Sports Nutrition Clinical Studies

Persistent and reversible cardiac dysfunction among amateur marathon runners (European Heart Journal, 2006)

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Tomas G. Neilan1, Danita M. Yoerger1, Pamela S. Douglas4, Jane E. Marshall1, Elkan F. Halpern3, David Lawlor2, Michael H. Picard1, and Malissa J. Wood1*


1
Cardiac Ultrasound Laboratory, Division of Cardiology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, VBK 508, Boston, MA 02114-2696, USA; 2Division of Pediatric Surgery, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; 3Institute for Technology Assessment, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; and 4 Division of Cardiology, Duke University Medical Center, Durham, NC, USA


European Heart Journal (2006) 27, 1079-1084; doi: '10.1 093/ eurheartj I ehi813

Introduction

Participation in endurance sports has increased in the past decade; in the USA alone, nearly 480 000 runners completed a marathon in 2001. Although the cardiovascular benefits of moderate exercise are well established, 1 cardiovascular effects of prolonged exertion are less clear. While the risk of sudden death associated with participation is small; 2 participation in such events is consistently associated with biochemical evidence of cardiac damage and dysfunction. 3 Previous echocardiographic studies have suggested that cardiac dysfunction or 'cardiac fatigue' occurs during prolonged exercise.4 These studies have documented minimal decreases in global left ventricular (LV) systolic function, alterations in LV diastolic function, and the appearance of wall motion abnormalities. 5,6  These studies may be limited by the contribution of alterations in loading conditions. Also, apart from the extent, the chronology of these changes is unclear. Less load-dependent echocardiographic techniques are now available, which can be used to quantify regional and global systolic and diastolic function with greater accuracy. These techniques include pulsed-tissue Doppler (TD)/strain and strain rate (SR) imaging. 8 Therefore, we aimed to characterize the extent and the chronology of the cardiac changes associated with endurance sports using both load-dependent and load-independent techniques among amateur participants.

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Effect of Ribose Supplementation on Resynthesis of Adenine Nucleotides after Intermittent Training in Humans (2004)

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Adapted from a study conducted by Hellsten Y, L Skadhauge, J Bangsbo.

American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 2004;286:R182-R188.

During intense exercise a fraction of the ATP pool in human skeletal muscle is degraded to inosine-5-monophosphate(IMP). While most IMP is retained in the cell for reamination to AMP at rest, a significant fraction of IMP is further degraded to inosine and hypoxanthine and enter the bloodstream lowering the adenine nucleotide pool. Lost nucleotides must be restored via the purine salvage pathway or the de novo pathway of adenine nucleotide metabolism. The limiting step in nucleotide synthesis de novo is the availability of phosphoribosylpyrophosphate (PRPP), which is formed from ribose-5-phosphate. The level of ribose in the muscle is limited; thus an increased availability of ribose may enhance the formation of PRPP and the rate of synthesis of adenine nucleotides. The aim of the present study was to assess the effect of oral intake of ribose after frequent, highintensity training on adenine nucleotide resynthesis. Such information will not only be useful for people performing regular physical exercise but may also be important for patients having impaired skeletal muscle metabolism, such as those with congestive heart failure and peripheral arterial disease.

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Effects of Ribose Supplementation on Repeated Sprint Performance in Men (2003)

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JOHN M. BERARDI AND TIM N. ZIEGENFUSS

Applied Physiology Laboratory, Eastern Michigan University, Ypsilanti, Michigan 48197.

ABSTRACT

This study used a randomized, placebo-controlled, crossover design to evaluate the effects of oral ribose supplementation on short-term anaerobic performance.  After familiarization, subjects performed 2 bouts of repeated cycle sprint exercise (six 10-second sprints with 60-second rest periods between sprints) in a single day. After the second exercise, bout subjects ingested 32 g of ribose or cellulose (4 3 8-g doses) during the next 36 hours. After supplementation, subjects returned to the laboratory to perform a single bout of cycle sprinting (as described above). After a 5-day washout period, subjects repeated the protocol, receiving the opposite supplement treatment. Ribose supplementation lead to statistically significant increases in mean power and peak power in sprint 2 (10.9 and 6.6%, respectively) and higher (although not significant) absolute values in sprints 1, 3, and 4. In conclusion, ribose supplementation did not show reproducible increases in performance across all 6 sprints. Therefore, within the framework of this investigation, it appears that ribose supplementation does not have a consistent or substantial effect on anaerobic cycle sprinting.

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Effects of Effervescent Creatine, Ribose, and Glutamine Supplementation on Muscular Strength, Muscular Endurance, and Body Composition (2003)

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DARIN J. FALK1, KATE A. HEELAN2, JOHN P. THYFAULT3, AND ALEX J. KOCH4

1Department of Exercise and Sport Sciences, College of Health and Human Performance, University of Florida, Grainesville, Florida 32611; 2Human Performance Laboratory, Department of Health, Physical Education, Recreation, and Leisure Studies, University of Nebraska at Kearney, Kearney, Nebraska; 3Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27858; 4Department of Health and Exercise Sciences, Truman State University, Kirksville, Missouri 63501.


