WO1991010441A1

WO1991010441A1 - Polypeptide and amino acid based composition

Info

Publication number: WO1991010441A1
Application number: PCT/FR1991/000029
Authority: WO
Inventors: François Mendy; Philippe Thonart; Dominique Delacroix
Original assignee: Medgenix Group S.A.
Priority date: 1990-01-18
Filing date: 1991-01-18
Publication date: 1991-07-25
Also published as: FR2657013A1; JPH04506080A; FR2657013B1; EP0463154A1

Abstract

A composition characterized in that it comprises essentially a polypeptide having a high content of tryptophane, and arginin and/or ornithin possibly in peptide form.

Description

- COMPOSITION BASED ON POLYPEPTIDES AND AMINO ACIDS

The present invention relates to a composition based on polypeptide (s) and amino acids.

Tryptophan is a precursor of serotonin and therefore has a serotonergic action. Consequently, it influences several functions and behaviors among which mainly appetite, the choice of foods low in carbohydrates (selective appetite) or satiety, that is to say food intake, and drowsiness or sedation. Serotonin has also been described as capable of influencing other functions and behaviors such as mood regulation, depression, sensitivity to pain, sexual behavior and aggression, temperature regulation.

It is indeed now established that the administration of L-tryptophan before meals decreases food intake and in particular the intake of carbohydrates. Tryptophan also has an influence on gastric emptying by slowing it down and an anti-acidic gastric secretion effect and thereby contributes to a general feeling of well-being and comfort.

Clinical tests of the effect of tryptophan on sleep have shown that it is effective in people with insomnia and who have a long period of falling asleep. Recent studies have shown that at high doses (500 mg) and combined with carbohydrates, tryptophan constitutes an effective sedative.

Tryptophan therefore has a weight-regulating effect of differential choice of food type and, if necessary, makes it possible to induce weight loss. Tryptophan, as it promotes the serotonergic pathway, also has a mood-regulating effect and potentiates anti-depressive drugs, the modes of action of which are serotonergic. Mention may be made, purely by way of illustration, of drugs such as Hoxypral or Prozac. However, free L-tryptophan has recently been banned in the United States and Europe following the appearance of toxic side effects, in particular the appearance of myalgia which has been observed in large doses. In addition, arginine is known to facilitate the presence of elevated levels of growth hormone at night and to have an anabolic and fortifying effect and in particular to promote growth.

The object of the present invention is to provide a composition generally having a serotonergic effect and, more precisely, having

- on subjects with an overweight a weight loss effect without inducing a drop in tone, and / or

- on subjects suffering from depression, a mood-regulating effect and potential for anti-depressive drugs, and this by overcoming the disadvantages of tryptophan in free form, such as the appearance of myalgia, a need for larger doses for same effect, and an abnormal metabolic regulation effect that this can induce.

According to a first essential characteristic, the invention consists in bringing L-tryptophan into the body in poly¬ peptide form. Until the present invention, the primary interest in the absorption of tryptophan in poly¬ peptide form has never been taken into account.

According to the present invention, it has been discovered that the whole of the metabolic regulation linked to the rate and the kinetics of the passage of tryptophan in the three barriers - intestinal, hepatic and cerebral - is dominated by the first (intestinal barrier).

It has been observed in particular, thanks to hydrolysates of milk proteins that the absorption efficiency and the metabolic effects between L-tryptophan, administered in free form, and in polypeptide and / or oligopeptide form, are very different with a kinetics d appearance in the portal vein completely different. L-tryptophan is preferentially absorbed with a completely different kinetics of appearance in the portal vein when it is administered in polypeptide form, that is to say in the form of a polypeptide with a high tryptophan content. According to a first characteristic of the invention, the compositions according to the invention therefore comprise a polypeptide with a high content of tryptophan. Suitably, the polypeptide has a tryptophan content greater than 2.2% by weight. This content is found in particular in albumin of animal origin and in particular dairy albumin, such as apha-lactalbumin, while the average value of this content of tryptophan in proteins is generally of the order of 1%. .

