GUEST ARTICLE

Enhancing Mitochondrial Function With D-Ribose

Jacob Teitelbaum, MD

Financial Disclosure: The author has been involved in the development

of nutritional supplements (all of his royalties for the products go to
charity) and he sells supplements, including D-ribose, on his website.

ach cell in the body contains mitochondria that produce

energy by burning calories. Many illnesses and diseases,
including genetic defects, nutritional deficiencies, and
Epstein Barr viral infections, can suppress mitochondrial function.1 Common syndromes associated with decreased mitochondrial function and associated drops in tissue levels of
adenosine triphosphate (ATP) include chronic fatigue syndrome (CFS) and fibromyalgia (FMS).2
Having had both CFS and FMS in 1975, which knocked
me out of medical school for a year and left me homeless during much of that time, I have devoted the last 30 years to
researching these syndromes. In that time, I have treated more
than 3000 CFS/FMS patients and authored a number of books,
studies, and articles on the topic.
In my early-published research, I performed a doubleblind, randomized, controlled trial to assess energy production.
We obtained highly positive results from use of what we termed
the SHINE Protocol (treatment for sleep disorders, hormonal
deficiencies, infections, nutritional support, and exercise
though exercise was not controlled for in the study). In the
study, published in 2001, patients reported an average 90%
improvement in quality of lifeas verified by using a visual
analog scale (VAS) measuring fatigue, pain, sleep, cognitive
dysfunction, and overall well-being. Highly significant improvement was also seen in the Tender Point Index, Fibromyalgia
Impact Questionnaire, and patient self-rating (P<.0001 vs placebo for all 4 outcome measures).3
It recently became clear, however, that both CFS and FMS
represent mitochondrial dysfunction, which, in turn, reduces
energy production to inefficient levels. This led me to research
ribose, which has turned out to be a very powerful tool for treating both CFS/FMS as well as many common cardiac problems.
In this article, I will discuss the use of D-ribose (often
shortened to ribose) to help mitochondria work properly and
explain how practitioners can use this information to dramatically help their fatigue, pain, and cardiac patients feel better.

The Role of Energy Production

Medical research shows there are many conditions that

drain energy from the body, leaving a person fatigued and with
such frequent complications as muscle pain, heart problems,
and depression.
Of course, athletes who participate in high-intensity,
endurance-type exercise often face fatigue and muscle pain

46

Integrative Medicine Vol. 7, No. 2 Apr/May 2008


Patient Handout

Heart and Energy Cocktail

Following is recipe for dramatically improving cardiac function and energy production. Try this for 6 to 12 weeks to see
the optimal effects, then use as needed.
Ribose: Take 5 g 3x/day for 6 weeks, then 5 g 2x/day for 6
more weeks. This nutrient is outstanding for heart disease.
Coenzyme Q10: Take 400 mg/day for 6 weeks, then 200 mg/
day for 6 more weeks. This nutrient is especially critical for
anyone on cholesterol-lowering medications, even if there are
no heart problems, as these medications cause Co-Q10 deficiency (a nutrient critical for energy production).
Magnesium: Take 200 mg/day for 12 weeks.
Vitamin B complex: Take 50+ mg/day for 12 weeks.
Acetyl-L-carnitine: Take 500 mg 2x day for 6 weeks, then
500 mg/day for 6 weeks (and it can often simply be stopped
after the first 6 weeks).
associated with energy depletion. Typically, however, a few
days of rest will allow an athletes muscles to recharge. For the
rest of our patient base, physiological factors that drain hearts
and muscles of energy are not as easily overcome. In particular,
aging has a decided effect on energy production. As the body
ages, it goes through many changes that affect its ability to
efficiently metabolize energy. For some, these changes occur
more rapidly and are more pronounced, while for others the
impact is seemingly absent.
As previously mentioned, illness and disease also have an
effect. People with CFS/FMS, for example, have almost 20% less
energy in their muscles than normal, and this lack of energy
causes poor exercise tolerance and lack of endurancemaking it
hard to perform even the most basic of lifes daily activities.4,5
The metabolic changes that occur in either an aging body
or one with the onset of CFS/FMS are varied. Many people are
found to have thickening of the capillary walls, making it
harder for oxygen to move from blood to muscle tissue, reducing the oxygen tension of the muscle, and slowing the rate of
energy synthesis.6,7 In others, the mitochondria are found to
be defective or inefficient, making them unable to keep up with
the energy demand of cells and tissues as they work through
daily activities.8-10 For still others, cells and tissues are deficient
in certain nutrients that are needed to process food into energy,
leaving the tissues energy starved.11-13 And in the most difficult
conditions, the muscle itself is affected, leaking vital cellular

