DIETA CETOGÊNICA

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DIETA CETOGÊNICA 
E SUAS APLICAÇÕES 
Danielle Lodetti de Jesus
Nutricionista pela Universidade Federal de Santa Catarina (2000)
Especialista em Fisiologia do Exercício pela Escola Paulista de Medicina (2002)
Especialista em Nutrição Estética pelo IPGS – Rio de Janeiro (2010)
Aperfeiçoamento em Bioquímica Aplicada à Patologia - Science Health- SP (2011 -2014)
Especializaçao em Nutrição Ortomolecular e Nutrigenômica – FAPES – SP (2012)
Especialização Fitoterapia Integrativa - Courses 4U – SP (2015)
Sócia Proprietária da Clínica REVIVA NUTRIÇAO – Fortaleza – CE 
Proprietária Reviva Sabor & Saúde – Refeições Saudáveis Congeladas 
Dieta/ 
Glicogênio 
ACIDOS GRAXOS
Alimentação / Tecido 
Adiposo 
Beta oxidação 
2 ATP
38 ATP
AMINOÁCIDOS 
TGO/ AST
TGP/ ALT
DESDE O TEMPO DE HIPOCRATES, A DIETA CETOGÊNICA FOI 
DESIGNADA PARA MIMETIZAR O JEJUM 
The Neuropharmacology of the Ketogenic Diet, Pediatr Neurol. 2007
DIETA CETOGENICA 
• PROMOVE MUDANCAS NEUROQUIMICAS
TIPOS 
• 1. CLÁSSICA ( WILDER, 1921) . LIP 4 : 1 NÃO LIPÍDEOS . 
Pode ter variações de 3:1, 2:1 e 1:1 
• 2. 1950 – INTRODUÇÃO DO TCM (ag capróico, caprílico, cáprico e 
láurico) ,
• MAIS PALATÁVEL – MAIOR CETOSE – AG 10 E 8C GERAM MAIS 
CETONAS . Mais facilmente absorvidos e transportados ao fígado
Ketogenic Diets: From Cancer to Mitochondrial Diseases and Beyond. Jan 2016
• 3. DIETA ATKINS MODIFICADA – MENOS RESTRITIVA E MAIS 
PALATAVEL, NÃO RESTRINGE PROTEINAS E CALORIAS
• 4. TRATAMENTO DE BAIXO ÍNDICE GLICÊMICO – PERMITE CONSUMO 
MODERADO DE ALIMENTOS DE IG ATÉ 50. MESMO QUE HAJA POUCO 
OU NENHUMA CETOSE, ELA EVITA VARIAÇÕES GLICEMICAS 
Ketogenic Diets: From Cancer to Mitochondrial Diseases and Beyond. Jan 2016
J Lipid Res. 2014 Nov; 55(11): 2211–2228.
Ketogenic diets, mitochondria, and neurological diseases
TCM X TCL
Albumina 
AGCL ALBUMINA
COA - B5
CARNITINA – LISINA, 
Fe, C, folato, B12
Ketogenic diets: from cancer to mitochondrial diseases and beyond
European Journal of Clinical Investigation
Volume 46, Issue 3, pages 285-298, 15 FEB 2016 DOI: 10.1111/eci.12591
http://onlinelibrary.wiley.com/doi/10.1111/eci.12591/full#eci12591-fig-0001
AGCM
Am J Physiol Heart Circ Physiol. 2013 Apr 15; 304(8):
Ketone body metabolism and cardiovascular disease
Am J Physiol Heart Circ Physiol. 2013 Apr 15; 304(8):
Ketone body metabolism and cardiovascular disease
Am J Physiol Heart Circ Physiol. 2013 Apr 15; 304(8):
Ketone body metabolism and cardiovascular disease
APLICAÇÕES DA DIETA 
CETOGÊNICA
1. DIETA CETOGÊNICA E 
CÂNCER 
O EFEITO WARBURG 
The last decade has witnessed a renaissance of 
Otto Warburg’s fundamental hypothesis, which he 
put forward more than 80 years ago, that 
mitochondrial malfunction and subsequent 
stimulation of cellular glucose utilization lead to the 
development of cancer.
