Royal Society of Medicine Forum Conference

A conference was organised by the Royal Society of Medicine Forum on Food and Health in July 2000, chaired by Professor Gilbert Thompson (Emeritus Professor of Clinical Lipidology, Imperial College, London).

The conference was held in order to focus on and to help resolve issues surrounding cholesterol intake and dietary recommendations.

The relationship between dietary cholesterol and cardiovascular disease is an area of some confusion. Since the late 1980s, it has been generally accepted that whereas the key dietary recommendation for reducing coronary heart disease risk is a reduction in saturated fatty acid intake, specific advice to reduce dietary cholesterol is unwarranted for most people (COMA, 1994).

Nevertheless, among the general public and even among some health professionals, reduction in dietary cholesterol, specifically from eggs, is still viewed as the appropriate way to reduce blood cholesterol levels.

There is also confusion concerning the differences between advice on cholesterol intake given in public health recommendations and that in more specific recommendations for patients with familial dyslipidaemias.

Furthermore, although it is now well established that cardiovascular risk is determined by a multitude of interacting risk factors, both modifiable (e.g. diet, smoking, physical activity) and non-modifiable (e.g. family history, gender, age) there is a tendency to focus on single simplified messages and to ignore the importance of overall modifications to lifestyle.

The conference proceedings have been collated and we have provided abstract versions of these for your reference. Please refer to the abstracts below.

Abstract 1: Dietary cholesterol: a review of research and practice over 30 years
Professor Jim Mann (Departments of Human Nutrition and Medicine, University of Otago)

The idea that dietary cholesterol might play an important role in the aetiology of heart disease dates back to early in the last century, when experimental models of atherosclerosis were developed by feeding cholesterol or cholesterol-rich foods, such as butter, to animals. Subsequently, during the second half of the twentieth century, a plethora of epidemiological and clinical studies were undertaken to determine the extent to which dietary cholesterol influenced coronary heart disease. In the first chapter of this publication, Professor Jim Mann reviews the key studies carried out prior to 1990.

Both cross-population and longitudinal studies show an association between dietary cholesterol and CHD, but Professor Mann concludes that these studies do not provide strong support that the association is causal. Most likely these results reflect the close association between intakes of dietary cholesterol and saturated fatty acids, both of which may be found in the same foods. He also points out that the observed blood cholesterol response to dietary cholesterol is accentuated when saturated fatty acid intake is high. Therefore, when saturated fatty acid intake is low, if cholesterol intakes at the upper and lower ends of the usual range of intakes are compared, there is little effect on blood cholesterol.

Professor Mann concludes that reducing saturated fatty acid intake is the cornerstone of dietary advice designed to reduce coronary risk and in this context there would appear little need to emphasise dietary cholesterol reduction.

Abstract 2: Current evidence for effects of dietary cholesterol
Dr Bruce Griffin (Centre for Nutrition and Food Safety, School of Biomedical and Life Sciences, University of Surrey)

The discovery of the low density lipoprotein (LDL) receptor pathway in the late 1970s prompted a series of cholesterol feeding studies, mainly using eggs as a source of cholesterol, which were designed to establish a quantitative link between dietary and serum cholesterol in humans.

In Chapter 2, Dr Bruce Griffin reviews the outcome of these studies and their implications for the dietary guidelines that emerged in the 1990s. He carefully underlines the point, also made in Chapter 1, that these studies used unphysiological intakes of cholesterol (750-1500 mg/day), which although they resulted in perturbations in LDL metabolism, were of limited value in formulating realistic dietary guidelines.

Dr Griffin also discusses the considerable variation between individuals in the LDL response to dietary cholesterol seen in most studies. The biochemical mechanisms for such susceptibility to increases in dietary cholesterol are believed to include differences in the rate and efficiency of cholesterol absorption from the gut, rates of cholesterol biosynthesis in the liver, the activity of the LDL receptor pathway, and the cholesterol content of bile acids. The variability occurs through the expression of genetic polymorphisms or functionally abnormal genes and Dr Griffin briefly examines the evidence for some of these suggested mechanisms.

