Full Terms & Conditions of access and use can be found at
https://www.tandfonline.com/action/journalInformation?journalCode=tejs20
European Journal of Sport Science
ISSN: 1746-1391 (Print) 1536-7290 (Online) Journal homepage: https://www.tandfonline.com/loi/tejs20
Rethinking fat as a fuel for endurance exercise
Jeff S. Volek, Timothy Noakes & Stephen D. Phinney
To cite this article: Jeff S. Volek, Timothy Noakes & Stephen D. Phinney (2015) Rethinking
fat as a fuel for endurance exercise, European Journal of Sport Science, 15:1, 13-20, DOI:
10.1080/17461391.2014.959564
To link to this article: https://doi.org/10.1080/17461391.2014.959564
Published online: 02 Oct 2014.
Submit your article to this journal
Article views: 20742
View Crossmark data
Citing articles: 58 View citing articles
ORIGINAL ARTICLE
Rethinking fat as a fuel for endurance exercise
JEFF S. VOLEK1
, TIMOTHY NOAKES2
, & STEPHEN D. PHINNEY3
1
Kinesiology Program, Department of Human Sciences, The Ohio State University, Columbus, OH, USA, 2
Discovery Health
Professor of Exercise and Sports Science, Department of Human Biology, University of Cape Town and Sports Science Institute
of South Africa, Newlands, South Africa, 3
School of Medicine (Emeritus), University of California Davis, Davis, CA, USA
Abstract
A key element contributing to deteriorating exercise capacity during physically demanding sport appears to be reduced
carbohydrate availability coupled with an inability to effectively utilize alternative lipid fuel sources. Paradoxically, cognitive
and physical decline associated with glycogen depletion occurs in the presence of an over-abundance of fuel stored as body
fat that the athlete is apparently unable to access effectively. Current fuelling tactics that emphasize high-carbohydrate
intakes before and during exercise inhibit fat utilization. The most efficient approach to accelerate the body’s ability to
oxidize fat is to lower dietary carbohydrate intake to a level that results in nutritional ketosis (i.e., circulating ketone levels
>0.5 mmol/L) while increasing fat intake for a period of several weeks. The coordinated set of metabolic adaptations that
ensures proper interorgan fuel supply in the face of low-carbohydrate availability is referred to as keto-adaptation. Beyond
simply providing a stable source of fuel for the brain, the major circulating ketone body, beta-hydroxybutyrate, has recently
been shown to act as a signalling molecule capable of altering gene expression, eliciting complementary effects of ketoadaptation
that could extend human physical and mental performance beyond current expectation. In this paper, we review
these new findings and propose that the shift to fatty acids and ketones as primary fuels when dietary carbohydrate is
restricted could be of benefit for some athletes.
Keywords: Metabolism, nutrition, performance
Historical perspective
Over evolutionary time, fat has played a major if not
dominant role in supplying the human body with fuel.
In times of plenty, the majority of the dietary energy of
hunter/gatherers, primary hunters and nomadic herders
came from fat. During lean times, the body energy
reserves we rely upon to tide us over consist almost
exclusively of fat. It would thus seem reasonable to
expect that in the 2 million plus years of evolution since
our ancestors parted company from the great apes, our
greater exposure to dietary fat would have equipped
us to effectively use it as our primary functional fuel.
As shown in Table I, a slender human – even as low as
7–14% body fat – still has in excess of 30,000 kcal of
adipose tissue reserves, an order of magnitude greater
than maximum carbohydrate stores in the body.
With the advent of agriculture, humans acquired
the ability to produce and store large reserves of
carbohydrate, facilitating continuous consumption
throughout the year. This has increasingly shifted
our daily caloric intake towards a majority of energy
coming from starches and sugars. For the earliest
agrarian societies in Asia and the Fertile Crescent,
this process began perhaps 10,000 years ago. This
process of exposure and acclimation to dietary carbohydrates
has been even shorter for peoples living
in temperate and colder regions. Thus, the proportion
of our evolutionary history available for adaptation
to a high-carbohydrate diet has been at most
one-half of 1% of the last 2 million years, and for
many humans with recent aboriginal hunting ancestors,
far less (Orr & Gilks, 1931).
Beginning a century ago, the modern science of
metabolism has paid a great deal of attention to
human fuel use during starvation, rest and exercise.
In particular, a major goal has been to determine the
Correspondence: J. S. Volek, Kinesiology Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210,
USA. E-mail: jvolek7@gmail.com
European Journal of Sport Science, 2015
Vol. 15, No. 1, 13–20, http://dx.doi.org/10.1080/17461391.2014.959564
© 2014 European College of Sport Science
ideal human diet before and during exercise to
optimize performance during both physical labour
and sport. In 1939, Christensen and Hansen (1939)
reported that athletes prescribed a high-carbohydrate
diet for seven days performed better during submaximal
exercise than when they ate a high-fat diet for
a week. Subsequently, Bergström et al. (Bergström,
Hermansen, Hultman, & Saltin, 1967; Bergström
& Hultman, 1966; Bergström & Hultman 1967)
demonstrated a positive association between preexercise
muscle glycogen concentrations and subsequent
submaximal exercise capacity. Furthermore,
they and others observed that a brief period of
carbohydrate restriction (and/or exercise-induced
glycogen depletion) followed by a few days of a highcarbohydrate
diet (aka, carbohydrate loading) maximized
pre-exercise muscle glycogen concentrations
and endurance capacity.