Thus, alpha-iactalbumin whose tryptophan content is of the order of 6.6%, or a mixture rich in alpha-lactalbumin bringing more than 2.2% of tryptophan, appeared entirely suitable in the compositions. according to the invention.

In addition, the ratio (tryptophan / phenylalanine + tyrosine) of alpha-iactalbumin is advantageously high, of the order of 0.45, against values of 0.06-0.3 for the other whey proteins and 0 , 13 for casein or total milk protein. However, the ratio (tryptophan / phenylalanine + tyrosine) is also very important according to the invention. Indeed, just as tryptophan has a serotonergic action, phenylalanine and tyrosine can have a dopaminergic action which it is necessary to lower because the stimulation of the dopaminergic system which they induce takes place at the expense of the serotonergic system. They are also the main competitors of tryptophan for the passage of the three intestinal, hepatic and cerebral barriers.

Alpha-iactalbumin also has a high ratio (tryptophane / phenylalanine + tyrosine + leucine + valine + isoleucine + methionine), namely around 0.195 against values of 0.038 for casein usually used in weight loss diets , or 0.038 for total milk protein, or 0.06 for total whey protein.

However, the ingested tryptophan influences the production of serotonin all the more since the ratio (tryptophan / phenylalanine + tyrosine + leucine + valine + isoleucine + methionine) is high. The passage of the brain barrier (third barrier) depends on the ratio existing in the blood circulating at a given time between certain neutral amino acids, know the ratio (tryptophan / phenylalanine + valine + isoleucine + leucine + tyrosine + methionine). The higher this ratio, the easier the passage of tryptophan at the expense of other amino acids.

Advantageously therefore, according to the present invention, the composition will be such that the overall ratio (tryptophan / phenylalanine * tyrosine + leucine + valine + isoleucine + methionine) is between 0.065 and 0.2. Similarly, according to the invention, the ratio (tryptophan / tyrosine + phenylalanine) is advantageously between 0.2 and 0.65, preferably between 0.29 and 0.45. However, proteins with a high tryptophan content, such as albumin, have a major drawback, namely that the ratio of lysine and arginine (Lys / Arg) contents is too high. The ratio of the lysine and arginine (Lys / Arg) contents in the blood circulation, induces an increase in the serum cholesterol level and also an increase in the circulating insulin / glucagon ratio, which is unfavorable in particular in the field of obesity, atherosclerosis because inducing the synthesis of lipids and cholesterol (Sanchez et al. Atherosclerosis, 1988, 71, 87).

This is why, according to the second essential characteristic of the present invention, the compositions comprise, in addition to a polypeptide with a high content of tryptophan, arginine, preferably in peptide form.

Preferably, the arginine intake will be such that the overall lysine / arginine content ratio, that is to say taking into account the amino acids in free form or used in the composition of the polypeptide, remains between 1 , and 2, which is the average acceptable value that can be found globally in cow or human milk (female milk: 1.4, casein: 2.07, total cow's milk protein: 2.24, total whey protein: 3.3). In addition, the drop in the lysine / arginine ratio, and hence the insulin / glucagon ratio, also induces a weight loss effect.

If the administration of alpha lactalbumin accelerates the feeling of satiety during meals, slows gastric emptying, decreases palatability carbohydrates, and generally produces a feeling of well-being, these various effects are not or little obtained with free tryptophan. The ratio (lysine / arginine) of alpha-iactalbumin which is 4.7 is however too high. This is why, according to a preferred variant embodiment of the compositions according to the invention, the composition will comprise the combination of alpha-lactalbumin and L-arginine.

