Ingredient Spotlight: Ribose

Chemically known as D-ribose, ribose is a 5-carbon sugar (pentose) that is found in every cell in the body. Due to its chemical structure, it is not used by the body as a typical sugar, such as glucose (6-carbons)-meaning it is not metabolized via glycolysis, the biochemical pathway in which sugar is converted into energy. Ribose serves as the carbohydrate backbone of ribonucleic acid/RNA (as ribose) and of deoxyribonucleic acid/DNA (as deoxyribose), both of which are involved in cell growth and function.

In addition to its role in genetics, ribose is a major component of the energy molecule known as ATP (adenosine triphosphate). ATP consists of a base, known as a purine; three phosphate (triphosphate) molecules; and the sugar ribose. Ribose is the only sugar used by the body to help regulate the metabolism of nucleotides-i.e., ATP, ADP (adenosine diphosphate), and AMP (adenosine monophosphate).

Ribose is the main molecule in energy recovery, helping to support the synthesis of energy compounds needed by the body for various metabolic processes. During times of metabolic stress or disease, ribose can help restore normal, healthy levels of ATP required for the intricate biochemical and physiological processes that help maintain life.
 

Cellular and Cardiovascular Function

The heart is a metabolic machine. On average, it beats approximately 100,000 times per day. This degree of metabolic activity requires a significant energy reserve and the constant recycling and/or production of energy molecules.

Cardiovascular disease (CVD) continues to be a leading cause of death worldwide. One of the common factors in CVD is a lack of oxygen (ischemia), which leads to a significant decrease in ATP production and overall heart function. Joanne Ingwall, PhD, of Brigham and Women’s Hospital proposed that a failing heart is energy starved.(1) Ribose helps improve the synthesis of adenine nucleotide reserves, which in turn helps increase ATP production and improves the heart’s tolerance to ischemia.(2)

How does ribose accomplish this? ATP recovery depends on increased levels of phosphoribosyl-pyrophosphate (PRPP), which is formed from ribose-5-phosphate by the enzyme ribosephosphate diphosphokinase. Increased levels of PRPP can aid in the production of ATP.

In addition to its major role in ATP synthesis, PRPP is the gatekeeper for maintaining purines inside the cells, helping to ensure a pool of these ATP precursors to support energy recovery. During transient myocardial ischemia, levels of ADP and AMP increase, while their rephosphorylation to ATP decreases significantly. After long periods of ischemia, AMP and ADP are broken down to adenosine, inosine, and other metabolites, which are then cleared from the cell. The loss of purines causes significant metabolic disturbances. If the cells lose purines such as adenine, they cannot resynthesize much-needed ATP. During times of extreme stress-such as heart attack or congestive heart failure (CHF)-purines are lost from heart cells, thereby limiting the heart’s ability to generate the ATP needed to regain normal heart function. Ribose quickly forms PRPP, which helps prevent the loss of purines and serves as the driver of ATP synthesis.

Studies show that providing daily ribose supplementation helps improve diastolic function, quality of life, and physical function scores in patients with CHF.(3) Ventilatory efficiency is recognized as an important predictor of survival and disease progression among patients with CHF. Ribose has been shown to improve ventilatory efficiency, and demonstrates a subjective improvement in quality of life in CHF patients. Patients given ribose were able to breathe more easily and with greater efficiency (noted by improved oxygen uptake).(4,5)

There are no good natural sources of ribose. The body, although capable of making ribose from glucose, does so very slowly and not efficiently enough to support an ailing cardiovascular system. In many cardiovascular conditions, including ischemia, CHF, and cardiomyopathy, supplemental ribose provides a significant benefit by increasing the speed of ATP repletion and enhancing functional recovery after injury in acute and chronic cardiovascular disease.(6)

