Psychiatric Disorder and Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a common yet poorly understood functional bowel disorder. A multi-factorial aetiology has been proposed, and abnormalities in colonic motility, small bowel motility, and visceral sensation have been observed experimentally. More recently, attention has turned to a quite distinct abnormality, namely psychological function. Studies have shown that for a significant proportion of the MS population, co-morbid psychiatric disturbance may be aetiopathological, with the physical abnormalities described occurring in response to stress or anxiety induced experimentally. Others have suggested that psychological distress may occur as a result of severe gastrointestinal symptoms, and that psychosocial factors may be related to the presentation rather than genesis of the symptoms. Many of these studies contain methodological inadequacies which may adversely affect the results obtained. Comparison between studies, which may provide further insight, is often difficult due to inconsistencies in the experimental protocol and the non-standard ways in which data have been presented. It is likely, however, that differences between methodologies may, in part, explain the variations in results between studies.

Keywords: irritable bowel syndrome, psychopathology, psychosocial.

INTRODUCTION

Irritable bowel syndrome (IBS) is a common, functional gastrointestinal disorder, characterized by abdominal pain and altered bowel habit in the absence of organic bowel disease. It is frequently associated with altered colonic motility [ 1, 2] and autonomic nervous system dysfunction [ 3].

IBS is thought to account for approximately 25% of referrals to gastrointestinal clinics [ 4]. Barsky [ 5] suggested that the characteristic symptoms are present in all of us to a certain degree. This is supported by prevalence data which suggest that 22% of people are significantly affected by the disorder at some point 16]. Only a minority, however, ever consult a doctor.

Until recently, the existence of the disorder was disputed by many physicians, and sufferers were frequently dismissed, being advised that their symptoms were `all in the mind'. Diagnostic problems were compounded by heterogeneous clinical experience of the syndrome, with both inter- and intra-subject variation. Well-defined diagnostic criteria [ 7, 8] and the identification of symptom subgroups [ 9] have now somewhat improved the clinical picture.

One significant subgroup in which there has been much interest is that in which subjects exhibit a concomitant psychiatric disorder. The incidence of psychiatric illness in IBS sufferers has been estimated at between 4% [ 10] and 100% [ 11]. Anxiety and depression are frequently encountered, their respective prevalences estimated at 98% [ 12] and 87% [ 13] (Table 1). Such psychoneuroses, however, are relatively common in the general population [ 14, 15] and their prevalence in IBS may simply be a reflection of this. Palmer et al. [ 16], however, showed that the levels of neuroticism in IBS patients fell midway between those identified in the general population and a group of psychiatric patients.

Other psychoneuroses have also been identified in IBS, including hysteria [ 17, 18], panic disorder [ 19], somatization [ 20, 21], abnormal illness behaviour [ 22, 23] and fear of organic disease [ 24]. Dotevall et al. [ 12] also identified a range of frequently occurring neurasthenic symptoms, including fatigue, hostility and sleep disturbance. Many of these are fundamentally associated with depression.

IBS sufferers are also thought to experience more stressful `life events' than the population as a whole [ 25-27]. Such events precede the onset of panic disorder [ 28] and contribute to gastrointestinal symptoms [ 29-31]. Specifically, they have been shown to affect colonic function [ 32], increasing colonic motility [ 33], whole gut transit time [ 34] and secretion of gastrointestinal hormones [ 35]. A reduction in the frequency of the migrating motor complex has also been observed, although not specifically in IBS [ 36].

In 1977, Engel [ 37] proposed a biopsychosocial medical model which could be applied to the irritable bowel. This delineated the biological and psychosocial factors which determine illness and a person's experience of it, and represented a significant advance upon previous two-dimensional biomedical models which paid scant regard to the psychological dimension. Bockus et al. [ 38] suggested that the `neurotic stigma' attached to IBS had prevented it from attaining the gastrointestinal recognition that it deserved. More recently, attention has been focused on the role of psychosocial factors in the aetiology of the disorder. Three possible hypotheses have been suggested:

