Composition for reducing homocysteine ​​levels

Abstract

The present invention provides a homocysteine-reducing composition that rapidly lowers blood homocysteine ​​levels to an appropriate level without causing any concerns about side effects. [Solution] A composition for reducing homocysteine ​​levels, comprising one or more B vitamins selected from vitamin B6, vitamin B12, and folic acid, and β-NMN as active ingredients. The β-NMN content is in the range of 22.32% to 89.29% by weight. Vitamin C and vitamin B2 may also be added.

Description

Technical Field

[0001] The present invention relates to a composition for reducing homocysteine levels, which has the effect of reducing homocysteine levels in the blood.

Background Art

[0002] Homocysteine is an intermediate product temporarily generated during the metabolism of methionine (an amino acid) in the bodies of humans and animals. Methionine is an essential amino acid contained in animal proteins such as meat, fish, eggs, and dairy products. Methionine is involved in many important physiological functions such as energy production, antioxidant defense, and regulation of nerve function through several metabolic pathways. The main metabolic pathway of methionine is as follows.

[0003] First, methionine binds to ATP (adenosine triphosphate) and is converted to S-adenosylmethionine (SAMe). S-adenosylmethionine (SAMe) functions as a methyl group donor and is involved in many biochemical reactions such as DNA methylation, synthesis of neurotransmitters, and lipid metabolism.

[0004] When S-adenosylmethionine (SAMe) donates a methyl group in a methylation reaction, it becomes S-adenosylhomocysteine (SAH). S-adenosylhomocysteine (SAH) is decomposed to generate homocysteine. This homocysteine receives a methyl group from a methyl group donor and is remethylated by methionine synthase (Methionine Synthase, MS) to return to methionine. This pathway is called the remethylation (re-methylation) pathway.

[0005] Here, as the methyl group donor that donates a methyl group to homocysteine, 5-methyltetrahydrofolate (5-MTHF) generated by the conversion of folic acid is used. Also, in the pathway where homocysteine is remethylated by methionine synthase (MS), vitamin B12 (cobalamin) is used as a coenzyme.

[0006] Furthermore, homocysteine ​​can also be converted to cysteine. Specifically, homocysteine ​​is converted to cystathionine by cystathionine β-synthase (CBS), and the converted cystathionine is then converted to cysteine ​​by cystathionine γ-lyase (CGL). This pathway is called the transsulfation pathway. Vitamin B6 (pyridoxal phosphate) is used as a coenzyme in these pathways.

[0007] Methionine and homocysteine ​​are converted into harmless substances such as methionine and cysteine ​​through the metabolic pathways described above, and normally, blood homocysteine ​​levels (homocysteine ​​concentration) are kept low. A blood homocysteine ​​concentration of 7 μmol / L or less is considered optimal.

[0008] However, factors such as aging, poor diet, stress, smoking, and excessive alcohol consumption can lead to deficiencies in vitamin B6, vitamin B12, or folic acid obtained from food, or failure of homocysteine ​​remethylation, resulting in improper homocysteine ​​metabolism and elevated blood homocysteine ​​levels.

[0009] Elevated homocysteine ​​levels in the blood increase the risk of cardiovascular disease (arteriosclerosis, thrombosis, hypertension) and cerebrovascular disease (stroke). Furthermore, homocysteine ​​is neurotoxic; elevated levels can damage brain nerve cells, leading to cognitive decline, brain atrophy, and an increased risk of Alzheimer's disease. It is known that brain atrophy accelerates when homocysteine ​​levels exceed 11 μmol / L.

[0010] As homocysteine ​​is harmful to the human body, it is necessary to metabolize it as much as possible and keep blood homocysteine ​​levels low. As mentioned above, vitamins B6, B12, and folic acid play important roles in the pathway that metabolizes homocysteine ​​in the blood. Therefore, in order to keep blood homocysteine ​​levels low, it is necessary to consume the required amounts of vitamins B6, B12, and folic acid.

