WO2013086330A1 - Nutritional compositions comprising curcumin and docosahexaenoic acid for improving cognition - Google Patents
Nutritional compositions comprising curcumin and docosahexaenoic acid for improving cognition Download PDFInfo
- Publication number
- WO2013086330A1 WO2013086330A1 PCT/US2012/068462 US2012068462W WO2013086330A1 WO 2013086330 A1 WO2013086330 A1 WO 2013086330A1 US 2012068462 W US2012068462 W US 2012068462W WO 2013086330 A1 WO2013086330 A1 WO 2013086330A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- curcumin
- individual
- composition
- docosahexaenoic acid
- nutritional
- Prior art date
Links
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 title claims abstract description 285
- 235000012754 curcumin Nutrition 0.000 title claims abstract description 144
- 239000004148 curcumin Substances 0.000 title claims abstract description 142
- 229940109262 curcumin Drugs 0.000 title claims abstract description 142
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 title claims abstract description 142
- MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 title claims abstract description 138
- 239000000203 mixture Substances 0.000 title claims abstract description 102
- 235000016709 nutrition Nutrition 0.000 title claims abstract description 95
- 235000020669 docosahexaenoic acid Nutrition 0.000 title claims abstract description 71
- 229940090949 docosahexaenoic acid Drugs 0.000 title claims abstract description 69
- 230000019771 cognition Effects 0.000 title description 4
- 230000015654 memory Effects 0.000 claims abstract description 36
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 19
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 18
- 230000003931 cognitive performance Effects 0.000 claims abstract description 14
- 230000007000 age related cognitive decline Effects 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 55
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 47
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 45
- 230000000971 hippocampal effect Effects 0.000 claims description 19
- 230000027928 long-term synaptic potentiation Effects 0.000 claims description 17
- 150000001720 carbohydrates Chemical class 0.000 claims description 14
- 235000014633 carbohydrates Nutrition 0.000 claims description 14
- 235000018102 proteins Nutrition 0.000 claims description 14
- 102000004169 proteins and genes Human genes 0.000 claims description 14
- 108090000623 proteins and genes Proteins 0.000 claims description 14
- 230000001419 dependent effect Effects 0.000 claims description 10
- 150000002632 lipids Chemical class 0.000 claims description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 235000021073 macronutrients Nutrition 0.000 claims description 8
- 230000007595 memory recall Effects 0.000 claims description 7
- 206010012289 Dementia Diseases 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- 230000003050 macronutrient Effects 0.000 claims description 2
- 208000010877 cognitive disease Diseases 0.000 abstract description 23
- 208000028698 Cognitive impairment Diseases 0.000 abstract description 14
- 230000005978 brain dysfunction Effects 0.000 abstract description 14
- 230000014759 maintenance of location Effects 0.000 abstract description 10
- 230000006999 cognitive decline Effects 0.000 abstract description 8
- 239000004615 ingredient Substances 0.000 description 26
- 239000000047 product Substances 0.000 description 24
- 239000007788 liquid Substances 0.000 description 18
- 239000003921 oil Substances 0.000 description 17
- 230000001404 mediated effect Effects 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- 239000000839 emulsion Substances 0.000 description 13
- 230000003492 excitotoxic effect Effects 0.000 description 13
- 231100000063 excitotoxicity Toxicity 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 11
- 210000004556 brain Anatomy 0.000 description 11
- 230000002708 enhancing effect Effects 0.000 description 11
- 230000016273 neuron death Effects 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 230000003956 synaptic plasticity Effects 0.000 description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
- 230000001537 neural effect Effects 0.000 description 8
- 230000004112 neuroprotection Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 235000010469 Glycine max Nutrition 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 239000000835 fiber Substances 0.000 description 7
- 230000000638 stimulation Effects 0.000 description 7
- 229940088594 vitamin Drugs 0.000 description 7
- 229930003231 vitamin Natural products 0.000 description 7
- 235000013343 vitamin Nutrition 0.000 description 7
- 239000011782 vitamin Substances 0.000 description 7
- 102000003678 AMPA Receptors Human genes 0.000 description 6
- 108090000078 AMPA Receptors Proteins 0.000 description 6
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 6
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 210000004295 hippocampal neuron Anatomy 0.000 description 6
- 239000011777 magnesium Substances 0.000 description 6
- 230000035764 nutrition Effects 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000011550 stock solution Substances 0.000 description 6
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 230000001149 cognitive effect Effects 0.000 description 5
- 230000003920 cognitive function Effects 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 229930195712 glutamate Natural products 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 235000010755 mineral Nutrition 0.000 description 5
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- VYGQUTWHTHXGQB-FFHKNEKCSA-N Retinol Palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-FFHKNEKCSA-N 0.000 description 4
- 240000008042 Zea mays Species 0.000 description 4
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 4
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000001896 anti-amyloidogenic effect Effects 0.000 description 4
- 230000009460 calcium influx Effects 0.000 description 4
- 235000005822 corn Nutrition 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 235000013336 milk Nutrition 0.000 description 4
- 239000008267 milk Substances 0.000 description 4
- 210000004080 milk Anatomy 0.000 description 4
- 230000009456 molecular mechanism Effects 0.000 description 4
- 230000036542 oxidative stress Effects 0.000 description 4
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- UEPVWRDHSPMIAZ-IZTHOABVSA-N (1e,4z,6e)-5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)hepta-1,4,6-trien-3-one Chemical compound C1=C(O)C(OC)=CC(\C=C\C(\O)=C\C(=O)\C=C\C=2C=CC(O)=CC=2)=C1 UEPVWRDHSPMIAZ-IZTHOABVSA-N 0.000 description 3
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- HJTVQHVGMGKONQ-LUZURFALSA-N Curcumin II Natural products C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=CC(O)=CC=2)=C1 HJTVQHVGMGKONQ-LUZURFALSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 240000007594 Oryza sativa Species 0.000 description 3
- 235000007164 Oryza sativa Nutrition 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 206010043376 Tetanus Diseases 0.000 description 3
- 102000040945 Transcription factor Human genes 0.000 description 3
- 108091023040 Transcription factor Proteins 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- JYTVKRNTTALBBZ-UHFFFAOYSA-N bis demethoxycurcumin Natural products C1=CC(O)=CC=C1C=CC(=O)CC(=O)C=CC1=CC=CC(O)=C1 JYTVKRNTTALBBZ-UHFFFAOYSA-N 0.000 description 3
- PREBVFJICNPEKM-YDWXAUTNSA-N bisdemethoxycurcumin Chemical compound C1=CC(O)=CC=C1\C=C\C(=O)CC(=O)\C=C\C1=CC=C(O)C=C1 PREBVFJICNPEKM-YDWXAUTNSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 235000010418 carrageenan Nutrition 0.000 description 3
- 239000000679 carrageenan Substances 0.000 description 3
- 229920001525 carrageenan Polymers 0.000 description 3
- 229940113118 carrageenan Drugs 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- NMRUIRRIQNAQEB-UHFFFAOYSA-N demethoxycurcumin Natural products OC(=CC(C=CC1=CC(=C(C=C1)O)OC)=O)C=CC1=CC=C(C=C1)O NMRUIRRIQNAQEB-UHFFFAOYSA-N 0.000 description 3
- YXAKCQIIROBKOP-UHFFFAOYSA-N di-p-hydroxycinnamoylmethane Natural products C=1C=C(O)C=CC=1C=CC(=O)C=C(O)C=CC1=CC=C(O)C=C1 YXAKCQIIROBKOP-UHFFFAOYSA-N 0.000 description 3
- 230000000378 dietary effect Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000001125 extrusion Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 210000001320 hippocampus Anatomy 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 230000000324 neuroprotective effect Effects 0.000 description 3
- UEPVWRDHSPMIAZ-UHFFFAOYSA-N p-hydroxycinnamoyl feruloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(O)=CC(=O)C=CC=2C=CC(O)=CC=2)=C1 UEPVWRDHSPMIAZ-UHFFFAOYSA-N 0.000 description 3
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 3
- 230000001242 postsynaptic effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 3
- 239000003642 reactive oxygen metabolite Substances 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 235000009566 rice Nutrition 0.000 description 3
- 239000003813 safflower oil Substances 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- -1 sucromalt Substances 0.000 description 3
- 150000003722 vitamin derivatives Chemical class 0.000 description 3
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- DVSZKTAMJJTWFG-SKCDLICFSA-N (2e,4e,6e,8e,10e,12e)-docosa-2,4,6,8,10,12-hexaenoic acid Chemical compound CCCCCCCCC\C=C\C=C\C=C\C=C\C=C\C=C\C(O)=O DVSZKTAMJJTWFG-SKCDLICFSA-N 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N 2,3,4,5-tetrahydroxypentanal Chemical compound OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- UQNAFPHGVPVTAL-UHFFFAOYSA-N 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+]([O-])=O)C1=C2C=CC=C1S(=O)(=O)N UQNAFPHGVPVTAL-UHFFFAOYSA-N 0.000 description 2
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 2
- GZJLLYHBALOKEX-UHFFFAOYSA-N 6-Ketone, O18-Me-Ussuriedine Natural products CC=CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O GZJLLYHBALOKEX-UHFFFAOYSA-N 0.000 description 2
- 235000007319 Avena orientalis Nutrition 0.000 description 2
- 235000007558 Avena sp Nutrition 0.000 description 2
- 102000019025 Calcium-Calmodulin-Dependent Protein Kinases Human genes 0.000 description 2
- 108010026870 Calcium-Calmodulin-Dependent Protein Kinases Proteins 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- 235000019743 Choline chloride Nutrition 0.000 description 2
- 244000163122 Curcuma domestica Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 229920002148 Gellan gum Polymers 0.000 description 2
- 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 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 240000005979 Hordeum vulgare Species 0.000 description 2
- 235000007340 Hordeum vulgare Nutrition 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 239000005913 Maltodextrin Substances 0.000 description 2
- 229920002774 Maltodextrin Polymers 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 235000010582 Pisum sativum Nutrition 0.000 description 2
- VYGQUTWHTHXGQB-UHFFFAOYSA-N Retinol hexadecanoate Natural products CCCCCCCCCCCCCCCC(=O)OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-UHFFFAOYSA-N 0.000 description 2
- 235000019485 Safflower oil Nutrition 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 235000019486 Sunflower oil Nutrition 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 description 2
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000013734 beta-carotene Nutrition 0.000 description 2
- 239000011648 beta-carotene Substances 0.000 description 2
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 2
- 229960002747 betacarotene Drugs 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 2
- 229960003178 choline chloride Drugs 0.000 description 2
- 239000003240 coconut oil Substances 0.000 description 2
- 235000019864 coconut oil Nutrition 0.000 description 2
- 235000003373 curcuma longa Nutrition 0.000 description 2
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000013325 dietary fiber Nutrition 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- KAUVQQXNCKESLC-UHFFFAOYSA-N docosahexaenoic acid (DHA) Natural products COC(=O)C(C)NOCC1=CC=CC=C1 KAUVQQXNCKESLC-UHFFFAOYSA-N 0.000 description 2
- 235000020673 eicosapentaenoic acid Nutrition 0.000 description 2
- 229960005135 eicosapentaenoic acid Drugs 0.000 description 2
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- FTSSQIKWUOOEGC-RULYVFMPSA-N fructooligosaccharide Chemical compound OC[C@H]1O[C@@](CO)(OC[C@@]2(OC[C@@]3(OC[C@@]4(OC[C@@]5(OC[C@@]6(OC[C@@]7(OC[C@@]8(OC[C@@]9(OC[C@@]%10(OC[C@@]%11(O[C@H]%12O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%12O)O[C@H](CO)[C@@H](O)[C@@H]%11O)O[C@H](CO)[C@@H](O)[C@@H]%10O)O[C@H](CO)[C@@H](O)[C@@H]9O)O[C@H](CO)[C@@H](O)[C@@H]8O)O[C@H](CO)[C@@H](O)[C@@H]7O)O[C@H](CO)[C@@H](O)[C@@H]6O)O[C@H](CO)[C@@H](O)[C@@H]5O)O[C@H](CO)[C@@H](O)[C@@H]4O)O[C@H](CO)[C@@H](O)[C@@H]3O)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@@H](O)[C@@H]1O FTSSQIKWUOOEGC-RULYVFMPSA-N 0.000 description 2
- 229940107187 fructooligosaccharide Drugs 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- 235000010492 gellan gum Nutrition 0.000 description 2
- 239000000216 gellan gum Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- WTIZXHYCCKUVHY-UHFFFAOYSA-N hept-1-ene-3,5-dione Chemical compound CCC(=O)CC(=O)C=C WTIZXHYCCKUVHY-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 229940035034 maltodextrin Drugs 0.000 description 2
- 230000028161 membrane depolarization Effects 0.000 description 2
- 230000006386 memory function Effects 0.000 description 2
- 230000003961 neuronal insult Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- MXXWOMGUGJBKIW-YPCIICBESA-N piperine Chemical compound C=1C=C2OCOC2=CC=1/C=C/C=C/C(=O)N1CCCCC1 MXXWOMGUGJBKIW-YPCIICBESA-N 0.000 description 2
- 229940075559 piperine Drugs 0.000 description 2
- WVWHRXVVAYXKDE-UHFFFAOYSA-N piperine Natural products O=C(C=CC=Cc1ccc2OCOc2c1)C3CCCCN3 WVWHRXVVAYXKDE-UHFFFAOYSA-N 0.000 description 2
- 235000019100 piperine Nutrition 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 210000001525 retina Anatomy 0.000 description 2
- 229940108325 retinyl palmitate Drugs 0.000 description 2
- 235000019172 retinyl palmitate Nutrition 0.000 description 2
- 239000011769 retinyl palmitate Substances 0.000 description 2
- 235000005713 safflower oil Nutrition 0.000 description 2
- 230000006403 short-term memory Effects 0.000 description 2
- 229910001415 sodium ion Inorganic materials 0.000 description 2
- 239000002600 sunflower oil Substances 0.000 description 2
- 230000000153 supplemental effect Effects 0.000 description 2
- 210000000225 synapse Anatomy 0.000 description 2
- 230000005062 synaptic transmission Effects 0.000 description 2
- 230000024587 synaptic transmission, glutamatergic Effects 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- KBPHJBAIARWVSC-XQIHNALSSA-N trans-lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C KBPHJBAIARWVSC-XQIHNALSSA-N 0.000 description 2
- 238000012384 transportation and delivery Methods 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- 229940011671 vitamin b6 Drugs 0.000 description 2
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 2
- VOROEQBFPPIACJ-SCSAIBSYSA-N (2r)-2-amino-5-phosphonopentanoic acid Chemical compound OC(=O)[C@H](N)CCCP(O)(O)=O VOROEQBFPPIACJ-SCSAIBSYSA-N 0.000 description 1
- JKQXZKUSFCKOGQ-JLGXGRJMSA-N (3R,3'R)-beta,beta-carotene-3,3'-diol Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-JLGXGRJMSA-N 0.000 description 1
- YUFFSWGQGVEMMI-JLNKQSITSA-N (7Z,10Z,13Z,16Z,19Z)-docosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCCCC(O)=O YUFFSWGQGVEMMI-JLNKQSITSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- PWKSKIMOESPYIA-UHFFFAOYSA-N 2-acetamido-3-sulfanylpropanoic acid Chemical compound CC(=O)NC(CS)C(O)=O PWKSKIMOESPYIA-UHFFFAOYSA-N 0.000 description 1
- PVXPPJIGRGXGCY-TZLCEDOOSA-N 6-O-alpha-D-glucopyranosyl-D-fructofuranose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)C(O)(CO)O1 PVXPPJIGRGXGCY-TZLCEDOOSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose 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](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 1