TeitelbaumEnhancing Mitochondrial Function With D-Ribose

constituents that include energy compounds and fuels needed

to restore energy levels in affected tissues.14
No matter the cause, the impact of energy depletion is to
propel a downward spiral of fatigue, muscle pain, soreness,
and stiffness that becomes self-sustaining until reversed. As
energy is used faster than it can be renewed, muscles become
more painful, stiff, and fatigued because it takes energy for
tight muscles to release and relax. This causes even more
energy to be used as the muscle struggles to recover, causing
even more fatigue, soreness, and stiffness,15-17 and the cycle is
perpetuated. If conditions leading to energy depletion are not
arrested in time, fatigue and myalgias can become overwhelming and debilitatingas occurs in CFS and FMS.
Consequences of Mitochondrial Dysfunction

Mitochondrial malfunction can create numerous problems, including particularly severe changes in the hypothalamus that result in hypothalamic suppression.18 The hypothalamus controls sleep and pituitary and autonomic functions.
Along with this, diseases of the mitochondria appear to cause
the most dysfunction in organs and systems that require a
great deal of energy: the brain, heart, skeletal muscles, liver,
and endocrine systems.19 The following outlines how all of
these can contribute to the myriad symptoms that occur in
CFS/FMS.
Hypothalamic suppression:
Sleep. The hypothalamus is becoming recognized as a
key center for regulating sleep.20 Insomnia is severe in
CFS/FMS, and sleep deprivation has been shown to be
a potent trigger for immune suppression.21
Autonomic function. The autonomic nervous system
controls blood pressure, pulse, sweating, and peristalsis. Dysfunction can lead to neurally mediated hypotension, bowel dysfunction with irritable bowel syndrome,
and small intestinal bacterial overgrowth (SIBO), as
well as the unusual sweating patterns commonly seen
in CFS/FMS.22
Pituitary/endocrine function. Disruptions result in
widespread hormonal dysfunction, including deficiencies of growth hormone as well as hypothalamicpituitary-adrenal and thyroid axis dysfunction.23-26
Dysfunction in the brain, heart, skeletal muscles, liver, and
endocrine systems:
Brain fog.
Heart dysfunction. In a 2007 personal communication
with noted CFS researcher Paul Cheney, MD, he related
that mitochondrial dysfunction associated with inadequate antioxidant production/function may contribute
to the severe cardiac dysfunction that he sees in CFS
patients undergoing echocardiography.
Post-exertion fatigue. Low energy production can
cause an accumulation of excessive amounts of lactic
acid in muscles, thus inhibiting recovery after exercise.
Volume and osmotic regulation. Secondary to hypothalamic

TeitelbaumEnhancing Mitochondrial Function With D-Ribose

Ribose Studies

For those who would like more information about ribose,

please see the following studies:
X Berthold HK, Naini A, Di Mauro S, et al. Effect of ezetimibe and/

or simvastatin on coenzyme Q10 levels in plasma: a randomised

trial. Drug Saf. 2006;29(8):703-712.
X Bliznakov E, Casey A, Premuzic E. Coenzymes Q: stimulants of
phagocytic activity in rats and immune response in mice.
Experientia. 1970;26(9):953-954.
X Dodd SL, Johnson CA, Fernholz K, St Cyr JA. The role of ribose in
human skeletal muscle metabolism. Med Hypotheses.
2004;62(5):819-824.
X Folkers K, Langsjoen P, Nara Y, et al. Biochemical deficiencies of
coenzyme Q10 in HIV-infection and exploratory treatment.
Biochem Biophys Res Commun. 1988;153(2):888-896.
X Folkers K, Shizukuishi S, Takemura K, et al. Increase in levels of
IgG in serum of patients treated with coenzyme Q10. Res Commun
Chem Pathol Pharmacol. 1982;38(2):335-338.
X Gaby AR. The role of coenzyme Q10 in clinical medicine. Part I.
Altern Med Rev. 1996;1(1):11-17.
X Gallagher PM, Williamson DL, Goddard MP, Trappe SW. Effects
of ribose supplementation on adenine nucleotide concentration in
skeletal muscle following high-intensity exercise. Med Sci Sport Exc.
2001;33(5) Suppl 1:S167.
X Geenen R, Jacobs JW, Bijlsma JW. Evaluation and management of
endocrine dysfunction in fibromyalgia. Rheum Dis Clin North Am.
2002;28(2):389-404.
X Grant GF, Gracey RW. Therapeutic nutraceutical treatments for
osteoarthritis and ischemia. Exp Opin Ther Patents.
2000;10(1):39-48.
X Guymer EK, Clauw DJ. Treatment of fatigue in fibromyalgia.
Rheum Dis Clin North Am. 2002;28(2):67-78.
X Ishihara Y, Uchida Y, Kitamura S, Takaku F. Effect of coenzyme
Q10, a quinone derivative, on guinea pig lung and tracheal tissue.
Arzneimittelforschung. 1985;35(6):929-933.
X Kuratsune H, Yamaguti K, Takahashi M, Misaki H, Tagawa S,
Kitani T. Acylcarnitine deficiency in chronic fatigue syndrome.
Clin Infect Dis. 1994;18 Suppl 1:S62-S67.
X Lockwood K, Moesgaard S, Hanoike T, Folkers K. Apparent partial remission of breast cancer in high risk patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Mol Aspects Med. 1994;15(Supplement):S231-S240.
X Lockwood K, Moesgaard S, Yamamoto T, Folkers K. Progress on
therapy of breast cancer with vitamin Q10 and the regression of
metastases. Biochem Biophys Res Commun. 1995;212(1):172-177.
X Mayer P, Hamberger H, Drew J. Differential effects of Ubiquinone
Q7 and Ubiquinone analogs on macrophage activation and
experimental infections in granulocytopenic mice. Infection.
1980;8(1):256-261.
X Mller C, Zimmer H, Gross M, et al. Effect of ribose on cardiac
adenine nucleotides in a donor model for heart transplantation.
Eur J Med Res. 1998;3(12):554-558.
X Palan PR, Connell K, Ramirez E, et al. Effects of menopause and
hormone replacement therapy on serum levels of coenzyme Q10
and other lipid-soluble antioxidants. Biofactors. 2005;25(1-4):61-66.
X Palan PR, Magneson AT, Castillo M, Dunne J, Mikhail MS. Effects of
menstrual cycle and oral contraceptive use on serum levels of lipidsoluble antioxidants. Am J Obstet Gynecol. 2006;194(5):e35-e38.
X Pauly D, Johnson C, St Cyr JA. The benefits of ribose in cardiovascular disease. Med Hypotheses. 2003;60(2):149-151.

