Entero-Hepatic Resuscitation in patients with Chronic Fatigue Syndrome: A Pyramid of Nutritional Therapy
By By: Paul R. Cheney, M.D., PhD, and Charles W •
December 1, 1994
Abnormalities of cellular metabolism have been identified in patients with chronic fatigue syndrome (CFS).1,2,3 While all cells of the body are at risk for these abnormalities, certain cells of vital organ systems such as the brain, liver or gut may be at greater risk. Such organ systems, if affected, may have a very large impact on symptoms. When the cells of these vital organs are functionally impaired they have a lowered capacity to defend against toxic metabolic by-products and the body's cellular detoxification systems can be easily overwhelmed. Detoxification of the blood by the liver is especially critical in protecting the brain and other organs. Thus, in CFS, exposure to previously well tolerated foods, medications, odors, smoke, alcohol or chemicals may overwhelm the body's detoxification system and cause or exacerbate multiple physical symptoms.
Reducing the Toxic Load
There are at least three ways to reduce toxic burden in a person with CFS (PWC):
Avoidance-stay away from foods and chemicals that strain the system.
Enhance entero-hepatic as well as general cellular metabolism to improve detoxification.
Reduce nitrogen load (protein) on the system.
Nitrogen reduction is quite complicated and won't be considered here. However, avoidance and metabolic enhancement are possible with a simple diet and specially-configured nutritional supplements.
Bland and Bralley4 have recently described the use of a hypoallergenic rice-based supplement that enhances hepatic (liver) metabolism. This product, UltraClear®, has been modified and extended to enhance the metabolism and function of the gastrointestinal system as well as the hepatic metabolism (UltraClear Sustain®). When coupled with a restricted diet, PWCs detoxify more efficiently, which can result in marked improvement of systems. Rigden has used such a diet in more than 100 PWCs and obtained over 50 percent improvement in their symptoms.
This program is indicated in PWCs with:
Recurrent stomach or intestinal problems
Food intolerance or sensitivities
Chemical or environmental sensitivities
Abnormal liver function tests
Chronic muscle or joint pain
According to Bland and Bralley, "the most significant reduction in symptoms occurred with 'tired eyes' and pain behind the eyes', headaches, gastrointestinal disturbances, morning pain and stiffness and chronic respiratory complaints."
Intolerance to UltraClearSustain® is seen in some PWCs. This usually consists of nausea, dyspepsia, cramps and diarrhea. Intolerance can often be solved by lowering the dose, sipping it slowly over the day or taking it with food.
"Magnesium may be the most critical single supplement to PWCs, as known intracellular magnesium deficiencies in CFS. Such deficiencies could definitely disrupt ATP synthesis in both the glycolytic and mitochondrial pathways. Since ATP drives the membranes pumps which transport magnesium into the cell, a viscous cycles would arise in which lower ATP gives rise to even lower intracellular magnesium causing still further ATP reduction."
Boosting ATP Production
Due to recent findings of cellular defects in energy production (ATP) in CFS, 1,2,3 we have elected to use specially-configured nutrient supplements, including Reliv® products, to support and stimulate cellular ATP production Reliv Innergize® is a fructose, chromium and zinc beverage which supports the glycolytic pathway, a major auxiliary source of cellular ATP. Reliv Classic® and Reliv Now® are complex products which include multiminerals and multivitamins plus nutritional substrates; primarily branched chain amino acids (BCAAs). BCAAs are known to be efficiently taken up by cells and transported into the mitochondria where they are converted to ATP.
Because of the known defects in transmembrane mitochondrial transport in CFS patients,3 these specially-configured nutrient supplements are a rational choice to help resuscitate mitochondrial function and cellular ATP generation. Many patients treated with these products note an improvement in energy and sometimes a reduction in pain over a 6 to 8 week period of time. However, maximum benefit can take as long as 3 to 6 months in the sickest patients. While at the moment anecdotal, the benefits from using these products appear to be substantial in an unknown subset of CFS patients. We have observed that mildly ill patients respond better than sicker patients. Reliv Classic® seems to work better than Reliv Now® and there may be a dose response to Reliv Classic. Care must be exercised to avoid vitamin A or D toxicity when using Reliv Classic® for many months in doses above two scoops per day.
