October 2017 | Volume 4 | Article 491
HYPOTHESIS AND THEORY
published: 12 October 2017
doi: 10.3389/fnut.2017.00049
Frontiers in Nutrition | www.frontiersin.org
Edited by:
Gareth A. Wallis,
University of Birmingham,
United Kingdom
Reviewed by:
Sam Shepherd,
Liverpool John Moores University,
United Kingdom
Chris Shaw,
Deakin University, Australia
*Correspondence:
Jonathan P. Little
jonathan.little@ubc.ca
Specialty section:
This article was submitted to
Sport and Exercise Nutrition,
a section of the journal
Frontiers in Nutrition
Received: 09August2017
Accepted: 27September2017
Published: 12October2017
Citation:
FrancoisME, GillenJB and LittleJP
(2017) Carbohydrate-Restriction with
High-Intensity Interval Training:
An Optimal Combination for
Treating Metabolic Diseases?
Front. Nutr. 4:49.
doi: 10.3389/fnut.2017.00049
Carbohydrate-Restriction with
High-Intensity Interval Training:
An Optimal Combination for
Treating Metabolic Diseases?
Monique E. Francois
1
, Jenna B. Gillen
2
and Jonathan P. Little
1
*
1
University of British Columbia Okanagan, Kelowna, BC, Canada,
2
University of Toronto, Toronto, ON, Canada
Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone
therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity
interval training (HIIT) have independently been shown to improve cardiovascular and
metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby
limiting potential deleterious metabolic and cardiovascular consequences of excessive
glucose excursions. Additionally, carbohydrate-restriction has been shown to improve
body composition and blood lipids. The benefits of exercise for improving insulin sen-
sitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose
control, endothelial function, and cardiorespiratory fitness. Here, we report the available
evidence for each strategy and speculate that the combination of carbohydrate-restriction
and HIIT will synergistically maximize the benefits of both approaches. We hypothesize
that this lifestyle strategy represents an optimal intervention to treat metabolic disease;
however, further research is warranted in order to harness the potential benefits of
carbohydrate-restriction and HIIT for improving cardiometabolic health.
Keywords: high-intensity interval training, glycemic control, metabolism, cardiometabolic disease, exercise,
low-carb diets
INTRODUCTION
Type 2 diabetes (T2D) is one of the fastest growing, yet largely preventable chronic diseases world-
wide (1). In addition to the hallmark feature of impaired glucose control, progression of T2D
presents with a number of co-morbidities, increasing risk of premature mortality. Of particular
concern is the high prevalence of atherosclerotic cardiovascular disease (CVD), which accounts for
~80% of T2D-related co-morbidities (2, 3). Furthermore, a clustering of cardiovascular risk factors
tend to manifest well before the diagnosis of T2D, accelerating the progression of CVD (4). ese
risk factors include central obesity, hypertension, hyperglycemia, and dyslipidemia, collectively
coined the metabolic syndrome (5). In addition, physical inactivity and/or low-cardiorespiratory
tness are emerging as important modiable risk factors for CVD and T2D (6). Importantly,
both exercise and dietary strategies can help prevent, or slow the progression of, T2D-related
co-morbidities. In this regard, lifestyle interventions incorporating both diet and exercise prescrip-
tions remain at the frontline of therapeutic options for treating metabolic disease (79).
e main treatment goal of metabolic diseases, including T2D and the metabolic syndrome,
is the prevention of atherosclerotic CVD (10, 11). To date, management of T2D and associated
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Frontiers in Nutrition | www.frontiersin.org October 2017 | Volume 4 | Article 49
co-morbidities depends upon pharmacological interventions
and the implementation of lifestyle changes (9, 11). Generally,
public health guidelines encourage weight loss by recommending
a calorie-restricted diet that is low in fat and added sugar, as well
as performing at least 150 min of moderate-intensity physical
activity each week (10, 11). While this general approach may be
eective for the prevention of T2D (12), it does not appear to
prevent, or alleviate, the burden of CVD in those with overt T2D
[(8), LOOK Ahead trial]. Given the signicant burden of CVD
and diabetes-related co-morbidities, novel intervention strate-
gies that can reduce cardiovascular risk factors, while imposing
minimal side eects, are urgently sought aer.