Integrative Medicine Vol. 7, No. 2 Apr/May 2008

47

dysfunction, low anti-diuretic hormone also contributes

to the increased thirst and urination seen in CFS/FMS.27
Sensitivities and allergies. So called leaky gut combined with a decreased ability of the liver to eliminate
toxins and medications can contribute to both medication and environmental sensitivities.
Thus, mitochondrial dysfunction might well be the root
cause ofor at least a contributing factor tohypothalamic,
nutritional, immune, cardiac, detoxification, and sleep disorders.
What can be done to make the cellular mitochondrial energy furnaces work better? Though a number of natural treatments
are available, I see D-ribose as the key to energy production.
D-RiboseThe Natural Body Energizer

When considering energy production, it helps to look at

the energy molecules such as ATP, nicotinamide adenine
dinucleotide, and the reduced form of flavin adenine dinucleotide. These represent the energy currency of the body and are
like the paper that money is printed on. A person can ingest all
the fuel he wants, but if it cannot be converted to these molecules, it is useless. In particular, ATP is important because the
amount of ATP people have in their tissues determines whether they will be fatigued or have the energy needed to live vital,
active lives.
For years I talked about the importance of B vitamins,
which are a key component of these energy molecules. The Bs
helped to a degree, but it was clear that some key component
was still missing. Then, in looking at the biochemistry of these
energy molecules, I saw they are made of 2 other critical components: adenine and ribose. Adenine is plentiful in the body
and supplementing with adenine does not help CFS. So my
coworkers and I then turned our attention to ribose.
D-ribose is a simple, 5-carbon sugar that is found naturally in our bodies. But ribose is not like any other sugar. The
familiar sugars, such as table sugar (sucrose), corn sugar (glucose), milk sugar (lactose), honey (predominantly fructose),
and others are used by the body as fuel. These sugars are consumed and, with the help of oxygen, burned by the body to
recycle energy. Ribose, on the other hand, is different. When
consumed as a supplement (ribose is not found in food), the
body recognizes that ribose is different from other sugars and
preserves it for the vital work of actually creating the energy
molecules that power the brain, heart, muscles, and every
other tissue in the body.
As it turns out, ribose provides the key building block of
ATP, and the presence of ribose in the cell stimulates the metabolic pathway our bodies use to actually produce the ATP we
require. If the cell does not have enough ribose, it cannot make
ATP. So, when cells and tissues become energy starved, the
availability of ribose is critical to energy recoveryand is often
the rate-limiting nutrient for ATP production.
Normal, healthy muscle and heart tissue has the capacity
to make all of the ribose it needs. When normal tissue is
stressed by overexertion, several days of rest will usually allow
it to fully recover. The muscle may be sore during recovery, but

48

Integrative Medicine Vol. 7, No. 2 Apr/May 2008

Ribose Studies (continued)

