Ribose

Introduction – What is Ribose
Cardiovascular Health
Research
.: Introduction
.: Ribose and its Role in the Pentose Phosphate Pathway
.: Ribose Metabolism
.: Ribose Effects in the Heart
.: Ribose Effects on Skeletal Muscle
.: Conclusion
.: References

What is Ribose?
Ribose is a carbohydrate, or sugar, used by all living cells and is an essential component in our body’s energy production.

Ribose is a new nutraceutical product that helps the body naturally restore its energy level. It’s used by the body’s cells to form the primary source of all the body’s energy - ATP. As a dietary supplement at recommended dosages, ribose provides known benefits by quickly restoring energy levels in heart and skeletal muscles. Until now, it wasn’t available for sale as a dietary supplement, due to high production costs. Now, thanks to ABR’s Research and Its’ ability to License, Patented cutting edge Biotechnology, Riboperine a patented proprietary blend of Natural Glucose polymer/metabolites/fractions including Ribose, Glycine, and a natural flavor is available..

Whether you’re just feeling sluggish and rundown, or suffer from poor cardiovascular health, or you’re a high performance athlete looking for that extra edge, Ribose is truly The Absolute Energy Source™.

Science Overview
According to the American Heart Association, 60 million Americans, more than one in four, suffer from cardiovascular disease.

One result of poor cardiovascular health is ischemia, a condition where poor blood flow decreases the amount of oxygen reaching various tissues in the body. When ischemia occurs, the body’s cells aren’t getting the oxygen they need to properly burn energy-producing fuels (such as ATP), and have less energy available for normal, everyday life.

In the heart, ischemic conditions may be caused by a number of factors, including coronary artery disease, infarction (caused by clotting in the heart) or cardiac surgery. When ischemia occurs, ATP levels may decrease by 50 percent or more, and research suggests that it may take seven to ten days for ATP levels to return to normal. Researchers found that supplemental ribose allowed the heart to recover 85 percent of its ATP levels within 24 hours. Another study found that, following a heart attack, supplemental ribose helped ATP levels and heart function return to normal within two days; without supplemental ribose heart function was still depressed after four weeks.

Health Benefits
Supplemental ribose can help the heart rebuild energy, and millions of Americans may significantly benefit from its effects. Ribose may help dramatically improve the quality of life for persons suffering from certain cardiac conditions, and research shows it has a direct effect on heart function for persons suffering from ischemia.

Under conditions of cardiac insufficiency blood flow to the heart is diminished. Some individuals have known cardiac insufficiencies, while a great many others may not even know that such conditions exist. In either case, cardiac function may be diminished, energy stores may be low and recovery to peak levels may be slow or never achieved. For these individuals, even simple activities required for daily living may be difficult and exercise may not be tolerated. Energy recovery is certainly a major concern.

Use Suggestions
Ribose increases both de novo (new) synthesis and salvage of nucleotides in heart, helps to optimize cardiovascular health and maintain peak function. Doses greater than or equal to 2.2 grams per day should be enough to improve nucleotide synthesis and salvage and keep heart ATP levels at their peak. Ribose is only effective, however, if it can reach the cells requiring an energy boost. If circulation to portions of the heart is diminished, it may take longer for enough ribose to reach the affected areas. Therefore, larger doses may be required. In individuals who are concerned about their cardiovascular energy stores, are overly tired following exercise, or are not able to exercise as much or as hard as they like, higher doses may be necessary.

For these individuals, it is suggested that they increase the frequency of dosage until they find a level most beneficial to them. In some, this may be 2.2 - 3.0 grams twice per day, but in others it may be more. Doses should be individually adjusted based on perceived benefit.

Ribose and its Effect on Energy Recovery in Heart and Skeletal Muscle

Terri L. Butler, Ph.D.

