Technical Data
DESCRIPTION
Corvalen is a medical food containing pure D-ribose, a simple sugar present in all living
cells and essential to life. Because ribose does not exist as a free standing compound in
foods, it must be produced in the body from other dietary nutrients.
Corvalen is used, under the direction of a licensed healthcare practitioner, in the dietary
management of diseases in which energy depleted tissues cannot produce ribose
quickly enough to meet cellular energy (ATP) demands. As such, Corvalen fulfills a
distinct nutritional requirement that can not be addressed through diet alone. Clinical
research has shown that conditions such as congestive heart failure, chronic ischemic
heart disease, post open-heart surgery or myocardial infarction, chronic fatigue
syndrome, fibromyalgia, AMP deaminase deficiency, and mitochondrial dysfunction, can
benefit from Corvalen administration.
Corvalen D-Ribose
•
More than 20 issued and pending patents protecting its use in a broad array of
applications
•
Clinically studied at a number of prestigious universities and medical institutions
•
Designated generally recognized as safe (GRAS) by an independent panel of
experts
•
Recommended by medical professionals, including Dr. Jacob Teitelbaum, board
certified internist, Director of the Center for Effective Chronic Fatigue
Syndrome/Fibromyalgia Therapies, and a member of the Integrative Therapeutics,
Inc. Scientific Advisory Board
As an alternative to the powder, which must be mixed with food or drink prior to
consumption, Corvalen is also available in chocolate-flavored chewable wafers. Three
chocolate-flavored wafers provide the same clinically studied D-ribose dose found in
one scoop of original powder. For advanced support, D-ribose is also offered in
combination with the cellular energy-building nutrients, magnesium and malic acid, as
CorvalenM.
INTRODUCTION
Glossary
•
Adenine: A purine consisting of a six-membered ring attached to five membered
ring, involved in many biochemical roles, including cellular respiration and protein
synthesis. A component of ATP, DNA, and RNA.
•
ATP: Adenosine triphosphate, the primary carrier of cellular energy.
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D-Ribose: A five-carbon sugar, and component of ATP. Also known as alpha-Dribofuranoside.
•
Nucleotide: A chemical compound consisting of a heterocyclic base (purine or
pyrimidine), a sugar (deoxyribose or ribose), and one or more phosphate groups.
DNA and RNA are examples.
•
Purine or Pyrimidine: A nitrogen-containing heterocyclic base, which makes up
a crucial part of both DNA and RNA. Adenine is one example of a purine.
ATP: Cellular Energy Currency
Every biological cell utilizes, stores, and transports energy in chemical form. Adenosine
triphosphate, more commonly referred to as ATP, is the primary carrier of chemical
energy in all cells. It transports energy within the cells for metabolism, is produced
through cellular respiration, and is consumed by certain enzymes and a number of
biochemical reactions in the body. 1
The structure of ATP consists of a purine base (adenine) attached to the 1' carbon atom
of a pentose sugar, called ribose. Three phosphate groups are attached at the 5' carbon
atom of the pentose sugar.1
Ribose: The Sugar of Life
D-Ribose, also known as alpha-D-ribofuranoside, is a naturally occurring five-carbon
sugar found in all living cells. Although it is found in two chemical configurations as Dand L-isomers, only the D-isomer has been shown to possess biological activity. Dribose is present in several molecules that are essential to ubiquitous biological
processes, including ATP (as mentioned above), all the nucleotides, nucleotide
coenzymes, and all forms of RNA (ribonucleic acid).2 Because ribose does not exist as
a free standing compound in food, it must be created in the body from other dietary
nutrients, namely glucose. Clinical research has shown that consumption of this sweet,
water-soluble substance is critical in the dietary management of diseases or conditions,
in which there is a deficiency of cellular energy. 3-9
HOW DOES IT WORK?
