Effectiveness of Oral and Topical Hydrogen for Sports-Related Soft Tissue Injuries

Abstract

Background:
Because hydrogen therapy has been found beneficial for the treatment of inflammation, ischemia-reperfusion injury, and oxidative stress in humans, it seems useful to evaluate the effects of exogenously administered hydrogen as an element in the immediate management of sports-related soft tissue injuries. The main aim of this pilot study was to examine the effects of 2-week administration of hydrogen on the biochemical markers of inflammation and functional recovery in male professional athletes after acute soft tissue injury.

Method:
During the 2013 season (from March to May), 36 professional athletes were recruited as participants and examined by a certified sports medicine specialist in the first 24 hours after an injury was sustained. Subjects were allocated to 3 randomly assigned trials in a single-blind design. Those in the control group received a traditional treatment protocol for soft tissue injury. Subjects in the first experimental group followed the same procedures as the control group but with additional administration throughout the study of oral hydrogen-rich tablets (2 g per day). Subjects in the second experimental group also followed the procedures of the control group, with additional administration throughout the study of both oral hydrogen-rich tablets (2 g per day) and topical hydrogen-rich packs (6 times per day for 20 minutes). Participants were evaluated at the time of the injury report and at 7 and 14 days after baseline testing.

Results:
Oral and topical hydrogen intervention was found to augment plasma viscosity decrease as compared with the control group (P = 0.04). Differences were found for range-of-motion recovery between the 3 groups; oral and topical hydrogen intervention resulted in a faster return to normal joint range of motion for both flexion and extension of the injured limb as compared with the control intervention (P < 0.05).

Conclusion:
These preliminary results support the hypothesis that the addition of hydrogen to traditional treatment protocols is potentially effective in the treatment of soft tissue injuries in male professional athletes. Trial identification: Clinicaltrials.gov number NCT01759498.

Full text

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CLINICAL FEATURES
Effectiveness of Oral and Topical Hydrogen for
Sports-Related Soft Tissue Injuries
Sergej M. Ostojic, MD,
PhD1,2
Boris Vukomanovic, MD1,3
Julio Calleja-Gonzalez,
PhD1,4
Jay R. Hoffman, PhD,
FACSM, FNSCA5
1Center for Health, Exercise, and
Sport Sciences, Stari DIF, Belgrade,
Serbia; 2Faculty of Sport and Physical
Education, University of Novi
Sad, Novi Sad, Serbia; 3Institute
of Orthopaedic-Surgical Diseases
“Banjica,” Belgrade, Serbia; 4Faculty
of Sport Sciences, University of the
Basque Country, Vitoria-Gasteiz,
Spain; 5Institute of Exercise Physiology
and Wellness, University of Central
Florida, Orlando, FL
Correspondence: Sergej M. Ostojic, MD,
PhD,
Center for Health, Exercise, and Sport
Sciences,
Stari DIF,
Deligradska 27,
Belgrade 11000, Serbia.
Tel: (++381)-11-2643-242
Fax: (++381)-11-2643-242
E-mail: sergej.ostojic@chess.edu.rs
DOI: 10.3810/pgm.2014.09.2813
Abstract
Background: Because hydrogen therapy has been found benecial for the treatment of inam-
mation, ischemia-reperfusion injury, and oxidative stress in humans, it seems useful to evaluate
the effects of exogenously administered hydrogen as an element in the immediate management
of sports-related soft tissue injuries. The main aim of this pilot study was to examine the effects
of 2-week administration of hydrogen on the biochemical markers of inammation and func-
tional recovery in male professional athletes after acute soft tissue injury. Method: During the
2013 season (from March to May), 36 professional athletes were recruited as participants and
examined by a certied sports medicine specialist in the rst 24 hours after an injury was sus-
tained. Subjects were allocated to 3 randomly assigned trials in a single-blind design. Those in
the control group received a traditional treatment protocol for soft tissue injury. Subjects in the
rst experimental group followed the same procedures as the control group but with additional
administration throughout the study of oral hydrogen-rich tablets (2 g per day). Subjects in the
second experimental group also followed the procedures of the control group, with additional
administration throughout the study of both oral hydrogen-rich tablets (2 g per day) and topical
hydrogen-rich packs (6 times per day for 20 minutes). Participants were evaluated at the time of
the injury report and at 7 and 14 days after baseline testing. Results: Oral and topical hydrogen
intervention was found to augment plasma viscosity decrease as compared with the control group
(P = 0.04). Differences were found for range-of-motion recovery between the 3 groups; oral and
topical hydrogen intervention resulted in a faster return to normal joint range of motion for both
exion and extension of the injured limb as compared with the control intervention (P , 0.05).
