L’ ALA è un coenzima presente in natura e prodotto in minima parte dall’organismo, balzato al centro di discussioni negli ultimi anni per via delle sue interessanti proprietà. Innanzitutto, ci sono da fare alcune differenziazioni, esistono 2 tipi di ALA:
l’enantiomero S(-) e l’enantiomero R(+). In commercio, esiste il cosiddetto ALA racemato, il quale contiene una mistura al 50% dei due isomeri i quali, come vedremo in seguito, hanno effetti diversi.
In natura e nell’organismo esiste solo il R(+), mentre il S(-) è una forma sintetica derivante come sottoprodotto della produzione dell’ ALA a livello industriale.
Il metabolismo del glucosio
Per funzionare correttamente, le cellule hanno bisogno di un continuo apporto di carburante. Lo zucchero nel sangue, è la chiave per la maggior parte delle cellule nel corpo e l’insulina è l’ormone che si occupa dello spostamento del glucosio sanguigno verso le cellule (anche quelle muscolari). L’insulina entra in contatto con il suo recettore, situato sulla superficie della cellula, e grazie a questo legame vengono mobilitati dei recettori (Glut 4) che aprono la strada al glucosio.
Alcuni fattori, come la sedentarietà, la dieta eccessivamente ricca di carboidrati ad alto indice glicemico, il non sottoporsi mai a regimi ipocalorici e l’invecchiamento in generale, possono compromettere l’efficacia di questo sistema, così accade che la risposta all’insulina diventa meno repentina. Questo, in forma grave, sfocia nella sindrome X (o diabete di tipo 2) e le relative conseguenze: adiposità, colesterolo elevato, pressione alta, varie patologie cardiovascolari, ecc…
Cosa c’entra l’ ALA in tutto questo?
Bene, trials controllati provano che la forma racemica dell’ ALA (o RS-ALA per comodità) aiuta l’organismo a diventare più sensibile all’azione dell’insulina.
Alcune ricerche, però, dimostrano ampiamente che solo il R(+) è responsabile dell’azione di insulino-mimetico, mentre il S(-) non fa assolutamente nulla o addirittura il contrario!!! Adesso resta da spiegare, mediante quale meccanismo il R(+) esplica la sua azione. Gli scienziati hanno comparato l’effetto dei 2 enantiomeri sugli animali da laboratorio (iniettando singolarmente la forma S(-) o R(+)) e hanno scoperto che nei muscoli di tali animali (trattati con la forma R(+) era presente il 31% di glucosio in più in risposta all’insulina, mentre il S(-) non ha dato alcun beneficio.
In seguito, furono esaminati gli effetti cronici dei due enantiomeri:
un gruppo di animali fu sottoposto ad una dieta regolare, l’altro ricevette in più uno dei due enantiomeri.
Stessi risultati!!!
In più, I livelli di insulina degli animali trattai con R(+) risultarono soppressi del 17% (insieme agli acidi grassi liberi), ciò significa che meno insulina è necessaria per mantenere costante la glicemia nel sangue. Invece, il S(-) ha causato un aumento della secrezione di insulina del 15% (nessun cambiamento nei FFA), a dimostrazione del fatto che ha un comportamento opposto a quello del R(+). La quantità dei recettori Glut-4 nelle cellule muscolari degli animali era ridotta del 19% in seguito a utilizzo di S(-).
Il R(+), contrariamente alle aspettative e a quanto solitamente si afferma, non ha mostrato nessuna abilità nell’aumentare il numero dei suddetti recettori, ma è stato visto che il R(+) aiuta la cellula a mobilizzare i trasportatori del glucosio, cosa invece su cui il S(-) interferisce!
Altri aspetti della risposta all’insulina furono migliorati dall’ R(+) ma non dall’ S(-), e cioè una ristorazione del 33% nell’abilità di bruciare glicogeno per energia e un aumento del 26% nella formazione di glicogeno.
L’ attività antiossidante
Quando ingoi una compressa di RS-ALA, entrambi gli isomeri finiscono nel flusso sanguigno e poi trasportati nelle cellule. Qui, scorgiamo un altro vantaggio del R(+): è più biodisponibile rispetto al S(-). Le concentrazione plasmatiche di picco dei due isomeri, a parità di dose, sono del doppio a favore del R(+) e il quantitativo totale di R(+) trasportato nel plasma è del 60-85% più grande della forma S(-). Per chiarire le differenze di assorbimento, gli scienziati hanno somministrato agli animali, in via parenterale, la forma R(+), S(-) e RS, in modo da bypassare il tratto gastrointestinale. Come ci si aspettava, le concentrazioni erano uguali in tutti e tre i gruppi, ma tre ore dopo, il gruppo che ha ricevuto R(+) aveva da 2 a 7 volte più R-ALA nelle lenti degli occhi, e tre volte di più degli animali che avevano ricevuto RS-ALA.
Nonostante ciò che leggiamo e sentiamo, il vero super-antiossidante, non è il R(+) o S(-) o RS, è un sottoprodotto dell’ ALA chiamato DHLA (Acido diidrolipoico).
In un altro studio, le cellule dei nervi prelevate da differenti parti del cervello, furono esposte ad una sufficiente quantità di buthionine sulfoxamine (BSO) per distruggere metà di essi. Aggiungere R(+) ha comportato un salvataggio tra ½ e 1/3 delle cellule nervose.