D-Ribose is used by cells and tissues to stimulate the biochemical pathways associated
with the salvage and de novo (“anew” or “beginning again”) synthesis of purine
nucleotides, such as ATP. D-Ribose also reduces cellular purine loss and accelerates
energy recovery in the cell. Through these actions, cellular energy, in the form of ATP,
is preserved and the physiological consequences of depleted cellular energy are
reduced. 2
Ribose is formed naturally via the pentose phosphate pathway (PPP) of glucose
metabolism (See Figure 1).2,10 In heart and skeletal tissues, the activities of the
enzymes controlling the PPP synthesis of ribose are low in contrast with those involving
the breakdown of glucose into pyruvate (a process known as glycolysis). As a result, the
pentose phosphate pathway is unable to synthesize a sufficient volume of ribose to
maintain energy levels when cells suffer metabolic stress. As such, the availability of
ribose, and its product, 5-phosphoribosyl-1-pyrophosphate (PRPP), are rate limiting for
adenine nucleotide synthesis or salvage. 2
ATP Depletion
The lack of oxygen to a tissue, a condition called hypoxia, has a direct impact on
cellular energy reserves. Depriving cells of oxygen causes energy (i.e., ATP) to be used
faster than it can be supplied. Research has documented that ATP depletion has a
significant impact on cardiac metabolism and performance. Ischemic heart disease and
congestive heart failure, for example, lead to a progressive decline in the heart's ability
to maintain normal energy pools. And as energy levels in the heart decline, diastolic
function, as measured by ventricular compliance and ventricular wall thickening, can
become compromised.2,11,12
Purine nucleotides (ATP and its precursors) lost due to ischemia (blood restriction),
hypoxia, or genetic predisposition, are replaced via the purine nucleotide pathway – a
pathway which is rate limited by the availability of ribose in tissue. 2
Corvalen® Medical Food
Research has demonstrated that D-ribose administration can bypass the slow, rate
limited pentose phosphate pathway to stimulate adenine nucleotide synthesis and
salvage.2,13-15 One animal model study measured synthesis of adenine nucleotides in
muscle tissue following administration of ribose. De novo synthesis was found to rise
three- to fourfold in each type of muscle fiber tested.13 Other studies have found that
ribose can also stimulate adenine and hypoxanthine (a purine derivative) salvage in
skeletal muscle. Ribose administration increased nucleotide salvage rates by three- to
eightfold or five- to sevenfold, depending on muscle fiber type and ribose concentration.
More noteworthy was the fact that even low dosages – as low as 0.15 mM of ribose –
had a significant and sustained impact on adenine and hypoxanthine salvage.13,14
Corvalen®, the patented, clinically proven form of D-Ribose, has been shown to help in
the dietary management of several diseases and conditions in which there is a
deficiency in energy. The following chart summarizes a few of the clinical studies using
Corvalen D-Ribose:
Condition
Clinical Research
Randomized, double blind, placebo controlled involving 20
patients with coronary artery disease and stable angina (chest
pain).
Coronary Artery
Disease
•
•
Ribose increased treadmill walking time to ST segment
depression; nearly 20% greater improvement versus
placebo
After 3 days, also improved the heart's tolerance to
ischemia3
Prospective, randomized, double blind, placebo controlled,
crossover design study to assess effects of D-ribose
supplementation in 15 patients with coronary artery disease and
congestive heart failure (Class II – III).
Coronary Artery
Disease/ Congestive
Heart Failure
•
•
Ribose led to an enhancement of atrial contribution to left
ventricular filling, a smaller left atrial dimension, and a
shortened E wave deceleration by echocardiography
Resulted in a 12% increase in quality of life as measured
on validated scale4
Fourteen congestive heart failure patients (NYHA Class II – III)
were enrolled in a double blind, placebo controlled, crossover
design. Maximal cycle ergometry with gas exchange was
monitored pre- and post- each treatment period.
Congestive Heart
Failure (CHF)
•
•
With exercise, ribose-treated CHF patients maintain
better ventilatory efficiency, a strong predictor of heart
failure survival
Also improved VO2max, reduced shortness of breath,
increased exercise tolerance, and increased hypoxic
threshold vs. placebo5
Randomized, double blind trial with 27 open heart patients.
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Open Heart Surgery
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Ejection fraction in placebo group significantly depressed
following 7-days of post-surgical recovery
At 7 days, 80% of placebo group demonstrated decline,
whereas only 20% of the ribose group experienced
decline6
A comparison of the results of 143 patients receiving D-ribose
as an oral “pre-op” versus 40 historical patients following a
similar protocol, without supplementation.
Coronary Artery
Disease
•
•
“Off” pump cardiopulmonary bypass with supplemental
ribose resulted in no peri-operative deaths and no postoperative myocardial infarctions
Ribose treated patients showed a 43% improvement in
cardiac index (cardiac output/surface area) vs. 13% with
historical controls without ribose7
An 8-week open-label clinical trial with 15 congestive heart
failure patients (Class III (9) and IV (6)) undergoing
cardiopulmonary testing.
Congestive Heart
Failure
Chronic Fatigue
Syndrome/
Fibromyalgia
•
O2 uptake efficiency, stroke volume (O2 pulse), and
ventilatory efficiency, the most powerful predictor of
patient survival, were significantly improved following
supplementation with D-ribose8
Open-label uncontrolled pilot study involving 41 participants.
