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Health and ergogenic potential of oral adenosine-5 ′ -triphosphate (ATP) supplementation

Authors:
  • MTI BioTech Inc.

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Adenosine triphosphate (ATP) is the primary compound that provides energy to drive many processes in living cells, including muscle contraction, neurotransmission, and cardiac function. Initial research used enteric-coated ATP that displayed no apparent efficacy. However, ATP disodium supplementation has demonstrated improved bioavailability and acute and chronic benefits to cardiovascular health, muscular performance, body composition , and recovery while attenuating muscle breakdown and fatigue. In this review, we provide a critical assessment of oral ATP's bioavailability and its various health and ergogenic benefits.
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Journal of Functional Foods 78 (2021) 104357
1756-4646/© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Health and ergogenic potential of oral adenosine-5-triphosphate
(ATP) supplementation
Ralf J¨
ager
a
,
*
, Martin Purpura
a
, John A. Rathmacher
b
,
c
, John C. Fuller Jr.
d
, Lisa M. Pitchford
b
,
e
,
Fabricio E. Rossi
f
, Chad M. Kerksick
g
a
Increnovo LLC, 2138 E Lafayette Pl, Milwaukee, WI 53202, USA
b
MTI BioTech, Inc., 2711 S. Loop Dr., Suite 4400, Ames, IA 50010, USA
c
Dept. of Animal Science, Iowa State University, Ames, IA 50011, USA
d
Metabolic Technologies, LLC, 135 W Main St, Suite B, Missoula, MT 59802, USA
e
Dept. of Kinesiology, Iowa State University, Ames, IA 50010, USA
f
Immunometabolism of Skeletal Muscle and Exercise Research Group, Department of Physical Education, Federal University of Piauí (UFPI), 64049-550 Teresina, Piauí,
Brazil
g
Exercise and Performance Nutrition Laboratory, School of Health Sciences, Lindenwood University, St. Charles, MO, USA
ARTICLE INFO
Keywords:
ATP
Exercise performance
Cardiovascular health
ABSTRACT
Adenosine triphosphate (ATP) is the primary compound that provides energy to drive many processes in living
cells, including muscle contraction, neurotransmission, and cardiac function. Initial research used enteric-coated
ATP that displayed no apparent efcacy. However, ATP disodium supplementation has demonstrated improved
bioavailability and acute and chronic benets to cardiovascular health, muscular performance, body composi-
tion, and recovery while attenuating muscle breakdown and fatigue. In this review, we provide a critical
assessment of oral ATPs bioavailability and its various health and ergogenic benets.
1. Introduction
1.1. ATP: Lifes energy reservoir
Adenosine triphosphate (ATP) was rst discovered in 1929 by the
German chemist Karl Lohmann, who isolated ATP from muscle and liver
extracts (Langen & Hucho, 2008). Found in every cell of the human
body, ATP has been dubbed as the currency of energy affecting virtually
every physiological process requiring energy. Energy, approximately
30.6 kJ/mole, is freed from the ATP molecule by a reaction that removes
one phosphate group. The resulting adenosine diphosphate (ADP) is
usually immediately recycled in the mitochondria where it is recharged
again into ATP via phosphorylation (i.e., the adding of a phosphate
group) (Fig. 1). Notably, each molecule of ATP in the human body will
be recycled 2,0003,000 times in a single day.
Beyond powering cellular processes, levels of and the presence (or
absence) of intracellular ATP can communicate signals across cells once
released into the extracellular space. Known as ATP signaling, and rst
detected between nerve cells and muscle tissue, ATP signaling occurs
between a wide variety of cell types in the body (Khakh & Burnstock,
2009). While ATPs role in increasing skeletal muscle calcium perme-
ability and other aspects of muscle contraction have been extensively
studied (Burnstock & Kennedy, 1985; Burnstock, 2007), ATP signaling,
due to the multiplicity of cell-surface ATP receptors found in a diverse
array of tissues and cell types (Burnstock & Wood, 1996), plays a crucial
role in a variety of biological processes including neurotransmission,
blocking of chloride efux, cardiac function, platelet function, vasodi-
latation and liver glycogen metabolism (Agteresch, Dagnelie, van den
Berg, & Wilson, 1999; Khakh & Burnstock, 2009). Initial research using
enteric-coated ATP questioned this formulations bioavailability after
oral administration. Recent studies, however, have demonstrated an
increased potential for oral ATP supplementation when administered as
ATP disodium. The purpose of this review was to summarize and assess
the available literature base surrounding the oral administration of ATP
relative to its bioavailability and health and physical performance
outcomes.
2. Methods
While conducting this systematic review, the checklist and owchart
* Corresponding author.
E-mail address: ralf.jaeger@increnovo.com (R. J¨
ager).
Contents lists available at ScienceDirect
Journal of Functional Foods
journal homepage: www.elsevier.com/locate/jff
https://doi.org/10.1016/j.jff.2021.104357
Received 22 September 2020; Received in revised form 1 January 2021; Accepted 2 January 2021
Journal of Functional Foods 78 (2021) 104357
2
of Preferred Reporting for Systematic Reviews and Meta-Analyses
(PRISMA) were used as a guide (Moher, Liberati, Tetzlaff, & Altman,
2009). The literature search process was performed in the PubMed,
Scopus and Google Scholar literature databases. The MeSh terms were
used and they included, Adenosine-5-triphosphate [Title] or ATP
[Title] AND exercise [Title] or athlete [Title] or physical activity [Title].
In order to increase the accuracy of the selection of articles searched on
Google Scholar, only articles that included related keywords were
selected. All clinical trials that involved humans and articles published
in the English language were included in this review. Articles excluded
were studies that used in vitro models, animal studies, reviews, journals
written in non-English language, and studies without access to full-text.
From the studies that met eligibility criteria, extraction of data was done
in which the author names, year of publication, study setting or location,
study design, denite description and sample size, description of expo-
sure, description of outcomes, description of the control group, the study
ndings, and covariates involving data processing were identied. Full-
length article and data extraction were reviewed by two investigators
independently. During the extraction process, the investigators dis-
cussed any discrepancies until they reached a mutual agreement. If
needed, the corresponding authors of eligible articles were contacted for
additional information. Fig. 2 provides a PRISMA ow diagram to
illustrate these methods, and Table 1 is a summary table that addresses
the major research design elements of the applicable literature.
3. Bioavailability
Continuous intravenous administration of ATP has been shown to
signicantly increase erythrocyte ATP pools by 4060% (Rapaport,
Salikhova, & Abraham, 2015). In addition, exogenously administered
ATP rapidly degrades to adenosine while ATP levels accumulate inside
erythrocytes. These changes suggest the presence of dynamic mecha-
nisms that facilitate the uptake of adenosine from blood plasma. From
here, ATP pools can then be released locally or globally from circulating
erythrocytes.
