WO1995011019A1

WO1995011019A1 - Glutamine-containing ingestible composition

Info

Publication number: WO1995011019A1
Application number: PCT/US1994/012013
Authority: WO
Inventors: Tomas C. Welbourne
Original assignee: Research Corporation Technologies, Inc.
Priority date: 1993-10-22
Filing date: 1994-10-20
Publication date: 1995-04-27

Abstract

The present invention relates to an ingestible composition designed to combine enhancement of physical performance with the reduction of body fat. More specifically, the present invention is directed to ingestible compositions comprising glutamine in an amount effective to induce a growth hormone response in the consumer, i.e. an increase in the blood levels of growth hormone in the body. The performance enhancing beverage compositions according to the present invention contain from about 1.0 to about 4.0 g of glutamine per 473 milliliters. The performance enhancing foodstuff compositions of the present invention contain at least about 1 g of glutamine.

Description

GLUTAMINE-CONTAINING INGESTIBLE COMPOSITION

The present invention relates generally to an ingestible composition which enhances physical performance while simultaneously aiding in the reduction of body fat. The ingestible compositions of the present invention may be used in connection with physical training, e.g. athletic or military training, and all types of athletic competitions, as well as simply for the purpose of toning the body and eliminating excess fat.

More particularly, the present invention involves ingestible compositions, such as beverage compositions and foodstuffs, containing the amino acid glutamine in amounts effective to induce a growth hormone response in the consumer. In other words, by raising the body's level of growth hormone, the glutamine activates the body's natural system which provides for peak physical performance. More specifically, the glutamine acts directly as a nutrient for the exercising muscles and indirectly as a signal molecule to activate mechanisms within the body which switch the metabolism into using fatty acid as fuel and generate base, while sparing proteins which would normally be broken down during exercise or athletic performance. If the ingestible composition is to be used in connection with an exercise program or athletic performance, it is to be administered prior to the initiation of the exercise or the performance. If, on the other hand, the ingestible composition is to be used for purposes of losing fat, it is generally preferred that the beverage be consumed shortly after normal or regular eating habits or snacking.

The present invention further relates to a method of administering an effective amount of glutamine at a particular pre-exercise point to attain the most beneficial effects the a ino acid has on the body's muscles and metabolism.

The use of health or sport drinks to satisfy various requirements of the human body during training and competition is known. Many of the health drinks on today's market, designed to provide energy and to replete the body of lost salt and water after heavy exercise or competition, are based on the assumption that the rates of water and salt loss during these times exceed the body's normal intake and the kidney's ability to process the blood. By repleting or refurbishing the salt and water which are lost, the purpose of the majority of health drinks is to attempt to maintain a state of constancy in the blood. Accordingly, many sport drinks contain water and/or electrolytes. Usually some sugar is added to restore glycogen stores and to make the drink more palatable to the consumer. Various other health or sport drinks may also contain some vitamins and minerals directed to meet particular nutritional needs of the athlete or consumer involved. Examples of such sport drinks include "Max", marketed by the Coca Cola Company, which contains a 5% solution of dextrose and malto-dextrin; "Gatorade", marketed by Stokely-Van Camp, Inc., which contains a 6% solution of sucrose and glucose, 220 mg of sodium and 50 mg of potassium per serving as well as some vitamin C; and "Exceed", marketed by the Ross division of Abbott Laboratories, which contains glucose polymers, fructose, 280 mg of sodium, 430 mg of potassium, 380 mg chloride and other electrolytes in every eight ounce serving. U.S. Patent No. 4,871,550 to Millman discloses a nutrient composition which is said to enable stressed marathon athletes to achieve superior performance. The composition contains essential and preferably also non- essential amino acids, nutrient factors which may include vitamins, trace elements and minerals, and may also include carbohydrates, electrolytes and one or more flavoring aids.

JP-59210872 assigned to Ajino oto Co., discloses a drink for athletes which contains various amino acids including histidine, lysine, arginine, leucine, i- leucine and valine. The drink may also include an acidulant and carbonic acid.

Other sport drinks may have more specific and narrow goals in mind. For example, JP-60160872 to Fukami, et al., discloses a beverage containing a branched chain amino acid which includes isoleucine, leucine and valine, useful for accelerating muscle activity. Similarly, JP-58165774, assigned to Ajinomoto Co. , discloses a beverage containing at least one branched chain amino acid selected from isoleucine and valine which improves the function of muscular motion.

Although a great variety of sport drinks are known, a very high percentage of these drinks are only to be consumed after the exercise or competitive event, i.e. after the damage has occurred. It would be preferable, therefore, to have a health drink or other ingestible composition that could prevent the deleterious effects of exercise before they occurred or developed, rather than trying to rectify the damaging situation after-the-fact. One drink which is administered prior to exercising is disclosed by U.S. Patent No. 4,687,782 to Brantman. This patent is directed to a diet supplement which employs a combination of amino acids mixed with water to form a drink which is said to be useful to promote muscle adaptation to strenuous exercise. It specifically requires the combination of the amino acids carnitine, glutamine, isoleucine, leucine and valine per se and can be supplemented with other proteins, vitamins and/or minerals. Braumann, et al., "Studies on the Effect of Amino Acid Preparations During an Eight Week Training Program", Deutsche Zeitschrift Fur Sportmedizin, March 1980, 78-84, reports the results after administration of an amino acid preparation administered in the form of a capsule, at a rate of 2.0 g/day to a number of athletes. The mixture contains varying amounts of some 17 amino acids, including about 10% by wt. glutamine. The article concluded that the amino acid preparation can augment the protein requirements of a training athlete and may be advantageous in endurance sports where oxygen transport capacity is an important factor.