[0011] Vitamins B6, B12, and folic acid are usually obtained from a balanced diet. However, the ability to absorb vitamins B6, B12, and folic acid from food tends to decline with age. As people age, they gradually become unable to obtain the necessary amounts of vitamins B6, B12, and folic acid. Therefore, compositions (health foods, supplements, drinks, etc.) containing high concentrations of vitamins B6, B12, and folic acid to reduce homocysteine ​​levels are available for the elderly.

[0012] This homocysteine-reducing composition contains high concentrations of vitamin B6, vitamin B12, and folic acid, so it is preferable to take an appropriate amount to avoid excessive intake. However, if the homocysteine ​​concentration in the blood does not decrease to an appropriate level even after taking an appropriate amount, people may try to reduce their blood homocysteine ​​levels by taking an excessive amount of this homocysteine-reducing composition.

[0013] However, attempting to lower blood homocysteine ​​levels by consuming excessive amounts of vitamin B6, vitamin B12, and folic acid carries the risk of side effects. Moreover, even with excessive intake of vitamin B6, vitamin B12, and folic acid, the effect of lowering blood homocysteine ​​levels may saturate, rendering the excessive intake meaningless and leaving only the risk of side effects.

[0014] Therefore, there was a need for a homocysteine-reducing composition that could effectively lower blood homocysteine ​​levels to an appropriate level without excessive intake of vitamin B6, vitamin B12, and folic acid. [Prior art documents] [Patent Documents]

[0015] [Patent Document 1] Japanese Patent Publication No. 2009-173640 [Patent Document 2] Japanese Patent Publication No. 2024-096784 [Non-patent literature]

[0016] [Non-Patent Document 1] "The metabolism and significance of homocysteine ​​in nutrition and health," Kumar Avinash, et al., Nutrition and Metabolism, 14(1), p78 (2017). [Overview of the Initiative] [Problems that the invention aims to solve]

[0017] The problem that this invention aims to solve is the need for a homocysteine-reducing composition that can rapidly lower blood homocysteine ​​levels to an appropriate level without causing concern about side effects. [Means for solving the problem]

[0018] The homocysteine-reducing composition according to the present invention contains one or more B vitamins, consisting of vitamin B6, vitamin B12, and folic acid, and β-NMN as active ingredients. β-NMN is a chemical substance having a structure in which nicotinamide (a derivative of vitamin B3) and ribose (a sugar) are linked via a phosphate group. β-NMN is a type of nucleotide whose formal chemical name is β-nicotinamide mononucleotide.

[0019] The content of β-NMN preferably ranges from 22.32% by weight to 89.29% by weight. If the content of β-NMN is within the range of 22.32% by weight to 89.29%, NAD⁺ involved in energy metabolism increases in the blood, the metabolism of homocysteine becomes active, and the homocysteine level (μmol / L) in the blood decreases. However, if it is less than 22.32% by weight, the energy for activating the metabolism of homocysteine becomes insufficient, the function of vitamin B group is not activated, and the homocysteine level in the blood does not decrease sufficiently. If it exceeds 89.29% by weight, although the effect of improving mitochondrial function may further increase, there is still not enough data on the safety of long-term large intake, and the risk of side effects is a concern.

[0020] In the composition for reducing homocysteine level according to the present invention, vitamin B6 in the composition for reducing homocysteine level has the function of supporting enzymes required in the process of converting homocysteine into cysteine or methionine in the transsulfuration pathway for metabolizing homocysteine, such as cysteine β-synthase or homocysteine methyltransferase.

[0021] The content of vitamin B6 in the composition for reducing homocysteine level according to the present invention preferably ranges from 3.57% by weight to 14.29% by weight. If the content of vitamin B6 is within the range of 3.57% by weight to 14.29% by weight, the effect of reducing the homocysteine level in the blood to a desired degree can be obtained. However, if it is less than 3.57% by weight, the action of vitamin B6 involved in homocysteine metabolism becomes weak, and the ability to suppress the risk of progression of dementia becomes insufficient. If it exceeds 14.29% by weight, the risk of neuropathy and the like may increase when taken for a long time.

[0022] Examples of vitamin B6 include pyridoxine, pyridoxal or their salts (such as hydrochloride, sulfate, nitrate, hydrobromide, phosphate, etc.), and preferably pyridoxine hydrochloride, pyridoxal phosphate, etc.

