Treatment of Chronic Fatigue Syndrome and Fibromyalgia with D-Ribose- An Open-label, Multicenter Study
Jacob Teitelbaum1: Endfatigue at aol.com, Janelle Jandrain2 and Ryan McGrew3
IKona Research Center, 76-6326 Kaheiau St, Kailua Kona, Hawaii 96740, and Fibromyalgia and Fatigue Centers, Addison, Texas, USA; 2,3Schwabe North America, 3051 West Maple Loop Dr., Lehi, UT 84043, USA
3 weeks of 15 grams daily of D-Ribose (over 3 sessions)
203 patients in 53 clinics
Improvement of 1.5 to 2 on a 7 point scale
Comment by Admin of VitaminDWiki
I DO NOT have CFS
I had been using 3 grams of D-Ribose occasionally for over a decade to relieve fatigue (exercise, sex)
After increasing my Vitamin D and Magnesium levels I no longer have fatigue, and no longer use D-Ribose
People suffering CFS should consider increasing Vitamin D, D-Ribose, Magnesium, and perhaps Iron
Download the PDF from VitaminDWiki.
Author has 3rd edition of a book: From Fatigued to Fantastic Amazon $14.30 paper - also Kindle
Vitamin D mentioned 11 times
- 11 Incredible Health Benefits of D-Ribose – with Side Effects Self-Hacked Oct 2017
1) Heart 2) Fibromyalgia, 3) Replenishes Energy Reserves. 4)Improves Muscular Strength
5) May Help with Restless Leg Syndrome, 6) May Improve Symptoms of Adenylosuccinase Deficiency
7) May Treat Myoadenylate Deaminase Deficiency. 8) May Protect the Kidneys
9) May Protect the Brain. 10)Improve Weight Loss, 11)May Reduce Testicular Toxicity Caused by Aluminum
- Using D-Ribose for Fibromyalgia Fibromyalgia Treating April 2017
- Fedup with Fatigue Sept 2015: Her personal wonderful experiece - great results
Chronic Fatigue Syndrome and Fibromyalgia (CFS/FMS) are debilitating syndromes affecting ~2- 4% of the population. Although they are heterogeneous conditions associated with many triggers, they appear to have the common pathology of being associated with impaired energy metabolism.
As D-ribose has been shown to increase cellular energy synthesis, and was shown to significantly improve clinical outcomes in CFS/FMS in an earlier study, we hypothesized that giving D-ribose would improve function in CFS/FMS patients.
Design, Location, and Subjects:
An open-label, unblinded study in which 53 US clinics enrolled 257 patients who had been given a diagnosis of CFS/FMS by a health practitioner.
Interventions: All subjects were given D-ribose (Corvalen™), a naturally occurring pentose carbohydrate, 5-g TID for 3 weeks.
All patients were assessed at baseline (1 week before treatment), and after 1,2, & 3 weeks using a Visual Analog Scale(1-7 points) rating energy, sleep, cognitive function, pain and overall well being.
203 patients completed the 3 week treatment trial. D-ribose treatment led to both statistically(p<.0001) and clinically highly important average improvements in all categories:
- 61.3 % increase in energy
- 37% increase in overall well being
- 29.3% improvement in sleep
- 30% improvement in mental clarity
- 15.6% decrease in pain
Improvement began in the first week of treatment, and continued to increase at the end of the 3 weeks of treatment. The D-ribose was well tolerated.
In this multicenter study, D-ribose resulted in markedly improved energy levels, sleep, mental clarity, pain relief, and well being in patients suffering from fibromyalgia and chronic fatigue syndrome. clinicaltrials.gov NCT01108549
Fibromyalgia (FMS), which currently affects an estimated 3 to 6 million Americans [1, 2], and Chronic Fatigue Syndrome (CFS) are two overlapping and disabling syndromes. CFS affects more than one million people in the United States. There are tens of millions of people with similar fatiguing illnesses who do not fully meet the strict research definition of CFS 3. Prevalence of these syndromes has been increasing rapidly over the last 2 decades, with European FMS prevalence rates in 5 countries being reported at ~ 3-5% , and CFS growing from .0002% to as high as 2.5% in the US  . Severe persistent fatigue, diffuse migratory pain, cognitive dysfunction, and disordered sleep are common symptoms reported by patients suffering with these syndromes.