The Warburg effect and mitochondrial stability in cancer cells
Molecular Aspects of Medicine
Volume 31, Issue 1, February 2010, Pages 60–74
Ketogenic diets: from cancer to mitochondrial diseases and beyond
European Journal of Clinical Investigation
Volume 46, Issue 3, pages 285-298, 15 FEB 2016 DOI: 10.1111/eci.12591
http://onlinelibrary.wiley.com/doi/10.1111/eci.12591/full#eci12591-fig-0002
• Cancer Res. 2005 Jan 15;65(2):613-21.
• Inhibition of glycolysis in cancer cells: a novel strategy to overcome 
drug resistance associated with mitochondrial respiratory defect and 
hypoxia
INFLEXIBILIDADE METABÓLICA
Int. J. Mol. Sci. 2015, 16(4), 7015-7026; Identification of an AMPK 
Phosphorylation Site in Drosophila TSC2 (gigas) that Regulate Cell Growth
• CELULAS CANCERÍGENAS SÃO ALTAMENTE DEPENDENTES DE 
DISPONIBILIDADE DE GLICOSE PARA CRESCIMENTO, PROLIFERAÇÃO, 
PRODUÇÃO DE ENERGIA E TRANSFORMAÇÃO 
• EM PACIENTES COM CA, HIPERGLICEMIA ESTÁ ASSOCIADA A UM 
PROGNÓSTICO RUIM 
Ketogenic Diets: From Cancer to Mitochondrial Diseases and Beyond. Jan 2016
DIETA CETOGENICA E TERAPIA ANTICANCER 
• FENÓTIPO PROLIFERATIVO TAMBÉM OCORRE VIA HIPERATIVAÇÃO DA 
VIA INSULINA / IGF-1 / P13K / AKT / mTOR, TANTO POR MUTAÇÕES 
NOS GENES QUE CODIFICAM ESTAS PROTEÍNAS QUANTO A 
HIPERGLICEMIA E HIPERINSULINEMIA CRÔNICOS ( estilo de vida). 
Ketogenic Diets: From Cancer to Mitochondrial Diseases and Beyond. Jan 2016
• CELULAS NEOPLÁSICAS – POSSUEM ANOMALIDADE METABÓLICA / INFLEXIBILIDADE
• GLICÓLISE ANAERÓBIA É A MAIOR VIA DE PRODUÇÃO DE ENERGIA GERANDO 
LACTATO 
• LACTATO ACIDIFICA O MEIO, PROMOVENDO AUMENTO DA INVASÃO E PROGRESSÃO 
TUMORAIS 
• BAIXA FUNÇÃO MITOCONDRIAL, BAIXA UTILIZAÇÃO DE OXIGENIO 
• GLICOSE – PIRUVATO – LACTATO – GERAÇÃO DE ENERGIA + ESQUELETOS DE 
CARBONO PARA BIOSSÍNTESE. 
• BAIXA FUNÇÃO MITOCONDRIAL – MUTAÇÃO NAS ENZIMAS DA C.T.E
• BAIXA CAPACIDADE DE NEUTRALIZAR ROS Ketogenic Diets: From Cancer to Mitochondrial 
Diseases and Beyond. Jan 2016
DIETA CETOGENICA E TERAPIA ANTICANCER
• 1. DIETAS CETOGENICAS PODEM SER BEM TOLERADAS POR 
PROMOVER GANHO DE PESO OU, AO MENOS, MANUTENÇÃO DO 
PESO,EVITANDO A CAQUEXIA E O HIPERCATABOLISMO
Ketogenic Diets: From Cancer to 
Mitochondrial Diseases and Beyond. 
Jan 2016
Crosstalk from Non-Cancerous Mitochondria Can Inhibit Tumor Properties of Metastatic Cells by 
Suppressing Oncogenic Pathways, 2013
Crosstalk from Non-Cancerous Mitochondria Can Inhibit Tumor Properties of Metastatic Cells by 
Suppressing Oncogenic Pathways, 2013
Crosstalk from Non-Cancerous Mitochondria Can Inhibit Tumor Properties of Metastatic Cells by 
Suppressing Oncogenic Pathways, 2013
• CÉLULAS NORMAIS : ADAPTAM-SE E METABOLIZAM CORPOS 
CETONICOS E ÁCIDOS GRAXOS ( MITOCONDRIAS)
• CÉLULAS TUMORAIS: INFLEXIBILIDADE METABÓLICA E 
INSTABILIDADE GENÔMICA
Ketogenic Diets: From Cancer to Mitochondrial Diseases and Beyond. Jan 
2016
Components Standard Diet (SD) KetoCal
®
Diet (KC)
Carbohydrate 65 3.3
Fat 6.9 80
Protein 28.1 16.7
Energy (Kcal/gr) 4.4 7.2
Table 1
Composition (%) of the Standard Diet and the KetoCal
®
Ketogenic diet
a
a
Values obtained from normalizing energy content (see Methods)
The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. 
