WO2008025116A1 - Composition and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle - Google Patents
Composition and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle Download PDFInfo
- Publication number
- WO2008025116A1 WO2008025116A1 PCT/CA2006/001431 CA2006001431W WO2008025116A1 WO 2008025116 A1 WO2008025116 A1 WO 2008025116A1 CA 2006001431 W CA2006001431 W CA 2006001431W WO 2008025116 A1 WO2008025116 A1 WO 2008025116A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- skeletal muscle
- insulin
- taurine
- enhancing
- alpha
- Prior art date
Links
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims abstract description 106
- 102000004877 Insulin Human genes 0.000 title claims abstract description 53
- 229940125396 insulin Drugs 0.000 title claims abstract description 53
- 108090001061 Insulin Proteins 0.000 title claims abstract description 52
- 210000002027 skeletal muscle Anatomy 0.000 title claims abstract description 38
- 230000000694 effects Effects 0.000 title claims abstract description 28
- 238000000034 method Methods 0.000 title claims abstract description 18
- 230000002708 enhancing effect Effects 0.000 title claims abstract description 17
- 230000001965 increasing effect Effects 0.000 title claims abstract description 13
- 230000001737 promoting effect Effects 0.000 title claims abstract description 10
- 230000004096 skeletal muscle tissue growth Effects 0.000 title claims abstract description 7
- 239000000203 mixture Substances 0.000 title claims description 45
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims abstract description 85
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims abstract description 48
- 229960003080 taurine Drugs 0.000 claims abstract description 42
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims abstract description 27
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims abstract description 24
- 235000015872 dietary supplement Nutrition 0.000 claims abstract description 24
- 235000019136 lipoic acid Nutrition 0.000 claims abstract description 24
- 229960002663 thioctic acid Drugs 0.000 claims abstract description 24
- DSCFFEYYQKSRSV-UHFFFAOYSA-N 1L-O1-methyl-muco-inositol Natural products COC1C(O)C(O)C(O)C(O)C1O DSCFFEYYQKSRSV-UHFFFAOYSA-N 0.000 claims abstract description 22
- VJXUJFAZXQOXMJ-UHFFFAOYSA-N D-1-O-Methyl-muco-inositol Natural products CC12C(OC)(C)OC(C)(C)C2CC(=O)C(C23OC2C(=O)O2)(C)C1CCC3(C)C2C=1C=COC=1 VJXUJFAZXQOXMJ-UHFFFAOYSA-N 0.000 claims abstract description 22
- DSCFFEYYQKSRSV-KLJZZCKASA-N D-pinitol Chemical compound CO[C@@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@H]1O DSCFFEYYQKSRSV-KLJZZCKASA-N 0.000 claims abstract description 22
- LUEWUZLMQUOBSB-FSKGGBMCSA-N (2s,3s,4s,5s,6r)-2-[(2r,3s,4r,5r,6s)-6-[(2r,3s,4r,5s,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5s,6r)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](O[C@@H]2[C@H](O[C@@H](OC3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-FSKGGBMCSA-N 0.000 claims abstract description 15
- BKAJNAXTPSGJCU-UHFFFAOYSA-N 4-methyl-2-oxopentanoic acid Chemical class CC(C)CC(=O)C(O)=O BKAJNAXTPSGJCU-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229920002581 Glucomannan Polymers 0.000 claims abstract description 15
- 229940046240 glucomannan Drugs 0.000 claims abstract description 15
- DSCFFEYYQKSRSV-HMSOCMLXSA-N D-pinitol Natural products CO[C@H]1[C@@H](O)[C@@H](O)[C@@H](O)[C@H](O)[C@H]1O DSCFFEYYQKSRSV-HMSOCMLXSA-N 0.000 claims abstract description 14
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 5
- KPGXRSRHYNQIFN-UHFFFAOYSA-L 2-oxoglutarate(2-) Chemical compound [O-]C(=O)CCC(=O)C([O-])=O KPGXRSRHYNQIFN-UHFFFAOYSA-L 0.000 claims description 19
- 241000282414 Homo sapiens Species 0.000 claims description 10
- 241001465754 Metazoa Species 0.000 claims description 5
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical class OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 abstract 1
- 230000000153 supplemental effect Effects 0.000 description 27
- 210000003205 muscle Anatomy 0.000 description 24
- 241000700159 Rattus Species 0.000 description 23
- 206010012601 diabetes mellitus Diseases 0.000 description 20
- 229960003136 leucine Drugs 0.000 description 20
- 108090000623 proteins and genes Proteins 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 16
- 230000014616 translation Effects 0.000 description 15
- 238000001243 protein synthesis Methods 0.000 description 14
- 230000015556 catabolic process Effects 0.000 description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 10
- 206010022489 Insulin Resistance Diseases 0.000 description 10
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 10
- 230000037361 pathway Effects 0.000 description 10
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 9
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 9
- 229940024606 amino acid Drugs 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 9
- 235000005911 diet Nutrition 0.000 description 9
- 239000008103 glucose Substances 0.000 description 9
- 229920002907 Guar gum Polymers 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 8
- 239000000665 guar gum Substances 0.000 description 8
- 229960002154 guar gum Drugs 0.000 description 8
- 235000010417 guar gum Nutrition 0.000 description 8
- 230000001419 dependent effect Effects 0.000 description 7
- 230000037213 diet Effects 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 102000008934 Muscle Proteins Human genes 0.000 description 6
- 108010074084 Muscle Proteins Proteins 0.000 description 6
- 102100028873 Sodium- and chloride-dependent taurine transporter Human genes 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 108010017629 taurine transporter Proteins 0.000 description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 6
- 244000068988 Glycine max Species 0.000 description 5
- 235000010469 Glycine max Nutrition 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 239000013589 supplement Substances 0.000 description 5
- 230000009469 supplementation Effects 0.000 description 5
- 230000032258 transport Effects 0.000 description 5
- 102000014156 AMP-Activated Protein Kinases Human genes 0.000 description 4
- 108010011376 AMP-Activated Protein Kinases Proteins 0.000 description 4
- 101000950981 Bacillus subtilis (strain 168) Catabolic NAD-specific glutamate dehydrogenase RocG Proteins 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 4
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 229960003624 creatine Drugs 0.000 description 4
- 239000006046 creatine Substances 0.000 description 4
- 230000037406 food intake Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000003999 initiator Substances 0.000 description 4
- 230000003914 insulin secretion Effects 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 210000000663 muscle cell Anatomy 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 230000017854 proteolysis Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 3
- 102000016901 Glutamate dehydrogenase Human genes 0.000 description 3
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 description 3
- 206010028289 Muscle atrophy Diseases 0.000 description 3
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 201000008980 hyperinsulinism Diseases 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 201000000585 muscular atrophy Diseases 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 230000004792 oxidative damage Effects 0.000 description 3
- 235000002949 phytic acid Nutrition 0.000 description 3
- 230000000291 postprandial effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 244000247812 Amorphophallus rivieri Species 0.000 description 2
- 235000001206 Amorphophallus rivieri Nutrition 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 244000303965 Cyamopsis psoralioides Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102100040669 F-box only protein 32 Human genes 0.000 description 2
- 101710191029 F-box only protein 32 Proteins 0.000 description 2
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 2
- 229920002752 Konjac Polymers 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 239000004395 L-leucine Substances 0.000 description 2
- 235000019454 L-leucine Nutrition 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 102000003923 Protein Kinase C Human genes 0.000 description 2
- 108090000315 Protein Kinase C Proteins 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 150000005693 branched-chain amino acids Chemical class 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000028023 exocytosis Effects 0.000 description 2
- 235000012631 food intake Nutrition 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 210000003904 glomerular cell Anatomy 0.000 description 2
- 230000004153 glucose metabolism Effects 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 230000002641 glycemic effect Effects 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 2
- 230000002267 hypothalamic effect Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000002608 insulinlike Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 150000004715 keto acids Chemical class 0.000 description 2
- 229940025902 konjac mannan Drugs 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000037323 metabolic rate Effects 0.000 description 2
- 230000004898 mitochondrial function Effects 0.000 description 2
- 230000037257 muscle growth Effects 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 230000037081 physical activity Effects 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 210000002363 skeletal muscle cell Anatomy 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000014621 translational initiation Effects 0.000 description 2
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 2
- DSCFFEYYQKSRSV-FEPQRWDDSA-N (1s,2s,4s,5r)-6-methoxycyclohexane-1,2,3,4,5-pentol Chemical compound COC1[C@@H](O)[C@@H](O)C(O)[C@H](O)[C@H]1O DSCFFEYYQKSRSV-FEPQRWDDSA-N 0.000 description 1
- QVJPPFAOCXDDPW-UHFFFAOYSA-N 5-[chloro(difluoro)methyl]-1,2-oxazole Chemical compound FC(F)(Cl)C1=CC=NO1 QVJPPFAOCXDDPW-UHFFFAOYSA-N 0.000 description 1
- 108010022579 ATP dependent 26S protease Proteins 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 241001316288 Bougainvillea spectabilis Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 244000007835 Cyamopsis tetragonoloba Species 0.000 description 1
- QIGLJVBIRIXQRN-UHFFFAOYSA-N DL-leucine ethyl ester Natural products CCOC(=O)C(N)CC(C)C QIGLJVBIRIXQRN-UHFFFAOYSA-N 0.000 description 1