As a result of this work, the idea has gained credence
that only a high-carbohydrate diet can optimize
human exercise capacity (Noakes, 2002). Despite the
important observation that none of these studies was
placebo-controlled, the only placebo-controlled study
of carbohydrate loading failed to show any beneficial
effect (Burke et al., 2000). A recent meta-analysis has
concluded that although high-carbohydrate diets
appear to improve performance over high-fat diets,
this may not be true in more well-trained individ‐
uals; therefore, “a conclusive endorsement of a highcarbohydrate
diet based on the literature is difficult to
make” (Erlenbusch, Haub, Munoz, MacConnie, &
Stillwell, 2005).
In addition to this published research experience,
those promoting the necessity of a high-carbohydrate
diet for optimum sports performance seem to have
missed the numerous empiric observations of Arctic
explorers who performed prodigious feats of prolonged
exercise (e.g., overland travel on foot, canoe
voyages) in the virtual absence of ingested dietary
carbohydrate. For example, from 1878 to 1880, Lt
Frederick Schwatka travelled 3000 nautical miles
on foot in the company of two Inuit families. This
overland expedition from the west coast of Hudson’s
Bay to the Arctic coast was undertaken to determine
the fate of the Royal Navy’s lost “Franklin Expedition”
last seen in 1845. Schwatka and his aboriginal
guides started this 13-month trek with one month’s
provisions and then “lived off the land” for the
duration. Schwatka observed in his diary (Stackpole,
1965):
When first thrown wholly on the diet of reindeer
meat, it seems inadequate to properly nourish the
system, and there is an apparent weakness and
inability to perform severe, exertive, fatiguing journeys.
But this soon passes away in the course of two
to three weeks.
This and the published observations of other
explorers (Rae’s Arctic Correspondence, 1953; Stefansson,
1921) indicate that well-being and perfect
human function can be maintained for a year or
more without ingesting appreciable dietary carbohydrate.
In fact, Stefansson spent most of the calendar
year of 1928 eating an Inuit diet (85% fat, 15%
protein) under close observation in Bellevue Hospital
in NYC without any impairment or signs of
nutrition deficiency (McClellan & Dubois, 1930).
It is accepted that high-carbohydrate intake can
offer advantages for athletes, but the effects are not
uniform. Equally clear is the reality that many athletes
are experimenting with low-carbohydrate diets
and experiencing a spectrum of self-perceived benefits.
This fact is verified by a growing number of
competitive ultra-endurance athletes who often win
races and in some cases set records after adapting to
a low-carbohydrate diet. This fact is not meant to
serve as proof that a low-carbohydrate diet is equal
or superior to a high-carbohydrate diet, but it does
provide provocative empirical evidence to pursue
critical research into their metabolic, physiological
and performance effects. The purpose of this brief
review is to provide an alternative perspective on the
role of fat for fuel and the role of dietary carbohydrate
restriction as a strategy to enhance performance
and recovery in athletes. Admittedly, there is a
scarcity of research specifically addressing longterm
ketogenic diets in athletes, so we present a
historical perspective of low-carbohydrate diets,
basic scientific knowledge of ketones as metabolic
fuel and regulator of gene transcription, and human
low-carbohydrate diet work that is relevant to
athletes.
Keto-adaptation
This body of historic empiric data suggesting recovery
of exercise capacity after two or more weeks on a
ketogenic diet remained hidden until re-discovered in
the early 1980s. At that time, stimulated by reports
of unimpaired performance from patients on ketogenic
weight-loss diets, Phinney et al. (Phinney, Bistrian,
Evans, Gervino, & Blackburn, 1983; Phinney, Bistrian,
Wolfe, & Blackburn, 1983; Phinney, Horton, Sims,
Hanson, & Danforth, 1980) conducted two studies
demonstrating the process of keto-adaptation. The first
Table I. Body energy reserves by habitus (1000 kcal)
Thin Normal Obese
Carbohydrate 2 2 2
Protein 25 30 35
Fat 30–60 100 200
14 J. S. Volek et al.
of these studies used overweight, untrained subjects on
a weight-loss diet, whereas the second study employed
lean, highly trained athletes fed a eucaloric diet patterned
after that in the original Stefansson Bellevue
study (McClellan & Dubois, 1930).
The endurance capacity and metabolic responses
of the cyclists in this latter study (Phinney, Bistrian,
Evans, et al., 1983) are shown in Table II. In both
studies (Phinney et al., 1980, Phinney, Bistrian,
Evans, et al., 1983), the dietary carbohydrate totalled
less than 10 grams per day, and protein intakes were
about 15% of daily energy expenditure. Blood betahydroxybutyrate
(BOHB) rose to the 1–3 mmol/L
range in the first week, but endurance capacity
lagged (both tested and self-reported) until 4–6
weeks of dietary carbohydrate restriction. By that
time, however, the extent to which both groups had
switched to fat oxidation was shown by changes in the
respiratory exchange ratio (RER) values during exercise.
