WO2013056048A2

WO2013056048A2 - Nutritional products comprising beta-alanine

Info

Publication number: WO2013056048A2
Application number: PCT/US2012/059954
Authority: WO
Inventors: Timothy M. CHAPMAN; Normanella T. Dewille; Douglas J. WEARLY; Jeffrey H. Baxter; Kelley J. LOWE; Terrance B. MAZER
Original assignee: Abbott Laboratories
Priority date: 2011-10-13
Filing date: 2012-10-12
Publication date: 2013-04-18
Also published as: TW201320908A; WO2013056048A3

Abstract

Disclosed are nutritional products, and particularly, nutritional liquids, comprising beta-alanine. The nutritional products not only provide benefits for individuals concerned with muscle health and functionality, but can also be administered without the adverse side-effect of paresthesia caused by ingestion of beta-alanine.

Description

NUTRITIONAL PRODUCTS COMPRISING BETA-ALANINE

FIELD OF THE DISCLOSURE

[0001] The present disclosure relates to nutritional products comprising beta-alanine that can be administered without the adverse side-effect of paresthesia. Additionally, the present disclosure relates to methods of reducing the incidence of paresthesia by administering the nutritional products.

BACKGROUND OF THE DISCLOSURE

[0002] Manufactured nutritional liquids comprising a targeted selection of nutrition ingredients are well known and widely available, some of which may provide a sole source of nutrition while others may provide a supplemental source. These nutritional liquids include powders that can be reconstituted with water or other aqueous liquid, as well as ready to drink nutritional liquids such as milk or protein based emulsions or non-emulsified or substantially clear liquids. These nutritional liquids are especially useful when formulated with selected nutritional ingredients.

[0003] One such nutritional ingredient is beta-hydroxy-beta-methylbutyrate (HMB). HMB is a naturally occurring amino acid metabolite that is known for use in a variety of nutritional products and supplements. HMB is known for use in such products to help build or maintain healthy muscle mass and strength in selected individuals. Calcium HMB is the most commonly used form of HMB when formulated into oral nutritional products, which products include tablets, capsules, reconstitutable powders, clear nutritional liquids and emulsions.

[0004] Since HMB is most often used in individuals to support the development and maintenance of healthy muscle mass and strength, many HMB products have been formulated with additional nutrients that may also be helpful in promoting healthy muscle. Some of these HMB-containing products contain additional nutrients such as fat, carbohydrate, protein, vitamins, minerals and so forth. [0005] Beta-alanine is an additional selected ingredient that may be useful in nutritional liquids or other nutritional products. Beta-alanine is considered a complement to HMB as it is used for maintaining muscle functionality during exercise or other physical activity. Beta-alanine is a non-essential amino acid and is the only naturally occurring beta-amino acid. Beta-alanine may be useful to increase muscle mass, delay muscular fatigue and increase aerobic and anaerobic endurance.

[0006] Although nutritional liquids containing these beneficial ingredients are known, ingestion of beta-alanine has been found to lead to paresthesia, a significant adverse side-effect with symptoms that include abnormal sensations such as burning, tingling, or a "pins-and-needles" feeling. Typically, administration of nutritional liquids or other nutritional products including beta-alanine result in a tingling flushing sensation in the face and lips minutes to hours after ingestion.

[0007] The present disclosure is therefore directed to nutritional products, in the form of nutritional liquids, comprising relatively high concentrations of beta- alanine, alone or in combination with calcium HMB, wherein the resulting nutritional product can be administered without the adverse side-effect of paresthesia caused by ingestion of the beta-alanine.

SUMMARY OF THE DISCLOSURE

[0008] One embodiment of the present disclosure is directed to a nutritional liquid comprising beta-alanine and protein, wherein at least a portion of the beta- alanine resides in a whey protein phospholipids concentrate and oil combination.

[0009] Another embodiment of the present disclosure is directed to a nutritional liquid comprising beta-alanine, protein, and glycine.

[0010] Another embodiment of the present disclosure is directed to a nutritional liquid comprising from about 0.26% to about 0.47% by weight beta- alanine, from about 3% to about 8% by weight protein, and from about 0.26% to about 0.38%) by weight glycine. [0011] Another embodiment is directed to a method of reducing the incidence of paresthesia caused by ingestion of beta-alanine. The method comprises: administering to an individual a nutritional liquid comprising beta-alanine and protein, wherein at least a portion of the beta-alanine resides in a whey protein phospholipids concentrate and oil combination.

[0012] Another embodiment of the present disclosure is directed to a method of reducing the incidence of paresthesia caused by ingestion of beta-alanine. The method comprises: administering to an individual a nutritional liquid comprising beta- alanine, protein, and glycine.

[0013] It has now been found that the sensation symptoms of paresthesia associated with the ingestion of beta-alanine can be reduced or eliminated by attenuating the rise in the blood-plasma concentration of beta-alanine. The nutritional products as described herein comprise specific combinations of beta-alanine, alone, or in combination with calcium HMB and other nutrients to not only provide benefits for individuals concerned with muscle health and functionality, but to reduce the rate at which beta-alanine enters the blood, thereby reducing the incidence of paresthesia associated with ingestion of beta-alanine.

[0014] Particularly, it has been found that by combining beta-alanine with high concentrations of protein, and particularly whey and soy proteins, gastric transit time is prolonged, which has been found to slow the absorption of beta-alanine into the blood, thereby reducing the blood-plasma concentration of beta-alanine and reducing incidences of paresthesia.

[0015] Additionally, incidences of paresthesia can be reduced by including thickening agents in combination with beta-alanine to increase the viscosity of the nutritional products. Increasing the viscosity of the nutritional products will prolong gastric transit time, which as noted above, slows the absorption of beta-alanine.

[0016] It has been additionally found that beta-alanine can reside within globules within the nutritional products to slow the release of beta-alanine, attenuating the rise of the blood-plasma beta-alanine concentration. In some embodiments, at least a portion, and suitably, all of the beta-alanine resides in whey protein

phospholipids concentrate and oil combinations to slow the release of beta-alanine.