Ne la forma S(-) ne la RS hanno mostrato un effetto simile.
Risultati ancora più inaspettati furono visti quando lo stesso team di ricerca decise di cercare una dose di RS-ALA sufficiente (o di uno dei 2 enantiomeri) per proteggere le cellule nervose dall’acido omocisteico. Senza sorpresa, gli scienziati hanno trovato che il R(+) ha protetto le cellule in questione con una dose del 38% inferiore richiesta dal S(-). Addirittura, la forma RS in questo caso si è dimostrata ancora più debole della forma S(-). Le tre forme, erano però efficaci nella stessa maniera nel proteggere le cellule nervose nella zona dell’ippocampo. Ancora uno studio, ha sperimentato le proprietà antiossidanti dell’ALA nei confronti della cataratta indotta negli animali con BSO.
Grazie ancora al R(+), il numero degli animali che ha contratto cataratta è stato del 55% in meno e la forma RS ha offerto lo stesso grado di protezione.
I metalli
Come abbiamo visto prima, l’ ALA offre una gran varietà di protezioni contro numerosi agenti tossici e in vari distretti dell’organismo (cuore, fegato, polmoni, cervello, sangue). L’ALA offre protezione anche dai cosiddetti “metalli di transizione” come ferro, cadmio e rame. Questi tre metalli non sono ossidanti di per se, ma posti a contatto con il perossido di idrogeno, spaccano la molecola a metà formando 2 radicali idrossilici tossici. L’ALA previene proprio questa reazione (chiamata reazione di Fenton).
Un eccesso di questi metalli nel cervello, è causa di molti disordini neuronali, tra cui anche morbo di Parkinson e di Alzaimer.
Ancora al riguardo del SNC, l’ ALA è in grado di proteggere dagli effetti neurotossici della MDMA (anfetamine).
ALA prevents 3,4-methylenedioxy-methamphetamine (MDMA)-induced neurotoxicity.
Aguirre N, Barrionuevo M, Ramirez MJ, Del Rio J, Lasheras B.
Department of Pharmacology, School of Medicine, University of Navarra, Pamplona, Spain.
A single administration of 3,4-methylenedioxymethamphetamine (MDMA, 20 mg/kg, i.p.), induced significant hyperthermia in rats and reduced 5-hydroxytryptamine (5-HT) content and [3H]paroxetine-labeled 5-HT transporter density in the frontal cortex, striatum and hippocampus by 40-60% 1 week later. MDMA treatment also increased glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus. Repeated administration of the metabolic antioxidant alpha-lipoic acid (100 mg/kg, i.p., b.i.d. for 2 consecutive days) 30 min prior to MDMA did not prevent the acute hyperthermia induced by the drug; however, it fully prevented the serotonergic deficits and the changes in the glial response induced by MDMA. These results further support the hypothesis that free radical formation is responsible for MDMA-induced neurotoxicity.
Lo stomaco
Uno studio interessante condotto sui ratti, ha dimostrato la capacità protettiva dell’ ALA dei confronti delle lesioni gastriche etanolo-indotte.
Thioctic acid protection against ethanol and indomethacin induced gastric mucosal lesions in rats.
Gutierrez-Cabano CA, Valenti JL.
Department of Surgical Pathology II, Faculty of Medical Sciences National University of Rosario, Argentina.
BACKGROUND/AIMS: The gastric protective effect of thioctic acid, a sulfhydryl compound, against chemically induced mucosal lesions has not been reported. METHODS: Fasted Wistar rats (24 h) were treated (gavage administration) with graded doses of thiotic acid (12.5, 25, 37.5, 50 mg/kg) followed 0.5 h later by the gavage administration of 1 ml 96% ethanol or intraperitoneal administered indomethacin. The gastric mucosa was examined grossly and histologically for an evaluation of the lesions. RESULTS: Pretreatment of rats with thiotic acid has shown a significant decline in the mean number, size, incidence and severity of mucosal lesions induced by both ethanol and indomethacin. CONCLUSIONS: This is the first evidence that thiotic acid protects the rat gastric mucosa against chemically induced damage. Its is speculated that this finding may prove to be important in the development of improved therapies for the prevention and treatment of gastric ulcers in humans.
Uso dell’ ALA
Bene, una volta che vi siete decisi su quale tipo di ALA orientarvi (se R(+) o RS), sarebbe il caso di imparare ad usarlo. Personalmente uso solo R(+) perché la forma RS mi da inappetenza e alcune crisi asteniche. Ma al di la di questo, sarei uno stupido se mettessi in discussione tutte le ricerche riportate qui. Una dose da epatoprotettore, consiste in almeno 500-1000mg al giorno, mentre come insulino-mimetico, si arriva anche fino a 3gr al giorno. Io uso 1500-2000mg al giorno di R(+). Chi lo usa solitamente riporta effetti visivi particolari alla muscolatura, in particolare aumento della densità e riduzione dell’adiposità. La dose va presa ad ogni pasto contenente carboidrati. Si può, volendo, combinare con il cromo per migliorarne l’effetto insulino mimetico. Io abbino 600mcg di cromo picolinato al giorno.
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