The untrained subjects posted RER values below
0.7, indicative of both a high proportion of fat use and
net ketogenesis (i.e., ketone production exceeding
ketone oxidation). The cyclists mean submaximal
exercise RER of 0.72 following four weeks of ketoadaptation
(determined after an overnight fast) establishes
that >90% of their fuel was derived from the
oxidation of fat while cycling at an intensity expending
930 kcal/hr.
These astounding whole-body fat oxidation rates
determined by indirect calorimetry are particularly
remarkable in the context of a subsequent study by
Venables, Achten, and Jeukendrup (2005), which to
the best of our knowledge represents the most
rigorous work to document peak rates of fat oxidation.
They developed a protocol to determine peak
fat oxidation rates during a graded exercise test in
300 adults ranging in fitness from the untrained and
obese to highly trained athletes. Their highest
reported value in any single individual was 60 grams
of fat oxidized per hour (1 g/min). In contrast,
among the five keto-adapted bicycle racers reported
by Phinney, Bistrian, Evans, et al. (1983), the lowest
value of fat oxidation was 84 g/hr (1.4 g/min) with a
mean of 90 g/hr (1.5 g/min; Figure 1). Another
important finding of the studies by Phinney, Bistrian,
Evans, et al. (1983) was that muscle glycogen
content was lowered but not totally depleted by these
very low-carbohydrate diets and that the rate of
glycogen use at the same power output was sharply
decreased following keto-adaptation (Table II).
The practical implications of the process of ketoadaptation
are that the human body can adapt to use
fat as its primary fuel during submaximal exercise,
while at the same time freeing itself from obligate
high rates of liver and muscle glycogen use. This can
be appreciated by translating 90 g/hr of fat oxidation
to 810 kcal/hr (56 kj/min) of fat use in the ketoadapted
bicycle racers when their total exercise
energy expenditure was 930 kcal/hr (65 kj/min),
thus leaving only 120 kcal/hr (8.4 kj/min) required
from all other substrates (e.g., glucose, glycerol,
amino acids). This demonstrates the degree to which
these athletes were able to release themselves from
carbohydrate dependence during endurance exercise,
relying upon their much more copious reserves
of body fat (see Table I).
A similar finding is predicted from a simulation of the
metabolic requirements of running a 2 hr 40 min
marathon at the end of the Ironman Triathlon (Noakes,
2002; pp. 141–143). Since high-carbohydrate-adapted
Ironman triathletes must have extremely low muscle
glycogen concentrations at the start of the final 26.2
mile marathon leg, they would require a minimal fat
oxidation rate of 1.15 g/min to complete the marathon
in 2 hr 40 min when the carbohydrate contribution to
Table II. Endurance capacity and fuel use before and after ketoadaptation
in athletes
Baseline
Four-week
ketosis
VO2max (L/min) 5.1 5.0
Endurance @65% VO2max (min) 147 151
Exercise RQ (VCO2/VO2) 0.83 0.72
Pre-exercise muscle glycogen
(mmol/kg w.w.)
143 76
Post-exercise muscle glycogen
(mmol/kg w.w.)
56 53
Change muscle glycogen
(mmol/kg)
87 23
Source: Adapted from Phinney, Bistrian, Evans, et al. (1983).
11
28
60
74
90
112
0
20
40
60
80
100
120
Peak fat oxidation during exercise
Venables et al. (2005) Phinney et al. (1983b)
Lowest
participant
Highest
parƟcipant
Group
average
Lowest
participant
Highest
participant
Group
average
Keto-adaptedNon-keto-adapted
(grams fat per hour)
Figure 1. The rate of fat use during exercise at 64% VO2max
in trained cyclist (Phinney et al., 1983) compared to peak fat
oxidation rates recorded in 300 people that included highly
trained individuals (Venables et al., 2005).
Rethinking fat as a fuel 15
energy production (from the oxidation of blood
glucose and lactate) would be less than about 43%.
An athlete able to oxidize fat at a rate of 1.5 g/min
would be able to produce 56 kj/min from fat oxidation
alone or 73% of the 76 kj/min needed to run at that
pace. Provided the athlete was able to produce 1.2 g/
min from liver gluconeogenesis, he or she would
be able to run at that pace without requiring any
external source of feeding. It remains to be determined
the importance of other substrates (e.g.,
ketones, lactate, glycerol, amino acids, very lowdensity
lipoprotein-triglyceride) to the fuel demands
in the keto-adapted athlete, but some of these alternative
fuel sources generally thought to contribute
minimally to energy expenditure, may take on a
proportionately greater role.
It is important to note that many studies have
examined so-called “high-fat” diets and reported
moderately higher levels of fat oxidation (Burke
et al., 2000, 2002; Helge, Watt, Richter, Rennie, &
Kiens, 2001; Lambert, Speechly, Dennis, & Noakes,
1994), but the level of carbohydrate restriction was
not at a level permitting nutritional ketosis. Alternatively,
the duration of adaptation was insufficient
to allow keto-adaptation, thus resulting in less
pronounced shifts in fuel use compared to those
observed by Phinney, Bistrian, Evans, et al. (1983).