ATP is rapidly dephosphorylated to ADP by hydrolysis in acidic en-
vironments such as that found in the stomach. The intraluminal pH
changes rapidly from highly acidic (pH ~ 2.0) in the stomach to a pH of
approximately 6.0 in the duodenum and then gradually increases to a pH
of about 7.4 in the terminal ileum. ATP exhibits stability between pH 6.8
7.4 (Alberty, 1998), thus to protect ATP from the acidic environment
in the stomach, enteric-coated oral ATP supplements were used in early
absorption studies (Arts et al., 2012; Coolen et al., 2011; Jordan et al.,
2004). However, oral administration of a single acute high-dose
(5,000 mg) (Arts et al., 2012), 14 days of 150 or 225 mg per day (Jor-
dan et al., 2004), and 28 days of 250, 1,250 or 5,000 mg per day (Coolen
et al., 2011) of enteric-coated ATP all failed to signicantly increase
blood concentrations of ATP or its metabolites.
Later development realized that for effective duodenal absorption of
ATP into the bloodstream, the enteric coating needs to dissolve at pH
5.5, the average pH of the proximal duodenum. Therefore, one potential
explanation for the lack of change in ATP levels after oral administration
of enteric-coated ATP could be the buffering capacity of ATP as diso-
dium salt at pH 4.04.5 (Metzler, 1977). The enteric coating of the ATP
disodium requires a pH of 5.5 for dissolution. The enteric coating might
only partly dissolve and allow duodenal contents and water to penetrate
in the moment of disintegration. As a result, the ATP disodium could
keep the pH below 5.5, which would limit the extent to which dissolu-
tion occurs compromising its breakdown and subsequently its release of
ATP disodium at the duodenum where it could be absorbed into the
bloodstream.
Absorption of orally administered non-coated ATP (5 mg/kg/day
ATP for 30 days) was tested in an animal model (Kichenin & Seman,
2000). In this study, improvements in adenosine uptake, ATP synthesis,
and ATP exportation by red cells were found to occur. Using a human
infusion model, Rapaport and investigators infused ATP into advanced
malignancy cancer patients for eight hours over eight weeks (Rapaport
et al., 2015). These authors posited that ATP itself does not transport
across plasma membranes and is rst broken down to adenosine. From
there adenosine is then taken up by erythrocytes and subsequently ex-
pands the total erythrocyte ATP pool. These data suggest that, despite its
expected gastric instability, oral ATP supplementation may not require
an enteric coating to exert benecial physiological effects. Subse-
quently, Purpura et al., 2017 used a human investigation involving oral
uncoated ATP disodium supplementation for 15 days at a dose of 400 mg
per day. While adenosine was not measured in this investigation,
Fig. 1. Energy is freed from ATP by removing one of the phosphate groups yielding ADP. ADP is then recharged into ATP via phosphorylation.
R. J¨
ager et al.
Journal of Functional Foods 78 (2021) 104357
3
supplementation was found to prevent decreases in ATP, ADP, and AMP
in the blood 30 min following high-intensity exercise in comparison to
the placebo (Purpura et al., 2017) (Fig. 3).
These ndings are important as prior investigations only examined
resting conditions and failed to identify any signicant increases in ATP
levels (Arts et al., 2012; Coolen et al., 2011; Jordan et al., 2004). It is,
therefore, hypothesized that an indirect mechanism for ATP re-synthesis
exists, whereby the chronic ingestion of oral non-enteric coated ATP
disodium increases the capacity of erythrocytes or other cellular com-
ponents or structures to synthesize and better sustain plasma ATP con-
centrations in response to the hypoxic perturbations, such as those
triggered by high-intensity exercise. It is further proposed that ATP and/
or its respective metabolites (i.e., ADP and AMP) may stimulate intra-
cellular ATP synthesis via reactions similar to the myokinase reaction or
by interacting with specic ATP and adenosine receptors on the cells
surface through a signalling effect (Freitas et al., 2019). As such, several
open questions remain regarding the potential or actual operative
functions which outline the observed bioavailability of oral ATP sup-
plementation, and more research is needed to better understand the
physiological and biochemical implications of these mechanisms with
and without external hypoxic triggers such as intense physical exercise.
4. Effects of ATP supplementation on muscular performance and
body composition
It is hypothesized that the improvement in ATP turnover (e.g., pre-
vention of ATP decline or improvement in ATP:ADP ratio) through oral
supplementation of ATP could allow athletes to maintain performance
through longer periods of exertion and consequently delay the onset of
fatigue. Theoretically, this heightened performance would allow for a
Fig. 2. Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) ow diagram for selection of eligible articles.
R. J¨
ager et al.
Journal of Functional Foods 78 (2021) 104357
4
Table 1
Summary table of studies examining outcomes related to ATP administration. Studies are rst grouped into absorption, sports, and then non-sports studies. Individual
references are sorted alphabetically within each group within the table.
Study Design Subjects Methods Supplementation Duration Main Findings (Effect of ATP)
Absorption Studies
Arts et al.
(2012)
Randomized,
placebo-
controlled, cross-
over
8 healthy men (2) and
women (6)
(age =27 ±6 yrs)
Blood sampling 5000 mg ATP disodium
as proximal-release and
distal-release pellets
1 Week No effect on blood ATP
concentrations.
Coolen et al.
(2011)
Randomized,
double-blind,
placebo-
controlled
32 healthy men (29 ±14
yrs)
Blood sampling 0, 250, 1250 or 5000 mg
ATP disodium. In
addition, 5000 mg dose
on days 0 and day 28.
4 Weeks All patterns of ATP
supplementation for 4 weeks did
not lead to changes in blood or
plasma ATP concentrations, only
resulted in increased uric acid
concentrations.
Jordan et al.
(2004)
Randomized,
double-blind,
placebo-
controlled
27 men (high dose ATP
N =9, 29 ±8 yrs; Low Dose
ATP N =9, 30 ±7 yrs;
placebo N =9, 29 ±6 yrs)
Blood sampling 150 mg or 225 mg of
enteric coated ATP
disodium
14 Days Acute supplementation non-
signicantly increased total blood
ATP levels (225 mg: +11%;
150 mg: +10%), chronic
supplementation had no effect on
whole blood ATP, or plasma ATP
concentrations.
Purpura et al.
(2017)
Randomized,
double-blind,
placebo-
controlled
42 resistance trained men
(ATP N =21, Placebo
N =21, age =20 ±3 yrs)
Blood sampling 400 mg ATP disodium
for 14 days
15 Days No effect on resting ATP levels,
but prevented exercise-induced
declines in ATP and ADP levels
(p <0.05).
Sports Studies
Freitas et al.
