Lasers Med Sci

https://doi.org/10.1007/s10103-017-2347-y

ORIGINAL ARTICLE

Low-level laser therapy improves the VO2 kinetics

in competitive cyclists
Fábio J. Lanferdini 1,2 & Renata L. Krüger 1,3 & Bruno M. Baroni 4 & Caetano Lazzari 5 &
Pedro Figueiredo 6,7 & Alvaro Reischak-Oliveira 1 & Marco A. Vaz 1

Received: 16 February 2017 / Accepted: 1 October 2017

# Springer-Verlag London Ltd. 2017

Abstract Some evidence supports that low-level laser therapy
(LLLT) reduces neuromuscular fatigue, so incrementing sports
performance. A previous randomized controlled trial of our
group showed increased exercise tolerance in male competitive
cyclists treated with three different LLLT doses (3, 6, and 9 J/
diode; or 135, 270, and 405 J/thigh) before time-to-exhaustion
cycling tests. Now, the present study was designed to evaluate
the effects of these LLLT doses on the VO2 kinetics of athletes
during cycling tests. Twenty male competitive cyclists (29 years)
participated in a crossover, randomized, double-blind, and
placebo-controlled trial. On the first day, the participants per-
formed an incremental cycling test to exhaustion to determine
maximal oxygen uptake (VO2MAX) and maximal power output
Renata L. Krüger is a researcher sponsored by the Brazilian National
Research Council (CNPq), Brazil.
(POMAX), as well as a familiarization with the time-to-
exhaustion test. In the following days (2 to 5), all participants
performed time-to-exhaustion tests at POMAX. Before the ex-
haustion test, different doses of LLLT (3, 6, and 9 J/diode; or
135, 270, and 405 J/thigh, respectively) or placebo were applied
bilaterally to the quadriceps muscle. All exhaustion tests were
monitored online by an open-circuit spirometry system in order
to analyze the VO2 amplitude, VO2 delay time, time constant
(tau), and O2 deficit. Tau and O2 deficit were decreased with
LLLT applications compared to the placebo condition
(p < 0.05). No differences (p > 0.05) were found between the
experimental conditions for VO2 amplitude and VO2 delay time.
In conclusion, LLLT decreases tau and O2 deficit during time-
to-exhaustion tests in competitive cyclists, and these changes in
VO2 kinetics response can be one of the possible mechanisms to
explain the ergogenic effect induced by LLLT.

* Fábio J. Lanferdini Keywords Phototherapy . Cycling . VO2 kinetics .

fabiolanferdini@gmail.com Time-to-exhaustion . Sport performance

1
Laboratório de Pesquisa do Exercício, Escola de Educação Física,
Fisioterapia e Dança, Universidade Federal do Rio Grande do Sul, Introduction
Porto Alegre, RS, Brazil
2
Universidade Regional Integrada do Alto Uruguai e das Missões, In the last decade, promising results have been found regard-
Santo Ângelo, RS, Brazil ing the effects of phototherapy [low-level laser therapy
3
University of Calgary, Calgary, AB, Canada (LLLT) and/or light-emitting diodes therapy (LEDT)] on mus-
4
Departamento de Fisioterapia, Universidade Federal de Ciências da
cle fatigue and exercise performance in humans {for a review,
Saúde de Porto Alegre, Porto Alegre, RS, Brazil see Ferraresi et al. [1]; Borsa et al. [2]; Leal Junior et al. [3]}.
5
Laboratório de Biomecânica, Universidade Federal de Santa
Nevertheless, despite the well-documented dose-response ef-
Catarina, Florianópolis, RS, Brazil fect of phototherapy [4], there is no consensus regarding the
6
Portugal Football School, Portuguese Football Federation,
optimal dosage to reduce fatigue in humans. Positive results
Oeiras, Portugal have been found in studies involving isolated quadriceps ex-
7
Research Center in Sports Sciences, Health Sciences and Human
ercise protocols after treatments with both 0.3–0.9 J/diode
Development, CIDESD, University Institute of Maia, (125 J/thigh) [5, 6] and 6 J/diode (180 J/thigh) [7]. Similarly,
ISMAI, Portugal dosages from 0.7 J/diode (37.5 J/thigh) [8] to 6 J/diode (180 J/