The present invention relates to an ingestible composition designed to combine enhancement of physical performance with the reduction of body fat. More specifically, the present invention is directed to ingestible compositions comprising glutamine in an amount effective to induce a growth hormone response in the consumer, i.e. an increase in the growth hormone level of the body. The performance enhancing beverage compositions according to the present invention contain from about 1.0 to about 4.0g of glutamine per 473 milliliters. The performance enhancing beverage foodstuff compositions of the present invention contain at least about lg of glutamine. The ingestible compositions of the present invention act upstream of most known health drinks in that they ameliorate the deleterious effects of exercise before they can develop. That is, the beverage or foodstuff compositions of the present invention control acid production in the muscles by accelerating base production and thereby prevent muscle fatigue. In addition, the glutamine beverage of the present invention promotes body toning, even in the absence of exercise, by facilitating the combustion of fat in place of protein.

More specifically, the present invention is directed to an ingestible composition comprising an effective amount of glutamine sufficient to induce a growth hormone response, said growth hormone response being an increase in the amount of growth hormone in blood. The present invention is further directed to a method of enhancing the physical performance of a human comprising administering to said human an ingestible composition an effective length of time prior to said physical performance, wherein said ingestible composition comprises an effective amount of glutamine sufficient to induce a growth hormone response, said growth hormone response being an increase in the amount of growth hormone in blood.

Still further, the present invention is directed to A method of inducing the etabolization of fat in a human comprising administering to said human an ingestible composition comprising an amount of glutamine sufficient to induce an increase in the amount of growth hormone in blood.

Still further, the present invention relates to an article of manufacture comprising a packaging material and an ingestible composition contained within said packaging material, wherein said ingestible composition comprises an effective amount of glutamine sufficient for increasing the blood levels of growth hormone in a human, and wherein said packaging material comprises a label which indicates that said ingestible composition can be used for enhancing physical performance, inducing the metabolization of fat, or increasing the blood levels of growth hormone level in a human.

Figures la through 9a are graphs illustrating the differences in plasma glutamine levels in Participants A through I, respectively, taken a week apart, and with the later measurements being taken after consumption of the beverage composition made in accordance with the present invention.

Figures lb through 9b are graphs illustrating the differences in plasma growth hormone levels in Participants A through I, respectively, taken a week apart, and with the later measurements being taken after consumption of the beverage composition made in accordance with the present invention.

In accordance with the present invention, it has surprisingly been found that by adding a specified amount of the amino acid glutamine to an ingestible composition which is to be consumed prior to physical exertion such as exercise or an athletic performance, a growth hormone response is evoked in the consumer which results in the physical performance of the human body being enhanced as fat is burned and proteins are spared. As used herein, the term "ingestible composition" is generally defined as any composition which may be orally ingested by the consumer. Ingestible compositions in accordance with the present invention include beverage compositions, such as regular or diet beverages, regular or diet soft drinks, regular or diet sports drinks, such as Gatorade-like drinks, water-based beverages, carbonated and non-carbonated beverages, powdered beverage formulations and the like, and foodstuff compositions, such as candy bars or power bars, cookies, wafers and the like, as well as a food ingredient which may be used or added to other foodstuffs.

As used herein, the term "enhancing" or any form thereof, is defined as improving or elevating one's normal abilities under similar circumstances. Thus "enhancing" one's physical performance means not only increasing one's capacity to perform for a greater amount of time but performing at a greater capacity of power and strength due to the minimization of any wear- and-tear on the muscles involved in the performance. Further, the phrase "reducing fat" refers to the consumption, conversion or elimination of fat present in the body as by the process of actually burning or consuming fat via the ingestion of the growth hormone elevating compositions according to the present invention. That is, the term "reducing fat" as used herein refers to the process of inducing the metabolization of fat. This process can thus be accompanied by realization of weight loss. The term "reducing fat" can also include the situation where the consumer's metabolism is consuming fat due to the ingestion of the glutamine compositions in accordance with the present invention, but not actually "reducing" his or her overall fat level due to a simultaneous ingestion of more fat. In other words, depending on the eating habits of the consumer, a "reduction" in fat level is not always achieved. Thus, the compositions of the present invention can also be used for weight control or the maintenance of one's weight. Even in this aspect, the present invention is useful as desirable body toning occurs as the body's metabolism is shifted to fat, in preference to protein, as the energy fuel.

A beverage or foodstuff composition in accordance with the present invention which is intended to be used in order to enhance the consumer's physical performance, should normally be ingested approximately 30 minutes before the particular physical exertion. The beverage or foodstuff composition, as is described below, will build up base in the body in anticipation of exertion- induced acid production by the muscle. It has been further found that by administering said ingestible compositions containing an effective amount of glutamine subsequent to regular eating habits or snacking, a reduction in fat also occurs even in the absence of exercise. Although a reduction of fat can be obtained by administering the ccmpositions of the present invention at any random time of the day, it has been found that the best results for fat loss are achieved when the composition is administered subsequent to eating or snacking. By the phrase "subsequent to eating or snacking" it is generally meant a period of up to about 60 minutes following eating.

Still further, the beverage compositions of the present invention can be calorie-free which further promotes the burning of fat without the need for exercise. The beverage compositions of the present invention may even contain calories which would then be offset by the fat burning quality of the composition.

Without being bound by any particular hypothesis, the present inventor has found that the ingestion of an effective amount of the natural amino acid glutamine in the manner described herein acts both directly and indirectly on the consumer's metabolic pathway in such a manner that results in enhanced physical performance as well as the burning of fat. More particularly, glutamine acts directly as an important critical nutrient for exercising muscle and the kidneys. By elevating the cellular level of glutamine, protein breakdown is prevented in the muscles and base is generated in the kidneys. In addition, it has been found that glutamine acts indirectly as a signal molecule to activate mechanisms, through growth hormone release, which switch the body's metabolism into using fat as a fuel and further influences the release of bicarbonate from the kidneys which offsets the lactic acidosis one experiences in exercising. Proteins, which are normally broken down during exercise or an athletic event, are consequently spared.

