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No Conflicts of Interest
Atlas Medical Publishing Ltd 2008
2008 John Wiley & Sons, Inc.
JANA Vol. 8, No. 2, 2005
Springer Science
+Business Media, LLC 2011
Cardiovascular
Therapeutics 28 (2010) 216–226
2008 by Taylor & Francis Group, LLC
Copyright © 2005 John Wiley
& Sons Ltd, The Atrium, Southern Gate, Chichester
2005 Humana Press Inc. Vol. 1, No. 3, 2008
• Circonferenza vita elevata Definizione specifica per popolazione e per paese
• Elevati trigliceridi (o terapia farmacologica per ipertrigliceridemia) ≥ 150 mg/dL
• Ridotto HDL colesterolo (o terapia farmacologica per ridotto HDL colesterolo) <40 mg/dl per i maschi e <50 mg/dl per le femmine
• Ipertensione arteriosa (o terapia farmacologica per ipertensione) Systolic ≥ 130 e/o diastolic ≥ 85 mmHg
• Elevata glicemia a digiuno (IFG) (o terapia farmacologica per presenza di iperglicemia) ≥100 mg/dl
sindrome metabolica come raggruppamento di fattori di rischio
Sindrome metabolica: presenza di tre dei cinque criteri elencati
Alberti, K.G. M. M., Eckel, R. H., Grundy, S. M., Zimmet, P Z., Cleeman, J. I., Donato, K. A., et al. (2009). Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; International Artherosclerosis Society; and International Association for the Study of Obesity. Circulation, 120, pp 1640-1645.
MetS linked to…
Heart Disease: 1.5 to 3-fold increase ASHD
Type 2 diabetes: 5-fold increase
Kidney disease: 3.5-fold increase CKD
Reproductive problems in women
Skin lesions: acanthosis nigricans, skin tags
Non-alcoholic fatty liver disease
Cancer: GI tract, prostate, breast, uterine
Sleep-disordered breathing
J Clin Invest. 2012 January 3; 122(1): 4–12.
Presenza di insulina ma mancata azione sull’inibizione di secrezione del glucagone ??
The Problem Is…
http://professional.diabetes.org/content/multimedia/images/lge/lge_qhscw16-metabolic%20syndrome-4%20copia.gif
Metabolic syndrome: Definition, pathophysiology, and mechanisms American Heart Journal, January 2005
TG and
HDL cholesterol
ß cell function
BG
Adipocytokines & FFA
Insulin resistance
CVS and renal complications
Aging
Family history
(Genetics or
shared environment)
Psychosocial
stress
Visceral fat GH and IGF-1
Testosterone (M)
Testosterone (F)
Cortisol
SNS
RAAS BP
Activated immunity
Adapted from Björntorp P. Obes Res 1993; 1: 206-22 and Chan JCN et al. Diabetes Care 1995; 18: 1013-6. Luk A and Chan JCN Diabetes Res Clin Pract 2008: 82 Suppl 1:S15-20
BP: blood pressure; BG: blood glucose; CVS: cardiovascular system; FFA: free fatty acids; GH: growth hormone; IGF-1: insulin-like growth factor-1; RAAS: renin-angiotensin-aldosterone system; SNS: sympathetic nervous system; TG: triglycerides
Possible link among environmental/dietary factors, genetic factors, oxidative stress, and aberrant methylation profile in MetS. Increased xenobiotic and synthetic-nutrient exposure may be the primary cause of Metabolic Syndrome ROS, reactive oxygen species.
• Zhou SS, Zhou YM, Li D, Lun YZ. Dietary methyl-consuming compounds and metabolic syndrome. Hypertens Res. 2011;34:1239–1245. doi: 10.1038/hr.2011.133.
• Shi-Sheng Zhou, Da Li, Yi-Ming Zhou, and Ji-Min Cao. The skin function: a factor of anti-metabolic syndrome. Diabetol Metab Syndr. 2012; 4: 15
A number of stimuli, such as hyperglycemia, high levels of circulating free fatty acid (FFA), and chronic inflammation, lead to increases in the production of reactive molecular species, and this in turn may lead to oxidative stress Oxidants activate the JNK/AP-1 and IKK–NFκB axes, leading to an upregulation in the transcription of proinflammatory cytokine genes and increased production of cytokines and acute-phase reactants. Cytokines impair the action of the insulin receptor substrate, resulting in impaired insulin action.
