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R E S E A R C H A R T I C L E Open Access
The effects of supplementation with
P-Synephrine alone and in combination with
caffeine on resistance exercise performance
Nicholas A. Ratamess
1*
, Jill A. Bush
1
, Jie Kang
1
, William J. Kraemer
2
, Sidney J. Stohs
3
, Vincenzo G. Nocera
1
,
Megan D. Leise
1
, Keith B. Diamond
1
and Avery D. Faigenbaum
1
Abstract
Background: Little is known concerning the potential ergogenic effects of p-synephrine supplementation.
Therefore, the purpose of the present study was to examine the effects of supplementation with p-synephrine
alone and in combination with caffeine on free-weight resistance exercise performance.
Methods: Twelve healthy, college-aged men performed a control (CT) resistance exercise protocol consisting of 6 sets
of squats for up to 10 repetitions per set using 80 % of their one repetition-maximum (1RM) with 2 min of rest in
between sets. Each subject was randomly assigned (in double-blind, balanced manner) to a treatment sequence
consisting of use of 3 supplements: p-synephrine (S; 100 mg), p-synephrine + caffeine (SCF; 100 mg of p-synephrine
plus 100 mg of caffeine), or a placebo (P). For each supplement treatment (separated by 1 week), subjects consumed
the supplement for 3 days prior to each protocol and the morning of each protocol, and subsequently did not
consume any supplements for 3 days following (i.e. wash-out period). On each protocol day, subjects reported to the
lab at a standard time, consumed a supplement, sat quietly for 45 min, performed the resistance exercise protocol, and
sat quietly for 30 min post exercise. Performance (repetition number, force, velocity and power), blood lactate, and
ratings of perceived exertion (RPE) data were collected during each protocol.
Results: Supplements SCF and S produced a significantly (P< 0.05) greater number of repetitions performed than CT
(by 11.0 ± 8.0 %) and P (by 6.0 ± 7.0 %) and a 10.6 ± 12.0 % greater increase in volume load per protocol than CT and P.
Most of the differences were seen during the last 3 sets. Mean power and velocity for all 6 sets were significantly
higher in SCF compared to CT and P by ~6.2 ± 8.0 %. No supplement effects were observed in RPE or blood lactate,
and no adverse side effects were observed or reported.
Conclusions: S and SCF augmented resistance exercise performance (total repetitions, volume load) without increasing
blood lactate or RPE. The addition of caffeine in SCF increased mean power and velocity of squat performance. These
results indicate supplementation with S and SCF can enhance local muscle endurance during resistance exercise.
Background
Thermogenic supplement use in various forms has
increased in popularity among athletes and individuals
targeting weight loss. These supplements target weight
loss by increasing energy expenditure, the rate of fat oxi-
dation, and by decreasing appetite [1–6]. Although their
effects on anaerobic exercise performance have been
equivocal [7–10], thermogenic supplements are thought
to have mild ergogenic properties. Many thermogenic
supplements contain compounds such as p-synephrine
and caffeine [11]. p-Synephrine is the primary protoalka-
loid derived from the immature fruits of Citrus auran-
tium (bitter orange, Seville orange). p-Synephrine also
occurs in other orange-related species as Marrs sweet
oranges, clementines and mandarin oranges [12, 13].
p-Synephrine has its hydroxyl group located in the para
position on its benzene ring which has been shown to
significantly alter its adrenergic receptor binding proper-
ties. It has low binding affinity for α-1 and α-2 as well as
β-1 and β-2 adrenoreceptors [14]. Therefore, it exhibits
* Correspondence: ratamess@tcnj.edu
1
Department of Health and Exercise Science, The College of New Jersey,
Ewing, NJ 08628, USA
Full list of author information is available at the end of the article
© 2015 Ratamess et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Ratamess et al. Journal of the International Society of Sports Nutrition (2015) 12:35
DOI 10.1186/s12970-015-0096-5
little or no cardiovascular stimulation compared to ephe-
drine, m-synephrine (phenylephrine), and the catechol-
amines [14]. The ergogenic actions of p-synephrine are
thoughttobemediatedmostlybyβ-3 adrenoreceptor
activation leading to increased metabolic rate, lipolysis,
and possibly reduced food intake [14, 15].
Stohs et al. [12] reviewed over 20 published and unpub-
lished human studies involving p-synephrine with doses
ranging from 5 to 80 mg (alone and in combination with
132 to 704 mg of caffeine). p-Synephrine alone or in com-
bination with other nutrients increased resting metabolic
rate and energy expenditure by up to ~13 %, and led to
modest reductions in body weight (all of the studies exam-
ining weight loss investigated p-synephrine in combin-
ation with other nutrients). However, potential ergogenic
effects of p-synephrine are poorly understood particularly
during resistance exercise.
Caffeine is a thermogenic methylxanthine alkaloid that
acts as a central nervous system stimulant. It has been
shown to increase energy expenditure and lipolysis and fat
oxidation [16]. Caffeine is thought to enhance performance
via several mechanisms including adenosine antagonism,
potentiated cyclic AMP via phosphodiesterase inhibition,
augmented muscle glycogen resynthesis, increased β-
endorphin and catecholamine secretion, increased nerve
conduction velocity and motor unit recruitment, reduced
pain perception, and enhanced permeability, mobilization,
and reduced uptake of intracellular calcium [16–22]. Some
studies have shown caffeine consumption of 3–6mg/kgof
body mass increases endurance performance [16]. How-
ever, caffeine consumption during resistance exercise has
produced equivocal findings. Some studies have shown er-
gogenic effects on muscle strength and endurance per-
formance [23, 24], while others have failed to show
performance augmentation [25, 26]. A meta-analysis has
shown that caffeine consumption increases muscle
strength and endurance but the effects may be muscle-
group specific [27].
