Effects of Ribose Supplementation Prior to and during Intense Exercise on Anaerobic Capacity and Metabolic Markers

Abstract

This study examined whether ribose supplementation before and during intense anaerobic exercise impacts anaerobic capacity and metabolic markers. Twelve moderately trained male cyclists (22.3 +/- 2.2 y; 181 +/- 6 cm, 74.8 +/- 9 kg) participated in the study. Subjects were familiarized and fasted for 8 h after standardizing nutritional intake. In a double blind and crossover manner subjects ingested either a 150 mL placebo or ribose (3 g ribose + 150 microg folate). Subjects rested for 25 min and completed 5 x 30 s anaerobic capacity tests with 3 min passive rest. Six capillary blood samples were taken prior to and after sprints for adenine nucleotide breakdown determination. The experiment was repeated 1 wk later with alternative drink. Data were analyzed by repeated measures ANOVA. No significant interactions were observed for any performance or blood variables. D-ribose supplementation has no impact on anaerobic exercise capacity and metabolic markers after high-intensity cycling exercise.

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Kerksick, Rasmussen, Bowden, Leutholtz, Harvey, Greenwood, and Kreider are with the
Exercise and
Sport Nutrition Laboratory, Center for Exercise, Nutrition and Preventive Health Research, Dept of
Health, Human Performance and Recreation. Baylor University, Waco, TX 76798-7313. Earnest is
with the Cooper Institute for Aerobics Research, Division of Epidemiology and Clinical Applications,
Dallas, TX 75230. Almada is with IMAGINutrition, Inc., Laguna Niguel, CA 92677.
International Journal of Sport Nutrition and Exercise Metabolism, 2005, 15, 653-664
© 2005 Human Kinetics, Inc.
Effects of Ribose Supplementation
Prior to and During Intense Exercise
on Anaerobic Capacity and
Metabolic Markers
C. Kerksick, C. Rasmussen, R. Bowden,
B. Leutholtz, T. Harvey, C. Earnest,
M. Greenwood, A. Almada, and R. Kreider
This study examined whether ribose supplementation before and during intense
anaerobic exercise impacts anaerobic capacity and metabolic markers. Twelve
moderately trained male cyclists (22.3 ± 2.2 y; 181 ± 6 cm, 74.8 ± 9 kg) partici-
pated in the study. Subjects were familiarized and fasted for 8 h after standard-
izing nutritional intake. In a double blind and crossover manner subjects ingested
either a 150 mL placebo or ribose (3 g ribose + 150 µg folate). Subjects rested
for 25 min and completed 5 × 30 s anaerobic capacity tests with 3 min passive
rest. Six capillary blood samples were taken prior to and after sprints for adenine
nucleotide breakdown determination. The experiment was repeated 1 wk later
with alternative drink. Data were analyzed by repeated measures ANOVA. No
signicant interactions were observed for any performance or blood variables.
D-ribose supplementation has no impact on anaerobic exercise capacity and
metabolic markers after high-intensity cycling exercise.
Key Words: ATP resynthesis, sport nutrition, ergogenic aids
Single bouts or repeated bouts of high-intensity sprint exercise have been shown to
cause drastic reductions in maximal power output, total work produced, and changes
in creatine phosphate concentration, lactate, ammonia, total adenine nucleotide
(TAN) pool, and inosine-5ʼ-monophosphate (IMP) which are all indications of
extreme fatigue (9, 11, 16, 18). Using muscle biopsies, Zhao (18) and Tullson (16)
concluded that purine inux and efux (TAN, IMP) is greatly increased after a
short-term supramaximal 30 s cycling exercise bout. Consequently, the ability to
effectively handle higher levels of stress is improved. These changes are observed
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Ribose Supplementation and Exercise 655
by improving the recovery and quantities of high-energy molecules, greater power
output, work performance, and/or metabolic responses (9).