Many of the problems seen in CFS/FMS may be associated with a decrease in tissue energy levels and altered energy metabolism. The consequences of dysfunctional energy metabolism frequently include pain from chronic muscle shortening , postexertional fatigue, and low exercise tolerance associated with decreased blood cell mass, cardiac output and stroke volumes [7, 8]. Adenosine triphosphate (ATP) levels have also been shown to be 80% higher in healthy vs. CFS patients . In addition, it has been suggested that decreased energy production also results in hypothalamic dysfunction, which can result in the disordered sleep, hormonal imbalances, and autonomic dysfunctions seen in these syndromes . Many causes and mechanisms for mitochondrial dysfunction have been proposed, including an alteration in muscle adenine nucleotide metabolism affecting ATP levels and depleting energy reserves [11, 12].
D-ribose, a naturally occurring pentose carbohydrate, is a key structural component of the DNA, RNA, ATP, FADH, Coenzyme-A, and NADH needed by the mitochondria to maintain cellular energy stasis. D-ribose was shown in earlier studies to be very helpful in improving clinical outcomes in those with CFS and FMS  and in a general population of people with fatigue , and has also been reported to be effective in restoring tissue energy levels following exercise . Because of these known benefits, it was hypothesized that D-ribose would increase energy production, and therefore decrease symptoms, in patients suffering from FMS and CFS. As the initial study  was done by a single practitioner, and CFS and FMS appear to be heterogeneous syndromes, this study was designed to test whether the benefits seen in the earlier study could be generalized to the CFS/FMS population at large, by doing a multicenter study recruiting and treating patients at 53 health care practitioners’ offices throughout the United States.
Fifty-three healthcare practitioners, practicing throughout the US, enrolled 257 patients who had been diagnosed with Fibromyalgia (FMS) and/or Chronic Fatigue Syndrome. All practitioners who purchased the Corvalen from Integrative Therapeutics, Inc. were invited to participate and invite patients who satisfied the entrance criteria below to volunteer for the study. Being a pilot study, where we were looking for widespread inclusion representing a broad patient and practitioner base, with neither of these receiving any payment for their involvement, the design (an open, unblinded trial) and outcome measure instruments were kept very simple to improve compliance.
Volunteers received information about the study product, Corvalen™ D-ribose, its potential benefits, and possible side-effects. All patients gave informed consent, and the study was approved by the ITI research review committee. The patients received free product for the study, but were otherwise not financially compensated for their participation.
Over 18 yo. Not limited by gender or race.
Diagnosed with Fibromyalgia (FMS) (defined by
American College of Rheumatology [ACR] criteria)
and/or Chronic Fatigue Syndrome (CFS- by Centers for Disease Control [CDC] criteria) by a health practitioner.
Having used D-ribose at over 5 grams a day for at least 3 weeks in the past or any D-ribose containing products in the 7 days prior to the study.
The study did not include any pregnant or nursing women or any participants with known severe medication or nutrient sensitivities. Otherwise, as we chose to have a cohort representative of the population carrying a diagnosis of CFS and/or FMS as a whole, including those with secondary fibromyalgia, patients with other medical conditions were included. Therefore, evaluation to rule out other conditions was not done, nor were subjects excluded who were on other treatments.
Formula and Dosage
The practitioners directed patients to use D-ribose (Corvalen™) at a dose of 5 grams, three times a day, for 3 weeks. They were instructed that the powder was to be mixed with food, water, or another beverage.