Biologics. 2011; 5: 7–19
The role of oxidative stress and inflammation in insulin resistance
Chronic Overnutrition impairs homeostasis, inducing stress reactions promoting inflammatory processes (cytokines),
especially of the immune system.
Balisteri CR. Et al. Mediators of Inflammation Volume 2010 (2010), Article ID 802078, 19 pagesdoi:10.1155/2010/802078
J Clin Invest. 2003; 112(12):1821–1830 doi:10.1172/JCI19451
The common characteristics of MetS and hypercortisolemic conditions such as Cushing’s syndrome (CS) suggest that the pathogenesis of MetS and central obesity might involve prolonged and excessive exposure to glucocorticoids.
Increased exposure to cortisol contributes to increased fat accumulation in visceral depots
However, cortisol metabolism is not only centrally regulated.
The action of 11β-hydroxysteroid dehydrogenase-1 at the tissue level also modulates cortisol metabolism.
Increased 11β-hydroxysteroid dehydrogenase-1 activity in adipose tissue and liver might contribute to the development of several features of the MetS.
Conclusions: MetS shares many characteristics of CS, and cortisol might play a role in the development of MetS at both a central and a peripheral level.
J Clin Endocrinol Metab 94: 2692–2701,2009
In agreement with this concept, in a study of
101 obese patients (BMI 34.4 ± 4.3 kg/m2) of
both sexes, impaired glucose tolerance and IR
was associated with increased adipose
11beta-HSD1 expression (Tomlinson et al.,
2008).
Arq Bras Endocrinol Metab 2007;51/8:1397-1403
The bulk of evidences points to an overexpression and increased activity of 11βHSD1 also in human adipose tissue
The nonselective 11βHSD1 inhibitor carbenoxolone improves insulin sensitivity in humans, and selective inhibitors enhance insulin action in diabetic mice liver, thereby lowering blood glucose.
Thus, 11βHSD1 is now emerging as a modulator of energy partitioning and a promising pharmacological target to treat the MS and diabetes.
Arq Bras Endocrinol Metab 2007;51/8:1397-1403
Based on these data, the suggestion crops up that insulin resistance is therefore not the main player in the pathophysiology of the metabolic syndrome, but a consequence of obesity
Journal of Nutrition and Metabolism Volume 2012, Article ID 525093, 9 pages
Glucocorticoids exert deleterious effects on the glucose metabolism, leading to a wide range of alterations, from insulin-resistance to overt and complicated diabetes. The complex net of mechanisms that link hypercortisolism (endogenous or exogenous) to the development of these abnormalities is only partially understood Understanding the mechanisms of glucocorticoid-induced glucose alterations could lead to the development of novel therapeutic anti-inflammatory drugs, with reduced impact on glucose metabolism. Finally, the link between hypercortisolism and metabolic syndrome deserves more interest: unravelling the open questions in this field could lead to a significant improvement in the treatment of obesity, diabetes, and its complications.
European Journal of Endocrinology (2010) 162 919–923
Candidate Genes Associated with Metabolic Syndrome
Adapted with permission from Reilly MP, Rader DJ. The metabolic syndrome: more than the sum of its parts? Circulation 2003;108:1549.) Genetics of the Metabolic Syndrome
Hospital Physician October 2006
A major challenge remains in understanding the interplay between brain and peripheral clocks and in determining how these interactions promote energy homeostasis across the sleep-wake cycle. In this Review, we evaluate how investigation of molecular timing may create new opportunities to understand and develop therapies for obesity and diabetes
J Clin Invest. 2011;121(6):2133–2141.