Given the paucity of studies examining p-synephrine
supplement consumption during resistance exercise, the
purpose of the present study was to examine resistance
exercise performance concomitant with consumption of
p-synephrine with or without a low dose of caffeine. It
was our hypothesis that p-synephrine with and without
caffeine would enhance repetition and power perform-
ance during resistance exercise.
Methods
Experimental design
In order to examine the primary hypotheses of the present
study, a double-blinded, randomized, within-group cross-
over study design was used. After familiarization and
preliminary baseline resistance exercise performance
testing, subjects were randomly assigned (using a balanced
design) to either a p-synephrine (100 mg; S), p-synephrine
+caffeine (100 mg p-synephrine plus 100 mg caffeine;
SCF), or placebo (P) treatment. The resistance exercise
protocol consisted of performing 6 sets of back squats for
up to 10 repetitions per set using 80 % of subjects’max-
imal strength with 2 min of rest in between sets at a
standard time early in the morning in a fasted state. The
protocol was performed 4 times (baseline and following
consumption of each supplement). Subjects consumed
each supplement in the form of chews for 3 days prior to
and upon arrival at the laboratory the day of each protocol
and then washed-out for 3 days following each protocol
day. The 3-day pre-protocol supplementation period was
utilized in order to expose subjects to the supplements on
multiple occasions (to examine how subjects tolerated the
supplemental doses) prior to performance assessment.
Performance (repetition number, force, velocity, and
power), blood lactate, and ratings of perceived exertion
data were collected during each protocol.
Subjects
The subjects were healthy, college-aged (e.g., 20–
26 years) men (N= 12) who were former athletes with at
least 2 years of resistance training experience from the
student population at The College of New Jersey.
Descriptive subject characteristics are shown in Table 1.
None of the subjects were taking any medications,
anabolic steroids, or nutritional supplements known to
affect resistance exercise performance. All subjects had
refrained from caffeine intake for at least 3 weeks prior
to starting the study. Each subject was monitored during
this time for symptoms such as headaches and fatigue in
order to minimize potential confounding effects of
caffeine withdrawal reversal. Three weeks was selected
as withdrawal effects from low-to-moderate caffeine
consumption typically subside within 10 days [28]. No
withdrawal effects were reported upon initiation of pre-
study familiarization and testing. Prior to this period, 5
subjects reported low daily caffeine intake (<10–20 mg/
day), 3 subjects reported moderate caffeine intake (100–
Table 1 Subject descriptive characteristics
Variable Mean ± SD
Age (yrs) 22.3 ± 1.6
Height (cm) 179.5 ± 7.8
Body mass (kg) 81.3 ± 9.2
RT experience (yrs) 5.8 ± 2.4
Percent body Fat (%) 10.7 ± 3.9
VO
2
max (ml ⋅kg
−1
⋅min
−1
) 50.3 ± 7.2
1RM squat (kg) 135.6 ± 24.4
80 % of 1RM squat (kg) 107.2 ± 19.2
Key: RT Resistance training, VO
2
Oxygen consumption, 1RM
One repetition-maximum
Ratamess et al. Journal of the International Society of Sports Nutrition (2015) 12:35 Page 2 of 11
200 mg/day), and 4 subjects reported high daily caffeine
intake (250–400 mg/day). Subjects were consistently
questioned, completed diet records, and instructed not
to consume known sources of caffeine during the experi-
mental period. None of the subjects had any physio-
logical or orthopedic limitations that could have affected
lifting performance as determined by completion of a
health history questionnaire prior to initiating the study.
Subjects were instructed to refrain from exercise for
2 days prior to each protocol. This study was approved
by The College of New Jersey’s Institutional Review
Board and each subject subsequently signed an informed
consent document prior to participation.
Preliminary screening and familiarization
During the first visit to the Human Performance Labora-
tory, subjects completed a medical history questionnaire,
informed consent document, were familiarized with the
equipment and procedures, and were instructed on how
to properly complete a 3-day dietary record. Height was
measured using a wall-mounted stadiometer and body
mass was measured using an electronic scale. VO
2
max
was assessed using a progressive, multi-stage ramp
protocol on a treadmill using a metabolic system (Med-
Graphics ULTIMA Metabolic System, MedGraphics
Corporation, St. Paul, MN). Percent body fat was esti-
mated via a three-site skinfold test. The sites measured
were the pectoral, anterior thigh, and abdominal skin-
folds [29]. The same research assistant performed all
skinfold assessments. Body density was calculated using
the equation of Jackson and Pollock [29] and percent
body fat was calculated using the equation of Siri [30].
Dietary records were used to ensure subjects maintained
normal kilocalorie and macronutrient intake throughout
the study, and were completed for 3 days prior to the
baseline protocol and for 3 days prior to each subse-
quent protocol. Each dietary record was analyzed using
the Nutrition Calc Plus Version 3.4 software program
(ESHA Research, Salem, OR). Total kilocalories, grams
of fat, carbohydrates, and protein, and percent dietary
intake of fats, carbohydrates, and protein were analyzed.
Strength testing
The one-repetition maximum (1RM) squat was used as
a measure of strength using a standard protocol [31]. A
warm-up set of 5–10 repetitions was performed using
40–60 % of the perceived 1RM. After a 1-min rest inter-
val, a set of 2–3 repetitions was performed at 60–80 %
of the perceived 1RM. Subsequently, 2–4 maximal trials
were performed to determine the 1RM with 2–3 min
rest intervals in between trials. A complete range of mo-
tion and proper technique was required for each suc-
cessful 1RM trial. Subjects descended with the bar on
the rear shoulders until their upper thighs were parallel
to the ground. At that point a “lift”signal was given by a
research assistant (to ensure proper depth) and the
subject ascended to the starting position. Assessment of
1RM strength enabled calculation of the protocol loads
(i.e. 80 % of 1RM).
