Metabolic Toxicity and Neuromuscular Pain, Joint Disorders and Fibromyalgia

By: Alan H. Pressman, DC

Note: The information on this website is not a substitute for the advice of & treatment by a qualified professional.

Alan H. Pressman, MS, DC, DACBN, CCSP, is past president of the Council on Nutrition of the American Chiropractic Association; former chairman, department of nutrition, New York Chiropractic College, and, associate professor of biology, University of Bridgeport, Conn. He is currently the director of research, Institute of Rehabilitative Nutrition, and maintains an active practice in New York City.

In a recent paper published in the journal Seminars in Arthritis and Rheumatism, rheumatologists Bland and Cooper reviewed the possible reversibility of degenerative joint disease.1 In this article they propose that the degeneration of hyaline cartilage occurs as a consequence of activation of monocytes, macrophages and neutrophils which re­lease oxidants that in turn attack connective tissue and the joint lubricant substance hyaluronic acid. The activation of white cells that in turn release alarm substances and oxidants occurs as a consequence of an inflammatory cascade modulated through receptor sites on the surface of white cells which are stimulated by the presence of foreign molecules. These foreign molecules have been termed metabolic toxins and are from exogenous and endogenous sources.

The proposed mechanism that describes the degeneration of connective tissue resulting in degenerative joint disease also applies to other neuromuscular degenerative problems including fibromyalgia.2 The accumulation of exogenous or endogenously produced substances that exceeds the threshold of activation is well acknowledged to produce an inflammatory cascade. This inflammatory cascade results in the production of alarm messenger substances called leucotrienes which in turn activate white cells such as the macrophages, monocytes and neutrophils to release oxidants, which include superoxide and its conversion products, hydrogen peroxide and hydroxyl radical. These very reactive non-specific oxidants in turn attack the localized tissue resulting in inflammation or irritation which in the long tern produces degeneration.3

There is now a considerable body of evidence indicating that many of these degenerative joint disease conditions are associated with a permeable gut, 4 liver detoxication pathways5 and activation of the pain-producing inflammatory cascade. 6

In the past there has been no effective way for evaluating hepatic detoxication pathways to examine whether a patient suffering from degenerative joint disease, neuromuscular problems or fibromyalgia has those symptom as a consequence of insufficient detoxication of exo- or endotoxins. Recently, however, a new non-invasive oral challenge protocol has been developed to evaluate functional liver capabilities for detoxicating substances which, if under-converted, can result in the stimulation of the inflammatory cascade. These tests include the oral caffeine challenge to evaluate hepatic cytochrome P450 activity7 and sodium benzoate loading to evaluate liver glycine conjugation activity.8 These tests involve the oral administration of two very safe substances. The first is caffeine, where the disappearance of salivary caffeine is a measurement of hepatic cytochrome P450 activity and the second is the oral administration of sodium benzoate (a generally regarded as safe FDA-approved food additive), with urine being collected for the measurement of hippuric acid. Hippuric acid is the glycine conjugate of sodium benzoate, and its appearance in the urine is a measurement of how effectively the liver is able to conjugate foreign molecules, preparing them for excretion.

By utilizing the salivary caffeine clearance test and the urinary hippuric acid excretion test, the clinician has the ability to probe the state of metabolic detoxication of endo- and exotoxins in a patient suffering from various forms of joint disorders and neuromuscular problems.

Once it has been determined that the patient is suffering from either a permeable gut, which increases the load of exotoxins on the body, or a functional inactivity of liver detoxifying enzymes as measured by the salivary caffeine clearance and urinary hippuric acid output studies, an intervention program can be applied which helps improve liver detoxication ability. This program utilizes specific macro- and micronutritional elements which have been demonstrated to promote upregulation of cytochrome P450 and liver conjugate activity. 9 This food-based program utilizes a nutritionally-balanced product consisting of an amino acid fortified rice protein concentrate, rice carbohydrate, medium-chain triglycerides, along with adequate vitamin and mineral enrichment to enhance hepatic cytochrome P450 activity. Research that has been done over the past two years indicates that significant enhancement of both cytochrome P450 and liver conjugase activity does occur in patients, when placed on this nutritional intervention program, who have depressed detoxicating ability.

Recent clinical reports have demonstrated the value of this assessment and nutritional intervention program in managing patients with a number of neuromuscular, degen­erative joint-related, and fibromyalgia symptoms. The underlying principle of this program is based on the concept of “primum non nocere” (first, do no harm) which is the basis of the Hippocratic oath. Because the nutritional intervention program is complete with respect to macro-and micronutrition and calories, it produces no untoward nutritional effects and does not expose the individual to therapeutic doses of nutrients that might be considered toxic in the long term. A positive benefit is that most patients will demonstrate a very significant improvement in detoxicating liver enzyme activities while lowering the body burden of metabolic toxins, which reduces the impact on the inflammatory cascade.

In a recent paper, Dr. J.O. Hunter, a well-known clinical immunologist from Cambridge Hospital in England, proposed that we could call these symptoms of joint pain, muscle pain and neuromuscular difficulties associated with metabolic toxicity as “enterometabolic disorders.”10 In this context, he suggests that substances which pass from the gastrointestinal tract into systemic circulation, if not properly detoxicated, can result in activation of the inflammatory cascade and immunological and endocrine systems producing diffuse muscular, skeletal and neuromuscular symptoms. The relationship of enterometabolic disorders to liver detoxicating ability is now seen from recent research as being very important. It is not only the load of po­tentially toxic substances that an individual is exposed to that enhances his or her risk to neuromuscular disorders, but it is also the relative ability of the liver to detoxify and excrete the endo- and exotoxic materials. Utilizing the salivary caffeine clearance and urinary hippuric output studies to evaluate liver detoxifying ability and the nutritional intervention program to upregulate cytochrome P450 and conjugase activities, a very effective program can now be applied for the management of these enterometabolic disorders which have a relationship to musculoskeletal pain and degeneration.


1. Bland, J.H., Cooper, S.M. Osteoarthriac A Review of the Cell Biology Involved and Evidence for Reversibility. Management Rationally Related to Known Gene­sis and Pathophysiology. Seminars in Arthritis and Rheumatism, Nov. 1.984, Vol. 14, No. 2.

2. Sokoloff, L.: Arthritis and Allied Dis­eases. Philadelphia, Lea and Febiger, 1978.

3. Peyron, J.: Inflammation in Osteoarthritis: Review of its role in clinical picture, disease progression, subsets and pathophysiology. Sernin. Arthritis Rheuma­lism,1981;11:115-116.

4, Finch, W. Arthritis and the gut. Post­graduate Medicine,1989; 86:229-234

5. Anderson, K.E., Conney, A.H., Kappas, A. 1979, Nutrition and oxidative drug metabolism in man: relative influence of dietary lipids, carbohydrate and protein. Clin Pharmacol Ther-26:493-501.

6. Muir, H.: Molecular approach to the un­derstanding of osteoarthritis. Am Rheum Dis,1977, 36:199-208.

7. Renner, E., Wietholtz, H., et al. Caffeine: A model compound for measuring liver function. Hepatology,1984; 4:38-46.

8. Tietz. N.W. Fundamentals of Clinical Chemistry. WB Saunders Company, 1976: 1057-1058.

9. Anderson. K.E., Kappas, A. Dietary reg­ulation of cytochrome P450. Annu Rev Nutr1991;11:141-67.

10. Hunter, J.0. Food allergy – or entero­metabolic disorder? Lancet 1991; 338:495-496.

Reprinted with permission of the
American Chiropractic Association for the
September 1993 issue © 1993.

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