Nutrition & metabolism 2007
The restricted KetoCal® diet reduced plasma glucose levels while
elevating plasma ketone body (β-hydroxybutyrate) levels.
Moreover, gene expression for the mitochondrial enzymes, β-
hydroxybutyrate dehydrogenase and succinyl-CoA: 3-ketoacid CoA
transferase, was lower in the tumors than in the contralateral normal 
brain suggesting that these brain tumors have reduced ability to
metabolize ketone bodies for energy.
The calorically restricted ketogenic diet, an effective alternative 
therapy for malignant brain cancer. Nutrition & metabolism 
2007
The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutrition & metabolism 2007
The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutrition & metabolism 2007
Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-D-glucose and the restricted ketogenic diet
SINERGIA DROGAS - DIETA
Estudo de caso: Quimioterapia + DC
ANTES 
DEPOIS 
Metabolic management of glioblastoma multiforme using standard
therapy together with arestricted ketogenic diet: Case Report.
Nutr Metab (Lond). 2010 Apr 22;7:33
Carcinogenesis vol.35 no.3 pp.515–527, 2014 Cancer as a 
metabolic disease: implications for novel therapeutics
PLoS One. 2013 Jun 5;8(6):e65522
The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer.
2. MELHORADE MEMÓRIA 
3. DIETA CETOGÊNICA E EPILEPSIA / 
REDUÇÃO DE CONVULSÕES 
TEORIAS ANTICONVULSIVANTES 
• GLUTAMATO – EXCITATÓRIO
• GABA – INIBITÓRIO 
J Lipid Res. 2014 Nov; 55(11): 2211–2228.
Ketogenic diets, mitochondria, and neurological diseases
GLUTAMATO
GABA
GAD
ASPARTATO
+ OXALACETATO
TEORIAS DA AÇÃO DOS CORPOS CETÔNICOS 
GLUTAMATO GABA 
1. REDUÇÃO DO GLUTAMATO NA FENDA SINÁPTICA ( BHB COMPETE COM Cl 
E INIBE A LIBERAÇÃO DE GLUTAMATO PELO TRANSPORTADOR PRÉ 
SINÁPTICO)
2. AUMENTO DE GABA ( MENOR USO DE GLUTAMATO PARA SINTETIZAR 
ASPARTATO)
3.AUMENTO DA EXPRESSÃO GÊNICA DE GAD (65, 67)
4.AUMENTO DA RECAPTAÇÃO DE GLUTAMATO NA FENDA SINÁPTICA PELOS 
ASTRÓCITOS 
5. ABERTURA DOS CANAIS DE K ATP, REDUZINDO A EXCITABILIDADE 
NEURONAL ( BAD) 
GAD
J Lipid Res. 2014 Nov; 55(11): 2211–2228.
Ketogenic diets, mitochondria, and neurological diseases
ALTERAÇÃO NA NEUROTRANSMISSÃO
The Neuropharmacology of the Ketogenic Diet, Pediatr Neurol. 2007
J Neurochem. 2012 Apr; 121(1): 28–35.
Ketogenic diets: from cancer to mitochondrial diseases and beyond
European Journal of Clinical Investigation
Volume 46, Issue 3, pages 285-298, 15 FEB 2016 DOI: 10.1111/eci.12591
http://onlinelibrary.wiley.com/doi/10.1111/eci.12591/full#eci12591-fig-0004
Trends Neurosci. 2013 Jan;36(1):32-40. doi: The ketogenic diet: 
metabolic influences on brain excitability and epilepsy.
Anticonvulsant Mechanisms of the Ketogenic Diet
Epilepsia
Volume 48, Issue 1, pages 43-58, 4 JAN 2007 DOI: 10.1111/j.1528-1167.2007.00915.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2007.00915.x/full#f2
Curr Opin Pharmacol. 2006 Feb;6(1):44-52. Epub 2005 Dec 20.