Control protocol
A control (no supplement) resistance exercise protocol
was performed first to establish baseline resistance exer-
cise performance. Subjects reported to the laboratory
early in the morning following a 10-h fast to minimize
any confounding influence from prior meal consump-
tion. Only water consumption was permitted. Upon
arrival, each subject was encouraged to drink water ad
libitum to pre-hydrate. Subjects had a cannula inserted
into an antecubital vein for blood sampling. Subse-
quently, each subject was positioned on a reclining chair
and sat quietly for 15 min prior to measurement of
baseline blood lactate. Subjects then proceeded to sit
quietly for an additional 45 min in a recumbent position.
The quiet sitting period was used to mimic the time of
supplement consumption during subsequent protocol
sessions.
Subjects performed a standard warm-up consisting of
3 min of stationary cycling or walking, light stretching,
and 2–3 light sets of squats with 30–65 % of 1RM.
Water was provided ad libitum during this time. The re-
sistance exercise protocol consisted of performing 6 sets
of up to 10 repetitions (i.e. when momentary muscular
failure was attained prior to the completion of 10 repeti-
tions) of the free-weight back squat with ~80 % of 1RM
using 2-min rest intervals in between sets. Standard
exercise technique was used and only those repetitions
that met the criteria were counted. Resistance remained
constant while total numbers of repetitions were
recorded. Subjects used a self-selected cadence (with no
rest in between repetitions) in order to maximize resist-
ance exercise performance. Following each set, ratings of
perceived exertion (RPE) were obtained using a category
ratio (CR) 10-point (0–10) scale. Volume load (kg) was
calculated as the number of completed repetitions x
resistance used.
Experimental protocol
Following the control session, subjects were randomly
assigned (in double-blind manner) to a balanced treat-
ment sequence. The treatments involved use of 3 supple-
ments: p-synephrine (100 mg), p-synephrine + caffeine
(100 mg of p-synephrine plus 100 mg of caffeine), or a
placebo treatment. Subjects consumed random treatment
1 for 3 consecutive days prior to returning to the labora-
tory. Subjects then reported to the laboratory the follow-
ing morning in a fasted state similar to the control
protocol session. After baseline measures and blood
Ratamess et al. Journal of the International Society of Sports Nutrition (2015) 12:35 Page 3 of 11
sampling, subjects consumed a dose of treatment 1. They
sat quietly for 45 min and subsequently initiated the resist-
ance exercise protocol discussed previously. Each subject
did not consume a supplement for the next 3 days (i.e. a
3-day “wash-out”period was used based on the half-lives
and patterns of elimination of p-synephrine and caffeine)
but then began supplementing with treatment 2 for 3 days
prior to their next scheduled protocol session. Subjects
arrived at the laboratory, consumed treatment 2, sat for
45 min, and repeated the protocol described above. Fol-
lowing a 3-day wash-out period, subjects consumed treat-
ment 3 for 3 days and repeated the protocol in a similar
manner. Each supplement protocol session was identical
to the control session with the exception of supplement
consumption prior to the 45 min quiet sitting period (fol-
lowing baseline assessments). This cross-over design
allowed each subject to experience all supplemental con-
ditions in random sequence.
Resistance exercise kinetics and kinematics
Each resistance exercise protocol was performed on a
portable force plate (Advanced Medical Technology Inc.,
Watertown, MA) with data collected at a frequency of
200 Hz. Average and peak concentric ground reaction
force per repetition were recorded and analyzed. Average
bar velocity and power for the each repetition was
measured with a Tendo™Power Output Unit (Tendo
Sports Machines, Trencin, Slovak Republic). The Tendo™
unit consists of a linear position transducer attached to
the end of the barbell which measured linear displace-
ment and time. Subsequently, average bar velocity and
power were determined for each repetition. Power and
velocity were averaged for each set (for all completed
repetitions) and for each protocol. Test-retest reliability
for the Tendo™unit in our laboratory has consistently
shown R> 0.90 [32].
Blood lactate measurements
Subjects arrived at the laboratory in the early morning
(at a standard time of day for all sessions) following an
overnight fast. Venous blood samples were collected
from subjects in a seated, semi-recumbent position at
rest (T1), following the 45 min quiet sitting protocol
(T2), immediately post-exercise (T3), and 15 min (T4),
and 30 min (T5) post exercise. All blood samples were
obtained using a 20-gauge Teflon cannula placed in a
superficial forearm vein. The cannula was maintained
patent via infusion of a heparin solution and blood was
removed via a plastic syringe connected to a 3-way
stopcock with a male luer lock adapter. T1 blood sam-
ples were drawn following a 15 min equilibration period.
T3 blood samples were taken within 30 s of exercise ces-
sation. Blood samples were collected into a Vacutainer®
tube containing SST® Gel and Clot Activator. An aliquot
of each whole blood sample was removed and immedi-
ately used for determination of blood lactate. Whole
blood lactate was analyzed in duplicate using an Analox
GM7 enzymatic metabolite analyzer (Analox Instru-
ments USA, Lunenburg, MA).
Supplement composition and procedures
The supplements used in the present study were in “chew”
form (Advantra Z®, Nutratech, Inc., West Caldwell, NJ).
Each chew was identical in appearance, chocolate flavored,
and identical in taste. All three supplements contained
isomalt, maltitol syrup, cocoa powder, natural flavors,
palm oil, soy lecithin, glycerin, and stevia. One serving
consisted of two chews. Each serving of chews contained
30 kcal from 8 g of carbohydrates. Thus, the placebo
contained only these nutrients. The chews contained these
nutrients with 100 mg of p-synephrine from Citrus auran-
tium extract in two chews. The p-synephrine + caffeine
chews consisted of the same nutrients plus 100 mg of p-
synephrine plus 100 mg of caffeine. The supplements were
administered to subjects in absolute doses. The rationale
was to examine the supplement in a manner consistent
with manufacturer’s recommendations and to expand the
p-synephrine literature base by providing a larger amount
compared to previous studies which have mostly investi-
gated absolute doses of 5–80 mg per day [12].
