sunnuntai 2. marraskuuta 2014

Ravinnon aminohapot ja metabolinen oireyhtymä: glysiini, metioniini, tauriini, GABA ja histidiini

Kirjoituksen englanninkielinen, täydennetty versio löytyy täältä.


1. Aminohappojen vaikutuksia metaboliseen oireyhtymään: Glysiini ja metioniini

Kesällä julkaistussa tanskalaistutkimuksessa havaittiin, että runsaasti rasvaa ja sokeria sisältävä “roskaruokavalio” aiheutti hiirille lihavuutta ja lipidiaineenvaihdunnan häiriöitä kun proteiininlähteenä käytettiin kanaa, turskaa tai rapua. Sen sijaan kampasimpukan syöminen esti kaikki edellämainitut ongelmat. Tutkijat vertasivat näiden proteiininlähteiden aminohappokoostumuksia, ja havaitsivat että kampasimpukka sisältää näistä eniten glysiiniä ja tauriinia, ja vähiten metioniinia.[1]


Kampasimpukkaryhmän (Scallop) hiiret olivat huomattavan
laihoja muihin ryhmiin nähden. Kuvassa näkyy eri
rasvakudosten massoja: esimerkiksi "AbWAT"
(abdominal white adipose tissue) viittaa vatsan
alueen rasvakudoksen massaan.  (Tastesen et al. 2014)

Tutkimuskirjallisuudesta löytyy muitakin raportteja, joissa tietty proteiinin lähde (esim. kalaproteiini tai riisiproteiini) on vähentänyt tulehdusta ja kolesteroliarvoja ihmisillä ja rotilla. Tutkijat yhdistävät kalaproteiinien anti-inflammatoriset vaikutukset niiden arginiini-, glysiini- ja tauriinisisältöihin.[2]

Olen erityisen suurella kiinnostuksella seurannut glysiiniin liittyvää tutkimusta, huomattuani ko. aminohapon myönteisen vaikutuksen useiden eri sairauksien eläinmalleihin. Koe-eläimillä glysiinin on havaittu suojaavan tehokkaasti mm. metaboliselta oireyhtymältä, syövältä, maksavaurioilta, diabeteksen haitoilta, eläinproteiinin haittavaikutuksilta, endotoksiinilta, hapenpuutteelta, verenvuotoshokilta, lyijyn ja kadmiumin myrkyllisyydeltä, hampaiden reikiintymiseltä, ruoansulatuskanavan vaurioilta ja raskausepämuodostumilta. Eräässä rottatutkimuksessa havaittiin myös 28 prosentin elinajan mediaanin pidennys. Havainnot viittaavat siihen, että glysiinillä saattaisi tietyissä tilanteissa olla hyvin laajamittaisia myönteisiä vaikutuksia elimistön toimintaan.[3]

Eräs meksikolainen tutkimusryhmä on havainnut tutkimuksissaan, että maltillinen määrä glysiiniä (noin 1.5% kaloreista) paransi lyhyessä ajassa lähes kaikki sokeriruokinnan koe-eläimille aiheuttamat haitat (verenpaine, rasvakudos, dyslipidemia, hyperinsulinemia) ja suojasi tehokkaasti myös alkoholin aiheuttamilta maksahaitoilta.[4]

Olen kuvaillut kyseisen tutkimusryhmän yhtä glysiinitutkimusta seuraavasti:
Vuonna 2004 julkaistussa meksikolaistutkimuksessa rottien juomaveteen lisättiin 30% sokeria, jolloin rottien ainoa veden lähde sisälsi sokeria lähes kolminkertaisesti verrattuna tyypilliseen tuoremehuun tai virvoitusjuomaan. Tämän vuoksi rotat saivat vedenjuonnin ohessa niin suuren määrän sokeria että varsinaiselle proteiinia, vitamiineja sekä mineraaleja sisältävälle ruoalle ei jäänyt juurikaan tilaa ja sen saanti vähenikin yli 50 prosentin verran.
Tuloksena syntynyt ravinneköyhä, äärimmäisen runsassokerinen ruokavalio aiheutti rotille huomattavaa verenpaineen nousua, keskivartalolihavuutta, veriarvojen huononemista sekä muita ongelmia. Kuitenkin, jos juomaveteen lisättiin sokerin lisäksi myös 1% glysiiniä, lähes kaikki ravinneköyhän ja sokeripitoisen ruokavalion haitat kumoutuivat neljässä viikossa - vaikka rotat olivat noudattaneet haitallista ruokavaliota tätä ennen kaksikymmentä viikkoa eli viisinkertaisen ajan.
Rottien verenpaineen lasku glysiinilisän myötä sekä rasvasolujen
 pienempi koko glysiiniryhmässä. (El Hafidi et al. 2004)

Ihmisillä glysiinin vaikutuksista on tehty kaksi kliinistä tutkimusta, joissa tarkastellaan ko. aminohapon runsaan ravintolisäkäytön vaikutusta metaboliseen oireyhtymään (15 grammaa päivässä, tutkimusten kesto 3kk).

Havaitut muutokset jäivät huomattavasti vähäisemmiksi kuin jyrsijätutkimuksissa, mutta kuitenkin esimerkiksi hapetusstressimarkkerien osalta glysiinistä saatiin hyötyä. Aihe kaivannee vielä pidempiaikaisia tutkimuksia mahdollisten hyötyjen selvittämiseksi.[5]

Ihmisillä on toteutettu myös muutama tutkimus, joissa koehenkilöt (diabeetikoita, ikäihmisiä, HIV-potilaita) saivat sekä glysiiniä että N-asetyyli-kysteiiniä (NAC) useita grammoja päivässä kahden viikon ajan. Yhdistelmä mm. tehosti koehenkilöiden glutationisynteesiä huomattavasti, ja lisäksi mm. palautti ikäihmisten energia-aineenvaihdunnan nuorten ihmisten tasolle, vähentäen samalla myös hapetusstressiä huomattavasti. Samansuuntaisia tuloksia saavutettiin ihmisten lisäksi myös hiirillä.[6]

Glysiini+NAC -yhdistelmä parantaa terveiden ikäihmisten
rasvanpolttokykyä (NEFA Ox), insuliiniherkkyyttä
(HOMA-IR) ja alentaa useita
hapetusstressin markkereita.
(Sekhar et al. 2011Nguyen et al. 2013)

Kyseiset lyhyellä aikavälillä havaitut muutokset koehenkilöiden biokemiassa ovat hyvin vaikuttavia, joten on sääli että tutkijat eivät mitanneet glysiinin ja NAC:n vaikutuksia erikseen vaan ainoastaan yhdessä. Emme täten tiedä, johtuuko vaikutus enemmän glysiinistä vai kysteiinistä. Kyseessä on mahdollisesti yhteisvaikutus eikä pelkästään glysiinin oma vaikutus.

Glysiinistä puhuessa voi olla hyödyllistä ottaa esille myös toinen aminohappo, metioniini. Eläintutkimusten perusteella metioniinin runsas saanti saattaa altistaa metaboliselle oireyhtymälle, ja täten joissakin tutkimuksissa kyseisen aminohapon saannin erityinen vähentäminen on suojannut koe-eläimiä lihavuudelta (ja pidentänyt elinikää).[7]

Useimmissa tutkimuksissa on metioniinirajoitus on ollut melko merkittävä (80%), mutta joitakin aineenvaihdunnallisia hyötyjä on saatu aikaan maltillisemmalla rajoituksella (40%).[7]


Maltillinen metioniinirajoitus (40%) näyttää suojaavan ainakin
rottien mitokondrioita erilaisilta hapetusvaurioilta.
[GSA: glutamic semialdehyde; AASA: aminoadipic semialdehyde;
CEL: carboxyethyl-lysine; CML: carboxymethyl-lysine; MDAL: malondialdehyde-lysine]
(Caro et al. 2008)

Toisaalta täytyy tiedostaa, että monissa tutkimuksissa metioniinirajoitus on toteutettu hyvin yksinkertaisilla ruokavalioilla, joista on saattanut esimerkiksi puuttua kysteiini-aminohappo kokonaan. Kysteiinin tuominen ruokavalioon on monissa tutkimuksissa estänyt metioniinirajoitukseen liittyvän laihtumisen ja eliniän pitenemisen, joten on syytä miettiä, onko joidenkin hyötyjen taustalla jonkinlainen puutostila.

Metioniinin ja glysiinin yhteyksiä tarkastelevassa kirjallisuudessa tarina kulkeekin hieman eri näkökulmasta. Metioniinin liikasaannin haittoja on perusteltu sillä, että ylimääräinen metioniini aktivoi GNMT-entsyymiä ja tätä kautta kuluttaa glysiiniä. Glysiinillä on tulehdusta hillitseviä ominaisuuksia, joten sen tasojen aleneminen runsasmetioniinisellä ruokavaliolla voi täten altistaa tulehdussairauksille. Tästä perspektiivistä ajatellen metioniinirajoituksen hyötyjen voisi kuvitella johtuvan osaltaan myös siitä, että GNMT-entsyymin vähäinen toiminta pitää glysiinitasot korkealla ja tulehduksen täten hallinnassa.[7]

Eläintutkimuksissa glysiini on suojannut metioniinin haitoilta myös muilla tavoin kuten vähentämällä homokysteiinitasoja huomattavasti. Mekanismi liittynee siihen, että glysiini muuttuu seriiniksi, joka lisää homokysteiinin muuntoa kystationiksi CBS-entsyymin avulla. Täten näyttäisi olevan parikin erilaista mekanismia, joilla metioniini voi aiheuttaa glysiinin puutosta, ja joilla glysiini voi suojata metioniinilta.

Jos pohditaan kasvisruokavalion ja lihapainotteisen ruokavalion keskeisiä eroja, niin kasviperäisissä proteiininlähteissä on huomattavan paljon glysiiniä ja tavallista vähemmän metioniinia. Näiden aminohappojen määriä voidaan kuvata esimerkiksi glysiini:metioniini -suhteella. (On tietysti mahdollista että aminohappojen määrien erotus toimisi paremmin kuin niiden määräsuhde, mutta määräsuhde lienee helpompi ymmärtää, sillä se ei voi saada negatiivisia lukuarvoja.)

Muun muassa perunan, soijan, riisin, manteleiden, härkäpavun, linssin ja papujen glysiini/metioniini -suhde on kohtalaisen hyvä, kun taas eläinkunnassa liha, maito ja munat sisältävät runsaasti metioniinia ja vähemmän glysiiniä. Olen välillä miettinyt, voisiko tämä ero selittää sen, miksi joissakin tutkimusaineistoissa kasviproteiinin kulutus yhdistyy jopa vähäisempään kuolleisuuteen.[7]

Soijan, perunan ja riisin proteiinien aminohappoprofiileja.
Maitoproteiini (kaseiini sisältää) enemmän metioniinia
ja vähemmän glysiiniä kuin kasviproteiinit.
(Morita et al. 1997)

Riisiproteiinia on tutkittu erilaisissa eläinkoeasetelmissa, ja on havaittu että maitoproteiinin (kaseiini) korvaaminen riisiproteiinilla saa eläimillä aikaan myönteisiä aineenvaihdunnallisia muutoksia. Riisiproteiini sisältää maitoproteiiniin verrattuna yli kaksinkertaisesti glysiiniä ja hieman vähemmän metioniinia, mikä saattaa osittain selittää tuloksia.[8]

Suomessa on myös tutkittu maidon heraproteiinien vaikutuksia hiirien painonhallintaan. Hera näyttäisi suojaavan hiiriä ylipainolta, ja vaikutus on liitetty erityisesti herassa olevaan alfa-laktalbumiiniin jota on herassa noin neljäsosa. Lisäksi on havaittu, että alfa-laktalbumiinin vaikutus selittyy ensisijaisesti sen aminohappokoostumuksella. Alfa-laktalbumiinin glysiini:metioniini -suhde (2.70) on noin 4.6-kertainen verrattuna kaseiiniin (0.59), ja olenkin pohtinut että siinä voisi olla mahdollinen selitys miksi joissakin tutkimuksissa kyseinen proteiini aiheutti aspiriiniin verrattavan anti-inflammatorisen vaikutuksen.[8] Laktoferriini ei tosin ole toiminut glysiinipitoisuuksistaan huolimatta yhtä hyvin, mutta sen 33% alempi histidiinipitoisuus saattaa selittää vaikutusta (ks. histidiinistä alla).

Näiden tulosten tulkintaa toisaalta hankaloittaa kysteiinin mahdollinen rooli. Kysteiini näyttäisi joissakin eläinkokeissa estävän metioniinirajoituksen tuomia hyötyjä, ja mikäli kokeellisesti käytämmekin glysiini:(metioniini+kysteiini) -suhdetta glysiini:metioniini -suhteen sijasta, kyseinen suhde on kaseiinilla (0.47) sama kuin alfa-laktalbumiinilla (0.47). Kasviproteiineilla se on edelleen hieman korkeampi.

On toki mahdollista, että vaikka metioniinin merkittävässä rajoituksessa tarvitaan myös kysteiinin yhtäaikainen rajoitus, ei kysteiini kuitenkaan vaikuta siihen mekanismiin jolla korkea glysiini:metioniini -suhde tuottaa hyötyvaikutuksia (glysiinitasojen ylläpito ja homokysteiinitasojen lasku). Mekanismeja joilla metioniinin ja kysteiinin yhtäaikainen puute on hyödyllistä, ovat mm. glutationin puute ja mahdollisesti ehkä SCD1:n aktiivisuuden väheneminen. Ja vielä, kuten yllä havaittiin, glysiinin ja kysteiinin yhteinen vaikutus aineenvaihduntaan näyttäisi olevan ihmisillä ja hiirillä mahdollisesti jopa myönteisempi kuin glysiinillä yksinään.[6,7]

Kollageeni on nisäkkäiden määrältään runsain proteiini ja itsessään hyvin merkittävä glysiinin lähde (22% kokonaismassasta). Länsimaisessa kulttuurissa eläimistä kuitenkin syödään harvoin kollageenia sisältäviä ruhonosia (nahka, rusto, luut), mistä johtuva ravinnon huono glysiini/metioniini -suhde saattaa selittää eläinproteiinin joissakin tutkimuksissa havaitun yhteyden elintapasairauksiin.




2. Aminohappojen vaikutuksia metaboliseen oireyhtymään: Tauriini, GABA ja histidiini

Tauriinin ja GABAn on havaittu ehkäisevän roskaruoan haittavaikutuksia ihmisillä ja jyrsijöillä.