Circ Res. 2010;106:447-462
An exciting aspect of the field has been the integration of behavioral and physiological approaches, and the emerging insight into both neural and peripheral tissues in disease pathogenesis. Consideration of the cell and molecular links between disorders of circadian rhythms and sleep with metabolic syndrome has begun to open new opportunities for mechanism-based therapeutics
65% Fitoterapici
18% Multivitaminici e salini
13% Probiotici (Fermenti)
4% Aminoacidi con o senza carboidrati (sportivi)
Action sites of western medicine in diabetes treatment. Hypoglycemic medicines restore euglycemia via several types, including insulin secretagogues (sulfonylureas, meglitinides), insulin sensitizers (biguanides, metformin, thiazolidinediones), alpha-glucosidase inhibitors (miglitol, acarbose).
Action sites of herbs in diabetes treatment. The efficacy of hypoglycemia herbs has been mediated by increasing insulin secretion (ginseng, bitter melon, aloes, biophytum sensitivum), enhancing glucose uptake by adipose and muscle tissues (ginseng, bitter melon and cinnamon), inhibiting glucose absorption from intestine (myrcia and sanzhi) and inhibiting glucose production from heptocytes (berberine, fenurgreek leaves).
Hypoglycemic herbs and their action mechanisms Chin Med. 2009; 4: 11.
General diagrammatic representation of the insulin-signaling cascade.
Dietary management of the metabolic syndrome beyond macronutrients Nutrition Reviews® 2008. Vol. 66(8):429–444
Cannella Clinical trials suggest that modest amounts (1–6 g) of cinnamon can favorably impact glucose and/or lipid levels in healthy subjects
Te Verde Consistent consumption of 5–6 or more cups daily or 200–300 mg of epigallocatechin gallate (EGCG), the primary polyphenol in green tea, has demonstrated benefit for cardiovascular and metabolic health
Berberina
numerous clinical studies from China have documented significant plasma glucose reductions when administering berberine (1.0– 1.5 g daily dose divided throughout the day) to subjects with type 2 diabetes
Most recent is the clinical study by Zhang et al., which indicated noteworthy reductions in fasting and postprandial plasma glucose, hemoglobin A1c, and relevant lipid biomarkers due to berberine supplementation of 1.0 g daily for 3 months compared with placebo.
Dietary management of the metabolic syndrome beyond macronutrients Nutrition Reviews® 2008. Vol. 66(8):429–444
Ginseng (Panax ginseng):
Like berberine, ginseng has been used as part of traditional Chinese medicine for thousands of years, particularly as a restorative tonic to increase blood flow and decrease fatigue
Vuksan et al. reported improvements in the postprandial plasma glucose measurements (decrease of 8–11%) and fasting and postprandial insulin (33–38%) with 6 g per day Panax ginseng
Dietary management of the metabolic syndrome beyond macronutrients Nutrition Reviews® 2008. Vol. 66(8):429–444
L’INTEGRAZIONE CON CURCUMINA RIDUCE LA SECREZIONE DI TNF-α, IL-6, IL-8 E
MCP-1 IN MONOCITI TRATTATI CON ALTI LIVELLI DI GLUCOSIO E I LIVELLI EMATICI DI
TNF-α, IL-6, MCP-1, GLUCOSIO ED EMOGLOBINA GLICATA NEI RATTI DIABETICI.
I risultati dello studio dimostrano che l’effetto degli alti livelli di glucosio sulla
perossidazione lipidica e sulla secrezione di IL-6, IL-8, MCP-1 e TNF-α viene inibito dalla
curcumina nei monociti.
Nel modello di ratto il diabete causa un significante aumento dei livelli ematici di IL-6, MCP-
1, TNF-α, glucosio, emoglobina glicata e stress ossidativo che possono essere
significativamente diminuiti dall’integrazione con curcumina.
LA CURCUMINA PUÒ ABBASSARE I MARKERS DELL’INFIAMMAZIONE
VASCOLARE E I LIVELLI DI STRESS OSSIDATIVO, CONTRIBUENDO A
RIDURRE LA GLICEMIA E IL RISCHIO DI INFIAMMAZIONE VASCOLARE
NEL DIABETE.
Hu G-X, Lin H, Lian Q-Q, Zhou S-H, Guo J, et al. (2013); PLoS ONE 8(3): e49976.