Energy Metabolism, Exercise Performance

In addition to its numerous benefits in cardiovascular health, ribose has been shown to support many other biochemical and physiological functions in the body. Jacob Teitelbaum, MD, and John St. Cyr, MD, PhD, noted experts on chronic fatigue syndrome (CFS) and D-ribose, respectively, conducted a pilot study in 41 patients diagnosed with CFS and/or fibromyalgia. Both conditions are associated with impaired cellular energy metabolism. With ribose supplementation, a significant improvement was seen in the five major areas of assessment: energy, sleep, mental clarity, pain intensity, and well being in patients receiving ribose.(7)

Ribose supplementation has also been shown to support exercise performance and recovery. One study investigated the effect of ribose on skeletal muscle total adenine nucleotide (TAN) concentration following high-intensity exercise (cycle sprints). Following the exercise period, muscle biopsies revealed a significantly greater TAN in the ribose-supplemented group.(8) This suggests ribose may provide an ergogenic effect over time in high-intensity cycling activity.

In a four-week study in recreational male body builders, ribose supplementation was shown to support an increase in strength and muscle endurance, but had no affect on body composition.(9) Supplementation of ribose demonstrates a significant benefit to cellular energy metabolism by limiting the depletion of TANs and supporting ATP resynthesis in muscle tissue, thereby helping to modulate key mechanisms involved in exercise performance.

In another study, one week of intense intermittent cycling was sufficient enough to markedly reduce muscle adenine nucleotide levels. Following this intense training, ribose supplementation significantly enhanced the rate of adenine nucleotide resynthesis, most likely by increasing PRPP synthesis. PRPP synthesis is an essential rate limiting factor for ATP resynthesis in skeletal muscle, and may in fact influence exercise performance.(10)
 

The Future of Ribose

Ribose is the fundamental building block of ATP and the only compound capable of regulating the amount of energy in the cell. Without ATP, cellular function is lost. Ribose is an inexpensive, safe, and efficacious tool, helping improve diastolic heart function and quality of life in patients with coronary artery disease, congestive heart failure, and cardiomyopathy.

As cardiovascular disease continues to be the leading cause of death worldwide, more healthcare practitioners need to be made aware of, and educated about, the potential benefits of ribose. There is significant clinical evidence, much of it based on randomized controlled studies, for the efficacy and safety of ribose in cellular energy metabolism related to cardiovascular health, exercise performance, chronic fatigue, and a host of other common conditions. Mainstream medicine needs to take a closer look at the wide-reaching clinical effects of ribose and allow more people to reap the benefits of this truly versatile compound. 

References:

1. Ingwall J.  On the hypothesis that the failing heart is energy starved: Lessons learned from the metabolism of ATP and creatine.  Current Hypertension Reports  2006;8:457-464.
2. Erdman E, et al.  Effects of ribose on exercise-induced ischemia in stable coronary artery disease.  Lancet  1992;340:507-510.         
3. Omran H, et al.  D-ribose improves diastolic function and quality of life in congestive heart failure patients: A prospective feasibility study. Eur J Heart Fail  2003;5:61 
4. Vijay N, et al.  D-ribose benefits heart failure patients.  J Med Food  2008;11:199-200.
5. Carter O, et al.  D-ribose supplementation improves peak exercise capacity and ventilatory  efficiency  in heart failure patients. JACC2005;45 Suppl A:185A.
6. Pauly D, Pepine C.  D-Ribose as a supplement for cardiac energy metabolism.  J Cardiovasc Pharmacol Therapeut  2000;5:249-258.
7. St. Cyr J, et al.  The use of D-ribose in chronic fatigue syndrome and fibromyalgia: A pilot study.  J Altern Complement Med
8. Gallagher P, et al.  Effects of ribose supplementation on adenine nucleotide concentration in skeletal muscle following high intensity exercise.Medicine and Science in Sports and Exercise  2001;33, S167.  
9. Antonio J, et al.  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;63:486-495.
10. Hellsten Y, et al.  Effect of ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humans.  Am J Physiol Regul Integr Comp Physiol   2004;286:R182-R188.