Integrazione alimentare nellepatologie neuro-degenerative

I MILLE VOLTI DELLA NUTRIZIONEUniversità degli Studi di Milano - Bicocca | Auditorium ‘Guido Martinotti’

www.digitalforacademy.com

Marco Marchetti

Marco Marchetti, CEO, FB Health

Nutraceuticals and Neurodegeneration

PATOLOGIE NEURODEGENERATIVE

How many dementia cases in the future?

?

Alzheimer: ogni anno si spende oltre l'1% del Pil mondiale

Rapporto Mondiale Alzheimer. Ogni 3 secondi un caso di demenza nel Mondo. Oltre la

metà sono di Alzheimer. In Italia ci sono 1.241.000 persone con demenza. L’Alzheimer

rappresenta circa il 50-60% delle demenze complessive.

In tutto il mondo sono 35,6 milioni i malati di demenza. Un numero destinato a raddoppiare

nel 2030 e a triplicare nel 2050. Sono queste le cifre preoccupanti contenute nel Rapporto

mondiale Alzheimer 2010 che lancia l’allarme pandemia sulla malattia. Un epidemia

inarrestabile che raggiunge costi sociali economici pari a 604 mld di dollari: oltre l’1% del

Pil mondiale.

"Se la cura della demenza fosse una nazione – hanno sottolineato nel Report Anders Wimo

(Karolinska Institute di Stoccolma) e Martin Prince (Istituto di psichiatria del King's College

di Londra) – sarebbe la 18esima al mondo per valore economico".

Nel 'Vecchio Continente' sono 7,3 milioni i pazienti affetti dalla malattia, e diventeranno 14,6

milioni nel 2040. Un milione solo in Italia, tra i 100-120 mila in Lombardia.

le famiglie italiane colpite spendono oltre 9 miliardi di euro per pagare badanti o altro

personale da dedicare all'assistenza del proprio caro.

How many dementia cases in the future?

6

Toward defining the preclinical stages of Alzheimer’s disease:

Recommendations from the National Institute on Aging and the Alzheimer’s

Association workgroup

Crawford MA, et al. Evidence for the unique

function of docosahexaenoic acid during the

evolution of the modern hominid brain. Lipids

1999;34 (Suppl):39–47.

Mediterranean Diet, Alzheimer Disease, and Vascular MediationNikolaos Scarmeas, Yaakov Stern, Richard Mayeux, Jose A. Luchsinger.

Arch Neurol. 2006;63:1709-1717

Higher adherence to the MeDi is associated

with a reduced risk for AD. The association

does not seem to be mediated by vascular

comorbidity. This could be the result of other

biological mechanisms (oxidative or

inflammatory) being implicated.

Key Features of Traditional

Okinawa Diet

1) Low Caloric Density (plant-based, low fat, moderate protein from soy, fish, lean meats)

2) High Nutrient Density (Vitamins A,C, E, potassium, magnesium, folate, and healthy oils)

3) Phyto-nutrient Rich (polyphenols, carotenoids mostly from green leafy, yellow root vegetables and seaweed)

4) Low in Glycemic Load (high quality carbohydrates from staple sweet potato)

5) Anti-inflammatory (CR, polyphenols, omega 3 fatty acids)

Ipomoera batatas

cultivar Ayamurasaki

Curcuma longa

Curcumin Anthocyanin

Healthy aging diets other than the Mediterranean: A focus on the Okinawan diet.

Willcox DC, Scapagnini G, Willcox BJ. Mech Ageing Dev. 2014 Jan 21.

Wakame

Undaria pinnatifida

Phlorotannin

Polyphenols

Bidirectional communication channels between the gut microbiome, the gut, and the brain.

Major pathways activated by polyphenols

OXI INFLAMMAGING

Oxidation and InflammationThe link with age related chronic diseases

Scapagnini G, Colombrita C, Amadio M, D'Agata V, Arcelli E, Sapienza M,

Quattrone A, Calabrese V.

Curcumin activates defensive genes and protects neurons against

oxidative stress. Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):395-403. Institute of Neurological Sciences, National Research Council (CNR), Catania, Italy.,

Blanchette Rockefeller Neurosciences Institute, West Virginia University, Rockville, Maryland.

