introduction to nutritional ketosis and clinical … · medit paleo . ornish diet standard american...
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Jeff S. Volek, Ph.D., R.D. Professor
Department of Human Sciences | Kinesiology Program
Columbus, OH 43210
INTRODUCTION TO NUTRITIONAL KETOSIS
AND CLINICAL APPLICATIONS
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1. Review the concept of ketogenesis, nutritional ketosis, and keto-adaptation
2. Discuss potential avenues for ketogenic diets in clinical practice
3. Learn about the potential for ketogenic approaches in exercise and physical performance
LEARNING OBJECTIVES
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Principle of Human
Carbohydrate Intolerance
Stems from >2 million years of evolution when most
humans had limited exposure to sugars/starches
Now that carb-based foods are ubiquitous, most of us
show signs of metabolic dysfunction
For a few, a modest ↓ carbs suffices to prevent overt
illness
But in many, metabolic correction requires greater
carb restriction that results in KETO-ADAPTATION
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Ketogenesis
Displace glucose TG
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Starvation Fed
0%
20%
40%
100%
80%
60%
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Ketone Terminology
Ketosis Hepatically-derived energy containing substances derived from
fatty acids that provide fuel to nearly every cell in the body
Nutritional
Ketosis
Process of accelerating production of ketones through restriction of
carbohydrate
Keto-
Acidosis A dangerous side effect of Type I diabetes
Keto-
Adaptation A health-promoting process of shifting to using predominately fat
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Blood Ketones (millimolar)
2.0 2.5 3.00.5 1.0 1.50 5.0 10+
Keto-
acidosis
Nutritional
Ketosis
Begins
Op
tim
al F
uel
Flo
w f
or
Bra
in a
nd
Mu
scle
s
Optimal
Ketone
Zone
Starvation
Ketosis
Post-Exercise
Ketosis
Keto-Adaptation happens
when you are in this zone over
consecutive weeks
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A metabolic blue print hard-wired into our
genetic code that sustains optimum fuel
flow to all organs (including the brain)
through use of pathways humans have
acquired >2 million years as
hunters/gatherers/herders.
Keto-Adaptation
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Enhanced fat oxidation facilitates
weight loss & broad spectrum
health benefits
Ketogenic
Diet
High-Carb
Diet
↑2x
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Note: Carbs (%) = Percent of dietary carbs relative to daily energy expenditure Protein (%) = Percent of dietary protein relative to daily energy expenditure Protein (g/kg RW) = Grams of dietary protein relative to reference body weight
Generally accepted upper
threshold of ‘Low Carb”
10 20 30 40 Protein (%)
Carbs (%)
10
20
30
40
50
60
Orn
Nutritional Ketosis Space
Protein (g/kg RW) 0.8 1.6 2.4 3.2
WFKD
SAD
Medit
Paleo
WFKD = Well formulated ketogenic diet
Ornish diet
Standard American Diet
Paleolithic diet
Mediterranean diet
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16
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1. Review the concept of ketogenesis, nutritional ketosis, and keto-adaptation
2. Discuss potential avenues for ketogenic diets in clinical practice
3. Learn about the potential for ketogenic approaches in exercise and physical performance
LEARNING OBJECTIVES
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The scientific consensus is such that diabetes
is a chronic disease that is irreversible.
1 in 4: Americans >65 yr w/ diabetes
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“…the prevalence of prediabetes
was 37% to 38% in the overall
population, and consequently
49% to 52% of the population
was estimated to have either
diabetes or prediabetes.”
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????
Metabolic
Syndrome Diabetes
SFA
Intake Plasma LDL
Heart
Disease
Carb
Intake
↓ SFA
Intake
Suppression of fat
oxidation/ketone metabolism Poor
Health
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CARBOHYDRATE
FAT
PROTEIN
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Ubiquitous amounts of carbs is the predominant environmental
pressure pushing us toward the insulin resistant phenotype;
now over half the population.