Eläinkokeissa tauriini on osoittautunut hyödylliseksi mm. metabolisen oireyhtymän ja maksasairauksien hoitoon. Epidemiologisissa tutkimuksissa on esitetty, että tauriini saattaisi olla korrelaatioiden perusteella tekijä, joka selittäisi japanilaisten pitkää elinikää. Joitakin heraproteiinin hyötyjä on selitetty sillä, että se voi lisätä elimistön kykyä tuottaa tauriinia.[9]

Kliinisissä ihmistutkimuksissa on alustavasti viitettä tauriinin hyödyllisyydestä mm. metaboliseen oireyhtymään, sydämen vajaatoimintaan, maksasairauksiin ja kemoterapian haittapuolien lievitykseen. Näiden tutkimusten laatu ei ole kuitenkaan ollut kovin korkea.[9]

Kala ja erityisesti äyriäiset ovat merkittäviä tauriinin lähteitä.
(Yamori et al. 2010, Fig. 12)

GABA suojaa jyrsijöitä tehokkaasti metaboliselta oireyhtymältä ja erityisesti haiman saarekesolujen vahingoilta. Monet hyödylliset vaikutukset ilmenevät kiinnostavasti jo hyvin pienilläkin annoksilla (0.06% GABAa juomaveteen). Kliinistä tutkimusta aiheesta on hyvin niukasti, mutta ainakin verenpainetta laskevasta vaikutuksesta on pari julkaisua.[9]

Histidiini sekä histidiiniä sisältävät dipeptidit (karnosiini/anseriini) suojaavat ihmisiä ja jyrsijöitä metaboliselta oireyhtymältä sekä tietyiltä muilta tulehdukseen liittyviltä ongelmilta.[10]

Eräässä kolmen kuukauden kestoisessa sadan hengen plasebokontrolloidussa tutkimuksessa histidiinin päivittäinen käyttö alensi ylipainoisten koehenkilöiden tulehdusmarkkereita (TNF-alpha, IL-6, CRP) noin 30% ja lisäksi koehenkilöiden rasvamassa aleni lähes kolme kiloa. Käytetty lisäannos oli 4 grammaa päivässä, kun normaalisti ruoasta saadaan histidiiniä noin 1.5 grammaa päivässä.[10]


Histidiiniryhmällä kaikki meni juuri nappiin:
rasvamassa (FM) aleni,
krooninen tulehdus väheni (TNF-α, IL-6),
hapetusstressi  väheni (SOD, GSH-Px),
insuliiniherkkyys parani (HOMA-IR),
vapaiden rasvahappojen määrä aleni (NEFA).
(Feng et al. 2013)

Toisaalta vastaavanlaista on kokeiltu hieman pienemmällä annoksella myös ylipainoisilla miehillä kahdeksan viikon tutkimuksessa, eikä erityisiä tuloksia havaittu. Eläinkokeissa histidiinin on havaittu toimivan paremmin naarailla, joten voi olla että vaikutus kohdistuu jostakin syystä erityisesti naissukupuoleen.[10]

Eräässä rottatutkimuksessa mm. glysiiniä ja histidiiniä sisältävä aminohapposeos ("NEAAs") esti käytännössä kaikki runsaasti fruktoosia sisältävän ruokavalion haitat.[10]

Näiden aminohappojen lisäksi hiirillä on havaittu, että myös alaniini saattaisi suojata lihavuudelta.[10]




3. Aminohappojen vaikutuksia metaboliseen oireyhtymään: ketogeeniset aminohapot

Ketogeeniset aminohapot ovat niitä aminohappoja, jotka voidaan muuntaa suoraan asetyyli-CoA:ksi, joka on ketoaineiden esiaste. Puhtaasti ketogeenisia aminohappoja ovat lysiini ja leusiini. Sekä ketogeenisia että glukogeenisia ovat isoleusiini, fenyylialaniini, treoniini, tryptofaani, tyrosiini.

Ketogeenisten aminohappojen lysiinin ja treoniinin puutosten on aikoinaan havaittu aiheuttavan koe-eläimissä maksan rasvoittumista. Viime vuosina japanilainen tutkimusryhmä on näyttänyt myös, että ketogeenisten aminohappojen lisääminen tavallisen ruoan tueksi suojaa hiiriä erittäin tehokkaasti runsasrasvaisen ruokavalion aiheuttamalta lihomiselta ja maksan rasvoittumiselta.[11]

Ketogeenisten aminohappojen on myös havaittu lisäävän maksan AMPK-aktivaatiota, mikä saattaisi osin selittää rasvoittumiselta suojaavaa vaikutusta.[11]




4. Aminohappojen vaikutusmekanismeja: Kloridikanavat, endotoksemia, tulehdus, sappihapot, antioksidanttivaikutukset, rasvan imeytyminen

Keskeisenä lähtökohtana tiettyjen aminohappojen metaboliselta oireyhtymältä suojaaville vaikutuksille voidaan nähdä se, että ne jollakin tavalla suojaavat metabolisen endotoksemian aiheuttamalta tulehdusreaktiolta. Olen aikaisemmassa kirjoituksessani esittänyt seuraavanlaisen kaavion siitä, miten yleisimpien kroonisten sairauksien voidaan nähdä syntyvän:



Glysiinin, tauriinin ja GABA:n luultavasti tärkeimmät vaikutusmekanismit liittyvät solutason inhibitioon (glysiinireseptori, GABA-reseptori, ym.). Glysiini hyperpolarisoi immuunisoluja ja endoteelisoluja glysiinireseptorin (glycine-gated chloride channel) kautta vähentäen täten mm. endotoksemian stimuloimaa tulehdussytokiinien eritystä, jolloin myöskään tulehduksen aiheuttamia metabolisia häiriöitä ei pääse syntymään.[12]

Osa kirjallisuudesta tarkastelee myös glysiinin ja tauriinin vaikutuksia sappihappojen konjugaatioon ja sitä kautta aineenvaihduntaan. Sappihapot suojaavat suolistoa bakteerien liikakasvulta (ja siten endotoksemialta) ja ne voivat myös tehostaa aineenvaihduntaa vaikuttamalla esim. solunsisäiseen kilpirauhashormoniaineenvaihduntaan.[13]

Sappihappojen aineenvaihdunta vaihtelee eläinlajista toiseen. Hiiret konjugoivat sappihapot lähinnä pelkästään tauriinilla. Rotat konjugoivat molemmilla (glysiini ja tauriini), mutta kuitenkin enimmäkseen tauriinilla. Ihmiset konjugoivat molemmilla, mutta enimmäkseen glysiinillä. Nämä erot voivat kyseisten erojen vuoksi vaikuttaa myös kyseisten ravintoaineiden terveysvaikutuksiin eläimillä.[13]

Tauriinin vaikutukset myös perustuvat osittain glysiinireseptorivaikutuksiin.[12]

Histidiinillä vaikutukset taas saattavat liittyä suoriin antioksidanttivaikutuksiin, metalli-ionien kelatointiin ja typpioksidilta suojaamiseen. Joissakin tutkimuksissa histidiinin ja/tai karnosiinin vaikutuksia perustellaan myös histamiiniaineenvaihdunnalla, mutta tietyissä tilanteissa histidiinin on jopa havaittu vaikuttavan päinvastaisesti histamiiniin nähden.[14]

Aminohappokoostumuksen lisäksi myös muut proteiinin ominaisuudet kuten sen rakenne ja kyky sitoa rasvaa voivat määrittää sen terveysvaikutuksia.[15]

Jos maitoproteiinin (kaseiini) annostelee hiirille hydrolysoituna eli jo valmiiksi pilkottuina peptideinä, se vähentää hiirien lihavuutta huomattavasti. Peptidien tämänkaltaisia vaikutuksia on selitetty kolekystokiniinin (CCK) ja glukagonin kaltaisen peptidin (GLP-1) vaikutuksilla, mutta asiaan liittyvä tutkimus on vasta alkuvaiheilla.[15]


Hydrolysoitua maitoproteiinia syöneillä hiirillä tutkittujen
rasvamassojen koko oli vain kolmasosan siitä mitä
ne olivat normaalia kaseiinia syöneillä hiirillä.
[I-16 = intact casein, 16E%
H-16 = hydrolyzed casein, 16%
eWAT = epididymal white adipose tissue
iWAT = inguinal white adipose tissue]
(Lillefosse et al. 2013)

Myös proteiininlähteiden erilaiset vaikutukset rasvan imeytymiseen saattavat selittää niiden terveysvaikutusten eroja. Maitoproteiini sisältää vähemmän glysiiniä kuin esimerkiksi lohi tai kana, mutta runsasrasvaisella ruokavaliolla kaseiinin on kuitenkin havaittu yhdistyvän vähempään lihomiseen. Tulosta on selitetty ensisijaisesti sillä, että maitoproteiini vähentää rasvan imeytymistä ohutsuolessa.[15]



5. Päätelmät

- Ravitsemustieteellinen keskustelu keskittyy usein pitkälti hiilihydraattien ja rasvojen laadun vertailuun, mutta vaikuttaa siltä että myös proteiinin laatu voi olla hyvin merkityksellistä.

- Proteiinin laadun vaikutus liittyy pääosin eri aminohappojen määriin ja määräsuhteisiin. Tietyt aminohapot kuten glysiini ja histidiini saattavat suojata elimistöä krooniselta matala-asteiselta tulehdukselta, kun taas metioniini saattaa olla haitaksi. Eläinkokeissa näiden aminohappojen vaikutuksista on hyvin kiinnostavaa näyttöä, mutta ihmisillä on saatu vasta alustavia ja yleisesti hieman maltillisempia tuloksia.

- Myös proteiinin muilla ominaisuuksilla voi olla vaikutusta. Peptideiksi pilkotun proteiinin on havaittu joissakin tutkimuksissa suojaavan lihavuudelta, mahdollisesti vaikuttamalla suolistohormonien eritykseen. Lisäksi maitoproteiini vähentää rasvan imeytymistä, mikä voi vähentää runsasrasvaisen ruokavalion haittoja.

- Insuliiniresistenssistä kärsivillä ihmisillä glysiinin ja histidiinin määrien aleneminen verenkierrossa (mahdollisesti glukoneogeneesin vuoksi) voi teoriassa johtaa tulehdusreaktion korostumiseen elimistössä, mikä voi altistaa entistä enemmän matala-asteisen tulehduksen haitoille. Tämän vuoksi insuliiniresistentit ihmiset saattaisivat hyötyä ko. aminohappojen käytöstä enemmän kuin muut ihmiset.[16]








Lisämerkinnät

1) Tauriini ei teknisesti ottaen ole aminohappo, vaan aminoryhmän sisältävä orgaaninen happo. Monissa tutkimusartikkeleissa tauriinia kuitenkin kutsutaan aminohapoksi, joten tietoisesti käytän artikkelissani samaa määritelmää.

2) Tämän kirjoituksen perusteella ei kannata tilata ulkomailta (iHerbistä) GABA:a tai glysiiniä, sillä molemmat luetellaan Fimean lääkeluettelossa. Glysiiniä myydään Suomessa kuluttajille mm. Aminopörssin verkkokaupassa.

3) Voi olla, että insuliiniresistenttien henkilöiden alhaisemmat histidiinitasot selittyvät osittain histamiiniaineenvaihdunnan muutoksilla tai muilla tekijöillä.



Tutkimuskirjallisuutta

[1] Kampasimpukan proteiinin vaikutuksia

[glycine-scallop] Amino Acids. 2014 Jul;46(7):1659-71. Scallop protein with endogenous high taurine and glycine content prevents high-fat, high-sucrose-induced obesity and improves plasma lipid profile in male C57BL/6J mice. Tastesen HS, Keenan AH, Madsen L, Kristiansen K, Liaset B.

[glycine-scallop] PhD Thesis by Hanne Sørup Tastesen: Dietary protein in the prevention of diet‐induced obesity and co‐morbidities (University of Copenhagen, 2014)



[2] Kalaproteiinin vaikutuksia

[fish-protein] Br J Nutr. 2013 Feb 28;109(4):648-57. A randomised study on the effects of fish protein supplement on glucose tolerance, lipids and body composition in overweight adults. Vikøren LA, Nygård OK, Lied E, Rostrup E, Gudbrandsen OA. “The intake of fish protein supplement was 3 g/d for the first 4 weeks and 6 g/d for the last 4 weeks. In this study, 8 weeks of fish protein supplementation resulted in lower values of fasting glucose (P< 0·05), 2 h postprandial glucose (P< 0·05) and glucose-area under the curve (AUC) (five measurements over 2 h, P< 0·05) after fish protein supplementation compared to controls. Glucose-AUC was decreased after 8 weeks with fish protein supplement compared to baseline (P< 0·05), concomitant with increased 30 min and decreased 90 min and 2 h insulin C-peptide level (P< 0·05), and reduced LDL-cholesterol (P< 0·05). Body muscle % was increased (P< 0·05) and body fat % was reduced (P< 0·05) after 4 weeks' supplementation”

[fish-protein] J Nutr. 2008 Dec;138(12):2386-91. doi: 10.3945/jn.108.092346. Dietary cod protein reduces plasma C-reactive protein in insulin-resistant men and women. Ouellet V, Weisnagel SJ, Marois J, Bergeron J, Julien P, Gougeon R, Tchernof A, Holub BJ, Jacques H.

[fish-protein] Biochim Biophys Acta. 2009 Apr;1791(4):254-62. Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats. Liaset B, Madsen L, Hao Q, Criales G, Mellgren G, Marschall HU, Hallenborg P, Espe M, Frøyland L, Kristiansen K.

[fish-protein] Diabetes Care. 2007 Nov;30(11):2816-21. Dietary cod protein improves insulin sensitivity in insulin-resistant men and women: a randomized controlled trial. Ouellet V, Marois J, Weisnagel SJ, Jacques H.

[fish-protein-bile] J Biol Chem. 2011 Aug 12;286(32):28382-95. Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome. Liaset B, Hao Q, Jørgensen H, Hallenborg P, Du ZY, Ma T, Marschall HU, Kruhøffer M, Li R, Li Q, Yde CC, Criales G, Bertram HC, Mellgren G, Ofjord ES, Lock EJ, Espe M, Frøyland L, Madsen L, Kristiansen K. “Here, we show that plasma BA concentration in rats was elevated by exchanging the dietary protein source from casein to salmon protein hydrolysate (SPH). Importantly, the SPH-treated rats were resistant to diet-induced obesity. [...] Pharmacological removal of BAs by inclusion of 0.5 weight % cholestyramine to the high fat SPH diet attenuated the reduction in abdominal obesity, the reduction in liver TAG, and the decrease in nonfasted plasma TAG and glucose levels. Induction of Ucp3 gene expression in muscle by SPH treatment was completely abolished by cholestyramine inclusion.” “[W]e conclude that the increased plasma BA level in the SPH-fed rats was likely due to higher intestinal influx. “

“The benefits of activating Tgr5 or Fxr for the prevention of the metabolic syndrome have stimulated the development of synthetic ligands for these receptors (24, 25). Another strategy to increase Tgr5 and/or Fxr signaling would be to alter endogenous BA metabolism. As hepatic bile acid conjugation is important for secretion of BAs into bile (2) and rats conjugate BAs to both taurine and glycine with high efficiency (26), the dietary levels of these amino acids might be crucial for BA conjugation and secretion (27).”