In the growing eld of health and exercise science, a number of
lifestyle approaches are currently gaining momentum. For example,
dietary modications such as carbohydrate-restriction and time-
restricted feeding (including intermittent fasting) are emerging as
alternative treatment strategies for persons with, and at risk for,
metabolic diseases. Likewise, novel exercise prescriptions including
high-intensity interval training (HIIT), and the concept of breaking
up sedentary time with light physical activity, have revealed sig-
nicant promise for improving or mitigating the deleterious eects
of an inactive lifestyle. Innovative and eective strategies such as
these have rearmed the strong inuence of lifestyle modication
on metabolic disease progression. While some of these individual
approaches are beginning to inform public health guidelines (9),
it is our belief that combining both diet and exercise modication
will synergistically aid in the management of metabolic disease. In
this regard, carbohydrate-restriction is loosely dened as restricting
carbohydrates to less than 30% of caloric intake, and HIIT is char-
acterized by brief periods of high-intensity exercise interspersed
with low-intensity exercise for recovery. We acknowledge there
are several other promising lifestyle interventions that we have not
mentioned, however, the focus of this paper is to highlight the pro-
pensity for synergistic eects when carbohydrate-restriction and
HIIT are combined. As with any lifestyle intervention, adherence
is critical, and behavior change research on how to implement and
support both HIIT and carbohydrate-restriction is needed. Initial
work on adherence to HIIT is showing promise (13) and low-CHO
diets appear to have similar adherence to other diets (14), but it
will be necessary to assess the tolerability and adherence to our
hypothesized approach moving forward.
HYPOTHESIS
In light of recent evidence, we hypothesize that the novel com-
bination of a carbohydrate-restricted diet and HIIT represents
a promising lifestyle strategy for the treatment of T2D. e
purpose of this Hypothesis & eory piece is to briey summarize
the evidence that supports the individual therapeutic benets of
carbohydrate-restriction and HIIT, as well as present the idea
that combining these approaches may represent the most potent
lifestyle therapy for this costly disease.
CARBOHYDRATE-RESTRICTION IN T2D
Due to the growing prevalence of metabolic disease and the
apparent ineectiveness of the current dietary guidelines
(15, 16), alternative dietary approaches need to be considered.
ere is increasing evidence from scientic research [reviewed
in Ref. (17)] and patient groups (UK Diabetes low-carb initiative;
www.diabetes.org.uk) to support carbohydrate-restriction as a
primary dietary treatment strategy for individuals with T2D. It has
long been known that a diet high in carbohydrate elevates post-
prandial hyperglycemia and insulin responses, together accelerat-
ing the progression of T2D and atherosclerotic CVD (1820). To
this end, diets low in carbohydrate was recommended for T2D in
1800s and during the early twentieth century. More recently, low-
carbohydrate diets are recognized in the ADA medical nutrition
therapy guidelines (21) although the ocial dietary guidelines
for individuals with T2D still do not advocate a low-carbohydrate
approach. In comparison with standard low-fat caloric restric-
tive dietary interventions, energy-matched diets that restrict
carbohydrates to <30g/day have been shown to result in greater
reductions in HbA
1c
and fat mass (22, 23), as well as superior
improvements in the blood lipid prole (24, 25). Typically, low-
carbohydrate diets are not explicitly prescribed to be hypocaloric,
but due to the satiating eects of protein and fat, energy intake
is oen lower (22, 2628). However, while the energy intake is
reduced relative to participants habitual intake or when a low-fat
diet is prescribed, low-carbohydrate diets reduce energy intake
relative to energy requirements (2628). For example, Boden
etal. (26) observed a 1,027cal/day reduction in energy intake
when patients with T2D followed an adlibitum low-carbohydrate
diet for 14days; interestingly, the energy intake was reduced to a
level that was appropriate to their weight. Moreover, the benets
of low-carbohydrate diets can occur without weight loss (29, 30).
For a comprehensive review of carbohydrate-restriction for the
management of T2D, an interested reader is directed to Feinman
etal. (28).
While optimal guidelines for carbohydrate-restriction are
not established, a carbohydrate-restrictive diet generally con-
stitutes <30% of caloric intake from carbohydrate food-sources
(approximating <130g/day) (31). Very low-carbohydrate diets
on the other hand, oen referred to as ketogenic diets, involve
more extreme reductions in carbohydrate of less than ~30g/day
to permit nutritional ketosis (32). e optimal amount of car-
bohydrate in the diet (degree of carbohydrate-restriction) likely
depends on the state of insulin resistance of the individual.