CURCUMIN

heme oxygenase 1

ferritin

thioredoxin

GSH transferases

UDP-glucoronosyltransferases

NAD(P)H:quinone oxidoreductase 1

-glutamylcysteine synthetase

GSH-reductase

catalase

biliverdin/bilirubinCO

Fe

GSH synthesis

regeneration of ubiquinol and tocopherol

regeneration of GSH and dehydroascorbate

multifunctional roles

regeneration of oxidized thioredoxinand dehydroascorbate

AN

TIO

XID

AN

T A

ND

CY

TOP

RO

TEC

TIV

E A

CTI

ON

Phase 2 Response Phase 2 ResponseNrf2/keap1/ARE CytoprotectionPhase 2 Response

AN

TIO

XID

AN

T R

ESP

ON

SIV

E EL

EMEN

T (A

RE)

O

OR2

HO

OH

OH

R1

HO

Keap1

Nrf2

antioxidant

Regulation of inflammatory cytokines through activation of NF-κB

NFkBNrf2Keap1 IkB

Inflammation Inflammation

Nrf2 NFkB

Defensive ResponseDetox enzymes type II

HO-1

Inflammatory ResponseCytokines

NOSCOX

DNA

OxidativeStress

Curcumin OxidativeStress

Chandra V, Pandav R, Dodge HH, Johnston JM, Belle SH, DeKosky ST, and Ganguli

M. Incidence of Alzheimer's disease in a rural community in India: the Indo-US

study. Neurology 57: 985-989, 2001.

Muthane U, Yasha TC, and Shankar SK. Low numbers and no loss of melanized

nigral neurons with increasing age in normal human brains from India.

Ann Neurol 43: 283-287, 1998.

Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH. Curry consumption and

cognitive function in the elderly. Am J Epidemiol 164(9):898-9, 2006

Epidemiological studies showed that in India, where curcumin is widely used

in daily diet, there is a reduced age-adjusted prevalence of AD (in patients

between 70 and 79 years of age is 4.4 fold less than that of the United

States), as well as a lower prevalence of Parkinson’s disease.

Proc Natl Acad Sci U S A. 2007 July 31; 104(31): 12849–12854.

Innate immunity and transcription of MGAT-III and

Toll-like receptors in Alzheimer's disease patients

are improved by bisdemethoxycurcumin

Fiala M. et al.Department of Medicine, Greater Los Angeles Veteran's Affairs

Medical Center

J Clin Psychopharmacol. 2008 Feb;28(1):110-3.

Six-month randomized, placebo-controlled, double-

blind, pilot clinical trial of curcumin in patients with

Alzheimer disease.

Baum L. et al

Delphinidin

Low bioavailability Better bioavailability

Epicatechin

Blueberry

Cocoa

(Theobroma cacao)

Polyphenols bioavailability is a critical aspect

Cocoa phytochemicals, a story of positive biology

ProcyanidinsMonomers

Chemical structures of cocoa flavanols

In a controlled randomized trial, healthy 50–69-year-old

subjects consumed either a high or low cocoa flavanol–

containing diet for 3 months. A high-flavanol intervention

was found to enhance DG function, as measured by fMRIand by cognitive testing.

Cocoa epicatechins improve cognition

The Connection Between Fats and Heart Diseases

1969, Bang & Dyerberg: investigation in Greenlandnear absence of thrombotic heart diseases inGreenlanders

Clinical Interventions in Aging 2010:5 45–61

Gregory A Jicha & William R Markesbery

Roles of PUFAs in the brain

Bazinet RP and Layé S, 2014NATURE REVIEWS NEUROSCIENCE 15

NH2

SOH

O O

• Homotaurine (Tramiprosate) :

• Taurine

37

Homotaurine Reduces Amyloid Deposition in hAPPTransgenic Mouse Brain

RS

CC

RS

CC

(8 weeks of treatment)

Control (untreated) Homotaurine (100mg/kg/day)

Gervais F et al. Neurobiol Aging 2007; 28(4):537-47.

38

Studies N Population Duration Endpoints

10 Phase I 288 Healthy 7-10 days Safety/PK

Phase II 58 AD 3 monthsCognitive function,

Amyloid Aβ CSF level

Phase II Open-label extension

42 AD 41 months Cognitive function

Phase II 24Cerebral Amyloid

Angiopathy3 months

Neurological function, cognitive function

Phase III North America

1,052 AD 18 monthsCognitive function,

brain volume

Phase III North America Open-label

extension738 AD 12 months Cognitive function

Phase III Europe 975 AD 18 monthsCognitive function,

brain volume

16 Clinical Trials Involving > 2,000 Subjects

AiguoWu a, Emily E. Noble a, Ethika Tyagi a, Zhe Ying a, Yumei Zhuang a, Fernando

Gomez-Pinilla

Biochimica et Biophysica Acta (2014)

Synergy research: Approaching a new generation of nutraceuticals

www.digitalforacademy.com | info@digitalforacademy.com