HUT75085A - 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

Improve the growth and milking of ruminants

The present invention relates to the field of feeding ruminants, such as cattle and sheep. In one particular aspect, the present invention provides a method of feeding or infusing ruminants to a composition for improving the intestinal content of milk produced by animal growth and / or dairy animals, such as by increasing the solid non-fat component of milk. The composition of the invention for nutrition or infusion of ruminant animals comprises carnitine such as L-carnitine or an L-carnitine salt. The amount present in the feed or infusion is such that the growth of the animals is increased and / or the desired particular component of milk produced by the dairy animals is increased relative to animals that do not consume this infusion or receive the infusion.

Recent studies on the role of carnitine in the metabolism of dairy ruminants have shown that carnitine enhances palmitate ketogenesis in bovine hepatocytes [Faulkner et al., Comp. Biochem. Physiol [B] 98, (2-3), 283-286 (1991)] and enhances hepatic oxidation in beef liver (Drackley et al., J. Dairy Sci. 74 (9): 3014-24, 1991). . The presence of propionate blocks both of these effects. Both studies were carried out at the cellular level and included in vitro administration of carnitine and propionate.

Carnitine has been used as a nutritional supplement for starter piglets [Blum et al., U.S.P. 5,192,804], in combination with lysine for fattening piglets [Blum et al., U.S.P. 5,124,357] and was used to feed poultry [Blum et al. 5,030,657] and for the feeding of domestic dogs and cats [Keene et al., U.S.P. No. 4,883,672], JP 0 126 420 teaches the administration of a carnitine animal and a human as a growth stimulant. One of those foods

Case No: 84293-1940-GA / KmO is not formulated to be used in ruminant animals, nor is there any suggestion that this nutrition would lead to growth of ruminants or improve the intestinal content of milk or milk components or that dairy animals by the administration of carnitine. the digestibility of your diet would be improved. Furthermore, there is no mention in the literature that carnitine is to be directly infused into the animal's stomach.

Tables 1 and 2 show the number of patents for processes which generally include nutritional additives that increase the growth rate and / or milk of ruminants. However, neither of these methods uses carnitine.

Table 1

Improve growth rate

Patent- song Date Inventor additive Target 5,202,136 April 13, 1993 Evans and staff saturated fat (at least 10C) weight gain rate 4,760,909 July 26, 1988 Nissen and staff ketoisocaproic weight gain or cotton increase quantity 4,353,902 12.10.1982 Hedde and staff histamine H2 receptor agonist growth increase 4,258,031 March 24, 1981 Fletcher and staff Ronn / monersin growth increase 4,211,775 07/08/1980 Lose Ronne growth increase 4,186,212 January 29, 1980 Howell HMW / aliphatic alcohols metabolic energy enhancement

• · · · · »»

Table 1 (continued)

Patent- song Date Inventor additive Target 4,087,554 05/02/1978 Haydock and staff iodonium growth growth- BESSEGA / táphaté- enhancing agility 3,953,606 27.4.1976. Demkovich et al uroidotetralin increase growth rate 3,210,194 10/05/1965 Burroughs 2-mercapto imidazole / carotene growth rate- of / táphaszno- increase of skiing 2,951,759 06/09/1960 DeZeiw and staff glucocorticoid growth stimulation

Table 2 Improve milking

Patent- song Date Inventor additive Target 5,141,922 January 29, 1980 Krivi at ¹²⁶ BGH yield of milk increase 5,041,452 08.08.1991. White diamides feed utilization / milk yield enhancement 4,978,682 December 12, 1990 White diethanolamine triacetic acid feed utilization / milk yield enhancement 4,966,917 30.10.1990. White tetramethyl- feed utilization / milk yield enhancement

k

Table 2 (continued)

Patent- song Date Inventor additive Target 4,895,951 08.08.1991. White 1 heterocyclic diamides feed utilization / milk yield enhancement 4,883,820 11/28/1989 White tetramethyl- feed utilization / milk yield enhancement 4,882,355 December 12, 1990 White diethanolamine / tri- acid tri- amides feed utilization / milk yield enhancement 4,801,618 11/28/1989 White diamino-tetra amides feed utilization / milk yield enhancement 4,800,213 December 12, 1990 White diethanolamine / tri- acid tri- amides feed utilization / milk yield enhancement 4,783,524 08/11/1988 Kotts and staff bovine IGF-II (Peptides) gain / milk yield enhancement 4,704,276 11/3/1987 Cantor LL-E19020 antibiotic gain / power recovery / milk yield enhancement 4,534,969 08/08/1985 Phillips TEICHOMYCIN antibiotic milk yield enhancement 4,430,328 07/02/1984 Scheifinger glycopeptide antibiotics milk yield enhancement 4,336,250 6/22/1982 Scheifinger virginiamyan / ELFA bleomycin milk yield enhancement

None of the compounds administered in the protected methods are carnitine, many of which are expensive and may have undesirable effects. Therefore, there continues to be a need in the art for inexpensive and undesirable solutions to ruminant health that increase the rate of growth of ruminant and / or alter the intestinal content of milk from ruminant or increase digestion of food.

Accordingly, one aspect of the invention is a food for ruminants comprising an effective amount of carnitine,

Wherein the desired effect is to increase the rate of growth and / or to alter the intestinal content of milk produced by the ruminant milk.

Another aspect of the present invention is a method of increasing the rate of growth of ruminants which comprises feeding a ruminant with a conventional diet supplemented with an effective amount of carnitine. This procedure can also be accomplished by direct infusion of carnitine into the animal's gut.

In a further aspect of the invention there is provided a method of altering the composition of milk produced by a ruminant milk comprising the step of adding an effective amount of carnitine to the ruminant's normal diet. As described above, this method may also be accomplished by infusing the chitin directly into the grafting animal of the animal.

The following is a summary of the invention.

