Dietary cholesterol has been suggested to increase the risk of cardiovascular disease (CVD), which has led to US recommendations to reduce cholesterol intake.
The authors examine the effects of ...dietary cholesterol on CVD risk in healthy adults by using systematic review and meta-analysis.
MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau Abstracts databases were searched through December 2013 for prospective studies that quantified dietary cholesterol. Investigators independently screened citations and verified extracted data on study and participant characteristics, outcomes, and quality. Random-effect models meta-analysis was used when at least 3 studies reported the same CVD outcome.
Forty studies (17 cohorts in 19 publications with 361,923 subjects and 19 trials in 21 publications with 632 subjects) published between 1979 and 2013 were eligible for review. Dietary cholesterol was not statistically significantly associated with any coronary artery disease (4 cohorts; no summary RR), ischemic stroke (4 cohorts; summary RR: 1.13; 95% CI: 0.99, 1.28), or hemorrhagic stroke (3 cohorts; summary RR: 1.09; 95% CI: 0.79, 1.50). Dietary cholesterol statistically significantly increased both serum total cholesterol (17 trials; net change: 11.2 mg/dL; 95% CI: 6.4, 15.9) and low-density lipoprotein (LDL) cholesterol (14 trials; net change: 6.7 mg/dL; 95% CI: 1.7, 11.7 mg/dL). Increases in LDL cholesterol were no longer statistically significant when intervention doses exceeded 900 mg/d. Dietary cholesterol also statistically significantly increased serum high-density lipoprotein cholesterol (13 trials; net change: 3.2 mg/dL; 95% CI: 0.9, 9.7 mg/dL) and the LDL to high-density lipoprotein ratio (5 trials; net change: 0.2; 95% CI: 0.0, 0.3). Dietary cholesterol did not statistically significantly change serum triglycerides or very-low-density lipoprotein concentrations.
Reviewed studies were heterogeneous and lacked the methodologic rigor to draw any conclusions regarding the effects of dietary cholesterol on CVD risk. Carefully adjusted and well-conducted cohort studies would be useful to identify the relative effects of dietary cholesterol on CVD risk.
Elevated low-density lipoprotein (LDL) cholesterol is a major risk factor for cardiovascular disease. Dietary guidance recommends reducing saturated fatty acid, trans fatty acid, and cholesterol ...intakes to reduce circulating LDL cholesterol. Cholesterol intake may also affect high-density lipoprotein (HDL)–cholesterol concentrations, but its impact has not been fully quantified.
The aims of this study were to investigate the dose-response relation between changes in dietary cholesterol intake and changes in lipoprotein-cholesterol markers for cardiovascular disease risk and to provide a reference for clinicians on how changes in dietary cholesterol intake affect circulating cholesterol concentrations, after accounting for intakes of fatty acids.
We used a Bayesian approach to meta-regression analysis, which uses Markov chain Monte Carlo techniques, to assess the relation between the change in dietary cholesterol (adjusted for dietary fatty acids) and changes in LDL and HDL cholesterol based on the use of data from randomized dietary intervention trials.
Fifty-five studies (2652 subjects) were included in the analysis. The nonlinear Michaelis-Menten (MM) and Hill models best described the data across the full spectrum of dietary cholesterol changes studied (0–1500 mg/d). Mean predicted changes in LDL cholesterol for an increase of 100 mg dietary cholesterol/d were 1.90, 4.46, and 4.58 mg/dL for the linear, nonlinear MM, and Hill models, respectively.
The change in dietary cholesterol was positively associated with the change in LDL-cholesterol concentration. The linear and MM models indicate that the change in dietary cholesterol is modestly inversely related to the change in circulating HDL-cholesterol concentrations in men but is positively related in women. The clinical implications of HDL-cholesterol changes associated with dietary cholesterol remain uncertain.
Cholesterol plays a vital role in cell biology. Dietary cholesterol or "exogenous" cholesterol accounts for approximately one-third of the pooled body cholesterol, and the remaining 70% is ...synthesized in the body (endogenous cholesterol). Increased dietary cholesterol intake may result in increased serum cholesterol in some individuals, while other subjects may not respond to dietary cholesterol. However, diet-increased serum cholesterol levels do not increase the low-density lipoprotein/high-density lipoprotein (LDL/HDL) cholesterol ratio, nor do they decrease the size of LDL particles or HDL cholesterol levels. Elevated levels of LDL cholesterol, reduced HDL cholesterol levels, and small, dense LDL particles are independent risk factors for coronary artery disease. Dietary cholesterol is the primary approach for treatment of conditions such as the Smith-Lemli-Opitz syndrome. Recent studies have highlighted mechanisms for absorption of dietary cholesterol. These studies have help understand how dietary and/or pharmaceutical agents inhibit cholesterol absorption and thereby reduce LDL cholesterol concentrations. In this article, various aspects of cholesterol metabolism, including dietary sources, absorption, and abnormalities in cholesterol metabolism, have been summarized and discussed.
Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition ...of de novo cholesterol synthesis has not been clearly established. Using three different statins, we investigated the effects on cholesterol metabolism in mice in detail. Surprisingly, direct measurement of whole body cholesterol synthesis revealed that cholesterol synthesis was robustly increased in statin-treated mice. Measurement of organ-specific cholesterol synthesis demonstrated that the liver is predominantly responsible for the increase in cholesterol synthesis. Excess synthesized cholesterol did not accumulate in the plasma, as plasma cholesterol decreased. However, statin treatment led to an increase in cholesterol removal via the feces. Interestingly, enhanced cholesterol excretion in response to rosuvastatin and lovastatin treatment was mainly mediated via biliary cholesterol secretion, whereas atorvastatin mainly stimulated cholesterol removal via the transintestinal cholesterol excretion pathway. Moreover, we show that plasma cholesterol precursor levels do not reflect cholesterol synthesis rates during statin treatment in mice. In conclusion, cholesterol synthesis is paradoxically increased upon statin treatment in mice. However, statins potently stimulate the excretion of cholesterol from the body, which sheds new light on possible mechanisms underlying the cholesterol-lowering effects of statins.
Cholesterol homeostasis is vital for proper cellular and systemic functions. Disturbed cholesterol balance underlies not only cardiovascular disease but also an increasing number of other diseases ...such as neurodegenerative diseases and cancers. The cellular cholesterol level reflects the dynamic balance between biosynthesis, uptake, export and esterification - a process in which cholesterol is converted to neutral cholesteryl esters either for storage in lipid droplets or for secretion as constituents of lipoproteins. In this Review, we discuss the latest advances regarding how each of the four parts of cholesterol metabolism is executed and regulated. The key factors governing these pathways and the major mechanisms by which they respond to varying sterol levels are described. Finally, we discuss how these pathways function in a concerted manner to maintain cholesterol homeostasis.
A new series of low molecular weight gelators, namely compounds 1-4, have been synthesized and investigated the gelation ability in various organic solvents for the purpose of probing the rational ...design criteria in creating optimized steroid-based A(LS).sub.3-type gelators. To generate compounds 1-4, we designed identical cholesterol moieties and amide bonds, and fine-tuned the structures of functionalized linkers or aromatic units. The gelation ability indicated that compounds 1 and 4 were poor gelators, and compound 2 was an efficient gelator for some aromatic solvents, while compound 3 was a highly efficient gelator. To facilitate understanding the reason of this phenomenon, a close investigation of the supramolecular structures in the xerogels of compounds 1-4 was carried out using TEM and AFM characterizations. The investigation showed that a slight change in the molecular structure of gelator could greatly affect the gelation ability as well as the morphology of the supramolecular self-assembly. Especially, it was highlighted that an appropriate aromatic unit as a backbone of gelator and a flexible linker were welcomed in order to obtain an effective A(LS).sub.3 type gelator. The formation mechanism of organogels has also been proposed. Moreover, we explained from a molecular level why the gelling ability as well as thermal stability of organogels formed by compound 3 or 2 was better than that formed by compound 1 or 4. The results described herein possibly provide the rational design criteria in creating optimized steroid-based A(LS).sub.3-type gelators toward functional gels with unusual properties.
The joint consensus panel of the
(EAS) and the
(EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol (TC), triglycerides ...(TG), high-density lipoprotein cholesterol (HDLC), LDL cholesterol (LDLC), and calculated non-HDLC (=total – HDLC) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDLC is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDLC shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a) Lp(a)-cholesterol is part of measured or calculated LDLC and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDLC declines poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDLC or apolipoprotein B (apoB), especially in patients with mild-to-moderate hypertriglyceridemia (2–10 mmol/L). Non-HDLC includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apoB measurement can detect elevated LDL particle (LDLP) numbers often unidentified on the basis of LDLC alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20–100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds.
Scope
Dietary cholesterol has been shown to play a role in the development of Alzheimer's disease (AD). It is proposed that oxysterol especially 27‐hydroxycholesterol (27‐OHC) may play a potential ...role in β‐amyloid peptides (Aβ) production and accumulation during AD progression.
Methods and results
To investigate the mechanisms of dietary cholesterol and 27‐OHC on learning and memory impairment, male Sprague‐Dawley rats are fed with cholesterol diet with or without 27‐OHC synthetase inhibitor (anastrozole) injection. The levels of cholesterol, 27‐OHC, 24‐hydroxycholesterol (24S‐OHC), 7α‐hydroxycholesterol, and 7β‐hydroxycholesterol in plasma are determined; apolipoprotein A (ApoA), apolipoprotein B (ApoB), HDL‐cholesterol (HDL‐C), and LDL‐cholesterol (LDL‐C) in plasma or brain; CYP27A1 and CYP7A1 in liver and CYP46A1 and CYP7B1 in brain; cathepsin B, cathepsin D, and acid phosphatase in lysosome; and Aβ1‐40 and Aβ1‐42 in brain. Results show increased levels of 27‐OHC (p < 0.01), LDL‐C (p < 0.01), and ApoB (p < 0.01), and decreased level of HDL‐C (p < 0.05) in plasma, upregulated CYP27A1 (p < 0.01) and CYP7A1 (p < 0.01) expression in liver, altered lysosomal function, and increased level of Aβ in brain (p < 0.05).
Conclusions
This study indicates that the mechanisms of dietary cholesterol on learning and memory impairment may be involved in cholesterol metabolism and lysosome function with the increase of plasma 27‐OHC, thus resulting in Aβ formation and accumulation.
Increased levels of 27‐hydroxycholesterol induced by dietary cholesterol in brain impairs the learning and memory of rats via disrupting cholesterol metabolism and lysosome dysfunction, resulting in Aβ formation and accumulation.