Monday, June 2, 2008

D-Ribose—A Very Powerful and Natural Body Energizer

D-Ribose—A Very Powerful and Natural Body Energizer

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(Used with permission from the book "From Fatigued to Fantastic!" Avery/Penguin, October 2007)

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.

Several of the patients participating in the study have contacted me regarding the relief they found with Ribose therapy. Most importantly, they speak to the profound joy they feel when they are able to begin living normal, active lives after sometimes years of fatigue, pain, and suffering. Here is a sample of what one patient, Julie (Minnesota), an elementary teacher, wrote: "I had so much pain and fatigue I thought I was going to have to quit teaching. When I take [Ribose], I feel like a huge weight is being lifted from my chest, and I'm ready to take on those kids again!" The relief patients feel with Ribose therapy is heartwarming, and goes directly to the dramatic impact Ribose has on increasing energy, overcoming fatigue, enhancing exercise tolerance, and raising the patient's quality of life.

I found this report intriguing and decided to design the larger study in patients with fibromyalgia or chronic fatigue syndrome which I began to discuss earlier. Along with two research collaborators, I recently published a scientific paper describing the results of this research. The study we designed was intended to determine whether or not Ribose would be effective in relieving the overwhelming fatigue, pain, soreness, and stiffness suffered by patients having this debilitating condition. Our study included41 patients with a diagnosis of fibromyalgia or chronic fatigue syndrome who were given Ribose at a dose of 5 grams three times per day for an average of three weeks. We found the Ribose treatment led to significant improvement in energy levels, sleep patterns, mental clarity, pain intensity, and well being. Of the patients participating in the study, 65.7 % experienced significant improvement while on Ribose, with an average increase in energy of 44.7% and overall well being of 30%—remarkable results from a single nutrient!19 The only significant side effects were that 2 people felt too energized and hyper/anxious on the Ribose. This is simply dealt with by lowering the dose and/or taking it with food.

To further validate these findings, we are currently conducting a much larger placebo controlled study, and hope to have the results published in the coming year. Interestingly, one of our study patients had an abnormal heart rhythm called atrial fibrillation. Ribose is outstanding in the treatment of heart disease as well, because it restores energy production in the heart muscle. Because of this, it was not surprising that this man's atrial fibrillation also went away on the Ribose and he was able to stop his heart medications as well! Because of its importance and the research showing marked heart muscle dysfunction (because of low energy) in CFS, let's look at Ribose and the heart in more detail.

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

corvalen-d-ribose 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. (Buy Corvalen Ribose best lowest price free shipping)
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.

Sunday, June 1, 2008

The Use of D-Ribose in Chronic Fatigue Syndrome

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Volume 12, Number 9, 2006, pp. 857–862, © Mary Ann Liebert, Inc.

The Use of D-Ribose in Chronic Fatigue Syndrome and Fibromyalgia: A Pilot Study


Objectives: Fibromyalgia (FMS) and chronic fatigue syndrome (CFS) are debilitating syndromes that are often associated with impaired cellular energy metabolism. As D-ribose has been shown to increase cellular energy synthesis in heart and skeletal muscle, this open-label uncontrolled pilot study was done to evaluate if D-ribose could improve symptoms in fibromyalgia and/or chronic fatigue syndrome patients.

Design: Forty-one (41) patients with a diagnosis of FMS and/or CFS were given D-ribose, a naturally occurring pentose carbohydrate, at a dose of 5 g t.i.d. for a total of 280 g. All patients completed questionnaires containing discrete visual analog scales and a global assessment pre– and post–D-ribose administration.