It has been found that feeding the ruminant with chitosan or infusing it into the inoculum stomach increases the growth rate of the animal. Furthermore, in the case of a milk ruminant, a desirable change in the intestinal content of the milk produced occurs. This is achieved by providing the ruminant with an effective amount of carnitine containing food. Alternatively, the carnitine may be infused directly into the animal's gut. More specifically, that felisI

we have found that carnitine supplementation increases daily average weight gain, indicating an increase in growth rate. In dairy ruminants, we have found that carnitine supplementation increases the solid non-fat content of milk, which may be important in several markets that seek to determine the price of milk based on the solid non-fat or protein component. We have discovered that this treatment alters nitrogen retention and utilization, which is important for production efficiency and is increasingly important for reducing nitrogen excretion into the environment. Finally, the increased digestion of fatty acids, fiber, energy, and crude protein in dairy cows, when consumed with carnitine-supplemented food, promises the potential for increased production efficiency.

The following is a detailed description of the invention.

All patent applications, patents, and references cited herein are incorporated by reference in their entirety.

The present invention relates to a nutrition or infusion for ruminants which comprises a carnitine supplement. Carnitine is present in concentrations sufficient to make the feed or infusion suitable for use in the method of the invention. The process of the present invention increases the rate of growth of the fruit, as shown by the increase in average daily gain, and changes the milk composition of the dairy ruminant treated by this process, as indicated by an increase in the solid non-fat component of the milk produced. Carnitine has also been shown to increase nitrogen retention and improve the digestibility of certain ingredients in cows' feed. Based on the increase in the solid non-fat component, it is expected that carnitine will increase the milk volume and / or the percentage of milk fat or protein component.

The mammals to which the food of the present invention may conveniently be administered include, but are not limited to, beef cattle, dairy cattle and sheep. This treatment procedure is suitable for any age animal. For example, young animals whose rumen is still immature will respond to carnitine and a milk replacement diet in the same way as older animals will infuse carnitine into the gut. The feeding of such food is applicable from birth to 5 months.

Carnitine may be any isomer of carnitine, preferably L-carnitine, may be synthetic, microbiologically produced or naturally occurring. Carnitine salts, such as acetylcarnitine, are also suitable for preparing the food or infusion of the present invention. Carnitine is present in these in an effective amount, which is understood to mean an increase in growth rate or a desired change in the intestinal content of the milk produced.

It will be within the skill of those skilled in the art to determine the range of carnitine concentration in a feeding experiment to optimize concentration for a particular species or species to be fed or infused. Table 3 shows the average feed intake of ruminants of various sizes and types intended to be combined with carnitine. Average daily feed intake values are reported in Clinical and Diagnostic Veterinary Toxicology, 2nd Edition, by William B. Buck et al., Kendall / Hunt Publishing Co., Dubuque, USA. according to the literature. Generally, the effective concentration of carnitine is about 125 mg / person / day to about 20 g / person / day. The preferred amount will depend on the species and body weight of the animal being treated. For precise nutritional requirements, reference is made to publications such as the NRC 1985 Notice for Sheep, the 1984 Notice for Cattle and the NRC 1978 Notice for Cattle (these references are incorporated herein by reference) and similar publications well known in the art. In the case of feeding or infusion of dairy cattle, the preferred amount is about 5 g / person / day. In the case of feeding beef cattle or infusion, the preferred amount is about 2 g / person / day.

Table 3

Weight kg Nutritional intake as a percentage of body weight Beef Cattle 136 2.3 204 2.5 295 2.4 454 2.1 Dairy cattle 350 I 1.4 500 1.2 Non-dairy dairy cattle 350 1.8 800 1.2 27 4.5 45 3.9

The feeds most commonly used in the process of the present invention consist of various seed mixtures and / or fiber-rich feeds, such as hay, cottonseed hulls, rice hulls, silage feeds or other high-fiber feed materials for meat, milk and / or cotton production. usually used in different combinations. The diet generally contains from 40 to 60% by weight of highly concentrated nutrients and additionally has a high fiber content. A 50 to 50% mixture is preferred. Such foods are known to shift the rumen volatile fatty acid profile from acetate production to propionate production. This can lead to increased energy utilization and therefore higher milk volume.

The diet regimen and nutrition ratio may be any of the usual regimens and ratios used in the art, including dietary restriction programs.

The increase in growth rate can be determined by increasing the average daily gain, measuring the increase in fat thickness over the back or rib, increasing nutritional conversion, or using any other commonly accepted method of measuring growth rates.

The amount of crude protein and protein components in the milk, solid non-fat component, fat and fat components can be determined by methods well known in the art.

The following examples illustrate the invention without limiting it.

Studies were conducted on the effects of carnitine supplementation on feeding cattle heifers and steers with a diet containing good quality hay diet with corn and soybean meal supplement during grazing. Rabbits fed cannulae into their rumen were fed with diets to determine volatile fatty acid content, rumen fluid, and plasma carnitine concentration over 24 hours. Finally, a study was conducted with dairy cows to evaluate the nutritional effects of carnitine on milk production and milk intestine and on the cows themselves.

Example 1

Heifer test '

Assay Method: Heifers of approximately 9 months old with a mean initial weight of 214.9 kg were divided into six groups of 7 heifers each, according to breed and body weight. Two groups of heifers were selected at random for each of the three test regimens; A = no L-carnitine addition; B = 0.6 g L-carnitine / day, C = 1.2 g L-carnitine / day (see Table 4, Table 10). The L-carnitine premixes (treatments B and C) were added in an amount of 1.0% (9.1 kg / tonne) to the final finished feed consisting of 75% ground corn and 25% soybean meal (see Table 5). The final feed is given to the heifers at a rate of 2.5 kg / day during the 42 days of grazing. 25 to 27.2 kg square Tifton 85 square bales are placed freely on the feed rack. Unused hay is periodically weighed back to accurately determine hay consumption.

