D-Ribose

Last Updated: September 28, 2022

D-ribose is a pentose sugar that plays a role in the production of energy intermediates, DNA, and RNA. It is due to this reasoning that D-ribose is investigated in instances where ATP concentrations (relative to total nucleotides) seem to be reduced, namely cardiac insults and prolonged physical exercise.

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1.

Sources and Structure

1.1

Biological Significance

D-ribose is a pentose sugar (with five carbons in its ring structure) produced in the body where it then binds to various nucleic acids. Such a process allows these nucleic acids to act as energy intermediates (NADH, FADH, and ATP) or to form the structural basis of DNA and RNA.

2.

Molecular Targets

2.1

ATP Synthesis

The basic premise of D-ribose lies in its role as a constituent of nucleotides, with most focus on adenosine triphosphate (ATP) which is a union of the nitrogenous base known as adenine with D-ribose via a phosphate group.

When ATP is used in energy production it loses phosphate groups to form adenosine monophosphate (AMP) which can be replenished by various enzymes. At times ATP itself can degrade into inosine 5'-monophosphate (IMP) which does not serve a bioenergetic role, and while it can be restored into ATP if kept in a cell it can also be effluxed out of the cell in the form of inosine or hypoxanthine which is then eliminated from the body.

Cells have some pathways used to salvage nucleotide bases (purine and pyrimidine salvage pathways) but can also directly synthesize new nucleotide bases within the cell. This latter process, which has been noted to be relatively slow in rat skeletal tissue,[1] involves D-ribose (as ribose-5-phosphate) being converted into phosphoribosyl pyrophosphate (PRPP) via the enzyme ribose-phosphate diphosphokinase and subsequently converted into phosphoribosylamine and then into IMP itself; as IMP has now been synthesized, it can be converted into ATP to participate in metabolic processes as a source of energy.

As infusion of D-ribose itself seems to increase the synthesis rate of all the subsequent products,[2] it is thought that availability of D-ribose is the limiting factor in nucleotide synthesis. It is due to this reasoning that D-ribose is investigated in instances where ATP concentrations (relative to total nucleotides) seem to be reduced, namely cardiac insults[3] and prolonged physical exercise.[4]

3.

Cardiovascular Health

3.1

Cardiac Tissue

There appears to be a few small studies in subjects with various heart disorders where supplementation of D-ribose at a dose of 15g daily (three doses of 5g) has been found effective during exercise. These include subjects with congestive heart failure (CHF) experiencing more atrial contribution towards circulation during cycle ergometry,[5] subjects with advanced ischemic heart failure improving ventilatory parameters during exercise after eight weeks,[6] and on ischemia during exericse in subjects with stable coronary artery disease[7] or during dobutamine stress echiocardiography (using an infusion of D-ribose[8]).

4.

Skeletal Muscle and Exercise Performance

4.1

Bioenergetics

During exercise, ATP is eventually degraded to inosine 5'-monophosphate (IMP)[9] which does not serve an energy role and (if remaining in the cell) can be restored into ATP once a rest state is entered. Some IMP does leave the cell in the forms of inosine or hypoxanthine, generally with higher intensities for longer periods[10][11] and in the context of heavy and frequent training there is overall purine loss.[12]

Purines appear to be restored in skeletal muscle either via synthesis of new purines, which appears to be a relatively slow rate in rats[1] thought to also occur in humans due to restoration of ATP after intense training being prolonged (not being replenished after three days of rest[13][4]), or via the purine salvage pathway. D-ribose is thought to have a role for muscle recovery in regards to the slower process, as infusion of D-ribose into skeletal muscle of rats increases nucleotide synthesis rates[2] (thought[4] to be related to how ribose availability limits the amount of phosphoribosyl pyrophosphate (PRPP) produced from D-ribose, which may be a bottleneck in nucleotide synthesis).

In accordance with the above, one study using high dose oral D-ribose supplementation[4] has shown that the rate of ATP replenishment over three days of rest is greater with a surplus of D-ribose in the diet (approximately 150g over the course of three days) when compared to maltodextrin as placebo sugar.

4.2

Soreness, Injury, and Recovery

When D-ribose (200mg/kg) is compared to maltodextrin (200mg/kg), both paired with an equal amount of sucrose, D-ribose does not appear to elevate serum glucose as much as maltodextrin for up to 90 minutes after ingestion[4] and when measured after three days (where this supplement is taken nine more times) they appear equivalent in restoring glycogen after repeated cycling exercises.[4]

In otherwise healthy male subjects who were subject to a week of twice daily cycling exercises, supplementation of a mixture of 200mg/kg D-ribose (17.25g average dose) and an equivalent amount of sucrose after the last training session and again thrice daily for three days was compared to placebo (same timing protocol, but maltodextrin was used in placebo of D-ribose).[4] The group given D-ribose was able to restore muscle ATP concentrations to a level statistically comparable to before their exhaustive exercise while the placebo group only saw partial restoration, with neither group having effects after a single day of supplementation and overall approximately 150g of D-ribose being consumed over the three days and final session.[4]

Based on one study assessing a rest from exhaustive exercise, it seems supplementing high dose D-ribose for a few days may be more effective than traditional dietary sugars at restoring ATP concentrations; a high dose was required, however

5.