Conclusion: These preliminary results support the hypothesis that the addition of hydrogen to
traditional treatment protocols is potentially effective in the treatment of soft tissue injuries in
male professional athletes. Trial identication: Clinicaltrials.gov number NCT01759498.
Keywords: plasma viscosity; interleukin-6; range of motion; RICE protocol; hydrogen
Introduction
Increased participation in sports during the last 2 decades has been accompanied by an
increase in rates of sports injuries among both professional and recreational athletes,
with soft tissue injuries (eg, muscle sprain, ligament strain, tendonitis, contusion)
accounting for . 75% of all injuries.1–3 Timely and effective management of sports-
related soft tissue injuries is a key factor contributing to a quicker recovery and return
to regular training and competition.4 Soft tissue repair is often facilitated by conser-
vative procedures such as the RICE (rest, ice, compression, and elevation) protocol
and topical or oral administration of nonsteroidal anti-inammatory drugs to relieve
pain, swelling, or bruising and to improve functional movement.5 An added problem
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with soft tissue injuries is the further cell damage that can be
caused by tissue hypoxia and acute reactive oxygen species
(ROS) produced at the site of the injury. This subsequent
tissue damage is often referred to as the secondary zone of
injury, to distinguish it from the initial damage caused by
the actual mechanism of injury.6 As secondary injury fol-
lowing musculoskeletal trauma causes serious damage to
soft tissues,6 an intervention that focuses on the damaging
effects of ROS may have several potential advantages over
current therapies for achieving prompt recovery. Hydrogen
therapy has been found to be benecial in the treatment of
inammation, ischemia-reperfusion injury, and oxidative
stress in humans,7 and it therefore seems useful to evaluate
the effects of hydrogen as an element in the management of
acute sports-related soft tissue injuries.
Hydrogen is known to act as a potent antioxidant that
rapidly diffuses to subcellular compartments and directly
eliminates hydroxyl radical, a highly cytotoxic species
produced in inamed tissues.8 Other biochemical effects of
hydrogen therapy may also be relevant (eg, hydrogen func-
tioning as a gaseous signaling molecule).9 The prominent
effects of hydrogen in preventive and therapeutic applications
have previously been observed in cases of cerebral infarc-
tion,10 chronic inammation in patients with hemodialysis,11
inammatory myopathies,12 metabolic syndrome,13 diabetes
mellitus,14 Parkinson’s disease,15 and rheumatoid arthritis.16
It seems likely that hydrogen treatment might effectively
protect cells, tissues, and organs against oxidative injury
and help them to recover from dysfunction. In particular,
hydrogen delivery to cardiomyocytes has efciently amelio-
rated secondary injury of muscle cells due to ischemia and
reperfusion,17 suggesting a possible therapeutic application
for hydrogen in common soft tissue injuries. However, no
study has so far validated this therapeutic potential for the
treatment of soft tissue injuries in the eld of sports medi-
cine. The main aim of this preliminary study was to examine
the effects of 2-week oral and/or topical administration of
hydrogen on inammation, recovery, functional ability, and
pain intensity in competitive male athletes after acute soft
tissue injury. We hypothesized that the addition of hydrogen
to traditional treatment protocol would enhance recovery
and reduce inammation in male athletes following a sports-
related soft tissue injury.
Method
Study Population
Athletes were eligible to participate in the study if they had
a recent history of acute soft tissue sports injury and clinical
ndings consistent with trauma. Acute soft tissue sports
injury was dened as a direct or indirect trauma incurred
during any sports-related activity that caused absence from
training or competition. During the 2013 season (from March
to May), 36 professional athletes were recruited and exam-
ined by a certied sports medicine specialist in the outpatient
clinics of the Center for Health, Exercise, and Sport Sciences
(Belgrade, Serbia) within 24 hours of sustaining an injury.