Additional supplements, including high dose B12 injections, sublingual CoQ10 and magnesium injections or elixirs have also been selected for their potential importance in supporting cellular energy (ATP) production. B12 is a cofactor in the further conversion of branched chain amino acids into the citric acid cycle intermediate succinyl CoA.6 The rationale for high doses of B12 includes the ability of high doses of B-vitamins to drive their relevant cofactor dependent enzymes if they are deficient.7 This effect may, as in homocystinuria, require a 1,000-fold increase in the B-vitamin even when there is no B-vitamin deficiency in the blood. CoQ10 has been added due to its important role in the final synthesis of ATP within the electron transport chain inside the mitochondria.
Magnesium is Essential
Magnesium may be the most critical single supplement to PWCs, as known intracellular magnesium deficiencies exist in CFS.9 Such deficiencies would definitely disrupt ATP synthesis in both the glycolytic and mitochondrial pathways. Since ATP drives the membrane pumps which transport magnesium into the cell, a vicious cycle could arise in which low ATP levels give rise to even lower intracellular magnesium causing still further ATP reduction. This may in fact occur in CFS patients who "crash". All this can happen with essentially normal blood levels of magnesium. Because of the normal blood levels, oral, slowly-digested solid form magnesium (tablets or solid food source) would simply be excreted by the kidneys with no benefit in terms of correcting the intracellular magnesium deficiency. By contrast, injectable (or perhaps elixirs) of magnesium would rapidly raise blood levels before the kidney could react and therefore influence intracellular magnesium; a sort of "rising tide lifts all boats" phenomenon. This would also explain the extended benefit of injectable magnesium that we have observed. Once intracellular levels rise, more ATP can be generated and then ATP dependent membrane pumps will drive in more dietary-derived magnesium from the blood.
An additional element in nutritional supplementation is the use o antioxidants. The antioxidants include high doses of vitamins C and E, beta carotene (provitamin A) and CoQ10. Antioxidants protect critical intracellular components of cells as well as the cell membrane from damage. The metabolic derangements discussed above, as well as the excess cytokine state known to exist in PWCs10 substantially increase the need for antioxidant support.
Nutritional Supplements Support Restoration
We believe it is imperative to include additional supplements in the entero-hepatic resuscitation scheme represented by UltraClear Sustain®. Organ system resuscitation itself places increased demands on cellular ATP production. Without sufficient cellular ATP to meet the demands of organ resuscitation, this can lead to treatment failures, or even the possible worsening of entero-hepatic function. Likewise, attention to intracellular homeostasis with magnesium and antioxidants may be critical to the success of supplements such as Reliv®, B12 and CoQ10. In effect, success is built on a pyramid with cellular homeostasis as the base, intracellular energy production in the middle and organ system resuscitation at the top of the pyramid.
It is, at this point, a guess as to whether or not we have addressed enough of the elements in the pyramid to achieve success in most patients. This is, of course, the reason for further studies. Fortunately, pilot studies at this clinic and elsewhere have been encouraging. We hope that by integrating these different approaches in a coherent manner, a greater response will be achieved in more patients.
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2. Cheney PR, Lapp CW, Davidson M, Nagele C: Bicycle ergometry with gas analysis and neuroendocrine responses to exercise in chronic fatigue syndrome. The 4th Annual Conference on the Medical Neurobiology of Chronic Fatigue Syndrome and Fibromyalgia Bel Air, CA; May 1993.
3. Kuratsune H, Yamaguti K, Takashi M, Misaki H, and Kitani T: Acylcarnitine deficiency in chronic fatigue syndrome. Proceedings. International CFS/ME Research Conference Albany, New York; October 1992.
4. Bland J, Bralley A: Nutritional upregulation of hapatic detoxification enzymes. J Appl Nurit 1992; 44.
5. Rigden S: Research study — CFIDS study preliminary report. Advances in the Diagnosis and Treatment of the Chronically Ill Patient. Seattle, Washington, 1991.
6. Stryer L: Biochemistry, Third edition. W.H. Freeman & Co, New York, 1988; 506.
7. Wyngaarden & Smith (Eds: Ceco; Textbook of Medicine, 16th Edition. Philadelphia: WB Saunders Co, 1988; 1:1107.
8. Perry TL, Dunn HG, Hansen S, MacDougall L, Warrington PD: Early diagnosis and therapy of homocystinuria. Pediatrics 1966; 37:502.
9. Cox IM, Campbell MJ, Dowson D: Red blood cell magnesium and chronic fatigue syndrome. Lancet 1991; 337-757.
10. Klimas N, Salvato F, Morgan R., Fletcher M: Immunological abnormalities in chronic fatigue syndrome. J Clin Microbio 1990, 28:1403-1410.
Reprinted with permission from The CFIDS Chronicle, Fall 1993 and The Cheney Clinic, P.A., Charlotte, NC.
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