Interconversion of cortisol and cortisone by two 11bhydroxysteroid dehydrogenase (11b-HSD) isoforms. 11b-HSD1 catalyzes the conversion of cortisone into cortisol in the liver or fat tissues, and 11b-HSD2 catalyzes the conversion of cortisol into cortisone in kidney or colon tissues
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm 2007;4:807-818.
poor stability of curcumin, which is highly unstable at intestinal pH (half-life at pH 7 <10 min), and low oral absorption
Plasma concentrations barely reach 50 ng/mL of phase II metabolites (glucuronides and sulfates) after oral administration of dosages as high as 12 g/day.
Once in the plasma, however, curcumin enjoys a surprising stability and even permeability to tissues hard to reach like the brain
The interrelationship between metabolic syndrome, diet, phytochemicals, and insulin signaling
Dietary management of the metabolic syndrome beyond macronutrients Nutrition Reviews 2008. Vol. 66(8):429–444
L’azione biologica di un composto è legato alla quota
che raggiunge la circolazione plasmatica
Intoppi ?
Composti idrofili non assorbiti Assorbimento seguito da estrusione Effetti di “primo passaggio” epatico
Enzimi di classe 1 Enzimi di classe 2
Stabilità ed esatto sito d’azione (tempo e pH-dipendenze)
Detoxification pathways. Potentially noxious chemicals ingested with food undergo enzymatic metabolism in a coordinated process involving phase I, II and III enzymes; metabolites are then excreted from the body.
Hormetic Dietary Phytochemicals Neuromolecular Med. 2008; 10(4): 236–246.
Some such phytochemicals induce the expression of phase II enzymes via the Nrf2/ARE (the antioxidant response element) pathway.
Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) has been called the “master redox switch”. antioxidant enzymes that combat oxidative stress and inflammation Collectively, they are known as the Phase II antioxidant enzymes: glutathione transferase glutathione peroxidase glucuronysyl transferase quinone reductase epoxide hydrolase superoxide dismutase gamma glutamylcysteine So how can it be that supplementing with antioxidants can actually dampen the body’s internal antioxidant defense system?
ARE
Stress
signaling
Nrf2 P
Nrf2 P
Nrf2 released
Kinase
(Antioxidant Response Element)
Nrf2
Antioxidant enzymes
Nrf2 binds to the Antioxidant Response
Element (ARE) and promotes transcription of antioxidant
genes
activate the transcription factor Nrf2, which activates genes that are involved in detoxification of chemicals and antioxidant defense**. This is thought to be due to the fact that polyphenols, just like radiation, may temporarily increase the level of oxidative stress inside cells.
**
• Modulation of Nrf2-mediated antioxidant and detoxifying enzyme induction by the green tea polyphenol EGCG. Food Chem Toxicol. 2008 Apr;46(4):1271-8.
• Upregulation of endogenous antioxidants and phase 2 enzymes by the red wine polyphenol, resveratrol in cultured aortic smooth muscle cells leads to cytoprotection against oxidative and electrophilic stress. Pharmacol Res. 2006 Jan;53(1):6-15.
• Coffee,broccoli and spices are strong inducers of electrophile response element-dependent transcription in vitro and in vivo - studies in electrophile response element transgenic mice. Mol Nutr Food Res.2011 Feb;55(2):185-97.
• Ionizing radiation activates the Nrf2 antioxidant response. Cancer Res. 2010 Nov 1;70(21):8886-95
The body treats polyphenols as potentially harmful foreign chemicals, or "xenobiotics"
Certain other plant chemicals, such as sulforaphane found in cruciferous vegetables, and allicin found in garlic, exhibit similar effects and may also act by hormesis Some of the best-studied polyphenol-rich foods are tea (particularly green tea), blueberries, extra-virgin olive oil, red wine, citrus fruits, hibiscus tea, soy, dark chocolate, coffee, turmeric and other herbs and spices, and a number of traditional medicinal herbs.
• Coffee,broccoli and spices are strong inducers of electrophile response element-dependent transcription in vitro and in vivo - studies in electrophile response element transgenic mice. Mol Nutr Food Res.2011 Feb;55(2):185-97.
the evidence suggests that polyphenol-rich foods are healthy in moderation, and eating them on a regular basis is generally a good idea.
Diabetes 60:2465–2473, 2011
Diabetes 61:3208–3218, 2012
Hormetic Dietary Phytochemicals Neuromolecular Med. 2008; 10(4): 236–246.
