ITPD20140288A1 - L-INTEGRA - Google Patents
L-INTEGRA Download PDFInfo
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- ITPD20140288A1 ITPD20140288A1 ITPD2014A000288A ITPD20140288A ITPD20140288A1 IT PD20140288 A1 ITPD20140288 A1 IT PD20140288A1 IT PD2014A000288 A ITPD2014A000288 A IT PD2014A000288A IT PD20140288 A ITPD20140288 A IT PD20140288A IT PD20140288 A1 ITPD20140288 A1 IT PD20140288A1
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- IT
- Italy
- Prior art keywords
- vitamin
- bone
- intake
- calcium
- study
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- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 claims description 22
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- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 8
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Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/16—Inorganic salts, minerals or trace elements
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
- A23L33/155—Vitamins A or D
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Mechanical Treatment Of Semiconductor (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
- Apparatus For Radiation Diagnosis (AREA)
Description
TITOLO TITLE
ASSOCIAZIONE DI VITAMERI K PER INTEGRARE LA CARENZA NELLA DIETA DI TALE VITAMINA. ASSOCIATION OF K-VITAMERS TO INTEGRATE THE DEFICIENCY IN THE DIET OF THIS VITAMIN.
DESCRIZIONE DESCRIPTION
I dati a disposizione in ambito medico circa l?associazione tra il trattamento clinico delle fratture ossee e l?assunzione di calcio, vitamina D e vitamina K meritano qualche riflessione. Un punto importante circa la supplementazione di calcio e vitamina D, sia nella popolazione generale che nei pazienti affetti da fratture ossee, ? che, senza un?adeguata somministrazione di vitamina K, il calcio ha scarse possibilit? di depositarsi nella matrice ossea e, al contrario, pu? favorire l?insorgere o il peggioramento di calcificazioni vascolari o, pi? in generale, di alterazioni nel sistema cardiovascolare. The data available in the medical field about the association between the clinical treatment of bone fractures and the intake of calcium, vitamin D and vitamin K deserve some reflection. An important point about calcium and vitamin D supplementation, both in the general population and in patients with bone fractures,? that, without an adequate supply of vitamin K, calcium has little chance? to settle in the bone matrix and, on the contrary, can? favor the onset or worsening of vascular calcifications or, more? in general, of alterations in the cardiovascular system.
Gli studi effettuati hanno dimostrato che la dieta occidentale ? particolarmente carente nell?assunzione di vitamina K, quindi la supplementazione di adeguati livelli della vitamina in oggetto pu? favorire la corretta deposizione di calcio nelle ossa mantenendo la salute delle stesse e dei vasi. Studies have shown that the Western diet? particularly deficient in the intake of vitamin K, therefore the supplementation of adequate levels of the vitamin in question can? promote the correct deposition of calcium in the bones while maintaining the health of the same and of the vessels.
II presente brevetto pu? avere rilevanti ed innovativi impatti clinici nella prevenzione dell?osteoporosi e delle alterazioni nel sistema cardiovascolare in quanto la somministrazione di adeguati livelli di vitamina K consente di evitare un eccesso di calcio nei vasi e una corretta deposizione nell?osso (evitando quello che viene difinito ?paradosso del calcio?, con un?eccessiva e dannosa calcificazione dei vasi sanguigni dovuta alla carenza di assunzione della vitamina K nella dieta occidentale). This patent can have relevant and innovative clinical impacts in the prevention of osteoporosis and alterations in the cardiovascular system as the administration of adequate levels of vitamin K allows to avoid an excess of calcium in the vessels and a correct deposition in the bone (avoiding what is called? calcium paradox ?, with excessive and harmful calcification of blood vessels due to the lack of vitamin K intake in the Western diet).