Results: D-ribose, which was well-tolerated, resulted in a significant improvement in all five visual analog scale (VAS) categories: energy; sleep; mental clarity; pain intensity; and well-being, as well as an improvement in patients’ global assessment. Approximately 66% of patients experienced significant improvement while on D-ribose, with an average increase in energy on the VAS of 45% and an average improvement in overall well-being of 30% (p 0.0001).
Conclusions: D-ribose significantly reduced clinical symptoms in patients suffering from fibromyalgia and chronic fatigue syndrome. 857

Fibromyalgia (FMS), which currently affects an estimated 3 to 6 million Americans,1,2 and chronic fatigue syndrome (CFS) are disabling syndromes that often coexist. Patients suffering with these syndromes commonly report severe persistent fatigue, diffuse migratory pain, cognitive dysfunction, and disordered sleep. Many of the clinical symptoms found in FMS/CFS may be related to a decrease in tissue energy levels with altered energy metabolism. Previous reports claim that abnormal muscular energy metabolism frequently can be reflected in pain because of chronic muscle shortening,3 postexertional fatigue, and low exercise tolerance associated with decreased cardiac output and stroke volumes.4 In addition, it has been postulated that decreased energy production in these syndromes also may result in hypothalamic dysfunction, which can be reflected clinically as disordered sleep, hormonal imbalances, and autonomic dysfunctions.5 Causes and mechanisms for this mitochondrial dysfunction are unknown; however, an alteration in muscle adenine nucleotide
metabolism is found, mainly in lower adenosine triphosphate (ATP) levels and depleted energy reserves.6,7

D-Ribose, a naturally occurring pentose carbohydrate, is a key structural component in the DNA, RNA, ATP, FADH, coenzyme-A, and NADH needed by the mitochondria to maintain cellular energy homeostasis. Supplemental doses of D-ribose in patients with congestive heart failure and ischemic heart disease have shown a significant improvement in diastolic dysfunction, physical function, exercise tolerance, and quality of life.8 D-Ribose has also been reported to be effective in restoring tissue energy levels following intense exercise9 and in an isolated case report of a patient with FMS.10 Because of the known energy and functional 1Fibromyalgia and Fatigue Centers, Dallas, TX. 2Valen Labs, Minneapolis, MN. benefits of D-ribose, an open-label uncontrolled pilot study was performed to assess whether D-ribose would decrease symptoms in patients suffering from FMS and CFS.

Patient enrollment
Forty-one (41) adult patients, diagnosed by their physicians as having FMS (by ACR Criteria) and/or CFS (by CDC criteria), were found eligible for this study. In addition, patients also had to be without known severe medication or nutrient sensitivities, and not have taken D-ribose in the past. Recruitment of patients was through the FMS and CFS e-mail newsletter associated with the Annapolis Research Center and the web site. Readers with an established diagnosis of FMS or CFS were informed about the nature of the study and were invited to participate if they satisfied the entrance criteria. All patients were thoroughly
informed about D-ribose, its potential benefits, and possible adverse side-effects and gave informed consent. The protocol is consistent with the principles of the Declaration of Helsinki. Except for a free container of D-ribose, patients received no compensation.

Design of study
A 280-g container of D-ribose (CORvalen, Valen Labs, Minneapolis, MN) and a questionnaire (outcome measures) were mailed to each subject once the patient was enrolled. Each patient was instructed to take one scoop (5-g) of D-ribose three times per day (t.i.d.) mixed with food, water, or another beverage until the container was empty and then to return the container and questionnaires in a prepaid envelope. They were instructed to stay on their current treatment
regimen and not change dosing or add or delete any treatments during the study.

Outcome measures
Subjective outcome measures were assessed using discrete Visual Analog Scale questions (DVAS) pre- and postintervention. Measured DVAS parameters were energy levels,
sleep disturbances, mental clarity, pain, and an overall sense of well-being. Patients were asked to individually rate each of these five areas on a 1 to 10 scale as shown below:
A. How is your energy?
1 2 3 4 5 6 7 8 9 10
1  near dead and 10  excellent
B. How is your sleep?
1 2 3 4 5 6 7 8 9 10
1  no sleep and 10  8 hours of sleep a night without waking
C. How is your mental clarity?
1 2 3 4 5 6 7 8 9 10
1  brain dead and 10  good clarity
D. How bad is your pain?
1 2 3 4 5 6 7 8 9 10
1  very severe pain and 10  pain free
E. How is your overall sense of well-being?
1 3 4 5 6 7 8 9 10
1  near dead and 10  excellent

Compliance was addressed in each patient by asking how many doses were missed and noting how long it took to finish the 280-g container, as well as by weighing the received container at the completion of the study. Each patient was asked if any adverse side effects occurred while on D-ribose. Finally, each patient commented on his or her overall subjective feeling while taking D-ribose: much better, somewhat better, no change, somewhat worse, or much worse.

