ArticlePDF Available

Multienzyme-complex for the management of delayed onset musclesoreness after eccentric exercise a randomized double blind placebo controlled study

Authors:
  • Sabinsa Corporation
  • Sami-Sabinsa Group Limited, Bangalore, India

Abstract and Figures

Background: Delayed onset muscle soreness (DOMS) results from muscle overload or strenuous exercise that goes beyond the intensity or duration for which the muscle is accustomed to performing. It is accompanied with the sensation of pain, tenderness, deep ache, and stiffness in muscles that usually begins several hours after the unaccustomed exercise. The aim of this study was to compare the efficacy of multi enzyme complex with a matching placebo in reducing pain associated with DOMS induced by standardized eccentric exercise. Methods: Twenty healthy males (10 pairs) were randomized in this double blind, placebo controlled trial to receive a placebo or multi enzyme complex capsule (50 mg) thrice a day for a period of 3 days. Mean differences within the group and between groups were assessed at each data collection time-point using Analysis of Covariance (ANCOVA) and Wilcox on signed rank sum test for all outcome measures. Results: In this controlled clinical study, intake of multi enzyme complex for 3 days resulted in no statistically significant changes in the descriptive statistics and efficacy analysis in muscle power and grip strength measured by hand held dynamometer. Algometer readings of thigh muscle, showed statistical significance (p<0.043). Decrements were observed in McGill Pain Questionnaire showing high statistical significance. Reducing trend was observed in bio markers of muscle damage (creatine kinase and lactate dehydrogenase) as well. Conclusion: The study results suggest that compared to placebo, Multi enzyme complex supplementation improves the outcome measures related to DOMS induced by standardized eccentric exercise.
Content may be subject to copyright.
Volume 1 • Issue 3 • 1000113Sports Nutr Ther, an open access journal
ISSN: 2473-6449
OMICS International
Research Article
Majeed et al., Sports Nutr Ther 2016, 1:3
DOI: 10.4172/2473-6449.1000113
Sports Nutrition and Therapy
S
p
o
r
t
s
N
u
t
r
i
t
i
o
n
a
n
d
T
h
e
r
a
p
y
ISSN: 2473-6449
Keywords: Delayed onset muscle soreness (DOMS); Muscle soreness
questionnaire (MSQ); Pressure pain threshold (PPT); Hand held
dynamometer; Illinois agility run test; Multi-enzyme complex
Introduction
Delayed onset muscle soreness is related to muscle damage
occurring several hours aer unaccustomed exercise, particularly
when eccentric muscle activity is involved [1,2]. Contracting muscles
are forcibly lengthened with eccentric exercise like downhill running
which limits physical function for several days [3,4]. is triggers an
inammatory response and the production of reactive oxygen species
(ROS) that sustain inammation and oxidative stress by promoting
the activation of transcription factors like the nuclear factor-κβ (NF—
κβ), a pro-inammatory master switch that controls the production of
inammatory markers and mediators [5]. e inammatory response
ensures musculoskeletal injury; uncontrolled inammation may
prolong skeletal muscle recovery [4].
Delayed onset muscle soreness (DOMS) is a well-documented
phenomenon, oen occurring as the result of the unaccustomed or
high intensity eccentric exercise. Associated symptoms include muscle
shortening, increased passive stiness, swelling, decreases in strength
and power, localized soreness and disturbed proprioception. Symptoms
will oen occur within 24 h post-exercise and typically subside aer 3-4
days. e severity of damage and soreness varies as a function of several
factors [6].
Considerable amount of research on the treatment of DOMS has
been carried out till date but no single treatment has been proven
successful in consistently preventing or treating DOMS. Treatment
strategies have oen integrated multiple therapeutic approaches such
as cryo therapy, ultrasound, compression therapy, stretching and deep
tissue massage [7-11]. ere is some evidence that ibuprofen, naproxen,
and massage may accelerate the resolution of DOMS [12]. In addition,
several dietary supplements have been tested in the treatment of DOMS
including protein, vitamin C, proteases (enzymes), phosphatidylserine,
chondroitin sulphate, and sh oil, all with variable success [4,12-18].
Non-steroidal anti-inammatory drugs (NSAIDs) like ibuprofen
are used widely as anti-DOMS recourse. NSAIDs are known to
interfere with chemo taxis of monocytes as well as inhibit neutrophil
aggregation [19]. Monocytes produce cytokines, which are responsible
for most of the physiological responses accompanying injury, and
neutrophils produce elastase and collagenase, which increase vascular
permeability via degradation of the vasculature and healthy tissue near
the injury site [20]. It is possible that the use of NSAIDs may impair
and lengthen the healing process.
In spite of inconsistencies, dose and timing of various NSAIDs also
in dierent studies there are side eects such as gastrointestinal distress
and hypertension. Hence NSAIDs are not an optimal choice for treating
DOMS [12]. Using enzymes to combat DOMS is also well established.
*Corresponding author: Vuppala KK, M.Ph, ClinWorld Private Limited, Peenya
Industrial Area, Bangalore, Karnataka, Tel: +917760956367; E-mail: kiran@clinworld.org
Received September 24, 2016; Accepted October 25, 2016; Published
November 11, 2016
Citation: Majeed M, Siva KA,Shaheen M,Priti V and Kiran KV (2016) Multi-Enzyme
Complex for the Management of Delayed Onset Muscle Soreness after Eccentric
Exercise: A Randomized, Double Blind, Placebo Controlled Study. Sports Nutr
Ther 1: 113. doi: 10.4172/2473-6449.1000113
Copyright: © 2016 Majeed et al. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
Abstract
Background: Delayed onset muscle soreness (DOMS) results from muscle overload or strenuous exercise
that goes beyond the intensity or duration for which the muscle is accustomed to perform. It is accompanied with
the sensation of pain, tenderness, deep ache, and stiffness in muscles that usually begins several hours after the
unaccustomed exercise. The aim of this study was to compare the efcacy of multi enzyme complex with a matching
placebo in reducing pain associated with DOMS induced by standardized eccentric exercise.
Methods: Twenty healthy males (10 pairs) were randomized in this double blind, placebo controlled trial to
receive a placebo or multi enzyme complex capsule (50 mg) thrice a day for a period of 3 days. Mean differences
within the group and between groups were assessed at each data collection time-point using Analysis of Covariance
(ANCOVA) and Wilcoxon signed rank sum test for all outcome measures.