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000219310 Beta vulgaris subsp. vulgaris Species 0.000 description 1
- 241000237519 Bivalvia Species 0.000 description 1
- 240000007124 Brassica oleracea Species 0.000 description 1
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000004657 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Human genes 0.000 description 1
- 108010003721 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Proteins 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 241000252203 Clupea harengus Species 0.000 description 1
- 241001454694 Clupeiformes Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 235000003392 Curcuma domestica Nutrition 0.000 description 1
- 229930153442 Curcuminoid Natural products 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- 235000021294 Docosapentaenoic acid Nutrition 0.000 description 1
- 239000004097 EU approved flavor enhancer Substances 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 241000276438 Gadus morhua Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 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
- 241000282412 Homo Species 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
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 229930195722 L-methionine Natural products 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 description 1
- JEVVKJMRZMXFBT-XWDZUXABSA-N Lycophyll Natural products OC/C(=C/CC/C(=C\C=C\C(=C/C=C/C(=C\C=C\C=C(/C=C/C=C(\C=C\C=C(/CC/C=C(/CO)\C)\C)/C)\C)/C)\C)/C)/C JEVVKJMRZMXFBT-XWDZUXABSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 102000004108 Neurotransmitter Receptors Human genes 0.000 description 1
- 108090000590 Neurotransmitter Receptors Proteins 0.000 description 1
- 235000019482 Palm oil Nutrition 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 244000203593 Piper nigrum Species 0.000 description 1
- 235000008184 Piper nigrum Nutrition 0.000 description 1
- 244000134552 Plantago ovata Species 0.000 description 1
- 235000003421 Plantago ovata Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000009223 Psyllium Substances 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 241000277331 Salmonidae Species 0.000 description 1
- 241001125046 Sardina pilchardus Species 0.000 description 1
- 241000269821 Scombridae Species 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 235000021536 Sugar beet Nutrition 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003537 Vitamin B3 Natural products 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- 235000019742 Vitamins premix Nutrition 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- JKQXZKUSFCKOGQ-LQFQNGICSA-N Z-zeaxanthin Natural products C([C@H](O)CC=1C)C(C)(C)C=1C=CC(C)=CC=CC(C)=CC=CC=C(C)C=CC=C(C)C=CC1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-LQFQNGICSA-N 0.000 description 1
- QOPRSMDTRDMBNK-RNUUUQFGSA-N Zeaxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCC(O)C1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C QOPRSMDTRDMBNK-RNUUUQFGSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010358 acesulfame potassium Nutrition 0.000 description 1
- 229960004998 acesulfame potassium Drugs 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 210000003626 afferent pathway Anatomy 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- JKQXZKUSFCKOGQ-LOFNIBRQSA-N all-trans-Zeaxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C JKQXZKUSFCKOGQ-LOFNIBRQSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000001949 anaesthesia Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 235000019513 anchovy Nutrition 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 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 1
- 230000013629 beta-amyloid clearance Effects 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 235000013614 black pepper Nutrition 0.000 description 1
- 239000010473 blackcurrant seed oil Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 235000021324 borage oil Nutrition 0.000 description 1
- 230000036995 brain health Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000019519 canola oil Nutrition 0.000 description 1
- 239000000828 canola oil Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 239000009194 citrus pectin Substances 0.000 description 1
- 229940040387 citrus pectin Drugs 0.000 description 1
- 235000020639 clam Nutrition 0.000 description 1
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 235000000639 cyanocobalamin Nutrition 0.000 description 1
- 239000011666 cyanocobalamin Substances 0.000 description 1
- 229960002104 cyanocobalamin Drugs 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000021196 dietary intervention Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000008524 evening primrose extract Nutrition 0.000 description 1
- 239000010475 evening primrose oil Substances 0.000 description 1
- 229940089020 evening primrose oil Drugs 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 230000036749 excitatory postsynaptic potential Effects 0.000 description 1
- 231100000318 excitotoxic Toxicity 0.000 description 1
- 235000019688 fish Nutrition 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000000848 glutamatergic effect Effects 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- ZPGYUDWZVQOWNY-UHFFFAOYSA-N hept-4-en-3-one Chemical group CCC=CC(=O)CC ZPGYUDWZVQOWNY-UHFFFAOYSA-N 0.000 description 1
- 235000019514 herring Nutrition 0.000 description 1
- 235000019534 high fructose corn syrup Nutrition 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 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 1
- 229960000367 inositol Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000944 linseed oil Substances 0.000 description 1
- 235000021388 linseed oil Nutrition 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000012680 lutein Nutrition 0.000 description 1
- 239000001656 lutein Substances 0.000 description 1
- 229960005375 lutein Drugs 0.000 description 1
- KBPHJBAIARWVSC-RGZFRNHPSA-N lutein Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\[C@H]1C(C)=C[C@H](O)CC1(C)C KBPHJBAIARWVSC-RGZFRNHPSA-N 0.000 description 1
- ORAKUVXRZWMARG-WZLJTJAWSA-N lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C ORAKUVXRZWMARG-WZLJTJAWSA-N 0.000 description 1
- 235000012661 lycopene Nutrition 0.000 description 1
- 239000001751 lycopene Substances 0.000 description 1
- 229960004999 lycopene Drugs 0.000 description 1
- OAIJSZIZWZSQBC-GYZMGTAESA-N lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C=C(/C)CCC=C(C)C OAIJSZIZWZSQBC-GYZMGTAESA-N 0.000 description 1
- 235000020640 mackerel Nutrition 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940057917 medium chain triglycerides Drugs 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 230000008555 neuronal activation Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000003957 neurotransmitter release Effects 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000013588 oral product Substances 0.000 description 1
- 229940023486 oral product Drugs 0.000 description 1
- 239000003346 palm kernel oil Substances 0.000 description 1
- 235000019865 palm kernel oil Nutrition 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 235000015277 pork Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 229940070687 psyllium Drugs 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 235000008160 pyridoxine Nutrition 0.000 description 1
- 239000011677 pyridoxine Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000019512 sardine Nutrition 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
- 239000011669 selenium Substances 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- IFGCUJZIWBUILZ-UHFFFAOYSA-N sodium 2-[[2-[[hydroxy-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyphosphoryl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid Chemical compound [Na+].C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O IFGCUJZIWBUILZ-UHFFFAOYSA-N 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- ZCIHMQAPACOQHT-ZGMPDRQDSA-N trans-isorenieratene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/c1c(C)ccc(C)c1C)C=CC=C(/C)C=Cc2c(C)ccc(C)c2C ZCIHMQAPACOQHT-ZGMPDRQDSA-N 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
- 235000013976 turmeric Nutrition 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019160 vitamin B3 Nutrition 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 235000020985 whole grains Nutrition 0.000 description 1
- FJHBOVDFOQMZRV-XQIHNALSSA-N xanthophyll Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C=C(C)C(O)CC2(C)C FJHBOVDFOQMZRV-XQIHNALSSA-N 0.000 description 1
- 235000010930 zeaxanthin Nutrition 0.000 description 1
- 239000001775 zeaxanthin Substances 0.000 description 1
- 229940043269 zeaxanthin Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
-
- 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
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
-
- 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
- A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
-
- 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
- A61K31/12—Ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
-
- 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
- A23V2200/00—Function of food ingredients
-
- 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
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
-
- 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
- A23V2250/00—Food ingredients
- A23V2250/18—Lipids
- A23V2250/186—Fatty acids
- A23V2250/1868—Docosahexaenoic acid
-
- 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
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/21—Plant extracts
- A23V2250/2112—Curcumin, turmeric
Definitions
- the present disclosure relates to nutritional compositions comprising Curcumin and docosahexaenoic acid (DHA) and to the methods of administering the compositions for improving cognitive performance and/or memory, enhancing memory acquisition, memory retention and recall in an individual, as well as reducing brain dysfunction and cognitive decline.
- DHA docosahexaenoic acid
- Curcumin is utilized in combination with the DHA.
- Manufactured nutritional liquids and powders comprising a targeted selection of nutrition ingredients are well known and widely available, some of which may provide a sole source of nutrition while others may provide a supplemental source.
- These nutritionals include powders that can be reconstituted with water or other aqueous liquid, as well as ready to drink nutritional liquids such as milk or protein based emulsions or non-emulsified liquids. These nutritional liquids are especially useful when formulated with selected nutritional ingredients.
- Cognitive failure which includes dysfunction or loss of cognitive function (e.g., learning, thinking and memory), commonly occurs in association with central nervous system (CNS) disorders or conditions, including neurodegenerative diseases. Cognitive dysfunction may cause significant impairment of social and/or occupational functioning, which can interfere with the ability of an individual to perform activities of daily living and greatly impact the autonomy and quality of life of the individual.
- CNS central nervous system
- One embodiment is directed to a method for improving memory acquisition and memory retention and recall in an individual.
- the method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
- Another embodiment is directed to a method for improving cognitive performance in an individual.
- the method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
- Another embodiment is directed to a method for improving memory acquisition in an individual. The method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
- Another embodiment is directed to a method for improving memory retention and recall in an individual.
- the method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
- Another embodiment is directed to a method for enhancing N- Methyl-D-aspartate receptor (NMDAR) dependent hippocampal long-term
- the method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
- Another embodiment is directed to a method for enhancing the NMDAR and 2-amino-3-(5-methyl-3-oxo-l,2-oxazol-4-yl)propanoic acid receptor (AMPAR) mediated hippocampal synaptic plasticity, which may be another key mechanism underlying learning and memory.
- the method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
- Another embodiment is directed to a method for preventing the over- activation of NMDAR, which may result in neuronal death.
- the method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
- Another embodiment is directed to a method for enhancing neuronal membrane fluidity.
- the method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
- Another embodiment is directed to a nutritional composition for improving cognitive performance.
- the composition comprises an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
- Nutritional compositions including Curcumin, and in particular bioavailable Curcumin, and DHA in combination provide enhanced bioavailability of the individual components of Curcumin and DHA to an individual upon
- this combination of components is more efficacious in providing improved cognitive functioning and/or performance to an individual, as well as reducing cognitive impairment and/or brain dysfunction in an individual.
- Curcumin or bioavailable Curcumin and DHA produces an added benefit on cognitive functioning by producing an effect in enhancing NMDAR and AMPAR dependent hippocampal synaptic plasticity, which is a molecular mechanism involved in learning and memory.
- Curcumin or bioavailable Curcumin and DHA produces a sequential action by improving memory acquisition that is essential for the process of learning, and by improving memory retention and recall that is necessary for the retrieval of learned processes.
- Curcumin or bioavailable Curcumin and DHA may also provide benefits to an individual by its complementary mode of action on neuroprotection.
- Neuronal death due to the oxidative stress resulting from NMDAR over-activation i.e., NMDAR mediated excitotoxicity
- NMDAR mediated excitotoxicity is a major problem associated with cognitive impairment, brain dysfunction, and neurodegenerative diseases (e.g., Alzheimer's Disease).
- Curcumin, and particularly bioavailable Curcumin offers significant neuroprotection by preventing NMDAR mediated excitotoxicity and resulting neuronal death.
- DHA offers benefits such as the maintenance of neuronal membrane fluidity, which is essential for synaptic receptor function, and neurotransmitter release, which is essential for the cognitive performance of an individual. While DHA may be taken up by the brain from the diet to provide the above benefits, DHA is highly susceptible to oxidation and may therefore induce oxidative stress in neuronal membranes that may, in turn, negatively affect the neuronal health and function.
- Curcumin and in particular bioavailable Curcumin, which possesses strong antioxidant properties, can prevent the oxidation of DHA as well as provide neuroprotection and prevention of neuronal death due to oxidative stress, which is induced by increased calcium influx, thereby allowing the subsequent release of proteolytic enzymes, transcription factors, and reactive oxygen species. Therefore, a Curcumin or bioavailable Curcumin and DHA combination will have a
- Curcumin, and in particular bioavailable Curcumin, and DHA act in combination to further provide anti-inflammatory and anti-amyloidogenic properties to an individual.
- Neuronal inflammation and amyloid ⁇ protein deposition are associated with cognitive impairment and/or brain dysfunction that results from age- related cognitive decline and/or cognitive decline associated with neurodegenerative diseases.
- These anti-inflammatory and anti-amyloidogenic properties of Curcumin or bioavailable Curcumin and DHA therefore, provide added benefits when used in combination, thereby reducing cognitive impairment and/or brain dysfunction.