Keto-
Adapted
Phenotype
Insulin
Resistant
Phenotype T2D
Disease Robust
Health
Carbs Carbs
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-60
-50
-40
-30
-20
-10
0
10
Perc
en
t C
han
ge
Ketogenic Low Fat
Body
Mass
Ab
Fat TG
TG
AUC Glu
Small
LDL
ApoB/
ApoA-1
ApoB
TG/
HDL
HDL
Insulin HOMA Leptin
Total
SFA
Results after 3 months in 40 subjects with metabolic syndrome randomized to
either a ketogenic or low fat diet (Forsythe et al. 2008).
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JMIR Diabetes. 2017;2(1):e5, published March 7, 2017.
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N = 378
262 with type 2 diabetes
(T2D)
116 with pre-diabetes
Location
Greater Lafayette, Indiana
T2D Mean
Characteristics
Starting age: 54 yrs
Starting BMI: 41 kg/m2
Starting weight: 257 lbs
(117 kg)
67% female
Patients
CLINICAL TRIAL
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For the N=262 T2DM participants at 10 wk. Intent to treat analysis & completers analysis.
Average reduction in HbA1c (from 7.6 to 6.6) 1.0
Eliminated or reduced insulin 87%
Reduced HbA1c < 6.5* 56%
Of completers experienced clinically significant weight loss of >5% 75%
Completed Virta protocol 91%
Average reduction in triglycerides 20%
* 48% Reduced A1c < 6.5 and eliminated all diabetes medications or used
metformin only
Key Results
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Cancer
Type-2 Diabetes
Pediatric Obesity
Fatty Liver
Parkinson Disease
Alzheimer’s Disease
Type-1 Diabetes
Autism
Polycystic Ovary Syndrome (PCOS)
Epilepsy
Adult Obesity
Hypertension/Vascular Function
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Less stimulation of
insulin, its receptor,
and signaling
pathways
Less generation of
reactive oxygen
species (ROS)
Endogenous
inhibitor of HDACs
Increased
antioxidant defense
Greater efficiency in
providing cellular
energy
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1. Review the concept of ketogenesis, nutritional ketosis, and keto-adaptation
2. Discuss potential avenues for ketogenic diets in clinical practice
3. Learn about the potential for ketogenic approaches in exercise and physical performance
LEARNING OBJECTIVES
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Tim Olsen Wins 2012 Western States 100
Zach Bitter
American 100 Mile Track
Record Holder (11:47:21)
Mike Morton
American 24-hr Distance
Running Record (172 Miles)
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Froome in 2015 and 2009. When he turned pro in 2007 he weighed 167 pounds. In his 3
Tour de France victories — 2013, 2015, & 2016 — he has weighed as little as 145 lbs.
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“I switched to a low-carbohydrate/high-fat lifestyle
in 202 and was able to win back to back 100 mile
races one week apart including setting a course
record. The diet has transformed my health and
performance.“ -MIKE MORTON, MASTER SERGEANT US ARMY
SPECIAL OPERATIONS COMMAND, AMERICAN
24-HR DISTANCE RUNNING RECORD (172
MILES)
All
Blacks
Columbu
s Crew
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Fat Adapted Substrate Oxidation in Trained Elite Runners
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Take a deeper look into the keto-adapted athlete
Figure 2. Habitual diets.
HCD
Protein 15%Fat
25%
Carb 60%
Fat 70%
Protein 20%
Carb 10-12%
LCD
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0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
0 1 2 3
HCD LCD
Pea
k Fa
t O
xid
atio
n (
g/m
in)
X = 0.67
X = 1.54
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Minutes During Exercise
HCD LCD
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 60 120 150 180
Fat
Carbohydrate
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 60 120 150 180
Fat
Carbohydrate
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0
20
40
60
80
100
120
140
160
180
Baseline IP IP-120
HC LC
Mu
scle
Gly
coge
n(m
mo
l/kg
w.w
.) A
*
*†
0
50
100
150
200
250
BL IP IP-120 BL IP IP-120
Mu
scle
Gly
coge
n (
mm
ol/
kg w
.w.)
HC LC
B
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SUMMARY
1. Ketosis & keto-adaption are natural, if not
preferred, metabolic states for humans
2. Sustained restriction of carbs to achieve
nutritional ketosis results in a shift from an
insulin-resistant (unhealthy) to a keto-
adapted (healthy) phenotype
3. Because it gets at the root cause, keto-
adaptation has broad applications for
managing disease & promoting health