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 1
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 1
- 102000058061 Glucose Transporter Type 4 Human genes 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 102000015779 HDL Lipoproteins Human genes 0.000 description 1
- 108010010234 HDL Lipoproteins Proteins 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 206010020575 Hyperammonaemia Diseases 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 102100036721 Insulin receptor Human genes 0.000 description 1
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
- 102100021496 Insulin-degrading enzyme Human genes 0.000 description 1
- 101710092928 Insulin-like peptide-1 Proteins 0.000 description 1
- 108090000828 Insulysin Proteins 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- 241000699673 Mesocricetus auratus Species 0.000 description 1
- 102000015494 Mitochondrial Uncoupling Proteins Human genes 0.000 description 1
- 108010050258 Mitochondrial Uncoupling Proteins Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010028347 Muscle twitching Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 241000906034 Orthops Species 0.000 description 1
- 102100026459 POU domain, class 3, transcription factor 2 Human genes 0.000 description 1
- 101710133394 POU domain, class 3, transcription factor 2 Proteins 0.000 description 1
- 102000005877 Peptide Initiation Factors Human genes 0.000 description 1
- 108010044843 Peptide Initiation Factors Proteins 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 102000014458 Protein Kinase C-epsilon Human genes 0.000 description 1
- 108010078137 Protein Kinase C-epsilon Proteins 0.000 description 1
- 108091006300 SLC2A4 Proteins 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- -1 alpha-keto acid anions Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000003579 anti-obesity Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000006583 body weight regulation Effects 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 1
- 230000014107 chromosome localization Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000008828 contractile function Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000013325 dietary fiber Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- QIGLJVBIRIXQRN-ZETCQYMHSA-N ethyl (2s)-2-amino-4-methylpentanoate Chemical compound CCOC(=O)[C@@H](N)CC(C)C QIGLJVBIRIXQRN-ZETCQYMHSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 235000020650 eye health related herbal supplements Nutrition 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 150000002306 glutamic acid derivatives Chemical class 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000000871 hypocholesterolemic effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 238000005213 imbibition Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 230000006362 insulin response pathway Effects 0.000 description 1
- 230000002310 insulinopenic effect Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 239000000252 konjac Substances 0.000 description 1
- 235000010485 konjac Nutrition 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 235000021374 legumes Nutrition 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- QVDXUKJJGUSGLS-LURJTMIESA-N methyl L-leucinate Chemical compound COC(=O)[C@@H](N)CC(C)C QVDXUKJJGUSGLS-LURJTMIESA-N 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 210000001700 mitochondrial membrane Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000020763 muscle atrophy Effects 0.000 description 1
- 230000004220 muscle function Effects 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- 230000004070 myogenic differentiation Effects 0.000 description 1
- 230000023837 negative regulation of proteolysis Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- 230000004844 protein turnover Effects 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000019464 regulation of glucose import Effects 0.000 description 1
- 230000003578 releasing effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000001908 sarcoplasmic reticulum Anatomy 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000021309 simple sugar Nutrition 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 230000007279 water homeostasis Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/075—Ethers or acetals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- Composition and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle Composition and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle.
- the present invention relates to the composition of a dietary supplement and methods for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy
- the most common role associated with insulin is the carbohydrate- induced uptake of glucose by cells.
- the release of glucose from cells is also concomitantly inhibited by insulin and its storage as glycogen and triglycerides is promoted (Khan AH, Pessin JE. Insulin regulation of glucose uptake: a complex interplay of intracellular signalling pathways. Diabetologia. 2002 Nov;45(11 ):1475-83).
- insulin also has an important role with respect to the inhibition of muscle protein catabolism, or inhibition of protein breakdown, (Volpi E and Wolfe B. Insulin and Protein Metabolism. In: Handbook of Physiology, L. Jefferson and A. Cherrington editors. New York: Oxford, 2001 , p. 735-757).
- Insulin drivers are substances which may enhance or promote the normal activity of endogenous insulin. For example, enhancing or promoting the action of insulin may promote the development of muscle through several mechanisms. For example, through the promotion of the uptake of glucose by muscle cells, insulin supplies muscles with a source of fuel. Additionally, insulin has also been shown to stimulate the uptake of amino acids by muscle cells and further stimulate protein synthesis (Biolo G, Declan Fleming RY, Wolfe RR. Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle. J Clin Invest. 1995 Feb;95(2):811-9), particularly following exercise (Biolo G, Williams BD, Fleming RY, Wolfe RR. Insulin action on muscle protein kinetics and amino acid transport during recovery after resistance exercise. Diabetes. 1999 May;48(5):949-57).
- insulin has been shown to inhibit protein degradation (Hamel FG, Bennett RG, Harmon KS, Duckworth WC. Insulin inhibition of proteasome activity in intact cells. Biochem Biophys Res Commun. 1997 May 29;234(3):671- 4; Bennett RG, Hamel FG, Duckworth WC. Insulin inhibits the ubiquitin- dependent degrading activity of the 26S proteasome. Endocrinology. 2000 Jul;141(7):2508-17) which may lead to muscle loss.
- the inhibition of proteolysis by insulin has experimentally been shown to be due to multiple mechanisms. First, insulin directly inhibits the catalytic activity of the proteasome by inhibiting its peptide-degrading action (Duckworth WC, Bennett RG, Hamel FG.
- a dietary supplement for enhancing or promoting the natural action of insulin or any individual aspect or combination of aspects thereof.
- the dietary supplement is advantageous for individuals wishing to enhance the growth of skeletal muscle, reduce the loss of skeletal muscle or increase the energy supply to active muscles.
- the composition of the present invention comprises at least D-Pinitol and Leucine or derivatives thereof.
- the present invention may comprise at least one of Alpha Lipoic Acid, Glucomannan, D-Myo-lnositol, Guar Gum, Taurine or derivative thereof, Ketoisocaproic Acid or derivative thereof, Alpha-Ketoglutarate or derivative thereof, and a source of Peptide C12.
- the present invention also provides, by consumption of the dietary supplement by an individual, e.g., a human or an animal, a method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle.
- the present invention is directed to enhancing or promoting the natural activity of endogenous insulin within the body of an individual, e.g., a human or an animal, enhancing the growth of skeletal muscle, reducing the loss of skeletal muscle via protein degradation, and increasing the energy supply of active muscles.
- D-Pinitol a human or an animal
- Pinitol (CAS Registry No 484-68-4) is the active principle found in Bougainvillea spectabilis, a traditional anti-diabetic plant. It is known to be in many legumes and pine wood. Futhermore, Pinitol may also be derived from the processing of soybeans (Nordin P. Preferential Leaching of Pinitol from Soybeans during Imbibition. Plant Physiol. 1984 Oct;76(2):313-315). It has been demonstrated to have insulin-like effects in animal models of diabetes (Bates SH, Jones RB, Bailey CJ. Insulin-like effect of pinitol. Br J Pharmacol. 2000 Aug;130(8): 1944-8).
- Pinitol When Pinitol has been isolated from soybeans, it has been clinically shown to reduce risk factors in cardiovascular disease (Kim Jl, Kim JC, Kang MJ, Lee MS, Kim JJ, Cha IJ. Effects of pinitol isolated from soybeans on glycaemic control and cardiovascular risk factors in Korean patients with type Il diabetes mellitus: a randomized controlled study. Eur J Clin Nutr. 2005 Mar;59(3):456-88) and postprandial blood glucose levels in patients with diabetes (Kang MJ, Kim Jl, Yoon SY, Kim JC, Cha IJ. Pinitol from soybeans reduces postprandial blood glucose in patients with type 2 diabetes mellitus. J Med Food. 2006 Summer;9(2): 182-6).
- Pinitol has also been reported to increase creatine retention in muscle (Rasmussen C, Greenwood M, Kreider R, Earnest C, Almada A, Greenhaff P. Influence of D-Pinitol on whole body creatine retention. Medicine and Science in Sport and Exercise. 33(5): S204, 2001 ; Greenwood M, Kreider RB, Rasmussen C, Almada AL, Earnest CP. D-Pinitol augments whole body creatine retention in man. J Exerc Physiolonline 2001 ; 4:41-47).
- the supplemental composition includes D-Pinitol or a derivative thereof.
- a serving of the supplemental composition may include from about 0.5 ⁇ g to about 10 ⁇ g of D-Pinitol.
- the preferred dosage of a serving of the supplemental composition comprises about 2 ⁇ g of D-Pinitol.
- Leucine (CAS Registry No 328-39-2) is one of three branched chain amino acids and is important for skeletal muscle protein synthesis. Leucine is known to stimulate the mammalian target of rapamycin (mTOR) pathway (Anthony JC, Yoshizawa F, Anthony TG, Vary TC, Jefferson LS, Kimball SR. Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway. J Nutr. 2000 Oct;130(10):2413-9), a factor extremely important in muscle growth.
