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Special Issue "Dietary Cholesterol:Is It Related to Chronic Disease"

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (30 April 2018)

Special Issue Editors

Guest Editor
Prof. Maria Luz Fernandez

Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA
Website | E-Mail
Phone: 860-486-5547
Interests: lipoprotein metabolism; functional foods; eggs; metabolic syndrome; diabetes
Guest Editor
Dr. Christopher Blesso

Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA
Website | E-Mail
Phone: 860-486-9049
Fax: 860-486-3674
Interests: Sphingolipids, Phospholipids, Cholesterol, Lipoproteins, Obesity, Inflammation, HDL, Polyphenols, Anthocyanins, Atherosclerosis

Special Issue Information

Dear Colleagues:

Dietary cholesterol is a controversial nutrient, which needs to be further discussed. On the one hand, many countries, including the United States, do not have specific recommendations to limit the intake of cholesterol while, on the other hand, dietary cholesterol is used to induce disease states in animal models. These two contradictory statements bring a high level of uncertainty regarding the role of dietary cholesterol in promoting disease. It is important to understand that in the case of animal models, dietary cholesterol is used in pharmacological doses as a means for developing atherosclerosis, increasing systemic inflammation, and promoting non-alcoholic fatty liver disease. In most cases, the extreme doses given to animal models are to study specific metabolic alterations or pathways associated with the disease, and are not used as models of the human response to dietary cholesterol. The scientific community should be able to unequivocally distinguish between the amount of cholesterol provided in the typical human diet, versus the much larger doses of dietary cholesterol used to induce chronic disease in animal models.

This Special Issue will include topics related to the effects of dietary cholesterol on 1) epidemiological studies of dietary cholesterol and human disease, 2) clinical studies examining dietary cholesterol provided by the regular diet (including high cholesterol foods) and disease risk, and 3) the relationship of dietary cholesterol to development of chronic disease in animal models.

Prof. Maria Luz Fernandez
Prof. Christopher Blesso
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Dietary cholesterol
  • clinical studies
  • epidemiology
  • plasma lipoproteins
  • reverse cholesterol transport
  • animal studies
  • atherosclerosis
  • inflammation
  • fatty liver
  • oxidative stress

Published Papers (9 papers)