With regard to the effects of diets higher in fat, but
not ketogenic diets, on exercise capacity, some studies
in the past 35 years of short-term (7–14 days)
adaptation to low-carbohydrate diets have shown a
beneficial effect on exercise capacity (Lambert et al.,
1994, 2001); others suggest a beneficial effect (Burke
et al., 2000; Carey et al., 2001; Havemann, 2008;
Rowlands & Hopkins, 2002) but are limited by small
subject numbers; yet others found no effect (Burke
et al., 2002; Helge, Wulff, & Kiens, 1998; Phinney,
Bistrian, Evans, et al., 1983; Vogt et al., 2003),
whereas bouts of higher intensity exercise interspersed
during a 100-km laboratory time trial were
negatively affected (Havemann et al., 2006). Perhaps
expectedly the longest laboratory time trial yet studied
(200 km lasting up to eight hours; Havemann, 2008)
produced suggestive evidence for a benefit during the
most difficult part of the test – a simulated mountain
climb that occurred after about ~four hours cycling –
but the conclusions are limited by small subject
numbers. Exercise capacity during the mountain
climb was improved in eight of nine subjects when
eating the low-carbohydrate diet. For the overall trial,
five of nine subjects improved their exercise capacity
on the low-carbohydrate diet. Interestingly, subjects
with low-habitual RER improved on the mountain
climb by an average of 375 seconds compared to their
performance when eating the high-carbohydrate diet.
The author concluded that athletes with low-habitual
RER may be the more likely to benefit from the lowcarbohydrate
dietary intervention.
Although it is difficult to make definitive conclusions
from these studies due to methodological
differences, especially as it relates to the composition
and adherence to the diets and duration of intervention,
these studies clearly provide encouragement
that adaptation to a low-carbohydrate diet can produce
a positive effect, especially when the diet has
been maintained for an extended period, and the
duration of exercise is long. There is clearly an
ongoing need for appropriately designed and conducted
studies of long-term low-carbohydrate diets
on human physiology and performance, especially
during prolonged exercise when the probability of a
beneficial effect is more likely (Havemann, 2008).
Brain fuel
The other apparent benefit to exercise in the ketoadapted
state is the steady supply of energy to the brain
in the form of ketones. Although it is commonly stated
that the brain is a glucose-dependent organ (Dietary
Guidelines for Americans, 2010), elegant studies
have clearly shown that ketones supply the majority
of fuel for the brain when carbohydrate availability is
reduced and circulating BOHB concentrations are in
the 1–5 millimolar range. A brain capable of deriving
the majority of its energy needs from ketones would
have been an essential survival mechanism during
prolonged periods of carbohydrate deprivation, and
perhaps no more spectacular example of this evolutionary
advantage is the experimental data showing
complete protection from any signs or symptoms of
profound hypoglycemia in the keto-adapted state
(Cahill & Aoki, 1980; Owen et al., 1967).
Whereas prolonged intense exercise when one is
dependent upon glucose/glycogen progressively
depletes fuel reserves available to sustain the brain,
the keto-adapted athlete may benefit from the
opposite effect. As endurance exercise progresses,
unlike the blood glucose concentration, the blood
ketone concentration does not decline but tends to
rise somewhat, ensuring a stable supply of fuels to
the brain. Consistent with this improved cerebral
fuel delivery, ultra-endurance athletes frequently
report that mental clarity is maintained better during
prolonged exercise in the keto-adapted state. This is
in stark contrast to the problems of central fatigue
and “hitting the wall” that commonly occur in
athletes who follow a high-carbohydrate fuelling
strategy and to which a progressive hypoglycemia
that develops during prolonged exercise may contribute
to fatigue. While ingesting carbohydrate
during exercise may delay these fuel flow problems
in athletes consuming high-carbohydrate diets, it
does not always prevent them.
16 J. S. Volek et al.
Recovery
Another reported benefit of performing high-volume
training in the keto-adapted state may be reduced
delayed onset muscle soreness and accelerated postexercise
recovery. Whereas it is common to take many
weeks off from training after a 100-mile running
event, keto-adapted athletes report that they can
resume training and even competition within a week
or two.
These empiric observations are interesting in contrast
to the considerable literature linking “high-fat
diets” with increased inflammation and oxidative
stress (Djuric et al., 2001; Erhardt, Lim, Bode, &
Bode, 1997). When examined carefully, however, the
bulk of these studies (often performed in rodents)
utilized “high-fat diets” consisting of 40–60% of
energy as fat and 20–40% of energy as carbohydrate.
Given these macronutrient distributions, none of
these diets resulted in nutritional ketosis (i.e., serum
BOHB concentrations >0.5 mmol/L) because they
are too high in carbohydrates. Thus, these diets would
more accurately be described as “moderate high-fat,
moderate carbohydrate non-ketogenic” diets. Moreover,
the link between dietary fat and inflammation
is often made on the grounds that high-fat meals promote
a pro-inflammatory state (Herieka & Erridge,
2014), but these studies involve ingestion of a single
fat-rich meal by individuals not habitually accustomed
to eating the majority of calories from fat and
who are definitely not keto-adapted. Volek et al.
(2009; Sharman, Gómez, Kraemer, & Volek, 2004)
have repeatedly shown that keto-adaptation is associated
with significantly enhanced postprandial processing
of dietary fat and improved metabolic-risk
markers including those relating to vascular function
and flow-mediated dilation of the brachial artery.
