Irritable Bowel Syndrome (IBS) is a chronic disorder affecting an estimated 15 – 22% of western populations, and is the major cause of referrals to gastroenterology clinics in the western world . The symptoms may include abdominal pain, diarrhoea, urgency to have a bowel movement, a feeling of incomplete evacuation after a bowel movement, flatulence and bloating. Some sufferers experience constipation, or an alternation between constipation and diarrhoea. IBS is more common among women than men, with a 2:1 female: male ratio . Current medical treatments are directed at symptomatic relief, and although these can give some relief, there is no one treatment which has been shown to be lastingly effective. Although IBS is not a life-threatening disease, the symptoms and the effects of the symptoms on daily life can have a great impact on sufferers . IBS is also associated with large healthcare and economic costs in terms of hospital investigations, repeated visits to GPs, prescription medicines, and loss of time from work . Although hospital investigations for more serious diseases such as cancer or Inflammatory Bowel Disease are negative in people with IBS, some abnormalities in the gut have been found. For instance, some patients have been found to have a degree of mucosal inflammation, which may be in response to some foods . It is possible that people with IBS have immunological reactions to dietary antigens as food elimination based on serum immunoglobulin G antibodies has been found to result in a significant decrease in symptoms of IBS. Both numbers of mast cells and their mediators have been shown to be increased in intestinal mucosa in patients with irritable bowel syndrome, especially in the close proximity of intestinal nerves . Kalliomäki  suggests that food antigens induce mast cells to secrete mediators which regulate gastrointestinal motility, resulting in alterations in peristalsis and an increase in abdominal pain and discomfort. Furthermore, the mast cell-derived mediators have effects on immune cell functions. It may be then, that the nutrition of people with IBS is more important than has been traditionally thought. As people with IBS tend to believe that their symptoms are affected by diet, they often attempt to manage their disorder by dietary control. However, the only consistent advice given to people with IBS is usually simply to eat a "healthy" diet which includes fruit, vegetables and fibre. In an early study of people with IBS, Dancey & Backhouse  found that although the majority of their sample of 148 people (70%) stated that they were trying to follow a "healthy" diet with large amounts of fruit and vegetables; for many of these people, such a strategy had not led to symptom improvement, and in an attempt to control their IBS, 14% were eating very restricted diets. Some of these diets involved avoiding complete groups of foods, e.g. carbohydrates. Whilst such a strategy may reduce bloating, for instance, such a diet is not likely to enhance wellbeing. As well as eating a sufficient quantity of a wide variety of foods from each food group, micronutrients and nucleotides may also be important for health, especially in the sub-well. It is nucleotides which are the focus of this study.
Nucleotides are substances which are synthesised endogenously – they have important effects on the growth and development of cells which have a rapid turnover, such as those in the immune system and the gastrointestinal tract. The intestinal epithelium is a rapidly proliferating tissue with a high cellular turnover rate. A complete cell cycle in humans is 24 hours, with a replacement of the entire enteric epithelium within 3–6 days. In healthy people, dietary nucleotides are probably not essential, and in fact most will be metabolised and rapidly excreted from the system. However, under certain circumstances (e.g. in the sub-well, diseased, or under conditions of stress or poor diet) dietary nucleotides may be what Maldonado, Navorro, Narbona, & Gil  call "semi-essential", optimising the function of the gastrointestinal and immune systems. In relation to the gastrointestinal system work has shown that dietary nucleotides enhance the intestinal absorption of iron . Dietary sources of nucleotides are nucleoproteins and nucleic acids, and these are found to varying degrees in many foods – lamb, liver, mushrooms (but not fruit and other vegetables) all are rich in nucleotides. Rapidly dividing tissue requires a constant supply of nucleotides in order to manufacture essential nucleic acids. Exogenous supplies of nucleotides may optimise tissue function particularly during recovery from mucosal injuries when the endogenous supply may limit the synthesis of nucleic acids.
Holen & Jonsson  found that dietary nucleotides had beneficial effects, especially when the nutrition supply was inadequate. Work with infants has shown that the incidence and duration of acute diarrhoea is lower in infants when dietary nucleotides are included in their diets . Previous work on the effect of nucleotide supplementation in animals has found that such supplements are important for the repair mechanism of immune cells . In piglets, nucleotide supplementation had effects on the gastrointestinal system by increasing villi height and crypt depth. . Evans, Tian, Gu, Jones & Ziegler , using rats to model short-bowel syndrome, found that nucleotide supplementation is associated with increased jejunal adaptive growth after massive small bowel resection in rats. Dietary nucleotides have been found to help athletes by reducing the release of stress related hormones and chemicals in the body, and by maintaining a higher level of antibodies, which enables the immune system to work more effectively . In people with a chronic illness such as IBS whose primary symptoms relate to the gastrointestinal tract, nucleotide supplementation may improve symptoms via improved gut function or by an enhancement of the immune system.
There are particular problems in assessing the benefits of treatments of people with IBS, and some of the problems of this patient group in relation to clinical trials have been discussed in detail by Spiller . People with IBS show great variability in frequency and severity of symptoms, both when compared to others and also from day-to-day in their own symptoms. Spiller  has shown there are clear benefits to participating in clinical trials; people with IBS tend to be helped by placebo alone. This is thought to be due to a reduction in anxiety and/or depression as a result of help and reassurance given by the people running the trial. If this is the case, then anxiety and depression should reduce over the length of the trial. One would also expect that, if symptoms improve, then psychological well-being should in some way improve also. Thus although our primary aim was to determine whether nucleotide supplementation improved the symptoms of irritable bowel, we also wished to determine whether ratings of anxiety and/or depression would show any change as a result of symptom change.