The concept and biphasic dose-response characteristic of hormesis
- Composti idrofili non assorbiti
“Since most drug absorption from the
gastrointestinal tract occurs via passive processes,
absorption is favoured when the drug is in lipophilic
form.”
GINKGOSELECT PHYTOSOME® 160 mg p.o. as GBE
Ginkgo Biloba Extract (GBE) 160 mg p.o.
GINKGOSELECT PHYTOSOME®
PLASMA LEVELS OF GINKGOLIDE A IN HEALTHY VOLUNTEERS
ng
/ m
L p
las
ma
0
140
80
40
20
60
min 0 60 120 180 240 300 360
120
100
L’integratore Nutrizionale; 2009, 12(1)
Concentrazione plasmatica di Curcumina in ratti:
• Curcumina Phytosoma (linea continua);
• Curcumina non-complessata (linea tratteggiata)
450 mg di Meriva (90 mg di curcumina complessata con fosfatidilcolina o fitosoma) è stata
assorbita in maniera similare a 4 g di Curcuma longa (al 95% in curcumina) non complessata,
dimostrando un AUMENTO DI BIODISPONIBILITÀ DI 45-50 VOLTE.
Assorbimento di 450 mg di Meriva paragonati a 4 g di curcumina sola.
CONFRONTO TRA LA BIODISPONIBILITA’ DELLA CURCUMINA RISPETTO
ALLA CURCUMINA FORMULATA CON FOSFATIDILCOLINA.
Nello studio ratti Wistar maschi hanno ricevuto oralmente 340 mg/kg
di curcumina o curcumina complessata con fosfatidilcolina (fitosoma - Meriva).
La curcumina e i suoi metaboliti sono stati identificati solo nel plasma
dei ratti trattati con Meriva.
I risultati suggeriscono che la curcumina complessata con
fosfatidilcolina fornisce livelli sistemici maggiori rispetto alla
curcumina non complessata.
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm 2007;4:807-818.
poor stability of curcumin, which is highly unstable at intestinal pH (half-life at pH 7 <10 min), and low oral absorption
Plasma concentrations barely reach 50 ng/mL of phase II metabolites (glucuronides and sulfates) after oral administration of dosages as high as 12 g/day.
Once in the plasma, however, curcumin enjoys a surprising stability and even permeability to tissues hard to reach like the brain
Quale altro ostacolo?
Assorbimento seguito da estrusione
Assorbimento seguito da estrusione
Principali distretti corporei in cui si trova la P-glycoproteina
The Oncologist August 2007 vol. 12 no. 8 927-941
Pharmacol Res. 2003 Oct;48(4):347-59. P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement. Varma MV, Ashokraj Y, Dey CS, Panchagnula R.
INIBITORI DELLA GLICOPROTEINA-P E LORO SCREENING:
UNA PROSPETTIVA PER L’AUMENTO DELLA
BIODISPONIBILITA’.
Gli inibitori della glicoproteina-P aumentano
l’assorbimento intestinale e la distribuzione tissutale, mentre
riducono il metabolismo dei substrati e la loro eliminazione.
In questa review vengono discusse le tecniche utilizzate per lo
screening degli inibitori della glicoproteina-P e lo scopo di
questi inibitori per ottimizzare l’assorbimento orale e la
farmacocinetica dei farmaci
curcumina fitosoma associata a piperina pura
incrementa la biodisponibilità orale di curcumina di
circa 260 volte rispetto alla somministrazione della medesima quantità di curcumina pura
1
2
Biodisponibilità Curcumina nel volontario sano
Trattamento AUC*
1) 400 mg di curcumina pura 2240±197
3) 4000 mg di curcumina pura 23800±1212
4) 400 mg di curcumina fitosoma 24404±1857
2) 400 mg di curcumina fitosoma 596080±29872
4 mg di piperina
La piperina
è un inibitore degli enzimi di fase 2
preposti a creare coniugati
con acido glucuronico
Può aumentare fino a 20 volte la biodisponibilità
della curcumina
La piperina inibisce gli enzimi di metabolismo dei farmaci ed aumenta
la concentrazione plasmatica di diversi farmaci.