Characteristics of the participants are presented in Table 1.
Based on amount of pain, weakness, and loss of motion,
clinical ndings were categorized as follows: grade I, mild,
with some swelling and pain on stretch, but function and
strength are mostly unaffected; grade II, moderate, with
pain and swelling at the site, and some loss of function and
strength; and grade III, severe, with considerable loss of func-
tion and strength, and with injuries that often need surgical
repair.18 Patients who were not ambulatory or who had clini-
cal ndings classied as more signicant than grade II were
excluded from the study. For diagnostic consistency of inclu-
sion criteria for soft tissue injury and the grading of clinical
ndings, the same observer evaluated all study participants;
all participants provided informed consent and volunteered
to participate in the study. The protocol was approved by
the local institutional review board in accordance with the
Declaration of Helsinki. At the rst assessment session, par-
ticipants were fully informed, verbally and in writing, about
the nature and demands of the study as well as the known
health risks. They completed a health history questionnaire
and were informed that they could withdraw from the study
at any time, even after giving their written consent. All sub-
jects were in good health (eg, no evidence of diabetes, heart
disease, or cancer), were nonsmokers, participated in regular
training (average of 12 hours per week) for the past 5+ years,
and were not currently taking a drug or dietary supplement
that contained hydrogen (or any similar preparation).
Table 1. Characteristics of the Study Population (n = 36)
Age (mean ± SD) 23.1 ± 2.3 years
Professional experience (mean ± SD) 5.2 ± 1.1 years
Sport played Soccer (n = 17)
Basketball (n = 10)
Track and eld (n = 4)
Other (n = 5)
Type of injury Ligament sprain (n = 21)
Muscle strain (n = 8)
Contusion (n = 6)
Other (n = 3)
Location of injury Lower limb (n = 19)
Upper limb (n = 10)
Other (n = 7)
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Experimental Procedures
This is an early evaluation study of hydrogen effectiveness for
sports injuries, with follow-up at 2 weeks. In a single-blind
design, participants were randomly assigned to 1 of 3 trials
using a computer-generated list. During the 2-week study
period, subjects in the control group received a traditional
treatment protocol for soft tissue injuries that included the
RICE protocol (rest, ice packs for 20 minutes every 2 hours,
compression with elastic bandage, and elevation at all pos-
sible times of the injured area above the level of the heart)
during the rst 48 hours, and a subacute protocol thereafter
(passive stretching 3 times per day for 90 seconds, 3 sets of
isometric strength exercises with 15 repetitions, and 30 min-
utes of pain-free weight-bearing exercises).
Subjects in the rst experimental group (HYD1) followed
the procedures for the control group, with the additional
administration throughout the study of oral hydrogen-rich
tablets (2 g per day). Subjects in the second experimental
group (HYD2) also followed the control group procedures,
with the additional administration throughout the study of
both oral hydrogen-rich tablets (2 g per day) and topical
hydrogen-rich packs (6 times per day for 20 minutes). The
oral hydrogen treatment formulation was provided in tablet
form by SevenPoint2 (7.2 Recovery with HydroFX, Newport
Beach, CA), and participants were instructed to take 4 tablets
3 times a day, before main meals. The topical hydrogen
treatment formulation was provided by NORP Inc. (San
Diego, CA), and participants were instructed to administer
the hydrogen pack directly to the skin above the site of the
injury, using elastic wrap to secure the pack. During the
administration period, all subjects refrained from training.
No other interventions were performed.
Participant Evaluation
Participants were evaluated at the beginning of the study
(at the time of injury report) and at 7 and 14 days after the
report of injury. For baseline testing prior to administration,
fasting blood was collected from a radial vein into a gel
Vacutainer for biochemical measures; serum C-reactive pro-
tein (CRP) and serum interleukin-6 (IL-6) were determined
using a highly sensitive enzyme-linked immunosorbent
assay (ELISA) procedure (eBioscience, San Diego, CA);
and plasma viscosity at 25oC was measured using a capil-
lary viscometer (Coulter Viscometer II, Electronics Ltd.,
Luton, UK). Pain intensity was assessed using a visual
analogue scale of 1 to 15.19 Participants completed 2 visual
analogue assessments at each visit, 1 representing pain
intensity while at rest, and the other representing pain while
walking. Passive joint exibility of the injured limb in the
sagittal plane was measured using a modied goniometer
with spirit level (Creative Health Inc., Plymouth, CA),
recording decits of exion and extension. The degree
of limb swelling at the site of injury was measured with
anthropometric tape (Creative Health Inc.) and compared
with the uninjured limb. To assess potential side effects of
the treatment regimen, all subjects were instructed to report
any adverse effects of administration (eg, skin irritation, rush)
during each visit to the medical center.
