Cardiovascular Risk Prevention With a Mediterranean Dietary Pattern Reduced in Saturated Fat (CADIMED): Randomized Controlled Dietary Intervention Study With Metabolomic and Gut Microbiome Analyses

1. BACKGROUND

Globally, cardiovascular diseases (CVD) are the leading cause of mortality. The World Health Organization estimates that, in 2019, 32% of deaths worldwide were due to CVD, mainly acute myocardial infarction. The most important cardiovascular risk factors are modifiable and are associated with poor diet, lack of physical activity, tobacco and alcohol consumption. Among them, it has been shown that an adequate diet is essential for the prevention of CVD given its effects on blood pressure, lipids, obesity, inflammation and endothelial function Amongst all dietary risk factors, saturated fatty acids (SFA) are of great interest because of their effects on low-density lipoprotein cholesterol (LDL-C) and total cholesterol, which are associated with increased cardiovascular risk due to endothelial dysfunction and atherosclerosis. Because of this, different organizations and institutions, such as the American Heart Association and the European Society of Cardiology, advise that SFA should represent less than 10% of total energy intake, preferably between 5% and 6% to prevent CVD. A Cochrane meta-analysis of clinical trials has shown that reducing SFA consumption decreases LDL-C significantly and up to 17% of cardiovascular events.

Current clinical practice guidelines on the prevention and treatment of CVD generally recommend a low-SFA healthy diet but do not offer detailed or specific advice for effective interventions. This is important as different food sources of SFA may have different health risks. Foods contain complex mixtures of SFA, and evidence suggests that some fatty acids, such as lauric, myristic, and palmitic acid, may pose different risks. In particular, red meat contains a high proportion of palmitic acid [long-chain SFA (16:0)] and, although the current evidence is inconsistent and mainly based on observational studies, an increased risk of CVD has been associated with a higher intake of red and processed meat compared to plant protein sources, probably mediated by changes in lipid profile, inflammation or insulin resistance. However, other SFA-rich foods, such as milk and cheese, contain high proportions of shorter-chain fatty acids [lauric (12:0) and myristic (14:0)] and have not shown an association with CVD. It has been suggested that dairy products have other elements, such as calcium, which may counteract the unfavorable physiological effects of SFA.

The principal investigator of this project has recently conducted an intervention study to reduce dietary SFA in a population at cardiovascular risk, which found a non-significant decrease in SFA intake. However, beneficial changes in blood lipid profile were observed among those participants who reduced their consumption of red and processed meats the most, compared to those who reduced other sources of SFA as dairy. In general, the current evidence is limited but suggests that different sources of SFA and individual proportions of SFA in red and processed meat may influence the cardiovascular profile differently; therefore robust intervention studies are required to confirm this. Also, changes in the fatty acid and blood lipid profile resulting from a dietary approach based on a Mediterranean dietary pattern without red and processed meat are widely unknown. It is relevant to investigate how these dietary modifications affect cardiovascular risk factors in the context of a Mediterranean diet in which consumption of unsaturated fats from olive oil or nuts confers benefits for CVD prevention.

On the other hand, despite recent public health efforts, the reduction of SFA consumption through education or information programs in the population has not been sufficient. Previous research has established that it is possible to reduce the intake of SFA-rich foods by providing foods that replace them, and/or through intensive and adapted eating advice, requiring specialized staff and behavioral support. However, there is limited evidence on the effectiveness of less intensive and lower-cost interventions that can reach a greater number of people and have a significant effect on the population. Simple dietary guidelines that target specific foods (e.g., red meat) that are related to cardiovascular risk may have a greater potential to be adopted by an increasing number of people who need help to improve their diet quality and thus decrease their cardiovascular risk.