GLYCOPROTEINS/GLYCOCONJUGATE SUGARS (Mannose, Mannans) GLYCOPROTEINS/GLYCOCONJUGATE SUGARS (Mannose, Mannans)Common Uses
Immune diseases, arthritis, asthma, wound healing
Glycoproteins are protein molecules bound to carbohydrate molecules. Glycoprotein molecules coat the surface of every cell with a nucleus in the human body. The body uses the glycoproteins on cell surface glycoconjugates as communication or recognition molecules. These communications may then result in other cellular events, including secretion of bioactive substances (interferon, interleukin-1, complement), ingestion of bacteria and cell debris, inhibition of adherence necessary for bacterial infection, and the spread of cancer cell metastasis.
Scientists have identified eight sugars, glycoforms, found on human cell surfaces that are involved in cellular recognition processes. Of the 200 such sugars occurring naturally in plants, to date only these eight had been identified as components of cellular glycoproteins. These eight sugars that are essential for glycoconjugate synthesis (mannose, galactose, fucose, xylose, glucose, sialic acid, N-acetylglucosamine, N-acetylgalactosamine) can be readily absorbed and directly incorporated into glycoproteins and glycolipids.
Recent research has found specific cell surface glycoforms to be characteristic of many disease conditions. In some people with rheumatoid arthritis, some of these patients’ defense cells (IgG antibody) bear malformed glycoproteins. These cells are missing required galactose molecules; the extent to which the galactose molecules are missing correlates with disease severity and reverses in disease remission. In people with cancer, more than 20 different malignancies are known to be associated with characteristic glycoproteins. Many diseases, including some autoimmune diseases, have been found to be associated with altered cell surface glycoproteins.
Glyconutritional supplements are designed to provide substrates for the body to use in building part of the glycoconjugates on cell surfaces. These supplements, most commonly acemannan and mannose, are designed to make the necessary sugars available to the cells quicker and in greater quantity.
Acemannan is a glycoprotein (a long chain of mannan polymers with random o-acetyl groups) derived from the aloe vera plant that has been shown to increase the body’s production of immune-modulating chemicals including interleukins-1 and 6, interferon-gamma, and Prostaglandin E2 and tumor necrosis factor alpha by macrophages. Acemannan also enhances macrophage phagocytosis and nonspecific cytotoxicity, which increases the ability of white blood cells (macrophages) to destroy infectious organisms. Glycoproteins such as acemannan also offer antiviral activity as well as bone marrow stimulating activity.
Acemannan has been approved as an adjunct therapy for solid tumors called fibrosarcomas. Intralesional injection into the tumor (2 mg weekly for up to 6 weeks), combined with intraperitoneal injections (1 mg/kg of body weight given weekly for 6 weeks, followed by monthly injections for 1 year), has been shown to be effective in shrinking tumors (via necrosis and inflammation). Acemannan has been proposed as an adjunctive therapy for cats with feline leukemia virus infection and feline immunodeficiency infection.
Acemannan has been anecdotally reported to help pets with atopic dermatitis; however, the immune-modulating chemicals are pro-inflammatory and studies in people have shown them to be involved in the increase in inflammation seen in people with atopic dermatitis. Therefore it does not make sense (from a biochemical point of view) that they would be useful in treating atopic pets despite the anecdotal reports in the literature showing effectiveness in some pets. Since acemannan can increase the ability of the white blood cells to destroy microbes, it may be helpful in pets with skin infections. Also, acemannan probably has other properties that have not yet been defined that might allow it to function to relieve itching and inflammation in atopic pets. Product literature for some of these products hint that the ingredients might support cellular communication through a dietary supplement of monosaccharides needed for glycoconjugate synthesis. Good communication between cells is necessary for proper gland and organ function, proper system function, and optimal health.
Acemannan has also been shown to enhance wound healing when applied topically.
There are a number of potential uses for the various glycosugars in disease conditions of people and pets. For example, one of the glycosugars, mannose, has been shown to activate white blood cells called macrophages. These influence the release of substances that modulate the immune response and tissue inflammation and also remove bacteria and cellular debris. Acemannan, a glycoprotein from the aloe vera plant, is also effective in this manner. Both acemannan and mannose enhance the killing of the yeast Candida albicans by macrophages.
Wound healing can be improved with mannose and acemannan by decreasing tissue damage and inflammation.
Galactose stimulates macrophages, activates killing of microorganisms, and enhances wound healing.
No definitive studies of large numbers of cats with feline leukemia virus infection have shown the cats to revert to a negative viral status, although the administration of acemannan did appear to prolong the life of the cats. In sick cats with leukemia virus infection, 29 out of 41 cats survived a 12-week study period using intraperitoneal acemannan (2 mg/kg weekly for the first 6 weeks of the study). Two months following the 12-week study, 21 cats were still alive (1 had died, 5 cats could not be followed up as their owners had moved). In a similar study of sick cats who were leukemia positive and not treated with acemannan, 40 out of 46 cats died or were euthanized within 5 days of diagnosis.
In one study of feline immunodeficiency virus (FIV) infections, 75% survival rate was obtained for cats in Stage 3, 4, or 5 (seriously ill cats for which life expectancy is up to 1 year for Stage 4 cats and 1 to 6 months for Stage 5 cats). Cats showed increased body weight, decreased lymph node size, and a reduction in sepsis (infections that are commonly seen in end stage FIV cats). Neutrophil counts improved, as well as lymphocyte counts, indicating an improvement in the immune status of the infected cats. Cats responded regardless of route of administration of acemannan (weekly IV injection or weekly subcutaneous injection, of 2 mg/kg acemannan, or daily oral administration of 100 mg/cat acemannan). No signs of toxicity were noted in any cats, although four cats given the IV injections showed an immediate allergic reaction, which commonly occurs in cats given IV push injections of very large molecular weight compounds such as acemannan.
