Original Paper

D-Ribose, A Metabolic Substrate for CongestiveHeart FailureSusan Wagner, RN;1 James Herrick, MSc, FASHP;2 Linda M. Shecterle, PhD;3 John A. St. Cyr, MD, PhD2

The incidence of congestive heartfailure continues to escalate with

at least 5 million patients currentlyafflicted in the United States, anestimated 8% yearly increase, approx-imately 3.1 million hospital admis-sions/year, costing over $23 billiondollars annually.1 Diastolic dysfunc-tion is a common finding in these pa-tients with mortality rates comparablewith patients with a depressed left ven-tricular ejection fraction.2 Redfield etal.3 reported that approximately 20%of individuals over the age of 40 are ata risk of developing heart failure duringtheir lifetime and the presence or ab-sence of diastolic dysfunction is pre-dictive of all-cause mortality.

Patients with diastolic dysfunctionor impaired relaxation of the heart andloss of ventricular compliance are atherapeutic challenge because cur-rently therapies have not demon-strated a benefit for a significantnumber of patients in long-term out-comes. Current conventional therapiesfocus on clinical management, such aslowering systolic and diastolic bloodpressure, controlling the ventricularrate in atrial fibrillation, and decreas-ing the volume overload.4 However,in most patients, these measures havedemonstrated limited success, whicheventually leads to progression in theirdisease. Therefore, future efforts muststrive to at least stabilize and hopefullyimprove a patient’s clinical course.

There is no cure for heart failure;however, current ‘‘main stream’’ ther-apies continue to tax our health caresystem. These predominantly pharma-ceutical therapies include agents suchas diuretics, angiotensin-converting

enzyme, angiotensin II receptor block-ers, b-blockers, vasopressin receptorantagonists, nitrates, inotropes, aldo-sterone receptor antagonists, direct-acting vasodilators, and recombinantneuroendocrine hormones,5 whichpromote lessening symptoms andpotentially delay the progression ofdisease. However, most patients expe-rience an escalation in their pharma-ceutical dose, in an effort to obtainsuccess. This escalation is commonlyaccompanied by undesirable side ef-fects, affecting patient compliance.Therefore, many patients seek othertreatment options, including device-related technologies, such as cardiacresynchronization therapy. The use ofthis technology in heart failure has in-

creased due to reduced symptoms, animproved quality of life (QOL), andpotentially lower rehospitalizationrates. However, even with theseclaims, there still exists a high nonre-sponder rate6 and long-term benefitshave yet to be determined.2 The ther-apeutic goal in heart failure resides inproducing a relief in symptoms and toimprove QOL. However, currenttherapies have not addressed the po-tential underlying cellular metabolicdeficiency found in heart failure. Nu-merous publications have repeatedlyreported the energy-deficient state inthe failing heart. Ingwall and Weiss7

reported that the failing heart is energystarved, also supported by others.8

‘‘Running out-of-gas,’’ as in energy

The incidence of congestive heart failure continues to escalate worldwide, taxinghealth care systems. Current therapies focus on clinical management. Currentaccepted regimens have provided some success; however, most patients showprogression of their disease. Because of this failure, research continues to exploretherapies directed at stabilization of their disease and hopefully to improve thedownward spiral. Publications have asserted that the failing heart is energy starved.D-ribose, a naturally occurring pentose carbohydrate and a key component in theadenosine triphosphate (ATP) molecule, has demonstrated an ability to replenishATP levels and improve diastolic dysfunction following myocardial ischemia, whichhas been shown to improve the clinical state of patients afflicted with congestive heartfailure. D-ribose may provide the necessary metabolic substrate to benefit this energy-deficient state found in heart failure. Prog Cardiovasc Nurs. 2009;24:59–60.&2009 Wiley Periodicals, Inc.

From the Saddleback Memorial Hospital, Laguna, CA;1 Bioenergy Life ScienceInc., Minneapolis, MN;2 and Jacqmar Inc., Minneapolis, MN3

Address for correspondence:Linda M. Shecterle, PhD, Jacqmar Inc., 10965 53rd Avenue, North Plymouth,MN 55442E-mail: lms94@aol.comManuscript received November 25, 2008; revised January 22, 2009; acceptedFebruary 17, 2009

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depletion of the cardiac myocyte, wasdescribed decades ago,9 and yet noneof the current therapies have ade-quately addressed this state. Myocar-dial adenosine triphosphate (ATP)levels are important to maintain thecell’s integrity and function. For ex-ample, ATP plays a key role in theinteraction between calcium and thesarcoplasmic reticulum, a functioncrucial for ventricular relaxation.10

Insufficient ATP levels can alter thishomeostasis, producing diastolicdysfunction and a noncompliant ven-tricle.

