Product Description

Glìalia

Food for special medical purposes. Without: gluten, lactose, sugars.
Glìalia is to be used under medical supervision in individuals with disorders sustained by neuroinflammatory processes associated with: transient ischemic events (TIAs); ischemic-based post-stroke states; CNS post-traumatic states; states of cognitive decline (Mild Neurocognitive Disorder - Mild-NCD); early-stage dementia; early-stage parkinsonism; inflammatory demyelinating diseases; motor neuron disease; and mood altered states.
       Palmitoylethanolamide
It is an endogenous natural substance of lipidic nature with N-acylethanolamide structure that in the body has the function of physiologically intervening to maintain intersystem tissue homeostasis.
       Luteolin
It too is a natural substance belonging to the flavone family, endowed with considerable and distinctive antioxidant effects.
The association Palmitoylethanolamide and Luteolin in co-ultramicronized form (PEALUT ultramicrocomposite) allows the two active ingredients to exert a synergistic effect in the control of neuroinflammation induced by different endogenous and exogenous noxae affecting the Central Nervous System; this control is carried out through the inhibitory modulation of non-neuronal cells - astrocytes, microglia, mast cells - normally deputed to ensure the homeodynamic balance of central nervous tissue.

Ingredients

	for 1 bag
Palmitoylethanolamide	700 mg
Luteolin in co-ultramicronized form (Ultramicrocomposite PEALUT®)	70 mg
Mixture of excipients (Sorbitol, Polysorbate 80, Sucrose Palmitate)	500.00 mg

Mode of use.
Glìalia microgranules for sublingual use should 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 initial states of promptly diagnosed neurodegenerative diseases; 2 sachets daily for cycles of 20-30 days possibly repeated using the sublingual route when possible is recommended.

Warnings and precautions for use
Use under medical supervision.
Product cannot be the sole source of nutrition.
Keep out of reach of children under 3 years old.
Interactions: not highlighted.
Pregnancy: administration of the product during the period of established or presumed pregnancy is not recommended, due to insufficient adequate data regarding the use of the association Palmitoylethanolamide and Luteolin in these situations.
Effects on ability to drive vehicles and operate machinery: Palmitoylethanolamide and Luteolin, at recommended doses, do not interfere with the ability to drive vehicles or operate machinery.
Undesirable effects: no undesirable effects have been reported even after long-time and high-dose administration of Palmitoylethanolamide, nor have cases of addiction or dependence been reported. In humans, 4-month administration of 100 mg/day of Luteolin has been shown to be excellently tolerated and safe.
Overdose: There are no known clinical cases of overdose.

Pharmacological properties
Health Authorization Category (Ministry of Health): Special Medical Purpose Food.
       Pharmacodynamic properties
Palmitoylethanolamide is an endogenous N-acylethanolamide with no psychotropic effects. Preclinical studies have shown that Palmitoylethanolamide acts, in a pleiotropic manner, on neuroinflammation mechanisms by exerting an effective neuroprotective effect. The use of translational experimental models has clearly demonstrated that Palmitoylethanolamide is able to act on central neuroinflammation through synchronic modulation of non-neuronal cells (astrocyte, microglia, mast cell) thereby determining effective neuroprotection.
Luteolin exerts a high normalization of the local oxidative state associated with neuroinflammation in the CNS. Available data show that the association between Palmitoylethanolamide and Luteolin, administered as ultramicrocompound. Pealut obtained by co-ultramicronization, appears to be 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 Pealut ultramicro-composite obtained by co-ultramicronization in the mass ratio 10:1, increases cell viability of both macrophage and astrocytic lines subjected to oxidative stress. The Pealut ultramicrocomposite synergistically inhibits lipid peroxidation, mitochondrial dysfunction associated with cell apoptosis, nitric oxide (NO) production, and the expression of inducible enzymes (NO-synthase and cyclo-oxygenase-2). Similar results were observed in organotypic cultures of hippocampus damaged by amyloid protein fragment Ab1-42. In models of ischemia the Pealut ultramicrocomposite was shown to completely protect neurons from cell death confirming the synergistic effect of the two molecules in the co-ultramicronized form. Pealut has demonstrated its in vivo efficacy in models of CNS trauma and mood alteration.

Pharmacokinetic properties
The time profile of Palmitoylethanolamide in human plasma after single oral intake of amounts between 300 and 1200 mg shows a dose-dependent increase of the molecule. Peak plasma levels of Palmitoylethanolamide are observed at one hour after intake; thereafter, plasma levels begin to decline and reach baseline within six hours. At one hour, plasma levels of Palmitoylethanolamide double from baseline after intake of 300 mg, while they increase sevenfold after intake of 1200 mg. Experimental studies have shown that after oral administration Palmitoylethanolamide is evenly distributed in tissues; a percentage of the administered dose crosses the blood-brain barrier and reaches brain tissues. Free luteolin was found in plasma in both experimental animals and humans after oral administration, demonstrating that a portion of luteolin escapes degradation due to hepatic first passage, in each case prevented by sublingual administration. In the rat, after oral administration the maximum peak of luteolin in plasma is reached after 1 hour, while 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 the dog is more than 400 mg/kg, and in the rat, after single administration by gastric gavage, exceeds 5000 mg/kg, and after repeated administration also by gastric gavage, exceeds 500 mg/kg/day.
Clinical studies in a large number of patients demonstrate the excellent tolerability of Palmitoylethanolamide even for very high doses and the absence of clinically relevant changes in hematologic and hematochemical tests performed. Toxicological studies in the rat have shown that administration up to 1 g/kg of Luteolin does not induce toxic effects. Chronic administration of Luteolin at a dose of 23, 48 and 87 mg/kg for 26 weeks, respectively, showed no toxic effects relative to body weight, hematologic, hematochemical and histopathologic examinations performed.
       Palmitoylethanolamide and embryotoxicity: no teratogenic or embryotoxic effect of Palmitoylethanolamide was shown after pregnancy administration of 50 mg/kg body weight for 12 days. In addition, infants from mothers receiving PEA before delivery and up to 10 days after delivery were more resistant to Shigella Shigae toxin. Similarly, infants of mothers receiving PEA after delivery showed increasing resistance evident as early as 5 days after birth: these data suggest that mothers may have transferred PEA to infants through milk.
       Mutagenicity: although a potential mutagenic effect of Palmitoylethanolamide can be ruled out since it is already physiologically ?lìalia® present in the mammalian organism, the mutagenicity of PEA was verified using the Ames test, using 5 mutant species of S. typhimurium (TA 1535-TA1537-TA1538-TA98 and TA 100). With the Ames test, Palmitoylethanolamide used at dosages between 10,000 and 1,000 µg/ ml did not significantly change the number of revertants. Luteolin in the Ames test, using concentrations between 12.1 and 225.0 nmol/ml, also showed no mutagenic effects.
       Palmitoylethanolamide and gastric tolerability: oral administration of Palmitoylethanolamide at a dose of 50mg/kg (approximately 5 times the active dose), and at a dose of 10 mg/kg in repeated administrations for 5 days does not induce ulcer formation. In addition, when administered at a dose of 50 mg/kg simultaneously with diclofenac 15 mg/kg, a dosage known to induce gastric injury, PEA decreases the ulcerogenic potential of NSAIDs, lowering the number of animals that develop ulceration and mitigating any damage.

Conservation
Store at room temperature.
Validity in unopened package: 36 months.

Format
Pack of 20 heat-sealed sachets.

Code. 8060