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101. Chronic Fatigue Syndrome:
Immunomodulatory Effects of Glyconutrients
Recent Research Results on Chronic Fatigue Syndrome in Humans
In humans, eight monosaccharides are required for the synthesis of glycoproteins. Dietary supplements that supply these crucial sugars are known as glyconutrients. The in vitro immunomodulatory effects of a glyconutrient compound were recently investigated in patients with the Chronic Fatigue Syndrome (CFS), a disease associated with immune dysregulation.
Peripheral Blood Mononuclear Cells (PBMC) were isolated from normal controls and patients with CFS. Cell surface expression of the glycoproteins CD5, CD8 and CD11 were found to be significantly reduced in patients with CFS compared to normal controls.
Addition of glyconutrient homogenate to PBMC from patients with CFS stimulated with phytohemaglutinin significantly increased the expression of each glycoprotein. Furthermore, Natural Killer (NK) cell function was reduced in CFS patients. Thus, glyconutrients improved abnormal immune parameters in vitro in patients with CFS.
This study has shown that the majority of patients with CFS had defects in one or more of the immune parameters studied. In vitro treatment with a glycoprotein (more info) formulation improved each of these.
Chronic Fatigue Syndrome: Some More Facts
Chronic Fatigue Syndrome (CFS) is a debilitating disorder of unknown cause. Its diagnosis is currently based upon clinical criteria established by the Center for Disease Control (CDC) (Holmes et al, 1988). Many studies have suggested that immune dysfunction is a hallmark of this disease (Straus S et al, 1993; Lloyd A et al, 1989; Klimas et al, 1990; Tirelli et al, 1994).
Immune Dysfunction
For example, patients with CFS often have diminished natural killer (NK) cell function and there are studies which have demonstrated a beneficial clinical effect when NK function was increased (See et al, 1996; See et al, 1997). Other studies have demonstrated a decrease (Behan et al, 1985) or an increase (Straus et al, 1985) in certain glycoprotein-based receptors found on mononuclear cell membranes. Recent evidence indicates that apoptosis (cell death) is abnormally accelerated in CFS (Mordechai et al, 1997). Other studies have shown normal immune function in CFS patients (Kruesi et al, 1989; Demitrack et al, 1991).
CFS is a Heterogeneous Disorder
It is therefore apparent that CFS is a heterogeneous disorder with multiple subgroups. Recent research in this disease has focused on identifying specific subgroups and targeting treatment toward these groups. In the current study, it was found that 43 percent of the 212 patients screened had diminished cell surface receptor expression of CD5, CD8 and CD11, decreased NK function and spontaneous apoptosis of over 20 percent. At least one of these findings was present in 87 percent of the patients.
Glyconutritionals
Glyconutritionals provide the body with essential monosaccharides, most of which are not present in sufficient amounts in the average Western diet. Of the eight essential saccharides necessary for optimal metabolic function in humans, only glucose and galactose are normally present in sufficient quantities in the diet.
Missing Sugars
Mannose, fucose, xylose, N-acetylglucosamine, N-acetylgalactosamine and sialic acid are typically deficient. These sugars act as substrates for crucial biochemical pathways and for the production of cell surface glycoproteins. Furthermore, these sugars provide sufficient substrate for biochemical products within the cell, an adequate quantity of which is vital for regulating the kinetics of enzymatic reactions. Thus these sugars help restore normal cell surface number and function. They do this by allowing the cell membrane to carry out its crucial functions, namely:
Immune System Dysfunctions in CFS Patients
The results of the current study confirm previous studies which suggest that immune dysfunction is present in some CFS patients. The abnormalities that are most consistently evident in the literature were assessed in the current study. It was found in the current study that the majority of patients carefully diagnosed with CFS by CDC criteria had an abnormality in at least one parameter studied. In keeping with the CDC mandate to study therapeutic modalities in homogenous populations of patients with CFS, given that it is a heterogeneous disease, only those patients with abnormalities for each parameter studied were included in the analysis.
Glyconutrients are excellent candidates for the treatment of some subgroups of CFS. Intracellular metabolic defects (Russel et al, 1992) and abnormal expression of cell surface glycoproteins (Altmann et al, 1988) have been noted in some patients with the disorder. Nutritional supplementation has been shown by Dykman et al to be one of the only effective therapies for the management of CFS (Dykman et al, 1997). In a follow-up of this study, the subjects were interviewed nine months after the initiation of nutritional supplementation. Initial symptom severity showed remarkable reduction, with continued improvement in the period between initial assessment and follow-up (Dykman et al, 1997). The American diet has been shown to be deficient in 6 or 7 of the 8 essential saccharides necessary for optimal glycoprotein synthesis and as substrate for many intracellular enzymatic reactions. Since some CFS patients have obvious B deficiencies in these processes, the need to supplement these saccharides becomes even more compelling.
Missing Glycoproteins
This study demonstrated a lack of CD5, CD8 and CD11 in many patients with CFS. CD5 is crucial for B cell function; CD8 is an important T cell surface glycoprotein both in cytotoxic and suppressor cells; and CD11 is important for immune cell communication. Thus, a defect in immune function should result, accounting for the observed abnormality of pro-inflammatory cytokine production (Gupta et al, 1997) and reactivation of latent microorganisms suggested by previous studies (Buchwald et al, 1990).
NK (Killer) Cell Deficiency
A deficiency in NK cell function has been shown to increase the severity of CFS (Ojo-Amaize et al, 1994). The glyconutrient preparation increased NK function in vitro. Other studies (See et al, 1996) have suggested that increasing NK function in CFS patients can result in improvement of their symptoms. An interesting finding in the current study was that NK function was also increased in normals. NK cells function can be decreased by a variety of common factors including stress, pregnancy and vigorous exercise (See et al, 1997). The cells are important in lysing cancerous cells and protecting the body from viruses and other intracellular microorganisms (See et al, 1997). Thus, further studies may be warranted to assess if glyconutrient supplementation may decrease the incidence of cancer or infections in the normal population.
Apoptosis
Apoptosis is a normal physiologic function that is required to assure that cancerous or autoreactive immune cell clones "self-destruct" before they can harm the body. Glyconutrient supplementation did not change the percentage of apoptotic cells in normal individuals. However, accelerated apoptosis, found in the CFS patients in the current study, can lead to dysfunctional immune system homeostasis. Glyconutrients decreased the percentage of apoptotic cells, having the potential to stabilize immune system equilibrium in CFS patients.
Results
Thus, in vitro addition of (glycoproteins) improved several parameters of immune function in a carefully controlled population of patients with CFS, suggesting that they may be of therapeutic benefit in these patients.
References - Chronic Fatigue Syndrome
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