In a particular embodiment, the arginine is supplied in the form of the arginine aspartate salt or arginine glutamate or a mixture of these salts. Studies on new lean genetic breeds obtained in Zootechnics, show that they are characterized in large mammals by higher plasma concentrations of growth hormone and lower insulin levels. It appears that there is interest in acting throughout life on the growth hormone so as to keep lean body mass intact for as long as possible. Arginine, which induces nocturnal secretion of growth hormone, therefore also has a role in the conservation and reconstitution of lean mass.

The combination of polypeptides with a high content of tryptophane such as in particular alpha-iactalbumin or a mixture rich in alpha-lactaibumine, and arginine, therefore provides a composition providing, in general, a feeling of well-being. being and of comfort having an anti-depressive or rebalancing effect of mood, but also an effect of regulation of the appetite and, if necessary, of reduction of food intake and selection of foods lower in carbohydrate, and therefore promoting weight loss without inducing a drop in tone. It still has an anabolic and growth-promoting effect as well as an increase in lean mass, a sine qua non condition for maintaining weight loss, or not increasing weight with an equal caloric intake at the end of the diet.

The compositions according to the invention also correct the side effects linked to the administration of drugs whose mechanisms of action use the serotonergic pathways and prolong their effectiveness. The compositions according to the invention can therefore be used as dietetic or nutritional compositions, in particular as a meal replacement, or as compositions having an anti-depressive and mood-balancing effect, complement of serotonergic psychotropic substances.

According to another characteristic of the present invention, it is possible to correct the negative effects of the ratio (lysine / arginine) when it is too high in the polypeptide according to the invention, in particular with regard to the maintenance or the increase in lean mass, correcting the ratio (lysine / ornithine) by ornithine intake, insofar as it is as a precursor of ornithine that arginine acts on the maintenance of high nocturnal levels of the hormone growth.

In its most general aspect, the present invention therefore relates to a composition characterized in that it essentially comprises a polypeptide with a high content of tryptophan, and arginine or a peptide rich in arginine so as to correct the content ratio (lysine / arginine) if it is too high, and / or ornithine or a peptide rich in ornithine to compensate for the negative effects of the ratio (lysine / arginine) if it is too high. Mention may be made, as arginine-rich peptide, of arginine aspartate or arginine glutamate, and as ornithine-rich peptide, mention may be made of ornithine acetoglutarate. More generally, the term “peptide” is understood here to mean 2 to 8 amino acids.

According to one embodiment of the invention, the compositions according to the invention will comprise the association of a polypeptide with a high content of tryptophan in particular of alpha-iactalbumin and of L-ornithine.

The replacement of arginine by ornithine will be specially indicated when the effect on growth hormone is most sought after, that is to say during the night phase. In one embodiment, therefore, 1 to 10% will preferably be added around 5%, for example 3 to 7%, by weight of arginine or ornithine in the form of free amino acids or aspartate dipeptides arginine, arginine glutamate or ornithine acetoglutarate relative to the weight of total proteins used in the composition.

Ornithine will be added so that the lysine / ornithine ratio is between 0.7 and 2.

Advantageously, the compositions according to the invention will comprise a taurine supply of 2.5 to 7 mg per gram of polypeptide (s) entering into the composition, that is to say one to two times the rate of female milk, this especially in the case where the protein has a low methionine or sulfur amino acid level. This is the case for alpha-iactalbumin. Taurine is a protection when the polyunsaturated fatty acids contained in adipose reserves are released during weight loss diets.

The alpha-iactalbumin in the compositions according to the invention can be used in pure form or in admixture with other whey proteins such as beta-lactoglobulin and serum albumin.

Advantageously, a mixture of whey proteins will be used, comprising the protein CMP (Casein Macro Peptide) which has an effect against gastric "cramps" and an anti-gastrin effect limiting nocturnal acid secretion.

