Role of human nutrition in the pathophysiology of cardiovascular disease; effects of diet on blood lipids and lipoprotein metabolism; genetic and environmental determinants of coronary atherosclerosis.
Research Studies 1996-2009
1996: Can the metabolic effects of dietary N-3 PUFA be explained by changes in the expression of lipase genes in adipose tissue?
1997: The influence of dietary N-3 PUFA on the structure, function and metabolism of TAG-rich lipoproteins in healthy individuals.
1998: Importance of alpha-linolenic acid as a source of long chain N-3 PUFA and its influence on risk factors of cardiovascular disease.
2000: Vitamin E biokinetics and metabolism in dyslipidaemia.
2000: Quantification of the optimal N-6 / N-3 ratio in the UK diet. The OPTILIP study
2003: Effect of low glycaemic index foods on blood lipids in type 2 diabetes
Impact of the amount and composition of dietary fat and carbohydrate on metabolic syndrome and CVD risk; The ‘RISCK’ Study.
2005: Effects of increased egg consumption on a weight-reducing diet on blood cholesterol & related biomarkers of CHD risk
2008: Dietary intervention study to determine the effects of prawns on serum cholesterol and related biomarkers of CHD risk
2009: How does dietary carbohydrate influence the formation of an atherogenic lipoprotein phenotype?
I teach and examine on five undergraduate modules associated with BSc Degree programmes in Nutrition, Nutrition & Dietetics, Nutrition & Food Science and Biochemistry, and three MSc programmes.
Admissions Tutor for MSc in Clinical biochemistry
Supervise MSc and PhD research programmes
Chairman for the Exam Board in Nutritional Medicine 2006 to date
Degree programme review panel member for BSc Undergraduate Framework for Lifelong Learning in Health and Social Care Practice, EIHMS, University of Surrey (2007)
Member of the Faculty’s Research Advisory Board, FHMS, University of Surrey
Editorial board membership:
Find me on campus Room: 32 PG 00
We examined the impact of APOE genotype on plasma lipids and glucose in a secondary analysis of data from a five-arm, randomised controlled, parallel dietary intervention trial (‘RISCK’ study), to investigate the impact of replacing saturated fatty acids (SFA) with either monounsaturated fat (MUFA) or carbohydrate of high or low glycaemic index (GI) on CVD risk factors and insulin sensitivity. We tested the impact of APOE genotype (carriage of E2 and E4 alleles versus E3/E3), determined retrospectively, on plasma lipids, lipoproteins and glucose homeostasis at baseline (n = 469), and on the change in these variables after 24 weeks of dietary intervention (n = 389). At baseline, carriers of E2 (n = 70), E4 (n = 125) and E3/E3 (n = 274) expressed marked differences in total plasma cholesterol (TC, p = 0.001), low density lipoprotein cholesterol (LDL-C, p < 0.0001), apolipoprotein B (apo B, p < 0.0001) and total to high density lipoprotein cholesterol ratio (TC:HDL-C, p = 0.002), with plasma concentrations decreasing in the order E4 > E3/E3 > E2. Following intervention, there was evidence of a significant diet x genotype interaction with significantly greater decreases in TC (p = 0.02) and apo B (p = 0.006) among carriers of E4 when SFA was replaced with low GI carbohydrate on a lower fat diet (TC −0.28 mmol/L p = 0.03; apo B −0.1 g/L p = 0.02), and a relative increase in TC (in comparison to E3/E3) when SFA was replaced with MUFA and high GI carbohydrates (TC 0.3 mmol/L, p = 0.03). Among carriers of E2 (compared with E3/E3) there was an increase in triacylglycerol (TAG) when SFA was replaced with MUFA and low GI carbohydrates 0.46 mmol/L p = 0.001). There were no significant interactions between APOE genotype and diet for changes in indices of glucose homeostasis. In conclusion, variations in APOE genotype led to differential effects on the lipid response to the replacement of SFA with MUFA and low GI carbohydrates.
When advising patients on diet and health, the general practitioner (GP) makes judgements based on the evidence available. Since current evidence on diet and cardiovascular disease is conflicted and confusing, we surveyed the current consensus amongst GPs. The aim of this study was to determine the views of GPs on dietary saturated fat, carbohydrates and long chain omega-3 fatty acids in the management of cardiovascular disease.Method:
An online questionnaire inviting participants to comment on seven contentious statements on diet and cardiovascular disease. Questionnaire circulated to the 1800 members of South West Thames Faculty of the Royal College of General Practitioners (RCGP). Participants were invited to tick “ Agree ” , “ Disagree ” or “ Not sure ” and were encouraged to add comments for each question. The results were analysed with a combination of statistical analysis and thematic analysis of comments.Results:
There were 89 responses. Most GPs seem well aware that drug treatment alone is inadequate and that dietary advice is important. However, there was con siderable disagreement about the roles of saturated fats and carbohydrates in ca rdiovascular disease and “ Not sure ” responses ranged from 12 to 40.7%. The 40. 7% related to a statement on long chain omega-3 fatty acids. Analysis of comments revealed more opinions including an awareness of the need to warn patients about trans -fatty acids.Conclusions:
Although the GP response rate was poor, responders do seem to see dietary advice as part of their role but do not consider themselves as experts. Education in this area should have a higher priority.