(2019)
Randomized,
double-blind,
placebo-
controlled, cross-
over
11 recreationally resistance
trained men (28 ±6 yrs)
Lower body
resistance exercise
400 mg ATP disodium;
30 min pre-exercise
Single dose Signicantly improved athletic
performance: higher total weight
lifted (p =0.05). Signicantly
greater oxygen consumption
during exercise (p =0.021).
J¨
ager et al.
(2014)
Pilot study 12 resistance-trained men
(age =24 ±4 yrs)
Acute arm exercise 400 mg ATP disodium
30 min pre-breakfast
12 Weeks Signicantly increased blood ow
and brachial dilation at weeks 1,
8, and 12 (p <0.05).
Jordan et al.
(2004)
Randomized,
double-blind,
placebo-
controlled
27 men (high dose ATP
N =9, 29 ±8 yrs; Low Dose
ATP N =9, 30 ±7 yrs;
placebo N =9, 29 ±6 yrs)
Anaerobic exercise
performance
150 mg or 225 mg of
enteric coated ATP
disodium
14 Days At 225 mg dose, increased 1RM,
repetitions to fatigue, and total
lifting volume at post-test
Purpura et al.
(2017)
Randomized,
double-blind,
placebo-
controlled
42 resistance trained men
(ATP N =21, Placebo
N =21, 20 ±3 yrs)
Sprint protocol 400 mg ATP disodium
before breakfast; on day
15, 30 min pre-exercise
15 Days Signicantly increased Wingate
peak power in later bouts
compared to baseline. Prevented
the decline in muscle excitability
in later bouts (p <0.0001).
Rathmacher
et al.
(2012)
Randomized,
double-blind,
placebo-
controlled, cross-
over
16 recreationally active men
(N =8) and women (N =8)
(25 ±3.9 yrs)
Strength and fatigue
testing
2 ×200 mg ATP
disodium; pre-
breakfast/dinner
15 Days Improved leg muscle low peak
torque in set 2 (p <0.01); tended
to decrease leg muscle fatigue in
set 3 (p <0.10).
Wilson et al.
(2013)
Randomized,
double-blind,
placebo- and diet-
controlled
21 resistance-trained men
(ATP N =11, Placebo
N =10, age =23 ±1 yrs)
Phase 1 - periodized
resistance-training,
Phase 2 -
overreaching cycle,
Phase 3 - two-week
taper
400 mg ATP disodium
on non-training days
pre-breakfast or 30 min
pre-exercise
12 Weeks Signicantly increased lean body
mass (p <0.001) and muscle
thickness (p <0.02) over training
alone. Signicantly increased
total strength and vertical jump
power (p <0.001).
Non-Sports Studies
Bannwarth
et al.
(2005)
Randomized,
double-blind,
parallel-group,
placebo-
controlled
162 men and women (ATP
N =81, 43 ±10 yrs; placebo
N =80 41 ±10 yrs) with a
diagnosis of subacute lower
back pain.
One-month therapy 90 mg ATP disodium One Month Signicantly improved RDQ at
day 7 (p =0.02). Signicantly less
use of rescue analgesic.
de Freitas
et al.
(2018)
Randomized,
double-blind,
placebo-
controlled, cross-
over
11 hypertensive women
(62 ±5 yrs)
Walking exercise 400 mg ATP disodium;
30 min pre-exercise
Single dose Faster recovery of heart rate
variability; reduced systolic blood
pressure after exercise (p <0.05).
Hirsch et al.
(2017)
Randomized,
double-blind,
placebo-
controlled
53 subjects (23 men, 30
women; 55 ±6 yrs)
Weight loss
parameters and ow
mediated dilation
200 mg ATP disodium,
200 mg ATP disodium
plus 1,000 mg
GlycoCarn, 1,000 mg
GlycoCarn
90 Days Signicantly decreased in blood
glucose, malondialdehyde levels,
waist and hip circumference, and
waist/height ratio; signicantly
increased ow-mediated dilation
(p 0.05).
Ju et al.
(2016)
Case study 7-year-old boy with ATP1A3
mutation, presenting with
recurrent hemiplegic
episodes
2 Year therapy 20-to100 mg ATP
disodium twice a day;
gradually increased
2 Years Signicantly lower frequency and
shorter duration of hemiplegic
episodes. Marked amelioration of
alternating hemiplegia of
childhood episodes, and
(continued on next page)
R. J¨
ager et al.
Journal of Functional Foods 78 (2021) 104357
5
greater completion of work, which sets the stage for greater exercise
training adaptations. These potential benets of ATP disodium supple-
mentation were investigated in a series of clinical studies (Freitas et al.,
2019; Jordan et al., 2004; Purpura et al., 2017; Rathmacher et al., 2012;
Wilson et al., 2013).
Jordan et al. published one of the rst investigations to examine the
acute impact of two different doses (150 and 225 mg) of non-enteric
coated ATP (Jordan et al., 2004). Twenty-seven healthy, previously
active males were supplemented in a randomized, double-blind fashion
to either a placebo, 150 mg, or 225 mg doses of ATP for a period of
14 days. After 7 and 14 days of supplementation, participants completed
two Wingate tests and three sets of maximal bench press repetitions with
70% of a pre-determined one-repetition maximum (1RM). Results from
this study showed that 225 mg of enteric-coated ATP signicantly
increased the number of repetitions to fatigue during the rst of three
sets of bench press repetitions (+18.5%, p <0.007) as well as total
lifting volume (+22%, p <0.003) in comparison to baseline. These
changes, however, were not statistically different than the non-
signicant improvements also observed in the placebo and low dose
group (150 mg enteric-coated ATP) for repetitions completed and total
lifting volume. No changes were observed in sets 2 or 3 of completed
bench press repetitions nor any anaerobic power metrics collected
during the Wingate tests. No within or between-group differences were
observed for lactate or blood ATP concentrations. Results from this
study are challenging to reconcile as the authors used an enteric-coated
ATP formulation and a lower dose than most other investigations
(225 mg vs. 400 mg). Further, from a timing perspective, the authors
administered the supplements three hours before testing versus the more
typical 30-min window and as such, timing of ATP administration may
be another factor to consider when evaluating these results.
Freitas and investigators examined the impact of a single 400 mg
dose of non-enteric coated ATP in a randomized, double-blind, crossover
study design in 11 healthy, previously active males (Freitas et al., 2019).
Thirty minutes after ingestion, participants completed a series of half-
squat repetitions with 80% of their 1RM. Performance was recorded
as total repetitions completed, and oxygen consumption, lactate and
hemodynamic parameters were also assessed. In comparison to placebo,
the total weight lifted was signicantly increased (Placebo:
3995.7 ±1137.8 vs. ATP: 4967.4 ±1497.9 kg, p =0.005) when the ATP
dose was provided. Signicant group effects were found whereby heart
rates were higher after the 4th set (p <0.001) and oxygen consumption
(p =0.021) was higher in ATP when compared to placebo. No differ-
ences between conditions were found for lactate or blood pressure
(Fig. 4).
