ulJOl~.lLe 0.75 M~.~ei,iu-,. oxide 0.15 Dicalcium ph~ P l.oo T .imPctrnP 0.85 Sodium chloride 0.20 DI Dairy Min/Vit 0.15 CHEMICAL COMPOSITION OF TOTAL MIXED DIET
l~-~li.,.lt % of DM
Organic matter 91.3 Crude protein 19.3 NDF 30.2 ADF 16.5 C~PIIIIIOS~P 14.7 T-TemirP~ nsp 13.6 Ash 8.7 Ether e~tract 5.7 Fatty acids 4.8 Gross energy' 4.52 -Mcal/kg The experimental design was b~l~nred with respect to carry-over effects, and all variables were tested st~ti~tir~lly for presence of ~i~nifir~nt carry-over affects.

WO95/22259 2 1 ~3 3 4 1 8 PCT/US95/02211 If carry-over effects were detected, direct-effect means were calc~ t~, which in effect are means "adjusted" to remove the carry-over affects.
St~ti~tir~l contrasts used were 1) control vs. L-ca.,.i~ tre~ ont~ and 2) run~inally delivered L-c~ vs. abomasally infused L-c~.l.il;.-t-.
As seen in Table 12, feed intake and milk production were not affected si~nifir~ntly by L-c~...;l;l-~. However, the content of solids - not-fat (SNF) in milk was increased by either ruminal or abomasal L-CA---;I;-~P (see, line 6). Because miL~
protein fractions were not altered si~nifirantly by L-c~...il;..P (Table 13), the increase in SNF may be attributable to increased lactose content (which was not measured 10 directly). Abomasally infused L-c~. ..;I;..P tended to decrease milk fat content and decreased milk fat yield. The fatty acid composition of milk fat was not altered appreciably by L-c~ P (Tables 14 and 15).

EFFECT OF ADMINISTRATION OF L-CARNITINE INTO THE RUMAN OR ABOMASUM ON
15 DMI.
MILK YIELD AND MILK COMPOSITION
Treatments Contrast (P) Item Control Ruman Abonasu SEMControl vs. Ruman vs.
m L-Carnitine Abomasu 20 DMI, kg/d' 26.3 26.3 26.0 0.590.89 0.79 Milk, kg/d 41.6 42.2 41.0 0.680.99 0.26 3.5% FCM, kg/d42.2 43.1 40.8 0.410.64 0.01 CP, %2 3.09 3.08 3.08 0.020.57 0.84 CP, kg/d 1.29 1.30 1.27 0.020.96 0.35 25 SNF, % 7.94 8.16 8.09 0.050.02 0.34 SNF, kg/d 3.31 3.45 3.32 0.070.41 0.25 Fat, % 3.59 3.64 3.47 0.060.52 0.51 Fat, kg/d 1.49 1.63 1.42 0.010.41 0.002 'Carryover effect p = 0.095 30 Direct effect means 26.0 25.2 27.3 0.76 0.08 2Carryover effect p= 0.042 Direct effect means 3.05 3.05 3.14 0.19 0.04 SUBSTITUTE SHEET (RULE 26) ;7 C 11 1 ~I U A . I t~ L ~ u--;~ I r ~ L I J .~ ~ L .~ J ~ L A~
2133418 ~ 9 5I G221~

57 Rec'~ PCTIPTO 2 5 MAR 1996 T~u~l l3 o~ ,~n~rN~ ~oP T~ T0 T~
pUM~ OR ~BOM~SUM ON N cQ~o~fi~rs O~ ~
Item TN~tm~t~ S~ CP) Co~ltrol 12~ ~b Cotlt~l Rumu ~r~. v~.
r--~ Abom~JU