thigh) [9] have been effective in improving the exercise toler-
ance in running incremental tests. But none of these studies
has tested a series of phototherapy doses in order to clarify the
optimal dosage to promote increased performance in sports.
Interestingly, most of the previous studies involving cy-
cling protocols found no effect of phototherapy on exercise
performance [10–13]. These studies involved healthy un-
trained subjects [10], professional volleyball players [11,
13], and young soccer players [12, 13]; thus, the absence of
performance improvements might be related to the partici-
pants’ low familiarization to cycling motion. In view of this
issue, our group performed a randomized, double-blind, and
placebo-controlled trial with crossover design with 20 male
competitive cyclists [14]. All athletes performed time-to-
exhaustion cycling tests immediately after treatments with
four different doses of LLLT (3, 6, and 9 J/diode; or 135,
270, and 405 J/thigh, respectively) or placebo on their quad-
riceps muscles, and all LLLT doses led to higher exercise
tolerance than placebo application. Now, the mechanisms re-
sponsible by this enhanced exercise performance should be
clarified to further support phototherapy as an effective ergo-
genic agent in cycling and other sports. Phototherapy is able to
stimulate mitochondrial metabolism and increase energy
availability to the muscle cells [15–17], which might reduce
some mechanisms of muscle fatigue and contribute to the
performance enhancement. In view of this phototherapy effect
on the mitochondrial metabolism, photon absorption can oc-
cur by cytochrome c oxidase. Thus, the greater the activity of
cytochrome c oxidase, the greater is the oxygen uptake (VO2)
consumption and greater is the metabolic energy that is pro-
duced by mitochondrial oxidative phosphorylation [17] and
its kinetics which may also be affected by phototherapy [18].
Furthermore, increased activity of cytochrome c oxidase leads
to increased rates of ATP synthesis and enhanced RNA and
protein synthesis, as well as a shift in overall cell redox poten-
tial and a greater nitric oxide release [2, 4] (Fig. 1). This
increased nitric oxide release, in turn, can be related to in-
creased local muscle oxygenation (e.g., increased concentra-
tion of hemoglobin), measured by near-infrared spectroscopy
(NIRS), which makes it possible to identify the LLLT action
on muscle tissue during exercise in vivo [17].
However, action of LLLT in performance during progressive
running tests in healthy untrained subjects has found conflicting
results [9, 10, 20]. De Marchi et al. [9] and Da Silva Alves et al.
[10] reported higher values of VO2 peak in phototherapy com-
pared to placebo conditions, while Miranda et al. [20] found no
effect of phototherapy on this outcome. In addition, to the best of
our knowledge, only one phototherapy study assessed the VO2
kinetics [8], an analysis on the efficiency of the oxygen delivery
by cardiopulmonary system and the oxygen utilization by the
mitochondria [18, 21]. Findings from this pioneer study suggest
the enhanced performance induced by LEDT is associated with a
reduction in the O2 deficit, tau [that represents rapid response of
Lasers Med Sci
oxygen consumption at the start of the test (~ 20 s)], and increased
amplitude VO2 [8]. However, it is important to note that Ferraresi
et al. [8] assessed a single male runner; thus, additional studies are
necessary to elucidate the effect of phototherapy on VO2 kinetics.
Accordingly, the enhanced exercise performance induced
by phototherapy still needs a mechanistic explanation. Due to
the phototherapy effect on mitochondrial metabolism, we hy-
pothesized the VO2 kinetics analysis would help us to under-
stand the higher exercise tolerance observed in competitive
cyclists assessed in our previous study [14]. Therefore, the
objective of this study was to investigate the effects of differ-
ent LLLT doses (placebo; 3, 6, and 9 J/diode) on VO2 kinetics
(deficit O2, tau, amplitude of VO2, and time delay) during a
cycling time-to-exhaustion test.
Materials and methods
Participants
Twenty male cyclists participated in this study (Table 1).
Subjects had about 2.5 years of cycling experience and train-
ing volume equivalent of 4.6 days/week (~ 260 km/week)
classified as club category according to Ansley and Cangley
[22]. All participants provided written informed consent and
this study was approved by the Ethics Committee of Human
Research of the Federal University of Rio Grande do Sul
(number 708.362).
Experimental design
This study is characterized as a crossover, randomized, dou-
ble-blinded, and placebo-controlled trial. Each volunteer came
to the laboratory on 5 days with a 72-h interval period between
visits. At the first testing session, anthropometric assessment
was followed by a progressive cycling test to determine the
maximal power output (POMAX). Then, participants were ran-
domly assigned to perform four time-to-exhaustion tests (days
2 to 5) after application of different LLLT dosages (3, 6, or 9 J/
diode) or placebo at the quadriceps muscles. Randomization
was performed by the therapist responsible for phototherapy
application and used a simple drawing of lots (A = LLLT-3 J;
B = LLLT-6 J; C = LLLT-9 J; D = placebo). The therapist was
instructed to not communicate the type of treatment neither to
the participants nor to the other researchers before the end of
data collection.
First session: anthropometry and progressive cycling test
In the first session, anthropometric data were measured ac-
cording to the International Society for Advancement of
Kineanthropometry, and body composition was calculated
using a five-component method [23]. Thereafter, the
Lasers Med Sci

