Glycobiology: could sugars be the new route to sweet success for athletes?

Although the discovery of DNA marked the start of a revolution in biology and medicine, if you think that DNA and proteins hold the sole key to understanding life, you’re in for a rude awakening. Scientists are now beginning to realise that a few humble sugar molecules make up the alphabet of a new code – a code that governs, guides and regulates the day-today functioning of all the cells in our bodies. ‘Glycobiology’, the study of how sugars are involved in almost every aspect of biology, is set to be the next revolution in medicine. And now some experts are beginning to wonder whether increasing our intake of these sugars could also improve health and boost physical performance, writes Andrew Hamilton.

For example, we now know that sugars play a pivotal role in immunity (by recognising foreign invaders), in blood clotting and even in the creation of life itself (by helping sperm to penetrate an ovum)! Sugars also regulate how quickly hormones are cleared from the blood, direct the development of embryos in the womb and act as ‘address codes’, telling the billions of cells and proteins on the move in your body exactly where to go!

The language of sugars

To understand how this is all possible, we first need to consider a few basic facts about sugar. Although most people tend to think of sugar as a single substance, there are, in fact, a large number of different sugars, which can be classified into four distinct groups:

• Sugar building blocks All sugars are small, single, sweet-tasting molecules with a ring-like structure containing six carbon atoms. Familiar examples include glucose (found in honey, sports drinks, etc) and fructose (found in fruits). Although all simple sugars have the same basic ring structure, it’s the distribution of the hydrogen and oxygen atoms around the ring that determines exactly what kind of sugar it is. Biological systems use glucose and about 10 other different simple sugar molecules as building blocks for larger, more complex chains of sugar molecules. These building blocks are often referred to as the ‘essential sugars’ (see table 1, below).
• Disaccharides As the name suggests, these are sugar molecules constructed from two sugar building blocks bonded together. The classic example is sucrose, the table sugar you stir into your tea, which is built from an essential sugar (glucose) and a non-essential sugar (fructose) bonded together. Another example is the milk sugar lactose, which is built from glucose and another essential sugar building block called galactose.
• Oligosaccharides These are short chains of sugars containing just a few sugar building blocks bonded to each other, a classic example being dextrose, found in most sports drinks, which consists of short chains of glucose molecules bonded together. However, much more complex oligosaccharides can be formed by constructing short chains with a variety of different essential sugar building blocks (see figure 2, below).
• Polysaccharides These are very long chains of sugar building blocks bonded together – sometimes in their hundreds. Common examples include starchy carbohydrates, found in bread, pasta etc, cellulose in plants and stored muscle carbohydrate (muscle glycogen). All of these examples are built from long chains of glucose molecules, but the difference is in the way the individual glucose building blocks link to each other, which in turn gives rise to different patterns of chain branching and overall ‘macro-structure’.

Table 1: the eight sugars essential for humans

Although they’re sometimes referred to as the ‘essential’ sugars, our bodies can, in fact, synthesise all of these sugars from glucose. However, some scientists believe that supplying plenty of these other sugar building blocks in the diet can lead to health benefits, partly because the body won’t need to expend as much metabolic energy on synthesising them, and partly because, in some people, one or more of these synthetic pathways may be operating at less than optimum efficiency.

Table 1: the eight sugars essential for humans

Essential sugar	Good dietary sources
Glucose (Glu)	Almost all fruits, most vegetables and starchy foods, eg pasta, bread, rice etc
Galactose (Gal)	Carrot, beet, cauliflower, broccoli, kale, lettuce, parsley, rhubarb, Brussel sprouts, red cabbage, asparagus
Mannose (Man)	As for galactose
Fucose (Fuc)	Virtually no dietary sources
Xylose (Xy)	As for galactose, above, plus wheat
N-Acetylglucosamine (GlcNAc)	Small amounts in some seeds and plant saps, some fungi, some algae and milk
N-Acetylgalactocosamine (GalNAc)	Small amounts in milk
N-Acetylneuraminic Acid or Sialic Acid (NANA)	Small amounts in milk

Figure 1: Glucose, the fundamental essential sugar

Figure 2: Blood groups and sugar chains

The fact that there are over 10 different essential sugar building blocks, and that each building block can be joined to another in a number of different ways, allows for incredible complexity and diversity in biological systems, even in short sugar chains. Nature uses this infinite variability and the 3-D shape of sugar chains as a way of identifying cells and helping them to communicate with each other.

