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Glyconutrients - The Missing Link?

by Peter Smith and Kelly Ramsey(more info)

listed in nutraceuticals, originally published in issue 73 - February 2002

Introduction

Science and medicine are on an unending quest to break the biocode by which the cells of the human body communicate with one another. This complex code is literally the language of life. As the field of glycoscience emerges, we may consider this cellular language to be the sweet language of life. Glyco is the Greek word meaning sweet.

Glycoscience is the study of structure and function of carbohydrates – biological sugars.

Glycoprotein Synthesis

Although there are more than 200 known sugars in nature, only eight have been identified as essential. These eight essential saccharides, when combined with proteins and or fats/lipids, provide the building blocks for the manufacture of larger molecules called glycoforms. In fact, glycoprotein molecules coat the surface of every cell with a nucleus in the human body and are required by the body to: maintain healthy endocrine function; modulate immune function (i.e. increase or decrease, where necessary); facilitate cell-to-cell communication; enable the uptake of the other essential substances (the essential fatty acids, essential amino acids, essential vitamins and essential minerals); regulate metabolism.

Until recently the scientific community has primarily focused on the study of proteins. For the past few decades we believed that proteins were responsible for cellular communication and cellular recognition.

However, in the last ten years, as a result of the emergence of glycobiology (the study of sugars), it has become apparent that glyconutrients may play a vital role in cellular communication and may represent a new category of nutrients or dietary supplements.

This new technology demonstrates that by providing the body with the raw nutrients in the form of these simple sugars our bodies are often able to heal, correct and repair themselves, As is mentioned in a recent review of Dr Emil Mondoa's new book, Sugars that Heal[1]:

"Even tiny amounts of these sugars or lack of them have profound effects. In test after test conducted at leading institutes around the world these saccharides have been shown to lower cholesterol, increase lean muscle mass, decrease body fat, accelerate wound healing, ease allergy symptoms and allay auto immune diseases such as arthritis; psoriasis and diabetes; bacterial infections including the recurrent infections that plague toddlers often respond remarkably to these saccharides, as do many viruses from the common cold to the flu, from herpes to HIV, to the debilitating symptoms of chronic fatigue syndrome, fibromyalgia, Gulf War Syndrome which frequently abate after adding these saccharides. For cancer patients: saccharides mitigate the toxic effects of radiation in chemotherapy while augmenting their cancer killing effects resulting, in prolonged survival and improved quality of life..."

Eight Essential Saccharides Required for Glycoprotein Synthesis

Glucose (Glu)
Galactose (Gal)
Mannose (Man)
Fucose (Fuc)
Xylose (Xy)
N-Acetylglucosamine (GlcNAc)
N-Acetylgalactosamine (GalNAc)
N-Acetyineuraminic acid – sialic acid (NANA)

A Little History

Traditionally we think of sugar as plain cane sugar or table sugar. Most of us are not lacking in that dietary nutrient. In 1996, a new class of nutrients was actually established and it was documented in medical textbooks that there were eight essential saccharides that are necessary for the building blocks of all of our cells. They are: mannose, fucose, galactose, xylose, glucose, n-acetylglucosamine (GlcNAc), n-acetylgalactosamine (GalNAc), n-acetylneuraminic acid (NANA). We now know that nature uses these carbohydrates on cell surface glycoconjugates as communication - or cellular recognition - molecules.

Why did it take so long for their importance to be discovered? Sheer complexity. Science has identified four major classes of biological molecules: proteins, nucleic acids, lipids (fats) and carbohydrates. Until recently carbohydrates were the Cinderella of the biological family and never went to the ball. In fact, researchers often washed off what they considered to be these 'contaminant sugars' from the precious proteins.

The reality is that carbohydrates are significantly more complex than proteins or nucleic acids or any of the other biological components that have so far been studied, including DNA.

For example, where two amino acids can be combined to form one single molecule or 'message', two monosaccharides if combined form eleven other molecules or messages. Four amino acids can only be combined in every different configuration to equal 24 different molecules. Four saccharides can actually be combined in a multitude of different combinations to create 35,560 different molecules called tetrasaccharides or different messages. Another way we like to speak of it - as different letters of the alphabet, letters of the language of life for us.