Statistical Analyses
The primary efcacy outcome was change in serum CRP
level at 2 weeks after administration (effect size of 1.0)
in the HYD1 group as compared with the control group.
Allowing for . 80% power, it was estimated that 10 par-
ticipants per group would be required in the nal analyses;
this was adjusted to 12 subjects per group to accommodate
a predicted 20% dropout rate. All results were expressed as
mean ± standard deviation. For group comparison at a series
of time points during intervention, the area under the curve
(AUC) was rst identied and calculated for all dependent
variables for each subject.20 The Shapiro-Wilk test was then
applied to summary measures (mean AUC) for each group to
assess normality of distribution, and Bartlett’s test was used to
assess homogeneity of variances. Where homogeneous vari-
ances were veried for normally distributed data, summary
measures were compared by analysis of variance (ANOVA).
In the event of a signicant F ratio (the ratio of the variance
between groups to the variance within groups), post-hoc
Tukey honest signicant difference tests were employed to
identify differences between individual sample pairs. Where
nonhomogeneous variances were identied, mean AUCs
were compared using the 3 independent samples Kruskal-
Wallis test, and the Games-Howell post-hoc test was used to
identify signicant differences between any 2 groups. Effect
size (Cohen’s d) was calculated for all variables; a Cohen’s
d . 0.5 and # 0.8 is considered moderately strong, and a
value . 0.8 is considered strong. For all statistical tests,
a criterion alpha level of P # 0.05 was used to determine sta-
tistical signicance. All statistical analyses were performed
using SPSS (Version 21, SPSS Inc., Chicago, IL).
Results
A total of 36 participants completed the study, with no partici-
pants lost on follow-up. Most participants received all inter-
ventions regularly, but a few omitted some quantity of tablets
and/or packs. Total compliance with the hydrogen regimen
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was 83% for the HYD1 group and 75% for the HYD2 group.
Two participants from the HYD1 group reported mild diar-
rhea during the rst 2 days of the intervention. No additional
side effects were reported, and no serious adverse events
occurred during the study.
Changes in plasma inammatory markers during the
study are presented in Table 2. The HYD2 intervention was
found to augment plasma viscosity decrease as compared
with the control group (P = 0.04), whereas the magnitude
of alteration for other markers of inammation (CRP, IL-6)
did not differ signicantly between the control group and
hydrogen regimens (P . 0.05). However, Table 3 shows that
small-to-medium effect sizes were found for plasma viscosity
and IL-6 for both hydrogen protocols (d . 0.35).
In all 3 groups, signicant decreases in pain scores,
at rest and while walking, were observed after the rst
and second week, respectively (Figure 1). No differences
were found for pain score changes between the groups
(P . 0.05). However, for pain scores at walking, a moderate-
to-large effect size was found for the HYD2 intervention as
compared with the control group (d = 0.74). Injured limb
swelling decreased throughout the study (Figure 2), but no
differences were found between groups for degree of swell-
ing reduction (P . 0.05). Finally, differences were found
between the 3 groups for range of motion (ROM) recovery
(Figure 3); as compared with the control intervention, the
HYD2 intervention resulted in faster return to normal joint
ROM for both exion and extension of the injured limb
(P , 0.05).
Discussion
In this preliminary study, we had the unenviable task of
trying to improve upon an already very effective traditional
treatment for mild-to-moderate soft tissue sports injuries
with the addition of hydrogen. We have shown that 2-week
oral and topical hydrogen intervention augments the plasma
viscosity decrease and enhances recovery of joint exibility
in male athletes following a sports-related soft tissue injury,
as compared with the control intervention. Hydrogen admin-
istration (in either tablet or topical form) did not result in
a statistically signicant difference in plasma CRP, IL-6,
pain scores, or limb swelling as compared with control. The
primary ndings here provide evidence that oral and topical
hydrogen may be effective as an adjunct agent in traditional
conservative treatment of soft tissue injuries.
