| Revision as of 13:22, 16 March 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers from ChemSpider, CommonChemistry and FDA for the Chem/Drugbox validation project - Updated: ChEMBL.← Previous edit |
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{{cs1 config|name-list-style=vanc}} |
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{{Use dmy dates|date=March 2023}} |
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{{chembox |
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{{chembox |
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| Verifiedfields = changed |
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| verifiedrevid = 399169109 |
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| Watchedfields = changed |
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|ImageFile=Betain2.svg |
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| verifiedrevid = 419118341 |
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|ImageSize= |
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| ImageFile=Betain2.svg |
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|ImageFile1=Betaine-from-xtal-1999-3D-balls.png |
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| ImageSize= |
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|IUPACName=2-trimethylammonioacetate |
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| ImageFile1=Betaine-from-xtal-1999-3D-balls.png |
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|OtherNames= Betaine, TMG, glycine betaine, betaine anhydrous, N,N,N-trimethylglycine |
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| IUPACName=(Trimethylammonio)acetate |
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|Section1= {{Chembox Identifiers |
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| OtherNames= {{unbulleted list|Betaine|TMG|glycine betaine|''N'',''N'',''N''-trimethylglycine|Cystadane|Amversio}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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|Section1={{Chembox Identifiers |
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| IUPHAR_ligand = 4550 |
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| IUPHAR_ligand_Comment = |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 3SCV180C9W |
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| UNII = 3SCV180C9W |
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| UNII_Comment = |
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| InChI = 1/C5H11NO2/c1-6(2,3)4-5(7)8/h4H2,1-3H3 |
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| InChI = 1/C5H11NO2/c1-6(2,3)4-5(7)8/h4H2,1-3H3 |
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| InChI_Comment = |
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| InChIKey = KWIUHFFTVRNATP-UHFFFAOYAI |
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| InChIKey = KWIUHFFTVRNATP-UHFFFAOYAI |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 1182 |
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| ChEMBL = 1182 |
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| ChEMBL_Comment = |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C5H11NO2/c1-6(2,3)4-5(7)8/h4H2,1-3H3 |
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| StdInChI = 1S/C5H11NO2/c1-6(2,3)4-5(7)8/h4H2,1-3H3 |
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| StdInChI_Comment = |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = KWIUHFFTVRNATP-UHFFFAOYSA-N |
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| StdInChIKey = KWIUHFFTVRNATP-UHFFFAOYSA-N |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo=107-43-7 |
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| CASNo=107-43-7 |
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| CASNo_Comment = |
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| PubChem=247 |
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| PubChem=247 |
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| SMILES=C(C)(C)CC(=O) |
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| PubChem_Comment = |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| KEGG = C00719 |
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| KEGG_Comment = |
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| 3DMet = |
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| Gmelin = 26434 |
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| Beilstein = 3537113 |
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| EC_number = 203-490-6 |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| DrugBank = DB06756 |
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| DrugBank_Comment = |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI = 17750 |
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| ChEBI_Comment = |
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| SMILES=C(C)(C)CC(=O) |
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| SMILES_Comment = |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 242 |
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| ChemSpiderID = 242 |
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| ChemSpiderID_Comment = |
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| MeSHName=Betaine |
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| MeSHName=Betaine |
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}} |