Dr Griffin believes that there is an overemphasis of serum cholesterol as a therapeutic target. He points out that the majority of free-living individuals who succumb to premature cardiovascular disease are not at risk from excessively high serum cholesterol levels, but from moderately raised cholesterol levels, co-existing with other risk factors. He highlights the importance of elevated serum triglycerides in this context, concluding that elevated triglycerides represent a significant source of cardiovascular risk that may be modifiable by means of diet, but not by manipulating dietary cholesterol.

Abstract 3: Genetic influence on cholesterol absorption and its therapeutic consequences
Professor Gilbert Thompson (Emeritus Professor of Clinical Lipidology, Imperial College, London)

The issue of individual and genetically determined variations in the response of serum cholesterol to changes in dietary cholesterol intake, and specifically the factors regulating cholesterol absorption, are considered in more detail by Professor Gilbert Thompson in Chapter 3. Evidence from both animal and human studies suggests that individuals with higher rates of cholesterol synthesis are less efficient absorbers of cholesterol and are less likely to respond to increasing dietary cholesterol intake with increases in serum cholesterol. The precise mechanism by which cholesterol is transported into the intestinal cells during absorption is still uncertain, but several candidate genes have been put forward as possible determinants of genetic variability in cholesterol absorption.

Recent data suggest that an important determinant of the net absorption of cholesterol is the amount which effluxes back into the intestinal lumen. Animal studies have demonstrated that this process is regulated by the ATP-binding cassette transporter 1 gene (ABC1). It is possible that genetic variation in this key regulatory step could explain, at least partially, the observed hypo- and hyper-responses to dietary cholesterol.

Professor Thompson suggests that another probable genetic influence is possession of an apoE 4 allele, which is associated with high serum cholesterol concentrations (Chapter 2) and which has been observed to predispose individuals to a failure in response to the statin drugs used to treat hypercholesterolaemia.

Abstract 4: Dietary cholesterol as a cardiac risk factor — current dietetic practice
Dr Gary Frost (Department of Nutrition and Dietetics, Hammersmith Hospital, London)

It is essential that attempts to reduce serum cholesterol by both dietary and pharmacological approaches are seen in the context of other dietary and lifestyle modification. This is underlined by Dr Gary Frost in Chapter 4. Dr Frost reviews the various aspects of dietary risk management as part of overall cardiac risk management where the dietitian works as part of a team, whether in a hospital setting or GP practice, and which aims to improve an individual's risk profile.

Patients frequently present with a constellation of metabolic risk factors in association with raised serum cholesterol levels, including abnormalities in insulin and blood glucose concentrations, low levels of high density lipoprotein (HDL) cholesterol, hypertriglyceridaemia, abnormal postprandial lipaemia, hypertension and abnormal clotting factors. This clustering of risk factors has been termed the 'insulin resistance syndrome' and another characteristic factor is upper abdominal obesity. With more than 50% of the UK population now classified as overweight and almost 20% obese, the importance of effective weight management cannot be overemphasised.

Dr Frost stresses that recent reports have highlighted the effectiveness of relatively small degrees of weight loss (5% of body weight) in improving cardiovascular risk profile. Such amounts of weight loss represent realistic targets for most people and are more likely to be achieved than the higher targets set in the past.

The approach to dietary advice on fats is also changing, with more advice on individual fatty acids including omega-3 fatty acids derived from fish oils. The role of certain functional foods in the dietary management of cardiovascular disease is now acknowledged, with the acceptance of foods enriched with plant stanols and sterols, which have been shown to achieve a 15-20% reduction in total serum cholesterol levels in randomised controlled trials. Finally, Dr Frost emphasises the need for further research into counselling models that assist people to make the necessary changes in diet and lifestyle.

