In 1959 a landmark clinical trial, often referred to as the LA Veterans Study, began with the aim to investigate the effects of replacing dietary saturated fats with polyunsaturated fats, on the progression of atherosclerosis and cardiovascular outcomes.
The Lyon Diet Heart Study is often cited as one of the pivotal studies that helped establish the Mediterranean diet as a recognized and recommended dietary pattern for cardiovascular health. It showed significant reduction in cardiac death could be achieved in secondary prevention patients using a dietary intervention. Here we dig into some of the deatils.
Could this trial undermine the common conclusions that replacing saturated fat with polyunsatured fat decreases heart disease risk?
The study made a huge splash due to the rarity in nutrition of having large RCTs with hard endpoints. In addition, it had results of a large magnitude; showing a 30% reduction in cardiovascular events.
The Multiple Risk Factor Intervention Trial (MRFIT) was a groundbreaking clinical trial conducted in the 1970s and 1980s. Its main objective was to investigate the relationship between various risk factors and the incidence of heart disease.
In this episode we take a look at why this is such seminal research, as well as the contribution of one of the greatest researchers ever in the field, Jeramiah Stamler.
One of the most important and influential papers in nutrition science is one by Ancel Keys and his colleagues that was published in The Lancet in 1957. This seminal paper examined the relationship between dietary fat intake and serum cholesterol levels. The most important aspect of this paper is the presentation of the ‘Keys Equation’; a predictive equation for the impacts of saturated, monounsaturated, and polyunsaturated fats, and dietary cholesterol, on blood cholesterol levels.
It has been clearly demonstrated that elevated LDL-cholesterol (LDL-C), or perhaps more specifically pro-atherogenic lipoproteins, is causal in atherosclerosis development in humans. One crucial concept within this is that the risk relates not only to the magnitude of elevated LDL-C, but the duration of exposure. Thus, the role of LDL-C in driving atherosclerosis is referred to as a “cumulative, integrated exposure over the lifecourse”.
Ask Me Anything (AMA) episode with Dr. Alan Flanagan, PhD.
While it has long been acknowledged that high intakes of saturated can increase risk of atherosclerotic cardiovascular disease due to their impact on blood lipids, there are some who question the association between saturated fat and heart disease.
Specifically, they may state that the evidence for this association is weak or non-existant, typically by pointing to some commonly cited studies that show null associations between saturated fat and CVD outcomes.
On this basis, they may conclude that there is no basis to aim to limit saturated fat intake to current recommended levels or that reducing saturated fat intake will not actually improve health outcomes.
In this episode, Alan and Danny look at the four most commonly cited publications showing a null association, highlighting some key issues. Beyond that, they look at a number of other lines of evidence on saturated fat that allows one to come to a confident answer on this question.
So does reducing saturated fat intake to recommended levels actually reduce heart disease risk? Let’s discuss…
Substantial evidence shows that a high intake of saturated fat in the diet has the potential to significantly raise LDL-C and ApoB-containing lipoproteins in many people, and in turn increase their risk of developing atherosclerotic cardiovascular disease (ASCVD).
However, people may raise what seems to some contradictory evidence, or what is sometimes thought of as a paradox: the impact of full-fat dairy on CVD risk.
This paradox arises because given the saturated fat content of full-fat milk, yogurt and cheese, we typically don’t see the same impact on blood lipid profiles. In addition, epidemiology can often show such foods in a favourable light. And the dairy fat story gets more interesting when we look at evidence showing there is a huge difference in the impact of consuming different dairy foods (e.g. butter vs cheese/yogurt).
Introduction Discordance between low-density lipoprotein particle (LDL-p) and low-density lipoprotein cholesterol (LDL-C) occurs when the levels of these two biomarkers do not match up as expected. Discordance between Apolipoprotein B (ApoB) and low-density lipoprotein cholesterol (LDL-C) is similar, except rather than counting just LDL particles, ApoB is a measure of the numbers of lipoproteins that have an ApoB attached. Discordance between ApoB and LDL-C can lead to either an underestimate or overestimate of ASCVD risk. And therefore there may be important implications for someone who does have discordance. Additionally, it is such cases that suggest that a measurement of ApoB …
Introduction Hypertension (elevated blood pressure) is a condition that significantly increases the risk of several diseases and is a major cause of premature death worldwide. In the US, recent estimates suggest that about half of the adult population has hypertension. At a population level, high sodium intake is one of the main dietary risk factors. All population health guidelines recommend keeping sodium intake below certain levels. While, on average, blood pressure correlates with sodium intake, there is a wide range of responses on an individual level. People who see increasing sodium intake lead to increased blood pressure are termed “salt …
It has been consistently shown in research that elevated dietary sodium consumption is associated with high blood pressure and an increased risk of cardiovascular disease. In addition, low levels of dietary potassium intake are associated with these same risks. However, there is some debate on how to characterize these relationships.
