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D-Ribose—A Very Powerful and Natural Body Energizer

In looking at energy production, it helps to look at the "energy molecules" such as ATP, NADH, and FADH. These represent the energy currency in your body, and are like the paper that money is printed on. You can have all the fuel you want, but if it cannot be converted to these molecules, it is useless!

For years, I talked about the importance of B vitamins, which are a key component of these molecules. These helped to a degree, but it was clear that a key component was missing. In looking at the biochemistry of these energy molecules, they are also made of 2 other key components—adenine and Ribose. Adenine is plentiful in the body and supplementing with adenine did not help CFS. We then turned our attention to Ribose. Ribose is made in your body in a slow, laborious process and cannot be found in food. We knew that CFS/FMS causes your body to dump other key energy molecules like Acetyl-L-Carnitine. We then found that the body did the same with Ribose, making it hard to get your furnaces working again even after the other problems were treated.

This was like one of those "Eureka!" moments where things came together. Not having Ribose would be like trying to build a fire without kindling-nothing would happen. We wondered if giving Ribose to people with CFS would jump-start their energy furnaces. The answer was a resounding yes!
Our recently published study (see the study abstract in Appendix B) showed an average 44.7% increase in energy after only 3 weeks (improvement began at 12 days) and an average overall improvement in quality of life of 30%. Two thirds of the CFS/FMS patients felt they had improved.19 Usually a 10% improvement for a single nutrient is considered excellent. A 44.7% increase left us amazed, and I am now recommending Ribose for all of my CFS/FMS patients, for athletes, and any one with pain, fatigue or heart problems. Ribose recently became available (over the counter) to physicians, and is one of the few natural products actually starting with physicians and then moving out into health food stores.

It is critical to use the proper dose for the first 3 weeks, which is 5 grams (5000 mg) three times a day. It can then be dropped to twice a day. I recommend the Corvalen form of Ribose as it is the least expensive and highest quality and is packaged with a 5 gm dosing scoop in it. One 280 gm container will be enough to tell you if it will work. Corvalen M (which has Ribose plus magnesium and malic acid) is also available, but if you are also taking the Energy Revitalization System vitamin powder (see chapter X), you are already getting the magnesium and malic acid, and the regular Corvalen is a better deal financially. Bioenergy, which makes Corvalen, also conducts almost all of the research on Ribose, knows the most about it, and has outstanding customer service in case you have any questions. Because of its importance, it's worth looking at energy production and Ribose in greater detail. Having had the chance to explore the research and speak with a number of the researchers, below is what I've learned from them.

D-Ribose Accelerates Energy Recovery

D-Ribose (which is what I am referring to when I say Ribose) is a simple, five-carbon sugar (known as a pentose by biochemists) that is found naturally in our bodies. But Ribose is not like any other sugar. Sugars we are all familiar with, such as table sugar (sucrose), corn sugar (glucose), milk sugar (lactose), honey (predominantly fructose), and others are used by the body as fuel. These sugars are consumed and, with the help of the oxygen we breathe, are "burned" by the body to recycle energy. Because they are used excessively, they can also be toxic, as we've discussed earlier. Ribose, on the other hand, is special. When we consume Ribose, the body recognizes that it is different from other sugars and preserves it for the vital work of actually making the energy molecule that powers our hearts, muscles, brains, and every other tissue in the body.

A key molecule, called adenosine triphosphate (or ATP for short), is known as the energy currency of the cell because the amount of ATP we have in our tissues determines whether we will be fatigued, or will have the energy we need to live vital, active lives. Ribose provides the key building block of ATP, and the presence of Ribose in the cell stimulates the metabolic pathway our bodies use to actually make this vital compound. If the cell does not have enough Ribose, it cannot make ATP. So, when cells and tissues become energy starved, the availability of Ribose is critical to energy recovery.

Normal, healthy heart and muscle tissue has the capacity to make all the Ribose it needs. When normal tissue is stressed by overexertion, several days of rest will usually allow it to fully recover. The muscle may be sore during recovery, as we frequently see for the three or four days after a hard day of yard work or after a weekend pick up football game, but eventually energy levels will be restored and the soreness will disappear. But when the muscle is chronically stressed by disease or conditions that affect tissue energy metabolism, the cells and tissues simply cannot make enough Ribose quickly enough to recover. Hearts and muscles just don't have the metabolic machinery they need to make Ribose very efficiently. The result is chronic, persistent pain, stiffness, soreness, and overwhelming fatigue that may never go away.