In these studies, all cats remained virus positive but experienced a noticeable improvement in the quality of life. While acemannan (and other glycoproteins) may be helpful for cats with leukemia or immunodeficiency viral infections, more studies are needed to determine what, if any, true long-term benefit infected cats might experience. At the current time, acemannan and other glycoproteins such as mannose, one of eight glycoproteins found in the oral supplement, ambrotose, probably serve as a useful treatment option for these chronic feline viral diseases for which conventional therapies really do not exist (conventional therapies are of no particular benefit and serve mainly to support the sick cat).
All eight of the glycoconjugate sugars are readily absorbed from the intestines when taken orally. Studies have shown intact mannose molecules are rapidly absorbed from the intestine of rats into the blood, elevating the blood mannose levels by 3- to 10-fold, and mannose is cleared from the blood within hours. The conclusion reached was that mannose was absorbed from the intestinal tract into the blood and from the blood into the cells. These studies suggest that dietary mannose may make a significant contribution to glycoform synthesis in mammals.
Other human and animal ingestion studies show that mannose is readily absorbed, and is cleared from the blood over several hours; some of the mannose was incorporated into glycoproteins. After absorption into the blood, glycoconjugate sugars generally become distributed (usually as glycoproteins and glycolipids) into body fluids, organs, and various body tissues.
In one study, healthy humans were given radiolabeled galactose, mannose, or glucose. This study showed that galactose and mannose were directly incorporated into human glycoproteins without first being broken down into glucose. The conclusion was that specific dietary sugars could represent a new class of nutrients and that the use of these nutrients could have important consequences. Therapy with mannose offers a treatment that is easy to administer and is nontoxic.
The glycoprotein N-acetylglucosamine (discussed in more depth under N-TK) inhibits oxygen radical production by neutrophils and also release of neutrophil-derived elastase, limiting tissue damage and inflammation. This has been shown in studies to substantially reduce pain and increase joint flexion and active mobility in arthritis patients.
The data show that there is scientific basis for potential therapeutic benefits from these sugars in the treatment of common immune system diseases, such as arthritis and asthma, and in wound healing.
Most of the essential glycoconjugate sugars have demonstrated an ability to inhibit cancer growth and the spread of tumor cells both in vitro and in vivo (in experiments in pets and people.) The ability of the glycoproteins to inhibit tumor growth may be related to their ability to alter the activities of the immune system. Glycoconjugate sugars stimulate white blood cells (macrophages), which secrete interferons. The interferons activate natural killer cells that help eliminate cancer cells. The glycoproteins may inhibit the spread of tumor cells by preventing tumor cells from adhering to each other as a result of competitive inhibition of glycoconjugate receptor binding.
Glycoconjugate sugars have been shown to kill bacteria and viruses and prevent infection by them. For example, mannose acts to prevent bacterial infection by binding to the sites on the bacteria and preventing attachment of the bacteria to sites on the cells of the host. Glycoconjugate sugars display antiviral activity as a result of their ability to stimulate macrophages to release interferon. They also interfere with normal virus function.
Glycoconjugate sugars may offer hope for treating disorders such as diabetes, as some glycoconjugate sugars share membrane transporters and metabolism pathways with glucose. For example, galactose might be expected to stimulate insulin secretion by stimulating intestinal release of gastric inhibitory polypeptide (GIP). GIP stimulates the intestinal regulation of insulin secretion (at least in intestinal perfusion techniques in experimental studies in rats). Possible roles for specific glycoconjugate sugars in diabetes are unclear and much more additional research is needed. In vitro and in vivo studies in diabetic rats indicate that mannose may protect the diabetic lens from developing cataracts.
Acarbose (Precose) is an oligosaccharide that inhibits alpha-glucosidase enzymes in the intestinal tract and pancreatic alpha-amylase. This results in delayed digestion of carbohydrates, delayed glucose absorption from the intestines, and decreased post-feeding glucose concentrations. Preliminary studies in dogs with type I diabetes have shown positive response when acarbose is given at the time of feeding at a dose of 25 mg per dog twice daily. Side effects (diarrhea and weight loss) are commonly seen in dogs treated with higher doses (100 to 200 mg per dog).
There are other potential uses for glycoprotein supplementation in pets. A derivative of glucosamine (1-deoxy-glucosamine) suppresses feeding activity in rats, apparently by acting through histamine neurons in the hypothalamus of the brain. This sugar might suppress hunger in people or pets and could possibly be useful as an adjunct to dietary calorie restriction in obese patients.
As with so many of our complementary therapies, a number of anecdotal reports show success in some pets when using glycoprotein therapy. More controlled studies are encouraged to give us a better idea of just how effective glycoproteins might be in the treatment of illness in pets.
Popular glycoprotein supplements used in pets are manufactured by Carrington Laboratories and Mannatech Laboratories.
Adverse effects caused by glycoconjugate sugars are rare and usually occur when they are injected or when doses greatly exceed levels that would be expected in normal diets. For pets being treated with the most commonly used glycproteins (acemannan and mannose), side effects would not be expected.