Effects of Glyconutrients on the Individuals Well Being - Essay Example

Table of Contents PAGE LIST OF TABLES .................................4 Table1. Sources and health benefits of glyconutrients............ 4 Table 2. Concentration of glycoproteins on different tissues ......5 Table 3.Peripheral neutrophil counts and other therapy parameters during discontinuation and resumption of fucose therapy.. 5 LIST OF FIGURES .......6 Figure 1. Functions of glyconutrients ..6 Figure 2. Monosaccharide Interconversions 6 ABSTRACT 7 1. INTRODUCTION ..8 2. Effects of Glyconutrients on the Individuals' Well Being as Claimed By Companies Selling Glyconutrients ......... 8 3. Absorption and Metabolism of Glyconutrients ...9 4. Scientific Researches on the Effects of Glyconutritional Supplements ...........10 Effects on the Brain Function 10 Fucose Supplementation in Leukocyte Adhesion Deficiency Type II .......10 Effects on the Immune Response 11 Antiviral Activity of Glyconutrients .. 11 Failure-to-Thrive Syndrome (FTT) and Glyconutrients .12 Macrophage Activity and Glyconutrients .. 12 5. Future of Glyconutrients on Health Care....13 CONCLUSION ..... 15 REFERENCES .. 16 LIST OF TABLES Table 1: Sources and health benefits of glyconutrients (Ramberg & McAnalley 2002, Mondoa & Kitei 2001 & I Found Health Glyconutrients 2005) Glyconutrients Food sources Main feature Effects of individuals well being as claimed by drug companies Mannose carrot, beet, cauliflower, broccoli, kale, lettuce, rhubarb, Brussels, sprouts, red cabbage, asparagus and Aloe Vera major player in tissue remodelling and intelligent interactions between cells plays essential role in the production of cytokines accelerate the process of cellular communication and healing inhibit tumour growth and spread; prevent bacterial, viral, parasitic, and fungal infections. Fucose Flaxseed gum, algae, breast milk, certain mushrooms found in junction between nerves, kidneys, testis and outer layer of skin Inhibit tumour growth and spread, guard against respiratory tract infection and inhibits allergic reaction N-acetylglucosamine Breast milk Glucosamine a metabolic product helps repair cartilage, decrease pain and inflammation and increases range of motion in osteoarthritis Antitumour properties, vital in learning and improve symptoms of Crohn's, ulcerative colitis, and interstitial cystitis N-acetylneuraminic acid Breast milk Important for brain development and learning lowers the LDL and inhibits strains of influenza A and B, bacteria and other pathogens Glyconutrients Food sources Main feature Effects of individuals well being as claimed by drug companies Xylose Grains- wheat, rye and barley Carrot, beet, cauliflower, broccoli, kale, lettuce, parsley, rhubarb, Brussels sprouts, red cabbage and asparagus Used as a substitute for sucrose and corn sweeteners Antibacterial, antifungal and prevent cancer Galactose Dairy products, legumes, algae, many fruits and vegetables Found in combination with glucose to form a disaccharide called lactose Inhibit tumour growth, enhances healing of wounds , decrease inflammation and triggers long-term memory formation Glucose Milk, mushrooms, various fruits and vegetables and grains Ubiquitous saccharide Memory enhancement, proper calcium absorption Table 2. Concentration of glycoprotein on different tissues. The graph shows the specific activity of radio labelled glycoprotein administered to rats at 1 and 8 hrs expressed as d.p.m/gm wet weight of tissue. As noted , "only the liver and intestines decrease whereas all the other organs show a 2- to 6-fold increase in specific activity" (Alton et al 1997 Figure 7). Table 3. "Peripheral neutrophil counts and other therapy parameters during discontinuation and resumption of fucose therapy. Peripheral neutrophil counts, fucose doses, serum fucose levels, body temperature, and C reactive protein (CRP) were recorded for each time point as indicated." (Luhn et al. 2001, Figure 1) LIST OF FIGURES Figure 1. Functions of the Glycoprotein (Nature 1995 cited in GoGlyco 2005) Figure 2. Illustration of the enzymes needed to convert one form of sugar to another in the body. (Zubay, Parson & Vance 1995) ABSTRACT As evidenced by the increasing literature, one of the "hottest" new fields of medical and nutritional break through is glycobiology. Glyconutrients are monosaccharides or carbohydrates that are attached to proteins or lipids and are collectively called glycocongugates. These glycocongugates, found in surface of cells play an important role in biological activities and any imbalance of these glyconutrients would then result to disease. Controlled clinical studies in humans and animals utilizing state-of-the-art analytical and diagnostic are presented in this report showing that glyconutrients 1) play important roles in both normal physiology and disease, 2) can be effectively assimilated when provided as dietary supplements, 3) have biological activities that are beneficial or potentially therapeutic for certain diseases and 4) are safe when provided in the diet. However, the claim of drug companies that glyconutrients "heals" diseases is still vague; more research still needs to be conducted. 