La Vitamina K1, PK, costituisce la forma preponderante nella dieta, poich? ? presente nei vegetali a foglia verde, es: spinaci, cavolo, verza, cavolini di bruxelles) (Bugel S et al, 2003) ed Vitamin K1, PK, constitutes the predominant form in the diet, since? ? present in green leafy vegetables, e.g. spinach, cabbage, savoy cabbage, Brussels sprouts) (Bugel S et al, 2003) and
in alcuni frutti, es: avocado e kiwi. La Vitamina K2, MK, pu? avere origine o alimentare: carne di manzo, Pollo (petto e fegatini), nel fegato bovino, tuorlo d?uovo, burro, ( The EFSA lournal 2008; Shurgers LJ, 2000 ; o microbiologica: alimenti fermentati (es. Formaggi Cagliati) o prodotta dalla flora batterica intestinale, in particolar modo dall?Escherichia Coli ( The EFSA lournal 2008:822, 1-32; Shurgers LJ, 2000). Il natto ? un Tipico cibo della colazione giapponese: fagioli di soia fatti fermentare dal batterio Gram Positivo: Bacillus Subtilis Natto ; ? ricco di MK-7 e in minor misura di MK6 (contiene inoltre Vitamina B2 e un enzima fibrinolitico detto Nattokinase). La dieta occidentale ? molto povera di MK, basti pensare che per assumerne 45mcg dovremo assumere 5 litri di latte o 4 Kg di carne di manzo o 8 tuorli d?uovo e cos? via. L?intake giornaliero raccomandato ? di 90-120mcg. Di recente la Societ? Italiana di Nutrizione Umana (SINU) ha aggiornato i Livelli di Assunzione di Riferimento di Nutrienti ( LARN 2012) ed energia per la popolazione Italiana: per gli adulti, maschi e femmine, sotto i 60 anni ? 140 microgrammi poi sale a 170. in some fruits, eg: avocado and kiwi. Vitamin K2, MK, can? have origin or food: beef, chicken (breast and livers), in bovine liver, egg yolk, butter, (The EFSA lournal 2008; Shurgers LJ, 2000; o microbiological: fermented foods (eg curd cheeses) or produced by intestinal bacterial flora, especially by Escherichia Coli (The EFSA lournal 2008: 822, 1-32; Shurgers LJ, 2000). Natto is a typical Japanese breakfast food: soy beans fermented by the Gram Positive bacterium : Bacillus Subtilis Natto; it is rich in MK-7 and to a lesser extent in MK6 (it also contains Vitamin B2 and a fibrinolytic enzyme called Nattokinase). The Western diet is very low in MK, just think that to take 45mcg we will have to take 5 liters of milk or 4 kg of beef or 8 egg yolks and so on. The recommended daily intake is 90-120mcg. Recently the Italian Society of Human Nutrition (SINU) has updated the Reference Intake Levels of Nutrients (LARN 2012) and energy for the population Italian ion: for adults, males and females, under 60? 140 micrograms then rises to 170.
Relativamente alla carenza di Vitamina K, uno studio condotto sulla popolazione generale (672 partecipanti), studio Framingham, fu evidenziato un deficit di vitamina K (K1) con una prevalenza pari al 24% ottenuta considerando un cut-off della vitamina K pari a 0,5 nmol/L (Neogi T, 2006). Questo studio, rende presumibile che nella popolazione con Insufficienza Renale Cronica (IRC) terminale (stadio V), il deficit di vitamina K (K1) possa avere una prevalenza pi? alta, pari circa al 30% come riscontrato da Pilkey et al in 142 pazienti emodializzati (Pilkey RM et al, 2007). Dato confermato da Fusaro et al, in uno studio preliminare su 68 pz in HD pari al 32.08% ( Fusaro et al, 2010). Inoltre, sebbene la Vitamina K sia una vitamina liposolubile, il corpo ne immagazzina molto poca e senza un?assunzione dietetica regolare le sue riserve vengono radipamente espulse. L?organismo, verosimilmente proprio per compensare la limitata capacit? di conservare la Vitamina k, la ricicla attraverso un processo chiamato ciclo della Vitamina K. In particolare, la Vitamina K ? un coenzima. La Forma coenzimatica della Vitamina K, che corrisponde alla forma attiva della Vitamina stessa, ? l' drochinone (KH2). Quest?ultimo ? prodotto da una Quinone Reduttasi, a spese di NADPH (ossia la riduttasi ? dipendente da NADPFI) . L?enzima coinvolto ? ?