The medical application of hydrogen in humans was
rst reported nearly 40 years ago,21 and has subsequently
been evaluated in a number of experimental and clini-
cal contexts. Although research on the health benets of
hydrogen remains limited, with scant data on long-term
effects, hydrogen has been identied as benecial in the
prevention and treatment of a wide range of diseases.10–16
The therapeutic effects of hydrogen have been attributed to
4 major molecular mechanisms: specic scavenging activi-
ties of hydroxyl radical and of peroxynitrite, alterations of
gene expression, and signal-modulating activities.7 Because
hydrogen is known to scavenge toxic ROS and to induce
a number of antioxidant proteins during inammation,22
its use is likely to have a signicant impact, especially
Table 2. Changes in Plasma Inammatory Markers During the Studya
Baseline Week 1 Week 2 AUC P value Post-hoc differencesb
C-reactive protein (mg/L)
CON 60.2 ± 38.3 34.3 ± 21.3 18.7 ± 10.4 73.7 ± 44.4 0.97c–
HYD1 75.0 ± 71.1 47.5 ± 44.5 29.4 ± 29.8 99.7 ± 93.4
HYD2 62.6 ± 36.0 37.0 ± 24.3 21.9 ± 12.1 79.2 ± 47.1
Interleukin-6 (pg/mL)
CON 92.5 ± 24.3 72.3 ± 10.5 68.6 ± 6.9 152.9 ± 24.4 0.45c–
HYD1 105.7 ± 35.7 77.2 ± 11.5 68.1 ± 8.6 164.1 ± 31.2
HYD2 101.0 ± 22.8 74.1 ± 12.5 67.3 ± 7.7 158.3 ± 25.4
Viscosity (mPa⋅s)
CON 1.45 ± 0.12 1.34 ± 0.10 1.26 ± 0.10 2.70 ± 0.20 0.04d e
HYD1 1.42 ± 0.15 1.26 ± 0.08 1.19 ± 0.07 2.57 ± 0.17
HYD2 1.39 ± 0.14 1.25 ± 0.07 1.16 ± 0.06 2.52 ± 0.15
aValues are mean ± SD (n = 36). AUC is dened as the area under the plot of serum concentration of selected outcome (not logarithm of the concentration) against time
after intervention administration.
bSignicant difference at P , 0.05.
cP value from independent samples Kruskal-Wallis test.
dP value from 3-sample unpaired ANOVA test.
eCON vs HYD2.
Abbreviations: AUC, area under the curve; CON, control group; HYD1, group supplemented with oral hydrogen; HYD2, group supplemented with oral hydrogen and
topical hydrogen packs.
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on oxidative stress-mediated disorders and inammatory
diseases in humans.
As has previously been reported, oxidative stress is a
signicant factor in cell damage arising from sports-related
soft tissue injuries.23 The acute response to trauma includes
a drastic activation of immunocompetent cells and fac-
tors, interstitial edema, and reduction of the microvascular
blood supply, when highly toxic ROS are released during
the peroxidation of membrane lipids.24 This results in cell
destruction and subsequent pain, swelling, bruising, and loss
of function.25 The standard medical treatment involves the
RICE protocol, which reduces associated swelling and pain,
but rapid elimination of ROS and inammation markers in
athletes suffering soft tissue injuries may be benecial for
enhanced recovery in terms of clinical markers and functional
abilities. Our results suggest that the addition of hydrogen
to traditional soft tissue injury treatment positively affects
selected clinical and biochemical indicators of postinjury
recovery such as plasma viscosity and exibility of the
injured area.