Of the 41 patients enrolled in the study, five patients were considered noncompliant; therefore, they were excluded from the study and final analysis. Noncompliance was defined as having consumed half or less of the provided D-ribose during the study. Of the 36 remaining patients, the average age was 48 years, 78% were female. Patients had been ill with CFS/FMS for an average of 7.15 years. Further demographics are summarized in Table 1. The average length
of time on D-ribose was 25 days (range, 17 to 35 days). Subjectively, significant improvements were found in energy levels (p 0.0001), sleep patterns (p 0.0001), mental clarity (p 0.003), pain threshold (p 0.026), and the patient’s state of well-being (p 0.0001) when comparing
questionnaires at enrollment and at the completion of the study in all of the patients (Table 2). Table 3 denotes the pre- and postribose assessments in patient categories for each separate syndrome. At the completion of the study, patients also felt a positive subjective improvement while taking D-ribose (Table 4). Twenty-three (23) of the 35 patients (65.7%) completing
the assessment experienced improvement during the course of the study (somewhat better to much better) while taking D-ribose. The responses were compared to the null 858 TEITELBAUM ET AL.

Patient demographics
Sex Female: 28 (78%)
Average age 48 years (21–62)
Previous diagnosis: FMS 75%
Previous diagnosis: CFS 58%
Average duration CORvalen therapya 28 days (17–35)
FMS, fibromyalgia; CFS, chronic fatigue syndrome.
aValen Labs, Minneapolis, MN. response of “No Change” in a one-sample nonparametric
sign test and signed rank test. Both tests resulted in statistical
significance (p 0.0001).

The following subgroup analyses were also performed: gender, age, CFS, and FMS. Gender was at least a marginally significant predictor of measured outcomes: energy levels (p 0.02), sleep patterns (p 0.001), mental clarity (p 0.002), pain threshold (p 0.06), state of well-being
(p 0.03), and total score (p 0.001). Age was not associated with any of the outcome parameters: energy levels (p 0.80), sleep patterns (p 0.32), mental clarity (p 0.97), pain threshold (p 0.50), a state of well-being (p 0.45), and total score (p 0.58). A prior diagnosis of CFS was not associated with any of the outcomes: energy levels (p 0.59), sleep patterns (p 0.28), mental clarity (p 0.33), pain threshold (p 0.39), state of well-being (p 0.39), and total score (p 0.27). Likewise, a prior diagnosis of FMS was not associated with any of the measured outcomes: energy levels (p 0.58), sleep patterns (p 0.29), mental clarity (p 0.20), pain threshold (p 0.43), state of well-being (p 0.33), and total score (p 0.24). Of the five patients that were found to be noncompliant,
three stopped taking D-ribose because of a hyperanxious feeling (one patient), lightheadedness (one patient), and increased appetite (one patient). Two others changed their mind and simply did not begin the study. Of the remaining 36 patients who completed the study, one patient experienced transient nausea and another felt mild anxiety. Both of these reactions were reversed by simply lowering the dose of D-ribose.

Fibromyalgia and CFS are common, nonarticular, debilitating syndromes that affect approximately 2%–4% of the population worldwide. Patients with FMS and/or CFS generally
demonstrate reduced sustained exercise capacity, with lack of muscular contractile force and endurance.11,12 Similar conditions are frequently associated with abnormal metabolism. Therefore, many FMS and/or CFS studies have investigated potential alterations in muscle metabolism. 6,13,14–19

Pre Post Difference
Category N mean (std) mean (std) (95% CI) p-Value
Energy level 36 3.8 (1.1) 5.5 (1.5) 1.7 0.0001
(1.1, 2.2)
Sleep 36 4.8 (1.6) 6.0 (1.9) 1.2 0.0001
(0.6, 1.7)
Mental clarity 36 4.9 (1.5) 5.7 (1.7) 0.8 0.003
(0.3, 1.3)
Pain 36 4.9 (2.3) 5.6 (2.2) 0.7 0.026
(0.1, 1.3)
Well-being 36 4.3 (1.3) 5.6 (1.5) 1.3 0.0001
(0.8, 1.9)
CI, confidence interval.