X Pauly

D, Pepine C. D-Ribose as a supplement for cardiac energy

metabolism. J Cardiovasc Pharmacol Ther. 2000;5(4):249-258.
X Pauly DF, Pepine CJ. Ischemic heart disease: metabolic approaches to management. Clin Cardiol. 2004;27(8):439-441.
X Pliml W, von Arnim T, Stblein 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.
X Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome. Neuropsychobiology.
1997;35(1):16-23.
X Rooks DS, Silverman CB, Kantrowitz FG. The effects of progressive strength training and aerobic exercise on muscle strength
and cardiovascular fitness in women with fibromyalgia: a pilot
study. Arthritis Rheum. 2002;47(1):22-28.
X Rusciani L, Proietti I, Rusciani A, et al. Low plasma coenzyme
Q10 levels as an independent prognostic factor for melanoma
progression. J Am Acad Dermatol. 2006;54(2):234-241.
X Salerno C, Celli M, Finocchiaro R, et al. Effect of D-ribose administration to a patient with inherited defect of adenylosuccinase.
In: Griesmacher A, Chiba P, Mller MM, eds. Purine Metabolism
in Man IX. New York: Plenum Press; 1998: 177-180.
X Salerno C, DEufermia P, Finocchiaro R, et al. Effect of D-ribose
on purine synthesis and neurological symptoms in a patient
with adenylsuccinase deficiency. Biochim Biophys Acta.
1999;1453(1):135-140.
X Sander S, Coleman SI, Patel AA, Kluger J, White CM. The impact
of coenzyme Q10 on systolic function in patients with chronic
heart failure. J Card Fail. 2006;12(6):464-472.
X Sndor PS, Di Clemente L, Coppola G, et al. Efficacy of coenzyme
Q10 in migraine prophylaxis: a randomized controlled trial.
Neurology. 2005;64(4):713-715.
X Schachter CL, Busch AJ, Peloso PM, Shepard MS. Effects of short
versus long bouts of aerobic exercise in sedentary women with
fibromyalgia: a randomized controlled trial. Phys Ther.
2003;83(4):340-358.
X Van Gaal L, de Leeuw ID, Vadhanavikit S, et al. Exploratory study
of coenzyme Q10 in obesity. In: Folkers K, Yamamura Y, eds.
Biomedical and Clinical Aspects of Coenzyme Q. Vol. 4. New York,
NY: Elsevier Publishers; 1984:235-373.
X Van Gammeren D, Faulk D, Antonio J. 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(8):486-495.
X Wallen WJ, Belanger MP, Wittnich C. Preischemic administration of ribose to delay the onset of irreversible ischemic injury and
improve function: studies in normal and hypertrophied hearts.
Can J Physiol Pharmacol. 2003;81(1):40-47.
X Weant KA, Smith KM. The role of coenzyme Q10 in heart failure.
Ann Pharmacother. 2005;39(9):1522-1526.
X Wilson R, MacCarter D, St Cyr J. D-Ribose enhances the identification of hibernating myocardium. Heart Drug.
2003:3(1):61-62.
X 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(4):1775-1781.
X Zlner N, Reiter S, Gross M, et al. Myoadenylate deaminase deficiency: successful symptomatic therapy by high dose oral administration of ribose. Klin Wochenschr. 1986;64(24):1281-1290.

TeitelbaumEnhancing Mitochondrial Function With D-Ribose

eventually energy levels will be restored and the soreness will

disappear. But when the muscle is chronically stressed in heart
disease, fibromyalgia, or other conditions that affect tissue
energy metabolism, the cells and tissues simply cannot make
enough ribose quickly enough to recover. The result is chronic,
persistent pain, stiffness, soreness, and overwhelming fatigue
that may never go away unless energy production is restored.

have to quit teaching. When I take [ribose], I feel like a huge

weight is being lifted from my chest, and Im ready to take on
those kids again! The relief patients feel with ribose therapy is
heartwarming, and goes directly to the dramatic impact ribose
has on increasing energy, overcoming fatigue, enhancing exercise tolerance, and raising the patients quality of life.
The Link Between Ribose, Energy, and Fatigue

Ribose Research

As mentioned above, ribose does not come from food; it

is made in the body by a slow, laborious process (the pentose
phosphate shunt). From published research, we knew that
CFS/FMS causes the body to dump certain key energy molecules like carnitine. Looking further, we then found that the
body did the same with ribose, dumping it as well, and making
it hard to get the mitochondrial furnaces working again even
after other problems had been treated.
This was one of those exhilarating Eureka! moments
where things came together. Not having ribose would be like
trying to build a fire without kindlingnothing would happen.
We wondered if giving ribose to people with CFS would jumpstart their energy furnaces. The answer was a resounding yes.
This discovery led me and 2 research collaborators to
design an open-label, uncontrolled pilot study on 41 patients
with either CFS or FMS.28 Our study, published in 2006, was
intended to determine whether or not ribose would be effective in relieving the overwhelming fatigue, pain, soreness, and
stiffness suffered by patients with these debilitating symptoms. For an average of 3 weeks, patients were given ribose at
a dose of 5 g 3 times per day.
We found that ribose treatment led to significant improvement in energy levels, sleep patterns, mental clarity, pain
intensity, and well-being. Of the patients participating in the
study, 65.7% experienced significant improvement while on
ribose (rating themselves as better or much better). On average, improvement began at 12 days. The studys primary outcome measure was the patients individual rating of fatigue,
pain, sleep, cognitive function, and overall well being on a VAS.
Patients rated themselves as having an average increase in
energy of 44.7% and in overall well being of 30% on their
VASremarkable results from a single nutrient (normally a
10% improvement for a single nutrient is considered excellent).28 A 44.7% increase left us amazed, and I am now recommending ribose for all of my CFS/FMS patients, for athletes,
and for anyone with pain, fatigue, or heart problems. The only
significant side effects were that 2 people felt too energized
and hyper/anxious on the ribose. That was dealt with simply
by lowering the dose and/or having the patients take the
ribose with food.
On a personal note, several of the patients participating in
the study have contacted me regarding the relief they found
with ribose therapy. Most importantly, they speak to the profound joy they feel when they are able to begin living normal,
active lives after sometimes years of fatigue, pain, and suffering.
Here is a sample of what one patient, an elementary teacher,
wrote: I had so much pain and fatigue I thought I was going to