Table 4

Heifer and stall experiment design and experimental pastures

Object L-carnitine, g / hd day 0 0.6 1.2 Heifers test Number of pastures (0.81 ha) 2 2 2 Number of heifers 14 14 14 Initial body weight (kg) 214.3 215.7 215.2 Steer test Number of pastures (0.81 ha) 2 2 2 Number of steers 14 14 14 Initial body weight (kg) 230.6 231.5 231.5

Table 5. Premix and Ready Nutrition

Object Premix formula The premix ³ B premix C premix Ground maize, kg 0 35.409 34.537 L-carnitine, kg 0 0.872 1,744 9 / kg 0 24.3 48.06 Altogether 36.28 36.28

·· ··· · · · · · · · · ·

Final treatment L-Kamitin, g / hd day ^b completion (A) 0 (B) 0.6 (C) 1.2 Maize 680.4 671.3 671.3 Soya bean flour 226.8 226.8 226.8 Premix (A, B or C), kg 0 9.1 9.1

^a No premix A was prepared - 0 carnitine ^b Treatment supplements containing premix A, B or C are given to each member of the 7 heifers at 2.5 kg / day / person (17.5 kg / day, repent) 0, 0.6 or 1.2 g carnitine per day. There is no limit to hay consumption.

Each heifer is measured at the beginning and end of the test for two consecutive days and the mean of these two measurements is given as initial and final body weights. Heifers are measured at 21-day intervals, thereby creating two measurement periods. On day 21, the heifers are rotated to different pastures to eliminate the effect of the pasture. On the first day of the study, each calf was injected with Vitamin A and D and Discovery 4L5® (IBR, PI3, pneumonia, leptospirosis vaccine) and Tramisol®. Trace element and vitamin supplementation (Vitaminde®) was freely available with free water throughout the study.

Two 0.81 hectares of pasture (see Table 4) were used for resting Bermuda grass stubble during the study period from November to January. Therefore, cattle received most, if not all, of the nutrients from supplemental cereals and straw in each test. The heifers were weaned in early September, so there was ample time to recover from the weaning stress and to get used to the seed / hay diet, from which they were weaned to the start of the study. All heifers were born and weaned at the University of Georgia Research Farm and received similar pre-weaning and post-weaning treatments. All cattle were apparently healthy at the start of the study. '

In the heifer tests, all the hay used as a basic fiber feed came from the same, well-fertilized Tifton 85 feed for grasses. The hay contained an average of 13.91% crude protein and 90.16% dry matter (w / w), smelled of fresh straw and had a light green color. Hay dry matter consumption represented an average of 56.5% of total dry matter intake (b.a.) in the heifer study (see

Table 6).

Table 6

Growth of weaned heifers fed with L-carnitine and hay

Object control X ^f 0.6 g L- I -kamitin X 1.2 g L- -kamitin X NEITHER Ri r ₂ Ri r ₂ Ri r ₂ Song 7 7 7 7 7 7 Initial weight, kg 214.8 213.8 214.3 216.1 214.8 215.7 214.3 215.7 215.2 5.53 21st Daily Mass (Kg) 219.3 215.2 217.5 230.2 225.2 227.5 222.0 224.7 223.4 5.58 42 days gain, kg ^a 22.7 18.2 20.4 25.9 25.4 25.4 25.0 25.0 25.0 1.59 ÁNT, kg 21 days ^b 42 days ^c 0.22 0.54 0.09 0.44 0.15 0.49 0.64 0.62 0.49 0.61 0.58 0.61 0.37 0.59 0.43 0.59 0.40 0.59 0.06 0.04

i

Table 6 (continued)

Object control X ' 0.6 g L- carnitine X 1.2 gL- carnitine X NEITHER Ri r ₂ Ri r ₂ Ri r ₂ Feed intake kg completion 2.49 2.49 2.49 2.49 2.49 2.49 2.49 2.49 2.49 Supplement, incl. ⁰ 2.27 2.27 2.27 2.27 2.27 2.27 2.27 2.27 2.27 Hay feed 3.45 3.18 3.31 3.18 3.40 3.27 3.36 3.13 3.22 Hay, Sat ^d 3.1 2.9 3.0 2.9 3.0 2.9 3.0 2.8 2.9 total number of years 5.4 5.1 5.3 5.1 5.3 5.2 5.3 5.1 5.2 42 daily b.c. 225 215 221 215 223 219 223 213 217 Feed / Growth (dd) ⁸ 9.9 11.9 10.9 8.3 8.8 8.6 8.9 8.5 8.7 0.6

^a Mean of treated group is different from control (P <0.06) ^b Mean of treated group is different from control (P <0.01) ^c 2.5 kg / day / person supplement (17.5 kg / pen / day) ); Ups. = 90.9%. ^d The dry matter content of the hay samples (6 samples from 5 bales; samples from 3 places of the bale) is 90.16%, CP = 12.91%.

^e Mean of treatments is different from control (P <0.12).

^f Treatment averages; ÁNT = average daily weight gain.

In the heifer studies (Table 6), the mean daily gain was parallel and parallel between treatments, but the mean daily gain for 21 days was greater for L-carnitine supplemented treatments (P <0.01) than for the control (26% and 21%, respectively). % for 0.6 and 1.2 g treatments14). The 42-day average daily gain and 42-day increase in heifers were greater in the L-carnitine supplemented fed group than in the control group (P <0.06). The 42-day average daily gain was very similar in the parallel for all L-carnitine treatments, and the 42-day average daily gain did not increase at 1.2 g / day / person compared to 0.6 g / day / person. Although hay was freely consumed by animals, there was only a small difference between the groups in hay consumption. The hay consumption was checked daily and the amount of fresh hay expected to be consumed by the animals within 24 hours was added. The dry matter intake of hay decreased with increasing levels of L-carnitine supplementation (P> 0.10). Higher growth and similar dry matter intake with L-carnitine treatment showed improved feed conversion efficiency (P <0.12), improvement with 0.6 g and 1.2 g L-carnitine treatments, respectively, compared to controls compared to 26.7% and 25.3% respectively.

