John Yudkin's hypothesis: sugar is a major dietary culprit in the development of cardiovascular disease.

To date, the risk of developing atherosclerosis has extended beyond Western countries and now affecting individuals from various ethnic backgrounds and age groups. Traditional risk factors of atherosclerosis, such as hypercholesterolemia, has been better controlled than before due to highly effective and inexpensive therapies at lowering plasma cholesterol levels. However, the role of reducing dietary cholesterol intake, as a public healthy strategy, in preventing the occurrence of cardiovascular mortalities has been recently challenged. Indeed, despite our continuous decline of dietary cholesterol intake within the last 50 years, the incidence of cardiovascular mortalities has continued to rise, thus raising the possibility that other dietary factors, such as fructose-containing sugars, are the major culprit. In the 1970s, John Yudkin first proposed that sugar was the predominant dietary factor that underlies the majority of cardiovascular mortalities, yet his hypothesis was dismissed. However, over the last 25 years substantial scientific evidence has been accumulated to support Yudkin's hypothesis. The objectives of this review are to highlight Yudkin's significant contribution to nutritional science by reviewing his hypothesis and summarizing the recent advances in our understanding of fructose metabolism. The metabolic consequences of fructose metabolism, such as fructose-induced uricemia, insulin resistance, lipoprotein hyperproduction and chronic inflammation, and how they are linked to atherosclerosis as risk factors will be discussed. Finally, the review will explore areas that warrant future research and raise important considerations that we need to evaluate when designing future studies.