-Glutammil-carbossilasi (GGC). La reazione catalizzata consiste nella carbossilazione dei residui di Acido Glutammico (Giu) che si trasformano nell?acido y-Carbossiglutammico (Gi?). Questa reazione comporta l?ossidazione dell?KH2 ad Epossido (KO). In questa azione coenzimatica sta la rilevante e fondamentale importanza di livelli adeguati di vitamina K nell?organismo, poich? da essa dipende la carbossilazione e quindi l?attivazione di proteine essenziali (proteine Vitamina K dipendenti), quali quelle della Coagulazione (Protrombina o Fattore II, Fattore VII, IX e X, Proteine C, S e Z), dell?Osso (Osteocalcina o Bone Gi? Protein:BGP, Periostin, Matrix Gi? Protein o MGP) e dei Vasi Sanguigni ( MGP, Growth arrest-specific 6 o Gas6). E? quindi consequenziale che un deficit di Vitamina K sia esso per ridotto apporto alimentare o per patologie concomitanti (IRC, Stato Infiammatorio, Diabete), porti ad una riduzione della quota attiva (carbossilata) delle proteine Vitamina K dipendenti ed incremento di quella inattiva (decarbossilata). L?impatto clinico di tale carenza porter? ad un difetto della corretta mineralizzazione ossea ( Osteoporosi e incremento evento Fratturativo) e calcificazione dei vasi Regarding Vitamin K deficiency, a study conducted on the general population (672 participants), Framingham study, showed a vitamin K (K1) deficiency with a prevalence of 24% obtained considering a vitamin K cut-off equal to 0 , 5 nmol / L (Neogi T, 2006). This study makes it possible to assume that in the population with terminal Chronic Renal Failure (CRI) (stage V), vitamin K (K1) deficiency may have a higher prevalence. high, approximately 30% as found by Pilkey et al in 142 hemodialysis patients (Pilkey RM et al, 2007). This figure was confirmed by Fusaro et al, in a preliminary study on 68 HD patients equal to 32.08% (Fusaro et al, 2010). Furthermore, although Vitamin K is a fat-soluble vitamin, the body stores very little of it and without a regular dietary intake its reserves are rapidly expelled. The organism, probably just to compensate for the limited capacity? to store Vitamin K, recycle it through a process called the Vitamin K cycle. Specifically, Vitamin K? a coenzyme. The coenzyme form of Vitamin K, which corresponds to the active form of the Vitamin itself,? droquinone (KH2). The latter ? produced by a Quinone Reductase, at the expense of NADPH (ie reductase? dependent on NADPFI). The enzyme involved? ? -Glutamyl-carboxylase (GGC). The catalyzed reaction consists in the carboxylation of glutamic acid residues (Giu) which are transformed into y-carboxyglutamic acid (Gi?). This reaction involves the oxidation of KH2 to Epoxide (KO). In this coenzymatic action lies the relevant and fundamental importance of adequate levels of vitamin K in the organism, since? the carboxylation and therefore the activation of essential proteins (Vitamin K dependent proteins), such as those of Coagulation (Prothrombin or Factor II, Factor VII, IX and X, Proteins C, S and Z), of Bone (Osteocalcin o Bone Gi? Protein: BGP, Periostin, Matrix Gi? Protein or MGP) and Blood Vessels (MGP, Growth arrest-specific 6 or Gas6). AND? therefore consequential that a Vitamin K deficiency, whether due to a reduced dietary intake or concomitant pathologies (CRI, Inflammatory State, Diabetes), leads to a reduction in the active (carboxylated) portion of Vitamin K dependent proteins and an increase in the inactive (decarboxylated) portion . The clinical impact of this deficiency will bring? to a defect in the correct bone mineralization (Osteoporosis and increased fracture event) and calcification of the vessels
(in particolre arteriosclerosi, ossia tutte quelle forme di indurimento, ispessimento e perdita di elasticit? della parete arteriosa, quali l'aterosclerosi, l'arteriolosclerosi e la sclerosi calcifica di M?nckeberg). (in particular arteriosclerosis, that is all those forms of hardening, thickening and loss of elasticity of the arterial wall, such as atherosclerosis, arteriolosclerosis and calcific sclerosis of M? nckeberg).
