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Are probiotics and other functional foods the medicines of the future?

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Susan Holmes, PhD, BSc, SRN, FRSH.

Director of Research and Development and Professor of Nursing, Faculty of Health, Canterbury Christ Church University College, Canterbury

People have believed for centuries that food is capable of both preventing and treating disease. This is true, at least to some extent, and it is clear that the nutrients food provides play vital roles in preventing and managing disease. In more recent history, there has been a move away from food towards drugs, which have been increasingly used to prevent, alleviate or treat disease. However, the discovery of nutrients, and the development of nutritional science, has led to an increasing recognition of the role of nutrition in maintaining health and, in turn, to the rise of so-called ‘healthy eating’ during the 1970s and 1980s. Continuing research has provided new evidence and a change in emphasis from the negative or harmful aspects of food towards the idea that food or its components may benefit health; this, in turn, has led to the development of a range of products known as ‘functional foods’ (Sheehy and Morrissey, 1998).

People have believed for centuries that food is capable of both preventing and treating disease. This is true, at least to some extent, and it is clear that the nutrients food provides play vital roles in preventing and managing disease. In more recent history, there has been a move away from food towards drugs, which have been increasingly used to prevent, alleviate or treat disease. However, the discovery of nutrients, and the development of nutritional science, has led to an increasing recognition of the role of nutrition in maintaining health and, in turn, to the rise of so-called ‘healthy eating’ during the 1970s and 1980s. Continuing research has provided new evidence and a change in emphasis from the negative or harmful aspects of food towards the idea that food or its components may benefit health; this, in turn, has led to the development of a range of products known as ‘functional foods’ (Sheehy and Morrissey, 1998).




Functional foods
Although there is no universally accepted definition, functional foods generally refer to those believed to prevent or treat diseases (Goldberg, 1994). Although it can be argued that all food is ‘functional’, the modern concept is that such foods must provide benefits over and above the nutrients required for normal health. Thus Goldberg defined functional foods as ‘any food or food ingredient that has a positive effect on an individual’s health, physical performance or state of mind, in addition to its nutritive value’. Such components may include specific minerals, vitamins, fatty acids or dietary fibre and/or biologically active substances such as phytochemicals or other antioxidants and probiotics that contain live beneficial bacterial cultures (EUFIC, 2003).




According to the consensus document Scientific Concepts of Functional Foods in Europe (1999), functional foods must be in the form of normal foods and their effects must be demonstrated in amounts that are normally consumed in the diet. They may be a natural ‘whole food’, a food to which a component has been added or one from which a component has been removed; they may also be foods in which the nature or bioavailability of one or more of their components has been modified. Finally, they may rely upon any combination of these factors.




A variety of such foods is now available, some targeted at the whole population and others at particular groups, such as older people. Despite this, their benefits are not always entirely clear and many scientific and regulatory organisations are actively seeking ways of establishing the scientific basis to support their many claims and protect consumers from false and/or misleading claims.




Growing awareness of the importance of nutrition, combines with socio-economic changes and the increasing costs of health care to increase the demand for foods with added health benefits. Nowhere is this more apparent than in the area of the gastrointestinal tract (GIT).




The gastrointestinal tract
The many physiological functions of the GIT, such as digestion and absorption, colonic fermentation, and gastrointestinal tract-associated immune activities, among many others (Robertfroid, 2002), make this the focus of much attention primarily due to the large number and variety of bacteria that live symbiotically with the host. Indeed, human adults carry over 1kg of bacteria in their gastrointestinal tract and excrete their own weight in bacteria every year (EUFIC, 2003). Robertfroid (2002) points out that such bacteria play a number of important physiological and/or metabolic roles (Box 1).




Although we generally think of bacteria as undesirable and the cause of many unpleasant infections, they appear to have beneficial effects and, perhaps, improve human health. This is particularly true of some members of the intestinal microflora that are believed to be health-promoting, even though others may pose threats to health, particularly if they overgrow. The composition of the intestinal microflora is therefore important.




The colonic microflora must be ‘balanced’ so that those bacteria known to be beneficial, such as lactobacilli and bifidobacteria, dominate over those that are potentially harmful or that may be pathological (EUFIC, 2003).