For example, Cornier etal. (33) reported greater weight loss in
insulin-sensitive individuals following a high- compared with
a low-carbohydrate hypocaloric diet, whereas the opposite was
true for insulin-resistant individuals (i.e., greater weight loss and
improved insulin sensitivity on a low-carbohydrate hypocaloric
diet). e implications of this study are noteworthy, given that
more than 35% of adults are insulin resistant (34). erefore,
speculatively, more insulin-resistant individuals, particularly
those with T2D, may require greater degrees of carbohydrate-
restriction for diet-induced improvements in metabolic health.
In longer-term interventions, a carbohydrate-restricted diet
appears highly eective at promoting weight loss in patients
with T2D (25, 27, 35). is dietary strategy has also been shown
to reduce visceral adiposity (22, 27, 36), and lower medication
requirements in adults with T2D (25, 37). Such reductions in
central adiposity, insulin resistance, and hyperglycemia are
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Francois et al. Optimal Prescription: Carbohydrate-Restriction and HIIT
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central to preventing the development of CVD (38). Importantly,
even in the absence of weight loss, carbohydrate-restrictive diets
have also been shown to improve glycemic control (29, 39). For
example, Gannon and colleagues found that despite no change
in total body mass, an isocaloric diet comprising 30% protein,
50% fat, and 20% carbohydrate reduced HbA
1c
by 2% (absolute
reduction) and improved fasting and postprandial blood glucose
control in patients with T2D (30, 40). Such improvements in glu-
cose control in the absence of weight loss may be due to improved
insulin sensitivity and/or beta-cell function. Indeed, Boden etal.
(26) showed that just 2weeks of an isocaloric low-carbohydrate
diet improves insulin sensitivity by 75% in T2D individuals, using
the gold standard hyperinsulinemic euglycemic clamp technique.
Although we are unaware of any direct evidence for improved
beta-cell function with carbohydrate-restriction in individuals
with T2D, associative evidence supports that providing beta-cell
rest by removing hyperglycemia can reverse the insulin secretory
defects present in animal models of T2D (41, 42).
EXERCISE IN T2D: IT IS A HIIT!
Physical inactivity presents one of the greatest public health
concerns of our time (43). Indeed inactivity, or perhaps more
accurately termed insucient physical activity, is the fourth
leading cause of death (44). Physical activity is broadly dened
as any bodily movement produced by skeletal muscle, encom-
passing both activities of daily living and structured exercise.
Exercise is dened as purposeful physical activity carried out to
sustain or improve health or tness, and if provided in a sucient
stimulus (dependent upon intensity and duration) is very eec-
tive to improve cardiometabolic health (45). e protective and
therapeutic eects of regular exercise for the prevention of many
chronic diseases are well-established and have been comprehen-
sively reviewed by Pedersen and Saltin (46).
In order to achieve such health benets, it is recommended
that 150min of moderate-to-vigorous intensity physical activ-
ity be performed each week. Perhaps one of the greatest health
benets of a regular exercise regimen is an improvement in
cardiorespiratory tness (47). Indeed, improving cardiorespira-
tory tness is associated with a lower risk of both all-cause
and CVD mortality (48, 49). e positive relationship between
regular exercise and improvements in cardiorespiratory tness
appears to be intensity-dependent, however, with higher intensity
exercise conferring larger improvements in tness (50, 51). In
fact, several systematic reviews and meta-analyses have reported
that in comparison with moderate-intensity exercise, exercise
performed at a higher intensity elicits greater improvements in
markers of cardiovascular, and metabolic health in individuals
with T2D (5255). In agreement, a recent review by Baldi etal.
(56), suggested that even public health guidelines, which recom-
mend moderate-intensity continuous training (MICT), may not
provide a sucient stimulus for improving cardiovascular func-
tion. us, performing exercise at a vigorous intensity (relative to
the individuals baseline tness level) may be required to improve
cardiovascular and metabolic health (57).
High-intensity interval training, which involves alternating
periods of relatively intense exercise with periods of rest or
low-intensity exercise for recovery (58, 59), is an attractive strat-
egy enabling vigorous-intensity exercise to be incorporated in an
exercise program. In comparison with MICT, HIIT is performed
in an intermittent pattern, which results in only brief periods
of relatively high-intensity eort, followed by recovery periods.
