COMPOSITIONS OF LIPASES AND PREGASTRIC ESTERASES FOR MAMMALIA NUTRITION SUPPORT

Abstract

Compositions and methods are disclosed containing lingual lipase or another pregastric esterase as a nutritional composition for use in neonatal mammals or mammals with fat maldigestion. The compositions may be used as a stand-alone feed, or an additive to milk, milk or replacers. The composition may also include micronutrients, macronutrients, and bioactive dietary components for neonate mammals or mammals of any age with fat maldigestion Mammals include ruminants, porcines, horses, camelids, dogs, cats, or humans. Lingual lipase or pregastric esterase as a nutritional supplement may substantially improve the digestion of fats in mammals unable to effectively digest fats. The lingual lipase or esterase is preferably from an animal source. The composition may contain butterfat, micellar casein, whey, non-denatured proteins, and a source of lactose. Methods of treating fat maldigestion with the compositions are also disclosed.

Claims

1. A nutritional composition for a mammal comprising a combination of: a. a preduodenal lipase or esterase that does not require a co-factor for activity, selected from lingual lipase, pregastric lipase, gastric lipase, and pregastric esterase, or a combination thereof, wherein the preduodenal lipase or esterase is from a mammalian source or is a mammalian-derived protein produced biosynthetically; b. butterfat; and c. a probiotic and a prebiotic.

2. A nutritional composition comprising a combination of: a. a preduodenal lipase or esterase that does not require a co-factor for activity, selected from lingual lipase, pregastric lipase, gastric lipase, and pregastric esterase, or a combination thereof, wherein the preduodenal lipase or esterase is from a mammalian source or is a mammalian-derived protein produced biosynthetically; b. butterfat; and c. a probiotic and a prebiotic, wherein the composition is administered to neonatal mammals or a mammal with fat maldigestion.

3-5. (canceled)

6. The nutritional composition of claim 1 wherein the mammal is a ruminant, a porcine, a horse, a camelid, a dog, a cat, or a human.

7. The nutritional composition of claim 1 wherein the mammal is a ruminant selected from a bovine, a buffalo, a deer, a goat, and a sheep.

8. The nutritional composition of claim 1 wherein the mammal is less than 48 hours old.

9. The nutritional composition of claim 1 wherein the mammal is suffering from an inability to effectively digest fats.

10. The nutritional composition of claim 1 wherein the mammal is suffering from malnutrition from an inability to effectively digest fats.

11. The nutritional composition of claim 1, wherein the composition further comprises milk from the same species as the mammal or a different species of mammal.

12. The nutritional composition of claim 1, wherein the composition further comprises an artificial milk.

13. The nutritional composition of claim 1, wherein the composition further comprises an additive selected from one or more of kelp, omega-3 fatty acids,

14. The composition of claim 1, wherein the preduodenal lipase or esterase does not require a co-factor for activity, and the preduodenal lipase or esterase is selected from lingual lipase, pregastric lipase, gastric lipase, and pregastric esterase, or a combination thereof, wherein the preduodenal lipase or esterase is from a mammalian source or is a mammalian-derived protein produced biosynthetically, and butterfat, a probiotic and a prebiotic in the manufacture of a liquid composition for the treatment of fat maldigestion in a mammal.

15. A nutritional composition for neonatal mammals or mammals with fat maldigestion comprising a combination of: a. a preduodenal lipase or esterase that does not require a co-factor for activity, selected from lingual lipase, pregastric lipase, gastric lipase, and pregastric esterase, or a combination thereof wherein the preduodenal lipase or esterase is from a mammalian source or is a mammalian-derived protein produced biosynthetically; b. butterfat; c. a probiotic and a prebiotic; and d. micellar casein or non-denatured whey protein or both.

16. The composition of claim 15 further comprising lactose.

17. The composition of claim 15 further comprising a vitamin supplement, a mineral supplement, or an omega-3 fatty acid supplement, or a combination thereof.

18. A complete milk replacement for neonatal mammals or mammals with fat maldigestion comprising the composition of claim 15.

