WO2010027014A1 - Method for improving absorption of s-adenosyl-l-methionine, and composition having improved s-adenosyl-l-methionine absorption - Google Patents

Abstract

The absorption of S-adenosyl-L-methionine can be improved by ingesting S-adenosyl-L-methionine concomitantly with a polycarboxylic acid.  S-Adenosyl-L-methionine is mixed with a polycarboxylic acid to provide a composition which is improved in the absorption of S-adenosyl-L-methionine.  The composition thus produced can be used as a food, a food with a nutrient function, a food for specified health uses, a nutritional supplement, a nutrient, a beverage, a veterinary medicine, a feed, a cosmetic, a quasi drug, a drug, a therapeutic agent, a prophylactic agent or the like without any modification, or can be processed into the above-mentioned product.

Description

Method for enhancing absorbency of S-adenosyl-L-methionine and composition with enhanced absorbability of S-adenosyl-L-methionine

The present invention relates to a method for enhancing the absorbability of S-adenosyl-L-methionine and a composition having an enhanced absorbability of S-adenosyl-L-methionine.

S-adenosyl-L-methionine (hereinafter abbreviated as SAM) is widely present in living tissues, and is a methyl group donor or enzyme activated in the synthesis and metabolism of nucleic acids, neurotransmitters, phospholipids, hormones, proteins, etc. It is a substance involved in many biological reactions as a factor. SAM is also known to be effective for alcoholic hepatitis and other liver disorders, depression, osteoarthritis, and senile dementia.

As described above, SAM is an important substance for the living body. However, when SAM is orally ingested, it has been clarified that the absorption rate is low and the bioavailability is low (Non-patent Document 1). There is a need to improve the performance. Thus, several attempts have been made to increase the oral absorbability of SAM.

For example, a gastric resistant enteric therapeutic composition for oral use containing a salt of SAM, based on the fact that when administered directly to the intestine, the salt of SAM is absorbed to a significant extent The thing is disclosed (patent document 1). Further, it has been shown that the coexistence of a SAM salt and a monocarboxylic acid and / or a salt thereof improves SAM absorbability and bioavailability (Patent Document 2). Furthermore, it is disclosed that the absorption rate is improved by a composition comprising a water-soluble SAM salt and an organic sodium salt (Patent Document 3).

However, these attempts involve problems such as the need to entericity, problems with the safety of additives added to improve absorption, and insufficient improvement in absorption rate. Therefore, it is hard to say that it is truly practical, and it is not a situation in which attempts to improve the absorbability of SAM have been sufficiently performed so far.

Japanese Laid-Open Patent Publication No. 60-72815 Japanese Laid-Open Patent Publication No. 59-175433 Japanese Laid-Open Patent Publication No. 60-255735

J. Pharmacol. Exp. Ther., R209, 323 (1979)

The present invention has been made in view of the above points, and an object of the present invention is to provide a method for increasing SAM absorbability, a composition having enhanced SAM absorbability, and a method for producing the same. is there.

As a result of intensive studies conducted by the present inventors to solve the above problems, it has been found that the combined use of SAM and polyvalent carboxylic acid can enhance the absorbability of SAM. Therefore, by taking SAM and polyvalent carboxylic acid in combination, it is expected to be highly effective for all symptoms / pathological conditions that SAM is considered to work effectively, such as liver function improvement, depression, bone indirect disease, and senile dementia. can do.

That is, the present invention relates to the following contents.

One of the characteristics of the present invention is a method for enhancing the absorbability of SAM, characterized by ingesting SAM and polyvalent carboxylic acid in combination.

One of the characteristics of the present invention is a composition with enhanced SAM absorbability, which includes SAM and polyvalent carboxylic acid.

One of the characteristics of the present invention is a food comprising the above composition, a functional nutrition food, a food for specified health use, a nutritional supplement, a nutrient, a beverage, an animal medicine, a feed, a cosmetic, a quasi-drug, a pharmaceutical, It is a therapeutic or prophylactic agent.

One of the features of the present invention is an antidepressant comprising the above composition.

One of the features of the present invention is a method for producing a SAM-containing composition, wherein a polyvalent carboxylic acid is added to SAM.