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}} |
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|Section2= {{Chembox Properties |
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|Section2={{Chembox Properties |
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| Formula=C<sub>5</sub>H<sub>11</sub>NO<sub>2</sub> |
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| Formula=C<sub>5</sub>H<sub>11</sub>NO<sub>2</sub> |
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| MolarMass=117.146 |
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| MolarMass=117.146 |
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| Appearance= |
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| Appearance=White solid |
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| Density= |
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| MeltingPt= |
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| Density= |
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| MeltingPt_ref = |
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| BoilingPt= |
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| MeltingPt_notes = (decomposes) |
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| Solubility= |
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| MeltingPtC = 180 |
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}} |
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| BoilingPt= |
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|Section3= {{Chembox Hazards |
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| pKa = 1.84 |
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| MainHazards= |
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| Solubility= Soluble |
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| FlashPt= |
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| SolubleOther = Methanol |
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| Autoignition= |
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}} |
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}} |
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|Section8= {{Chembox Related |
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|Section6={{Chembox Pharmacology |
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| Pharmacology_ref = |
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| OtherFunctn= ]<br>]<br>] |
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| ATCCode_prefix = A16 |
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| Function= ]s |
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| ATCCode_suffix = AA06 |
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}} |
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| ATC_Supplemental = |
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| ATCvet = |
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| Licence_EU=yes |
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| INN = |
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| INN_EMA=Betaine anhydrous |
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| Licence_US = |
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| Legal_status = |
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| Legal_AU = |
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| Legal_AU_comment = |
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| Legal_CA = OTC |
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| Legal_CA_comment = <ref>{{cite web | title=Notice of Amendment: Betaine removed from the Prescription Drug List (PDL) | website=] | date=6 January 2023 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list/notices-changes/amendment-betaine-removed.html | access-date=3 January 2024}}</ref> |
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| Legal_NZ = |
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| Legal_NZ_comment = |
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| Legal_UK = |
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| Legal_UK_comment = |
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| Legal_US = Rx-only |
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| Legal_US_comment = <ref name="Cystadane FDA label">{{cite web | title=Cystadane- betaine powder, for solution | website=DailyMed | date=3 October 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31a684d0-cd98-4e46-b43a-ccbd17c41559 | access-date=29 July 2022 | archive-date=4 August 2021 | archive-url=https://web.archive.org/web/20210804030248/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31a684d0-cd98-4e46-b43a-ccbd17c41559 | url-status=live }}</ref> |
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| Legal_EU = Rx-only |
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| Legal_EU_comment = <ref name="Cystadane EPAR">{{cite web | title=Cystadane EPAR | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/cystadane | access-date=29 July 2022 | archive-date=1 July 2022 | archive-url=https://web.archive.org/web/20220701191037/https://www.ema.europa.eu/en/medicines/human/EPAR/cystadane | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref name="Amversio EPAR">{{cite web | title=Amversio EPAR | website=European Medicines Agency | date=21 February 2022 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/amversio | access-date=29 July 2022 | archive-date=30 July 2022 | archive-url=https://web.archive.org/web/20220730050722/https://www.ema.europa.eu/en/medicines/human/EPAR/amversio | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> |