- mTOR mammalian target of rapamycin pathway
- mTOR is a complex protein pathway containing several regulatory sites as well as sites for interaction with multiple other proteins which acts to integrate signals pertaining to the energetic status of the cell as well as environmental stimuli to control protein synthesis, protein breakdown and, therefore, cell growth (Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004 Aug 15;18(16):1926-45).
- the mTOR kinase controls the translation machinery, in response to amino acids and growth factors, such as insulin. Leucine appears to stimulate mTOR in a manner similar to insulin, however acting via different mechanism.
- Leucine has been shown to stimulate protein synthesis in the skeletal muscle of rats (Crazier SJ, Kimball SR, Emmert SW, Anthony JC, Jefferson LS. Oral leucine administration stimulates protein synthesis in rat skeletal muscle. J Nutr. 2005 Mar;135(3):376-82). This may be mediated by the ability of Leucine to phosphorylate elF4G, thereby facilitating the formation of a complex of elF4G with the initiation factor elF4E, a complex necessary for protein sysnthesis (Bolster DR, Vary TC, Kimball SR, Jefferson LS.
- the supplemental composition includes Leucine or derivatives thereof.
- a serving of the supplemental composition may include from about 1 ⁇ g to about 15 ⁇ g of Leucine or derivatives thereof.
- the preferred dosage of a serving of the supplemental composition comprises about 5 ⁇ g of Leucine or derivatives thereof.
- Alpha Lipoic Acid (CAS Registry No 62-46-4) is an enzyme found in the cellular energy-producing structures, the mitochondria. Additionally, Alpha Lipoic Acid works in synergy with vitamins C and E as an antioxidant in both water- and fat- soluble environments.
- Alpha Lipoic Acid has been linked to a beneficial increase in high-density lipoproteins (Wollin SD, Wang Y, Kubow S, Jones PJ. Effects of a medium chain triglyceride oil mixture and alpha-lipoic acid diet on body composition, antioxidant status, and plasma lipid levels in the Golden Syrian hamster. J Nutr Biochem. 2004 Jul;15(7):402-10). Furthermore, Alpha Lipoic Acid appears to possess a dual action related to hunger and ⁇ -oxidation of fat.
- Alpha Lipoic Acid increases Uncoupling Protein-1 in rodent adipocytes while increasing AMP-activated protein kinase in skeletal muscle cells and increasing glucose uptake and energy expenditure (Lee WJ, Koh EH, Won JC, Kim MS, Park JY, Lee KU. Obesity: the role of hypothalamic AMP-activated protein kinase in body weight regulation, lnt J Biochem Cell Biol. 2005 Nov;37(11 ):2254-9).
- Alpha Lipoic Acid seemingly has different effects in different tissues.
- Alpha Lipoic Acid increases fatty acid oxidation, leading to an increase in energy expenditure and concomitant decreases in body weight and food intake.
- U.S. Patent Nos. 6,136,339 and 6,620,425 disclose compositions and methods for enhancing an athlete's muscle size or strength using a combination of Creatine, Alpha Lipoic Acid and optionally dextrose, to be taken mixed with water daily following exercise.
- the supplemental composition may include Alpha Lipoic Acid or derivatives thereof.
- a serving of the supplemental composition may include from about 1 ⁇ g to about 30 ⁇ g of Alpha Lipoic Acid or derivatives thereof.
- the preferred dosage of a serving of the supplemental composition comprises about 15 ⁇ g of Alpha Lipoic Acid or derivatives thereof.
- Glucomannan is a polysaccharide composed of long chains of simple sugars, primarily mannose and glucose. It is classified as a soluble fiber. Glucomannan can be obtained from several plants, however, the primary source is an Asian origin plant named Amorphophallus Konjac.
- Glucomannan has been shown to improve glycemic control and offer potential treatment for type 2 diabetes (Vuksan V, Jenkins DJ, Spadafora P, Sievenpiper JL, Owen R, Vidgen E, Brighenti F, Josse R, Leiter LA, Bruce- Thompson C. Konjac-mannan (glucomannan) improves glycemia and other associated risk factors for coronary heart disease in type 2 diabetes. A randomized controlled metabolic trial. Diabetes Care. 1999 Jun;22(6):913-9; Chen HL, Sheu WH, Tai TS, Liaw YP, Chen YC. Konjac supplement alleviated hypercholesterolemia and hyperglycemia in type 2 diabetic subjects--a randomized double-blind trial.
- the supplemental composition may include Glucomannan.
- a serving of the supplemental composition may include from about 0.01 g to about 0.5 g of Glucomannan.
- the preferred dosage of a serving of the supplemental composition comprises about 0.09 g of Glucomannan.
- D-myo-inositol (CAS Registry No 87-89-8) is a distinct isomer of inositol, which is vital to a diverse range of biological processes. D-myo-inositol has the effect of priming the secretion of insulin (Hoy M, Berggren PO, Gromada J. Involvement of protein kinase C-epsilon in inositol hexakisphosphate-induced exocytosis in mouse pancreatic beta-cells. J Biol Chem. 2003 Sep 12;278(37):35168-71 ; Barker CJ, Berggren PO. Inositol hexakisphosphate and beta-cell stimulus-secretion coupling. Anticancer Res.
- the supplemental composition may include D-myo- inositol.
- a serving of the supplemental composition may include from about 0.05 g to about 1 g of D-myo-inositol.
- the preferred dosage of a serving of the supplemental composition comprises about 0.2 g of D-myo-inositol.
- Guar Gum Guar gum (CAS Registry No 9000-30-0) is a water soluble polysaccharide obtained from the guar bean (Cyamopsis tetragonoloba). In animal models of diabetes, guar gum has been shown to improve insulin sensitivity (Cameron- Smith D, Habito R, Barnett M, Collier GR.
- Guar Gum The benefits conferred by Guar Gum are believed to be, at least partially, due to slowed glucose absorption (Russo A, Stevens JE, Wilson T, Wells F,
- the supplemental composition may include Guar Gum.
- a serving of the supplemental composition may include from about 0.1 g to about 1.5 g of Guar Gum.
- the preferred dosage of a serving of the supplemental composition comprises about 0.5 g of Guar Gum.
- Taurine (CAS Registry No 107-35-7) is an amino acid found primarily in nerve and muscle tissue. Taurine is generally considered to be a conditionally- essential amino acid, wherein it is only required under certain circumstances. Although not utilized for protein synthesis, Taurine is found in free-form or in some small peptides.
- Taurine transporter is mediated by a high affinity sodium-dependent transporter (Ramamoorthy S, Leibach FH, Mahesh VB, Han H, Yang-Feng T, Blakely RD, Ganapathy V. Functional characterization and chromosomal localization of a cloned taurine transporter from human placenta. Biochem J. 1994 Jun 15;300 ( Pt 3):893-900).
- the expression of this Taurine transporter is induced by a differentiation program of myocytes (muscle cells) (Uozumi Y, lto T, Hoshino Y, Mohri T, Maeda M, Takahashi K, Fujio Y, Azuma J.
- mice lacking the Taurine transporter have depleted Taurine levels in all muscle and have impaired skeletal muscle function (Warskulat U, Flogel U, Jacoby C, Hartwig HG, The Giveaway M, Merx MW, Molojavyi A, Heller-Stilb B, Schrader J, Haussinger D. Taurine transporter knockout depletes muscle taurine levels and results in severe skeletal muscle impairment but leaves cardiac function uncompromised. FASEB J. 2004 Mar;18(3):577-9)
- Taurine is the regulation of fluid balance. Contracting muscles also release Taurine (Cuisinier C, Michotte De Welle J, Verbeeck RK, Poortmans JR, Ward R, Sturbois X, Francaux M. Role of taurine in osmoregulation during endurance exercise. Eur J Appl Physiol. 2002 Oct;87(6):489-95) as it has also been shown to modulate the contractile function of mammalian skeletal muscle (Bakker AJ, Berg HM. Effect of taurine on sarcoplasmic reticulum function and force in skinned fast-twitch skeletal muscle fibres of the rat. J Physiol. 2002 Jan 1 ;538(Pt 1):185-94).
- Taurine supplemented rats had improved insulin sensitivity (Nakaya Y, Minami A, Harada N, Sakamoto S, Niwa Y, Ohnaka M. Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes. Am J Clin Nutr. 2000 Jan;71(1 ):54-8). Furthermore, Taurine improves glucose metabolism in insulin resistant rats (Nandhini AT, Anuradha CV. Taurine modulates kallikrein activity and glucose metabolism in insulin resistant rats. Amino Acids. 2002;22(1 ):27-38).
- the supplemental composition may include Taurine or derivatives thereof.
- a serving of the supplemental composition may include from about 0.02 g to about 1 g of Taurine or derivatives thereof.
- the preferred dosage of a serving of the supplemental composition comprises about 0.1 g of Taurine or derivatives thereof.
- Taurine Ketoisocaporic Acid serves in the present invention as an additional source of Taurine in addition to providing Alpha-ketoisocaproate (CAS Registry No 816-66-0).
- Alpha-ketoisocaproate is a keto acid of the branched chain amino acid, Leucine.
