Association between ApoE status, circulating vitamin A and vitamin E levels with dyslipidemia in aging Chinese adults

Xiaojun Ma, Yujie Guo, Pengfei Li, Jingjing Xu, Yanyan Gao, Xiuwen Ren, Nicholas Van Halm-Lutterodt, Linhong Yuan

Arch Med Res . 2021 May 3;S0188-4409(21)00113-2. doi: 10.1016/j.arcmed.2021.04.007. Online ahead of print.

Abstract

Background: The influence of ApoE or lipid-soluble vitamins on lipid profile has been well documented. However, the association between ApoE status, vitamin A (VA) and vitamin E (VE) with dyslipidemia has been seldom reported. The aim of the present study was to investigate the impact of ApoE status on circulating VA and VE in aging adults with dyslipidemia.

Methods: A total of 1754 Chinese aged 55-75 was recruited from community health centers. They were interviewed to obtain demographic information. Food frequency questionnaire (FFQ) was used to investigate daily food intakes of the participants. Fasting venous blood samples were taken and used for serum lipid profile measurement and ApoE genotyping. Serum VA and VE concentrations were determined by using high-performance liquid chromatography (HPLC).

Results: Serum VE and VA concentrations were circulating lipids and ApoE status dependent. Dyslipidemia subjects showed higher serum TC, TG, HDL-c/LDL-c ratio, VE and lipid-adjusted VE levels than normal subjects. ApoE genotype-dependent differences in serum lipid profile, VE and VA levels were observed in both normal and dyslipidemia subjects. The relationship between circulating VA with dyslipidemia is modifiable by lipid status.

Conclusion: Higher serum VE and lipid adjusted VE levels associated with increased risk of dyslipidemia in aging Chinese adults, especially in ApoE4 carriers. Large scale longitudinal study is required to determine the optimal circulating VE levels in the elderly based on different lipid profiles and ApoE status.

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Effect of Statin Therapy on the Plasma Concentrations of Retinol, Alpha-Tocopherol and Coenzyme Q10 in Children with Familial Hypercholesterolemia

Radosław Motkowski, Mateusz Maciejczyk, Marta Hryniewicka, Joanna Karpińska, Bożena Mikołuć

Cardiovasc Drugs Ther . 2020 Oct 14. doi: 10.1007/s10557-020-07091-w. Online ahead of print.

Abstract

Purpose: Familial hypercholesterolemia (FH) requires early treatment. However, statins, which are regarded the first-line therapy, have an influence on redox balance. Antioxidant vitamins are important for many metabolic processes in the developing body. There are few data available on the long-term safety of statin use in children. The aim of this study was to evaluate the influence of statin treatment in children with FH on plasma concentrations of antioxidant vitamins: retinol, alpha-tocopherol and coenzyme Q10.

Methods: The first study group consisted of 13 children aged 10-18 years treated with simvastatin for at least 6 months, and the second group comprised 13 age- and sex-matched children with hypercholesterolemia, in whom pharmacological treatment had not been applied yet. Analyses were performed using a high-performance liquid chromatograph coupled with a MS detector.

Results: The analysis did not reveal significant differences in the concentration of retinol, alpha-tocopherol or coenzyme Q10 between the studied groups. The adjustment of the concentrations of the vitamins to the cholesterol level also indicated no significant differences. We found no deficits in antioxidant vitamins in patients treated with statins, or any risk of adverse effects associated with an increase in their concentration.

Conclusion: There is no rationale for additional supplementation using antioxidant vitamins or modification of low-fat and low-cholesterol diet in pediatric patients treated with statins.

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The effects of tocotrienol supplementation on lipid profile: A meta-analysis of randomized controlled trials

Shuping Zuo, Guiping Wang, QuanLe Han, Hongling Xiao, Heitor O Santos, David Avelar Rodriguez, Vahid Khani, Jianlei Tang

Complement Ther Med . 2020 Aug;52:102450. doi: 10.1016/j.ctim.2020.102450. Epub 2020 May 25.