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| Legal_UN = |
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| Legal_UN_comment = |
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| Pregnancy_category = |
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| Pregnancy_AU = |
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| Pregnancy_AU_comment = |
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| Dependence_liability = |
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| AdminRoutes = ] |
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| Bioavail = |
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| ProteinBound = |
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}} |
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|Section7={{Chembox Hazards |
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| MainHazards= |
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| FlashPt= |
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| AutoignitionPt = |
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| GHSPictograms = {{GHS07}} |
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| GHSSignalWord = Warning |
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| HPhrases = {{H-phrases|315|319}} |
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| PPhrases = {{P-phrases|264|280|302+352|305+351+338|321|332+313|337+313|362}} |
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}} |
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|Section8={{Chembox Related |
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| OtherFunction = ]<br>]<br>] |
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| OtherFunction_label = ]s |
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'''Trimethylglycine''' ('''TMG''') is an ] that occurs in plants as either '''glycine betaine''' or a choline-containing glycine betaine compound. Trimethylglycine was the first ] discovered by science; originally it was simply called '''betaine''' because, in the 19th century, it was discovered in ]s.<ref name=Ullmann>Hubert Schiweck, Margaret Clarke, Günter Pollach "Sugar” in Ullmann’s Encyclopedia of Industrial Chemistry 2007, Wiley-VCH, Weinheim.{{DOI|10.1002/14356007.a25_345.pub2}}</ref> Since then, many other betaines have been discovered, and the more specific name ''glycine betaine'' distinguishes this one. |
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'''Trimethylglycine''' is an ] derivative with the formula {{chem2|(CH3)3N+CH2CO2-}}. A colorless, water-soluble solid, it occurs in plants.<ref name=Ashraf>{{cite journal |doi=10.1016/j.envexpbot.2005.12.006 |title=Roles of glycine betaine and proline in improving plant abiotic stress resistance |date=2007 |last1=Ashraf |first1=M. |last2=Foolad |first2=M.R. |journal=Environmental and Experimental Botany |volume=59 |issue=2 |pages=206–216 }}</ref> Trimethylglycine is a ]: the molecule contains both a ] group and a carboxylate group. Trimethylglycine was the first ] discovered; originally it was simply called '''betaine''' because it was discovered in ]s (''Beta vulgaris'' subsp. ''vulgaris'').<ref name=Ullmann>{{Ullmann|first1=Hubert|last1=Schiweck|first2=Margaret|last2=Clarke|first3=Günter|last3=Pollach|title=Sugar|doi=10.1002/14356007.a25_345.pub2}}</ref> Several other betaines are now known. |
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== Medical uses == |
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==Structure and reactions== |
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Betaine, sold under the brand name '''Cystadane''' is ] for the adjunctive treatment of homocystinuria, involving deficiencies or defects in cystathionine beta-synthase (CBS), 5,10-methylene-tetrahydrofolate reductase (MTHFR), or cobalamin cofactor metabolism (cbl).<ref name="Cystadane FDA label" /><ref name="Cystadane EPAR" /><ref name="Amversio EPAR" /><ref>{{Cite journal |last1=Arumugam |first1=Madan Kumar |last2=Paal |first2=Matthew C. |last3=Donohue |first3=Terrence M. |last4=Ganesan |first4=Murali |last5=Osna |first5=Natalia A. |last6=Kharbanda |first6=Kusum K. |date=2021-05-22 |title=Beneficial Effects of Betaine: A Comprehensive Review |journal=Biology |language=en |volume=10 |issue=6 |pages=456 |doi=10.3390/biology10060456 |doi-access=free |pmid=34067313 |pmc=8224793 |issn=2079-7737 }}</ref> |
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Trimethylglycine is an N-trimethylated amino acid. This ] exists as the ] at neutral pH. Strong acids such as ] converts TMG to the salt betaine hydrochloride: |
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:(CH<sub>3</sub>)<sub>3</sub>N<sup>+</sup>CH<sub>2</sub>CO<sub>2</sub><sup>-</sup> + HCl → <sup>+</sup>Cl<sup>-</sup> |
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] of TMG gives ]. Degradation of TMG yields ], the scent of putrifying fish. |
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The most common side effect is elevated levels of ] in the blood.<ref name="Cystadane EPAR" /> |
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==Production and biochemical processes== |
