Journal of Dietary Supplements

ISSN: 1939-0211 (Print) 1939-022X (Online) Journal homepage: http://www.tandfonline.com/loi/ijds20

Effects of a Multi-Ingredient Energy Supplement

on Cognitive Performance and Cerebral-Cortical
Activation

Marcos Daou, Julia Montagner Sassi, Matthew W. Miller & Adam M. Gonzalez

To cite this article: Marcos Daou, Julia Montagner Sassi, Matthew W. Miller & Adam M. Gonzalez
(2018): Effects of a Multi-Ingredient Energy Supplement on Cognitive Performance and Cerebral-
Cortical Activation, Journal of Dietary Supplements, DOI: 10.1080/19390211.2018.1440686

To link to this article: https://doi.org/10.1080/19390211.2018.1440686

Published online: 13 Mar 2018.

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JOURNAL OF DIETARY SUPPLEMENTS
https://doi.org/./..

ARTICLE

Effects of a Multi-Ingredient Energy Supplement on

Cognitive Performance and Cerebral-Cortical Activation
Marcos Daou, MSa , Julia Montagner Sassi, BSa , Matthew W. Miller, PhDa ,
and Adam M. Gonzalez, PhDb
a
School of Kinesiology, Auburn University, Auburn, AL, USA; b Department of Health Professions,
Hofstra University, Hempstead, NY, USA

ABSTRACT KEYWORDS
This study assessed whether a multi-ingredient energy supplement attention; brain activity;
(MIES) could enhance cerebral-cortical activation and cognitive perfor- caffeine; L-theanine;
mance during an attention-switching task. Cerebral-cortical activation theacrine
was recorded in 24 young adults (12 males, 12 females; 22.8 ± 3.8 yrs) via
electroencephalography (EEG) both at rest and during the attention-
switching task before (pretest) and 30 min after (posttest) consumption
of a single serving of a MIES (MIES-1), two servings of a MIES (MIES-2), or
a placebo (PL) in a double-blinded, randomized crossover experimental
design. EEG upper-alpha power was assessed at rest and during the
task, wherein d (Z[hit rate]–Z[false alarm rate]) and median reaction
time (RT) for correct responses to targets on attention-hold and
attention-switch trials were analyzed. For both d and RT, the Session
(MIES-1, MIES-2, PL) × Time (pretest, posttest) interaction approached
statistical significance (p = .07, η2 p = 0.106). Exploring these interactions
with linear contrasts, a significant linear effect of supplement dose
on the linear effect of time was observed (ps ࣘ.034), suggesting the
pretest-to-posttest improvement in sensitivity to task target stimuli
(d ) and RT increased as a function of supplement dose. With respect
to upper-alpha power, the Session × Time interaction was significant
(p < .001, η2 p = 0.422). Exploring this interaction with linear contrasts, a
significant linear effect of supplement dose on the linear effect of time
was observed (p < .001), suggesting pretest-to-posttest increases in
cerebral-cortical activation were a function of supplement dose. In con-
clusion, our findings suggest that MIES can increase cerebral-cortical
activation and RT during task performance while increasing sensitivity
to target stimuli in a dose-dependent manner.

Introduction
Energy drinks are among the most popular supplements in adult populations (Froiland,
Koszewski, Hingst, & Kopecky, 2004; Hoffman et al., 2008). The central nervous system stim-
ulant, caffeine, is the most common component of energy drinks. Caffeine acts through the
blockade of central and peripheral adenosine receptors, contributing to an increase in neu-
rotransmitter release and motor firing rate (Souza, Del Coso, Casonatto, & Polito, 2016).

CONTACT Adam M. Gonzalez, PhD Adam.Gonzalez@hofstra.edu Department of Health Professions, Hofstra University,
Hempstead, NY  --.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/ijds.
©  Taylor & Francis Group, LLC
2 M. DAOU ET AL.