More specifically, the ingestion of glutamine into the body sets in motion interorgan signals resulting in base production, fat oxidation and the sparing of protein. The glutamine is absorbed and is metabolized by the small intestine. Generally, about 80% of the glutamine remains glutamine. The remainder is broken down to form<citrulline, alanine and ammonia. Both the glutamine and the citrulline leave the small intestine and are transported to the kidneys and other organs. The citrulline by-passes the liver, heart and lungs and goes directly to the kidney where it is converted into the amino acid arginine. The arginine from the kidney in turn stimulates growth hormone secretion in the pituitary gland by suppressing somatostatin secretion. So atostatin is a growth hormone inhibiting factor.

While the citrulline is transported directly to the kidney, the glutamine not only goes to the kidney but goes to other organs as well. Upon entering the kidney, glutamine is converted to glutamate, the glutamate is converted into α-ketoglutarate which in turn is finally converted into two bicarbonates. In the brain, glutamine is again converted into glutamate. However, in the brain, glutamate acts as a direct stimulus on the pituitary gland resulting in the release of growth hormone. In the liver, glutamine is converted into glutamate after which it is exported under the influence of growth hormone. It is the ultimate release of growth hormone, i.e. an increase in the level of growth hormone, as the result of the ingestion of an effective amount of glutamine, which effects base generation, in support of glutamine's direct renal effect, and fat combustion in the human body while simultaneously sparing protein. More particularly, growth hormone stimulates the kidney to secrete acid into the urine and release bicarbonate or base into the renal vein.

The additional bicarbonate added to the blood as a result of the ingestion of the glutamine compositions of the present invention and the subsequent increase in the blood levels of growth hormone, represents a build¬ up of bicarbonate in advance of the acid which is to be produced by the soon-to-be exercised muscle. The effects of increased blood levels of bicarbonate on physical performance are shown by McNaughton, L.R. , J. of Sports Sciences, 10, pp. 415-423 (1992) and Lavender, G. et al., Br. J. Sports Med. , Vol. 23, No. 1 pp. 41-45 (1989). Both articles show that with an increase in bicarbonate levels in the blood, the physical performance of the subject significantly improves.

Acting concurrently with the production of base, the released growth hormone enters the liver and accelerates the uptake of fatty acids. By making fatty acids available, the ingestion of the glutamine compositions of the present invention and the subsequent increase in the blood levels of growth hormone leads to a toning of the physique, i.e. the consumption or elimination of fat. The increased utilization of fatty acids yields α-ketoglutarate which serves to substitute for the α-ketoglutarate derived from the utilization of the glutamine. As mentioned above, growth hormone facilitates the release of glutamate and glutamine from the liver, which spares the glutamine for utilization, repair and maintenance of other cells such as muscles. The existence of a relationship between growth hormone and fatty acids and/or lipids is discussed by Keller, U. et al., Horm. Res., 26 (suppl 1), pp. 36-40 (1991) and Davidson, M.B., Endocrine Reviews, Vol. 8, No. 2, pp. 115-131 (1987). With respect to the muscle cells, growth hormone causes these cells to increase their uptake of fatty acids as well. And as stated earlier, the increased levels of bicarbonate from the kidney act to buffer any acid build-up which may occur in the muscle cells as a result of muscle activity and thus offsets the onset of muscle fatigue.

It is further noted that by eliminating glutamine combustion and accelerating glutamine synthesis in the kidney and liver, the intake of an effective amount of glutamine and the resulting increase in growth hormone results in the sparing of protein. That is, under normal conditions, muscle cells are required to release glutamine during acidic states to supply the kidney's requirements for bicarbonate production. In order to supply this demand, muscle proteins must be metabolized. However, due to the higher level of glutamine already in the muscle cells due to the ingestion of compositions in accordance with the present invention, the proteins are spared during the acidic state as exogeneously supplied glutamine substitutes for muscle protein-derived glutamine.

Apart from glutamine's effect on increasing the systemic growth hormone level and consequently its ability to enhance one's physical performance and ability to lose weight, glutamine also has a functional effect on the consumer of the compositions of the present invention. That is, the glutamine compositions of the present invention also serve to elevate or improve the mood of the consumer. The term "mood" refers to the consumer's psychosocial status or feelings of well-being and includes the consumer's perception of tension, depression, anger, vigor, fatigue and confusion. See Young, L.S. et al., J. of Parenteral and Enteral Nutrition, Vol. 17 No. 5, pp. 422-427 (1993). Glutamine has been available in tabular form (which was found to be ineffective) and as a powder supplement for enteral and parenteral elemental diets used for the treatment of catabolic disease. Glutamine has not been administered or available as proposed by the composition of the present invention. In accordance with the practice of the present invention, the beverage compositions which are successful in obtaining glutamine's previously unrecognized effects on growth hormone release as noted above are comprised of acidic liquid vehicles, e.g. such as Gatorade or any commercial diet cola. The acidic liquid acts to stabilize the glutamine and provides an appealing and functional, i.e. thirst-quenching, vehicle for the administration of an effective amount of glutamine.