In contrast to these moderate-fat diets and singlemeal
feeding studies, the bicycle racers ingesting
>80% of their dietary energy as fat (Phinney,
Bistrian, Evans, et al., 1983) showed no evidence
of increased inflammation. In fact, after four weeks
of nutritional ketosis, their total white blood cell
counts declined significantly from 5.1 to 4.5 × 109
/
L. Furthermore, in studies using mild caloric restriction,
Volek’s group has reported significant reductions
in biomarkers of inflammation in those
ingesting a low-carbohydrate ketogenic diet compared
to those eating a hypocaloric, high-carbohydrate,
low-fat diet (Ballard et al., 2013; Forsythe et al.,
2008). In addition, other studies of low-carbohydrate
diets have reported reduced levels of the
inflammatory marker, C-reactive protein (Ruth et al.,
2013; Seshadri et al., 2004).
In all of these ketogenic diet studies, dietary fat
(including the contribution of endogenous fat during
hypocaloric studies) provided more than 60% of daily
energy expenditure. Thus, there appears to be a
discontinuity in the inflammatory response as one
progresses from low-fat to moderate-fat (i.e.,
40–60% of energy) to high-fat (>60% from fat).
This paradox might be explained by the increasing
evidence that BOHB is a potent signalling molecule
acting at the gene expression level and in the
regulation of mitochondrial proteins (Shimazu et al.,
2013).
Non-metabolic effects of ketones
Shimazu et al. (2013) have demonstrated that BOHB
levels characteristic of nutritional ketosis, whether
induced by fasting or by BOHB infusion in the fed
state, potently down-regulated expression of Class-I
histone deacetylase (HDAC) enzymes in mice. When
active, these gene-silencing enzymes turn off the
body’s endogenous defences against oxidative stress
and inflammation. By reducing the activity of these
HDAC enzymes, BOHB reduces oxidative stress,
as confirmed in the experiments by Shimazu et al.
which showed reduced levels of hydroxynonenal and
oxylipids after exposure to carbon tetrachloride.
The other place where HDAC enzymes are known
to have an important role is in the regulation of
mitochondrial protein activity, roughly a third of
which are regulated by acetylation/deacetylation processes
(Anderson & Hirschey, 2012). It has been
observed that nutritional ketosis is associated with
a reduction in the generation of reactive oxygen
species (ROS) by mitochondria (Sato et al., 1995).
While this may be a direct result of BOHB oxidation,
it could also result from an indirect effect of BOHB
on mitochondrial protein functions via reduced
HDAC activity.
Nutritional ketosis: a new paradigm
Nutritional ketosis may offer a range of benefits for
both recreational and performance athletes working
through both energetic and epigenetic mechanisms
(Figure 2). The classic role of BOHB is to fuel the
brain, as incontrovertibly demonstrated by Cahill
and Aoki (1980), whereas muscles prefer to rely on
fatty acids in the keto-adapted state, providing more
consistent fuel flow during extended training or
competition. The greater reliance on fatty acids and
ketones and dramatically reduced dependence on
glycogen and flux through glycolysis are associated
with less generation of free radicals and hydrogen
ions. Reduced generation of ROS during exercise
will potentially translate into less tissue damage,
better protection of critical membrane essential
fatty acids (Forsythe et al., 2008), which correlate
highly with insulin sensitivity (Borkman et al., 1993),
and thus more rapid recovery. These effects are
Rethinking fat as a fuel 17
commonly reported by athletes who have pioneered
the use of ketogenic diets in a variety of sports.
The other benefit for athletes on a well-formulated
ketogenic diet is the relative ease with which excess
body fat can be lost, while maintaining or even
building muscle mass, thus benefitting one’s powerto-weight
ratio. In addition to endurance athletes,
this can benefit strength and power athletes who
must “make weight” or for appearance competition
in which body shape is important. A ketogenic diet is
highly effective at improving body composition,
especially when combined with resistance training
(Paoli et al., 2012; Volek, Quann, & Forsythe,
2010), while preserving strength and power performance
in the keto-adapted state. Low-carbohydrate
diets have also been employed by ageing athletes for
whom progressive insulin resistance with increasing
weight and oxidative stress threaten to become
career-ending consequences.
While there are many recent individual examples
of athletes who have made effective use of lowcarbohydrate
or ketogenic diets, the sport where this
dietary paradigm shift is becoming dominant is in
ultra-marathon running. In addition to the near
certainty of bonking/hitting the wall unless copious
amounts of carbohydrates are ingested, ultra-runners
commonly experience a range of additional problems
such as mental confusion and gastrointestinal distress.
Gastric erosions have been documented by
endoscopy in humans after a marathon (Oktedalen,
Lunde, Opstad, Aabakken, & Kvernebo, 1992), and
frank gastrointestinal bleeding is common in sled
dogs running events like the Iditarod.
Ultra-runners who have previously experienced
gastrointestinal distress with a high-carbohydrate diet
commonly report dramatic improvement when competing
after keto-adaptation (Volek & Phinney, 2012).
Perhaps this is simply due to less need to consume
calories during the event. Common lore dictates
consuming about 6000 kcal of carbohydrates during
a competitive 100-mile race, but low-carbohydrate
runners commonly finish (and often now win) these
events on 1500 or less “in-race” calories. However, the
improved recovery following such events implies less
tissue damage, and this may be why the gastrointestinal
tract is less affected in low-carbohydrate runners
(i.e., less ROS means less membrane damage which
leads to better mucosal cytoprotection during and
after the event).