The Link between Ribose, Energy, and Fatigue

Clinical and scientific research has repeatedly shown that giving Ribose to energy deficient hearts and muscles stimulates energy recovery. One important study involved healthy athletes participating in high-intensity, endurance exercise over the course of one week. After exercise the energy level in the athlete's muscle was reduced by almost 30%. Giving 10 grams of Ribose per day for three days following exercise restored muscle energy levels to normal, while treatment with placebo provided virtually no effect.20 This study clearly showed that Ribose stimulated the energy recovery pathways in the body, helping the muscle rebuild its energy supply quickly and completely. Even after three days of rest, muscle that was not treated with Ribose remained energy starved and fatigued.

Two very interesting studies in animals showed how dramatic the effect of Ribose could be on energy recovery in fatigued muscle. These studies were conducted by Dr. Ron Terjung, one of the top muscle physiologists in the U.S. In their research, Dr. Terjung and his co-investigators found that Ribose administration in fatigued muscle increased the rate of energy recovery by 340% to 430%, depending on which type of muscle was tested.21 He also found that even very small amounts of Ribose had the effect of helping the muscle cell preserve energy, a process known as energy salvage, and the higher the Ribose dose, the more dramatic the effect on energy preservation.22 Although this groundbreaking research was done in animals it was instrumental in defining the biochemistry and physiology associated with the use of Ribose in overcoming heart and muscle fatigue. But most of us with CFS and FMS are neither top athletes nor animals, so the question remains, "How will Ribose affect me?"

Research in Ribose and CFS/FMS began with a case study that was published in the prestigious journal Pharmacotherapy in 2004.23 This case study told the story of a veterinary surgeon diagnosed with fibromyalgia. For months, this dedicated doctor found herself becoming more and more fatigued, with pain becoming so profound she was finally unable to stand during surgery. As a result, she was forced to all but give up the practice she loved.

Upon hearing that a clinical study on Ribose in congestive heart failure was underway in the university where she worked, she asked if she could try the Ribose to see if it might help her overcome the mind-numbing fatigue she experienced from her disease. After three weeks of Ribose therapy she was back in the operating room, practicing normally with no muscle pain or stiffness, and without the fatigue that had kept her bedridden for many months.

Being a doctor, she was skeptical, not believing that a simple sugar could have such a dramatic effect on her condition. Within two weeks of stopping the Ribose therapy, however, she was out of the operating room and back in bed. So, to again test the theory, she began Ribose therapy a second time. The result was similar to her first experience, and she was back doing surgery in days. After yet a third round of stopping (with the return of symptoms) and starting (with the reduction of symptoms) the Ribose therapy, she was convinced, and has been on Ribose therapy since that time.

Ribose and the Fatigue Associated with Heart Disease

Decades of research have shown that Ribose has a profound effect on heart function in patients with congestive heart failure, coronary artery disease, and cardiomyopathy (a weakened heart muscle). Like the muscles in patients with fibromyalgia, sick hearts are energy starved.24 This energy deprivation keeps the heart from relaxing between heartbeats, making it impossible for the heart to completely fill with blood25 (it surprisingly takes more energy for the heart muscle to relax than contract). Because the heart does not fill completely, less blood is pumped to the body with each heartbeat. The heart then gets stiff and it strains to contract. Ultimately, the heart becomes enlarged, a condition known as hypertrophy, and it is unable to pump normally.

You can compare this to the effect of weight training on the muscles in the bicep of the upper arm. Over time, weight training against more and more weight makes the muscle larger and harder. Similarly, when the heart becomes stiff it is forced to contract against more and more pressure, making the heart muscle grow. While in the case of the bicep this may be a desirable outcome, in the heart it can be deadly. In contrast to the biceps muscle, hearts must remain supple so they can fill properly and empty fully with each contraction. If hearts cannot pump normal volumes of blood, muscles of the arms and legs and brain tissue become oxygen starved. The result is fatigue, pain on standing or walking, loss of interest in, or the ability to perform any physical activity, brain fog, and depression. In the end, the heart cannot pump enough blood to even supply itself with life-giving oxygen and a heart attack can be the result.

Using Ribose to restore the energy level in the heart allows it to fully relax, fill, and empty completely to circulate blood to the outer reaches of the body.26 Circulating more blood means muscles in the arms and legs, and the tissues of the brain, get the oxygen they need to function normally. This result was made evident in several important studies in patients with congestive heart failure and angina.