In order to achieve the effects mentioned above, the beverage compositions of the present invention are comprised of from about 1.0 to about 4.0g of glutamine per 473 milliliters (16 fluid oz.). Preferably, glutamine should be added in an amount of 2g per 473ml or in a concentration of about 15 to about 60mM or preferably in a concentration of about 20 to about 30mM and most preferably in a concentration of about 28.2mM. Higher doses than the range indicated above may negate the beneficial effect of the glutamine. See Welbourne, T.C. and Joshi, S., "Interorgan glutamine metabolism during acidosis", J. Parent Enter. Nutr. , 14: 775-855 (1990). However, it is noted that 40g of glutamine per one liter of water has been ingested without the occurrence of any negative effects. Lower doses than that indicated above fail to raise the systemic glutamine levels.

For best results, the glutamine used in making the compositions of the present invention should be essentially pure, i.e. greater than 99% pure. Glutamine is purified in the crystalline form after extraction from its plant source and is available as such.

In accordance with the present invention, the glutamine-containing beverage composition must be acidic in nature. By having the glutamine dissolved in an acidic liquid vehicle, two functions are served. One is that the low pH of the beverage stabilizes the glutamine and prevents its breakdown (i.e., ensures maximum potency) . This provides a highly desirable shelf-life stability to the acidic beverage. The stability of glutamine in an acidic pH environment over a period of time was studied by adding 2g of glutamine powder to

5473ml of a diet cola, maintaining the beverage in a refrigerator at 4°C and repetitively sampling the pH of the beverage. The results are shown in Table 1.

Table 1. Stability of Glutamine at acidic pH fo: 0 II 1 prolonged time periods

Time (days) (Gin (mM)pH units

0 28.19 5.15

1 28.00 5.17

26.03 (28.16)* 5.19

6 27.47 (27.15)* 5.22 5 8 27.34 5.31

11 29.82

22 33.40

52 29.94 5.25

* The values in parenthesis represent measurements taken at room temperature. 0

It is clear from the data shown in Table 1 that the amount of glutamine present in the acidic environment was very stable, even with a pH ranging upward from 5.15 to 5.25, over a period of 52 days. 5 The second function which is served by having the glutamine in an acidic environment is that the low pH allows for the manufacturing of the product without the necessity for the process of pasteurization. This too is critical as the pasteurization process would result 0in the hydrolysis of the glutamine's amide bonded ammonium.

5 For the purpose of the present invention, a pH value for the beverage composition in the range of about 3.0 to about 5 is generally preferred, with a pH of about 3.8 to about 4.0 being most preferred. A combination of citric acid and phosphoric acid has been found to stabilize glutamine as well as to make the beverage more drinkable to the consumer as compared to a majority of other sport drinks. Generally speaking, a sufficient amount of citric acid is used to adjust the pH to the desired level and sufficient amounts of phosphoric acid are used to maintain the pH at the desired level. One skilled in the art would easily be able to determine the exact amount of citric and phosphoric acid required for this purpose. In any case, for a source of phosphoric acid the beverage compositions of the present invention may contain sodium dihydrogen phosphate (NaH-,PO_Λ) in an amount effective to buffer the compositions at the appropriate pH. The presence of the NaH₂P0₄ ensures that the beverage compositions maintain flavor and stability after exposure to atmospheric conditions. Generally, the NaH₂P0₄ is present in amounts from about 5mM to about 20mM, with an amount of from about lOmM to about 15mM being preferred. As discussed earlier, citrulline is converted into arginine in the kidney and plays an active role as it inhibits the inhibitor of growth hormone, i.e. somatostatin. Consequently, the ingestible compositions of the present invention may additionally be comprised of from about 1.0 to about 4.0g of arginine per 473 milliliters, with an amount of about 2.0g being most preferred. The added arginine in the compositions of the present invention assures that an elevation of the systemic arginine level in the blood takes place. Finally, the ingestible compositions of the present invention may also contain benzoate, which appears to channel the glutamine through the liver and to the muscles. Generally, benzoate is present in amounts from about 0.1 to about lg, with an amount of from about 0.2 to about 0.3g being preferred. With respect to the foodstuff compositions, or powdered beverage formulations, contemplated by the present invention, it has been found that similar results to those obtained by the beverage compositions of the present invention will be obtained where the foodstuff compositions contain from about 1.0 to about 4.0g of glutamine.

With respect to the beverage compositions in accordance with the present invention, it has been found that a liquid volume of about 473ml (or 16 fluid oz.) ensures that administration of the optimal amount of glutamine present therein is more easily "smoothed out", i.e. sufficiently dissolved in the beverage to allow for easy consumption and delivery to the body's metabolism. As such, consumption of the glutamine acidic beverage over a 15 to 20 minute period of time adequately elevates the systemic glutamine concentration in the human body consistent with the delivery thereof to muscle prior to exercise. It is further noted that consumption of the foostuff compositions contemplated by the present invention over a period of about 15 to about 20 minutes prior to any exercise is also sufficient to 1 adequately elevate the systematic glutamine concentration in the human body. This is the "direct effect" of the glutamine beverage of the present invention stated above. The fact that the glutamine

5 beverage made in accordance with the present invention indeed elevates systemic plasma glutamine was determined by having a human consume the glutamine beverage over a 15 minute period and sampling the blood at the brachiocephalic venous site at three 30 minute intervals 0 thereafter. The results are shown in Table 2.

Table 2. Effects of Glutamine beverages on systemic plasma glutamine

Time (min) Control 30 60 90 c Gin (μM) 574 691 536 502

As can be clearly seen by the results given in Table 2, the systemic plasma glutamine was raised considerably, i.e. from 574 μM to 691 μM, within the _Q first 30 minutes. A more in depth study of this effect was conducted and is discussed in the Example below.