- the nutritional compositions and methods of the present disclosure offer an alternative therapeutic or nutritional intervention option that may contribute to the improvement of cognitive performance, as well as to the reduction of cognitive impairment and brain dysfunction, in individuals, and particularly in adults, older adults, and the elderly.
- FIG. 1A is a chart depicting the effect of the combination of
- FIGS. IB- ID are graphs depicting the effect of the combination of Curcumin and DHA on NMDAR dependent hippocampal LTP as analyzed in
- FIG. 2A is a chart depicting the neuroprotective effect of Curcumin on primary hippocampal neurons from NMDAR mediated excitotoxicity.
- FIG. 2B is a chart depicting the neuroprotective effect of DHA on primary hippocampal neurons from NMDAR mediated excitotoxicity.
- compositions and methods herein are directed to nutritional compositions comprising Curcumin, and in particular bioavailable Curcumin, and DHA that can improve general cognitive performance in an individual, including memory acquisition, memory retention and recall.
- age refers to an individual of at least 45 years of age, including at least 50 years of age, including at least 55 years of age, including at least 60 years of age, including at least 65 years of age, including at least 70 years of age, including at least 75 years of age, including at least 80 years of age, further including from about 55 years of age to about 80 years of age.
- Curcumin refers to Curcumin and derivatives and analogs thereof.
- bioavailable refers to the ability of a compound to enter into and remain in the bloodstream of an individual such that the substance can be absorbed into cells in the body. As the degree of bioavailability of a compound increases, the compound becomes more likely to enter into and remain in the bloodstream where it can be absorbed and used by the body. As the degree of bioavailability of a compound decreases, the compound becomes more likely to go directly into the gastrointestinal area and be expelled from the body before entering the bloodstream.
- the nutritional composition may further comprise vitamins, minerals, and other ingredients and represent a sole, primary, or supplemental source of nutrition.
- fat lipid
- oil oil
- synthetic lipid materials so long as such synthetic materials are suitable for oral administration to humans.
- susceptible means having little resistance to a certain condition or disease, including being genetically predisposed, having a family history of, and/or having symptoms of the condition or disease.
- cognitive performance refers to the learning, thinking, and memory functions (i.e., memory acquisition, memory retention and recall) of the brain. Accordingly, the term “improving cognitive performance” as used herein, unless otherwise specified, refers to improving the learning, thinking, and/or memory (memory acquisition, memory retention, and memory recall) functions of an individual.
- age-related cognitive decline refers to a gradual decline in learning, thinking, and/or memory functions that are normal consequences of aging.
- neurodegenerative disease refers to the progressive loss of structure or function of neurons, including the death of neurons and includes diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, dementia, amyotrophic lateral sclerosis, stroke, and schizophrenia.
- the various embodiments of the nutritional compositions of the present disclosure may also be substantially free of any optional or selected essential ingredient or feature described herein, provided that the remaining composition or powder still contains all of the required ingredients or features as described herein.
- the term "substantially free” means that the selected composition contains less than a functional amount of the optional ingredient, typically less than about 1%, including less than about 0.5%, including less than about 0.1%, and also including zero percent, by weight of such optional or selected essential ingredient.
- the nutritional compositions may comprise, consist of, or consist essentially of the essential elements of the products as described herein, as well as any additional or optional element described herein or otherwise useful in nutritional product applications.
- the nutritional compositions of the present disclosure may be formulated and administered in any known or otherwise suitable oral product form. Any solid, liquid, or powder form, including combinations or variations thereof, are suitable for use herein, provided that such forms allow for safe and effective oral delivery to the individual of the essential ingredients as also defined herein.
- the nutritional compositions are most suitably formed as aqueous emulsions, including water-in-oil emulsions, oil-in-water emulsions, or complex (e.g., oil-in- water-in-oil emulsions) or other emulsion systems.
- the nutritional emulsion embodiments are most typically oil-in- water emulsions comprising an internal or discontinuous oil phase that comprises the Curcumin or bioavailable Curcumin and DHA as defined herein.
- Curcumin is the principal Curcuminoid of turmeric. Conventionally, Curcumin has suffered lower bioavailability when taken orally, and thus when formulated at higher concentrations to counter its inherent poor bioavailability to achieve the desired systemic delivery, the products often take on an intense undesirable yellow color. In some embodiments, the present nutritional compositions use "bioavailable
- Curcumin which has an improved bioavailability as compared to conventionally used Curcumin.
- the bioavailable Curcumin can be utilized in lower concentrations in the nutritional compositions and methods of the present disclosure, while still maintaining its anti-inflammatory, antioxidative, and anti-amyloidogenic activity.
- bioavailable Curcumin refers to Curcumin and derivatives and analogs thereof, including natural and synthetic derivatives of Curcumin, as well as any combination of one or more of Curcumin and a derivative and/or analog.
- bioavailable Curcumin should be understood to encompass compounds having a 1,7-bis (4-hydroxyphenyl)-l,6-heptadiene-3,5- dione or l,7-bis(4-hydroxyphenyl) hept-4-en-3-one skeleton wherein the phenyl groups independently may bear one or more alkoxy residues, especially one methoxy residue in the 3-position.
- additional Curcuminoids such as demethoxyCurcumin and bisdemethoxyCurcumin, may also be present in the nutritional compositions. When present, demethoxyCurcumin and
- bisdemethoxyCurcumin may be present as part of a complex with Curcumin.
- the "bioavailable Curcumin” used in the nutritional compositions of the present disclosure shows improved oral bioavailability as compared to Curcumins that are not substantially “bioavailable.”
- the oral bioavailability can be determined in experiments involving oral administration of the bioavailable Curcumin composition of the present disclosure (and/or a corresponding amount of non-bioavailable
- Curcumin to a subject and measuring the level of the Curcumin in a biological sample obtained from the subject over time
- the biological sample may be derived from a body fluid, for example serum, plasma, whole blood, or cerebrospinal fluid, and/or a tissue, e.g. from brain, liver, kidney, or heart.
- AUC area under the curve
- a higher AUC relative to the AUC obtained by administration of non- bioavailable Curcumin indicates an improved bioavailability.
- the absolute bioavailability may be calculated from the resulting AUC data as a percentage based on the corresponding AUC data obtained from intravenous administration of
- the bioavailable Curcumin amount in the blood determined as AUC0-6H after a single oral administration of a dose of the bioavailable Curcumin-containing nutritional composition of the present disclosure corresponding to 20 mg of total Curcumin to a human subject or an animal subject, preferably a rat, is significantly higher than after oral administration of the same amount of non-bioavailable Curcumin in the composition, preferably at least 2 times, at least 3 times, at least 4 times, at least 6 times, at least 8 times, at least 10 times, or at least 15 times, and, for example, up to 30 times higher.
- Bioavailable Curcumin can be prepared in a number of ways including, for example, using Meltrex® or similar melt-extrusion technology to prepare extruded solids and improve the bioavailability of the Curcumin as compared to Curcumin not produced by melt extrusion.
- Meltrex® or similar melt-extrusion technology methods are known in the art and can be applied to produce bioavailable Curcumin by one skilled in the art based on the disclosure herein.
- Curcumin or bioavailable Curcumin can be co-supplemented with piperine (generally extracted from black pepper) to increase the bioavailability and hence the absorbability of Curcumin.
- the piperine is co-supplemented in an amount of about 20 mg to increase the
- the Curcumin or bioavailable Curcumin may be solubilized in an oil having an HLB of from about 0.7 to about 14 (polar oils) such that the resulting oil mixture provides increased bioavailability of Curcumin.
- polar oils a medium chain triglyceride oil (MCT oil).
- the bioavailable Curcumin is a mixture of Curcuminoids (i.e., Curcumin, demethoxyCurcumin and bisdemethoxyCurcumin) obtained from the rhizomes of Curcuma Longa.
- Curcumin is obtained using Meltrex® technology (Abbott Nutrition, Columbus, Ohio).
- the bioavailable Curcumin is Meriva Bioavailable Curcumin, commercially available from Idena SPA (Milan, Italy).
- the Curcumin or bioavailable Curcumin concentration in the nutritional compositions may range from at least about 0.001%, including from about 0.002% to about 3.36%, including from about 0.005%) to about 1.87%, also including from about 0.03%> to about 0.935%), also including from about 0.1 % to about 0.467%), and also including from about 0.234% to about 0.3%, by weight of the nutritional composition.
- Exemplary embodiments of the present disclosure include nutritional compositions having Curcumin or bioavailable Curcumin in amounts ranging from about 0.002% to about 0.25%, from 0.002% to about 0.234%, from about 0.005% to about 0.467%, from about 0.03% to about 0.935%, from about 0.1% to about 1.9%, from about 0.1% to about 1.87%, and from about 0.3% to about 3.36%, by weight of the nutritional composition.
- the nutritional compositions of the present disclosure desirably include sufficient Curcumin or bioavailable Curcumin to provide an individual with at least about 1 milligram, including at least about 3 milligrams, including from about 10 milligrams to about 10,000 milligrams, including from about 100 milligrams to about 4000 milligrams, including from about 400 milligrams to about 2000 milligrams, including from about 1200 milligrams to about 1800 milligrams, per day of Curcumin or bioavailable Curcumin.
- the total daily amount of Curcumin or bioavailable Curcumin may be administered to an individual in a single undivided dose, or may be split into one, two, three, four or more doses per day.
- DHA Docosahexaenoic acid
- the nutritional compositions of the present disclosure include DHA.
- DHA cis-docosa-4,7,10,13,16,19-hexa-enoic acid
- PUFA omega-3 polyunsaturated fatty acid
- DHA is essential for the proper functioning of adult brains and the central nervous system, deficiencies of which have been associated with cognitive decline.
- DHA is either directly obtained from the diet or derived from eicosapentaenoic acid (EPA) via docosapentaenoic acid (DP A) as an intermediate.
- EPA eicosapentaenoic acid
- DP A docosapentaenoic acid
- Common dietary sources of DHA include marine, plant and animal sources such as mackerel, chicken, herring, eel, pig, tuna, clams, veal, beef, pork, turkey, cod, anchovy, and trout and/or plant sources such as soybeans, cabbage, whole-grain barley, rice, and carrots.
- the DHA concentration in the nutritional compositions may range from at least about 0.001%, including from about 0.001% to about 4.6%>, including from about 0.01%> to about 2.8%, including from about 0.02% to about 1.4%, also including from about 0.02% to about 0.7%, also including from about 0.02% to about 0.4%), and also including from about 0.025%) to about 0.34%, by weight of the nutritional composition.
- the nutritional compositions of the present disclosure desirably include sufficient DHA to provide an individual with from about 100 milligrams to about 2000 milligrams, including from about 200 milligrams to about 2000 milligrams, including from about 200 milligrams to about 1000 milligrams, including from about 500 milligrams to about 1500 milligrams, including from about 1000 milligrams to about 1400 milligrams, per day of DHA.
- the total daily amount of DHA may be administered to an individual in a single undivided dose, or may be split into one, two, three, four or more doses per day.
- the nutritional compositions of the present disclosure may further comprise one or more optional macronutrients in addition to the Curcumin or bioavailable Curcumin and DHA described herein.
- the optional macronutrients include proteins, lipids, carbohydrates, and combinations thereof.
- the nutritional compositions are desirably formulated as dietary products containing all three macronutrients.
- Micronutrients suitable for use herein include any protein, lipid, or carbohydrate or source thereof that is known for or otherwise suitable for use in an oral nutritional composition, provided that the optional macronutrient is safe and effective for oral administration and is otherwise compatible with the other ingredients in the nutritional composition.
- the concentration or amount of optional lipid, carbohydrate, and protein in the nutritional composition can vary considerably depending upon the particular product form (e.g., bars or other solid dosage forms, milk or soy-based liquids or other clear beverages, reconstitutable powders, etc.) and the various other formulations and targeted dietary needs.
- These optional macronutrients are most typically formulated within any of the embodied ranges described in the following tables.
- compositions may be simple, complex, or variations or combinations thereof, all of which are optionally in addition to the Curcumin or bioavailable Curcumin as described herein.
- suitable carbohydrates include hydrolyzed or modified starch or cornstarch, maltodextrin, isomaltulose, sucromalt, glucose polymers, sucrose, corn syrup, corn syrup solids, rice-derived carbohydrate, glucose, fructose, lactose, high fructose corn syrup, honey, sugar alcohols (e.g., maltitol, erythritol, sorbitol), and combinations thereof.
- Optional carbohydrates suitable for use herein also include soluble dietary fiber, non-limiting examples of which include gum Arabic,
- fructooligosaccharide FOS
- Insoluble dietary fiber is also suitable as a carbohydrate source herein, non-limiting examples of which include oat hull fiber, pea hull fiber, soy hull fiber, soy cotyledon fiber, sugar beet fiber, cellulose, corn bran, and combinations thereof.
- Optional proteins suitable for use in the nutritional compositions include hydrolyzed, partially hydrolyzed or non-hydro lyzed proteins or protein sources, and can be derived from any known or otherwise suitable source such as milk (e.g., casein, whey), animal (e.g., meat, fish, egg albumen), cereal (e.g., rice, corn), vegetable (e.g., soy, pea, potato), or combinations thereof.
- milk e.g., casein, whey
- animal e.g., meat, fish, egg albumen
- cereal e.g., rice, corn
- vegetable e.g., soy, pea, potato
- the proteins for use herein can also include, or be entirely or partially replaced by, free amino acids known for use in nutritional products, non-limiting examples of which include L-tryptophan, L- glutamine, L-tyrosine, L-methionine, L-cysteine, taurine, L-arginine, L-carnitine, and combinations thereof.
- Optional lipids suitable for use in the nutritional compositions include coconut oil, fractionated coconut oil, soy oil, corn oil, olive oil, safflower oil, high oleic safflower oil, high GLA-safflower oil, MCT oil (medium chain triglycerides), sunflower oil, high oleic sunflower oil, palm and palm kernel oils, palm olein, canola oil, flaxseed oil, borage oil, cottonseed oils, evening primrose oil, blackcurrant seed oil, transgenic oil sources, fungal oils, marine oils (e.g., tuna, sardine) and so forth.