- Ketoisocaproic acid is known to stimulate insulin release (Heissig H, Urban KA, Hastedt K, Zunkler BJ, Panten U. Mechanism of the insulin-releasing action of alpha-ketoisocaproate and related alpha-keto acid anions. MoI Pharmacol. 2005 Oct;68(4):1097-105; Rabaglia ME, Gray-Keller MP, Frey BL, Shortreed MR, Smith LM, Attie AD.
- the supplemental composition may include Ketoisocaproic Acid or derivatives thereof.
- a serving of the supplemental composition may include from about 0.02 ⁇ g to about 5 ⁇ g of Ketoisocaproic Acid or derivatives thereof.
- the preferred dosage of a serving of the supplemental composition comprises about 1 ⁇ g of Ketoisocaproic Acid or derivatives thereof.
- Alpha-Ketoglutarate serves as a source of Taurine as well as a source providing Alpha-Ketoglutarate.
- Alpha-Ketoglutarate (CAS Registry No 64- 15-3) is an intermediate formed during the metabolism of glutamate.
- Alpha- Ketoglutarate also has a role in energy production via entry in to the tricarboxylic acid-cycle and oxidation to CO 2 . Additionally, Alpha-Ketoglutarate is important for tissue healing (Aussel C, Coudray-Lucas C, Lasnier E, Cynober L, Ekindjian OG. alpha-Ketoglutarate uptake in human fibroblasts. Cell Biol Int.
- Alpha-Ketoglutarate by glutamate dehydrogenase stimulates insulin secretion by supplying substrate for the tricarboxylic acid-cycle (Anno T, Uehara S, Katagiri H, Ohta Y, Ueda K, Mizuguchi H, Moriyama Y, Oka Y, Tanizawa Y.
- Overexpression of constitutively activated glutamate dehydrogenase induces insulin secretion through enhanced glutamate oxidation. Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E280-5).
- the supplemental composition may include Alpha- Ketoglutarate or derivatives thereof.
- a serving of the supplemental composition may include from about 5 ⁇ g to about 30 ⁇ g of Alpha-Ketoglutarate or derivatives thereof.
- the preferred dosage of a serving of the supplemental composition comprises about 15 ⁇ g of Alpha-Ketoglutarate or derivatives thereof. Promoting the Activity of Insulin to Enhance Skeletal Muscle Growth
- insulin drivers may promote the growth of skeletal muscle in response to resistance exercise. It is an object of the present invention that insulin drivers may promote the maintenance of skeletal muscle during periods of inactivity. Another object of the present invention it that insulin drivers may promote the uptake of glucose by skeletal muscle to provide ample energy during strenuous or prolonged physical activity. From consideration of this specification and the foregoing example, other embodiments may be obvious to those skilled in the art.
- Leucine, and other branch chain amino acids are known to activate the mTOR pathway of protein synthesis and decrease protein catabolism. Therefore, in terms of muscle building, it has been determined by the inventors of the present invention that it may be advantageous to provide compounds such a D-pinitol and derivatives thereof, which are known to mimic the actions of insulin and compounds such Leucine which are known be initiators of protein synthesis and inhibitors of protein catabolism.
- compounds such a D-pinitol and derivatives thereof which are known to mimic the actions of insulin and compounds such Leucine which are known be initiators of protein synthesis and inhibitors of protein catabolism.
- nutrients can be more readily taken into the cell to facilitate the synthesis of protein commenced by known initiators of the mTOR pathway.
- both insulin and Leucine act to inhibit the catabolism of protein. Therefore, it has been determined by the inventors of the present invention that the co-administration of insulin-mimicking substances and initiators of the mTOR pathway is advantageous in terms of muscle building.
- the dietary supplement may be consumed in any form.
- the dosage form of the diet supplement may be provided as, e.g., a powder beverage mix, a liquid beverage, a ready-to-eat bar or drink product, a capsule, a liquid capsule, a tablet, a caplet, or as a dietary gel.
- the preferred dosage forms of the present invention is as a powdered beverage mix.
- the dietary supplement may be provided alone or as part of a larger composition.
- the dosage form of the dietary supplement may be provided in accordance with customary processing techniques for herbal and dietary supplements in any of the forms mentioned above.
- the diet supplement set forth in the example embodiments herein may contain any appropriate number and type of excipients, as is well known in the art.
- the dietary supplement is consumed by an individual in accordance with the following method:
- a serving of said dietary supplement may be taken with an 8 oz. glass of water at least one time daily wherein each serving is comprised of approximately 1 g of said dietary supplement.
- Said dietary supplement may be consumed approximately 30 to 60 minutes before each meal, preferably in the morning and afternoon as well as after a workout.
- the dietary supplement may enhance the growth of skeletal muscle, reduce the loss of skeletal muscle or increase the energy supply to active muscles of an individual, e.g. a human or an animal for an extended period of time, e.g., all day.
- the present diet supplement or those similarly envisioned by one of skill in the art may be utilized in compositions and methods to enhance the growth of skeletal muscle, reduce the loss of skeletal muscle or increase the energy supply to active muscles in an individual, e.g. a human or an animal.
- an individual e.g. a human or an animal.
- the ingredients of the dietary supplement may be mixed with 8 ounces of water for consumption.
- the composition of the dietary supplement includes: D-Pinitol (2 ⁇ g), L-Leucine (3 ⁇ g), Leucine methyl ester HCI (1 ⁇ g), Leucine ethyl ester HCI (1 ⁇ g), Alpha Lipoic Acid (15 ⁇ g), Glucomannan (0.09 g), D-Myo-lnositol (0.2 g), Guar Gum (0.5 g), Taurine (0.05 g), Taurine Ketoisocaproic Acid (0.025 g), Taurine Alpha-Ketoglutarate (0.025 g) and Peptide C12 (1 ⁇ g).
- the dietary supplement may be consumed two to three times daily and prior to exercise.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nutrition Science (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Botany (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
A dietary supplement and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle of an individual comprising at least D-Pinitol and Leucine or derivatives thereof. The dietary supplement may further comprise at least one of Alpha Lipoic Acid, Glucomannan, D-Myo-lnositol, Guar Gum, Taurine or derivative thereof, a derivative of Ketoisocaproic Acid, a derivative of Alpha-Ketoglutarate, and a source of Peptide C12.
Description
Composition and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle.
Field of the Invention
The present invention relates to the composition of a dietary supplement and methods for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy
supply to skeletal muscle.
Background of the Invention
The most common role associated with insulin is the carbohydrate- induced uptake of glucose by cells. The release of glucose from cells is also concomitantly inhibited by insulin and its storage as glycogen and triglycerides is promoted (Khan AH, Pessin JE. Insulin regulation of glucose uptake: a complex interplay of intracellular signalling pathways. Diabetologia. 2002 Nov;45(11 ):1475-83). However, insulin also has an important role with respect to the inhibition of muscle protein catabolism, or inhibition of protein breakdown, (Volpi E and Wolfe B. Insulin and Protein Metabolism. In: Handbook of Physiology, L. Jefferson and A. Cherrington editors. New York: Oxford, 2001 , p. 735-757). Insulin drivers are substances which may enhance or promote the normal activity of endogenous insulin. For example, enhancing or promoting the action of insulin may promote the development of muscle through several mechanisms. For example, through the promotion of the uptake of glucose by muscle cells, insulin supplies muscles with a source of fuel. Additionally, insulin
has also been shown to stimulate the uptake of amino acids by muscle cells and further stimulate protein synthesis (Biolo G, Declan Fleming RY, Wolfe RR. Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle. J Clin Invest. 1995 Feb;95(2):811-9), particularly following exercise (Biolo G, Williams BD, Fleming RY, Wolfe RR. Insulin action on muscle protein kinetics and amino acid transport during recovery after resistance exercise. Diabetes. 1999 May;48(5):949-57).
Moreover, insulin has been shown to inhibit protein degradation (Hamel FG, Bennett RG, Harmon KS, Duckworth WC. Insulin inhibition of proteasome activity in intact cells. Biochem Biophys Res Commun. 1997 May 29;234(3):671- 4; Bennett RG, Hamel FG, Duckworth WC. Insulin inhibits the ubiquitin- dependent degrading activity of the 26S proteasome. Endocrinology. 2000 Jul;141(7):2508-17) which may lead to muscle loss. The inhibition of proteolysis by insulin has experimentally been shown to be due to multiple mechanisms. First, insulin directly inhibits the catalytic activity of the proteasome by inhibiting its peptide-degrading action (Duckworth WC, Bennett RG, Hamel FG. A direct inhibitory effect of insulin on a cytosolic proteolytic complex containing insulin- degrading enzyme and multicatalytic proteinase. J Biol Chem. 1994 Oct 7;269(40):24575-80). Second, insulin has been shown to interfere with and downregulate the ATP-dependent ubiquitin (Ub) pathway (Price SR, Bailey JL, Wang X, Jurkovitz C, England BK, Ding X, Phillips LS, Mitch WE. Muscle wasting in insulinopenic rats results from activation of the ATP-dependent, ubiquitin- proteasome proteolytic pathway by a mechanism including gene transcription. J
Clin Invest. 1996 Oct 15;98(8):1703-8; Mitch WE, Bailey JL, Wang X, Jurkovitz C, Newby D, Price SR. Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting. Am J Physiol. 1999 May;276(5 Pt 1 ):C1132-8). Third, insulin reduces the expression of MAFbx, a muscle-specific Ub-ligase required for muscle atrophy. Sacheck JM, Ohtsuka A, McLary SC, Goldberg AL. IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRFI . Am J Physiol Endocrinol Metab. 2004 Oct;287(4):E591-601 ). In combination, the aforementioned mechanisms may lead to the inhibition of muscle catabolism via insulin dependent mechanisms.
