Butylated hydroxyanisole (BHA) is a synthetic substance commonly used as dietary antioxidant which plays an important role in protecting foods from oxidation. It has been reported that this compound caused an increase in glutathione-s-transferase specific activity, which is responsible for resistance to oxidative stress, i.e., there was some evidence that it could act as a pro-oxidant. In the present study, BHA was found to be toxic towards yeast and this was investigated further by determining its effect on the viability of a variety of yeast mutants lacking key genes required for resistance to oxidative stress. The results showed that the cell viability of the mutants was not significantly different from the wild type parental strains. This suggests that BHA toxicity was unlikely to involve reactive oxygen species (O2 - and H2O2) and might not directly involve the classical oxidant stress responses found in yeast cells. Interestingly, the pre-treatment of yeast cells with low concentrations of BHA (0.2 mM) and subsequent exposure to higher concentrations of either BHA or hydrogen peroxide (H2O2) resulted in pre-treated yeast cells becoming more resistant to both toxic levels of BHA and H2O2 than non pre-treated cells. These findings indicated that low level of BHA could induce an adaptive response to BHA and induce cross-protection against H2O2. A genetic approach was adopted to identify genes involved in this process, involving the isolation and characterisation of BHA sensitive mutants. The results demonstrated that the yeast genes TYR1, KRE6 and GPH1 play role in the cells response towards BHA.

How ‘responsibility’ for healthy eating is perceived and allocated has implications for the way people act, with consequences for population health. Although ‘responsibility’ features in health policy and corporate strategy, its meaning is equivocal. The aim of this research is to determine how selected, key actors in the food system discursively construct responsibility for diet and concomitant population health, and what supports or constrains their ability to be ‘responsible’. This project uses a qualitative approach, contextualised in a complex systems framework. Three types of data were gathered: existing corporate and government publications, focus groups with members of the public and semi-structured interviews with representatives from government, industry and NGOs. Foucauldian discourse analysis was carried out on the dataset to explore the discourse of responsibility in the food system and the power dynamics that underpin it. Analysis showed that perceptions of responsibility mediate behaviours within the food system and that the seemingly common sense discourse of individual responsibility for healthy eating is undermined by others such as those of choice and complexity. Yet the discourse of choice belies the degree to which individuals are constrained in making rational, truly ‘free’ choices in the food system. Indeed, power over, and therefore responsibility for the main determinants of food choice e.g. taste, cost, convenience and promotions, were seen to lie with government and industry. The findings suggest that discourses of responsibility mask the commercial determinants of food choice, sanctioned by government, underpinned by neoliberal commitments to the free market and individualism. Overall, the data showed that responsibility for healthy eating is not proportional to the power different actors have over determinants of dietary choice. The concept of ‘proportional responsibility’ is proposed as a potential framework for apportioning fair responsibility between actors in the food system.

1. The effect of some drugs on nutritional status has been studied in the guinea pig, rat and man. 2. The chronic administration of chlordiazepoxide (Librium) to the guinea pig increases the dietary requirements of ascorbic acid. The possible underlying mechanisms and implications of this observation are discussed. 3. The chronic administration of prednisone to the guinea pig causes only an initial increase in the dietary requirements of ascorbic acid. Evidence is presented pertaining to the induction of de novo synthesis of the vitamin by the drug. 4. Patients suffering from rheumatoid arthritis and treated with antirheumatic drugs have lower plasma tryptophan and excrete increased quantities of kynurenine, 3-hydroxy-anthranilic acid and xanthurenic acid in the urine. The significance of these findings is discussed in relation to the nutritional requirements of these patients. 5. The prolonged administration of anticonvulsants and pheno- thiazines in man may lead to folate deficiency. Evidence is presented to the effect that folate deficiency may be the result of the increased activity of the hepatic microsomal drug-metabolising enzymes brought about by the potent inducing properties of these drugs. 6. When anticonvulsants, singly or in combination, or the tricyclic drug, imipramine, are administered for 12 weeks to rats fed on diets containing different concentrations of folic acid, they exacerbate, induce, or have no effect on folic acid status depending on the dietary intake of the vitamin. Furthermore, a deficiency of folic acid impairs or diminishes the extent of induction of cytochrome enzymes by these drugs. 7. The combined administration of phenobarbitone and dilantin for 12 weeks to female rats fed on diets of different folate content increases the frequency of certain congenital abnormalities in the offspring. The implications are discussed.

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A high prevalence of diabetes exists globally and in particular in Saudi Arabia. Several dietary and lifestyle factors are implicated although dietary carbohydrates (CHOs) have a key role in influencing diabetes risk. The physiological impact of CHOs on postprandial blood profiles can be measured in vivo or predicted from in vitro digestion rates. This thesis examined the relationship between CHO digestibility in vitro and CHO bioavailability in vivo by assessing a variety of UK and Saudi Arabian foods. Our hypothesis was that traditional Saudi foods could have better health impacts on blood glucose and insulin levels. The CHO digestibility method of Englyst was established to determine rapidly available glucose (RAG) and slowly available glucose (SAG) parameters. RAG and SAG were determined for some food standards, and some Saudi and UK foods. Also, glycaemic and insulinaemic indices (GI and II) of Saudi Arabian Hassawi Rice and dates were tested using FAO/WHO protocols and compared with Uncle Ben's rice and dates with Arabic coffee respectively. Once the RAG, SAG and GI values for some Saudi and UK foods were determined, the role of the SAG index was assessed in terms of its ability to differentiate between two meals with essentially identical macronutrient contents and GI values. Our results demonstrated the method for RAG and SAG measurements to be reproducible and to show good agreement with the observations in the literature. In terms of GI and II values for Hassawi rice and Uncle Ben's rice, no significant differences were observed between the two types of rice in terms of plasma glucose responses, however, a lower insulin response were noted for Hassawi rice (p < 0.007). For Arabic coffee consumed with dates, there was an increase in glucose response at 45 and 60 min (p < 0.05) although the insulin response was not significantly affected. For the high and low SAG meals, despite the similarity between the two meals it was evident that the high SAG meal resulted in a modestly lower incremental area under the glucose curve (p=0.21) and a lower insulin response, particularly at 45 min (p=0.053). In conclusion, these studies showed that some traditional Saudi foods could have beneficial effects in terms of plasma glucose and insulin responses. Furthermore, RAG and SAG values can be used as important predictors of GI. Nevertheless, the SAG value can show important metabolic differences between the impact of foods with the same GI. The observations for staple foods may be important for people with diabetes in Saudi Arabia.