TeitelbaumEnhancing Mitochondrial Function With D-Ribose

Clinical and scientific research has repeatedly shown that

giving ribose to energy-deficient hearts and muscles stimulates
energy recovery. One important study involved healthy athletes participating in high-intensity, endurance exercise over
the course of 1 week. After exercise, the energy level in the
athletes muscle was reduced by almost 30%. Giving 10 g of
ribose per day for 3 days following exercise restored muscle
energy levels to normal, while treatment with placebo provided virtually no effect.29 This study clearly showed that ribose
stimulated the energy recovery pathways in the body, helping
the muscle rebuild its energy supply quickly and completely.
Even after 3 days of rest, muscle that was not treated with
ribose remained energy starved and fatigued.
Two very interesting animal studies showed how dramatically ribose could affect energy recovery in fatigued muscle.
Researchers found that ribose administration in fatigued
muscle shortened the duration of recovery by 340% to 430%,
depending on the type of muscle.30 They also found that even
very small amounts of ribose had the effect of helping the
muscle cell preserve energy, a process known as energy salvage, and that the higher the ribose dose, the more dramatic its
effect on energy preservation.31 Although this groundbreaking
research was done in animals, it was instrumental in defining
the biochemistry and physiology associated with use of ribose
in overcoming heart and muscle fatigue.
Research on ribose and CFS/FMS began with a case study
that was published in the journal Pharmacotherapy in 2004.32
This case study told the story of a veterinary surgeon diagnosed with fibromyalgia. For months, this dedicated doctor
found herself becoming more and more fatigued, with pain
becoming so profound she was finally unable to stand during
surgery. As a result, she was forced to all but give up the practice she loved.
Upon hearing that a clinical study on ribose in congestive
heart failure was underway in the university where she worked,
she asked if she could try the ribose to see if it might help her
overcome the mind-numbing fatigue she experienced from her
disease. After 3 weeks of ribose therapy she was back in the
operating room, practicing normally with no muscle pain or
stiffness, and without the fatigue that had kept her bedridden
for many months.
Being a doctor, she was skeptical, not believing that a
simple sugar could have such a dramatic effect on her condition. Within 2 weeks of stopping the ribose therapy, however,
she was out of the operating room and back in bed. So, again to
test the theory, she began ribose therapy a second time. The
result was similar to her first experience and she was back doing
surgery in days. After yet a third round of ribose stopping (with

Integrative Medicine Vol. 7, No. 2 Apr/May 2008

49

return of symptoms) and starting (with reduction of symptoms), she was finally convinced, and has since remained on
ribose therapy.
To further validate such research on ribose and to continue
with our own published research began earlier, we are currently
conducting a placebo-controlled study using ribose in fibromyalgia; we hope to have the results published in the coming year.
Interestingly, one of our earlier ribose pilot study patients had
atrial fibrillation. Ribose is also outstanding in treatment of
heart disease because it restores energy production in the heart
muscle. Because of this, it was not surprising that this mans
atrial fibrillation went away within a few weeks on the ribose and
he was able to stop his heart medications as well. I use ribose in
all of my cardiac patients, as improving muscle efficiency can
decrease tissue oxygen needs, and, therefore, congestive heart
failure, in addition to arrhythmias and angina. Because of its
importance and the research showing marked heart muscle
dysfunction (because of low energy) in CFS, let us take a closer
look at ribose and the heart.
Ribose and Heart Disease