Caffeine-containing supplements are well known to exert favorable physical and mental out-
comes, including increasing exercise performance and enhancing alertness, mental focus, and
choice reaction time (Campbell et al., 2013; Souza, Del Coso, Casonatto, & Polito, 2016). How-
ever, several studies have shown that caffeine, in isolation, may not enhance cognitive perfor-
mance or impact subjective feelings related to energy and mood (Adan and Serra-Grabulosa,
2010; Gonzalez et al., 2015; Kuhman, Joyner, & Bloomer, 2015). Thus, multi-ingredient energy
supplements (MIES) often contain a variety of ingredients, which may work synergistically to
enhance various aspects of performance (Martin et al., 2017).
Dietary supplementation with MIES represents a potentially attractive intervention for
increasing cognitive performance during a variety of daily tasks that require a high degree
of concentration and awareness (e.g., occupational or educational performance). In addition,
cognition and mental flexibility have important implications for athletes required to make
quick decisions during competition; therefore, enhanced cognition may offer the “edge” that
many athletes seek (Huijgen et al., 2015; Voss, Kramer, Basak, Prakash, & Roberts, 2010).
Ingredients found in MIES include, but are not limited to, theacrine, L-theanine, ashwa-
gandha, and coffee fruit extract. Theacrine (1,3,7,9-tetramethyluric acid) is a purine alka-
loid found in certain coffee (Coffea) species, fruits (Cupuacu [Theobroma grandiflorum]),
and tea (Camellia assamica, var. kucha) that appears to act through both the adenosine and
dopamine systems to provide a mild stimulant effect, as well as a calming effect (Feduccia et al.,
2012; Taylor et al., 2016). Acute supplementation of theacrine has been shown to improve
energy, concentration, and mood while reducing fatigue (Ziegenfuss et al., 2016). Kuhman,
Joyner, and Bloomer (2015) also demonstrated that the combination of theacrine and caffeine
improved multiple subjective feelings related to energy and mood compared to placebo and
caffeine alone; however, cognitive performance was not significantly altered (Kuhman, Joyner,
& Bloomer, 2015). The amino acid L-theanine is found almost exclusively in tea and may inter-
act with caffeine to improve attention-switching performance and the ability to ignore dis-
traction (Giesbrecht, Rycroft, Rowson, & De Bruin, 2010; Haskell, Kennedy, Milne, & Wesnes,
Scholey, 2008; Owen, Parnell, De Bruin, & Rycroft, 2008). Furthermore, L-theanine acts in the
brain to promote an awake, alert, and relaxed physical and mental condition (Bryan, 2008;
Juneja, Chu, Okubo, Nagato, & Yokogoshi, 1999). Other ingredients such as ashwagandha
(Withania somnifera) may also aid in reducing feelings of anxiety and stress (Pratte, Nanavati,
Young, & Morley, 2014), while coffee fruit extract has been shown to increase blood levels
of brain-derived neurotrophic factor (BDNF), a secreted protein involved in development,
maintenance, and function of the central nervous system (Reyes-Izquierdo et al., 2013).
Electroencephalography (EEG) is a sensitive method that assesses the effects of dietary
interventions on the human brain (Siepmann & Kirch, 2002). Recent neuropharmacological
research has suggested that certain dietary ingredients may have modulatory effects on brain
activity, which may be associated with cognition. Specifically, L-theanine has been shown
to affect brain activity by reducing alpha frequency bandwidth of the EEG spectrum (∼8-
13 Hz), which has been associated with arousal states in addition to selective attention mech-
anisms (Gomez-Ramirez, Kelly, Montesi, & Foxe, 2009; Kelly, Gomez-Ramirez, Montesi, &
Foxe, 2008). We focused our analysis on the upper-alpha frequency bandwidth (10–13 Hz),
because it is related to task-specific cerebral-cortical activation (Pfurtscheller, Stancak, & Neu-
per, 1996). Further investigations into the efficacy of ingredients commonly found in MIES
are needed to determine their effects on physical and mental performance.
Recently, a MIES, Reckless (Maximum Human Performance [MHP], LLC), has been
designed in an effort to take advantage of the potential synergistic effects of the aforemen-
tioned ingredients, along with additional ingredients that may acutely increase blood flow
 JOURNAL OF DIETARY SUPPLEMENTS 3

(e.g., L-citrulline, L-norvaline, creatine) (Martin et al., 2017), enhance circulating ATP lev-
els (e.g., ancient peat and apple fruit extract; Reyes-Izquierdo, Shu, Argumedo, Nemzer, &
Pietrzkowski, 2014), and serve as antioxidants (e.g., Spectra; Nemzer, Fink, & Fink, 2014).
This study set out to assess whether this MIES could enhance cognitive performance during
an attention-switching task. In addition, the impact of the MIES on cerebral-cortical activa-
tion was assessed via EEG both at rest and during the attention-switching task.