Abstract 5: Science into practice: management of hypercholesterolaemia in primary care
Dr John Ferguson (Medical Director, Prescription Pricing Authority, Newcastle upon Tyne)

In Chapter 5 Dr John Ferguson discusses the pharmacological management of hypercholesterolaemia in primary health care. In common with the other contributors he believes that there is a danger of focusing on cholesterol because it is a relatively easy risk factor to modify, and, in so doing, to disregard the multifactorial nature of cardiovascular disease. A review of prescribing patterns in England during the 1990s indicates a steady growth in the use of statin drugs, whilst the use of fibrates has remained static. The popularity of the specific statins prescribed has varied with time over the past 5 years. There are also distinct regional variations in statin prescription with a 3.7 fold variation in different health authorities around the country. Dr Ferguson also examines the association between mortality from CHD and statin prescribing across the country, although such comparisons are open to confounding by the recognised geographical variations in CHD mortality, which is higher in Northern regions. He concludes from his data that there was no association between statin spending and heart disease mortality in 1995, but by 1999, there was a closer relationship between the two.

By 1999 there was generally more statin prescribing and the cross-country variation was reduced from 3.7 to 2.6 fold. However there are real concerns that we may be prescribing these drugs at an inappropriate level. Better targeting of statins is required, so that they are prescribed to those people who would benefit most in terms of CHD risk reduction. Dr Ferguson also raises concerns about the risk of treating a biochemical diagnosis, i.e. a high cholesterol level, rather than treating the underlying disease and re-emphasises the importance of also focusing on other key risk factors, most notably smoking.

Abstract 6: Eggs, dietary cholesterol and cardiac risk — a US perspective
Dr Donald McNamara (Executive Director of the Egg Nutrition Centre, Washington, USA)

Historically, the approach to dietary cholesterol modification, and specifically egg restriction, has been more stringent in the US than in the UK. In Chapter 6 of this book, Dr Donald McNamara reviews the changing picture of the scientific evidence over the past three decades and questions the validity of the need for restrictions in egg intake. The persisting recommendation in the US is the restriction of dietary cholesterol intake to 300mg per day. This recommendation is based on the results from animal studies, epidemiological surveys and clinical feeding trials.

Dr McNamara points out that animal studies are compromised both by species variability in the response to dietary cholesterol and the non-human-like plasma lipoprotein profiles of most animal models. The analysis of epidemiological data using simple correlations suggest that dietary cholesterol is positively related to cardiovascular disease, whereas multiple correlation analyses indicate that dietary cholesterol is not associated with increased cardiovascular risk. Meta-analyses of clinical feeding studies show that the increase in plasma cholesterol in response to a 100mg change in dietary cholesterol is very small (0.00062 mmol/l). This increase involves an increase in both atherogenic LDL and anti-atherogenic HDL concentrations, with little effect on the LDL: HDL ratio, an accepted determinant of cardiovascular risk.

Dr McNamara concludes that available data fail to validate the need for dietary cholesterol restrictions to lower risk of coronary heart disease and reminds us that eggs are low in saturated fatty acids and a valuable source of may essential nutrients.

Discussion and summary
A summary of the discussion sessions of the conference and the Chairman’s summing up is also included. The evidence debated indicates that dietary cholesterol is not a major cause of hypercholesterolaemia or a major contributor of CHD. If people have normal blood cholesterol levels and are eating a balanced diet, them they need not be concerned about their egg consumption. Nevertheless, in the UK, blood cholesterol level and CHD rates are high and certain caveats are necessary. Firstly, restrictions in saturated fatty acid intake should be encouraged. Secondly, if a person is hypercholesterolaemic they may fall into the category of hyper-responders and at present should continue to restrict egg consumption to 3-4 per week.

Since the conference was held, the American Heart Association (Krauss et al, 2000) has announced that although it will continue to recommend a daily dietary cholesterol intake of 300 mg per day, it has relaxed its recommendations concerning eggs and other high cholesterol foods. It is to be hoped that the outcome of the conference published in this book and the revision in thinking in the US will encourage health professionals in the UK to review their own thinking concerning dietary cholesterol and egg intake in relation to cardiovascular disease.

References

COMA (Committee on Medical Aspects of Food Policy) Nutritional Aspects of Cardiovascular Disease. Department of Health Report on Health and Social Subjects No. 46. London: HMSO, 1994.

Krauss RM, Eckel RH, Howard B et al. (2000) AHA dietary guidelines. Circulation 102: 2284-2315