Example 2

Tino test A day-old slaughter cattle test was performed using the same diet, experimental protocol and treatment procedure as described above, L-carnitine treatment, hay and grain supplementation and grazing. The steers were 10 months old at the start of the study and had an average body weight of 231 kg. The injections and treatments given at the start of the study are the same as the injections and treatments given to the heifers on the first day of the study. The initial and final body weights of the animals were measured at the beginning and end of the study for two consecutive days. On day 42 of the strain test, each fat layer on the back of the strain was determined with a Renco® electronic back fat meter.

As before, the steers were weaned in early September, all steers were born and weaned at the University of Georgia Research Farm. At the start of the study, all steers are apparently healthy. The hay collected ·· ··· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · On average, hay dry matter intake is 65.2% of the daily intake of dry matter for the tino test.

In this study (see Table 7), the control steers increased significantly more than those treated with L-carnitine, both at 21 days and throughout the entire 42 days of the experiment. However, there was no significant difference (P <0.10) between the treatments in this study. One of the two stallions showed less growth than the other stallion and the control stallions at each L-carnitine treatment. The causes of these developmental differences are not yet known.

Table 7

Growth of weaned steers fed with L-carnitine and hay

Object control X ^f 0.6 g L-chimney X 1.2 gL-carnitine X NEITHER Ri r ₂ Ri r ₂ Ri r ₂ Song 7 7 7 7 7 7 Weight of steers, kg Initial weight, kg 266 230 230 232 231 231 232 231 231 3.8 21st Daily Mass (Kg) 249 250 250 252 247 249 254 245 249 4.2 42nd daily weight (Kg) 259 262 261 263 252 249 261 256 259 3.9 42 days gain, kg 29.0 31.2 30.1 31.1 21.3 26.4 29.7 24.7 27.2 2.1 ÁNT, kg 21 days 42 days 0.90 0.69 0.95 0.74 0.93 0.72 0.97 0.74 0.78 0.51 0.86 0.63 1.04 0.71 0.68 0.59 0.86 0.65 0.09 0.05

- Table 7 7 (continued)

Object control X ^f 0.6 g L-chimney X 1.2 gL-carnitine X NEITHER Ri r ₂ Ri r ₂ Ri r ₂ Feed intake, kg completion 2.49 2.49 2.49 2.49 2.49 2.49 2.49 2.49 2.49 supplement, Ups. 2.27 2.27 2.27 2.27 2.27 2.27 2.27 2.27 2.27 Hay feed 4.54 4.67 4.63 4.76 4.58 4.67 4.63 4.90 4.76 Hay, b.s. 4.1 4.2 4.2 4.3 4.1 4.2 4.2 4.4 4.3 Div.b. 6.4 6.4 6.4 6.5 6.4 6.49 6.4 6.8 6.6 42 daily b.c. 269 270 269 274 269 271 270 280 275 Forage/ growth (Ups.) 9.25 8.68 8.94 8.81 12.60 10.2 9.10 11.34 10.11 1.3 Fat thickness on the back, mm One day 10.9 10.6 10.7 10.6 11.1 10.9 11.1 12.0 11.6 0.5 Day 42 12.1 12.3 12.2 13.1 12.4 13.9 13.4 11.9 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

ÁNT = average daily weight gain.

The hay consumption was higher in the rams than in the heifers (Tables 6 and 7), mainly due to the colder weather during the rearing experiments and the higher initial body weight of the rams. The difference in hay consumption between treatments is minimal (Table 7). The feed / gain ratio was lowest in the controls, 15.1 and 13.1% higher in the 0.6 g and 1.2 g L-carnitine treatments, respectively (P <0.20).

The depth of fat on the back of each rabbit was measured on days 1 and 42 of the study (Table 7). The 0.6 g L-carnitine-fed steers clearly have the highest growth rate of • ·· ···· · ·, followed by the control steers, while the higher-L-carnitine-fed steers (1.2 g / day) show the smallest change. The variation in the measurement of the back fat layer is very large, therefore the treatments are not significant (P> 0.20). Note that in one of the 1.2 g L-carnitine treated parallel animals,

It was 2.3 mm while the other showed a decrease of 0.1 mm. The largest numerical change in fat depth was measured in the two L-carnitine treated steers.

Example 3 f

Studies with rabbits with cannulae inserted into the rumen

Three adult rabbits with cannulae in the rumen (average weight 500 kg) were fed 6.58 kg of the same hay and 5.0 kg of the same diet supplemented with the same L-carnitine (one of the control animals, the other 0.6 g, the third is 1.2 g of L-carnitine supplement daily). The average metabolic size of the three rabbits with cannulae in their rumen is about twice the average body weight of the rabbits and heifers involved in the previous experiments, so it is assumed that their rumen volume is also about twice that of the former. Accordingly, the daily grain / protein supplement and the amount of carbon were doubled and kept constant so that the intake of L-carnitine in these rabbits was 0, 1.2 or 2.4 g / tino / day.

f

The steers were subjected to the appropriate L-carnitine treatment in a 3x3 Latin square experimental system to ensure that each stallion was included in each L-carnitine dosing regimen. The steers were randomly selected for the first treatment and then subjected to the treatment rotation in a statistically designed fashion. Each stallion was fed with the appropriate diet for 10 days in each period and a sample was collected for a period of 24 hours starting from the morning of the last day of each period. All steins were exposed internally to parasitic prevention (Tramisol®) and prevented respiratory infection • · • · · ·

- 18 f (Discovery 4L5®) and were injected with vitamin A and D 2 days before the start of the study.

