LA DIETA CHETOGENICA: Generalità e applicazioni nell'epilessia Anna Tagliabue Dipartimento Sanità Pubblica Medicina - Aice Padova
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LA DIETA CHETOGENICA:
Generalità e applicazioni nell’epilessia
Anna Tagliabue
Dipartimento Sanità Pubblica Medicina
Sperimentale e Forense - Università of Pavia 1
• 1.12 Ketogenic diet
• 1.12.1 Refer children and young people with
epilepsy whose seizures have not responded
to appropriate AEDs to a tertiary paediatric
epilepsy specialist for consideration of the use
of a ketogenic diet. [new 2012]
2
3
Neurology® 2016;87:2483–2489
ABSTRACT
Treatment goals for epilepsy are no seizures, no side effects, as soon as possible, but these
goals are too often unmet.
Approximately 1 million people in the United States continue to have seizures despite
adequate treatment with antiseizure drugs, representing 40% of those with epilepsy, and 80%
of the cost of epilepsy.
Drug-resistant epilepsy (DRE) can be associated with developmental delay in infants and
young children, and severe disability and morbidity in older children and adults,
as well as a mortality rate 5–10 times that of the general population.
A variety of alternative treatment approaches are offered in addition to surgery,
Other approaches, such as the ketogenic diet or modified
Atkins diet, which can be extremely effective in some patients
4
Cos’è la dieta chetogenica?
• Un regime dietetico che mantiene l’organismo in
uno stato metabolico di chetosi
• La chetosi è dovuta all’aumento in circolo dei corpi
chetonici derivanti dall’aumento dell’ossidazione
dei grassi
• In condizioni fisiologiche il livello di chetoni in
circolo è trascurabile
• In condizioni fisiologiche la produzione di corpi
chetonici aumenta in due situazioni: digiuno o
semidigiuno o dieta fortemente ipoglucidica
5
ketogenesis
FFA di origine:
a)endogena
(digiuno)
b)esogena
(dieta fortemente
ipoglucidica
iperlipidica
normoproteica)
6
DIETA CHETOGENICA: epilessia
• Nel 1920 il figlio epilettico
di un notaio di New York fu
affidato alle cure di un
osteopata del Michigan,
Hugh Conklin che ritenendo
“l’epilessia conseguenza di
un’intossicazione cerebrale
da parte di sostanze
provenienti dall’intestino.”
sottopose a preghiere e
dieta liquida (acqua) per
qualche settimana e ottenne
buoni risultati
7
DIETA CHETOGENICA: epilessia
• Per ovvie ragioni questo approccio basato sul digiuno
ebbe un limitato sviluppo finchè Wilder (1921) alla Mayo
Clinic mise a punto una dieta che mirava a mimare
l’effetto del digiuno
• Per ottenere una chetosi sovrapponibile a quella indotta
dal digiuno è necessario ridurre drasticamente la quota
glucidica e controllare anche la quota proteica.
• Tale risultato si ottiene calcolando la dieta secondo un
rapporto prefissato tra i nutrienti definito chetogenico
(termine coniato da Peterman nel 1925) ancora
utilizzato.
8
Beta idrossi butirrato
Aceto acetato
Acetone
Chetosi in corso di KD classica
(lipidi/non lipidi 4:1)
GF Cahil Annu. Rev. Nutr. 2006. 26:1–22
(Bergqvist et al 2005) 9
Children were randomly assigned to receive a ketogenic diet, either immediately or after a 3-month delay, with no other changes to treatment (control group). 54 on the ketogenic diet and 49 controls. After 3 months, 28 children (38%) in the diet group had greater than 50% seizure reduction compared with four (6%) controls (p
Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD001903
Main results
Eleven (seven in 2016) randomised controlled trials that generated 15 publications.
778: 712 children and adolescents and 66 adults ( no adults in 2016).
No meta-analysis due to the heterogeneity of the studies.
After three months (dropout rates about 30%: lack efficacy, non-acceptance of the diet, adverse
effects)
Classical 4 : 1 KD group: reported rates of seizure freedom and seizure reduction reached as high
as 55% and 85 %
Alternative protocol ( MAD) reported rates of seizure freedom and reduction reached as high as 0
- 35% (adults) and 25– 60% (children)
Authors’ conclusions
For people who have medically intractable epilepsy or people who are not suitable for
surgical intervention, a KD remains a valid option; however, further research is required
11Epilepsia Open :1–18, 2018
doi: 10.1002/epi4.12225
12Linee guida esistenti
• Optimal clinical management of children receiving the ketogenic
diet: Recommendations of the International Ketogenic Diet
Study Group. Epilepsia open 1-18, 2018
• The ketogenic diet for Dravet syndrome and other epileptic
encephalopathies: An Italian consensus. Epilepsia, 52(Suppl.
