Glialia 700Mg+70Mg 20Bst

Glìalia

Food for special medical purposes. Free from: gluten, lactose, sugars.
Glìalia is to be used under medical supervision in subjects with disorders supported by neuroinflammatory processes associated with: transient ischemic events (TIA); post-ictal states of ischemic origin; post-traumatic states of the CNS; cognitive decline states (Mild Neurocognitive Disorder - Mild-NCD); early-stage dementias; early-stage parkinsonism; demyelinating inflammatory diseases; motor neuron diseases; mood disturbance states.
       Palmitoylethanolamide
It is a natural endogenous lipidic substance with a N-acylethanolamide structure that has the physiological function of intervening to maintain tissue homeostasis between systems.
       Luteolin
It is also a natural substance belonging to the flavonoid family, endowed with significant and peculiar antioxidant effects.
The combination of Palmitoylethanolamide and Luteolin in a co-ultramicronized form (ultramicrocomposite PEALUT) allows the two active principles to exert a synergistic effect in controlling neuroinflammation induced by different endo- and exogenous noxae affecting the Central Nervous System; this control is achieved through the inhibitory modulation of non-neuronal cells - astrocytes, microglia, mast cells - normally responsible for ensuring the homeodynamic balance of the central nervous tissue.

Ingredients

	per 1 bag
Palmitoylethanolamide	700 mg
Luteolin in co-ultramicronized form (Ultramicrocomposite PEALUT®)	70 mg
Excipient mixture (Sorbitol, Polysorbate 80, Sucrose Palmitate)	500.00 mg

Usage instructions
Glìalia microgranules for sublingual use should be used under medical supervision after acute events associated with neuroinflammation in the CNS (post-ictal, post-traumatic situations) or, as an attack therapy, in the early stages of newly diagnosed neurodegenerative diseases; it is recommended to take 2 sachets per day for cycles of 20-30 days possibly repeated using, whenever possible, the sublingual route.

Warnings and precautions for use
Use under medical supervision.
The product cannot be the only source of nourishment.
Keep out of reach of children under 3 years old.
Interactions: none identified.
Pregnancy: the administration of the product is not recommended during confirmed or suspected pregnancy due to lack of adequate data regarding the use of the Palmitoylethanolamide and Luteolin combination in these situations.
Effects on the ability to drive vehicles and use machinery: Palmitoylethanolamide and Luteolin, at the recommended doses, do not interfere with the ability to drive vehicles and operate machinery.
Undesirable effects: no adverse effects have been reported even after long-term administration and at high doses of Palmitoylethanolamide, nor have cases of addiction or dependency been reported. In humans, administration of 100 mg/die of Luteolin for 4 months was well tolerated and safe.
Overdose: no clinical cases of overdose are known.

Pharmacological properties
Sanitary Authorization Category (Ministry of Health): Food for special medical purposes.
       Pharmacodynamic properties
Palmitoylethanolamide is an endogenous N-acYLEthanolamide, free of psychotropic effects. Preclinical studies have shown that Palmitoylethanolamide acts pleiotropically on neuroinflammatory mechanisms, exerting an effective neuroprotective effect. The use of translational experimental models clearly demonstrated that Palmitoylethanolamide can act on central neuroinflammation through the synchronized modulation of non-neuronal cells (astrocytes, microglia, mast cells), thus providing effective neuroprotection.
The Luteolin exerts a high normalization of the local oxidative state associated with neuroinflammation in the CNS. The available data demonstrate how the combination of Palmitoylethanolamide and Luteolin, administered in the form of an ultramicrocomposite PEALUT obtained by co-ultramicronization, is highly synergistic on the mechanisms of neuroinflammation in the CNS.
       Mechanisms of action
Recent studies have shown that administration of Palmitoylethanolamide + Luteolin, in the form of the ultramicrocomposite Pealut obtained by co-ultramicronization at a 10:1 ratio by mass, increases cell vitality in both macrophage and astrocyte lines subjected to oxidative stress. The ultramicrocomposite Pealut synergistically inhibits lipid peroxidation, mitochondrial dysfunction associated with cellular apoptosis, nitric oxide (NO) production, and the expression of inducible enzymes (NO synthase and cyclooxygenase-2). Similar results were observed in organotypic hippocampal cultures damaged by amyloid protein fragment Ab1-42. In ischemia models, the ultramicrocomposite Pealut demonstrated complete protection of neurons from cell death, confirming the synergistic effect of the two molecules in the co-ultramicronized form. Pealut has demonstrated its effectiveness in vivo in models of CNS trauma and mood disorders.