At ^7:00 am on the morning of the 10th day of each study period, the animals were immediately fed with daily grain / L-carnitine supplementation and hay. Jugular blood and rumen fluid samples were taken at 0 hours prior to feeding and 1, 2, 3, 4, 6, 8, 12, 16, 20 and 24 hours after feeding. The rumen fluid was filtered through a six-layer cheese tissue and its pH was immediately determined. Plasma was separated from the blood samples and plasma urea nitrogen, plasma cholesterol, plasma triglyceride and plasma carnitine were determined. The rumen fluid samples were treated with perchloric acid at 1.5 ml / dl total rumen fluid to eliminate microbiological activity and centrifuged at 10,000 rpm to remove large particles prior to freezing. The volatile fatty acid content and the concentration of carnitine in the rumen fluid samples were then determined.

Data from all three studies were processed by appropriate statistical analysis with the assistance of a statistical consultant (Department of Computer and Statistical Services, CPES, Tifton).

Rams with 0, 1.2 or 2.4 g / day of L-carnitine fed rabbit cannula were given the same hay feed and L-carnitine-containing protein supplement, and the same hay-to-seed ratio was set by adjusting the hay intake as consumed by the animals shown in Examples 1 and 2. The procedure was designed to account for differences in the rumen size and body weight of rabbits cannulated with their rumen from similar data from younger weaners and heifers tested in the above experiments. The studies were set up to provide information on the rate of L-carnitine degradation in the rumen, the effects of L-carnitine supplementation on rumen volatile fatty acid production, which affect ruminal energy meta-muscles, and to observe plasma chitin •

- changes in levels over time when relatively high levels of dietary L-carnitine are digested.

Plasma urea nitrogen (PKN), plasma cholesterol and plasma triglyceride concentrations for the three treatment groups treated with L-carnitine are shown in Table 8 and represent the average of 11 samples taken within 24 hours. No difference (P> 0.20) in dietary L-carnitine treatment was observed in PKN, cholesterol and triglyceride values, although PKN concentrations were different over time (P <0.01). Cholesterol and triglyceride concentrations were unaffected by sampling time (P> 0.10). The data show that PKN levels increase in all three groups after feeding, followed by a gradual decrease after 12 hours, and after 24 hours, concentrations return to pre-feeding levels at 0 hours. These results support the hypothesis that high levels of L-carnitine supplementation in relatively high fiber diets have little, if any, effect on rumen nitrogen uptake.

Table 8 Plasma urea nitrogen, plasma cholesterol, and plasma triglyceride values for steers fed with various amounts of L-carnitine

Added L - carnitine (g / na P) Object 0 1.2 g 2.4 g NEITHER The number of observations is ³ 33 33 33 PCN, mg / dl 19.6 19.2 19.6 0.6 Plasma cholesterol mg / dl 96.5 99.2 102.0 1.0 Plasma triglyceride mg / dl 22.1 22.1 22.8 0.6

In experiment 3 steers 3x3 Latin Square test regimen of ^the cannulated Bendőjükben, the average data of 11 samples taken during a 24 hour time period

Table 9 shows the volatile fatty acid content of the rumen fluid expressed as mole% of the 6 samples taken over a 24 hour period. Main sampling times are 0, • ·

- 20, 2, 4, 9, 16 and 24 hours. Previous research on L-carnitine supplementation has shown that treatment does not work when L-carnitine is fed to cattle at high concentrations. The mean volatile fatty acid values shown in Table 8 are significantly similar to the individual volatile fatty acid values tested (P> 0.10). Mean values of rumen fluid were unaffected by L-carnitine supplementation (P> 0.10), but pH was influenced by sampling time (P <0.06), values 1-6 after feeding. hours showed a slight decrease. During the test, the pH of the rumen fluid was in the range 6.3-6.6, which is substantially within the range of the fed diet.

Table 9

Mean volatile fatty acid and pH values of rumen fluid over time in L-carnitine fed steers and 3 different concentrations of L-carnitine

Nutritional L-Carnitine (g / day) Object 0 1.2 g 2.4 g NEITHER The number of observations is ³ 18 18 18 Volatile fatty acid, mol / 100 mol acetic acid 67.0 67.2 67.5 0.32 propionic 17.2 17.5 17.0 0.8 isobutyric 1.6 1.5 1.6 0.1 butyric 11.0 10.7 10.8 0.5 isovaleric 2.1 2.0 2.0 0.03 Valeric acid 1.1 1.1 1.1 0.01 Acetate / propionate 3.9 3.9 4.0 0.2 Total volatile fatty acids μηηόΙ / Ι 93.1 92.6 94.4 1.2 Rumen fluid pH ^b 6.41 β 41 6.38 0.04 ³ 3, with cannulae in his mouth pierced tino 3x3 latin four routine examination-

average of six samples over a period of 24 hours. ^b 3 mean rabbit cannula 3x3 latin squared average of 33 samples per tin over a period of 3 24 hours at 11 sampling times ·······················• · · * »· * · · *

- 21 Data obtained show the following changes in volatile fatty acid concentration over time. Acetate and propionate levels were not affected by treatment during the 24-hour period (see Table 9), but ace ₍ tat and propionate) concentrations were affected by sampling time (P <0.05). and

It showed a decrease in 16-hour samples and a sharp increase between 16 and 24 hours. A corresponding increase in propionate concentrations was observed when acetate concentrations decreased, and a slight decrease in propionate concentration occurred after 16 hours when the acetate concentration increased. Such trends in acetate and propionate concentrations can be explained by the digestion of the grain portion of the feed over a period of 2 to 16 hours, presumably contributing to the classic shift in acetate and propionate concentrations. Although not statistically significant, propionate concentrations are lower with L-carnitine treatment 4-16 after feeding. hours compared to control animals. Acetate to propionate ratios are affected by time (P <0.05) but mean values over 24 hours are not affected by treatment (Table 9).