Results: In this controlled clinical study, intake of multi enzyme complex for 3 days resulted in no statistically
signicant changes in the descriptive statistics and efcacy analysis in muscle power and grip strength measured by
hand held dynamometer. Algometer readings of thigh muscle showed statistical signicance (p<0.043). Decrements
were observed in McGill Pain Questionnaire showing high statistical signicance. Reducing trend was observed in
bio markers of muscle damage (creatine kinase and lactate dehydrogenase) as well.
Conclusion: The study results suggest that compared to placebo, Multi enzyme complex supplementation
improves the outcome measures related to DOMS induced by standardized eccentric exercise.
MultiEnzyme Complex for the Management of Delayed Onset Muscle
Soreness after Eccentric Exercise: A Randomized, Double Blind, Placebo
Controlled Study
Majeed M, Siva KA,Shaheen M,Priti V and Kiran KV*
ClinWorld Private Limited, Peenya Industrial Area, Bangalore, Karnataka
Citation: Majeed M, Siva KA,Shaheen M,Priti V and Kiran KV (2016) Multi-Enzyme Complex for the Management of Delayed Onset Muscle Soreness
after Eccentric Exercise: A Randomized, Double Blind, Placebo Controlled Study. Sports Nutr Ther 1: 113. doi: 10.4172/2473-6449.1000113
Page 2 of 7
Volume 1 • Issue 3 • 1000113Sports Nutr Ther, an open access journal
ISSN: 2473-6449
Advanced Surgeries, #146, Infantry Road, Bangalore prior to the
initiation of the study. e study documents reviewed were (protocol,
informed consent form, investigator brochure, and case record form).
e aforesaid Ethics Committee was registered under central drugs
standard control organization as per the gazette notication number
F.28-10/45-H(1), dated 21 Dec 1945 and last amended vide notication
number G.S.R. 76(E) dated 08 FEB 2012.
Informed consent
is study included a total of 20 healthy volunteers. An initial
screening visit was scheduled during which all subjects rst signed
written informed consent. Before the signing of the informed consent
adequate oral and written information concerning the study was
provided to the subjects and subjects were provided with ample
opportunity to consider their participation in the study. Aer obtaining
a signed informed consent subjects were screened for the study.
Study design
For the DOMS model under study, we selected the following
design features: prospective, double blind, randomized, and placebo
controlled. e analgesic ecacy of DigeZyme® was compared with a
matching placebo. e pre specied ecacy end points of the study
were assessed on Day 0 (pre exercise) and 72 hours post exercise.
Participants
Twenty healthy males with no known musculoskeletal pathology
participated in the study. Subjects were excluded if they met one
or more of the following exclusion criteria: treatment with anti-
inammatory/analgesic/antioxidant drugs in the previous month,
abnormal liver or renal function tests, laboratory ndings suggestive
of an active inammatory or infectious process and presence of any
known disease.
e participants also completed a health history questionnaire
designed to identify the degree of risk for cardiovascular or orthopaedic
complications during exercise.
Supplementation with multi enzyme complex
All participants in the experimental group received multi enzyme
complex supplementation over a 3 day period. During this period,
they consumed one capsule of multi enzyme complex thrice a day.
e participants in the placebo group received capsules of similar
size and colour. ey were given identical instructions on dosage of
study supplement to be followed. Study supplements were prepared
and provided by Sami Labs Limited, Bangalore. e administration of
treatment and placebo was blinded for both the participants and the
investigator. ere were no side eects reported by the participants as
a result of the supplementation.
Data collection protocol
Subjects visited the clinic on day 0 (baseline visit) and subsequent
visits on day 1, day 2 and day 3. Aer recording vital signs (blood
pressure, pulse rate, heart rate and respiratory rate), medical and
medication history, physical examination was conducted.
Randomisation and allocation concealment
e randomisation sequence was prepared by an independent
statistician, independent of the sponsoring organization and not
involved in conduct or reporting of the study. An alpha numeric
code was generated for both the active and placebo to improve the
A study by inner eld in 1957 examined the anti-inammatory
eects of protease enzyme therapy and showed that protease enzyme
supplementation may have anti-inammatory eects [21].
Commercially, digestive enzymes are isolated from various
sources such as the pancreas of higher animals (swine and cattle),
higher vegetables (barley), and microorganisms including bacteria and
fungi. e multi enzyme complex (DigeZyme®) consists of MO free
broad acting enzymes obtained from the fermentation process with
Aspergillusoryzae, including amylase, protease and lipase; this group
of enzymes breaks carbohydrates, proteins and fats and all three groups
of enzymes are resistant to the action of gastric juices, while retaining
their digestive activity. DigeZyme® was also clinically evaluated for
enhanced absorption of minerals and vitamins.
Absorption issues and the destruction of enzymes in the gut have
severely limited the eectiveness of traditional anti-DOMS enzyme
therapy. Sitosterols -- plant sterols and protease enzymes can help
reduce the inammation associated with DOMS. Earlier research has
suggested protease oral supplementation to shorten recovery time
post injury through the inhibition of arachidonic cascade. Protease is
also believed to inhibit the biosynthesis of pro-inammatory agents
[22], increase tissue permeability, facilitate resorption of oedema and
accelerate the restructuring of damaged tissue [23]. Protease utilization
is generally considered safe.
e current clinical study aims at investigating the ecacy of multi-
enzyme complex, a multi-enzyme complex which is a combination of ve
digestive enzymes (alpha-amylase, neutral protease, cellulase, lactase
and lipase), as a dietary supplement in the management of DOMS.
erefore, the current randomized, double blind placebo
controlled trial was conducted to evaluate the eect of multi-enzyme
complex (amylase, lipase, lactase, cellulose and neutral protease) for the
management of delayed onset muscle soreness aer eccentric exercise.
Materials and Methods
Product description
DigeZyme® is an “o - white to creamy white powder of multi-
enzyme complex”. is multi-enzyme complex consists of amylase,
protease, lipase, cellulase and lactase. Placebo capsules containing
equivalent weight of maltodextrin. No dierences in colour, taste,
texture or packaging were detectable between the two products. Capsules
were sealed in identically-appearing, high-density polyethylene bottles
with desiccant. e enzyme activity of multi-enzyme complex was
determined by following standard methods as per Food Chemicals
Codex guidelines (Table 1).