SAM absorption can be enhanced by ingesting SAM and polyvalent carboxylic acid in combination.

Hereinafter, the present invention will be described in detail based on embodiments. The scope of the present invention is not limited by the embodiments and examples.

The production method of the SAM used in the present invention is not particularly limited, and may be a chemical synthesis method or a culture method of microorganisms. Usually, SAM is composed of (SS) -S-adenosyl-L-methionine (hereinafter abbreviated as (SS) -SAM) and (RS) -S-adenosyl-L-methionine (hereinafter abbreviated as (RS) -SAM). Consists of a mixture of two diastereoisomers. However, of the two diastereoisomers, only (SS) -SAM has the activity of an enzymatic methyl group transfer reaction, and this (SS) -SAM is not effective due to non-enzymatic epimerization. It is known that active (RS) -SAM is produced. Regarding the industrial production of SAM, the above-described chemical synthesis method and the method of culturing microorganisms (for example, Saccharomyces yeast) are known. The diastereomeric ratio of active (SS) -SAM From the viewpoint of using a high SAM, the latter method is desirable.

The SAM used in the present invention is not particularly limited, and may be a purified product having high purity, an extract of a microorganism containing SAM, or a microorganism containing SAM. . From the viewpoint of ingesting the active form (SS) -SAM at a low cost, it is preferable to ingest a microorganism or microbial extract sufficiently containing (SS) -SAM.

When a microorganism containing SAM is used in the present invention, any microorganism may be used as long as it contains SAM, but a microorganism containing 1% by weight or more of SAM per dry weight is preferable. Further, it is preferably a microorganism containing 5% by weight or more of SAM per dry weight, and more preferably a microorganism containing SAM of 10% by weight or more per dry weight. Moreover, it is preferable that it is a microorganism with a food experience from a viewpoint used for a foodstuff or a supplement use.

The microorganism used in the present invention is not particularly limited, but includes, for example, Saccharomyces, Candida, Pichia, Mucoa, Rhizopus, Brevibacterium, Corynebacterium, Escherichia, Streptomyces, and the like. Microorganisms belonging to the genus Saccharomyces are preferred. Specific examples include microorganisms such as sake yeast, baker's yeast, beer yeast and wine yeast. More preferred is Saccharomyces cerevisiae K-6 strain (Sake Yeast Association No. 6).

The microorganism used in the present invention may be a wild strain of the above-mentioned microorganism or a mutant strain with improved mutation. Mutant strains can be obtained by methods well known to those skilled in the art, such as UV irradiation and treatment with drugs such as N-methyl-N′-nitro-N-nitrosoguanidine (NTG) and ethylmethanesulfonate (EMS). it can. Furthermore, a transformed microorganism prepared so as to produce SAM at a high level using a method such as gene recombination can also be used. The SAM-containing microorganism may be a live cell or a dead cell, or a wet cell or a dry cell.

In the present invention, when a microbial extract containing SAM is used, the above microbial cells can be crushed and, if necessary, insoluble matter can be removed by centrifugation, filtration or the like. The method of crushing microbial cells is not particularly limited. For example, a method of crushing by high-pressure crushing such as high-pressure dispersion treatment, a method of crushing by mechanical crushing such as a bead mill, a method of crushing by adding acid or alkali, an interface Method of crushing by adding activator, method of crushing by freeze-thawing, method of crushing by heat treatment, method of crushing using proteolytic enzyme, cell wall lytic enzyme, etc., self-digestion using enzymes in yeast And the like.

Preferably, a method of crushing by high-pressure crushing such as high-pressure dispersion treatment, a method of crushing by adding acid or alkali, a method of crushing by heat treatment, and more preferably crushing by high-pressure crushing such as high-pressure dispersion treatment, etc. A method is mentioned. Needless to say, two or more of these crushing methods can be used in combination.

The upper limit of the SAM content in the SAM-containing microbial extract used in the present invention is preferably 99% by weight or less, more preferably 90% by weight or less, and 80% by weight or less. Further preferred. The lower limit of the SAM content in the SAM-containing microbial extract used in the present invention is preferably 1% by weight or more, more preferably 2% by weight or more, and more preferably 5% by weight or more. More preferably.