( 1) Psychosomatic hypothesis. This suggests that psychiatric disturbance is, in effect, the root cause of gastrointestinal distress. The hypothesis is supported by studies which have shown that psychoneuroses antedate gastrointestinal symptoms [ 17, 19, 39] and that psychologically oriented treatment ameliorates such distress [ 40-44]. The newly emerging scientific discipline of `neuropsychoimmunology' focuses on the relationship between psychiatric and somatic health, and implicates a range of biogenic vectors, which in IBS may include bile acids [ 45]. Latimer et al. [ 11] found similar patterns of myoelectrical activity in psychoneurotic subjects and sufferers of IBS. This pattern was significantly different from that found in `normals'. Ryan et al. [ 46] suggested that anxiety and somatization (the somatic manifestation of a psychiatric illness) in IBS patients was greater than in patients hospitalized for a primarily physical illness. This suggests that anxiety regarding symptoms cannot alone explain somatization behaviour in IBS. Ryan et al. [ 46,p. 141] concluded that anxiety is therefore "more causally related to irritable bowel syndrome than a consequence of such symptoms", while a recent study by Kirkmayer et al. [ 47] showed that the majority of psychological illness is presented somatically in the primary care environment.

( 2) Somatopsychic hypothesis. It has also been suggested that psychiatric disturbance occurs as a result of the severe gastrointestinal distress experienced by IBS sufferers [ 48, 49], and a link between severe physical distress and psychological distress has been identified for somatic illness as a whole [ 50]. However, high levels of psychopathology are not found in other bowel disorders, such as inflammatory bowel disease, despite equally severe symptoms [ 3]. Patients with peptic ulcers, but not gallstones, were identified as having similar psychological profiles to sufferers of IBS [ 30], and it has been suggested that the presence of gastrointestinal symptoms contributes to introspection, anxiety and a consequent over-concern about nongastrointestinal symptoms [ 48].

( 3) Illness behaviour hypothesis. The third possibility is that psychiatric disorder is notdirectly associated with the symptomatology, but influences the decision of a subject to seek health care. This would certainly explain the extremely high occurrence of concomitant psychiatric disturbance in some studies of IBS sufferers, the assumption being that patients who seek medical attention for their symptoms are by their nature predisposed to psychological disturbance. Certainly, illness behaviour is known to be a learned trait in IBS patients [ 51]. It has been demonstrated that those who become `consulters' exhibit more minor somatic complaints, visit the doctor more frequently and are more likely to have had prolonged absence from school as children [ 52]. The implication is that subjects exhibiting chronic illness behaviour consult more frequently with routine symptoms. Given the prevalence of gastrointestinal symptoms in the community, such patients may assume symptoms in order to legitimize a consultation [ 5]. They are also more likely to have been given `comfort' gifts such as toys or a favourite food by their parents during episodes of illness, and so may have subconsciously come to associate the adoption of the sick role with pleasant reward.

The aim of this review is to provide a greater insight into the prevalence and role of psychosocial factors in the pathogenesis of IBS, by re-examining the available data, both quantitatively and qualitatively, with the focus on methodological aspects. There are many experimental variables which may affect the outcome of studies which, by their very nature, examine a complex interaction of biological and psychological factors. Such discrepancies are compounded by the myriad ways of displaying data, and so data presentation issues will also be addressed.

AGE

Presentation of IBS is more common in the third and fourth decades of life [ 53], yet many studies fail to provide this basic demographic information [ 54] and few provide the age at onset of the disorder in addition to that at the time of investigation [ 53]. Comparison between studies is not always possible and, therefore, the application of data to the wider IBS population is restricted if information regarding the age of the subjects is not known. The problems are exacerbated where summary data regarding the subjects' age are attributed to the parent population, but may not be applied to the subsequent study population [ 19, 55], or where subjects are classified by psychiatric rather than gastrointestinal status [ 56].

GENDER PREVALENCE

IBS predominates in females in Western populations [ 49], while in the East the opposite is true [ 57] (Table 1). This is often cited as evidence that psychosocial factors are associated more with illness behaviour than with gastrointestinal symptomatology, as in Western populations females are more likely to seek health care than their male counterparts and vice versa.

Given the variation in bowel function attributed to gender [ 58] and the doubt cast upon the appropriateness of the Manning diagnostic criteria for male subjects [ 59], it is apparent that the results derived from studies of predominantly female populations may not be appropriate to male subjects.