As the presence of excess muscle glutamine was found to reduce protein breakdown, by providing an increase in muscle glutamine, the beverage of the _t- present invention limits the wear-and-tear associated with exercise. An index of protein breakdown is the amount of the amino acid alanine which is released by muscle. The smaller or lower amount of alanine which is present correlates directly to a lower or less amount of

__nprotein breakdown. Following the same procedure as that disclosed in connection with Table 2, it is clearly

35 shown by the results given in Table 3 that a reduction in alanine concentration does indeed take place following the consumption of the beverage made in accordance with the present invention. Compared to the control which had an alanine concentration of 552mM, the human body following consumption of the glutamine beverage of the present invention had a reduced concentration after 30 minutes of 511mM and a further reduced concentration after 90 minutes of 415mM.

Table 3. Effects of Glutamine beverages on alanine concentration

Time (min) Control 30 60 90 Ala (mM) 552 511 426 415

In addition to the direct effects exemplified above, and with regards to the indirect effect noted earlier, the acidic glutamine beverage of the present invention also sets in motion a secondary glutamate flux from the liver which causes glutamate to be recycled back into the glutamine present at the muscle and thus reinforce the primary glutamine effect.

Perhaps most importantly, it has been found that the glutamine beverage composition of the present invention also acts to increase growth hormone levels. Similar to conditions disclosed in connection with Tables 2 and 3, the results shown in Table 4 clearly demonstrate the increase in plasma growth hormone concentration following consumption of the beverage made in accordance with the present invention. 1 Table 4. Effects of Glutamine beverages on growth hormone concentration

Time (min) Control 30 60 90

Growth Hormone 0.48 0.50 0.54 0.80 (ng/ml)

5

The amino acid arginine, by inhibiting somatostatin release, is a potent stimulator of the growth hormone release. Consequently, an increase of growth hormone concentration should be coupled with an

10. . . . increase in arginine concentration. As the results show in Table 5, this is indeed the case and acts to confirm the results given in Table 4. Plasma arginine levels do increase following the consumption of the beverage of the present invention. Clinical testing of the effect

15of the beverage composition of the present invention on the level of plasma growth hormone was conducted and is discussed below in the example.

Table 5. Effects of Glutamine beverage on plasma 20 arginine concentration

Time (min) Control 30 60 90 Arg (μM) 127 198 182 128

As disclosed earlier, the production of growth 25hormone in turn effects two critical actions, i.e. causing the metabolism to switch to using fatty acids as fuel and to generate base. An increase in alkaline reserves was demonstrated in the plasma of humans as a result of consumption of the beverage of the present 30invention (see Table 6) and in animals (see Table 7) as a result of an increase in growth hormone.

35 Table 6. Effects of Glutamine beverage on plasma alkaline reserves in humans

Time (min) Control 30 60 90 HC0₃ ^" (mM) 25.5 - 26.2 27.0

Table 7. Effects of growth hormone (GH) increase on alkaline reserves of hypophysectomized (hypox) rats.

Acid Intake Arterial HC0₃ ^~

(μmol/lOOg/day) (mM)

Hypox Hypox + GH Hypox Hypox +

GH 1 1947 1472 13.2 21.1 2 1388 1334 12.0 21.3 3 1615 1952 10.5 15.1 4 2347 1869 13.2 18.3 5 1087 1294 6.1 13.0

Avg, 1677 1584 11.0 17.8

±438 ±274 ±2.6 ±3.3

With respect to Table 7, the hypophysectomized (hypox) rats or growth hormone administered rats (100 μg/lOOg bodyweight) were given 0.7% NH₄C1 in 5% glucose and 24 hour urine collections were made from paired animals with the concentration of HC0₃- determined on the third day. An obvious increase in arterial alkaline reserves was noted with the addition of the growth hormone.

The effects of the beverage of the present invention on fatty acid levels was studied in clinical testing and is discussed below in the Example. The indirect effects of the beverage compositions of the present invention noted above, i.e. generating base and switching the metabolism to using fatty acids as fuel, both further spare protein breakdown as well.

See Welbourne, T.C, Joshi, S. and McVie, R. , Am. J.

Physio1. 257: E959-962 (1987) and Welbourne, T.C. and Cronin, M.J., "Growth hormone accelerates tubular acid secretion", Am. J. Physiol 260: R 1036-1042 (1991).

The following examples are provided to illustrate the present invention.

EXAMPLE 1

16 fluid oz. of a commercial diet cola was mixed with 2g. pure glutamine, .Olg NaH₂P0₄ and .Olg benzoate. Said beverage composition had a pH of 4.0. Nine human participants were chosen for clinical testing on two successive Saturdays in which the participants' blood was sampled at 0, 30, 60 and 90 minutes. The levels of glutamine, growth hormone, bicarbonate and fatty acids were determined. One week later, the same 9 participants were sampled at the same time intervals, however, each consumed the 16oz. beverages indicated above which contained 2g. glutamine after time 0 and before 30 minutes.

The particular statistics of the participants are given in Table 8.

Table 8. Participants in Clinical Testing

Subjects Sex Age t . Ht . Wt/Ht (kg/cm)

A male 50 155 5 ' 8" ( 70.4/173 ) 40.69

B male 64 210 6 ' 3" (95.34/190.5 ) 50.05

C male 35 150 5 ' 10" ( 68.1/177.8) 38.30

D female 44 250 5 ' 11" ( 113 .5/180.34 ) 62.94

E male 40 175 6' 1" (79.45/185.42) 42.85

F male 42 165 5 ' 6" ( 74.91/167.64 ) 44.69

G female 36 148 5 ' 3" (67.19/160.02 ) 41.99

H male 32 275 5 ' 11" ( 124.85/180.34 ) 69.23

I female 37 123 5 ' 2" ( 55.84/157.48) 35.46

The results of the clinical testing with respect to the nine participants listed in Table 8 are given in Tables 9 and 10. Table 9 includes the results with respect to the glutamine, growth hormone and bicarbonate levels in the plasma and Table 10 sets forth the results with respect to the fatty acid levels in the participants.