[fish-protein] J Nutr. 2004 Jun;134(6):1320-7. Fish protein hydrolysate reduces plasma total cholesterol, increases the proportion of HDL cholesterol, and lowers acyl-CoA:cholesterol acyltransferase activity in liver of Zucker rats. Wergedahl H, Liaset B, Gudbrandsen OA, Lied E, Espe M, Muna Z, Mørk S, Berge RK.

[fish-protein] Int J Mol Med. 2012 Feb;29(2):311-8. doi: 10.3892/ijmm.2011.836. Epub 2011 Nov 11. Dietary sardine protein lowers insulin resistance, leptin and TNF-α and beneficially affects adipose tissue oxidative stress in rats with fructose-induced metabolic syndrome. Madani Z, Louchami K, Sener A, Malaisse WJ, Ait Yahia D.

[fish-protein] Physiol Genomics. 2010 Feb 4;40(3):189-94. Fish nutrients decrease expression levels of tumor necrosis factor-alpha in cultured human macrophages. Rudkowska I1, Marcotte B, Pilon G, Lavigne C, Marette A, Vohl MC.

[fish-protein] PLoS One. 2013 Oct 4;8(10):e77274. Beneficial effects of cod protein on inflammatory cell accumulation in rat skeletal muscle after injury are driven by its high levels of arginine, glycine, taurine and lysine. Dort J, Leblanc N, Maltais-Giguère J, Liaset B, Côté CH, Jacques H.

[fish-protein] Appl Physiol Nutr Metab. 2012 Jun;37(3):489-98. doi: 10.1139/h2012-021. Epub 2012 Apr 17. Beneficial effects of cod protein on skeletal muscle repair following injury. Dort J, Sirois A, Leblanc N, Côté CH, Jacques H.

[fish-protein-humans] Nutr Metab Cardiovasc Dis. 2009 Dec;19(10):690-6. Consumption of cod and weight loss in young overweight and obese adults on an energy reduced diet for 8-weeks. Ramel A, Jonsdottir MT, Thorsdottir I. “According to linear models weight loss was 1.7 kg greater among subjects consuming 150 g 5x/week compared to the control group"

[sardine-protein] Br J Nutr. 2015 Oct 28:1-8. Effect of sardine proteins on hyperglycaemia, hyperlipidaemia and lecithin:cholesterol acyltransferase activity, in high-fat diet-induced type 2 diabetic rats. Benaicheta N, Labbaci FZ, Bouchenak M, Boukortt FO. "HFD-induced hyperglycaemia, insulin resistance and hyperlipidaemia in rats fed HFD, regardless of the consumed protein. In contrast, these parameters lowered in rats fed SP combined with 5 or 30 % lipids, and serum insulin values reduced in SP v. CAS."



[3] Glysiinin yleisiä vaikutuksia

[glycine] Vladimir Heiskanen: Health Benefits of Glycine (2013)

[glycine] Amino Acids. 2013 Sep;45(3):463-77. doi: 10.1007/s00726-013-1493-1. Epub 2013 Apr 25. Glycine metabolism in animals and humans: implications for nutrition and health. Wang W, Wu Z, Dai Z, Yang Y, Wang J, Wu G.

[glycine] The FASEB Journal. 2011;25:528.2. Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats. Brind J , Malloy V, Augie I, Caliendo N, Vogelman JH, Zimmerman JA, Orentreich N. "Seven-week-old male Fisher 344 rats were fed diets containing 0.43% Met/2.3% glycine (control fed; CF) or 0.43% Met/4%, 8% or 12% glycine until natural death. In 8% or 12% GS rats, median lifespan increased from 88 weeks (w) to 113 w, and maximum lifespan increased from 91 w to 119 w v CF."




[4] Glysiinin vaikutus metaboliseen oireyhtymään (eläimillä)

[glycine-metabolic-syndrome] Am J Physiol Regul Integr Comp Physiol. 2004 Dec;287(6):R1387-93. Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats. El Hafidi M, Pérez I, Zamora J, Soto V, Carvajal-Sandoval G, Baños G.

[glycine-metabolic-syndrome] Clin Sci (Lond). 2014 Jan 1;126(1):19-29. Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats. Ruiz-Ramírez A, Ortiz-Balderas E, Cardozo-Saldaña G, Diaz-Diaz E, El-Hafidi M.

[glycine-metabolic-syndrome] Amino Acids. 2014 Mar 23. Scallop protein with endogenous high taurine and glycine content prevents high-fat, high-sucrose-induced obesity and improves plasma lipid profile in male C57BL/6J mice. Tastesen HS, Keenan AH, Madsen L, Kristiansen K, Liaset B.

[glycine-metabolic-syndrome] Can J Physiol Pharmacol. 2011 Dec;89(12):899-910. Effect of glycine on the cyclooxygenase pathway of the kidney arachidonic acid metabolism in a rat model of metabolic syndrome. Pérez-Torres I1, Ibarra B, Soria-Castro E, Torrico-Lavayen R, Pavón N, Diaz-Diaz E, Flores PL, Infante O, Baños G.

[glycine-metabolic-syndrome] Cell Biochem Funct. 2004 Mar-Apr;22(2):123-8. Protective effect of glycine supplementation on the levels of lipid peroxidation and antioxidant enzymes in the erythrocyte of rats with alcohol-induced liver injury. Senthilkumar R, Sengottuvelan M, Nalini N



[5] Glysiinin vaikutus metaboliseen oireyhtymään ja aivohalvaukseen (ihmisillä)

[glycine-humans] J Endocrinol Invest. 2008 Aug;31(8):694-9. Glycine treatment decreases proinflammatory cytokines and increases interferon-gamma in patients with type 2 diabetes. Cruz M, Maldonado-Bernal C, Mondragón-Gonzalez R, Sanchez-Barrera R, Wacher NH, Carvajal-Sandoval G, Kumate J.

[glycine-humans] Can J Physiol Pharmacol. 2013 Oct;91(10):855-60. Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure. Díaz-Flores M, Cruz M, Duran-Reyes G, Munguia-Miranda C, Loza-Rodríguez H, Pulido-Casas E, Torres-Ramírez N, Gaja-Rodriguez O, Kumate J, Baiza-Gutman LA, Hernández-Saavedra D.

[glycine-humans-stroke] Cerebrovasc Dis. 2000 Jan-Feb;10(1):49-60. Neuroprotective effects of glycine for therapy of acute ischaemic stroke. Gusev EI, Skvortsova VI, Dambinova SA, Raevskiy KS, Alekseev AA, Bashkatova VG, Kovalenko AV, Kudrin VS, Yakovleva EV.



[6] Glysiinin ja kysteiinin vaikutus metaboliseen oireyhtymään ikäihmisillä, diabeetikoilla ja HIV-potilailla

[glycine-cysteine-humans] Diabetes Care. 2011 Jan;34(1):162-7. Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Sekhar RV, McKay SV, Patel SG, Guthikonda AP, Reddy VT, Balasubramanyam A, Jahoor F. [dose was 100mg/kg/d, according to the calculation of the author of this paper]

[glycine-cysteine-humans] Am J Clin Nutr. 2011 Sep;94(3):847-53. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Sekhar RV, Patel SG, Guthikonda AP, Reid M, Balasubramanyam A, Taffet GE, Jahoor F.

[glycine-cysteine-humans] Aging Cell. 2013 Jun;12(3):415-25. Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione. Nguyen D, Samson SL, Reddy VT, Gonzalez EV, Sekhar RV.

[glycine-cysteine-humans] J Clin Endocrinol Metab. 2014 Jan;99(1):169-77. Effect of increasing glutathione with cysteine and glycine supplementation on mitochondrial fuel oxidation, insulin sensitivity, and body composition in older HIV-infected patients. Nguyen D1, Hsu JW, Jahoor F, Sekhar RV.



[7] Metioniinin vaikutuksia, sekä glysiinin vaikutus metioniiniaineenvaihduntaan + kasvissyönti

[methionine] Aging Cell. 2006 Aug;5(4):305-14. Methionine restriction decreases visceral fat mass and preserves insulin action in aging male Fischer 344 rats independent of energy restriction. Malloy VL, Krajcik RA, Bailey SJ, Hristopoulos G, Plummer JD, Orentreich N. “Conversely, MR rats show significantly reduced visceral fat compared to CF and PF with concomitant decreases in basal insulin, glucose, and leptin, and increased adiponectin and triiodothyronine. Daily energy expenditure in MR animals significantly exceeds that of both PF and CF.”

[methionine] Am J Physiol Regul Integr Comp Physiol. 2010 Sep;299(3):R728-39. Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states. Hasek BE, Stewart LK, Henagan TM, Boudreau A, Lenard NR, Black C, Shin J, Huypens P, Malloy VL, Plaisance EP, Krajcik RA, Orentreich N, Gettys TW.

[methionine] Exp Gerontol. 2013 Jul;48(7):654-60. Metabolic adaptations to methionine restriction that benefit health and lifespan in rodents. Perrone CE, Malloy VL, Orentreich DS, Orentreich N. “These beneficial effects of MR involve a host of metabolic adaptations leading to increased mitochondrial biogenesis and function, elevated energy expenditure, changes of lipid and carbohydrate homeostasis, and decreased oxidative damage and inflammation.”

[methionine] PLoS One. 2012;7(12):e51357. Methionine-restricted C57BL/6J mice are resistant to diet-induced obesity and insulin resistance but have low bone density. Ables GP, Perrone CE, Orentreich D, Orentreich N.

[methionine] Biogerontology. 2008 Jun;9(3):183-96. Forty percent and eighty percent methionine restriction decrease mitochondrial ROS generation and oxidative stress in rat liver. Caro P, Gómez J, López-Torres M, Sánchez I, Naudí A, Jove M, Pamplona R, Barja G.

[methionine] Rejuvenation Res. 2009 Dec;12(6):421-34. Forty percent methionine restriction decreases mitochondrial oxygen radical production and leak at complex I during forward electron flow and lowers oxidative damage to proteins and mitochondrial DNA in rat kidney and brain mitochondria. Caro P, Gomez J, Sanchez I, Naudi A, Ayala V, López-Torres M, Pamplona R, Barja G.

[methionine] Mol Cell Biochem. 2016 Oct 17. [Epub ahead of print] Methionine and methionine sulfoxide treatment induces M1/classical macrophage polarization and modulates oxidative stress and purinergic signaling parameters. Dos Santos LM, da Silva TM, Azambuja JH, Ramos PT, Oliveira PS, da Silveira EF, Pedra NS, Galdino K, do Couto CA, Soares MS, Tavares RG, Spanevello RM, Stefanello FM, Braganhol E.

[methionine-restriction-cysteine-supplementation] J Lipid Res. 2011 Jan;52(1):104-12. Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase. Elshorbagy AK, Valdivia-Garcia M, Mattocks DA, Plummer JD, Smith AD, Drevon CA, Refsum H, Perrone CE. 

[methionine-restriction-cysteine-supplementation] J Nutrigenet Nutrigenomics. 2012;5(3):132-57. Genomic and metabolic responses to methionine-restricted and methionine-restricted, cysteine-supplemented diets in Fischer 344 rat inguinal adipose tissue, liver and quadriceps muscle. Perrone CE, Mattocks DA, Plummer JD, Chittur SV, Mohney R, Vignola K, Orentreich DS, Orentreich N.

[methionine-restriction-cysteine-supplementation] Metabolism. 2013 Apr;62(4):509-17. Effect of taurine and N-acetylcysteine on methionine restriction-mediated adiposity resistance. Elshorbagy AK, Valdivia-Garcia M, Mattocks DA, Plummer JD, Orentreich DS, Orentreich N, Refsum H, Perrone CE. "The results rule out taurine as a mediator of increased adiposity produced by cysteine in MR, and show that NAC, similar to L-cysteine, blocks anti-obesity effects of MR. Our data show that dietary SAA can influence adiposity in part through mechanisms that converge on SCD1 function."

[methionine-restriction-cysteine-supplementation] Exp Gerontol. 2013 Jul;48(7):654-60. Metabolic adaptations to methionine restriction that benefit health and lifespan in rodents. Perrone CE, Malloy VL, Orentreich DS, Orentreich N. "MR mediated effects are reversed by cysteine supplementation of the MR diet."

[glycine-methionine] The FASEB Journal. 2011;25:528.2. Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats. Brind J , Malloy V, Augie I, Caliendo N, Vogelman JH, Zimmerman JA, Orentreich N. "We propose that more efficient Met clearance via GNMT with GS could be reducing chronic Met toxicity due to rogue methylations from chronic excess methylation capacity or oxidative stress from generation of toxic by-products such as formaldehyde."

[glycine-methionine] J Nutr Sci Vitaminol (Tokyo). 1987 Jun;33(3):195-205. Effect of dietary glycine on methionine metabolism in rats fed a high-methionine diet. Sugiyama K, Kushima Y, Muramatsu K. "In rats fed a high methionine diet, the hepatic methionine level was significantly increased with a concomitant decrease in the levels of glycine, serine, and threonine. The addition of glycine to the high methionine diet effectively suppressed the enhancement of the hepatic methionine level and almost completely restored the glycine level, but it only partially restored the serine level and further decreased the threonine level. From these results, it is suggested that the alleviating effect of dietary glycine on methionine toxicity is primarily elicited by the restoration of the hepatic glycine level rather than by an increase in hepatic enzyme activity."

[glycine-methionine-GNMT] J Nutr. 2002 Sep;132(9):2545-50. Hepatic glycine N-methyltransferase is up-regulated by excess dietary methionine in rats. Rowling MJ, McMullen MH, Chipman DC, Schalinske KL.

[glycine-methionine] Proc Soc Exp Biol Med. 1949 Feb;70(2):327-30. The effect of feeding excess glycine, L-arginine, and DL-methionine to rats on a casein diet. ROTH JS, ALLISON JB.

[glycine-methionine] Biosci Biotechnol Biochem. 2006 Oct;70(10):2403-9. Suppression of methionine-induced hyperhomocysteinemia by glycine and serine in rats. Fukada S, Shimada Y, Morita T, Sugiyama K.

