Jeff S. Volek, Ph.D., R.D. Professor

Department of Human Sciences | Kinesiology Program

Columbus, OH 43210

volek.1@osu.edu

INTRODUCTION TO NUTRITIONAL KETOSIS

AND CLINICAL APPLICATIONS

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

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

Ketogenesis

Displace glucose TG

Starvation Fed

0%

20%

40%

100%

80%

60%

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

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

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

Enhanced fat oxidation facilitates

weight loss & broad spectrum

health benefits

Ketogenic

Diet

High-Carb

Diet

↑2x

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

16

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

The scientific consensus is such that diabetes

is a chronic disease that is irreversible.

1 in 4: Americans >65 yr w/ diabetes

“…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.”

????

Metabolic

Syndrome Diabetes

SFA

Intake Plasma LDL

Heart

Disease

Carb

Intake

↓ SFA

Intake

Suppression of fat

oxidation/ketone metabolism Poor

Health

CARBOHYDRATE

FAT

PROTEIN

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

-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).

JMIR Diabetes. 2017;2(1):e5, published March 7, 2017.

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

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

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

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

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

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)

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.

“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

Fat Adapted Substrate Oxidation in Trained Elite Runners

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

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

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

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

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