La piperina inibisce sia il trasportatore glicoproteina-P e l’enzima
principale nel metabolismo dei farmaci, il CYP3A4, quindi può
interferire con la concentrazione plasmatica dei substrati della
glicoproteina-P e del CYP3A4 soprattutto se somministrati oralmente
LA PIPERINA, IL COSTITUENTE MAGGIORE DEL PEPE NERO, INIBISCE LA GLICOPROTEINA-P UMANA E IL CYP3A4
COINVOLGIMENTO DELLA GLICOPROTEINA-P
NELL’ASSORBIMENTO DELLA BERBERINA.
La glicoproteina-P contribuisce allo scarso assorbimento
intestinale della berberina.
Utilizzando inibitori della glicoproteina-P, L’ASSORBIMENTO
DELLA BERBERINA VIENE AUMENTATO DI 6 VOLTE.
La glicoproteina-P sembra essere la causa dello scarso
assorbimento della berberina e ciò suggerisce che inibitori
della glicoproteina-P potrebbero avere valore terapeutico
aumentando la biodisponibilità della berberina stessa.
Pharmacol Toxicol. 2002 Oct;91(4):193-7.
Drug Metab Rev. 2004 Feb;36(1):57-104 Herbal modulation of P-glycoprotein. Zhou S, Lim LY, Chowbay B.
MODULAZIONE “ERBALE” DELLA GLICOPROTEINA-P.
Nello studio viene riportato che CURCUMINA, GINSENOSIDI,
PIPERINA, alcune CATECHINE DEL TE VERDE e SILIMARINA
sono INIBITORI DELLA GLICOPROTEINA –P.
La silimarina è l’erbale che presenta un’attività inibitoria più
efficace.
Berberina: 1000 mg; Silybum Marianum: 200mg
berberina
berberina berberina
silimarina
Rappresentazione grafica dell’inibizione della glicoproteina-P da parte della silimarina.
Nel 2° disegno la berberina viene assorbita.
Risultati del trattamento di 60 gg con 2 compresse di Berberol:
il colesterolo si è ridotto di oltre il 32% e l’emoglobina glicata di 1%
26 pazienti con diabete mellito di tipo 2 in stabilità metabolica con
compenso glicemico non ottimale e con profilo lipidico alterato
(4 casi in terapia con statine e 1 con fenofibrato).
A tutti è stato aggiunto un prodotto con Berberina e Silimarina
Dopo 3 mesi si è osservata una
riduzione statisticamente significativa dell’HbA1c (da 8,15% a 7,57%),
colesterolo totale (da 192 a 162 mg/dL)
colesterolo LDL (da 109 a 89 mg/dL),
dei trigliceridi (da 175 a 136 mg/dL).
Berberine Improves Glucose Metabolism in Diabetic Rats by Inhibition of Hepatic Gluconeogenesis
PLoS ONE 1 February 2011:Volume 6, Issue 2, e16556
The data suggest that BBR improves fasting blood glucose by direct
inhibition of gluconeogenesis in liver.
This activity is not dependent on insulin action.
The gluconeogenic inhibition is likely a result of mitochondria inhibition by BBR.
The observation supports that BBR improves glucose metabolism through an insulin-independent pathway.
BBR, berberine; Diab+BBR, diabetic rats treated with berberine; Nor, normal lean rats; Nor+BBR, normal rats treated with berberine; FBG, fasting blood glucose; FINS, fasting serum insulin; TC, total cholesterol; TG, triglycerides; ALT, alanine aminotransferase; AST, aspartate transaminase. Data are presented as mean 6 SE (n = 9).
PLoS ONE 1 February 2011:Volume 6, Issue 2, e16556
Schematic model of BBR signaling pathway.
BBR inhibits mitochondria function and decrease intracellular ATP.
This leads to a reduction in gluconeogenic and lipogenic transcription factors (FoxO1, SREBP1, and ChREBP).
As a result, expression of gluconeogenic genes (PEPCK and G6Pase) and lipogenic gene (FAS) are decreased.
These molecular changes represent a signaling pathway for improvement of fasting glucose and liver steatosis in the BBR-treated diabetic rats.