1. Introduction Glycobiology, dubbed by Science Magazine (2001) as the Cinderella, is now the new wave moving through the walls of modern medicine and science. In the last two decades, a huge and growing body of research has demonstrated that aside from the four essential nutrients: carbohydrates, amino acids, fatty acids and vitamins and minerals there is a fifth set of essential nutrients that have been completely overlooked. Research has discovered that there are at least eight essential carbohydrates called glyconutrients (Berger et al. 1998 & Martin et al. 1998). Glyconutrients comes from the Greek word "glyco" which means "sweet", so "glyconutrients" means sweet nutrients and they are also known as essential saccharides or essential sugars. Glyconutrients refers to eight naturally occurring plant monosaccharides namely: glucose, galactose, fucose, xylose, mannose, N-acetylneuraminic acid, N-acetylglucosamine and N-acetylgalactosamine. These essential saccharides, which was originally considered to function only as a source of energy, were now believed to be building blocks for the manufacture of human cell surface glycoforms or glycoconjugates ( the generic term that refers to sugar in combination with protein- glycoprotein and/or lipid-glycolipid) ( Alton et al. 1997 & Rambal et al. 1995). Glycoproteins found on the surface of all cells, form a complex code, sending a specific message to a specific target, whether it is another cell, substance within the same cell, a circulating hormone, even an invading bacterium or virus (Figure 1). These glycoproteins are said to be vital for communication, in the cellular level, and are responsible for nearly every physiological process from conception until death (Mondoa and Kitei 2001). So any imbalance in these essential saccharides would result to disease (Matthijs et al.1997a, b, Paneerselvam & Freeze 1996 a, b, Orntoft & Vestergaard 1999). This has been the focus of different companies in advertising glyconutrients as a dietary supplement and they claim that by providing glyconutrients in excess the body can actually "heal" itself from varying sorts of diseases. In order for us to establish the feasibility of using glyconutrients as dietary supplements we must first determine: if the body can actually utilize these glyconutrients provided as dietary supplements, for the glycoprotein synthesis , then (1) they should be observed routinely in the blood of mammals, (2) each individual glyconutrient should have specific transporters that account for the glyconutrient flux, (3) physiological concentration of each individual glyconutrient should make a significant contribution to glycoprotein synthesis even with normal levels of glucose, (4) each glyconutrient should be efficiently absorbed through the gut and incorporated into tissue and plasma glycoprotein. This report investigates the plausibility of these theories, provides several scientific studies regarding the effects of using glyconutrients as dietary supplements and the forthcoming impact of glyconutrients in our health care system. 2. Effects of Glyconutrients to Individuals' Well Being as Claimed by Companies Selling Glyconutrients As stated by different web sites marketing glyconutrients, essential sugars work best as a team and most have overlapping functions in the body, so supplementation with essential sugars works best when they are taken in combination. Table I provides a detailed source and specific health benefits associated with each glyconutrients as claimed by these companies. These eight essential saccharides are found in different plants and fruits. However, Mannatech (2003) claims that of the eight sugars only two are found in our diet since sources are not as saturated with these vital glyconutrients as they once were. Due to green harvest, soil depletions, and our utilization of processed foods, our bodies are not receiving these glyconutrients in the amounts that we need to maintain optimal health. Furthermore, profound lack of glyconutrients in our daily diets leads to breakdown of the bodies systems resulting in the illnesses which varies form infection to cancer (Matthijs et al.1997a, b & Paneerselvam & Freeze 1996a) Glyconutrients serve not only as source of energy, but also as the building blocks for the manufacture of large molecules made