Subjects were instructed to consume each supplement
for 3 days prior to arriving to the Human Performance
Laboratory. Subjects were given the chews (6 in total) in
bags labeled “A”,“B”,or“C”, specific instructions on
consumption, forms to complete by recording the time
of day each supplement was consumed, and were
instructed to return the empty wrappers as documenta-
tion of use. Two chews were consumed each day gener-
ally during the late morning, early afternoon hours. Both
chews were consumed simultaneously and subjects were
instructed to chew them completely and hold remnants
under the tongue for at least 2 min prior to swallowing.
Subjects were also given two chews during each resist-
ance exercise protocol, i.e. prior to the 45-min quiet
sitting period resulting in consumption of 8 chews in
total per treatment condition.
Statistical analyses
Descriptive statistics (means ± SD) were calculated for all
dependent variables. A 2-way (treatment x time point)
analysis of variance (ANOVA) with repeated measures
was used to analyze all within-subject data. Subsequent
Tukey’spost hoc tests were utilized to determine differ-
ences when significant main effects were obtained. A
one-way ANOVA was used to analyze diet records and
body weight changes. Pearson-product moment correla-
tions were calculated for selected variables. For all
Ratamess et al. Journal of the International Society of Sports Nutrition (2015) 12:35 Page 4 of 11
statistical tests, a probability level of P≤0.05 denoted
statistical significance.
Results
Dietary intake, body weight, and side effects
Statistical analysis of the 3-day dietary records showed
that subject nutritional intake did not vary between the
four experimental conditions. Subjects consumed an aver-
age of 2,594.2± 568.3 kcals per day. Daily intake of pro-
tein, carbohydrates, and fat averaged 159.3 ± 53.8, 279.4 ±
96.7 and 95.3 ± 27.8 g, respectively. This equated to 24.6 ±
6.9, 42.4 ± 5.9 and 32.3 ± 5.4 % of daily kilocaloric intake,
respectively. Body mass did not significantly differ during
each experimental protocol; CT = 82.0 ± 9.2 kg; P = 81.7 ±
9.4 kg; S = 82.0 ± 9.8 kg; and SCF = 81.6 ± 9.4 kg. Subjects
reported no difference in taste between supplements as
the chocolate flavor masked any potential bitter taste of
the nutrients. In addition, no adverse side effects were
reported throughout the experimental period.
Repetition performance and volume load
Table 2 presents repetition performance data. No sup-
plement effect was observed when analyzing repetition
number per set. However, significant differences were
observed [P= 0.05] between treatments when total repe-
titions were analyzed. Supplements SCF and S produced
significantly greater numbers of repetitions performed
than CT and P. SCF and S produced ~11.0 ± 8.0 %
greater repetition numbers than the CT condition and
~6.0 ± 7.0 % greater repetition numbers than the P treat-
ment. In addition, a trend (P= 0.06) was observed where
most of the differences shown between supplement con-
ditions occurred between sets 4 and 6. A significant
difference was observed [P= 0.03] between treatments.
Supplements SCF (4,609.1 ± 1,175.2 kg) and S (4,623.0 ±
1,117.5 kg) produced a significantly greater volume load
per protocol than CT (4,128.0 ± 1,258.1 kg) and P
(4,321.6 ± 1,136 kg). A significant main effect was ob-
served [P< 0.0001] where repetition performance de-
creased with each successive set during all treatments.
Specific differences are shown in Table 2.
Ratings of Perceived Exertion (RPE)
Table 3 presents RPE data following each set of resist-
ance exercise. No treatment effects were observed over
all 6 sets and no significant treatments effects were
observed for the mean session RPE [P= 0.18]. RPE ob-
tained during each set was significantly [P< 0.001] nega-
tively correlated with repetitions completed (r=−0.48 to
−0.67). A significant time effect was observed between
the 1st and 6th set of resistance exercise [P< 0.0001]
where RPE values increased with each successive set.
Average and peak power
Average power data are presented in Table 4. No sup-
plement effect was observed with regard to the pattern
of reduction during each set. The mean power for all 6
sets was significantly higher in SCF compared to CT
and P by ~6.2 ± 8.0 % [P= 0.03]. Although mean power
during S was higher than CT and P, this value did not
reach statistical significance. Average power was signifi-
cantly negatively correlated to blood lactate values at
T3 (r=−0.29 to −0.48). A significant time effect was
observed [P< 0.0001] where average power decreased
with each successive set. No supplement effects were
observed with regard to the pattern of peak power re-
duction during each set. No significant differences were
observed [P= 0.67] between treatments when examin-
ing the mean peak powers of all 6 sets (CT = 1315.2 ±
195.9 W; P = 1289.8 ± 170.6 W; S = 1294.0 ± 174.4 W;
SCF = 1329.1 ± 197.2 W). A significant time effect was
observed [P< 0.0001] where peak powers decreased
with each successive set (data not shown).