Bioenergy, Inc.
13840 Johnson Street N.E.
Ham Lake, Minnesota 55304 USA

.:: Introduction
.:: Ribose and its Role in the Pentose Phosphate Pathway
.:: Ribose Metabolism
.:: Ribose Effects in the Heart
.:: Ribose Effects on Skeletal Muscle
.:: Conclusion
.:: References

Introduction
Under conditions of physical duress the body's energy resources become depleted. In particular, intracellular levels of the body's primary energy carrying molecule, adenosine triphosphate (ATP), are lowered significantly. Since cells and organs need adequate energy in order to maintain integrity and function, it is essential that the supply of ATP be replenished soon after it is consumed. This is possible over the short term in the presence of oxygen via the respiratory metabolic pathways. However, when the oxygen supply is inadequate, even temporarily, energy metabolism is impaired and ATP molecules are not regenerated quickly enough to meet the body's energy demands.

For example, when the myocardium becomes oxygen depleted due to ischemia (restricted blood flow to the heart) resulting from occluded arteries, heart attack, heart surgery, organ transplantation or other surgery, myocardial levels of ATP will fall dramatically and can take up to 10 days to recover.1,2,3,4,5,6 Under conditions of such energetic depletion myocardial function is compromised and there is an increased risk of permanent loss of myocardial tissue.

Even in lower risk situations, such as healthy individuals who are pushing their physical limits by intense exercise, ATP reserves can become depleted and take several days to recover.7, 8, 9, 10, 11

Slow replenishment of ATP in both myocardial and skeletal muscle tissues has been attributed to the low rate of de novo synthesis and slow recovery of ATP and its precursors via the salvage pathways.2, 3, 10, 12. Since replenishment of ATP is likely to enhance the functional recovery of these tissues investigators have sought methods of improving the salvage rates and increasing de novo synthesis. Interestingly, in a wide range of studies several investigators have found that ATP recovery can be stimulated in both myocardial and skeletal muscle tissues by administering a simple sugar called ribose. 3, 6, 10, 12, 13, 14, 15, 16, 17, 18, 19

Ribose and its Role in the Pentose Phosphate Pathway

Ribose is a naturally occurring pentose monosaccharide. It is used by the body to synthesize nucleotides, nucleic acids, glycogen, and other important metabolic products. Ribose is formed in the body from conversion of glucose via the pentose phosphate pathway (PPP, also known as the hexosemonophosphate shunt or the phosphogluconate pathway, Figure 1).

Figure 1. Figure 1. The pentose phosphate pathway (PPP) and the point of entry for ribose into the pathway. 5-phosphoribosyl-1-pyrophosphate is represented as PRPP.

Supplemental ribose enters the PPP by being phosphorylated to R-5-P by ribokinase. The R-5-P thus formed can be utilized to a) generate glucose by reverse flux up the PPP 20, 21; b) form pyruvate through glycolysis 21, 22; or c) synthesize nucleotides 23 which are needed for ATP production. In this way ribose is utilized in animals and man in many different tissues, including the heart and skeletal muscle.

Ribose Metabolism
Ribose is the substrate for formation of 5-phosphoribosyl-1-pyrophosphate (PRPP). PRPP is, in turn, used in de novo synthesis of nucleotides such as ATP, adenosine, and inosine (Figure 2).3, 12, 14, 24 PRPP is also an essential participant in the salvage pathways for ATP regeneration (Figure 3).3, 12, 14, 24 Nucleotides, including ATP, are essential energy sources for basic metabolic reactions and play important roles in protein, glycogen and nucleic acid synthesis (ribonucleotides and deoxyribonucleotides), cyclic nucleotide metabolism, and energy transfer reactions.

Figure 2. The role of ribose in de novo synthesis of ATP.

Figure 3. The role of 5-phosphoribosyl-1-pyrophosphate (PRPP) in the ATP salvage pathway.

