Associations of Dietary Cholesterol, Serum Cholesterol, and Egg Consumption With Overall and Cause-Specific Mortality: Systematic Review and Updated Meta-Analysis.

BACKGROUND: Despite substantial research highlighting the importance of exogenous dietary cholesterol intake and endogenous serum cholesterol level in human health, a thorough evaluation of the associations is lacking. Our study objective was to examine overall and cause-specific mortality in relation to dietary and serum cholesterol, as well as egg consumption, and conduct an updated meta-regression analysis of cohort studies. METHODS: We conducted a prospective analysis of 27 078 men in the ATBC Study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention). Multivariable-controlled cause-specific Cox proportional hazards regression models were used to calculate hazard ratios and 31-year absolute mortality risk differences. A systematic review and meta-analysis of cohort studies was also performed (PROSPERO [URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021272756]). RESULTS: Based on 482 316 person-years of follow-up, we identified 22 035 deaths, including 9110 deaths from cardiovascular disease (CVD). Greater dietary cholesterol and egg consumption were associated with increased risk of overall and CVD-related mortality. Hazard ratios for each additional 300 mg cholesterol intake per day were 1.10 and 1.13 for overall and CVD-related mortality, respectively; for each additional 50-g egg consumed daily, hazard ratios were 1.06 and 1.09, respectively, for overall and CVD-related mortality (all P values<0.0001). After multivariable adjustment, higher serum total cholesterol concentrations were associated with increased risk of CVD-related mortality (hazard ratios per 1 SD increment, 1.14; P<0.0001). The observed associations were generally similar across cohort subgroups. The updated meta-analysis of cohort studies on the basis of 49 risk estimates, 3 601 401 participants, and 255 479 events showed consumption of 1 additional 50-g egg daily was associated with significantly increased CVD risk (pooled relative risk, 1.04 [95% CI, 1.00-1.08]; I2=80.1%). In the subgroup analysis of geographic regions (Pinteraction=0.02), an increase of 50-g egg consumed daily was associated with a higher risk of CVD in US cohorts (pooled relative risk, 1.08 [95% CI, 1.02-1.14]) and appeared related to a higher CVD risk in European cohorts with borderline significance (pooled relative risk, 1.05), but was not associated with CVD risk in Asian cohorts. CONCLUSIONS: In this prospective cohort study and updated meta-analysis, greater dietary cholesterol and egg consumption were associated with increased risk of overall and CVD-related mortality. Our findings support restricted consumption of dietary cholesterol as a means to improve long-term health and longevity.

Disrupted cholesterol metabolism promotes age-related photoreceptor neurodegeneration.

Photoreceptors have high intrinsic metabolic demand and are exquisitely sensitive to metabolic perturbation. In addition, they shed a large portion of their outer segment lipid membranes in a circadian manner, increasing the metabolic burden on the outer retina associated with the resynthesis of cell membranes and disposal of the cellular cargo. Here, we demonstrate that deletion of both ABCA1 and ABCG1 in rod photoreceptors leads to age-related accumulation of cholesterol metabolites in the outer retina, photoreceptor dysfunction, degeneration of rod outer segments, and ultimately blindness. A high-fat diet significantly accelerates rod neurodegeneration and vision loss, further highlighting the role of lipid homeostasis in regulating photoreceptor neurodegeneration and vision.

Alexander I. Ignatowski: a pioneer in the study of atherosclerosis.

In 1908, Alexander I. Ignatowski (1875-1955) published his pioneering work that first revealed a relationship between cholesterol-rich food and experimental atherosclerosis. This early experimental work paved a way to the metabolic study of the mechanism of atherosclerosis. Herein, we present a brief account of Ignatowski's work and life.

A rat carotid atherosclerosis modal induced by artery clamping with high-cholesterol diet and vitamin D3 / 国际脑血管病杂志