Unravelling the brain targets of gamma-hydroxybutyric acid.
AÇÃO DEPENDENTE DE QUANTIDADE
CUIDADO COM OVERDOSES 
J Lipid Res. 2014 Nov; 55(11): 2211–2228.
Ketogenic diets, mitochondria, and neurological diseases
Anticonvulsant Mechanisms of the Ketogenic Diet
Epilepsia
Volume 48, Issue 1, pages 43-58, 4 JAN 2007 DOI: 10.1111/j.1528-1167.2007.00915.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2007.00915.x/full#f4
1. All supplements listed should be provided as carbohydrate-free preparations whenever possible.
Universal recommendations
Multivitamin with minerals (and trace minerals)
Calcium with vitamin D
Optional extra supplementation
Oral citrates (Polycitra K)
Laxatives: Miralax, mineral oil, glycerin suppository
Additional selenium, magnesium, zinc, phosphorus, vitamin D
Carnitine (Carnitor)
MCT oil or coconut oil (source of MCT)
Salt (sodium to add to modular formulas if used for greater than age 1 year)
Table 4. Supplementation recommended for children receiving the KD
Optimal clinical management of children receiving the ketogenic diet: Recommendations of the 
International Ketogenic Diet Study Group
CUIDADOS !!!! 
Ketogenic diets: from cancer to mitochondrial diseases and beyond
European Journal of Clinical Investigation
Volume 46, Issue 3, pages 285-298, 15 FEB 2016 DOI: 10.1111/eci.12591
http://onlinelibrary.wiley.com/doi/10.1111/eci.12591/full#eci12591-fig-0005
The monocarboxylate transporter family—Role and regulation
IUBMB Life
Volume 64, Issue 2, pages 109-119, 9 DEC 2011 DOI: 10.1002/iub.572
http://onlinelibrary.wiley.com/doi/10.1002/iub.572/full#fig1
• POLIMORFIMOS NAS ENZIMAS QUE SINTETIZAM CORPOS CETONICOS
• POLIMORFISMOS NAS ENZIMAS DE BETA OXIDAÇÃO 
• POLIMORFISMOS NAS ENZIMAS QUE CONVERTEM CORPOS CETONICOS 
EM ACETIL COA
4. MELHORA DE 
MITOCONDRIOPATIAS COM 
DIETA CETOGENICA 
Carcinogenesis vol.35 no.3 pp.515–527, 2014 
Cancer as a metabolic disease: implications for novel therapeutics
C T E fica nas cristas mitocondriais
DEFICIENTE 
Carcinogenesis vol.35 no.3 pp.515–527, 2014 
Cancer as a metabolic disease: implications for novel therapeutics
J Lipid Res. 2014 Nov; 55(11): 2211–2228.
Ketogenic diets, mitochondria, and neurological diseases
•Ketogenic diet slows down mitochondrial myopathy 
progression in mice
http://hmg.oxfordjournals.org/content/19/10/1974.long
Epilepsy Res. 2012 Jul;100(3):295-303. doi: Modulation of oxidative stress and 
mitochondrial function by the ketogenic diet.
Ketogenic diets: from cancer to mitochondrial diseases and beyond
European Journal of Clinical Investigation
Volume 46, Issue 3, pages 285-298, 15 FEB 2016 DOI: 10.1111/eci.12591
http://onlinelibrary.wiley.com/doi/10.1111/eci.12591/full#eci12591-fig-0003
The demonstration that ketone bodies can distinguish between 
normal and respiratorily compromised cells points to the 
potential use of a ketogenic diet to treat patients with 
heteroplasmic mtDNA disorders. Ann Neurol 2004
Ketogenic treatment reduces deleted mitochondrial DNAs in 
cultured human cells
TERAPIAS PARA 
MELHORA DE FUNÇÃO MITOCONDRIAL 
Medication Dosage (pediatric) Dosage (adult) Monitoring Adverse effects Comments
CoQ10 as 
ubiquinol
(preferred)
2–8 mg/kgpo daily divided 
in two doses
50–600 mg po daily May obtain pretherapy 
level and monitor CoQ1 
level in leukocytes or 
plasma
Wakefulness, 
sleep 
disruption; may 
reduce warfarin 
concentration
Solubilized bioavailable formulation 
preferred. Absorption may be 
improved when taken with meals
CoQI0as 
ubiquinone
10–30 mg/kg po daily 
divided in 2 doses
300–2400 mg po
daily divided 2–3 
times a day
May obtain pretherapy 
level and monitor 
CoQ10evel in 
leukocytes or plasma
Wakefulness, 
sleep 
disruption; may 
reduce warfarin 
concentration
Less potent than ubiquinol and less 
well absorbed; solubilized bio 
available formulation preferred. 
