Systematic Enzymes in Fibromyalgia


Elusive as it is, fibromyalgia (FM) is equally baffling, exasperating and challenging to physicians and patients alike. Described commonly as dif fuse, nondescript pain with palpable stiffness in soft tissue, syndromes associated with FM have been simultaneously dismissed out of hand and deemed as a cause célèbre. This divide may be inherent in attempts to define, in a narrative, a disorder as intangible as FM.

The core symptom of FM is widespread pain, perceived as arising from the muscle, even though joint pain may well be concomitant. Typically, FM pain and stiffness have a diurnal variation, whereby the symptoms are least bothersome between late morning and mid-afternoon hours. Further, FM symptoms wax and wane in intensity over days and weeks and are subject to flare-up upon exertion, systemic infections, soft tissue injuries, non-restorative or lack of, sleep and psychological and emotional stress. The most telling of symptoms is easy fatigability upon even moderate exertion, which could be potentially debilitating and, worse yet, frustrate therapeutic outcomes.

While a clear cut cause has not yet been identified, FM is usually associated with physical trauma, infections and psychological distress. Interestingly, in some cases, physical trauma or injury may not manifest itself as FM until some time has elapsed after an injury. Irrespective of the underlying cause of FM, secondary manifestations of the disease exacerbate the primary symptoms. As such, the boundary between what triggers and perpetuates FM becomes quite blurred indeed. This is because the overlap between physical symptoms and psychological components cannot be teased apart.

Accordingly, two different sets of factors aggravate FM and complicate both its natural history and clinical course. On the one hand are components that predispose to and precipitate FM whereas, on the other, are perpetuating factors of the disease. The overlap and interactions among these factors are nearly impossible to dissect. For instance, restless legs syndrome (RSL) may be presented with FM. While there is no evidence that RLS necessarily follows or precedes FM, its concurrent presentation is yet another complication that must be reckoned with. By the same token, the normal tendency while experiencing pain is to hold bands of achy muscles in position to minimize discomfort. The upshot is that the muscle in question becomes even more taut, which invariably deepens the pain when it inevitably has to be moved. Furthermore, psychogenic factors could paradoxically "feed" FM symptoms, as the sufferer attempts to alleviate them, inducing more stress, which further intensifies the symptoms. Given this multiplicity of factors, FM is being increasingly described as a somatized (medically unexplained symptoms) functional disorder.

This categorization should bode well for therapeutic outcomes in FM. Presently, therapeutic/corrective regimens predominantly focus on mitigating pain, be it with non-steroidal anti-inflammatory drugs (NSAIDs), opioid analgesics, muscle relaxants or antidepressants. The focus on pain in FM is predicated both because it is widespread and has changing areas of emphasis. Whereas the severity of FM symptoms may fluctuate, it is seldom that the disease completely remits. In short, the tangible projection of FM is unrelenting, unresolved pain for duration, which becomes refractory to intervention.

As a part of the chronic pain spectrum, FM is characterized by non-malignant, persistent pain. In the general population, two percent of people (both men and women) are prone to FM syndromes. Analyses of published reports suggest that among FM patients, 25.2 percent of women and 6.8 percent of men had 11 or more tender points, as defined by the ACR criteria.

Tellingly, pain-free subjects show a logarithmic (i.e., accentuated, almost startled) response to increase in pain intensity disproportionate to the strength of the pain-inducing stimulus. However FM patients have a linear response, as pain perception increases commensurate with the stimulus against a background of generalized pain. This bespeaks that the sensory switch of pain perception has been thrown open and is not reversible. As such, FM represents a syndrome in which pain is experienced independent of physical damage and must be seen rather as an issue of pain processing. This is a matter of some sensitivity for FM sufferers, as the pain experienced is all too real. Nonetheless, recent evidence has begun to shed light on the curious paradox of chronic pain.

The mechanistic minutiae of pain notwithstanding, it is well-known that some of the conditions associated with FM such as irritable bowel syndrome and irritable bladder syndrome have identical central mechanisms that amplify pain. Similarly, pain perception is exacerbated in many cases of low back pain, despite the lack of inflammation. Hence, FM is but one among the numerous conditions resulting in chronic pain without any obvious trigger. In fact, it could be argued that in conditions with yet unexplained, somatic symptoms--for example, chronic fatigue and cognitive dysfunction, to name merely two, would likely be explicated by pain amplification mechanisms.