In conclusion, after a period of 3–4 weeks with
total daily carbohydrates at a level that induces
nutritional ketosis, the human body adapts to be
able to use almost all fat for its fuel. In athletes, we
posit that this may facilitate extended performance
without the need for the frequent ingestion of
carbohydrate-based fuels during exercise. In addition
to these direct fuelling benefits in the ketoadapted
athlete, BOHB is associated with reduced
oxidative stress and inflammation, and its signalling
Keto-
adaptation
BOHB
fuel source
BOHB
signalling
Alternative fuel
for brain
Decreased
central fatigue
Better cognitive
functioning
Improved
insulin
sensitivity
Less H+
Glycogen
sparing
Improved
power-to-
weight
Better fuel flow
/fat loss
HDAC
inhibition
Metabolic
health/longevity
Endurance
performance
Decreased
oxidative stress
Stress
resistance
Membrane
protection
Enhance fat
oxidation
Gut health
Improved
recovery
Less ROS
Figure 2. Theoretical paradigm by which ketogenic diets may benefit athletes. Very low-carbohydrate ketogenic diets result in elevated
BOHB, which has both energetic effects affecting metabolism and epigenetic effects altering gene expression. The physiologic
manifestations of nutritional ketosis may positively impact performance, recovery and health.
18 J. S. Volek et al.
mirrors many of the pathways associated with stress
resistance and longevity (Newman & Verdin, 2014).
In stark contrast to long-standing dogma (Erlenbusch
et al., 2005) in sports nutrition emphasizing
the essential need for dietary carbohydrate in all
forms of exercise regardless of duration or intensity,
these observations have brought us to a threshold
beyond which exercise capacity may be improved by
those who reduce their dependence on dietary sugars
and starches before and during especially prolonged
exercise. There is a need to better understand the
level of carbohydrate restriction (and the overall
composition of the diet) necessary to elicit these
effects, as well as the factors contributing to interindividual
variability in responses to these diets.
References
Anderson, K. A., & Hirschey, M. D. (2012). Mitochondrial
protein acetylation regulates metabolism. Essays in Biochemistry,
52, 23–35. doi:10.1042/bse052002.3
Ballard, K. D., Quann, E. E., Kupchak, B. R., Volk, B. M.,
Kawiecki D. M., Fernandez M. L., …Volek, J. S. (2013).
Dietary carbohydrate restriction improves insulin sensitivity,
blood pressure, microvascular function, and cellular adhesion
markers in individuals taking statins. Nutrition Research, 33,
905–912. doi:10.1016/j.nutres.2013.07.022
Bergström, J., Hermansen, L., Hultman, E., Saltin, B. (1967).
Diet, muscle glycogen and physical performance. Acta Physiologica
Scandinavica, 71, 140–150. doi:10.1111/j.1748-
1716.1967.tb03720.x
Bergström, J., & Hultman, E. (1966). Muscle glycogen synthesis
after exercise: An enhancing factor localized to the muscle cells
in man. Nature, 210, 309–310. doi:10.1038/210309a0
Bergström, J., & Hultman, E. (1967). A study of the glycogen
metabolism during exercise in man. Scandinavian Journal of
Clinical Laboratory Investigation, 19, 218–228. doi:10.3109/00
365516709090629
Borkman, M., Storlien, L. H., Pan, D. A., Jenkins, A. B.,
Chisholm, D. J., & Campbell, L. V. (1993) The relation
between insulin sensitivity and the fatty-acid composition of
skeletal-muscle phospholipids. New England Journal of Medicine,
328, 238–244. doi:10.1056/NEJM199301283280404
Burke, L. M., Angus, D. J., Cox, G. R., Cummings, N. K.,
Febbraio, M. A., Gawthorn, K., …Hargreaves, M. (2000)
Effect of fat adaptation and carbohydrate restoration on
metabolism and performance during prolonged cycling. Journal
of Applied Physiology, 89, 2413–2421.
Burke, L. M., Hawley, J. A., Angus, D. J., Cox, G. R., Clark, S. A.,
Cummings, N. K., …Hargreaves, M. (2002). Adaptations to
short-term high-fat diet persist during exercise despite high
carbohydrate availability. Medicine and Sciencein Sports and Exercise,
34(1), 83–91. doi:10.1097/00005768-200201000-00014
Burke, L. M., Hawley, J. A., Schabort, E. J., St Clair Gibson, A.,
Mujika, I., & Noakes, T. D. (2000). Carbohydrate loading
failed to improve 100-km cycling performance in a placebocontrolled
trial. Journal of Applied Physiology, 88, 1284–1290.
Cahill, G. F., & Aoki, T. T. (1980). Alternate fuel utilization by
brain. In J. V. Passonneau, R. A. Hawkins, W. D. Lust, & F. A.
Welsh (Eds.). Cerebral metabolism and neural function. Baltimore,
MD: Williams & Wilkins.
Carey, A. L., Staudacher, H. M., Cummings, N. K., Stepto, N.
K., Nikolopoulos, V., Burke, L. M., & Hawley, J. A. (2001).