S Tot~l N
%1 0.~8S 0.482 0.483 0.0~0.57 0.8 - g~t 201.8 203.8 198.7 3,6 0.890.35 ISue N
9~ 0.451 O.~S0 O.~S0 0.003 0.630.89 g/d 188.0 190.0 18S.0 3.3 0.920.33 ~ of tot~l N93.16 g3.21 93.20 .08 0.670.9S
C~i~ N
9~ 0.3S3 0.3S3 0.349 0.002 0.330. 15 e/t 1~7.2 149.1 14S.4 a. ~ 0.730.10 S of tot l N72.98 73.34 72.23 0,42 0.720.11 J ~ of ~uo ~Y 78.34 78.71 ~7.51 0.4O 0.69 0.1 ~Vh~y N
_, % 0.099 O.W 0.101 0.00~ 0.800.21 ~ld 40.8 40.9 41.7 1.4 0.790.69 % of to~20.18 19.86 20.90 0.43 0.670.12 % of tr N21.66 21.30 22.49 0.46 0.690.12 NP~ .
~ 0.0332 0.0327 0.0329 0.0004 0.37 0.66 &Id 13.9 13.9 13.6 0.30 0.660.65 2S ~ of tob~ N5.84 5.80 6 80 0.08 0.670.9S
'C~ur~ov~-p~.041 effoct .479 475 .490 0.190 04 DL~ct effoct mo~

~r r,_ . ~p= .019 effect .446 .445 .460 0.130.02 D~ct effect m~ .

.~MEN~

WO9Sl22259 2 1 ~ 3 4 1 8 PCT/US95/02211 COMPOSITION OF MILK FAT FROM COWS ADMINSTERED
WITH L-CARNITINE INTO THE RUMEN OR ABOMASUM

Item T~ SEM Contrast (P) Control Rumen Abo~,l~ Control Rumen vs.
vs. Abo C~rnitinP
Fatty acids Weight percentage 4:0 2.0 1.8 2.0 0.1 0.89 0.26 6:0 2.2 2.0 2.1 0.04 0.02 0.02 8:0 1.3 1.1 1.2 0.04 0.16 0.38 10:0 3.0 2.9 3.0 0.1 0.65 0.75 12:0 3.6 3.6 3.6 0.2 0.89 0.98 14:0 10.6 10.6 10.6 0.3 0.96 0.98 14: 1 1.2 1.2 1.2 0.02 0.36 0.85 15:0 1.2 1.2 1.2 0.1 0.51 0.80 16:0 28.4 28.6 29.1 0.2 0.10 0.12 16:1 1.6 1.7 1.6 0.04 0.03 0.19 17:0 0.7 0.7 0.7 0.01 0.43 0.68 18:0 8.5 8.0 8.3 0.3 0.28 0.41 18: 1 20.6 21.2 20.0 0.6 0.96 0.26 18:2 2.8 2.8 2.7 0.1 0.57 0.24 18:3 0.5 0.7 0.5 0.2 0.56 0.38 Glycerol 12.1 12.1 12.1 0.03 0.29 0.36 SUBSTITUTE SHEET (RULE 26) WO95/22259 2 1 5~ J 4 1 8 PCT/US95/02211 PRODUCTION OF FATTY ACIDS AND GYCEROL
IN MILK FAT OF COWS

Fatty Acids Tl~al~ SEM Contrast (P) ControlRumenAbo~ll Control Rumen vs.
vs. ~h.,.. ~
C~rnitin~
( I/d) 4:0 29.4 28.7 28.7 1.3 0.67 0.98 6:0 32.9 29.9 30.2 0.6 0.006 0.76 8:0 18.6 17.3 17.0 0.6 0.09 0.71 10:0 44.8 44.3 42.5 1.8 0.53 0.51 12:0 53.8 54.5 51.6 2.5 0.92 0.44 14:0 157.0 161.0151.7 4.3 0.91 0.17 14: 1 17.5 17.4 16.5 0.4 0.37 0.19 15:0 17.5 18.6 18.1 1.0 0.51 0.72 16:0 421.9 437.1415.5 5.8 0.65 0.04 16: 1 22.0 25.5 22.6 0.7 0.06 0.03 17:0 10.0 10.5 9.7 0.2 0.73 0.04 18:0 129.2 123.5117.6 4.0 0.13 0.33 18: 1 308.9 326.4285.1 11.8 0.83 0.05 18:2 41.0 42.6 38.4 0.5 0.40 0.0006 18:3 7.9 11.2 7.8 2.2 0.58 0.31 Glycerol181.1 184.9172.4 1.4 0.20 0.0007 SUBSTITUTE SHEET (RULE 26) ~tNI ~r:xerox lelec~pler ~lu~u i 4-~U-YU i ~ M i ~ O~O~J'I- IUJ ~uo 1~4~
-- ` 2if33438 --P~TIUS ~ 2 ~ 1 1 23 ~It ~ dP~T~TO 25l~AR1996 T~RT.~ 16 RR~ ~ U I r I ~- 7T n~fii7CTrRll rl~ POR COWS
TH~ R~=L~:~