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Research

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Open AccessArticle Dietary Cholesterol, Lipid Levels, and Cardiovascular Risk among Adults with Diabetes or Impaired Fasting Glucose in the Framingham Offspring Study
Nutrients 2018, 10(6), 770; https://doi.org/10.3390/nu10060770
Received: 1 May 2018 / Revised: 7 June 2018 / Accepted: 11 June 2018 / Published: 14 June 2018
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Abstract
Previous recommendations to limit dietary cholesterol intake have been eliminated for most adults. Questions remain about whether dietary cholesterol has adverse cardiovascular effects among individuals with impaired fasting glucose or diabetes (IFG/T2DM). We used data for 993 adults (40.9% female), ages 35–<65 years,
[...] Read more.
Previous recommendations to limit dietary cholesterol intake have been eliminated for most adults. Questions remain about whether dietary cholesterol has adverse cardiovascular effects among individuals with impaired fasting glucose or diabetes (IFG/T2DM). We used data for 993 adults (40.9% female), ages 35–<65 years, with prevalent IFG/T2DM in the prospective Framingham Offspring Study to address this question. Dietary cholesterol was assessed using 3-day diet records at exams 3 and 5 and used to classify subjects into sex-specific tertiles of mean cholesterol intake. Outcomes included fasting lipid levels over 20 years and incident cardiovascular disease (CVD). Statistical analyses included repeated measures mixed regression models and Cox proportional hazards models to adjust for confounding. Among adults with T2DM/IFG, there was no consistent association between dietary cholesterol intake and fasting low-density lipoprotein (LDL), high-density lipoprotein (HDL), LDL/HDL ratio, or triglycerides over 20 years of follow-up. In longitudinal analyses, the adjusted hazard ratio for CVD in the highest (vs. lowest) sex-specific tertile of cholesterol intake was 0.61 (95% CI: 0.41, 0.90). These analyses provide no evidence of an adverse association between dietary cholesterol and serum lipid levels or atherosclerotic CVD risk among adults with prevalent IFG/T2DM. Full article
(This article belongs to the Special Issue Dietary Cholesterol:Is It Related to Chronic Disease)
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Open AccessArticle Dietary Cholesterol Intake Is Not Associated with Risk of Type 2 Diabetes in the Framingham Offspring Study
Nutrients 2018, 10(6), 665; https://doi.org/10.3390/nu10060665
Received: 1 May 2018 / Revised: 15 May 2018 / Accepted: 18 May 2018 / Published: 24 May 2018
PDF Full-text (635 KB) | HTML Full-text | XML Full-text
Abstract
Identification of diet and lifestyle risk factors for prevention of type 2 diabetes mellitus (T2DM) is of great importance. The specific role of dietary cholesterol (DC) in T2DM risk is unclear. This study uses data from 2192 Framingham Offspring Study subjects to estimate
[...] Read more.
Identification of diet and lifestyle risk factors for prevention of type 2 diabetes mellitus (T2DM) is of great importance. The specific role of dietary cholesterol (DC) in T2DM risk is unclear. This study uses data from 2192 Framingham Offspring Study subjects to estimate the effects of DC alone and in combination with markers of a healthy diet and other lifestyle factors on fasting glucose and risk of T2DM or impaired fasting glucose (IFG) over 20 years of follow-up. Dietary data were derived from two sets of three-day food records. Statistical methods included mixed linear regression and Cox proportional hazard’s modeling to adjust for confounding. There were no statistically significant differences in glucose levels over 20 years of follow-up across DC intake categories (<200, 200–<300, and ≥300 mg/day) and no increased risk of T2DM/IFG associated with higher intakes. The HR for T2DM/IFG associated with consumption of ≥300 mg/day of DC was 0.87 (95% CI: 0.68–1.10). In contrast, subjects with lower intakes of fish, whole grains, and fiber had higher T2DM/IFG risk. DC consumption was not associated with fasting glucose levels or risk of T2DM/IFG over 20 years of follow-up. Full article
(This article belongs to the Special Issue Dietary Cholesterol:Is It Related to Chronic Disease)
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Open AccessArticle Intake of 3 Eggs per Day When Compared to a Choline Bitartrate Supplement, Downregulates Cholesterol Synthesis without Changing the LDL/HDL Ratio
Nutrients 2018, 10(2), 258; https://doi.org/10.3390/nu10020258
Received: 15 January 2018 / Revised: 8 February 2018 / Accepted: 17 February 2018 / Published: 24 February 2018
Cited by 3 | PDF Full-text (744 KB) | HTML Full-text | XML Full-text
Abstract
Cardiovascular disease (CVD) risk is associated with high concentrations of low-density lipoprotein cholesterol (LDL-C). The impact of dietary cholesterol on plasma lipid concentrations still remains a concern. The effects of egg intake in comparison to choline bitartrate supplement was studied in a young,
[...] Read more.
Cardiovascular disease (CVD) risk is associated with high concentrations of low-density lipoprotein cholesterol (LDL-C). The impact of dietary cholesterol on plasma lipid concentrations still remains a concern. The effects of egg intake in comparison to choline bitartrate supplement was studied in a young, healthy population. Thirty participants were enrolled for a 13-week intervention. After a 2-week run-in period, subjects were randomized to consume either 3 eggs/day or a choline bitartrate supplement (~400 mg choline for both treatments) for 4-weeks each. After a 3-week washout period, they were allocated to the alternate treatment. Dietary records, plasma lipids, apolipoproteins (apo) concentrations, and peripheral blood mononuclear cell expression of regulatory genes for cholesterol homeostasis were assessed at the end of each intervention. Dietary intakes of saturated and monounsaturated fat were higher with the consumption of eggs compared to the choline period. In addition, higher plasma concentrations of total cholesterol (7.5%), high density lipoprotein cholesterol (HDL-C) (5%) and LDL-C (8.1%) were observed with egg consumption (p < 0.01), while no change was seen in LDL-C/HDL-C ratio, a key marker of heart disease risk. Compared to choline supplementation, intake of eggs resulted in higher concentrations of plasma apoA-I (8%) and apoE (17%) with no changes in apoB. Sterol regulatory element-binding protein 2 and 3-hydroxy-3-methylglutaryl-CoA reductase expression were lower with egg consumption by 18% and 31%, respectively (p < 0.05), suggesting a compensation to the increased dietary cholesterol load. Therefore, dietary cholesterol from eggs appears to regulate endogenous synthesis of cholesterol in such a way that the LDL-C/HDL-C ratio is maintained. Full article
(This article belongs to the Special Issue Dietary Cholesterol:Is It Related to Chronic Disease)
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Review