- coconut oil fractionated coconut oil, soy oil, corn oil, olive oil, safflower oil, high oleic safflower oil, high GLA-safflower oil, MCT oil (medium chain triglycerides), sunflower oil, high oleic sunflower oil, palm and palm kernel oils, palm olein, canola oil, flaxseed oil,
- the nutritional compositions may further comprise other optional ingredients that may modify the physical, nutritional, chemical, hedonic or processing characteristics of the products or serve as pharmaceutical or additional nutritional components when used in a targeted population.
- optional ingredients are known or otherwise suitable for use in other nutritional products and may also be used in the nutritional compositions described herein, provided that such optional ingredients are safe and effective for oral administration and are compatible with the essential and other ingredients in the composition.
- Non-limiting examples of such other optional ingredients include preservatives, anti-oxidants, buffers, pharmaceutical actives, sweeteners, colorants, flavors, flavor enhancers, thickening agents and stabilizers, emulsifying agents, lubricants, and combinations thereof.
- the nutritional compositions may further include one or more minerals, non-limiting examples of which include phosphorus, sodium, chloride, magnesium, manganese, iron, copper, zinc, iodine, calcium, potassium, chromium, molybdenum, selenium, and combinations thereof.
- minerals non-limiting examples of which include phosphorus, sodium, chloride, magnesium, manganese, iron, copper, zinc, iodine, calcium, potassium, chromium, molybdenum, selenium, and combinations thereof.
- the nutritional compositions may also include one or more vitamins, non-limiting examples of which include carotenoids (e.g., beta-carotene, zeaxanthin, lutein, lycopene), biotin, choline, inositol, folic acid, pantothenic acid, TP AN, choline, vitamin A, thiamine (vitamin Bl), riboflavin (vitamin B2) niacin (vitamin B3), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), ascorbic acid (vitamin C), vitamin D, vitamin E, vitamin K, and various salts, esters, or other derivatives thereof, and combinations thereof.
- carotenoids e.g., beta-carotene, zeaxanthin, lutein, lycopene
- biotin choline
- inositol folic acid
- pantothenic acid TP AN
- choline vitamin A
- the nutritional compositions may be prepared by any known or otherwise effective manufacturing technique for preparing the selected product form. Many such techniques are known for any given product form such as nutritional liquids and nutritional powders and can easily be applied by one of ordinary skill in the nutrition and formulation arts to the nutritional products described herein.
- Liquid, milk or soy-based nutritional liquids may be prepared by first forming an oil and fiber blend containing all formulation oils, any emulsifier, fiber and fat-soluble vitamins. Additional slurries (typically a
- carbohydrate and two protein slurries are prepared separately by mixing the carbohydrate and minerals together and the protein in water. The slurries are then mixed together with the oil blend. The resulting mixture is homogenized, heat processed, standardized with any water-soluble vitamins, flavored and the liquid terminally sterilized or aseptically filled or dried to produce a powder.
- compositions of the present disclosure may also be manufactured by other known or otherwise suitable techniques not specifically described herein without departing from the spirit and scope of the present disclosure.
- the present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive and that all changes and equivalents also come within the description of the present disclosure.
- the methods include the oral administration of the nutritional compositions that include Curcumin or bioavailable Curcumin in combination with DHA, to improve cognitive performance in any individual.
- the combination of bioavailable Curcumin and DHA may improve general cognition by producing a sequential action on memory acquisition, memory retention and memory recall that contributes to the cognitive functions of learning, thinking, and memory.
- the nutritional compositions including the combination of Curcumin or bioavailable Curcumin and DHA may have a complementary mode of action in maintaining neuronal membrane fluidity, allowing for proper hormone and neurotransmitter function. This may further improve cognitive performance.
- the nutritional compositions can be utilized to improve a cognitive impairment and/or brain dysfunction that may be associated with a neurodegenerative disease.
- the combination of Curcumin or bioavailable Curcumin and DHA shows anti-amyloidogenic properties and anti-inflammation properties, thereby reducing neuronal inflammation and clearance of amyloid ⁇ protein deposit that can lead to a cognitive impairment and/or brain dysfunction associated with neurodegenerative diseases or conditions such as Alzheimer's disease, Huntington's disease, Parkinson's disease, dementia, amyotrophic lateral sclerosis, stroke, and/or schizophrenia.
- cognitive function may be improved.
- the nutritional compositions of the present disclosure may improve a cognitive impairment and/or brain dysfunction associated with age-related cognitive decline or cognitive decline associated with a neurodegenerative disease by enhancing synaptic plasticity, which is controlled by N- methyl-D-aspartate receptor (NMDAR).
- NMDAR N- methyl-D-aspartate receptor
- the composition restores the suboptimum level of NMDAR activity to optimum levels, even during weak stimulation, and, at the same time, prevents neuronal death from NMDAR over-activation. Consequently, NMDAR dependent hippocampal long term potentiation (LTP) is enhanced, which is one key underlying molecular mechanism of learning and memory.
- NMDAR dependent hippocampal long term potentiation LTP
- the nutritional compositions may improve learning and memory in an individual by enhancing the NMDAR and 2-amino-3-(5-methyl-3-oxo-l,2- oxazol-4-yl) propanoic acid receptor (AMPAR) mediated hippocampal synoptic plasticity.
- AMPAR 2-amino-3-(5-methyl-3-oxo-l,2- oxazol-4-yl) propanoic acid receptor
- the methods of the present disclosure may be directed to individuals who have a neurodegenerative disease or condition, or a disease or condition related to a neurodegenerative disease or condition
- the methods of the present disclosure as described herein are also intended in some embodiments to include the use of such methods in "at risk" individuals, including individuals unaffected by or not otherwise afflicted with neurodegenerative diseases or conditions such as those described above, for the purpose of preventing, minimizing, or delaying the development of such diseases or conditions over time.
- the methods of the present disclosure preferably include continuous, daily administration of the compositions as described herein.
- Such preventive methods may be directed at adults or others, particularly older adults, who are susceptible to developing neurodegenerative diseases due to hereditary considerations, environmental considerations, and the like.
- the individual desirably consumes at least one serving of the nutritional composition daily, and in some embodiments, may consume two, three, or even more servings per day.
- Each serving is desirably administered as a single, undivided dose, although the serving may also be divided into two or more partial or divided servings to be taken at two or more times during the day.
- the methods of the present disclosure include continuous day after day administration, as well as periodic or limited administration, although continuous day after day administration is generally desirable.
- the methods of the present disclosure are preferably applied on a daily basis, wherein the daily administration is maintained continuously for at least 3 days, including at least 5 days, including at least 1 month, including at least 6 weeks, including at least 8 weeks, including at least 2 months, including at least 6 months, desirably for at least about 18-24 months, desirably as a long term, continuous, daily, dietary supplement.
- the exemplified products are nutritional products prepared in accordance with manufacturing methods well known in the nutrition industry for preparing nutritional liquids (e.g., emulsions and clear liquids) and powders.
- Examples 1-5 illustrate nutritional emulsions of the present disclosure, the ingredients of which are listed in the table below. All ingredient amounts are listed as kg per 1000 kg batch of product, unless otherwise specified.
- Flavoring agent 3.5 3.5 3.5 3.5 3.5 3.5 3.5
- Vitamin/mineral premix 0.280 0.280 0.280 0.280 0.280 0.280
- Vitamin E 0.039 0.039 0.039 0.039 0.039 0.039 0.039 0.039 0.039 0.039
- Vitamin A palmitate 0.003 0.003 0.003 0.003 0.003 0.003
- Vitamin D 3 0.002 0.002 0.002 0.002 0.002
- Examples 6-10 illustrate nutritional emulsions of the present disclosure, the ingredients of which are listed in the table below. All ingredient amounts are listed as kg per 1000 kg batch of product, unless otherwise specified.
- Liquid sucralose (25%) 0.500 0.500 0.500 0.500 0.500 0.500 0.500 0.500 0.500 0.500 0.500
- Vitamin/mineral premix 0.222 0.222 0.222 0.222 0.222 0.222
- Examples 11-15 illustrate nutritional clear liquids of the present disclosure, the ingredients of which are listed in the table below. All ingredient amounts are listed as kg per 1000 kg batch of product, unless otherwise specified.
- Examples 16-20 illustrate nutritional powders of the present disclosure, the ingredients of which are listed in the table below. These products are prepared by spray drying methods in separate batches, and are reconstituted with water prior to use to the desired target ingredient concentrations. All ingredient amounts are listed as kg per 1000 kg batch of product, unless otherwise specified.
- neuronal activation leads to pre-synaptic release of glutamate resulting in the activation of post-synaptic AMPA and NMDA receptors.
- Activation of post-synaptic AMPA receptors results in the flow of Na + ions, causing the depolarization of post-synaptic neuron. This depolarization abolishes the blocking
- NMDA receptors by Mg , resulting in the opening of NMDA receptor channels for Na + and Ca 2+ ions.
- Ca 2+ influx through NMDA receptors is known to trigger
- CaMKII Ca /calmodulin-dependent protein kinase
- NMDAR dependant hippocampal LTP was used as a physiological marker to assess the efficacy of Curcumin and DHA in enhancing cognitive function.
- NMDAR dependant LTP was recorded on hippocampal brain slices in vitro.
- mice were housed and used in accordance to the French and European legislations for animal care. The mice were sacrificed by fast decapitation, without previous anaesthesia. The brain was quickly removed and soaked in ice-cold oxygenated buffer with the following composition:
- Hippocampus slices 350 ⁇ were cut with a Macllwain tissue- chopper and incubated at room temperature for at least 60 minutes in Artificial Cerebro-Spinal Fluid (ACSF) having the following composition:
- Curcumin was prepared as a 150, 100, 50, or 25 mM Stock solution in Cremphor El (ref.: C5135, Sigma, batch: 1439553 13509161) from powder on each day of experimentation. This stock solution was then 10000X diluted in ACSF to reach the final 15, 10, 5.0, or 2.5 ⁇ concentration.
- D-AP5 (ref: Asc-271, ASCENT, batch: APN08163-1-1) was dissolved as a 30 mM stock solution in water, aliquoted and stored at -20°C until use. Aliquots were thawed and vortexed each day of experiment and then 1000X or 10000X diluted in ACSF to reach the final concentration of 30 ⁇ or 3 ⁇ .
- NBQX (ref: Asc-045, ASCENT, batch: APN07044-8-3) was dissolved as a 10 mM stock solution in water, aliquoted and stored at -20°C until use. Aliquots were thawed and vortexed each day of experiment and then 1000X diluted in ACSF to reach the final concentration of 10 ⁇ .
- a 350- ⁇ thick mouse hippocampal slice was disposed on the multi- electrode array (100 ⁇ distant electrodes).
- One electrode was chosen to stimulate Schaeffer collaterals at the CA3/CA1 interface.
- An I/O curve was performed to monitor evoked-responses for stimulations between 100 and 800 ⁇ , by 100 ⁇ steps.
- the stimulus was a monopolar biphasic current pulse (negative for 60 ⁇ and then positive for 60 ⁇ ), settled to evoke 40% of the maximal amplitude response (as determined with the I/O curve) and applied every 30 seconds to evoke "responses" (i.e. field Excitatory Post Synaptic Potentials; fEPSP) in the CA1 region.
- fEPSP field Excitatory Post Synaptic Potentials
- Evoked-responses were recorded if they satisfied quality criteria described in Standard Operating Procedures: correct location, stable baseline (fluctuation within +/- 10 % during ten consecutive minutes), amplitude > 100 ⁇ after background noise subtraction.
- the fEPSP from selected electrodes were simultaneously sampled at 5 kHz and recorded on the hard disk of a PC until offline analysis.
- fEPSP amplitudes of selected electrodes were compiled online (with MC Rack program) to monitor and to follow the good performance of the experiments. Data was plotted in a standard spreadsheet file for off-line analysis. The fEPSP resulted from glutamatergic synaptic transmission consecutive to afferent pathway stimulation.
- the slices were continuously perfused with ACSF solutions (bubbled with 95% 0 2 -5% C0 2 ) at the rate of 3 mL/min with a peristaltic pump (ME A chamber volume: ⁇ 1 mL). Complete solution exchange in the ME A chamber was achieved 20 seconds after the switch of solutions.
- the perfusion liquid was continuously pre-heated at 37 °C just before reaching the MEA chamber with a heated-perfusion cannula (PH01, Multichannel Systems, Reutlingen,
- the temperature of the MEA chamber was maintained at 37 +/- 0.1 °C with a Peltier element located in the MEA amplifier headstage.
- Curcumin and DHA showed significant enhancement of hippocampal LTP by modulating the NMDAR activity.
- NMDAR neurodegenerative diseases
- Glutamate is the major excitatory neurotransmitter in the brain that activates the major ion channel receptors such as NMDAR and AMPAR that contribute to synaptic plasticity.
- NMDAR and AMPAR major ion channel receptors
- NMDA is a specific agonist of NMDAR that is capable of causing the excitotoxic neuronal death due to
- NMDA NMDAR mediated excitotoxicity
- Hippocampal neurons were plated in 96-well plates and cultured for 10 days. NMDA and glutamate neurotoxicity assays were performed as detailed below. All preincubation experiments were performed in neurobasal medium
- Curcumin showed a comparatively significant neuroprotection by inhibiting the over-activation of NMDAR mediated excitotoxicity as compared to DHA (FIGS. 2 A and 2B). Curcumin offers significant
- neuroprotection by preventing NMDAR mediated excitotoxicity and resulting neuronal death due to the oxidative stress induced by the increased calcium influx and subsequent release of proteolytic enzymes, transcription factors and reactive oxygen species.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Mycology (AREA)
- Medicinal Chemistry (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Botany (AREA)
- Neurosurgery (AREA)
- Pediatric Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Psychiatry (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Disclosed are nutritional compositions including a combination of Curcumin and/or bioavailable Curcumin and docosahexaenoic acid. The combination improves cognitive performance in an individual, and, in one embodiment, improves a cognitive impairment and/or brain dysfunction associated with age-related cognitive decline or cognitive decline resulting from a neurodegenerative disease. This combination is also effective in improving memory acquisition, memory retention and recall in an individual.