This was an open, unblinded trial. After confirming that the subjects met the entry criteria, the practitioners completed an optional information sheet including a demographic summary, whether the patient had CFS, FMS or both, and recorded supplements, over-the-counter drugs (OTCs) and prescription drugs that the patient used regularly. The practitioners gave subjects the study product, a baseline questionnaire, three weekly follow up questionnaires, and four prepaid and addressed envelopes. Patients were allowed to take their other treatments in addition to the D-ribose.
The patients rated five FMS/CFS symptoms at baseline (1 week before they began treatment), and after 1, 2, and 3 weeks of treatment using a 7-point hedonic scale. The assessed symptoms were energy level, sleep quality, mental clarity, pain level, and overall sense of well being (based on the subjects’ individual interpretation of these symptoms and using the guidelines given to them- see symptom scales in Table 1). Average scores with 1 SD were calculated for each of the 5 symptoms at baseline and weeks 1,2, and 3. P values were measured relative to the baseline period.
The patients answered (on the questionnaire) if they had taken the directed dosage after each week of treatment and if they experienced any adverse side effects.
Thirty-one of the 257 patients who entered the study and completed 1 week of use did not complete 2 weeks of use, and another 23 patients did not complete 3 weeks of use, with 203 patients completing the study. Four of the 257 patients noted that they discontinued the D-ribose because of adverse effects (see the adverse effects section). No other patients reported reasons for discontinuing the study. All patients who completed week 2 of the treatment study questionnaires were included in the study analysis. 201 patients completed self-evaluation for compliance with the dosing instructions. Of those, 117 (58%) patients reported
Table 1. D-Ribose Questionnaire, 7-Point Hedonic Scale Questions
Table 2. Patient Demographics
Demographic information was collected from a representative sample, which included over 60% of the enrolled study population (see Table 2).
Significant improvements in all 5 primary outcome measures (energy, sleep, cognitive function, pain and overall well being) were seen after 1 week of product use (p<0.0001 for all). The improvement increased through the second and third week of product use (p<0.0001 for all). After 3 weeks of product use, the average improvements in energy levels was 61%, overall well being 37%, sleep 29%, mental clarity 30%, and pain decreased an average of 16%. See Table 3 and Fig. (1) below. Outcome measures broken down by groups “CFS only”, “FMS only” and “both CFS & FMS” showed similar outcomes to the group as a whole except for the “FMS group” showing significant differences in pain relief compared to the total cohort (see Table 3) .
Two of the patients who enrolled in the study cited that they discontinued use because they became ill (unrelated to product use). Another patient recorded that they discontinued use during the second week of product use because of nausea. One more patient indicated that they discontinued use because of increased insomnia.
This study supports earlier research in subjects with CFS and/or Fibromyalgia 13 showing that using D-ribose significantly increased energy, sleep quality, mental clarity, and well being, while also decreasing pain. The earlier study was done in subjects recruited by a single physician, and experience has suggested that CFS and FMS are very heterogeneous conditions. This study was done to assess whether the earlier pilot study findings would be confirmed, and also could be generalized to a broader population, by performing a multicenter trial including 53 health practitioners. It is very promising that this safe and relatively low cost treatment was able to significantly improve patients’ clinical outcomes, with subjects reporting an average 61% increase in energy after only 3 weeks, and significant improvement beginning at the 1 week follow up.