The sheer complexity of glyconutrients actually makes DNA appear simplistic. The DNA can be described as simply the passive 'hardware'; glyconutrients as the 'living, interactive software' that orchestrate homeostasis.

In the early 1990s scientists generally began to realize that the study of proteins had fallen short of expectations whilst none but a small handful of scientists saw the true potential of the newly emerging field of glycobiology.

As will become clear, the true cost of not having discovered the importance of glyconutrients until this last decade is literally fantastic: in the United States alone a staggering $1.3 trillion was spent on health care in the year 2000 - but the Americans are still losing the battle. 120 million people are suffering with chronic diseases and 50-plus million people report autoimmune diseases. As we all know, antibiotic resistance is climbing steadily, and although science has actually finished mapping the human genome, we still don't have a cure or really a treatment for genetic disorders.

What is missing? In the search for this missing link the field of glycobiology has emerged as arguably the single most important breakthrough in the whole field of non-drug medicine.

Cell-to-Cell Communication...the Language of Life Itself

Scientists have positively established that cell-surface glycoconjugates (or glycoforms) are actually the key to the healthy functioning of the entire body.

In a paper titled 'Capitalizing on carbohydrates', Hodgson gives examples of the importance of cell-surface carbohydrates to health. As early as 1990, he perceived a connection between cell-surface glycoforms and the immune system.

"Almost without exception, whenever two or more living cells interact in a specific way, cell-surface carbohydrates will be involved. From the first meeting of sperm and egg, through embryogenesis, development and growth, carbohydrate molecules confer exquisite specificity upon cell-cell interactions. Complex carbohydrates are essential in the correct functioning of the body's immune defences and, paradoxically, in initiating microbial and viral infections with which the immune system has to cope. And when cells turn against the body, as in cancer and autoimmunity, their cell-surface carbohydrate profiles become altered. As Nathan Sharon of the Weizmann Institute (Rehovot, Israel) has put it, 'the specificity of many natural polymers is written in terms of sugar residues and not of amino acids or nucleotides'."[2],[3]

In the 1998 edition of Acta Anatomica, the editor commented on the importance of this "sugar code of biological information":

"Glycosylation is the most common form of protein and lipid modification but its biological significance has long been underestimated. The last decade, however, has witnessed the rapid emergence of the concept of the sugar code of biological information; indeed, monosaccharides represent an alphabet of biological information similar to amino acids and nucleic acids, but with unsurpassed coding capacity."

The significance of the coding capacity of sugar components of glycoproteins is illustrated by the different blood types. Figure 3 shows terminal sugars on the various human blood group glycoproteins. The only difference between Type O blood and Types A and B blood is that Types A and B contain an additional sugar molecule. Types A and B differ only in the terminal sugar. Type A contains N-acetylgalactosamine (GalNAc), while Type B contains galactose (Gal). Yet such a seemingly minor distinction makes the difference between life and death for a person given the wrong blood type.[4]

Although these eight essential saccharides are now well documented in scientific literature, surprisingly, we only get two of those essential sugars in our diet. Glucose is readily available in the form of table sugar while galactose is present in milk products. Before the essential nature of these glyconutrients was understood, nobody raised the question as to why such a paucity of these sugars in our diet even presented a problem. Even now, many people still labour under the misconception that as long as we have glucose in our diet we are able to manufacture these essential sugars ourselves, through glycosylation, ergo there is no problem.

The Myth of the Glucose-Only Theory

So whilst the theory of modern science has it that our body can take glucose and can convert it into all the other essential saccharides by glycosylation, the reality is that in many medical or genetic conditions something is missing that prevents this from happening.

A healthy person who has all of the proper substrates and enzymes can carry out glycosylation and can create the other eight essential saccharides, but it is a prerequisite that all the components of the many biochemical steps, substrates, enzymatic conversions, etc., be present or functioning correctly. The major drawback is that this entire process does require relatively large amounts of energy and effort to achieve the desired aims.

The reason for this is that we are requiring our body to use what are essentially its emergency back-up mechanisms to achieve what should literally be served up on our (silver) platters! More of this later.