Importantly, HIIT is a highly potent strategy to improve cardi-
orespiratory tness (59). Indeed, a recent meta-analysis reported
that HIIT-induced improvements in cardiorespiratory tness
were nearly one metabolic equivalent (+3ml/kg/min) higher than
in response to MICT in individuals with lifestyle induced chronic
disease (59). Improvements of this magnitude correspond to a
~15% greater risk reduction for CVD morality (49), highlighting
the potency of HIIT for reducing cardiovascular risk.
Various iterations of HIIT have been tested in small trials
of T2D patients with reported benefits to cardiorespiratory
fitness, glucose control, hepatic fat, vascular function, and
body composition. While direct comparisons with standard
care MICT are less common, recent investigations have
reported superior improvements in many of these risk fac-
tors following HIIT (5961). For example, an HIIT protocol
involving 4× 4 min intervals at ~90% of maximal aerobic
capacity, interspersed with 3min of recovery has consistently
yielded superior cardiovascular adaptations compared with
an energy-matched MICT protocol. Following 12 weeks of
training, endothelial function (62, 63), diastolic and systolic
function (63) as well as cardiorespiratory fitness (6264) were
improved to a greater extent following HIIT compared with
MICT.
Given the prevailing hyperglycemia among patients with
T2D, the impact of HIIT on glycemic control has received much
attention (6366). In a landmark study, Karsto et al. (65, 67)
compared 60 min of interval-walking 5 days per week, to an
energy-expenditure matched continuous-walking protocol in
T2D. e interval-walking group performed 3 min periods of
fast walking (above 70% VO
2
peak), followed by 3min of slow
walking (below 70% VO
2
peak) for 60min three times per week,
while the continuous protocol involved 60min of walking at 55%
VO
2
peak. Following 16weeks of training, the interval-walking
group displayed greater reductions in mean 24-h blood glucose
concentration assessed with continuous glucose monitor-
ing, which were accompanied by superior improvements in
cardiorespiratory tness and body composition. In a follow-up
publication in the same participants, authors reported improved
insulin sensitivity in the interval-walking group only, as meas-
ured by hyperglycemic clamp with glucose tracers. ese superior
improvements in glucose control are reinforced by a recent meta-
analysis demonstrating that HIIT improves fasting blood glucose
and HbA
Ic
to a greater extent than MICT in individuals at risk for,
or aicted with, T2D (60). Specically, in those with T2D, HIIT
was found to lower fasting glucose and HbA
1c
by 0.92mmol/l
and 0.5%, respectively, which is of comparable magnitude to
pharmacological-induced improvements in glycemia (68). e
pronounced improvements in glucose control following HIIT
are likely mediated by many factors, some of which may include
greater beta-cell function (67, 69), improved skeletal muscle
insulin signaling (62, 67), and reductions in total body (62, 64, 65)
and hepatic (66, 70) fat content.
FIGURE 1 | The independent, and proposed reciprocal benefits of high-intensity interval training and carbohydrate-restriction for cardiometabolic health.
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Francois et al. Optimal Prescription: Carbohydrate-Restriction and HIIT
Frontiers in Nutrition | www.frontiersin.org October 2017 | Volume 4 | Article 49
While these ndings are compelling, the time commitment
associated with many HIIT protocols is oen higher (150–
300min/week) than that obtained by the general population,
which questions whether such exercise is attainable for many
individuals who report a “lack of time” as a barrier to regular
exercise (71). With this in mind, low-volume HIIT protocols
involving a reduced exercise volume and time commitment
may represent a viable strategy. We have previously shown
that 2weeks of HIIT involving six sessions of 10× 60s cycling
intervals at ~90% of maximal heart rate, interspersed with 60s
of rest, improved 24-h mean blood glucose concentration, and
lowered postprandial glucose excursions in patients with T2D
(72). Using this same protocol, Madsen etal. (69) reported a
0.5% reduction in HbA
1c
and increased glucose tolerance and
beta-cell function aer 8weeks of training in T2D. In addition to
improvements in glycemic control, we (73) and others (74) have
reported increases in cardiorespiratory tness and total body
lean mass as well as reductions in body fat following 12weeks
of low-volume HIIT in patients with T2D. ese ndings are
quite intriguing, given that total exercise time was only ~30min/
week within a 75-min weekly time commitment. Importantly,
low-volume HIIT has been reported to be enjoyable (13, 75, 76),
which may be attributable to the low-time commitment and/or
short interval duration (77).
e mechanisms by which HIIT improves metabolic and
cardiovascular health are likely multifaceted, and may relate to
the high rates of muscle ber recruitment, rapid muscle glycogen
depletion, and repetitive shear stress during exercise (78, 79). e
intermittent cardiorespiratory and metabolic demands imposed
also appear to be important in regulating chronic adaptations
to HIIT (79). Indeed, it has been suggested that training with
alternating intensity, and not solely measuring training volume
and mean intensity, is important for improving cardiovascular
and metabolic health in individuals with T2D (65, 67, 80).