Objective To investigate the feasibility of a rat carotid atherosclerosis model induced by artery clamping with high-cholesterol diet and vitamin D3.Methods Twenty Wista rats were randomly divided into either a general diet group (n =5) or a high cholesterol diet group (n =15).After clamping the right common carotid arteries of the rats in the high cholesterol diet group,they were fed with high fat diet,and vitamin D3 (600 000 IU/kg) was injected intraperitoneally.The lipid levels of the general diet group and the high cholesterol diet group were detected at 6 and 12 weeks respectively.The bilateral cormmon carotid arteries were selected for preparing paraffin sections and were stained with HE staining.The pathological changes in blood vessels were observed.Results The levels of serum total cholesterol at 12 weeks (2.803 ± 1.307 mmol/L vs.1.513 ±0.281 mmol/L; P=0.017) and low-density lipoprotein cholesterol (0.660± 0.260 mmol/L vs.0.311 ±0.078 mmol/L; P =0.003) in the high-cholesterol diet group were significantly higher than those at 6 weeks.The histopathological examination showed that the common carotid artery intimas on the clamping sides were incomplete,the foam cell deposition was observed under intima,the atherosclerotic plaques or fibrous plaques were observed on the surface of cavity,inside the plaques contained necrotic tissue,and thrombosis was observed in the cavity.The common carotid artery intima-media thickness in the general diet group (n =5) at 12 weeks was 8.3 ± 1.1 μm.The sham-operated sides (n =20) and clamping sides (n =20) were 8.8 ± 0.7 μm and 97.4 ±25.7 μm,respectively.There were significant differences among the three groups (F =116.313,P=0.000).The clamping sides in the high-cholesterol diet group were significantly higher than the shamoperated sides in the high-cholesterol diet group (P=0.000) and the general diet group (P =0.000).Conclusions Common carotid artery clamping with high-cholesterol diet and vitamin D3 is a simple and feasible method for inducing a rat carotid atherosclerosis model.

Changes of caveolin-1 in the livers of mice with nonalcoholic fatty liver disease caused by high-fat diet / 中华消化杂志

Objective To explore the role of caveolin-1 in nonalcoholic fatty liver disease (NAFLD) caused by high-fat diet.Methods A total of 12 ten-week-old male C57BL/6 mice were fed with high-fat and high-cholesterol diet for 14 weeks to establish the NAFLD animal model.And six syngeneic mice fed with normal diet at the same time were taken as control.All the mice were sacrificed by the end of 14th week,body weight,liver weight and the changes of serum lipids of the two groups were compared.The changes of caveolin-1 at mRNA and protein levels in the liver of mice with NAFLD were detected by quantitative polymerase chain reaction (qPCR) and Western blot.The liver steatosis of the mice was observed under light microscopy after stained by hematoxylin and eosin.The changes of distribution of caveolin-1 in liver were examined by immunohistochemistry.The differences of caveolin-1 at mRNA and protein level in livers between the two groups were compared by t test.The differences of immunohistochemical scores of caveolin-1 expression in the livers of mice with different degree of fatty liver were analyzed by ordinal variables of two independent samples ranksum test analysis.Results After 14 weeks high-fat and high-cholesterol diet,all the mice of experiment group developed NAFLD.Nine of which were severe and three were moderate.Compared with the control group,serum total cholesterol,high density lipoprotein cholesterol and low density lipoprotein cholesterol of experiment group significantly increased ((1.940 ± 0.300) mmol/L vs (3.771±0.800) mmol/L,(1.120±0.066) mmol/L vs (2.224±0.420) mmol/L,(0.510±0.191) mmol/L vs (1.241±0.660) mmol/L,t=-3.760,-5.474,-3.332,all P＜0.01),however there was no significant difference in triglyceride (P＞0.05).The caveolin-1 of experiment group significantly increased at mRNA (1.536 ±0.226 vs 0.980± 0.272,t=3.371,P＜0.05) and protein levels (0.643±0.240 vs 0.100±0.130,t=4.847,P＜0.01).The immunohistochemical results indicated that the increased caveolin-1 expression mainly distributed in the membrane of hepatocytes,cytoplasm and membrane of lipid droplets.Conclusion The up-regulated caveolin-1 expression in the livers of NAFLD mice induced by high-fat and high-cholesterol may be involved in the mechanism of NAFLD.