Description
NUTRITIONAL COMPOSITIONS COMPRISING CURCUMIN AND DOCOSAHEXAENOIC ACID FOR IMPROVING COGNITION
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 61/568,329, filed on December 8, 2011, the contents of which are incorporated by reference herein.
FIELD OF THE DISCLOSURE
[0002] The present disclosure relates to nutritional compositions comprising Curcumin and docosahexaenoic acid (DHA) and to the methods of administering the compositions for improving cognitive performance and/or memory, enhancing memory acquisition, memory retention and recall in an individual, as well as reducing brain dysfunction and cognitive decline. In some embodiments, bioavailable
Curcumin is utilized in combination with the DHA.
BACKGROUND OF THE DISCLOSURE
[0003] Manufactured nutritional liquids and powders comprising a targeted selection of nutrition ingredients are well known and widely available, some of which may provide a sole source of nutrition while others may provide a supplemental source. These nutritionals include powders that can be reconstituted with water or other aqueous liquid, as well as ready to drink nutritional liquids such as milk or protein based emulsions or non-emulsified liquids. These nutritional liquids are especially useful when formulated with selected nutritional ingredients.
[0004] An estimated 4 to 5 million Americans, about 15% of those older than age 65, have some form and degree of cognitive failure. Cognitive failure, which includes dysfunction or loss of cognitive function (e.g., learning, thinking and memory), commonly occurs in association with central nervous system (CNS) disorders or conditions, including neurodegenerative diseases. Cognitive dysfunction may cause significant impairment of social and/or occupational functioning, which can interfere with the ability of an individual to perform activities of daily living and greatly impact the autonomy and quality of life of the individual.
[0005] Accordingly, there has recently been an increased interest in designing and marketing so-called "smart formulations" that include nutritional products designed specifically for brain health and nourishment. Many of these products are specifically designed for improving cognition and preventing
neurodegenerative diseases and related cognitive decline. To date, these formulations and products have had limited success.
[0006] As such, there is a need for nutritional compositions and methods for enhancing cognitive performance, and particularly, memory acquisition, memory retention, and memory recall that may contribute to the learning and memory processes. It would be beneficial if such nutritional compositions and methods could also improve a cognitive impairment and/or brain dysfunction, such as from age- related cognitive decline or from neurodegenerative diseases.
SUMMARY OF THE DISCLOSURE
[0007] One embodiment is directed to a method for improving memory acquisition and memory retention and recall in an individual. The method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
[0008] Another embodiment is directed to a method for improving cognitive performance in an individual. The method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
[0009] Another embodiment is directed to a method for improving memory acquisition in an individual. The method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
[0010] Another embodiment is directed to a method for improving memory retention and recall in an individual. The method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
[0011] Another embodiment is directed to a method for enhancing N- Methyl-D-aspartate receptor (NMDAR) dependent hippocampal long-term
potentiation (LTP), a physiological correlate or a measure of synaptic plasticity, which may be a key underlying molecular mechanism of learning and memory. The method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
[0012] Another embodiment is directed to a method for enhancing the NMDAR and 2-amino-3-(5-methyl-3-oxo-l,2-oxazol-4-yl)propanoic acid receptor (AMPAR) mediated hippocampal synaptic plasticity, which may be another key mechanism underlying learning and memory. The method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
[0013] Another embodiment is directed to a method for preventing the over- activation of NMDAR, which may result in neuronal death. The method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
[0014] Another embodiment is directed to a method for enhancing neuronal membrane fluidity. The method comprises administering to the individual a composition comprising an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
[0015] Another embodiment is directed to a nutritional composition for improving cognitive performance. The composition comprises an effective amount of Curcumin or bioavailable Curcumin and docosahexaenoic acid.
[0016] Nutritional compositions including Curcumin, and in particular bioavailable Curcumin, and DHA in combination provide enhanced bioavailability of the individual components of Curcumin and DHA to an individual upon
administration. Therefore, this combination of components is more efficacious in providing improved cognitive functioning and/or performance to an individual, as well as reducing cognitive impairment and/or brain dysfunction in an individual. Specifically, the combination of Curcumin or bioavailable Curcumin and DHA produces an added benefit on cognitive functioning by producing an effect in enhancing NMDAR and AMPAR dependent hippocampal synaptic plasticity, which is a molecular mechanism involved in learning and memory. In addition, Curcumin or bioavailable Curcumin and DHA produces a sequential action by improving memory acquisition that is essential for the process of learning, and by improving memory retention and recall that is necessary for the retrieval of learned processes.
[0017] The combination of Curcumin or bioavailable Curcumin and DHA may also provide benefits to an individual by its complementary mode of action on neuroprotection. Neuronal death due to the oxidative stress resulting from NMDAR over-activation (i.e., NMDAR mediated excitotoxicity) is a major problem associated with cognitive impairment, brain dysfunction, and neurodegenerative diseases (e.g., Alzheimer's Disease). It has now been found that Curcumin, and particularly bioavailable Curcumin, offers significant neuroprotection by preventing NMDAR mediated excitotoxicity and resulting neuronal death.
[0018] Additionally, DHA offers benefits such as the maintenance of neuronal membrane fluidity, which is essential for synaptic receptor function, and neurotransmitter release, which is essential for the cognitive performance of an individual. While DHA may be taken up by the brain from the diet to provide the above benefits, DHA is highly susceptible to oxidation and may therefore induce oxidative stress in neuronal membranes that may, in turn, negatively affect the
neuronal health and function. It has now been found, however, that administration of Curcumin, and in particular bioavailable Curcumin, which possesses strong antioxidant properties, can prevent the oxidation of DHA as well as provide neuroprotection and prevention of neuronal death due to oxidative stress, which is induced by increased calcium influx, thereby allowing the subsequent release of proteolytic enzymes, transcription factors, and reactive oxygen species. Therefore, a Curcumin or bioavailable Curcumin and DHA combination will have a
complementary mode of action to provide cognitive benefits.
[0019] Curcumin, and in particular bioavailable Curcumin, and DHA act in combination to further provide anti-inflammatory and anti-amyloidogenic properties to an individual. Neuronal inflammation and amyloid β protein deposition are associated with cognitive impairment and/or brain dysfunction that results from age- related cognitive decline and/or cognitive decline associated with neurodegenerative diseases. These anti-inflammatory and anti-amyloidogenic properties of Curcumin or bioavailable Curcumin and DHA, therefore, provide added benefits when used in combination, thereby reducing cognitive impairment and/or brain dysfunction.
[0020] Accordingly, the nutritional compositions and methods of the present disclosure offer an alternative therapeutic or nutritional intervention option that may contribute to the improvement of cognitive performance, as well as to the reduction of cognitive impairment and brain dysfunction, in individuals, and particularly in adults, older adults, and the elderly.
BRIEF DESCRIPTION OF THE FIGURES
[0021] FIG. 1A is a chart depicting the effect of the combination of
Curcumin and DHA on NMDAR dependent hippocampal LTP as analyzed in
Example 21.
[0022] FIGS. IB- ID are graphs depicting the effect of the combination of Curcumin and DHA on NMDAR dependent hippocampal LTP as analyzed in
Example 21.
[0023] FIG. 2A is a chart depicting the neuroprotective effect of Curcumin on primary hippocampal neurons from NMDAR mediated excitotoxicity.
[0024] FIG. 2B is a chart depicting the neuroprotective effect of DHA on primary hippocampal neurons from NMDAR mediated excitotoxicity.
DETAILED DESCRIPTION OF THE DISCLOSURE
[0025] The compositions and methods herein are directed to nutritional compositions comprising Curcumin, and in particular bioavailable Curcumin, and DHA that can improve general cognitive performance in an individual, including memory acquisition, memory retention and recall. These and other essential or optional elements or features of the various embodiments are described in detail hereafter.
[0026] The term "older adult" as used herein, unless otherwise specified, refers to an individual of at least 45 years of age, including at least 50 years of age, including at least 55 years of age, including at least 60 years of age, including at least 65 years of age, including at least 70 years of age, including at least 75 years of age, including at least 80 years of age, further including from about 55 years of age to about 80 years of age.
[0027] The term "Curcumin" refers to Curcumin and derivatives and analogs thereof.
[0028] The term "bioavailable" as used herein, unless otherwise specified, refers to the ability of a compound to enter into and remain in the bloodstream of an individual such that the substance can be absorbed into cells in the body. As the degree of bioavailability of a compound increases, the compound becomes more likely to enter into and remain in the bloodstream where it can be absorbed and used by the body. As the degree of bioavailability of a compound decreases, the compound becomes more likely to go directly into the gastrointestinal area and be expelled from the body before entering the bloodstream.
[0029] The term "nutritional composition" as used herein, unless otherwise specified, refers to nutritional liquids and nutritional powders that comprise at least one of protein, fat, and carbohydrate and is suitable for oral administration to a human. The nutritional composition may further comprise vitamins, minerals, and other ingredients and represent a sole, primary, or supplemental source of nutrition.
[0030] The terms "fat," "lipid" and "oil" as used herein, unless otherwise specified, are used interchangeably to refer to lipid materials derived or processed from plants or animals. These terms also include synthetic lipid materials so long as such synthetic materials are suitable for oral administration to humans.
[0031] The term "susceptible" as used herein, unless otherwise specified, means having little resistance to a certain condition or disease, including being genetically predisposed, having a family history of, and/or having symptoms of the condition or disease.
[0032] The term "synergy" or "synergistic amount" as used herein, unless otherwise specified, refers to the interaction of two or more compounds so that their combined effect is greater than the additive sum of their individual effects.
[0033] The term "cognitive performance" as used herein, unless otherwise specified, refers to the learning, thinking, and memory functions (i.e., memory acquisition, memory retention and recall) of the brain. Accordingly, the term "improving cognitive performance" as used herein, unless otherwise specified, refers to improving the learning, thinking, and/or memory (memory acquisition, memory retention, and memory recall) functions of an individual.
[0034] The term "improving a cognitive impairment and/or brain dysfunction" as used herein, unless otherwise specified, refers to the treating, preventing, and/or reducing the incidence or severity of cognitive decline associated with age-related cognitive decline or neurodegenerative disease.
[0035] The term "age-related cognitive decline" as used herein, unless otherwise specified, refers to a gradual decline in learning, thinking, and/or memory functions that are normal consequences of aging.
[0036] The term "neurodegenerative disease" as used herein, unless otherwise specified, refers to the progressive loss of structure or function of neurons, including the death of neurons and includes diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, dementia, amyotrophic lateral sclerosis, stroke, and schizophrenia.
[0037] All percentages, parts and ratios as used herein, are by weight of the total product, unless otherwise specified. All such weights as they pertain to listed ingredients are based on the active level and, therefore, do not include solvents or byproducts that may be included in commercially available materials, unless otherwise specified.
[0038] All references to singular characteristics or limitations of the present disclosure shall include the corresponding plural characteristic or limitation, and vice versa, unless otherwise specified or clearly implied to the contrary by the context in which the reference is made.
[0039] All combinations of method or process steps as used herein can be performed in any order, unless otherwise specified or clearly implied to the contrary by the context in which the referenced combination is made.
[0040] The various embodiments of the nutritional compositions of the present disclosure may also be substantially free of any optional or selected essential ingredient or feature described herein, provided that the remaining composition or powder still contains all of the required ingredients or features as described herein. In this context, and unless otherwise specified, the term "substantially free" means that the selected composition contains less than a functional amount of the optional ingredient, typically less than about 1%, including less than about 0.5%, including less than about 0.1%, and also including zero percent, by weight of such optional or selected essential ingredient.
[0041] The nutritional compositions may comprise, consist of, or consist essentially of the essential elements of the products as described herein, as well as any additional or optional element described herein or otherwise useful in nutritional product applications.
Product Form
[0042] The nutritional compositions of the present disclosure may be formulated and administered in any known or otherwise suitable oral product form. Any solid, liquid, or powder form, including combinations or variations thereof, are suitable for use herein, provided that such forms allow for safe and effective oral delivery to the individual of the essential ingredients as also defined herein.
[0043] The nutritional compositions are most suitably formed as aqueous emulsions, including water-in-oil emulsions, oil-in-water emulsions, or complex (e.g., oil-in- water-in-oil emulsions) or other emulsion systems. As applied to the nutritional compositions herein, the nutritional emulsion embodiments are most typically oil-in- water emulsions comprising an internal or discontinuous oil phase that comprises the Curcumin or bioavailable Curcumin and DHA as defined herein.
Curcumin and Bioavailable Curcumin
[0044] Curcumin, 1,7-bis (4-hydroxyphenyl)-l,6-heptadiene-3,5-dione and having the formula
is the principal Curcuminoid of turmeric. Conventionally, Curcumin has suffered lower bioavailability when taken orally, and thus when formulated at higher concentrations to counter its inherent poor bioavailability to achieve the desired systemic delivery, the products often take on an intense undesirable yellow color. In some embodiments, the present nutritional compositions use "bioavailable
Curcumin", which has an improved bioavailability as compared to conventionally
used Curcumin. As such, the bioavailable Curcumin can be utilized in lower concentrations in the nutritional compositions and methods of the present disclosure, while still maintaining its anti-inflammatory, antioxidative, and anti-amyloidogenic activity.
[0045] The term "bioavailable Curcumin" refers to Curcumin and derivatives and analogs thereof, including natural and synthetic derivatives of Curcumin, as well as any combination of one or more of Curcumin and a derivative and/or analog. In particular, the term "bioavailable Curcumin" should be understood to encompass compounds having a 1,7-bis (4-hydroxyphenyl)-l,6-heptadiene-3,5- dione or l,7-bis(4-hydroxyphenyl) hept-4-en-3-one skeleton wherein the phenyl groups independently may bear one or more alkoxy residues, especially one methoxy residue in the 3-position. In some embodiments, additional Curcuminoids, such as demethoxyCurcumin and bisdemethoxyCurcumin, may also be present in the nutritional compositions. When present, demethoxyCurcumin and
bisdemethoxyCurcumin may be present as part of a complex with Curcumin.