Itom T ~ Sl~Co~t~t (~) Control Ru~ Ab Cal~trol R~ v~.
v~
C~ -in~
(9~) D~ ~r 6S.4 65.6 64.S 0.8 0.13 0.34 0 Cn~d~ pro~i~l 63.~ 66.6 64.5 1.1 0.18 0.2~;
l~th o~ ct 74.4 18.1 19.3 1.0 0.008 0.10 ADP 34.0 38.4 34.6 1.8 0.29 0. l9 NDP 4~.0 46.9 ~4.1 1.2 0.36 0.1S
~ " S6.0 S~.2 SS.S 1.0 0.83 0.29 15 r~ 48.5 50.6 48.6 0.9 0.38 0.19 ~ ~6.S Sl.4 4C.4 2.9 0.52 0.26 8~r~y 61.9 64.1 63.3 0.S 0.03 0.33 OrSp~ic m~ttor 6S.2 67.1 66.3 0.C0.08 0.41 Solu~ t~l~u~ 66.6 68. 1 6-.3 0.9 0.26 0.89 AMEND~D SHEET

._ _. . . , ~ _ _ . __ .... ...

APPARENT DIGESTIBILITIES OF FATTY ACIDS
FOR COWS ADMINISTERED WITH L-CARNITINE

Tl~ia~ SEM Contrast (P) Fatty Acids Control Rumen Ab~ulll Control vs. Rumen vs.
L-carnitine AbG~.

1012:0 89.1 B9.1 89.9 0.8 0.53 0.35 14:0 49.0 51.8 49.3 1.05 0.28 0.14 16:0 56.4 58.9 58.7 0.7 0.04 0.82 10:0 5.0 9.1 13.3 3.5 0.27 0.42 18:1 83.3 84.4 84.4 0.3 0.05 0.91 1518:2 91.4 92.0 92.8 0.4 0.09 0.20 18:3 96.8 97.1 0.1 0.09 0.66 Total 18 58.1 60.3 61.6 1.2 0.10 0.49 Total 16 57.2 59.7 59.4 0.7 0.04 0.77 Total 68.9 61.3 61.3 0.8 0.05 0.98 L-~rnitinP supplem~nt~tion tended to increase total tract disgestabilities of dry matter and organic matter and significantly increase energy digestibility (Tables 16 and 17). This was largely attributable to the signi~ ntly increased digestibility of 25 total fatty acids (also reflected in increased ether extract digestibility). Ruminal L-c~rnitine tended to increase digestibilities of neutral detel~ent fiber (NDF) and cellulose. Ruminal L-c~ P also tended to increase total volatile fatty acid (VFA) concel~ ion in the rumen, suggesting an enh~n~enn~nt of rumen fennPnt~tion (Table 18). L-C~rnhin~, especially into the rumen, tended to increase proportion of 30 propionate and decrease proportion of acetate in ruminal contents.

WO 95/222592 1 ~ 3 4 1 8 PCT/US95/02211 RUMINAL FERMENTATION CHARACTERISTICS FOR COWS
ADMINISTERED WITH L-CARNITINE INTO
S THE RUMEN OR ABOMASUM
Item Tlc~ ls SEM Contrast (P) Control Rumen Abomasu ControlRumen m vs. L- vs.
carnitine Abomasu pH 5.75 5.68 5.71 0.05 0.42 0.70 NH3, mg/dl10.2 9.2 9.2 0.7 0.20 0.94 Total VFA, mM 120.2 125.5 120.2 1.9 0.29 0.09 10 VFA, mol/100 mol Acetate 50.5 57.2 57.4 0.5 0.08 0.61 ~u~io~L~ 29.7 30.4 29.8 0.4 0.05 0.35 Butyrate 10.0 9.7 10.0 0.3 0.84 0.48 Isovalerate 1.1 1.0 1.0 0.4 0.02 0.74 Valerate 1.7 1.6 1.7 0.05 0.30 0.57 Acetate:
~.ù~ 2.06 1.90 1.96 0.05 0.08 0.43 20L-C~rnitin~ tended to decrease concentration of none~Lelirled fatty acids (NEFA) and increase c~rnitin~ col~cellLIdLion of glucose in blood plasma. Abomasal L-c~...ili..~ tended to decrease cholesterol in plasma (Table 19).

