DEFINITION: Serplus® and α-lactalbumin
Serplus® is a nutraceutic, used for the treatment of drug-resistent epilepsy, its active component is α-lactalbumin, also known as LALBA. The supplement of LALBA, rich in tryptophan, enhances the synthesis of serotonin in the central nervous system.
In humans α-Lactalbumin is a protein that is encoded by the LALBA gene. α-Lactalbumin is a protein present in the whey of milk of almost all mammalian species. In primates, alpha-lactalbumin expression is upregulated in response to the hormone prolactin and increases the production of lactose. α-Lactalbumin forms the regulatory subunit of the lactose synthase (LS) heterodimer and β-1,4-galactosyltransferase(beta4Gal-T1) forms the catalytic component.
THE GENE
CHEMICAL STRUCTURE AND IMAGES
Protein Aminoacids Percentage
CLASSIFICATION
Nutraceutic, triptophan-rich protein
INDICATIONS
• Drug resistent epilepsy
• Osteoporosis
• Fibromyalgia
• Parkinson Disease
PHARMACOKINETICS
The bioavailability of Serplus® is maximal: the entire dose administered orally is rapidly demolished into peptides, which are fully absorbed by the gastro-intestinal system, mainly as short peptides.
While casein proteins form curds in the stomach, resulting in rapid hydrolysis and slowing gastric emptying, whey proteins, as LALBA, do not coagulate under acidic conditions. They are considered to be ‘‘fast proteins’’, as they reach the jejunum quickly after ingestion. After reaching the small intestine, the hydrolysis of whey is slower than that of casein, allowing for gradual absorption over the length of the small intestine.
A randomized, single-blind study found that whey protein produces a higher postprandial level of plasma amino acids compared to casein.
To potentiate the activity of the brain serotonin control system, the plasma Tryptophan/LNAAs ratio has to be increased.
LNAA are neutral acids and branched chain amino acids of large dimensions, specifically they are tyrosine, valine, methionine, isoleucine, leucine and phenalanine.
Tryptophan is actively transported into the brain by a carrier protein that is common for the transport of LNAA. In the brain the levels of tryptophan are affected not only by its plasma concentration, but also by the plasma concentrations of the other amino acids that compete for carrier absorption brain.
Nevertheless, free amino acids are not freely absorbed by the gut. (Potentiation of brain serotonin activity may inhibit seizures, especially in drug-resistant epilepsy. 2007)
Alpha-lactoalbumine has the highest Trp-LNAAs ratio among all quantitatively relevant, food-derived proteins. It has been shown that LALBA can increase the plasma Trp–LNAAs ratio of up to 48% compared to casein.
The effect of LALBA as anti-epileptic drug showed a significant dose-dependent relationship, and was maintained for up to 24 h after the last administration, with a clear attenuation after 48 h and complete recovery after 1 week.
MOLECULAR MECHANISM
Tryptophan is a polar essential amino acid and is the precursor of the group of compounds of tryptamines. It is the precursor of the neurotransmitter 5-hydroxi tryptamine or serotonin. Since brain serotonin is synthesized only from tryptophan (Trp), a decreased brain influx of Trp is expected to affect brain serotonin synthesis.
Serotonin system acts to control epileptic crisis: several data indicate that, in addition to alterations in GABAergic and glutamatergic systems, serotoninergic mechanisms play a role in the triggering and maintenance of epileptiform activity. (Preclinical activity profile of alpha-lactoalbumin, a whey protein rich in tryptophan, in rodent models of seizures and epilepsy. 2011)
Serotonin can inhibit epileptic-form activity in a variety of accepted epilepsy cellular models and that inhibition of epileptic-form bursts by serotonin may be mediated by activation of the 5-HT1A receptor subtype. An alternative speculative explanation could relate to the observation that tryptophan, in addition to acting as a 5-HT precursor, can be converted by cerebral indoleamine 2,3-dioxygenase to kynurenine and then to kynurenic acid, which acts as an NMDA receptor antagonist. (Protective activity of alpha-lactoalbumin(ALAC), a whey protein rich in tryptophan, in rodent models of epileptogenesis, 2012)
The average percent decrease of the number of seizures in patients was 60%.
SIDE EFFECTS
Not known, compound present in milk protein
TOXICITY
Not known, compound present in milk protein
RESISTANCE
The average percent decrease of the number of seizures in patients was 60% but there still be uncontrolled crisis.
DEPENDENCE AND WITHDRAW
Not known
Brasso Claudio
Mbachu Elena Nneka
Nicolì Vito