Gender is a factor which must also be considered when interpreting data pertaining to the role of stress in IBS. Craig and Brown [ 26] suggested that men were more likely than women to suffer as a result of `competitive' life events, due to their exaggerated roles in business, industry and commerce. This is unlikely to be the case, however, as it is known that women suffering from IBS are often well educated and successful. Whitehead et al. [ 51] showed that subjects with IBS and other functional bowel disorders were more likely to have graduated from college than a control population without such disorders, although the difference did not reach statistical significance. Such a factor will inevitably become irrelevant in time, as professional, educational and social opportunities for women continue to increase, and it is a pertinent example of how sociocultural shift influences the pattern of disease.

What is more likely is that males and females are exposed to a different range of stressors, although there will inevitably be a degree of overlap. Johnsen et al. [ 60] identified a range of lifestyle factors that were associated with an increased number of symptoms in both sexes. For males, these included low levels of physical activity and increased meat consumption, while in females the relevant factors included high levels of smoking and milk consumption.

Information regarding gender may be presented as discrete numerical data [ 61], relative percentages [ 3] or as a ratio [ 56]. As a result, considerable mathematical exertion may be required before study comparisons can be made. The relative conformity of the ratios obtained, however, may reflect favourably upon the reproducibility of the data obtained (Table 1).

DISEASE STATUS (GASTROINTESTINAL)

Many of the classic studies of psychosocial factors in IBS were performed before the development of well-defined diagnostic criteria, when identification of the disorder was largely based upon the exclusion of organic disease [ 17, 40, 62, 63]. Such investigations may therefore over-represent the prevalence of psychoneuroses, as it has been shown by Thornton et al. [ 64] that the level of psychopathology identified by a study depends upon the criteria used to identify the patient group, and by Whitehead et al. [ 65] that studies based upon conventional diagnostic criteria elicit a higher degree of psychopathology than those based on more restrictive criteria.

It is therefore somewhat surprising that, in a number of studies, although diagnosis is based upon the clinical identification of IBS, the diagnostic criteria used are not stated [ 53, 63]. High levels of psychopathology have been found, however, despite the application of more restrictive diagnostic criteria [ 39].

Studies investigating psychiatric co-morbidity in IBS [ 66] are less common than those with more heterogeneous populations composed of functional bowel disorder patients. Ford et al. [ 25] provided a dangerous misnomer in the title of their 1987 paper, which refers specifically to IBS, yet assesses a patient population composed of those with either IBS or functional dyspepsia.

Diagnosis of IBS is itself a quandary. This is perhaps inherent in the nature of a syndrome, which by definition encompasses a range of experiences. Hislop [ 40] employed a definition based upon abdominal pain and altered bowel habit in the absence of organic disease, while others have excluded the need for an altered bowel habit, or abdominal pain [ 12], the latter allowing the inclusion of patients with painless diarrhoea, which by some criteria falls outside the definition of the syndrome.

Subsequent definitions of diarrhoea and constipation also vary widely. Whitehead et al. [ 61] defined diarrhoea as a frequency of stool exceeding two per day, while Sandler et al. [ 67] specified al least 21 motions in a week (the equivalent of three per day). Clearly, some subjects who would have been identified as diarrhoeals by the former definition would have been excluded by the latter. Similar discrepancies exist for all parameters of bowel function, identifying the need for the establishment of widely accepted definitions for commonly used terms.

Patient status is a further area of discrepancy. Sufferers may be classified as `consulters' (having sought treatment for their condition) or `non-consulters'. The two groups exhibit markedly different psychological profiles [ 61] and illness behaviour [ 68]. As it has been suggested that psychosocial factors may be related to symptom presentation rather than severity [ 69], studies based upon populations of consulters will be likely to elicit a higher degree of psychopathology. Sammons and Karoly [ 70] suggested that non-consulters exhibit symptoms at subclinical levels. When subsequently affected by a stressor, the symptoms become relevant at a clinical level, prompting consultation.

Even a population of non-consulters may not be homogeneous. Dancey et al. [ 71] derived their subjects from an IBS self-help group. By definition, those comprising such a group exhibit a degree of self-motivation and may fall part way between true consulters and non-consulters, although it is conceivable that some may have consulted a physician and be attending the self-help group simultaneously, and therefore be among the most motivated of subjects.