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Open AccessReview Dietary Cholesterol and the Lack of Evidence in Cardiovascular Disease
Nutrients 2018, 10(6), 780; https://doi.org/10.3390/nu10060780
Received: 18 May 2018 / Revised: 9 June 2018 / Accepted: 13 June 2018 / Published: 16 June 2018
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Abstract
Cardiovascular disease (CVD) is the leading cause of death in the United States. For years, dietary cholesterol was implicated in increasing blood cholesterol levels leading to the elevated risk of CVD. To date, extensive research did not show evidence to support a role
[...] Read more.
Cardiovascular disease (CVD) is the leading cause of death in the United States. For years, dietary cholesterol was implicated in increasing blood cholesterol levels leading to the elevated risk of CVD. To date, extensive research did not show evidence to support a role of dietary cholesterol in the development of CVD. As a result, the 2015–2020 Dietary Guidelines for Americans removed the recommendations of restricting dietary cholesterol to 300 mg/day. This review summarizes the current literature regarding dietary cholesterol intake and CVD. It is worth noting that most foods that are rich in cholesterol are also high in saturated fatty acids and thus may increase the risk of CVD due to the saturated fatty acid content. The exceptions are eggs and shrimp. Considering that eggs are affordable and nutrient-dense food items, containing high-quality protein with minimal saturated fatty acids (1.56 gm/egg) and are rich in several micronutrients including vitamins and minerals, it would be worthwhile to include eggs in moderation as a part of a healthy eating pattern. This recommendation is particularly relevant when individual’s intakes of nutrients are suboptimal, or with limited income and food access, and to help ensure dietary intake of sufficient nutrients in growing children and older adults. Full article
(This article belongs to the Special Issue Dietary Cholesterol:Is It Related to Chronic Disease)
Open AccessReview Impact of Dietary Cholesterol on the Pathophysiology of Infectious and Autoimmune Disease
Nutrients 2018, 10(6), 764; https://doi.org/10.3390/nu10060764
Received: 11 May 2018 / Revised: 2 June 2018 / Accepted: 11 June 2018 / Published: 13 June 2018
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Abstract
Cellular cholesterol metabolism, lipid raft formation, and lipoprotein interactions contribute to the regulation of immune-mediated inflammation and response to pathogens. Lipid pathways have been implicated in the pathogenesis of bacterial and viral infections, whereas altered lipid metabolism may contribute to immune dysfunction in
[...] Read more.
Cellular cholesterol metabolism, lipid raft formation, and lipoprotein interactions contribute to the regulation of immune-mediated inflammation and response to pathogens. Lipid pathways have been implicated in the pathogenesis of bacterial and viral infections, whereas altered lipid metabolism may contribute to immune dysfunction in autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. Interestingly, dietary cholesterol may exert protective or detrimental effects on risk, progression, and treatment of different infectious and autoimmune diseases, although current findings suggest that these effects are variable across populations and different diseases. Research evaluating the effects of dietary cholesterol, often provided by eggs or as a component of Western-style diets, demonstrates that cholesterol-rich dietary patterns affect markers of immune inflammation and cellular cholesterol metabolism, while additionally modulating lipoprotein profiles and functional properties of HDL. Further, cholesterol-rich diets appear to differentially impact immunomodulatory lipid pathways across human populations of variable metabolic status, suggesting that these complex mechanisms may underlie the relationship between dietary cholesterol and immunity. Given the Dietary Guidelines for Americans 2015–2020 revision to no longer include limitations on dietary cholesterol, evaluation of dietary cholesterol recommendations beyond the context of cardiovascular disease risk is particularly timely. This review provides a comprehensive and comparative analysis of significant and controversial studies on the role of dietary cholesterol and lipid metabolism in the pathophysiology of infectious disease and autoimmune disorders, highlighting the need for further investigation in this developing area of research. Full article