Table 2 Repetition performance data
CT P S SCF
Set 1 10.0 ± 0.0 10.0 ± 0.0 10.0 ± 0.0 10.0 ± 0.0
Set 2 8.1 ± 2.3
a
9.2 ± 1.1 9.3 ± 1.2 8.9 ± 1.7
Set 3 6.6 ± 2.5
ab
6.7 ± 3.0
ab
7.8 ± 3.2
ab
7.7 ± 2.3
ab
Set 4 6.0 ± 2.7
abc
5.9 ± 3.1
ab
6.8 ± 3.1
ab
6.5 ± 2.8
abc
Set 5 4.8 ± 3.0
abcd
5.4 ± 3.4
abc
5.4 ± 2.8
abcd
5.7 ± 3.1
abcd
Set 6 4.0 ± 2.7
abcd
4.1 ± 2.5
abcde
4.9 ± 3.0
abcd
5.3 ± 3.4
abcd
Reps sets 1 –3 24.7 ± 4.3 25.9 ± 3.6 27.1 ± 3.8 26.6 ± 3.7
Reps sets 4 –6 14.8 ± 8.1 15.4 ± 8.7 17.1 ± 8.5
#
17.5 ± 9.2
#
Total reps 39.5 ± 12.1 41.3 ± 11.9 44.2 ± 11.7* 44.1 ± 12.4*
Values are mean ± SD
Key: CT Control protocol, PPlacebo treatment, Sp-synephrine treatment, SCF p-synephrine plus caffeine treatment
a
–P≤0.05 from set 1;
b
–P≤0.05 from set 2;
c
–P≤0.05 from set 3;
d
–P≤0.05 from set 4;
e
–P≤0.05 from set 5; * - P≤0.05 from CT and P;
#
-P= 0.06 from CT
and P
Ratamess et al. Journal of the International Society of Sports Nutrition (2015) 12:35 Page 5 of 11
Average and peak velocity (m/s)
Average velocity data are presented in Table 5. No
supplement effect was observed with regard to the pat-
tern of reduction during each set. The mean velocity
per set was significantly greater [P= 0.04] in SCF than
CT and P by ~6.5 ± 8.0 %. Although mean velocity dur-
ing S was higher than CT and P, this value did not
reach statistical significance. A significant time effect
was observed [P< 0.0001] where average velocity de-
creased with each successive set. No supplement effect
was observed with regard to the pattern of peak vel-
ocity reduction during each set. No significant differ-
ences were observed [P=0.84] between treatments
when examining the mean peak velocities of all 6 sets
(CT = 0.71 ± 0.06 m⋅s
−1
;P=0.70±0.10m⋅s
−1
;S=0.70
±0.07 m⋅s
−1
;SCF=0.72±0.08m⋅s
−1
). A significant
time effect was observed [P< 0.0001] where peak vel-
ocities decreased with each successive set (data not
shown).
Peak and average concentric force (N)
Peak concentric force data are presented in Table 6.
No supplement effect was observed with regard to
the pattern of peak force reduction during each set.
No significant differences were observed [P= 0.21]
between treatments when examining the mean peak
concentric force of all 6 sets. Although S and SCF
yielded higher peak concentric force (up to ~2.5 %)
than CT and P, respectively, these differences did not
reach statistical significance. A significant time effect
was observed [P< 0.0001] where peak concentric force
decreased with each successive set. No supplement ef-
fect was observed with regard to the pattern of average
force reduction during each set. The mean concentric
force across all 6 sets did not significantly differ
among conditions (CT = 1875.9 ± 229.6 N; P = 1901.1
± 210.5 N; S = 1898.1 ± 217.0 N; SCF = 1902.7 ±
222.9 N) [P= 0.24]. A significant time effect was ob-
served [P= 0.03] where average concentric force de-
creased from set 1 through set 6 at various points
(data not shown).
Blood lactate
Blood lactate data are shown in Fig. 1. No significant
supplement effects were observed [P= 0.98]. The lactate
responses in S and SCF were similar to CT and P despite
a greater volume load and repetition number performed
during each protocol. A significant time effect was ob-
served [P< 0.0001] where blood lactate was significantly
elevated at T3, T4, and T5 compared to T1 and T2 with
T3 showing the highest values immediately post resist-
ance exercise.
Table 3 Ratings of perceived exertion
CT P S SCF
Set 1 5.36 ± 1.5 5.18 ± 1.60 5.14 ± 1.27 5.41 ± 1.46
Set 2 6.55 ± 1.6
a
6.55 ± 2.02
a
6.23 ± 1.57
a
6.36 ± 1.63
a
Set 3 7.14 ± 1.10
ab
7.05 ± 1.98
ab
6.73 ± 1.79
ab
7.00 ± 1.84
ab
Set 4 7.55 ± 1.29
abc
7.59 ± 1.71
abc
7.18 ± 1.94
abc
7.50 ± 1.72
abc
Set 5 7.91 ± 1.22
abc
7.91 ± 1.51
abc
7.50 ± 1.66
abc
7.73 ± 1.68
abc
Set 6 8.91 ± 1.22
abcde
8.55 ± 1.37
abcde
8.27 ± 1.49
abcde
8.36 ± 1.36
abcde
Mean 7.23 ± 1.12 7.14 ± 1.58 6.84 ± 1.49 7.06 ± 1.44
Values are mean ± SD
Key: CT Control protocol, PPlacebo treatment, Sp-synephrine treatment, SCF p-synephrine plus caffeine treatment
a
–P≤0.05 from set 1;
b
–P≤0.05 from set 2;
c
–P≤0.05 from set 3;
d
–P≤0.05 from set 4;
e
–P≤0.05 from set 5
Table 4 Average power data (Watts)
CT P S SCF
Set 1 827.7 ± 160.8 870.4 ± 153.9 860.8 ± 155.0 875.6 ± 160.4
Set 2 734.3 ± 127.2
a
756.7 ± 144.3
a
777.5 ± 160.9
a
794.4 ± 152.5
a
Set 3 681.2 ± 126.6
ab
677.1 ± 119.2
ab
703.6 ± 186.4
ab
729.7 ± 150.5
ab
Set 4 653.1 ± 134.1
ab
622.6 ± 133.7
abc
642.8 ± 169.4
abc
682.4 ± 144.6
abc
Set 5 600.9 ± 113.8
abcd
598.2 ± 131.2
abc
622.8 ± 140.2
abc
644.7 ± 153.0
abcd
Set 6 595.1 ± 100.5
abcd
574.4 ± 114.6
abcde
561.4 ± 121.4
abcde
614.8 ± 141.8
abcde
Mean 697 ± 108.6 697 ± 106.5 718.8 ± 124.6 743.0 ± 129.3*
Values are mean ± SD
Key: CT Control protocol, PPlacebo treatment, Sp-synephrine treatment, SCF p-synephrine plus caffeine treatment
a
–P≤0.05 from set 1;
b
–P≤0.05 from set 2;
c
–P≤0.05 from set 3;
d
–P≤0.05 from set 4;
e
–P≤0.05 from set 5; * - P≤0.05 compared to CT and P
Ratamess et al. Journal of the International Society of Sports Nutrition (2015) 12:35 Page 6 of 11
Discussion
The unique finding of the present study was that supple-
mentation with 100 mg of p-synephrine alone and in
combination with 100 mg of caffeine significantly aug-
mented resistance exercise performance compared to P
and CT treatments. The SCF and S treatments produced
significantly greater numbers of repetitions performed
than CT and P and a 10.6 ± 12.0 % greater increase in
volume load per protocol than CT and P. Mean power
and velocity for all 6 sets were significantly higher in
SCF compared to CT and P. No supplement effects were
observed in RPE or blood lactate and no side effects
were reported throughout the experimental period.