Stress, food, drug therapy and environmental factors may all stimulate or inhibit the growth of different types of micro-organisms (Figure 1).




This concept of a ‘balanced microflora’ is now used to describe attempts to maintain a healthy balance of bacteria, stimulate gut immunity and help to prevent colonisation by pathogenic organisms that cause intestinal disturbances and diarrhoea (EUFIC, 2003). Foods believed to promote this include probiotics, prebiotics and synbiotics (Box 2).




Although there are many definitions of probiotics, they can be simply described as ‘non-pathogenic micro-organisms that, when ingested, exert a positive influence in the health or physiology of the host’ (Marteau et al, 2002).




They are added to foods either as live microbial cultures or as a supplement (EUFIC, 2003). The critical factor in their definition is that the bacteria are added to ‘normal’ food and that consumption of that bacteria must have clear and distinct health benefit(s) (Guarner and Schaafsma, 1998). Current examples include the Lactobacilli spp and Bifidobacterium spp, both of which are commonly used in food products including dairy products (for example yoghurt, fermented milk products) (Jonkers and Stockbrügger, 2003).




Box 3 outlines some of the beneficial effects claimed for probiotics.




Historical perspective The original belief that probiotics might exist arose from studies of the longevity of the Bulgarian population. It was suggested that this longevity might be due to their consumption of large amounts of yoghurt (Metchnikoff, 1907). This yoghurt was made using Lactobacillus bulgaris, which was claimed both to improve health and to extend the healthy lifespan. It was from this that the concept of manipulation of the intestinal flora arose and, since then, research has been designed to investigate its benefits in terms of human health.




Scientific/clinical evidence Although many claims are made for the benefits of probiotics (Box 4) and their mode of action, there is currently little scientific or clinical justification for their use (CedgArd, 2002). Indeed, it is only comparatively recently that serious scientific investigation has sought to evaluate such claims. Even now, data are limited and few studies are placebo-controlled, so that there is scepticism about their use (Robertfroid, 2002). This, to some extent at least, reflects the lack of markers of GI well-being and health.




It appears, however, that consumption of fermented dairy products is associated with a lower incidence of some conditions, for example, bladder cancer and ulcers, in some populations but not in all (Robertfroid, 2002). Animal studies reveal that some micro-organisms can increase the incidence of colonic tumours, while others prevent tumourigenesis (Wollowski et al, 2001).




Human studies reveal that a low risk of colon cancer is associated with many of the lactobacilli (for example L. acidophilus and L. SO6) and bifidobacteria (Moore and Moore, 1995; Horie et al, 1999) while the bacteroides and clostridia increase the incidence and growth rate of colonic tumours (Horie et al, 1999). Although this suggests that the intestinal microflora may be influential in moderating the risk of colonic tumours, the evidence is not yet conclusive; it is, however, suggested that probiotics may modify the ability of other micro-organisms to produce carcinogens (Guarner and Malagelada, 2003).




This is supported by the findings of epidemiological and intervention studies, which provide some evidence for the protective effects of probiotics against cancer (Burns and Rowland, 2000). Although most studies on the anticarcinogenic effects focus on colorectal cancer, there are also some studies on breast and bladder disease (Rafter, 2002); the findings are encouraging. For example, a study in Finland revealed that, despite a high fat intake, the incidence of colorectal cancer is low due to the high consumption of milk, yoghurt and other dairy products (Intestinal Microecology Group, 1977) while two later population-based, case-control studies revealed an inverse association for both cultured milk (Young and Wolf, 1988) and yoghurt (Peters et al, 1992).




Breast cancer in women is similarly lower in those who consume yoghurt and other fermented milk products (Le et al, 1986; van’t Veer et al, 1989), while consuming such products reduces incidence of both gastric ulceration and bladder cancer in certain populations (Burns and Rowland, 2000). That said, two further prospective studies in the US did not reveal similar findings in either health professionals (Kampman et al, 1994a) or older people (Kampman et al, 1994b).




It is believed that a significant mode of action for probiotics is that of providing protection for GI epithelial surfaces, which encounter a wide variety of environmental micro-organisms and constitute the ideal surface for pathogenic processes; evidence suggests probiotics may prevent or reduce such effects. For example, in two randomised controlled trials, one in liver transplant recipients and the other in patients with acute pancreatitis, patients were fed using a fibre-containing solution together with live or heat-killed L. plantarum 299, by nasojejunal tube.