19-21. (canceled)

21. A nutritional supplement that is added to milk or a milk substitute for neonatal mammals or mammals with fat maldigestion comprising the composition of claim 1.

22. (canceled)

23. (canceled)

Description

DETAILED DESCRIPTION

[0029] The present invention addresses the problem of malnutrition in newborn mammals, especially those that are not naturally fed at the breast or udder (in the case of bovines), those with failure-to-thrive, premature, nutritionally stressed, and more mature mammals with a fat maldigestion disorder. With regard to neonates, it is postulated by the present inventors that malnutrition can occur because of a lack of hydrolase activity in a newborn that is not naturally suckled. Accordingly, this invention provides compositions and methods containing lipases or esterases from mammalian sources that may address these issues. This invention is particularly applicable to infants in their first 48 hours post-partum, where nutritional deficiencies may first appear. However, the compositions and methods of this invention may also be of value in older infants or more mature mammals suffering from a fat maldigestion disorder.

[0030] A fat maldigestion disorder is any condition in which fats are not normally digested. The absorption of dietary fat is very efficient in healthy adults and as little as 4-5% of the ingested fat is excreted..sup.19 By contrast, the process is much less efficient in newborns and especially in premature infants, where it has been measured (by fat in the feces) as low as 65% absorption,.sup.20 i.e., at least 35% of dietary fat is not absorbed. It has also been reported that as little as 79% of fat in cystic fibrosis patients is absorbed..sup.21 These all represent fat maldisgestive conditions in which the mammal is unable to effectively digest fats. The problem is particularly severe if it results in malnutrition. .sup.19 Margit Hamosh, n. 1..sup.20 Id..sup.21 Mini Kalivianakis, et al. “Fat malabsorption in cystic fibrosis patients receiving enzyme replacement therapy is due to impaired intestinal uptake of long-chain fatty acids”, Am. J. Clinical Nutrition, 1999 69(1) 127-134, doi: 10.1093/ajcn/69.1.127

[0031] Infant bovines born into the industrial farming model, especially dairy farming, are typically removed from the mother and the calving environment almost immediately after birth. Mis-mothering, calf-cow rejection, and adverse environmental or hygiene conditions mean that leaving the calf on the cow is often not effective or desirable. The cow joins the milking herd. Calves are raised separately from their mother, using milk or milk replacers. These infants frequently fail to thrive, meaning their weight gain, energy level, and overall health may be inferior to naturally-fed calves.

[0032] The present inventors have observed that raw milk, including colostrum, or milk replacers including reconstituted milk from milk powders, when fed to bovine newborns often makes the calf ill, resulting in a failure-to-thrive. This failure-to-thrive can be a significant economic problem. By contrast, calves that are sustained by the natural suckling off the mother thrive, compared to animal infants who are removed from their mother and reared using other less-natural systems. In modern dairy farming, bottle and tube feeding are employed with newborn calves that are taken away from the mother shortly after birth. These latter animals often fail to thrive.

[0033] Accordingly, the present inventors postulate that infants who do not, for whatever reason, naturally suckle at the udder or breast (i.e., the mothers' mammary glands) are susceptible to fat maldigestion disorders in the first few days after birth and may suffer from malnutrition, diarrhea, dehydration and needless mortality. Although the above discussion mentions bovines, infants from other species, including humans, may experience the same problems.

[0034] Bovine calves given lingual lipase with artificially fed milk (i.e., not at the mother's udder) are less sickly, more energetic, have shiny coats, sweet good smelling stools (indicating better digestion), grew faster and put on more weight in a fixed amount of time due to being able to digest milk more efficiently, and also consume more milk than those not fed naturally from the mother.

[0035] The lack of stimulation of the lingual glands on the tongue may deny the infant the necessary lipase to immediately modify the butterfat in milk by contact with the secreted lipase. Moreover, the presence of abundant free fatty acids (FFAs) creates an environment that is positive for desirable flora and negative to undesirable flora, i.e., it improves the health of the microbiome.