Enzyme units were dened as per Food Chemical Codex (FCC), 5th
ed. 2004. e National Academy Press Washington DC.
Ethics approval
Ethics approval was obtained through the Sparsh Hospital for
S. No. Enzyme Enzyme activity (Units/g)
1 Alpha-amylase 24000 DU/g (Dextrinizing Unit/gram)
2 Cellulase 1100 CU/g (Cellulase Unit/gram)
3 Lipase 200 FIP/g
(FédérationInternationalePharmaceutiqueUnit/gram)
4 Lactase 4000 ALU/g (Acid Lactase Unit/gram)
5 Neutral
Protease
6000 PC/g (Protease Unit on L-tyrosine basis/gram)
Table 1: Composition detail of multi-enzyme complex (DigeZyme) formulation.
Citation: Majeed M, Siva KA,Shaheen M,Priti V and Kiran KV (2016) Multi-Enzyme Complex for the Management of Delayed Onset Muscle Soreness
after Eccentric Exercise: A Randomized, Double Blind, Placebo Controlled Study. Sports Nutr Ther 1: 113. doi: 10.4172/2473-6449.1000113
Page 3 of 7
Volume 1 • Issue 3 • 1000113Sports Nutr Ther, an open access journal
ISSN: 2473-6449
blindness of the study and concealment of allocations. Computer
generated random allocation soware (version 2.0) was used for the
allocation of concealment. Block randomization (only one block) was
followed wherein the subjects were randomized to receive either active
or placebo. e randomization codes were kept strictly condential
and were accessible only to authorized persons on an emergency basis
as per the Sponsor standard operating procedures until the time of
unblinding.
Blinding
e study was double blinded wherein neither the Investigator nor
the trial participants knew whether they would receive the active or
the placebo. e investigational products were provided in pre labelled
containers to avoid bias.
Procedures Followed
Protocol for inducing DOMS
Subjects were instructed to ingest the study supplement and report
to the site aer 24-hours for the baseline readings. Aer 10 hours
fasting, heart rate and ratings of perceived exertion were monitored at
rest, every 5 minutes during exercise and 10 minutes into recovery. e
participants mounted a level motorized treadmill and warmed up for
5 minutes at a self-selected pace. Post 5-min warm up, treadmill speed
was increased until a heart rate of 80% of predicted maximal heart rate
was achieved and were instructed to maintain this pace for 5 min. e
treadmill grade at this time was adjusted to 10% and was maintained
for 30 minutes. Subjects then completed a 5 minutes active cool-down
at a self-selected pace and a 5 minutes seated passive recovery period.
Subjects were restricted from indulging in any other physical activity
24 hours prior and 72 hours aer the exercise session [24].
Quantifying muscle soreness using algometer
e Muscle Soreness Questionnaires (MSQ) required participants
to rate their general soreness on a scale of 1 (normal) to 10 (very, very
sore) for the right front thigh and right back thigh. An algometer was
used to quantify muscle pain by applying direct pressure over the
muscle. It involves documenting the threshold at which the applied
pressure over the muscle is perceived as a sensation of pain rather than
a pressure; this is referred to as the pressure pain threshold (PPT). e
PPT has been demonstrated to be reliable for measuring pain threshold.
e algometer standard is to increase pressure linearly to 5 kg/cm2 over
5 seconds according to the method recommended by Fischer. e
instrument has a 1cm2 rubber footplate and a scale marked from 2 to 20
kg/cm2, in increments of 0.2 kg/cm2. Subjects were instructed to report
as soon as the sensation of pressure changes to pain by saying ‘pain’,
and ‘I will stop’. e footplate of the algometer was held perpendicular
to the muscle belly with the gauge turned away from the subject and
the examiner. Pressure was increased at a rate of approximately 1 kg/
cm2/s until the subject reported ‘pain’. e examiner then released
the pressure and lied the algometer o the muscle to read the gauge
and record the measurement. e needle on the gauge was returned
to baseline before each trial using the pressure release button on the
algometer [24].
For muscular strength and power using hand held
dynamometer
A Hand-Held Dynamometer (HHD) was used to quantify changes
in muscle strength by measuring strength during maximal voluntary
isometric contraction (MVC) of the muscle. Each participant was
asked to perform three repetitions of maximal knee extension and
exion contractions (MVC) at three dierent positions of knee range
of motion (0 degrees, 90 degrees, 120 degrees). e test angles were
chosen to account for changes in muscle strength that could occur due
to alteration in the length of the muscle at dierent positions of the
knee [25].
Illinois agility run test
Agility was measured using Illinois agility run test. e tests were
conducted on a course 10 meters in length and 5 meters in width.
Agility time was recorded using a stopwatch. e start, nish and the
two turning points were marked with four cones and another four
cones were placed down the center equal distance spaced 3.3 meters
apart. Subjects were made to lie on their front (head to the start line)
and hands by their shoulders. e run started from a standing start on
the command ‘Go’ the stopwatch was started, and the subjects were
instructed to get up as quickly as possible and run around the course in
the direction indicated, without knocking the cones over, to the nish
line, at which the timer was stopped [26].
Outcome measures
McGill pain questionnaire comprising of 10 subscales from 0 (no
pain) to 10 (worst possible pain) was used to assess pain [27,28]. An
algometer was used to experimentally induce pain on a predened
point on the patellar tendon ve centimetres above the center of the
patella, tenderness was assessed.
Subjects ranked their pain perception on a scale from 0 to 10. On
day 3, assessments were taken at baseline (pre-exercise), post-exercise
and further at 24, 48 and 72 hours post-exercise for each arm of the
study. Secondary outcomes included assessments of inammation,
muscle damage, exibility, and the amount of energy expended prior
to exercise.
Biomarkers creatine kinase and lactate dehydrogenase were
monitored pre exercise and 72 hours post exercise.
Safety prole of the supplement was assessed by routine
haematology, kidney and liver function tests. Adverse events were
monitored throughout the study.