ABSTRACT

The purpose of this study was to examine the effects of a combination of effervescent creatine, ribose, and glutamine on muscular strength (MS), muscular endurance (ME) and body composition (BC) in resistance-trained men. Subjects were 28 men (age: 22.3 6 1.7 years; weight: 85.8 6 12.1 kg; height: 1.8 6 0.1 m) who had 2 or more years of resistance training experience. A double blind, randomized trial was completed involving supplementation or placebo control and a progressive resistance-training program for 8 weeks. Dependent measures were assessed at baseline and after 8 weeks of resistance training. Both groups significantly improved MS and ME while the supplement group significantly increased body weight and fat-free mass. Control decreased body fat and increased fat-free mass. This study demonstrated that the supplement group did not enhance MS, ME, or BC significantly more than control after an 8-week resistance-training program.

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The Effects of Four Weeks of Ribose Supplementation on Body Composition and Exercise Performance in Healthy, Young, Male Recreational Bodybuilders: A Double-Blind, Placebo-Controlled Trial (2002)

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Darin Van Gammeren, MA.Ed, CSCS, 1 Darin Falk, MA.Ed,Z and Jose Antonio, PhD2

1Center for Exercise Science, University of Florida, Gainesville, Florida, and 2Human

Performance Laboratory, University of Nebraska, Kearney, Nebraska

Current Therapeutic Research, Volume 63, Issue 8, August 2002, Pages 486–495

 

INTRODUCTION

Ribose is a pentose sugar that is present in ribonucleic acids, riboflavin, nucleotides.and adenosine triphosphate (ATP). 1 In addition, ribose is used to synthesize ATP by the pentose phosphate pathway. 1 Under normal physiologic conditions, levels of the adenine nucleotides are maintained easily. However, intense exercise has been shown to have a profound impact on total adenine nucleotide (TAN) levels. Thus, it is possible that providing exogenous ribose might affect the resynthesis of ATP, thereby affecting skeletal muscle function.

 
For instance, in a study by Stathis et al.2 high-intensity sprint training for 7 weeks decreased resting concentrations of ATP and TA\ (TA1'\/ = ATP +adenosine diphosphate + adenosine monophosphate) by IS% to 19%. Van der Meulen et are found that in rat tibialis anterior muscles that had been lengthened forcibly, ATP concentrations decreased by 9,  whereas no significant change was observed in isometrically exercised muscles. In a placebo-controlled study by Gross et al4 in 9 healthy men, the acute ingestion of ribose (2 g every 5 minutes for 30 minutes) during bicycle exercise blunted the increase in plasma hypoxanthine level suggesting a reduction in the ATP degradation due to the fact that hypoxanthine is the primary metabolite of ATP degradation in humans.

 

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AMP deamination and purine exchange in human skeletal muscle during and after intense exercise (The Journal of Physiology, 1999)

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Y. Hellsten, E.A. Richter, B. Kiens and J. Bangsbo

The Journal of Physiology. 1999;520;909-920

  1. The present study examined the regulation of human skeletal muscle AMP deamination during intense exercise and quantified muscle accumulation and release of purines during and after intense exercise.
  2. Seven healthy males performed knee extensor exercise at 64·3 W (range: 50-70 W) to exhaustion (234 s; 191-259 s). In addition, on two separate days the subjects performed exercise at the same intensity for 30 s and SO% of exhaustion time (mean, 186 s; range, 153-207 s), respectively. Muscle biopsies were obtained from m.v. lateralis before and after each of the exercise bouts. For the exhaustive bout femoral arterio-venous concentration differences and blood flow were also determined.
  3. During the first 30 s of exercise there was no change in muscle adenosine triphosphate (ATP), inosine monophosphate (IMP) and ammonia (NH3), although estimated free ADP and AMP increased 5- and 45-fold, respectively, during this period. After 186 sand at exhaustion muscle ATP had decreased (P < 0·05) by 15 and 19%, respectively, muscle IMP was elevated (P < 0·05) from 0·20 to 3·65 and 5·67 mmol (kg dry weightf\ respectively, and muscle NH3 had increased (P < 0·05) from 0·47 to 2·55 and 2·33 mmol (kg d.w.f1 , respectively. The concentration of H+ did not change during the first 30 s of exercise, but increased (P < 0·05) to 245·9 nmoll-1 (pH 6·61) after 186 sand to 374·5 nmoll-1 (pH 6·43) at exhaustion.
  4. Muscle inosine and hypoxanthine did not change during exercise. In the first 10 min after exercise the muscle IMP concentration decreased (P < 0·05) by 2·96 mmol (kg d.w.f1 of which inosine and hypoxanthine formation could account for 30%. The total release of inosine and hypoxanthine during exercise and 90 min of recovery amounted to 1·07 mmol corresponding to 46% of the net ATP decrease during exercise or 9% of ATP at rest.
  5. The present data suggest that AMP deamination is inhibited during the initial phase of intense exercise, probably due to accumulation of orthophosphate, and that lowered pH is an important positive modulator of AMP deaminase in contracting human skeletal muscle in vivo. Furthermore, formation and release of purines occurs mainly after intense exercise and leads to a considerable loss of nucleotides.