[glycine-methionine] Arch Biochem Biophys. 1993 Feb 1;300(2):598-607. Methionine toxicity in the rat in relation to hepatic accumulation of S-adenosylmethionine: prevention by dietary stimulation of the hepatic transsulfuration pathway. Regina M, Korhonen VP, Smith TK, Alakuijala L, Eloranta TO. "Hepatic accumulation of S-adenosylmethionine was accompanied by 40% stimulation of methionine adenosyltransferase and 40% repression of spermine synthase over a 2-week period. Simultaneous dietary supplements of glycine and serine combined with toxic levels of methionine markedly stimulated hepatic methionine catabolism. As a result, tissue distribution of methionine and glutathione returned close to normal in all tissues measured and accumulation of hepatic S-adenosylmethionine and its catabolites was prevented."

[glycine-methionine] J Nutr Sci Vitaminol (Tokyo). 1990 Oct;36 Suppl 2:S105-10. Significance of the amino acid composition of dietary protein in the regulation of plasma cholesterol. Sugiyama K, Muramatsu K. "diets high in methionine and low in cystine and glycine content tend to increase the plasma cholesterol level and diets of opposite amino acid content tend to decrease the plasma cholesterol level."

[glycine-methionine] Br J Nutr. 2005 Sep;94(3):321-30. Dietary proteins with high isoflavone content or low methionine-glycine and lysine-arginine ratios are hypocholesterolaemic and lower the plasma homocysteine level in male Zucker fa/fa rats. Gudbrandsen OA, Wergedahl H, Liaset B, Espe M, Berge RK.

[glycine-methionine-cholesterol] J Nutr. 1997 Mar;127(3):470-7. Cholesterol-lowering effects of soybean, potato and rice proteins depend on their low methionine contents in rats fed a cholesterol-free purified diet. Morita T, Oh-hashi A, Takei K, Ikai M, Kasaoka S, Kiriyama S. "There was a significant negative correlation between serum cholesterol concentration and fecal total steroid excretion (r = -0.490, P = 0.01). However, a stronger positive correlation was observed between serum cholesterol concentration and dietary methionine concentration (r = 0.674, P = 0.0003) or methionine:glycine ratios (r = 0.656, P = 0.0005). In a separate experiment in rats fed diets containing amino acid mixtures simulating the RP, PP and SP diets, serum total cholesterol concentrations were lower than in rats fed simulated casein."

[glycine-methionine-cholesterol-vegetarians] Bratisl Lek Listy. 2005;106(6-7):231-4. Health benefits and risks of plant proteins. Krajcovicova-Kudlackova M, Babinska K, Valachovicova M. "Vegetarians have a significantly higher intake of non-essential amino acids arginine and pyruvigenic amino acids glycine, alanine, serine."

[glycine-methionine-cholesterol-vegetarians] Med Hypotheses. 2009 Feb;72(2):125-8. The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. McCarty MF, Barroso-Aranda J, Contreras F. "Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation)." 


[plant-protein] JAMA Intern Med. 2016 Oct 1;176(10):1453-1463. Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality. Song M, Fung TT, Hu FB, Willett WC, Longo VD, Chan AT, Giovannucci EL.




[8] Riisiproteiinin ja alfa-laktalbumiinin hyötyjä (koe-eläimillä) + muita kiinnostavia proteiininlähteitä

[rice-protein] Br J Nutr. 2013 Oct;110(7):1211-9. Rice protein ameliorates the progression of diabetic nephropathy in Goto-Kakizaki rats with high-sucrose feeding. Kubota M, Watanabe R, Kabasawa H, Iino N, Saito A, Kumagai T, Fujimura S, Kadowaki M. “These results strongly indicate that dietary RP can ameliorate the progression of diabetic nephropathy at an early stage compared with C.” “RP had higher arginine and proline contents, but a lower lysine content compared with C (P,0·01).” [rice protein also did also contain 148% more glycine than casein]

[rice-protein] Prev Nutr Food Sci. 2013 Sep;18(3):210-3. Cholesterol-lowering Effect of Rice Protein by Enhancing Fecal Excretion of Lipids in Rats. Um MY, Ahn J, Jung CH, Ha TY. “Compared with rats fed a HCD with casein, the total cholesterol (TC) level in the plasma was significantly reduced in the rats fed rice protein. However, no significant differences were observed in the triglycerides, high-density lipoprotein (HDL), and glucose levels among the experimental groups. [...] In addition, rice protein significantly increased the levels of TC and bile acids in the feces."

[rice-protein] Life Sci. 2012 Oct 5;91(11-12):389-94. Rice protein improves oxidative stress by regulating glutathione metabolism and attenuating oxidative damage to lipids and proteins in rats. Yang L, Chen JH, Xu T, Zhou AS, Yang HK. “These results suggest that RP can prevent hyperlipidemia in part through modifying glutathione metabolism, and sulfur amino acids may be the main modulator of this antioxidative mechanism.”

[rice-protein] Lipids Health Dis. 2012 Feb 13;11:24. Rice protein improves adiposity, body weight and reduces lipids level in rats through modification of triglyceride metabolism. Yang L, Chen JH, Lv J, Wu Q, Xu T, Zhang H, Liu QH, Yang HK. “Compared with CAS, plasma concentrations of glucose and lipids were significantly reduced by RP-feeding (P < 0.05), as well as hepatic accumulation of lipids (P < 0.05). RP-A and RP-E significantly depressed the hepatic activities of fatty acid synthase (FAS), glucose 6-phosphate dehydrogenase (G6PD) and malate dehydrogenase (MDH) (P < 0.05), whereas the activities of lipoprotein lipase (PL) and hepatic lipase (HL) were significantly stimulated (P < 0.05), as compared to CAS.” “[H]igher contents of glycine were found in RP groups, as compared with CAS (P < 0.05).”

[rice-protein] J Agric Food Chem. 2011 Oct 26;59(20):10927-33. Lower weight gain and hepatic lipid content in hamsters fed high fat diets supplemented with white rice protein, brown rice protein, soy protein, and their hydrolysates. Zhang H, Bartley GE, Mitchell CR, Zhang H, Yokoyama W. “The brown rice protein hydrolysate (BRPH) diet group reduced weight gain 76% compared with the control. Animals fed the BRPH supplemented diet also had lower final body weight, liver weight, very low density lipoprotein cholesterol (VLDL-C), and liver cholesterol, and higher fecal fat and bile acid excretion than the control.”

[rice-protein] Atherosclerosis. 2010 Sep;212(1):107-15. Dietary rice protein isolate attenuates atherosclerosis in apoE-deficient mice by upregulating antioxidant enzymes. Burris RL, Xie CH, Thampi P, Wu X, Melnyk SB, Nagarajan S. “The mean lesion areas for apoE−/− mice fed the RPI diet were lower (55% reduction) compared to those in CAS-fed mice (P < 0.01; Fig. 1B).”

[rice-protein] Exp Biol Med (Maywood). 2010 Sep;235(9):1102-13. Rice protein isolate improves lipid and glucose homeostasis in rats fed high fat/high cholesterol diets. Ronis MJ, Badeaux J, Chen Y, Badger TM.


[whey-alpha-lactalbumin] Br J Nutr. 2009 Aug;102(3):337-41. doi: 10.1017/S0007114508199445. Effects of high-calcium diets with different whey proteins on weight loss and weight regain in high-fat-fed C57BL/6J mice. Pilvi TK, Harala S, Korpela R, Mervaala EM. "only the ALA diet significantly reduced fat accumulation during weight regain" "The glycine content of LF and ALA is greater than in BLG or WPI and it may contribute to the effect on adipocyte size, since glycine intake has been shown to reduce adipocyte size(25). Interestingly, adipocyte size after weight loss was significantly smaller only in the ALA group even though body fat percentage decreased significantly also in the LF group."


[whey-alpha-lactalbumin] Shi, J., Ahlroos-Lehmus, A., Pilvi, T. K., Korpela, R., Tossavainen, O., & Mervaala, E. M. (2012). Metabolic effects of a novel microfiltered native whey protein in diet-induced obese mice. Journal of functional foods, 4(2), 440-449. "Our findings indicate that MFNW protects against diet-induced obesity, and suggest that the beneficial effects of MFNW are due, to a great extent, to its α-lactalbumin content."


[whey-alpha-lactalbumin] Shi, J., Ahlroos-Lehmus, A., Pilvi, T. K., Kekkonen, R., Korpela, R., & Mervaala, E. M. (2011). Comparison of the metabolic effects of milk-derived α-lactalbumin and amino acids mixture with equal composition in diet-induced obese mice. Journal of Functional Foods, 3(2), 70-78. "The anti-obesity effects of -lactalbumin are mediated mainly via its amino acids."

[whey-alpha-lactalbumin] Biosci Biotechnol Biochem. 2014;78(4):672-9. Bovine milk-derived α-lactalbumin inhibits colon inflammation and carcinogenesis in azoxymethane and dextran sodium sulfate-treated mice. Yamaguchi M, Takai S, Hosono A, Seki T. "Dietary treatment with α-lactalbumin decreased fecal occult blood score at 3 days after DSS intake. α-Lactalbumin also decreased the colon tumor at week 9. [...] α-Lactalbumin decreased PGE2 in both plasma and colon." [a diet high in α-lactalbumin (7% casein, 7% α-lactalbumin) inhibits inflammation as powerfully as 0.1% aspirin contained diet]

[whey-alpha-lactalbumin] Br J Nutr. 2013 Oct;110(7):1336-46. The effects of native whey and α-lactalbumin on the social and individual behaviour of C57BL/6J mice. Vekovischeva OY1 Peuhkuri K, Bäckström P, Sihvola N, Pilvi T, Korpela R. "The study shows that the long-term ingestion of whey proteins may modulate behaviour when compared with casein. Diet enriched with a-lac exhibited anxiolytic and antidepressive activities while the whey diet improved sociability."

[whey-alpha-lactalbumin-humans] Am J Clin Nutr. 2002 Jun;75(6):1051-6. Whey protein rich in alpha-lactalbumin increases the ratio of plasma tryptophan to the sum of the other large neutral amino acids and improves cognitive performance in stress-vulnerable subjects. Markus CR, Olivier B, de Haan EH. 

[whey-alpha-lactalbumin] Biosci Biotechnol Biochem. 2001 May;65(5):1104-11. New biological function of bovine alpha-lactalbumin: protective effect against ethanol- and stress-induced gastric mucosal injury in rats. Matsumoto H, Shimokawa Y, Ushida Y, Toida T, Hayasawa H. "Alpha-LA showed dose-dependent protection against gastric injury induced by stress as well as ethanol. Pretreatment with indomethacin (10 mg/kg body weight, s.c.), which is a potent inhibitor of endogenous prostaglandin synthesis, resulted in a significant reduction in the protective effect of alpha-LA."

[whey-lactoferrin] Shi, J., Finckenberg, P., Martonen, E., Ahlroos-Lehmus, A., Pilvi, T. K., Korpela, R., & Mervaala, E. M. (2012). Metabolic effects of lactoferrin during energy restriction and weight regain in diet-induced obese mice. Journal of Functional Foods, 4(1), 66-78. "In conclusion, LF supplementation enhances the outcome of weight loss and subsequent weight regain, ameliorates fatty liver formation, and exerts beneficial effects on glucose tolerance and adipocyte tissue inflammation without interfering energy intake."

[porcine-placenta-protein] Can J Physiol Pharmacol. 2014 Sep 15:1-8. Anti-fatigue effects of porcine placenta and its amino acids in a behavioral test on mice. Moon PD, Kim KY, Rew KH, Kim HM, Jeong HJ. "Whole PE or individual amino acids decreased immobility times in the FST. PE, Pro, and Arg all lowered blood levels of lactic acid and alanine aminotransferase (ALT). PE and Gly improved glycogen content and catalase activity. As determined from the serum after the FST: PE regulated the effects of interferon (IFN)-γ and tumor necrosis factor (TNF)-α; GA regulated the effects of IFN-γ; Gly and Arg regulated the effects of interleukin (IL)-6; and all of the amino acids present in PE regulated the effects of TNF-α. As determined from the spleen after the FST: Gly and Arg regulated the effects of IL-1β; Gly, Pro, and Arg regulated the effects of IL-6; PE and all of the amino acids present in PE regulated the effects of TNF-α."

[porcine-placenta-protein] Nutrition. 2013 Nov-Dec;29(11-12):1381-7. Porcine placenta mitigates protein-energy malnutrition-induced fatigue. Han NR, Kim KY, Kim MJ, Kim MH, Kim HM, Jeong HJ.


[pork-liver-protein] Biosci Biotechnol Biochem. 2006 Jan;70(1):112-8. Consumption of pork-liver protein hydrolysate reduces body fat in Otsuka Long-Evans Tokushima Fatty rats by suppressing hepatic lipogenesis. Shimizu M, Tanabe S, Morimatsu F, Nagao K, Yanagita T, Kato N, Nishimura T. 

[single-cell-protein] Br J Nutr. 2008 Oct;100(4):776-85. Dietary single cell protein reduces fatty liver in obese Zucker rats. Gudbrandsen OA, Wergedahl H, Liaset B, Espe M, Mørk S, Berge RK. "We therefore examined the effects of feeding obese Zucker rats a single cell protein (SCP) with low ratios of methionine:glycine and lysine:arginine for 6 weeks. SCP feeding reduced the hepatic steatosis and lowered the plasma transaminase levels when compared with casein-fed rats (controls). The fatty acid oxidation was increased in liver mitochondria and peroxisomes, whereas the activities of enzymes involved in lipogenesis and TAG biosynthesis were unaffected."

[chicken-protein-extract-gly-met-ratio] Nutrients. 2015 Jun 4;7(6):4498-511. doi: 10.3390/nu7064498. A Protein Extract from Chicken Reduces Plasma Homocysteine in Rats. Lysne V, Bjørndal B, Vik R, Nordrehaug JE, Skorve J, Nygård O, Berge RK. "The present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP), with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism."



[9] GABA:n ja tauriinin vaikutuksia ihmisillä ja eläimillä

[taurine-review] Amino Acids. 2014 Jan;46(1):89-100. Taurine chloramine produced from taurine under inflammation provides anti-inflammatory and cytoprotective effects. Kim C, Cha YN.

[taurine-review] Amino Acids. 2014 Jan;46(1):7-20. Taurine and inflammatory diseases. Marcinkiewicz J, Kontny E.