In one embodiment, the whey proteins will be recovered after separation of the immunoglobulins (with a molecular weight greater than 100,000). The latter, although having a tryptophan content of 3%, have a tryptophan / phenylalanine + tyrosine ratio of 0.29 and tryptophan / phenylalanine + tyrosine + leucine + valine + isoleucine + methione of 0.09. In addition, they are difficult to digest and allergenic. A mixture of whey proteins enriched in alpha-lactalbumin can be obtained for example by precipitating beta-lactoglobulin in the cheese curd. The precipitation of beta-lactoglobulin can be combined with the extraction of immunoglobulins. The compositions according to the invention of the polypeptide type associated with arginine will rather be intended to be administered in the day before meals and the compositions comprising a polypeptide associated with L-ornithine will rather be intended to be administered in the evening at bedtime. . The compositions according to the invention will advantageously comprise polyunsaturated fatty acids in particular those having a double bond in delta 9 and / or delta 6 such as gamma-linolenic or stearidonic acids as well as those having an unsaturation in delta 4 and / or delta 5 or else the compositions according to the invention will comprise an oil comprising such as blackcurrant or borage seed oils or an oil fraction enriched in polyunsaturated fatty acids such as gamma-linolenic or stearidonic acid.

The compositions according to the invention may also include vitamins, in particular niacin and vitamin C. The compositions to be taken before sleep with an effect more focused on the regulation of mood and sleep will advantageously include carbohydrates. long chains (dextrins-maltoses) in a protein / carbohydrate weight ratio of 1/4 to 2/1.

Suitably, the daily dose will consist of one, two or three unit doses and will include an equivalent of 200 to 650 mg of L-tryptophan supplied in polypeptide form, that is to say in the case of alpha-iactalbumin 5 to 20 g of polypeptide, in combination if necessary up to 850 mg of L-arginine or L-ornithine, for example from 200 to 850 mg. The compositions according to the invention may also be supplemented with L-tryptophan in free form at low dose, for example in a daily dose of 90 to 200 mg. In any event, the overall amount of L-tryptophan in free or bound form should not exceed the amount of tryptophan in bound form contained in alpha-iactalbumin if the composition only contained pure alpha-iactalbumin. Very advantageously, the drop in the ratio (Lysine / Arginine) can also be obtained by replacing part of the alpha-lactalbumin protein with a vegetable protein or a fraction of vegetable protein rich in arginine and preferably low in tyrosine and phenylalanine .

According to another characteristic, therefore, the compositions according to the invention comprise a vegetable protein, such as a soy protein, a bean protein, a pea or bean protein in an amount ranging up to 30% by weight of the total poiypeptides and proteins contained in the composition.

The vegetable proteins mentioned have a very high arginine content: 8 to 9% for soy protein and up to 10 to 11% for bean protein. Their tryptophan content is also of the order of 2 to 3% by weight. But above all these vegetable proteins improve the relationship between (Tryptophan / Phenylalanine + Tyrosine) and therefore stimulate the serotoninergic system at the expense of the dopaminergic system.

In one embodiment, the compositions according to the invention comprise, as vegetable protein, a fraction of vegetable protein poor in phenylalanine and tyrosine and with a low Lysine / Arginine ratio. Mention may in particular be made, with regard to soy protein, of the 7 S fraction (JAOC5 vol. 67, no. 5, p. 265). This 7 S fraction decreases the Lysine / Arginine ratio and increases the Tryptophan / Phenylalanine + Tyrosine ratio but also increases the ratio (Tryp / Phe + Tyr + Leu + Val + Iso + Meth). We can also cite the legume fraction of pea protein (CRC Criticai revie s in plant science 1984, Vol. 1, page 287) as well as the total globulin fraction of sunflower protein (CETIOM Technical Information No. 102 1988/1 , pages 18 and 53.

The examples of compositions given above and below can be modified by replacing 30% by weight of the proteins of the composition with a vegetable protein or fraction of vegetable protein, as mentioned above. A number of nonlimiting examples of compositions according to the invention are given below.