Decades of research have shown that ribose has a profound effect on heart function in patients with congestive
heart failure, coronary artery disease, and cardiomyopathy (a
weakened heart muscle). Like the muscles in patients with
fibromyalgia, sick hearts are energy starved.33 This energy
deprivation keeps the heart from relaxing between heartbeats,
making it impossible for the heart to completely fill with blood
(it takes more energy for the heart muscle to relax than contract).34 Because the heart does not fill completely, less blood
is pumped to the body with each heartbeat. The heart then
gets stiff as it strains to contract. Ultimately, the heart becomes
hypertrophic (enlarged) and is unable to pump normally.
You can compare this to the effect of weight training on
the biceps of the upper arm. Over time, weight training against
more and more weight makes the muscle larger and harder.
Similarly, when the heart becomes stiff, it is forced to contract
against more and more pressure, making the heart muscle
grow. While in the case of the biceps this may be a desirable
outcome, in the heart it can be deadly. In contrast to the biceps
muscle, hearts must remain supple so they can fill properly
and empty fully with each contraction. If a heart cannot pump
normal volumes of blood, muscles of the arms and legs as well
as brain tissue become oxygen starved. The result is fatigue,
shortness of breath and/or pain on standing or walking, loss of
interest in or the inability to perform any physical activity,
brain fog, and depression. In the end, the heart cannot pump
enough blood to supply even itself with life-giving oxygen. The
result can be a heart attack.
Using ribose to optimize the energy level in the heart
allows it to fully relax and fill and completely empty so as to
more efficiently circulate blood to the outer reaches of the
body.35 Circulating more blood means muscles in the arms
and legs, and in the tissues of the brain, get the oxygen they
need to function normally. This result was made evident in
several important studies in patients with congestive heart

50

Integrative Medicine Vol. 7, No. 2 Apr/May 2008

failure and angina, described below.

In one study conducted at the University of Bonn in
Germany, patients with congestive heart failure were treated
every day for 3 weeks with either 10 g of ribose or a sugar placebo. 36 They were then tested for heart function, exercise tolerance (a measure of fatigue), and quality of life using a questionnaire designed for this purpose. In this study, ribose therapy had a significant effect on all measures of diastolic heart
function, showing that increased energy in the heart allowed
the heart to relax, fill, and pump more normally. When they
were on ribose, patients in the study were also much more
tolerant to exercise and, through their responses to the questionnaire, showed they had a resultant higher quality of life.
Two additional studies went on to help explain how
ribose therapy in congestive heart failure may positively affect
fatigue and exercise tolerance.37,38 These studies showed that
ribose treatment increased ventilatory and oxygen utilization
efficiency, meaning that the patients were able to breathe better and use the oxygen they inhaled more efficiently. Improving
the patients ability to use oxygen means more oxygen is available to be carried by the blood out to the tissues. Having more
oxygen available allows the muscle to burn fuel more efficiently, helping it keep pace with its energy demand. The result is
less fatigue, a greater ability to tolerate exercise, and a higher
quality of life. An added benefit to improving ventilatory efficiency is that ventilatory efficiency is a dominant predictor of
mortality in congestive heart failure. Increasing ventilatory
efficiency with ribose therapy is, therefore, a direct correlate to
prolonging life in this patient population.
Side Effects

The main side effect seen with ribose is that some 4% to 5%

of patients feel hyper or over energized on it. If this occurs,
simply have them take the supplement with food and lower the
dose. This side effect occurs because ribose has a negative glycemic index, lowering blood sugar. Diabetics using it mostly need
to watch for a drop in blood sugar, although rarely a rise in
blood sugar can occur.
Additionally, I would use it very carefully in bipolar
patients to avoid activation (we have not seen this, but it is
possible). When used in conjunction with prescription medications, caution is required. If ribose is used with Coumadin
(warfarin), for example, it is important to check initial bleeding times.
Conclusion

Very few nutritional therapies can legitimately boast of

having such a profound effect on the tissues they target, especially such an effect in cell or tissue energy metabolism. Ribose
is a unique and powerful addition to our complement of metabolic therapies in that it is completely natural, safeproven by
strong, well-designed clinical and scientific evidenceand
fundamental to vital metabolic processes in the body.39-43
Ribose regulates how much energy we have in our bodies,
and for those suffering from fatigue, muscle soreness, stiffness,
heart disease, and a host of related medical complications, the