[taurine-humans] Eur J Nutr. 2014 Apr;53(3):823-30. Oxidative stress and inflammation in obesity after taurine supplementation: a double-blind, placebo-controlled study. Rosa FT, Freitas EC, Deminice R, Jordão AA, Marchini JS. “Plasma taurine levels were significantly decreased (41%) in the obese volunteers. Both the placebo and taurine groups showed significant reduction in weight (3%), with no differences between groups. Different from placebo, taurine-supplemented group showed significant increase in plasma taurine (97%) and adiponectin (12%) and significant reduction in the inflammatory marker hs-C-reactive protein (29%) and in the lipid peroxidation marker thiobarbituric acid reactive substances (TBARS) (20%).”

[taurine-humans] Diab Vasc Dis Res. 2010 Oct;7(4):300-10. Two weeks taurine supplementation reverses endothelial dysfunction in young male type 1 diabetics. Moloney MA, Casey RG, O'Donnell DH, Fitzgerald P, Thompson C, Bouchier-Hayes DJ.

[taurine-humans] Amino Acids. 2008 Aug;35(2):469-73. Dietary amino acid taurine ameliorates liver injury in chronic hepatitis patients. Hu YH, Lin CL, Huang YW, Liu PE, Hwang DF.

[taurine-humans] Food Funct. 2014 Jul 25;5(7):1529-35. Effect of taurine in chronic alcoholic patients. Hsieh YL, Yeh YH, Lee YT, Huang CY. 

[taurine-humans] Am J Clin Nutr. 1995 May;61(5):1115-9. Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation. Franconi F, Bennardini F, Mattana A, Miceli M, Ciuti M, Mian M, Gironi A, Anichini R, Seghieri G. "The effective dose (mean +/- SEM) of arachidonic acid required for platelets to aggregate was significantly lower in diabetic patients than in control subjects (0.44 +/- 0.07 mmol compared with 0.77 +/- 0.02 mmol, P < 0.001, whereas after taurine supplementation it equaled the mean value for healthy control subjects (0.72 +/- 0.04 mmol)."

[taurine-humans] Clin Cardiol. 1985 May;8(5):276-82. Therapeutic effect of taurine in congestive heart failure: a double-blind crossover trial. Azuma J, Sawamura A, Awata N, Ohta H, Hamaguchi T, Harada H, Takihara K, Hasegawa H, Yamagami T, Ishiyama T, et al. 

[taurine-humans] Adv Exp Med Biol. 2009;643:13-25. Taurine as the nutritional factor for the longevity of the Japanese revealed by a world-wide epidemiological survey. Yamori Y, Liu L, Mori M, Sagara M, Murakami S, Nara Y, Mizushima S.

[taurine-humans] J Biomed Sci. 2010 Aug 24;17 Suppl 1:S6. Taurine in health and diseases: consistent evidence from experimental and epidemiological studies. Yamori Y, Taguchi T, Hamada A, Kunimasa K, Mori H, Mori M. "The preventive effects of T, good for health and longevity, first noted experimentally, were also proven epidemiologically in humans."

[taurine-humans] Adv Exp Med Biol. 1996;403:615-22. Effects of oral taurine supplementation on lipids and sympathetic nerve tone. Mizushima S, Nara Y, Sawamura M, Yamori Y. "To assess effects of oral taurine [...] 
in healthy young men on experimental high fat and cholesterol diets. [...] Significant increases in total CHO (25.4 +/- 17.5 mg/dl, mean +/- SD), LDL-CHO (17.1 +/- 14.5) and LDL (43.9 +/- 37.6) were observed in C-group but were attenuated in the T-group. [...] Significantly lower urinary norepinephrine excretion observed by the taurine administration implies the suppression of the sympathetic nervous system."

[taurine-humans] Amino Acids. 2014 Oct 17. Taurine attenuates chemotherapy-induced nausea and vomiting in acute lymphoblastic leukemia. Islambulchilar M, Asvadi I, Sanaat Z, Esfahani A, Sattari M. "The present study successfully demonstrated that taurine can decrease the incidence of chemotherapy-induced nausea and vomiting and attenuate chemotherapy-induced taste and smell impairment and fatigue in ALL patients during their maintenance chemotherapy. Furthermore taurine supplementation could lead to a more tolerable chemotherapeutic treatment for the patients."

[taurine-humans] Eur J Clin Nutr. 2004 Sep;58(9):1239-47. Effect of taurine treatment on insulin secretion and action, and on serum lipid levels in overweight men with a genetic predisposition for type II diabetes mellitus. Brøns C, Spohr C, Storgaard H, Dyerberg J, Vaag A. "Daily supplementation with 1.5 g taurine for 8 weeks had no effect on insulin secretion or sensitivity, or on blood lipid levels."

[taurine-humans] Diabetologia. 2008 Jan;51(1):139-46. Oral taurine but not N-acetylcysteine ameliorates NEFA-induced impairment in insulin sensitivity and beta cell function in obese and overweight, non-diabetic men. Xiao C, Giacca A, Lewis GF. "NAC failed to prevent the lipid-induced increase in levels of the plasma oxidative stress marker malondialdehyde and did not prevent the lipid-induced reduction in S(I) or DI, whereas TAU completely prevented the rise in malondialdehyde and decreased 4-hydroxynonenal, and significantly improved S(I) (91% of SAL) and DI (81% of SAL)."

[taurine-humans] Amino Acids. 2004 Feb;26(1):59-63. Effects of taurine supplementation on VDT work induced visual stress. Zhang M, Bi LF, Ai YD, Yang LP, Wang HB, Liu ZY, Sekine M, Kagamimori S. "After 12 days of taurine supplementation, the reduction in P100 amplitude after VDT work alleviated significantly [...] The results suggest that taurine supplementation alleviates visual fatigue induced by [visual display terminals] work."


[taurine-humans] Hypertension. 2016 Mar;67(3):541-9. Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study. Sun Q, Wang B, Li Y, Sun F, Li P, Xia W, Zhou X, Li Q, Wang X, Chen J, Zeng X, Zhao Z, He H, Liu D, Zhu Z.

[taurine-humans] Appl Physiol Nutr Metab. 2016 Jun;41(6):618-23. Taurine supplementation attenuates delayed increase in exercise-induced arterial stiffness. Ra SG, Choi Y, Akazawa N, Ohmori H, Maeda S.

[taurine-humans] Hypertens Res. 2016 Jul 14. Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats. Katakawa M, Fukuda N, Tsunemi A, Mori M, Maruyama T, Matsumoto T, Abe M, Yamori Y.

[taurine] Am J Clin Nutr. 1994 Aug;60(2):203-6. Taurine supplementation at three different dosages and its effect on trauma patients. Paauw JD, Davis AT. "Even 7 d of a high-dose taurine supplementation does not fully correct the hypotaurinemia of trauma."

[taurine] Am J Physiol. 1995 Sep;269(3 Pt 2):F429-38. Taurine ameliorates chronic streptozocin-induced diabetic nephropathy in rats. Trachtman H, Futterweit S, Maesaka J, Ma C, Valderrama E, Fuchs A, Tarectecan AA, Rao PS, Sturman JA, Boles TH, et al.

[taurine] Free Radic Biol Med. 2014 Apr;69:403-16. Chronic ethanol ingestion induces oxidative kidney injury through taurine-inhibitable inflammation. Latchoumycandane C, Nagy LE, McIntyre TM.

[taurine] Singapore Med J. 2005 Feb;46(2):82-7. Effect of taurine on biomarkers of oxidative stress in tissues of fructose-fed insulin-resistant rats. Nandhini AT, Thirunavukkarasu V, Ravichandran MK, Anuradha CV.

[taurine] Amino Acids. 2012 Jun;42(6):2223-32. Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Jong CJ, Azuma J, Schaffer S.

[taurine] Life Sci. 1999;64(1):83-91. Improvement in cholesterol metabolism in mice given chronic treatment of taurine and fed a high-fat diet. Murakami S, Kondo-Ohta Y, Tomisawa K. “These observations, together with prior findings, suggest that the cholesterol-lowering action of taurine may relate to the increased conversion of cholesterol to bile acids via stimulation of cholesterol 7a-hydroxylase activity.”

[taurine] J Nutr. 1999 Sep;129(9):1705-12. Dietary taurine enhances cholesterol degradation and reduces serum and liver cholesterol concentrations in rats fed a high-cholesterol diet. Yokogoshi H, Mochizuki H, Nanami K, Hida Y, Miyachi F, Oda H. “These results suggest that the hypocholesterolemic effects of taurine observed in the hypocholesterolemic rats fed the HC diet were mainly due to the enhancement of cholesterol degradation and the excretion of bile acid.”

[taurine] J Nutr Sci Vitaminol (Tokyo). 2011;57(2):144-9. Dietary taurine reduces hepatic secretion of cholesteryl ester and enhances fatty acid oxidation in rats fed a high-cholesterol diet. Fukuda N, Yoshitama A, Sugita S, Fujita M, Murakami S. “These results suggest that taurine-induced reduction in hepatic accumulation of cholesteryl ester was associated with reduced hepatic secretion of this lipid molecule, and was inversely related to enhanced ketone body production and fatty acid oxidation.”

[taurine] Amino Acids. 2011 Oct;41(4):901-8. Taurine prevents fat deposition and ameliorates plasma lipid profile in monosodium glutamate-obese rats. Nardelli TR, Ribeiro RA, Balbo SL, Vanzela EC, Carneiro EM, Boschero AC, Bonfleur ML. “TAU supplementation did not change glucose homeostasis, insulin secretion and action, but reduced plasma and liver lipid levels in MSG rats.”

[taurine-chemotherapy] Can J Physiol Pharmacol. 2015 Jul 18:1-9. Cardiorenal protective effect of taurine against cyclophosphamide-induced toxicity in albino rats. Alhumaidha KA, Saleh DO, Abd El Fattah MA, El-Eraky WI, Moawad H.

[taurine] Endocrinology. 2006 Jul;147(7):3276-84. Taurine (2-aminoethanesulfonic acid) deficiency creates a vicious circle promoting obesity. Tsuboyama-Kasaoka N, Shozawa C, Sano K, Kamei Y, Kasaoka S, Hosokawa Y, Ezaki O. “In high-fat diet-induced and/or genetically obese mice, a decrease in the blood taurine concentration was observed along with a decrease in CDO expression in adipose tissue but not in liver. Dietary taurine supplementation prevented high-fat diet-induced obesity with increased resting energy expenditure. Thus, taurine deficiency observed in association with obesity may create a vicious circle promoting obesity. Dietary taurine supplementation interrupts this vicious circle and may prevent obesity.”

[taurine] Amino Acids. 2016 May 7. Protective effects of taurine in traumatic brain injury via mitochondria and cerebral blood flow. Wang Q, Fan W, Cai Y, Wu Q, Mo L, Huang Z, Huang H. "Neuronal damage was prevented by 7 days taurine. Mitochondrial electron transport chain complexes I and II showed greater activity with the taurine group. The improvement by taurine of CBF may alleviate edema and elevation in intracranial pressure. Importantly taurine improved the hypercoagulable state."

[whey-protein-taurine-synthesis] PLoS One. 2013 Aug 30;8(8):e71134. Whey protein hydrolysate increases translocation of GLUT-4 to the plasma membrane independent of insulin in wistar rats. Morato PN, Lollo PC, Moura CS, Batista TM, Camargo RL, Carneiro EM, Amaya-Farfan J. "Translocation of GLUT-4 to the PM can also be stimulated in an insulin-independent manner. Carneiro et al. [28] accomplished this through taurine activation of the insulin pathway, thus raising the GLUT-4 concentration in the plasma membrane independent of insulin. [...] In the exercised animals of the WP and WPH groups, the plasma concentrations of taurine (Table 4) were greater [...] than those in the control group consuming CAS. This could explain, at least in part, the greater translocation of GLUT-4 in the WP and WPH groups. After investigating the amino acid composition of the WP and WPH, it was found they were rich in sulfur amino acids (Table 2), and methionine and cysteine are endogenous precursors of taurine [28]. Thus, the consumption of WP or WPH provided a greater amount of substrate for the endogenous production of taurine than casein, and the presence of this amino acid may have facilitated activation of the insulin pathway and cell capture of glucose, as indicated in the literature."

[gaba] Clin Exp Hypertens. 2009 Jun;31(4):342-54. Anti-hypertensive effect of gamma-aminobutyric acid (GABA)-rich Chlorella on high-normal blood pressure and borderline hypertension in placebo-controlled double blind study. Shimada M, Hasegawa T, Nishimura C, Kan H, Kanno T, Nakamura T, Matsubayashi T.

[gaba] J Anim Physiol Anim Nutr (Berl). 2014 Sep 30. Effect of GABA on oxidative stress in the skeletal muscles and plasma free amino acids in mice fed high-fat diet. Xie ZX, Xia SF, Qiao Y, Shi YH, Le GW. “One hundred male C57BL/6 mice were randomly divided into five groups that were fed with control diet, HFD and HFD supplied with 0.2%, 0.12% and 0.06% GABA in drinking water for 20 weeks respectively. HFD feeding led to muscular oxidative stress, protein oxidation, pFAA disorders, hyperglycaemia and augmented plasma GABA levels. Treatment with GABA restored normally fasting blood glucose level and dose-dependently inhibited body weight gains, muscular oxidation and protein degradation.”

[gaba] PLoS One. 2011;6(9):e25338. Oral treatment with γ-aminobutyric acid improves glucose tolerance and insulin sensitivity by inhibiting inflammation in high fat diet-fed mice. Tian J, Dang HN, Yong J, Chui WS, Dizon MP, Yaw CK, Kaufman DL. “Collectively, our data indicated that activation of peripheral GABA receptors inhibited the HFD-induced glucose intolerance, insulin resistance, and obesity by inhibiting obesity-related inflammation and up-regulating Treg responses in vivo. Given that GABA is safe for human consumption, activators of GABA receptors may be valuable for the prevention of obesity and intervention of T2DM in the clinic.”


[gaba] Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11692-7. GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes. Soltani N, Qiu H, Aleksic M, Glinka Y, Zhao F, Liu R, Li Y, Zhang N, Chakrabarti R, Ng T, Jin T, Zhang H, Lu WY, Feng ZP, Prud'homme GJ, Wang Q. “Remarkably, in severely diabetic mice, GABA restores β-cell mass and reverses the disease. Furthermore, GABA suppresses insulitis and systemic inflammatory cytokine production.”

[gaba] Transplantation. 2013 Oct 15;96(7):616-23. GABA protects human islet cells against the deleterious effects of immunosuppressive drugs and exerts immunoinhibitory effects alone. Prud'homme GJ, Glinka Y, Hasilo C, Paraskevas S, Li X, Wang Q. “GABA improved human islet cell survival and had suppressive effects on human immune cells. It inhibited canonical NF-κB activation in both islet and immune cells.”