Ribose plays a vital role in both myocardial and skeletal muscle metabolism, largely through its participation (as a precursor to PRPP) in the synthesis of ATP, adenine nucleotides, and nucleic acids. In these tissues the PPP is inefficient due to low availability of glucose-6-phosphate dehydrogenase.13 Supplemental ribose administration allows the rate-limiting glucose-6-phosphate dehydrogenase step in the PPP to be bypassed, thereby directly elevating PRPP levels.14, 15, 18, 24, 25 Elevated PRPP levels are then available for increased adenine nucleotide biosynthesis which accelerates replenishment of depleted cardiac and skeletal muscle adenine nucleotide pools. This is the key to recovery of depleted ATP levels after ischemia or strenuous exercise.

The metabolic basis for the effectiveness of ribose is apparently not species specific because glucose-6-phosphate dehydrogenase is the rate limiting enzyme in the heart and skeletal muscle PPP for rats, dogs, and swine, as well as humans.14 Since this enzymatic reaction is the rate-limiting step in the PPP that limits the available PRPP pool and thus the adenine nucleotide levels, the enzymatic basis for the effectiveness of ribose, i.e., the formation of PRPP by bypassing the G-6-PDH reaction step, is the same for these different species.

Ribose Effects in the Heart

Knowledge concerning the effect of ribose in the heart has been gathered from many laboratory and clinical studies of human and animal myocardial tissue and function. These studies have documented several positive effects of ribose including improved ventricular function and enhanced recovery of myocardial ATP and adenine nucleotide levels following ischemia, increased exercise tolerance in patients with stable coronary artery disease, and improved thallium-201 redistribution in cardiac imaging applications.

Myocardial tissue becomes oxygen depleted when blood flow to the heart is restricted. A persistent consequence of this ischemia is a substantial lowering of tissue energy, as evidenced by decreased myocardial ATP levels. These lowered energy levels are in turn correlated with depressed cardiac function.2,3 The correlation between decreased ATP levels and depressed myocardial performance has spurred researchers to develop methods of metabolic intervention into adenine nucleotide degradation and/or biosynthesis in order to restore myocardial ATP levels.

In a series of oxygen depletion studies in the myocardium using asphyxia recovery and ATP depletion models evidence was gathered that PRPP availability limits adenine nucleotide synthesis by both the de novo and salvage pathways.12,13,24,25 By providing ribose to the myocardium a pronounced stimulatory effect on PRPP synthesis occurs. The presence of ribose allows the rate-limiting step in the pentose phosphate pathway, the G-6-PDH enzymatic reaction, to be bypassed, leading to the production of PRPP. This increase in PRPP levels is noted to be accompanied by accelerated cardiac adenine nucleotide synthesis and improved global heart function. Thus, ribose restores cardiac energy reserves and positively affects myocardial function.

The effect of orally-administered ribose on exercise tolerance in stable coronary artery disease patients has also been studied.26 Two positive baseline treadmill studies were performed for eligibility into this study. The criterion for inclusion was development of moderate angina and/or ST-segment depression (an indicator of ischemia) on the electrocardiogram. Patients were randomized into two groups. Ten patients received placebo (glucose) for three days and another 10 patients received ribose dissolved in water for the same time period. A final treadmill evaluation was performed in all patients after taking the supplement. In the ribose-treated group, the mean walking time to ST-segment depression was significantly greater than in the placebo group (p < 0.002). The time to both ST-segment depression and onset of moderate angina was also prolonged significantly in the ribose group compared to its pre-ribose baseline (p<0.005). These results show that patients who had been given ribose were able to exercise longer without chest pain or evidence of ischemia than patients who did not receive ribose.

