Escolar Documentos
Profissional Documentos
Cultura Documentos
Solutions
Thomas N. Seyfried
Boston College
Provocative Question
Is cancer a nuclear
genetic disease or a
mitochondrial metabolic
disease?
Current Dogma:
Cancer is a Genetic Disease
Seyfried, Cancer as a Metabolic Disease, 2012 John Wiley Press; Seyfried et al., 2014, Carcinogenesis
If somatic mutations are not the origin of
cancer, then how do cancer cells arise?
Otto Warburg (Science, 24 February,1956)
Glucose Glutamine
Mitochondrial Morphology
cristolysis
Oncogenic Paradox
ROS
Seyfried, Cancer as a Metabolic Disease, 2012 John Wiley Press; Seyfried et al., 2014, Carcinogenesis
If most cancers express the Warburg
effect as the result of impaired
respiration, then what therapies might be
effective for managing tumors?
One strategy is to reduce levels
of fermentable fuels while elevating
levels non-fermentable fuels
Calorie Restriction (CR): A Metabolic Cancer
Intervention
AL CR
40% CR initiated 3 days post-inoculation
Plasma glucose predicts ketone body levels and
CT-2A tumor growth
3 150
2 100
1.5
1 50
0.5
0 0
0 5 10 15 20 0 5 10 15 20
2. Anti-inflammatory
Mulrooney et al., PLOS One, 2011
3. Pro-apoptotic
Mukherjee et al., Brit. J. Cancer 2002
Research Question
W e t w e ig h t (m g )
W e t w e ig h t (m g )
60
100
80
50 *
40
60
* 30
40
20 *
20 10
0 0
SD-UR KD-UR
1 KD-R SD-UR KD-UR
1 KD-R
mM
mM
8
* 1
6 * 0.8
4 * * 0.6
0.4
2 0.2
0 0
SD-UR KD-UR
1 KD-R SD-UR KD-UR
1 KD-R
n = 11-14 mice/group
Zhou et al., Nut & Met, 2007
* P < 0.01
Metabolic management of cancer following
changes in plasma glucose & ketones
Clinical Question
The Metabolic
Zone
Influence of a natural ketogenic diet on blood glucose and
ketone levels in an adult patient with a diffuse,
infiltrative brainstem glioma
ç
7 7
6 6
5 5
Ketones (mM)
Glucose (mM)
4 4
3 3
2 2
Data is
1 represented 1
as mean ±
95% CI
0 0
Apr-14
May-14
Jun-12
Jan-13
Jun-13
Jan-14
Mar-13
Jun-14
Aug-12
Mar-14
Jul-14
Jul-12
Sep-12
Oct-12
Apr-13
Nov-12
Dec-12
Feb-13
May-13
Aug-13
Jul-13
Sep-13
Oct-13
Nov-13
Dec-13
Feb-14
Month-Year
Glucose (mmol)/Ketone (mmol) = GKI
0
1
2
3
4
5
6
7
8
Jun-12
Jul-12
Aug-12
Sep-12
Oct-12
Nov-12
Dec-12
Jan-13
Feb-13
Mar-13
Apr-13
May-13
Jun-13
Jul-13
Aug-13
Month-Year
Sep-13
Oct-13
Nov-13
Dec-13
Jan-14
Feb-14
Mar-14
Apr-14
May-14
Jun-14
Jul-14
Influence of a natural ketogenic diet alone on the G/K Index
in an adult patient with a diffuse, infiltrative brainstem glioma
The Press-Pulse Paradigm: A Novel
Therapeutic Strategy for the Metabolic
Management of Cancer
SD