[0023] In the composition for reducing homocysteine value according to the present invention, vitamin B12 acts as a cofactor for an enzyme that converts homocysteine to methionine, methylcobalamin, in the remethylation pathway of homocysteine, and vitamin B12 and folic acid cooperate to convert homocysteine to methionine. Through this cooperation, normal metabolism of homocysteine is ensured.

[0024] The content of vitamin B12 in the composition for reducing homocysteine value according to the present invention is preferably in the range of 0.09% to 0.36% by weight. If the content of vitamin B12 is within the range of 0.09% to 0.36% by weight, the effect of reducing the homocysteine value in the blood to a desired level can be obtained. However, if it is less than 0.09% by weight, the function of vitamin B12 in homocysteine metabolism becomes weak, and the ability to suppress the risk of progression of dementia becomes insufficient. If it exceeds 0.36% by weight, there is a risk of allergy in some people. Since vitamin B12 is water-soluble and is generally excreted in urine even when over-ingested, there is no major problem even if it exceeds 0.36% by weight.

[0025] Examples of vitamin B12 include cyanocobalamin, hydroxocobalamin, mecobalamin, or salts thereof (such as hydrochloride, sulfate, nitrate, hydrobromide, phosphate, etc.). Preferably, cyanocobalamin, hydroxocobalamin hydrochloride, hydroxocobalamin acetate, mecobalamin, etc. can be mentioned.

[0026] In the composition for reducing homocysteine value according to the present invention, folic acid acts as a cofactor for an enzyme (MTHFR) necessary for converting homocysteine to methionine in the remethylation pathway of homocysteine. Folic acid supports the process of converting homocysteine to methionine in the form of methylene tetrahydrofolate. When this reaction is properly carried out, the homocysteine value in the blood decreases.

[0027] The folic acid content in the homocysteine-reducing composition according to the present invention is preferably in the range of 0.14% to 0.57% by weight. When the folic acid content is in the range of 0.14% to 0.57% by weight, the effect of reducing blood homocysteine ​​levels to the desired extent can be obtained. However, if the content is less than 0.14% by weight, the effect of folic acid, which is important for homocysteine ​​metabolism and DNA repair, decreases, and the effect of suppressing the progression of AMD (age-related macular degeneration) weakens. If it exceeds 0.57% by weight, excessive intake may mask the symptoms of vitamin B12 deficiency, so caution is required with long-term intake. Note that 5-MTHF (L-methylfolic acid) is a form of folic acid that is easily metabolized, so even if it exceeds 0.57% by weight, there is no problem within the normal intake range.

[0028] In a broad sense, folic acid can include pteroylglutamate, 7,8-dihydropteroylglutamate, and their polyglutamine derivatives.

[0029] The homocysteine-reducing composition according to the present invention preferably contains vitamin C. Vitamin C has antioxidant properties, preventing the breakdown of folic acid and maintaining its stability. Since folic acid is susceptible to oxidation, vitamin C contributes to its protection. Vitamin C promotes the secretion of gastric acid, which aids in the absorption of folic acid. Gastric acid is an essential element for converting folic acid into its active form, and an increase in its amount improves the absorption efficiency of folic acid.

[0030] The vitamin C content in the homocysteine-reducing composition according to the present invention is preferably in the range of 8.93% to 71.43% by weight. While the desired effect can be obtained with a vitamin C content in this range, if it is less than 8.93% by weight, the antioxidant effect decreases, and the role of vitamin C in inhibiting the progression of AMD may become insufficient. If it exceeds 71.43% by weight, prolonged excessive intake may cause gastrointestinal problems or diarrhea. However, even if the vitamin C content exceeds 71.43% by weight, it is generally considered to be harmless and even enhance the antioxidant effect.

[0031] The homocysteine-reducing composition according to the present invention preferably contains vitamin B2. Vitamin B2 works in conjunction with vitamin B6 and vitamin B12 to participate in homocysteine ​​metabolism, assisting the activity of enzymes necessary to remethylate homocysteine ​​back to methionine.