D-ribose is a naturally occurring 5-carbon carbohydrate that for the last several
years has been marketed with little physiological rationale as an ergogenic aid to
athletes who engage in high-intensity activity. Ribose is a vital molecule for de
novo synthesis and salvage of adenine nucleotides (ATP, ADP, and AMP) which
are intimately involved with energy metabolism. Substantial de novo synthesis of
adenine nucleotides is a lengthy process which could limit the actual ability of any
de novo pathway or ribose supplementation to actually increase ATP resynthesis
during acute, intermittent bouts of high-intensity exercise. Research has suggested,
however, that enhancing the availability of ATP, increasing salvage pathway activ-
ity, and/or maintaining the TAN pool to a greater degree during a single bout or
repeated bouts of high-intensity sprint-type activities increases exercise capacity
(9, 16, 18). Further, research has shown ribose supplementation to increase the
availability of purine nucleotides through either enhanced synthesis or increased
turnover via salvage pathways during exercise (5, 15).
Previous research in clinical populations has provided some promise for ribose
supplementation as an energy-providing supplement (8), enhancing de novo syn-
thesis of purine nucleotides (19), reducing muscle cramping (17), and increasing
exercise tolerance (13). For example, Pliml et al. showed ingestion of ribose in
doses of 60 g/d for 3 d prior to a maximal treadmill test signicantly increased
time until termination in previously diagnosed men with severe coronary artery
disease (13). In addition, Wagner et al. supplemented patients with AMP deaminase
deciency with ribose to determine any possible changes in energy provision and
exercise performance. Every 10 min patients were given 3 g of either placebo or
ribose prior to completing an incremental maximal exercise test. While exercise
performance was not changed, plasma concentrations of lactate and inosine were
increased (P < 0.05). The authors concluded that ribose administration might have
served as an energy source or enhanced the de novo synthesis of purine nucleotides.
In this regard, and despite inconclusive evidence, ribose has been marketed heavily
to athletes for its purported ability to maintain power production during repeated
bouts of intense exercise or to increase the peak power production seen during
these types of activities. Studies in support of ribose supplementation before or
after high-intensity exercise have demonstrated a greater work production during
the exercise bout in addition to an increased recovery of ATP levels in the muscle
several days after exercise (10). To date, no conclusive, performance-enhancing
effect has been reported.
Consequently, several studies have sought to determine an ergogenic property
to ribose supplementation during high-intensity exercise. Results from these stud-
ies have concluded that supplementation with ribose for 3 to 6 d in doses ranging
from 8 to 50 g/d while participating in repeated bouts of high-intensity exercise
(e.g., Wingate sprints or maximal knee extensions) did not increase performance
over those subjects who were taking a placebo (4, 11, 12). While some ndings did
indicate improved maintenance of total work (11) or peak power (4) with ribose,
the authorsʼ in these studies concluded that ribose did not signicantly improve
performance.
More research is needed to investigate the potential ergogenic value of ribose
supplementation particularly at the dosages recommended by various supplement
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Ribose Supplementation and Exercise 655
manufacturers. Currently, studies need to be conducted to investigate any possible
role of ribose administration prior to maximal exercise and/or during recovery from
a maximal exercise bout. Subsequently, the purpose of this study was to determine
if acute supplementation of ribose in dosages that are commonly marketed as an
ergogenic aid (2 doses of 3 g ribose + 150 µg folate) prior to a maximal exercise bout
or during the recovery period prior to a subsequent exercise bout has any benecial
impact on the performance of repeated sprint exercise with limited recovery.
Methods
Subjects
Twelve apparently healthy moderately trained male cyclists between the ages of
18 and 40 were recruited for this investigation. All subjects signed informed con-
sent documents and the study was approved by the Baylor University Institutional
Review Board prior to any data collection. To qualify for participation, all subjects
were: 1) experienced cyclists who had been previously involved in a cycling pro-
gram for at least 3 h/wk for 3 months and were part of a competitive club cycling
program at large National Collegiate Athletic Association Division I institution; 2)
not taking any nutritional supplements purported to have ergogenic effects (e.g.,
creatine monohydrate, ribose, caffeine, sodium phosphates, bicarbonates, etc.);
and 3) not taking or have never taken any anabolic steroids.
During initial familiarization sessions, subjects were informed of testing pro-
cedures, completed all necessary paperwork, and were familiarized to all exercise
testing on two different occasions prior to beginning the experimental protocol.