Statistical analysis
All testing was done using Statistical Analysis Soware (SAS)
having version 9.2. All analyses was conducted using the intent-to-treat
population. Patients with no data recorded for a particular parameter
were automatically excluded from the analyses of that parameter. For
all the data set variables analysis of covariance (ANCOVA) and Wilcox
on signed rank sum test were used and the level of signicance was set
as P<0.05.
Results
Subject disposition
A total of 20 subjects were enrolled into the study. ere were no
subject withdrawals or dropouts in this study.
Physical characteristics
e population was essentially healthy without signicant
concomitant disease or medication intake. Screening characteristics
of participants are presented in (Table2). ere were no statistically
signicant dierences between subjects in the placebo (n=10) and the
DigeZyme® (n=10) group. On the day of screening, the mean weight of
Citation: Majeed M, Siva KA,Shaheen M,Priti V and Kiran KV (2016) Multi-Enzyme Complex for the Management of Delayed Onset Muscle Soreness
after Eccentric Exercise: A Randomized, Double Blind, Placebo Controlled Study. Sports Nutr Ther 1: 113. doi: 10.4172/2473-6449.1000113
Page 4 of 7
Volume 1 • Issue 3 • 1000113Sports Nutr Ther, an open access journal
ISSN: 2473-6449
all the enrolled subjects was 59.3 ± 4.64 kgs; mean height was 163.8 ±
4.99 cm and the mean BMI was 22.2 ± 1.50 kg/m2.
Ecacy evaluation
Delayed Onset Muscle Soreness-quality of life was analyzed
throughout the study period as primary ecacy measure. e ‘p
value suggests that there was a statistically signicant change in these
symptoms from baseline to nal visits, between the placebo and active
arms. Statistical analysis using Analysis of Co-Variance (ANCOVA)
showed the primary ecacy parameters were statistically signicant
(p<0.05) between the multienzyme complex and placebo groups (Table
3). Furthermore, comparative mean values of ecacy assessments
between Multi enzyme complex and placebo groups across various
visits (baseline, day 1, day 2 and day 3) are presented for ecacy
parameters (Figures 1-8). Patients who were on Multi enzyme complex
had statistically signicant dierence for the ecacy parameters on day
3 when compared with placebo.
Pain assessment
McGill pain questionnaire is a multidimensional pain instrument;
the nal score is a sum of all the ten individual pain questions. e
rst nine McGill pain questionnaires were based on assessment of pain
(current pain, least pain, and worst pain) while the tenth on the degree
of numbness and its interference with function.
When dierences between multi enzyme complex and placebo
were compared, the pain score showed high statistical signicance
(p=0.0061).
Demographics Values
Height (cm)
N 20
Mean(SD) 163.8 (4.99)
Median 164.5
Min, Max 154, 172
Weight (kg)
N 20
Mean(SD) 59.3 (4.64)
Median 59.2
Min, Max 51, 67
Body Mass Index (kg/m2)
N 20
Mean(SD) 22.2(1.50)
Median 22.3
Min, Max 20, 25
Race
Central American 0
East Asian 0
South Asian 20
South American 0
South East Asian 0
Western European 0
White 0
Table 2: Subject demographics characteristics.
Subjective Parameters
Measure Investigational Products Signicance
Hand held Dynamometer readings
result [grip strength] kg
DigeZyme®
Baseline 72 hours
Post
Exercise
Placebo
Baseline 72 hours
Post
Exercise
0.4956
36.2 (7.86) 37.6 (8.32) 35.2 (6.84) 36.2 (5.26)
Thigh muscle
(point of pain)
Algometer Reading’s kg/cm2
9.5 (0.58) 5.3 (1.18) 9.3 (1.03) 3.9 (1.45) 0.0436*
Calf muscle
(point of pain)
Algometer Reading’s kg/cm2
9.1 (1.09) 3.9 (1.20) 9.4 (1.11) 3.3 (1.03) 0.1397
Total Time Taken
Illinois Agility Run test (Seconds)
25.6 (3.43) 24.6 (4.11) 25.2 (1.69) 23.8 (2.91) 0.7246
The McGill pain questionnaire
(total pain score) 29.5 (2.55) 48.7 (8.86) 28.1 (1.45) 61.3 (7.07) 0.0061*
Objective Parameters (Serum markers (U/L)
Serum Creatine Kinase 42.4 (11.69) 45.8 (10.49) 36.7 (4.30) 40.5 (5.42) 0.5735
Serum Lactate De-hydrogenase 161.1 (35.56) 164.2 (31.17) 162.6 (28.40) 161.4 (25.44) 0.2556
Table 3: Efcacy analysis.
Figure 1: Flow chart.
Citation: Majeed M, Siva KA,Shaheen M,Priti V and Kiran KV (2016) Multi-Enzyme Complex for the Management of Delayed Onset Muscle Soreness
after Eccentric Exercise: A Randomized, Double Blind, Placebo Controlled Study. Sports Nutr Ther 1: 113. doi: 10.4172/2473-6449.1000113
Page 5 of 7
Volume 1 • Issue 3 • 1000113Sports Nutr Ther, an open access journal
ISSN: 2473-6449
Tenderness assessment
On the tenderness quotient, subjects taking multi enzyme complex
demonstrated signicantly less tenderness, 72 hours aer exercise
(p=0.042).
Muscle damage assessments
Liberation of biochemical substances such as creatine kinase,
lactate dehydrogenase, protein metabolites and myoglobin occurs
from muscle cells approximately 24 hours post exercise and have
been found in plasma up to 48 hours [29]. Creatine kinase being a
surrogate index of muscle damages more indicative of damage or gaps
in the sarcolemma [30]. e CK response was less in the multi enzyme
complex group suggesting the membrane integrity was maintained to
greater extent than the placebo group.
24 hours post exercise, subjects on the placebo group showed trend
towards a higher level of CK than the multi enzyme complex group.
is trend continued through the 72 hour assessment. Dierence
between the multi enzyme complex group and placebo in CK values
was not statistically signicant. Lactate dehydrogenase also showed a
similar phenomenon, which trended higher at 24 and 72 hours post-
exercise in the placebo group (Figures 7-8).
Flexion and extension measurements
On analysing the pre exercise leg exion measurements, they were
found to be equal between the groups for the le leg. Whereas the
exion measurement was found to be signicantly greater (p=0.049)
for the right leg in the placebo group.