(N  15) (N  9) (N  12)
Pre mean Post mean Improvement Pre mean Post mean Improvement Pre mean Post mean Improvement
Category (std) (std) (%) (std) (std) (%) (std) (std) (%)
Energy 3.7 5.5 1.8 4.2 6.1 1.9 3.7 4.9 1.2
(1.0) (1.5) (48%) (1.4) (1.5) (45%) (1.2) (1.4) (32%)
Sleep 4.4 5.9 1.5 5.6 7.2 1.6 4.8 5.2 0.4
(1.2) (1.6) (34%) (1.7) (1.7) (29%) (1.9) (2.2) (8%)
Mental clarity (14..07) (15..87) (211.%0 ) (25..02) (16..76) (217.%4 ) (15..71) (15..31) 0
Pain (24..35) (25..05) (212.%0 ) (62..73) (71..86) (116.%1 ) (41..16) (41..12) 0
Well-being 4.1 5.7 1.6 4.6 6.3 1.7 4.3 5.0 0.7
(1.0) (1.5) (39%) (1.7) (1.2) (37%) (1.3) (1.5) (16%)
FMS, fibromyalgia; CFS, chronic fatigue syndrome. Adenosine triphosphate (ATP) is the primary energy source of all living cells. In tissues subjected to metabolic stress, such as hypoxia, ischemia, or known conditions of mitochondrial dysfunction, ATP is catabolized with compromised metabolic recovery. With ATP catabolism, adenosine diphosphate (ADP) levels accumulate, forcing the cell to try to balance ATP/ADP ratios in order to maintain energy
stasis. However, these reactions ultimately lead to an increased intracellular concentration of adenosine monophosphate (AMP). In an effort to try to control energy balance, the cell catabolizes AMP, ultimately forming inosine, hypoxanthine, and adenine. These catabolic end products are washed out of the cell, resulting in a net loss of purines and an ultimate reduction in the total pool of adenine nucleotides. Potentially, up to 90% of these produced catabolites can be biochemically salvaged and recycled. 9,20,21
The rate of recovery of these energy substrates in metabolically stressed cells is important for functional recovery of the cell, including muscle.20,21–23 Therapeutic solutions that could
try to maintain a cell’s energy stasis include either blocking the degradation of adenine nucleotides or providing metabolic supplementation to enhance nucleotide recovery via the salvage or de novo pathways of purine synthesis. The availability of 5-phosphoribosyl-L-pyrophosphate (PRPP) is rate limiting in adenine nucleotide de novo synthesis and salvage pathways, which is necessary to preserve or rebuild cellular energy stores.9,20,21 5-Phosphoribosyl-Lpyrophasphate is formed through pyrophosphorylation of ribose-
5-phosphate that is, itself, synthesized from glucose via the pentose phosphate pathway (PPP; or hexose monophosphate shunt). The rate-limiting enzymes in the PPP, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, are poorly expressed in heart and muscle cells. As such, in skeletal muscle the PPP is suppressed, limiting ribose availability as a substrate to drive the purine nucleotide pathway and retarding purine nucleotide synthesis
during or following a metabolic insult. The energy reserve, phosphorylation potential (PP), and
the ability to use oxygen (total oxidative capacity or Vmax) have been determined using P-31 MRS in both normal and fibromyalgic muscle.16 Both mean PP and Vmax values are found to be significantly reduced in FMS.16 These findings are consistent with reduced oxidative phosphorylation and ATP synthesis, which translate clinically to muscle fatigue, soreness, and stiffness.24 Impairment in mitochondrial oxidative phosphorylation and potentially diminished glucose metabolism impact ATP turnover, suggesting that the muscles of fibromyalgia patients are energy starved. Further, decreased ATP concentrations with accompanying changes in
energy metabolism have been found in the red blood cells of fibromyalgia patients,25 suggesting that this energy deficiency may be systemic.