Table 9. Glutamine, Growth Hormone and Bicarbonate Levels in Participants Gin Gin AGln GH GH AGH HCO-T HC0₃ ^"

Time Control Test Test to Control Test Test to Control Test Subject (min) (nmol/mL) (nmol/mL) Control (no/ml) (no/ml) Control (mM) (mM)

A 0 803 713 -90 0.39 0.39 0 24.16 18.38

30 728 816 88 0.33 0.35 0.02

60 690 859 169 0.33 0.30 -0.03

90 699 675 -24 0.34 0.52 0.18 23.46 23.53

B 0 864 781 -83 0.19 0.13 -0.06 24.01 18.26

30 787 928 141 0.20 0.12 -0.08

60 742 922 180 0.20 0.16 -0.04

90 767 746 -21 0.21 0.87 0.66 22.30 19.97

C 0 864 754 -110 0.26 0.23 -0.03 28.42 24.87

30 742 835 93 0.30 0.40 0.10

60 655 707 52 0.38 0.83 0.45

90 614 670 56 0.42 0.21 -0.21 26.20 28.80

D 0 734 563 -171 0.45 0.80 0.35 25.72 19.36

30 737 663 -74 0.50 0.48 -0.02

60 677 567 -110 0.38 0.81 0.43

90 683 570 -113 0.44 1.15 0.71 24.60 20.09

E 0 714 817 103 0.26 0.31 0.05 24.75 21.74

30 682 857 175 0.42 0.50 0.08

60 643 723 80 0.31 0.72 0.41

90 624 624 0 0.47 0.42 -0.05 24.75 23.65

F 0 662 921 259 0.19 0.11 -0.08 27.84 21.87

30 652 959 307 0.17 0.34 0.17

60 651 746 95 0.21 0.29 0.08

90 656 735 79 0.25 0.16 -0.09 28.80 25.17

G 0 756 642 -114 0.28 0.95 0.67 24.87 22.42

30 653 699 46 0.27 2.29 2.02

60 657 772 115 0.70 2.33 1.63

90 652 695 43 0.46 3.20 2.74 24.50 28.20

0 483 529 46 0.17 0.13 -0.04 22.79 25.97

30 515 540 25 0.16 0.16 0.00

60 526 485 -41 0.18 0.13 -0.05

90 506 507 1 0.16 0.11 -0.05 21.32 23.03

I 0 559 606 47 3.03 1.24 -1.79 23.40 20.82

30 471 733 262 1.08 2.68 1.60

60 445 500 55 0.56 11.66 11.10

90 406 565 159 0.48 8.17 7.69 21.68 22.55 UM Fatty Acids

0 minutes 30 minutes 60 minutes 90 minutes

Subject Control Test Control Test Control Test Control Te A 1.66 3.05 1.14 1.86 1.16 1.27 1.33 1. c 0.95 0.61 0.80 0.52 0.08 0.50 0.61 0.

D 1.70 1.97 1.19 1.64 1.04 1.50 1.46 1.

F 1.37 2.31 1.12 2.04 0.09 1.39 1.22 1.

G 1.16 1.26 1.20 1.05 1.06 0.80 0.93 1.

I 1.07 1.17 0.88 0.71 0.75 0.61 0.66 1.

Avg. 3.32 1.72 1.06 1.31 0.95 1.00 1.04 1.

Studying the results shown in Table 9, three conclusions can be drawn. The beverage made in accordance with the present invention: (1) increases plasma glutamine; (2) elevates plasma growth hormone levels; and (3) augments base reserves. Figures 1 through 9 are graphs illustrating the differences in glutamine and growth hormone levels in the nine participants, respectively. The shaded areas at the bottom left hand corners of the graph represent the time at which the beverage containing the glutamine was consumed by the participants. The Figure "a"'s represent plasma glutamine levels and the Figure "b"'s represent the growth hormone levels. A guick review of these graphs of the data obtained clearly show a marked increase in both glutamine and growth hormone levels. The difference between the control (i.e., each participant not having consumed the beverage of the present invention) and the test (i.e., each participant having consumed the beverage of the present invention) data has been highlighted by shading in the area between the two sets of data. The increase in both the glutamine and growth hormone levels are easily seen. The one exception concerned participant H, who did not respond to the beverage of the present invention as did the others. It is suspected that his weight and height came into play and that said participant would require a higher amount of glutamine to achieve results similar to the others.

By comparing the degree of change in bicarbonate levels from time 0 to time 90 from the results given in Table 9, it is clearly shown as well that the beverage made in accordance with the present invention causes a significant increase in bicarbonate. The comparison of these figures is given in Table 11. Except for Participant H, all others showed a definitive increase in base production.

Table 11. Comparison of Bicarbonate

Levels at Time 0 and 90

ΔHC0₃-

Subject Control Test

A -0.70 +5.14

B -1.71 +1.71

C -2.22 +3.93

D -1.72 +0.73

E 0 +1.91

F +0.96 +3.30

G -0.37 +5.78

H -1.49 -2.94

I -1.72 +1.73

Based on the technical and clinical results discussed above, it is easy to recognize that upon the _ consumption of the beverage made in accordance with the present invention, the consumer is fully "primed" and

5 ready for an intensive workout, an enhanced athletic performance or merely a resculpturing of his or her physique. That is, by consuming the health beverage made in accordance with the present invention before the onset of exercise, the body's mechanism for natural bicarbonate generation is activated via the kidneys. The bicarbonate generation occurs prior to any excess acid generation by the muscle as a result of any impending exercise or activity. Since accumulation of acid becomes rate limiting for performance, the ingestion of the beverage composition of the present invention and the generation of bicarbonate offsets the acid generation and thereby eliminates this barrier to perform. Further, the beverage of the present invention causes the body's metabolism to switch to fat as a fuel even in the absence of exercise.