[0036] The proposed lack of lingual lipase or pregastric esterase exists in bottle fed calves, even though such calves may suckle on a bottle or other artificial teat. Since these devices are much more efficient at delivering milk than a natural teat, the feeding time is much shorter, which may account for the lack of lingual lipase. Moreover, many calves do not suckle well. Compromised calves (cold, premature, difficult birth, mis-mothered, abandoned, etc.) often have temporary neurological challenges, which compromises the suckling reflex and mechanisms, and may therefore reduce the stimulation of natural lingual lipase. Another issue is that in the dairy industry, some calves are bucket fed from day one, so they do not suckle at all. Yet another factor is that bottle fed system producers and extension services may recommend limited milk volumes as a cost and labor saver, and to mitigate nutritional scours (diarrhea) that commonly occur when calves are fed to appetite. Diarrhea and insufficient nutrition can lead to dehydration and death. This advice may underestimate how much milk calves can consume if their digestive systems are healthy. Another factor is that artificial systems usually have an environment that stresses the calf to some degree—different smells, tastes, touches (for example, the mother licking the calf) etc. This may diminish normal suckling effects and natural lipase production.

[0037] Another issue is that fat maldigestion results in malabsorption of nutrients. This problem may be addressed in the inventive formulations by the addition of nutrients, both macro and micro nutrients, in various forms and bioactive nutrient components, For example, a macro nutrient may be micellar casein or isolated soy protein or omega 3 fatty acids or a carbohydrate such as lactose or glucose, or a digestive aid including enzymes. For example, bioactive nutrition components may be caffeine, isoflavones, growth factors, anti-inflammatory components or anti-oxidant plant pigments.

Lipases and Esterases

[0038] The present inventors postulate that a lack of essential preduodenal lipases, such as pregastric esterases or lipases (PGE's) in non-naturally fed infants deprives the infant of correct nutrition. The absence of PGE's in raw milk, pasteurized milk, or substitute milk formulae can result in infant ill-thrift or illness due to inefficient digestion. This may be caused by the known low activity of pancreatic and intestinal lipases in newborn mammals..sup.22 Thus, in the absence of PGE, there may be insufficient lipase activity further down the digestive tract to break down the triglyceride fats in butterfat in milk. This same principle may apply in other fat maldigestion conditions not involving neonates or infants, such as cystic fibrosis, pancreatic lipase insufficiency, non-alcoholic fatty liver, alcoholic fatty liver or post-surgical conditions. In these situations, lipases may be useful as a component of a nutritional supplement to aid in fat digestion. Cystic fibrosis patients often have pancreatic insufficiency and fail to produce sufficient pancreatic lipase which can cause fat maldigestion. .sup.22 Note 1, at 615, col. 2, third para.

[0039] The inventors have found that the addition of any of several esterases or lipases to infant formula for non-naturally suckling infants significantly improves the thrive factor in the infant, which presumably is a result of improved digestion of fats and development of a functional digestive microbiome.

[0040] In addition, the present inventors have found that the addition of lingual lipase to milk fed artificially to calves improves survival and reduces infant mortality. A potentially important element however is that different species have different lipases, and the present inventors believe the lipase must be matched to the species. Preferably, the lipase used is native to the species, for example bovine lingual lipase being added to feed for bovine calves. Similarly, human lingual lipase will perform better in humans. Conversely, microbial or plant lipases are unlikely to confer significant dietary benefits when fed to e.g., calves or humans, when required to work in situ.

[0041] Lingual lipase is a member of a family of digestive enzymes called triacylglycerol lipases, EC 3.1.1.3, that use the catalytic triad of aspartate, histidine, and serine to hydrolyze medium and long-chain triglycerides into partial glycerides and free fatty acids. The enzyme, released into the mouth along with the saliva, catalyzes the first reaction in the digestion of dietary lipid, with diglycerides being the primary reaction product. Lingual lipase has pH optimum pH of 4.5-5.4, and catalyzes the hydrolysis of esters in that absence of bile salts. The lipolytic activity continues in the stomach after food is swallowed, and it has been proposed that fats generally may not digest properly in neonates in the absence of lingual lipase..sup.23 Enzyme release is signaled by autonomic nervous system after ingestion, at which time the serous glands under the circumvallate and foliate lingual papillae on the surface of the tongue secrete lingual lipase to the grooves of the circumvallate and foliate papillae. .sup.23 Note 1