[0017] Alternative means found to reduce the incidences of paresthesia include site competition and masking by other ingredients that may be included in the nutritional products.

DETAILED DESCRIPTION OF THE DISCLOSURE

[0018] The nutritional products comprise beta-alanine and calcium HMB. In some embodiments, the nutritional products additionally include high concentrations of protein. These and other essential features of the nutritional products, as well as some of the many optional variations and additions, are described in detail hereafter.

[0019] The term "substantially clear nutritional liquid" and "non-emulsion" as used herein, unless otherwise specified, are used interchangeably to refer to a non- emulsified or similar other liquid having a visibly clear or translucent appearance, which liquid may and typically will have a thin or watery texture with a consistency similar to that of a clear juice and most typically having a viscosity of less than about 25 centipoise as determined by a Brookfield viscometer at 22°C using a #1 spindle at 60 rpm.

[0020] The term "calcium HMB" as used herein, unless otherwise specified, refers to the calcium salt of beta-hydroxy-beta-methylbutyrate (also referred to as 3 - hydroxy-3 -methyl butyrate, beta-hydroxy isovalerate, or HMB), which is most typically in a monohydrate form. All weights, percentages, and concentrations as used herein to characterize calcium HMB are based on the weight of calcium HMB monohydrate, unless otherwise specified.

[0021] The terms "fat" and "oil" as used herein, unless otherwise specified, are used interchangeably to refer to lipid materials derived or processed from plants or animals. These terms also include synthetic lipid materials so long as such synthetic materials are suitable for oral administration to humans. [0022] The term "shelf stable" as used herein, unless otherwise specified, refers to a nutritional liquid that remains commercially stable after being packaged and then stored at 18-24°C for at least 3 months, including from about 6 months to about 24 months, and also including from about 12 months to about 18 months.

[0023] The term "resides in" as used herein, unless otherwise specified, refers to at least a portion of the beta-alanine being partially or completely located within the whey protein phospholipids concentrate and oil combination.

[0024] All percentages, parts and ratios as used herein, are by weight of the total composition, unless otherwise specified. All such weights as they pertain to listed ingredients are based on the active level and, therefore, do not include solvents or by-products that may be included in commercially available materials, unless otherwise specified.

[0025] All references to singular characteristics or limitations of the present disclosure shall include the corresponding plural characteristic or limitation, and vice versa, unless otherwise specified or clearly implied to the contrary by the context in which the reference is made.

[0026] All combinations of method or process steps as used herein can be performed in any order, unless otherwise specified or clearly implied to the contrary by the context in which the referenced combination is made.

[0027] The various embodiments of the nutritional products of the present disclosure may also be substantially free of any optional or selected essential ingredient or feature described herein, provided that the remaining nutritional product still contains all of the required ingredients or features as described herein. In this context, and unless otherwise specified, the term "substantially free" means that the selected nutritional product contains less than a functional amount of the optional ingredient, typically less than about 1%, including less than about 0.5%, including less than about 0.1%, and also including zero percent, by weight of such optional or selected essential ingredient. [0028] The nutritional products may comprise, consist of, or consist essentially of the essential elements of the products as described herein, as well as any additional or optional element described herein or otherwise useful in nutritional product applications.

Product Form

[0029] The nutritional products of the present disclosure may be in the form of nutritional liquids, which include shelf-stable, ready-to-feed liquids in emulsion or non-emulsion forms, and as a non-emulsion form may be formulated as clear or substantially clear nutritional liquids as described herein.

[0030] The nutritional products may be formulated with sufficient kinds and amounts of nutrients to provide a sole, primary, or supplemental source of nutrition, or to provide a specialized nutritional product for use in individuals afflicted with specific diseases or conditions or with a targeted nutritional benefit.

[0031] The nutritional liquids comprise beta-alanine, alone, or in

combination with calcium HMB. These embodiments include aqueous emulsions comprising fat, typically emulsified fat, as well as non-emulsions that are typically fat free. The term "fat free" as used herein, unless otherwise specified, means that the nutritional liquid typically contains less than 1.0%, more typically less than 0.5%, and more typically less than 0.1%, including zero percent, fat by weight of the nutritional liquid. The fat free formulations are typically devoid of added fat except for the fat that is inherent to other raw materials or added fat at low concentrations to aid in the manufacture the liquid.

[0032] The non-emulsion or fat free embodiments are most typically clear or translucent liquids having a thin or watery texture at room temperature or at the temperature at which the product is consumed.

[0033] The emulsion embodiments, by contrast, may comprise fat at concentrations ranging from about 1% to about 30%, including from about 2% to about 15%, and also including from about 4% to about 10%>, by weight of the nutritional emulsion.

[0034] The nutritional liquid embodiments typically contain up to about 98%o by weight of water, including from about 50%> to about 95%, also including from about 60%) to about 90%>, and also including from about 70%> to about 85%, of water by weight of the nutritional liquids.

[0035] The nutritional liquids may also have a caloric density tailored to the nutritional needs of the ultimate user, although in most instances the liquids comprise from about 100 to about 500 kcal/240 ml, including from about 150 to about 350 kcal/240 ml, and also including from about 200 to about 320 kcal/240 ml.

[0036] The nutritional liquids may also have a pH ranging from about 2.8 to about 8.0, but most typically have a pH of from about 2.8 to about 7.3, including from about 6.8 to about 8.0 and also including from about 2.8 to about 4.6, including from about 2.9 to about 4.2, and also including from about 3.1 to about 3.9. When the product pH is maintained at between about 2.8 and about 4.6, the calcium HMB in the formulation does not interact with the soluble proteins in the liquid. This avoids the formation of sediment, gelation, and coagulation. Within this low pH range, the undesirable sediment, gelation and coagulation is prevented even at temperatures greater than 180°F, which is the minimum temperature required for a suitable process for acidified products.