of sugars in combination with proteins and/or fats called glycoforms, which cover the surface of all cells (Berger et al. 1998 & Martin et al. 1998). "Promoters of glyconutritional formulas espouse a popularised view that some of the polysaccharide components are being materially hydrolysed and absorbed as monosaccharides for beneficial use in human cells. Based on this long unsubstantiated claim of significant digestion of monosaccharides and the popularised notion of "8 essential sugars (monosaccharides)"(Mannatech 2003), these promoters further claim physiological connections, broadly not accepted, to the established science of glycobiology (study of the biological function of glyconutrients). These popularised notions have little support in science and medicine and have no significantly documented basis." 3. Absorption and Metabolism of Glyconutrients Previous knowledge dictates that glucose is the most important dietary sugar ( Murray 2000), however recent studies conducted by Berger et al. (1998) and Alton et al. (1997) on animals and humans have proven that glycosylation reaction actually prefers to utilize non-glucose essential saccharides (e.g. Mannose) provided in diet as substrates. These experiments confirmed the existence of transporters specific for certain sugars e.g. Mannose apparently uses its own specific transporter (Lee et al. 2002) while glucose and galactose share the same transporters in humans. However, there are factors that may affect these transporters (e.g. Diseases) which would then have a direct consequence on the absorption of these saccharides (Dykman, Ford & Gardiner 2000, Orntoft & Vesergaard 1999 & Matthijs et al. 1997a). After these essential saccharides are absorbed into the blood stream they are then distributed, as glycoproteins and glycolipids into, organs, body fluids and various cells (Table 2). Glycoform sugars can then be assimilated directly into glycocongugates with little or no metabolism into other sugars (Alton et al. 1997 & Panneerselvam & Freeze 1996b). The glycoconjugate sugars are metabolised by glycolytic enzymes (e.g. Mutase, kinase and pyrophosphorylase, Figure2) to phosphorylated substrate that can be utilized in, the production of energy, incorporated into glycoforms, or oxidized to Carbon dioxide (Martin et al. 1998 & Berger et al.1998). However we should keep in mind these sugars can be synthesized from glucose via the glycolytic enzymes. 4. Scientific Research on the Effects of Glyconutional Supplements (GN): Effects on the Brain Function In order to determine the effects a single dose of glyconutrients on the brain functioning of 20 healthy college students, McAnalley et al. (2002) conducted a double- blind, placebo controlled study. They have found out that glyconutrients enhanced brain wave frequencies that are associated with attention and alertness. Also, the subjects when given the supplements showed increase speed in information processing, reaction time and enhanced concentration. These results shows the possible usefulness of supplement in the management on conditions such as attention deficit, hyperactivity disorder (ADHD) and alcoholism. However like our knowledge with regards to glyconutrients, the study of brain physiology is still in its infancy and still needs further research and study. Fucose supplementation in leukocyte adhesion deficiency type II (LADII) LADII is a rare inherited disorder of fucose metabolism, which leads to immunodeficiency caused by the absence of carbohydrate-based selectin ligands on the surface of neutrophils, severe psychomotor and mental retardation. Luhn et al. (2001) described a simple and effective therapy for LADII and that is oral supplementation of fucose in LADII patients. Parallel to this treatment, the lack of fucosylated selectin ligands where corrected, the high peripheral neutrophil count in the subjects went back to normal levels and fever disappeared. Table 2, shows the result of tests conducted to check whether the results were merely coincidental, the therapy was discontinued for 9 days, during which the patients pre supplementation therapy symptoms came back, however there was a prompt reappearance of selectin ligands, disappearance of fever and normalization of neutrophils after therapy was resumed. This study shows oral supplementation of LAD II patient can improve neutrophil adhesion function, reduce developmental delay and improve immune system permanently. Effects on The Immune Response Scharhag et al. (2005) conducted a double blind, placebo- controlled research to examine the acute immune response after three standardized cycling session of 4-hour duration in the field with varying concentration of 6 or 12% carbohydrate beverage. The carbohydrate supplement was