The form of the microbial extract containing SAM may be a water extract or a solvent extract with alcohol or the like, and a concentrated or dried product obtained by concentrating and drying these. Also good. Examples of the microbial extract containing SAM include SAM-containing dry yeast cell extract.

The presence mode of the SAM used in the present invention in the composition is not particularly limited, and may be, for example, a free form or a salt, or may be in a mixed state.

The polyvalent carboxylic acid used in the present invention is not particularly limited as long as it has the property of enhancing the SAM absorbability. However, the method for increasing the SAM absorbability of the present invention and the SAM absorbability are not particularly limited. From the viewpoint of using the enhanced composition for food and supplement applications, it is preferable to use a polyvalent carboxylic acid that can be used as a food additive. For example, adipic acid, oxalic acid, citric acid, fumaric acid, succinic acid, Tartaric acid, malic acid, glutamic acid, folic acid and the like can be mentioned, among which fumaric acid and tartaric acid are preferable.

Concomitant intake in the present invention means ingestion so that SAM and polycarboxylic acid coexist in the stomach, and SAM and polycarboxylic acid may be ingested simultaneously or continuously. May be. In the case of continuously ingesting SAM and polyvalent carboxylic acid, the order of ingestion is not particularly limited.

Further, the composition having enhanced SAM absorbability in the present invention may be in a liquid form or a dried solid form. Although it does not specifically limit as a drying method, For example, spray drying, freeze drying, reduced pressure drying, aeration drying etc. can be mentioned. Further, two or more of these drying methods can be used in combination.

In the case of drying, the timing for adding the polycarboxylic acid may be either before or after drying. However, from the viewpoint of stably maintaining SAM, which is an unstable substance, the polycarboxylic acid is added after drying. Is preferred. The term “after drying” as used herein refers to the period from the drying step to the actual ingestion, and it is preferable to mix with the polyvalent carboxylic acid as soon as possible.

The lower limit of the amount of polyvalent carboxylic acid used in the present invention is not particularly limited, but is preferably 0.5 parts by weight or more with respect to 100 parts by weight of SAM, and is 5 parts by weight or more. Is more preferable, and 100 parts by weight or more is more preferable. Alternatively, it is preferably 0.1 parts by weight or more, more preferably 1 part by weight or more, and more preferably 20 parts by weight with respect to 100 parts by weight of the SAM-containing microorganism and / or the SAM-containing microorganism extract. More preferably, it is the above.

The upper limit of the amount of polyvalent carboxylic acid used in the present invention is not particularly limited, but is preferably 500 parts by weight or less, and 350 parts by weight or less with respect to 100 parts by weight of SAM. Is more preferably 250 parts by weight or less. Alternatively, it is preferably 100 parts by weight or less, more preferably 70 parts by weight or less, and more preferably 50 parts by weight or less with respect to 100 parts by weight of the microorganism containing SAM and / or the microorganism extract containing SAM. More preferably it is.

Further, the polyvalent carboxylic acid used in the present invention preferably has a pKa1 value of 4 or less, more preferably 3.5 or less, and particularly preferably 3 or less.

In addition, in order to improve the stability of SAM in the composition obtained by the present invention, a stabilizer having an effect of suppressing chemical decomposition and / or epimerization of SAM can be added. The stabilizer is not particularly limited as long as it has the property of suppressing the chemical degradation and / or epimerization of SAM. From the viewpoint of using the composition of the present invention for foods and supplements, food additives It is preferable to use a compound that can be used as a product.

Examples of the stabilizer include inorganic acids and salts thereof, organic acids and salts thereof, saccharides and derivatives thereof, amino acids or peptides and salts thereof, and the like. A salt formed from a divalent cation and an acid is preferable, and examples thereof include zinc sulfate and copper sulfate. More preferably, it is magnesium or a salt formed from calcium and an acid, and examples thereof include magnesium sulfate and calcium sulfate. These stabilizers may be used alone or in combination of two or more kinds of stabilizers.

In the preparation of the composition disclosed in the present invention, the timing of adding the polyvalent carboxylic acid is not particularly limited, but when using the stabilizer, it is preferable to add the acid after adding the stabilizer. .