The impact of ATP supplementation on repeated bouts of maximal
exercise performance was investigated by Purpura et al. using a ran-
domized, double-blind, placebo-controlled approach (Purpura et al.,
2017). Healthy males (n =42) completed a 14-day supplementation
protocol of 400 mg/day and on the 15th day took their prescribed dose
30 min before completing ten repeated 6-second cycling sprints with
Table 1 (continued )
Study Design Subjects Methods Supplementation Duration Main Findings (Effect of ATP)
improved psychomotor
development.
Long and
Zhang
(2014)
Randomized,
double-blind,
placebo-
controlled
244 total knee replacement
patients (ATP N =119,
60 ±5 yrs; placebo N =113,
59 ±5 yrs)
4 Weeks therapy 120 mg ATP disodium
three times a day
4 Weeks Signicantly improved
quadriceps strength and pain
scores at postoperative days 7, 14,
21, and 28 (p 0.05). Decreased
need for analgesics by 5% and
shortened the length of hospital
stay by 12%.
Rossignol
et al.
(2005)
Double-blind
(only trial 1),
randomized
placebo-
controlled
Trial 1 (ATP N =80, 41 ±10
yrs; placebo N =80, 43 ±10
yrs); Trial 2 (ATP N =81,
41 ±11 yrs; without ATP
N =76, 44 ±10 yrs)
30 Days therapy 90 mg ATP disodium 90 days ±5 days Improved RDQ (p =0.02). ATP
group patients were three times
less likely to report a condition
that had worsened or remained
unimproved at 90 days (p =0.02).
Fig. 3. Delta changes in blood ATP (A), ADP (B), and AMP (C) levels from pre-
exercise to 30 min post-Wingate exercise in participants supplemented with
ATP disodium or a placebo for 15 days (*p <0.05 different from placebo group)
(Purpura et al., 2017).
R. J¨
ager et al.
Journal of Functional Foods 78 (2021) 104357
6
30 s of rest between each sprint. As expected, maximal power output
decreased in both groups, but performance was better maintained dur-
ing the latter bouts (8th bout [Mean difference: 102.6 W; 95% CI:
21.6183.5 W] and 10th bout [Mean difference: 90.8 W; 95% CI:
9.8171.8 W]) when ATP was provided. Moreover, effect sizes were
calculated for each of the ten sprint cycling bouts before and after
supplementation. The average effect sizes (d) were 0.128 (range:
d = − 0.01 to 0.29) and 0.314 (range: d = − 0.18 to 0.79) for the placebo
group and ATP supplemented groups, respectively. No impact was re-
ported for vertical jump power, reaction time, or muscle activation;
however, muscle excitability increased signicantly in the ATP group
(+21.5%, p <0.02) after bout 2 and helped to prevent the decline
observed in the placebo group. While more research is needed, the lack
of observed change for some outcomes (vertical jump) and not others
(maximal power output) could be explained by the bioenergetic demand
initiated by the repeated bouts of exercise. In an additional study that
examined the impact of ATP supplementation on fatigue prevention,
Rathmacher et al. had participants complete three sets of 50 maximal
knee extensions to induce fatigue after supplementing with ATP (two
doses of 200 mg/day) or placebo using a randomized, double-blind,
placebo-controlled, crossover design (Rathmacher et al., 2012). No
differences were detected in high peak torque, power, or total work with
ATP supplementation. ATP supplementation did, however, improve low
peak torque in set number two (ATP: 67.2 N-m vs. placebo: 62.3 N-m,
p <0.01), and torque fatigue tended to be improved with ATP (ATP:
57.8% vs. placebo: 60.5%, p <0.10) in the third set of maximal repeti-
tions (Fig. 5). Two key discussion points arise from this study. First,
results from this study provide additional evidence that ATP supple-
mentation may lack the ability to exert ergogenic outcomes during the
early phases of an intense bout of exercise, but it does seem to enhance
resistance to the accumulation of fatigue that inevitably results from
maximal muscular contractions. Second, this study used a split dose
(2 ×200 mg) supplementation protocol and, it is important to note,
participants did not supplement on the day of the testing, missing out on
the potential acute benets of ATP supplementation.
Wilson and colleagues had 21 resistance-trained males supplement
with either 400 mg/day of ATP or placebo in a randomized, double-
blind, placebo-controlled fashion in conjunction with a 12-week heavy
resistance training program (Wilson et al., 2013). The 12-week protocol
consisted of an eight week periodized resistance-training program, two
weeks of an overreaching cycle, and two weeks of tapering. Using this
approach, ATP supplementation led to signicantly greater improve-
ments in muscle thickness (as determined by ultrasound) and maximal
strength and vertical jump power (Wilson et al., 2013). Specically, the
ATP group experienced signicant increases in squat 1RM (p <0.001)
and deadlift 1RM (p <0.001) resulting in signicantly greater im-
provements in total strength (PLA: +5.9% [22.4 ±7.1 kg] vs. ATP:
+12.6% [55.3 ±6.0 kg], p <0.001). Additionally, signicantly greater
improvements in vertical jump power were found for ATP supplemen-
tation (PLA: +11.6% [614 ±52 W] vs. ATP: 15.7% [796 ±75 W],
p <0.001). Interestingly, no changes were observed for bench press 1RM
(p =0.65) or Wingate peak power (p =0.48). The discordance of
observed change in upper-body strength and lower-body strength is
somewhat surprising; however, the amount of musculature involved
may be a key consideration as previous work involving caffeine and
acute resistance training performance has resulted in a similar pattern of
outcomes. Additionally, no change was observed in Wingate peak power
(p =0.48) between PLA and ATP supplemented individuals. While both
outcomes are intended to assess a representation of power, the time and
relative energetic demand between a vertical jump and Wingate
anaerobic capacity test are noticeably different and the role of ATP in
energy homeostasis can seemingly operate as a key difference in these
outcomes and their associated ndings from this study. Wilson et al. also
assessed changes in body composition. Lean mass gains occurred in both
groups, but changes were found to be signicantly greater in the ATP
supplemented group (PLA: +2.92% [~2 kg increase] vs. ATP: +5.91%
[~4 kg increase], p <0.009) (Wilson et al., 2013). Similarly, muscle
thickness levels were found to also increase to a greater extent in the
ATP group (PLA: +4.9% [2.5 ±0.6 mm] vs. ATP: +9.4%
[4.9 ±1.0 mm], p <0.02). (Fig. 6). Notably, the improvements in body
Fig. 4. Acute ATP supplementation signicantly increased training volume and
number of repetitions (*p <0.05 different from placebo group) (Freitas
et al., 2019). Fig. 5. ATP supplementation improved peak torque (A) and reduced fatigue in
later sets of 50 maximal knee extensions (B) (*p <0.05 and
#
p <0.1, different
from placebo group) adopted from Rathmacher et al. (2012).
