Individuals with CFS/FMS are found to have: 20% less energy in their muscles,, defective or inefficient mitochondria, nutrient deficiencies in cells and tissues needed to process food into energy, and thickened capillary walls slowing the rate of synthesizing energy.

As cellular energy is depleted, fatigue and muscle pain become more and more severe and the muscles require additional energy in their recovery efforts. Energy is used faster than fuel is made available to renew it, and the fatigue, soreness, pain and stiffness continue to progress. Energy depletion reaches a critical point and CFS/FMS becomes a state in which the mechanisms for recovery are overwhelmed.

D-Ribose is a naturally occurring five-carbon sugar found in all living cells. It is the D-isomer of ribose that has been shown to possess biological activity. The body naturally converts glucose into ribose. Ribose is then used to drive the pathways of energy metabolism. One of the problems faced when the body’s ribose stores have been depleted, is that tissues such as heart and muscle are unable to produce it quickly enough to restore this depleted energy store. It is this delay that slows cellular and tissue energy recovery.

D-ribose is a component of ATP, RNA, NADH, and coenzyme-A, all needed by the mitochondria to maintain cellular energy homeostasis. In the body, we form ribose through the pentose phosphate pathway (PPP) or through the hexose monophosphate shunt. In heart and muscle tissue, the PPP is fairly slow because these tissues lack the enzymes needed to shunt the glucose in the pathway of ribose synthesis. These tissues instead prefer to use glucose to fuel ATP. The enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase preserve glucose metabolism, at a cost to ribose synthesis. When ribose is needed to rebuild the ATP pools, the process is slow. This is the main rationale for providing supplemental ribose for heart and muscle tissue, the purpose being to speed up the rebuilding of depleted ATP pools, thereby promoting a quicker more efficient tissue recovery.

Most body tissues cannot make enough ribose to restore energy levels to normal once they have been depleted. When cells suffer metabolic stress or mitochondrial dysfunction, ATP is catabolized and metabolic recovery is compromised. These mechanisms may be similar to what occurs in individuals with CFS. Under these conditions, adenosine diphosphate (ADP) accumulates and the cells try to balance the ratios of ATP with ADP to maintain energy. These reactions lead to catabolic end products that are washed out of the cell with a subsequent loss in purines and adenine nucleotides. One therapeutic option is to try to restore these energy substrates in order to recover the function of the cell, including muscle cells. By providing supplementation in the form of ribose, it is possible to enhance the nucleotide recovery, and preserve or even rebuild cellular energy stores.

D-ribose research in CFS/FMS was initiated with a case study in 2004 of a veterinary surgeon with fibromyalgia. After 3 weeks of ribose she was back to full time work, with her profound fatigue and muscle pain having disappeared. An important study was also done involving high-intensity athletes. Post exercise, muscle energy levels were reduced by almost 30%. Supplementing with 10 g of ribose per day for 3 days following the exercise restored muscle levels to normal while those treated with placebo received no effect.

An open-label uncontrolled pilot study was done to evaluate the effect of D-ribose on symptoms in forty-one CFS and FMS patients D-ribose was given at a dose of 5 grams t.i.d. for an average of three weeks. Questionnaires pre and post D-ribose intervention were compared and showed a significant improvement in five categories: energy, sleep, mental clarity, pain intensity and well being. At the end of the study, approximately 66% of patients experienced significant improvement while using D-ribose. These patients had a 45% average increase in energy and a 30% overall improvement in well-being.

Many individual nutrients and botanicals are utilized in the treatment of CFS/FMS: magnesium, CoQ10, malic acid, vitamin D, rhodiola, licorice, ginseng, resveratrol, carnitine and more. While most alternative minded practitioners embrace a whole system, mind/body, functional approach in working with these challenging clinical situations, I have found D-ribose to be the single most important nutrient in the search for alleviation of symptoms and a path towards health. I thank Jacob Teitelbaum, M.D. and other D-ribose researchers for pointing us in the right direction.

References

• No authors listed. Symptoms of mitochondrial cytopathies. United Mitochondrial Disease Foundation. Avalable at http://www.umdf.org/site/c.dnJEKLNqFoG/b.3042207/. Accessed March 4, 2008.
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• Douche-Aourik F, Berlier W, Feasson L, et al. Detection of enterovirus in human skeletal muscle from patients with inflammatory muscle disease or fibromyalgia and healthy subjects. J Med Virol. 2003;71(4):540-547.
• Park J, Phothimat P, Oates C, Hernanz-Schulman M, Olson N. Use of P-31 magnetic resonance spectroscopy to detect metabolic abnormalities in muscles of patients with fibromyalgia. Arthritis Rheum. 1998; 41(3):406-413.
• Kushmerick M. Muscle energy metabolism, nuclear magnetic resonance spectroscopy and their potential in the study of fibromyalgia. J Rheumatol Suppl. 1989 Nov; 19:40-46.
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• 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.
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• Gebhart B, Jorgenson J. Benefit of ribose in a patient with fibromyalgia. Pharmacotherapy. 2004;24(11):1646-1648.
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• Teitelbaum J, 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):857-862.