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Both accelerated and suppressed bone remodelling can lead to the development of a stress fracture injury. A stress fracture injury can threaten an athlete’s performance by causing months of missed training time if a stress fracture is sustained during a crucial phase of the season. This thesis presents a series of studies that investigated bone metabolism in endurance athletes and potential ways to improve bone health and reduce the risk of stress fracture injury. Triathletes are endurance athletes that anecdotally have a high incidence of stress fracture injury, but there is limited research into bone health in these athletes. Therefore, the first two studies in this thesis investigated bone metabolism in a group of elite British triathletes during off-season and pre-competition training. The results showed that elite triathletes had elevated bone turnover at both phases of the season, although this was highest during off-season training. The high bone turnover may be related to large training volumes, low energy intakes and high dermal calcium losses in the sweat. Given the potential contribution of high dermal calcium losses to the disruption of calcium homeostasis and the different rates of losses in different types of training sessions, the timing of calcium ingestion around training sessions may be more important than total calcium intakes throughout the day. As such, the third study in this thesis investigated the mechanism and timeframe of Parathyroid hormone (PTH) and calcium regulation during exercise and recovery. The results showed that PTH secretion was controlled by a combination of changes in ionised calcium (Ca2+) and phosphate (PO4) and that the mechanism might be different during exercise and recovery. Taken together these results advocate the use of pre-exercise calcium supplementation, which may prevent the disruption of calcium homeostasis and attenuate the PTH and bone resorption response to intense exercise, although further research is required before this can be implemented in elite triathletes. The large training volumes performed by elite triathletes, meant that daily energy expenditures and energy requirements were high, although consuming almost 6,000 kcal.d-1 was difficult when three or four training sessions were regularly performed each day. Therefore, a practical nutritional intervention was needed to help triathletes ingest some of the required nutrients. The fourth study in this thesis investigated the effect of a post-exercise carbohydrate and protein (CHO+PRO) recovery solution on the bone metabolism response to an intense running bout. The results showed that consuming a CHO+PRO recovery solution immediately after exercise created a more positive bone turnover balance in the acute recovery period from exercise, by suppressing bone resorption and increasing bone formation. Further research is required to explore the long-term effects of post-exercise suppression of bone resorption. This thesis had direct impact on elite British triathletes, by influencing athlete behaviour and nutritional practices in the daily training environment. The research has also influenced British Triathlon coaches and sports science and medicine staff by increasing the importance placed on bone health and by providing information that will allow training and nutritional practices to be improved or altered to promote a more anabolic environment for bone.

Background: During ageing, there are changes in many physiological systems including the gastrointestinal tract which may result in decreased absorption of micronutrients such as zinc. Decreased dietary absorption efficiency and/or inadequate zinc intake are contributing factors to the decline in plasma zinc concentration that has been reported in older adults. This decline in plasma zinc concentration may have important implications for health, e.g. through reduced immune function. To date, there is limited information on the relationships between zinc intake and plasma zinc concentration during ageing among adults in Saudi Arabia or on the molecular mechanisms responsible for age-related effects. Thus, the aims of this study were to test the hypothesis that changes in expression of zinc transporters including ZnT1, ZnT5 and ZIP4 are associated with changes in zinc status in young and older Saudi adults. Methods: Two hundred and two young and older Saudi adults of both sexes were recruited from Jeddah city in the western region of Saudi Arabia. Intakes of zinc and of zinc absorption modifiers in diet were assessed using an FFQ (designed and validated for this purpose) while plasma zinc concentration was determined by ICP-OES. RNA was extracted from white blood cells and qPCR was used to quantitatively measure expression of the ZnT1, ZnT5 and ZIP4 genes at the mRNA level. Results: Intakes of zinc and of protein were significantly higher in males than in females (P < 0.05). A substantial proportion of the participants appeared to have inadequate zinc intake with the risk of inadequacy being greatest for young males (15%) and young females (4%). Plasma zinc concentrations in older adults were significantly higher than in young adults (P < 0.05). Older males had significantly higher ZIP4 expression compared with young adults (P < 0.05). Although older adults had apparently higher ZnT1 and ZnT5 expression than young adults, these differences were statistically non-significant. Several age and sex-specific correlations between zinc intake, zinc status and expression of zinc transporters were observed. Young and older adults who had apple-shaped fat distribution pattern, had significantly higher expression of ZnT1, ZnT5 and ZIP4 and plasma zinc status compared with participants who had pear-shaped fat distribution pattern (P<0.05). Discussion: Despite the changes in food availability in Saudi Arabia over recent decades, the prevalence of low zinc intake remains substantial. Contrary to reports from elsewhere, the prevalence of low plasma II zinc concentrations was greater in younger than in older Saudi adults. This study also identified relationships between expression of zinc transporters and zinc intake, zinc status and abdominal fatness in Saudi adults.

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