From Sugar versus Fat to the Biology of Atherosclerosis
How Nutrition Moved from Single-Nutrient Explanations to a Multifactorial Understanding of Coronary Heart Disease
by:
lim ju boo, BSc, MD, Post-Grad Dip Nutr., MSc, PhD (Med), FRSPH, FRSM
Introduction
For much of the twentieth century, nutrition science was preoccupied with a deceptively simple question: Was coronary heart disease caused principally by sugar, or by dietary fat and cholesterol?
The question arose during an era when coronary heart disease was becoming a major cause of death in industrialised societies. Researchers understandably searched for a dietary culprit. Yet the resulting debate became increasingly polarised, with dietary sucrose on one side and saturated fat and cholesterol on the other.
Looking back from the perspective of modern cardiovascular biology, the controversy appears both important and incomplete. Neither sugar nor fat can adequately explain coronary heart disease by itself. Nor can cholesterol, inflammation, oxidative stress, hypertension, smoking, diabetes, obesity, physical inactivity or ageing be considered entirely in isolation.
Coronary atherosclerosis is now understood as a long biological process involving the interaction of atherogenic lipoproteins, the arterial wall, endothelial and immune biology, metabolism, blood pressure, smoking and other environmental influences, genetic susceptibility and the passage of time. Modern research has therefore not simply selected another single culprit. Rather, it has progressively assembled a more integrated picture of disease.
For me, this history is not merely an academic subject. During my postgraduate training in nutrition at Queen Elizabeth College (QEC), University of London, I had the privilege of learning directly from two important figures in the history of British nutrition: Professor John Yudkin, who established nutrition as a major academic discipline at QEC, and Professor Arnold E. Bender, whose work connected nutrition with food science, food chemistry and the biological utilisation of nutrients.
I therefore encountered some of these ideas not only through textbooks and scientific papers, but also through direct postgraduate teaching. My personal experience does not determine which scientific hypothesis was correct; rather, it provides me with a firsthand perspective on an important period in the development of nutritional science.
The Mid-Century Dietary Controversy: Yudkin, Keys and Two Competing Hypotheses
Professor John Yudkin became one of the earliest major academic figures in British nutrition. At Queen Elizabeth College he helped establish nutrition as a university discipline and developed a broad programme of teaching and research. Historical accounts of the department also record his involvement in establishing Food Science at the College.
Yudkin became increasingly interested in the possible relationship between the consumption of refined sugars and cardiovascular disease. He examined dietary patterns, epidemiological observations and experimental evidence and argued that the rapidly increasing consumption of refined sugar deserved considerably more attention than it was receiving.
His ideas eventually became widely known through his 1972 book, Pure, White and Deadly, in which he warned that excessive sugar consumption might contribute substantially to chronic disease.
At approximately the same historical period, another influential hypothesis was developing.
American physiologist Ancel Keys argued that dietary saturated fat influenced blood cholesterol and that elevated cholesterol was related to coronary heart disease. His work, particularly the Seven Countries Study, became highly influential in shaping the diet-heart hypothesis.
The historical debate between Yudkin and Keys is sometimes portrayed retrospectively as a simple confrontation between a scientist who blamed sugar and another who blamed fat. The actual scientific history was more complicated. Both hypotheses attempted to explain an extremely complex disease using the scientific tools available at the time.
Keys' work contributed substantially to the modern understanding of the relationship between dietary fat, blood lipids and coronary disease. At the same time, Yudkin raised questions about refined sugar and metabolic health that have received renewed scientific attention many decades later.
It would therefore be misleading to rewrite history as though one man was simply right and the other simply wrong. The more important lesson is that a complex disease can contain several interacting causal pathways, and the importance of one pathway does not automatically eliminate the importance of another.
My Own Perspective from Queen Elizabeth College
My connection with this history was unusually direct.
As a postgraduate student in nutrition at Queen Elizabeth College, I studied under Professor John Yudkin and Professor Arnold E. Bender. These were not simply names in the literature to me; they were teachers and mentors during my own scientific formation.
This experience also exposed me to an important distinction between studying individual nutrients and studying food as a biological system.
Yudkin's interest in sugar encouraged students to question prevailing assumptions rather than accept nutritional fashions unquestioningly. Bender, meanwhile, brought a particularly broad perspective to the relationship between food science and nutrition.
This historical connection is important because the subsequent development of nutrition was not simply a march from one nutritional doctrine to another. Different researchers were examining different levels of the same biological problem.
Arnold E. Bender and the Wider Food Matrix
Professor Arnold E. Bender occupies an important place in this story.
Historical records of his career show that he joined Queen Elizabeth College during the period when Yudkin was developing Food Science alongside Nutrition. Bender came from a background that combined academic and food-industry research and was particularly well placed to connect food science with nutrition.
This broader perspective is important because food is not simply a collection of isolated chemicals.