[0037] Although the serving size for the nutritional products can vary depending upon a number of variables, a typical serving size ranges from about 100 to about 300 ml (approximately 3 ounces to 10 ounces), including from about 150 to about 250 ml (approximately 5 ounces to 8.4 ounces), including from about 190 ml to about 240 ml approximately 6.4 ounces to 8.4 ounces), and including about 237 ml (approximately 8 ounces). Beta-Alanine

[0038] The nutritional products comprise beta-alanine. Beta-alanine can be included in the nutritional liquids in amounts ranging from about 0.8 grams to about 1.2 grams per 8-ounce serving, including from about 0.9 grams to about 1.1 grams per 8-ounce serving, and including about 1.0 gram per 8-ounce serving.

[0039] In particular embodiments, the nutritional liquids include beta- alanine in concentrations ranging from about 0.25% to about 0.50% by weight, including from about 0.26% to about 0.47% by weight. When the nutritional product is a substantially clear nutritional liquid, the liquid includes from about 0.26% to about 0.40% by weight of beta-alanine. When the nutritional liquid is an emulsion, the emulsion includes beta-alanine in concentrations of from about 0.31% to about 0.47% by weight.

[0040] The nutritional products may be formulated with the addition of beta- alanine, or may otherwise be prepared so as to contain beta-alanine in the finished product. Any source of beta-alanine is suitable for use in the products described herein provided that the finished product contains beta-alanine at the desired level. Such sources may and typically do include free beta-alanine as well as other sources that provide free beta-alanine in the nutritional product during or after formulation.

[0041] In some particularly suitable embodiments, at least a portion of the beta-alanine resides in a whey protein phospholipids concentrate and oil combination. Milk fat is secreted from mammary epithelial cells as fat globules which are primarily composed of a globule of triglyceride surrounded by a lipid bilayer membrane similar to the apical membrane of the epithelial cells. This whey protein phospholipids concentrate (WPPC) helps to stabilize the fat globules in an emulsion within the aqueous environment of milk.

[0042] The whey protein phospholipids concentrate and oil combination includes the soy lecithin and oils and oil-soluble vitamins described herein in combination with whey protein phospholipids concentrate. The whey protein phospholipids concentrate in combination with the oil encapsulates the beta-alanine. Through encapsulation, it is possible to provide a sustained, slower release of beta- alanine into the blood, thereby reducing the adverse side-effect of paresthesia typically caused by the ingestion of beta-alanine. The amount of whey protein phospholipids concentrate for use in the nutritional liquids of these embodiments range from about 0.5 grams to about 5.0 grams per 8-ounce serving, including from about 0.6 grams to about 3.0 grams per 8-ounce serving, including from about 0.7 grams to about 1.0 gram per 8-ounce serving, and including about 0.8 grams per 8- ounce serving.

[0043] At least about 10% of the beta-alanine resides in the whey protein phospholipids concentrate and oil combination, including at least about 25%, including at least about 50%>, including at least about 60%>, including at least about 70%), including at least about 80%>, including at least bout 90%>, and including 100% of the total beta-alanine in the nutritional liquid may reside in the whey protein phospholipids concentrate and oil combination.

[0044] Although the present formulations may further comprise proteins or hydrolyzed proteins that contain peptides having beta-alanine moieties, the beta- alanine from such peptide-bound moieties are not considered part of the beta-alanine feature when defining the present disclosure. One suitable source of beta-alanine is commercially available from Compounds Solutions (Escondido, California).

Calcium HMB

[0045] In some embodiments, the nutritional products may additionally comprise calcium HMB in combination with the beta-alanine. In these embodiments, the products are either formulated with the addition of calcium HMB, most typically as a monohydrate, or are otherwise prepared so as to contain calcium and HMB in the finished product. Any source of HMB is suitable for use herein provided that the finished product contains calcium and HMB, although such a source is preferably calcium HMB and is most typically added as such to the nutritional product during formulation. [0046] The term "added calcium HMB" as used herein means a calcium salt of HMB, most typically as monohydrate calcium salt of HMB, as the HMB source added to the nutritional product.

[0047] Although calcium HMB monohydrate is the preferred source of HMB for use herein, other suitable sources may include HMB as the free acid, a salt, an anhydrous salt, an ester, a lactone, or other product forms that otherwise provide a bioavailable form of HMB from the nutritional product. Non- limiting examples of suitable salts of HMB for use herein include HMB salts, hydrated or anhydrous, of sodium, potassium, magnesium, chromium, calcium, or other non-toxic salt form. Calcium HMB monohydrate is preferred and is commercially available from

Technical Sourcing International (TSI) of Salt Lake City, Utah.

[0048] Calcium HMB may be included in the nutritional liquids in amounts ranging from about 1.0 grams to about 2.0 grams per 8-ounce serving, including from about 1.1 grams to about 1.8 grams per 8-ounce serving, and including about 1.5 grams per 8-ounce serving.

[0049] The nutritional liquids may include calcium HMB in concentrations ranging from about 0.40% to about 0.60%> by weight, including from about 0.42% to about 0.45%) by weight, and including about 0.44%> by weight. In one embodiment, when used in an emulsion, the nutritional liquid may include calcium HMB in a concentration of about 0.47% by weight. In another embodiment, when used in a substantially clear liquid, the nutritional liquid may include calcium HMB in a concentration of about 0.40% by weight.

Protein

[0050] The nutritional products may further comprise any protein or sources thereof that are suitable for use in oral nutritional products and are compatible with the essential elements and features of such products. Total protein concentrations in the nutritional liquids may range from about 0.5% to about 30%, including from about 1%) to about 15%), including from about 2%> to about 10%>, and also including from about 3%) to about 8%>, including from about 3%> to about 7%>, and including from about 3% to about 6.72% by weight of the nutritional liquid. In one particular embodiment, when the nutritional product is an emulsion, the emulsion includes protein in a total concentration of about 6.77% by weight. When the nutritional product is a substantially clear liquid, the clear liquid includes protein in a total concentration of from about 3.00% to about 4.47% by weight.