Pregnancy is demanding in it’s own unique way: hormonal changes, increased nutritional demands, changes in sleep and eating patterns. Regular exercise, good healthy eating habits, a prenatal supplement, regular sleep, and moderating one’s work load, are usually enough to maintain energy throughout the pregnancy. Some women may become anemic during pregnancy and simple tests can detect this followed by simple nutrients as supplementation. At times, other health problems emerge during the pregnancy that can cause fatigue such as hypothyroid and diabetes. With good prenatal care, these can be detected and treated appropriately.

The cycles or phases of hormonal change such as the monthly premenstrual time, and the perimenopause transition can challenge what is called our stress adaptation mechanisms. There are three phases to this stress response which are regulated in large part, by our adrenal glands. The initial phase is the alarm reaction, or fight-or-flight response. This is triggered by reactions in the brain that cause the pituitary gland to produce a hormone, which causes the adrenals to secrete adrenaline as well as other stress related hormones. The alarm phase is usually very short lived. The next phase is the resistance reaction, which allows us to continue to deal with stress, after the fight-or-flight response has worn off. Hormones such as cortisol and other corticosteroids secreted by the adrenal cortex are in motion here and responsible for the resistance reaction. These hormones stimulate the conversion of protein to energy so that we have adequate fuel, after our glucose reservoirs have been used. The resistance reaction provides the energy and stabilizes our circulation under times of stress, as well as enabling us to deal with the emotional aspects of stress, fight infections and continue to perform our tasks. If the stress insult is prolonged and the resistance reaction is extended beyond our body’s capabilities to maintain balance, we become at risk for significant health care problems and end up in the final stage of general adaptation syndrome— exhaustion. In the exhaustion phase, our adrenal glands
have become depleted of hormones called glucocorticoids, and our body has a loss of potassium. In this phase, the body’s cells and tissues do not receive enough glucose or other nutrients to function properly.

As the exhaustion phase continues, our cells and organs in general feel the tremendous demand, and our metabolism is extremely challenged. Now we enter what we might call cellular fatigue and literally, our cells don’t get enough fuel to drive their function. This stress to our system takes a toll and nutritional status declines and disease status increases.

Premenstrual syndrome and perimenopause are their own kind of stress on the system. During these times, many women find their threshold of tolerating stress decreases. The complicated interaction of our hormones and our brain chemistry challenges our stress adaptation mechanisms, and fatigue can result. These fluctuating levels, both decreases and increases, in hormones such as estrogen, progesterone, cortisol and thyroid, interact with brain neurotransmitters such as serotonin, dopamine, GABA, and others, that affect our emotional and physical responses to life, to stressors in our environment, to insults, and even to infections.

Different circumstances call for different approaches, and if persistent fatigue is something that plagues you, it is important to consult with a licensed health care practitioner to determine the cause. A good medical history, physical exam, and selected laboratory tests can determine if the cause is low thyroid, anemia, an infectious agent, low or high blood sugar, or a serious illness. Licensed alternative practitioners will also have tools and perspectives to consider food sensitivities, toxicities, neurotransmitter imbalances, hormonal status and something we call adrenal fatigue syndrome.

A condition alternative medicine often calls “adrenal fatigue”, is a unique contribution to understanding a sometimes elusive problem such as fatigue.

Adrenal gland function and its production of hormones are vital performance tasks in our response to stress and our larger responses in our general adaptation syndrome. Nutritional and herbal support for a person who displays symptoms of intense or prolonged stress, and/or a fatiguing of the ability to adapt to the stress, can play a critical role in supporting our adrenal glands to adapt. An abnormal adrenal response, whether it is deficient or excessive hormone release, can be in large part addressed with key nutrients such as pantothene, B6, zinc, magnesium and vitamin C. These nutrients play a critical role in the optimal function of the adrenal glad and in the manufacture of adrenal hormones. Levels of these nutrients can be diminished during times of stress. Urinary excretion of vitamin C is increased during stress. Pantothene is also important during times of high stress or in individuals with adrenal fatigue. A deficiency of pantothenic acid results in fatigue, headaches, insomnia and more. Notable botanicals can also support adrenal function and enhance resistance to stress such as Siberian and Panax ginseng. These ginsengs are referred to as general tonics or adaptogens. Both Chinese and Siberian ginseng can be used to restore vitality in individuals who are chronically fatigued or who have decreased mental and physical performance and/or stamina. These ginseng species have been shown to act as tonics and anti-stress agents, enhancing the ability to cope with both physical and emotional stressors., , Individuals who take ginseng often report an increase in vitality, well being, increased mood, competence at work, mental and physical performance and reduced feelings of stress and anxiety. Rhodiola is well known amongst the Eastern Europeans for its ability to enhance energy, stamina and endurance. rhodiola appears to increase the chemicals that provide energy to the muscle of the heart and to prevent the depletion of adrenal hormones induced by acute stress.