It would therefore be advantageous to enhance or promote the activity of insulin for the general preservation or growth of skeletal muscle, particularly for individuals involved in physical activity or training. In such individuals, the breakdown of muscle protein stimulated by exercise (Rennie MJ, Edwards RH, Krywawych S, Davies CT, Halliday D, Waterlow JC, Millward DJ. Effect of exercise on protein turnover in man. Clin Sci (Lond). 1981 Nov;61(5):627-39) is of concern and it is desired to be advantageously avoided or minimized.
There are a number of potential processes or variables which may be affected by insulin drivers in order to enhance or promote the activity of insulin. These steps may include, but not be limited to: insulin sensitivity, insulin secretion, binding of insulin to an insulin receptor, and transporter function (e.g. GLUT4 translocation).
Summary of the Invention
The foregoing needs and other needs and objectives that will become apparent for the following description are achieved in the present invention which comprises, according to various embodiments, a dietary supplement for enhancing or promoting the natural action of insulin or any individual aspect or combination of aspects thereof. The dietary supplement is advantageous for individuals wishing to enhance the growth of skeletal muscle, reduce the loss of skeletal muscle or increase the energy supply to active muscles. The composition of the present invention comprises at least D-Pinitol and Leucine or derivatives thereof. Furthermore, the present invention may comprise at least one of Alpha Lipoic Acid, Glucomannan, D-Myo-lnositol, Guar Gum, Taurine or derivative thereof, Ketoisocaproic Acid or derivative thereof, Alpha-Ketoglutarate or derivative thereof, and a source of Peptide C12.
The present invention also provides, by consumption of the dietary supplement by an individual, e.g., a human or an animal, a method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle.
Detailed Description of the Invention
The present invention, according to various embodiments, is directed to enhancing or promoting the natural activity of endogenous insulin within the body of an individual, e.g., a human or an animal, enhancing the growth of skeletal muscle, reducing the loss of skeletal muscle via protein degradation, and increasing the energy supply of active muscles.
D-Pinitol
Pinitol (CAS Registry No 484-68-4) is the active principle found in Bougainvillea spectabilis, a traditional anti-diabetic plant. It is known to be in many legumes and pine wood. Futhermore, Pinitol may also be derived from the processing of soybeans (Nordin P. Preferential Leaching of Pinitol from Soybeans during Imbibition. Plant Physiol. 1984 Oct;76(2):313-315). It has been demonstrated to have insulin-like effects in animal models of diabetes (Bates SH, Jones RB, Bailey CJ. Insulin-like effect of pinitol. Br J Pharmacol. 2000 Aug;130(8): 1944-8). When Pinitol has been isolated from soybeans, it has been clinically shown to reduce risk factors in cardiovascular disease (Kim Jl, Kim JC, Kang MJ, Lee MS, Kim JJ, Cha IJ. Effects of pinitol isolated from soybeans on glycaemic control and cardiovascular risk factors in Korean patients with type Il diabetes mellitus: a randomized controlled study. Eur J Clin Nutr. 2005 Mar;59(3):456-8) and postprandial blood glucose levels in patients with diabetes (Kang MJ, Kim Jl, Yoon SY, Kim JC, Cha IJ. Pinitol from soybeans reduces postprandial blood glucose in patients with type 2 diabetes mellitus. J Med Food. 2006 Summer;9(2): 182-6).
Of particular interest to the invention, Pinitol has also been reported to increase creatine retention in muscle (Rasmussen C, Greenwood M, Kreider R, Earnest C, Almada A, Greenhaff P. Influence of D-Pinitol on whole body creatine retention. Medicine and Science in Sport and Exercise. 33(5): S204, 2001 ; Greenwood M, Kreider RB, Rasmussen C, Almada AL, Earnest CP. D-Pinitol augments whole body creatine retention in man. J Exerc Physiolonline 2001 ; 4:41-47).
In an embodiment of the present invention, which is set forth in greater detail in the example below, the supplemental composition includes D-Pinitol or a derivative thereof. A serving of the supplemental composition may include from about 0.5 μg to about 10 μg of D-Pinitol. The preferred dosage of a serving of the supplemental composition comprises about 2 μg of D-Pinitol. L-Leucine
Leucine (CAS Registry No 328-39-2) is one of three branched chain amino acids and is important for skeletal muscle protein synthesis. Leucine is known to stimulate the mammalian target of rapamycin (mTOR) pathway (Anthony JC, Yoshizawa F, Anthony TG, Vary TC, Jefferson LS, Kimball SR. Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats
via a rapamycin-sensitive pathway. J Nutr. 2000 Oct;130(10):2413-9), a factor extremely important in muscle growth. mTOR is a complex protein pathway containing several regulatory sites as well as sites for interaction with multiple other proteins which acts to integrate signals pertaining to the energetic status of the cell as well as environmental stimuli to control protein synthesis, protein breakdown and, therefore, cell growth (Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004 Aug 15;18(16):1926-45). The mTOR kinase controls the translation machinery, in response to amino acids and growth factors, such as insulin. Leucine appears to stimulate mTOR in a manner similar to insulin, however acting via different mechanism.
The ingestion of Leucine combined with protein and carbohydrates has been shown to stimulate a reduction in protein breakdown and an increase in skeletal muscle protein synthesis to a greater degree than protein plus carbohydrate and carbohydrate alone (Koopman R, Wagenmakers AJ, Manders RJ, Zorenc AH, Senden JM, Gorselink M, Keizer HA, van Loon LJ. Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects. Am J Physiol Endocrinol Metab. 2005 Apr;288(4):E645-53). Furthermore, oral administration of Leucine has been shown to stimulate protein synthesis in the skeletal muscle of rats (Crazier SJ, Kimball SR, Emmert SW, Anthony JC, Jefferson LS. Oral leucine administration stimulates protein synthesis in rat skeletal muscle. J Nutr. 2005 Mar;135(3):376-82). This may be mediated by the ability of Leucine to phosphorylate elF4G, thereby facilitating the formation of a complex of elF4G
with the initiation factor elF4E, a complex necessary for protein sysnthesis (Bolster DR, Vary TC, Kimball SR, Jefferson LS. Leucine regulates translation initiation in rat skeletal muscle via enhanced elF4G phosphorylation. J Nutr. 2004 Jul;134(7):1704-10). In an embodiment of the present invention, which is set forth in greater detail in the example below, the supplemental composition includes Leucine or derivatives thereof. A serving of the supplemental composition may include from about 1 μg to about 15 μg of Leucine or derivatives thereof. The preferred dosage of a serving of the supplemental composition comprises about 5 μg of Leucine or derivatives thereof. Alpha Lipoic Acid
Alpha Lipoic Acid (CAS Registry No 62-46-4) is an enzyme found in the cellular energy-producing structures, the mitochondria. Additionally, Alpha Lipoic Acid works in synergy with vitamins C and E as an antioxidant in both water- and fat- soluble environments.
In rats supplemented with Alpha Lipoic Acid the negative age-related changes in mitochondrial function, accumulated oxidative damage and the metabolic rate were all improved (Hagen TM, lngersoll RT, Lykkesfeldt J, Liu J,
Wehr CM, Vinarsky V, Bartholomew JC, Ames AB. (R)-alpha-lipoic acid- supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB J. 1999 Feb;13(2):411- 8). The antioxidant activity of Alpha Lipoic Acid is likely involved in the prevention of cell death due to oxidative stress (Arivazhagan P, Juliet P, Panneerselvam C. Effect of dl-alpha-lipoic acid on the status of lipid peroxidation and antioxidants in aged rats. Pharmacol Res. 2000 Mar;41(3):299-303) and likely increased mitochondrial membrane permeability. Possibly related to these effects, Alpha Lipoic Acid has been linked to a beneficial increase in high-density lipoproteins (Wollin SD, Wang Y, Kubow S, Jones PJ. Effects of a medium chain triglyceride oil mixture and alpha-lipoic acid diet on body composition, antioxidant status, and plasma lipid levels in the Golden Syrian hamster. J Nutr Biochem. 2004 Jul;15(7):402-10). Furthermore, Alpha Lipoic Acid appears to possess a dual action related to hunger and β-oxidation of fat. First, the activity of AMP-activated protein kinase, which acts as an energy sensor in the hypothalamus, is reduced by Alpha Lipoic Acid in rodents, this results in a profound weight loss by reducing food intake and enhancing energy expenditure (Kim MS, Park JY, Namkoong C, Jang PG, Ryu JW, Song HS, Yun JY, Namgoong IS, Ha J, Park IS, Lee IK, Viollet B, Youn JH, Lee HK, Lee KU. Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. Nat Med. 2004 Jul;10(7):727-33). Second, Alpha Lipoic Acid increases Uncoupling Protein-1 in rodent adipocytes while increasing AMP-activated protein kinase in skeletal muscle cells and increasing glucose uptake and energy expenditure (Lee
WJ, Koh EH, Won JC, Kim MS, Park JY, Lee KU. Obesity: the role of hypothalamic AMP-activated protein kinase in body weight regulation, lnt J Biochem Cell Biol. 2005 Nov;37(11 ):2254-9). Thus Alpha Lipoic Acid seemingly has different effects in different tissues. However, in adipocytes or muscle cells Alpha Lipoic Acid increases fatty acid oxidation, leading to an increase in energy expenditure and concomitant decreases in body weight and food intake.