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] ] from sugar beets yields glycine betaine as a ]. The value of the TMG rivals that of the sugar content in sugar beets.<ref name=Makela/> Glycine betaine production involves ]. |
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The EU has authorized the health claim that betaine "contributes to normal ] metabolism.".<ref name="efsa2014">{{cite book |author1=K.K. Tiihonen |author2=K. Riihinen |author3=M. Lyyra |author4=E. Sarkkinen |author5=S.A.S. Craig |author6=P. Tenning |editor1-last=Sadler |editor1-first=M.J. |title=Foods, Nutrients and Food Ingredients with Authorised EU Health Claims |date=2014 |publisher=Woodhead Publishing |isbn=978-0-85709-842-9 |pages=251–273 |url=https://www.sciencedirect.com/book/9780857098429/foods-nutrients-and-food-ingredients-with-authorised-eu-health-claims |access-date=19 February 2024 |chapter=12 - Authorised EU health claims for betaine |quote=The European Food Safety Authority (EFSA) agreed that there is sufficient substantiation of the health claim for betaine concerning its contribution to normal homocysteine metabolism (EFSA, 2011a).}}</ref> |
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===Biosynthesis=== |
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In most organisms, glycine betaine is biosynthesized by oxidation of ] in two steps. The intermediate, ], is generated by the action of the enzyme mitochondrial choline oxidase (], EC 1.1.99.1). Betaine aldehyde is further oxidised in the ] or cytoplasm to betaine by the enzyme called betaine aldehyde dehydrogenase (EC 1.1.1.8).<ref name=Kempf>Kempf, B.; Bremer, E."Uptake and synthesis of compatible solutes as microbial stress responses to high-osmolality environments" Arch Microbiol. 1998, volume 170, pp. 319-30. {{DOI|10.1074/jbc.M210970200}}<!--PMID: 981835--></ref> |
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===Biological function=== |
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==Biological function== |
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=== Biosynthesis === |
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TMG is an organic ] that occurs in high concentrations (10s of millimolar) in many marine invertebrates, such as crustaceans and molluscs. It serves as a potent appetitive attractant to generalist carnivores such as the predatory sea-slug ''Pleurobranchaea californica''.<ref>Gillette R, Huang R-C, Hatcher N, Moroz LL (2000)''Cost-benefit analysis potential in feeding behavior of a predatory snail by integration of hunger, taste and pain.'' Proc Natl Acad Sci USA '''97''': 3585-90 PMID: 10737805</ref> |
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In most organisms, glycine betaine is biosynthesized by oxidation of ]. The intermediate, ], is generated by the action of the enzyme mitochondrial choline oxidase (], EC 1.1.99.1). In mice, betaine aldehyde is further oxidised in the ] by the enzyme ] (EC 1.2.1.8).<ref name=Kempf>{{cite journal | last1 = Kempf | first1 = B. | last2 = Bremer | first2 = E. | s2cid = 8045279 | year = 1998 | title = Uptake and synthesis of compatible solutes as microbial stress responses to high-osmolality environments | journal = Arch. Microbiol. | volume = 170 | issue = 5| pages = 319–330 | pmid = 9818351 | doi=10.1007/s002030050649| bibcode = 1998ArMic.170..319K }}</ref><ref>{{cite web |url=http://www.brenda-enzymes.org/enzyme.php?ecno=1.2.1.8 |title=BRENDA – Information on EC 1.2.1.8 – betaine-aldehyde dehydrogenase |website=Brenda-enzymes.org |access-date=7 July 2016 |archive-date=29 June 2016 |archive-url=https://web.archive.org/web/20160629164045/http://www.brenda-enzymes.org/enzyme.php?ecno=1.2.1.8 |url-status=live }}</ref> In humans betaine aldehyde activity is performed by a nonspecific ] enzyme (EC 1.2.1.3) <ref>{{cite journal | last1 = Chern | first1 = M. K. | last2 = Pietruszko | first2 = R. | year = 1999 | title = Evidence for mitochondrial localization of betaine aldehyde dehydrogenase in rat liver: purification, characterization, and comparison with human cytoplasmic E3 isoenzyme | journal = Biochemistry and Cell Biology | volume = 77 | issue = 3| pages = 179–187 | pmid = 10505788 | doi=10.1139/o99-030}}</ref> |
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Trimethylglycine is produced by some ], as established by ]. It is proposed to protect for some ] by ] and ].<ref name="Rhodes-Hanson-1993">{{cite journal | last1=Rhodes | first1=D. | last2=Hanson | first2=A. D. | title=Quaternary Ammonium and Tertiary Sulfonium Compounds in Higher Plants | journal=] | publisher=] | volume=44 | issue=1 | year=1993 | issn=1040-2519 | doi=10.1146/annurev.pp.44.060193.002041 | pages=357–384}}</ref> |
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TMG is an important ] in ], a process that occurs in every cell of mammals to synthesize and donate ]s (CH<sub>3</sub>) for other processes in the body. These processes include the synthesis of ]s such as ], ]. Methylation is also required for the biosynthesis of ] and the ] constituent ]. |
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====Osmolyte==== |