Isobutyrate is unaffected by time or treatment. Butyrate concentrations are affected by time (P <0.01) but not by treatment (P> 0.10). Butyrate concentrations tend to increase with all treatments after 0 hours of feeding and remain slightly elevated until 16 hours after feeding, followed by a decrease in all treatments, with concentrations around 24 hours approximately equal to the initial 0 hour concentration. The significance of these changes is unknown, especially since plasma triglycerides remain unchanged regardless of time and treatment.

Table 9 shows the concentration of branched isovalerate and valerate volatile fatty acids, which are often considered minor volatile fatty acids for ruminant nutrition. The isovalerate concentration results in a time-varying time effect (P <0.05) and the trend of the isovalerate concentration is reduced over the 24-hour period (P> 0.10) relative to the control. The valera

Concentrations of 22 increase with time between 0 and 4 hours (P <0.01) and gradually decrease over the course of 4 to 16 hours, reaching levels at 0

They remain stable until 24 hours. Statistical analysis showed a statistical difference for valerate treatments (P <0.01). .

Example 4

Milk cow test

Test procedure

The study was performed in duplicate 3x3 latin squares with six repeatedly born Holstein cows that were milked at an average of 51 days at the start of the study. Therefore, six observations were available for each variable per treatment. The periods were 21 days long, of which the first 14 days were for adaptation and the last seven days for data collection. Treatments include: 1) control (no carnitine), 2) L-carnitine administered to the rumen, 3) L-carnitine continuously injected into the inoculum stomach by infusion. Digestibility, energy and nitrogen balance were measured by collecting faeces and urine. '

The cows were given complete mixed nutrition. The ingredients of this diet are:

Table 10 shows their chemical composition in Table 11. L-carnitine was added at an average of 5.96 g / day, which corresponds to 227 ppm / feed dry matter of the actual dry matter intake.

Table 10

The composition of a complete mixed diet

Ingredients % Of dry matter Lucerated alfalfa 30.00 Silage corn 20.00 Soybean pellets r 4.00 soy flour 14.00

• · ·

- Table 10 (continued)

Ingredients % Of dry matter Ground, loose corn 25.90 Energy booster 3.00 Sodium bicarbonate 0.75 Magnesium oxide 0.15 Dicalcium phosphate 1.00 Lime 0.85 NaCI 0.20 Dl Milk mineral / vitamin 0.15 Table 11 A complete mixed diet spy 's composition Ingredients % Of dry matter Organic material 91.3 Crude protein 19.3 NDF 30.2 ADF 16.5 Cellulose 14.7 hemicellulose 13.6 Ash 8.7 Ether extract 5.7 fatty acids 4.8 total energy ¹ 18.92

¹ MJ / kg

The study design was balanced for transmission effects, all variables were statistically examined for the presence of significant transmission effects.

- 24 to determine. If transmission effects were observed, direct effect averages were calculated, which is in fact an adjusted average to eliminate transmission effects.

Statistical counterparts were used 1) in control relative to L-carnitine treatment and 2) in the rumen compared to L-carnitine infused into the gut.

As shown in Table 12, there was no significant effect of L-carnitine on feed intake and milk production. However, the non-fat solids content (SNF) in milk was increased when L-carnitine was administered to both rumen and inoculum (see line 6 of the table). Since milk protein fractions were not significantly altered by L-carnitine administration (Table 13), the increase in solid non-fat content was attributable to the increased lactose content (not directly measured). The infusion of L-carnitine into the renal stomach tended to reduce the milk fat content and milk fat yield. The fatty acid composition of milk was not significantly altered by L-carnitine administration (Tables 14 and 15).

Table 12

Effect of administration of L-carnitine on rumen or inoculum stomach on dry matter intake

Treatment Contrast (P) Object control Rumen extinguishing gastric SEM Control / - carnitine Maw / ol tógyomor Dry matter content, kg / day ¹ 26.3 26.3 26.0 0.59 0.89 0.79 Milk, kg / day 41.6 42.2 41.0 0.68 0.99 0.26 3.5% FCM, kg / day 42.2 43.1 40.8 0.41 0.64 0.01 CP,% ² 3.09 3.08 3.08 0.02 0.57 0.84 CP, kg / day 1.29 1.30 1.27 0.02 0.96 0.35

- 25 • · ··· · · · · ······· «

Table 12 (continued)

Treatment Contrast (P) Object control Rumen extinguishing gastric SEM Control / - carnitine Maw / ol tógyomor SNF% 7.94 8.16 8.09 0.05 0.02 0.34 SNF, kg / day 3.31 3.45 3.32 0.07 0.41 0.25 Fat% 3.59 3.64 3 (47 0.06 0.52 0.51 Fat, kg / day 1.49 1.63 <42 0.01 0.41 0,002 ¹ Transmission effect Direct effect average p = 0.095 26.0 25.2 27.3 0.76 0.08 ² Transmission effect Direct effect average p = 0.042 3.05 3.05 3.14 0.19 0.04

Table 13

Effect of L-Carnitine Administration on the Nitrogen Components of Milk

Treatment Contrast (P) Object control Rumen extinguishing SEM Control / - Maw / ol gastric karrttin tógyomor Total-N % ¹ 0,485 .482 0.483 0,003 0.57 0.84 g / day 201.8 203.8 198.7 3.6 0.89 0.35

• ·

- Table 13 (continued)