The results of the present study showed ergogenic
effects of S and SCF supplementation for increasing repe-
tition performance and volume load during resistance
exercise. Both S and SCF treatments led to a nearly 3-
repetition augmented performance across all sets although
most of the enhancement was seen during the last 3–4
sets. To our knowledge, this is first study to demonstrate
an ergogenic potential of p-synephrine supplementation
when consumed solely or in combination with caffeine
during resistance exercise.
The mechanism(s) leading to the enhanced perform-
ance remains unknown. The thermogenic actions of p-
synephrine are thought to be mediated mostly by β-3
adrenoceptor activation predominantly in adipose tissue
with weak binding affinity to β-1 and β-2-adrenoceptors
[14, 15]. Other studies have shown p-synephrine can
increase liver glycogenolysis [33] and increase skeletal
muscle glucose uptake [34]. The extent to which these
lipolytic and metabolic effects of p-synephrine augment
resistance exercise performance remains unknown and
may depend upon how much substrate depletion serves
as a performance limiting factor (i.e. for 6 sets of barbell
squats in the present study). Recent evidence has shown
skeletal muscle possesses β-3 adrenoceptors [35, 36] al-
though specific activation pathways influencing muscle
strength, power, and endurance remain speculative.
Murphy et al. [35] studied the effects of the β-3 agonist
BRL 37344 on rat soleus muscles and reported increased
Na+/K+ ATPase pump activity that was mediated through
β-2 adrenoceptors. BRL 37344 facilitated intracellular Na+
removal and induced rapid force recovery after rat soleus
muscles were fatigued by 16 % following incubation with
potassium. Using a more selective β-3 agonist CL 316,243,
Miniaci et al. [36] reported increased skeletal muscle pro-
tein synthesis via the PI3K-mTOR-p70(S6k) signaling
pathway. Taken together, there is growing evidence that β-
3 receptor agonists may influence skeletal muscle con-
tractility either directly or indirectly through β-2 adreno-
ceptor activation. Although the mechanism(s) remains to
be elucidated, the effects of p-synephrine on skeletal
muscle performance via either β-3 adrenoceptor stimula-
tion, possible cell signaling from other βadrenoceptors, or
CNS activation requires further study.
Interestingly, the addition of 100 mg of caffeine to
100 mg p-synephrine did not augment repetition perform-
ance and volume load. Similar findings were reported
where the addition of caffeine failed to augment the effects
of ephedrine [37, 38]. Caffeine, by itself and in combin-
ation with other nutrients, has been shown to be ergo-
genic for various components of sports performance,
aerobic endurance, and anaerobic power [16, 18, 20].
Various studies have shown caffeine enhances resistance
Table 6 Peak concentric force data (N)
CT P S SCF
Set 1 2256.5 ± 290.3 2295.1 ± 281.6 2287.8 ± 286.2 2328.8 ± 306.5
Set 2 2232.6 ± 276.9 2262.0 ± 296.4
a
2265.9 ± 283.2 2301.0 ± 289.7
Set 3 2217.4 ± 249.5 2249.4 ± 272.0
a
2252.7 ± 259.0
a
2277.1 ± 283.6
ab
Set 4 2207.0 ± 254.8
a
2224.5 ± 270.8
a
2251.9 ± 280.7
a
2262.0 ± 287.0
ab
Set 5 2184.1 ± 258.4
ab
2208.4 ± 251.9
abc
2224.9 ± 267.8
ab
2227.5 ± 268.6
abcd
Set 6 2175.3 ± 252.9
ab
2170.9 ± 240.4
abcde
2209.7 ± 244.0
abc
2214.3 ± 241.6
abcd
Mean 2212.1 ± 258.0 2235.0 ± 266.7 2248.8 ± 266.9 2268.5 ± 277.1
Values are mean ± SD
Key: CT Control protocol, PPlacebo treatment, Sp-synephrine treatment, SCF p-synephrine plus caffeine treatment
a
–P≤0.05 from set 1;
b
–P≤0.05 from set 2;
c
–P≤0.05 from set 3;
d
–P≤0.05 from set 4;
e
–P≤0.05 from set 5
Table 5 Average velocity data (m ⋅s
−1
)
CT P S SCF
Set 1 0.46 ± 0.06 0.49 ± 0.06 0.47 ± 0.06 0.48 ± 0.05
Set 2 0.41 ± 0.05
a
0.42 ± 0.07
a
0.43 ± 0.07
a
0.44 ± 0.07
a
Set 3 0.38 ± 0.06
ab
0.38 ± 0.07
ab
0.38 ± 0.09
ab
0.40 ± 0.07
ab
Set 4 0.36 ± 0.06
ab
0.34 ± 0.07
abc
0.35 ± 0.09
abc
0.38 ± 0.08
abc
Set 5 0.33 ± 0.06
abcd
0.33 ± 0.08
abc
0.34 ± 0.07
abc
0.35 ± 0.08
abcd
Set 6 0.33 ± 0.06
abcd
0.32 ± 0.07
abcde
0.31 ± 0.07
abcde
0.34 ± 0.08
abcde
Mean 0.38 ± 0.05 0.38 ± 0.06 0.39 ± 0.07 0.40 ± 0.07*
Values are mean ± SD
Key: CT Control protocol, PPlacebo treatment, Sp-synephrine treatment, SCF
p-synephrine plus caffeine treatment
a
–P≤0.05 from set 1;
b
–P≤0.05 from set 2;
c
–P≤0.05 from set 3;
d
–P≤
0.05 from set 4;
e
–P≤0.05 from set 5; * - P≤0.05 compared to CT and P
Ratamess et al. Journal of the International Society of Sports Nutrition (2015) 12:35 Page 7 of 11
exercise performance [18], isometric and isokinetic peak
torque and power [19, 21, 23, 39], the number of repetitions
performed to failure [24, 40–42] and maximal strength
[43], and attenuates reductions in maximal strength and
power seen during morning hours [44]. However, some
studies have shown caffeine consumption did not augment
peak torque [45], 1RM strength [25, 43, 46], or maximal
repetition performance/volume load for at least some exer-
cises assessed [38, 43, 46].
