GLIALIA 700MG+70MG 20BUST

Glìalia

Food for special medical purposes. Without: gluten, lactose, sugars.
Glìalia should be used under medical supervision in subjects with disorders sustained by neuroinflammatory processes associated with: transient ischemic attacks (TIA); post-ischemic ictal states; post-traumatic states of the CNS; states of cognitive decline (Mild Neurocognitive Disorder - Mild-NCD); early-stage dementia; early-stage parkinsonisms; demyelinating inflammatory diseases; motor neuron diseases; mood alteration states.
       Palmitoylethanolamide
It is a natural endogenous substance of lipid nature with an N-acylethanolamide structure that in the body functions physiologically to maintain intersystemic tissue homeostasis.
       Luteolin
It is also a natural substance belonging to the flavone family, endowed with considerable and peculiar antioxidant effects.
The association of Palmitoylethanolamide and Luteolin in co-ultramicronized form (ultramicrocomposite PEALUT) allows the two active ingredients to exert a synergistic effect in controlling neuroinflammation induced by different endogenous noxae affecting the Central Nervous System; this control is expressed 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 sachet
Palmitoylethanolamide	700 mg
Luteolin in co-ultramicronized form (Ultramicrocomposite PEALUT®)	70 mg
Mixture of excipients (Sorbitol, Polysorbate 80, Palmitate Sucrose)	500.00 mg

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

Warnings and precautions for use
Use under medical supervision.
The product cannot be the sole source of nutrition.
Keep out of reach of children under 3 years.
Interactions: not highlighted.
Pregnancy: administration of the product is not recommended during established or presumed pregnancy, due to a lack of adequate data regarding the use of the association of Palmitoylethanolamide and Luteolin 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.
Side effects: no side effects have been reported even after long-term administration and at high doses of Palmitoylethanolamide, nor have cases of tolerance or dependence been reported. In humans, administration of 100 mg/day of Luteolin for 4 months has proven to be very well tolerated and safe.
Overdose: no clinical cases of overdose are known.

Pharmacological properties
Health Authorization Category (Ministry of Health): Food for Special Medical Purposes.
       Pharmacodynamic properties
Palmitoylethanolamide is an endogenous N-acylethanolamide, devoid of psychotropic effects. Preclinical studies have demonstrated that Palmitoylethanolamide acts, in a pleiotropic manner, on the mechanisms of neuroinflammation exerting an effective neuroprotective effect. The use of translational experimental models has clearly demonstrated that Palmitoylethanolamide is capable of acting on central neuroinflammation through the synchronized modulation of non-neuronal cells (astrocytes, microglia, mast cells) thus providing effective neuroprotection.
Luteolin exerts a high normalization of the local oxidative state associated with neuroinflammation in the CNS. Available data demonstrate that the combination of Palmitoylethanolamide and Luteolin, administered in the form of 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 the administration of Palmitoylethanolamide + Luteolin, in the form of ultramicro-composite Pealut obtained by co-ultramicronization in a mass ratio of 10:1, increases the cellular vitality of both macrophagic and astrocytic lines subjected to oxidative stress. The ultramicrocomposite Pealut synergistically inhibits lipid peroxidation, mitochondrial dysfunctions associated with cellular apoptosis, nitric oxide (NO) production, and the expression of inducible enzymes (NO-synthase and cyclooxygenase-2). Similar results have been observed in organotypic cultures of hippocampus damaged by amyloid protein fragment Ab1-42. In ischemia models, the ultramicrocomposite Pealut has shown to completely protect neurons from cell death confirming the synergistic effect of the two molecules in co-ultramicronized form. Pealut has demonstrated its effectiveness in vivo in models of CNS trauma and mood alteration.

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

Toxicology and Tolerability
Toxicology studies have shown that the LD/50 of Palmitoylethanolamide administered by injection (intraperitoneal) in dogs is greater than 400 mg/kg, and in rats, after a single administration via a gastric probe, exceeds 5000 mg/kg, while after repeated administration also via gastric probe, exceeds 500 mg/kg/day.
Clinical studies carried out on a substantial number of patients demonstrate the optimal tolerability of Palmitoylethanolamide even for very high doses and the absence of clinically relevant changes in hematological and hemato-chemical tests conducted. Toxicological studies in rats have shown that administration 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, did not show any toxic effect relative to body weight, hematological, hemato-chemical, and histopathological examinations performed.
       Palmitoylethanolamide and embryotoxicity: no teratogenic or embryotoxic effect of Palmitoylethanolamide has been evidenced after administration during pregnancy of 50 mg/kg body weight for 12 days. Moreover, newborns from mothers who received PEA before childbirth and up to 10 days after childbirth were more resistant to the toxin of Shigella Shigae. Similarly, newborns of mothers who received PEA after childbirth have shown increasing resistance evident already 5 days after birth: these data suggest that mothers may have transferred PEA to newborns through milk.
       Mutagenicity: although a potential mutagenic effect of Palmitoylethanolamide can be excluded since it is already physiologically present in the organism of mammals, the mutagenicity of PEA has been verified using the Ames test, using 5 mutant strains of S. typhimurium (TA 1535-TA1537-TA1538-TA98 and TA 100). In the Ames test, Palmitoylethanolamide, used at doses ranging from 10,000 to 1,000 µg/ml did not significantly change the number of revertants. Also, Luteolin in the Ames test, using concentrations ranging from 12.1 to 225.0 nmoles/ml, did not show mutagenic effects.
       Palmitoylethanolamide and gastric tolerability: oral administration of Palmitoylethanolamide at a dose of 50 mg/kg (dose approximately 5 times higher than the active dose), and at a dose of 10 mg/kg in repeated administrations for 5 days does not induce ulcer formation. Furthermore, when administered at a dose of 50 mg/kg simultaneously with diclofenac 15 mg/kg, a dosage known to induce gastric lesions, PEA reduces the ulcerogenic potential of NSAIDs, lowering the number of animals that develop ulcerations and mitigating any damage.

Storage
Store at room temperature.

Format
Pack of 20 heat-sealed sachets.

Code 8060