[gaba] Hepatology. 1984 Mar-Apr;4(2):180-5. Identification of an acceptor system for gamma-aminobutyric acid on isolated rat hepatocytes. Minuk GY, Vergalla J, Ferenci P, Jones EA. "gamma-Aminobutyric acid (GABA) is a potent inhibitory neurotransmitter which is synthesized by the enteric bacterial flora and delivered into portal venous blood. To determine whether the liver is likely to play an important role in regulating serum GABA levels, the uptake and metabolism of [3H]GABA by three populations of cells isolated from rat liver were studied. GABA was specifically taken up by hepatocytes but not by endothelial or Kupffer cells."



[10] Histidiinin, karnosiinin ja anseriinin vaikutuksia ihmisillä ja eläimillä

[histidine-humans] Diabetologia. 2013 May;56(5):985-94. Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial. Feng RN, Niu YC, Sun XW, Li Q, Zhao C, Wang C, Guo FC, Sun CH, Li Y.

[histidine-humans] Arch Gerontol Geriatr. 2014 May 2. Anserine and carnosine supplementation in the elderly: Effects on cognitive functioning and physical capacity. Szcześniak D, Budzeń S, Kopeć W, Rymaszewska J. [13 weeks, 0.33g/d carnosine + 0.66g/d anserine -> BMI decreased by 0.51]

[histidine-humans] Rajashekar, Varsha, et al. "Metabolic effects of long-term oral ingestion of L-histidine in overweight and obese men." Proceedings of the Nutrition Society 67.OCE8 (2008): E380. 

[histidine-humans] Nutr Clin Pract. 2013 Oct;28(5):609-16. Effects of L-carnosine and its zinc complex (Polaprezinc) on pressure ulcer healing. Sakae K, Agata T, Kamide R, Yanagisawa H. "After 4 weeks, the rate of pressure ulcer healing, assessed by the mean weekly improvement in PUSH score, was significantly greater in the CAR (1.6 ± 0.2, P = .02) and PLZ groups (1.8 ± 0.2, P = .009) than in the control group (0.8 ± 0.2)."

[histidine] Br Med J. Jun 6, 1936; 1(3935): 1156–1158.  Histidine Treatment of Peptic Ulcer. Alec Wingfield

[histidine] Br J Nutr. 2014 Aug 28;112(4):477-85. Histidine supplementation alleviates inflammation in the adipose tissue of high-fat diet-induced obese rats via the NF-κB- and PPARγ-involved pathways. Sun X, Feng R, Li Y, Lin S, Zhang W, Li Y, Sun C, Li S.

[histidine] Nutrition. 2004 Nov-Dec;20(11-12):991-6. Histidine supplementation suppresses food intake and fat accumulation in rats. Kasaoka S, Tsuboyama-Kasaoka N, Kawahara Y, Inoue S, Tsuji M, Ezaki O, Kato H, Tsuchiya T, Okuda H, Nakajima S. "According to our nutrition survey [12] and [13], the Japanese consume about 1.5 g/d of histidine"


[histidine] Nutrition. 2005 Jul-Aug;21(7-8):855-8. Gender effects in dietary histidine-induced anorexia. Kasaoka S, Kawahara Y, Inoue S, Tsuji M, Kato H, Tsuchiya T, Okuda H, Nakajima S. "The suppressive effect of histidine on food intake was greater in female rats than in male rats, and the suppressive effect of histidine on food intake was less in ovariectomized rats than in female rats."


[histidine] Neurosci Lett. 2007 Jun 13;420(2):106-9. Bitter taste and blood glucose are not involved in the suppressive effect of dietary histidine on food intake. Goto K, Kasaoka S, Takizawa M, Ogawa M, Tsuchiya T, Nakajima S.


[histidine] Eur J Pharmacol. 2011 Feb 25;653(1-3):82-8. Histidine and carnosine alleviated hepatic steatosis in mice consumed high saturated fat diet. Mong MC, Chao CY, Yin MC. [Histidine and carnosine concentrations of liver are significantly decreased by a high-fat diet (by 33% and 78%). Supplementing either histidine OR carnosine counteracted the decreases in both histidine and carnosine almost equally, and both supplements had almost equivalent effects on metabolic parameters. It seems that both histidine and carnosine can be used interchangeably with similar biological effects.]

[histidine] Eur J Pharmacol. 2005 Apr 18;513(1-2):145-50. Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation. Lee YT, Hsu CC, Lin MH, Liu KS, Yin MC. "1 g/l histidine and carnosine treatments significantly reduced cholesterol level in heart and liver (P < 0.05). The administration of histidine or carnosine significantly enhanced catalase activity and decreased lipid oxidation levels in kidney and liver (P < 0.05); however, only 1 g/l histidine and carnosine treatments significantly increased glutathione peroxidase activity (P < 0.05). The increased interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in diabetic mice were significantly suppressed by the intake of histidine or carnosine (P < 0.05)."

[histidine] Food Chem Toxicol. 2008 May;46(5):1503-9. Beneficial effects of histidine and carnosine on ethanol-induced chronic liver injury. Liu WH, Liu TC, Yin MC.

[histidine] J Food Sci. 2009 Oct;74(8):H259-65. Protective effects from carnosine and histidine on acetaminophen-induced liver injury. Yan SL, Wu ST, Yin MC, Chen HT, Chen HC.

[histidine] Tohoku J Exp Med. 2000 Jun;191(2):85-99. Effect of carnosine on rats under experimental brain ischemia. Gallant S, Kukley M, Stvolinsky S, Bulygina E, Boldyrev A.

[histidine] Nutr Res Pract. 2011 Oct;5(5):421-8. Effects of α-lipoic acid and L-carnosine supplementation on antioxidant activities and lipid profiles in rats. Kim MY, Kim EJ, Kim YN, Choi C, Lee BH.

[histidine] PLoS One. 2011 Mar 15;6(3):e17971. Effects of dietary supplementation of carnosine on mitochondrial dysfunction, amyloid pathology, and cognitive deficits in 3xTg-AD mice. Corona C, Frazzini V, Silvestri E, Lattanzio R, La Sorda R, Piantelli M, Canzoniero LM, Ciavardelli D, Rizzarelli E, Sensi SL.

[histidine] J Physiol Biochem. 2014 Jun;70(2):385-95. Effect of carnosine alone or combined with α-tocopherol on hepatic steatosis and oxidative stress in fructose-induced insulin-resistant rats. Giriş M, Doğru-Abbasoğlu S, Kumral A, Olgaç V, Koçak-Toker N, Uysal M.

[histidine] J Neurochem. 2007 May;101(3):729-36. Epub 2007 Jan 24. Neuroprotective actions of a histidine analogue in models of ischemic stroke. Tang SC, Arumugam TV, Cutler RG, Jo DG, Magnus T, Chan SL, Mughal MR, Telljohann RS, Nassar M, Ouyang X, Calderan A, Ruzza P, Guiotto A, Mattson MP. "We recently synthesized and characterized histidine analogues related to the natural dipeptide carnosine, which selectively scavenge the toxic lipid peroxidation product 4-hydroxynonenal (HNE)[...]"

[histidine] Drug Chem Toxicol. 2014 Nov 27:1-6. [Epub ahead of print] Effects of histidine and n-acetylcysteine on experimental lesions induced by doxorubicin in sciatic nerve of rats. Farshid AA, Tamaddonfard E, Najafi S "Histidine and especially n-acetylcysteine at a same dose of 20 mg/kg suppressed cold and mechanical allodynia, improved sciatic nerve lesions and reversed MDA and TAC levels in DOX-treated groups. Combination treatment with histidine and n-acetylcysteine showed better responses when compared with them used alone." [cool results!]

[histidine] Cardiovasc Toxicol. 2014 Jun;14(2):153-61. doi: 10.1007/s12012-013-9239-6. Effects of histidine and N-acetylcysteine on doxorubicin-induced cardiomyopathy in rats. Farshid AA, Tamaddonfard E, Simaee N, Mansouri S, Najafi S, Asri-Rezaee S, Alavi H. "Histidine and especially NAC at a same dose of 40 mg/kg recovered ECG changes, improved heart lesions and prevented biochemical changes induced by DOX. Co-administration of histidine and NAC showed better responses when compared with them used alone."

[histidine] Gastroenterology. 2009 Feb;136(2):564-74.e2. Dietary histidine ameliorates murine colitis by inhibition of proinflammatory cytokine production from macrophages. Andou A, Hisamatsu T, Okamoto S, Chinen H, Kamada N, Kobayashi T, Hashimoto M, Okutsu T, Shimbo K, Takeda T, Matsumoto H, Sato A, Ohtsu H, Suzuki M, Hibi T.

[histidine] Am J Physiol Lung Cell Mol Physiol. 2007 May;292(5):L1095-104. Epub 2007 Jan 12. Protective effect of orally administered carnosine on bleomycin-induced lung injury. Cuzzocrea S, Genovese T, Failla M, Vecchio G, Fruciano M, Mazzon E, Di Paola R, Muià C, La Rosa C, Crimi N, Rizzarelli E, Vancheri C.

[histidine] Neurosci Lett. 2015 Feb 19;588:95-100. doi: 10.1016/j.neulet.2014.12.061. Epub 2015 Jan 3. Protective effect of carnosine on febrile seizures in immature mice. Dai YJ, Wu DC, Feng B, Hou WW, Xu CL, Ohtsu H, Chen Z, Hu WW. "Injection of carnosine significantly increased the latency and decreased the duration of FSs in a dose-dependent manner. In addition, histidine had similar effects on FSs as carnosine. The protective effect of carnosine or histidine was completely abolished by α-fluoromethylhistidine (α-FMH), a selective and irreversible histidine decarboxylase inhibitor, or in histidine decarboxylase deficient (HDC-KO) mice."

[histidine] Recent Pat Drug Deliv Formul. 2015;9(1):1-64. An "enigmatic" L-carnosine (β-alanyl-L-histidine)? Cell proliferative activity as a fundamental property of a natural dipeptide inherent to traditional antioxidant, anti-aging biological activities: balancing and a hormonally correct agent, novel patented oral therapy dosage formulation for mobility, skeletal muscle power and functional performance, hypothalamic-pituitary- brain relationship in health, aging and stress studies. Babizhayev MA, Yegorov YE. "Carnosine released from skeletal muscle during exercise acts as a powerful afferent physiological signaling stimulus for hypothalamus, may be transported into the hypothalamic tuberomammillary nucleus (TMN), specifically to TMN-histamine neurons and hydrolyzed herewith via activities of carnosine-degrading enzyme (carnosinase 2) localized in situ. Through the colocalized enzymatic activity of Histidine decarboxylase in the histaminergic neurons, the resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and physiological function. [...] This work originally emphasizes that overall data indicate the signaling activities of carnosine in skeletal and cardiac muscles switching on the mechanisms of exercise-induced telomere protection and point to the stress response and growth/cellular proliferation pathways as high-priority candidates for the ongoing studies and therapeutic concepts."

[histidine] Diabetes. 2013 Jul;62(7):2266-77. Histidine augments the suppression of hepatic glucose production by central insulin action. Kimura K, Nakamura Y, Inaba Y, Matsumoto M, Kido Y, Asahara S, Matsuda T, Watanabe H, Maeda A, Inagaki F, Mukai C, Takeda K, Akira S, Ota T, Nakabayashi H, Kaneko S, Kasuga M, Inoue H.

[histidine] Hum Exp Toxicol. 2010 Aug;29(8):659-65. The effect of carnosine pretreatment on oxidative stress and hepatotoxicity in binge ethanol administered rats. Artun BC, Küskü-Kiraz Z, Güllüoğlu M, Cevikbaş U, Koçak-Toker N, Uysal M. "In conclusion, carnosine prevented the increases in serum transaminase activities and lipid peroxides in liver of ethanol-treated rats, without any change on steatosis in liver."

[histidine] Neurosci Lett. 2012 Feb 21;510(1):1-5. Effects of L-carnosine on splenic sympathetic nerve activity and tumor proliferation. Horii Y, Shen J, Fujisaki Y, Yoshida K, Nagai K. "The tumor volumes of the control mice given water gradually and markedly increased and reached a value of 869.8 ± 132.9 mm3 on day 22 after implantation (Fig. 3b). The tumor volumes of the l-carnosine group also increased; however, the increase was less than that of the control group, reaching a value of 407.8 ± 121.7 mm3 (46.9% of the tumor volume of the control group) on day 22."

[histidine] Stroke. 2014 Aug;45(8):2438-43. Modulation of mitochondrial function and autophagy mediates carnosine neuroprotection against ischemic brain damage. Baek SH, Noh AR, Kim KA, Akram M, Shin YJ, Kim ES, Yu SW, Majid A, Bae ON. "However, treatment with carnosine significantly attenuated autophagic signaling in the ischemic brain, with improvement of brain mitochondrial function and mitophagy signaling. The protective effect of carnosine against autophagy was also confirmed in primary cortical neurons."


[histidine] Brain Res. 2005 Mar 28;1039(1-2):220-3. Prevention of brain infarction by postischemic administration of histidine in rats. Adachi N1, Liu K, Arai T. "The infarct size in the histidine (200 mg/kg, 500 mg/kg, and 1000 mg/kg, each time) groups was 71%, 39%, and 7% of that in the control group, respectively. [...] These findings indicate that postischemic administration of histidine prevents development of brain infarction by stimulating central histamine H2 receptors."

[histidine] Bull Exp Biol Med. 2002 Jun;133(6):559-61. Effect of carnosine on Drosophila melanogaster lifespan. Yuneva AO, Kramarenko GG, Vetreshchak TV, Gallant S, Boldyrev AA. "A positive dose-dependent effect of carnosine (beta-alanyl-L-histidine) on the lifespan of male Drosophila melanogaster flies was shown. The mean lifespan of male flies receiving 200 mg/liter carnosine approached that of females. [...] Addition of 200 mg/liter histidine and beta-alanine (separately or in combination) had no effect on the mean lifespan of flies."

[histidine] Br Poult Sci. 2013;54(4):454-65. Influence of different histidine sources and zinc supplementation of broiler diets on dipeptide content and antioxidant status of blood and meat. Kopeć W, Jamroz D, Wiliczkiewicz A, Biazik E, Pudlo A, Hikawczuk T, Skiba T, Korzeniowska M. "Histidine supplementation of the diet increased glutathione peroxidase activity in plasma and superoxide dismutase activity in erythrocytes. Moreover, the addition of SDBC or pure histidine in the diet increased histidine dipeptide content and activated enzymatic and non-enzymatic antioxidant systems in chicken blood and muscles. However, it led to lower growth performance indices."