Why might D-ribose be beneficial in CFS/FMS? Patients with fMs [16, 17] and /or CFS  generally demonstrate reduced sustained and next day exercise capacity, requiring much longer to recover from exercise (postexertional fatigue). These problems are frequently associated with abnormal metabolism, and many FMS studies have been designed to investigate alterations in muscle metabolism using both traditional biopsy techniques 11 and nuclear magnetic resonance spectroscopy (P-31 MRS) [19-24]. Decreased ATP concentrations with accompanying changes in energy metabolism have also been found in the red blood
Table 3. Baseline and Post-Weeks 1, 2, and 3 Assessments for All Patients, CFS Patients, FMS Patients, and Patients with Both CFS and FMS
Adenine nucleotide adenosine triphosphate (ATP) is the primary energy source of all living cells. In tissues subjected to the metabolic stress of hypoxia, ischemia, or mitochondrial dysfunction, ATP is broken down and the ability to recycle expended energy is disrupted. As such, adenosine diphosphate (ADP) levels accumulate leading to a series of reactions in the cell to balance ATP/ADP ratios and maintain energy stasis. These reactions ultimately lead to increased intracellular concentrations of adenosine monophosphate (AMP). In an effort to control energy balance, cells catabolize AMP in reactions catalyzed by 5’- nucleotidase (heart) and AMP deaminase (skeletal muscle) ultimately forming inosine, hypoxanthine and adenine. These catabolic end products are washed out of the cell netting a loss of purines and a reduction in the total pool of adenine nucleotides available to the tissue, lowering its phosphorylation potential. Up to 90% of these catabolites can potentially be biochemically salvaged and recycled [15, 27, 28]. Supplemental D-ribose bypasses the rate limiting enzymes of the pentose phosphate pathway ( PPP), going directly to purine synthesis. D-ribose has been shown to accelerate energy recovery in skeletal muscle and to relieve fatigue, soreness, and stiffness after intense exercise [15, 27, 28]. This could explain D-ribose’s mechanism of action in CFS and Fibromyalgia, and the biochemistry of D-ribose is discussed in more detail in our earlier study 13.
D-ribose has been extensively studied in both heart and muscle. Safety data is well accepted, with no significant adverse reactions. Investigators have concluded that D-ribose is well tolerated at dosages of up to 60 g/day [29, 30].
This study has several limitations, one of which is the lack of a placebo control group. Doing an RCT will be the next key step, but in the interim it was considered important to see whether the clinical benefits seen in the earlier study would also occur in a larger and multicenter study.
A second limitation is that the inclusion criteria simply required that the subject had been diagnosed with CFS or FMS by a healthcare practitioner, and did not require repeating the testing needed to rule out other conditions. It also did not proscribe the use of other treatments. This study, however, was meant to be a clinical study testing simply whether people in the general public who carried a diagnosis of CFS or FMS would improve with D-ribose, while receiving their concurrent care. Also, unlike CFS, underlying other diagnoses do not exclude a diagnosis of fibromyalgia.
A third limitation is that only subjective outcome measures were used. The diagnoses of FMS and CFS are largely subjective, however, as there are no laboratory tests that have adequate sensitivity and specificity to be generally accepted as disease marker(s). As a result, diagnosis (as well as the patient’s disability) is based on subjective criteria and these criteria were also therefore used as our outcome measures.
The fourth concern is that 3 weeks may not be long enough to achieve steady-state, maximum treatment effects/benefits from the treatment. In future research, the researchers should consider evaluating patients for a longer period, to see when benefits level off, and to confirm that they persist.
This follow up study reproduced the benefits of D-ribose seen in our earlier study. As it was a multicenter study involving 53 health practitioners and a larger number of patients, it also suggests that these findings will apply to many of the diverse subsets seen in this patient population.
That subjects reported an average 61% increase in energy and 37% improvement in overall well being, along with improved cognitive function and sleep (and decreased pain), is encouraging. Although it is important to do a randomized, placebo controlled trial with a longer treatment period, these 2 preliminary studies suggest that D-ribose may be a promising therapeutic option for patients with CFS and FMS, offering a significant improvement in their quality of life.
AUTHOR DISCLOSURE STATEMENT
Teitelbaum notes that he sells natural supplements, including ribose, on his website (ribose is widely available). All of his royalties for products he designs or work with go to charity, including the Teitelbaum Family Foundation. Jandrain and McGrew are employees of Schwabe North America, which funded this study. Practitioners involved in the study received no payment for being part of the study, and were customers of (rather than employees of) Integrative Therapeutics.
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