Trained subjects may be more responsive to caffeine
intake [18, 21, 47] and the likelihood of improvement
increases with large muscle group size and location
[18, 23, 27, 42, 48]. In a meta-analysis, Warren et al.
[27] reported that caffeine exhibited some level of er-
gogenic improvements in 23 of 27 studies [augmented
maximal voluntary contractile (MVC) strength of ~4 %
and local muscle endurance by 14 %]. Astorino &
Roberson [47] reviewed 11 studies and concluded that
caffeine was more likely to increase resistance exercise
repetition number (mean improvement of approxi-
mately 9.4 %) than 1RM strength.
The vehicle of consumption and dose of caffeine af-
fects the acute response. Most studies demonstrating
ergogenic effects of caffeine utilized anhydrous caffeine
consumption at moderate-to-high doses typically ran-
ging from 2 to 9 mg/kg of body mass [27, 47]. Astorino
et al. [49] reported only a higher dose of caffeine (5
versus 2 mg/kg) improved isokinetic resistance exercise
performance by 5–8 % thereby demonstrating a dose–
response relationship. In the present study caffeine in-
take was low and given in a standard absolute amount
within each chew averaging 1.23 mg/kg of body mass.
Thus, it is possible that a higher dose of caffeine is
needed to augment repetition performance and volume
load. However, the potentiating effect of p-synephrine
consumed in combination with caffeine needs to be con-
sidered. p-Synephrine alone augmented resistance exer-
cise performance similarly to the SCF treatment. The
amount of p-synephrine consumed in the present study
was higher than most studies [11] but similar to one
study [13] although these studies did not examine resist-
ance exercise performance. Our data indicate that the
addition of only 100 mg of caffeine to the chews may
not be sufficient to augment further increases in local
muscle endurance.
The addition of caffeine to p-synephrine did augment
repetition average velocity and power. Average power
and velocity for all 6 sets were significantly higher in
SCF compared to CT and P by ~6.2 ± 8.0 %. Although
mean power during S was higher than CT and P (by
~3 %), these values did not reach statistical significance.
The mechanisms of caffeine’s ergogenic effects are vast
and difficult to isolate during exercise. Caffeine is a cen-
tral nervous system stimulant that increases lipolysis,
potentiates cyclic AMP via phosphodiesterase inhibition,
and augments post-exercise muscle glycogen storage
[20]. However, during high-intensity resistance exercise
other mechanisms appear more plausible. Caffeine may
increase contractile force through mobilization of intra-
cellular calcium, increased calcium release from the
sarcoplasmic reticulum, and decreased calcium uptake
[20]. Other resistance exercise studies have shown
Fig. 1 Blood Lactate Response. Key: CT Control protocol, PPlacebo treatment, Sp-synephrine treatment, SCF p-synephrine plus caffeine
treatment; * –P≤0.05 from T1, T2, T4, and T5; # –P≤0.05 from T1, T2, T3, and T5; @ –P≤0.05 from T1, T2, T3, and T4. No differences were
observed in between treatments. Data presented are means ± SD
Ratamess et al. Journal of the International Society of Sports Nutrition (2015) 12:35 Page 8 of 11
increased muscle fiber conduction velocity [19] and
EMG activity [39] following caffeine consumption pos-
sibly indicative of greater motor unit recruitment [27].
Adenosine antagonism, reduced pain perception, and
blunted perceived exertion during high-intensity exercise
performance may also play pivotal roles [18, 24, 40].
Thus, it appears multiple mechanisms in combination
could contribute to caffeine’s ergogenic effects of average
velocity and power observed during each set.
An interesting finding was that the addition of 100 mg
of caffeine to 100 mg of p-synephrine augmented aver-
age power during each set despite similar total repeti-
tions and volume load performed between S and SCF
treatments. Further analysis showed that the average and
peak power obtained during each repetition that pre-
ceded muscular failure was still greater in SCF. This
indicates that the subjects performed more powerful
repetitions up until the point of momentary muscular
exhaustion. However, the enhanced power did not result
in a greater number of repetitions or volume load per-
formed in SCF compared to S. In fact, no significant
correlations were shown between average or peak power
values and the number of repetitions completed. Similar
findings were reported by Behrens et al. [50] who
showed that caffeine consumption increased power per-
formance of the plantar flexor muscles but did not
increase MVC strength. One plausible reason may be
that maximal and near-maximal squat performance is
limited by the sticking region (area where bar velocity is
minimal) located superior to the bottom parallel position
close to an absolute thigh angle of approximately 30°
[51]. Surpassing the sticking region increases the likeli-
hood of completing a successful repetition as bar velocity
increases during the remainder of the range of motion
until the deceleration phase ensues [51]. Although power
and velocity were higher during each repetition, it is
possible the greater power did not transfer through the
sticking region when fatigue reached maximal levels.