[histidine] Neurol Res. 2010 Feb;32(1):101-5. Carnosine inhibits ATP production in cells from malignant glioma. Renner C1, Asperger A, Seyffarth A, Meixensberger J, Gebhardt R, Gaunitz F. "Carnosine might be considered as a potential drug for the treatment of malignant glioma or other tumors since it inhibits the glycolytic energy metabolism that is crucial for cancer cells and malignant gliomas as shown in the current study."


[histidine] Clin Res Hepatol Gastroenterol 2017 Mar 7. pii: S2210-7401(17)30009-8. [Epub ahead of print] Carnosine ameliorates liver fibrosis and hyperammonemia in cirrhotic rats. Jamshidzadeh A, Heidari R, Latifpour Z, Ommati MM, Abdoli N, Mousavi S, Azarpira N, Zarei A, Zarei M, Asadi B, Abasvali M, Yeganeh Y, Jafari F, Saeedi A, Najibi A, Mardani E. 

[histidine-glycine-proline-etc-fructose] J Nutr. 2015 Aug 5. pii: jn218982. Citrulline and Nonessential Amino Acids Prevent Fructose-Induced Nonalcoholic Fatty Liver Disease in Rats. Jegatheesan P, Beutheu S, Ventura G, Nubret E, Sarfati G, Bergheim I, De Bandt JP.

[alanine-mice-hfd] Eur J Nutr. 2016 Jun 17. Benefits of L-alanine or L-arginine supplementation against adiposity and glucose intolerance in monosodium glutamate-induced obesity. Araujo TR, Freitas IN, Vettorazzi JF, Batista TM, Santos-Silva JC, Bonfleur ML, Balbo SL, Boschero AC, Carneiro EM, Ribeiro RA.


[11] Ketogeeniset aminohapot

[threonine-lysine-liver-fat] J Biol Chem. 1953 Feb;200(2):867-74. The production of fatty livers in rats on threonine-and lysine-deficient diets. SINGAL SA, HAZAN SJ, SYDENSTRICKER VP, LITTLEJOHN JM.

[ketogenic-amino-acids] Biochim Biophys Acta. 2013 Oct;1832(10):1605-12. Ketogenic essential amino acids replacement diet ameliorated hepatosteatosis with altering autophagy-associated molecules. Xu L, Kanasaki M, He J, Kitada M, Nagao K, Jinzu H, Noguchi Y, Maegawa H, Kanasaki K, Koya D.

[ketogenic-amino-acids] PLoS One. 2010 Aug 10;5(8):e12057. Ketogenic essential amino acids modulate lipid synthetic pathways and prevent hepatic steatosis in mice. Noguchi Y, Nishikata N, Shikata N, Kimura Y, Aleman JO, Young JD, Koyama N, Kelleher JK, Takahashi M, Stephanopoulos G.




[12] Glysiinireseptori (glycine-gated chloride channel)

[glycine-receptor] Am J Physiol. 1997 Jun;272(6 Pt 1):G1581-6. Kupffer cells contain a glycine-gated chloride channel. Ikejima K, Qu W, Stachlewitz RF, Thurman RG.

[glycine-receptor] Nutr Cancer. 2001;40(2):197-204. Endothelial cells contain a glycine-gated chloride channel. Yamashina S, Konno A, Wheeler MD, Rusyn I, Rusyn EV, Cox AD, Thurman RG. "Importantly, glycine diminished serum-stimulated proliferation and migration of endothelial cells. Collectively, these data indicate that the inhibitory effect of glycine on growth and migration of endothelial cells is due to activation of a glycine-gated Cl- channel. This hyperpolarizes the cell membrane and blocks influx of Ca2+, thereby minimizing growth factor-mediated signaling."

[glycine-receptor] Infect Immun. 2001 Sep;69(9):5883-91. Dietary glycine prevents peptidoglycan polysaccharide-induced reactive arthritis in the rat: role for glycine-gated chloride channel. Li X, Bradford BU, Wheeler MD, Stimpson SA, Pink HM, Brodie TA, Schwab JH, Thurman RG.

[glycine-receptor] FASEB J. 2000 Mar;14(3):476-84. Glycine-gated chloride channels in neutrophils attenuate calcium influx and superoxide production. Wheeler M, Stachlewitz RF, Yamashina S, Ikejima K, Morrow AL, Thurman RG.

[taurine-GlyR] J Leukoc Biol. 1998 Nov;64(5):615-21. Taurine blunts LPS-induced increases in intracellular calcium and TNF-alpha production by Kupffer cells. Seabra V, Stachlewitz RF, Thurman RG. "Taurine significantly blunted the LPS-induced increase in [Ca2+]i in a dose-dependent manner (IC50, 0.1 mM). This effect was reversed by strychnine (1 microM) and was prevented when chloride was removed from the extracellular media. Moreover, taurine increased 36Cl- uptake by Kupffer cells in a dose-dependent manner (EC50, 0.2 mM). [...] These results indicate that taurine activates a glycine-gated chloride channel in Kupffer cells causing chloride influx. In addition, LPS-induced TNF-alpha production was reduced by more than 40% by taurine, an effect that was also reversed by strychnine."

[taurine-GlyR] Am J Clin Nutr. 1990 Oct;52(4):758-64. Taurine concentrations in plasma and whole blood in humans: estimation of error from intra- and interindividual variation and sampling technique. Trautwein EA, Hayes KC. “The normal plasma taurine concentration was 44 +/- 9 mumol/L (mean +/- SD; n = 40) in fasting subjects”

[taurine-GlyR] Ann Nutr Metab. 2007;51(4):379-86. Taurine induces anti-anxiety by activating strychnine-sensitive glycine receptor in vivo. Zhang CG, Kim SJ.



[13] Sappihapot, tauriini, glysiini, suolisto, lihavuus, kilpirauhashormonin aktivaatio, ym.

[bile] Hepatology. 2003 Mar;37(3):551-7. Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats. Lorenzo-Zúñiga V, Bartolí R, Planas R, Hofmann AF, Viñado B, Hagey LR, Hernández JM, Mañé J, Alvarez MA, Ausina V, Gassull MA.

[bile] Am Surg. 1992 May;58(5):305-10. Absence of intestinal bile promotes bacterial translocation. Slocum MM, Sittig KM, Specian RD, Deitch EA.

[bile] 2007 Oct;35(10):2367-74. Conjugated primary bile salts reduce permeability of endotoxin through intestinal epithelial cells and synergize with phosphatidylcholine in suppression of inflammatory cytokine production. Parlesak A, Schaeckeler S, Moser L, Bode C.

[bile] Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3920-5. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Inagaki T, Moschetta A, Lee YK, Peng L, Zhao G, Downes M, Yu RT, Shelton JM, Richardson JA, Repa JJ, Mangelsdorf DJ, Kliewer SA. “Obstruction of bile flow results in bacterial proliferation and mucosal injury in the small intestine that can lead to the translocation of bacteria across the epithelial barrier and systemic infection. These adverse effects of biliary obstruction can be inhibited by administration of bile acids. Here we show that the farnesoid X receptor (FXR), a nuclear receptor for bile acids, induces genes involved in enteroprotection and inhibits bacterial overgrowth and mucosal injury in ileum caused by bile duct ligation. Mice lacking FXR have increased ileal levels of bacteria and a compromised epithelial barrier.”

[bile] Best Pract Res Clin Gastroenterol. 2014 Aug;28(4):573-583. Bile acids, obesity, and the metabolic syndrome. Ma H, Patti ME. ”Bile acids are synthesized from cholesterol through two dominant pathways: the classic pathway and the alternative pathway (Fig. 1). In the classic (or neutral) pathway, CYP7A1 catalyses the initial and rate-limiting step converting cholesterol into 7α-hydroxycholesterol, with CYP8B1 subsequently regulating synthesis of 12α-hydroxysterols including cholic acid (CA). In the alternative (or acidic) pathway, CYP27A1 first hydroxylates the cholesterol side chain, converting cholesterol into 27-hydroxycholesterol, which is then 7α-hydroxylated by CYP7B1 prior to CYP8B1 action. In humans, the classical pathway produces the primary BA cholic acid (CA) and chenodeoxycholic acid (CDCA) in roughly equal amounts, whereas the alternative pathway produces mainly CDCA [8]. Most bile acids are conjugated with either glycine or taurine, with a 3:1 predominance of glycine over taurine [3], [5] and [9].”

[bile-farnesoid-x-receptor-intestines] Gut. 2011 Apr;60(4):463-72. Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gadaleta RM, van Erpecum KJ, Oldenburg B, Willemsen EC, Renooij W, Murzilli S, Klomp LW, Siersema PD, Schipper ME, Danese S, Penna G, Laverny G, Adorini L, Moschetta A, van Mil SW.

[bile-farnesoid-x-receptor-inflammation] Biochim Biophys Acta. 2011 Aug;1812(8):851-8. Activation of bile salt nuclear receptor FXR is repressed by pro-inflammatory cytokines activating NF-κB signaling in the intestine. Gadaleta RM, Oldenburg B, Willemsen EC, Spit M, Murzilli S, Salvatore L, Klomp LW, Siersema PD, van Erpecum KJ, van Mil SW. “Together, these results indicate that intestinal inflammation strongly reduces FXR activation, probably via NF-κB-dependent tethering of FXR. Therefore, FXR not only inhibits inflammation, but also is targeted by the inflammatory response itself. This could result in a vicious cycle where reduced FXR activity results in less repression of inflammation, contributing to development of chronic intestinal inflammation.”

[bile-protective-mechanism-thyroid] Nature. 2006 Jan 26;439(7075):484-9. Epub 2006 Jan 8. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, Messaddeq N, Harney JW, Ezaki O, Kodama T, Schoonjans K, Bianco AC, Auwerx J. “Here we show that the administration of BAs to mice increases energy expenditure in brown adipose tissue, preventing obesity and resistance to insulin. This novel metabolic effect of BAs is critically dependent on induction of the cyclic-AMP-dependent thyroid hormone activating enzyme type 2 iodothyronine deiodinase (D2) because it is lost in D2-/- mice. Treatment of brown adipocytes and human skeletal myocytes with BA increases D2 activity and oxygen consumption.”

[taurine-bile-thyroid-hormone-activation] FEBS Lett. 2011 Feb 4;585(3):539-44. The chemical chaperones tauroursodeoxycholic and 4-phenylbutyric acid accelerate thyroid hormone activation and energy expenditure. da-Silva WS, Ribich S, Arrojo e Drigo R, Castillo M, Patti ME, Bianco AC.

[bile] PhD Thesis by Hanne Sørup Tastesen: Dietary protein in the prevention of diet‐induced obesity and co‐morbidities (University of Copenhagen, 2014) "The affinity of the bile salt export pump is greater for conjugated than for non‐conjugated BA [137]. Conjugation of BA therefore increases biliary secretion of BA [138] and may thus in turn enhance BA synthesis leading to the increase in BA pool seen with increased dietary taurine and glycine in rats [123, 124]. The conjugation of bile acids is highly species specific [139, 140]; rats conjugate primarily with taurine but also to some extend with glycine, rabbits conjugate exclusively with glycine, mice conjugate almost exclusively with taurine, while human subjects conjugate with both glycine and taurine, usually in the proportions 3:1 [141]. It has been demonstrated that taurine and glycine supplementation increases BA pool in hamsters [142] and as described above that seafood protein rich in glycine and taurine increases plasma BA in rats [123, 124]."



[14] Histidiinin (ja karnosiinin) vaikutusmekanismeja

[histidine-carnosine-mechanisms] Physiol Rev. 2013 Oct;93(4):1803-45. Physiology and pathophysiology of carnosine. Boldyrev AA, Aldini G, Derave W. “Also the pathophysiological relevance of serum carnosinase, the enzyme actively degrading carnosine into l-histidine and β-alanine, is discussed. The carnosine system has evolved as a pluripotent solution to a number of homeostatic challenges. l-Histidine, and more specifically its imidazole moiety, appears to be the prime bioactive component, whereas β-alanine is mainly regulating the synthesis of the dipeptide.”

[histidine-carnosine-mechanisms] Peptides. 2009 Jul;30(7):1306-12. Inhibitory effect of carnosine and N-acetyl carnosine on LPS-induced microglial oxidative stress and inflammation. Fleisher-Berkovich S, Abramovitch-Dahan C, Ben-Shabat S, Apte R, Beit-Yannai E.

[histidine-carnosine-mechanisms] J Neurosci Res. 2007 Aug 1;85(10):2239-45. Carnosine interaction with nitric oxide and astroglial cell protection. Nicoletti VG, Santoro AM, Grasso G, Vagliasindi LI, Giuffrida ML, Cuppari C, Purrello VS, Stella  AM, Rizzarelli E. "A comparison of carnosine with its homologues or derivatives (homocarnosine and carcinine) as well as with its amino acid constituents (L-histidine and beta-alanine) highlighted that only histidine showed significant scavenging activity."

[histidine-carnosine-mechanisms] Neurochem Res. 2005 Jun-Jul;30(6-7):797-807. Protective effect of carnosine during nitrosative stress in astroglial cell cultures. Calabrese V, Colombrita C, Guagliano E, Sapienza M, Ravagna A, Cardile V, Scapagnini G, Santoro AM, Mangiameli A, Butterfield DA, Giuffrida Stella AM, Rizzarelli E.


[histidine-histamine] Clin Exp Pharmacol Physiol. 2010 Jan;37(1):62-8. Oral L-histidine exerts antihypertensive effects via central histamine H3 receptors and decreases nitric oxide content in the rostral ventrolateral medulla in spontaneously hypertensive rats. Toba H, Nakamori A, Tanaka Y, Yukiya R, Tatsuoka K, Narutaki M, Tokitaka M, Hariu H, Kobara M, Nakata T. "These results suggest that L-histidine decreases blood pressure by attenuating sympathetic output via the central histamine H3 receptor in SHR. In addition, the antihypertensive effects of L-histidine appear to be associated with an increase in nitric oxide in the RVLM."

[histidine-histamine] The American Journal of Digestive Diseases July 1944, Volume 11, Issue 7, pp 209-223 The therapeutic use of the amino acid histidine in allergy and shock— “Histidine as a factor in histamine epinephrine balance” Simon L. Ruskin "A role of therapeutic usefulness of the amino acid histidine is indicated in allergic and related conditions. Histidine is antagonistic to histamine and plays an important part in histamine-adrenalin balance in shock. Histidine produces a feeling of well being and energy that could be useful in the care of post-operative patients and the treatment of shock."