When the post exercise exion measurements were analysed, only
the 24-hour right leg exion measurement was found to be signicant
(p=0.004) in the multi enzyme complex group.
Safety evaluations
Vital signs such as Blood Pressure, Respiratory Rate, Pulse Rate
and any abnormal laboratory parameters were considered for safety
evaluations. No clinically signicant changes were recorded for
descriptive physical examination in both the groups (Multi enzyme
complex and placebo). e safety of multi enzyme complex was assessed
using adverse event data (occurrence, intensity, and relationship to
study drug). No adverse events were noticed in the study.
Discussion
Multi enzyme complex capsules contain alpha-amylase, neutral
protease, lipase, lactase and cellulase. e capsule containsfree
broad acting enzymes obtained from the fermentation process
Figure 2: Hand-held dynamometer (HHD) readings of maximal voluntary
isometric contraction (MVC) at three different positions of knee range of motion
(0 degrees, 90 degrees, 120 degrees) of both active and placebo.
Figure 3: Aglometer readings to quantify pressure pain threshold (ppt) of thigh
muscle. P<0.05 between the treatment groups.
Figure 4: Aglometer readings to quantify pressure pain threshold (ppt) calf
muscle.
Figure 5: Illinois agility run test on length of 10 meters and the width (distance
between star and nish points) 5 meters.
Figure 6: The muscle soreness questionnaires (MSQ) on scale of 1 to 10 of
both active and placebo. p<0.05 between the treatments groups.
Citation: Majeed M, Siva KA,Shaheen M,Priti V and Kiran KV (2016) Multi-Enzyme Complex for the Management of Delayed Onset Muscle Soreness
after Eccentric Exercise: A Randomized, Double Blind, Placebo Controlled Study. Sports Nutr Ther 1: 113. doi: 10.4172/2473-6449.1000113
Page 6 of 7
Volume 1 • Issue 3 • 1000113Sports Nutr Ther, an open access journal
ISSN: 2473-6449
with Aspergillusoryzae, including amylase, protease and lipase. is
manufacturing technique ensures that the gastric enzymes from
Aspergillusoryzae are delivered at distinct sites, the stomach and the
small intestine, respectively. Various studies have shown protease
supplementation may attenuate muscle soreness aer downhill
running [31].
A subsequent series of four studies have evaluated papain, in
combination with other proteases, in small samples of male athletes,
especially with regard to its eectiveness in attenuating DOMS post
eccentric exercise. Two of the studies were able to show better exion
in the tested limb post eccentric load which was hypothesised to be
mediated by regulation of leukocyte activity and inammation. Two
further studies showed an improvement in contractile function and
subjective pain and tenderness ratings but not in biochemical measures
of DOMS. Further interpretation of these studies is dicult as all four
used a combination of papain with other proteolytic enzymes (e.g.
bromelain, amylase, lysozyme, and trypsin) [8].
In the present study we sought to investigate the eects of multi
enzyme complex on delayed onset muscle soreness induced by
eccentric exercise.
Delayed onset muscle soreness (DOMS) due to eccentric muscle
activity is associated with inammatory responses and production of
reactive oxygen species (ROS) that sustain both inammation and oxidative
stress. Aer eccentric exercise, damage to the contractile element of the
muscle leads to the occurrence of DOMS. e results of this study suggest
that supplementation with Multi enzyme complex supplementation helps
in the recovery of this contractile fraction of the muscles.
In the present study multi-enzyme complex capsules demonstrated
signicant improvement in subjective pain and tenderness, with no
signicant improvement in levels of markers of inammation, muscle
damage or muscle exion. Multi-enzyme complex contains a multiple
enzymes that are indicated for relieving the symptoms of DOMS.
e ndings of this study suggest that multi enzyme complex can
have several potential clinical applications. Protease supplementation
when coupled with a well-managed training programme can result in
more rapid recovery of the damage caused to contractile mechanism
by DOMS.
Registration
e trial was registered on the Clinical Trial Registry of India with
the registration number CTRI/2015/09/006148.
References
1. Dierking JKATC, Bemben MG (1998) Delayed onset muscle soreness. Strength
& Conditioning 20: 44-48.
2. Armstrong RB (1990) Initial events in exercise-induced muscular injury. Med
Sci Sports Exerc 22: 429-435.
3. Francis KT, Hobbler T (1987) Effects of aspirin on delayed muscle soreness. J
sports Med Physical Fitness 27: 333-337.
4. Proske U, Morgan DL (2001) Muscle damage from eccentric exercise:
mechanism, mechanical signs, adaptation and clinical applications. J Physiol
537: 333-345.
5. Aoi W, Naito Y, Takanami Y, Kawai Y, Sakuma K, et al. (2004) Oxidative stress
and delayed-onset muscle damage after exercise. Free Radic Biol Med 37:
480-487.
6. Joanna Vaile, Shona Halson, Nicholas Gil, Brian Dawson (2008) Effect of
hydrotherapy on the signs and symptoms of delayed onset muscle soreness.
Eur J Appl Physiol 102: 447-455.
7. Sellwood KL, Brukner P, Williams D, Nicol A, Hinman R (2007) Ice-water
immersion and delayed-onset muscle soreness: a randomised controlled trial.
Br J Sports Med 41: 392-397.
8. Craig JA, Bradley J, Walsh DM, Baxter GD, Allen JM (1999) Delayed onset
muscle soreness: lack of effect of therapeutic ultrasound in humans. Arch Phys
Med Rehabil 80: 318-323.
9. Kraemer WJ, Bush JA, Wickham RB, Denegar CR, Gómez AL, et al. (2001)
Inuence of compression therapy on symptoms following soft tissue injury from
maximal eccentric exercise. J Orthop Sports PhysTher 31: 282-290.
10. Frey LLA, Evans S, Knudtson J, Nus S, Scholl K (2008) Massage reduces
pain perception and hyperalgesia in experimental muscle pain: a randomized,
controlled trial. J Pain 9: 714-721.
11. Herbert RD, de NM (2007) Stretching to prevent or reduce muscle soreness
after exercise. Cochrane Database Syst Rev.
12. Connolly DA, Sayers SP, McHugh MP (2003) Treatment and prevention of
delayed onset muscle soreness. J Strength Cond Res 17: 197-298.