In one study conducted at the University of Bonn in Germany, patients with congestive heart failure were treated with either 10 grams of Ribose or a sugar placebo every day for three weeks.27 They were then tested for heart function, exercise tolerance (a measure of fatigue), and quality of life using a questionnaire designed for this purpose. In this study, Ribose therapy had a significant effect on all measures of diastolic heart function, showing that increased energy in the heart allowed the heart to relax, fill, and pump more normally. Patients in the study were also much more tolerant to exercise when they were on Ribose, and, through their responses to the questionnaire, showed they had a higher quality of life as a result.
Two additional studies went on to help explain how Ribose therapy in congestive heart failure may affect fatigue and exercise tolerance.28,29 These studies showed that Ribose treatment increased ventilatory and oxygen utilization efficiency, a medical way of saying that the patients were able to breathe better and use the oxygen they inhaled more efficiently. Improving the patient's ability to use oxygen means more oxygen is available to go into the blood and out to the tissues. Having more oxygen available allows the muscle to burn fuel more efficiently, helping it keep pace with its energy demand. The result is less fatigue, a greater ability to tolerate exercise, and a higher quality of life. An added benefit to improving ventilatory efficiency is that ventilatory efficiency is a dominant predictor of mortality in congestive heart failure. Increasing ventilatory efficiency with Ribose therapy is, therefore, a direct correlate to prolonging life in this patient population.

There are very few nutritional therapies that can legitimately boast of having this profound of an effect on the tissues they target. None, other than Ribose, can claim such an effect in cell or tissue energy metabolism. Ribose is a unique and powerful addition to our complement of metabolic therapies in that it is completely safe, proven by strong, well designed clinical and scientific evidence, natural, and fundamental to a vital metabolic process in the body.30-34 I have added a few more study references for those who would like more information about Ribose.35-56
Ribose regulates how much energy we have in our bodies, and for those suffering from fatigue, muscle soreness, stiffness, and a host of related medical complications, the relief found in energy restoration can be life changing. This is why I recommend that all CFS/FMS patients begin with D-Ribose 5 grams (1 scoop of Corvalen) 3x day for 2-3 weeks then twice a day. It is critical to take the 3 scoops a day for the first few weeks to see the optimal effects. Although many of the treatments in this book take 6-12 weeks to start working, most people feel the difference by the end of a single 280 gm container. For the few who don't, retry it again once you are 12-16 weeks into the other treatments well discuss. You'll be glad you did!
Although Ribose is the most promising energy nutrient, others are also worth looking at as well. Most of these only need to be taken for 4-9 months, though some people choose to take them longer (I take my Ribose every day even though I feel great. It makes me feel even better!). You will know by how you feel on them.

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Footnotes:

19. Teitelbaum JE, JA St.Cyr, C Johnson. The use of D-Ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J Alternative and Complementary Medicine 2006;12(9):857-862.

20. Hellsten Y, Skadgauge L, Bangsbo J. Effect of Ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humans. American Journal of Physiology 2004; 286(1): R182-R188.

21. Tullson PC, Terjung RL. Adenine nucleotide synthesis in exercising and endurance-trained skeletal muscle. American Journal of Physiology 1991; 261: C342-C347.

22. Brault JJ, Terjung RL. Purine salvage to adenine nucleotides in different skeletal muscle fiber types. Journal of Applied Physiology 2001; 91: 231-238.

23. Gebhart B, JA Jorgenson. Benefit of Ribose in a patient with fibromyalgia. Pharmacotherapy 2004;24(11):1146-1648.

24. 22. Ingwall JS. ATP and the Heart. Kluwer Academic Publishers, Boston, Massachusetts.

25. Reibel D, Rovetto M. Myocardial ATP Synthesis and Mechanical Function Following Oxygen Deficiency. American Journal of Physiology 1978; 234(5): H620-H624.

26. Zimmer HG, Ibel H, Suchner U. Ribose Intervention in the Cardiac Pentose Phosphate Pathway is Not Species-Specific. Science 1984; 223: 712-714.

27. Omran H, S Illien, D MacCarter, JA St. Cyr, B Luderitz. D-Ribose improves diastolic function and quality of life in congestive heart failure patients: A prospective feasibility study. European Journal of Heart Failure 2003;5:615-619.

28. Vijay N, D MacCarter, M Washam, J St.Cyr. Ventilatory efficiency improves with d-Ribose in congestive Heart Failure patients. Journal of Molecular and Cellular Cardiology 2005;38(5):820.

29. Carter O, D MacCarter, S Mannebach, J Biskupiak, G Stoddard, EM Gilbert, MA Munger. D-Ribose improves peak exercise capacity and ventilatory efficiency in heart failure patients. Journal of the American College of Cardiology 2005;45(3 Suppl A):185A.

30. Griffiths JC, JF Borzelleca, J St.Cyr. Lack of oral embryotoxicity/teratogenicity with D-Ribose in Wistar rats. Journal of Food and Chemical Toxicology 2007;45(3):388-395.

31. Griffiths JC, JF Borzelleca, J St. Cyr. Sub-chronic (13-week) oral toxicity study with D-Ribose in Wistar rats. Journal of Food and Chemical Toxicology 2007:45(1):144-152.

32. Gross M, Dormann B, Zollner N. Ribose administration during exercise: effects on substrates and products of energy metabolism in healthy subjects and a patient with myoadenylate deaminase deficiency. Klin Wochenschr 1991; 69: 151-155.