U.S. Patent Nos. 6,136,339 and 6,620,425 disclose compositions and methods for enhancing an athlete's muscle size or strength using a combination of Creatine, Alpha Lipoic Acid and optionally dextrose, to be taken mixed with water daily following exercise.
In an embodiment of the present invention, which is set forth in greater detail in the example below, the supplemental composition may include Alpha Lipoic Acid or derivatives thereof. A serving of the supplemental composition may include from about 1 μg to about 30 μg of Alpha Lipoic Acid or derivatives thereof. The preferred dosage of a serving of the supplemental composition comprises about 15 μg of Alpha Lipoic Acid or derivatives thereof. Glucomannan
Glucomannan is a polysaccharide composed of long chains of simple sugars, primarily mannose and glucose. It is classified as a soluble fiber. Glucomannan can be obtained from several plants, however, the primary source is an Asian origin plant named Amorphophallus Konjac.
Glucomannan has been shown to improve glycemic control and offer potential treatment for type 2 diabetes (Vuksan V, Jenkins DJ, Spadafora P,
Sievenpiper JL, Owen R, Vidgen E, Brighenti F, Josse R, Leiter LA, Bruce- Thompson C. Konjac-mannan (glucomannan) improves glycemia and other associated risk factors for coronary heart disease in type 2 diabetes. A randomized controlled metabolic trial. Diabetes Care. 1999 Jun;22(6):913-9; Chen HL, Sheu WH, Tai TS, Liaw YP, Chen YC. Konjac supplement alleviated hypercholesterolemia and hyperglycemia in type 2 diabetic subjects--a randomized double-blind trial. J Am Coll Nutr. 2003 Feb;22(1 ):36-42) and improve insulin resistance in humans (Vuksan V, Sievenpiper JL, Owen R, Swilley JA, Spadafora P, Jenkins DJ, Vidgen E, Brighenti F, Josse RG, Leiter LA, Xu Z, Novokmet R. Beneficial effects of viscous dietary fiber from Konjac- mannan in subjects with the insulin resistance syndrome: results of a controlled metabolic trial. Diabetes Care. 2000 Jan;23(1 ):9-14).
In an embodiment of the present invention, which is set forth in greater detail in the example below, the supplemental composition may include Glucomannan. A serving of the supplemental composition may include from about 0.01 g to about 0.5 g of Glucomannan. The preferred dosage of a serving of the supplemental composition comprises about 0.09 g of Glucomannan. D-myo-inositol
In an embodiment of the present invention, which is set forth in greater detail in the example below, the supplemental composition may include D-myo- inositol. A serving of the supplemental composition may include from about 0.05 g to about 1 g of D-myo-inositol. The preferred dosage of a serving of the supplemental composition comprises about 0.2 g of D-myo-inositol. Guar Gum
Guar gum (CAS Registry No 9000-30-0) is a water soluble polysaccharide obtained from the guar bean (Cyamopsis tetragonoloba). In animal models of diabetes, guar gum has been shown to improve insulin sensitivity (Cameron- Smith D, Habito R, Barnett M, Collier GR. Dietary guar gum improves insulin sensitivity in streptozotocin-induced diabetic rats. J Nutr. 1997 Feb;127(2):359- 64). In healthy rats, Guar Gum has the effect of improving insulin response (Prieto PG, Cancelas J, Villanueva-Penacarrillo ML, Malaisse WJ, Valverde I. Short-term and Long-term Effects of Guar on Postprandial Plasma Glucose, Insulin and Glucagon-like Peptide 1 Concentration in Healthy Rats. Horm Metab Res. 2006 Jun;38(6):397-404). Supplementation with Guar Gum in humans allowed for better control of diabetes (Aro A, Uusitupa M, Voutilainen E, Hersio K, Korhonen T, Siitonen O. Improved diabetic control and hypocholesterolaemic effect induced by long-term dietary supplementation with guar gum in type 2 (insulin-independent) diabetes. Diabetologia. 1981 Jul;21(1 ):29-33) and reduced the associated cardiovascular risks (Uusitupa M, Tuomilehto J, Karttunen P, Wolf E. Long term effects of guar gum on metabolic control, serum cholesterol and blood pressure levels in type 2 (non-insulin-dependent) diabetic patients with high blood pressure. Ann Clin Res. 1984;16 Suppl 43:126-31 ) as shown by long- term studies. Additionally, the addition of low amounts of Guar Gum to the diet of humans has been shown to improve insulin sensitivity (Tagliaferro V, Cassader M, Bozzo C, Pisu E, Bruno A, Marena S, Cavallo-Perin P, Cravero L, Pagano G. Moderate guar-gum addition to usual diet improves peripheral sensitivity to insulin and lipaemic profile in NIDDM. Diabete Metab. 1985 Dec;11(6):380-5). In
healthy humans insulin sensitivity is also improved (Landin K, Holm G, Tengborn L, Smith U. Guar gum improves insulin sensitivity, blood lipids, blood pressure, and fibrinolysis in healthy men. Am J Clin Nutr. 1992 Dec;56(6):1061-5).
The benefits conferred by Guar Gum are believed to be, at least partially, due to slowed glucose absorption (Russo A, Stevens JE, Wilson T, Wells F,
Tonkin A, Horowitz M, Jones KL. Guar attenuates fall in postprandial blood pressure and slows gastric emptying of oral glucose in type 2 diabetes. Dig Dis
Sci. 2003 Jul;48(7):1221-9), thereby improving insulin sensitivity.
In an embodiment of the present invention, which is set forth in greater detail in the example below, the supplemental composition may include Guar Gum. A serving of the supplemental composition may include from about 0.1 g to about 1.5 g of Guar Gum. The preferred dosage of a serving of the supplemental composition comprises about 0.5 g of Guar Gum. Taurine
o o
S
H2N ' "OH
Taurine (CAS Registry No 107-35-7) is an amino acid found primarily in nerve and muscle tissue. Taurine is generally considered to be a conditionally- essential amino acid, wherein it is only required under certain circumstances.
Although not utilized for protein synthesis, Taurine is found in free-form or in some small peptides.
Moreover, the accumulation of Taurine within cells is mediated by a high affinity sodium-dependent transporter (Ramamoorthy S, Leibach FH, Mahesh VB, Han H, Yang-Feng T, Blakely RD, Ganapathy V. Functional characterization and chromosomal localization of a cloned taurine transporter from human placenta. Biochem J. 1994 Jun 15;300 ( Pt 3):893-900). The expression of this Taurine transporter is induced by a differentiation program of myocytes (muscle cells) (Uozumi Y, lto T, Hoshino Y, Mohri T, Maeda M, Takahashi K, Fujio Y, Azuma J. Myogenic differentiation induces taurine transporter in association with taurine-mediated cytoprotection in skeletal muscles. Biochem J. 2006 Mar 15;394(Pt 3):699-706). Exercise-induced hormones also activate the Taurine transporter (Park SH, Lee H, Park T. Cortisol and IGF-1 synergistically up- regulate taurine transport by the rat skeletal muscle cell line, L6. Biofactors. 2004;21(1-4):403-6). Genetically modified mice lacking the Taurine transporter have depleted Taurine levels in all muscle and have impaired skeletal muscle function (Warskulat U, Flogel U, Jacoby C, Hartwig HG, Thewissen M, Merx MW, Molojavyi A, Heller-Stilb B, Schrader J, Haussinger D. Taurine transporter knockout depletes muscle taurine levels and results in severe skeletal muscle impairment but leaves cardiac function uncompromised. FASEB J. 2004 Mar;18(3):577-9)
One of the main roles of Taurine is the regulation of fluid balance. Contracting muscles also release Taurine (Cuisinier C, Michotte De Welle J,
Verbeeck RK, Poortmans JR, Ward R, Sturbois X, Francaux M. Role of taurine in osmoregulation during endurance exercise. Eur J Appl Physiol. 2002 Oct;87(6):489-95) as it has also been shown to modulate the contractile function of mammalian skeletal muscle (Bakker AJ, Berg HM. Effect of taurine on sarcoplasmic reticulum function and force in skinned fast-twitch skeletal muscle fibres of the rat. J Physiol. 2002 Jan 1 ;538(Pt 1):185-94). In rats, the Taurine concentration in muscle decreases as a result of exercise (Matsuzaki Y, Miyazaki T, Miyakawa S, Bouscarel B, lkegami T, Tanaka N. Decreased taurine concentration in skeletal muscles after exercise for various durations. Med Sci Sports Exerc. 2002 May;34(5):793-7) and oral supplementation with Taurine can maintain the concentration of Taurine in muscle and prolong exercise performance (Miyazaki T, Matsuzaki Y, lkegami T, Miyakawa S, Doy M, Tanaka N, Bouscarel B. Optimal and effective oral dose of taurine to prolong exercise performance in rat. Amino Acids. 2004 Dec;27(3-4):291-8; Yatabe Y, Miyakawa S, Miyazaki T, Matsuzaki Y, Ochiai N. Effects of taurine administration in rat skeletal muscles on exercise. J Orthop Sci. 2003;8(3):415-9).