Example 2

16 fluid oz. (473 ml) of Gatorade was mixed with 4g pure glutamine. Said beverage composition had a pH of 4.0. Said beverage was consumed and the levels of glutamine, glutamate, alanine, growth hormone and bicarbonate were determined at periods of 30, 60 and 90 minutes following ingestion of the beverage. The results are shown below in Table 12.

Table 12 :. Gatorade/glutamine beverage

Glutamate Glutamine Alanine Growth hormone Bicarbonate

Concentration Concentration Concentration Concentration Concentration

Time (nmol/ral) (nmol/ml) (nmol/ml) (ng/ml) (mM)

8:59 60 602 209 0.30 24.00

(beverage consumed) ^9!30 90 741 220 0.24 26.00

10:00 105 721 196 0.61 26.50

10:30 105 610 191 0.51 27.25

As can be seen by a review of the results given in Table 12, comparative results to the tests performed in conjunction with the diet cola were achieved with the use of Gatorade.

In summary, consumption of the beverage or foodstuff compositions according to the present invention not only affords enhanced physical performance, but also aids in the reduction of fat, even in the absence of exercise. The beverage accelerates a beneficial physiological process which is ideal in the anticipation of a physical challenge.

Based on the above, the present invention is further directed generally to an article of manufacture comprising a packaging material and an ingestible composition according to the present invention contained within said packaging material, wherein said ingestible composition comprises an effective amount of glutamine sufficient for accomplishing the results discussed above, and wherein said packaging material comprises a label which indicates that said ingestible composition can be used for obtaining said results.

The ingestible compositions contained in the packaging material can be either the beverage or foodstuff compositions made in accordance with the present invention. The packaging material is any material which can sufficiently contain the ingestible composition and is capable of having a label affixed thereto. For example, for an article of manufacture comprising a beverage composition in accordance with the present invention, the packaging material can be that which is used for any typical beverage compositions, e.g. an aluminum can, glass bottle, and the like. For a solid product, the packaging material can be a box or can, or simply a wrapper on which the label is printed. The label on the packaging material can take on any form sufficient to indicate to the consumer what the ingestible composition can be used for. In the instant case, the label can indicate that the ingestible composition can be used for increasing the blood levels of growth hormone, for enhancing physical performance and/or for reducing fat.

The above preferred embodiments and example are given to illustrate the scope and spirit of the present invention. The embodiments and examples described herein will make apparent, to those skilled in the art, other embodiments and examples. These other embodiments and examples are within the contemplation of the present invention. Therefore, the present invention should be limited only by the appended claims.

Claims

WHAT IS CLAIMED IS:

1. An ingestible composition comprising an effective amount of glutamine sufficient to induce a growth hormone response, said growth hormone response being an increase in the amount of growth hormone in blood.

2. The ingestible composition according to Claim 1 wherein said composition is a liquid beverage composition.

3. The ingestible composition according to Claim 1 wherein said composition is a powdered beverage formulation.

4. The ingestible composition according to Claim

1 wherein said composition is a foodstuff.

5. The ingestible composition according to Claim

2 wherein said liquid beverage composition comprises glutamine in an acidic liquid vehicle.

6. The ingestible composition according to Claim 5 wherein said glutamine is present in an amount from about 1.0 to about 4.0g per 473ml of the acidic liquid vehicle.

7. The ingestible composition according to Claim 6 wherein said glutamine is present in an amount of from about 1.5g to about 2.5g per 473 ml of the acidic liquid.

8. The ingestible composition according to Claim 5 wherein said acidic liquid vehicle has a pH value of about 3.0 to about 5.0.

9. The ingestible composition according to Claim 8 wherein said acidic liquid vehicle has a pH value of about 3.8 to about 4.2.

10. The ingestible composition according to Claim 8 further comprising acid selected from the group consisting of citric acid, phosphoric acid and mixtures thereof, in an amount of said acid sufficient to maintain said pH value.

11. The ingestible composition according to Claim 5 further comprising an effective amount of sodium dihydrogen phosphate sufficient to buffer the acidic liquid vehicle.

12. The ingestible composition according to Claim 11 wherein said effective amount of sodium dihydrogen phosphate is from about 0.01 to about 0.2g.

13. The ingestible composition according to Claim 1 further comprising an effective amount of benzoate sufficient to channel the glutamine through the blood from the liver to the muscles.

14. The ingestible composition according to Claim 13 wherein said effective amount of benzoate is from about .Olg to about l.Og.

15. The ingestible composition according to Claim 14 wherein said effective amount of benzoate is from about .02g to about .3g.

16. The ingestible composition according to Claim 1 further comprising an effective amount of arginine sufficient to elevate blood levels of arginine.

17. The ingestible composition according to Claim 16 wherein said effective amount of arginine is from about 1.0 to about 4.0g.

18. The ingestible composition according to Claim 16 wherein said effective amount of arginine is from about 1.0 to about 3.0g.

19. The ingestible composition according to Claim 3 wherein said powdered beverage formulation comprises glutamine in an amount from about 1.0 to about 4.0g.

20. The ingestible composition according to

Claim 4 wherein said foodstuff comprises glutamine in an amount of at least l.Og.

21. A method of enhancing the physical performance of a human comprising administering to said human an ingestible composition an effective length of time prior to said physical performance, wherein said ingestible composition comprises an effective amount of glutamine sufficient to induce a growth hormone response, said growth hormone response being an increase in the amount of growth hormone in blood.

22. The method according to Claim 21 wherein said ingestible composition is administered in a period of about 5 to about 20 minutes prior to said physical performance.