We’ve long known that sugars are a prime source of fuel and that many living systems use long chains of sugars for building structures; for example, the main structural component of plants is cellulose. However, apart from that, sugars were until recently dismissed as unimportant and scientists who observed the complex sugar chains attached to the surfaces of cells assumed that they were there for ‘decoration’!

But with the advance of genetic science, we now know that Mother Nature has harnessed the incredible complexity of sugar structures for no less a task than to orchestrate the symphony of life! The chains of sugars attached to proteins and fats on the surfaces of cells (more technically known as ‘glycoconjugates’), far from being merely decorative, are absolutely vital for the correct functioning of those cells. In fact, these sugar chains act as ‘labels’, allowing cells to communicate with each other and interact with the immune system. If this sugar labelling system becomes impaired or defective, the consequences can be grave.

Studies on mice have shown that when certain glycosylation enzymes are impaired, the adverse effects on health can range from heart defects to autoimmune disease (where the body attacks its own tissues). And people who lack a key sugar label on a protein called transferrin, which transports iron into cells, are prone to a host of problems, including delayed mental and physical development, liver and skin problems.

Indeed, scientists and doctors are fast realising that the sugar residues residing on cell surfaces are critical to almost every aspect of health. Already 13 different genetic disorders have been identified and classified as ‘disorders of glycosylation’ – ie incorrect or impaired labelling of cells with sugars. Moreover, many common diseases are linked to sugar disorders. In the mid-1980s scientists discovered that all people with rheumatoid arthritis have an abnormality in the enzyme that attaches the sugar galactose to a type of antibody in the immune system. And we now know that sugars missing from a cell-surface protein are to blame for some forms of muscular dystrophy.

Can extra sugars improve health?

As our understanding of glycobiology has grown and we have begun to appreciate the importance of the essential sugars in both health and disease processes, some scientists have begun to ask whether we could benefit from sugar supplementation. A number of essential sugar supplements described as ‘glyconutrients’ have begun to appear on the market, with the claim that they promote improved immunity, boost physical and mental performance and increase resistance to disease.

Advocates of glyconutrients argue that modern diets supply very little in the way of essential sugars other than glucose ⁽¹⁾ and that, even when these sugars are consumed, our reduced consumption of fibre and our use of alcohol, food preservatives and antibiotics contribute to a colonic environment that is ill-equipped to break down the dietary polysaccharides that contain these essential sugars.

However, other nutritional scientists remain sceptical because most healthy people can synthesise all the essential sugars required in the body from glucose, which is normally supplied in abundance in the diet. They argue that, unless someone has a defect in the enzyme pathways that convert glucose to the other essential sugars, taking extra essential sugars in the diet is completely unnecessary. So where does the truth lie?

Survey the literature and you’ll find literally thousands of scientific studies confirming the myriad roles of essential sugar chains in cell functioning and, consequently, in human health. Many of these studies are cited by companies promoting glyconutrients as proof of the benefits of supplementation.

However, real scientific proof can only emerge from the kind of study that compares the effects of treatment with essential sugar supplements with those of an inactive or ‘dummy’ treatment, technically known as placebo.

The researchers found that the cell surface expression of certain glycoproteins associated with a healthy immune system were significantly lower in CFS patients than in controls. They also measured the activity of another type of immune cell called natural killer (NK) cells and found it to be significantly lower in the CFS group. However, when they added a glyconutrient mix to the extracted cells, it not only increased glycoprotein expression on the PBMCs but also increased the activation of the NK cells against the human herpes virus. They concluded that supplementary glyconutrients had significantly improved the patients’ abnormal immune parameters.

A second study investigated the effects of glyconutrient supplements on the symptoms of fibromyalgiaand chronic fatigue syndrome ⁽³⁾. Fifty subjects with a doctor’s diagnosis of fibromyalgia (FM) and/or chronic fatigue syndrome (CFS) were interviewed at the outset of the study and nine months later. In the intervening period, they consumed various nutritional supplements designed to supply high levels of essential sugars, and a multi vitamin/mineral formulation. After nine months’ supplementation, they demonstrated a remarkable reduction in initial symptom severity.

Nevertheless, these results need to be interpreted with caution, for three reasons:

1. No untreated control group was included for comparison, which means the favourable results could have been due to the well-known ‘placebo effect’;
2. No before-and-after physiological measurements were taken, with all improvements being subjective and self-reported;
3. Since the subjects also took vitamins/minerals, it is not clear exactly what was responsible for their improved condition.