Influência da dieta hipercolesterolêmica na remodelação do colágeno da matriz extracelular da parede vesical em ratos / Influence of the hypercholesterolemic diet on the collagen remodeling of the bladder wall extracellular matrix in rats

Introdução: A bexiga é responsável em armazenar urina em volume adequado e de esvaziar seu conteúdo de forma plena. Suas propriedades miogênicas intrínsecas e viscoelásticas são as responsáveis por esta função. Disfunções vesicais podem ser decorrentes, dentre outras causas, de anormalidades intrínsecas da musculatura detrusora ou da composição de sua matriz extracelular (MEC). O colágeno corresponde a 50% do estroma vesical, possuindo importante papel na adaptação vesical a condições fisiopatológicas específicas. Os colágenos tipo I e III são os mais comuns, sendo o colágeno tipo III o primeiro a ser sintetizado em processos de reparação e fibrose. Diversas afecções como a obstrução infravesical (OIV) parcial crônica podem induzir estes processos através da remodelação da MEC e conseqüentemente alterar a função vesical. Acredita-se que a hipercolesterolemia também o faça, porém ainda não foi reproduzida tal associação a nível morfológico. O objetivo deste estudo é avaliar se dieta hipercolesterolêmica promove alterações estruturais vesicais em ratos, especialmente no que diz respeito à remodelação colágena. Método: Foram utilizadas 45 ratas da raça Wistar, de quatro semanas de idade, divididas em três grupos: 1) controle com dieta comum padrão para roedores (DN); 2) modelo de OIV com DN e 3) controle com dieta de alto teor lipídico (DATL 1,25% colesterol). Análise sérica do colesterol e fração LDL e medição do peso corporal foram realizadas em todos os animais inicialmente e no final do estudo. Com quatro semanas de estudo, as ratas dos grupos 1 e 3 foram submetidas à cirurgia simulada, enquanto os animais do grupo 2 foram efetivamente submetidos à cirurgia de OIV parcial. Após dissecção da uretra, fez-se uma ligadura parcial com Nylon 5-0, com um lúmen residual de aproximadamente 1 mm. Após seis semanas, todos os animais foram submetidos à remoção de suas bexigas e então sacrificados. Análise morfológica foi realizada através da coloração...

Purpose: Preserved bladder function is defined as the adequate storage and emptying of its urinary content. Compliance is an important factor for these functions and is directly related to the extracellular matrix composition. Its abnormalities can lead to bladder dysfunctions. The collagen represents 50% of bladder stroma, playing an important role in the bladder adaptation to specific pathologic conditions. Types I and III collagens are the most prevalent in bladder wall whereas type III collagen is the first synthesized in reparation and fibrosis processes. Bladder outlet obstruction (BOO) promotes this process and hypercholesterolemia is also believed to create conditions for it, although no morphologic association has already been demonstrated. In this study we aimed to verify if hypercholesterolemic diet promotes structural bladder wall modifications, regarding the collagen remodeling. Methods: Forty-five female heterogenic Wistar 4 weeks-old rats were divided into three groups: 1) control fed on a normal diet (ND); 2) BOO model fed on a ND and 3) control fed on a hypercholesterolemic diet (HCD 1.25% cholesterol). Initially, serum cholesterol, LDL-cholesterol and body weight were measured. Four weeks later groups 1 and 3 underwent a sham operation while group 2 underwent a partial BOO operation. After the urethra was dissected a 5-zero nylon suture was passed and tied loosely around the urethra with a 22G needle besides it. Six weeks later the bladders of all animals were removed, serum cholesterol and LDL-cholesterol analysis was performed, body weight was measured and then they were sacrificed. Morphological analysis was performed by Picrosirius red staining and immunohistochemistry for types I and III collagen. Statistical analysis was done comparing groups by the Oneway-Anova method and Tukey multiple comparisons when needed. Significance was considered when p < 0.05. Results: Wistar rats fed on a HC diet had a significant increase...

[Metabolic effects of Ramadan fasting on type 2 diabetes]

We assessed the effects of Ramadan fasting on metabolic control, particularly change of HDL-cholesterol in 25 type 2 diabetic patients treated with diet or oral agents, with good metabolic control. Clinical and biochemical parameters and food intake were evaluated 3 weeks before Ramadan, in the fourth week of Ramadan and 3 weeks after Ramadan.There were no changes in body weight and blood pressure nor any metabolic complications. The mean plasma fasting glucose, serum fructosamin and haemoglobin A1c did not change. We found a negative relation between cholesterol intake during Ramadan and the change of HDL-cholesterol. When cholesterol intake was lower than 400 mg/day, plasma HDL-cholesterol increased by 13% at the end of Ramadan and by 23% 3 weeks after Ramadan

Effects of high fat/high cholesterol diet on differentially expressed gene of the liver in treble genes mutant mice / 中国病理生理杂志