The analogy of an assembly line is accurate: every process requires components, and if one department either runs out of materials or breaks down it shuts down the whole line. Similarly, glycosylation can be looked at the same way: if one biochemic step or process cannot take place the process breaks down. Put more technically, inbuilt errors of metabolism (the lack of an enzyme or vitamin) prevent the creation of the essential substrates.

What Happens When the Glycosylation Pathway Fails?

Without the hair-like glycoprotein structures protruding from our cells our macrophages are unable to perform their proper functions, some of which are to identify the 'friendliness' of cells, and either to organize the repair of any damaged ones or to devour and carry them away.

A useful analogy to better understand cell-to-cell communication would be to take Braille as an example. A blind person will feel the Braille sign on a door to discover what is inside. Depending on the sign, they will make a decision either to enter or move on. Similarly, the macrophage will sidle up to a cell and 'dock' onto it by attaching itself to one of the protruding glycoproteins. It will then 'ask', "Do you belong to us?" Upon receiving a positive reply it will then ask, "Do you need anything?" If the answer is "Yes", it will arrange for the delivery of spare parts, repairing molecules, etc. If the answer is "No, I'm fine, thanks", it will release the cell and move on.

It is not hard to imagine what would happen to the blind person if someone failed to attach the sign to the door or someone knocked the sign off the door. Chaos. The person would either have to risk going into the room or wandering on. Similarly, the macrophage will either ignore a cell it does not recognize (cancer) or attack it as a foe (autoimmune disease). Whilst this is obviously a very simplistic analogy, it does make the point that glycoproteins are critically important to our well-being and literally to our survival.

From a more technically-minded viewpoint:

A 1998 review addressed the association of many cancers with changes in glycoconjugates. Cancers in which such changes have been noted include leukaemia, and intestinal, pancreatic, liver, ovarian, endometrial, prostate, urinary tract, lung, and breast cancers. Diseases that have been clearly related to deficiencies in the ability of cells to synthesize glycoproteins include leukocyte adhesion deficiency, hereditary erythroblastic multinuclearity with positive acidified serum lysis test, and carbohydrate-deficient glycoprotein syndrome. Cystic fibrosis and inflammatory diseases, such as rheumatoid arthritis, osteoarthritis, ulcerative colitis and Crohn's disease all are associated with alterations in glycoforms. Some blood-related and vascular disorders, including many diseases of the cardiovascular system, exhibit abnormal glycoproteins. Finally, changes in molecular carbohydrate biostructures in association with parasitic, bacterial and viral infections (including AIDS) are all being studied.[5],[6]

Acta Anatomica goes on to say that "...in cancer alone more than 20 different malignancies are known to be associated with characteristic glycoproteins".[7]

With rheumatoid arthritis we find a similar thing. It has been scientifically shown that people with rheumatoid arthritis have a malformed glycoprotein on their defense cell, specifically on their IgG antibody, where they are missing a terminal galactose. In fact the extent to which this galactose molecule is missing correlates directly with the disease severity.

Because viruses can hide within our cells, an immune-compromised person will suffer relapsing and debilitating diseases such as chronic fatigue syndrome and fibromyalgia, because the immune system will be unable to detect their presence as a result of failures in glycosylation. The 'information' cannot be passed from the 'occupied' or 'infested' cell to the macrophage.

The increasing incidence in recent years of cancer, genetic defects, autoimmune diseases and many other diseases should tell us that our bodies are struggling.

Part of this struggle is to do with the environmental pollution and toxins to which our bodies are exposed on a daily basis. It is documented that there are more toxins inside the home than outside the home. Amazingly, autopsies now reveal that there are 400 new toxins shown in the human body that didn't even exist 45 years ago. (Also, on a somewhat macabre note it has been observed that, thanks to preservatives in our diet, our corpses take much longer to decompose!)

Simply and bluntly put, both conventional medicine and complementary and alternative medicine are losing the 'battle' against disease, bacteria and viruses.

Additionally, our general diet, or rather its woeful shortcomings, must play a very large part and be largely to blame for our declining health. When you have read about the range of diseases that have shown to respond to glyconutrient supplementation, you will doubtless share our view.