[0032] The vitamin B2 content in the homocysteine-reducing composition according to the present invention is preferably in the range of 0.46% to 1.86% by weight. A vitamin B2 content in the range of 0.46% to 1.86% by weight provides the desired effect, but if it falls below 0.46% by weight, the effect of vitamin B2 weakens and its interaction with other B vitamins decreases. While a vitamin B2 content exceeding 1.86% by weight does not pose any particular problem, 1.86% by weight was set as the upper limit considering cost considerations.

[0033] In the composition of the present invention, in addition to vitamin B6, vitamin B12, folic acid, and β-NMN, any other active ingredient having any physiological effect may be included, as long as it does not impair the effect. Furthermore, the composition of the present invention is not particularly limited in form and can be prepared in any form, such as a solid form like powder, granules, or tablets; a liquid form like solution, emulsion, or dispersion; or a semi-solid form like paste. [Effects of the Invention]

[0034] The present invention adds β-NMN to a composition containing vitamins B6, B12, and folic acid. When ingested, β-NMN increases NAD+ (nicotinamide adenine dinucleotide) in the blood, which in turn provides the necessary energy for the metabolism of homocysteine ​​in the blood. Vitamins B6, B12, and folic acid rapidly metabolize homocysteine ​​in the blood, resulting in a rapid decrease in blood homocysteine ​​levels.

[0035] The present invention, by adding β-NMN to a composition containing vitamins B6, B12, and folic acid, has the effect of rapidly metabolizing homocysteine ​​in the blood, and therefore shortening the time required to reduce homocysteine ​​levels in the blood.

[0036] The present invention adds β-NMN to a composition containing vitamins B6, B12, and folic acid, thereby enabling vitamins B6, B12, and folic acid to function effectively in homocysteine ​​metabolism, allowing for rapid metabolism of homocysteine ​​in the blood. This eliminates the need for excessive intake of vitamins B6, B12, and folic acid, and consequently, eliminates concerns about side effects from excessive intake of vitamins B6, B12, and folic acid.

[0037] The present invention is a composition for reducing homocysteine ​​levels. This invention not only reduces the concentration of homocysteine, but also has the effect of suppressing the increase in homocysteine ​​levels. [Modes for carrying out the invention]

[0038] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples. [Examples]

[0039] First, Composition 1 was prepared using 20 mg of vitamin B6, 500 μg of vitamin B12, 800 μg of folic acid (monoglutamate type), 50 mg of vitamin C, 2.6 mg of vitamin B2, 79.5 mg of dextrin, and 1.6 mg of calcium stearate. Composition 1 is a homocysteine ​​reduction composition expected from known information and serves as a comparative composition to confirm the effects of the present invention.

[0040] Composition 1 was administered twice a day after meals to three subjects, distinguished as A, B, and C. The subjects' blood homocysteine ​​levels were measured before administration, one month after administration, and two months after administration. The subjects' blood homocysteine ​​levels (μmol / L) before administration, one month after administration, and two months after administration are shown in Table 1.

[0041] [Table 1]

[0042] The results shown in Table 1 indicate that composition 1 has the effect of lowering homocysteine ​​levels in the blood.

[0043] Next, Composition 2 was prepared by adding 125 mg of β-NMN to Composition 1 described above. Composition 2 is the homocysteine ​​level reduction composition according to the present invention. Composition 2 was administered twice a day to three subjects, distinguished as D, E, and F, and the homocysteine ​​concentration in the subjects' blood was measured before administration, one month after administration, and two months after administration. The homocysteine ​​levels (μmol / L) in the subjects' blood before administration, one month after administration, and two months after administration are shown in Table 2.

[0044] [Table 2]

[0045] The results shown in Table 2 indicate that ingestion of composition 2 lowers the homocysteine ​​concentration in the blood (μmol / L) more quickly and significantly than with composition 1. Previous clinical studies have shown that it took approximately two years to lower homocysteine ​​levels from 13 to 9, but the addition of β-NMN significantly shortens this period.

[0046] The reason why these results were obtained by adding β-NMN is discussed below.