Descriptive characteristics of the subjects were as follows: age, 22.3 ± 2.2 y; body
weight, 74.9 ± 9.6 kg; height, 180.9 ± 6.1 cm; and body fat, 18.2 ± 5.4%. Prior to
data collection, all subjects had been training for competitive events which were
typically shorter distance (20 to 30 miles), higher-paced events which led them to
maintain an average of 1.8 ± 0.5 h/d, 3.1 ± 1.3 d/wk for 76.8 ± 51.6 miles/wk.
Experimental Design
Throughout two familiarization sessions, subjects completed informed consent
documents, medical and training history questionnaires, and personal informa-
tion sheets, and were then familiarized with the testing protocol. Subjects were
instructed to record their training for 5 d and food and uid intake for 24 h prior
to their initial testing session (T1). All training and dietary intake was then subse-
quently replicated prior to the second testing session (T2). Subjects were required
to refrain from exercise for 48 h and fast for 8 h prior to their testing sessions. All
subjects consumed a standardized carbohydrate/protein (240 kcals, 40 g protein,
16 g carbohydrate, 3 g fat) meal replacement drink (RTD40 Met-Rx, Boca Raton,
FL) 4 h prior to their testing session to standardize nutritional intake for 12 h prior
to testing.
Figure 1 illustrates the testing design. Subjects provided their rst blood
sample from a clean, pre-warmed nger prior to consuming the rst dose of the
supplement. Pre-exercise blood samples were taken within 15 min of reporting to
the lab and followed by 25 min of quiet rest. Subjects warmed up for 5 min on a
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Ribose Supplementation and Exercise 657
Figure 1—Schematic diagram of testing conditions.
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Ribose Supplementation and Exercise 657
bicycle ergometer at a standardized work rate (2 kg @ 60 rpm; 120 W) and rested
for 5 min. Subjects then performed 3 × 30 s Wingate anaerobic capacity tests each
separated by 3 min of standardized passive recovery. Immediately after the third
sprint, a second blood sample was taken and a second identical dose of the supple-
ment was ingested. The second dose of the supplement was consumed within 5 min
of completion of the third sprint and all subjects consumed the drink within 30 s in
view of the investigators. Five minutes after ingestion of the supplement, a third
blood sample was taken and subjects then sat at quiet rest for a total of 25 min. A
fourth blood sample was then obtained. Subjects began to free spin at 80 rpm with
no resistance for 30 s prior to the each Wingate test. Subjects then completed the
fourth and fth Wingate tests with 3 min passive rest between both trials; a fth
blood sample was taken immediately upon completion of the fth sprint. A sixth
and nal blood sample was taken 5 min after completion of the last sprint.
In a double blind, randomized, and crossover manner, subjects were admin-
istered either 3 g of D-ribose with 150 µg of the vitamin folate (folic acid) or 3
g of a maltodextrin placebo. Folate was included for its role in normal ribose
metabolism but it does not possess any known ergogenic properties. All supple-
ments were prepared in powdered form and packaged in ready-to-mix containers
for double blind administration by Royal Numico Research B.V. (Wageningen,
The Netherlands) to ensure similar taste, color, consistency, and texture. Supple-
ments were mixed immediately prior to ingestion with 150 mL of cold water and
consumed in front of researchers to ensure proper administration. Subsequent
testing sessions were completed 1 wk later at the same time of day in an identical
fashion as described above.
Procedures
Total body mass was measured on a calibrated digital scale with a precision of ±
0.02 kg (Sterling Scale Co., Southeld, MI). Skinfold body composition measures
were taken prior to each testing session for descriptive purposes using standard
skinfold techniques (Lange calipers) following American College of Sports Medi-
cine guidelines (2). Standard nger-stick phlebotomy techniques from a clean,
pre-warmed nger were used to collect each 200 to 400 µL whole blood sample
into lithium heparin-treated Microtainer tubes (Becton Dickinson, Franklin
Lakes, NJ). The tubes were centrifuged for 15 min using a bench-top centrifuge
(VanGuard V6500, Hamilton Bell Co., Montvale, NJ). Plasma was assayed
for ammonia, lactate, and glucose using an Analox MicroStat GM7 analyzer
(Analox Instruments, Ltd., London, UK). Inter-assay variances for ammonia,
lactate, and glucose were ±10 µmol/L, ±0.05-0.07 mmol/L, and 1.4% at 10
mmol/L, respectively.