Fig. 1 A mechanism of action of

the low-level laser therapy
(LLLT) application in skeletal
muscle to improve performance.
Adenosine triphosphate (ATP),
deoxyribonucleic acid (DNA),
ribonucleic acid (RNA), reactive
oxygen species (ROS), and nitric
oxide (NO), adapted from Huang
et al. [4] and Gupta et al. [19]

participants performed a warm-up at 150 W for 10 min. stage of the incremental test, along with POMAX [26]. The
Cyclists were tested using a standard road cycling bicycle recovery consisted of cycling for 30 min at 50 W. After that,
(Giant TCR Advanced, USA) with configuration of handle- a familiarization with the time-to-exhaustion test was
bars and saddle position set to their anthropometrical charac- performed.
teristics [24]. The bicycle was mounted on a stationary cycling
trainer (CompuTrainer, ProLab 3D, Racermate Inc., Seattle, LLLT or placebo treatment
WA, USA) to determine maximal power output (POMAX).
Before testing, pressure of the bicycle rear wheel was calibrat- LLLT or placebo treatment was applied at nine sites on each
ed according to manufacturer instructions (~ 100 psi). thigh prior to the exhaustion test (Fig. 2). The probe was held
Laboratorial temperature (26–28°) and humidity (~ 50%) stationary above the skin at a 90° angle. Treatments were
were controlled during all testing to minimize temperature delivered using a THOR DD2 Control Unit (THOR®—
effects on bicycle tire pressure and power output measure- London, UK), with a near-infrared laser cluster consisting of
ments [25]. An incremental exercise test was performed to five 810-nm diodes, each one with 200 mW of output power.
determine maximal oxygen uptake (VO2MAX) and POMAX. Previous trials from our research group applied 30 s in each
The progressive test consisted of an initial workload of site, totalizing 6 J per diode (30 J per site) [7, 27]. In the
150 W followed by a constant rate of increments of 25 W/ present study, we also tested a smaller and larger dosages of
min (~ 1 W every 2 s) until exhaustion. The exercise test was LLLT which are 3 J/diode (15 s of therapy per site) and 9 J/
conducted using a custom-made script in cycling trainer soft- diode (45 s of therapy per site). Placebo treatment was per-
ware (CompuTrainer, CS 1.6, Racermate Inc., Seattle, WA, formed exactly the same way as LLLT treatment, with 30 s per
USA). The participants were asked to maintain a pedaling application site, but with the device switched off. Athletes
cadence close to ~ 95 rpm throughout the test using a visual used opaque goggles for protection and to block their view
feedback from the cycling trainer head set. Oxygen uptake on the phototherapy device. To ensure blinding, the device
(VO2) was measured by an open-circuit indirect gas exchange emitted the same sounds regardless of the programmed mode
system (CPX/D, Medical Graphics Corp., St Louis, USA) and (LLLT or placebo), that is, during the placebo treatment, the
VO2MAX was defined as the greatest value obtained in the last device was turned on and immediately turned off so that the
athlete did not receive any type of visual and/or auditory feed-
Table 1 Cyclists back that could identify what type of treatment was being
characterization in terms Cyclists characterization N = 20
performed [14]. In addition, the application of LLLT did not
of antropometric
measurements, body Age (years) 29 ± 7.2 cause an increase in temperature at the application site, as
composition, maximal Body mass (kg) 77 ± 10.1 discussed by Wang et al. [28].
power output (POMAX), Height (cm) 179 ± 7.9
and maximal oxygen
Muscle mass (kg) 39 ± 5.7 Time-to-exhaustion tests
uptake (VO2MAX) during
a maximal incremental Fat mass (kg) 18 ± 4.2
cycling test POMAX (W) 378 ± 34.5 In sessions 2 to 5, the participants performed a warm-up at
VO2MAX (ml kg min−1) 57 ± 7.8 150 W for 10 min and soon after time-to-exhaustion tests
were performed about 4–5 min after LLLT or placebo