? Difetto della corretta mineralizzazione ossea ( Osteoporosi e incremento evento Fratturativo) ? Defect of correct bone mineralization (Osteoporosis and increased fracture event)
Topi geneticamente modificati per BGP, Knock-out, sviluppano iperostosi, a conferma del suo importante ruolo nel promuovere la normale mineralizzazione ossea ( Ducy P et al, 1996). Mice genetically modified for BGP, Knock-out, develop hyperostosis, confirming its important role in promoting normal bone mineralization (Ducy P et al, 1996).
Oltre portare la carbossilazione della BGP, la Vitamina K2 a livello osseo verosimilmente diminuisce il riassorbimento osseo attraverso: stimolazione della produzione di Osteoprotegerina (OPG: detta Decoy Receptor: recettore esca), la quale impedisce il legame tra RANKL (Receptor Activactor of Nuclear Factor KappaB) e RANK; ed inibizione dell?espressione del RANK Ligand (RANKL). E? evidente che senza adeguati livelli di vitamina K, si avr? una riduzione della resistenza ossea che predispone a un aumento del rischio di frattura ( Osteoporosi ). L?osteoporosi e le fratture osteoporotiche sono in aumento in tutto il mondo visto l?allungamento dell?et? della vita. In addition to bringing the carboxylation of BGP, Vitamin K2 at the bone level probably decreases bone resorption through: stimulation of the production of Osteoprotegerin (OPG: called Decoy Receptor: decoy receptor), which prevents the link between RANKL (Receptor Activactor of Nuclear Factor KappaB ) and RANK; and inhibition of the expression of RANK Ligand (RANKL). AND? evident that without adequate levels of vitamin K, you will have? a reduction in bone strength which predisposes to an increased risk of fracture (osteoporosis). Osteoporosis and osteoporotic fractures are on the rise around the world as we get older. of life.
Secondo lo studio di Strom O et al (2011), si stima che in futuro un uomo su cinque e una donna su tre sopra i 50 anni di et? presenter? una frattura da osteoporosi, con un carico di forti dolori e sofferenze, disabilit? e persino morte. La stima attuale di 30,7 miliardi di euro per eventi fratturativi per appena sei Paesi dell?Unione Europea riflette l'aumento del numero di fratture dovuto all'invecchiamento. Nel 2025, il numero di fratture aumenter? del 29% raggiungendo i 3,2 milioni e si stima che i costi per l'assistenza sanitaria saliranno a 38,5 miliardi di euro. Risulta quindi essenziale un trattamento alternativo all?attuale, il quale affianchi alle stratagie terapeutiche in uso la somministrazione di Vitamina K. In particolare, Cheung et al (2008), trovarono in uno studio randomizzato e controllato (440 donne in postmenopausa), dove veniva somministrata K1, PK, alla dose di 5mg die (in associazione all?intake di Cacio e Vitamina D), s? aveva una ridotta incidenza dell?evento fratturativo nelle pazienti trattate rispetto alle non trattate; e tale dato veniva confermato sia da Nakano et al (2011), in cui il PK ? risultato predittivo per frattura d?anca (OR 0.072, p=0.016), in una popolazione di anziani giapponesi che presentavano ipovitaminosi K e D, che da Fusaro et al ( VIKI Study JBMR, 2012) in una popolazione di 387 pazienti in trattamento emodialitico. Entrambe questi autori non trovaro associazione tra evento fratturativo e vitamina K2, MK. According to the study by Strom O et al (2011), it is estimated that in the future one in five men and one in three women over 50 years of age? presenter? an osteoporosis fracture, with a load of severe pain and suffering, disability? and even death. The current estimate of € 30.7 billion for fracture events for just six EU countries reflects the increase in the number of fractures due to aging. In 2025, the number of fractures will increase? by 29% to reach 3.2 million and it is estimated that health care costs will rise to 38.5 billion euros. It is therefore essential an alternative treatment to the current one, which alongside the therapeutic strategies in use the administration of Vitamin K. In particular, Cheung et al (2008), found in a randomized and controlled study (440 postmenopausal women), where it was administered K1, PK, at a dose of 5mg per day (in association with the intake of Cacio and Vitamin D), s? had a reduced incidence of the fracture event in treated compared to untreated patients; and this data was confirmed both by Nakano et al (2011), in which the PK? predictive result for hip fracture (OR 0.072, p = 0.016), in a population of Japanese elderly with hypovitaminosis K and D, which from Fusaro et al (VIKI Study JBMR, 2012) in a population of 387 patients on hemodialysis . Both of these authors found no association between the fracture event and vitamin K2, MK.