In a study published in European Heart Journal in July 2022, using data from the EPIC-Norfolk study, researchers attempted to answer whether the associations between potassium and both blood pressure and cardiovascular disease: 1) differ between men and women? and 2) depend on daily sodium intake.
In this episode Dr. Alan Flanagan and Danny Lennon discuss the details of this study and then link it to the overall evidence base and what this may mean for potassium (and sodium) intake considerations.
Dr. David Jenkins and collegegues put forward the idea of a “portfolio” of specific nutrients/foods that could lower LDL-C further than the typical dietary changes. This became known as the Portfolio Diet. The four primary pillars of this portfolio diet are: soy protein, viscous fibers, nuts, and plant sterols.
In this episode Alan and Danny discuss the role of cholesterol in the body and claims that are made suggesting low levels of blood cholesterol are harmful to health. Starting with the premise that cholesterol is an important molecule in the body and plays a role in many processes, the guys discuss two related claims: 1) we should avoid low cholesterol levels as it can harm our health, and 2) elevated levels of cholesterol may actually be protective against disease or mortality.
The episode also critiques claims about cholesterol being “conditionally essential” and that low LDL-C/ApoB increases risk of mortality, cancer and infection.
Bruce Neal is Executive Director at The George Institute for Global Health Australia; and Professor of Medicine, UNSW Sydney. Bruce has a longstanding interest in high blood pressure and diabetes and the potential for both clinical interventions and changes in the food supply to deliver health gains.
Guest InformationProfessor Chris Packard Prof. Chris Packard holds an Honorary Professorship of Vascular Biochemistry at the University of Glasgow. Over his career, Professor Packard has focussed on two aspects of atherosclerosis research, lipoprotein metabolism and how it is affected by diets and drugs, and large-scale clinical trials of lipid lowering agents. He is acknowledged as one of the leading researchers in the world in this field. Prof Packard has published widely on the kinetics of apolipoprotein B and apolipoprotein A metabolism. Key contributions include evaluation of the role of the LDL receptor in vivo, the discovery of metabolic channelling in the …
Today’s Topic in Focus: [00:51] In this episode Danny and Alan discuss the debate over the impact of dietary cholesterol on LDL-C levels and heart disease risk. Are eggs & cholesterol-rich foods a problem? Let’s dive into the research to find out! Referenced Material: Dietary Guidelines for Americans 2020 – 2025 Hegsted et al., 1993 – Dietary fat and serum lipids: an evaluation of the experimental data Human Atherosclerosis and the Diet – Ancel Keys Keys et al., 1965 – Serum cholesterol response to changes in the diet: II. The effect of cholesterol in the diet Nakamura et al., 2013 …
In This Episode We DiscussThis episode is a supplemental/follow-up episode to the ‘Diet & Cardiovascular Disease’ Series of Sigma Statements. If you have not read those statements, you can find them here: Cholesterol, Lipoproteins & Lipids: Understanding CVD Risk The Impact of Diet on Blood Lipids How Diet Influences Heart Disease Risk In this podcast Danny and Alan will be re-capping the main important points from each statement, in addition to addressing follow-up questions or potential conflicting points. We’ll cover issues such as: Does ApoB testing make LDL-C irrelevant? “I heard PUFA/omega-6 increases inflammation and therefore should be restricted. Is …
Guest BioSamia Mora, MD, MHS Dr. Samia Mora is an Associate Professor of Medicine at Harvard Medical School, Boston, Massachusetts. She is a cardiovascular medicine specialist at the Brigham and Women’s Hospital, where she is the Director of the Center for Lipid Metabolomics. Dr. Mora’s research focuses on risk factors and prevention of cardiovascular disease. Dr. Mora received her undergraduate degree from Harvard University, and her medical degree from Harvard Medical School. She completed an internal medicine residency at Massachusetts General Hospital and a cardiovascular disease fellowship at The Johns Hopkins Hospital, where she also obtained a Masters in Health …