Materials and methods

Participants
Twenty-four healthy young adults (12 males, 12 females; 22.8 ± 3.8 y) volunteered to
participate in this acute randomized, crossover design, double-blind, placebo-controlled
study. All participants submitted written consent forms to an institution-approved research
protocol (Auburn University, 15–465 EP 1511). Inclusion criteria consisted of being between
18–35 years old and right-handed, as well as being a low-to-moderate caffeine user (i.e., ࣘ 2
servings of caffeine-containing beverages per day). Participants were compensated $50 upon
the completion of the study. Prior to data collection, sample size was determined with an
a priori power calculation designed to provide 80% power to detect a medium-sized effect
(f2 = 0.25) with a minimum of six measurements (pretest and posttest for each of three
supplements) within a single group of participants, assuming a correlation among repeated
measures of 0.5, an α = 0.05, and a nonsphericity correction ε = 1 (Faul, Erdfelder, Lang, &
Buchner, 2007). Sample size was calculated to be 19 but was rounded up to 24 to ensure that
the six supplement order permutations were completely counterbalanced within each sex,
yielding an actual power of 91.3%.

Study protocol
Participants reported to the laboratory for three experimental sessions after 12:00 noon and
having abstained from caffeine for 24 h. Participants completed a familiarization trial with the
attention-switching task, which involved completing two practice blocks consisting of 21 trials
with a 1-min break after the first block and a 10-min break after the second block. Upon arrival
at the laboratory for experimental trials, participants were prepared for scalp EEG assess-
ment. Scalp EEG was recorded during 5-min rest. Then participants completed an attention-
switching task preintake while having EEG recorded. Subsequently, participants consumed
either a single serving of a multi-ingredient energy supplement (MIES-1), two servings of a
multi-ingredient energy supplement (MIES-2), or a placebo (PL) within 5 min. Thirty min-
utes after participants started to consume the supplement, scalp EEG was again recorded dur-
ing 5-min rest and while participants completed an attention-switching task posttest. The
order of experimental sessions was counterbalanced among participants and separated by a
minimum of 6 days and a maximum of 14 days.

Supplements
All supplements were ingested in liquid form (440 mL) and were the same in appearance and
taste. The ingredients in MIES-1 and MIES-2 are displayed in Table 1. PL contained 1.7 g mal-
todextrin and 1.7 g glycine. The multi-ingredient energy supplement was supplied by Maxi-
mum Human Performance, LLC (trade name Reckless; West Caldwell, NJ, USA).
4 M. DAOU ET AL.

Table . Multi-ingredient energy supplement (MIES; RecklessTM ) ingredients.

MIES- MIES-

Ingredients
Niacin (as niacinamide)  mg  mg
Folate  mcg  mcg
Yerba mate (leaf) (llex paraguaniensis (: ext), (% natural caffeine, %  mg  mg
theophylline)
Caffeine anhydrous  mg  mg
Ashwagandha (Withania somnifera) root and leaf (% withanolides) (as  mg  mg
®
Sensoril )
Whole coffee (Coffea arabica) fruit extract (as NeuroFactorTM )  mg  mg
L-theanine  mg  mg
®
Theacrine (as TeaCrine )  mg  mg

Creatine monohydrate
®
Beta-alanine (as CarnoSyn )  mg
 mg
, mg
, mg
Creatine-HCl  mg  mg
Creatine-AAB (alpha amino-butyrate)  mg  mg

L-citrulline
®
Ancient peat and apple fruit extract (from Malus domestica) (as elevATP )  mg
 mg
 mg
, mg
L-norvaline  mg  mg
SpectraTM (consisting of green coffee extract, green tea extract, broccoli sprout  mg  mg
concentrate, onion extract, apple extract, acerola extract, camu camu
concentrate, quercetin, tomato concentrate, broccoli concentrate, acai
concentrate, basil concentrate, cinnamon concentrate, garlic concentrate,
oregano concentrate, turmeric concentrate, carrot concentrate, elderberry
concentrate, mangosteen concentrate, blackberry concentrate, blackcurrant
extract, blueberry extract, chokeberry concentrate, raspberry concentrate,
sweet cherry concentrate, spinach concentrate, kale concentrate, bilberry
extract, brussels sprout concentrate)
®
Black pepper (Piper nigrum) fruit extract (as Bioperine ) . mg  mg