When we eat a meal, we do not normally consume carbohydrate, fat, protein, vitamins and minerals as independent laboratory substances. We consume foods containing complex mixtures of nutrients, fibre, bioactive compounds and varying physical structures. Food processing, cooking, storage, digestion, absorption, metabolism and interactions among nutrients can all influence the biological response.
Bender's scientific work also included the development, with D. S. Miller, of methods for assessing protein utilisation, including the well-known work on Net Protein Utilization (NPU). This work belongs to the history of nutritional methodology and should not be interpreted as proof that NPU itself demonstrated the entire concept of holistic nutrition. Its importance lies more specifically in demonstrating the need to evaluate how nutrients are actually utilised biologically rather than merely measuring their chemical presence in food.
His broader career, however, illustrates a valuable principle: nutrition cannot be completely understood by looking at isolated nutrients without considering food, processing, biological utilisation and the human organism as a whole.
That principle has become increasingly important as nutrition science has moved from classical nutritional deficiency diseases towards chronic diseases such as diabetes, obesity and cardiovascular disease.
What Modern Atherosclerosis Research Has Revealed
The modern understanding of coronary heart disease is considerably more sophisticated than the old metaphor of cholesterol simply “clogging the pipes.”
At the same time, modern science has not discarded the importance of LDL cholesterol. On the contrary, a large body of genetic, epidemiological and clinical evidence now establishes that LDL and other apoB-containing lipoproteins play a causal role in atherosclerotic cardiovascular disease.
The crucial insight is that LDL is not acting alone.
Atherosclerosis begins, in simplified terms, when cholesterol-rich apoB-containing lipoproteins enter and become retained within susceptible regions of the arterial wall. This retention can initiate a complex biological response involving endothelial cells, smooth-muscle cells and the immune system.
The retained lipoproteins can undergo a variety of modifications. Oxidative processes are among these, but the modern picture is considerably more complicated than the old formulation that LDL simply becomes “oxidised” because there are insufficient dietary antioxidants.
Modified and retained lipoproteins can stimulate inflammatory and immune pathways. Monocytes are recruited into the arterial wall and differentiate into macrophages. These macrophages take up modified lipoproteins and can become lipid-rich foam cells.
Thus, lipid accumulation and inflammation are not competing explanations. They are parts of the same pathological process.
Inflammation can promote plaque growth and contribute to the transformation of relatively stable lesions into plaques that are more vulnerable to rupture. When a vulnerable plaque ruptures or erodes, thrombogenic material is exposed to circulating blood, potentially producing an acute thrombus and myocardial infarction.
The modern model therefore resembles a biological ecosystem rather than a blocked water pipe.
Where Does Sugar Fit into the Picture?
This more sophisticated understanding does not make Yudkin's questions irrelevant.
Excessive consumption of refined carbohydrates and added sugars can contribute, particularly in susceptible individuals and in the context of excess energy intake and insulin resistance, to metabolic abnormalities including hypertriglyceridaemia and an atherogenic lipoprotein pattern.
Insulin resistance, obesity, elevated triglycerides, reduced insulin sensitivity and abnormalities in lipoprotein metabolism often occur together. Under these circumstances, small dense LDL particles may become more prominent. Small dense LDL is associated with an atherogenic metabolic phenotype, although particle size itself should not be treated as an independent replacement for the much stronger evidence concerning the overall burden of apoB-containing particles.
The important point is therefore not that sugar “replaces” LDL as the cause of coronary disease.
Rather, dietary carbohydrate quality and metabolic health can influence the environment in which atherogenic lipoproteins operate.
This is a far more defensible interpretation of Yudkin's historical contribution.
And Where Does Saturated Fat Fit?
The same principle applies to saturated fat.
Modern evidence does not support the idea that every saturated fat-containing food has an identical cardiovascular effect regardless of what replaces it in the diet or what food matrix it belongs to.
The metabolic consequences of replacing saturated fat with polyunsaturated fat, monounsaturated fat or refined carbohydrate are not necessarily the same.
This is one reason why nutritional science has gradually moved away from asking only:
“How much fat should we eat?”
and towards more informative questions:
Which fats? In which foods? Replacing what? Within which dietary pattern? And in what metabolic context?
This shift from isolated nutrients to dietary patterns represents a major conceptual advance.
From Nutrients to Dietary Patterns
The Mediterranean dietary pattern provides a useful example of this change in thinking.
Its traditional form contains vegetables, fruits, legumes, whole grains, nuts, olive oil, fish and other minimally processed foods, with relatively limited intake of highly processed foods and excessive refined sugars.
Its possible cardiovascular benefits cannot reasonably be attributed to one molecule alone.
The pattern influences several biological pathways simultaneously, including lipid metabolism, blood pressure, insulin sensitivity, endothelial function and inflammatory processes. Clinical research, including the PREDIMED trial and its subsequent republication after correction of methodological irregularities, has provided evidence supporting cardiovascular benefits of Mediterranean-style dietary patterns in appropriate populations.