The term "aipha-lactalbumin" is understood below as "mixture quality" (220 mg of L-tryptophan per 10 g of alpha-lactalbumin), the whey protein mixture enriched in alpha-lactalbumin. Milk seroproteins are in fact made up of 50% beta-lactoglobulin, 22% alpha-lactalbumin, 12% immunogiobulin, 5% serum albumin and 10% proteoses / peptones. The alpha-lactalbumin-beta-lactoglobulin mixture comes from a whey depleted in beta-lactoglobulin like most whey residues from the cheese industry and secondarily depleted in immunoglobulin.

The amino acid composition of this mixture is as follows: per 100 g of amino acid

- aspartic acid: 14.1 - threonine: 5.7

- serine: 5.0

- glutamic acid: 17.1

- proline: 4.7

- methionine: 1.5

- leucine: 11.0 - isoleucine: 6.2

- tyrosine: 5.1

- phenylalanine: 4.4

- histidine: 3.0

- lysine: 10.5 - arginine: 2.3

- tryptophan: 2.2

If a product bringing CMP is desired, the product chosen will be a rennet whey, depleted in beta-lactoglobulin, then secondarily in immunoglobulin as above. EXAMPLE 1: COMPOSITIONS FOR MAINTAINING Lean MASS.

A. Mixture of 2 or 3 active principles based exclusively on peptide Tryptophan

A.l. Unit dose

1. 220 to 400 mg of L-Tryptophan brought in the form of: - 10 g of alpha-lactalbumin "quality mix"

(220 mg of bound tryptophan) or - 10 g of "pure" alpha-lactalbumin (400 mg of bound tryptophan).

2. 420 mg of arginine supplied in the form of L-arginine or aspartate salt or arginine glutamate.

The lysine / arginine ratio of this composition is 1.63 and the Try / Phe + Tyr + Leu + Val + Iso + Leu + Met ratio is 0.06.

A.2. Unit dose

1.5g of pure alpha-lactalbumin (200 mg of bound tryptophan)

2. 5 g of fraction 7S (conglycinin) of soy protein, rich or arginine.

This mixture provides 250 mg of bound Tryptophan and reduces the lysine / arginine ratio to 1.6 without correction by the

L-Arginine. A.3. Unit dose

1. 7 g of alpha-lactalbumin 3% Trp (210 mg of bound Trp).

2. 3 g of fraction 7S (conglycinin) of soy protein rich in arginine.

3. 200 mg of L-Arginine in the form of aspartate salt or glutamate.

This mixture provides 240 mg of bound Tryptophan and reduces the lysine / arginine ratio to 1.6.

A.4. Unit dose

1. 12 g of alpha-lactalbumin 3% Trp (360 mg of bound Trp).

2. 8 g of soy milk, rich in arginine.

3. 12 g of carbohydrate in the form of Dextrin maltose.

B. Mixture of 3 active ingredients containing Tryptophan in peptide form and in free form

B.l. Unit dose

1. 110 mg of L-Tryptophan brought in the form of alpha-lactalbu¬ mine "blend quality", ie 5 g of lactalbumin blend quality.

2. 90 mg of free quality CODEX L-Tryptophan.

3. 210 mg of L-arginine in the form of aspartate salt or glutamate. The Tyr / Phe + Tyr + Leu + Val + Iso + Leu + Met ratio of this composition is 0.10.

B.2. Daily dose or 1 or 2 unit doses

1. 10 g of alpha-lactalbumin "quality mix" bringing 220 mg of tryptophan.

2. 180 mg of CODEX quality L-tryptophan.

10

3. 420 mg of L-Arginine in the form of aspartate or glutamate.

4. 100 mg of Vitamin C.

1 These mixtures can enter into the composition of meal replacements and products for convalescents, products for sportsmen when they are supplemented with polyunsaturated fatty acids in C 18 in appropriate carbohydrates, in macro and mineral microelements, lipo and water soluble vitamins, micro-nutrients, like taurine,

20 choline and carnitine, according to the laws in force in the various countries.