A later study on mice examined the effects of glyconutrients on the ability of immune cells called macrophages to engulf and kill three types of micro-organism ⁽⁴⁾:

• the yeast candida albicans
• the bacteria E-coli
• the bacteria staphylococcus aureus.

The macrophages were collected from the mice and then mixed with a glyconutrient mixture and incubated for either 10 or 60 minutes, after which the researchers measured the ability of the cells to engulf and kill the three types of micro-organisms. They found that the longer the cells were exposed to the glyconutrients, and the higher the concentration of the latter, the more efficient the macrophages were at killing the micro-organisms.

Other studies have suggested that glyconutrients can improve brain function. In one such study, on children with attention deficit hyperactivity disorder (ADHD), 17 children were given glyconutrients for a period of six weeks, while their behaviour was ranked by their teachers and parents ⁽⁵⁾. The researchers found that all of them demonstrated markedly improved behaviour for the first two weeks, which was maintained throughout the six- week study period. However, once again caution is required in interpreting these results because the study included no controls.

In a more rigorous study into glyconutrients, brain function and alertness/activity, carried out last year, 20 healthy male college students took a pure glucose supplement (placebo) and a glyconutrient supplement in random order ⁽⁶⁾. Electrical brain activity was monitored for 30 minutes following ingestion of both supplements.

The researchers found that, by comparison with pure glucose, the glyconutrient supplement significantly enhanced power in three brain wave frequencies (theta, alpha, and beta) that are known to be associated with attention and arousal, suggesting that it also enhanced brain activity. However, the question whether this enhanced activity is associated with improved task performance has yet to be determined.

What does this mean for athletes?

There is certainly some persuasive evidence that glyconutrients may enhance immunity (particularly if you also consider the in vitro studies that have been carried out); and there is also some limited data supporting the notion that glyconutrients can enhance mental function. But what do glyconutrients have to offer athletes and sportsmen?

Browse the websites of some of the companies marketing these products and you’ll find plenty of talk about the potential benefits of glyconutrients in relation to exercise, in terms both of improving tolerance to heat stress during exercise and of recovery afterwards. And it is true that part of the process of building heat tolerance requires an increased ability of the body to ‘label’ special cell proteins with sugar chains (glycosylation), which in turn requires a greater usage of essential sugars ^(7-9).

Likewise, scientists also know that the increases in blood acidity and calcium ion concentration and the decrease in oxygen content during exercise are all signs of physiological stress. During exercise, special glycoproteins involved in helping the body combat this stress are synthesised much more rapidly ⁽¹⁰⁾. The process of recovery from exercise also requires an increase in other types of these essential sugar-containing glycoproteins.

However, it’s a big jump from these facts to the assumption that extra dietary glyconutrients can improve performance. Remember that, unless you are one of the unfortunate few suffering from genetically impaired glycosylation, your body can readily synthesise the small amounts of essential sugars it requires from glucose; and unless you’re on a very low-carbohydrate diet, glucose is available in abundance!

The fact is that at present there are no reliable scientific studies demonstrating the benefits of glyconutrients for athletes. That’s not to say that there are no such benefits, but simply that, if there are, they have not been demonstrated in a scientifically acceptable fashion.

Given the rapidly growing interest in ‘glycobiology’, what’s the best advice for sportsmen and woman seeking to optimise performance? There is little doubt that the coming years will see tremendous advances in our understanding of how sugars impact on health, disease and performance.

But, while we need to keep an open mind, there is simply not enough evidence at present to suggest that healthy people have anything to gain from glyconutrient supplementation. My advice is to save your pennies for the time being or, even better, use them to improve the basic quality of your diet! One of the best ways for most athletes to do that is by increasing the quantity and variety of fresh fruit and vegetables consumed, which will simultaneously boost your intake of naturally occurring glyconutrients.

Figure 3: Changing carbohydrate intake patterns

References

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6. Integr Physiol Behav Sci 2004; 39(2):126-38
7. J Neurochem 1988 Sep; 51: 960-966
8. Int J Hyperthermia 1997 Nov; 13:621-636
9. Biochem Biophys Res Commun 1997 Mar; 232:26-32
10. Can J Appl Physiol 1995 Jun; 155-167