®
TeaCrine is a registered trademark and protected by Patents Pending, Serial No. /,; under exclusive global distribution
by Compound Solutions Inc. Natural Alternatives International (NAI) is the owner of patents as listed on www.carnosyn.com
®
and registered trademark CarnoSyn . NeuroFactor, elevATP, and Spectra are trademarks of VDF FutureCeuticals Inc. Sensoril
®
is a trademark of Natreon, Inc. and is protected under U.S. Patents ,, & ,,. BioPerine is a registered trademark
of Sabinsa Corp . ®
Attention-switching task
Participants completed an attention-switching task (Rogers and Monsell, 1995) on a com-
puter with a 38.5 cm monitor. The task consisted of two blocks of 144 trials with a 1-min
break between blocks. On each trial, a letter (A, E, G, I, K, M, R, or U) and number (2–9)
appeared 1° left and right of center (letters and numbers appeared randomly on left or right)
for 1,000 ms followed by a blank screen for 1,700 ms. The letter and number were never the
same as the previous trial in a block. On each given trial, the letter and number were the
same color: red or purple. Prior to each block, participants read instructions indicating they
should respond to the text on the monitor by pressing the computer keyboard’s space bar if
the letter was a vowel and the color was red, or if the number was even and the color was
purple; otherwise, participants should withhold a response. The color of the text switched
every three trials, and the instructions changed between blocks (i.e., on the second block of
each testing session, participants were instructed to respond to vowels if the text was purple
and to respond to even numbers if the text was red). Trials in which the color of the text was
the same as the preceding trial are known as “hold trials,” and trials in which the color of the
text was different from the preceding trial are known as “switch trials.” Switch trials demand
attention switching. Four dependent variables were extracted: (1) d for hold trials, (2) d for
switch trials, (3) median reaction time (RT) for hit hold trials, and (4) RT for hit switch trials.
The d measured sensitivity to target stimuli and was defined as Z(hit rate) – Z(false alarm
rate). RTs were natural log transformed prior to statistical analysis.
 JOURNAL OF DIETARY SUPPLEMENTS 5

EEG recording and processing

EEG recording was conducted with typical parameters (e.g., Meadows, Gable, Lohse,
& Miller, 2016). Specifically, scalp EEG was collected from the following sites (asterisk
[∗ ] indicates electrodes used in analyses): FP1, FP2, F3∗ , Fz, F4∗ , C3∗ , Cz, C4∗ , P3∗ ,
Pz, P4∗ , O1∗ , Oz, and O2∗ using an EEG cap housing a 64-channel BrainVision acti-
CAP system (Brain Products GmbH, Munich, Germany) labeled in accordance with an
extended international 10–20 system (Oostenveld & Praamstra, 2001). EEG data were
online referenced (i.e., difference between actual voltage and a reference electrode) to
the left earlobe, and a common ground was employed at the FPz electrode site. Elec-
trode impedances were maintained below 25 k throughout the study and a high-pass
filter was set at 0.016 Hz with a sampling rate of 250 Hz. The EEG signal was ampli-
fied and digitized with a BrainAmp Direct Current amplifier (Brain Products GmbH,
Munich, Germany) linked to BrainVision Recorder software (Brain Products GmbH, Munich,
Germany).
Signal processing was conducted with common procedures (e.g., Meadows, Gable,
Lohse, & Miller, 2016). Specifically, signal processing was conducted with BrainVision
Analyzer 2.1 software (Brain Products GmbH, Munich, Germany). Data were rereferenced
to an averaged ears montage (i.e., average voltage between both ears) band-passed fil-
tered between 0.1 and 45 Hz with fourth-order roll-offs and a 60 Hz notch employing a
zero-phase shift Butterworth filter. Subsequently, eye blinks were reduced employing the
independent component analysis– (ICA-) based ocular artifact rejection function within
the BrainVision Analyzer software (electrode FP2 served as the vertical electrooculog-
raphy channel) (Plank, 2013). This function searches for an ocular artifact template in
channel FP2 and then finds ICA-derived components that account for a user-specified
(70%) amount of variance in the template-matched portion of the signal from FP2. These
components were removed from the EEG signal, which was then reconstructed for further
processing. Next, data were segmented into epochs of the 1,000 ms with 50% overlaps.
Epochs wherein there was more than a 50 µV change from one data point to the next
were discarded. Next, a fast Fourier transformation was employed using 0.977 Hz bins
and a Hamming window (50% taper). Epochs were averaged for each pretest and posttest
condition (i.e., 5-min rest and attention-switching task). Spectral power was then averaged
across the upper-alpha frequency bandwidth (10–13 Hz) and natural log transformed to
approximate a normal distribution. Crucially, power in the upper-alpha frequency band-
width is inversely related to cerebral-cortical activation (Klimesch, Sauseng, & Hanslmayr,
2007).