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The major step in the methylation cycle is the remethylation of homocysteine, which can occur via either of two pathways. The major pathway involves the enzyme ], which requires vitamin B<sub>12</sub> as a cofactor, and also depends indirectly on ] and various other B vitamins. The minor pathway involves ] and requires TMG as a cofactor. Betaine is thus involved in the synthesis of many biologically important molecules, and may be even more important in situations where the major pathway for the regeneration of methionine from homocysteine has been compromised by genetic polymorphisms. |
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Trimethylglycine is an ], a water-soluble salt-like substance. Sugar beet was cultivated from ], which requires osmolytes in order to survive the salty soils of coastal areas. Trimethylglycine also occurs in high concentrations (~10 mM) in many marine invertebrates, such as ]s and ]s. It serves as a appetitive attractant to generalist carnivores such as the predatory ] '']''.<ref>{{cite journal | pmid = 10737805 | volume=97 | issue=7 | title=Cost-benefit analysis potential in feeding behavior of a predatory snail by integration of hunger, taste, and pain | pmc=16283 |date=March 2000 | journal=Proc. Natl. Acad. Sci. USA | pages=3585–3590 |last1=Gillette |first1=R. |last2=Huang |first2=R. C. |last3=Hatcher |first3=N. |last4=Moroz |first4=L. L. | doi=10.1073/pnas.97.7.3585| bibcode=2000PNAS...97.3585G | doi-access=free | title-link=doi }}</ref> |
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====Methyl donor==== |
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==TMG in agriculture and aquaculture== |
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Trimethylglycine is a ] in ], a process that occurs in all mammals. These processes include the synthesis of ]s such as ] and ]. Methylation is also required for the biosynthesis of ] and the ] constituent ], as well as the methylation of DNA for epigenetics. One step in the methylation cycle is the ] of ], a compound which is naturally generated during demethylation of the essential amino acid ]. Despite its natural formation, homocysteine has been linked to inflammation, depression, specific forms of dementia, and various types of vascular disease. The remethylation process that detoxifies homocysteine and converts it back to methionine can occur via either of two pathways. The pathway present in virtually all cells involves the enzyme ] (MS), which requires ] as a cofactor, and also depends indirectly on ] and other ]. The second pathway (restricted to liver and kidney in most mammals) involves ] and requires trimethylglycine as a cofactor. During normal physiological conditions, the two pathways contribute equally to removal of homocysteine in the body.<ref>{{Cite journal|last=Finkelstein|first=J. D.|date=24 March 1998|title=The metabolism of homocysteine: pathways and regulation|journal=European Journal of Pediatrics|language=en|volume=157|issue=S2|pages=S40–S44|doi=10.1007/pl00014300|pmid=9587024|s2cid=38134977|issn=0340-6199}}</ref> Further degradation of betaine, via the enzyme ] produces folate, thus contributing back to methionine synthase. Betaine is thus involved in the synthesis of many biologically important molecules, and may be even more important in situations where the major pathway for the regeneration of methionine from homocysteine has been compromised by genetic polymorphisms such as mutations in the MS gene. |
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The largest use of TMG is as a food supplement in livestock industry. Even though TMG is biosynthesized by all animals in the usual way, TMG is helpful for raising beef and chicken. |
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==Agriculture and aquaculture== |
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] apply TMG to relieve the osmotic pressure on salmons' cells when workers transfer the fish from freshwater to saltwater.<ref name=Makela>P. Mäkelä "Agro-industrial uses of glycinebetaine" Sugar Tech 2004 Volume 6, 207-212. {{DOI|10.1007/BF02942500}}</ref><ref>Xue, M. Xie, S. & Cui Y. (2004). Effect of a feeding stimulant on feeding adaptation of gibel carp ''Carassius auratus gibelio'' (Bloch), fed diets with replacement of fish meal by meat and bone meal. Aquaculture Research, 35: 473-482.</ref> |
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Trimethylglycine is used as a supplement for both animals and plants.<ref name=Ashraf/> ] ] from sugar beets yields glycine betaine as a ]. The economic significance of trimethylglycine is comparable to that of sugar in sugar beets.<ref name=Makela/> |
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]s apply trimethylglycine to relieve the osmotic pressure on the fishes' cells when workers transfer the fish from freshwater to saltwater.<ref name="Makela">{{cite journal|first=P.|last=Mäkelä|s2cid=25219649|title=Agro-industrial uses of glycinebetaine|journal=Sugar Tech.|date=2004|volume=6|issue=4|pages=207–212|doi=10.1007/BF02942500|hdl=10138/312331|hdl-access=free | title-link=doi }}</ref><ref name="Xue">{{cite journal|last1=Xue|first1=M.|last2=Xie|first2=S.|last3=Cui|first3=Y.|date=2004|title=Effect of a feeding stimulant on feeding adaptation of gibel carp ''Carassius auratus gibelio'' (Bloch), fed diets with replacement of fish meal by meat and bone meal|journal=Aquaculture Research|volume=35|issue=5|pages=473–482|doi=10.1111/j.1365-2109.2004.01041.x|s2cid=84304519 |doi-access=free}}</ref> |