In the composition obtained by the present invention, an ingredient having an antidepressant effect other than SAM may be added. Ingredients other than SAM that are considered to have antidepressant effects are not particularly limited. For example, tyrosine, acetyltyrosine, tryptophan, 5-hydroxytryptophan, methionine, phenylalanine, St. John's wort, zinc, manganese, magnesium Vitamin B12, niacin, folic acid and the like.

The composition obtained in the present invention can be used as it is or after processing, food, nutritional functional food, food for specified health use, nutritional supplement, nutrient, beverage, animal medicine, feed, cosmetics, quasi-drug, pharmaceutical, treatment It can be used for drugs or preventive drugs. As processing forms of the composition of the present invention, oral administration of capsules such as microcapsules, hard capsules, soft capsules (preferably microcapsules, soft capsules), tablets, powders, chewable tablets, granules, pills, syrups, beverages, etc. It can also be used by further processing into forms, such as creams, suppositories, and toothpastes. Preferred processing forms are capsules, tablets, powders, granules, chewable tablets and pills, and particularly preferably tablets, chewable tablets and capsules.

In the case of a capsule, the capsule base is not particularly limited, and can be used as other bases (for example, food additives) including gelatin derived from cow bone, cow skin, pig skin, fish skin, etc. Thickening stabilizers such as carrageenan, alginic acid and other seaweed-derived products, plant seed-derived products such as locust bean gum and guar gum, and plant secretion-derived products such as gum arabic and production agents containing celluloses may also be used.

The lower limit of the pH when adding water to the composition obtained in the present invention to obtain a solution or suspension having a SAM concentration of 20 mg / mL is preferably 0 or more, more preferably 1 or more. The upper limit of the pH when adding water to the composition obtained in the present invention to make a solution or suspension having a SAM concentration of 20 mg / mL is preferably 4 or less, more preferably 3 or less. preferable.

Specific examples of the present invention are shown below, but the present invention is not limited to these examples.

Reference Example 1 Culture of SAM-Containing Microorganism Saccharomyces cerevisiae K-6 strain was sucrose 150 g / L, ethanol 18 g / L, yeast extract 10 g / L, L-methionine 10 g / L, urea 18 g / L, Glycine 2 g / L, potassium dihydrogen phosphate 4 g / L, magnesium sulfate heptahydrate 0.2 g / L, biotin 2 mg / L, calcium chloride dihydrate 0.2 g / L, zinc sulfate heptahydrate 10 mg / L, ferrous sulfate heptahydrate 5 mg / L, manganese sulfate tetrahydrate 5 mg / L, cobalt chloride hexahydrate 0.2 mg / L, copper sulfate pentahydrate 0.1 mg / L, iodine The inoculum was inoculated into a medium consisting of 0.1 mg / L of potassium halide and cultured for 4 days in an 5 L jar incubator at 30 ° C. with aeration and stirring. Yeast cells were collected from the obtained culture broth by centrifugation. The yeast cells were suspended by adding the same amount of deionized water as the culture solution, and then washed twice to collect the yeast cells by centrifugation to obtain yeast cells containing SAM.

The SAM content in the obtained yeast cells was 12% by weight based on the dry weight of the yeast cells. In addition, the content of SAM contained in yeast cells was analyzed using high performance liquid chromatography as follows.

[HPLC analysis conditions]
Column: Develosil ODS-HG5 (4.6 mmφ × 250 mm, manufactured by Nomura Chemical Co., Ltd.), eluent: 60 mM potassium phosphate buffer (pH 2.5), 8 mM sodium decanesulfonate / methanol = 53/47, flow rate: 0 0.5 ml / min, column temperature: 25 ° C., measurement wavelength: 254 nm.

(Reference Example 2)
The yeast cells obtained in Reference Example 1 were suspended in 1/6 volume of deionized water of the culture solution, and after crushing the cells by pressure crushing (using HOMOGENIZER Rannie 2000 type), the pH was adjusted to 4. Insoluble matter was removed by centrifugation to obtain a yeast cell extract. To the obtained yeast cell extract, 3 mol of magnesium sulfate per 1 mol of SAM and 20% by weight of dextrin of dry weight of yeast cell extract were added, frozen at −80 ° C. and then freeze-dried. This was designated as SAM-containing dry yeast cell extract.