13. Cockburn E, Hayes PR, French DN, Stevenson E, St Clair GA (2008) Acute
milk-based protein-CHO supplementation attenuates exercise-induced muscle
damage. Appl Physiol Nutr Metab 33: 775-783.
14. Connolly DA, Lauzon C, Agnew J, Dunn M, Reed B (2006) The effects of
vitamin C supplementation on symptoms of delayed onset muscle soreness. J
Sports Med Phys Fitness 46: 462-467.
15. Beck TW, Housh TJ, Johnson GO, Schmidt RJ, Housh DJ, et al. (2007) Effects
of a protease supplement on eccentric exercise-induced markers of delayed-
onset muscle soreness and muscle damage. J Strength Cond Res 21: 661-667.
16. Kingsley MI, Kilduff LP, McEneny J, Dietzig RE, Benton D (2006)
Phosphatidylserine supplementation and recovery following downhill running.
Med Sci Sports Exerc 38: 1617-1625.
17. Braun WA, Flynn MG, Armstrong WJ, Jacks DD (2005) The effects of
chondroitin sulfate supplementation on indices of muscle damage induced by
eccentric arm exercise. J Sports Med Phys Fitness 45: 553-560.
Figure 7: Effect of multi enzyme complex on the serum creatine kinase (U/L).
serum creatine kinase was quantied at the baseline, day1, day 2 and end of
the study (day 3) of both active and placebo.
Figure 8: Effect of multi enzyme complex on the serum lactase de-hydrogenase
(U/L). Serum lactase de-hydrogenase was qualied at the baseline, day 1, day
2 and end of the study (day 3) of both active and placebo.
Citation: Majeed M, Siva KA,Shaheen M,Priti V and Kiran KV (2016) Multi-Enzyme Complex for the Management of Delayed Onset Muscle Soreness
after Eccentric Exercise: A Randomized, Double Blind, Placebo Controlled Study. Sports Nutr Ther 1: 113. doi: 10.4172/2473-6449.1000113
Page 7 of 7
Volume 1 • Issue 3 • 1000113Sports Nutr Ther, an open access journal
ISSN: 2473-6449
18. Lenn J, Uhl T, Mattacola C, Boissonneault G, Yates J, et al. (2002) The effects
of sh oil and isoavones on delayed onset muscle soreness. Med Sci Sports
Exerc 34: 1605-1613.
19. Goodwin JS (1984) Mechanism of action of nonsteroidal anti-inammatory
agents. Am J Med 104:2S-8S.
20. Evans WJ, Cannon JG (1991) The metabolic effects of exercise-induced
muscle damage. Exerc Sport Sci Rev 19: 99-125.
21. Inner eld I (1957) The anti-inammatory effect of parenterally administered
proteases. Ann N Y Acad Sci 68: 167-77.
22. Woolf RM, Snow JW, Walker JH, Broadbent T (1965) Resolution of an articially
induced hematoma and the inuence of a proteolytic enzyme. J Trauma 5:
491-493.
23. Cirelli MG (1964) Clinical experience with bromelains in proteolytic enzyme
therapy of inammation and edema. Medical Times 92: 919-922.
24. Miller PC, Derr JS, Bailey SP, Hall EE, Barnes ME (2004) The effects of
protease supplementation on skeletal muscle function and DOMS following
downhill running. Journal of Sports Sciences 22: 365-372.
25. Kelln BM, McKeon PO, Gontkof LM, Hertel J (2008) Hand-held dynamometry:
reliability of lower extremity muscle testing in healthy, physically active, young
adults. J Sport Rehabil 17: 160-170.
26. Getchell B (1979) Physical tness: a way of life. Wiley J Sons, New York.
27. Melzack R (1975) The McGill pain questionnaire: major properties and scoring
methods. Pain 1: 277-299.
28. Sullivan MJL, Rodgers W, Wilson MP, Fraser SN (2002) An experimental
investigation of the relation between catastrophizing and activity intolerance.
Pain 100: 47-53.
29. Clarkson PM, Nosaka K, Braun B (1992) Muscle functions after exercise-
induced muscle damage and rapid adaptation. Med Sci Sports Exerc 24: 512-520.
30. Jackman SR, Witard OC, Jeukendrup AE, Tipton KD (2010) Branched-chain
amino acid ingestion can ameliorate soreness from eccentric exercise. Med Sci
Sports Exerc 42: 962-970.
31. Au RY, Al-Talib TK, Au AY, Phan PV, Frondoza CG (2007) Avocado soybean
unsaponiables (ASU) suppress TNF-alpha, IL-1beta, COX-2, iNOS gene
expression, and prostaglandin E2 and nitric oxide production in articular
chondrocytes and monocyte/macrophages. Osteoarthr Cartil 15: 1249-1255.
Citation: Vuppala KK, Majeed M, Kumar AS, Majeed S, Vaidyanathan P
(2016) Multi-Enzyme Complex for the Management of Delayed Onset Muscle
Soreness after Eccentric Exercise: A Randomized, Double Blind, Placebo
Controlled Study. Sports Nutr Ther 1: 113. doi: 10.4172/2473-6449.1000113
OMICS International: Open Access Publication Benefits &
Features
Unique features:
• Increasedglobalvisibilityofarticlesthroughworldwidedistributionandindexing
• Showcasingrecentresearchoutputinatimelyandupdatedmanner
• Specialissuesonthecurrenttrendsofscienticresearch
Special features:
• 700+OpenAccessJournals
• 50,000+editorialteam
• Rapidreviewprocess
• Qualityandquickeditorial,reviewandpublicationprocessing
• Indexingatmajorindexingservices
• SharingOption:SocialNetworkingEnabled
• Authors,ReviewersandEditorsrewardedwithonlineScienticCredits
• Betterdiscountforyoursubsequentarticles
Submityourmanuscriptat:http://www.omicsonline.org/submission
... In a recent study, MEC was able to decrease delayed onset muscle sorenessassociated pain and tenderness in healthy volunteers. 25 ...