Statistical analysis
Attention-switching task variables were submitted to separate 3 (Session: PL, MIES-1, MIES-
2) × 2 (Time: pretest, posttest) × 2 (Trial Type: hold, switch) repeated measures analysis of
variance (ANOVAs). EEG upper-alpha power during rest and task were submitted to separate
3 (Session: PL, MIES-1, MIES-2) × 2 (Time: pretest, posttest) × 4 (Scalp Region: frontal, cen-
tral, parietal, occipital) × 2 (Scalp Hemisphere: left, right) repeated measures ANOVAs. For
all analyses, a Greenhouse-Geisser correction was applied for violations of sphericity, and cor-
rected degrees of freedom and p values are reported. Interactions involving Session and Time
were predicted since they would indicate significant differences in the effect of supplement on
pretest-to-posttest changes.
6 M. DAOU ET AL.

Figure . d at pretest and posttest on hold trials (left panel) and switch trials (right panel). d measured
sensitivity to target stimuli and was defined as Z(hit rate) – Z(false alarm rate). MIES- = single serving of
a multi-ingredient energy supplement; MIES- = two servings of a multi-ingredient energy supplement;
PL = placebo. Data are presented as mean ± standard error. Within-subject linear contrasts reveal a
significant linear effect of supplement dose on the linear effect of time (pretest-posttest change) (p = .).
Trial type (hold, switch) did not interact with this effect.

Results

Attention-switching task
Changes in performance during the attention-switching task can be seen in Figures 1 and 2.
With respect to d , a trend was noted for the Session × Time interaction (F(2, 46) = 2.73,
p = .076, η2 p = 0.106). Exploring this interaction with linear contrasts, a significant linear
effect of supplement dose on the linear effect of time was observed (F(1, 23) = 5.11, p = .034,
η2 p = 0.182). There was no Session × Time × Trial Type interaction (p = .642, η2 p = 0.019).
With respect to RT, a trend was also noted for the Session × Time interaction (F(2, 46) = 2.72,
p = .077, η2 p = 0.106). Exploring this interaction with linear contrasts, a significant linear
effect of supplement dose on the linear effect of time was observed (F(1, 23) = 5.66, p = .026,
η2 p = 0.197). There was no Session × Time × Trial Type interaction (p = .233, η2 p = 0.061).

EEG results
Changes in upper-alpha power (cerebral-cortical activation) can be seen in Figures 3 and
4. With respect to the resting condition, the Session × Time interaction failed to reach

Figure . Natural log transformed reaction time, ln(RT), at pretest and posttest on hold trials (left panel) and
switch trials (right panel). MIES- = single serving of a multi-ingredient energy supplement; MIES- = two
servings of a multi-ingredient energy supplement; PL = placebo. Data are presented as mean ± standard
error. Within-subject linear contrasts reveal a significant linear effect of supplement dose on the linear effect
of time (pretest-posttest change) (p = .). Trial type (hold, switch) did not interact with this effect.
 JOURNAL OF DIETARY SUPPLEMENTS 7

Figure . Natural log transformed upper-alpha power at pretest and posttest averaged across scalp region
(frontal, central, parietal, and occipital) and scalp hemisphere (left and right) at rest (left panel) and during
task (right panel). MIES- = single serving of a multi-ingredient energy supplement; MIES- = two serv-
ings of a multi-ingredient energy supplement; PL = placebo. Data are presented as mean ± standard error.
Within-subject linear contrasts reveal a significant linear effect of supplement dose on the linear effect of
time (pretest-posttest change) (p < .) during task.

significance (p = .101, η2 p = 0.095). With respect to the task condition, the Session × Time
interaction was significant (F(2, 46) = 5.74, p < .001, η2 p = 0.422). Exploring this interaction
with linear contrasts, a significant linear effect of supplement dose on the linear effect of time
was observed (F(1, 23) = 28.1, p < .001, η2 p = 0.550).