(This article belongs to the Special Issue Dietary Cholesterol:Is It Related to Chronic Disease)
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Open AccessReview Molecular Pathways Underlying Cholesterol Homeostasis
Nutrients 2018, 10(6), 760; https://doi.org/10.3390/nu10060760
Received: 26 May 2018 / Revised: 10 June 2018 / Accepted: 11 June 2018 / Published: 13 June 2018
PDF Full-text (1431 KB) | HTML Full-text | XML Full-text
Abstract
Cholesterol is an essential molecule that exerts pleiotropic actions. Although its presence is vital to the cell, its excess can be harmful and, therefore, sustaining cholesterol homeostasis is crucial to maintaining proper cellular functioning. It is well documented that high plasma cholesterol concentration
[...] Read more.
Cholesterol is an essential molecule that exerts pleiotropic actions. Although its presence is vital to the cell, its excess can be harmful and, therefore, sustaining cholesterol homeostasis is crucial to maintaining proper cellular functioning. It is well documented that high plasma cholesterol concentration increases the risk of atherosclerotic heart disease. In the last decades, several studies have investigated the association of plasma cholesterol concentrations and the risk of cardiovascular diseases as well as the signaling pathways involved in cholesterol homeostasis. Here, we present an overview of several mechanisms involved in intestinal cholesterol absorption, the regulation of cholesterol synthesis and uptake. We also discuss the importance of reverse cholesterol transport and transintestinal cholesterol transport to maintain cholesterol homeostasis and prevent atherosclerosis development. Additionally, we discuss the influence of dietary cholesterol on plasma cholesterol concentration and the new recommendations for cholesterol intake in a context of a healthy dietary pattern. Full article
(This article belongs to the Special Issue Dietary Cholesterol:Is It Related to Chronic Disease)
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Open AccessReview Inflammation, not Cholesterol, Is a Cause of Chronic Disease
Nutrients 2018, 10(5), 604; https://doi.org/10.3390/nu10050604
Received: 23 April 2018 / Revised: 3 May 2018 / Accepted: 9 May 2018 / Published: 12 May 2018
Cited by 3 | PDF Full-text (2417 KB) | HTML Full-text | XML Full-text
Abstract
Since the Seven Countries Study, dietary cholesterol and the levels of serum cholesterol in relation to the development of chronic diseases have been somewhat demonised. However, the principles of the Mediterranean diet and relevant data linked to the examples of people living in
[...] Read more.
Since the Seven Countries Study, dietary cholesterol and the levels of serum cholesterol in relation to the development of chronic diseases have been somewhat demonised. However, the principles of the Mediterranean diet and relevant data linked to the examples of people living in the five blue zones demonstrate that the key to longevity and the prevention of chronic disease development is not the reduction of dietary or serum cholesterol but the control of systemic inflammation. In this review, we present all the relevant data that supports the view that it is inflammation induced by several factors, such as platelet-activating factor (PAF), that leads to the onset of cardiovascular diseases (CVD) rather than serum cholesterol. The key to reducing the incidence of CVD is to control the activities of PAF and other inflammatory mediators via diet, exercise, and healthy lifestyle choices. The relevant studies and data supporting these views are discussed in this review. Full article
(This article belongs to the Special Issue Dietary Cholesterol:Is It Related to Chronic Disease)
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Open AccessReview Dietary Cholesterol, Serum Lipids, and Heart Disease: Are Eggs Working for or Against You?
Nutrients 2018, 10(4), 426; https://doi.org/10.3390/nu10040426
Received: 13 February 2018 / Revised: 24 March 2018 / Accepted: 27 March 2018 / Published: 29 March 2018
Cited by 4 | PDF Full-text (1464 KB) | HTML Full-text | XML Full-text
Abstract
The relationship between blood cholesterol and heart disease is well-established, with the lowering of serum low-density lipoprotein (LDL)-cholesterol being the primary target of preventive therapy. Furthermore, epidemiological studies report lower risk for heart disease with higher concentrations of high-density lipoprotein (HDL)-cholesterol. There has