Empirically, if something responds to the supplementation of adequate amounts of simple foodstuffs, it would lead one to deduce that our denatured 'diet' is actually responsible for nothing less than our chronic starvation and all the concomitant sequelae of starvation.

The Fallacy of Pursuing the Chimera of Drug Research

Modern medical science has medications that suppress symptoms but it fails to deliver the ability to cure, in the true sense of the word and in the vast majority of cases. In fact the fourth highest cause of death in the US is listed as "properly prescribed, properly taken pharmaceutical medication"; this is also known as iatrogenic disease.

That is certainly not to say that there is not a role for drugs and there is not a role for medication - this is not yet a perfect world - and too many people are irrevocably dependent on them. However, it is obvious that medication is no long-term answer.

The body does not become sick because it is lacking medications in its diet; it becomes sick for want of good nutrition, for without good nutrition it does not have the wherewithal to repair and detoxify itself.

The fact is that the six top causes of death are diet related, which is where this new category of nutrients really fits in: glyconutrients are literally the missing link.

DIABETES

In diabetes a reduced serum antioxidant level has been documented as contributing to increased antioxidative stress in diabetics. Glyconutrient therapy has been shown to actually increase glutathioneperoxidase, which is regarded as the most important antioxidant enzyme in the body.

The same study, involving 32 patients showed "...statistically significant improvement in Candida infections, (p=<.001), recurrent/persistent infections (p=.002), vision problems (p=.016), high blood pressure (p=.031), gastrointestinal tract problems (p=.0.31), and numbness, pain or burning in the lower extremities (p=.031) were also reported after the addition of nutraceuticals to the diet".[10]

Why Are We Not Getting These Nutrients in Our Diet Today?

Our modern diet is very limited and the foodstuffs very highly processed. As we are all well aware, the emphasis of food production nowadays is that it should suit commercial interests: foods should keep as long as possible. To achieve this artificial goal, foods are picked before they have reached their optimum state. They are not vine-ripened in the sun, thus not permitted to produce vital phytonutrients; convenient for both the producers and end-users, perhaps...but it unfortunately has very little to do with providing nutritional value.

Our hunter-gatherer ancestors probably did get these eight essential saccharides or biological sugars in their diet, but, like most of us, you are probably not eating a whole lot of grasshoppers, locusts, crickets, wild berries, roots, fresh herbs, fungi, etc., – and presumably are not getting breast milk in your daily diet! (Having said that, human breast milk is rich in over 130 different oligosaccharides – a combination of 3-6 saccharides.) Hypothetically, it may be that one of the reasons that breast-fed infants flourish significantly better than bottle-fed infants is purely and simply down to these glyconutrients; correspondingly, their absence in the same form or composition in pasteurized cow's milk may explain the allergic reactions suffered by so many babies.)

If We Are Starving, Why Are We So Fat?

As we have seen, our endocrine system depends on correct cell-to-cell communication to enable all the required nutrients, amino acids and hormones to be carried into the cells where they are needed and indeed for their own proper function. Dependent on this system is our very metabolism.

The crisis that exists in the major industrialized nations in terms of obesity and its attendant ills is nothing short of disastrous, with almost 60% of Americans labelled obese, and with the UK hot on their heels at well over 50%. The high-glycaemic diet, the low-fat diets and fads have achieved the very opposite of what they were presumably designed to avoid. These approaches patently do not work in the long run, whereas a correct low-glycaemic, properly balanced diet with the correct supplementation - and adequate exercise, of course - will enable the body to replace fat with lean muscle and to maintain its optimum, healthy weight...sustainably.

Running on Fumes

As has been said, not only were these sugars in the diets of our ancestors years and years ago but they did not have to deal with all our modern pollution, etc., and perhaps this is why we did not have as many autoimmune diseases even as little as a hundred years ago.

Even though there were significantly larger amounts of these glyconutrients readily available in the past, there would have been times of famine and stress, which might indeed explain one reason why the body has a back-up system for making these sugars – the process of glycosylation.