During intense exercise the rate of ATP utilisation in skeletal muscle is higher than the rate of ATP regeneration, which leads to an accumulation of ADP and AMP. To avoid a large accumulation of AMP within the cell, AMP is deaminated to IMP and ammonia/ammonium (in this paper we will represent both as 'NH3 ') via the enzyme AMP deaminase (Lowenstein, t990). The maximal activity of AMP deaminase is high in skeletal muscle and the accumulation of IMP and NH3 in human muscle after intense exercise may amount to t 0 mmol (kg d.w.f1 (Sahlin et al. 1978; Graham et al. 1990; Bangsbo et al. 1992a; Tullson et al. 1995). The mechanism underlying the regulation of AMP deamination in human skeletal muscle is, however, unclear.

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Decreased resting levels of adenine nucleotides in human skeletal muscle after high-intensity training (J. Appl. Physiol. 74(5): 2523-2528, 1993)

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Ylva Hellsten-Westing, Barbarba Norman, Paul D. Balsom, and Bertil Sjodin

Department of Physiology 111, Karolinska Institute, S-11486 Stockholm; and Department of Clinical Physiology, Huddinge Hospital, S14186 Huddinge, Sweden

J. Appl. Physiol. 74(5): 2523-2528, 1993

The effect of high-intensity intermittent training on the adenine nucleotide content of skeletal muscle was studied. Eleven male subjects (group A) performed high-intensity intermittent training on a cycle ergometer three times per week for 6 wk, followed by 1 wk of the same kind of training with two sessions per day. Nine males (group B) exclusively performed 1 wk of training with two sessions per day. In group A, skeletal muscle total adenine nucleotide (TAN) levels decreased from 25.1 ± 0.7 (SE) to 22.0 ± 0.6 mmollkg dry wt over the 6-wk period (P < 0.01). The subsequent intensive week did not further alter TAN levels. In group B, the intensive week of training reduced TAN levels from 25.1 ± 0.5 to 19.4 ± 0.6 mmol/kg dry wt (P < 0.001). The decrease was sustained 72 h after training (P < 0.001). During the intensive week, there was no change in plasma creatine kinase activity in either group A or group B. The plasma activity was, however, higher in group B than in group A on days 4 and 7 of the intensive week (P < 0.05). The results from this study indicate that high-intensity intermittent exercise causes a decrease in resting levels of skeletal muscle adenine nucleotides without a concomitant indication of muscle damage. A training-induced adaptation appears to occur with training by which a further loss of adenine nucleotides is prevented despite an increased training dose.

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Effects of Oral Ribose on Muscle Metabolism during Bicycle Ergometer in AMPD-Deficient Patients (Ann Nutr Metab, 1991)

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D.R. Wagner, U.Gresser, N. Zollner

Medizinishe Poliklinik der Universitat Munchen, FRG

Ann Nutr Metab 1991:35:297-302

Abstract. Three patients with AMP deaminase deficiency (AMPD deficiency) performed exercise on a bicycle ergometer with increasing work load \~hout and with administration of ribose (3 g p.o. every l 0 min. beginning l h before exercise until the end). The patients performed exercise until heart rate was 200 minus age. Maximum capacity was not increased by administration of ribose. but postexertional muscle stiffness and cramps disappeared almost completely in 2 of 3 AMPD-deficient patients. Plasma concentrations of lactate and inosine were increased in AMPD-deficient patients after oral administration of ribose. Our data suggest that ribose may both serve as an energy source and enhance the de novo synthesis of purine nucleotides.

AMP deaminase deficiency (AMPD deficiency) is a relatively frequent enzyme defect of skeletal muscle ( 1.5% of muscle biopsies) [ 1]. Clinically, it is characterized by postexertional muscle stiffness and cramps. AMP deaminase (myoadenylate deaminase) is one component of the purine nucleotide cycle. The disruption of the purine nucleotide cycle induced by AMPD deficiency is probably the cause of the muscular disorder. So far, the only successful therapeutic approach has been the oral administration of ribose. The beneficial effect of ribose in AMPD deficiency has only been achieved by high oral doses (3-4 g) administered continuously (every I 0 min) during exercise, as first described by Zollner et al. [2]. Lower and not exercise-related doses of 500 mg ribose 4 times a day were not successful. Besides occasionally occurring diarrhea no side effects have been noted during ribose therapy. The beneficial effect of ribose has mainly been attributed to an additional energy source [2] and possibly also to enhanced de novo synthesis of purine nucleotides [3].

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