[0042] Other lipases, such as pancreatic lipases, lipases present in milk, and lipases from plant or fungal/biosynthetic sources, typically require a co-factor for the lipase activity, in particular, bile salts. No co-factor is required for animal-derived PGE's, including lingual lipase..sup.24 This is a potentially important feature for the lipases of this invention. .sup.24 Note 1 at 143, bottom.

[0043] The lipase for this invention may be obtained from mammalian sources. For example, lingual lipase used in cheese manufacture is obtained from tongues from calves, kids, lambs. Bovine and other mammalian lingual lipases are commercially available.

[0044] In an embodiment, the lipases or esterases for this invention may be mammalian enzymes produced synthetically, for example by inserted an appropriate DNA sequence into an expression system and cultivating the organism to produce the enzyme. Exemplary expression systems include bacteria such as E. coli and B. subtilis, and yeasts such as Saccharomyces. Many other expression systems are well known in the art for making heterologous peptides..sup.25 .sup.25 See, e.g, Joan Lin Cereghino James M. Cregg, “Heterologous protein expression in the methylotrophic yeast Pichia pastoris,” FEMS Microbiology Reviews, Volume 24, Issue 1, 1 Jan. 2000, Pages 45-66, https://doi.org/10.1111/j.1574-6976.2000.tb00532.x

[0045] The amino acid sequence of potential human and animal lingual lipase and pregastric esterases is known..sup.26 .sup.26 See for example “Cloning and expression of cDNA encoding human lysosomal acid lipase/cholesteryl ester hydrolase. Similarities to gastric and lingual lipases” J. Biol. Chem. 266 (33), 22479-22484 (1991). The sequence of bovine pregastric esterase is also known, (Timmermans, M. Y., Teuchy, H. and Kupers, L. P., The cDNA sequence encoding bovine pregastric esterase, Gene 147 (2), 259-262 (1994); NCBI NP_776528.

[0046] The lipases and esterases of value in this invention may be, but are not necessarily, species specific. That is, a lipase from one species, for example a bovine, may not be useful, or may have reduced efficiency, in hogs for example. In any event, the inventors believe that lipases from non-mammalian sources, such as plants or bacteria, which have been suggested previously as supplemental feeds, are unlikely to confer any significant benefit to humans or economically important animals when required to work in situ.

Components of Natural Milk

[0047] In an embodiment, this invention discloses a feed or nutritional supplement product containing lingual lipase and or other lipases or esterases from mammalian sources that do not require bile acids for activation, for use with neonate or infant and older mammals. In an embodiment, the feed product is natural or artificial milk or a nutritional supplement. As used herein, “natural milk” is milk or colostrum from the same species as the neonate. As used herein “formulated natural milk” is milk that is not obtained from a lactating mother of the same species (for example, bovine milk fed to human infants). “Artificial milk” includes any liquid feed product or a manufactured formula that may be based on milk (for example, bovine milk) but has significant additional ingredients, or a manufactured formula not based on milk at all. In an embodiment, this invention discloses lingual lipase or lipases from mammalian sources as a nutritional supplement in natural or artificial milk fed artificially to neonatal mammals.

[0048] Casein is the primary protein in bovine milk. Approximately 80% of the proteins in bovine milk and between 20% and 45% of the proteins in human milk are casein. Casein is relatively hydrophobic, making it weakly soluble in water. It occurs natively in milk as a suspension of particles, called casein micelles (also termed herein “micellar casein”), which show a limited resemblance to surfactant-type micelles in the sense that the hydrophilic parts reside at the surface of the micelles and casein micelles are spherical. However, in contrast to surfactant micelles, the interior of a casein micelle is highly hydrated. The caseins in the micelles are held together by calcium ions and hydrophobic interactions. Any of several molecular models could account for the special conformation of casein in the micelles. Casein is a principal component of milk protein concentrate (MPC), which is commercially available and used as an additive in many food products.