Deficient ATP levels are found inischemic heart disease and heart fail-ure. Kriett et al.,11 reported a declinein ATP levels with an accompanyingdiastolic dysfunction following myo-cardial ischemia with complete recov-ery required 49 days. Supplementshave been investigated to hasten therecovery of this deficient energy state,with mixed results. D-ribose, a natu-rally occurring pentose carbohydrate,plays many roles: as an important

component of ATP, a role in RNAand DNA synthesis, as well as in otherintracellular processes. Exogenous sup-plementation of ribose enhances theregeneration of ATP levels by bypass-ing rate-limiting, slow enzymaticsteps.12,13 Unlike the lengthy time re-covery that normally occurs followingischemia, ribose substantially shortensthis time interval.14

Clinically, physicians have ob-served the benefits of D-ribose. Plimlet al.15 reported that D-ribose enabledpatients with stable coronary arterydisease to exercise longer withoutdeveloping angina or electrocardio-graphic changes. Omran et al.16 re-ported that D-ribose improveddiastolic dysfunction, and improvedQOL, and physical function in con-gestive heart failure patients. Likewise,Vijay et al.17 found improvements inventilatory efficiency with D-ribose inheart failure patients. Perkowski etal.18 reported on the hemodynamicbenefits of D-ribose, peri-operatively,in patients undergoing off-pump cor-

onary artery bypass, and Vance et al.19

also found these hemodynamic bene-fits of D-ribose following aortic valvereplacement.

In summary, D-ribose offers anenergetic benefit in patients withischemic cardiovascular diseases,including congestive heart failure.D-ribose has been shown to improvediastolic dysfunction, commonlyfound in heart failure; and therefore,D-ribose provides the metabolic linkneeded for this functional improve-ment, which is not present in anycurrent pharmaceuticals. A recent ar-ticle, by Baliga and Young2 called at-tention to the relationship between ametabolic deficiency and diastolic dys-function, stating that ‘‘modulatingmyocardial energetics could emergeas an important strategy to improveoutcomes in diastolic heart failure; thefuture could very well be in ‘revving-up’ diastole.’’ D-ribose may providethe additive agent to this perplexingand unsolved dilemma.

REFERENCES1 Website of American Heart Association Available

from: http://www.americaheartassociation.com2 Baliga R, Young JB. Editorial. Energizing diastole.

Heart Fail Clin. 2008;4:ix–xiii.3 Redfield MM, Jacobson SJ, Burnett JC, et al. Bur-

den of systolic and diastolic ventricular dysfunctionin the community. Appreciating the scope of theheart failure epidemic. JAMA. 2003;289(2):194–202.

4 Hunt SA, Abraham WT, Chin MH, et al. Amer-ican College of Cardiology; American Heart Asso-ciation Task Force on Practice Guidelines;American College of Chest Physicians; Interna-tional Society for Heart and Lung Transplantation;Heart Rhythm Society. ACC/AHA 2005 Guide-line Update for the Diagnosis and Management ofChronic Heart Failure in the Adult: a report of theAmerican College of Cardiology/American HeartAssociation Task Force on Practice Guidelines(Writing Committee to Update the 2001 Guide-lines for the Evaluation and Management of HeartFailure): developed in collaboration with the Amer-ican College of Chest Physicians and the Interna-tional Society for Heart and Lung Transplantation:

endorsed by the Heart Rhythm Society. Circula-tion. 2005;112(12):e154–e235.

5 Heart Failure-Wikipedia (The Internet). Availablefrom: http://en.widipedia.org/wiki/Congestive_heart-failure:1–15.

6 Adigum AZ, Rist KE. Cardiac resynchronizationtherapy for treatment of congestive heart failure.Hosp Physician. 2005;41(1):15–24.

7 Ingwall JS, Weiss RG. Is the failing heart energystarved? On using chemical energy to support car-diac function. Circ Res. 2004;95:135–145.

8 Neubauer S. The failing heart—an engine out offuel. N Engl J Med. 2007;356(11):1140–1151.

9 Goodale WT, Olson RE, Hackel DB. The effect offasting and cardiac failure upon heart muscle me-tabolism in man. J Clin Invest. 1950;29(6):816.

10 Pauly DF, Pepine CJ. D-ribose as a supplement forcardiac energy metabolism. J Cardiovasc PharmacolTherapeut. 2000;5(4):249–258.

11 Kriett JM, Ward HB, Bianco RW, et al. Recoveryof adenine nucleotides and cardiac functionfollowing ischemia. Circulation. 1983;68(III):389.

12 St.Cyr JA, Bianco RW, Schneider JR, et al. En-hanced high energy phosphate recovery with ribose

infusion after global myocardial ischemia in a ca-nine model. J Surg Res. 1989;46(2):157–162.

13 Zimmer HG. Normalization of depressed heart func-tion in rats by ribose. Science. 1983;220(4592):81–82.

14 Schneider JR, St.Cyr JA, Mahoney JR, et al. Re-covery of ATP and return of function after globalischemia. Circulation. 1985;72(4):III-298.

15 Pliml W, von Arnim T, Stablein A, et al. Effects ofribose on exercise-induced ischaemia in stable cor-onary artery disease. Lancet. 1992;340:507–510.

16 Omran H, Illien S, MacCarter D, et al. D-riboseimproves diastolic function and quality of life incongestive heart failure patients: a prospective fea-sibility study. Eur J Heart Fail. 2003;5:615–619.

17 Vijay N, MacCarter D, Shecterle LM, et al. Letterto the Editor. D-ribose benefits heart failure pa-tients. J Med Food. 2008;11(1):199–200.

18 Perkowski D, Wagner S, Marcus A, et al. D-riboseimproves cardiac indices in patients undergoing‘‘off’’ pump coronary arterial revascularization.J Surg Res. 2007;137(2):295.

19 Vance R, Einzig S, Kreisler K, et al. D-ribosemaintains ejection fraction following aortic valvesurgery. FASEB J. 2000;14(4):A419.

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