Treatment Contrast (P) Object control Rumen extinguishing gastric SEM Control V- carnitine Maw / ol tógyomor Real N % ² .451 0.450 0.450 0,003 0.63 0.89 g / day 188.0 190.0 185.0 3.3 0.92 0.33 azösszN% of 93.16 93.21 93.20 0.08 0.67 0.95 -I Casein N % 0.353 0.353 0.349 0,002 0.33 0.15 g / day 147.2 149.1 143.4 2.1 0.73 0.10 azösszN% of 72.98 73.34 72.23 0.42 0.72 0.11 is the true N% 78.34 78.71 77.51 0.46 0.69 0.12 whey % 0.099 0,096 0.101 0,002 0.80 0.21 g / day 40.8 40.9 41.7 1.4 0.79 0.69 azösszN% of 20.18 19.86 20.96 0.43 0.67 0.12 is the true N% 21.66 21.30 22.49 0.46 0.69 0.12 Not protein N I % .0332 .0327 .0329 0.0004 0.37 0.66 g / day 13.9 13.9 13.6 0.30 0.66 0.65 azösszN% of 5.84 5.80 6.80 0.08 0.67 0.95 ¹ Transmission effect Direct effect average p = 0.041 .479 0.475 0.490 0.19 0.04 ² Transmission effect Direct effect average p = 0.019 .446 0.445 0.460 0.13 0.02

• · ·

- 27 Table 14

The composition of milk fat in cows receiving L-carnitine in their rumen or graft

Object Treatment SEM Contrast (P) control Rumen extinguishing gastric Control 1 / - carnitine Maw / ol tógyomor 7circa <a \ zolz .... ......... Q / n --- - L.őlludVdf \ Luincy / o - ....... - ....... 4: 0 2.0 1.8 -1 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 i 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

- 28 Table 15

Fatty acid and glycerol content of milk fat in cows receiving L-carnitine in their rumen or inoculum

Object Treatment SEM Contrast (P) control Rumen extinguishing gastric control / carnitine Maw / ol tógyomor ^J - (y / day ------------------- - 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: 0 157.0 161.0 151.7 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: 0 421.9 437.1 415.5 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 97 0.2 0.73 0.04 18: 0 129.2 123.5 117.6 4.0 0.13 0.33 18: 1 308.9 326.4 285.1 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 Glycerol 181.1 184.9 172.4 1.4 0.20 0.0007

- 29 Table 16.

Nutrient digestion of cows receiving L-carnitine in their rumen or inoculum

Object Treatment SEM Contrast (P) control Rumen extinguishing gastric control / carnitine Maw / ol tógyomor ---------------------------- _(%) ------------- Solids 63.4 65.6 64.5 0.8 0.13 0.34 Crude protein 63.4 66.6 64.5 1.1 0.18 0.26 Ether extract 74.4 78.7 79.3 1.0 0,008 0.70 ADF 34.0 38.4 34.6 1.8 0.29 0.19 NDF 44.0 46.9 44.1 1.2 0.36 0.15 hemicellulose 56.0 57.2 55.5 1.0 0.83 0.29 Cellulose 48.5 50.6 48.6 0.9 0.38 0.19 Ash 46.5 51.4 46.4 2.9 0.52 0.26 Energy 61.9 64.1 63.3 0.5 0.03 0.33 Organic material 65.2 67.1 66.3 0.6 0.08 0.41 Soluble residue 66.6 68.1 68.3 0.9 0.26 0.89

Table 17

Fatty acid digestion of cows receiving L-carnitine in their rumen or inoculum

Object treatment SEM Contrast (P) control Rumen extinguishing gastric Control / - carnitine Maw / ol tógyomor 12: 0 89.1 89.1 89.9 0.8 0.53 0.35 14: 0 49.0 51.8 49.3 1.05 0.28 0.14

- Table 17 (continued)

Object Treatment SEM Contrast (P) control Rumen Oltó'- gastric Control I / - carnitine Maw / ol tógyomor 16: 0 56.4 58.9 58.7 0.7 0.04 0.82 18: 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 18: 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 All 18 58.1 60.3 61.6 1.2 0.10 0.49 all 16 57.2 59.7 59.4 0.7 0.04 0.77 All 68.9 61.3 61.3 0.8 0.05 0.98

The L-carnitine supplement had the effect of increasing the total digestion of solids and organic matter and significantly increasing the digestion of energy (Tables 16 and 17). This is largely due to the increased digestibility of total fatty acids (which is also reflected in the increased digestibility of the ether extract). L-carnitine added to the rumen had an effect on increasing the digestion of neutral detergent fiber (NDF) and cellulose. In addition, L-carnitine administered to the rumen increased the total volatile fatty acid concentration in the rumen, suggesting an increase in rumen fermentation (Table 18). L-carnitine, particularly in the rumen, acts to increase the proportion of propionate and decrease the proportion of acetate in the rumen.

Table 18

Cows receiving L-carnitine in their rumen or in the gut

<ezelés Contrast (P) Object control Rumen extinguishing gastric SEM Control / - carnitine Maw / ol tógyomor pH 5.75 5.68 5.71 0.05 0.42 0.70 NH ₃ , mg / dl 10.2 9.2 9.2 0.7 0.20 0.94 Table 18 (cont'd as TAS) Object Treatment Contrast (P) control Rumen extinguishing gastric SEM Control / - carnitine Maw / ol tógyomor Total volatile fatty acids, mmol 120.2 125.5 120.2 1.9 0.29 0.09 Volatile fatty acid, mol / 100 mmol Acetate 50.5 57.2 57.4 0.5 0.08 0.61 propionate 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: Propionate 2.06 1.90 1.96 0.05 0.08 0.43

L-carnitine administration has the effect of increasing plasma glucose levels and decreasing levels of non-esterified fatty acids (NEFAs). L-carnitine added to the inoculum stomach acts towards a decrease in plasma cholesterol (Table 19).

Table 19

Plasma concentrations of metabolites of cows receiving L-carnitine in their rumen or graft

Treatment Contrast (P) Object control Rumen extinguishing gastric SEM Control / - carnitine Maw / ol tógyomor NEFA, ppm / ml 181.5 167.3 163.9 * 8.6 0.18 0.79 Cholesterol, mg / dl 224.4 224.6 210.0 4.7 0.27 0.07 Glucose mg / dl 81.0 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

L-carnitine administered to the rumen results in improved nitrogen retention and productive nitrogen, mainly due to slightly improved nitrogen digestion (Table 20). L-Carnitine increases the energy that can be digested and metabolized from food but does not increase the energy excretion in milk, indicating that the excess energy is stored in the body (Tables 21 and 22).