Example 1
To 100 parts by weight of the SAM-containing dry yeast cell extract obtained in Reference Example 2, citric acid was added and mixed so as to be 50 parts by weight, and a composition containing citric acid and the SAM-containing dry yeast cell extract was prepared. Obtained.

(Example 2)
Tartaric acid was added to and mixed with 100 parts by weight of the SAM-containing dry yeast cell extract obtained in Reference Example 2 to obtain a composition containing tartaric acid and the SAM-containing dry yeast cell extract. .

(Example 3)
To 100 parts by weight of the SAM-containing dry yeast cell extract obtained in Reference Example 2, fumaric acid is added and mixed so as to be 50 parts by weight, and a composition containing fumaric acid and the SAM-containing dry yeast cell extract is prepared. Obtained.

Example 4
To 100 parts by weight of the SAM-containing dry yeast cell extract obtained in Reference Example 2, succinic acid is added and mixed so as to be 50 parts by weight, and a composition containing succinic acid and the SAM-containing dry yeast cell extract is prepared. Obtained.

(Example 5)
To 100 parts by weight of the SAM-containing dry yeast cell extract obtained in Reference Example 2, malic acid was added and mixed so as to be 50 parts by weight, and a composition containing malic acid and the SAM-containing dry yeast cell extract was obtained. Obtained.

(Example 6)
The composition obtained in Examples 1 to 5 was dissolved or suspended by adding distilled water so that the SAM concentration was 20 mg / mL, and was administered to SD rats (male, 10 weeks old) at a dose of 5 mL per kg body weight. Orally. Further, as a comparative control example, the SAM-containing dry yeast cell extract obtained in Reference Example 2 was orally administered in the same manner in which SAM was dissolved in distilled water so as to have the same concentration. In this example, three rats were used for each composition. 1, 2, 3, and 5 hours after administration, blood was collected from the jugular vein using heparin as an anticoagulant without anesthesia, and plasma components were obtained by centrifugation. 40 μL of 0.4 g / L trichloroacetic acid aqueous solution was added to 200 μL of the obtained plasma, mixed and centrifuged, and the SAM concentration in the resulting supernatant was measured using HPLC. The results are shown in Table 1. It was.

As shown in Table 1, the plasma concentration 1 hour after administration was about 0.6 μg / mL in the SAM-containing dry yeast cell extract administration group obtained in Reference Example 2, whereas The composition administration groups obtained in Examples 1 to 5 showed a high value of 1.0 μg / mL or more.

Further, as a result of confirming the pH of each administration liquid with a commercially available pH test paper, the administration liquids prepared from the compositions of Examples 1 to 5 were pH 2 to 3, that is, pH 3.5 or less. The pH of the administration solution prepared from Reference Example 2 was 4.

(Example 7)
To 100 parts by weight of the SAM-containing dry yeast cell extract obtained in Reference Example 2, citric acid is added and mixed so as to be 20 parts by weight, and a composition containing citric acid and the SAM-containing dry yeast cell extract is prepared. Obtained.

(Example 8)
Tartaric acid was added to and mixed with 100 parts by weight of the SAM-containing dry yeast cell extract obtained in Reference Example 2 to obtain a composition containing tartaric acid and the SAM-containing dry yeast cell extract. .

Example 9
To 100 parts by weight of the SAM-containing dry yeast cell extract obtained in Reference Example 2, fumaric acid is added and mixed so as to be 20 parts by weight, and a composition containing fumaric acid and the SAM-containing dry yeast cell extract is prepared. Obtained.

(Example 10)
The composition obtained in Examples 7 to 9 was dissolved or suspended by adding distilled water so that the SAM concentration was 20 mg / mL, and was administered to SD rats (male, 10 weeks old) at a dose of 5 mL per kg body weight. Orally. Further, as a comparative control example, the SAM-containing dry yeast cell extract obtained in Reference Example 2 was orally administered in the same manner in which SAM was dissolved in distilled water so as to have the same concentration. In this example, three rats were used for each composition. At 0.5, 1, 2, 3, and 5 hours after administration, blood was collected from the jugular vein using heparin as an anticoagulant without anesthesia, and plasma components were obtained by centrifugation. 40 μL of 0.4 g / L trichloroacetic acid aqueous solution was added to 200 μL of the obtained plasma, mixed and centrifuged, and the SAM concentration in the obtained supernatant was measured using HPLC. The results are shown in Table 2. It was.