In a model of spontaneous diabetes, Taurine supplemented rats had improved insulin sensitivity (Nakaya Y, Minami A, Harada N, Sakamoto S, Niwa Y, Ohnaka M. Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes. Am J Clin Nutr. 2000 Jan;71(1 ):54-8). Furthermore, Taurine improves glucose metabolism in insulin resistant rats (Nandhini AT, Anuradha CV. Taurine modulates kallikrein activity and glucose metabolism in insulin resistant rats. Amino Acids.
2002;22(1 ):27-38). Supplementation with Taurine has been shown to reduce exercise-induced oxidative damage and enhance recovery (Zhang M, Izumi I, Kagamimori S, Sokejima S, Yamagami T, Liu Z, Qi B. Role of taurine supplementation to prevent exercise-induced oxidative stress in healthy young men. Amino Acids. 2004 Mar;26(2):203-7).
In an embodiment of the present invention, which is set forth in greater detail in the example below, the supplemental composition may include Taurine or derivatives thereof. A serving of the supplemental composition may include from about 0.02 g to about 1 g of Taurine or derivatives thereof. The preferred dosage of a serving of the supplemental composition comprises about 0.1 g of Taurine or derivatives thereof. Taurine Ketoisocaproic Acid
Taurine Ketoisocaporic Acid serves in the present invention as an additional source of Taurine in addition to providing Alpha-ketoisocaproate (CAS Registry No 816-66-0). Alpha-ketoisocaproate is a keto acid of the branched chain amino acid, Leucine. Moreover, Ketoisocaproic acid is known to stimulate insulin release (Heissig H, Urban KA, Hastedt K, Zunkler BJ, Panten U. Mechanism of the insulin-releasing action of alpha-ketoisocaproate and related
alpha-keto acid anions. MoI Pharmacol. 2005 Oct;68(4):1097-105; Rabaglia ME, Gray-Keller MP, Frey BL, Shortreed MR, Smith LM, Attie AD. Alpha- Ketoisocaproate-induced hypersecretion of insulin by islets from diabetes- susceptible mice. Am J Physiol Endocrinol Metab. 2005 Aug;289(2):E218-24) and Ketoisocaproic Acid has been shown to reduce protein catabolism as well as prevent muscle loss (Stewart PM, Walser M, Drachman DB. Branched-chain ketoacids reduce muscle protein degradation in Duchenne muscular dystrophy. Muscle Nerve. 1982 Mar;5(3):197-201 ).
In an embodiment of the present invention, which is set forth in greater detail in the example below, the supplemental composition may include Ketoisocaproic Acid or derivatives thereof. A serving of the supplemental composition may include from about 0.02 μg to about 5 μg of Ketoisocaproic Acid or derivatives thereof. The preferred dosage of a serving of the supplemental composition comprises about 1 μg of Ketoisocaproic Acid or derivatives thereof. Taurine Alpha-Ketoglutarate
Taurine Alpha-Ketoglutarate serves as a source of Taurine as well as a source providing Alpha-Ketoglutarate. Alpha-Ketoglutarate (CAS Registry No 64- 15-3) is an intermediate formed during the metabolism of glutamate. Alpha-
Ketoglutarate also has a role in energy production via entry in to the tricarboxylic acid-cycle and oxidation to CO2. Additionally, Alpha-Ketoglutarate is important for tissue healing (Aussel C, Coudray-Lucas C, Lasnier E, Cynober L, Ekindjian OG. alpha-Ketoglutarate uptake in human fibroblasts. Cell Biol Int. 1996 May;20(5):359-63), particularly in muscle (Wernerman J, Hammarqvist F, Vinnars E. Alpha-ketoglutarate and postoperative muscle catabolism. Lancet. 1990 Mar 24;335(8691 ):701-3) where Alpha-Ketoglutarate can preserve protein synthesis and prevent muscle loss (Hammarqvist F, Wernerman J, von der Decken A, Vinnars E. Alpha-ketoglutarate preserves protein synthesis and free glutamine in skeletal muscle after surgery. Surgery. 1991 Jan;109(1 ):28-36). Mutations in glutamate dehydrogenase, an enzyme involved in the formation of Alpha-Ketoglutarate, leads to the accumulation of Alpha-Ketoglutarate. This leads to chronic hyper-insulinemia which subsequently results in severe hypoglycemia (Stanley CA, Lieu YK, Hsu BY, Burlina AB, Greenberg CR, Hopwood NJ, Perlman K, Rich BH, Zammarchi E, Poncz M. Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med. 1998 May 7;338(19):1352-7). It is further believed that the formation of Alpha-Ketoglutarate by glutamate dehydrogenase stimulates insulin secretion by supplying substrate for the tricarboxylic acid-cycle (Anno T, Uehara S, Katagiri H, Ohta Y, Ueda K, Mizuguchi H, Moriyama Y, Oka Y, Tanizawa Y. Overexpression of constitutively activated glutamate dehydrogenase induces insulin secretion through enhanced glutamate oxidation. Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E280-5).
In an embodiment of the present invention, which is set forth in greater detail in the example below, the supplemental composition may include Alpha- Ketoglutarate or derivatives thereof. A serving of the supplemental composition may include from about 5 μg to about 30 μg of Alpha-Ketoglutarate or derivatives thereof. The preferred dosage of a serving of the supplemental composition comprises about 15 μg of Alpha-Ketoglutarate or derivatives thereof. Promoting the Activity of Insulin to Enhance Skeletal Muscle Growth
Based on the aforementioned research, it has been determined by the inventors of the present invention that substances which enhance or promote the activity of insulin, or similar such insulin drivers, would be of benefit in terms of the natural role of insulin. In an embodiment of the present invention, insulin drivers may promote the growth of skeletal muscle in response to resistance exercise. It is an object of the present invention that insulin drivers may promote the maintenance of skeletal muscle during periods of inactivity. Another object of the present invention it that insulin drivers may promote the uptake of glucose by skeletal muscle to provide ample energy during strenuous or prolonged physical activity. From consideration of this specification and the foregoing example, other embodiments may be obvious to those skilled in the art.
Furthermore, Leucine, and other branch chain amino acids are known to activate the mTOR pathway of protein synthesis and decrease protein catabolism. Therefore, in terms of muscle building, it has been determined by the inventors of the present invention that it may be advantageous to provide compounds such a D-pinitol and derivatives thereof, which are known to mimic
the actions of insulin and compounds such Leucine which are known be initiators of protein synthesis and inhibitors of protein catabolism. Through the concomitant administration of insulin-mimicking compounds and initiators of protein synthesis pathways and inhibitors of protein catabolism, it has been determined by the inventors of the present invention that nutrients can be more readily taken into the cell to facilitate the synthesis of protein commenced by known initiators of the mTOR pathway. Moreover, both insulin and Leucine act to inhibit the catabolism of protein. Therefore, it has been determined by the inventors of the present invention that the co-administration of insulin-mimicking substances and initiators of the mTOR pathway is advantageous in terms of muscle building.
According to various embodiments of the present invention, the dietary supplement may be consumed in any form. For instance, the dosage form of the diet supplement may be provided as, e.g., a powder beverage mix, a liquid beverage, a ready-to-eat bar or drink product, a capsule, a liquid capsule, a tablet, a caplet, or as a dietary gel. The preferred dosage forms of the present invention is as a powdered beverage mix. The dietary supplement may be provided alone or as part of a larger composition.
Furthermore, the dosage form of the dietary supplement may be provided in accordance with customary processing techniques for herbal and dietary supplements in any of the forms mentioned above. Additionally, the diet supplement set forth in the example embodiments herein may contain any appropriate number and type of excipients, as is well known in the art.
Preferably, the dietary supplement is consumed by an individual in accordance with the following method: As a diet supplement, a serving of said dietary supplement may be taken with an 8 oz. glass of water at least one time daily wherein each serving is comprised of approximately 1 g of said dietary supplement. Said dietary supplement may be consumed approximately 30 to 60 minutes before each meal, preferably in the morning and afternoon as well as after a workout. In this manner, the dietary supplement may enhance the growth of skeletal muscle, reduce the loss of skeletal muscle or increase the energy supply to active muscles of an individual, e.g. a human or an animal for an extended period of time, e.g., all day.