Likewise, C1 8 polyunsaturated fatty acids having a delta 6, stearidonic or gammalinolenic acid double bond may be added:

- in the form of oils, enriched triglycerides, fatty acid esters,

30 - in a ratio of 50 to 400 mg per 20 gr of protein.

B.3. Daily dose or 1 or 2 unit doses

1. 10 g of alpha-lactalbumin "quality mix" bringing 220 mg ^ of tryptophan. 2. 180 mg of Codex free quality L-Tryptophan.

3.330 mg of L-Ornithine.

4. 100 mg of vitamin C.

C. Mixture of 3 active ingredients containing carbohydrates

l. 5 g of "pure" alpha-lactalbumin (200 mg of bound TRP).

2.5 g of fraction 7S (conglycinin) of soy protein, rich in arginine.

3.5 g of carbohydrates in the form of dextrin maltose.

EXAMPLE 2 COMPOSITIONS FOR THE REGULATION OF MOOD AND SLEEP AND FOR THE PREVENTION OF AGING.

A. Mixtures of 2 active ingredients

A.l. 1. 10 g of "pure" alpha-lactalbumin (400 mg of bound Tryptophan).

2. 420 mg of arginine in the form of aspartate.

A.2.

1. 10 g of "pure" alpha-lactalbumin (400 mg of bound Tryptophan). 2. 330 mg of L-Ornithine. A.3.

1.5 g of "pure" alpha-lactalbumin (200 mg of bound Trp)

2. 5 g of fraction 7S (conglycinin) of soy protein or fraction called "reserve protein", "storage proteins", of proteolaginous or proteamylaceous bringing an amount at least equivalent in arginine, a low amount in lysine:

- sunflower globulin, pea or bean legume or low molecular weight fraction of proteins with a more metabolic role in proteologic seeds bringing an equivalent amount of arginine, a small amount of lysine, a greater amount than the first fraction of acids sulfur amines:

- low molecular weight sunflower albumin.

B. Mixture of 3 active ingredients + flavor

1. 5 g of "pure" alpha-lactalbumin (200 mg of bound TRP).

2.5 g of fraction 75 (conglycinin) of soy protein.

3. 20 g of carbohydrates in the form of dextrin maltose. (4) Chocolate flavor

These protein mixtures can enter into the composition of nutritional supplements, as long as they are complemented with essential polyunsaturated C 18 fatty acids (and / or essential), with suitable carbohydrates, with macro and mineral microelements, water-soluble vitamins , micro-nutrients like taurine, choline and carnitine, according to the laws in force in the various countries.

Similarly, they can be added with polyunsaturated fatty acids C18 having a double bond in delta 6, stearidonic or gammalinolenic acid:

- in the form of oils, enriched triglycerides, fatty acid esters,

- in a ratio of 50 to 400 mg per 20 gr of protein. They can also enter into the composition of pharmaceutical products, for example by being enriched with highly unsaturated fatty acids in C20 and / or C22 having a double bond, in delta 8, delta 7, in delta 5 and / or delta 4.

- in the form of enriched triglycerides, esters of these fatty acids, added with vitamin E

- in a ratio of 10 to 400 mg per 20 gr of protein.

EXAMPLE 3 COMPOSITIONS FOR THE PREVENTION OF "CRAMPS" OR GASTRIC PAIN, TO REGULATE NIGHT GASTRIC SECRETIONS.

Cl. Mixture of 4 active ingredients

- 10 g of "pure" aiphalactalbumin (400 mg of bound tryptophan)

- 1 g of CMP

- 330 mg of ornithine in the form of l-ornithine or of a dipeptide

60 mg taurine

C2. Mix of 5 active ingredients

- 10 g of a mixture of proteins rich in alpha-lactalbumin and CMP bringing 230 mg of peptide tryptophan,

- 1 g of CMP. These protein mixtures can enter into the composition of nutritional supplements, as soon as they are complemented with essential polyunsaturated C 18 fatty acids (and / or essential), appropriate carbohydrates, macro and mineral microelements, lipo and water-soluble vitamins , micro-nutrients like choline and carnitine, according to the laws in force in the various countries.