Effects of fat adaptation and carbohydrate restoration on
prolonged endurance exercise. Journal of Applied Physiology,
91, 115–122.
Christensen, E. H., & Hansen, O. (1939). Arbeitsfähigkeit und
Ernährung. Skandinavisches Archiv Für Physiologie, 81, 160–
171. doi:10.1111/j.1748-1716.1939.tb01320.x
Djuric, Z., Lewis, S. M., Lu, M. H., Mayhugh, M., Tang, N., &
Hart, R. W. (2001). Effect of varying dietary fat levels on rat
growth and oxidative DNA damage. Nutrition and Cancer, 39,
214–219.doi:10.1207/S15327914nc392_9
Erhardt, J. G., Lim, S. S., Bode, J. C., & Bode, C. (1997). A diet
rich in fat and poor in dietary fiber increases the in vitro
formation of reactive oxygen species in human feces. Journal of
Nutrition, 127, 706–709.
Erlenbusch, M., Haub, M., Munoz, K., MacConnie, S., &
Stillwell, B. (2005). Effect of high-fat or high-carbohydrate
diets on endurance exercise: A meta-analysis. International
Journal of Sports Nutrition and Exercise Metabolism, 15, 1–14.
Forsythe, C. E., Phinney, S. D., Fernandez, M. L., Quann, E. E.,
Wood, R. J., Bibus, D. M., … Volek, J. S. (2008). Comparison
of low fat and low carbohydrate diets on circulating fatty acid
composition and markers of inflammation. Lipids, 43(1), 65–
77. doi: 10.1007/s11745-007-3132-7
Havemann, L. (2008). The effect of fat-adaptation followed by
carbohydrate-loading on simulated ultra-endurance race performance.
Chapter 5: In: Nutritional Strategies for Endurance and
Ultra-Endurance Cycling (PhD Thesis). University of Cape
Town, Cape Town.
Havemann, L., West, S. J., Goedecke, J. H., Macdonald, I. A., St
Clair Gibson, A., Noakes, T. D., & Lambert, E. V. (2006). Fat
adaptation followed by carbohydrate loading compromises
high-intensity sprint performance. Journal of Applied Physiology,
100, 194–202. doi: 10.1152/japplphysiol.00813.2005
Helge, J. W., Watt, P. W., Richter, E. A., Rennie, M. J., & Kiens,
B. (2001). Fat utilization during exercise: Adaptation to a fatrich
diet increases utilization of plasma fatty acids and very low
density lipoprotein-triacylglycerol in humans. Journal of Physiology,
537, 1009–1020. doi:10.1113/jphysiol.2001.012933
Helge, J. W., Wulff, B., & Kiens, B. (1998) Impact of a fat-rich
diet on endurance in man: Role of the dietary period. Medicine
and Science in Sports and Exercise, 30, 456–461. doi:10.1097/
00005768-199803000-00018
Herieka, M., & Erridge, C. (2014) High-fat meal induced
postprandial inflammation. Molecular Nutrition and Food
Research, 58, 136–146. doi:10.1002/mnfr.201300104
Hoppeler, H., Billeter, R., Horvath, P. J., Leddy, J. J., &
Pendergast, D. R. (1999). Muscle structure with low- and
high-fat diets in well-trained male runners. International Journal
of Sports Medicine, 20: 522–526. doi:10.1055/s-1999-8838
Lambert, E. V., Goedecke, J. H., van Zyl, C., Murphy, K.,
Hawley, J. A., Dennis, S. C., & Noakes, T. D. (2001). High-fat
versus habitual diet prior to carbohydrate loading. Effects on
exercise metabolism and cycling performance. International
Journal of Sports Nutrition and Exercise Metabolism, 11, 209–225.
Lambert, E. V., Speechly, D. P., Dennis, S. C., & Noakes, T. D.
(1994). Enhanced endurance in trained cyclists during moderate
intensity exercise following 2 weeks adaptation to a high fat
diet. European Journal of Applied Physiology and Occupational
Physiology, 69, 287–293. doi:10.1007/BF00392032
McClellan, W. S., & Dubois, E.F. (1930). Clinical calorimetry.
XLV: Prolonged meat diets with a study of kidney function and
ketosis. The Journal of Biological Chemistry, 87, 651–668.
Newman, J. C., & Verdin, E. (2014). Ketone bodies as signaling
metabolites. Trends in Endocrinology and Metabolism, 25(1),
42–52. doi:10.1016/j.tem.2013.09.002
Noakes, T. D. (2002). Lore of running (4th ed.). Champaign, IL:
Human kinetics.
Oktedalen, O., Lunde, O. C., Opstad, P. K., Aabakken, L., &
Kvernebo, K. (1992). Changes in the gastrointestinal mucosa
Rethinking fat as a fuel 19
after long-distance running. Scandinavian Journal of Gastroenterology,
27, 270–274. doi:10.3109/00365529209000073
Orr, J. B., & Gilks, J. L. (1931). The physique and health of two
African tribes. London: His Majesty’s Stationary office.