LA BERBERINA STIMOLA IL TRASPORTO DI GLUCOSIO ATTRAVERSO UN MECCANISMO DIVERSO DA QUELLO DELL’INSULINA.
Il meccanismo dell’effetto ipoglicemizzante della berberina non è
conosciuto.
Lo studio dimostra che la berberina stimola il trasporto del
glucosio. L’AMPK sembra essere coinvolta nell’effetto metabolico
della berberina.
L’attivazione della protein chinasi AMP dipendente (AMPK) sembra
essere il meccanismo d’azione della metformina.
AMPK (adenosine monophosphate-activated protein kinase ) è
un enzima che gioca un ruolo nell’omeostasi energetica cellulare,
tra l’altro modulando la secrezione di insulina dalle cellule beta del
pancreas
Metabolism. 2007 Mar;56(3):405-12.
LA BERBERINA DIMINUISCE LA GLICEMIA NEI
PAZIENTI CON DIABETE DI TIPO 2 ATTRAVERSO
L’AUMENTO DELL’ESPRESSIONE DEL RECETTORE
DELL’INSULINA.
La berberina aumenta l’RNA messaggero del
recettore dell’insulina in una grande varietà di linee
cellulari umane.
Metabolism. 2010 Feb;59(2):285-92
Lo studio ha investigato la DL50 (dose letale mediana)
della berberina attraverso tre vie di somministrazione:
iniezione intravenosa (IV), iniezione intraperitoneale (IP)
e somministrazione orale.
La somministrazione orale è stata fatta a diversi
dosaggi: 10.4, 20.8, 41.6 e 83.2 g/kg.
La DL 50 per iniezione IV è stata di 9,0386 mg/kg,
mentre quella per iniezione IP è stata di 57,6103 mg/kg.
Nel gruppo per somministrazione orale non è stata
raggiunta nessuna DL50.
Pycnogenol® Supplementation Improves Health Risk Factors in Subjects with Metabolic Syndrome
Phytotherapy Research; 28 JAN 2013 DOI: 10.1002/ptr.4883
evaluated the effects of 6 month supplementation with Pycnogenol® maritime pine bark extract on health risk factors in subjects with metabolic syndrome.
(range 45–55 years) presenting with all five risk factors of metabolic syndrome were included
Pycnogenol® was administered for 6 months (50-mg Pycnogenol were taken three times a day at approximately 8 am, 4 pm and 10 pm)
A group of 66 equivalent subjects were followed up as controls
In the 6-month study Pycnogenol® supplementation 150 mg/day decreased waist circumference, TG levels, blood pressure and increased the HDL cholesterol levels in subjects
Pycnogenol® Supplementation Improves Health Risk Factors in Subjects with Metabolic Syndrome
Phytotherapy Research; 28 JAN 2013 DOI: 10.1002/ptr.4883
Pycnogenol lowered fasting glucose from baseline
123 ± 8.6 mg/dl to 106.4 ± 5.3 after 3 months and to 105.3 ± 2.5 at the end of the study (p < 0.05 vs controls)
Men's waist circumference decreased with Pycnogenol
from 106.2 ± 2.2 cm to 98.8 ± 2.3 cm and to 98.3 ± 2.1 after 3 and 6 months
Women's waist decreased
from 90.9 ± 1.6 cm to 84.6 ± 2.1 cm and to 83.6 ± 2.2 cm after 3 and 6 months
In addition, plasma free radicals decrease in the Pycnogenol group was more effective than in the control group (−34.6%; p < 0.05).
Phytotherapy Research; 28 JAN 2013 DOI: 10.1002/ptr.4883
Pycnogenol® Supplementation Improves Health Risk Factors in Subjects with Metabolic Syndrome
Role of vitamin D deficiency in insulin resistance
Review Article Role of Vitamin D in Insulin Resistance Journal of Biomedicine and Biotechnology Volume 2012, Article ID 634195, 11 pages
• The association of vitamin D status and cardiometabolic disorders (cardiovascular disease, diabetes, and metabolic syndrome) was reviewed recently in a meta-analysis of 28 independently published studies.