Discussion
The use of nutritional supplements to improve energy, alertness, and cognition continues to
grow in popularity (Froiland, Koszewski, Hingst, & Kopecky, 2004; Hoffman et al., 2008).
Much of the proposed usefulness of these energy-boosting supplements is based on data on
their individual ingredients rather than finished, multi-ingredient products. The purpose of
this study was to extend our knowledge of the effects of a MIES on cerebral-cortical activation

Figure . Scalp topographies for the upper-alpha frequency bandwidth at pretest and posttest during rest
and task for each supplement. Cooler colors indicate less upper-alpha power (increased cerebral-cortical
activation). MIES- = single serving of a multi-ingredient energy supplement; MIES- = two servings of a
multi-ingredient energy supplement; PL = placebo. Within-subject linear contrasts reveal a significant linear
effect of supplement dose on the linear effect of time (pretest-posttest change) (p < .) during task.
8 M. DAOU ET AL.

and performance during an attention-switching task. Our findings suggest MIES significantly
decreased upper-alpha power (increased cerebral-cortical activation) in a dose-dependent
manner. In addition, MIES significantly improved sensitivity to target stimuli (d ) and RT
during cognitive task performance. In summary, this study suggests dose-dependent benefits
of the MIES.
Notably, the effect of MIES was not significantly more pronounced on attention-switching
trials than attention-holding trials, as indicated by a nonsignificant Session × Time × Trial
Type interaction. The failure to find a significant interaction with trial type may be due to
the predictable nature of the switch trials (occurring every third trial) and the long intertrial
interval (1,700 ms) (Rogers & Monsell, 1995). It is possible that attention-switching trials may
have revealed relatively greater effects of MIES if less-predictable switch trials and/or shorter
intertrial intervals were employed. Further, the attention-switching task employed a go/no-go
format, as opposed to a forced-choice format. That is, the attention-switching task required
participants to either make a response (go) or withhold a response (no-go), as opposed to
make either one response (e.g., press button 1) or another response (e.g., press button 2). The
disadvantage of the go/no-go format is that go trials benefit from motor priming if the previ-
ous trial required a response, whereas no-go trials involve inhibitory control if the previous
trial required a response. Thus, performance on the attention-switching task employed in the
present experiment involved several cognitive-motor processes, and it is unclear which of
these processes MIES benefited.
A main finding of this study was the ability of the MIES to modulate upper-alpha power
(i.e., change cerebral-cortical activation). Alpha power has been measured in several behav-
ioral and neuropharmacological studies. These studies have shown both a dose-dependent
and synergistic effect of caffeine and L-theanine on alpha power. A significant decrease in
absolute alpha power has been reported under resting conditions following ingestion of
caffeine at higher dosages, for example, 200 mg (Siepmann & Kirch, 2002) and 400 mg
(Deslandes et al., 2005), yet not at lower dosages, for example, 50 mg (Kelly, Gomez-Ramirez,
Montesi, & Foxe, 2008). Alternatively, L-theanine ingestion has been shown to increase
alpha power during a resting state, which has been taken to indicate relaxation without
increasing drowsiness (Juneja, Chu, Okubo, Nagato, & Yokogoshi, 1999). However, during
demanding attentional tasks, L-theanine appears to reduce alpha power, which may play a
role in attentional processing (Gomez-Ramirez et al., 2007; Gomez-Ramirez, Kelly, Mon-
tesi, & Foxe, 2009; Kelly, Gomez-Ramirez, Montesi, & Foxe, 2008). Kelly, Gomez-Ramirez,
Montesi, & Foxe (2008) investigated the effect of L-theanine (100 mg) and caffeine (50 mg)
on behavioral measures and EEG and found no behavioral or electrophysiological effects for
caffeine or L-theanine alone; however, the combination of caffeine and L-theanine improved
performance on a visuospatial cueing task and modulated alpha brain activity. Giesbrecht and
colleagues (2010) also demonstrated that L-theanine (97 mg) in combination with caffeine
(40 mg) helps to focus attention during a demanding cognitive task. Overall, behavioral and
neuropharmacological studies seem to indicate that L-theanine and caffeine together have
greater positive effects on cognitive performance and attention than either ingredient alone
(Giesbrecht, Rycroft, Rowson, & De Bruin, 2010; Haskell, Kennedy, Milne, & Wesnes, Scho-
ley, 2008; Kelly, Gomez-Ramirez, Montesi, & Foxe, 2008; Owen, Parnell, De Bruin, & Rycroft,
2008). In the current study, MIES-1 and MIES-2 (containing 50 mg L-theanine/195 mg
caffeine and 100 mg L-theanine/390 mg caffeine, respectively, in combination with other
potentially ergogenic ingredients) significantly decreased upper-alpha power as well as RT
and increased target sensitivity during task performance in a dose-dependent manner.
 JOURNAL OF DIETARY SUPPLEMENTS 9

