Whole grain intake, diet quality and cardio-metabolic health in two UK cohorts A thesis submitted for the degree of Doctor of Philosophy Kay D Mann Institute of Health and Society, Faculty of Medical Sciences, Newcastle University April 2017 Declaration I hereby declare that the contents of this thesis are my own, have not been submitted or accepted in any previous application for a degree or other qualification, and are a true record of the work carried out by myself unless stated otherwise. All quotations have been distinguished by quotation marks and all sources of information are referenced. Kay D Mann April 2017 i ii Abstract Processed grains that retain all three component parts - bran, germ and endosperm are known as whole grains. Epidemiological evidence suggests an inverse association between whole grain (WG) consumption and the risk of non-communicable diseases, such as cardio-vascular disease, type 2 diabetes, obesity and some cancers. The USA and Denmark have quantity- specific WG dietary recommendations, but other countries, including the UK, do not. Despite recognition that WG is an important component of a healthy diet, monitoring of WG intake in the UK is poor. Thus, there is a need to assess WG intake and its consequences in the UK population. The purpose of this work was to calculate WG intake and investigate potential associations with cardio-metabolic measures, nutrient intakes and intakes of other foods in the most recent UK National Diet and Nutrition Survey (NDNS) data and in the Newcastle Thousand Families Study (NTFS), a birth cohort from Newcastle upon Tyne. The estimated WG content of whole-grain foods identified in 3073 four-day food diaries was used to calculate WG intake of adults and children from the NDNS 2008-2011. A cereal food frequency questionnaire was developed with estimated portion sizes to estimate WG intake. WG intake was also calculated in the NTFS at 50- and 60-year follow-up. WG intake, which came mainly from breads and breakfast cereals, was low with an average of 20g/d in adults and 13 g/d in children of the NDNS and 19, 21 and 33g/d in the NTFS at ages 50, 60 and 67 years, respectively. In both studies WG was inversely associated with some, but not all, cardio-metabolic measures, after adjustment for confounding factors. Associations were small, but significant, suggesting that WG may have an important role in disease prevention. For example, a significant decrease in NDNS white blood cell counts were seen across tertiles of increasing WG intake, after adjustment for age, sex and total energy intake. In the NTFS members at 50-year follow-up, each 10g/d increase in WG intake was associated with a 0.1mmol/L reduction in total and LDL cholesterol concentrations, after adjustment for confounders such as sex, SES, medication use and smoking status. WG consumers also had overall better dietary profiles, with higher intakes of fibre, iron and magnesium and lower intakes of fats. iii The recent UK recommendation to increase dietary fibre intake will require a greater emphasis on consuming more WG. Specific recommendations on WG intake in the UK are warranted as is the development of a public health policy to promote the consumption of these important foods. iv Acknowledgements I should like to thank all the people who have helped me in the preparation of this thesis. First and foremost my supervisors, Professor Chris Seal and Professor Mark Pearce, for their continual support and guidance throughout this work. They have provided their time, expertise and kept me inspired. I am forever grateful to Professor Pearce who has always had the belief in my abilities and encouraged me to undertake this PhD. I am also indebted to Professor Seal for his knowledge and exceptional ability to explain mechanisms and theories to me. His willingness to introduce me to colleagues during conferences and meetings has been invaluable. I have learnt an incredible amount from both my supervisors and I have the utmost respect for them. I should like to acknowledge and thank all the participants of the UK NDNS rolling programme and NatCen Social Research, MRC Human Nutrition Research and University College London Medical School for conducting and coordinating the NDNS rolling programme and the UK data service for supply of the survey data. I should also like to acknowledge and thank the NTFS members for their continued participation. I am grateful to the past and present study team. In particular, Sir James Spence who initiated the study, Dr Fred Miller who continued the study after Spence’s death, Professor George Alberti, Sir Alan Craft and Dr Louse Parker, who re-established the cohort in the 1990s and the current study director Professor Mark Pearce. I should also like to thank Katharine