Nevertheless, the higher power and velocity values ob-
served during the SCF treatment may be viewed as benefi-
cial and could potentially lead to greater power gains
during long-term training periods.
Average and peak concentric force decreased from set
1 through set 6 at various points. However, no supple-
ment effect was observed with regard to the pattern of
reduction during each set. Although S and SCF treat-
ments yielded higher peak concentric force values (of up
to 2.5 %) than CT and P, respectively, these differences
did not reach statistical significance. These data demon-
strate that the velocity increase was the main contribu-
tor to increased power seen in SCF. Although force and
velocity are positively related, the small relative peak
concentric force increases observed in SCF and S did
not reach statistical significance. Nevertheless, this small
mean difference appeared large enough to increase bar
velocity and subsequent power performance.
The results of the present study showed a progressive
increase in RPE during each successive set with no supple-
ment effects observed. Numerous studies have examined
the effects of caffeine on RPE. These studies have shown
either no effect of caffeine on RPE [41–43, 46, 49] or a
reduced RPE response [24, 40] during resistance exercise.
Doherty and Smith [52] conducted a meta-analysis of
studies examining caffeine effects on RPE during exercise
and concluded that caffeine reduced RPE by 5.6 % with a
concomitant 11.2 % increase in performance. RPE
accounted for 29 % of the variance in exercise perform-
ance [52]. Haller et al. [11] examined Ripped Fuel (21 mg
of synephrine and 304 mg of caffeine) during 30 min of
cycling at 75–80 % VO
2
max and reported lower RPE
during exercise. Thus, our data support studies during re-
sistance exercise showing similar RPE values between caf-
feine and placebo conditions. The results of the present
study indicated that p-synephrine alone or in combination
with caffeine yielded similar RPE during resistance exer-
cise. Considering that significant performance improve-
ments were seen in both S and SCF treatments, these data
indicate that both supplements can blunt acute increases
in RPE that would be expected with a greater volume load
of resistance exercise.
A similar finding was observed in blood lactate. Signifi-
cant elevations in blood lactate were seen at T3, T4, and
T5 with no differences observed between treatments.
Haller et al. [11] reported no difference in blood lactate
response between Ripped Fuel and placebo treatments
during cycling. Studies examining the effects of caffeine
consumption on blood lactate response to resistance exer-
cise have shown no differences [40] or greater blood
lactate concentrations [24] as performance enhancement
was shown. The results of the present study indicate that
100 mg of p-synephrine increased repetition performance
and volume load without increasing the blood lactate
response. The addition of 100 mg of caffeine did not aug-
ment the response. Thus, both the S and SCF supplements
enhanced performance without eliciting a greater lactate
response.
The results of the present study should be viewed
within the design limitations. The supplementation
protocol was based on using absolute dosing in lieu of
relative dosing as the intent was to examine the supple-
ments in their available chew form. In addition, sub-
jects consumed the supplements for three days prior to
performing each protocol. Thus, the acute resistance
exercise response to a single dose remains to be seen.
Future studies should address p-synephrine supple-
mentation using a variety of doses for different types of
resistance exercise programs and should examine po-
tential chronic training effects.
Ratamess et al. Journal of the International Society of Sports Nutrition (2015) 12:35 Page 9 of 11
Conclusions
This study demonstrated that 100 mg of p-synephrine alone
or in combination with 100 mg of caffeine significantly
augmented resistance exercise repetition performance and
volume load. The addition of caffeine to p-synephrine re-
sulted in faster, more powerful repetitions. These changes
took place without a concomitant increase in RPE or blood
lactate indicating that p-synephrine (with and without caf-
feine) supplementation can blunt acute increases in RPE
and blood lactate known to accompany a greater volume of
exercise. The resultant effects are increased local muscular
endurance and more powerful repetitions (when caffeine is
added) with no additional perceived exertion or lactate
accumulation.
Competing interests
SJS has served as a consultant to Nutratech, Inc. All other authors report no
competing interests.
Authors’contributions
NAR, JAB, and JK were involved with study design, subject recruitment,
scheduling and coordination, protocol setup and supervision, data
acquisition, data analysis and interpretation, and preparation of the
manuscript. SJS, WJK, and ADF were involved in study design, data
interpretation, and preparation of the manuscript. VGN, MDL, and KBD were
involved in subject scheduling and coordination, equipment calibration,
protocol setup, data acquisition, data entry, and analysis. All authors read
and approved the final manuscript.
Acknowledgments
We would like to thank a dedicated group of subjects for their participation
in this study. We would like to thank Lauren Pigott, Joshua Pacifico,
Cassandra Noonan, Ryan Kar, Victoria Davila, and Amber Schlosser for their
assistance with data collection and analysis. This study was funded from a
grant from Nutratech, Inc., West Caldwell, NJ.
Author details
1
Department of Health and Exercise Science, The College of New Jersey,
Ewing, NJ 08628, USA.
2
Department of Human Sciences, The Ohio State
University, Columbus, OH 43210, USA.
3
School of Pharmacy and Health
Professions, Creighton University, Omaha, NE 68178, USA.
Received: 10 April 2015 Accepted: 2 September 2015
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Ratamess et al. Journal of the International Society of Sports Nutrition (2015) 12:35 Page 11 of 11