Owen, O. E., Morgan, A. P., Kemp, H.G., Sullivan, J. M.,
Herrera, M. G., & Cahill G. F. Jr. (1967). Brain metabolism
during fasting. Journal of Clinical Investigation, 46, 1589–1595.
doi:10.1172/JCI105650
Paoli, A., Grimaldi, K., D'Agostino, D., Cenci, L., Moro, T.,
Bianco, A., & Palma, A. (2012). Ketogenic diet does not affect
strength performance in elite artistic gymnasts. Journal of
International Society of Sports Nutrition, 9(1), 34. doi:10.1186/
1550-2783-9-34
Phinney, S. D., Bistrian, B. R., Evans, W. J., Gervino, E., &
Blackburn, G. L. (1983). The human metabolic response to
chronic ketosis without caloric restriction: Preservation of
submaximal exercise capability with reduced carbohydrate
oxidation. Metabolism, 32, 769–776. doi:10.1016/0026-0495
(83)90106-3
Phinney, S. D., Bistrian, B. R., Wolfe, R. R., & Blackburn, G. L.
(1983). The human metabolic response to chronic ketosis
without caloric restriction: Physical and biochemical adaptation.
Metabolism, 32, 757–768. doi:10.1016/0026-0495(83)
90105-1
Phinney, S. D., Horton, E. S., Sims, E. A. H., Hanson, J. S., &
Danforth, E., Jr. (1980). Capacity for Moderate Exercise in
Obese Subjects after Adaptation to a Hypocaloric, Ketogenic
Diet. Journal of Clinical Investigation, 66, 1152–1161.
doi:10.1172/JCI109945
Rae’s Arctic Correspondence 1844–1855. (1953). London: Hudson’s
Bay Record Society.
Report of the DGAC on the Dietary Guidelines for Americans,
2010. Retrieved from http://www.health.gov/dietaryguidelines/
2010.asp
Rowlands, D. S., & Hopkins, W. G. (2002). Effects of high-fat
and high-carbohydrate diets on metabolism and performance
in cycling. Metabolism, 51, 678–690. doi:10.1053/meta.200
2.32723
Ruth, M. R., Port, A. M., Shah, M., Bourland, A. C., Istfan, N.
W., Nelson, K. P., … Apovian, C. M.(2013). Consuming a
hypocaloric high fat low carbohydrate diet for 12 weeks lowers
C-reactive protein, and raises serum adiponectin and high
density lipoprotein-cholesterol in obese subjects. Metabolism,
62, 1779–1787. doi:10.1016/j.metabol.2013.07.006
Sato, K., Kashiwaya, Y., Keon, C. A., Tsuchiya, N., King, M. T.,
Radda, G. K., … Veech, R. L. (1995). Insulin, ketone bodies,
and mitochondrial energy transduction. FASEB Journal, 9,
651–658.
Seshadri, P., Iqbal, N., Stern, L., Williams, M., Chicano, K. L.,
Daily, D. A., … Samaha, F. F. (2004). A randomized study
comparing the effects of a low-carbohydrate diet and a
conventional diet on lipoprotein subfractions and C-reactive
protein levels in patients with severe obesity. American Journal
of Medicine, 117, 398–405. doi:10.1016/j.amjmed.2004.04.009
Sharman, M. J., Gómez, A. L., Kraemer, W. J., & Volek, J. S.
(2004). Very low-carbohydrate and low-fat diets affect fasting
lipids and postprandial lipemia differently in overweight men.
Journal of Nutrition, 134, 880–885.
Shimazu, T., Hirschey, M. D., Newman, J., He, W., Shirakawa,
K., Le Moan, N., … Verdin, E. (2013). Suppression of
oxidative stress by β-hydroxybutyrate, an endogenous histone
deacetylase inhibitor. Science, 339, 211–214. doi:10.1126/
science.1227166
Stackpole, E. A. (1965) The long arctic search: The narrative of
lieutenant Frederick Schwatka. New Bedford, MA: The Marine
Historical Society.
Stefansson, V. (1921). The friendly arctic. New York, NY: The
Macmillan Co.
Venables, M. C., Achten, J., & Jeukendrup, A. E. (2005).
Determinants of fat oxidation during exercise in healthy men
and women: A cross-sectional study. Journal of Applied Physiology,
98, 160–167. doi:10.1152/japplphysiol.00662.2003
Vogt, M., Puntschart, A., Howald, H., Mueller, B., Mannhart, C.,
Gfeller-Tuescher, L., … Hoppeler, H. (2003). Effects of
dietary fat on muscle substrates, metabolism and performance
in athletes. Medicine and Science in Sports and Exercise, 35, 952–
960. doi:10.1249/01.MSS.0000069336.30649.BD
Volek, J. S., Ballard, K. D., Silvestre, R., Judelson, D. A., Quann,
E. E., & Forsythe, C. E. (2009). Effects of dietary carbohydrate
restriction versus low-fat diet on flow-mediated dilation. Metabolism,
58, 1769–1777. doi:10.1016/j.metabol.2009.06.005
Volek, J. S., & Phinney, S. D. (2012). The art and science of low
carbohydrate performance. Beyond Obesity. Miami, FL: LLC,
126–127.
Volek J. S., Quann E. E., & Forsythe C. E. (2010): Low
carbohydrate diets promote a more favorable body composition
than low fat diets. Strength and Conditioning Journal, 32(1),
42–47. doi:10.1519/SSC.0b013e3181c16c41
20 J. S. Volek et al.