[0051] In some embodiments, it is desirable to have higher protein concentrations in the nutritional products to provide for a prolonged gastric transit time, which attenuates the rise in blood-plasma concentration of beta-alanine. This has been found to reduce the incidences of paresthesia caused by the ingestion of nutritional products with beta-alanine. In these embodiments, total protein is included in the nutritional liquids in amounts of from about 9 grams to less than 20 grams per 8-ounce serving. Particularly, when used in emulsion products, the protein is included in amounts of from about 12 grams to less than 20 grams per 8-ounce serving, including about 17 grams per 8-ounce serving. When used in substantially clear liquids, the protein is included in amounts of from about 9 grams to about 14 grams per 8-ounce serving, including from about 10 grams to about 12 grams per 8- ounce serving.

[0052] Non-limiting examples of suitable protein or sources thereof for use in the nutritional products include hydrolyzed, partially hydrolyzed or non-hydrolyzed (i.e., intact) proteins or protein sources, which may be derived from any known or otherwise suitable source such as milk (e.g., casein, whey), animal (e.g., meat, fish), cereal (e.g., rice, corn), vegetable (e.g., soy, pea) or combinations thereof. Non- limiting examples of such proteins include milk protein isolates, milk protein concentrates, whey protein, sodium or calcium casemates, whole cow's milk, partially or completely defatted milk, soy protein isolates, soy protein concentrates, and so forth.

[0053] The protein in the nutritional products may include intact proteins as that term is defined herein to improve product stability and minimize the development of bitter flavors and after taste in the formulation during shelf life. Carbohydrate

[0054] The nutritional products may further comprise any carbohydrates that are suitable for use in an oral nutritional product and are compatible with the essential elements and features of such products. Carbohydrate concentrations in the nutritional liquids, for example, may range from about 5% to about 40%, including from about 7% to about 30%>, including from about 10%> to about 25%, by weight of the nutritional liquid.

[0055] Non-limiting examples of suitable carbohydrates or sources thereof for use in the nutritional products described herein may include maltodextrin, hydrolyzed or modified starch or cornstarch, glucose polymers, corn syrup, corn syrup solids, rice-derived carbohydrates, sucrose, glucose, fructose, lactose, high fructose corn syrup, honey, sugar alcohols (e.g., maltitol, erythritol, sorbitol), artificial sweeteners (e.g., sucralose, acesulfame potassium, stevia) and combinations thereof.

Fat

[0056] The nutritional products may further comprise fat, most typically as emulsified fat, concentrations of which may range from about 1% to about 30%, including from about 2% to about 15%, and also including from about 4% to about 10%), by weight of the nutritional liquid.

[0057] Suitable sources of fat for use herein include any fat or fat source that is suitable for use in an oral nutritional product and is compatible with the essential elements and features of such products.

[0058] Non-limiting examples of suitable fats or sources thereof for use in the nutritional emulsions described herein include coconut oil, fractionated coconut oil, soy oil, corn oil, olive oil, safflower oil, high oleic safflower oil, MCT oil (medium chain triglycerides), sunflower oil, high oleic sunflower oil, palm and palm kernel oils, palm olein, canola oil, marine oils, cottonseed oils, and combinations thereof. Optional Ingredients

Thickeners

[0059] The nutritional products may additionally comprise one or more thickeners (i.e., thickening agents). The addition of thickeners reduces the incidences of paresthesia by inducing the feeling of satiety, which prolongs gastric transit time as discussed above.

[0060] Exemplary thickeners include gum arabic, sodium

carboxymethylcellulose, methylcellulose, guar gum, gellan gum, locust bean gum, konjac flour, hydroxypropyl methylcellulose, tragacanth gum, karaya gum, gum acacia, chitosan, arabinogalactins, glucomannan, xanthan gum, alginate, pectin, low and high methoxy pectin, cereal beta-glucans (i.e., oat beta-glucan, barley beta- glucan), carrageenan and psyllium.

[0061] One particularly preferred thickener for use in the nutritional liquids is gellan gum. Gellan gum is a water-soluble polysaccharide produced by

Pseudomonas elodea. As gellan gum is shear thinning, it can be used in the nutritional liquids without producing a viscous, unappealing textured product.

Particularly preferred for use in the nutritional products of the present disclosure includes low acyl gellan gum. "Low acyl" gellan gum (also known as and commonly referred to as deacylated gellan gum) means that the gellan gum has been treated such that it forms firm, non-elastic, brittle gels, that are heat stable, as compared to "high acyl" which forms soft, very elastic, non-brittle gels. One suitable commercially available low acyl gellan gum is Kelcogel F (CP Kelco U.S. Inc., Atlanta Georgia).

[0062] The thickeners, and particularly gellan gum, are present in the nutritional liquids in concentrations ranging from about 0.03% to about 0.05%, including from about 0.035%) to about 0.045%), and including about 0.04%> by weight of the nutritional liquid. Site Competitor

[0063] The nutritional products may optionally include an ingredient that competes with beta-alanine by binding to receptors in the small intestines, including GABA receptors. By reducing the rate of delivery of the beta-alanine to these receptors, it is believed that peak blood levels of beta-alanine will be reduced, thereby diminishing the paresthesia effect. Exemplary site competitors for use in the nutritional liquids include glycine and taurine. Suitable commercially available sources of glycine and taurine can be obtained from Ajinomoto, Chicago, Illinois.

[0064] The nutritional products may include one or more site competitors in the range of from about 0.04 grams to about 1.6 grams per 8-ounce serving, including about 0.1 grams to about 1.0 gram per 8-ounce serving, including about 0.5 grams to about 1.0 gram per 8-ounce serving, and including about 0.8 grams per 8-ounce serving.

[0065] The nutritional liquids include one or more site competitors in concentrations ranging from about 0.26% to about 0.95% by weight, including from about 0.26%) to about 0.47%> by weight. For example, in some embodiments, the nutritional liquid is an emulsion, and the emulsion includes a site competitor in an amount of from about 0.32% to about 0.47% by weight. In other embodiments, the nutritional liquid is a substantially clear liquid including a site competitor in concentrations ranging from about 0.26% to about 0.38% by weight.