Similarly, they can be added with polyunsaturated fatty acids in Cl 8 having a double bond in delta 6, stearidonic acid, or gammalinolenic:

- in the form of oils, enriched triglycerides, fatty acid esters,

- in a ratio of 50 to 400 mg per 20 gr of protein.

They can also enter into the composition of pharmaceutical products, for example by being enriched with highly unsaturated fatty acids in C20 and / or C22 having a double bond, in delta 8, delta 7, in delta 5 and / or delta 4.

- in a ratio of 10 to 400 mg per 20 gr of protein.

Claims

1) Composition characterized in that it essentially comprises a polypeptide with a high content of tryptophan, and arginine or ornithine in free or peptide form.

2) Composition according to claim 1, characterized in that the polypeptide has a tryptophan content greater than 2.2%.

3) Composition according to one of the preceding claims, characterized in that the ratio (Tryptophan / Phenylalanine + Tyrosine) is between 0.2 and 0.65, preferably 0.29 and 0.45.

4) Composition according to one of the preceding claims, characterized in that the ratio (Tryptophan / Phenylalanine + Tyrosine + Leucine + Valine + Isoleucine + Methionine) is between 0.065 and 0.2.

5) Composition according to one of the preceding claims, characterized in that the polypeptide rich in tryptophan is an albumin of animal origin, in particular dairy.

6) Composition according to one of the preceding claims, characterized in that the polypeptide rich in tryptophan is alpha-lactalbumin.

7) Composition according to one of the preceding claims, characterized in that it comprises the combination of said polypeptide and the amino acid L-arginine in free or peptide form and / or L-ornithine in free or peptide form .

8) Composition according to one of the preceding claims, characterized in that the amount of arginine is such that the overall ratio in the composition (lysine / arginine) is between 1.4 and 2. 9) Composition according to one of claims 1 to 7, characterized in that it comprises the combination of said polypeptide and the amino acid L-ornithine such that the overall ratio in the composition (lysine / ornithine) is between 0.7 and 2.

10) Composition according to one of claims 1 to 9, characterized in that it comprises taurine in an intake of 2.5 to 7 mg per gram of polypeptide.

H) Composition according to one of the preceding claims, characterized in that it also comprises L-tryptophan in free form.

12) Composition according to one of the preceding claims, characterized in that the arginine is in the form of the arginine aspartate salt, the arginine glutamate salt or a mixture of these salts.

13) Composition according to claim 12, characterized in that the arginine aspartate and / or arginine glutamate represents 1 to 10%, preferably 3 to 7%, by weight relative to the weight of the total of proteins entering the composition.

14) Composition according to one of the preceding claims, characterized in that it further comprises polyunsaturated fatty acids or an oil comprising them.

15) Composition according to one of the preceding claims, characterized in that the daily dose of one or two unit doses is 200 to 650 mg of L-tryptophan supplied in the form of a polypeptide.

16) Composition according to one of the preceding claims, characterized in that the daily dose of one, two or three unit doses of arginine or ornithine is between 200 and 850 mg. 17) Composition according to one of the preceding claims, characterized in that it comprises a vegetable protein or a fraction of vegetable protein rich in arginine and poor in tyrosine and phenyl¬ alanine chosen from soy proteins, beans, peas, broad beans , sunflower, hazelnut and peanut, the latter representing up to 30% by weight of the total protein used in the composition.

18) Composition according to claim 17, characterized in that the vegetable protein is a fraction of soy protein concentrated in fraction 7 S.

19) Use of a composition according to one of the preceding claims as anti-depressive composition and / or nutritional composition-meal replacement.