Ribose also enhances the detection of hibernating myocardium during diagnostic procedures such as thallium imaging or dobutamine stress echocardiography. In two swine models, ribose infusion after transient ischemia modified thallium-201 (201TI) clearance in both ischemic and non-ischemic myocardial regions, resulting in faster 201TI redistribution.27,28 Furthermore, placebo-controlled clinical trials have also found that intravenous ribose infusion enhances thallium-201 redistribution in humans.29,30 One such trial addressed whether or not an intravenous infusion of ribose could facilitate 201TI redistribution after transient myocardial ischemia in patients with coronary artery disease and thus improve the ability to detect jeopardized but viable myocardium.29 Seventeen patients with documented coronary artery disease and chronic, stable angina were enrolled. Each patient underwent two separate exercise tests, one with saline infusion and one with ribose, performed 1 - 2 weeks apart. In each test an injection of 201TI was given and two subsequent imaging procedures were performed. Post-exercise and initial imaging, patients received the infusion of either ribose or saline. Imaging was performed again at 1 hour, followed by a rest period of 4 hours. Following the rest period imaging was performed one final time. The results revealed that at both 1 and 4 hours post-exercise there were significantly more reversible defects identified when patients were given ribose versus saline. In another 201TI study with a similar protocol, but with imaging at 4 and 24 hours, results showed that there were more defects detected at 4 hours post-exercise when ribose infusion was given than at 4 and 24 hours with saline infusion.30 The conclusions from both of these studies imply that ribose substantially improves the identification of viable ischemic myocardium using 201TI imaging after exercise, suggesting improved post-ischemic myocardial function with ribose administration.

Another research study reported that ribose infusion in conjunction with dobutamine stress echocardiography increases the contractile response in hibernating regions of the heart.31 In a placebo-controlled double-blind study twenty-five patients with ischemic cardiomyopathy were infused with either D-ribose or dextrose placebo for the 4 hours prior to dobutamine stress echocardiography. On day two the patients were crossed over to the alternate treatment. During dobutamine stress echocardiography more dysfunctional wall segments responded with improved wall motion when D-ribose was infused prior to the procedure as compared to placebo (p = 0.02). In patients who then underwent coronary artery bypass surgery the predictive sensitivity for functional recovery of the segments identified during the D-ribose infusion was greater than those identified during placebo infusion.

A recent review provides the background and rationale for the use of ribose in metabolic support of the heart.32 Evidence such as that discussed above is presented in support of the main hypothesis that ribose is the rate-limiting component in the pathways necessary for the heart to restore depleted adenine nucleotide levels.

Conclusion

ATP, the body's primary energy-carrying molecule, is necessary for maintenance of cellular integrity and function. Ribose plays a key role in the generation and recovery of ATP. Adding ribose to the ATP-depleted myocardial or skeletal muscle environment stimulates recovery of ATP levels. This enhancement of ATP recovery may play an important role in improving the overall health, lifestyle, and level of fitness in people with cardiovascular disease as well as in athletes who are pushing their exercise limits and depleting their energy reserves.

References

1. Benson, E. S., G. T. Evans, and B. E. Hallaway. Myocardial creatine phosphate and nucleotides in anoxic cardiac arrest and recovery. Am. J. Physiol. 201: 687, 1961.

2. Foker, J. E., S. Einzig, and T. Wang. Adenosine metabolism and myocardial preservation. J. Thorac. Cardiovasc. Surg. 80: 506-516, 1980.

3. Pasque, M. K. and A. Wechsler. Metabolic intervention to affect myocardial recovery following ischemia. Annals of Surgery 200: 1-10, 1984.

4. Lee, H. T., R. J. LaFaro, and G. E. Reed. Pretreatment of human myocardium with adenosine during open heart surgery. J Card. Surg. 10: 665-676, 1995.

5. Jennings, R. B. and C. Stanbergen, Jr. Nucleotide metabolism and cellular damage in myocardial ischemia. Annual Rev. Physiol. 47: 727 - 749, 1985.

6. Ward, H. B., J. A. St. Cyr, J. A. Cogordan, D. Alyono, R. W. Bianco, J. M. Kriett, & J. E. Foker. Recovery of adenine nucleotide levels after global myocardial ischemia in dogs, Surgery 96(2): 248-255, 1984.