Flavoring Agent

[0066] The nutritional products may optionally include one or more flavoring agents to mask the sensations experienced during incidences of paresthesia. For example, menthol provides a cooling sensation that can mask the tingling/prickly sensations induced by paresthesia. Further, menthol binds to a number of taste receptors as well as kappa opioid receptors that may further mask the sensations induced by paresthesia. [0067] When used in the nutritional products, menthol is included in concentrations ranging from about 0.01% to about 1.0% by weight, including from about 0.02%) to about 0.5%> by weight, including from about 0.03%> to about 0.1 % by weight, and including about 0.05%> by weight of the nutritional liquid.

[0068] The nutritional products described herein may further comprise other optional ingredients that may modify the physical, chemical, hedonic or processing characteristics of the products or serve as pharmaceutical or additional nutritional components when used in the targeted population. Many such optional ingredients are known or otherwise suitable for use in other nutritional products and may also be used in the nutritional products described herein, provided that such optional ingredients are safe and effective for oral administration and are compatible with the essential and other ingredients in the selected product form.

[0069] Non-limiting examples of such optional ingredients include preservatives, antioxidants, emulsifying agents, buffers, pharmaceutical actives, additional nutrients as described herein, colorants, and stabilizers, and so forth.

[0070] The products may further comprise vitamins or related nutrients, non- limiting examples of which include vitamin A, vitamin D, vitamin E, vitamin K, thiamine, riboflavin, pyridoxine, vitamin B12, carotenoids, niacin, folic acid, pantothenic acid, biotin, vitamin C, choline, inositol, salts, and derivatives thereof, and combinations thereof.

[0071] The products may further comprise minerals, non- limiting examples of which include phosphorus, magnesium, calcium, iron, zinc, manganese, copper, sodium, potassium, molybdenum, chromium, selenium, chloride, and combinations thereof.

Methods of Manufacture

[0072] The nutritional products for use herein may be manufactured by any known or otherwise suitable method for making the nutritional product form selected. Nutritional liquids may be prepared, for example, by any of the well known methods of formulating nutritional liquids by way of retort, aseptic packaging, or hot fill processing methods. Such methods are well known in the nutrition formulation and manufacturing arts.

[0073] In one suitable manufacturing process, a nutritional liquid is prepared using at least a carbohydrate -mineral (CHO-MIN) slurry, and if the composition includes protein and or fat, a protein-in-fat (PIF) slurry and a protein-in-water (PIW) slurry. The CHO-MIN slurry is formed by adding with heated agitation to water: minerals (e.g., potassium citrate, dipotassium phosphate, sodium citrate, etc.), trace and ultra trace minerals (TM/UTM premix), thickening or suspending agents (e.g. Avicel, gellan gum), additional fiber, and calcium HMB, if present. The resulting CHO-MIN slurry is held for 10 minutes with continued heat and agitation before adding additional minerals (e.g., potassium chloride, magnesium carbonate, potassium iodide, etc.) and/or carbohydrates (e.g., fructooligosaccharide, sucrose, corn syrup, etc.). The PIF slurry is formed by heating and mixing the selected oils (e.g., canola oil, corn oil, fish oil, etc.) and then adding an emulsifier (e.g., lecithin), fat soluble vitamins, and a portion of the total protein (e.g., whey protein concentrate, etc.) with continued heat and agitation. The PIW slurry is then formed by mixing with heat and agitation the remaining protein (e.g., milk protein concentrate, soy protein isolate, etc.) into water. Beta-alanine is added alone as an additional slurry or can be included in the oil blend of the PIF slurry.

[0074] The resulting slurries are then blended together with heated agitation and the pH adjusted to the desired range, typically from 6.6-7.0, after which the composition is subjected to high-temperature short-time (HTST) processing during which the composition is heat treated, emulsified and homogenized, and then allowed to cool. Water soluble vitamins and ascorbic acid are added, the pH is again adjusted to the desired range if necessary, fiavors are added, and water is added to achieve the desired total solid level. The composition is then aseptically packaged to form an aseptically packaged nutritional liquid, or the composition is added to retort stable containers and then subjected to retort sterilization to form retort sterilized nutritional liquids. [0075] In the embodiments in which beta-alanine resides in a whey protein phospholipids concentrate and oil combination, the beta-alanine that resides in the whey protein phospholipids concentrate and oil combination is added into the PIF slurry. Particularly, all oils are added to form the oil blend described above (e.g., canola oil, corn oil, fish oil, etc.) and then whey protein phospholipids concentrate are added with beta-alanine into the oil blend. The remaining oil soluble ingredients are then added and the PIF slurry is blended with the other slurries as described above.

Methods of Use

[0076] The nutritional products are useful as a nutrition source as well as to help promote healthy muscle development and maintenance and for enhancing performance endurance in individuals. Additionally, the nutritional products may be particularly suitable for use in older and elderly individuals in need of maintaining healthy muscle mass, strength and functionality. The nutritional products may help in reducing the frailty of older adults and improve muscle tone.

[0077] The nutritional products further can be administered to individuals without the adverse side-effect of paresthesia caused by ingestion of beta-alanine. Particularly, the products are formulated such to attenuate the rise of beta-alanine concentration in the blood-plasma, which reduces sensations common of paresthesia, including burning, flushing, headaches, heart palpitations, itching, numbness, prickly/tingling, and swollenness.

EXAMPLES

[0078] The following examples illustrate specific embodiments and or features of the nutritional products of the present disclosure. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present disclosure, as many variations thereof are possible without departing from the spirit and scope of the disclosure. All exemplified amounts are weight percentages based upon the total weight of the composition, unless otherwise specified. Example 1

[0079] In this Example, nutritional compositions including various levels of protein and fat were evaluated after ingestion for their effect on reducing the symptoms of paresthesia caused by beta-alanine. Particularly, subjects administered the nutritional compositions were evaluated for paresthesia sensations including: burning, flushed, headache, heart palpitations, itching, numbness, prickly/tingling, and swollenness.