Fig. 2 Low-level laser therapy (LLLT) parameters and application sites for LLLT application or placebo condition prior time-to-exhaustion test and
illustration of application in one cyclist
treatment. Cyclists performed the tests at their POMAX with
a road bicycle (Giant TCR Advanced, USA) mounted at
the stationary cycling trainer (Computrainer, ProLab 3D,
Racermate Inc., Seattle, WA, USA). The bicycle with con-
figuration of handlebars and saddle position set to their
anthropometrical characteristics [24, 29], and in all condi-
tions with load corresponding at POMAX and cadence fixed
95 ± 5 rpm for all athletes using visual feedback from the
cycling trainer head set. Exhaustion was defined as the
moment that each cyclist was no longer capable of main-
taining a cadence above 70 rpm. During the tests, pulmo-
nary gas exchange and ventilation were measured breath-
by-breath by an open-circuit indirect gas exchange system
(CPX/D, Medical Graphics Corp., St Louis, USA). The gas
analyzers were calibrated before each test to exhaustion
with gases of known concentration, and the turbine volume
transducer was calibrated with a 3-l syringe [30].
Data analysis
As the initial VO2 phase (first 20 s) is mainly attributed to
the increase in cardiac output and pulmonary blood flow,
the onset of exercise was not considered for the modeling
(cadiodynamic phase). Errant breaths (e.g., caused by
swallowing, coughing, and signal interruptions) were omit-
ted from the VO2 analysis by including only those that were
between VO2 mean ± four standard deviations. After this
process, individual VO2 responses were smoothed using a
3-breath moving average and time average every 5 s [31].
The VO2 kinetics analysis was implemented in MatLab
Software (Mathworks, USA). Data were modeled using a
single exponential model to characterize the VO2 responses
Lasers Med Sci
during maximal exhaustion test in cycling. Single exponen-
tial model was used because the maximum exhaust tests
lasting about 3 min [21] did not show the slow component
of the VO2 curve of data analysis (Eq. 1).
VO2 ðt Þ ¼ VO2 baseline þ H ðt−TDpÞ
 Apðl−e−ðt−TDp=τpÞÞ ð1Þ
where VO2 (t) represents the absolute VO2 at a given time
(t); VO2 baseline represents the mean VO2 in the baseline
period; Ap, TDp, and p represent the amplitude VO2, time
delay, and time constant (tau = τ), respectively. H repre-
sents the Heaviside step function as described by Ma et al.
[32]. Furthermore, it also calculated total muscular oxygen
deficit [deficit O2 = (τ + TDp) Ap] descript function by
Whipp and Casaburi [33].
Statistical analysis
Data normality and sphericity were assessed by the
Shapiro-Wilk and Mauchly’s tests, respectively. A one-
way ANOVA with repeated measures was used to compare
the VO2 kinetics variables (O2 deficit, tau, VO2 amplitude,
and time delay) among the four different phototherapy con-
ditions (placebo, LLLT-3 J, LLLT-6 J, LLLT-9 J). If the