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Trimethylglycine supplementation decreases the amount of ] in pigs; however, research in human subjects has shown no effect on body weight, body composition, or resting energy expenditure.<ref name="pmid12399266">{{cite journal |last1=Schwab |first1=U. |last2=Törrönen |first2=A. |last3=Toppinen |first3=L. |display-authors=etal |title=Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects |journal=Am. J. Clin. Nutr. |volume=76 |issue=5 |pages=961–967 |date=November 2002 |pmid=12399266 |doi= 10.1093/ajcn/76.5.961|doi-access=free | title-link=doi }}</ref> |
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== Nutrition == |
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Nutritionally, betaine is not needed when sufficient dietary choline is present for synthesis.<ref name=ze>{{Cite book|title=Handbook of vitamins |url=https://archive.org/details/handbookvitamins00jzem |url-access=limited |vauthors= Rucker RB, Zempleni J, Suttie JW, McCormick DB |publisher=Taylor & Francis |year=2007 |isbn=978-0-8493-4022-2 |edition=4th |pages=–477 }}</ref> When insufficient betaine is available, elevated homocysteine levels and decreased SAM levels in blood occur. Supplementation of betaine in this situation would resolve these blood marker issues, but not compensate for other functions of choline.<ref name=eu>{{Cite journal|date=2016|title=Dietary reference values for choline|journal=EFSA Journal|volume=14|issue=8|doi=10.2903/j.efsa.2016.4484|doi-access=free}}</ref> |
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TMG is also beneficial to crop yields, e.g. ] and ].<ref name=Makela/> |
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==TMG in the human diet== |
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{| class="wikitable" |
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{| class="wikitable" |
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|+ Betaine in foods<ref name="usda-choline">{{Cite journal |date=1 November 2019 |title=USDA Database for the Choline Content of Common Foods, Release 2 (2008) |url=https://data.nal.usda.gov/dataset/usda-database-choline-content-common-foods-release-2-2008 |access-date=2 February 2021 |website=] |doi=10.15482/USDA.ADC/1178141 |archive-date=30 July 2022 |archive-url=https://web.archive.org/web/20220730040040/https://data.nal.usda.gov/dataset/usda-database-choline-content-common-foods-release-2-2008 |url-status=live |last1=Patterson |first1=Kristine Y. |last2=Bhagwat |first2=Seema A. |last3=Williams |first3=Juhi R. |last4=Howe |first4=Juliette C. |last5=Holden |first5=Joanne M. |last6=Zeisel |first6=Steven H. |last7=Dacosta |first7=Kerry A. |last8=Mar |first8=Mei-Heng }}</ref> |
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|+ TMG in foods |
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|- |
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! Food |
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! Food |
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! Betaine (mg/100 g) |
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! TMG per 100g |
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|- |
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| ], toasted<ref name="zeisel2003">{{cite journal |author1=Steven H Zeisel |author2=Mei-Heng Mar |author3=Juliette C Howe |author4=Joanne M Holden |title=Concentrations of choline-containing compounds and betaine in common foods |journal=The Journal of Nutrition |date=May 2003 |volume=133 |issue=5 |pages=1302–7 |doi=10.1093/jn/133.5.1302 |pmid=12730414 |doi-access=free }}</ref> |
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| 1240 |
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|- |
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|- |
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| ] |
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| ] |
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| 630 mg |
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| 630 |
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|- |
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|- |
|
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| ] |
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| ] |
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|
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| 410 |
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| 577 mg |
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|- |
|
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| ] |
|
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| 330 |
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|- |
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|- |
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| ] ] |
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| ] ] |
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| 320 |
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| 360 mg |
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|- |
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|- |
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| ] |
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| Canned ] |
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| 260 |