[0080] The following proteins, amino acids, and fat were added to the nutritional compositions for evaluation of reducing the symptoms of paresthesia.

[0081] Subjects ingested an 8-ounce serving of at least one of the nutritional compositions and reported any paresthesia sensations experienced immediately after ingestion and 45 minutes after ingestion. Subjects rated any sensations using the following scale: 1 = none; 2 = slight sensation; 3 = moderate sensation; 4 = strong sensation; 5 = extreme sensation. The results are shown in the Table below.

Immediate 1.1 1.0 1.0 1.0 1.0 1.0 1.0

Post 45 Min. 1.0 1.2 1.0 1.0 1.0 1.0 1.0

Heart Palpitation

Immediate 1.0 1.0 1.0 1.2 1.0 1.4 1.0

Post 45 Min. 1.0 1.0 1.0 1.2 1.0 1.4 1.0

Itchy

Immediate 1.0 1.0 1.0 1.3 1.0 1.0 1.7

Post 45 Min. 1.0 1.0 1.0 1.2 1.0 1.8 1.3

Numb

Immediate 1.0 1.0 1.0 1.0 1.0 1.0 1.0

Post 45 Min. 1.0 1.0 1.0 1.0 1.0 1.2 1.7

Swollen

Immediate 1.0 1.0 1.0 1.0 1.0 1.0 1.0

Post 45 Min. 1.0 1.0 1.0 1.2 1.0 1.4 1.0

Prickly/Tingly

Immediate 1.1 1.8 1.3 1.3 1.3 1.8 2.0

Post 45 Min. 1.0 1.0 1.7 1.4 1.1 2.0 2.0

¹ To calculate average sensations sum, add up sensations greater than 1 (none) and divide by # of subjects.

[0082] As shown in the Table above, the addition of protein at a level of 17 grams/serving significantly reduced the sensations of paresthesia. It is believed that protein addition at this level prolongs gastric transit time, which attenuates the rise in blood-plasma concentration of beta-alanine, thereby reducing the incidences of paresthesia.

Example 2

[0083] In this Example, nutritional compositions including various gums and fibers were evaluated after ingestion for their effect on reducing the symptoms of paresthesia caused by beta-alanine. Particularly, subjects administered the nutritional compositions were evaluated for paresthesia sensations including: burning, flushed, headache, heart palpitations, itching, numbness, prickly/tingling, and swollenness.

[0084] All nutritional compositions evaluated included 12 grams per 8- ounce serving of protein (80% by weight milk protein concentrate and 20% by weight soy protein isolate) and 6 grams per 8-ounce serving of fat (blend of soy oil, corn oil, canola oil, and soy lecithin). The following gums and fibers were added to the nutritional compositions for evaluation of reducing the symptoms of paresthesia.

[0085] Subjects ingested an 8-ounce serving of at least one of the nutritional compositions and reported any paresthesia sensations experienced immediately after ingestion and 45 minutes after ingestion. Subjects rated any sensations using the following scale: 1 = none; 2 = slight sensation; 3 = moderate sensation; 4 = strong sensation; 5 = extreme sensation. The results are shown in the Table below.

Post 45 Min. 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0

Prickly/Tingly

Immediate 1.1 1.3 1.4 1.0 1.2 1.5 1.0 1.1

Post 45 Min. 1.0 1.7 1.0 1.1 1.2 1.0 1.3 1.1

[0086] As shown in the Table above, the addition of gellan gum in an amount of 0.04% by weight increased the viscosity of the nutritional composition, prolonging gastric transit time. The prolonged gastric transit time attenuates the rise in blood-plasma concentration of beta-alanine, reducing the incidences of paresthesia sensations.

Example 3

[0087] In this Example, nutritional compositions were evaluated after ingestion for their effects on reducing the symptoms of paresthesia caused by beta- alanine. Particularly, subjects administered the nutritional compositions were evaluated for paresthesia sensations including: burning, flushed, headache, heart palpitations, itching, numbness, prickly/tingling, and swollenness.

[0088] All nutritional compositions evaluated included 12 grams per 8- ounce serving of protein (80% by weight milk protein concentrate and 20% by weight soy protein isolate) and 6 grams per 8-ounce serving of fat (blend of soy oil, corn oil, canola oil, and soy lecithin). The following additional ingredients added to the nutritional compositions are shown below.

[0089] Subjects ingested an 8-ounce serving of at least one of the nutritional compositions and reported any paresthesia sensations experienced immediately after ingestion and 45 minutes after ingestion. Subjects rated any sensations using the following scale: 1 = none; 2 = slight sensation; 3 = moderate sensation; 4 = strong sensation; 5 = extreme sensation. The results are shown in the Table below. Control 1 Control 2 1 2

Avg. Sensation 0.7 2.0 1.7 1.5

Sum¹

# Subjects 37 3 7 4

% Subjects 16% 67% 43% 25%

Experiencing

Sensation

Burn

Immediate 1.0 1.0 1.3 1.3

Post 45 Min. 1.0 1.0 1.0 1.0

Flushed

Immediate 1.1 1.0 1.0 1.0

Post 45 Min. 1.0 1.0 1.0 1.0

Headache

Immediate 1.1 1.0 1.0 1.0

Post 45 Min. 1.0 1.0 1.0 1.0

Heart Palpitation

Immediate 1.0 1.0 1.0 1.0

Post 45 Min. 1.0 1.0 1.0 1.3

Itchy

Immediate 1.0 1.0 1.0 1.0

Post 45 Min. 1.0 1.0 1.1 1.0

Numb

Immediate 1.0 1.0 1.3 1.3

Post 45 Min. 1.0 1.0 1.1 1.0

Swollen

Immediate 1.0 1.0 1.0 1.0

Post 45 Min. 1.0 1.0 1.0 1.0

Prickly/Tingly

Immediate 1.1 1.3 1.1 1.0

Post 45 Min. 1.0 1.7 1.0 1.0

[0090] As shown in the above Table, the addition of menthol and glycine reduced the incidences of paresthesia. As glycine competes for the same receptor site as beta-alanine, it is believed that glycine blocks the receptor for beta-alanine, blocking the ability of beta-alanine to cause the sensations of paresthesia.