main effects were significant, post-hoc LSD tests were
used to identify significant differences. Statistical analysis
was performed with SPSS 20.0 for Windows, with a sig-
nificance level of α = 0.05 and observed power β
(OP ≥ 0.80).
Lasers Med Sci
Results
Cyclists completed the four trials adequately, since the target
cadence (100 ± 5 rpm) was maintained during the tests [pla-
cebo = ~ 95 rpm; LLLT-3 J = ~ 96 rpm; LLLT-6 J = ~ 96 rpm;
LLLT-9 J = ~ 95 rpm (p > 0.05 and OP < 0.10)]. No changes in
power output were observed during the test or between trials
[placebo = ~ 407 W; LLLT-3 J = ~ 414 W; LLLT-
6 J = ~ 411 W; LLLT-9 J = ~ 411 W (p > 0.05 and
OP < 0.30)]. As presented in the previous study of our group
[14], time-to-exhaustion was increased in LLLT-3 J (15%),
LLLT-6 J (9%), and LLLT-9 J (9%) tests compared to the
placebo test.
Phototherapy LLLT-3 J, 6 J, and 9 J applied pre-exercise
reduced the O2 deficit and tau compared with the placebo
treatment. LLLT-3 J reduced deficit O2 by 23% (p < 0.01
and OP = 0.81) and tau by 37% (p < 0.01 and OP = 0.86)
compared with placebo, whereas LLLT-6 J reduced deficit
O2 by 17% (p = 0.02 and OP = 0.81) and tau by 33% (p = 0.01
and OP = 0.86); and LLLT-9 J presented reduction ~ 18% in
deficit O2 (p = 0.01 and OP = 0.81) and ~ 33% in tau (p = 0.01
and OP = 0.86) compared with placebo. There were no dif-
ferences between phototherapy conditions for amplitude
VO2 and time delay compared with the placebo condition
(p > 0.05 and OP < 0.80) Fig. 3.
Fig. 3 Results of kinetics VO2 (deficit O2, tau, amplitude of VO2, and time delay). *Significant difference between phototherapy conditions compared
with placebo for deficit O2 and tau (p ≤ 0.02 and OP > 0.80)
Discussion
According to our findings, there was a reduction of O2 deficit
and tau induced by different doses of LLLT previously applied
to time-to-exhaustion test, compared with the placebo situa-
tion in competitive cyclists. These changes in VO2 kinetics
response can be one of the possible mechanisms to explain the
increased performance (9 to 15%) in the time-to-exhaustion
test in our previous study, with application of all doses LLLT
compared to placebo [14].
VO2 kinetics and time-to-exhaustion
The reduction of O2 deficit associated with reduced tau, VO2
increased rate during the square wave transition from rest to
POMAX according to Hughson et al. [34], involves two as-
pects: central (oxygen transport) and peripheral (extraction
and utilization of mitochondrial O2). The results of this study
demonstrate that the different doses of LLLT cause reduction
of O2 deficit associated with tau reduction (faster kinetics)
compared with the placebo condition. These results may be
associated with greater efficiency in the transport and utiliza-
tion of ATP by the aerobic metabolism (oxidative phosphor-
ylation) and the alactic anaerobic metabolism {PCr system
[35]}. Moreover, the results suggest a greater breakdown of