[0049] During digestion, casein becomes truly insoluble from the action of chymosin, which cleaves off the kappa casein and destabilizes the micelle, allowing the modified micelle to have both negative and positive charges. The micelles rotate allowing positive to attach to negative charged regions of the modified micelles and a gel is formed in the stomach.

[0050] Whey protein is another macronutrient derived from milk with potent nutritive value. Preferably, non-denatured whey is used. Whey/immunoglobulin (antibody carrying) compounds are a component in MPC in non-denatured form, or it may be added, for example as sweet whey powder (which is non-denatured but may be pasteurized) to the inventive formulations.

[0051] In an embodiment, the feed product of this invention also includes lactose, the sugar in natural mammalian milk. The feed product of this invention ideally will contain about 2% to 7% by weight of lactose. Lactose may be added directly as lactose powder to the inventive formulations, or a component such as sweet whey or sweet cream may used, both of which contain lactose.

Additional Ingredients

[0052] The inventive compositions and methods may include supplemental vitamins, minerals, or other nutrients. Supplemental nutrients may include, for example, kelp (a source of vitamins), additional vitamins or minerals (also termed “micronutrients”), macronutrients such as proteins, carbohydrate, and fats. Macronutrients for the inventive compositions and methods include isolated soy proteins, omega-3 fatty acids such as alpha-linolenic acid (ALA), docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA), or a combination thereof, lactose, a prebiotic, and a probiotic.

[0053] A potential issue with newborns is that no bacteria are present in the digestive tract of a newborn animal, which can cause digestive problems. Colostrum can be collected from mothers mechanically and then fed to calves artificially by bottles or a feeding tube down the throat directly into the stomach. But in the absence of appropriate flora in the gut, the colostrum may not digest properly. This problem may be addressed in the inventive formulations by the addition of a probiotic with or without a prebiotic.

[0054] A probiotic adds beneficial digestive bacteria, which are an additional requirement for nutrition. Prebiotics are food ingredients that induce the growth or activity of beneficial microorganisms in the gut..sup.27 Prebiotics can alter the composition of organisms in the gut microbiome. The addition of prebiotics and probiotics can populate the gut with appropriate bacteria that are required for digestion. .sup.27 Hutkins R W et al., “Prebiotics: why definitions matter” Curr Opin Biotechnol. 2016 February; 37:1-7. doi: 10.1016/j.copbio.2015.09.001. Epub 2015 Sep. 29.

[0055] Prebiotics stimulate the growth or activity of advantageous bacteria that colonize the large bowel by acting as substrate for them. In an embodiment, a prebiotic may be a composition of inulin, fructo-oligosaccharides (FOS), galactooligosaccharides (GalOS), lactulose, or pectin..sup.28 Inulin is a polysaccharide composed mainly of fructose units (fructans), and typically has a terminal glucose. It consists of chain-terminating glucosyl moieties and a repetitive fructosyl moiety, which are linked by β(2,1) bonds. Because of the β(2,1) linkages, inulin is indigestible by the human enzymes ptyalin and amylase, which are adapted to digest starch. As a result, it passes through the upper digestive tract intact. Only in the colon do bacteria metabolize inulin contributing to its functional properties: reduced calorie value, dietary fiber, and prebiotic effects. Without color and odor, it has little impact on sensory characteristics of food products. After reaching the large intestine, inulin is converted by colonic bacteria to a prebiotic gel that is highly nourishing to gut microflora. Sources of inulin include bananas, chicory root, and Jerusalem Artichoke (a tuber vegetable native to North America). .sup.28 Belén Gómez, et al., “Purification, Characterization, and Prebiotic Properties of Pectic Oligosaccharides from Orange Peel Wastes,” J. Ag. Food Chem., 2014 62 (40), 9769-9782 DOI: 10.1021/jf503475b

[0056] Significantly, the enzymes mentioned above, ptyalin and amylase, are presumably not limited to humans. In particular, immature ruminant animals such as bovines or goats are not actually ruminants with a multichamber stomach at birth. Bovines and goats have a monogastric digestive tract at birth until age 6-12 weeks, and it is believed that a prebiotic such as inulin will pass through the digestive tract of young ruminants to lodge in the large intestine and exert a prebiotic effect before these young animals develop a true ruminant upper digestive tract.