•
Subjective patient questionnaires revealed significant
•
•
improvement in all five visual analog scale (VAS)
categories: energy; sleep; mental clarity; pain intensity;
and well-being
Improvement in patients' global assessment also
demonstrated
Approximately 66% of patients experienced significant
improvement, with an average increase in energy on the
VAS of 45% and an average improvement in overall wellbeing of 30% (p < 0.0001)9
Safety
Following almost three years of laboratory, animal, and human studies, an independent
expert panel of highly qualified food scientists and toxicologists evaluated the safety of
Corvalen® D-Ribose. The panel concluded that Corvalen D-Ribose is generally
recognized as safe (GRAS) for use in specific foods when manufactured according to
stringent process and quality specifications.
Corvalen has been very well tolerated with few reports of side effects. Occasionally,
mild diarrhea and lightheadedness has been reported in fasting individuals consuming
doses greater than 10 grams at a time.
Conclusion
The medical food, Corvalen, provides pure D-ribose, to assist in the dietary
management of conditions, such as congestive heart failure, chronic ischemic heart
disease, chronic fatigue syndrome, and fibromyalgia. Corvalen provides the rate limiting
nutrient, ribose, to address the cellular energy depletion associated with such diseases.
Corvalen medical food should be used under the direction of a licensed healthcare
practitioner.
RECOMMENDATIONS
Congestive Heart Failure/Ischemic Heart Disease
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3 chewable wafers 2 times daily with food
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3 chewable wafers 3 times daily with food for advanced stages
Chronic Fatigue Syndrome/Fibromyalgia
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Initially, 3 chewable wafers 3 times daily with food for 2-3 weeks
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Then 3 chewable wafers 2 times daily with food thereafter
PRECAUTIONS
Insulin-dependent diabetics, pregnant women, and those with elevated uric acid levels
(associated with gout) should consult their physician before use.
HOW IS IT SUPPLIED?
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70479; 90 chewable wafers
STORAGE RECOMMENDATIONS
Store at controlled room temperature, 59° to 86°F (15° – 30°C).
REFERENCES
1.
Lehninger AL, Nelson DL, Cox MM. The Molecular Logic of Life. In: Foundations
of Biochemistry. New York, NY: Worth Publishers, Inc.; 1993: 3-19.
2.
Fleming T, ed. D-Ribose. In: PDR for Nutritional Supplements. Montvale, NJ:
Medical Economics Company, Inc.; 2001: 139-41.
3.
Pliml W, von Arnim T, Stablein A, Hofmann H, Zimmer HG, Erdmann E. Effects
of ribose on exercise-induced ischaemia in stable coronary artery disease. Lancet.
1992;340(8818):507-510.
4.
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
Failure. 2003;5:615-619.
5.
Carter O, MacCarter D, Manneback S, et al. D-ribose supplementation improves
peak exercise capacity and ventilator efficiency in heart failure patients. JACC.
2005;45(3 Suppl A):185A.
6.
Vance R, Einzig S, Kreisler K, St. Cyr J. D-ribose maintains ejection fraction
following aortic valve surgery. FASEB J. 2000; 14(4): A419.
7.
Perkowski, Wagner S, Marcus A, St.Cyr J. D-ribose improves cardiac indices in
patients undergoing “off” pump coronary arterial revascularization. J Surg Res.
2007;137(2):295.
8.
Vijay N, MacCarter D, Washam M, St.Cyr J. Ventilatory efficiency improves with
D-ribose in congestive heart failure patients. J Mol Cell Cardiol. 2005;38(5):820.
9.
Teitelbaum JE, Johnson C, St Cyr J. The use of D-ribose in chronic fatigue
syndrome and fibromyalgia: a pilot study. J Altern Complement Med. 2006
Nov;12(9):857-62..
10. Gumaa KA,P McLean. The pentose phosphate pathway of glucose metabolism.
Biochem J. 1969;115:1009-1029.
11. Ingwall JS, Weiss RG. Is the Failing Heart Energy Starved? On Using Chemical
Energy to Support Cardiac Function. Circ Res. 2004;95:135-145.
12. Neubauer S. The Failing Heart — An Engine Out of Fuel. N Engl J Med.
2007;356:1140-51.
13. Tullson PC, Terjung RL. Adenine nucleotide degradation in striated muscle. Int J
Sports Med. 1990;11:S47-S55.
14. Brault JJ, Terjung RL. Purine salvage to adenine nucleotides in different skeletal
muscle fiber types. J Appl Physiol. 2001;91:231-238.
15. Zarzeczny R, Brault JJ, Abraham KA, Hancock CR, Terjung RL. Influence of
ribose on adenine salvage after intense muscle contractions. J Appl Physiol.
2001;91:1775-1781.