Our state of nutritional exhaustion means that our glycosylation pathways are stretched to their very limits and beyond. We are using our emergency system all the time. Is it any wonder that we see such generalized exhaustion? Even worse, instead of using fructose, impoverished as it is, we find the dreaded sucrose in so many of our foodstuffs that shopping in a supermarket is nothing if not a challenge.

So What is the Answer?

Until we can change the way that we organize the food industry, we are left with very few options except supplementation. It appears that it is only by flooding the system with these raw nutrients that we can relieve the burden placed upon the body's energy reserves, thus freeing up resources for its other critical biochemical activities.

What about the 'only-glucose-is-necessary' theory that we have so long held fast to? Can supplementing these sugars help? Will the body absorb and utilize these sugars rather than contribute to 'expensive urine syndrome'?

In 1998, published research began to disprove the 'glucose-only' theory.

A study published in March 1998 by Alton et al. showed that intact mannose molecules are rapidly absorbed from the intestine of rats into the blood, and that mannose is cleared from the blood within hours.[8] This study also showed that, contrary to current thinking, liver cells in tissue culture absorb most of the mannose for glycoprotein synthesis directly from mannose, not from glucose. One concludes from these experiments that mannose is absorbed, intact and unchanged, from the intestine into the blood and from the blood into the cells. These studies indicate, therefore, that dietary mannose may make a significant contribution to glycoform synthesis in mammals. These authors state:

Direct utilizations of mannose for glycoprotein biosynthesis has not been studied because cellular mannose is assumed to be derived entirely from glucose. However, animal sera contain sufficient mannose to force uptake through glucose-tolerant, mannose-specific transporters. Under physiological conditions this transport system provides 75% of the mannose for protein glycosylation in human hepatoma cells despite a 50- to 100-fold higher concentration of glucose. This suggests that direct use of mannose is more important than conversion from glucose.

In 1998 the same group of humans were given radioactively-labelled galactose, mannose and glucose. The study showed that the galactose and mannose were directly incorporated into human glycoprotein without first being broken down into glucose, therefore concluding that specific dietary sugars could represent a new class of nutrients.[9]

Summary

As we have pointed out, we find ourselves literally in an Armageddon scenario.

On the one hand our nutritional status is critical, the drugs are not working, disease is rampant, obesity is climbing inexorably, exhaustion is commonplace and as a result stress levels - on all levels - are high.

On the other hand, glycobiology has demonstrated that these sugars are essential from a biochemical standpoint.

The questions that remain are:

1. Can we take these dietary sugars and put them into the form of a dietary supplement?
2. Is the body capable of absorbing them?
3. If so, will these supplements have an impact on these disease processes?

The answer to all three questions is undoubtedly and resoundingly "Yes!" as the last two studies above have demonstrated.

Be Sceptical By All Means...But At Least Do Your Homework

On first being introduced to this subject most health-care professionals will be, as were the authors, rightly wary of what seems like yet another potion or another magic pill. Most conventional practitioners have been trained in the traditional Western medical model of one disease, one drug, one cure, so will have less resistance than their more holistic colleagues. However, like every earth-shaking paradigm shift before it, the concept that much disease will respond to simple sugars is an extremely challenging concept for most traditionally-trained practitioners.

Initially, many complementary and alternative medical (CAM) practitioners will also likely react negatively to the idea that life can be as simple as one intervention cures all. However, when they really start researching this topic for themselves and the initial reaction gives way to a growing realization that this promises to be a truly holistic and fundamental intervention, they will be left with a rising sense that at last we appear to have within our mental and physical grasp the very substances that will allow the body to absorb all the other essential nutrients and to return the body to homeostasis.

Of course there will be a need for all of us practitioners for generations to come; of course there will be a need for surgery, trauma medicine and continuing needs for all the panoply of CAM interventions, but the greatest overwhelming demand will be that of the education of the whole of 'society' – that is you and us – so that we can begin to turn the supertanker of health care away from the rocks towards which it is sailing at full steam.

From a homeopathic perspective, certainly we will continue to need to deal with the 'dynamis', certainly we will continue to stimulate the body to recognize its lack of ease, its disease, but for the first time we have at our fingertips the supplementary technology that gives the body the very fuel with which to be able to heal itself.