Compositions

[0057] In an embodiment, the inventive methods and compositions includes lipases or esterases, and may include ingredients such as one or more of milk (dried or fresh), kelp, additional vitamins or minerals, macronutrients such as micellar or native casein, isolated soy proteins, omega-3 fatty acids, carbohydrates including lactose, a prebiotic, and a probiotic. In an embodiment, for example, the milk is a carrier, and the kelp is a source of minerals and vitamins beneficial to the newborn.

[0058] The amount of lipases in the feed supplement can be adjusted based on the amount of fat in natural milk for the species or the amount of fat in the diet or nutritional supplement as appropriate for the mammalian species. For example, domestic cattle milk has about 4-5% butterfat, buffalo milk has 7-9% butterfat in natural milk, domestic pig milk has about 7-8% fat, and human milk has about 4.5% fat. For example, additional lipase would be added to a high fat content natural milk like that from a buffalo. Diets for mammals with fat maldigestion, failure-to-thrive, nutritional stress and post surgical conditions will vary according to recommended nutrition protocols for each species, varying ages, conditions and sizes. Thus lipases and additional components and amounts of each will vary.

[0059] In an embodiment, the feed product of this invention may include added butterfat. Butterfat may be a superior form of fat for newborns, especially bovines. Normally, the butterfat of this embodiment is from whole milk, and the butterfat is the natural fat (cream) present in natural milk.

[0060] The inventive compositions and methods are expected to be equally valid for other mammals besides bovines, including other economically important farm or domestic animals, such as other ruminants such as buffalo, deer, goats, sheep, porcines (hogs), horses, camelids (camels, llamas, or alpacas), and domestic pets such as dogs, or cats. For example, in species such as porcines that produce large litters, one or two infants may be excluded and left to die naturally. This invention allows these potentially valuable animals to be rescued and raised to maturity.

[0061] This invention may also be of value to exotic and endangered animals such as those raised in zoos or nature reserves. Newborns are often removed from mother at birth or shortly thereafter in these environments to enhance survival prospects.

[0062] This inventive compositions and methods may also be of value for humans, and used in human infant formulas and in humans with fat maldigestion. Current guidelines suggest that humans should be fed at the breast exclusively for the first six months of life,.sup.29 yet many mothers are unable or unwilling to do that. Even where there is not obvious malnutrition, the addition of lipases to infant formula or natural human milk may improve digestion and infant health in neonates. The addition of lipase containing nutritional supplements formulated with nutrients and bioactive nutritional components to diets for specific malnutrition conditions in humans may improve health. .sup.29 World Health Organization, “Infant and young child feeding” Fact sheet, http://www.who.int/en/news-room/fact-sheets/detail/infant-and-young-child-feeding (downloaded Jul. 4, 2018)

EMBODIMENTS

[0063] A feed of this invention provides a nutritional supplement added to natural milk or a milk replacer or formulated into a non-milk nutritional supplement. In an embodiment, the supplement may include a range of ingredients depending on the species, weight, age or health condition. An example for calves may be: [0064] Lipase powder 0.001 to 10 grams [0065] Prebiotic 0.001 to 10 grams [0066] Probiotic 0.001 to 10 grams [0067] Dried powdered kelp 0.001 to 10 grams [0068] Mineral mix 0.001 to 3 grams [0069] Powdered Non-fat dried milk 1.0-20 grams

[0070] These ingredients would be blended into sufficient natural milk or a milk substitute so that there is approximately 5 g of this supplement in 4 liters (about one US gallon).