As shown in Table 2, it was obtained in Examples 7 to 9 from the SAM-containing dry yeast cell extract administration group obtained in Reference Example 2 from 0.5 hours to 5 hours after administration. In the composition administration group, a high concentration transition was shown.

Further, as a result of confirming the pH of each administration liquid with a commercially available pH test paper, the administration liquid prepared from the compositions of Examples 7 to 9 had a pH of 2.5 to 3.5, and the administration liquid prepared from Reference Example 2 was used. The pH of the solution was 4.

Example 11
Folic acid was added to and mixed with 100 parts by weight of the SAM-containing dry yeast cell extract obtained in Reference Example 2 to obtain a composition containing folic acid and the SAM-containing dry yeast cell extract. .

(Example 12)
Folic acid was added to and mixed with 100 parts by weight of the SAM-containing dry yeast cell extract obtained in Reference Example 2 to obtain a composition containing folic acid and the SAM-containing dry yeast cell extract. .

(Example 13)
The composition obtained in Examples 11 and 12 was dissolved or suspended by adding distilled water so that the SAM concentration was 20 mg / mL, and a dose of 5 mL per kg body weight was given to SD rats (male, 9 weeks old). Orally. Further, as a comparative control example, the SAM-containing dry yeast cell extract obtained in Reference Example 2 was orally administered in the same manner in which SAM was dissolved in distilled water so as to have the same concentration. In this example, three rats were used for each composition. One hour after administration, blood was collected from the jugular vein using heparin as an anticoagulant without anesthesia, and a plasma component was obtained by centrifugation. 40 μL of 0.4 g / L trichloroacetic acid aqueous solution was added to 200 μL of the obtained plasma, mixed and centrifuged, and the SAM concentration in the obtained supernatant was measured using HPLC. The results are shown in Table 3. It was.

As shown in Table 3, the plasma concentration 1 hour after administration was about 0.8 μg / mL in the SAM-containing dry yeast cell extract administration group obtained in Reference Example 2, whereas The composition administration groups obtained in Examples 11 and 12 had a high value of about 1.0 μg / mL.

(Reference Example 3)
Ascorbic acid is added to and mixed with 100 parts by weight of the SAM-containing dry yeast cell extract obtained in Reference Example 2 so that the composition contains ascorbic acid and the SAM-containing dry yeast cell extract. Obtained.

(Reference Example 4)
Distilled water was added to the composition obtained in Reference Example 3 to dissolve it so that the SAM concentration was 20 mg / mL, and it was orally administered to SD rats (male, 10 weeks old) at a dose of 5 mL / kg body weight. . Further, as a comparative control example, the SAM-containing dry yeast cell extract obtained in Reference Example 2 was orally administered in the same manner in which SAM was dissolved in distilled water so as to have the same concentration. In this reference example, three rats were used for each composition. 1, 2, 3, and 5 hours after administration, blood was collected from the jugular vein using heparin as an anticoagulant without anesthesia, and plasma components were obtained by centrifugation. 40 μL of 0.4 g / L trichloroacetic acid aqueous solution was added to 200 μL of the obtained plasma, mixed and centrifuged, and the SAM concentration in the obtained supernatant was measured using HPLC. The results are shown in Table 4. It was.

As shown in Table 4, from 1 hour to 5 hours after administration, the composition administration group obtained in Reference Example 3 was more effective than the SAM-containing dry yeast cell extract administration group obtained in Reference Example 2. Also showed a low concentration transition.