R. J¨
ager et al.
Journal of Functional Foods 78 (2021) 104357
7
composition in resistance-trained males over 12 weeks align with earlier
ndings that 90 days of ATP supplementation in a healthy, older
(~55 years) population improved waist (-3.05 cm, p =0.04) and hip
circumference (-3.05 cm, p =0.007), and waist-hip ratio (-0.02,
p =0.03), independent of any exercise or physical activity intervention
(Hirsch et al., 2017).
5. ATP supplementation and recovery
Unaccustomed exercise stress or high volumes of exercise are com-
mon circumstances for physically active individuals and can result in
brief periods of overreaching, a period where the body is too stressed to
adequately recover. Twelve weeks of oral supplementation with ATP
(400 mg/day) in young, resistance-trained males has been shown to
attenuate losses of strength and power during a two-week overreaching
period (Wilson et al., 2013). Total strength (sum of squat, bench press,
deadlift 1RM) decreased in the control group (5.0%, 22.6 ±5.1 kg)
whereby total strength loss was signicantly attenuated in the ATP
supplemented group (2.2%, 12.0 ±2.5 kg, p <0.007). Moreover, the
two-week overreaching protocol led to a 5.0% decrease in vertical jump
power in the PLA group, whereas a signicantly smaller decline (only
2.2%) was observed in the ATP group (p <0.001) (Fig. 7).
Outcomes reported by Long et al. on performance and clinical out-
comes in 232 patients who underwent total knee arthroplasty indicated
greater recovery of force production in ATP supplemented individuals 7
(92.8 vs. 82.9 N), 14 (119.3 vs. 105.2 N), 21 (130.8 vs. 121.2 N), and 28
(190.2 vs. 175.3 N) days after surgery (all p <0.05 between groups) as
well as decreases in reported pain levels 7 (3.05 vs. 3.68), 14 (2.58 vs.
2.96), 21 (2.10 vs. 2.48), and 28 (1.56 vs. 1.98) days after surgery (in all
instances data is presented as ATP vs. PLA, p <0.05 between groups)
(Fig. 8, Long & Zhang, 2014). However, no differences were observed
between groups in either outcome at one or three days after surgery.
These outcomes are intriguing, as they suggest that, while a measurable
benet of ATP supplementation in recovery from surgery may not be
realized until at least day three of supplementation, the benets may
extend beyond 28 days of supplementation. Additional studies have
highlighted the potential for ATP administration to impact medical re-
covery and to have implications related to pain. For example, ATP
supplementation signicantly shortened the length of hospital stay by
12% (PLA: 2.5 ±0.7 days vs. ATP: 2.2 ±0.8 days, p =0.003) and
reduced the need for rescue pain medication by 5% (PLA:
Fig. 6. ATP supplementation signicantly increased lean body mass (A), muscle thickness (B), strength (C), and power (D) during a multi-week, controlled resistance
training program (*p <0.05 different from placebo group) (16). Adapted from Wilson et al. (Wilson et al., 2013).
Fig. 7. ATP supplementation reduces losses of strength (A) and power (B)
during an overreaching cycle (*p <0.05 different from placebo group) (Wilson
et al., 2013).
R. J¨
ager et al.
Journal of Functional Foods 78 (2021) 104357
8
1300 ±202 mg vs. ATP: 1235 ±185 mg, p =0.012) (Long & Zhang,
2014). Two other studies, one by Moriyama et al. (2004) and another by
Hayashida et al. (2005) both indicated positive potential for ATP infu-
sion in terms of pain management. The Moriyama study infused ATP
(dosage of 1 mg /kg) or a glucose control once per week for 12 weeks in
eight patients with postherpetic neuralgia and found improvements in
continuous and paroxysmal pain. Additionally, the Hayashida et al.
study infused 12 postherpetic neuralgia with either ketamine, lidocaine,
or ATP and found that ATP responders developed signicant pain relief
over a nine-hour period of time.
The potential for ATP to favorably impact recovery of lost strength
and power after overtraining or surgical intervention points to some
interaction of ATP availability with skeletal muscle health. Rates of
muscle protein breakdown are increased during injury, inactivity
(muscle disuse atrophy), energy restriction, and as a normal process of
aging (age-related muscle loss or sarcopenia) (Tipton, Hamilton, &
Gallagher, 2018). Wilson and investigators (Wilson et al., 2013)
collected 24-hour urine samples from healthy, resistance-trained males
who supplemented with 400 mg/day of ATP or placebo in a randomized,
double-blind fashion to assess changes in urinary 3-methyl-histidine, a
marker of myobrillar protein breakdown. ATP supplementation was
found to signicantly (p <0.007) prevent (Week 8: 0.143 ±0.007 vs.
Week 10: 0.131 ±0.012
μ
mol/mg) the 23.7 ±4.5% increase in level of
urinary 3-methyl-histidine observed in the placebo group (Week 8:
0.123 ±0.004 vs. Week 10: 0.152 ±0.005
μ
mol/mg, (Fig. 9). ATP sup-
plementation did not appear to have an impact, however, over changes
in C-reactive protein (p =0.99), cortisol (p =0.86), free testosterone
(p =0.93), total testosterone (p =0.83), creatine kinase (p =0.91) or
perceived recovery score (p =0.61).
6. Health and clinical applications of ATP supplementation
ATP has varying effects within the cardiovascular system, including
constriction, dilation, and the repair of blood vessels (Khakh & Burn-
stock, 2009). If an endothelial cell is damaged at a wound site, it spills
ATP which breaks down to ADP. ADP then binds to receptors on plate-
lets, which respond by aggregating to form a blood clot that closes the
wound (Khakh & Burnstock, 2009). Moreover, changes in blood ow
produce shear stresson endothelial cells lining blood vessel walls,
causing the endothelial cells to release ATP, which activates receptors
on nearby endothelial cells that respond by releasing nitric oxide, which
makes the vessels relax (Khakh & Burnstock, 2009). Potential implica-
tions of ATP supplementation on vascular health have been studied
using ow-mediated dilation (FMD), which measures the ability of an
artery to dilate in response to a shear stress stimulus. In a pilot study,
twelve healthy, resistance-trained males were supplemented for
12 weeks with 400 mg/day of ATP supplementation. No placebo was
administered in the pilot trial. After 0, 1, 4, 8, and 12 weeks of supple-
mentation, blood ow changes in the brachial artery were assessed using
ow-mediated dilation in conjunction with an acute upper-arm exercise
protocol (J¨
ager et al., 2014). Blood ow and brachial artery diameter
signicantly increased when ATP supplementation was provided, but
the lack of control group in this study compromises the ability to more
fully understand the potential of ATP to impact blood ow (Fig. 10). In
addition, acute and long-term benets of ATP supplementation on car-
diovascular health in non-athletic populations have been reported (de
Freitas et al., 2018). In 11 hypertensive older women (61.8 ±5.0 years),
a randomized, double-blind, placebo-controlled trial with a single
Fig. 8. ATP supplementation decreases losses in strength (A) and improved perceived pain (B) following total knee replacement surgery (*p <0.05 different from
placebo group) (Long & Zhang, 2014).