Yet such considerations do not exclude an organic basis for FM. Thus FM patients consistently show low tryptophan levels, an amino acid necessary for the production of serotonin, a neurotransmitter, which affects numerous loci in the brain, including the sleep locus. This explains non-restorative sleep in FM sufferers and implies alterations in the hypopituitary-adrenal axis. Also, the amounts of substance P, another neurotransmitter, are increased in the cerebrospinal fluid of FM patients. Substance P enhances pain perception by as much as three times the normal levels. Furthermore, severe fatigue after exercise, prolonged standing or stressful situations may subject FM patients to neurally mediated hypotension.

In turn, this leads to the breakdown of the muscle tissue, which contributes to pain typically associated with FM. Accordingly, if hypoxia were reversed and the muscle could produce sufficient energy, fatigue and exhaustion in FM might be meaningfully managed. Whereas therapeutic regimens by and large zero in on pain to ensure functionality and personal autonomy, it is equally necessary to target those processes that aggravate the FM symptomatology.

Since no pharmaceuticals yet appear on the horizon to correct the metabolic context of the disease, nutritional intervention offers an alternative to at least keep the severity of symptoms in check. Specifically, with respect to energy replenishment, the nutritive malic acid could potentially help the muscle produce more energy. A metabolite in the Kreb's cycle, which funnels requisite metabolites to mitochondria for energy production, malic acid may have an important role in increasing cellular energy under both aerobic and anaerobic conditions. As such, nutritive supplementation with malic acid should increase its intracellular levels to offset energy deficit due to exertion or physical activity. Additionally, S-adenosylmethionine (SAMe), which alleviates stress and anxiety, has been in use to help cope with FM.

In general, the importance of maintaining sundry nutritives well within their requisite ranges cannot be emphasized enough. For instance, magnesium is a mineral critical to muscle relaxation, and may be beneficial, especially with concomitant restless leg syndrome and/or easy fatigability. Likewise, vitamins B1 and B6 are usually low in FM sufferers as well as among those with mild depression and their supplementation should be useful.

The natural history of FM is somewhat singular in that conditions, concurrent to and secondary ramifications of the disease itself, become inextricably intertwined. These, in part at least, make FM refractory to corrective regimens. Therefore, it stands to reason that management of secondary presentations is just as relevant in any therapeutic/corrective regimen.

Consequently, if these conditions are adequately managed, the course of FM may be significantly improved. For instance, irritable bowel syndrome (IBS) is typically presented in some cases, which is as intractable as FM itself. As yet, no satisfactory therapies are available to manage IBS, let alone its simultaneous handling with FM. Importantly, no organic cause has yet been identified and, given the broad range of its symptoms, IBS is a prototypical case of a disease where structure and function coalesce. As such, IBS is uniquely suited for nutritional intervention. One of the hallmarks of IBS is an imbalance in the intestinal flora. Accordingly, if the floral balance were to be restored, cases of simultaneous FM-IBS presentation should become far more amenable to favorable outcomes. Floral balance in the colon is optimally restored with prebiotics, principally with inulin isolated from the root of Jerusalem artichokes. In fact, the Jerusalem artichoke inulin is a prebiotic par excellence in that it isolates naturally with magnesium organically linked to it, among other trace and essential minerals. What is more, oral intake of inulin not only delivers these minerals effectively but it also facilitates absorption of dietary and supplemental minerals efficiently.

Among the nutritives, though, systemic enzymes in the management of FM quite stand out. Their benefits rest on the premise that (an) organic trigger(s) skew(s) the balance between the pro- and anti-inflammatory cytokines. Independent reports show that NSAIDs relieve FM symptoms, in at least a subset of FM patients, suggesting that FM does not have to become a sentence for a life of unremitting pain. In fact, evidence points to sub-threshold inflammation as underlying FM, despite the fact that clinical examination is not suggestive of frank inflammatory response. This contention is corroborated by the observations that pro-inflammatory cytokines interleukin(IL)-6 and tumor necrosis factor-? (TNF-?) can cause heightened sensitivity to pain. That is, overproduction of IL-6 and TNF-? may be operative in perpetuation of FM. After all, FM is commonly attendant to rheumatoid arthritis, low-back pain, and osteoarthritis--all conditions in which pro-inflammatory cytokines are pivotal. Accordingly, modulation of such cytokines promises to relieve discomfort associated with FM.