TeitelbaumEnhancing Mitochondrial Function With D-Ribose

relief found in energy restoration can be life changing. This is

why I recommend that all CFS/FMS and cardiac patients begin
with D-ribose. Ribose recently became available (over the counter) to physicians, and is one of the few natural products actually starting with physicians and then moving out into health
food stores.
I take my ribose every day because, even though I feel
great, it makes me feel even better!
Jacob Teitelbaum, MD, is medical director of the Fibromyalgia and
Fatigue Centers, a nationwide group of clinics. He is senior author of Effective
Treatment of CFS and FMS: A Randomized, Double-Blind Placebo Controlled
Study, Journal of Chronic Fatigue Syndrome 2001;8(2):3-24), and The Use of
D-ribose in Chronic Fatigue Syndrome and Fibromyalgia: A Pilot Study,
Journal of Alternative and Complementary Medicine 2006;12(9):857-862. Dr
Teitelbaum is also author of From Fatigued to Fantastic! (3rd ed, Penguin/
Avery, 2007), Three Steps to Happiness! Healing through Joy (Deva Press), and
Pain Free 1-2-3 A Proven Program to Get YOU Pain Free! (McGraw Hill, 2006). Dr
Teitelbaum lives in Kona, Hawaii.
References
1. Vernon SD, Whistler T, Cameron B, Hickie IB, Reeves WC, Lloyd A. Preliminary
evidence of mitochondrial dysfunction associated with post-infective fatigue after
acute infection with Epstein Barr Virus. BMC Infect Dis. 2006 Jan;31(6):15.
2. Bengtsson A, Henriksson KG. The muscle in fibromyalgiaa review of Swedish
studies. J Rheumatol Suppl. 1989 Nov;19:144-149.
3. Teitelbaum JE, Bird B, Weiss A, et al. Effective treatment of CFS and FMS: A randomized, double-blind placebo controlled study. J Chronic Fatigue Syndrome.
2001;8(2):3-24.
4. Eisinger J, Plantamura A, Ayavou T. Glycolysis abnormalities in fibromyalgia. J
Am Coll Nutr. 1994;13(2):144-148.
5. Bengtsson A. The muscle in fibromyalgia. Rheumatology (Oxford). 2002
Jul;41(7):721-724.
6. Lund N, Bengtsson A, Thorborg P. Muscle tissue oxygen pressure in primary
fibromyalgia. Scand J Rheumatol. 1986;15(2):165-173.
7. Strobel ES, Krapf M, Suckfll M, Brckle W, Fleckenstein W, Mller W. Tissue
oxygen measurement and 31P magnetic resonance spectroscopy in patients with
muscle tension and fibromyalgia. Rheumatol Int. 1997;16(5):175-180.
8. Douche-Aourik F, Berlier W, Fasson L, et al. Detection of enterovirus in human
skeletal muscle from patients with chronic inflammatory muscle disease or fibromyalgia and healthy subjects. J Med Virol. 2003;71(4):540-547.
9. Park JH, Phothimat P, Oates CT, Hernanz-Schulman M, Olson NJ. Use of P-31
magnetic resonance spectroscopy to detect metabolic abnormalities in muscles of
patients with fibromyalgia. Arthritis Rheum. 1998;41(3):406-413.
10. Kushmerick MJ. Muscle energy metabolism, nuclear magnetic resonance spectroscopy and their potential in the study of fibromyalgia. J Rheumatol Suppl. 1989
Nov;19:40-46.
11. Bengtsson A, Henriksson KG, Larsson J. Reduced high-energy phosphate levels in
the painful muscles of patients with primary fibromyalgia. Arthritis Rheum.
1986;29(7):817-821.
12. Lund E, Kendall SA, Janerot-Sjoberg B, Bengtsson A. Muscle metabolism in fibromyalgia studied by P-31 magnetic resonance spectroscopy during aerobic and
anaerobic exercise. Scand J Rheumatol. 2003;32(3):138-145.
13. Eisinger J, Bagneres D, Arroyo P, Plantamura A, Ayavou T. Effects of magnesium,
high-energy phosphates, piracetam and thiamin on erythrocyte transketolase.
Magnes Res. 1994;7(1):59-61.
14. Jacobsen S, Jensen KE, Thomsen C, Danneskiold-Samsoe B, Henriksen O.
Magnetic resonance spectroscopy in fibromyalgia. A study of phosphate-31 spectra from skeletal muscles during rest and after exercise. Ugeskr Laeger.
1994;156(46):6841-6844.
15. Olsen NJ, Park JH. Skeletal muscle abnormalities in patients with fibromyalgia.
Am J Med Sci. 1998;315(6):351-358.
16. Henriksson KG. Muscle pain in neuromuscular disorders and primary fibromyalgia. Neurologija. 1989;38(3):213-221.
17. Krapf MW, Mller S, Mennet P, Stratz T, Samborski W, Mller W. Recording
muscle spasm in the musculus erector spinae using in vivo 31P magnetic resonance spectroscopy in patients with chronic lumbalgia and generalized tendomyopathies [article in German]. Z Rheumatol. 1992;51(5):229-237.
18. Behan PO. Post-viral fatigue syndrome research. In: Goldstein J, Hyde B, Levine P,
eds. The Clinical and Scientific Basis of Myalgic Encephalitis and Chronic Fatigue
Syndrome. Ottawa, Ontario: Nightingale Research Foundation; 1992: 238.
19. No authors listed. Symptoms of mitochondrial cytopathies. United Mitochondrial
D i s e a s e Fo u n d a t i o n . Ava i l a b l e at : h t t p : / / w w w. u m d f . o r g / s i t e / c .
dnJEKLNqFoG/b.3042207/. Accessed March 4, 2008.
20. Mignot E, Taheri S, Nishino S. Sleeping with the hypothalamus: emerging therapeutic targets for sleep disorders. Nat Neurosci. 2002 Nov;5 Suppl:1071-1075.