7. Stathis, C. G., M. A. Febbraio, M. F. Carey, and R. J. Snow. Influence of sprint training on human muscle purine nucleotide metabolism. J. of Appl. Physiol. 76(4): 1802-1809, 1994.

8. Hellsten-Westing, Y., P. D. Balsom, B. Norman, and B. Sjodin. The effect of high-intensity training on purine metabolism in man. Acta Physiol. Scand. 149: 405-412, 1993.

9. Hellsten-Westing, Y., B. Norman, P. D. Balsom, and B. Sjodin. Decreased resting levels of adenine nucleotides in human skeletal muscle after high-intensity training. J. Appl. Physiol. 74(5): 2523-2528, 1993.

10. Tullson, P. C. and R. L. Terjung. Adenine nucleotide synthesis in exercising and endurance-trained skeletal muscle. Am. J. Physiol. 261: C342-C347, 1991.

11. Tullson, P. C., J. Bangsbo, Y. Hellsten, and E. A. Richter. IMP metabolism in human skeletal muscle after exhaustive exercise. J. Appl. Physiol. 78: 146-152, 1995.

12. Zimmer, H.-G. and E. Gerlach. Stimulation of myocardial adenine nucleotide biosynthesis by pentoses and pentitols. Pflugers Arch. 376: 223 - 227, 1978.

13. Zimmer, H.-G. Restitution of myocardial adenine nucleotides: acceleration be administration of ribose. J. Physiol., Paris 76(7): 769 - 775, 1980.

14. Zimmer, H.-G. and J. Schad. Ribose intervention in the cardiac pentose phosphate pathway is not species-specific. Science 223: 712 - 713, 1984.

15. Zimmer, H.-G. Regulation of and intervention into the oxidative pentose phosphate pathway and adenine nucleotide metabolism in the heart. Molec. Cell. Biochem. 160/161: 101 - 109, 1996.

16. Pasque, M. K., T. L. Spray, G. L. Pellom, P. Van Trigt, R. B. Peyton, W. D. Currie, and A. S. Wechsler. Ribose-enhanced myocardial recovery following ischemia in the isolated working rat heart, J. Thorac. Cardiovasc. Surg. 83(3): 390-398, 1982.

17. St. Cyr, J. A., H. Ward, J. Kriett, D. Alyono, S. Einzig, R. Bianco, R. Andersoon, and J. Foker. Long term model for evaluation of myocardial metabolic recovery following global ischemia. In: N. Bratbar (ed.) Myocardial and Skeletal Muscle Bioenergetics pp. 401 -414, Plenum, New York, 1986.

18. St. Cyr, J. A., R. W. Bianco, J. R. Schneider, J. R. Mahoney, K. Tveter, S. Einzig, and J. E. Foker. Enhanced high energy phosphate recovery with ribose infusion after global myocardial ischemia in a canine model. J. Surg. Res. 46, 157 - 162, 1989.

19. Chatham, J. C., R. A. J. Challiss, G. K. Radda, and A-M. L. Seymour. Studies of the protective effect of ribose in myocardial ischaemia by using 31P-nuclear-magnetic-resonance spectroscopy. Biochem. Soc. Trans. 13: 885 - 886, 1985.

20. Hiatt, H. H. Glycogen formation via the pentose phosphate pathway in mice in vivo. J. Biol. Chem. 224: 851 - 859, 1957.

21. Segal, S. and J. Foley. The metabolism of D-ribose in man. J. Clinical Invest. 37: 719 - 735, 1958.

22. Bloom, B., F. J. Eisenberg, and D. J. Stetten. Glucose catabolism in liver slices via the phospho-gluconate oxidation pathway, J. Biol., Chem. 215: 461 - 466, 1954.