[0071] In an alternative embodiment for a calf feed, the ingredients may be: [0072] Lipase powder 0.001 to 10 grams [0073] Prebiotic 0.001 to 10 grams [0074] Probiotic 0.001 to 10 grams [0075] Dried powdered kelp 0.001 to 10 grams [0076] Mineral mix 0.001 to 3 grams

[0077] This would be diluted to about 4-5 g of solid in 4 liters of milk or a milk substitute.

[0078] In a more specific embodiment for bovine calves, the following materials may be used: [0079] Lipase powder 1.0 gram [0080] Prebiotic 3.0 grams [0081] Probiotic 4.5 grams [0082] Dried powdered kelp 3.0 grams [0083] Mineral mix 3.0 grams [0084] Powdered Non-fat dried milk 1.0 grams [0085] This mixture is diluted in 16 liters of natural milk or a milk substitute.

EXAMPLES

Example 1

[0086] A supplement for calves was prepared with the following ingredients: [0087] Lipase powder 1.0 gram [0088] Prebiotic 3.0 grams [0089] Probiotic 4.5 grams [0090] Dried powdered kelp 3.0 grams [0091] Mineral mix 3.0 grams [0092] Powdered Non-fat dried milk 1.0 grams [0093] All ingredients are commercially available in the USA.

[0094] This mixture was blended into 4 US gallons (15.1 liters) of natural cows milk.

Evidence of Efficacy

[0095] A Missouri dairy farm with about 850 milking cows used this lingual lipase supplement as part of their calf rearing operation. Over a thirty-month period, the supplemented milk was given to more than 1,600 heifer calves, along with more than 400 male calves. The addition of the lingual lipase supplement was continued for up to 5 weeks, or in the case of the retained male calves, up until they were sold at 1-4 weeks of age. Animals were allowed to suckle vigorously on artificial “calfetaria” teats, including continued suckling for 4-5 minutes after the provided milk was consumed. Performance of the calves improved subsequent to the inclusion of lipase. The calf rearing system, the management, and the feed and feeding systems remained the same as previous years without the lingual lipase supplement. Changes measured or observed included: [0096] improved digestion as evidenced by stool condition and consistency; [0097] zero nutritional scours; [0098] improved intelligence as evidenced by improved vigor, mobility, and herd instincts; [0099] stronger appetite; [0100] improved immunity; [0101] improved and accelerated growth rate; [0102] improved performance as juveniles and adults [0103] Lower mortality; [0104] increased survival rates of calves compromised by factors such as difficult birth, abandonment by their mother, extreme cold or heat stress;

[0105] The improved start to life enabled by the inclusion of lingual lipase translated to accelerated growth and vigor and enabled these calves to thrive and show better weight gain through to weaning weights.

Example 2

[0106] A commercial Missouri deer farm calving 80-90 hinds each spring added the same lipase supplement from Example 1, in the milk or milk substitutes given to orphaned or mis-mothered fawns. Mortality of these fawns dropped from over 50% average for the previous four seasons, to less than 5% for the two years that lipase was added. No other factors changed during that time.

Example 3

[0107] This is an adjunct formula for supplemental feeding of animals also receiving whole milk. There is no fat in this formula.

TABLE-US-00001 Material Amount % (w/w) NFDM 80.00 Lipase (bovine source) 13.33 Chicory Flour (prebiotic) 6.67 Total 100.00 NFDM = nonfat dry milk.
For bovine calves, the lipase is of bovine origin, which is commercially available.

[0108] For use, 13.33 g of this formula is added to 26 gals (98 L) of milk (natural or artificial).

Example 4

[0109] This is a complete milk replacer formula.

TABLE-US-00002 Material Amount % (w/w) MPC 70 17.06 Sweet Whey 24.53 Lipase (bovine source) 7.76 Chicory Flour (prebiotic) 3.88 Sweet Cream 46.76 Total 100.00 MPC = milk protein concentrate 70% (commercially available)
For bovine calves, the lipase is of bovine origin, which is commercially available. The sweet whey in this experiment was not denatured.

[0110] This formula is reconstituted by adding 100 g to 900 mL of water to make 1 L of formula.