Several inammatory markers (eg, CRP, erythrocyte
sedimentation rate, brinogen, ferritin, IL-6, and plasma
viscosity) are monitored in musculoskeletal medicine
after the injury and inammation.26 These biomarkers are
elevated immediately after a soft tissue injury, with levels
correlating to the clinical stages of the condition.27 Evaluation
of the time course of biomarkers after injury is relevant for
monitoring management and recovery.26 In the present study,
a decrease in selected blood inammatory markers was
noted throughout, for all experimental protocols, indicating
reduced inammation during recovery. However, signicant
differences were found between groups for changes in plasma
viscosity; athletes who supplemented with both topical and
oral hydrogen experienced a much faster decline in plasma
viscosity relative to the control group. Because plasma
viscosity sensitivity and specicity are better than those of
erythrocyte sedimentation rate or CRP in inammation,28
we can assume that the hydrogen treatment may have posi-
tively affected the inammation process in injured athletes.
Although oxidative stress is involved in the development of
postinjury inammation, the antioxidant effect of hydrogen
may not be the only driving factor causing positive anti-
inammatory effects of administration; the possible impact of
hydrogen on downregulation of proinammatory citokines12
after musculoskeletal injury requires further investigation.
Although most sports-related soft tissue injuries recover
rapidly, different therapy protocols are implemented to
accelerate the process of return to sport after injury.29 With
restoration of function of the injured limb as a main goal of
injury treatment, aggressive acute and subacute treatment
protocols during healing will facilitate recovery in athletes.25
Traditional medical treatment of soft tissue injury is designed
to decrease swelling and pain, and to regain the mobility of
the injured limb. The present study demonstrates similar
positive dynamics of recovery for limb swelling and pain
among groups, both at rest and while walking. It seems that
the addition of hydrogen to the traditional treatment proto-
col did not affect pain reduction or edema during recovery
when compared with traditional treatment only. However,
comparison of effect size for pain while walking revealed
a moderate-to-large effect of treatment between the control
group and the group supplemented with both oral and topical
hydrogen (d = 0.74). Although the P value was insignicant,
it seems that the hydrogen group clinically outperformed the
control group in respect to pain control. This is meaningful in
a clinical context, suggesting that adding hydrogen to tradi-
tional treatment methods may be more effective in reducing
pain during recovery.
Interestingly, subjects supplemented with hydrogen
showed statistically signicant improvement in range of
motion of the injured limb during recovery. Although some
improvements were seen in both exion and extension of
injured limb after hydrogen administration, the effects were
no more than small to moderate, indicating modest clinical
relevance for health care providers. However, it seems that
the use of a control group consisting of an active treat-
ment (ie, RICE protocol) along with a limited number of
participants recruited probably made it harder to show the
benecial effects of intervention. We attempted to improve
on this active and effective treatment for soft tissue injuries
with the addition of hydrogen, yet the use of a true control
Table 3. Effect Size Between Groups for Mean Gain Scores
During the Studya
HYD1 vs
CON
HYD2 vs
CON
HYD1 vs
HYD2
C-reactive protein 0.03 0.01 0.03
Interleukin-6 0.38 0.41 0.12
Viscosity 0.32 0.44 0.08
Pain at rest 0.20 0.09 0.29
Pain at walking 0.35 0.74 0.46
Degree of swelling 0.18 0.05 0.03
ROM decit in exion 0.09 0.08 0.05
ROM decit in extension 0.27 0.14 0.31
aEffect sizes are indicated as small (d = 0.20–0.49), medium (d = 0.50–0.79), and
large (d $ 0.80).
Abbreviations: CON, control group; HYD1, group supplemented with oral
hydrogen; HYD2, group supplemented with oral hydrogen and topical hydrogen
packs; ROM, range of motion.
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group without any treatment probably would augment the
favorable effects of hydrogen, both statistical and clinical,
which requires further research.
Previous studies found no serious adverse events of oral
hydrogen administration, which is reported to be safe and
easily applicable to humans.10–16,30 This aligns with the results
of the present study, in which there were no reports of severe
side effects that might have limited participation, although
2 participants from the HYD1 group reported early diarrhea
that was resolved after a few days of treatment. Although the
diarrhea was reported to be mild in intensity, the abdominal
side effects of hydrogen need further investigation.
Based on the data presented here, there is insufcient
evidence to conclude that administration of hydrogen is
a safe therapeutic strategy for soft tissue injuries. Fur-
thermore, neither the long-term safety of hydrogen use in
humans nor the pharmacokinetics of oral or topical hydro-
gen administration have as yet been studied in depth. It fol-
lows that phase II clinical studies are warranted on hydrogen
biotransformation and removal, along with postmarketing
Figure 1. Pain at rest and while walking during the study.