33. Wagner DR, Gresser U, Zollner N. Effects of oral Ribose on muscle metabolism during bicycle ergometer in AMPD-deficient patients. Annals of Nutrition and Metabolism 1991; 35: 297-302.

34.Gross M, S Reiter, N Zollner. Metabolism of D-Ribose administered to healthy persons and to patients with myoadenylate deaminase deficiency. Klin Wochenschr 1989; 67: 1205-1213.

35. Guymer EK, KJ Clauw. Treatment of fatigue in fibromyalgia. Rheum Dis Clin North Am 2002;28(2):67-78.

36.Rooks DS, CB Silverman, FG Kantrowitz. The effects of progressive strength training and aerobic exercise on muscle strength and cardiovascular fitness in women with fibromyalgia: a pilot study. Arthritis Rheum 2002;47(1):22-28.

37.Geenen R, JW Jacobs, JW Bijlsma. Evaluation and management of endocrine dysfunction in fibromyalgia. Rheum Dis Clin North Am 2002;28(2):389-404.

38.Schachter CL, AJ Busch, PM Peloso, MS Shepard. Effects of short versus long bouts of aerobic exercise in sedentary women with fibromyalgia: a randomized controlled trial. Phys Ther 2003;83(4):340-358.

39.Williamson DL, PM Gallagher, MP Goddard, SW Trappe. Effects of Ribose supplementation on adenine nucleotide concentration in skeletal muscle following high-intensity exercise. Med Sci Sport Exc 2001; 33(5 suppl).

40.Zollner N, Reiter S, Gross M, Pongratz D, Reimers CD, Gerbitz K, Paetzke I, Deufel T, Hubner G. Myoadenylate deaminase deficiency: successful symptomatic therapy by high dose oral administration of Ribose. Klin Wochenschr 1986; 64: 1281-1290.

41.Patton BM. Beneficial effect of D-Ribose in patients with myoadenylate deaminase deficiency. Lancet May 1982; 1701.

42.Salerno C, D'Eufermia P, Finocchiaro R, Celli M, Spalice A, Crifo C, Giardini O. Effect of D-Ribose on purine synthesis and neurological symptoms in a patient with adenylsuccinase deficiency. Biochim Biophys Acta 1999; 1453: 135-140.

43.Salerno C, M Celli, R Finocchiaro, P D'Eufemia, P Iannetti, C Crifo, O Giardini. Effect of D-Ribose administration to a patient with inherited defect of adenylosuccinase. Purine Metabolism in Man IX. Plenum Press, New York, 1998.

44.Pauly D, C Pepine. D-Ribose as a supplement for cardiac energy metabolism. J Cardiovasc Pharmacol Ther 2000;5(4):249-258.

45.Pauly D, C Johnson, JA St. Cyr. The benefits of Ribose in cardiovascular disease. Med Hypoth 2003;60(2):149-151.

46.Pauly DF, CJ Pepine. Ischemic heart disease: Metabolic approaches to management. Clin Cardiol 2004;27(8):439-441.

47.Dodd SL, CA Johnson, K Fernholz, JA St.Cyr. The role of Ribose in human skeletal muscle metabolism. Med Hypoth 2004;62(5):819-824.

48. Zarzeczny R, JJ Brault, KA Abraham, CR Hancock, RL Terjung. Influence of Ribose on adenine salvage after intense muscle contractions. J Appl Physiol 2001;91:1775-1781.

49.Wallen JW, MP Belanger, C Wittnich. Preischemic administration of Ribose to delay the onset of irreversible ischemic injury and improve function: studies in normal and hypertrophied hearts. Can J Physiol Pharmacol 2003;81:40-47.

50. Wilson R, D MacCarter, J St. Cyr. D-Ribose enhances the identification of hibernating myocardium. Heart Drug 2003:3:61-62.

51.Van Gammeren D, D Faulk, J Antonio. 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. Curr Ther Res 2002;63(8):486-495.

52.Sharma R, M Munger, S Litwin, O Vardeny, D MacCarter, JA St. Cyr. D-Ribose improves Doppler TEI myocardial performance index and maximal exercise capacity in stage C heart failure. J Mol Cell Cardiol 2005;38(5):853.

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

54. Perkowski D, S Wagner, A Marcus, J St. Cyr. D-Ribose improves cardiac indices in patients undergoing "off" pump coronary arterial revascularization. J Surg Res 2007;173(2):295.

55. Muller C, H Zimmer, M Gross, U Gresser, I Brotsack, M Wehling, W Pliml. Effect of Ribose on cardiac adenine nucleotides in a donor model for heart transplantation. Eur J Med Res 1998;3:554-558.

56. Grant GF, RW Gracey. Therapeutic nutraceutical treatments for osteoarthritis and ischemia. Exp Opin Ther Patents 2000;10(1): 1-10.