high serum 25-dihydroxyvitamin D concentration showed
• 55% reduction in the risk of diabetes (9 studies)
• 33% reduction in the risk of cardiovascular diseases (16 studies)
• 51% reduction in metabolic syndrome (8 studies)
(Maturitas, vol. 65, no. 3, pp. 225–236, 2010)
Role of vitamin D deficiency in insulin resistance
Vitamin D has been proposed to play an important role and to be a risk factor in the development of insulin resistance and the pathogenesis of type 2 DM by affecting either insulin sensitivity or β-cell function, or both
[The American Journal of Clinical Nutrition, vol. 79, no. 5, pp. 820–825, 2004; Diabetologia, vol. 55, pp. 1668–1678, 2012; Diabetologia, vol. 55, no. 8, pp. 2173–2182, 2012.].
Vitamin D plasma level and clinical data were determined from 1,818 subjects from the Canadian Health Measures Survey
Vitamin D plasma levels are associated with the occurrence of metabolic syndrome components and insulin resistance among Canadians and are linked to increased level of insulin resistance
Clin Invest Med. 2011 Dec 1;34(6):E377.
Effects of vitamin D supplementation in insulin resistance
Review Article Role of Vitamin D in Insulin Resistance Journal of Biomedicine and Biotechnology Volume 2012, Article ID 634195, 11 pages
Quantità, modo di somministrazione,
genetica
Over 40 studies show inverse correlations of vitamin D status [serum 25(OH)D] with metabolic syndrome risk or with the incidence or severity of its components.
Intake of 600 IU/ day are estimated to achieve mean serum 25(OH)Ds of 54–55 nmol/l, IOM target levels known to reduce overt bone disease risks. For values of >= 50nmol/l, at the population level, intakes of ~930 IU/day are needed, supporting the need for intakes higher than the recent IOM recommendations
Am J Clin Nutr 2007; 85:649-50; Br J Nutr 2011; 105: 144-56; J Bone Miner Res 2011; 26:455-7;
To achieve 25(OH)Ds of 75–85 nmol/l where notable reductions in insulin resistance have been achieved and at which other beneficial effects are seen
Diabetes 2008; 57:298-305; J Nutr 2010; 103:549-55; J Clin Endocrinol Metab 2006; 91:2612-7;
J Clin Endocrinol Metab 2011; 96:53-8; Anticancer Res 2011; 31:607-11; BMC Med 2011; 9:48;
J Clin Endocrinol Metab 2011; 96:1911-30; J Hypertens 2012; 30:284-9;
needs intakes of 1,000–2,000 IU/day, doses already suggested to be necessary for adults by many vitamin D workers and medical advisory bodies
28 Adults given 4000iu/d x 5 months ◦ Levels averaged 40ng/ml
Vieth. Am J Clin Nutr 2001.73(2):288.
67 men given higher doses x 20 weeks ◦ 5000iu/d – avg 25OHVitD level 60ng/ml
◦ 10,000iu/d – average level 90ng/ml
◦ No toxicity seen Heany et al. Am J Clin Nutr. 2004;79(3):362.
PLoS ONE March 2013; 8(3): e58278
The results of this study indicate that higher dietary magnesium intake is strongly associated with the attenuation of insulin resistance and is more beneficial for overweight and obese individuals Moreover, the inverse correlation between insulin resistance and dietary magnesium intake is stronger when adjusting for %BF than BMI.
Journal of the American College of Nutrition, Vol. 29, No. 1, 31–40 (2010)
35 persone con obesità e sindrome metabolica divisi in 3 gruppi: 1) 4 tazze di acqua 2) 4 tazze di te verde 3) 2 capsule di estratto di te verde + 4 tazze di acqua
Journal of the American College of Nutrition, Vol. 29, No. 1, 31–40 (2010)
• green tea beverage and green tea extracts caused a significant decrease in body weight and body mass index (BMI) versus controls at 8 weeks (22.5 kg and 21.9 respectively)
• Green tea beverage showed a decreasing trend in LDL-cholesterol and LDL/high-density lipoprotein (HDL) versus controls
• Green tea beverage also significantly decreased MDA and HNE versus controls
Biomarker dello stress ossidativo malondialdehyde (MDA) hydroxynonenals (HNE)
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