COMBINING CARBOHYDRATE-
RESTRICTION AND HIIT FOR IMPROVED
CARDIOMETABOLIC HEALTH
While the independent improvements in cardiometabolic health
following carbohydrate-restriction and HIIT have been well
investigated, the combined impact of these lifestyle strategies in
patients with T2D has yet to be explored. It is our hypothesis
that supplementing a carbohydrate-restrictive diet with HIIT, or
likewise, strategically limiting carbohydrate availability during
HIIT, may enhance the therapeutic eects of either interven-
tion alone (Figure 1). Specically, we believe that a combined
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Francois et al. Optimal Prescription: Carbohydrate-Restriction and HIIT
Frontiers in Nutrition | www.frontiersin.org October 2017 | Volume 4 | Article 49
approach will synergistically improve the acute and chronic
regulation of glycemic control and endothelial function while
maximally improving cardiorespiratory tness, resulting in the
optimal lifestyle strategy to limit the progression of T2D, and
related co-morbidities.
Adding HIIT to a Carbohydrate-Restrictive
Diet
While a carbohydrate-restrictive diet eectively reduces hyper-
glycemic excursions and improves glycemic control in patients
with T2D (29, 39), a perceived limitation of this dietary approach
is that it is inevitably higher in dietary fat. Studies in rodents (81,
82) and epidemiology evidence in humans suggests that a high-
fat diet (which is also low in carbohydrate) promotes insulin
resistance (83, 84). Specically, it appears that in the short-term,
high-fat diets (for 1week) in humans may impair glucose tol-
erance (when tested by providing a high-glucose load), at least
from trials in healthy adults (85, 86). In healthy insulin-sensitive
participants, a reduction in insulin sensitivity and/or glucose
tolerance following a switch to a low-carbohydrate high-fat
diet is likely an adaptive response as the body transitions over
to higher baseline fat utilization (87, 88). However, individuals
with obesity and insulin resistance experience some degree of
metabolic inexibility; an inability to modulate daily fat and
carbohydrate oxidation based upon substrate availability (89).
Consequently, exaggerated blood glucose and lipid responses to
meals are prevalent in individuals with insulin resistance (90).
is suggests that if one is to follow a low-carbohydrate diet, it
must be followed consistently (i.e., no “cheating” or consumption
of high-glycemic index foods) or that exercise should be incor-
porated to mitigate any detrimental eects on insulin sensitivity.
Indeed, the most important determinant of the eectiveness
of dietary interventions is adherence (91). However, we have
shown that a single session of low-volume HIIT performed aer
breakfast lowers postprandial glucose excursions throughout
the day in patients with T2D (92) and “small snacks” of interval
exercise distributed before meals signicantly lowers postpran-
dial hyperglycemia and mean glucose concentration over 24h
(93). erefore, exercise, of a sucient stimulus, strategically
timed to dispose of postprandial glucose and/or to increase fat
utilization is a highly eective strategy to reduce postprandial
excursions. In considering the glycemic response to a meal is
primarily determined by the quantity and type of carbohydrate
(94), restricting carbohydrate inevitably will lower postprandial
glucose and insulin excursions (95, 96). us, it would appear
that the combination of carbohydrate-restriction with HIIT
may promote synergistic improvements for acutely reducing
postprandial glucose spikes, increasing muscle glucose uptake,
and augmenting insulin sensitivity.
Furthermore, exercising before or aer a high-fat meal has
been shown to ameliorate the detrimental eects on endothelial
function (9799). Endothelial function is an important prog-
nostic indicator of cardiovascular health as the endothelium is
the barrier protecting the artery from thrombosis, inamma-
tion, and stiening (100, 101). Postprandial increases in lipids
and glucose are independent risk factors for CVD (102). e
postprandial impairment in endothelial function may be related
to excessive postprandial hypertriglyceridemia, inammation,
and oxidative stress following the meal (103, 104). Given that
several studies have supported the notion that “high-fat” meals
[which are oen also high in rened carbohydrate (105107)]
can promote endothelial dysfunction, there appears to be some
apprehension around adopting a low-carbohydrate high-fat diet.