Fig. 9. ATP supplementation decreases urinary levels of 3-methyl-hisitidine
(3MH), a marker of myobrillar protein breakdown during an overreaching
cycle (*p <0.05 different from placebo group) (Wilson et al., 2013).
Fig. 10. Release of ATP activates receptors on endothelial cells which respond
by releasing nitric oxide, inducing improved blood ow (A). ATP supplemen-
tation alone did not increase blood ow, but ATP did signicantly enhance the
post-exercise increase in blood ow (B), as measured by ultrasonography of the
brachial artery. (*p <0.05 different from placebo group) (19). Adapted from
J¨
ager et al. (2014).
R. J¨
ager et al.
Journal of Functional Foods 78 (2021) 104357
9
400 mg ATP disodium dose induced faster recovery of heart rate vari-
ability and reduced systolic blood pressure after 30 min of aerobic ex-
ercise. Hirsh et al. completed a randomized, double-blind, placebo-
controlled investigation in 53 overweight and obese elderly men and
women over a 90-day protocol of 100 mg/day, 2x/day of ATP supple-
mentation (Hirsch et al., 2017). While no statistically signicant
changes were observed in comparison to the changes observed in the
placebo group, the ATP group experienced signicant increases (from its
respective baseline) in blood ow (2.8%, p =0.003) and malondialde-
hyde (0.92
μ
M, p =0.02) and decreases in blood glucose (6.3 mg/dL,
p =0.02), waist circumference (3.05 cm, p =0.04), hip circumference
(3.05 cm, p =0.007), waist-to-hip ratio (0.02, p =0.03).
Finally, several clinical applications of ATP and adenosine have been
reported (Agteresch et al., 1999). Oral ATP supplementation at a dosage
of 90 mg/day signicantly reduced participants self-assessment of their
disability levels and reduced the usage of rescue analgesics in 181 men
and women with category 1 or 2 subacute lower back pain (Bannwarth
et al., 2005). In a separate publication from the same research group,
patients who supplemented with ATP were three times less likely to
report a condition that had worsened or remained unimproved and took
fewer rescue drugs (Rossignol et al., 2005). Finally, in a pediatric case
study of a child with alternating hemiplegia, an intractable neurological
disorder, reported that oral ATP supplementation reduced both the
frequency and duration of hemiplegic episodes (Ju et al., 2016). While
the results of these early studies are promising, additional studies on oral
ATP supplementation in clinical conditions are warranted.
7. Future perspectives
Currently, ATP disodium has demonstrated the potential to impact
several physiologic effects which may confer acute to long-term benets
on exercise performance and health. While preliminary bioavailability
research has been completed, more research is needed to fully under-
stand the kinetics and specics of how the ingested molecules are
transported through the digestive system and deposited in the circula-
tion. Thus, immediate research efforts should focus on elucidation of the
mechanism responsible for the observed outcomes in the literature.
Future studies should investigate the potential ability of acute ATP
disodium supplementation to impact various types of exercise perfor-
mance and evaluate if there is a dose-dependent effect. As the knowl-
edge base surrounding ATP supplementation and exercise performance
matures, the next wave of research should investigate the potential for
additive or even synergistic effects of co-administering ATP with other
nutritional supplements that possess different or similar mechanisms-of-
action. As an example, co-administration of ATP with beta-hydroxy-
beta-methylbutyrate (HMB) has previously been shown to result in
signicant improvements in resistance training adaptations observed in
resistance-trained males who followed a resistance training and sup-
plemented with a combination of HMB and ATP for a period of 12 weeks
(Lowery et al., 2016). Results of this study have been criticized for
discrepancies in how the data was reported and methodological ap-
proaches used (Phillips et al., 2017), thus more follow-up work should
be completed with this and other potential combinations of candidate
nutrients. Of interest are supplements known to demonstrate buffering
capacity in the body (i.e., creatine, beta-alanine, and bicarbonate) which
could potentiate the half-life of ATP either in the gut or possibly the
blood when co-administered.
Future research should also ascertain if these physiological mecha-
nisms may differ between populations, such as in young vs. old, men vs.
women, and untrained vs. trained individuals. In reference to aging,
signicant interest exists involving the role and impact of mitochondrial
health as it relates to the aging process and longevity (Vendelbo & Nair,
2011). While the relationship between mitochondrial health and aging
has been found in some but not all studies, a relationship between ATP
production and aging has been observed in some studies and subse-
quently deserves more detailed investigation into its potential.
Moreover, clinical populations such as individuals with chronic
obstructive pulmonary disease or intermittent claudication are both
characterized by peripheral muscle weakness that can limit exercise
capacity resulting in a reduction in quality of life in these patients. As
such, supplementation of ATP disodium could be an important strategy
to improve oxygen delivery or utilization by the peripheral muscles and
improve quality of life in these people.
8. Conclusion
The available literature on ATP disodium when provided in a dose of
at least 400 mg approximately 30 min before a workout or 2030 min
before breakfast on non-exercise days provides insight into its potential
to reduce fatigue (Purpura et al., 2017; Rathmacher et al., 2012), in-
crease strength and power (Wilson et al., 2013), improve body compo-
sition (Hirsch et al., 2017; Wilson et al., 2013), maintain muscle health
during stress (Long & Zhang, 2014; Wilson et al., 2013), increase re-
covery and reduce pain (de Freitas et al., 2018; Khakh & Burnstock,
2009; Wilson et al., 2013). Additionally, other literature indicates a role
for ATP in improving cardiovascular health (Hirsch et al., 2017; Ju et al.,
2016; Rossignol et al., 2005). The divergent ndings surrounding ATP
supplementation and an unidentied mechanism of action continue to
preclude stronger conclusions from being made at this time. Therefore,
additional research is needed to identify and clarify the cellular mech-
anism responsible for the observed changes as well as to replicate the
ndings already published in the literature.
9. Ethics statement
This manuscript is a review article and did not include any human
subjects and animal experiments.
Author contribution
RJ and MP took the lead in writing the manuscript. All authors dis-
cussed the results and contributed to the nal manuscript.