CONCENTRATIONS OF METABOLITES IN PLASMA OF COWS ADMINISTERED

Item Treatment SEM Contrast (P) Control Rum Abomasu Control vs. Rumen vs.
en m L-carnitine abo~
NEFA, ~Eq/ml 181.5 167.3 163.9 8.6 0.18 0.79 Cholesterol, mg/dl 224.4 224.6 210.04.7 0.27 0.07 Glucose, mg/dl81.0 82.4 82.5 0.8 0.17 0.87 Urea N, mg/dl 14.8 13.4 13.7 0.6 0.16 0.73 Ruminal L-c~. ..iLi~.~ resulted in improvements in nitrogen retention and productive nitrogen, arising mostly from slightly improved nitrogen digestibility (Table SUBSTITUTE SHEET (RULE 26) ~C1~ . . C I C ~ .1 L C I / ~ L ~ L r 1-1 ~ ~ I L ~
- 218341~ -PCTl~S q5 I n ~ 2 1 1 26 57 Rec'd PCT/PTC 2 5 MAR t996 20). L-C~itine ~ lted in increa8e8 in digettible and ~ i7~hle energg f~m thediet, but t~ig did not ~crea~e mllk energy 6ecIl:tion, i~ ; .g that ~ n~
wa~ directed wu ~ ~ to body 8to~ge (Table8 21 aDt 22).
T~RT.l~ 20 s ~T7~Trn~ E~OR COWS ~)~T~
~T ~CA~T[N~ T~ T~R ~ OR

Itc:n Tn ~ ~ SI~M Co~t~ t r,.nerol ~m~ ,~l Conerol Rume~
''' Y~
~itlllo m 10 N Intd~e, /t 782 784 771 lS 0.~50.35 N eJWret~ 6/t Poco~ 285 260 274 9 0. i4 0.32 Uri~o 2~8 228 22~7 10 0.990.93 M~llcN, ~d 202 20~ 199 4 0.960.35 15 N.1 ~ It 496 S24 498 lS 0.4S0.Z5 N ~i~, ~1 67 92 72 6 0.0~0.0S
-S~"N, ~/t 268 296 211 8 0.170.06 N, 9~ of Lblko .~ P~ 36.6 33.5- 95.5 1.1 0.180.2S
20 Un~le 29.3 29.0 29.S 0.9 0.980.75 2S.9 Z6.3 25.7 0.9 0.~60. 1S
Rot-i~ 8.2 11.2 9.3 0.7 0.060.11 P~ 34.2 37.5 3S.0 0.9 0.090.09 N, 9~ of ~orW
25 U~ 6.S 43.7 45.7 1.1 0.230.23 Mill~ 40.8 39.~ 40.1 0.8 0.40_0.~1 Rot inct 12.1 16.6 14.1 1.2 0.110.18 iv~, S3.6 S6.3 S~.3 1.~ 0.~30.23 ~C~yo~ ff ct p=.08 30 Direet ~ff~ct me~- 263.7 247.4307.9 0.49 0.85 ~o~ r ofPoct p~
Di~:t offoct m--nJ 2S.8 Z7. 124.8 0.72 0.8Z