ATP by aerobic metabolism in fast-twitch fibers [18], resulting
in increased muscle activation of the fast-twitch fibers (high-
frequency band), and thus causing increased time-to-
exhaustion with the use of LLLT, compared with the placebo
condition [14]. It has been reported that phototherapy can
increase the activity of complex IV {cytochrome c oxidase;
[36]}, as well as other electrical mitochondrial transport chain
complexes [37]. Thus, improved blood oxygen transport and
delivery into muscle cells, together with the increased mito-
chondrial metabolism, can modulate the O2 response during
exercise, explaining the results of O2 kinetics. Therefore, the
analysis of VO2 kinetics can show how effective is the devel-
opment of oxygen supply (the cardiorespiratory system) and
oxygen utilization (the mitochondria). Thus, between the cur-
rent methods for the analysis, and exponential modeling O2
data, kinetic, it seems to provide the best information on the
O2 response during exercise {e.g., VO2 response speed exer-
cise, that take place tau and changes in the O2 deficit [38, 39]}.
In addition, animal studies have shown that the application of
LLLTcan improve mitochondrial function, resulting in increased
release of ATP [16, 18] and increased microcirculation and tissue
oxygenation [40, 41]. Furthermore, studies in healthy humans
have shown improvement in muscle function, fatigue resistance,
and increased oxygen consumption and increased time-to-
exhaustion tests [1, 8, 9], and reducing the blood lactate concen-
tration and muscle damage markers [9, 13, 42]. In addition, pre-
vious studies have investigated the effect of LLLT on the hemo-
dynamic and mitochondrial function in vivo. Their results
showed an increase of cytochrome c oxidase action [17, 43],
which resulted in increased ATP synthesis as well as increase in
RNA and protein synthesis, leading to changes in intracellular
redox potential and increased release of nitric oxide [4].
Therefore, these biochemical cascade reactions induced by pho-
totherapy can lead to improved muscle function and, consequent-
ly, improve exercise performance.
However, there were no changes between different dosages
of LLLT and VO2 kinetics on the performance in time-to-
exhaustion test [14]. The absence of difference between LLLT
dosages may be related to the mass volume differences quadri-
ceps muscle between cyclists evaluated in our study. Different
muscle volumes may require different dosages LLLT to pro-
mote changes in performance over a maximum test until ex-
haustion in cycling. Borsa et al. [2] suggest that lower doses
(under-dosing) have no or minimal effect on cellular function,
while moderate to strong doses may positively increase cellular
function. On the other hand, very high doses (overdosing) can
suppress or inhibit cell function. Therefore, the three LLLT
dosages tested in this study may have promoted different effects
on different cyclists. Recently, a meta-analysis [3] suggested
that the optimal doses of LLLT vary between 5 and 6 J/diode,
however, even if the investigation offurther studies in humans is
necessary to elucidate which are the optimal dose of photother-
apy muscle group, different exercises, and populations.
Lasers Med Sci
Furthermore, previous studies using cycling tests [10, 11, 13,
44] applied LLLT or LEDT of 12 J to 83 J doses of each muscle
group quadriceps, which are considerably smaller than those
applied in our study (135, 270, and 405 J/quadriceps) or in studies
focusing on isolated exercises of the knee extensors {125–180 J/
muscle group [5–7]}. These lower dosages of phototherapy ap-
pear to be insufficient to promote increased cycling performance.
De Marchi et al. [9] and Miranda et al. [20] observed positive
results of applied phototherapy (180–270 J/quadriceps muscle)
in performance and increase in maximal oxygen consumption
during maximal incremental test of running.
Our results showed that doses of LLLT 135 to 405 J
applied on the quadriceps muscle caused an increase in
time-to-exhaustion (improve performance) in cyclists
[14]. However, the optimum dosage LLLT, and the influ-
ence of different light sources (LLLT or LEDT) and other
phototherapy parameters (e.g., wavelength, output power,
and application time) to increase cycling performance or
even in the race remain unclear. The effect of the dose-
response has been well described in animal studies involv-
ing phototherapy and exercise [45–47], but only a few
human studies have investigated the effects of different
LLLT doses on muscle performance [48, 49].
Limitations and strengths
The limitations of this study are associated with no use of
any fatigue marker (e.g., lactate) and muscle damage mark-
er (e.g., creatine kinase, interleukin-6, and C-reactive pro-
tein). Another limitation is not measuring concentrations of
oxyhemoglobin, deoxyhemoglobin, and total hemoglobin
with infrared spectroscopy equipment (NIRS) in order to
investigate the effect of LLLT on the local oxygen concen-
tration. Moreover, evidence suggests the best time for
LLLT application is about 10 min prior to exercise [8]
and the best wavelength/light should be between 600 and
900 nm [15] or combination of wavelengths/light sources
[48]. Therefore, these aspects should be clarified in future
studies. The decisive and natural step will be the future use
of LLLT in field tests, such as during a cycling race in
order to identify the use of LLLT as a possible ergogenic
agent in high-performance sports.
Conclusion
In summary, LLLT demonstrated that phototherapy is able to
improve VO2 kinetics, reducing tau and O2 deficit compared
with the placebo trial. This dose-response effect requires fur-
ther research for the establishment of phototherapy (e.g.,
LLLT) optimal dosages for different size of muscle mass and
types of exercise.
Lasers Med Sci
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Ethical approval All procedures performed in studies involving hu-
man participants were in accordance with the ethical standards of the
institutional and/or national research committee, approved by the Ethics
Committee of Human Research where the study was conducted (number
708.362) and with the 1964 Helsinki declaration and its later amendments
or comparable ethical standards.
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