The transplant trial revealed that those receiving live bacteria experienced significantly fewer post-operative infections (Rayes et al, 2002); similar differences were found in the pancreatitis study (Olah et al, 2002) and in both there was a noticeable decrease in the length of hospital stay. Such findings suggest beneficial effects, though it was pointed out that probiotics alone are not enough and that a substrate for bacterial growth, in this case fibre, must also be given (see prebiotics section, below).




Ongoing studies are seeking to find out whether it is possible to prevent or cure intestinal infections and inflammatory bowel disease, Crohn’s disease and ulcerative colitis with probiotics. This is particularly true in terms of infection with Clostridium difficile or Escherichia coli (Marteau et al, 2001). This is not surprising, since colonisation of the gastric mucosa by Helicobacter pylori is the prime cause of gastritis and ulceration and is strongly associated with gastric lymphoma and cancer. Studies reveal that some probiotics exert antagonistic effects against H. pylori in vitro (Coconnier et al, 1998) and in vivo (Cremonini et al, 1998). This being so, it is an easy leap to consider the potential of probiotics against other GI bacteria which, undoubtedly, influence inflammation; most inflammatory bowel conditions are more severe in the presence of endogenous flora.




It can also be anticipated that probiotics might influence the course of inflammatory bowel diseases and, indeed, studies in animal models of colitis and human inflammatory bowel disease are promising (Jonkers and Stockbrügger, 2003). However, as in all areas, the data available are limited and few of the currently reported studies are placebo-controlled; the results remain conflicting and more work is needed.




The same is true of another potentially valuable use for probiotics, that of preventing antibiotic-associated diarrhoea (Gorbach, 1990; Campieri and Gionchetti, 1999). A recent meta-analysis (D’Souza et al, 2002) suggests that probiotics, particularly Saccharomyces boulardii and lactobacilli, may be useful, though there is little to suggest that probiotics have a role in treating such conditions; their clinical benefits remain to be proved.




There is better evidence that probiotics may be protective against allergy, particularly in infants in whom randomised, placebo-controlled trials suggest that the severity of eczema is significantly reduced in those given probiotic supplements (Isolauri et al, 2000; Kalliomaki et al, 2001). It is not, however, clear whether this would apply to all probiotic organisms or would be applied to the treatment of allergies at other times of life, though work in this area continues (Marteau et al, 2002).




Prebiotics and synbiotics
Since the value of probiotics remains to be proven, attention is increasingly turning to the use of prebiotics as a more certain way of securing potential benefits without associated difficulties (Rastall and Maitin, 2002). These, too, are treated as functional food ingredients and comprise complex oligosaccharides, such as dietary fibre, that are not digested by humans but are broken down in the gut by microbial action, thereby providing nutrients to promote the growth and colonisation of probiotic bacteria.




Although they are currently most widely used in Japan, their use is increasing in the UK and USA (Robertfroid et al, 1998). The market leaders are fructans, fructo-oligosaccharides and inulin, which are economical to manufacture and produce demonstrable prebiotic effects in humans (Tuohy et al, 2001a; Tuohy et al, 2001b). The value of prebiotics remains to be established, though this area holds promise for the future.




Synbiotics are another promising area for future development (Rastall and Maitin, 2002) as it is believed that using a probiotic and prebiotic in combination will make it possible to promote probiotic action within the GIT, thus allowing a more rational approach to their use and enhancing their beneficial effects.




Probiotics are believed to hold promise for the future as they clearly allow modulation of the endogenous intestinal microflora and the immune system (Marteau et al, 2002).




Although some health benefits have been shown, there are still questions about their value in clinical practice. Research is continuing and it is probable that, given time and good quality research, the situation will be clarified.




Despite the significant scepticism, probiotics are a major aspect of the emerging functional food market (Diplock et al, 1999; Shanahan and McCarthy, 2000) and there are many probiotic products on the market; our patients may well be using them for a variety of reasons. For this reason, if for no other, nurses must be aware of such products and be able to provide appropriate advice to their patients.



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