[0047] First, the supply of β-NMN increases NAD+. Vitamin B6, vitamin B12, and folic acid are involved in homocysteine ​​metabolism. Homocysteine ​​metabolism involving vitamins B6, B12, and folic acid is an energy-consuming process, and overall cellular metabolic efficiency is important. When NAD+ increases, the energy supply stabilizes, and homocysteine ​​metabolism proceeds more actively.

[0048] In other words, the folate cycle is involved in the remethylation of homocysteine ​​to methionine, but the reaction in the folate cycle (the process by which methylenetetrahydrofolate is converted to 5-MTHF) requires energy, and it is important that the overall cellular metabolism is activated to support this reaction. An increase in NAD+ supplies the energy used for metabolism, thereby improving metabolic efficiency.

[0049] Furthermore, the metabolism of homocysteine ​​through the transsulfation pathway (cystathionine pathway), which converts homocysteine ​​to cystathionine, also requires energy. For this process to proceed properly, it is important that the cellular energy balance is maintained. An increase in NAD+ supplies the energy necessary for the cystathionine pathway to function smoothly.

[0050] As explained above, the reason why composition 2 lowered homocysteine ​​levels more quickly and significantly is thought to be that β-NMN increased NAD+, which supplied more energy to the pathway that metabolizes homocysteine, thereby activating the metabolism involving B vitamins.

[0051] Therefore, the results in Table 2 were obtained because β-NMN supported metabolism involving B vitamins, and it is not thought that β-NMN, which has the effect of reducing homocysteine ​​levels, additively reduced homocysteine ​​levels. To confirm that β-NMN itself does not have the effect of reducing homocysteine ​​levels, the following clinical trial was conducted.

[0052] Composition 3 was prepared, containing 79.5 mg of dextrin, 1.6 mg of calcium stearate, and 125 mg of β-NMN. Composition 3 was administered once daily to three subjects, distinguished as G, H, and I, and their blood homocysteine ​​levels were measured. The subjects' blood homocysteine ​​levels were measured before administration, one month after administration, and two months after administration. The results are shown in Table 3.

[0053] [Table 3]

[0054] Table 3 shows that none of the three subjects, distinguished as G, H, and I, showed a tendency for homocysteine ​​levels to decrease over time with β-NMN administration. This confirms that β-NMN does not directly reduce homocysteine ​​levels in the blood. [Examples]

[0055] Table 4 shows examples of compositions prepared as capsules using the homocysteine-reducing composition according to the present invention. [Table 4] [Industrial applicability]

[0056] This invention is not limited to applications that reduce homocysteine ​​levels in the blood of humans, but can also be used to reduce homocysteine ​​levels in the blood of livestock, hunting dogs, racehorses, pets, and other animals.

Claims

1. A composition for reducing homocysteine ​​levels, comprising one or more B vitamins (vitamin B6, vitamin B12, and folic acid) and β-NMN as active ingredients.

2. The homocysteine ​​reduction composition according to claim 1, characterized in that the β-NMN content is in the range of 22.32% by weight to 89.29% by weight.

3. The homocysteine ​​level reducing composition according to claim 1, characterized in that the vitamin B group consists of vitamin B6, vitamin B12, and folic acid.

4. A composition for reducing homocysteine ​​levels according to claim 1 or 3, characterized in that the vitamin B6 content is in the range of 3.57% by weight to 14.29% by weight.

5. The homocysteine-reducing composition according to claim 1 or 3, characterized in that the vitamin B12 content is in the range of 0.09% by weight to 0.36% by weight.

6. A composition for reducing homocysteine ​​levels according to claim 1 or 3, characterized in that the folic acid content is in the range of 0.14% by weight to 0.57% by weight.

7. The homocysteine ​​level reducing composition according to claim 1, characterized in that it contains vitamin C.

8. The homocysteine ​​reduction composition according to claim 7, characterized in that the vitamin C content is in the range of 8.93% by weight to 71.43% by weight.

9. The homocysteine ​​level reducing composition according to claim 1, characterized in that it contains vitamin B2.

10. The homocysteine ​​level reducing composition according to claim 9, characterized in that the vitamin B2 content is in the range of 0.46% by weight to 1.86% by weight.

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