[histidine-histamine] Brain Res. 2013 Aug 21;1527:246-54. Role of histidine/histamine in carnosine-induced neuroprotection during ischemic brain damage. Bae ON, Majid A. "In primary astrocytes, carnosine significantly reduced ischemic cell death after oxygen-glucose deprivation, and this effect was abolished by histamine receptor type I antagonist. However, histidine or histamine did not exhibit a protective effect on ischemic astrocytic cell death."


[histidine-histamine] J Neurochem. 1972 Mar;19(3):801-10. Histamine formation in rat brain in vivo: effects of histidine loads. Schwartz JC, Lampart C, Rose C. "Administration of l-histidine at the rate of 500 mg/kg induced an increase of nearly 50 per cent in the level of histamine in rat brain which lasted several hours."

[histidine-mitochondria] Biochemistry. 1971 Jan 5;10(1):102-7. Participation of L-histidine in the maintenance of mitochondrial integrity. Connelly JL, Myron DR. 


[histidine-PDK4] Amino Acids. 2014 Apr;46(4):1009-19. The antineoplastic effect of carnosine is accompanied by induction of PDK4 and can be mimicked by L-histidine. Letzien U, Oppermann H, Meixensberger J, Gaunitz F. "The experiments identified a strong induction of expression of the gene encoding pyruvate dehydrogenase 4 (PDK4) under the influence of carnosine and L-histidine, but not by the other substances employed. In addition, inhibition of cell viability was only detected in cells treated with carnosine and L-histidine, with the latter showing a significantly stronger effect than carnosine. Since the tumor cells expressed the tissue form of carnosinase (CN2) but almost no serum carnosinase (CN1), we conclude that cleavage by CN2 is a prerequisite for the antineoplastic effect of carnosine. In addition, enhanced expression of PDK4 under the influence of carnosine/L-histidine opens a new perspective for the interpretation of the ergogenic potential of dietary β-alanine supplementation and adds a new contribution to a growing body of evidence that single amino acids can regulate key metabolic pathways important in health and disease."




[15] Proteiinien terveysvaikutusten aminohapoista riippumattomat mekanismit

[hydrolyzed-protein] PhD Thesis by Hanne Sørup Tastesen: Dietary protein in the prevention of diet‐induced obesity and co‐morbidities (University of Copenhagen, 2014) "GLP‐1 is important for maintaining normal glucose homeostasis as it induces glucose stimulated insulin secretion, while CCK stimulates digestion by inducing release of pancreatic digestive enzymes and bile from the gallbladder and both hormones furthermore reduces appetite and energy intake. These stimulatory effects of peptides on hormone release, compared to intact protein and free AA, suggest a way in which hydrolyzed proteins may affect DIO, impaired glucose and insulin metabolism and other morbidities"

[hydrolyzed-protein] J Nutr. 2013 Sep;143(9):1367-75. Hydrolyzed casein reduces diet-induced obesity in male C57BL/6J mice. Lillefosse HH, Tastesen HS, Du ZY, Ditlev DB, Thorsen FA, Madsen L, Kristiansen K, Liaset B. "The physiological changes induced by hydrolyzed casein ingestion translated into decreased body and adipose tissue masses"

[casein-vs-salmon] Ibrahim, M. M., Fjære, E., Lock, E. J., Naville, D., Amlund, H., Meugnier, E., ... & Ruzzin, J. (2011). Chronic consumption of farmed salmon containing persistent organic pollutants causes insulin resistance and obesity in mice. PloS one, 6(9), e25170.

[casein-vs-chicken] PhD Thesis by Hanne Sørup Tastesen: Dietary protein in the prevention of diet‐induced obesity and co‐morbidities (University of Copenhagen, 2014) [Paper 2: "A Mixture of Cod and Scallop Protein Reduces Adiposity and Improves Glucose Tolerance in High‐Fat, High‐Sucrose Fed Male C57BL/6J Mice"] "The reduced adiposity in the casein-fed, compared to the chicken-fed mice, was likely related to the three percent lower apparent fat digestibility in casein-fed compared to chicken- and cod/scallop-fed mice."


[casein-vs-chicken] PLoS One. 2014 Nov 12;9(11):e112859. A Mixture of Cod and Scallop Protein Reduces Adiposity and Improves Glucose Tolerance in High-Fat Fed Male C57BL/6J Mice. Tastesen HS, Rønnevik AK, Borkowski K, Madsen L, Kristiansen K, Liaset B.

[dairy-fecal-fat] Int J Obes (Lond). 2008 Dec;32(12):1816-24. Effect of dairy calcium on fecal fat excretion: a randomized crossover trial. Bendsen NT, Hother AL, Jensen SK, Lorenzen JK, Astrup A. "The main protein source in the low-Ca diet was pork meat, whereas most of the protein in the high-Ca diet was of dairy origin."

[salmon-protein-different-hydrolyzation] Food Chem. 2015 Sep 15;183:101-10. Three differently generated salmon protein hydrolysates reveal opposite effects on hepatic lipid metabolism in mice fed a high-fat diet. Vik R, Tillander V, Skorve J, Vihervaara T, Ekroos K, Alexson SE, Berge RK, Bjørndal B. "In conclusion, bioactive peptides with distinctive properties could potentially be isolated from salmon hydrolysates."



[16] Glysiinin ja histidiinin alhaisemmat seerumitasot insuliiniresistenteillä potilailla

[ínsulin-resistance-amino-acids] Br J Nutr. 2012 Jul 14;108(1):57-61. Histidine and arginine are associated with inflammation and oxidative stress in obese women. Niu YC, Feng RN, Hou Y, Li K, Kang Z, Wang J, Sun CH, Li Y. "Among the amino acids determined, serum histidine, arginine, threonine, glycine, lysine and serine were found to be significantly lower in obese women as compared to non-obese controls (P < 0·001). The difference was the greatest for histidine (P < 0·001)."

[insulin-resistance-amino-acids] PLoS One. 2013 Dec 31;8(12):e84034. Serum glycine is associated with regional body fat and insulin resistance in functionally-limited older adults. Lustgarten MS, Price LL, Phillips EM, Fielding RA.

[insulin-resistance-amino-acids] PLoS One. 2010 Dec 10;5(12):e15234. Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women. Fiehn O, Garvey WT, Newman JW, Lok KH, Hoppel CL, Adams SH. [Diabetic patients have 26% lower serum glycine levels than the "normal" population.]




[17] Muita lähteitä: Ruokavalio ja glysiinitasot

[red-meat-glycine-diabetes] Am J Clin Nutr. 2015 May 6. pii: ajcn099150. Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat conmption to type 2 diabetes. Wittenbecher C, Mühlenbruch K, Kröger J, Jacobs S, Kuxhaus O, Floegel A, Fritsche A, Pischon T, Prehn C, Adamski J, Joost HG, Boeing H, Schulze MB. "In our study, high ferritin, low glycine, and altered hepatic-derived lipid concentrations in the circulation were associated with total red meat consumption and, independent of red meat, with diabetes risk"

[lactovegetarian-diet-urinary-glycine] Anal Bioanal Chem. 2010 Feb;396(4):1451-63. Identification of biochemical changes in lactovegetarian urine using 1H NMR spectroscopy and pattern recognition. Xu J, Yang S, Cai S, Dong J, Li X, Chen Z. [Urinary glycine: VEGMALE 17.23 OMNMALE 15.39 VEGFEMALE 23.78 OMNFEMALE 14.50]

[prudent-diet-urinary-glycine] Am J Clin Nutr. 2011 Feb;93(2):314-21. Dietary intake patterns are reflected in metabolomic profiles: potential role in dietary assessment studies. O'Sullivan A, Gibney MJ, Brennan L. "In the current study, glycine was identified as an important variable in the differentiation of dietary clusters with higher concentrations evident in urine profiles from dietary cluster 1. The defining characteristics of dietary cluster 1 included a higher consumption of wholegrain breads and vegetables and lower consumption of meat products, poultry, and poultry dishes."

[meat-intake-glycine] Br J Nutr. 2013 Sep 14;110(5):810-22. Identification of biomarkers for intake of protein from meat, dairy products and grains: a controlled dietary intervention study. Altorf-van der Kuil W, Brink EJ, Boetje M, Siebelink E, Bijlsma S, Engberink MF, van 't Veer P, Tomé D, Bakker SJ, van Baak MA, Geleijnse JM. [Gly intakes: 1) Dairy-protein diet 48.5mg/(kg*d), Meat-protein diet 95.0mg/(kg*d), Grain-protein diet 64.1mg/(kg*d) ---- Plasma Gly: 12.5mg/l, 13.6mg/l and 14.3mg/l ---- Urinary Gly: 75.7mg/d, 81.0mg/d an 88.3mg/d]



[18] Muita lähteitä: Proteiinirajoitus koe-eläimillä

[extra] Cell Rep. 2015 May 28. pii: S2211-1247(15)00505-7. Dietary Protein to Carbohydrate Ratio and Caloric Restriction: Comparing Metabolic Outcomes in Mice. Solon-Biet SM, Mitchell SJ, Coogan SC, Cogger VC, Gokarn R, McMahon AC, Raubenheimer D, de Cabo R, Simpson SJ, Le Couteur DG. [Lyhytaikainen proteiinirajotus (8 viikkoa) tuntuu tuovan samoja hyötyjä kuin kalorirajotus (CR). Artikkelissa todetaan, että pitkässä juoksussa on kuitenkin havaittu haittoja.]

[extra] Cell Metab. 2014 Mar 4;19(3):418-30. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE, Cogger VC, Warren A, Huang X, Pichaud N, Melvin RG, Gokarn R, Khalil M, Turner N, Cooney GJ, Sinclair DA, Raubenheimer D, Le Couteur DG, Simpson SJ. [Runsaampi proteiinin [tässä tapauksessa kaseiinin] saanti korreloi muun muassa matalempien veren alaniini-, kysteiini-, seriini-, glysiini- ja histidiinitasojen kanssa. (Table 1) Toki voi olla että vaikutus liittyy esimerkiksi insuliiniin.]

[extra] Ageing Res Rev. 2017 Mar 6. pii: S1568-1637(17)30046-6. Dietary protein, aging and nutritional geometry. Simpson SJ, Le Couteur DG, Raubenheimer D, Solon-Biet SM, Cooney GJ, Cogger VC, Fontana L. "Nutritional geometry is a state-space modelling approach that explores how animals respond to and balance changes in nutrient availability. Such studies in insects and mice have shown that low protein, high carbohydrate diets are associated with longest lifespan in ad libitum fed animals suggesting that the interaction between macronutrients may be as important as their total intake."


[19] Muita lähteitä: Tryptofaanirajoitus

[tryptophan-restriction] Mech Ageing Dev. 1986 Oct;36(2):161-71. Influence of low tryptophan diet on survival and organ growth in mice. De Marte ML, Enesco HE. "The 50% survival point was reached by the tryptophan restricted group at 683 days, and by the control group at 616 days. [...] Both whole body weight and organ weight of liver, kidney, heart and spleen were about 30% lower in the tryptophan restricted group as compared to the controls, so that the ratio of organ weight to body weight remained at a constant value for both groups."

[tryptophan-restriction] Mech Ageing Dev. 1988 Apr;43(1):79-98. Histology and survival in age-delayed low-tryptophan-fed rats. Ooka H, Segall PE, Timiras PS. "Diets containing tryptophan in concentrations 30 and 40 percent of those fed to controls from weaning to 24-30 months or more, can delay aging in Long-Evans female rats. Mortality among low-tryptophan-fed rats was greater in the juvenile period, but substantially less than controls at late ages. Histological biomarkers of aging were also delayed after tryptophan restriction in some organs (liver, heart, uterus, ovary, adrenal and spleen) but not in others (kidney, lung, aorta)."

[tryptophan-restriction] Mech Ageing Dev. 1976 Mar-Apr;5(2):109-24. Patho-physiologic findings after chronic tryptophan deficiency in rats: a model for delayed growth and aging. Segall PE, Timiras PS. "Ability to reproduce, as indicated by litter production, was present at 17-28 months of age in rats which had been deprived of tryptophan, whereas no controls over 17 months of age produced any offspring. Other signs of delayed aging in the experimental group included, at advanced ages, greater longevity, as well as later onset in the appearance of obvious tumors, and better coat condition and hair regrowth. Many of these effects were also seen in pair-fed controls (fed a diet equal in amount to that eaten by the tryptophan-deprived rats, but with 1-tryptophan added)."

6 kommenttia:

  1. Oo! Mistä minä nyt saan noita histidiinejä ym.? Eiku riisiproteiinia syömään! Onkohan sitä kaupoissa.

    VastaaPoista
    Vastaukset
    1. Moi Anonyymi,

      Histidiinijauhetta tuntuu myyvän ainakin Mass.fi
      Glysiinijauhetta tuntuu myyvän ainakin Aminoporssi.fi
      Riisiproteiinista en tiedä. Luulen että ainakin Ruohonjuuri myy.

      Muista että tutkimusdatasta suurin osa on toteutettu jyrsijöillä, eli osa vaikutuksista ei välttämättä päde ihmisillä. :)

      Histidiinin kohdalla ihmistutkimuksen tulokset ovat hyvin innostavat, mutta pitkäaikaisdatan puuttuessa haluaisin todeta että histidiinin runsaan kulutuksen mahdollisia haittavaikutuksia ei tiedetä, koska aiheesta ei ole olemassa pitkäaikaista tutkimustietoa. Lyhyellä aikavälillä se vaikutti kuitenkin melko turvalliselta:

      "As a large dose of histidine (64 g/day) was reported to induce side effects of headache, weakness, drowsiness and nausea [22], and a low dose may not produce the significant effects we expected, we conducted a pilot experiment with 4 g/day and 8 g/day histidine supplementation to determine an effective and safe dose.

      We found that both doses could significantly increase SOD at week 2, with no side effects or suppressed appetite. For the sake of safety, we selected 4 g/day for this study. In this 12-week intervention, we did not observe any side effects or changes in liver enzymes or kidney variables."

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  2. Saako iherbistä tilata N-Acetyl-cysteiniä?

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    Vastaukset
    1. Asetyylikysteiini löytyy kyllä lääkeluettelosta, joten en valitettavasti osaa sanoa.

      Kannattaa ehkä Fimealta selvittää.

      Glysiinikin on lääkeluettelossa, mutta Fimean edustajan mukaan sitä voi näköjään tilata kuitenkin: http://valtsuhealth.blogspot.fi/2013/12/glysiinin-terveysvaikutuksia.html?showComment=1432158733459#c3970633444459218155

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    2. Kiitos Valtsu!

      Tiitu

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