[...] Read more.
The relationship between blood cholesterol and heart disease is well-established, with the lowering of serum low-density lipoprotein (LDL)-cholesterol being the primary target of preventive therapy. Furthermore, epidemiological studies report lower risk for heart disease with higher concentrations of high-density lipoprotein (HDL)-cholesterol. There has also been considerable interest in studying the relationship between dietary cholesterol intake and heart disease risk. Eggs are one of the richest sources of cholesterol in the diet. However, large-scale epidemiological studies have found only tenuous associations between the intake of eggs and cardiovascular disease risk. Well-controlled, clinical studies show the impact of dietary cholesterol challenges via egg intake on serum lipids is highly variable, with the majority of individuals (~2/3 of the population) having only minimal responses, while those with a significant response increase both LDL and HDL-cholesterol, typically with a maintenance of the LDL/HDL cholesterol ratio. Recent drug trials targeting HDL-cholesterol have been unsuccessful in reducing cardiovascular events, and thus it is unclear if raising HDL-cholesterol with chronic egg intake is beneficial. Other important changes with egg intake include potentially favorable effects on lipoprotein particle profiles and enhancing HDL function. Overall, the increased HDL-cholesterol commonly observed with dietary cholesterol feeding in humans appears to also coincide with improvements in other markers of HDL function. However, more investigation into the effects of dietary cholesterol on HDL functionality in humans is warranted. There are other factors found in eggs that may influence risk for heart disease by reducing serum lipids, such as phospholipids, and these may also modify the response to dietary cholesterol found in eggs. In this review, we discuss how eggs and dietary cholesterol affect serum cholesterol concentrations, as well as more advanced lipoprotein measures, such as lipoprotein particle profiles and HDL metabolism. Full article
(This article belongs to the Special Issue Dietary Cholesterol:Is It Related to Chronic Disease)
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Open AccessReview Dietary Cholesterol Intake and Risk of Lung Cancer: A Meta-Analysis
Nutrients 2018, 10(2), 185; https://doi.org/10.3390/nu10020185
Received: 12 December 2017 / Revised: 19 January 2018 / Accepted: 26 January 2018 / Published: 8 February 2018
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Abstract
Multiple epidemiologic studies have evaluated the relationship between dietary cholesterol and lung cancer risk, but the association is controversial and inconclusive. A meta-analysis of case-control studies and cohort studies was conducted to evaluate the relationship between dietary cholesterol intake and lung cancer risk
[...] Read more.
Multiple epidemiologic studies have evaluated the relationship between dietary cholesterol and lung cancer risk, but the association is controversial and inconclusive. A meta-analysis of case-control studies and cohort studies was conducted to evaluate the relationship between dietary cholesterol intake and lung cancer risk in this study. A relevant literature search up to October 2017 was performed in Web of Science, PubMed, China National Knowledge Infrastructure, Sinomed, and VIP Journal Integration Platform. Ten case-control studies and six cohort studies were included in the meta-analysis, and the risk estimates were pooled using either fixed or random effects models. The case-control studies with a total of 6894 lung cancer cases and 29,736 controls showed that dietary cholesterol intake was positively associated with lung cancer risk (Odds Ratio = 1.70, 95% Confidence Interval: 1.43–2.03). However, there was no evidence of an association between dietary cholesterol intake and risk of lung cancer among the 241,920 participants and 1769 lung cancer cases in the cohort studies (Relative Risk = 1.08, 95% Confidence Interval: 0.94–1.25). Due to inconsistent results from case-control and cohort studies, it is difficult to draw any conclusion regarding the effects of dietary cholesterol intake on lung cancer risk. Carefully designed and well-conducted cohort studies are needed to identify the association between dietary cholesterol and lung cancer risk. Full article
(This article belongs to the Special Issue Dietary Cholesterol:Is It Related to Chronic Disease)
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