Wingate anaerobic capacity tests were performed on a computerized Lode
Excalibur Sport (Lode BV, Groningen, The Netherlands) cycle ergometer equipped
with toe clips at a standardized torque factor 0.7. The torque factor setting was
set to the manufacturerʼs guidelines relative to the population being tested. Seat
position, seat height, handlebar height, and handlebar position were determined
during familiarization sessions and repeated for both testing sessions. Subjects
were instructed to begin sprinting 5 s prior to beginning of data collection to ensure
optimal force and power production at the beginning of the test and to remain
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658 Kerksick et al.
Ribose Supplementation and Exercise 659
sprinting for the entire duration of the test. All visual feedback was removed during
testing and subjects were instructed to remain in the saddle for the entire duration
of the test while researchers provided verbal encouragement. The ergometer was
connected via an RS-232 parallel interface to a Dell Optiplex GX 260 computer
(Dell Computer Corp., Austin, TX) using Wingate for Windows software version
1 (Lode BV, Groningen, The Netherlands). Crank frequency was measured using
magnetic encoders (4/revolution). The Excalibur Sport has a range of 0 to -2000 W
with typical variation of measurement less than 2% with the sampling frequency
of data at 5 times/s. Test to test variability in performing repeated Wingate tests in
our lab has yielded correlation coefcients of r = 0.981± 15% for mean power.
Statistical Analysis
Descriptive variables and all other data were analyzed using a 2 × 5 (group ×
sprints) repeated measures ANOVA for all performance variables and a 2 × 6
(group × blood sample) repeated measures ANOVA using SPSS for Windows
version 11.5 (SPSS Inc., Chicago, IL) with an added correction factor to control
test effect bias. Alpha level was set at 0.05. Effect sizes were calculated for any
signicant trends using the mean differences. Data was considered signicantly
different when the probability of a Type I error was 0.05 or less. Data are presented
as means ± standard deviation.
Results
Side Effects
No subjects reported adverse events or responses to the supplementation and
training protocol. No reports of medical problems or symptoms were indicated in
post-study questionnaires administered in a blinded manner.
Sprint Performance
Peak power (P = 0.006) and total work (P = 0.005) both signicantly decreased
across sprint trials with no signicant differences between groups. No signicant
interactions were found (P > 0.05) for average power, peak power, time to peak
power, rate of fatigue, and total work between the two groups. No signicant group ×
time interactions were found for any of the ve sprint tests throughout the study.
Metabolic Markers
The Wingate sprint tests signicantly increased lactate (P < 0.001) across time for
both groups. No signicant group × time interactions (P > 0.05) were observed
among groups in these metabolic parameters. Due to an inability to retrieve an
adequate amount of sample and/or to analyze some samples within a few hours after
exercise, ammonia analysis was only performed on 9 subjects (ribose = 4, placebo
= 5). Complete analysis was conducted on all other variables. Figure 2 indicates the
changes in peak power, mean power, rate of fatigue, glucose, lactate, and ammonia
levels throughout all ve sprint tests for both the ribose and placebo groups.
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Ribose Supplementation and Exercise 659
Figure 2—Peak power, average power, rate to fatigue, glucose, lactate and ammonia
values observed for the ribose (solid square) and placebo (grey diamond) groups prior to
and following supplementation. Peak power, average power and total work are shown top
to bottom in the left panel; plasma glucose, lactate and ammonia are shown top to bottom
in the right panel. Data are means ± standard deviation.
(continued)
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660 Kerksick et al.