Pharmacokinetic properties
The temporal profile of Palmitoylethanolamide in human plasma after a single oral intake of amounts between 300 and 1200 mg shows a dose-dependent increase of the molecule. The plasma peak of Palmitoylethanolamide occurs one hour after intake; afterwards, plasma levels start to decrease and reach baseline values within six hours. After one hour, plasma levels of Palmitoylethanolamide double compared to baseline after taking 300 mg, while increasing sevenfold after taking 1200 mg. Experimental studies have shown that after oral administration, Palmitoylethanolamide distributes evenly into tissues; a percentage of the administered dose crosses the blood-brain barrier and reaches brain tissues. Free Luteolin was found in plasma both in experimental animals and in humans, after oral administration, demonstrating that part of the Luteolin escapes degradation due to first-pass hepatic metabolism, which is avoided in any case by sublingual administration. In rats, after oral administration, the maximum plasma peak of Luteolin is reached after 1 hour, while the maximum excretion peak in feces and urine occurs around 8 hours.

Toxicology and tolerability
Toxicology studies have shown that the LD50 of Palmitoylethanolamide administered via injection (intraperitoneally) in dogs is greater than 400 mg/kg, and in rats, after a single gavage, exceeds 5000 mg/kg, while after repeated dosing via gavage, exceeds 500 mg/kg/day.
Clinical studies on a large number of patients demonstrate the excellent tolerability of Palmitoylethanolamide even at very high doses and the absence of clinically relevant changes in hematological and biochemical tests. Toxicological studies in rats have shown that administration of up to 1 g/kg of Luteolin does not induce toxic effects. Chronic administration of Luteolin at doses of 23, 48, and 87 mg/kg respectively for 26 weeks showed no toxic effects related to body weight, hematological, biochemical, and histopathological parameters.
       Palmitoylethanolamide and embryotoxicity: no teratogenic or embryotoxic effects of Palmitoylethanolamide were observed after administration during pregnancy at 50 mg/kg body weight for 12 days. Additionally, infants from mothers who received PEA before birth and up to 10 days after birth were more resistant to Shigella shigae toxin. Similarly, infants from mothers who received PEA after birth showed increased resistance already 5 days after birth: these data suggest mothers may have transferred PEA to the infants through breast milk.
       Mutagenicity: although a potential mutagenic effect of Palmitoylethanolamide cannot be excluded as it is already physiologically present in mammalian organisms, the mutagenicity of PEA was tested using the Ames test, using 5 mutant strains of S. typhimurium (TA 1535-TA1537-TA1538-TA98 and TA 100). With the Ames test, Palmitoylethanolamide, used at doses between 10,000 and 1,000 µg/ml, did not significantly alter the number of revertants. Also, Luteolin tested with the Ames test, using concentrations between 12.1 and 225.0 nmol/ml, did not show mutagenic effects.
       Palmitoylethanolamide and gastric tolerability: oral administration of Palmitoylethanolamide at a dose of 50 mg/kg (approximately 5 times higher than the active dose), and at 10 mg/kg in repeated administrations over 5 days, does not induce ulcer formation. Moreover, when administered at a dose of 50 mg/kg together with diclofenac 15 mg/kg, known to induce gastric lesions, PEA reduces the ulcerogenic potential of NSAIDs, decreasing the number of animals developing ulcers and mitigating any damage.

Storage
Store at room temperature.

Format
Package of 20 heat-sealed sachets.

Code 8060