Caffeine has been shown to increase self-reported alertness, improve mood, and enhance
psychomotor and cognitive performance (Smith, 2002). However, in addition to caffeine’s
synergistic effects with L-theanine, theacrine may act synergistically with caffeine. Theacrine
administration appears to enhance locomotor activity in a dose-dependent manner, medi-
ated by both adenosine and dopamine systems (Feduccia et al., 2012). Kuhman, Joyner,
and Bloomer (2015) demonstrated that the combination of theacrine and caffeine favorably
impacts multiple subjective feelings related to energy and mood compared to caffeine alone
and placebo. An acute dose of theacrine (200 mg) alone also has been shown to promote a
significant increase in energy, a reduction in fatigue, and a trend (p = .07) toward improved
concentration compared to a placebo (Habowski, Sandrock, Kedia, & Ziegenfuss, 2014).
Although the potential efficacy of theacrine supplementation is promising, more research is
warranted on its isolated and synergistic effects. In the current study, MIES-1 and MIES-2
contained 25 mg and 50 mg of theacrine, respectively, which may have also had a significant
impact on our findings.
The MIES administered in the current study includes several other potentially ergogenic
ingredients that may have also impacted our findings. While it is difficult to discern whether
the results were attributable to any one ingredient in particular, it is possible that the synergis-
tic effect of such ingredients allowed for the favorable outcomes. Ashwagandha is purported
to possess neuroprotective, immunomodulatory, and rejuvenating effects via the herb’s inter-
play with the nervous system and cardiopulmonary system. This may aid in reducing feel-
ings of anxiety and stress during an attentional task, thereby freeing up cognitive resources to
enhance performance (Beilock & Carr, 2005; Mishra, Singh, & Dagenais, 2000). Acute sup-
plementation with coffee fruit extract leads to an increase in plasma levels of BDNF (Reyes-
Izquierdo et al., 2013). BDNF concentrations have been reported to ameliorate the response
to stressful stimuli (Hoffman et al., 2015; Kozlovsky et al., 2007) and have been associated
with positive changes in memory and learning (Vaynman, Ying, & Gomez-Pinilla, 2004).
Furthermore, L-citrulline supplementation augments nitric oxide– (NO-) dependent signal-
ing in a dose-dependent manner (Schwedhelm et al., 2008). Due to its role in blood cir-
culation, and potentially cerebral circulation, NO-boosting supplements may also serve as
potential ergogenic aids to improve cognitive functioning (Talarowska et al., 2012). Thus,
in the context of the current study, the mechanisms underlying the reported effects can-
not be delineated. More research is warranted on the synergistic and isolated effects of
the ingredients found in MIES. We encourage future research to investigate the efficacy
of these ingredients during a variety of performance assessments employing strict dietary
control.
In conclusion, our findings suggest that a MIES containing several ingredients includ-
ing caffeine, L-theanine, teacrine, ashwagandha, coffee fruit extract, and L-citrulline can
decrease upper-alpha power (i.e., increase cerebral-cortical activation) and RT during task
performance while increasing sensitivity to target stimuli in a dose-dependent manner. This
study suggests that the MIES could provide an attractive option for individuals during
highly monotonous daily tasks or athletes seeking to enhance cognition, attention, and quick
decision-making skills.

Declaration of interest
The authors declare no conflicts of interest. The authors alone are responsible for the content and writing
of the article.
10 M. DAOU ET AL.

Funding
This work was supported by Maximum Human Performance (MHP), LLC.

About the authors

Marcos Daou, is affiliated with the School of Kinesiology at Auburn University. His research interests
include the use of psychophysiology to examine motor behavior.
Julia Montagner Sassi, is affiliated with the School of Kinesiology at Auburn University. Her research
interests include motor development.
Matthew W. Miller, is affiliated with the School of Kinesiology at Auburn University. His research inter-
ests include the use of psychophysiology to examine motor behavior.
Adam M. Gonzalez, is affiliated with the Department of Health Professions at Hofstra University. His
research interests include exercise and nutritional strategies to optimize body composition, maximize
health and performance, and enhance adaptations to resistance exercise.

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