Table 20

Nitrogen recovery of cows given L-carnitine in their rumen or in the gut

Object Treatment SEM Contrast (P) control Rumen extinguishing gastric Control I / - carnitine Maw / ol tógyomor N intake, g / day 782 784 771 15 0.85 0.35 N selection, g / day Stool ¹ 285 260 274 9 0.14 0.32 Urine 228 228 227 10 0.99 0.93 Milk N, g / day 202 204 199 4 0.96 0.35

Table 20 (continued)

Object Treatment SEM Contrast (P) control Rumen extinguishing gastric Control I / - carnitine Maw / ol tógyomor Absorbed N, g / day 496 524 498 15 0.45 0.25 Withheld N, g / day 67 92 72 6 0.07 0.05 Effective N, g / day 268 296 I 271 8 0.17 0.06 N,% intake Stool Urine Milk ² Withholding Effective 36.6 29.3 25.9 8.2 34.2 33.5 29.0 26.3 11.2 37.5 35.5 29.5 25.7 9.3 35.0 1.1 0.9 0.3 0.7 0.9 0.18 0.98 0.76 0.06 0.09 0.25 0.75 0.15 0.11 0.09 N%, absorbed Urine Milk detained Effective 46.5 40.8 12.7 53.6 43.7 39.7 16.6 56.3 45.7 40.1 14.1 _f 54.3 · 1.1 0.8 1.2 1.1 0.23 0.40 0.11 0.23 0.23 0.71 0.18 0.23 ^ Transmission effect Direct effect = 0.8 P 263.7 274.4 307.9 0.49 0.85 ² Transmission effect Direct effect p = 0.10 25.8 27.1 24.8 0.72 0.82

- 34 Table 21

The energy recovery of cows given L-carnitine in their rumen or graft

Object Treatment SEM Contrast (P) control Rumen extinguishing gastric Control / - carnitine Maw / ol tógyomor (MJ / day) Energy intake 498.2 499.0 494.0 11.3 3.8 3.3 Stool energy 190.1 178.8 181.2 3.8 0.33 2.7 Digestible energy 308.1 320.3 312.8 8.8 1.9 2.4 Urine energy 17.6 18.4 19.7 0.8 0.80 1.7 Gas power 23.4 24.3 23.4 0.8 3.2 2.34 metabolizable energy 267.1 277.6 269.6 7.5 2.1 2.01 Maintenance energy ¹ 65.7 65.3 64.9 ' 0.42 0.88 0.32 The maintenance surface is metabolizable energy 201.4 212.3 204.7 7.1 1.97 2.05 Milk energy 121.8 120.6 118.5 1.26 0.75 1.38 Weight ² 577 574 570 3 0.22 0.32 ¹ Transmission effect Direct effect p = 0.01 15.8 15.5 15.4 0,002 0.11 ² Transmission effect Direct effect p = 0.01 584 571 566 0,002 0.12

• ·· »··

-3 522. Spreadsheet

The energy distribution of cows receiving L-carnitine in their rumen or graft

Object Treatment SEM Contrast (P) control Rumen extinguishing gastric Control / - carnitine Maw / ol tógyomor (% total energy intake) Stool energy 38.1 35.9 36.7 0.6 0.03 0.33 Urine energy 3.5 3.7 4.0 0.2 0.13 0.17 Gas energy ¹ 4.7 4.9 4.8 0.1 0.33 0.31 metabolizable energy (ME) 53.6 55.6 54.5 ' 0.4 0.03 0.14 The maintenance above energy metabolizable energy 40.4 42.3 41.3 0.6 0.11 0.29 Milk energy 24.7 24.5 24.0 6 0.64 0.60 Raw efficiency ^2.3 % 64.2 58.5 58.4 2.0 0.32 0.99 ¹ Moe and Tyrrell (1979) calculated from a regression equation ² Milk Energy / Maintenance Energy Over ME ³ Transmission effect Direct effect averages p = 0.0497 62.0 62.2 i 53.9 0.15 0.03

Claims (17)

Claims I A method of increasing the rate of growth of ruminants comprising administering to the ruminant an effective amount of carnitine. The method of claim 1, wherein the carnitine is introduced into the feed or water to feed the ruminant. 3. The method of claim 1, wherein the ruminant is a beef cattle, a dairy cattle, a pig or a ram. The process of claim 1, wherein the carnitine is L-carnitine or a salt thereof. The method of claim 1, wherein the effective amount is about 125 mg to about 20 g / person / day of carnitine. 6. The method of claim 1, wherein the ruminant is a dairy cow and an effective amount of about 5 g / person / day of carnitine is added. 7. The method of claim 1, wherein the ruminant beef is an effective amount of about 2 g / person / day of carnitine. 8. A method of facilitating the separation of milk components in a milk ruminant, comprising administering to the ruminant an effective amount of carnitine orally. 9. The method of claim 8, wherein the carnitine is admixed with water or feed and fed to the ruminant. 10. The method of claim 8, wherein the ruminant is dairy cattle or goats. 11. The method of claim 8, wherein the carnitine is L-carnitine. - 37 ··· 12. The method of claim 8 wherein the effective amount is from about 125 mg / person / day to about 20 g / person / day of carnitine. 13. The method of claim 12, wherein the ruminant dairy cattle is an effective amount of about 5 g / person / day of carnitine. 14. The method of claim 12 wherein the ruminant beef is an effective amount of about 2 g / person / day of carnitine. 15. A nutritional composition for ruminants comprising between 125 mg and 20 g of carnitine per animal per day. 16. A composition according to claim 15, characterized in that it contains high amounts of green or fodder. 17. The composition of claim 15, wherein the carnitine is L-carnitine or a salt thereof.