New insights into cholesterol functions
Cholesterol is a sterol synthesized by animal cells and is also a component of the diet, being present in food of animal origin. Its main function is to maintain the integrity and fluidity of cell membranes and to serve as a precursor for the synthesis of substances that are vital for the organism including steroid hormones, bile acids, and vitamin D. Although a high dietary cholesterol intake was considered as a risk factor for cardiovascular diseases (CVD), recent evidence suggests that it does not increase significantly low-density lipoprotein cholesterol (LDL-C) levels in the circulation. Results, however, remain controversial, potentially due to the correlation with saturated fat intake. In view of these recent findings and the fact that cholesterol plays a vital role in major functions in the body, the special issue of Nutrients on “Cholesterol and Health” focused on the functions of cholesterol and the effects of dietary cholesterol in various metabolic processes.
Cholesterol and bile acid synthesis has a diurnal rhythm in the body, but the role of the circadian system in cholesterol homeostasis is still being investigated. A better understanding of this system is necessary for the development of targeted interventions to improve metabolic health before considering the effects of dietary cholesterol or the body’s cholesterol as a risk factor for specific diseases, with cardiovascular being the main. A study in this special issue of Nutrients systematically reviewed the literature on the diurnal rhythms of cholesterol synthesis and absorption markers, and of bile acid synthesis markers. In addition, it looked at the diurnal rhythms of the cholesterol synthesis markers lathosterol and desmosterol, and the cholesterol absorption markers cholestanol, campesterol, and sitosterol in serum samples from the Bispebjerg Study. The study came to the conclusion that although cholesterol and bile acid synthesis have a diurnal rhythm, no evidence was found for a diurnal rhythm of cholesterol absorption.
CVD risk factors are affected by nutrients, dietary patterns, and energy balance. Four very interesting studies on this issue have attempted to address these issues. First, data from the Hellenic National Nutrition and Health Survey (HNNHS) indicated and confirmed the results of other studies that, eggs are a major source of dietary cholesterol. The study found that everyone can eat eggs as part of a healthy diet rich in fibre and low in saturated fat, without consuming too much energy. Interestingly, the HNNHS results actually indicated that dyslipidemia risk was lowered with fewer than five moderate egg intakes per week, possibly due to a total balanced diet.
The second study was carried out during Ramadan, a very important religious period in the Muslim world. It is known that fasting during this period involves large changes in daily eating patterns, which strongly impacts the daily biorhythm and challenges the regular function of the digestive tract. This study assessed the effects of a high fibre cereal at dawn during the month of Ramadan on satiety, bowel habits, body composition, blood glycemia, and blood lipidemia and it was found that this consumption had a positive effect on satiety, and it improved bowel functions and blood lipid levels.
To change someone’s nutritional behaviour, primarily nutritional knowledge has to be assessed in order to set methods for improvement. A cross-sectional survey recruiting students in the United Arab Emirates investigated knowledge, attitudes, and practices related to dietary salt intake and a 24-h dietary recall among a subsample of the study population, to assess the dietary intake of total fat, cholesterol, saturated fat, trans fat, and sodium. The results of this study showed that students with low salt-related knowledge scores were correlated with a higher prevalence of overweight/obesity as well as hypertension. The results also revealed a high percentage of students exceeding the recommended intake of total fat (48% of the sample), saturated fat (90%), trans fat (64%), and sodium (89%), and all students did not meet potassium intake recommendations. The fact that foods high in saturated fat are also good sources of cholesterol indicates the combination may increase the risk of CVD, especially in relation to this population’s high salt and low potassium intake. Public health intervention programs to decrease red meat and its products, as well as dietary sodium, are of paramount importance in this region.
However, blood cholesterol levels must be low to reduce the risk of chronic diseases, as there are organs in the human body where cholesterol, such as eye is of great importance. In particular, the plasma layers of the human lens fibre cell are overloaded with cholesterol, which saturates the phospholipid bilayer of these layers and leads to the formation of pure cholesterol bilayer domains. A very interesting review in this issue focuses on the beneficial and harmful actions of cholesterol on the lens of the eye, especially high cholesterol, which has a different function in the lens of the eye compared to other tissues and organs. The main difference between the action of cholesterol on the lens in other tissues and organs is that the lens of the eye is avascular, so it is not exposed to its corresponding components, including blood and cholesterol transported in LDL and HDL. Also, cells in the lens fibre differentiate to form an organelle-free zone consisting of cells that are not present. Since the organelle-free zone in the lens contains only plasma membranes and cytosol, the high cholesterol content in the lens is important and beneficial.
Another important aspect that was presented in this cholesterol issue was the association between CVD and bone metabolism. A positive correlation between CVD and osteoporosis risk has been suggested, which implies a close relationship between hyperlipidemia and/or hypercholesterolemia and bone metabolism. Cholesterol and its metabolites influence bone homeostasis through modulating the differentiation and activation of osteoblasts and osteoclasts. In addition, the hematopoietic cells and bone marrow adipocytes take up the majority of space in the bone cavity and the effects of cholesterol on hematopoietic stem cells, including proliferation, migration, and differentiation, are also well-known and relate to atherosclerotic lesions. However, the correlation between circulating cholesterol and bone marrow adipocytes remains elusive. The latest progress on the effects of cholesterol on the regulation of bone metabolism and bone marrow microenvironment, including the hematopoiesis and marrow adiposity, were explored. Some mechanisms were proposed but it was underlined that the functions of bone marrow adipocyte tissue are still widely unknown. It was also noted that future research exploring the physiological and pathological functions of bone marrow adipocyte tissue could provide greater insight on the importance of bone marrow niche homeostasis in local hematopoiesis and osteogenesis, which could potentially act beneficially on therapeutic strategies for atherothrombosis and osteoporosis.
Finally, heated oils may also affect the risk of various diseases. It is widely known that heating oils and fats for a considerable length of time results in chemical reactions, leading to the aggravation of free radical processes, which ultimately contributes to the development of atherosclerosis. An animal study in this issue investigated the effects of feeding heated oils with or without dietary cholesterol on the development of atherosclerosis in rabbits since these animals are considered very good models for atherosclerosis research. The results of this study suggested that heated palm oil could protect against the development of atherosclerosis compared to heated polyunsaturated oils in a rabbit model. This can potentially be explained by the effect that heat has on the chemical structure of polyunsaturated fatty acids due to the presence of double bonds, compared to the absence of double bonds in the chemical structure of palm oil and consequently its insusceptibility to oxidation.