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| 332 mg |
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|- |
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|- |
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| ] |
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| Dark ] |
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| 150 |
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| 256 mg |
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|- |
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| ] |
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| 110-130 |
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|} |
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|} |
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===Nutritional supplement=== |
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=== Dietary supplement === |
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Although trimethylglycine supplementation decreases the amount of ] in pigs, research on human subjects has shown no effect on body weight, body composition, or resting energy expenditure when used in conjunction with a low calorie diet.<ref name="pmid12399266"/> The US ] (FDA) approved betaine trimethylglycine (also known by the brand name Cystadane) for the treatment of ], a disease caused by abnormally high ] levels at birth.<ref name="homocysteine">{{cite journal | pmid = 15550695 | doi=10.1161/01.ATV.0000151283.33976.e6 | volume=25 | issue=2 | title=Betaine and folate status as cooperative determinants of plasma homocysteine in humans |date=February 2005 | journal=Arterioscler. Thromb. Vasc. Biol. | pages=379–385 |last1=Holm |first1=P. I. |last2=Ueland |first2=P. M. |last3=Vollset |first3=S. E. |display-authors=etal |doi-access=free | title-link=doi }}</ref> Trimethylglycine is also used as the ] ] (marketed as betaine hydrochloride or betaine HCl). Betaine hydrochloride was sold ] as a purported gastric aid in the United States. US Code of Federal Regulations, Title 21, Section 310.540, which became effective in November 1993, banned the marketing of betaine hydrochloride as a digestive aid due to insufficient evidence to classify it as "generally recognized as safe and effective" for that specified use.<ref>{{Cite web|url=https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=310.545&SearchTerm=betaine%20hydrochloride|title=CFR - Code of Federal Regulations Title 21|website=U.S. Food & Drug Administration|access-date=4 September 2018|archive-date=27 July 2020|archive-url=https://web.archive.org/web/20200727002957/https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=310.545&SearchTerm=betaine+hydrochloride|url-status=live}}</ref> |
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Although TMG supplementation decreases the amount of ] in pigs, research on human subjects has shown no effect on body weight, body composition, or resting energy expenditure.<ref name="pmid12399266">{{cite journal |author=Schwab U, Törrönen A, Toppinen L, ''et al.'' |title=Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects |journal=Am. J. Clin. Nutr. |volume=76 |issue=5 |pages=961–7 |year=2002 |month=November |pmid=12399266 |doi= |url=http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=12399266}}</ref> |
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The Food and Drug Administration of the United States approved '''anhydrous trimethylglycine''' (also known by the brand name '''Cystadane''') for the treatment of ], a disease caused by abnormally high ] levels at birth.<ref name="homocysteine">Holm PI, Ueland PM, Vollset SE, Midttun O, Blom HJ, Keijzer MB, den Heijer M. (2005) ''Betaine and folate status as cooperative determinants of plasma homocysteine in humans.'' Arterioscler Thromb Vasc Biol. 379-85. PMID 15550695</ref> |
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==== Side effects ==== |
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TMG supplementation may cause ], stomach upset, or ]. Obese persons or those with kidney disease supplementing with TMG, ], and ] can experience an increase in total cholesterol levels.<ref>http://www.umm.edu/altmed/articles/betaine-000287.htm</ref> |
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Trimethylglycine supplementation may cause ], bloating, cramps, ], ] or vomiting.<ref name=":0">{{Citation |title=Betaine |date=2012 |url=http://www.ncbi.nlm.nih.gov/books/NBK548774/ |work=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury |access-date=2023-07-14 |place=Bethesda (MD) |publisher=National Institute of Diabetes and Digestive and Kidney Diseases |pmid=31644082}}</ref> Although rare, it can also causes excessive increases in serum methionine concentrations in the brain, which may lead to ], a life-threatening condition.<ref name=":0" /> |
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Trimethylglycine supplementation lowers homocysteine but also raises ] in obese individuals and renal patients.<ref>{{cite journal |vauthors=Olthof MR, van Vliet T, Verhoef P, Zock PL, Katan MB |title=Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans |journal=PLOS Med. |volume=2 |issue=5 |pages=e135 |year=2005 |pmid=15916468 |pmc=1140947 |doi=10.1371/journal.pmed.0020135 |doi-access=free }}</ref> |
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===Other uses: PCR===<!--seems highly specialized--> |