Claims (26)

A method for enhancing the absorbability of S-adenosyl-L-methionine, which comprises taking in combination S-adenosyl-L-methionine and a polyvalent carboxylic acid. The method according to claim 1, wherein the polyvalent carboxylic acid is at least one selected from adipic acid, oxalic acid, citric acid, tartaric acid, succinic acid, malic acid, fumaric acid, glutamic acid, and folic acid. The method according to claim 1 or 2, wherein the polycarboxylic acid is a polycarboxylic acid having a pKa1 value of 4 or less. The method according to any one of claims 1 to 3, wherein the S-adenosyl-L-methionine is a microorganism and / or a microorganism extract containing S-adenosyl-L-methionine. The method according to any one of claims 1 to 4, wherein the S-adenosyl-L-methionine is S-adenosyl-L-methionine after drying. 6. The method according to claim 5, wherein 0.5 parts by weight or more of polyvalent carboxylic acid is taken together with 100 parts by weight of S-adenosyl-L-methionine after drying. The polyhydric carboxylic acid of 0.1 part by weight or more is ingested in combination per 100 parts by weight of the microorganism and / or microorganism extract containing S-adenosyl-L-methionine after drying. the method of. A composition with enhanced absorbability of S-adenosyl-L-methionine, comprising S-adenosyl-L-methionine and a polyvalent carboxylic acid. The composition according to claim 8, wherein the polyvalent carboxylic acid is at least one selected from adipic acid, oxalic acid, citric acid, tartaric acid, succinic acid, malic acid, fumaric acid, glutamic acid, and folic acid. The composition according to claim 8 or 9, wherein the polycarboxylic acid is a polycarboxylic acid having a pKa1 value of 4 or less. The composition according to any one of claims 8 to 10, wherein the S-adenosyl-L-methionine is a microorganism and / or a microorganism extract containing S-adenosyl-L-methionine. The composition according to any one of claims 8 to 11, wherein the S-adenosyl-L-methionine is S-adenosyl-L-methionine after drying. The composition according to claim 12, comprising 0.5 parts by weight or more of polycarboxylic acid per 100 parts by weight of S-adenosyl-L-methionine after drying. The composition according to claim 12, comprising 0.1 part by weight or more of polyvalent carboxylic acid per 100 parts by weight of the microorganism and / or microorganism extract containing S-adenosyl-L-methionine after drying. object. The pH according to any one of claims 8 to 14, wherein the pH when adding water or a solution or suspension having an S-adenosyl-L-methionine concentration of 20 mg / mL is 4 or less. Composition. 16. A composition according to any one of claims 8 to 15 in an oral dosage form. A food comprising the composition according to any one of claims 8 to 16, a nutritional functional food, a food for specified health use, a nutritional supplement, a nutrient, a beverage, an animal drug, a feed, a cosmetic, and a quasi-drug. , Pharmaceuticals, therapeutics or preventives. An antidepressant comprising the composition according to any one of claims 8 to 16. Furthermore, tyrosine, acetyltyrosine, tryptophan, 5-hydroxytryptophan, methionine, phenylalanine, St. John's wort, zinc, manganese, magnesium, vitamin B12, niacin, and one or more agents selected from the group consisting of folic acid, The antidepressant according to claim 18. A method for producing an S-adenosyl-L-methionine-containing composition, which comprises adding a polycarboxylic acid to S-adenosyl-L-methionine. The production method according to claim 20, wherein the polyvalent carboxylic acid is at least one selected from adipic acid, oxalic acid, citric acid, tartaric acid, succinic acid, malic acid, fumaric acid, glutamic acid, and folic acid. The production method according to claim 20 or 21, wherein the polyvalent carboxylic acid is a polyvalent carboxylic acid having a pKa1 value of 4 or less. The production method according to any one of claims 20 to 22, wherein the S-adenosyl-L-methionine is a microorganism and / or a microorganism extract containing S-adenosyl-L-methionine. The production method according to any one of claims 20 to 23, wherein the S-adenosyl-L-methionine is S-adenosyl-L-methionine after drying. 25. The production method according to claim 24, wherein 0.5 part by weight or more of polyvalent carboxylic acid is added per 100 parts by weight of S-adenosyl-L-methionine after drying. 25. The polycarboxylic acid is added in an amount of 0.1 parts by weight or more per 100 parts by weight of the microorganism and / or microorganism extract containing S-adenosyl-L-methionine after drying. Production method.