composed of 60 g and 120 g maltodextrin (Agenamalt, Agrana, Vienna, Austria) were added to 1 litre of mineral water and plain mineral water for the placebo. This study revealed that carbohydrate supplementation influences the acute immune response during prolonged exercise, leading to attenuated affectations, in phagocytising cells like neutrophils and monocytes. The intake of at least 6% carbohydrate beverages during prolonged exercise seems to be sufficient to reduce the metabolic stress and change the exercise-induced immune stress, however higher concentrations of carbohydrate beverages do not seem to yield additional immunological advantages. Antiviral activity of glyconutrients Some glyconutrients have been found to have biological roles that can provide protection against viral infections enhancement of production of anti-viral antibodies and the amelioration of virus-induced pancreatitis. An 8-month study conducted on mice by Gauntt et al. (1999) was performed to evaluate the efficacy of sugar supplementation in alleviating the destructive effects of Coxsackie viral infection. This study revealed significant benefits to most animals in reversing virus induced pancreatitis. Another animal study showed that glyconutritional complex (GC) could prevent chemical depletion of free reduced glutathione (Busbee et al. 1999).However another clinical study by Campbell, Busbee & McDaniel (1997) revealed that some subject with either form of diabetes failed to derive health-promoting benefits from dietary glyconutritional supplements. In saying so, GC studies needs to be conducted as some cases of acute pancreatitis can be fatal and more research is also needed to focus on the treatment of viral infection in humans. Mastromarino et al. (1997) evaluated the antiviral activity of natural and synthetic polysaccharides on the early stages of rubella virus infection of Vero cells. Their results indicated that polysaccharides blocked a step in the viral replication and subsequently to viral attachment. This antiviral activity of polysaccharides is dependent on the shape of the macromolecule and/or on its electric charge. However, the inhibitory activity of the polysaccharides was only effective in the early stages of Rubella virus multiplication and not cells that have already been infected. Failure-to-Thrive Syndrome (FTT) and Glyconutrients FTT is a clinical syndrome that affects individuals of varying age and results to body wasting and weights loss. A recent pilot study by Dykman, Ford and Gardiner (2000) provides evidence that certain glyconutritional substances when given to FTT children can significantly reduce some of the signs and symptoms of Cachexia (general wasting). Thus, this result is suggestive of the possible roles that glyconutritional supplements (GN) may play in the prevention and repair of dysfunctional processes seen in FTT syndrome. Although it seems that glyconutritional supplements could benefit FTT patients, it should be noted that at rare instances where a deficiency in an enzyme necessary for the overall metabolism of a specific glycocongugate sugar might lead to harmful excessive levels of that sugar in the body. Macrophage activity and Glyconutrients Lefkowitz, S & Lefkowitz, D (1999) conducted an in vitro comparison of the effect of two dietary supplements on the human Natural Killer (NK) cells activity (a measure of the ability of NK cells to kill target cells). This study shows that a complete GN shows a greater immune response by enhanced killing of Candida albicans by macrophages as compared to aloe polymannose. The same principle was then proven by Campbell, Busbee & McDaniel (1997) when mice with sarcomas was given GN showed increased tumour regression and improved survival when compared with animal that did not receive supplementation. There are a lot of case report presented on different articles such as: improved tolerance of cancer therapy in a patient taking glyconutritional supplement (Hall, DDS & Boyd 2002), D-mannose (U-TRACT) ameliorating symptoms of acute UTI's (Blue 2003), Green- Bishop (2004 ) stated that a patient who had massive cerebral aneurysm and became a total invalid showed improvement after GN intake. But as stated these are case reports which could be purely circumstantial and can be attributed to marketing scheme of companies distributing GN products. A word of caution is needed when interpreting current analysis presented in this review. Most of the study covered a small number of subject human and non-human and some authors are sponsored by Mannatech Incorporated (a company that sells glyconutrients).This phenomenon can be partly attributed to publication bias, that is, the fact that small trials are more likely to be published if they show