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<!-- |
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Trimethylglycine can act as an ] of the ] (PCR) process, and other ]-based assays such as ]. By an unknown mechanism, it aids in the prevention of secondary structures in the DNA molecules, and prevents problems associated with the amplification and sequencing of GC-rich regions. Trimethylglycine makes ] and ] (strong binders) behave with thermodynamics similar to those of ] and ] (weak binders). It has been determined under experiment that it is best used at a final concentration of 1M <ref name="pmid9380524">{{cite journal |author=Henke W, Herdel K, Jung K, Schnorr D, Loening SA |title=Betaine improves the PCR amplification of GC-rich DNA sequences. |journal=Nucleic Acids Res |volume=25 |issue=19 |pages=3957–8 |year=1997 |month=October |pmid=9380524 |doi= 10.1093/nar/25.19.3957|url=http://www.pubmed.com/9380524 |pmc=146979}}</ref>. |
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== Other uses == |
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=== Polymerase chain reaction ===seems highly specialized |
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===Speculative uses<!--for lack of a better term-->=== |
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Trimethylglycine can act as an ] of the ] (PCR) process, and other ]-based assays such as ]. By an unknown mechanism, it aids in the prevention of secondary structures in the DNA molecules, and prevents problems associated with the amplification and sequencing of GC-rich regions. Trimethylglycine makes ] and ] (strong binders) behave with thermodynamics similar to those of ] and ] (weak binders). It has been determined under experiment that it is best used at a final concentration of 1 M.<ref name="pmid9380524">{{cite journal |last1=Henke |first1=W. |last2=Herdel |first2=K. |last3=Jung |first3=K. |last4=Schnorr |first4=D. |last5=Loening |first5=S. A. |title=Betaine improves the PCR amplification of GC-rich DNA sequences. |journal=Nucleic Acids Res. |volume=25 |issue=19 |pages=3957–3958 |date=October 1997 |pmid=9380524 |doi=10.1093/nar/25.19.3957 |url=http://www.pubmed.com/9380524 |archive-url=https://archive.today/20130731191555/http://www.pubmed.com/9380524 |url-status=dead |archive-date=31 July 2013 |pmc=146979 }}</ref>--> |
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Laboratory studies and two clinical trials have indicated that TMG is a potential treatment of non-alcoholic ].<ref>{{cite journal |
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| author = Angulo P, Lindor KD |
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| title = Treatment of nonalcoholic fatty liver: present and emerging therapies |
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| journal =Semin Liver Dis |
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| volume =21 |
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| issue =1 |
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| pages =81–88 |
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| year =2001 |
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| doi = 10.1055/s-2001-12931 |
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| pmid = 11296699}}</ref><ref>{{cite journal |author=Abdelmalek MF, Sanderson SO, Angulo P, ''et al.'' |title=Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial |journal=Hepatology |volume=50 |issue=6 |pages=1818–26 |year=2009 |month=December |pmid=19824078 |doi=10.1002/hep.23239 |url=}}</ref><ref>{{cite journal |author=Miglio F, Rovati LC, Santoro A, Setnikar I |title=Efficacy and safety of oral betaine glucuronate in non-alcoholic steatohepatitis. A double-blind, randomized, parallel-group, placebo-controlled prospective clinical study |journal=Arzneimittelforschung |volume=50 |issue=8 |pages=722–7 |year=2000 |month=August |pmid=10994156 |doi= |url=}}</ref> |
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== References == |
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TMG is sometimes used as a treatment for depression, as it can increase ] (SAMe) by remethylating homocysteine. SAMe has been shown to work as a nonspecific antidepressant in several studies.{{Citation needed|date=August 2010}} |
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{{Reflist}} |
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== External links == |
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==References== |
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* – including the data on choline metabolites, such as betaine, in 434 food items. |
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{{Reflist|2}} |
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{{Other alimentary tract and metabolism products}} |
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==External links== |
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{{Portal bar | Medicine}} |
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* - including the data on choline metabolites, such as betaine, in 434 food items. |
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{{Neurotransmitters}} |
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{{Glycinergics}} |
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