Ribose Supplementation and Exercise 661
Figure 2—(continued)
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Ribose Supplementation and Exercise 661
Discussion
This study was developed to determine if the pattern and timing of ribose supple-
mentation at acute dosage levels (2 doses of 3 g ribose + 150 µg folate) of what is
commonly marketed as an ergogenic aid affected the outcome of repeated sprint
performance with limited recovery. The timing of administration and dosages were
chosen to mimic both the dosage amounts marketed to athletes as well as provide
a similar layout to what is commonly experienced by many competitive athletes
(e.g., heats in swimming, sprinting, etc.). The pharmokinetics of ribose suggest that
88 to 100% of an oral dose (up to 200 mg × kg
-1
× h
-1
) is absorbed from the small
intestine and distributed to various tissues including skeletal muscle (1). The dosage
used in the present study (3 g) was only 20% of this expected upper limit of ribose
bioavailability, suggesting the doses of ribose were indeed able to be absorbed to
some degree prior to the exercise bouts. It was expected that the Wingate anaerobic
capacity tests would be a good, reliable measure of anaerobic capacity (6, 9). It
is possible that slight reductions in peak power performance might have occurred
due to a possible loss of optimal neuromuscular coordination and resulting force
production as a result of extremely high cadence rates (typically 180 to 200 rpm
during the 5 s “superspin” period prior to the beginning of the test). The authors,
however, believe that this effect is negligible due to the sprint cycling experience of
the participants and the standardization of the testing procedures. Furthermore, the
tests and protocol were anticipated to stimulate a degradation of the TAN pool in
addition to changes in metabolic activity based on previous research (6, 9, 11).
Following the theoretical rationale and marketing campaigns of nutritional
supplement companies for ribose supplementation, we hypothesized that if acute
ribose ingestion improves the availability of ATP (increase de novo synthesis or
increased salvage of these nucleotides) during the sprints and/or during recovery,
then: 1) an increase in peak power would have been determined after the rst or
fourth sprints; 2) a greater maintenance of power (average power) or total work
output would be observed after either group of sprints; or 3) an improved main-
tenance of the metabolic markers (i.e., glucose, lactate, and ammonia) measured
would have been observed between groups throughout the protocol. While many
different considerations could have been made that might have elucidated vary-
ing conclusions, the rest periods and end points (i.e., peak ammonia, glucose, and
lactate levels) chosen in this study were hypothesized to provide the most realistic
picture of what would be experienced by athletes using ribose supplementation
throughout their workouts (4, 6).
Results from the present study indicate that the exercise protocol employed
was successful at producing a signicant metabolic challenge. A 23% decrease in
total work output, a 16.5% decrease in peak power, a six-fold increase in blood
lactate, and a 180% increase in ammonia levels from the rst to the third sprint
was found, which was similar to the ndings of Hargreaves et al. when they had
subjects complete 3 × 30 s sprints on a cycle ergometer with 4 min rest between
each sprint. In this study, a 34% decrease in total work was found in addition to
a thirteen-fold increase in serum lactate (9). While the supplementation protocols
were different, the changes in the present study for total work, lactate, and ammonia
were similar to changes reported by Kreider et al. (11) in which they used only
2 × 30 s anaerobic capacity tests. Furthermore, the magnitude of change in the
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Ribose Supplementation and Exercise 663
present study is 1 to 4 times greater than previously reported by other investigators.
Opʼt Eijnde and colleagues (12) performed two bouts of isokinetic knee extensions
(15 sets × 12 contractions each with 15 s rest) which promoted a signicant 20 to
25% decrease in TAN. In comparison to these two previous studies, the present
study used subjects who had been participating in a cycling program that included
either sprint work or intense interval work compared to recreational subjects. The
specic adaptations made in response to their training status are thought to explain
the somewhat decreased magnitude of change in peak power and lactate response.
The present studyʼs ndings are limited due to the absence of any direct assess-
ment of muscle TAN levels via muscle biopsy. The present study, however, when
compared with other published reports (11, 12), provides evidence (e.g., changes in
indirect markers such as lactate, ammonia, and power output) that the study design
used likely produced a decrease in TAN in addition to challenging the metabolic
systems. For example, Zhao and colleagues had seven male subjects complete
only one 30 s maximal sprint and reported a ~ 33% decrease in TAN using muscle
biopsies (18) in addition to the ndings by Hargreaves in which he noted an ~ 11%
decrease in TAN after three maximal 30 s sprints (9)
In contrast to the present ndings in which no signicant increases or improve-
ment in performance were noted, recent studies have suggested that ribose could be
effective at maintaining or attenuating the amount of work completed in addition to
promoting a greater maintenance of high-energy compounds (e.g., ATP, ADP, etc.)