The present diet supplement or those similarly envisioned by one of skill in the art, may be utilized in compositions and methods to enhance the growth of skeletal muscle, reduce the loss of skeletal muscle or increase the energy supply to active muscles in an individual, e.g. a human or an animal. Although the following example illustrates the practice of the present invention in one of its embodiments, the example should not be construed as limiting the scope of the invention. Other embodiments will be apparent to one of skill in the art from consideration of the specifications and example.
Example 1
The ingredients of the dietary supplement, supplied in dry powder form, may be mixed with 8 ounces of water for consumption. The composition of the dietary supplement includes: D-Pinitol (2 μg), L-Leucine (3 μg), Leucine methyl ester HCI (1 μg), Leucine ethyl ester HCI (1 μg), Alpha Lipoic Acid (15 μg), Glucomannan (0.09 g), D-Myo-lnositol (0.2 g), Guar Gum (0.5 g), Taurine (0.05 g), Taurine Ketoisocaproic Acid (0.025 g), Taurine Alpha-Ketoglutarate (0.025 g) and Peptide C12 (1 μg). The dietary supplement may be consumed two to three times daily and prior to exercise.
In the foregoing specification, the invention has been described with specific embodiments thereof, however, it will be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the invention.
Claims
1. A composition comprising D-Pinitol and Leucine or derivatives thereof.
2. The composition of claim 1 , further comprising Alpha Lipoic Acid.
3. The composition of claim 1 , further comprising Glucomannan.
4. The composition of claim 1 , further comprising D-Myo-lnositol.
5. A dietary supplement comprising about 2 μg of D-Pinitol and about 5 μg of Leucine or derivatives thereof.
6. The dietary supplement of claim 5, further comprising about 15 μg of Alpha Lipoic Acid.
7. The dietary supplement of claim 5, further comprising about 0.09 g of Glucomannan.
8. The dietary supplement of claim 5, further comprising about 0.2 g D-Myo- lnositol.
9. The dietary supplement of claim 5, further comprising: about 0.5 g of Guar Gum; about 0.05 g of Taurine; about 0.025 g of Taurine Ketoisocaproic Acid; about 0.025 g of Taurine Alpha-Ketoglutarate; and about 1 μg of Peptide C12.
10. A method of enhancing or promoting the activity of insulin in a human or animal comprising at least the step of administering a composition comprising D-Pinitol and Leucine or derivatives thereof.
11.The method of claim 10, further comprising Alpha Lipoic Acid.
12. The method of claim 10, further comprising Glucomannan.
13. The method of claim 10, further comprising D-Myo-lnositol.
14. A method of increasing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle comprising at least the step of administering a composition comprising D-Pinitol and
Leucine or derivatives thereof.
15. The method of claim 14, further comprising Alpha Lipoic Acid.
16. The method of claim 14, further comprsing Glucomannan.
17. The method of claim 14, further comprising D-Myo-lnositol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CA2006/001431 WO2008025116A1 (en) | 2006-08-31 | 2006-08-31 | Composition and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CA2006/001431 WO2008025116A1 (en) | 2006-08-31 | 2006-08-31 | Composition and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2008025116A1 true WO2008025116A1 (en) | 2008-03-06 |
Family
ID=39135445
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CA2006/001431 WO2008025116A1 (en) | 2006-08-31 | 2006-08-31 | Composition and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2008025116A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102448452A (en) * | 2009-04-03 | 2012-05-09 | 赢创德固赛有限公司 | Dietary supplement comprising alpha keto acids for supporting diabetes therapy |
| WO2016150573A1 (en) * | 2015-03-26 | 2016-09-29 | Capri Sun Ag | Compositions for use in food products |
| EP3789018A1 (en) * | 2019-09-09 | 2021-03-10 | Servicio Andaluz De Salud | Composition and methods for enhancing or promoting the secretion of ghrelin to promote a healthy metabolic aging |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001028356A2 (en) * | 1999-10-18 | 2001-04-26 | Muscletech Research And Development Inc. | Food supplement for increasing lean mass and strength |
| US6514941B1 (en) * | 1999-12-10 | 2003-02-04 | Campina Melkunie B.V. | Method of preparing a casein hydrolysate enriched in anti-hypertensive peptides |
| WO2006026458A2 (en) * | 2004-08-25 | 2006-03-09 | Mtor Formulations Ltd. | Compositions and methods for activating protein synthesis and deactivating catabolic processes in skeletal muscle |
-
2006
- 2006-08-31 WO PCT/CA2006/001431 patent/WO2008025116A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001028356A2 (en) * | 1999-10-18 | 2001-04-26 | Muscletech Research And Development Inc. | Food supplement for increasing lean mass and strength |
| US6514941B1 (en) * | 1999-12-10 | 2003-02-04 | Campina Melkunie B.V. | Method of preparing a casein hydrolysate enriched in anti-hypertensive peptides |
| WO2006026458A2 (en) * | 2004-08-25 | 2006-03-09 | Mtor Formulations Ltd. | Compositions and methods for activating protein synthesis and deactivating catabolic processes in skeletal muscle |
Non-Patent Citations (1)
| Title |
|---|
| TAGLIAFERRO ET AL.: "Moderate guar-gum addition to usual diet improves peripheral sensitivity to insulin and lipaemic profile in niddm", DIABETE & METABOLISME, vol. 11, 1985, pages 380 - 385 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102448452A (en) * | 2009-04-03 | 2012-05-09 | 赢创德固赛有限公司 | Dietary supplement comprising alpha keto acids for supporting diabetes therapy |
| WO2016150573A1 (en) * | 2015-03-26 | 2016-09-29 | Capri Sun Ag | Compositions for use in food products |
| EP3789018A1 (en) * | 2019-09-09 | 2021-03-10 | Servicio Andaluz De Salud | Composition and methods for enhancing or promoting the secretion of ghrelin to promote a healthy metabolic aging |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20070015686A1 (en) | Dietary supplement for enhancing skeletal muscle mass, decreasing muscle protein degradation, downregulation of muscle catabolism pathways, and decreasing catabolism of muscle cells | |
| Aleixandre et al. | Dietary fiber and blood pressure control | |
| Zeng et al. | A high-selenium diet induces insulin resistance in gestating rats and their offspring | |
| Agca et al. | Taurine ameliorates neuropathy via regulating NF-κB and Nrf2/HO-1 signaling cascades in diabetic rats | |
| JP5788631B2 (en) | Methods and compositions for nutritionally improving glucose control and insulin action | |
| CA2566343C (en) | Nutritional composition for increasing creatine uptake in skeletal muscle | |
| Zhang et al. | Codonopsis lanceolata polysaccharide CLPS alleviates high fat/high sucrose diet-induced insulin resistance via anti-oxidative stress | |
| US20080317886A1 (en) | Compositions for Preventing and Reducing Delayed Onset Muscle Soreness | |
| US20110064712A1 (en) | Dietary Supplement Compositions and Methods of Making and Using the Same | |
| CA2560107A1 (en) | Nutritional composition and method for increasing creatine uptake and retention in skeletal muscle, increasing muscle mass and strength, increasing exercise capacity and for aiding recovery following exercise | |
| KR20080105470A (en) | Food composition containing ginseng fruit extract for preventing and improving obesity | |
| FR2981544A1 (en) | DIETETIC PRODUCT FOR PREVENTING CARDIOMETABOLIC RISK | |
| Bae et al. | Beneficial effects of taurine on metabolic parameters in animals and humans | |
| Cerretani et al. | Looking for organ damages due to anabolic-androgenic steroids (AAS): is oxidative stress the culprit? | |
| WO2008025116A1 (en) | Composition and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle | |
| Kim et al. | Codonopsis lanceolata and its active component Tangshenoside I ameliorate skeletal muscle atrophy via regulating the PI3K/Akt and SIRT1/PGC-1α pathways | |
| CA2558110A1 (en) | Composition and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle | |
| Ruan et al. | Nanomedicines based on trace elements for intervention of diabetes mellitus | |
| US20080058254A1 (en) | Composition and method for enhancing or promoting the activity of insulin, enhancing skeletal muscle growth, reducing skeletal muscle loss, and increasing the energy supply to skeletal muscle | |
| AU2012261503B2 (en) | A method and composition for nutritionally improving glucose control and insulin action | |
| Anwar et al. | Antidiabetic Activities of Fenugreek (Trigonella Foenum-Graecum) Seeds | |
| Park et al. | Anti-diabetic effect of Cyclo-His-Pro (CHP)-enriched yeast hydrolysate in streptozotocin-induced diabetic mice | |
| Belcaro et al. | Daily consumption of reliv glucaffect™ for 8 weeks significantly lowered blood glucose and body weight in 50 subjects | |
| Biolo | Can we increase protein synthesis by anabolic factors? | |
| Matada et al. | A study on plant based dietary patterns and cancer risk |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 06790609 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| NENP | Non-entry into the national phase |
Ref country code: RU |
|
| 32PN | Ep: public notification in the ep bulletin as address of the adressee cannot be established |
Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 06790609 Country of ref document: EP Kind code of ref document: A1 |