[0046] The "bioavailable Curcumin" used in the nutritional compositions of the present disclosure shows improved oral bioavailability as compared to Curcumins that are not substantially "bioavailable." The oral bioavailability can be determined in experiments involving oral administration of the bioavailable Curcumin composition of the present disclosure (and/or a corresponding amount of non-bioavailable
Curcumin) to a subject and measuring the level of the Curcumin in a biological sample obtained from the subject over time, wherein the biological sample may be derived from a body fluid, for example serum, plasma, whole blood, or cerebrospinal fluid, and/or a tissue, e.g. from brain, liver, kidney, or heart. For analysis, the Curcumin level in the examined body fluid or tissue may be plotted against time, and the area under the curve (AUC), for example the total area under the curve from t = 0 (time of administration) to t = infinity (= AUCO-infmity), or the area under the curve within a defined period, e.g. from t = 0 to t = 6 hours (AUC0-6H), may be calculated. In general, a higher AUC relative to the AUC obtained by administration of non- bioavailable Curcumin indicates an improved bioavailability. The absolute bioavailability may be calculated from the resulting AUC data as a percentage based
on the corresponding AUC data obtained from intravenous administration of
Curcumins.
[0047] In some embodiments, the bioavailable Curcumin amount in the blood, determined as AUC0-6H after a single oral administration of a dose of the bioavailable Curcumin-containing nutritional composition of the present disclosure corresponding to 20 mg of total Curcumin to a human subject or an animal subject, preferably a rat, is significantly higher than after oral administration of the same amount of non-bioavailable Curcumin in the composition, preferably at least 2 times, at least 3 times, at least 4 times, at least 6 times, at least 8 times, at least 10 times, or at least 15 times, and, for example, up to 30 times higher.
[0048] As used herein, the amount of Curcumin in the blood being
"significantly higher" means a statistically significant increase of this parameter in subjects after oral administration of 20 mg of bioavailable Curcumin in the nutritional composition of the present disclosure as compared to the control 20 mg of Curcumin that is not bioavailable. A statistical test known in the art, such as ANOVA or Student's t-test, may be used to determine the significance of this difference, wherein the p-value is at least <0.1, <0.5, <0.01, <0.005, <0.001 or <0.0001.
[0049] Bioavailable Curcumin can be prepared in a number of ways including, for example, using Meltrex® or similar melt-extrusion technology to prepare extruded solids and improve the bioavailability of the Curcumin as compared to Curcumin not produced by melt extrusion. Meltrex® or similar melt-extrusion technology methods are known in the art and can be applied to produce bioavailable Curcumin by one skilled in the art based on the disclosure herein.
[0050] In another embodiment, Curcumin or bioavailable Curcumin can be co-supplemented with piperine (generally extracted from black pepper) to increase the bioavailability and hence the absorbability of Curcumin. In one embodiment, the piperine is co-supplemented in an amount of about 20 mg to increase the
bioavailability of the Curcumin.
[0051] In another embodiment, the Curcumin or bioavailable Curcumin may be solubilized in an oil having an HLB of from about 0.7 to about 14 (polar oils) such that the resulting oil mixture provides increased bioavailability of Curcumin. One suitable polar oil for dissolving the Curcumin is a medium chain triglyceride oil (MCT oil).
[0052] In one embodiment of the present disclosure, the bioavailable Curcumin is a mixture of Curcuminoids (i.e., Curcumin, demethoxyCurcumin and bisdemethoxyCurcumin) obtained from the rhizomes of Curcuma Longa. In another embodiment, the bioavailable Curcumin is obtained using Meltrex® technology (Abbott Nutrition, Columbus, Ohio). In yet another embodiment, the bioavailable Curcumin is Meriva Bioavailable Curcumin, commercially available from Idena SPA (Milan, Italy).
[0053] The Curcumin or bioavailable Curcumin concentration in the nutritional compositions may range from at least about 0.001%, including from about 0.002% to about 3.36%, including from about 0.005%) to about 1.87%, also including from about 0.03%> to about 0.935%), also including from about 0.1 % to about 0.467%), and also including from about 0.234% to about 0.3%, by weight of the nutritional composition. Exemplary embodiments of the present disclosure include nutritional compositions having Curcumin or bioavailable Curcumin in amounts ranging from about 0.002% to about 0.25%, from 0.002% to about 0.234%, from about 0.005% to about 0.467%, from about 0.03% to about 0.935%, from about 0.1% to about 1.9%, from about 0.1% to about 1.87%, and from about 0.3% to about 3.36%, by weight of the nutritional composition.
[0054] The nutritional compositions of the present disclosure desirably include sufficient Curcumin or bioavailable Curcumin to provide an individual with at least about 1 milligram, including at least about 3 milligrams, including from about 10 milligrams to about 10,000 milligrams, including from about 100 milligrams to about 4000 milligrams, including from about 400 milligrams to about 2000 milligrams, including from about 1200 milligrams to about 1800 milligrams, per day of Curcumin or bioavailable Curcumin. The total daily amount of Curcumin or bioavailable
Curcumin may be administered to an individual in a single undivided dose, or may be split into one, two, three, four or more doses per day.
Docosahexaenoic acid (DHA)
[0055] In addition to the Curcumin, and in some embodiments, bioavailable Curcumin, the nutritional compositions of the present disclosure include DHA. DHA, cis-docosa-4,7,10,13,16,19-hexa-enoic acid, is an omega-3 polyunsaturated fatty acid (PUFA) and is the most abundant omega-3 PUFA in the brain and retina, accounting for 40% of the PUFAs in the brain and 60% of the PUFAs in the retina. DHA is essential for the proper functioning of adult brains and the central nervous system, deficiencies of which have been associated with cognitive decline.
[0056] In the human body, DHA is either directly obtained from the diet or derived from eicosapentaenoic acid (EPA) via docosapentaenoic acid (DP A) as an intermediate. Common dietary sources of DHA include marine, plant and animal sources such as mackerel, chicken, herring, eel, pig, tuna, clams, veal, beef, pork, turkey, cod, anchovy, and trout and/or plant sources such as soybeans, cabbage, whole-grain barley, rice, and carrots.
[0057] The DHA concentration in the nutritional compositions may range from at least about 0.001%, including from about 0.001% to about 4.6%>, including from about 0.01%> to about 2.8%, including from about 0.02% to about 1.4%, also including from about 0.02% to about 0.7%, also including from about 0.02% to about 0.4%), and also including from about 0.025%) to about 0.34%, by weight of the nutritional composition.
[0058] The nutritional compositions of the present disclosure desirably include sufficient DHA to provide an individual with from about 100 milligrams to about 2000 milligrams, including from about 200 milligrams to about 2000 milligrams, including from about 200 milligrams to about 1000 milligrams, including from about 500 milligrams to about 1500 milligrams, including from about 1000 milligrams to about 1400 milligrams, per day of DHA. The total daily amount of
DHA may be administered to an individual in a single undivided dose, or may be split into one, two, three, four or more doses per day.
Macronutrients
[0059] The nutritional compositions of the present disclosure may further comprise one or more optional macronutrients in addition to the Curcumin or bioavailable Curcumin and DHA described herein. The optional macronutrients include proteins, lipids, carbohydrates, and combinations thereof. The nutritional compositions are desirably formulated as dietary products containing all three macronutrients.
[0060] Macronutrients suitable for use herein include any protein, lipid, or carbohydrate or source thereof that is known for or otherwise suitable for use in an oral nutritional composition, provided that the optional macronutrient is safe and effective for oral administration and is otherwise compatible with the other ingredients in the nutritional composition.
[0061] The concentration or amount of optional lipid, carbohydrate, and protein in the nutritional composition can vary considerably depending upon the particular product form (e.g., bars or other solid dosage forms, milk or soy-based liquids or other clear beverages, reconstitutable powders, etc.) and the various other formulations and targeted dietary needs. These optional macronutrients are most typically formulated within any of the embodied ranges described in the following tables.
Lipid 0-98 1-30 3-15
Protein 0-98 1-30 2-10
Each numerical value preceded by the term "about"
Carbohydrate
[0062] Optional carbohydrates suitable for use in the nutritional
compositions may be simple, complex, or variations or combinations thereof, all of which are optionally in addition to the Curcumin or bioavailable Curcumin as described herein. Non-limiting examples of suitable carbohydrates include hydrolyzed or modified starch or cornstarch, maltodextrin, isomaltulose, sucromalt, glucose polymers, sucrose, corn syrup, corn syrup solids, rice-derived carbohydrate, glucose, fructose, lactose, high fructose corn syrup, honey, sugar alcohols (e.g., maltitol, erythritol, sorbitol), and combinations thereof.
[0063] Optional carbohydrates suitable for use herein also include soluble dietary fiber, non-limiting examples of which include gum Arabic,
fructooligosaccharide (FOS), sodium carboxymethyl cellulose, guar gum, citrus pectin, low and high methoxy pectin, oat and barley glucans, carrageenan, psyllium and combinations thereof. Insoluble dietary fiber is also suitable as a carbohydrate source herein, non-limiting examples of which include oat hull fiber, pea hull fiber, soy hull fiber, soy cotyledon fiber, sugar beet fiber, cellulose, corn bran, and combinations thereof.
Protein
[0064] Optional proteins suitable for use in the nutritional compositions include hydrolyzed, partially hydrolyzed or non-hydro lyzed proteins or protein sources, and can be derived from any known or otherwise suitable source such as milk (e.g., casein, whey), animal (e.g., meat, fish, egg albumen), cereal (e.g., rice, corn), vegetable (e.g., soy, pea, potato), or combinations thereof. The proteins for use herein can also include, or be entirely or partially replaced by, free amino acids known for
use in nutritional products, non-limiting examples of which include L-tryptophan, L- glutamine, L-tyrosine, L-methionine, L-cysteine, taurine, L-arginine, L-carnitine, and combinations thereof.
Lipid
[0065] Optional lipids suitable for use in the nutritional compositions, which are optionally in addition to the DHA as described herein, include coconut oil, fractionated coconut oil, soy oil, corn oil, olive oil, safflower oil, high oleic safflower oil, high GLA-safflower oil, MCT oil (medium chain triglycerides), sunflower oil, high oleic sunflower oil, palm and palm kernel oils, palm olein, canola oil, flaxseed oil, borage oil, cottonseed oils, evening primrose oil, blackcurrant seed oil, transgenic oil sources, fungal oils, marine oils (e.g., tuna, sardine) and so forth.
Optional Ingredients
[0066] The nutritional compositions may further comprise other optional ingredients that may modify the physical, nutritional, chemical, hedonic or processing characteristics of the products or serve as pharmaceutical or additional nutritional components when used in a targeted population. Many such optional ingredients are known or otherwise suitable for use in other nutritional products and may also be used in the nutritional compositions described herein, provided that such optional ingredients are safe and effective for oral administration and are compatible with the essential and other ingredients in the composition.
[0067] Non-limiting examples of such other optional ingredients include preservatives, anti-oxidants, buffers, pharmaceutical actives, sweeteners, colorants, flavors, flavor enhancers, thickening agents and stabilizers, emulsifying agents, lubricants, and combinations thereof.
[0068] The nutritional compositions may further include one or more minerals, non-limiting examples of which include phosphorus, sodium, chloride, magnesium, manganese, iron, copper, zinc, iodine, calcium, potassium, chromium, molybdenum, selenium, and combinations thereof.
[0069] The nutritional compositions may also include one or more vitamins, non-limiting examples of which include carotenoids (e.g., beta-carotene, zeaxanthin, lutein, lycopene), biotin, choline, inositol, folic acid, pantothenic acid, TP AN, choline, vitamin A, thiamine (vitamin Bl), riboflavin (vitamin B2) niacin (vitamin B3), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), ascorbic acid (vitamin C), vitamin D, vitamin E, vitamin K, and various salts, esters, or other derivatives thereof, and combinations thereof.
Methods of Manufacture
[0070] The nutritional compositions may be prepared by any known or otherwise effective manufacturing technique for preparing the selected product form. Many such techniques are known for any given product form such as nutritional liquids and nutritional powders and can easily be applied by one of ordinary skill in the nutrition and formulation arts to the nutritional products described herein.
[0071] Liquid, milk or soy-based nutritional liquids, for example, may be prepared by first forming an oil and fiber blend containing all formulation oils, any emulsifier, fiber and fat-soluble vitamins. Additional slurries (typically a
carbohydrate and two protein slurries) are prepared separately by mixing the carbohydrate and minerals together and the protein in water. The slurries are then mixed together with the oil blend. The resulting mixture is homogenized, heat processed, standardized with any water-soluble vitamins, flavored and the liquid terminally sterilized or aseptically filled or dried to produce a powder.
[0072] The compositions of the present disclosure may also be manufactured by other known or otherwise suitable techniques not specifically described herein without departing from the spirit and scope of the present disclosure. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive and that all changes and equivalents also come within the description of the present disclosure.
Methods of Use
[0073] The methods include the oral administration of the nutritional compositions that include Curcumin or bioavailable Curcumin in combination with DHA, to improve cognitive performance in any individual. Particularly, the combination of bioavailable Curcumin and DHA may improve general cognition by producing a sequential action on memory acquisition, memory retention and memory recall that contributes to the cognitive functions of learning, thinking, and memory.
[0074] In addition to memory acquisition and memory recall, the nutritional compositions including the combination of Curcumin or bioavailable Curcumin and DHA may have a complementary mode of action in maintaining neuronal membrane fluidity, allowing for proper hormone and neurotransmitter function. This may further improve cognitive performance.
[0075] Additionally, in some embodiments, the nutritional compositions can be utilized to improve a cognitive impairment and/or brain dysfunction that may be associated with a neurodegenerative disease. Particularly, the combination of Curcumin or bioavailable Curcumin and DHA shows anti-amyloidogenic properties and anti-inflammation properties, thereby reducing neuronal inflammation and clearance of amyloid β protein deposit that can lead to a cognitive impairment and/or brain dysfunction associated with neurodegenerative diseases or conditions such as Alzheimer's disease, Huntington's disease, Parkinson's disease, dementia, amyotrophic lateral sclerosis, stroke, and/or schizophrenia. By reducing this neuronal inflammation and clearing of the amyloid protein, cognitive function may be improved.