used during high-intensity exercise (3, 7, 10, 11, 14). Antonio and colleagues (3)
concluded that ribose supplementation (10 g/d in 5 g doses prior to and following
workouts) resulted in a greater number of repetitions performed during 10 sets to
failure in the bench press. Kreider and colleagues (11) reported that subjects who
were supplemented with ribose (50 g/d × 5 d) were better able to sustain total
work output after 2 × 30 s Wingate cycle ergometer sprints compared to a matched
double-blind placebo, which resulted in a more drastic decrease in total work output.
Lastly, Hellsten and colleagues (10) trained subjects for 7 d and then supplemented
subjects for 3 d in a double-blind manner (600 mg × kg
-1
× d
-1
) prior to completing
an identical exercise bout used in the training period. Muscle biopsy samples were
taken 5, 24, and 72 h after this exercise bout and found a signicantly increased
level of muscle ATP at 72 h post-exercise. Furthermore, ribose supplementation was
found in two related studies (20 g/d for 3 d prior to training, during a 5 d training
period, and for 3 d following training) to have no impact on performance but did
help to attenuate the decrease in the TAN pool following acute, intense exercise
as well as after a 65 h recovery period (7, 14). While limited evidence is provided
for ribose to increase performance, these ndings do support a possible benet
for ribose supplementation to sustain work production or promotion of long-term
recovery by enhancing ATP availability. In summary, these previously published
studies help to provide the collective evidence indicating why manufacturers of
ribose have marketed these supplements to athletes (3, 7, 10, 11, 14).
While some studies have suggested ergogenic properties for ribose administra-
tion, the results from the present study do not support any ergogenic role for acute
ribose supplementation compared with a placebo on markers of performance and
metabolic activity before or during repeated high-intensity intermittent exercise.
This provides additional support to previous research that has suggested no ergo-
genic benet of ribose supplementation (8 to 50 g/d for 3 to 6 d) while completing
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Ribose Supplementation and Exercise 663
various forms of high-intensity exercise (e.g., 6 to 15 × 10 to 30 s sprints with 60
to 180 s recovery as well as nding no difference in plasma metabolites (lactate,
ammonia, uric acid, glucose, or creatine kinase) and muscle adenine nucleotides
(ATP, ADP, AMP, IMP, or TAN) (4, 7, 11, 12). Lastly, and in accordance with the
ndings showing no performance increase after ribose supplementation, de novo
synthesis of ATP is a slow process with limited evidence of its ability to increase
resting muscle ATP levels during an acute bout of high-intensity, intermittent
exercise (7, 10). Under these circumstances, it is possible that any acute admin-
istration of ribose in a single day or exercise bout would not have enough time to
have a physiological impact; the popularity of ribose supplementation, however,
warranted the investigation.
In summary, the results of this study indicate that acute ribose supplementation
(2 doses of 3 g each) during ve repeated, high-intensity, short-term (30 s) exercise
bouts provides no ergogenic benet. Previous ndings have alluded that possible
benets from ribose supplementation might not be elucidated until several days
after supplementation (10) suggesting additional studies should evaluate the impact
on the TAN pool and performance of ingesting varying doses of ribose before,
during, and after exercise. Investigations should also focus on the pharmokinetic
pattern of ribose to the muscle during acute dosing studies and more research is
needed to evaluate the effects of ribose supplementation on recovery from intense
exercise and training adaptations. Nevertheless, results from this study indicate
that acute ribose supplementation does not improve performance or recovery in
trained cyclists.
Acknowledgments
We would like to thank the subjects who participated in this study and the laboratory assis-
tants in the Exercise and Sport Nutrition Laboratory at Baylor University who assisted
in data acquisition and analysis. This study was funded in part by Royal Numico;
none of the investigators who participated in the study have a nancial interest in the
outcome of this research. The conclusions and ndings of this study are not meant in
any way to suggest an endorsement of the products used or the companies that funded
the research.
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