Declaration of competing interest
The authors declare the following nancial interests/personal re-
lationships which may be considered as potential competing interests:
JCF is an employee of Metabolic Technologies, LLC an afliate of TSI
USA LLC, the manufacturer of Peak ATP. JAR and LMP are employees of
MTI BioTech, Inc. which has a partnership with TSI USA, LLC. RJ and
MP are consultants to TSI USA, LLC. All other authors do not declare
competing interests.
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R. J¨
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Alternating hemiplegia of childhood (AHC) is a rare neurological disorder that usually manifests before 18 months of age and is characterized by recurrent, alternating episodes of hemiparesis with variable frequency and can last from a few minutes to several days. We present a case of AHC in a little girl carrying a sporadic mutation in the ATP1A3 gene (p.Glu815Lys) refractory to flunarizine and non-compliant to topiramate due to adverse effects treated with oral compound of adenosine-5′-triphosphate (ATP) capsules. Outcome was evaluated through the follow-up and side effects and safety were monitored regularly. Compounded drug showed effectiveness and safety. Indeed, during the four-year follow-up, with the dose of adenosine-5′-triphosphate gradually increasing up to 21 mg/kg, the patient showed a substantial benefit in controlling the frequency and duration of hemiplegic episodes and an improvement in neurological deterioration.
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Mitochondrial dysfunction caused by aging leads to decreased energy metabolism, resulting in functional decline and increased frailty in multiple tissues. Strategies for protecting and activating mitochondria under stressful conditions are required to suppress aging and age-related diseases. However, it is challenging to develop drugs capable of boosting mitochondrial respiration and compensating for the reduced intracellular adenosine triphosphate (ATP) levels. In this study, we developed a prodrug that stimulates the metabolism of intracellular adenine nucleotides (AXP: adenosine monophosphate (AMP), adenosine diphosphate (ADP), and ATP). It enhances AMP-activated protein kinase activity, fatty acid oxidation, oxidative stress resistance, and mitochondrial respiration, thereby increasing the intracellular ATP levels. Furthermore, this prodrug markedly extended the lifespan of Caenorhabditis elegans. The stimulation of the AXP energy metabolism (AXP stimulation) proposed in this study is expected to offer a new strategy against aging and pave the way for a novel approach in the bioenergetic molecules drug discovery.
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The aim of this study was to verify the autonomic modulation and blood pressure after adenosine-5'-triphosphate (ATP) supplementation asso-ciated to acute aerobic exercise in hypertensive women. Eleven hyper-tensive women (age, 61.8±5.0 years) completed a randomized, double blind trial: ATP supplement condition (ATP=400 mg) or placebo. After 30 min of supplementation or placebo intake, the subjects performed 30 min of aerobic exercise (70%-75% of maximum heart rate). The auto-nomic modulation was assessed by heart rate variability during rest and recovery (postexercise until 30 min of recovery), the square root of the mean squared difference between adjacent RR intervals (RMSSD), standard deviation of successive values (SDNN), low frequency (LF) and high frequency (HF) were measured. The blood pressure (systolic blood pressure [SBP] and diastolic blood pressure, mmHg) were re-corded at rest, immediately postexercise, post-10, post-20, and post-30 min after exercise. For RMSSD, there was statistically significant differ-ence during recovery, with higher RMSSD for ATP compared to placebo (rest=16.4±8.5 vs. placebo=11.6±4.0; ATP=18.5±9.7 msec; P=0.020). When analyzing the delta (recovery minus rest), the RMSSD (ATP=2.1± 7.2 msec vs. placebo=-4.7±7.5 msec; P=0.009), LF (ATP=-19.8±122.7 vs. placebo=-94.1±200.2 msec²; P=0.02), and SDNN (ATP=-2.8±12.2 msec vs. placebo=-10.6±10.5 msec; P=0.010) were higher for ATP than placebo. Furthermore, there was a greater postexercise hypotension at 20 min for ATP (SBP: ATP=-13.2±8.4 mmHg vs. placebo=-6.1±9.9 mmHg; P=0.006). Acute ATP supplementation promoted greater postexercise hypotension for systolic blood pressure and induced faster recovery of heart rate variability in hypertensive women.
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Muscle protein breakdown (MPB) is an important metabolic component of muscle remodeling, adaptation to training, and increasing muscle mass. Degradation of muscle proteins occurs via the integration of three main systems—autophagy and the calpain and ubiquitin-proteasome systems. These systems do not operate independently, and the regulation is complex. Complete degradation of a protein requires some combination of the systems. Determination of MPB in humans is technically challenging, leading to a relative dearth of information. Available information on the dynamic response of MPB primarily comes from stable isotopic methods with expression and activity measures providing complementary information. It seems clear that resistance exercise increases MPB, but not as much as the increase in muscle protein synthesis. Both hyperaminoacidemia and hyperinsulinemia inhibit the post-exercise response of MPB. Available data do not allow a comprehensive examination of the mechanisms behind these responses. Practical nutrition recommendations for interventions to suppress MPB following exercise are often made. However, it is likely that some degree of increased MPB following exercise is an important component for optimal remodeling. At this time, it is not possible to determine the impact of nutrition on any individual muscle protein. Thus, until we can develop and employ better methods to elucidate the role of MPB following exercise and the response to nutrition, recommendations to optimize post exercise nutrition should focus on the response of muscle protein synthesis. The aim of this review is to provide a comprehensive examination of the state of knowledge, including methodological considerations, of the response of MPB to exercise and nutrition in humans.
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Background Alternating hemiplegia of childhood is an intractable neurological disorder characterized by recurrent episodes of alternating hemiplegia accompanied by other paroxysmal symptoms. Recent research has identified mutations in the ATP1A3 gene as the underlying cause. Adenosine-5'-triphosphate has a vasodilatory effect, can enhance muscle strength and physical performance, and was hypothesized to improve the symptoms of paroxysmal hemiplegia. MethodsA 7-year-old boy with alternating hemiplegia of childhood who was positive for a de novo ATP1A3 mutation was treated with adenosine- 5'- triphosphate supplementation orally as an innovative therapy for 2 years. Outcome was evaluated through the follow-up of improvement of hemiplegic episodes and psychomotor development. Side effects and safety were monitored in regularity. ResultsWith the dosage of adenosine-5'-triphosphate administration increased, the patient showed significantly less frequency and shorter duration of hemiplegic episodes. Treatment with adenosine-5'-triphosphate was correlated with a marked amelioration of alternating hemiplegia of childhood episodes, and psychomotor development has improved. The maximum dose of oral administration of adenosine-5'-triphosphate reached 25 mg/kg per day. Adenosine-5'-triphosphate therapy was well tolerated without complaint of discomfort and side effects. Conclusions The 2-year follow-up outcome of adenosine-5'-triphosphate therapy for alternating hemiplegia of childhood was successful.