~?~ ~!7~i~ r't ~ F . " ~

ac~ r.~erox lelecl pLer lu~u ~ 4-~u-ao, .~u.~rM, ~r~,~u~ r~ "t,~
- 2 1 ~334 1 i3 PC~lllS 95/0221i 27 57 Rec'd PCr/PTO 2 5 MAR 1996 T~l~r ~ 21 ~Rr.y u~T.T7.~Trn~ op CoW9 ~nMT~ H-- Hl WTT~ T ,~A~ lNTO T~F~ 12T~MP.~ OR ~RC~MASI~
.
Itc~ ne .~ SEM Contrlut (P) Control Run~ ~ Co~tol Rume~
carDl~ Abom--" um lld) bl~ ~r 119.0 119.2lla.0 2.10.91 0,7~
l~oc l ~rE~pr4S.4 42.t 43.3 0.90,08 0.6S
10 n~ ~reY 73.6 76.5 74.7 2.10.46 0.57 U~ en~y 4.2 4.4 4.? 0.20.19 0.41 a~ en~rgy S.6 S.8 S.6 0.20.76 O.S6 63.8 66.3 64.4 1.8O.SI 0.48 ~a 15 M~i~t~ e~erD~lS.7 lS.6 lS.S 0.10.21 0.32 ~' ' " `' 48. 1 50.~ 48.9 1.70.47 0.49 ~y ~ovo .
Mil~ ~'8~ 29. 1 28.8 28.3 0.30. 18 0.33 J 20 ~odrweu_ti . S?7 S7~, S70 3 0.22 0.32 Ir~, . . eff~ot pz 0.01 Dlroct offont mo~ lS.8 lS.5 15.4 0.002 0.11 rer effect p_ 0.01 Di~t offo~t meuu 584 S71 S66 0.002 0.12 AI~JIENDED SHEET

W095/22259 2 1 .3 3 4 1 ~ PCTIUS9S/02211 ENERGY PARTITIONING IN COWS ADMINISTERED
WITH L-CARNITINE INTO THE RUMEN OR ABOMASUM

Item TltaLm.,.. l~ SEM Contrast (P) Control RumenAbomasu ControlRumen m vs. L- vs.
carnitine Abomas um (% of gross energy intalce) Fecal energy 38.1 35.9 36.7 0.6 0.03 0.33 Urinary energy 3.5 3.7 4.0 0.2 0.13 0.17 Gaseous energy' 4.7 4.9 4.8 0.1 0.33 0.31 Metabolizable energy 53.6 55.6 54.5 0.4 0.03 0.14 (ME) MetPl-oli7~ 1e energy 40.4 42.3 41.3 0.6 0.11 0.29 above ~ ; t~ -~r~
Milk energy 24.7 24.5 24.0 6 0.64 0.60 Crude ~rr,-,;e.l~ %64.2 58.5 58.4 2.0 0.32 0.99 ~C~lc~llPt~d from l. ~ ,ssioll equation of Moe and Tyrrell (1979).
2Milk energy/ME above ~ t~ --- e 3Carryover effect p= 0.0497 Direct effect means 62.0 62.2 53.9 0.15 0.03 SUBSTITUTE SHEET (RULE 26)

Claims (17)

We claim:

1. A method for increasing the growth rate of ruminants which comprises administering orally to the ruminant an effective amount of carnitine.

2. The method of claim 1 wherein the carnitine is combined with feed or water and said combination is fed to said ruminant.

3. The method of claim 1 wherein the ruminant is beef cattle, dairy cattle, swine or a ram.

4. The method of claim 1 wherein the carnitine is L-carnitine or a salt thereof.

5. The method of claim 1 wherein the effective amount of carnitine is from about 125 mg per head per day to about 20 grams per head per day.

6. The method of claim 1 wherein said ruminants are dairy cattle and the effective amount of carnitine is about 5 grams per head per day.

7. The method of claim 1 wherein said ruminants are beef cattle and the effective amount of carnitine is about 2 grams per head per day.

8. A method to facilitate the partitioning of milk components in a lactating ruminant which comprises administering orally to the ruminant an effective amount of carnitine.

9. The method of claim 8 wherein the carnitine is combined with feed or water and said combination is fed to said ruminant.

10. The method of claim 8 wherein the ruminant is dairy cattle or a goat.

11. The method of claim 8 wherein the carnitine is L-carnitine.

12. The method of claim 8 wherein the effective amount of carnitine is from about 125 mg per head per day to about 20 grams per head per day.

13. The method of claim 12 wherein said ruminants are dairy cattle and the effective amount of carnitine is about 5 grams per head per day.

14. The method of claim 12 wherein said ruminants are beef cattle and the effective amount of carnitine is about 2 grams per head per day.

15. A feed formulation for ruminants comprising between 125 mg and 20 grams of carnitine per head per day.

16. The formulation of claim 15 which is high in forage or roughage.

17. The formulation of claim 15 wherein the carnitine is L-carnitine or a salt thereof.