Background & Aims:
Serum lipids and lipoproteins are established biomarkers of cardiovascular disease risk that could be influenced by impaired gut barrier function via effects on the absorption of dietary and biliary cholesterol. The aim of this study was to examine the potential relationship between gut barrier function (gut permeability) and concentration of serum lipids and lipoproteins, in an ancillary analysis of serum samples taken from a previous study.
Methods and Results:
Serum lipids, lipoproteins and functional gut permeability, as assessed by the percentage of the urinary recovery of 51-Cr-labelled EDTA absorbed within 24h, were measured in a group of 30 healthy men. Serum lipopolysaccharide, high sensitivity C-reactive protein and interleukin-6 were also measured as markers of low-grade inflammation. The group expressed a 5- fold variation in total gut permeability (1.11 - 5.03%). Gut permeability was unrelated to the concentration of both serum total and low density lipoprotein (LDL)-cholesterol, but was positively associated with serum high density lipoprotein (HDL)-cholesterol (r=0.434, P=0.015). Serum HDL cholesterol was also positively associated with serum endotoxaemia (r=0.415, p=0.023).
The significant association between increased gut permeability and elevated serum HDL-cholesterol is consistent with the role of HDL as an acute phase reactant, and in this situation, potentially dysfunctional lipoprotein. This finding may have negative implications for the putative role of HDL as a cardio-protective lipoprotein.
Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD (n=11) and low liver fat ‘controls’ (n= 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling. There were significant differences in the production and catabolic rates of VLDL subclasses between men with NAFLD and controls, in response to the high and low sugar diets. Men with NAFLD had higher plasma concentrations of VLDL1-triacylglycerol (TAG) after the high (P<0.02) and low sugar (P<0.0002) diets, a lower VLDL1-TAG fractional catabolic rate after the high sugar diet (P<0.01), and a higher VLDL1-TAG production rate after the low sugar diet (P<0.01), relative to controls. An effect of the high sugar diet, was to channel hepatic TAG into a higher production of VLDL1-TAG (P<0.02) in the controls, but in contrast, a higher production of VLDL2-TAG (P<0.05) in NAFLD. These dietary effects on VLDL subclass kinetics could be explained, in part, by differences in the contribution of fatty acids from intra-hepatic stores, and de novo lipogenesis. This study provides new evidence that liver fat accumulation leads to a differential partitioning of hepatic TAG into large and small VLDL subclasses, in response to high and low intakes of sugars.
Androgen deprivation therapy (ADT) is used widely as part of a combined modality for the treatment of prostate cancer. However, ADT has also been associated with the development of cardiometabolic complications that can increase mortality from cardiovascular events. There is emerging evidence to suggest that ADT-related cardiometabolic risk can be mitigated by diet and lifestyle modification. While the clinical focus for a nutritional approach for achieving this effect is unclear, it may depend upon the timely assessment and targeting of dietary changes to the specific risk phenotype of the patient. The present review aims to address the metabolic origins of ADT-related cardiometabolic risk, existing evidence for the effects of dietary intervention in modifying this risk, and the priorities for future dietary strategies.
The Oxford English Dictionary defines the word myth as; 'a popular idea concerning natural or historical phenomena ... that has no foundation in fact'. The popular idea in this context is that eating dietary cholesterol, typically from eggs, increases the risk of developing coronary heart disease (CHD), because it increases blood cholesterol. This contentious idea prevails, despite a lack of scientific foundation to support its existence, and almost global re-vamping of dietary recommendations to lift restrictions on the intake of cholesterol-rich foods. In an attempt to dispel the mythical status of dietary cholesterol and CHD, the following chapter will examine the role of dietary cholesterol in relation to what has been well established in terms of the relationships between blood cholesterol, diet and CHD. © 2011 Woodhead Publishing Limited All rights reserved.