? Calcificazione dei Vasi ( Arteriosclerosi) ? Vessel Calcification (Arteriosclerosis)
La MGP agisce come uno dei pi? importanti inibitori di Calcificazioni Vascolari verosimilmente attraverso il legame con una potente proteina osteoinduttiva e ne modula l?attivit?, tale proteina ? la BMP-2 (Bone Morphogenetic Protein 2) la quale fa parte della superfamiglia del TGF-?. E? un potente fattore di crescita che trasforma cellule indifferenziate e sottopopolazioni di cellule muscolari lisce vascolari (VSMC) in simil cellule osteoblastiche (Zebboudj AF et al 2002, Zheng Z et al WCN May 2009 ). La Gas6, ? invece un?altra proteina Vitamina K dipendente che verosimilmente previene l?apoptosi delle VSMC. Warfarin va ad interferire sul suo recettore (Axl) bloccandone il segnale (Krueger et al, Kl 2009). Quando i livelli di Vitamina K risultano adeguatamente sufficienti neH?organismo si ha che tutta la MGP sintetizzata nelle VSMC, a livello della tonaca media, ? attivata (carbossilata, cMGP) ad inibire la calcificazione (non essendoci MGP decarbossilata, ucMGP, non si avr? il legame con l?idrossipatite della matrice e quindi assenza di nodo calcifico), adeguata clearance delle vescicole della matrice (vm) e dei corpi apoptotici (ca), mediante fagocitosi, ed immissione in circolo di cMGP (Schurgers et al, 2008). Nel caso in cui vi sia invece una deficienza di Vitamina K (per esmpio dovuta ad un basso intake, all?uso di warfarin, a malattie: IRC, Infiammazione, Diabete), si avr? una ridotta clearance (fagocitosi) delle vm e dei ca, con incremento della MGP inattiva (ucMGP) che si legher? al calcio dell?idrossiapatite della matrice stessa dando luogo alla calcificazione dei vasi ( arteriosclerosi ) (Schurgers et al, 2008 e Murshed 2004). In tal modo il calcio rimane all?interno del vaso e non viene trasportato all?osso ( calcio paradosso : nei vasi in eccesso dove non se ne abbisogna e nell?osso dove necessita manca) The MGP acts as one of the most? important inhibitors of Vascular Calcifications probably through the binding with a powerful osteoinductive protein and modulates its activity, this protein? BMP-2 (Bone Morphogenetic Protein 2) which is part of the TGF-? superfamily. AND? a potent growth factor that transforms undifferentiated cells and vascular smooth muscle cell (VSMC) subpopulations into osteoblast-like cells (Zebboudj AF et al 2002, Zheng Z et al WCN May 2009). The Gas6,? instead another Vitamin K dependent protein that probably prevents VSMC apoptosis. Warfarin interferes on its receptor (Axl) by blocking its signal (Krueger et al, Kl 2009). When the levels of Vitamin K are adequately sufficient in the organism, there is that all the MGP synthesized in the VSMC, at the level of the media,? activated (carboxylated, cMGP) to inhibit calcification (since there is no decarboxylated MGP, ucMGP, there will be no binding with the hydroxypatite of the matrix and therefore absence of calcific node), adequate clearance of the vesicles