Kirton and Emma Thompson for helping with data entry and management of the NTFS. I am also grateful to Richard Hardy for help and support with IT issues and the NTFS database. I am appreciative of my assessors Dr Tom Hill and Dr Richard McNally for their advice, guidance, critique and praise. I am grateful to Dr Frank Thielecke, Dr Sinead Hopkins and Cereal Partners Worldwide who provided funding and support for the analysis of the NDNS data. Over the years, I have received invaluable advice and encouragement from friends and colleagues in the Institute of Health and Society, especially from Professor Ashley Adamson, Dr Angela Jones, Dr Morven Brown, Dr Kate Best, Dr Richard Harbon and Mona Dave. I must also give a thankful mention to Professors Rod Skinner and Simon Bailey for checking in on me in the office during evenings and weekends and making sure I had been home! v Finally, I would like to thank my family and friends for their interest and emotional support, particularly my mum Cynthia Mann, for her listening ear and sound advice, and my fiancé Michael Kirchner for his love, patience and belief in me. vi Contributions to PhD thesis Kay Mann compiled and wrote this thesis with guidance and advice from the supervisors. NDNS data were collected by the NDNS team (see acknowledgements) and obtained from the UK data service. The whole grain contents of UK foods file was established by Dr Angela Jones. Kay Mann added to this file by identifying and calculating the whole grain contents of foods reported in 4-day diet diary data from the NDNS rolling programme years 1-3 (Appendix A). Estimation of whole grain intake and statistical analysis of associations with diet and cardio-metabolic markers was performed and interpreted by Kay Mann (Chapter 3). Funding of Kay Mann’s time during this analysis from Cereal Partners Worldwide is gratefully acknowledged. Fifty and 60-year NTFS data were obtained from the study database at Newcastle University. Calculation of nutrient and food intakes from food frequency questionnaires was performed by Kay Mann using the FETA software. Socio-economic classification and achieved education level coding was previously done by the study team and checked by Kay Mann. Data on medication use, reported at both 50- and 60-year follow-up, were cleaned and coded by Kay Mann. Clinical data from the 50-year follow-up had been previously cleaned and were checked by Kay Mann. Clinical data from the 60-year follow-up was, cleaned and cross- checked with physical records, where appropriate, by Kay Mann. Ethical application for new data collection was prepared by Kay Mann. The Cereal Food Questionnaire was developed and distributed by Kay Mann. Data entry was done by Emma Thompson and Katharine Kirton and was cross-checked by Kay Mann. The online version of the questionnaire was programmed by Steven Hall (Appendix D). Online data were received and stored by Kay Mann. Food portion size estimation for the Cereal Food Questionnaire was conducted by Kay Mann (Appendix E). Estimation of whole grain intake and statistical analysis of associations with diet and cardio-metabolic markers was performed and interpreted by Kay Mann (Chapter 4). vii viii Publications The following journal articles have been published from work presented in this thesis: Mann, K.D., Pearce, M.S., McKevith, B., Thielecke, F. and Seal, C.J. (2015). Low whole grain intake in the UK: results from the National Diet and Nutrition Survey rolling programme 2008-11. British Journal of Nutrition, 113(10), pp. 1643-1651 Mann, K.D., Pearce, M.S., McKevith, B., Thielecke, F. and Seal, C.J. (2015). Whole grain intake and its association with intakes of other foods, nutrients and markers of health in the National Diet and Nutrition Survey rolling programme 2008-11. British Journal of Nutrition, 113(10), pp.1595-1602 Mann, K.D., Pearce, M.S. and Seal, C.J. (2016). Providing evidence to support the development of whole grain dietary recommendations in the United Kingdom. Proceedings of the Nutrition Society, pp.1–9. Jones, A.R., Mann, K.D., Kuznesof, S.A., Richardson, D.P. and Seal, C.J. (2017). The whole grain content of foods consumed in the UK. Food Chemistry, 214, pp.453-459 The whole grain databased produced from the work in this thesis was also applied to data from a study on whole grain intake in Singaporean infants: Neo, J.E., Binte Mohamed Salleh, S., Toh, Y.X., How, K.Y.L., Tee, M., Mann, K., Hopkins, S., Thielecke, F., Seal, C.J. and Brownlee, I. A. (2016). Whole-grain food consumption in Singaporean children aged 6–12 years. Journal of Nutritional Science, 5, e33. ix Peer reviewed abstracts presented at scientific meetings by Kay Mann. Healthgrain Forum Autumn Workshop 2013, VTT Technical Research Centre, Finland Mann, K.D.