Curiously, though, this approach has received less attention than it merits. In part, it may be for absence of means to directly interfere with the levels of pro-inflammatory cytokines. The challenge inherent in modulation of cytokines is that they comprise a rather large family of molecular messengers and their relative amounts are up- or down-regulated in concert with each other. Consequently, modulation of but one cytokine would likely disturb the exquisite balance among them--unless, of course, their respective amounts are coordinately regulated. Systemic enzymes, especially the combination of bromelain, papain, trypsin, chymotrypsin and pancreatin in the German formulation, have been shown to modulate the immune response and hence, down-regulate pro-inflammatory cytokines while, at the same time, upregulating anti-inflammatory cytokines.

Since IL-6 and TNF-? contribute to the inflammatory response, their levels are modulated sufficiently to take the edge out of the discomfort typical of FM. In fact, an exploratory study, carried out in Germany, suggests that dispensation of systemic enzymes helps manage FM symptoms. To an extent, the benefits of systemic enzymes administration may also be attributed to the bioflavonoid, rutin, contained in the systemic enzymes cocktail. It is known that in syndromes such as FM, chronic pain is accompanied with reduced thalamic blood flow. Thus, systemic enzymes, by virtue of their proteolytic (protein-degrading) activity, facilitate robust blood flow, whereas rutin also is instrumental in strengthening the vessel wall integrity. Cumulatively, then, this specific German systemic enzyme gemisch, along with rutin, should be beneficial as a nutritive regimen over the long run.

In summary, then, as nutritives, systemic enzymes in combination with rutin, are rather effectively employed to nutritionally manage FM symptoms, especially in conjunction with low-impact exercise. Aerobic exercise in the management of FM is strongly advised, as it improves pain and disturbed sleep and also reduces the tender points count. Of late, functional exercise, in which the routine movements are emphasized, has come in vogue, and should be invaluable to FM sufferers. It is well-known that systemic enzymes accentuate the benefits of physical exercise by both stimulating more robust blood flow and indeed, by strengthening the body's own repair processes.

As alluded to above, the many syndromes characterized by chronic pain--including but not limited to chronic fatigue syndrome, repetitive stress injuries and in fact, sports injuries, such as tennis elbow and golfer's frozen shoulder, would eventually form a continuum of conditions with a common final pathway to pain perception. With specific reference to FM, however, implementation of a nutritive regimen centered around systemic enzymes should encourage the body to marshal its own healing resources. Over time then, chronic pain lurking in the shadow of fibromyalgia might be sufficiently dulled so as not to be terribly intrusive.

References available upon request, send a SASE to totalhealth.

Fibromyalgia is a clinical construct developed primarily by rheumatologists and was clinically first described in 1904. To date its diagnosis is ascertained largely by exclusion, based on patient history and a thorough physical examination. The criteria set forth by the American College of Rheumatology (ACR) facilitate diagnosis considerably, which include presentation of persistent musculosketetal pain for at least three months and tenderness, or hypersensitivity, on digital palpation in at least 11 of 18 anatomical points ("tender points") in the occipital, neck, shoulder, thoracic and lumbar spine, hip, elbow, and among others, knees.

Fatigue, depletion of energy in the face of stress and reduced blood flow are reminiscent of inadequate supply of oxygen (hypoxia) to the muscle, When muscle becomes hypoxic, it cannot produce ATP (adenosine triphosphate), the high-energy substance the muscle produces to function at par.

Fibromyalgia is routinely associated with irritable bowel syndrome, systemic lupus and, among others, chronic fatigue syndrome.


By Aftab J. Ahmed, Ph.D.

Aftab J. Ahmed, Ph.D., is vice president of research and development and businesss development, Marlyn Nutraceuticals, Inc. Phoenix, Arizona. E-mail:

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