One wonders about the impact that glycoscience will have over the next ten, twenty and thirty years once the understanding of its ramifications reaches critical mass.

We may finally find that way back in c.400 BC Hippocrates was right all along when he said:

"Let your food be your medicine and your medicine be your food."

GLYCOSYLATION DISORDERS IN CHILDREN

In the most recent issue of Science magazine, in an article entitled 'Saving Lives with Sugar',[11] Dr Hudson Freeze and Dr Joseph Alper discussed glycosylation disorders in children. Children with glycosylation Type 1 (CDG1B) disorder which causes chronic gastrointestinal problems, vomiting, diarrhoea, and bleeding and blood clot formations, is related to an inherent sugar processing defect which causes neurological problems and even death. Children with CDG lack an enzyme: phosphomannoseisomerase, which converts the sugar fructose-6-phosphate into mannose-6-phosphate. It is known that the mannose compound is a critical intermediate to synthesize glycosylated proteins.

References

1. Mondoa,EI and Kitei M. Sugars that Heal. Ballantine Books. ISBN 0345441060. 2001.
2. Sharon N. Complex Carbohydrates: Their Chemistry, Biosynthesis and Functions. Addison-Wesley. Reading, Mass. 1975.
3. Hodgson J. Capitalizing on carbohydrates. Biotechnology (NY). 8: 108-111. Feb 1990.
4. Lehninger AL, Nelson DL and Cox MM. Principles of Biochemistry. Worth Publishers. New York. 1993.
5. Brockhausen I, Schutzbach J and Kuhns W. Glycoproteins and their relationship to human disease. Acta Anatomica. 161: 36-79. 1998.
6. McDowell G and Gahl WA. Inherited disorders of glycoprotein synthesis: cell biological insights. Proc Soc Exp Biol Med. 215: 145-157. June 1997.
7. Acta Anatomica. 161: 1-76. 1998.
8. Alton G, Hasilik M and Niehues R et al. Direct utilization of mannose for mammalian glycoprotein biosynthesis. Glycobiology. 8: 285-95. Mar 1998.
9. Berger V, Perier S, Pachiaudi C, Normand S, Louisot P and Martin A. Dietary specific sugars for serum protein enzymatic glycosylation in man.Metabolism. 47: 1499-1503. 1998.
10. McDaniel CF, Dykman KD, McDaniel HR, Ford CR and Tone CM. Effects of Nutraceutical Dietary Intervention in Diabetes Mellitus: A Retrospective Study. Proceedings of the Fisher Institute. 1(1): 19-23.
11. Alper J AND Freeze H. Saving lives with sugar. Science. 291(5512): 2339.

Comments:

  1. Elizabeth Topping said..

    Please could you advise whether it is safe and wise to take D-Mannose whilst taking Simvastatin and also taking Selexid antibiotics?

    Thank you.


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About Peter Smith and Kelly Ramsey

Peter Smith RSHom FSHom is a Registered Homeopath in practice in Cornwall, England since 1984. Since first becoming involved in the Lowermoor Water Poisoning Incident of 1988, which took place in N Cornwall in and around Camelford, he has been searching constantly for ways in which to help not only those affected by the aluminium sulphate but also the patients in his practice, to cope more effectively with the increasingly serious environmental toxic load which we all face. Drawn towards an eclectic approach, he has integrated Complex Homeopathy into his regular Classical/Practical homeopathic approach and, as this article explains, he is firmly convinced that glyconutrients literally provide our bodies with the wherewithal to heal and thus to maintain ongoing health. pcksmith@talktalk.net   http://www.pcksmith.com/      https://cosmic-unicycle.com/       https://www.gmracademy.co.uk/

Kelly D Ramsey PA-C received her degree in Physician Assistant Studies from The University of Texas Southwestern Medical School and is currently practising trauma emergency medicine in the United States. For the last year she has also been a nutraceutical consultant and has a special interest in the emerging field of glycobiology. As the owner of her own global wellness company, she has been educating others about glyconutrients - the 'missing link' - and the importance of wellness. She can be contacted on tel: +1 866 726 7393; e-mail: Kelly@totalwellnessgroup.com

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