Use of D-Ribose in ME/CFS & FM

[Guest guest]

For Dutch readers:

A good and cheap address for D-ribose is:

Creanite - owner Jan de Heij - racing cyclist and pharmacist:

http://www.creanite.com/DaviWB/Pagina13.html

~jvr

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From: Fred Springfield

Via: CO-CURE@...

The Use of D-Ribose in

Chronic Fatigue Syndrome and Fibromyalgia:

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A Pilot Study

Journal: J Altern Complement Med. 2006 Nov;12(9):857-862.

Authors: Teitelbaum JE, C, Cyr JS.

Affiliation: Fibromyalgia and Fatigue Centers, Dallas, TX.

NLM Citation: PMID: 17109576

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.

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as fair use I add the discussion section of this article

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DISCUSSION

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

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 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.

CONCLUSIONS

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.