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Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
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Introduction Extracellular adenosine triphosphate (ATP) stimulates vasodilation by binding to endothelial ATP-selective P2Y2 receptors; a phenomenon, which is posited to be accelerated during exercise. Herein, we used a rat model to examine how different dosages of acute oral ATP administration affected the femoral blood flow response prior to, during, and after an exercise bout. In addition, we performed a single dose chronic administration pilot study in resistance trained athletes. Methods Animal study: Male Wistar rats were gavage-fed the body surface area, species adjusted human equivalent dose (HED) of either 100 mg (n=4), 400 mg (n=4), 1,000 mg (n=5) or 1,600 mg (n=5) of oral ATP as a disodium salt (Peak ATP(R), TSI, Missoula, MT). Rats that were not gavage-fed were used as controls (CTL, n=5). Blood flow was monitored continuously: a) 60 min prior to, b) during and c) 90 min following an electrically-evoked leg-kicking exercise. Human Study: In a pilot study, 12 college-aged resistance-trained subjects were given 400 mg of ATP (Peak ATP(R), TSI, Missoula, MT) daily for 12 weeks, and prior to an acute arm exercise bout at weeks 1, 4, 8, and 12. Ultrasonography-determined volumetric blood flow and vessel dilation in the brachial artery was measured at rest, at rest 30 minutes after supplementation, and then at 0, 3, and 6 minutes after the exercise. Results Animal Study: Rats fed 1,000 mg HED demonstrated significantly greater recovery blood flow (p < 0.01) and total blood flow AUC values (p < 0.05) compared to CTL rats. Specifically, blood flow was elevated in rats fed 1,000 mg HED versus CTL rats at 20 to 90 min post exercise when examining 10-min blood flow intervals (p < 0.05). When examining within-group differences relative to baseline values, rats fed the 1,000 mg and 1,600 mg HED exhibited the most robust increases in blood flow during exercise and into the recovery period. Human study: At weeks 1, 8, and 12, ATP supplementation significantly increased blood flow, along with significant elevations in brachial dilation. Conclusions Oral ATP administration can increase post-exercise blood flow, and may be particularly effective during exercise recovery.
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The aim of this study was to investigate the acute effect of ATP supplementation on performance and physiological responses during resistance exercise in recreationally resistance trained males. Eleven men (age= 27.5±5.5 yrs, weight= 83.4±9.8 kg, height= 182±0.04 cm) completed two randomized, double-blind trials: ATP supplement condition (ATP=400mg) or a placebo condition. Thirty minutes after supplement consumption, subjects performed four sets of half-squats until momentary muscular failure at 80% of the 1RM with two minutes of recovery between sets. The total number of repetitions, blood pressure, heart rate, blood lactate, and oxygen consumption were evaluated. The total weight lifted were higher for the ATP condition compared to placebo (Placebo= 3995.7±1137.8, ATP= 4967.4±1497.9 Kg; p= 0.005). Heart rate was higher at set-4 for ATP compared to placebo (p<0.001) and oxygen consumption during exercise was greater for ATP (p=0.021). There were no differences between conditions for lactate and blood pressure. In summary, a single oral dose of ATP supplementation improved lower body resistance training performance and energy expenditure in recreational resistance trained males.
Article
Objective: Oral adenosine-5'-triphosphate (ATP) administration has failed to increase plasma ATP levels; however, chronic supplementation with ATP has shown to increase power, strength, lean body mass, and blood flow in trained athletes. The purpose of this study was to investigate the effects of ATP supplementation on postexercise ATP levels and on muscle activation and excitability and power following a repeated sprint bout. Methods: In a double-blind, placebo-controlled, randomized design, 42 healthy male individuals were given either 400 mg of ATP as disodium salt or placebo for 2 weeks prior to an exercise bout. During the exercise bout, muscle activation and excitability (ME, ratio of power output to muscle activation) and Wingate test peak power were measured during all sprints. ATP and metabolites were measured at baseline, after supplementation, and immediately following exercise. Results: Oral ATP supplementation prevented a drop in ATP, adenosine-5'-diphosphate (ADP), and adenosine-5'-monophosphate (AMP) levels postexercise (p < 0.05). No group by time interaction was observed for muscle activation. Following the supplementation period, muscle excitability significantly decreased in later bouts 8, 9, and 10 in the placebo group (-30.5, -28.3, and -27.9%, respectively; p < 0.02), whereas ATP supplementation prevented the decline in later bouts. ATP significantly increased Wingate peak power in later bouts compared to baseline (bout 8: +18.3%, bout 10: +16.3%). Conclusions: Oral ATP administration prevents exercise-induced declines in ATP and its metabolite and enhances peak power and muscular excitability, which may be beneficial for sports requiring repeated high-intensity sprinting bouts.
Article
The pharmacokinetics of adenosine 5'-triphosphate (ATP) was investigated in a clinical trial that included 15 patients with advanced malignancies (solid tumors). ATP was administered by continuous intravenous infusions of 8 h once weekly for 8 weeks. Three values of blood ATP levels were determined. These were total blood (erythrocyte) and blood plasma (extracellular) ATP pools along with the initial rate of release of ATP into the blood plasma. We found that values related to erythrocyte ATP pools showed great variability (diversity) among individuals (standard deviation of about 30-40 % of mean at baseline). It was discovered that erythrocyte baseline ATP pool sizes are unique to each individual and that they fall within a narrow range in each individual. At the end of an 8 h continuous intravenous infusion of ATP, intracellular erythrocyte ATP pools were increased in the range of 40-60 % and extracellular ATP declined from elevated levels achieved at the beginning and middle of the infusion, to baseline levels. The ability of erythrocytes to sequester exogenously administered ATP to this degree, after its initial conversion to adenosine in the blood plasma is unexpected, considering that some of the adenosine is likely to have been degraded by in vivo catabolic activities or taken up by organs. The data suggest that administration of ATP by short-term intravenous infusions, of up to 4 h, may be a favorable way for elevating extracellular ATP pools. A large fraction of the total exogenously administered ATP is sequestered into the intracellular compartments of the erythrocytes after an 8 h intravenous infusion. Erythrocytes loaded with ATP are known to release their ATP pools by the application of previously established agents or conditions applied locally or globally to circulating erythrocytes. Rapid degradation of intravenously administered ATP to adenosine and subsequent accumulation of ATP inside erythrocytes indicate the existence of very effective mechanisms for uptake of adenosine from blood plasma. These in vivo studies offer an understanding as to how both adenosine and ATP can act as purinergic transmission signals. ATP levels in blood are always accompanied by adenosine formed by catabolism of ATP. The continuous uptake of adenosine enables both to act in transmission of sometimes opposite functions.