Additionally, it is believed that the cooling sensation produced by menthol masks the sensations caused by paresthesia.

Example 4

[0091] In this Example, nutritional compositions including glycine were evaluated after ingestion for their effects on reducing the symptoms of paresthesia caused by beta-alanine. Particularly, subjects administered the nutritional compositions were evaluated for paresthesia sensations including: burning, flushed, headache, heart palpitations, itching, numbness, prickly/tingling, and swollenness. [0092] All nutritional compositions evaluated are clear nutritional liquids including 10 grams per 10-ounce serving of protein (100% by weight soy protein isolate). Beta-alanine and glycine concentrations added to the clear nutritional liquids are shown below.

[0093] Subjects ingested an 8-ounce serving of at least one of the nutritional compositions and reported any paresthesia sensations experienced immediately after ingestion and 45 minutes after ingestion. Subjects rated any sensations using the following scale: 1 = none; 2 = slight sensation; 3 = moderate sensation; 4 = strong sensation; 5 = extreme sensation. The results are shown in the Table below.

¹ To calculate average sensations sum, add up sensations greater than 1 (none) and divide by # of subjects. [0094] As shown in the above Table, the addition of glycine reduced the sensations of paresthesia.

Example 5

[0095] Example 5 illustrates an emulsion of the present disclosure including calcium HMB and beta-alanine, the ingredients of which are listed in the table below. All ingredient amounts are listed as pound per approximately 1000 pounds batch of product, unless otherwise specified.

Folic Acid 0.000611

Biotin 0.0005311

Cyanoconbalamin 0.00001203

Vitamin DEK Premix 0.0644

dl-Alpha-Tocopheryl Acetate 0.05392

Phylloquinone 0.00008012

Vitamin D3 0.00001308

Vitamin A Palmitate 0.00825

Potassium Iodide 0.000206

Example 6

[0096] Example 6 illustrates an emulsion of the present disclosure including calcium HMB and beta-alanine, the ingredients of which are listed in the table below. All ingredient amounts are listed as pound per approximately 1000 pounds batch of product, unless otherwise specified.

Carrageenan 0.350

Water Soluble Vitamin Premix 0.0727

Niacinamide 0.02726

Calcium Pantothenate 0.01763

Thiamine Chloride Hydrochloride 0.004504

Pyridoxine Hydrochloride 0.004337

Riboflavin 0.003519

Folic Acid 0.000611

Biotin 0.0005311

Cyanoconbalamin 0.00001203

Vitamin DEK Premix 0.0644

dl-Alpha-Tocopheryl Acetate 0.05392

Phylloquinone 0.00008012

Vitamin D3 0.00001308

Vitamin A Palmitate 0.00825

Potassium Iodide 0.000206

Example 7

[0097] Example 7 illustrates an emulsion of the present disclosure including calcium HMB and beta-alanine, the ingredients of which are listed in the table below. All ingredient amounts are listed as pound per approximately 1000 pounds batch of product, unless otherwise specified.

Cupric Sulfate, Pentahydrate 0.009248

Chromium Chloride, Hexahydrate 0.000573

Sodium Molybdate, Dihydrate 0.000463

Sodium Selencate, Anhydrous 0.000191

45% KOH 0.250

Potassium Hydroxide 0.1126

Carrageenan 0.350

Water Soluble Vitamin Premix 0.0727

Niacinamide 0.02726

Calcium Pantothenate 0.01763

Thiamine Chloride Hydrochloride 0.004504

Pyridoxine Hydrochloride 0.004337

Riboflavin 0.003519

Folic Acid 0.000611

Biotin 0.0005311

Cyanoconbalamin 0.00001203

Vitamin DEK Premix 0.0644

dl-Alpha-Tocopheryl Acetate 0.05392

Phylloquinone 0.00008012

Vitamin D3 0.00001308

Vitamin A Palmitate 0.00825

Potassium Iodide 0.000206

Example 8

[0098] Example 8 illustrates a substantially clear nutritional liquid of the present disclosure including calcium HMB and beta-alanine, the ingredients of which are listed in the table below. This liquid has a pH of between 2.9 and 4.0 and remains physically stable over a shelf life of about 18 months. All ingredient amounts are listed as pound per approximately 1000 pounds batch of product, unless otherwise specified.

Sucralose 0.0750

UTM/TM premix 0.230

Zinc Sulfate, monohydrate 0.0521

Ferrous sulfate, dried 0.0408

Citric Acid, anhydrous 0.0142

Manganese Sulfate, monohydrate 0.0130

Copper Sulfate, pentahydrate 0.00710

Chromium Chloride, hexahydrate 0.000430

Sodium Molybdate, dihydrate 0.000339

Sodium Selenate, anhydrous 0.000146

Water Dispersible ADEK premix 0.178

dl-Alpha-Tocopheryl Acetate 0.0454

Vitamin A Palmitate 0.00421

Phylloquinone 0.000127

Vitamin D3 0.0000231

Acesulfame Potassium 0.110

10% DMPS Anti-foam (Processing Aid) 0.0600

Dimethylpolysiloxane 0.0006

Water Soluble Vitamin premix 0.03790

Niacinamide 0.0142 d-Calcium pantothenate 0.00920

Thiamine chloride hydrochloride 0.00240

Pyridoxine hydrochloride 0.00230

Riboflavin 0.00180

Folic Acid 0.000350

Biotin 0.000277

Cyanocobalamin 0.00000630

Coloring Agent 0.00700

Folic Acid, USP 0.00337

Potassium Iodide 0.000204

Example 9

[0099] Example 9 illustrates a substantially clear nutritional liquid of the present disclosure including calcium HMB and beta-alanine, the ingredients of which are listed in the table below. This liquid has a pH of between 2.9 and 4.0 and remains physically stable over a shelf life of about 18 months. All ingredient amounts are listed as pound per approximately 1000 pounds batch of product, unless otherwise specified.