23. The method according to Claim 21 wherein said physical performance is an athletic performance.

24. The method according to Claim 21 wherein said physical performance is a form of exercise.

25. The method according to Claim 21 wherein said ingestible composition being administered is a liquid beverage composition.

26. The method according to Claim 21 wherein said ingestible composition being administered is a foodstuff.

27. The method according to Claim 25 wherein said liquid beverage composition being administered comprises glutamine in an acidic liquid vehicle.

28. The method according to Claim 27 wherein said glutamine is present in an amount from about 1.0 to about 4.0g per 473 ml of the acidic liquid vehicle.

29. The method according to Claim 28 wherein said glutamine is present in an amount of from about 1.5g to about 2.5g per 473ml of the acidic liquid vehicle.

30. The method according to Claim 27 wherein said acidic liquid vehicle has a pH value of about 3.0 to about 5.0.

31. The method according to Claim 30 wherein said acidic liquid vehicle has a pH value of about 3.8 to about 4.2.

32. The method according to Claim 27 wherein said liquid beverage composition being administered further comprises acid selected from the group consisting of citric acid, phosphoric acid, and mixtures thereof, in an amount effective to maintain said specific pH value.

33. The method according to Claim 27 wherein said liquid beverage composition being administered further comprises an effective amount of sodium dihydrogen phosphate sufficient to buffer the acidic liquid vehicle.

34. The method according to Claim 33 wherein said effective amount of sodium dihydrogen phosphate is from about O.Olg to about 0.2g.

35. The method according to Claim 21 wherein said ingestible composition being administered further comprises an effective amount of benzoate sufficient to channel the glutamine through the blood from the liver to the muscles.

36. The method according to Claim 35 wherein said effective amount of benzoate is from about 1.0 to about l.Og.

37. The method according to Claim 21 wherein said ingestible composition being administered further comprises an effective amount of arginine sufficient to elevate blood levels of arginine.

38. The method according to Claim 37 wherein said effective amount of arginine is from about 1.0 to about 4.0g.

39. The method according to Claim 38 wherein said effective amount of arginine is from about 1.0 about 3.0g.

40. The method according to Claim 26 wherein said foodstuff comprises glutamine in an amount of at least about l.Og.

41. A method of inducing the metabolization of fat in a human comprising administering to said human an ingestible composition comprising an amount of glutamine sufficient to induce an increase in the amount of growth hormone in blood.

42. The method according to Claim 40 wherein said ingestible composition is administered in a period of about 5 to about 60 minutes subsequent to eating.

43. The method according to Claim 41 wherein said ingestible composition being administered is a liquid beverage composition.

44. The method according to Claim 41 wherein said ingestible composition being administered is a foodstuff.

45. The method according to Claim 43 wherein said liquid beverage composition being administered comprises glutamine in an acidic liquid vehicle.

46. The method according to Claim 45 wherein said glutamine is present in an amount from about 1.0 to about 4.0g per 473ml of the acidic liquid vehicle.

47. The method according to Claim 46 wherein said glutamine is present in an amount of from about l.5g to about 2.5g per 473ml of the acidic liquid vehicle.

48. The method according to Claim 45 wherein said acidic liquid vehicle has a pH value of about 3.0 to about 5.0.

49. The method according to Claim 48 wherein said acidic liquid vehicle has a pH value of about 3.8 to about 4.2.

50. The method according to Claim 45 wherein said liquid beverage composition being administered further comprises acid selected from the group consisting of citric acid, phosphoric acid, and mixtures thereof, in an amount effective to maintain said specific pH value.

51. The method according to Claim 45 wherein said liquid beverage composition being administered further comprises an effective amount of sodium dihydrogen phosphate sufficient to buffer the acidic liquid vehicle.

52. The method according to Claim 51 wherein said effective amount of sodium dihydrogen phosphate is from about O.Olg to about 0.2g.

53. The method according to Claim 41 wherein said ingestible composition being administered further comprises an effective amount of benzoate sufficient to channel the glutamine through the blood from the liver to the muscles.

54. The method according to Claim 53 wherein said effective amount of benzoate is from about .01 to about l.Og.

55. The method according to Claim 41 wherein said ingestible composition being administered further comprises an effective amount of arginine sufficient to elevate blood levels of arginine.

56. The method according to Claim 55 wherein said effective amount of arginine is from about 1.0 to about 4.0g.

57. The method according to Claim 56 wherein said effective amount of arginine is from about 1.0 to about 3.0g.

58. The method according to Claim 44 wherein said foodstuff comprises glutamine in an amount of at least about l.Og.

59. An article of manufacture comprising a packaging material and an ingestible composition contained within said packaging material, wherein said ingestible composition comprises an effective amount of glutamine sufficient for increasing the blood levels of growth hormone in a human, and wherein said packaging material comprises a label which indicates that said ingestible composition can be used for enhancing physical performance.

60. The article of manufacture according to Claim 59 wherein said physical performance is an athletic performance.

61. The article of manufacture according to Claim 59 wherein said physical performance is a form of exercise.

62. An article of manufacture comprising a packaging material and an ingestible composition contained within said packaging material, wherein said ingestible composition comprises an effective amount of glutamine sufficient for increasing the blood levels of growth hormone in a human and wherein said packaging material comprises a label which indicates that said ingestible composition can be used for inducing the metabolization of fat.

63. An article of manufacture comprising a packaging material and an ingestible composition contained within said packaging material, wherein said ingestible composition comprises an effective amount of glutamine sufficient for increasing the blood levels of growth hormone in a human, and wherein said packaging material comprises a label which indicates that said ingestible composition can be used for increasing the blood levels of growth hormone level in a human.