2):83–89, 2011
• What are the minimum requirements for ketogenic diet services
in resource-limited regions? Recommendationsfrom the
International League Against Epilepsy Task Forcefor Dietary
Therapy Epilepsia, 56:1337–1342, 2015
• Ketogenic diet guidelines for infants with refractory epilepsy Eur
J Paediatr Neurol, 20:798-809, 2016
• Ketogenic dietary therapies in adults with epilepsy: a practical
guide Pract Neurol, 16: 208 – 214, 2016
University of Pavia 13
13Punti considerati nelle linee guida applicative
• Patient selection
• Pre–ketogenic diet counseling and assessment
• Setting of dietary induction of ketosis
• Dietary protocol (classic or alternative dietary
approaches, supplementation)
• Follow-up management (timing, side effects,
discontinuation)
University of Pavia 14Terapie dietetiche per epilessia
KD 3:1 Lipidi
Protidi
KD 4:1 Glucidi Glucidi
Protidi 6%
Lipidi
Dieta Mediterranea 6%
Lipidi Glucidi Protidi
Protidi Protidi 4% Glucidi
Glucidi 6%
Glucidi Lipidi
55% 30% Lipidi
87%
Lipidi
Protidi 90%
15%
LGIT Lipidi
MAD Lipidi Protidi
Protidi Glucidi
KD con MCT Glucidi Glucidi Glucidi
Protidi 11% Glucidi Protidi
Lipidi
5% 10%
7% MCT Protidi 30%
Protidi 30%
Glucidi
MCT
40%
Lipidi
Lipidi
Lipidi 65%
60%
82%
15 University of PaviaTerapie dietetiche per epilessia
KD con LCT KD MCT MAD LGIT
La dieta è ricca di grassi? SI SI SI SI
La dieta è povera di CHO? SI SI SI SI
E’ necessaria supervisione SI SI SI SI
medica?
E’ necessario fare uno SI SI SI SI
screening preliminare?
Sono richiesti integratori? SI SI SI SI
Possono esservi effetti SI SI SI SI
collaterali?
Rapporto chetogenico? 1:1; 2:1; 3:1: 4:1 variabile Medio basso
basso
E’ necessario pesare gli SI SI NO SI
alimenti?
Le calorie sono SI SI NO SI
controllate? 16Andamento chetosi in risposta a
vari protocollo dietetici
Klepper & Leiendecker J Child Neurol 2013
1718
Relazione tra chetosi ematica e
cerebrale
healthy adults
using high field (4-T)
magnetic resonance
spectroscopy, measured
in the nonfasted state
and after 2- and 3-day
fasting-induced ketosis
19Ø Blood beta;-hydroxybutyrate levels
statistically correlated with seizure
control (P = .003).
Ø The traditional measurement of
urine ketones by dipsticks in
children on the ketogenic diet
provides a less than optimal
assessment of the degree of blood
ketosis
20BHB measured during the 3- monthly visits correlated with seizure reduction at 3 and 6 months (p = 0.037 and 0.019, respectively). Urinary ketones measured at the same time did not correlate at any visit. Conclusions: BHB correlates better with seizure reduction than do ketones in urine. It is, therefore, better to use BHB to monitor KD even if BHB is measured less frequently than urinary ketones.
22
Pro
• Chetosi plasmatica aumenta beta idrossi e acetoacetato nel liquor
• Correlazione lineare tra liquor/plasma pari a circa 26%
• Dati sulla relazione tra efficacia e livelli circolanti
Contro
• Risultati contrastanti di studi in vivo o in vitro di modelli sperimentali
• Efficacia di protocolli solo modestamente chetogenici
Ipotesi autori: ruolo chetoni si esplica in modo indiretto attraverso
molteplici targets molecolari
23Our experience
Since1994: classic KD according
to the John Hopkins Hospital
protocol
Since 2008 :
•At home initiation
•Without fasting
•No calorie or fluid restriction
•Gradual increase in ketogenic ratio
•Classic and alternative dietary therapies
University of Pavia 24University of Pavia 25
18 soggetti
8 maschi; 10
18 children
femmine
8 males; 10 females
etàMean
media 12 anni
age 12 yrs
Clinical Nutrition 2012
University of Pavia 26After 3 months on classical diet:
no significant changes in
• visceral and subcutaneous adipose tissue
• lipid profile
• inflammatory and adipose tissue activity biomarkers
• blood glucose,
decrease in fasting insulin decreased and HOMA-IR index
Conclusions over a short period of time KD does not affect
inflammatory cytokines production and abdominal fat distribution
despite being a high-fat diet.
University of Pavia 27nOur data suggest that maintaining a KD for more than 5 y does not pose any
major negative effects on body composition, bone mineral content, and bone
mineral density in adults , a finding that is at variance with previous reports
focusing on children with intractable epilepsy.
nThe discrepant findings might be explained by the fact that our patients were
adults and had a normal bone mineralization at baseline. The observed increase in
muscle strength following the beginning of a KD and the use of multivitamin and
mineral supplements also might have been contributing factors that helped bone
health in our patients
nFurther studies with larger sizes are needed to confirm and expand our findings.
University of Pavia 29Problemi aperti
• La definizione dei livelli di chetosi efficaci
• La transizione dei pazienti pediatrici all’età adulta
• Il miglioramento dell’aderenza alla dieta
• Supporto dell’autogestione dei pazienti
• Disponibilità alimenti modificati erogabili SSN
• Messa a punto di integratori vitaminico minerali
specifici
• Monitoraggio e prevenzione effetti collaterali di tipo
medico e psicologico a lungo termine
University of Pavia 30Keto-team Pavia
Dietologia
Università Pavia
Monica Guglielmetti
Marilde Viale
Epilettologia Fondazione C. Mondino
Elisa Tamagni
Pavia
Claudia Trentani
Endocrinologia pediatrica
Cinzia Ferraris
Policlinico San Matteo
Sara Bellodi
Pavia
https://universitiamo.eu/campaigns/una-dieta-speciale-che-mi-cura-e-mi-fa-crescere/
University of Pavia 3132
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