Absorption may be improved when 
taken with meals
Riboflavin
(B2)
50–400 mg po daily 50–400 mg po daily Not usually done High doses may cause anorexia 
and nausea
Changes urine color and smell; 
effects may be minimized by giving 
at bedtime
L-Creatine 0.1 g/kg po daily; maximum 10 g/d
5 g po daily, given 
1–2 times per day
Renal function GI upset Primarily used in myopathy 
patients, though evidence exists for 
routine use in all mitochondrial 
disease patients; converted to 
creatinine in the gut
Curr Treat Options Neurol. 2013 Jan 31.A Modern Approach to the Treatment of Mitochondrial Disease
Mitochondrial medications and supplements
*
Medication Dosage (pediatric) Dosage (adult) Monitoring Adverse effects Comments
L-Arginine Acute 
stroke: 500 
mg/kg IV per 
day for 1 –3 
days;
Maintenance: 1
50–300 
mg/kgpo or IV 
daily divided 2–
3 times a day
Acute stroke: 500 
mg/kg IV per day for 
1–3 days;
Maintenance: 150–
300 mg/kg po or IV 
daily divided 2–3 
times a day
Plasma arginine in 
amino acid profile
Hypotension (with IV loading), 
hyponatremia, headache, 
nausea, diarrhea. Myelinolysis
reported with high dose in 
single case
Used with metabolic 
strokes, especially in 
MELAS or in those with 
low-normal plasma 
arginine; citrulline is used 
in urea cycle defects as an 
alternative to arginine
L-Carnitine 10–100 mg/kg 
per day IV or po
divided 3 times 
a day
100–1000 mg per 
dose, given IV or po
2–3 times a day
Pretherapy free 
and total plasma 
carnitine levels
GI upset, fishy odor (due to 
bacterial degradation; may be 
improved with antibiotic). 
Reports of cardiac rhythm 
disturbances in long-chain fatty 
acid oxidation defects
FDA-approved for 
metabolic diseases; 
available as prescription 
generic and brand. Only 
10%–20% absorbed. 
Acetyl-carnitine is an 
alternative
B50or B100 
(B vitamin
complexes)
1 tab po given 
1–2 times a day
1 tab po given 1–2 
times a day
Not usually done Toxic neuropathy may occur 
with chronicuse of larger doses 
than recommended
Poorly palatable
Curr Treat Options Neurol. 2013 Jan 31.A Modern Approach to the Treatment of Mitochondrial Disease
Medication Dosage (pediatric) Dosage (adult) Monitoring Adverse effects Comments
Vitamin E 1–2 IU/kg po daily 100–200 IU po daily Not usually 
done
Possible adverse 
cardiac risks at 
doses > 400 IU/d
Absorption may be improved when taken with 
meals
Vitamin C 5 mg/kg po daily 50–200 mg po daily Not usually 
done
Increases iron 
absorption; high 
doses may cause 
renal 
insufficiency 
(single case 
report)
Easily absorbed water-soluble vitamin
Alpha-lipoic acid 50–200 mg/d 50–200 mg/d Not usually 
done
None known None
Folinic acid as leucovorin, 
containing both D and L 
isomers
0.5–1.5 mg/kg po daily, 
given 1–2 times per day 
(higher doses are used in 
folinic acid-responsive 
epilepsy)
2.5–25 mg po daily 
given 1–2 times per 
day
May assess 
spinal fluid 
folate and 
plasma/urin
e pipecolic
acid
Rash and
pruritus
Cerebral folate can also be replenished with 
Isovorin (L-isomer, active form) or 5-methyl-
tetrahydrofolate (Deplin), the natural transport 
form of folate across the blood-brain barrier. 
Consider for patients with symptom worsening 
or with proven cerebral folate deficiency
Curr Treat Options Neurol. 2013 Jan 31.A Modern Approach to the Treatment of Mitochondrial Disease
Obrigada !! 
www.revivanutricao.com.br
@danylodetti
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Danielle Lodetti