Ashwagandha is also a significant adaptogen providing adrenal and immune support, , for increasing resistance to environmental stressors and as a general tonic. Ashwagandha contains several important active constituents including withanolides. Its mechanisms of action include pain relief, antioxidant effects, reducing inflammation, stimulating thyroid function, as well as respiratory and immune function. Some researchers have claimed that ashwagandha as an antistressor effect. It appears that it may suppress stress induced increases in dopamine receptors in the brain.

Astragalus has been used historically for strengthening and regulating the immune system, as a tonic, antioxidant, anti-inflammatory, antibacterial antiviral and to protect the liver. A lengthy list for sure. Although there is insufficient evidence to support the effectiveness of all of these uses, there is preliminary research that it is positive in some areas. Astragalus extracts seem to be able to restore or improve immune function in immune deficient cases. It may be able to restore suppressed T-cell function in cancer patients.7 Abnormal liver enzyme tests have improved in people chronic hepatitis when taking Astragalus. Astragalus is also thought to increase cardiac output and may be beneficial in individuals with congestive heart failure and compromised blood flow to the heart muscle. 8

We’re all familiar with our favorite spaghetti sauce that contains basil, but we may not know that this same plant, also known as Holy basil is a rich source of vitamin C, calcium, magnesium, potassium and iron. Holy basil has been gaining some attention due to experimental studies in humans on blood glucose. Elevated glucose levels were lowered by 21 mg/dl and lowering glucose after a meal, was also a positive effect of the basil. Many individuals with adrenal dysfunction, have increased glucose levels due to the increased cortisol as a result of stress.

Shisandra is plant most familiar to those who use Chinese herbs. In traditional Chinese medicine, schisandra is used for many common problems, including physical fatigue. Schisandra is used for improving immune function, recovery after surgery, increasing physical performance and endurance, and for increasing resistance to disease and stress. Schisandra is also possibly effective for improving concentration. It is thought that the variety of lignans found in the fruit, are the active constituents in schisandra.

Maca, or Peruvian Ginseng, may be one of the most important plants having a diverse effect on the female reproductive system. Traditionally, it has been used for chronic fatigue syndrome, enhancing energy, stamina and overall energy. In the female reproductive system, its use for enhancing fertility, regulating the menstrual cycle, treating common menopause symptoms and to increase libido has been familiar to the traditional peoples of Peru and elsewhere, for many a generation. Studies soon to be published, will be able to document some of its specific effects for menopausal women.

This type of herbal/nutritional support is especially helpful for those who have been determined to have adrenal fatigue. Symptoms such as fatigue, low vitality, low libido, depression, anxiety, poor memory, low stamina, and difficulty handling the premenstrual phase and the perimenopausal transition are key indications of adrenal fatigue.

Some women who have premenstrual fatigue or perimenopausal fatigue, may need additional hormonal support as well. This may include actually using hormones as medicines, but also may involve improving the metabolisim of our hormones. These considerations can best be addressed utilizing a comprehensive approach with a licensed naturopathic physician who has both the alternative medicine perspective, as well as the ability to prescribe various hormones such as progesterone, estrogen, testosterone, cortisol and thyroid.

The best approach to fatigue is to find out the cause. Don’t just ignore your fatigue and “gut it out” and don’t make assumptions about the cause of your fatigue. With good health care team approach utilizing your insights, your reading and natural foods store resources, a naturopathic physician, and possibly medical doctor or other allied practitioners, you can be more assured of understanding the cause and therefore the best solutions.

ReferencesÂ

• Farnsworth N, et al. Siberian Ginseng: Current status as an adaptogen. Economic Medicinal Plant Research 1985;1: 156-215.
• Hikino H. Traditional remedies and modern assessment: The ase of Ginseng. In R.O.B. Wijeskera, ed. The Medicinal Plant Industry (Boca Raton, FL: CRC Press, 1991), 149-166.
• Shibata S, et al. Chemistry and Pharmacology of Panax. Econ Med Plant Research 1985;1:217-284.
• Hallstrom C, Fulder S, Carruthers. Effect of Ginseng on the performance of nurses on night duty. Comp Med East and West 1982;6:277-282.
• Maslova L, Kondrat’ev B, Maslov L, Lishmanov I. The cardioprotective and antiadrenergic activity of an extract of Rhodiola rosea in stress. Eksp Klin Farmakol 1994;57:61-63. (Article in Russian).
• Upton R, ed. Ashwagandha root (Withania somnifera): Analytical, quality control, and therapeutic monograph. American Herbal Pharmacopoeia 2000;April: 1-25.
• Sun Y, Hersh E, Talpaz M, et al. Immune restoration and/or augmentation of local graft versus host reaction by traditional Chinese medicinal herbs. Cancer 1983;52(1): 70-3.
• Upton R, Ed. Astragalus Root: analytical, quality control, and therapeutic monograph. Santa Cruz, CA: Am Herbal pharmacopoeia; 1999; 1-25.
• Agrawal P, Rai V, Singh R. Randomized placebo-controlled, single blind trial of holy basil leaves in patients with noninsulin-dependent diabetes mellitus. Int J Clin Pharmacol Ther. 1996;34(9): 406-409.
• Upton R, ed. Schisandra Berry: Analytical, Quality and Control, and Therapeutic Monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 1999; 1-25.