AIM: To study the effects of dietary factor on liver gene expression profile in apoE~(-/-)/LDLR~(-/-)/Lepr~(db/db) mice and atherogenesis. METHODS: The gene expression profile was determined by using cDNA microarray. Total plasma TC and TG level were measured with COD-PAP and GPO-PAP methods respectively. The morphological characters of the aorta were also observed. RESULTS: Among the 4000 target genes, 78 and 114 genes were up-and down-regulated, respectively, in treble genes mutants fed with high fat high cholesterol diet compared with that of regular chow littermates, including lipid metabolism, carbohydrate, cell skeleton and immune related genes. Atherogenic diet induced severe plasma hyperlipidemia even in the early stage and also accelerated atherogenesis in the treble genes mutant mice. CONCLUSION: The data suggest that atherogenic diet aggravates abnormal plasma lipid metabolism and induces severe hyperlipidemia, and atherogenesis in the treble genes mutant mice as well.

Chronological effects of atherogenic diets on the aorta, liver and spleen of rabbits

To investigate the temporal progression of atherogenesis on the aorta and involvement of the monocyte-macrophage system in the liver and spleen, we fed 74 rabbits with high fat (14 or 7 gm+ACU-) and cholesterol (2 and 1+ACU-) diets for 4 to over 24 weeks. Using both light and electron microscopies, we found that the bro-fatty areas on the luminal surface of aortas was spread over along the eding time dependently. The fat deposits also in the liver and spleen worsened pending on the time of feeding the atherogenic diets. Not only nocyte-derived foam cells, but also parenchymatous cells in the liver and leen involved become fat-laden cells. According to these results, we propose at there are three stages: 1) the primary seeding, 2) the intermediate turing and 3) the advanced periods. These periods may play very important les in designing the management and treatment of atherosclerotic patients.

Chronological effects of atherogenic diets on the aorta, liver and spleen of rabbits

To investigate the temporal progression of atherogenesis on the aorta and involvement of the monocyte-macrophage system in the liver and spleen, we fed 74 rabbits with high fat (14 or 7 gm+ACU-) and cholesterol (2 and 1+ACU-) diets for 4 to over 24 weeks. Using both light and electron microscopies, we found that the bro-fatty areas on the luminal surface of aortas was spread over along the eding time dependently. The fat deposits also in the liver and spleen worsened pending on the time of feeding the atherogenic diets. Not only nocyte-derived foam cells, but also parenchymatous cells in the liver and leen involved become fat-laden cells. According to these results, we propose at there are three stages: 1) the primary seeding, 2) the intermediate turing and 3) the advanced periods. These periods may play very important les in designing the management and treatment of atherosclerotic patients.

THE EFFECT OF RADIX SALVIAE MILTORRHIZAE (RSM) ON LIPOPEROXIDATION OF LDL AND ISCHEMIC BRAIN INJURY IN CHOLESTEROL FED RABBITS / 解放军医学杂志

The blood lipids and lipid peroxide (LPO) were analysed in rabbits fed with 1% cholesterol in feeding ( n =19) and with standard feeding ( n =15) after 5 weeks of feeding.The plasma LDL was isolated and ox LDL was obtained by thin layer chromatography (TLC).Cerebral ischemia was induced by ligation of left common carotid artery.The antioxidation and antiischemia injury property of RSM was also observed with TLC and electron microscopy.The results showed that the plasma LPO,FFA,CH and PL levels in 1% cholesterol fed rabbits were much higher than those of rabbits with standard feeding( P

THE NUTRITIONAL VALUE OF A FLOUR MILLING BYPRODUCT VITAMIN-MINERAL ENRICHED FLOUR ON RATS / 营养学报

The vitamin-mineral enriched flour (VMF) was a byproduct obtained from a new processing technique of flour milling, and rich in vitamin B group, minerals and dietary fibers.The addition of 10 or 20% VMF to the stock diet composed mainly of white flour failed to improve PER and growth rate of young rats. When the rats were fed the tested diet for 6 weeks, in which the VMF served as the only diet source ot riboflavin, blood glutathione reductase activity coefficient was 1.13 and 1.09 respectively. This indicated that the amount of riboflavin supplied by VMF could maintain an adequate level in the body of the rats.Adult rats were fed high cholesterol plus 10, 20 and 30% VMF, the contents of serum cholesterol, liver lipids and liver cholesterol were similar to those of the normal diet group, these contents, however, in control group were increased obviously. The results suggested that VMF could protect the rats from the increment of serum cholesterol, liver lipids and cholesterol.