Phosphoric Acid 1.9

Maltrodextrin 20.1

Calcium HMB 5.29

Beta-Alanine 3.84

Taurine 2.56

Citric Acid 2.00

Flavoring Agent 2.00

Liquid Sucralose (25%) 0.300

Sucralose 0.0750

UTM/TM premix 0.230

Zinc Sulfate, monohydrate 0.0521

Ferrous sulfate, dried 0.0408

Citric Acid, anhydrous 0.0142

Manganese Sulfate, monohydrate 0.0130

Copper Sulfate, pentahydrate 0.00710

Chromium Chloride, hexahydrate 0.000430

Sodium Molybdate, dihydrate 0.000339

Sodium Selenate, anhydrous 0.000146

Water Dispersible ADEK premix 0.178 dl-Alpha-Tocopheryl Acetate 0.0454

Vitamin A Palmitate 0.00421

Phylloquinone 0.000127

Vitamin D3 0.0000231

Acesulfame Potassium 0.110

10% DMPS Anti-foam (Processing Aid) 0.0600

Dimethylpolysiloxane 0.0006

Water Soluble Vitamin premix 0.03790

Niacinamide 0.0142 d-Calcium pantothenate 0.00920

Thiamine chloride hydrochloride 0.00240

Pyridoxine hydrochloride 0.00230

Riboflavin 0.00180

Folic Acid 0.000350

Biotin 0.000277

Cyanocobalamin 0.00000630

Coloring Agent 0.00700

Folic Acid, USP 0.00337

Potassium Iodide 0.000204

Claims

WHAT IS CLAIMED IS:

1. A nutritional liquid comprising beta-alanine and protein, wherein at least a portion of the beta-alanine resides in a whey protein phospholipids concentrate and oil combination.

2. The nutritional liquid of claim 1 comprising from about 0.31% to about 0.47% by weight of beta-alanine.

3. The nutritional liquid of claim 1 further comprising calcium beta-hydroxy-beta methylbutyrate.

4. The nutritional liquid of claim 3 comprising from about 0.40% to about 0.60% by weight of calcium beta-hydroxy-beta methylbutyrate.

5. The nutritional liquid of claim 1 comprising from about 3% to about 8% by weight of protein.

6. The nutritional liquid of claim 1 further comprising gellan gum.

7. The nutritional liquid of claim 6 comprising from about 0.03% to about 0.05% by weight of gellan gum.

8. The nutritional liquid of claim 1 wherein at least about 10% of the beta- alanine resides in the whey protein phospholipids concentrate and oil combination.

9. The nutritional liquid of claim 1 wherein 100% of the beta-alanine resides in the whey protein phospholipids concentrate and oil combination.

10. The nutritional liquid of claim 1 further comprising menthol.

11. The nutritional liquid of claim 10 comprising from about 0.01% to about 1.0% by weight of menthol.

12. A nutritional liquid comprising beta-alanine, protein, and glycine.

13. The nutritional liquid of claim 12 comprising from about 0.26% to about 0.47% by weight of beta-alanine.

14. The nutritional liquid of claim 12 further comprising calcium beta-hydroxy- beta methylbutyrate.

15. The nutritional liquid of claim 14 comprising from about 0.40% to about 0.60% by weight of calcium beta-hydroxy-beta methylbutyrate.

16. The nutritional liquid of claim 12 comprising from about 3% to about 8% by weight of protein.

17. The nutritional liquid of claim 12 comprising from about 0.26% to about 0.95%) by weight of glycine.

18. The nutritional liquid of claim 17 comprising from about 0.26% to about 0.47%) by weight of glycine.

19. The nutritional liquid of claim 12 wherein the nutritional liquid is a substantially clear nutritional liquid.

20. A method of reducing the incidence of paresthesia caused by ingestion of beta- alanine, the method comprising: administering to an individual a nutritional liquid comprising beta-alanine and protein, wherein at least a portion of the beta-alanine resides in a whey protein phospholipids concentrate and oil combination.

21. The method of claim 20 wherein the nutritional liquid comprises from about 0.31% to about 0.47% by weight of beta-alanine.

22. The method of claim 20 wherein the nutritional liquid comprises from about 3%) to about 8%) by weight of protein.

23. The method of claim 20 wherein the nutritional liquid further comprises calcium beta-hydroxy-beta methylbutyrate.

24. The method of claim 23 wherein the nutritional liquid further comprises from about 0.40% to about 0.60% by weight of calcium beta-hydroxy-beta methylbutyrate.

25. The method of claim 20 wherein the nutritional liquid further comprises gellan gum.

26. The method of claim 20 wherein at least about 10% of the beta-alanine resides in the whey protein phospholipids concentrate and oil combination.

27. The method of claim 20 wherein the nutritional liquid further comprises menthol.

28. A method of reducing the incidence of paresthesia caused by ingestion of beta- alanine, the method comprising: administering to an individual a nutritional liquid comprising beta-alanine, protein, and glycine.

29. The method of claim 28 wherein the nutritional liquid comprises from about 0.26% to about 0.47% by weight of beta-alanine.

30. The method of claim 28 wherein the nutritional liquid comprises from 3% to about 8%) by weight of protein.

31. The method of claim 28 wherein the nutritional liquid comprises from about 0.26%) to about 0.38%> by weight of glycine.

32. The method of claim 28 wherein the nutritional liquid further comprises calcium beta-hydroxy-beta methylbutyrate.

33. The method of claim 28 wherein the nutritional liquid is a substantially clear nutritional liquid.

34. A nutritional liquid comprising from about 0.26% to about 0.47% by weight beta-alanine, from about 3.0% to about 8.0% by weight protein, and from about 0.26%) to about 0.38%> by weight glycine.

35. The nutritional liquid of claim 34 further comprising from about 0.40% to about 0.60% by weight calcium beta-hydroxy-beta methylbutyrate.