Objective SNPs identified from genome-wide association studies associate with lipid risk markers of cardiovascular disease. This study investigated whether these SNPs altered the plasma lipid response to diet in the ‘RISCK’ study cohort. Methods Participants (n = 490) from a dietary intervention to lower saturated fat by replacement with carbohydrate or monounsaturated fat, were genotyped for 39 lipid-associated SNPs. The association of each individual SNP, and of the SNPs combined (using genetic predisposition scores), with plasma lipid concentrations was assessed at baseline, and on change in response to 24 weeks on diets. Results The associations between SNPs and lipid concentrations were directionally consistent with previous findings. The genetic predisposition scores were associated with higher baseline concentrations of plasma total (P = 0.02) and LDL (P = 0.002) cholesterol, triglycerides (P = 0.001) and apolipoprotein B (P = 0.004), and with lower baseline concentrations of HDL cholesterol (P < 0.001) and apolipoprotein A-I (P < 0.001). None of the SNPs showed significant association with the reduction of plasma lipids in response to the dietary interventions and there was no evidence of diet-gene interactions. Conclusion Results from this exploratory study have shown that increased genetic predisposition was associated with an unfavourable plasma lipid profile at baseline, but did not influence the improvement in lipid profiles by the low-saturated-fat diets.
Objective: The PPARG SNP rs1801282 (Pro12Ala C>G) has shown variable association with metabolic syndrome traits in healthy subjects. We investigated genotype association with plasma lipids and the influence of dietary polyunsaturated:saturated fat ratio (P:S) in subjects at increased cardiometabolic risk. Methods: Habitual dietary intake was recorded at recruitment to the RISCK Study. PPARG rs1801282 was genotyped in 466 subjects aged 30-70 y. Genotype associations with plasma lipids were assessed at recruitment, after a 4-wk high-SFA (HS) diet and a 24-wk intervention with reference (HS), high-MUFA (HM) and low-fat (LF) diets. The interaction of habitual P:S intake x genotype on plasma lipid concentrations was investigated. Results: PPARG rs1801282 G-allele frequency was 0.09. At recruitment, G-allele carriers had higher plasma total cholesterol concentration (n=415; P=0.05) after adjustment for BMI, gender, age and ethnicity. Dietary P:S ratio x genotype interaction influenced plasma LDLcholesterol (P=0.02) and triglyceride (P=0.03) concentrations. At P:S ratio 0.33, mean LDLcholesterol concentration in G-allele carriers was higher than in non-carriers, but fell between 0.34-0.65. Triglyceride concentration followed a similar pattern. After the 4-wk HS diet, Gallele carriers had higher concentrations of total cholesterol (P=0.03), LDL-cholesterol (P=0.04) and apo B (P=0.04) than non-carriers, after adjustments. After the 24-wk interventions, diet x genotype interaction did not significantly influence either LDLcholesterol (P=0.58) or triglyceride (P=0.57) concentrations. Conclusion: A high dietary P:S ratio would help to reduce plasma LDL-cholesterol and triglyceride concentrations in PPARG rs1801282 G-allele carriers at increased cardiometabolic risk.
Lipids are body fats that are either synthesized within cells (endogenous lipids) or derived from dietary fat (exogenous lipids). They are typically characterized by their insolubility in water, and have a diverse range of biological functions in cell membranes as phospholipids, and as a major source of stored energy in adipose tissue as triacylglycerols (TAGs). Serum lipids, including TAGs, phospholipids, cholesterol and their component fatty acids, are transported between sites of synthesis in the liver and intestine to peripheral tissues, for utilization and storage in macromolecular complexes of lipid and protein called lipoproteins. The physiology of circulating lipoproteins is described in terms of the transport of exogenous and endogenous chylomicrons and very low-density lipoproteins, respectively. These TAG-rich lipoproteins are remodelled under the action of lipoprotein lipase and lipid transfer proteins into smaller chylomicron remnants and low-density lipoproteins (LDLs). These cholesterol-rich lipoproteins deliver cholesterol back to the liver and peripheral tissues via specific membrane receptors, but share an infamous role as pro-atherogenic lipoproteins by depositing themselves and their cholesterol in artery walls. In contrast to this forward transport of cholesterol into tissues, reverse cholesterol transport describes the efflux of cholesterol out of tissues and passage back to the liver. This function protects arteries against atherosclerosis and is performed by high-density lipoproteins (HDLs). The production and breakdown of TAG-rich lipoproteins and the inter-relationship between these processes and HDL, particularly in the post-prandial period, are critical determinants of the atherogenicity of chylomicron remnants and LDLs, and the patency of HDL as a cardioprotective lipoprotein. © 2008 Elsevier Ltd. All rights reserved.
The link between dietary fat and coronary heart disease has attracted much attention since the effect of long-chain fatty acids on gene transcription has been established. The aim of this study was to investigate the effects of long-chain fatty acids and clofibrate on mRNA levels of specific lipid metabolism-related genes and to determine their effects on global transcriptome levels in a cardiovascular cell-line.
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