TeitelbaumEnhancing Mitochondrial Function With D-Ribose

21. Everson CA. Sustained sleep deprivation impairs host defense. Am J Physiol.
1993;265(5 Pt 2):R1148-R1154.
22. Palkovits M. Interconnections between the neuroendocrine hypothalamus and
the central autonomic system. Geoffrey Harris Memorial Lecture, Kitakyushu,
Japan, October 1998. Front Neuroendocrinol. 1999;20(4):270-295.
23. Demitrack MA, Dale K, Straus SE, et al. Evidence for impaired activation of the
hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J
Clin Endocrinol Metab. 1991:73(6);1223-1234.
24. Neeck G, Riedel W. Thyroid function in patients with fibromyalgia syndrome. J
Rheumatol. 1992:19(7):1120-1122.
25. Calis M, Gkce C, Ates F, et al. Investigation of the hypothalamo-pituitary-adrenal
axis (HPA) by 1ug ACTH test and metyrapone test in patients with primary fibromyalgia syndrome. J Endocrinol Invest. 2004;27(1):42-46.
26. Cleare AJ, Miell J, Heap E, et al. Hypothalamo-pituitary-adrenal axis dysfunction
in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy. J
Clin Endocrinol Metab. 2001;86(8):3545-3554.
27. Bakheit AM, Behan PO, Watson WS, Morton JJ. Abnormal arginine-vasopressin
secretion and water metabolism in patients with post-viral fatigue syndrome. Acta
Neurol Scand. 1993;87(3):234-238.
28. 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;12(9):857-862.
29. Hellsten Y, Skadhauge L, Bangsbo J. Effect of ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humans. Am J
Physiol Regul Integr Comp Physiol. 2004;286(1):R182-R188.
30. Tullson PC, Terjung RL. Adenine nucleotide synthesis in exercising and endurance-trained skeletal muscle. Am J Physiol. 1991;261(2 Pt 1):C342-C347.
31. Brault JJ, Terjung RL. Purine salvage to adenine nucleotides in different skeletal
muscle fiber types. J Appl Physiol. 2001;91(1):231-238.
32. Gebhart B, Jorgenson JA. Benefit of ribose in a patient with fibromyalgia.
Pharmacotherapy. 2004;24(11):1646-1648.
33. Ingwall JS. ATP and the Heart. Norwell, MA: Kluwer Academic Publishers; 2002.
34. Reibel DK, Rovetto MJ. Myocardial ATP synthesis and mechanical function following oxygen deficiency. Am J Physiol. 1978;234(5):H620-H624.
35. Zimmer HG, Ibel H, Suchner U, Schad H. Ribose intervention in the cardiac pentose phosphate pathway is not species-specific. Science. 1984;223(4637):712-714.
36. Omran H, Illien S, MacCarter D, St Cyr JA, Lderitz B. D-Ribose improves diastolic function and quality of life in congestive heart failure patients: a prospective
feasibility study. Eur J Heart Fail. 2003;5(5):615-619.
37. Vijay N, MacCarter D, Washam M, St Cyr J. Ventilatory efficiency improves with
d-ribose in congestive heart failure patients. Paper presented at: Heart Failure
Society of America Conference; September 18-21, 2005; Boca Raton, Florida.
38. Carter O, MacCarter D, Mannebach S, et al. D-Ribose improves peak exercise
capacity and ventilatory efficiency in heart failure patients. Abstract presented at:
American College of Cardiology Annual Scientific Session 2005; March 6-9 2005;
Orlando, Florida.
39. Griffiths JC, Borzelleca JF, St Cyr J. Lack of oral embryotoxicity/teratogenicity with
D-ribose in Wistar rats. J Food Chem Toxicol. 2007;45(3):388-395.
40. Griffiths JC, Borzelleca JF, St Cyr J. Sub-chronic (13-week) oral toxicity study with
D-ribose in Wistar rats. J Food Chem Toxicol. 2007:45(1):144-152.
41. Gross M, Kormann B, Zllner N. Ribose administration during exercise: effects on
substrates and products of energy metabolism in healthy subjects and a patient
with myoadenylate deaminase deficiency. Klin Wochenschr. 1991;69(4):151-155.
42. Wagner DR, Gresser U, Zllner N. Effects of oral ribose on muscle metabolism
during bicycle ergometer in AMPD-deficient patients. Ann Nutr Metab.
1991;35(5):297-302.
43. Gross M, Reiter S, Zllner N. Metabolism of D-ribose administered to healthy
persons and to patients with myoadenylate deaminase deficiency. Klin Wochenschr.
1989;67(23):1205-1213.

Integrative Medicine Vol. 7, No. 2 Apr/May 2008

51