statistically significant treatment effects and that some studies are can only a part of the marketing scheme of distributing companies. Glycobiology is a relatively new field and the mechanisms by which glyconutrients affect the cells are only recently understood. What is known conclusively is that without glyconutrients the cells are not able to communicate completely (Alton et al. 1997& Lee et al. 2002). Further, without proper cellular nutrition and metabolism inside the cell oxidative stress results. Oxidative stress, a condition usually linked to aging process, is the result of a deficiency of antioxidants. It may be due to inadequate diet, environmental stress, exposure to environmental toxins or any combination (Cutler 1991 & Goux et al. 2001). 5. Future of Glyconutrients in Health Care The glycoscience is the last exciting frontier of biochemistry (Hurtley 2001). Of the four major classes of biomolecules--proteins, nucleic acids, lipids (fats) and carbohydrates the later are the most complex. Because of their complexity, technology has only recently developed the methods to study them, unlock their codes, and reveal their biological secrets. As expected with any complicated field of study, the more we learn the more questions we develop. What are the precise connections between specific diseases and changes in the sugar portions of cell-surface glycoforms How exactly does the body metabolise each of the necessary sugars when consumed in the diet Such questions will take many years to finally resolve. The research so far on metabolism of dietary sugars is only little more than a year old. Science has only just begun to decipher the sugar (glyco) code and its importance in communicating the language of life. At the same time that interest in glycoconjugates has been growing in the scientific community and in the pharmaceutical industry, the general population has begun to pay more and more attention to nutritional intervention. Most of us are aware of scientific research that has established diet as an important component of many disease conditions. Heart disease, cancer and diabetes are obvious examples (Brockheusen, Schutzbach & Kuhns 1998). Glyconutritionals came about as a combination of both trends--glycoconjugate research and the focus on nutritional supplementation for health. Glyconutritionals are nutritional dietary supplements designed to provide greater quantity of substrates for the body to use in building the glyco portion of glycoconjugates on cell surfaces . The field of glycobiology looks promising but has still a long way to go. The discovered connection of glycocongugates and disease will fuel a lot of research in the next coming years in the hope of finding novel treatments for many diseases (Sharon 1998). Among the immediate challenges in the near future is the scientific development of regulatory measures for the so-called 'functional foods', which can positively affect the consumers and improve the practice of medicine. The created awareness of the advertisement as seen on the web, magazines, journals, etc. regarding the use of glyconutrients as dietary supplements points to the fact that nutrition is directly related to diseases. Hopefully consumers would be more health conscious and start eating a balanced diet that would provide the body with the sufficient nutrients required to function well and possibly improve well being. 6. Conclusion Collecting all the evidences that I gathered from various resources it can be said that the eight sugars are necessary for glycocongugate synthesis, readily absorbed and can be directly incorporated. By providing the essential nutrients (i.e. Vitamins, mineral, carbohydrates), the body could possibly function to its full potential. Glyconutrients as said earlier, has been suggested for many health conditions and although no adverse effects in the use of glyconutrients has been reported in the available literature, we should keep in mind that glyconutrients are not "wonder" drugs as suggested by various companies. As of now, no research has been found to prove that glyconutritional supplementation to be 100% effective for any specific condition. Glyconutritional supplementation is only intended to be used as an adjunct to medical care, not to replace it, and should never be relied on as the sole therapy for medical problem. For patients suffering from Diabetes or other dangerous medical condition, seek the help of healthcare provider before the intended use of these supplements. Glyconutrients are indeed essential for biological functions however the available research on effects of glyconutritional supplements in health and disease is in its infancy and not definitive. 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