Article
Full-text available
Functional dyspepsia (FD) is a highly prevalent disorder having nonspecific symptoms and varied pathophysiology. Its treatment remains a challenge as therapeutic options are limited, unsatisfactory, and elusive. Thus, safety and efficacy of DigeZyme®, a proprietary multienzyme complex (MEC), was evaluated as a dietary supplement in FD patients. In this randomized, double-blind, placebo-controlled, parallel-group study, 40 patients were randomly assigned (1:1 ratio) to receive either MEC (50 mg, TID; n = 20) or placebo (n = 20) for 60 days. Reports of adverse or serious adverse events (AEs), abnormal results of vital signs, abnormal findings during physical examination, and abnormal laboratory investigations were monitored closely. Efficacy measures were change in Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ), Nepean Dyspepsia Index-Short Form (NDI-SF), Visual Analog Scale (VAS), Clinical Global Impression Severity Rating Scale (CGI-S), and Glasgow Dyspepsia Severity Score (GDSS) at baseline and follow-up visits on day 15, 30, and 60. Supplementation with MEC was associated with statistically significant differences (P value ranging from .0401 to .0033) in all efficacy parameters compared with placebo. The between-group comparison also revealed that MEC supplement had a significantly greater effect (P < .001) versus placebo. No investigation product-related AEs were reported. There were no clinically significant abnormalities in physical findings and no statistically significant changes in biochemical and hematological parameters, vital signs, body weight, and body mass index observed between the two groups at baseline and follow-up visits. MEC supplementation represents an effective and safe alternative to manage dyspepsia symptoms in FD patients.
Chapter
Enzymes have played crucial role in the production, fortification and preservation of food and beverages; one that is economical and eco-friendly. Most modern-day nutritional supplements used by athletes focus primarily on, enhancing physical endurance, maximizing nutrient absorption, and mitigating injuries induced in sports. Inclusion of bioactive compounds, such as enzymes, has dramatically improved the aforesaid attributes in supplements. Whey supplements fortified with proteolytic enzymes have been shown to enhance the bio-absorption of proteins by hydrolyzing into its basal amino acids. These supplements also contain Lactases for breaking down sugars for consumers who are lactose intolerant. Energy drinks used by athletes contain blends of ornithine alpha-ketoglutarate and aminotransferases that help in replenishing lost arginine pools during intense physical activity. Conversion of arginine to nitrous oxide in the cells has been directly related to increased blood flow to the muscles for enhanced workout and functioning. Amylases in energy drinks have been shown to restock the lost muscle glycogen by helping the conversion of complex carbohydrates to simple sugars, such as glucose. However, most of these enzymes are present in proprietary blends, with very less information on the ingredients. This chapter therefore discusses elaborately on numerous other enzymes, and their potential applications in sports supplementation.
Article
Full-text available
Adequate nutrition is one of the vital factors for participating in endurance sports with a specific focus on dietary modifications. A proper nutritional plan prior, during and post competition would be helpful in sports performance. A large body of clinical evidences supports the use of dietary supplements in sports performance. The health benefits include: replenishment of water by isotonic drinks, improvement of endurance, enhancement of muscle strength, prevention of muscle/joint injuries or fatigue and maintenance in immunity, decrease in muscle/fat mass, improving brain performance, decreasing delayed onset muscle soreness or pain (anti-inflammatory properties), reducing injury severity, enhancing recovery from injury, reducing gastrointestinal problems, and decreasing respiratory tract infection illness load. A number of dietary supplements have been reported to enhance sports performance. These include multienzyme complex, beet root extracts, and Coleus forskohlii extract. Multienzyme complex have been found to have significant effects on delaying the onset of muscle soreness post exercise. A significant reduction in McGill pain scores (p>0.05) was observed with multienzyme complex. Effects on LDH and inflammatory biomarkers like ESR and hs-CRP has been documented with betalains. A significant improvement in these parameters has been associated with cardiovascular health and exercise performance (p> 0.05). The bioactives like forskolin have been found to significantly promote lean body mass and weight loss (p> 0.05). A majority of athletes are inclined on the use of dietary supplements or engineered foods to gain a competitive edge for sports performance in recent times. However, health claims might provide misleading information associated with the safety, legality, and efficacy of dietary supplements. Therefore, a stringent regulatory framework has been adopted across globe for marketing authorization to ensure safety and efficacy for these sports nutrition foods. The regulatory requirements for risk assessment of dietary supplements for sports nutrition include data on the clinical efficacy and safety data, toxicity profile, historical use of the medicine.
Article
Full-text available
Eccentric exercise continues to receive attention as a productive means of exercise. Coupled with this has been the heightened study of the damage that occurs in early stages of exposure to eccentric exercise. This is commonly referred to as delayed onset muscle soreness (DOMS). To date, a sound and consistent treatment for DOMS has not been established. Although multiple practices exist for the treatment of DOMS, few have scientific support. Suggested treatments for DOMS are numerous and include pharmaceuticals, herbal remedies, stretching, massage, nutritional supplements, and many more. DOMS is particularly prevalent in resistance training; hence, this article may be of particular interest to the coach, trainer, or physical therapist to aid in selection of efficient treatments. First, we briefly review eccentric exercise and its characteristics and then proceed to a scientific and systematic overview and evaluation of treatments for DOMS. We have classified treatments into 3 sections, namely, pharmacological, conventional rehabilitation approaches, and a third section that collectively evaluates multiple additional practiced treatments. Literature that addresses most directly the question regarding the effectiveness of a particular treatment has been selected. The reader will note that selected treatments such as anti-inflammatory drugs and antioxidants appear to have a potential in the treatment of DOMS. Other conventional approaches, such as massage, ultrasound, and stretching appear less promising.
Article
Full-text available
Exercise-induced muscle damage (EIMD) leads to the degradation of protein structures within the muscle. This may subsequently lead to decrements in muscle performance and increases in intramuscular enzymes and delayed-onset muscle soreness (DOMS). Milk, which provides protein and carbohydrate (CHO), may lead to the attenuation of protein degradation and (or) an increase in protein synthesis that would limit the consequential effects of EIMD. This study examined the effects of acute milk and milk-based proteinCHO (CHO-P) supplementation on attenuating EIMD. Four independent groups of 6 healthy males consumed water (CON), CHO sports drink, milk-based CHO-P or milk (M), post EIMD. DOMS, isokinetic muscle performance, creatine kinase (CK), and myoglobin (Mb) were assessed immediately before and 24and 48h after EIMD. DOMS was not significantly different (p> 0.05) between groups at any time point. Peak torque (dominant) was significantly higher (p< 0.05) 48h after CHO-P compared with CHO and CON, and M compared with CHO. Total work of the set (dominant) was significantly higher (p< 0.05) 48h after CHO-P and M compared with CHO and CON. CK was significantly lower (p< 0.05) 48 h after CHO-P and M compared with CHO. Mb was significantly lower (p< 0.05) 48 h after CHO-P compared with CHO. At 48h post-EIMD, milk and milk-based proteinCHO supplementation resulted in the attenuation of decreases in isokinetic muscle performance and increases in CK and Mb.