Interactions with Medical Conditions

5.1

Fibromyalgia

D-Ribose is thought to interact with fibromyalgia based on the knowledge that there are perturbed skeletal muscle energetics in subjects with fibromyalgia,[14] most notably reduced ATP levels (of which D-ribose is a component),[15] and how D-ribose in high doses can influence this tissue in athletes.[4] One case study has noted that 5g of D-ribose taken twice daily alongside other medication in a subject with fibromyalgia greatly reduced symptoms, which returned after one week of supplement cessation.[16]

In subjects with fibromyalgia and/or chronic fatigue syndrome (CFS) who given D-ribose at 15g a day (three divided doses) for just under three weeks, supplementation was associated with subjective improvments in energy, sleep, and well-being with an increased pain threshold.[17] No placebo control was used in this study and there may be a conflict of interest (product supplied by a company of which produces D-ribose and employs one author).[17]

One study exists suggesting benefits to pain disorders with D-ribose supplementation, but failed to use a placebo control and may have a potential conflict of interest

References
1.^Tullson PC1, John-Alder HB, Hood DA, Terjung RLDe novo synthesis of adenine nucleotides in different skeletal muscle fiber typesAm J Physiol.(1988 Sep)
2.^Brault JJ1, Terjung RLPurine salvage to adenine nucleotides in different skeletal muscle fiber typesJ Appl Physiol (1985).(2001 Jul)
3.^Pauly DF1, Pepine CJD-Ribose as a supplement for cardiac energy metabolismJ Cardiovasc Pharmacol Ther.(2000 Oct)
4.^Hellsten Y1, Skadhauge L, Bangsbo JEffect of ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humansAm J Physiol Regul Integr Comp Physiol.(2004 Jan)
6.^MacCarter D, Vijay N, Washam M, Shecterle L, Sierminski H, St Cyr JAD-ribose aids advanced ischemic heart failure patientsInt J Cardiol.(2009 Sep 11)
7.^Pliml W1, von Arnim T, Stäblein A, Hofmann H, Zimmer HG, Erdmann EEffects of ribose on exercise-induced ischaemia in stable coronary artery diseaseLancet.(1992 Aug 29)
8.^Sawada SG1, Lewis S, Kovacs R, Khouri S, Gradus-Pizlo I, St Cyr JA, Feigenbaum HEvaluation of the anti-ischemic effects of D-ribose during dobutamine stress echocardiography: a pilot studyCardiovasc Ultrasound.(2009 Feb 7)
10.^Hellsten-Westing Y1, Balsom PD, Norman B, Sjödin BThe effect of high-intensity training on purine metabolism in manActa Physiol Scand.(1993 Dec)
11.^Hellsten Y1, Sjödin B, Richter EA, Bangsbo JUrate uptake and lowered ATP levels in human muscle after high-intensity intermittent exerciseAm J Physiol.(1998 Apr)
12.^Hellsten Y1, Richter EA, Kiens B, Bangsbo JAMP deamination and purine exchange in human skeletal muscle during and after intense exerciseJ Physiol.(1999 Nov 1)
13.^Hellsten-Westing Y1, Norman B, Balsom PD, Sjödin BDecreased resting levels of adenine nucleotides in human skeletal muscle after high-intensity trainingJ Appl Physiol (1985).(1993 May)
14.^Srikuea R1, Symons TB, Long DE, Lee JD, Shang Y, Chomentowski PJ, Yu G, Crofford LJ, Peterson CAAssociation of fibromyalgia with altered skeletal muscle characteristics which may contribute to postexertional fatigue in postmenopausal womenArthritis Rheum.(2013 Feb)
15.^Bengtsson A, Henriksson KG, Larsson JReduced high-energy phosphate levels in the painful muscles of patients with primary fibromyalgiaArthritis Rheum.(1986 Jul)
16.^Gebhart B1, Jorgenson JABenefit of ribose in a patient with fibromyalgiaPharmacotherapy.(2004 Nov)
17.^Teitelbaum JE1, Johnson C, St Cyr JThe use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot studyJ Altern Complement Med.(2006 Nov)