23. Coffey, R.G., Morse H., and Newburgh R.W. The synthesis of nucleic acid constituents in the early chick embryo, Biochim. Biophys. Acta 114: 547-558, 1965.

24. Zimmer, H.-G., H. Ibel, and G. Steinkopff. Studies on the hexose monophosphate shunt in the myocardium during development of hypertrophy. In: Advances in Myocardiology Volume 1 (eds. M Tajuddin, P. K. Das, M. Tariq, and N. S. Dhalla) pp. 487 - 492, University Park Press, Baltimore, 1980.

25. Zimmer, H.-G. and H. Ibel. Effects of ribose on cardiac metabolism and function in isoproterenol-treated rats. Am. J. Physiol. 245: H880 - H886, 1983.

26. Pliml, W, T. von Arnim, A. Stablein, H. Hofmann, H.-G. Zimmer, and E. Erdmann. Effects of ribose on exercise-induced ischaemia in stable coronary artery disease. Lancet 340: 507 - 510, 1992.

27. Angello, D. A., R. A. Wilson, D. Gee, and N. Perlmutter. Recovery of myocardial function and thallium-201 redistribution using ribose. Am. J. Card. Imaging 3(4): 256 - 265, 1989.

28. Angello, D. A., R. A. Wilson, and D. Gee. Effect of ribose on thallium-201 myocardial redistribution. J. Nucl. Med 29: 1943 - 1950, 1988.

29. Perlmutter, N. S., R. A. Wilson, D. A. Angello, R. T. Palac, J. Lin, and B. G. Brown. Ribose facilitates thallium-201 redistribution in patients with coronary artery disease. J. Nucl. Med. 32: 193- 200, 1991.

30. Hegewald, M. G., R. T. Palac, D. A. Angello, N. S. Perlmutter, and R. A. Wilson. Ribose infusion accelerates thallium redistribution with early imaging compared with late 24-hour imaging without ribose. J. Am. Coll. Cardiol. 18: 1671 - 1681, 1991.

31. Gradus-Pizlo, I., S. Sawada, S. Lewis, S. Khouri, D. Segar, R. Kovacs, and H. Feigenbaum. Effect of D-ribose on the detection of the hibernating myocardium during the low dose dobutamine stress echocardiography. Circulation Suppl. 100(18):3394, 1999.

32. Pauli, D.F. and C.J. Pepine. D-ribose as a supplement for cardiac energy metabolism. J. Cardiovasc. Pharmacol. Therapeut. 5:249-258, 2000.

33. Brault, J.J. and R.L. Terjung. Purine salvage rates differ among skeletal muscle fiber types and are limited by ribose supply. Med. Sci. Sports Exer. Suppl. 31(5): 1365, 1999.

34. Zarzeczny, R., J. Brault, K. Abraham, C. Hancock, and R.L. Terjung. Purine salvage is not reduced during recovery following intense contractions. Med. Sci. Sports Exer. Suppl. 32(5): 214, 2000.

35. Brault, J.J., R.L. Terjung. Attempted expansion of resting muscle ATP content by a prolonged period of adenine salvage Med. Sci. Sports Exer. Suppl. 32(5): 213, 2000.

36. Witter, J., P. Gallagher, D. Williamson, M. Godard, and S. Trappe. Effects of ribose supplementation on performance during repeated high-intensity cycle sprints. Midwest Regional Chapter of the ACSM, October 2000.

37. Gallagher, P.M., D.L. Williamson, M.P. Godard, J. Witter, S.W. Trappe. Effects of ribose supplementation on adenine nucleotide concentration in skeletal muscle following high-intensity exercise. Midwest Regional Chapter of the ACSM, October 2000.

38. Antonio, J. D. Van Gammeren, and D. Falk. The effects of ribose supplementation of exercise performance in recreational male bodybuilders. Data on file at Bioenergy, Inc., 13840 Johnson Street N.E., Ham Lake, Minnesota 55304 USA.