[0076] Furthermore, in some embodiments, the nutritional compositions of the present disclosure may improve a cognitive impairment and/or brain dysfunction associated with age-related cognitive decline or cognitive decline associated with a neurodegenerative disease by enhancing synaptic plasticity, which is controlled by N- methyl-D-aspartate receptor (NMDAR). Deficits in synaptic plasticity and/or neuronal death can result in cognitive impairment and/or brain dysfunction. The
composition restores the suboptimum level of NMDAR activity to optimum levels, even during weak stimulation, and, at the same time, prevents neuronal death from NMDAR over-activation. Consequently, NMDAR dependent hippocampal long term potentiation (LTP) is enhanced, which is one key underlying molecular mechanism of learning and memory. Further, by preventing neuronal death, the neuronal loss associated with cognitive impairment and brain dysfunction can be avoided. In another embodiment, the nutritional compositions may improve learning and memory in an individual by enhancing the NMDAR and 2-amino-3-(5-methyl-3-oxo-l,2- oxazol-4-yl) propanoic acid receptor (AMPAR) mediated hippocampal synoptic plasticity.
[0077] Although in some embodiments the methods of the present disclosure may be directed to individuals who have a neurodegenerative disease or condition, or a disease or condition related to a neurodegenerative disease or condition, the methods of the present disclosure as described herein are also intended in some embodiments to include the use of such methods in "at risk" individuals, including individuals unaffected by or not otherwise afflicted with neurodegenerative diseases or conditions such as those described above, for the purpose of preventing, minimizing, or delaying the development of such diseases or conditions over time. For such prevention purposes, the methods of the present disclosure preferably include continuous, daily administration of the compositions as described herein. Such preventive methods may be directed at adults or others, particularly older adults, who are susceptible to developing neurodegenerative diseases due to hereditary considerations, environmental considerations, and the like.
[0078] The individual desirably consumes at least one serving of the nutritional composition daily, and in some embodiments, may consume two, three, or even more servings per day. Each serving is desirably administered as a single, undivided dose, although the serving may also be divided into two or more partial or divided servings to be taken at two or more times during the day. The methods of the present disclosure include continuous day after day administration, as well as periodic or limited administration, although continuous day after day administration is generally desirable. The methods of the present disclosure are preferably applied on a
daily basis, wherein the daily administration is maintained continuously for at least 3 days, including at least 5 days, including at least 1 month, including at least 6 weeks, including at least 8 weeks, including at least 2 months, including at least 6 months, desirably for at least about 18-24 months, desirably as a long term, continuous, daily, dietary supplement.
EXAMPLES
[0079] The following examples illustrate specific embodiments and or features of the nutritional products of the present disclosure. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present disclosure, as many variations thereof are possible without departing from the spirit and scope of the disclosure.
[0080] The exemplified products are nutritional products prepared in accordance with manufacturing methods well known in the nutrition industry for preparing nutritional liquids (e.g., emulsions and clear liquids) and powders.
Examples 1-5
[0081] Examples 1-5 illustrate nutritional emulsions of the present disclosure, the ingredients of which are listed in the table below. All ingredient amounts are listed as kg per 1000 kg batch of product, unless otherwise specified.
Table 1: Nutritional Emulsions
Soy lecithin 1.6 1.6 1.6 1.6 1.6
Carrageenan 1.0 1.0 1.0 1.0 1.0
Magnesium carbonate 0.824 0.824 0.824 0.824 0.824
Choline chloride 0.750 0.750 0.750 0.750 0.750
Potassium phosphate dibasic 0.621 0.621 0.621 0.621 0.621
Potassium chloride 0.319 0.319 0.319 0.319 0.319
Vitamin/mineral premix 0.280 0.280 0.280 0.280 0.280
Ascorbic acid 0.250 0.250 0.250 0.250 0.250
Water soluble vitamin premix 0.242 0.242 0.242 0.242 0.242
L-carnitine 0.200 0.200 0.200 0.200 0.200
Potassium hydroxide 0.175 0.175 0.175 0.175 0.175
Vitamin E 0.039 0.039 0.039 0.039 0.039
Gellan gum 0.025 0.025 0.025 0.025 0.025
Beta carotene 0.014 0.014 0.014 0.014 0.014
Vitamin A palmitate 0.003 0.003 0.003 0.003 0.003
Vitamin D3 0.002 0.002 0.002 0.002 0.002
Potassium iodide 0.194 g 0.194 g 0.194 g 0.194 g 0.194 g
Examples 6-10
[0082] Examples 6-10 illustrate nutritional emulsions of the present disclosure, the ingredients of which are listed in the table below. All ingredient amounts are listed as kg per 1000 kg batch of product, unless otherwise specified.
Table 2: Nutritional Emulsions
Potassium chloride 0.735 0.735 0.735 0.735 0.735
Maltodextrin 0.692 0.692 0.692 0.692 0.692
Ascorbic acid 0.597 0.597 0.597 0.597 0.597
Choline chloride 0.532 0.532 0.532 0.532 0.532
Liquid sucralose (25%) 0.500 0.500 0.500 0.500 0.500
Potassium hydroxide 0.427 0.427 0.427 0.427 0.427
Sodium chloride 0.300 0.300 0.300 0.300 0.300
Carrageenan 0.250 0.250 0.250 0.250 0.250
Flavoring agent 0.250 0.250 0.250 0.250 0.250
Vitamin/mineral premix 0.222 0.222 0.222 0.222 0.222
Acesulfame potassium 0.075 0.075 0.075 0.075 0.075
Vitamin DEK premix 0.053 0.053 0.053 0.053 0.053
Gellan gum 0.050 0.050 0.050 0.050 0.050
Vitamin A palmitate 0.0074 0.0074 0.0074 0.0074 0.0074
Potassium iodide 0.00018 0.00018 0.00018 0.00018 0.00018
Cyanocobalamin 0.000013 0.000013 0.000013 0.000013 0.000013
Examples 11-15
[0083] Examples 11-15 illustrate nutritional clear liquids of the present disclosure, the ingredients of which are listed in the table below. All ingredient amounts are listed as kg per 1000 kg batch of product, unless otherwise specified.
Table 3: Clear Liquids
EXAMPLES 16-20
[0084] Examples 16-20 illustrate nutritional powders of the present disclosure, the ingredients of which are listed in the table below. These products are
prepared by spray drying methods in separate batches, and are reconstituted with water prior to use to the desired target ingredient concentrations. All ingredient amounts are listed as kg per 1000 kg batch of product, unless otherwise specified.
Table 4: Nutritional Powders
AN = As Needed
EXAMPLE 21
[0085] In this Example, the administration of Curcumin and DHA, alone and in combination, on NMDAR dependent hippocampal LTP was analyzed.
[0086] Long lasting changes in the strength of AMPA and NMDA receptor mediated glutamatergic synaptic transmission in the hippocampus, known as hippocampal synaptic plasticity, is a key underlying molecular mechanism in learning and memory. AMPA and NMDA dependant hippocampal synaptic plasticity is associated with trafficking and delivery of AMPA receptors at the synapse in response to NMDAR activation. Previous studies have shown that in cognitive decline associated with aging or Alzheimer's disease onset, the strength of AMPA and NMDA synaptic transmission is compromised due to the internalization of NMDA and AMPA receptors, leading to deficits in NMDAR and AMPAR expression at the synapse. During learning, neuronal activation leads to pre-synaptic release of glutamate resulting in the activation of post-synaptic AMPA and NMDA receptors. Activation of post-synaptic AMPA receptors results in the flow of Na+ ions, causing the depolarization of post-synaptic neuron. This depolarization abolishes the blocking
2_|_
of NMDA receptors by Mg , resulting in the opening of NMDA receptor channels for Na+ and Ca2+ ions. Ca2+ influx through NMDA receptors is known to trigger
2_|_
intracellular signaling cascades, notably the phosphorylation of Ca /calmodulin- dependent protein kinase (CaMKII) that phosphorylates AMPA receptors and modulates the channel properties, ultimately resulting in long-term potentiation (LTP), the physiological correlate of synaptic plasticity (learning and memory).
[0087] Therefore in this Example, NMDAR dependant hippocampal LTP was used as a physiological marker to assess the efficacy of Curcumin and DHA in enhancing cognitive function. To evaluate the efficacy of Curcumin and DHA in enhancing cognitive function, NMDAR dependant LTP was recorded on hippocampal brain slices in vitro.
[0088] Experiments were carried out with 7-9 weeks-old C57/Black6 mice (from Elevage Janvier, Le Genest St Isle, France). Animals were housed and used in
accordance to the French and European legislations for animal care. The mice were sacrificed by fast decapitation, without previous anaesthesia. The brain was quickly removed and soaked in ice-cold oxygenated buffer with the following composition:
[0089] Hippocampus slices (350 μιη) were cut with a Macllwain tissue- chopper and incubated at room temperature for at least 60 minutes in Artificial Cerebro-Spinal Fluid (ACSF) having the following composition:
During experiments, slices were continuously perfused with oxygenated ACSF.
[0090] 500 mg DHA was purchased as a 1.403 M stock solution in 1 ml of ethanol from Cayman Chemicals (ref : 9090310). This solution was diluted into ACSF to prepare 90, 60, 45, 30, or 15 mM stock solution, and then 1000X diluted into ACSF to reach a final 90, 60, 45, 30, or 15 μΜ concentration.
[0091] Curcumin was prepared as a 150, 100, 50, or 25 mM Stock solution in Cremphor El (ref.: C5135, Sigma, batch: 1439553 13509161) from powder on each day of experimentation. This stock solution was then 10000X diluted in ACSF to reach the final 15, 10, 5.0, or 2.5 μΜ concentration.
[0092] D-AP5 (ref: Asc-271, ASCENT, batch: APN08163-1-1) was dissolved as a 30 mM stock solution in water, aliquoted and stored at -20°C until use. Aliquots were thawed and vortexed each day of experiment and then 1000X or 10000X diluted in ACSF to reach the final concentration of 30 μΜ or 3 μΜ.
[0093] NBQX (ref: Asc-045, ASCENT, batch: APN07044-8-3) was dissolved as a 10 mM stock solution in water, aliquoted and stored at -20°C until use. Aliquots were thawed and vortexed each day of experiment and then 1000X diluted in ACSF to reach the final concentration of 10 μΜ.
[0094] All data was recorded with a MEA set-up, commercially available from Multichannel Systems MCS GmbH (Reutlingen, Germany), and composed of a 4-channel stimulus generator and a 60-channels amplifier head-stage connected to a 60-channels A/D card. Software for stimulation, recordings and analysis were commercially available from Multi Channel Systems: MC Stim (3.2.4 release) and MC Rack (4.0.0 release), respectively. All of the experiments were carried out with 3-dimensional MEA (Ayanda Biosystems, S.A., CH-1015 Lausanne, Switzerland) that consisted of 60 tip-shaped and 60^m-high electrodes spaced by 100 μιη. The MEA electrodes were made of platinum with kΩ 450 < impedance < 600 kΩ.
[0095] A 350-μιη thick mouse hippocampal slice was disposed on the multi- electrode array (100 μιη distant electrodes). One electrode was chosen to stimulate Schaeffer collaterals at the CA3/CA1 interface. An I/O curve was performed to monitor evoked-responses for stimulations between 100 and 800 μΑ, by 100 μΑ steps. The stimulus was a monopolar biphasic current pulse (negative for 60 μβ and then positive for 60 μβ), settled to evoke 40% of the maximal amplitude response (as determined with the I/O curve) and applied every 30 seconds to evoke "responses" (i.e. field Excitatory Post Synaptic Potentials; fEPSP) in the CA1 region.
[0096] Short term memory formation, accompanied by a weak potentiation, effect of Curcumun and DHA on LTP induced by a weak tetanus was also analyzed. Following a 10-minute period to verify the baseline stability of fEPSP to elicite a weak potentiation, a weak tetanus (10 stimuli at 100 Hz for 0.1 s at 20% of IMAX (Kanno et al., Brain research, 2004)) was used. Weak tetanus-induced potentiation was followed over a 40-minute period.
[0097] Evoked-responses (fEPSP) were recorded if they satisfied quality criteria described in Standard Operating Procedures: correct location, stable baseline (fluctuation within +/- 10 % during ten consecutive minutes), amplitude > 100 μν after background noise subtraction. The fEPSP from selected electrodes were simultaneously sampled at 5 kHz and recorded on the hard disk of a PC until offline analysis. In parallel, fEPSP amplitudes of selected electrodes were compiled online (with MC Rack program) to monitor and to follow the good performance of the experiments. Data was plotted in a standard spreadsheet file for off-line analysis. The fEPSP resulted from glutamatergic synaptic transmission consecutive to afferent pathway stimulation. At the end of each experiment, 10 μΜ NBQX were perfused on the slice to validate the glutamatergic nature of synaptic transmission as well as to subtract background noise at individual electrode level. Control LTP were recorded in parallel, with hippocampal slices prepared from the same animals as the ones used to evaluate the compounds.
[0098] During experiments, the slices were continuously perfused with ACSF solutions (bubbled with 95% 02-5% C02) at the rate of 3 mL/min with a peristaltic pump (ME A chamber volume: ~1 mL). Complete solution exchange in the ME A chamber was achieved 20 seconds after the switch of solutions. The perfusion liquid was continuously pre-heated at 37 °C just before reaching the MEA chamber with a heated-perfusion cannula (PH01, Multichannel Systems, Reutlingen,
Germany). The temperature of the MEA chamber was maintained at 37 +/- 0.1 °C with a Peltier element located in the MEA amplifier headstage.