of the matrix (vm) and of the bodies apoptotic (CA), through phagocytosis, and release of cMGP into the circulation (Schurgers et al, 2008). In the event that there is a deficiency of Vitamin K (for example due to a low intake, to the use of warfarin, to diseases: CRI, Inflammation, Diabetes), it will have? a reduced clearance (phagocytosis) of the vm and ca, with an increase in the inactive MGP (ucMGP) that will bind? to the calcium of the hydroxyapatite of the matrix itself, giving rise to the calcification of the vessels (arteriosclerosis) (Schurgers et al, 2008 and Murshed 2004). In this way the calcium remains inside the vessel and is not transported to the bone (paradoxical calcium: in the excess vessels where it is not needed and in the bone where it is lacking)
L?arteriosclerosi ? una malattia cardiovascolare che interessa le arterie di importanti organi del nostro organismo (cervello, cuore, reni e cos? via) e nel mondo occidentale resta tra le principali cause di mortalit?. Il Rotterdam Study (2004) ha investigato 4807 pazienti in cui l?intake di MK7 riduceva del 50% le CV e la mortalit? cardiovascolare ed inoltre per un 25% la mortalit? in toto. Fusaro et al (VIKI Study JBMR, 2012 ) ha anche dimostrato che l'??7 era un predittore per la calcificazione delle arterie Iliache (OR 1.61). Arteriosclerosis? a cardiovascular disease that affects the arteries of important organs of our organism (brain, heart, kidneys and so on) and in the Western world it remains among the main causes of mortality. The Rotterdam Study (2004) investigated 4807 patients whose MK7 intake reduced CVs and mortality by 50%. cardiovascular and also for a 25% mortality? in full. Fusaro et al (VIKI Study JBMR, 2012) also demonstrated that ?? 7 was a predictor for calcification of the iliac arteries (OR 1.61).
In conclusione, un adeguato intake di Vitamina K dovrebbe essere indicato in associazione all?intake di calcio e Vitamina D al fine di promuovere una corretta calcificazione dell'osso evitando la calcificazione dannosa dei vasi. Recenti studi (Bolland et al 2008 e 2011) infatti, hanno evidenziato come supplementazioni di Calcio, associate o meno alla vitamina D, in donne in postmenopausa al fine di prevenire l?osteoporosi, siano andate incontro ad un incremeto degli eventi cardiovascolari (effetto Calcio paradosso). La raccomandazione dell?intake di Vitamina K dovrebbe riguardare sia il PK che ? MK7. In conclusion, an adequate intake of Vitamin K should be indicated in association with the intake of calcium and Vitamin D in order to promote a correct calcification of the bone avoiding the harmful calcification of the vessels. In fact, recent studies (Bolland et al 2008 and 2011) have shown how calcium supplements, associated or not with vitamin D, in postmenopausal women in order to prevent osteoporosis, have undergone an increase in cardiovascular events (calcium effect paradox). The Vitamin K intake recommendation should cover both PK and? MK7.