DISEASE STATUS (PSYCHIATRIC)

A variety of diagnostic tools are available to identify the presence of psychoneuroses. While each may be well validated, unless the criteria for identification of particular neuroses are standardized, nuances will inevitably detract from comparisons between studies. Young et al. [ 63] found that the diagnoses obtained using research criteria did not match those given by an internist using a different tool for psychological assessment in 37.9% of cases. Hislop [ 40] appears not to have used a validated questionnaire at all, but to have based classification upon subjective assessment.

As with gastrointestinal status, psychiatric criteria will inevitably vary in their sensitivity and specificity. Blanchard et al. [ 72], for example, identified a considerably lower level of concomitant psychoneuroses in IBS patients than did an earlier study by Young et al. [ 63]. This was possibly due to the less restrictive criteria employed in the latter study, which included those with undiagnosed psychiatric disorders, which could not be identified as a specific neurosis. Blanchard's group also used the now well-recognized DSM-111-R diagnostic criteria, one of the few studies to have done so. Doubt has been cast on the validity of some of the earlier methods of psychoanalysis. It has been suggested, for example, that the Middlesex Hospital Questionnaire employed by Palmer et al. [ 16] does not adequately distinguish between anxiety and depression on the relevant subscales [ 73].

Many studies specifically seek to identify the existence of a current psychiatric disorder. Walker et al. [ 3], however, included patients with either a current or lifetime psychiatric disorder, which obviously expands the limits of inclusion.

The tool chosen for assessment must, of course, be suitable for the intended study population. In their investigation into the role of life events in the aetiology of IBS in an Indian population, Arun et al. [541 used the PSLE (presumptive stressful life events scale), which had been specifically designed to assess events relevant to an Asian population and had been validated using Indian subjects.

The definition of what constitutes a `life event' varies markedly between studies. It has been implied that only major events affect symptomatology [ 14], but also that minor, daily irritations are more significant [ 74, 75]. Ford et al. [ 25] suggested that life events are irrelevant unless they specifically provoke anxiety.

There has also been much debate as to whether such events are significant qualitatively or merely quantitatively [ 60, 76]. DeLongis et al. [ 74] suggested that both the frequency and intensity of an event may be relevant, yet many studies concentrate solely on the former. While many studies have investigated the role of such events, fewer seek to relate these temporally to the onset of symptoms, yet this would appear crucial to defining the pathological role.

It may be a logical inference that, if negative events (`hassles') are associated with symptomatic onset or deterioration, positive events (`uplifts') should be associated with symptomatic relief. Dancey et al. [ 71], however, showed this not to be the case. Their subjects, though, had not been pre-selected for concomitant psychiatric illness.

Differences in the perception of stress between subjects and independent observers have been identified [ 77]. While interpretation by an objective observer may be more relevant in terms of the scientific understanding of the role of such events, subject perception is evidently more relevant to the physician. A better understanding of the relationship between the two may provide greater insight into aetiological mechanisms.

CONTROL GROUPS

To be scientifically valid, control populations must clearly be comparable with study populations in terms of age, sex, disease status and size. This is not always so. The control group used by Ford et al. [ 25] was significantly smaller than their study population and so doubt may be cast upon the statistical validity of the data obtained.

Although medical outpatients are commonly used as control populations for gastrointestinal outpatients--presumbly to control for illness behaviour--`healthy' subjects have also been used [ 72]. Some studies do not include a control group at all [ 17, 38], a questionable practice in any research methodology.

BLINDING

As a result of the possible association between IBS and psychiatric disorder, physicians diagnosing one condition must be blind to the existence of the other. Few trials provide information regarding blinding status in the details of their methodology, yet the importance of this was acknowledged by Lydiard et al. [ 39], who, in their conclusion, cited nonblinding of the investigator as a possible reason for over-diagnosis of psychiatric conditions.

SCOPE OF INVESTIGATION

The method chosen for an assessment of psychiatric status will influence the range of disorders and the degree of total psychopathology identified. Lydiard et al. [ 39] used a mode of assessment which encompassed only those conditions which conformed to the DSM-111-R Axis-1 diagnosis of a psychiatric neurosis. That anxiety and depression are the most commonly encountered psychoneuroses may be a reflection of the fact that they are the most easily diagnosable or that they are identified by a wider range of assessment scales than other psychoneuroses. Where possible, therefore, the range of disorders to be investigated should be documented.