[0099] As shown in FIGS. 1A-1D, a combination of Curcumin at 2.5 μΜ and DHA at 22μΜ produced a significant effect in enhancing NMDAR dependant
hippocampal LTP induced by weak tetanic frequency stimulation (one trains of 100 Hz stimulations for 0.1 seconds) of Schaffer collaterals of CA1 region of
hippocampus. Weak stimulation resulted in weak potentiation that normally occurs during short term memory formation.
[00100] Accordingly, Curcumin and DHA showed significant enhancement of hippocampal LTP by modulating the NMDAR activity.
EXAMPLE 22
[0101] In this Example, the ability of Curcumin and DHA to provide neuroprotection to hippocampal neurons from NMDAR mediated excitotoxicity was analyzed.
[0102] One of the major molecular events that contribute to neuronal death or damage in brain malfunctioning, cognitive impairment and neurodegenerative diseases, including Alzheimer's disease (AD), is glutamate or NMDAR mediated excitotoxicity. Glutamate is the major excitatory neurotransmitter in the brain that activates the major ion channel receptors such as NMDAR and AMPAR that contribute to synaptic plasticity. However, excessive release of glutamate and overstimulation of NMDAR can cause neuronal death or damage due to increased calcium influx resulting in the release of proteolytic enzymes, transcription factors and reactive oxygen species. Therefore, compounds or ingredients that prevent NMDAR mediated excitotoxicity will offer neuroprotection. NMDA is a specific agonist of NMDAR that is capable of causing the excitotoxic neuronal death due to
2_|_
the over activation of NMDAR in Mg free medium. The NMDA receptor channel is highly permeable to Ca 2+ but is blocked by Mg 2+ in a voltage-dependent manner. Therefore, in this Example, to induce NMDAR mediated excitotoxicity, NMDA was
2_|_ applied in the presence of different concentrations of Curcumin and DHA in a Mg free medium to hippocampal neurons. Neuroprotective effects of Curcumin and DHA from NMDAR mediated excitotoxicity were evaluated from the amount of lactate dehydrogenase (LDH) enzyme, a stable cytoplasmic enzyme that is released when the
plasma membrane is damaged and released into the cell-culture supernatant in response to NMDAR mediated excitotoxicity.
[0103] Hippocampal neurons were plated in 96-well plates and cultured for 10 days. NMDA and glutamate neurotoxicity assays were performed as detailed below. All preincubation experiments were performed in neurobasal medium
2_|_
containing Mg , which was omitted only when NMDA was added for 15 minutes in Hanks' balanced salt solution containing 10 μΜ glycine and 2.7 mM CaCl2. After 10 days in culture, hippocampal neurons were incubated for 15 minutes with Curcumin (1, 5.0, 10, 20 and 40 μΜ) and DHA (15, 30, 45 and 60 μΜ) in the absence or presence of 200 μΜ NMDA. Cell viability was determined using cytotoxicity assay kits (LDH release, Roche) following the manufacturers' instructions.
[0104] The results demonstrated that Curcumin showed a significant inhibition of LDH release caused by NMDA induced cell death at 5, 10 and 20 μΜ (n=4, p<0.05, FIG. 2A). Curcumin at 1 μΜ showed a significant increase in LDH release caused by NMDA induced cell death. DHA did not show any inhibition of LDH release caused by NMDA induced cell death (i.e., offered neuroprotection) at 45 and 60 μΜ (FIG. 2B).
[0105] Accordingly, Curcumin showed a comparatively significant neuroprotection by inhibiting the over-activation of NMDAR mediated excitotoxicity as compared to DHA (FIGS. 2 A and 2B). Curcumin offers significant
neuroprotection by preventing NMDAR mediated excitotoxicity and resulting neuronal death due to the oxidative stress induced by the increased calcium influx and subsequent release of proteolytic enzymes, transcription factors and reactive oxygen species.
Claims
1. A method for improving in an individual at least one of cognitive performance, memory acquisition, memory recall, N-methyl-D-aspartate receptor dependent hippocampal long term potentiation, and combinations thereof, the method comprising administering to the individual a composition comprising an effective amount of bioavailable Curcumin and an effective amount of docosahexaenoic acid.
2. The method of claim 1 comprising from about 0.002% to about 0.25% bioavailable Curcumin by weight of the composition and from about 0.001% to about 4.6% docosahexaenoic acid by weight of the composition.
3. The method of claim 1 comprising from about 0.1% to about 1.9% bioavailable Curcumin by weight of the composition and from about 0.02% to about 0.4% docosahexaenoic acid by weight of the composition.
4. The method of claim 1 wherein the individual is administered from about 400 milligrams/day to about 2000 milligrams/day of bioavailable Curcumin and from about 100 milligrams/day to about 2000 milligrams/day of docosahexaenoic acid.
5. The method of claim 1 wherein the individual has age-related cognitive decline.
6. The method of claim 1 wherein the individual has a neurodegenerative disease selected from the group consisting of Alzheimer's disease, Huntington's disease, Parkinson's disease, dementia, amyotrophic lateral sclerosis, stroke, and schizophrenia.
7. The method of any one of claims 1 -6, wherein the method improves memory acquisition in the individual.
8. The method of any one of claims 1-6, wherein the method improves memory recall in the individual.
9. The method of any one of claims 1-6, wherein the method improves N- methyl-D-aspartate receptor dependent hippocampal long term potentiation in the individual.
10. A nutritional composition comprising an effective amount of bioavailable Curcumin and docosahexaenoic acid.
11. The nutritional composition of claim 10 comprising from about 0.002% to about 0.25% bioavailable Curcumin by weight of the composition and from about 0.001% to about 4.6% docosahexaenoic acid by weight of the
composition.
12. The nutritional composition of claim 10 comprising from about 0.1% to about 1.9% bioavailable Curcumin by weight of the composition and from about 0.02%) to about 0.4%> docosahexaenoic acid by weight of the composition.
13. The nutritional composition of any one of claims 10-12 further comprising at least one macronutrient selected from the group consisting of proteins, lipids, carbohydrates, sources thereof, and combinations thereof.
14. Use of bioavailable Curcumin and docosahexaenoic acid to improve at least one of cognitive performance, memory acquisition, memory recall, N-methyl-D- aspartate receptor dependent hippocampal long term potentiation, and combinations thereof in an individual.
15. Use according to claim 14, wherein the individual has age-related cognitive decline.
16. Use according to claim 14, wherein the individual has a
neurodegenerative disease selected from the group consisting of Alzheimer's disease, Huntington's disease, Parkinson's disease, dementia, amyotrophic lateral sclerosis, stroke, and schizophrenia.
17. Use according to any one of claims 14-16, wherein the bioavailable Curcumin and docosahexaenoic acid are contained within a nutritional composition
18. Use according to claim 17, wherein the nutritional composition comprises from about 0.002% to about 0.25% bioavailable Curcumin by weight of the nutritional composition and from about 0.001% to about 4.6% docosahexaenoic acid by weight of the nutritional composition.
19. Use according to claim 17, wherein the nutritional composition comprises from about 0.1% to about 1.9% bioavailable Curcumin by weight of the nutritional composition and from about 0.02% to about 0.4% docosahexaenoic acid by weight of the nutritional composition.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161568329P | 2011-12-08 | 2011-12-08 | |
US61/568,329 | 2011-12-08 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2013086330A1 true WO2013086330A1 (en) | 2013-06-13 |
Family
ID=47356320
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2012/068462 WO2013086330A1 (en) | 2011-12-08 | 2012-12-07 | Nutritional compositions comprising curcumin and docosahexaenoic acid for improving cognition |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2013086330A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ITUB20153895A1 (en) * | 2015-09-25 | 2017-03-25 | Pasquale Gualdiero | ASSOCIATION OF CURCUMINA, ARGININA AND VITAMIN D |
CN112888320A (en) * | 2018-11-05 | 2021-06-01 | 雀巢产品有限公司 | Compositions and methods for cellular energy using a combination of curcumin and omega-3 fatty acids |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060166935A1 (en) * | 2005-01-24 | 2006-07-27 | Morten Bryhn | Fatty acid composition for treatment of alzheimer's disease and cognitive dysfunction |
WO2006116755A2 (en) * | 2005-04-28 | 2006-11-02 | Trustees Of Tufts College | Synergitic effects of docosahexaenoic acid (dha) and carotenoid absorption of cognitive function |
US20080181937A1 (en) * | 2007-01-29 | 2008-07-31 | Majid Fotuhi | Dosage regimen and medicament for guarding memory and brain health and for preventing or reducing risk of onset of dementia by administration of specific vitamins and supplements (memoguard) |
US20090324703A1 (en) * | 2006-03-06 | 2009-12-31 | Frautschy Sally A | Bioavailable curcuminoid formulations for treating alzheimer's disease and other age-related disorders |
US20110177061A1 (en) * | 2009-07-10 | 2011-07-21 | Martek Biosciences Corporation | Methods of treating and preventing neurological disorders using docosahexaenoic acid |
-
2012
- 2012-12-07 WO PCT/US2012/068462 patent/WO2013086330A1/en active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060166935A1 (en) * | 2005-01-24 | 2006-07-27 | Morten Bryhn | Fatty acid composition for treatment of alzheimer's disease and cognitive dysfunction |
WO2006116755A2 (en) * | 2005-04-28 | 2006-11-02 | Trustees Of Tufts College | Synergitic effects of docosahexaenoic acid (dha) and carotenoid absorption of cognitive function |
US20090324703A1 (en) * | 2006-03-06 | 2009-12-31 | Frautschy Sally A | Bioavailable curcuminoid formulations for treating alzheimer's disease and other age-related disorders |
US20080181937A1 (en) * | 2007-01-29 | 2008-07-31 | Majid Fotuhi | Dosage regimen and medicament for guarding memory and brain health and for preventing or reducing risk of onset of dementia by administration of specific vitamins and supplements (memoguard) |
US20110177061A1 (en) * | 2009-07-10 | 2011-07-21 | Martek Biosciences Corporation | Methods of treating and preventing neurological disorders using docosahexaenoic acid |
Non-Patent Citations (4)
Title |
---|
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 2004, LIM G P ET AL: "Diets enriched with polyunsaturated DHA (docosahexanoic acid) can lower amyloid levels and plaque burden in an Alzheimer's disease mouse model", XP002369925, retrieved from BIOSIS Database accession no. PREV200400196106 * |
M. GARCIA-ALLOZA ET AL: "Curcumin labels amyloid pathology in�vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model", JOURNAL OF NEUROCHEMISTRY, vol. 102, no. 4, 1 August 2007 (2007-08-01), pages 1095 - 1104, XP055054058, ISSN: 0022-3042, DOI: 10.1111/j.1471-4159.2007.04613.x * |
MATTEUCCI A ET AL: "Curcumin treatment protects rat retinal neurons against excitotoxicity: effect on N-methyl-D-aspartate-induced intracellular Ca2+ increase", EXPERIMENTAL BRAIN RESEARCH, SPRINGER, BERLIN, DE, vol. 167, no. 4, 1 December 2005 (2005-12-01), pages 641 - 648, XP019329131, ISSN: 1432-1106, DOI: 10.1007/S00221-005-0068-0 * |
Q.-L. MA ET AL: "-Amyloid Oligomers Induce Phosphorylation of Tau and Inactivation of Insulin Receptor Substrate via c-Jun N-Terminal Kinase Signaling: Suppression by Omega-3 Fatty Acids and Curcumin", JOURNAL OF NEUROSCIENCE, vol. 29, no. 28, 15 July 2009 (2009-07-15), pages 9078 - 9089, XP055054057, ISSN: 0270-6474, DOI: 10.1523/JNEUROSCI.1071-09.2009 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ITUB20153895A1 (en) * | 2015-09-25 | 2017-03-25 | Pasquale Gualdiero | ASSOCIATION OF CURCUMINA, ARGININA AND VITAMIN D |
CN112888320A (en) * | 2018-11-05 | 2021-06-01 | 雀巢产品有限公司 | Compositions and methods for cellular energy using a combination of curcumin and omega-3 fatty acids |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2021107394A (en) | Nutritional product | |
US10398715B2 (en) | Methods for increasing brain functionality using 2-fucosyl-lactose | |
US9326956B2 (en) | Methods for improving brain development and cognitive function using beta-hydroxy-beta methylbutyrate | |
US20130108706A1 (en) | Dietary formulations | |
JP2005513010A (en) | Preparation for improving receptor action | |
WO2014028607A1 (en) | Low glycemic index nutritional compositions for preserving muscle mass and improving body composition in diabetics | |
EP2859889A1 (en) | Compositions and methods for improving cognitive function | |
Carrie et al. | PUFA for prevention and treatment of dementia? | |
WO2014047614A1 (en) | Nutritional compositions and methods for enhancing cognitive function and muscle function | |
AU2010229066A1 (en) | Nutritional composition comprising curcuminoids and methods of manufacture | |
WO2013086327A1 (en) | Nutritional compositions comprising curcumin and phosphatidylserine-docosahexaenoic acid for improving cognition | |
EP2476425B1 (en) | Composition comprising OPC and Omega-3 for preventing and/or inhibiting the development of diabetic retinopathy | |
CA2838976C (en) | Dha and epa in the reduction of oxidative stress | |
WO2013086330A1 (en) | Nutritional compositions comprising curcumin and docosahexaenoic acid for improving cognition | |
US8440245B2 (en) | Methods for making nutritional compositions comprising curcuminoids | |
CA2914671A1 (en) | Methods and compositions for enhancing cognitive performance | |
JP6067558B2 (en) | How to reduce fear memory | |
CA3167614C (en) | Nutritional compositions and methods containing a lignan and a methyl donor | |
US20100249031A1 (en) | Nutritional Composition Comprising Curcuminoids and Methods of Manufacture | |
Adriana et al. | Synaptosomes as a model to study fish oil and olive oil effect as neuroprotectors | |
Funk Ms | Select Dietary Fatty Acids Modulate Brain Long Chain Omega-3 and Omega-6 PUFA Content in Mice | |
WO2012119049A2 (en) | Nutritional compositions comprising prune extract and bioavailable curcumin |
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: 12799714 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 12799714 Country of ref document: EP Kind code of ref document: A1 |