Abbreviations: CON, control group; HYD1, group supplemented with oral hydrogen; HYD2, group supplemented with oral hydrogen and administered with topical
hydrogen-rich packs.
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surveillance trials to determine its distribution, metabolism,
and excretion, and evaluation of rare or long-term adverse
effects of hydrogen over a much larger patient population
and longer time period than was possible during the pilot
trials. In the present study, poor compliance within treat-
ment may be accounted for by participants’ perceptions of
the treatment as short-term, and by their improved sense
of well-being before the end of the study, which would
accord with earlier ndings of low adherence.31 However,
these compliance issues need more clarication before any
nal conclusion can be reached on hydrogen efcacy and
safety in sports medicine.
Despite the evidence presented here that hydrogen admin-
istration positively affects recovery from soft tissue injury
in male professional athletes, the present study has several
limitations. First, this early evaluation was conducted with
single-blinded design, no placebo control, and exclusion of
subjects with severe musculoskeletal injuries. Future stud-
ies should evaluate the efcacy of molecular hydrogen in
sports medicine using double-blind, randomized trials with
a placebo-controlled approach on large patient groups that
include both moderate and severe sports-related injuries.
Second, other possible confounding factors were not consid-
ered that might be responsible for variations in recovery out-
comes between groups, such as the site, mechanism, and type
of injury, the age and professional experience of participants,
and previous history of injuries. Third, the small size of the
experimental groups (n = 12) could be considered a limiting
factor, not least because compliance with the protocol was not
perfect, and as a consequence, observed differences between
the groups on several outcomes (eg, pain at rest and while
walking), although of small to moderate magnitude, did not
reach statistically signicant levels. The follow-up period
of 2 weeks is also too short, and future studies should use
long-term follow-up trials to evaluate the effectiveness and
safety of molecular hydrogen administration for widespread
clinical use.
This study assessed only a few important biochemical
components of soft tissue injury recovery, neglecting further
parameters that might be directly or indirectly connected to
hydrogen intake, such as creatine kinase, endothelial leuko-
cyte adherence, and mean protein content. Because hydrogen
affects derivatives of reactive oxidative metabolites, biologi-
cal antioxidant power, and superoxide dismutase in healthy
subjects,32 it would be interesting for future studies to assess
a range of antioxidant parameters during hydrogen admin-
istration in athletes who have suffered a soft tissue injury.
Additional clinical outcome measures, such as being able to
return to sports or to regain muscular strength, and the time it
takes to do so, should also be explored in future research.
Conclusion
As an additional agent to supplement traditional conservative
treatment of acute sports-related soft tissue injuries, 2-week
Figure 2. Degree of swelling during the study.
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Hydrogen for Sports-Related Injuries
© Postgraduate Medicine, Volume 126, Issue 5, September 2014, ISSN – 0032-5481, e-ISSN – 1941-9260 195
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administration of hydrogen improved the level of plasma
viscosity and boosted ROM recovery of the injured limb.
The use of oral and topical hydrogen potentially represents a
novel therapeutic strategy for the treatment of the soft tissue
injury in male professional athletes. However, larger, long-
term studies of the safety of hydrogen administration will
be needed before any conclusion can be reached concerning
the use of hydrogen as a safe therapeutic agent in a clinical
environment.
Acknowledgments
This study was supported by the Serbian Ministry of
Science (grant number 175037; principal investigator:
Aleksandar Nedeljkovic, PhD; co-principal investigator:
Figure 3. ROM decit in exion and extension during the study.
*Signicant difference between groups at P , 0.05.
Abbreviation: ROM, range-of-motion.
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Ostojic et al
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Sergej M. Ostojic, MD, PhD), and grant no. 012–12C from
the SevenPoint2 (Newport Beach, CA).
Conict of Interest Statement
Sergej M. Ostojic, MD, PhD, Boris Vukomanovic, MD, Julio
Calleja-Gonzalez, PhD, and Jay R. Hoffman, PhD, FACSM,
FNSCA, have no conicts of interest to declare.
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