STUDY DURATION

Few studies describe the duration of the study period yet, given the ambulatory nature of the symptoms characteristic of IBS [ 78], it seems reasonable to assume that such a variable could exert considerable influence on the results obtained. Maxton et al. [ 79] suggested that, in order to account for periods of relapse and remission, the study duration must be at least 12 weeks. Dancey et al. [ 71], however, assessed hassles and uplifts in their patients for a mere 5 weeks.

ETHNICITY AND CULTURE

Bowel differences exist between different ethnic groups [ 80]. This is thought to be mainly as a result of variation in dietary habits. Cultural differences are known to affect psychosocial behaviour in populations of similar ethnicity [ 51]. Gunaid et al. [ 55] suggested that aetiological factors relevant to their Yemeni population may be considerably different to those affecting Western populations.

SAMPLE SIZE

Subject numbers vary widely between studies (Table 1). While larger study populations improve the statistical validity of the results, studies which employ more restrictive diagnostic criteria as a method of improving the accuracy may not offer such large populations as a result of recruitment difficulties. Large populations may not always be preferable, as both quality and quantity must be considered. Ford et al. [ 25] cited too small a study population (n = 97) as a reason to interpret their results cautiously, yet it can be seen from Table I that many studies have employed considerably smaller sample populations.

TREATMENT

The alleviation of gastrointestinal symptoms using psychologically oriented treatment has been cited as evidence that psychiatric impairment causes gastrointestinal distress. Certainly, promising results have been obtained, yet not all workers have reported success [811,while others have found both behavioural and conventional medical treatments to be equally effective [ 82]. Comparison between studies is difficult due to the range of techniques available. Those that have been successfully employed include the administration of psychotropic drugs [ 19], hypnotherapy [ 42] and biofeedback [ 83].

The terms of improvement must be well defined. Hislop [ 40] reported improvement in 69% of his subjects after psychotherapy, yet it is not established whether this related to their physical or psychiatric status. In a later study, Hislop [ 41] reported improvement in subjects given very brief psychotherapy (mean time 2.2 h), but the results were not evaluated statistically.

The length of follow-up after a treatment trial may also influence the results obtained, a longer follow-up significantly increasing the scope for success. Harvey et al. [ 84] only followed up their patients for 3 months, whereas Svedlund et al. [ 44] continued their assessment for 12 months. Whorewell et al. [ 42] employed an 18-month follow-up period, but only examined those in the treatment group and may therefore not have derived sufficient data to make valid statistical comparisons over the entire study period.

Ritchie and Truelove [ 85] showed improvement in the somatic health of 65% of their subjects when treated with the psychoactive medication `Motival'. When incorporated in a multi-component treatment strategy, improvement was noted in 92% of the subjects.

Svedlund et al. [ 44] assigned 101 IBS outpatients to either a medical (n = 51) or medical plus psychotherapy (n = 50) treatment group. Improvement was significantly greater in the psychotherapy group in both the short and long term [ 44]. This supports the assertions that psychological treatment can provide both immediate and sustained relief, and is most effective when used in holistic therapy.

Whorewell et al. [ 42] investigated the effect of hypnotherapy, as compared to general psychotherapy, in a group of 30 IBS patients. The psychotherapy group showed some symptomatic improvement, although not in terms of bowel habit. The hypnotherapy group showed significantly greater improvement over the entire symptom range. Whether certain techniques are particularly applicable to specific symptoms has yet to be investigated, as the choice of therapy has so far been determined by psychiatric, not gastrointestinal, status.

CONCLUSIONS

Owing to methodological differences between studies and the fact that many of the classic studies were conducted before the development of positive diagnostic criteria for IBS, it is difficult to make conclusive judgements about either the extent to which psychiatric disorders are relevant or to their aetiological role. What does seem conclusive, however, is that psychosocial factors are particularly relevant to a significant subgroup of sufferers, as high levels of psychopathology have been identified despite the application of restrictive gastrointestinal and psychological inclusion criteria. Many of the studies which have identified significantly lower levels of psychiatric disturbance have suffered from methodological inadequacies such as an insufficient sample size or trial duration, an inappropriate study population, diagnostic criteria or statistical processing.