This is precisely why dietary patterns can sometimes tell us more about health than a single nutrient percentage.
Beyond Diet: The Other Half of the Story
Even the most sophisticated dietary explanation remains incomplete if lifestyle and other biological factors are ignored.
Smoking introduces numerous oxidant and toxic substances into the cardiovascular system and greatly increases vascular risk. Hypertension subjects arterial structures to chronic mechanical stress. Diabetes and insulin resistance alter metabolism and vascular biology. Physical inactivity, obesity, sleep disturbances and chronic psychosocial stress can influence several of these pathways simultaneously.
Ageing adds another dimension.
Atherosclerosis is not an event that suddenly begins on the morning of a myocardial infarction. It is usually the result of a long biological history extending over many years or decades.
The coronary artery therefore becomes a kind of biological diary, recording cumulative exposure to atherogenic lipoproteins, metabolic disturbances, blood pressure, smoking and other influences throughout life.
The Real Lesson of the Great Dietary Debate
Looking back at the sugar-versus-fat controversy, it is tempting to ask which scientist “won.”
I believe that this is the wrong question.
Yudkin drew attention to the possible importance of refined sugar and metabolic disturbances. Keys helped establish the importance of dietary fat, cholesterol and blood lipids in coronary disease. Subsequent researchers demonstrated the central causal importance of LDL and other apoB-containing lipoproteins. Modern vascular biology has shown how lipoprotein retention interacts with endothelial, cellular and immune mechanisms to produce atherosclerotic plaques.
Each layer has added something to the picture.
The history therefore illustrates not the failure of reductionist science, but the limitations of stopping at one level of reductionism.
Reductionism was indispensable for discovering cholesterol, lipoproteins, LDL receptors, inflammatory pathways, macrophages and many other components of cardiovascular disease. The problem arises only when one component is mistaken for the complete system.
From Reductionism to Integration
This may be the most important lesson I take from my years of studying nutrition.
A nutrient can be studied in isolation in a laboratory. But a human being does not live inside a laboratory test tube.
We eat meals rather than isolated nutrients. We live within environments rather than controlled experimental chambers. Our metabolism is influenced by age, genetics, physical activity, sleep, stress, body composition, medications and disease. Our arteries are exposed to these influences continuously over decades.
Consequently, the modern understanding of coronary heart disease is not that sugar was the villain and fat was innocent, nor that fat was the villain and sugar was innocent.
The deeper lesson is that human biology rarely obeys a single-cause explanation for a complex chronic disease.
The old question was:
“Is it sugar or fat?”
The more useful modern question is:
“How do diet, lipoproteins, metabolism, vascular biology, inflammation, lifestyle and ageing interact over time to produce disease?”
That is a much larger question—and, scientifically, a much more fruitful one.
The history of nutritional science is a reminder that scientific progress does not always occur by replacing one simple answer with another. Sometimes it occurs by discovering that the original question was too simple.
The debate between John Yudkin's concern about refined sugar and Ancel Keys' diet-heart hypothesis helped stimulate decades of research into the relationship between food and coronary disease. My own postgraduate years at Queen Elizabeth College, where I had the privilege of learning from both Professor John Yudkin and Professor Arnold E. Bender, gave me a personal window into this important period in nutritional science.
With the benefit of modern cardiovascular biology, we can now see the problem at several interconnected levels.
Atherogenic lipoproteins are central to the development of atherosclerosis. Their retention within the arterial wall initiates a complex interaction involving lipid modification, vascular cells and innate and adaptive immune responses. Metabolic disturbances, hypertension, smoking, physical inactivity, diet, environmental influences and ageing can modify the trajectory of this process.
The answer, therefore, was never simply hidden inside the carbohydrate or fat column of a food-composition table.
The real lesson of the great dietary controversy is that nutrition is biology—and biology is an interconnected system.
Perhaps the most enduring contribution of the pioneers of nutrition was not that any one of them discovered a single dietary villain, but that they taught subsequent generations to keep asking questions when apparently simple explanations failed.
And that, ultimately, is how science advances: not by choosing a permanent nutritional scapegoat, but by gradually replacing simple stories with deeper understanding.
References
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3. Yudkin J. Pure, White and Deadly: How Sugar Is Killing Us and What We Can Do to Stop It. Davis-Poynter; 1972.
4. Truswell AS. Cholesterol and Beyond: The Research on Diet and Coronary Heart Disease 1900–2000. Springer; 2010.
5. Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868–874.
6. Borén J, Chapman MJ, Krauss RM, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: evidence from genetic, epidemiologic, and clinical studies. European Heart Journal. 2017;38:2459–2472.
7. Borén J, Chapman MJ, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights. European Heart Journal. 2020;41:2313–2330.
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9. Estruch R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. New England Journal of Medicine. 2018;378.
10. Historical account of Arnold E. Bender's career at Queen Elizabeth College and his work linking food science and nutrition. Proceedings of the Nutrition Society.