FORMULAZIONE BREVETTABILE COME INTEGRA TORE* PATENTABLE FORMULATION AS A SUPPLEMENT *
Indicazione: supplire la carenza di Intake dipendente dalla dieta, attenendosi a quanto raccomandato dalle diverse Linee Guida (LARN 2012), con la contemporanea somministrazione di capsule contenenti K1 e MK7, alle seguenti dosi: Indication: compensate for the deficiency of diet-dependent Intake, following the recommendations of the various Guidelines (LARN 2012), with the simultaneous administration of capsules containing K1 and MK7, at the following doses:
?? Mg ? il secondo catione pi? contenuto a livello intracellulare . Il contenuto corporeo di Mg nell?organismo adulto ? aprossimativamente di 25g di cui:66% nell?osso, 33% intracellulare e 1% extracellulare. In particolare il Mg si pu? trovare nelle seguenti forme: 55% ionizzato libero (forma biologicamente attiva), 30% legato all?albumina e 15% ? legato ad anioni. A livello del digiuno l?assorbimento di Mg ? aumentato dalla Vitamina D. E? un competitor del Ca antagonizzandolo sia nel legame a livello dei siti di membrana (mantiene bassi gli ioni Ca a riposo) che nel legame con le proteine ( Kanbay M et al, 2010). Il magnesio in particolare ha uguale potenza di stimolazione sui calcio recettori sensibili nel rene mentre in altri tipi di cellule la sensibilit? per il Mg ? 2 - 3 volte inferiore vs Ca, es. nelle paratiroidi ( Vetter T et al, 2002). ?? Mg? the second cation pi? content at the intracellular level. The body content of Mg in the adult organism? approximately 25g of which: 66% in bone, 33% intracellular and 1% extracellular. In particular, the Mg you can? find in the following forms: 55% ionized free (biologically active form), 30% bound to albumin and 15%? bound to anions. At the level of fasting, the absorption of Mg? increased by Vitamin D. E? a competitor of Ca antagonizing it both in binding at the membrane site (keeps Ca ions low at rest) and in binding with proteins (Kanbay M et al, 2010). Magnesium in particular has equal stimulation power on sensitive calcium receptors in the kidney while in other types of cells the sensitivity? for Mg? 2 - 3 times lower vs Ca, eg. in the parathyroid glands (Vetter T et al, 2002).
La matrice extracellulare dell?osso oltre da idrossiapatite (Sali di calcio) ? formata anche da Sali di Mg per tale motivo anch?esso risulta essenziale nella prevenzione dell?Osteoporosi. Di recente Kircelli et al (2011) hanno dimostrato un ruolo protettivo del Mg nei confronti delle Calcificazioni Vascolari (CV) in uno studio su cellule muscolari liscie bovine dei vasi, in cui si sono visti The extracellular matrix of the bone in addition to hydroxyapatite (Calcium salts)? also formed by Mg salts for this reason it too is essential in the prevention of Osteoporosis. Recently Kircelli et al (2011) demonstrated a protective role of Mg against Vascular Calcifications (CV) in a study on bovine smooth muscle cells of the vessels, in which they were seen
Effetti del Mg Dose-Dipendenti quali: Inibizione attivit? della ALP, riduzione dell?espressione dei geni associati al processo di transdifferenziazione delle BVSMC a cellule Osteoblastiche(Cbfa1 , Msx2): processo attivo, riduzione dell?entrata di Ca (indotta dal fosfato) a livello della Media, aumentati livelli MGP, preservazione deH?apoptosi (indotta dal fosfato) delle BVSMC. Georgels et al (2010) inoltre ha evidenziato che l?intake simultaneo di Ca e Mg con la dieta riduce le CV. Effects of Mg Dose-Dependent such as: Inhibition of activity? of ALP, reduction of the expression of genes associated with the transdifferentiation process of BVSMC to Osteoblastic cells (Cbfa1, Msx2): active process, reduction of Ca entry (induced by phosphate) at the level of the Media, increased MGP levels, preservation of H - apoptosis (induced by phosphate) of BVSMC. Georgels et al (2010) also pointed out that the simultaneous intake of Ca and Mg with the diet reduces CV.
La dose giornaliera raccomandata ( Recommended Daily Allowance: RDA) per il magnesio, per et? maggiore ai 31 anni ? pari nei maschi a 420 mg al giorno e 320 mg nelle femmine (ancora di pi? in gravidanza e durante l'allattamento). The Recommended Daily Allowance (RDA) for magnesium, for age? over 31 years old? equal in males to 420 mg per day and 320 mg in females (even more during pregnancy and breastfeeding).
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| US20110293759A1 (en) * | 2010-06-01 | 2011-12-01 | Calitoga Llc | Nutritional supplement for recovery, repair, and maintenance |
| WO2014020004A1 (en) * | 2012-07-31 | 2014-02-06 | Nestec S.A. | Nutritional composition for promoting musculoskeletal health in patients with inflammatory bowel disease (ibd) |
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