Muscular metabolic abnormalities in fibromyalgia have been proposed.6 Dysfunctional metabolism has been shown to lead to cellular abnormalities6 that impact cellular function,
producing clinical symptoms. Muscle biopsies have shown that levels of phosphocreatine (PCr) and ATP are significantly reduced (21% and 17%, respectively) in muscle tissues of fibromyalgia patients and the synthesis of PCr, an important store of cellular high-energy phosphates, is deficient. Magnetic imaging of skeletal muscle has shown that resting levels of ATP are 15% lower in fibromyalgia patients than in normal controls and during exercise PCr and ATP levels remain significantly low.14,16,19 During exercise there is an increase in metabolic breakdown products of ATP (phosphodiesters) in fibromyalgic skeletal muscle groups, indicating abnormal adenine nucleotide metabolism and disruption of cell membranes, which are common in other muscular diseases. There has been speculation that these findings may be similar in patients afflicted with CFS.16 It also has been shown that there are a decreased numbers of capillaries within fibromyalgic muscle fibers, which can reduce the oxidative capacity, leading to limited energy turnover, purine pool depletion, and increased pain.24,26 Thickening of the capillary endothelium also contributes to restricted oxygen transport or delivery, further lowering oxygen tension in the muscle, affecting energy metabolism and contributing to functional fatigue and weakness. In general, the fibromyalgic muscle has lower ATP concentrations than normal muscle. Further, these factors can alter calcium and cellular ion stasis, which, clinically can produce muscle soreness, stiffness, fatigue, and diminished exercise capacity. Patients with FMS and/or CFS may therefore have an alteration in muscular energy use and metabolism. Fibromyalgic muscle reaches anaerobic threshold earlier in exercise, thereby potentially using less available energy-rich phosphate metabolites at maximal work capacity. Patients with FMS may have abnormal high-energy phosphate metabolism with significantly lower levels of ATP and ADP in affected muscles as compared to normal controls.24

The findings in this pilot study, using daily D-ribose, revealed an increased improvement in the quality of life in patients afflicted with FMS/CFS. However, there are several limitations noted in this study. A major limitation centers on a lack of a placebo group. This was, however, meant as
an initial pilot study with each patient acting as their own control. A follow-up RCT is, of course, critical and currently 860 TEITELBAUM ET AL.

Response N (%)
Much better 5 (14.3%)
Somewhat better 17 (48.6%)
Somewhat better/no change 1 (2.9%)
No change 9 (25.7%)
No change/somewhat worse 1 (2.9%)
Somewhat worse 2 (5.7%)
Much worse 0 (0%)
under way using information (and impetus) gained from this pilot study. In addition, as patients were not seen in a clinic, initial assessment of each patient relied on their own personal physician providing an accurate clinical diagnosis of FMS/CFS. This pilot assessment was designed as a clinically focused, community-based study, and this reflects what occurs in most patients’ cases.
Subjective outcome measures were only assessed in this study. The diagnoses and effectiveness of therapies of FMS and CFS are largely based on subjective symptoms. As no accepted diagnostic laboratory tests are available to confirm the diagnoses of and monitor progress in these syndromes, it is reasonable to rely on subjective outcome measurements in this clinical setting. Also, patients did not eliminate other stable treatment modalities they had been on during the study. However, patients were instructed not to make any changes in their treatment regimen during the study. D-Ribose produced a subjective beneficial outcome in these patients;
therefore, the addition of D-ribose may offer an added benefit to their concurrent therapies.

This pilot study suggests that D-ribose may provide subjective benefits in patients with FMS and/or CFS. Given the biochemical benefits of D-ribose on increasing muscular energy pools and reducing metabolic strain in affected muscles, the use of this supplement may offer a valuable option for improving quality of life in patients afflicted with FMS and/or CFS.

The authors thank Valen Labs, Inc. (Minneapolis, MN) for providing the oral D-ribose. Dr. Teitelbaum has no financial conflict of interest and his payment for doing the study was donated to charity. Dr. St. Cyr is a consultant for Valen Labs, and Mr. Johnson is on staff at Valen Labs.

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Jacob E. Teitelbaum, M.D.
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Kailua-Kona, HI 96740