With respect to the role of psychosocial factors, it seems more likely that psychiatric disturbances are the cause of gastrointestinal symptoms, rather than an effect resulting from them, although many workers agree that further investigation with more appropriate methodologies is required. Studies showing that sufferers of IBS exhibit considerably more psychiatric disturbance than organic bowel disease patients despite comparable intensity of pain [ 3], and that the gastrointestinal symptoms tend to conform to the pattern of psychiatric illness [ 17], seem to confirm this, although a more detailed investigation into the prevalence of the symptoms of IBS in psychoneurotic patients is required to support this theory. There is also a considerable body of evidence to suggest that psychosocial factors influence patient status rather than the genesis of gastrointestinal symptoms per se. Such data must be interpreted cautiously, however, as much of it was collected retrospectively and many of the psychometric tests used to identify the condition have not been scientifically validated.

In the absence of standardized criteria for the gastrointestinal and psychological assessment of subjects, it is critical that the parameters to be measured are clearly defined. With the knowledge that both gastrointestinal and psychological function may vary according to the population on which the study is based, documentation of the procedures is an essential feature of any investigation. The development of a standard protocol for the recording of demographic information would allow simpler and more accurate comparison between trials. It is likely that methodological differences may explain in part the variation in results between studies.

ACKNOWLEDGEMENT

The authors gratefully acknowledge financial assistance from Reckitt & Colman Products Ltd.

TABLE 1. Studies of psychiatric disorders in IBS
Legend for Table:

A - n
B - Age (mean)
C - Male: female ratio
D - Disease status
E - Proportion with psychiatric disorder (%)
F - Depression (%)
G - Anxiety (%)
H - Precedes gastrointestinal distress (%)

Source A B C D

Hislop (1971) 67 - 1:2.4 IBS
OUT
Liss et al. (1973) 25 43.6 1:2.1 IBS
OUT
Young et al. (1976) 29 49.0 1:3.76 IBS
OUT
Latimer et al. (1981) 16 45.0 1:1.29 IBS
Sandler et al. (1984) 33 23.6 1:1.75 GI
Craig and Brown (1984) 79 34.6 1:2.8 FGI
OUT
Kapoor et al. (1985) 55 28.6 1:2.93 IBS
Bergeron and Mono (1985) 82 - - IBS
Dotevall et al. (1986) 101 34.0 1:2.26 IBS
Rose et al. (1986) 100 - 1:1.4 GI
OUT
Drossman et al. (1988) 72 30.4 1:6.09 IBS
Colgan et al. (1988) 57 41.5 - FGI
Creed et al. (1988) 79 34.0 1:3.8 FGI
Blanchard et al. (1990) 68 42.5 1:2.78 IBS
Walker et al. (1990) 39 37.1 1:2.7 IBS
Lydiard et al. (1993) 35 45.1 1:6 IBS
OUT
Gunaid et al. (1996) 247 - 1:1.02 IBS
OUT
Dewsnap et al. (1996) 31 - 1:1.6 PIBS

Source E F G H

Hislop (1971) - 73.1 68.7 50.7

Liss et al. (1973) 92.0 8.0 24.0 68.0

Young et al. (1976) 72.0 17.0 3.5 37.9

Latimer et al. (1981) 100.0 - 18.8 -
Sandler et al. (1984) - - 85.0
Craig and Brown (1984) - - - 67.0

Kapoor et al. (1985) 81.9 16.4 7.3 -
Bergeron and Mono (1985) 70.0 16.0 -
Dotevall et al. (1986) - 77.0 98.0
Rose et al. (1986) 50.0 -

Drossman et al. (1988) - 21.0 8.0
Colgan et al. (1988) 57.0 - -
Creed et al. (1988) 34.0 - - -
Blanchard et al. (1990) 55.9 25.9 20.6
Walker et al. (1990) 93.0 61.0 54.0 82.0
Lydiard et al. (1993) 94.0 37.0 28.0 40.0

Gunaid et al. (1996) 93.1 6.5 56.3 -

Dewsnap et al. (1996) - 87.1 13.0 3.2

IBS, irritable bowel syndrome; GI, gastroenterplogical disorder;
F, functional; P, psychiatric disorder; OUT, outpatient,
IN, inpatient.
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By A. D. SHAW BSc, G. J. DAVIES BED MSC PHD AND J. W. T. DICKERSON PHD FIBIOL CBIOL, Nutrition Research Centre, School of Applied Science, South Bank University, 103 Borough Road, London SKI OAA, UK