Dr. Ronald Krauss on LDL Cholesterol, Particle Size, Heart Disease & Atherogenic Dyslipidemia

Posted on January 3rd 2016 (almost 4 years)

Ronald M. Krauss, M.D., is Senior Scientist and Director of Atherosclerosis Research at Children’s Hospital Oakland Research Institute. He serves as an adjunct professor in the Department of Medicine at UCSF and in the Department of Nutritional Sciences at UC Berkeley. Dr. Krauss’s pioneering research revolutionized the way in which the scientific and lay communities think about cholesterol and saturated fat and their effects on human health.

Dr. Krauss received his undergraduate and medical degrees from Harvard University. He served on the staff of the National Heart, Lung, and Blood Institute and is currently a member of the U.S. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. He also founded and served as Chair of the American Heart Association Council on Nutrition, Physical Activity, and Metabolism.

Dr. Krauss has published nearly 400 research articles and reviews on genetic, dietary, and drug effects on plasma lipoproteins and coronary artery disease. He is the Associate Editor of Obesity and serves on the editorial boards of several other journals.

Dr. Krauss and his colleagues developed an assay that quantifies low-density lipoprotein particle size and concentration (known to the wider world as LDL cholesterol). The test relies on a technique that determines the size of the particle based on a principle of physics called ion mobility – the speed at which the particle flies through the air. Determining particle size is a more precise approach to assessing a person’s lipoprotein status and may help clinicians better identify patients with cholesterol problems.

In this episode, Rhonda and Dr. Krauss discuss what HDL and LDL cholesterol are, what they do in the body, and how they may play roles in heart disease. We talk about what small, dense LDL particles are and how they form; what effect eating saturated fat versus refined carbohydrates have on LDL particle size and heart disease risk; and what the main risk factors for heart disease are. Dr. Krauss also talks about the good, the bad, and the ugly of the LDL-lowering drugs known as statins and much more.

The failures of a reductionist approach.

"The fundamental role of cholesterol is one that promotes health. Where we get into trouble is when it exceeds the ability of cells to take cholesterol out of the blood quickly through the liver." - Ronald Krauss, M.D. Click To Tweet

Cholesterol is vital to human health, and every cell in the body is capable of producing its own. For decades, however, a reductionist approach to describing the relationship between cholesterol and heart disease has influenced far-ranging aspects of our lives, from what we eat to what drugs we take. This oversimplified view of cholesterol — that high-density lipoprotein (HDL) cholesterol is good, and low-density lipoprotein (LDL) cholesterol is bad — has led to a gross misunderstanding of the subtle nuances that define the differences in cholesterol-containing lipoproteins and how these differences influence cardiovascular disease risk and human health.

In this episode, Dr. Robert Krauss explains that the size and content of lipoproteins vary considerably, falling on a wide, heterogeneous spectrum that includes small, dense particles and ranging to large, buoyant ones – sometimes described as “fluffy.” These variations confer different metabolic and pathologic properties on the particles, which in turn influence disease risk.

The two faces of inflammation in modulating human health.

"Inflammation is a key regulator of lipoprotein metabolism in a positive way, historically, evolutionary-wise, but in an adverse way in our current environment." - Ronald Krauss, M.D. Click To Tweet

Cholesterol and its attendant lipoprotein particles don’t exist in a vacuum, however. A wide array of influences modulates their formation and metabolic disposition – perhaps the strongest of which is inflammation. Inflammation drives the production of smaller, more dense lipoprotein particles, which are not cleared by the liver as efficiently as larger particles. As a result, these small particles circulate in the plasma longer, where they can bind with toxic molecules called lipopolysaccharides, intensifying the deleterious effects of their activities within arteries and promoting plaque formation and subsequent blockages – the hallmarks of atherosclerosis.

But inflammation is critical to a healthy immune response, of which lipoproteins play a part. The liver constantly produces apoprotein B - the protein that forms the backbone of all lipoproteins - to facilitate the speedy production of lipoproteins. This provides a means to quickly deliver pro-inflammatory factors that the body needs to launch a healthy response to a threat. This ancient system of lipoprotein regulation and metabolism ensured our survival in the past when modern drug therapies such as antibiotics were unavailable.

In modern times, however, the threat is more likely to be an arterial plaque, but the response is the same. Unfortunately, these small, dense lipoprotein particles can circulate for long periods of time – providing them sufficient opportunity to interact with arteries and undergo transformations that enhance their pro-inflammatory status. Avoiding chronic exposure to inflammation may be one of the single most important factors in promoting longevity that actually increases in importance as we age.

A broader understanding of the role of diet.

The early research also fueled the adoption of a set of restrictive dietary tenets based on the idea that intake of cholesterol and saturated-fat raises a person’s heart disease risk. The response to these tenets was the expansion of a low-fat, high carbohydrate diet industry that remains in vogue today, despite the evidence demonstrating that such dietary practices may promote atherogenic dyslipidemia and increase heart disease risk.

This problem is exacerbated in the context of eating refined simple sugars, especially fructose, which Dr. Krauss describes as one of the chief culprits in inducing what he calls the "atherogenic dyslipidemic trait" - a trio of pathological lipoprotein levels that increases risk of atherosclerosis. Although fructose is a common ingredient in sweet baked goods and soft drinks, it's also present in healthy foods like fruit. It’s really the dose and the "packaging" of this sugar that matters: in other words, whether we consume refined sugars in a bolus of empty calories or in a smaller amount wrapped up in a nutrient-rich food matrix makes a difference in our health.

Learn more about Dr. Ronald Krauss

Relevant studies

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