Article
Objective: To evaluate the effects of avocado soybean unsaponifiables (ASU) on proinflammatory mediators in chondrocytes and monocyte/ macrophage-like cells. Design: To determine the dose response of ASU, chondrocytes (5 x 10(5) cells/well) were incubated at 5% CO2, 37 degrees C for 72 h with (1) control media alone or (2) ASU at concentrations of 0.3, 0.9, 2.7, 8.3, and 25 mu g/ml. Cells were activated with 20 ng/ml lipopolysaccharide (LPS) for 24 h and cell supernatants were analyzed for prostaglandin E-2 (PGE(2)) and nitrite content. Chondrocytes and THP-1 monocyte/macrophages (5 x 105 cells/well) were incubated at 5% CO2, 37 degrees C for 72 h with (1) control media alone or (2) ASU (25 mu g/ml). One set of cells was activated for I h with LPS (20 ng/ml) for both reverse-transcriptase PCR and real-time PCR analysis of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 -beta (IL-1 beta), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (NOS) expression. One set of cells was activated for 24 h to analyze secreted PGE2 and nitrite levels in the cellular supernatant. Results: ASU reduced TNF-alpha, IL-1 beta, COX-2, and NOS expression in LPS-activated chondrocytes to levels similar to nonactivated control levels. The suppression of COX-2 and NOS expression was paralleled by a significant reduction in PGE(2) and nitrite, respectively, in the cellular supernatant. ASU also reduced TNF-a and IL-1 expression in LPS-activated monocyte/macrophage-like cells. Conclusion: The present study demonstrates that the anti-inflammatory activity of ASU is not restricted to chondrocytes, but also affects monocyte/macrophage-like cells that serve as a prototype for macrophages in the synovial membrane. These observations provide a scientific rationale for the pain-reducing and anti-inflammatory effects of ASU observed in osteoarthritis patients. (c) 2007 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Article
The basics of physical fitness and information for developing a systematic program of exercise and physical activity for the individual are outlined. This book is divided into three major areas. Part one contains chapters dealing with basic physical fitness, understanding the human body and its needs, and methods of appraising individual fitness. In the second section chapters deal with individual conditioning exercises, conditioning for cardiorespiratory endurance, advanced conditioning methods, and weight training. The final part examines additional concerns related to physical fitness. Nutrition, weight control, and exercise are discussed as well as activity and heart disease. The relative merits of various sports and physical fitness are also considered. The appendix includes test scores for women and men, a body composition chart, and physical fitness profile charts. A glossary of terms is included. (JD)
Article
KEY POINTS: • Numerous strategies exist to ameliorate delayed-onset muscle soreness (DOMS) after strenuous activity, but a theoretically sound and consistent treatment has not been established. • Treatments showing promise for the relief of DOMS after exercise-induced damage include use of some non-steroidal anti-inflammatory drugs, compression, yoga training, and increases in light muscle activity. • For the athlete, preventing muscle damage through gradual adaptation to stressful exercise may be the best treatment strategy for DOMS.
Article
The purpose of this study was to examine the role of branched-chain amino acid (BCAA) supplementation during recovery from intense eccentric exercise. Twenty-four non-weight-trained males were assigned to one of two groups: one group (supplementary, SUP) ingested BCAA beverages (n = 12); the second group (placebo, PLA) ingested artificially flavored water (n = 12). Diet was controlled throughout the testing period to match habitual intake. The eccentric exercise protocol consisted of 12 x 10 repetitions of unilateral eccentric knee extension exercise at 120% concentric one repetition maximum. On the day of the exercise, supplements were consumed 30 min before exercise, 1.5 h after exercise, between lunch and dinner, and before bed. On the following 2 d, four supplements were consumed between meals. Muscle soreness, muscle function, and putative blood markers of muscle damage were assessed before and after (1, 8, 24, 48, and 72 h) exercise. Muscle function decreased after the eccentric exercise (P < 0.0001), but the degree of force loss was unaffected by BCAA ingestion (51% +/- 3% with SUP vs -48% +/- 7% with PLA). A decrease in flexed muscle soreness was observed in SUP compared with PLA at 48 h (21 +/- 3 mm vs 32 +/- 3 mm, P = 0.02) and 72 h (17 +/- 3 mm vs 27 +/- 4 mm, P = 0.038). Flexed muscle soreness, expressed as area under the curve, was lower in SUP than in PLA (P = 0.024). BCAA supplementation may attenuate muscle soreness, but it does not ameliorate eccentric exercise-induced decrements in muscle function or increases in reputed blood markers of muscle damage, when consumed before exercise and for 3 d after an eccentric exercise bout.
Article
The McGill Pain Questionnaire consists primarily of 3 major classes of word descriptors--sensory, affective and evaluative--that are used by patients to specify subjective pain experience. It also contains an intensity scale and other items to determine the properties of pain experience. The questionnaire was designed to provide quantitative measures of clinical pain that can be treated statistically. This paper describes the procedures for administration of the questionnaire and the various measures that can be derived from it. The 3 major measures are: (1) the pain rating index, based on two types of numerical values that can be assigned to each word descriptor, (2) the number of words chosen; and (3) the present pain intensity based on a 1-5 intensity scale. Correlation coefficients among these measures, based on data obtained with 297 patients suffering several kinds of pain, are presented. In addition, an experimental study which utilized the questionnaire is analyzed in order to describe the nature of the information that is obtained. The data, taken together, indicate that the McGill Pain Questionnaire provides quantitative information that can be treated statistically, and is sufficiently sensitive to detect differences among different methods to relieve pain.