However, this is despite the fact that high-carbohydrate meals
can elicit similar dysmetabolism and endothelial dysfunction
(105). Regardless, if a typical low-carbohydrate high-fat meal
does acutely impair endothelial function this may not be an ideal
strategy for participants at elevated CVD risk. However, Tyldum
et al. (99) reported that a single bout of HIIT, but not MICT,
performed ~16-h prior to a high-fat meal protected against
endothelial dysfunction. Interestingly, this was tightly related
to exercise-induced increases in antioxidant capacity with HIIT,
as measured by the colorimetric total antioxidant capacity assay
(99). Tjønna etal. (108) also showed that endothelial function
and nitric oxide bioavailability were increased ~72 h aer an
acute session of HIIT in individuals with T2D. Collectively,
it appears that exercise can negate the detrimental eects of a
high-fat meal on endothelial function, with HIIT as a promising
strategy to improve endothelial function. erefore, strategically
timing HIIT sessions could reduce any potential negative eects
of low-carbohydrate high-fat meals that are oen incorporated
into carbohydrate-restricted meal plans.
Lastly, over the long term, reductions in fat mass and
increases in lean mass appear critical for sustained improve-
ments in metabolic health following lifestyle interventions (109,
110). In this regard, the combination of diet and exercise may
be superior for preserving lean mass and reducing body fat in
patients with T2D (111, 112). Energy restriction interventions,
in the absence of exercise, oen result in the loss of lean body
mass in addition to fat loss (113, 114). Given the strong relation-
ship between lean body mass, metabolic health, and functional
capacity (115), preserving lean body mass with exercise during
any energy-restricted diet (whether low-carbohydrate or not) is
of primary importance. Moreover, preserving lean body mass
in individuals with T2D is particularly important given the
accelerated loss of skeletal muscle with insulin resistance, and
the concomitant worsening of glycemic control with decreased
skeletal muscle mass (116, 117). In view of this, HIIT has recently
been shown to increase skeletal muscle protein synthesis of
young and older adults, an eect linked to improved insulin
sensitivity, and mitochondrial function (118). Relative to MICT
and resistance training, HIIT resulted in the greatest increase
in gene expression for mitochondrial function, muscle growth,
and insulin signaling pathways in older adults (118). In both
obese adults and those with and T2D, HIIT has been shown to
reduce fat mass and increase lean mass (62, 64, 65, 69, 73, 74).
Although the impact of a low-carbohydrate diet combined with
HIIT has not been adequately studied, there is evidence that
a low-carbohydrate diet promotes favorable changes in body
composition when combined with resistance training in women
with obesity (119). us, the combination of HIIT with a low-
carbohydrate diet may help to preserve or increase lean mass in
individuals with T2D.
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Francois et al. Optimal Prescription: Carbohydrate-Restriction and HIIT
Frontiers in Nutrition | www.frontiersin.org October 2017 | Volume 4 | Article 49
EXERCISE AND NUTRIENT
INTERACTIONS: ADDING
CARBOHYDRATE-RESTRICTION TO HIIT
It is well known that nutrient ingestion in-and-around the exer-
cise period impacts the molecular signaling and thus metabolic
responses to exercise (120). Accumulating evidence has revealed
that nutrient availability, in addition to exercise components
(e.g., mode, intensity, and duration), play a putative role in
determining the adaptive response to exercise training (121).
Indeed energy status (whether surplus or decit) has been shown
to modify the neuroendocrine, acute molecular signaling, and
gene transcription response to exercise (121, 122). For example,
low-skeletal muscle glycogen prior to exercise augments AMPK
signaling and up-regulates the transcription of PGC1a and
mitochondrial enzymes (123125). It has also been suggested
that delaying glycogen restoration aer exercise may enhance the
adaptive response for proteins involved in glucose uptake (i.e.,
glucose transporter GLUT-4) (126, 127). erefore, restricting
carbohydrates and/or training fasted may increase the adaptive
(i.e., training-induced increase in metabolic signaling) response
to exercise (121, 128, 129). In contrast, providing carbohydrate
in proximity to exercise can in fact blunt the activation of key
regulatory genes for metabolizing fat postexercise (123). us,
it is tempting to speculate that combining HIIT with a low-
carbohydrate diet in T2D could enhance molecular signaling and
metabolic adaptations in skeletal muscle.
In support of this, Newsom etal. (130) reported that an energy
decit aer exercise does not contribute to the exercised-induced
improvements in insulin sensitivity if ample carbohydrate is pro-
vided. However, withholding carbohydrate (but providing ample
energy) postexercise resulted in improved insulin sensitivity the
following day. Furthermore, restricting carbohydrate before and
between interval training sessions has been shown to augment
the cellular signaling and upregulate skeletal muscle metabolic
enzyme adaptations in young healthy participants (131, 132).
is suggests that strategically restricting carbohydrate during
HIIT could potentiate exercise-induced skeletal muscle adapta-
tions in patients with T2D. To our knowledge, however, this
strategy has not been examined in clinical populations. In the
only study we are aware of, Sartor etal. (133) reported increased
resting fat oxidation and cardiorespiratory tness following a
2-week HIIT plus carbohydrate-restricted diet intervention in
obese men. However, changes in insulin sensitivity and glucose
control were not reported and thus future long-term studies are
warranted.
PERSPECTIVES FOR FUTURE RESEARCH
Carbohydrate-restriction and HIIT have independently been
shown to improve several indices of cardiometabolic health. Taken
together, it is our opinion that an adjunct therapy incorporating
both carbohydrate-restriction and HIIT would be a particularly
eective treatment for metabolic and CVDs (Figure1). However
promising, several key questions require further research, namely
(i) the level of carbohydrate-restriction that is eective, safe, and
feasible for dierent individuals over the long-term and (ii) the
most eective HIIT protocol to complement a carbohydrate-
restrictive diet. For example, low-volume HIIT protocols have
been shown to improve a host of cardiometabolic risk factors,
and are well-tolerated and enjoyed by individuals with T2D (13,
70, 73), however, future research on the integration of HIIT with
carbohydrate-restriction is needed. In this regard, using rating
of perceived exertion as an indication of exercise intensity may
be more appropriate than heart rate (70) given the tolerance to
HIIT during carbohydrate-restriction may be reduced. Sartor
etal. (133) showed promising eects of carbohydrate-restriction
with interval training (4× 4-min intervals) over 14days in obese
individuals. However, further research is needed in this area to
determine the exercise dose that is feasible and well-tolerated
during carbohydrate-restriction. In this regard and with the
advancement of personalized and precision medicine, the devel-
opment of an algorithm that could be used to adjust the level
of carbohydrate-restriction and corresponding HIIT protocol
according to age, underlying insulin resistance, tness, prefer-
ence, and genetics could prove useful. Considering there are
many eective HIIT protocols, the “optimal” protocol may in fact
be based on preference rather than physiology.
CONCLUSION: HIIT WITH
CARBOHYDRATE-RESTRICTION:
AN OPTIMAL COMBINATION FOR
INDIVIDUALS WITH T2D?
We hypothesize that the combination of HIIT with a carbohydrate-
restrictive diet may be the most eective strategy to reduce hyper-
glycemia, improve insulin sensitivity, promote favorable changes in
body composition, and preserve (or increase) endothelial function
in patients with T2D. While the combination of diet and exercise for
the treatment of T2D is self-evident, the optimal combination is yet
to be determined. Strategically timing HIIT in proximity to low-car-
bohydrate high-fat meals may synergistically maximize the benets
of both approaches, as well as minimize any potential negative eects
of postprandial lipemia if one is following a low-carbohydrate high-
fat diet. Such a strategy is indeed testable and warranted to improve
cardiometabolic health and reduce cardiovascular risk in T2D.
AUTHOR CONTRIBUTIONS
MF, JG, and JL contributed to the ideas and hypotheses presented
in this manuscript; draed, revised, and edited the manuscript.
FUNDING
JBG is supported by a CIHR Postdoctoral Research Fellowship.
JPL is supported by a CIHR New Investigator Award (MSH-
141980) and MSFHR Scholar Award (16890).
7
Francois et al. Optimal Prescription: Carbohydrate-Restriction and HIIT
Frontiers in Nutrition | www.frontiersin.org October 2017 | Volume 4 | Article 49
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