Abstract

Background & objective: Tocotrienol supplementation has been emerged as a potent candidate for the treatment of dyslipidemia. In the present study, a systematic review and meta-analysis of randomized controlled trials was performed with the aim of examining the effects of tocotrienol supplementation on the lipid profile.

Methods: Four databases (Scopus, PubMed/Medline, Web of Science and Embase) were used to accomplish the literature search up to November 2019. Clinical trials encompassing the impact of tocotrienol supplementation on lipid profile were extracted regardless of clinical condition, with studies included involving only adults patients.

Results: A total of 15 articles with 20 arms were eligible and included in the meta-analysis to estimate the pooled effect size. Overall results showed a significant effect of tocotrienol supplementation on increasing high-density lipoprotein cholesterol (HDL-C) levels (weight mean difference (WMD): 0.146 mmol/L, I2 = 85.9%) and a non-significant influence on total cholesterol (TC) (WMD: 0.010 mmol/L, I2 = 64.5%), low-density lipoprotein cholesterol (LDL-C) (WMD: 0.095 mmol/L, I2 = 87.4%), and triglycerides (TG) (WMD: -0.112 mmol/L, I2 = 67.4%) levels. Increment in HDL-C levels was significant greater for the tocotrienol dosage ≥ 200 mg/d (WMD: 0.202 mmol/L) and ≤8 weeks (WMD: 0.278 mmol/L). Moreover, studies that investigated tocotrienol dose ≥200 mg had no heterogeneity, while showing a significant decrease in TG levels (WMD: -0.177 mmol/L).

Conclusion: The present meta-analysis demonstrated that supplementing with tocotrienols does not decrease the concentrations of LDL-C, TC and TG. However, tocotrienol supplementation was considered a candidate for increasing HDL-C levels.

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Effect of High Fructose-Induced Metabolic Syndrome on Tissue Vitamin E and Lipid Peroxide Levels in Rats

Akira Kitagawa, Yoshiji Ohta, Koji Ohashi, Koji Yashiro, Kenji Fukuzawa

J Nutr Sci Vitaminol (Tokyo) . 2020;66(2):200-206. doi: 10.3177/jnsv.66.200.

Abstract

In the present study, we examined the effect of high fructose-induced metabolic syndrome (MetS) on tissue vitamin E and lipid peroxide (LPO) levels in rats. Feeding of a diet containing 60% fructose (HFD) to Wistar rats for 2, 4, and 6 wk caused week-dependent increases in HOMA-IR score and serum insulin, triglyceride, total cholesterol, and free fatty acid concentrations. Each week HFD feeding increased serum vitamin E concentration. Six-week HFD feeding reduced vitamin E status (the serum ratio of vitamin E/triglyceride+total cholesterol). Four- and 6-wk HFD feeding increased serum LPO concentration. Two-week HFD feeding increased liver, heart, kidney, and skeletal muscle (SM) vitamin E contents and decreased white adipose tissue (WAT) vitamin E content. Four- and 6-wk HFD feeding further reduced WAT vitamin E content without affecting the increased kidney and SM vitamin E contents. Six-week HFD feeding reduced the increased liver and heart vitamin E contents below the level of non-HFD feeding. Four-week HFD feeding increased heart and WAT LPO contents. Six-week HFD feeding increased liver LPO content and further increased heart and WAT LPO contents. Kidney and SM LPO contents remained unchanged. These results indicate that HFD-rats with early MetS have increased liver, kidney, heart, and SM vitamin E contents and decreased WAT vitamin E content under unchanged tissue LPO content and vitamin E status, while HFD-fed rats with progressed MetS have both decreased liver, heart, and WAT vitamin E contents under increased tissue LPO content and disrupted vitamin E status.

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High-throughput Profiling Reveals Perturbation of Endoplasmic Reticulum Stress-Related Genes in Atherosclerosis Induced by High-Cholesterol Diet and the Protective Role of Vitamin E

Perinur Bozaykut, Ruchan Ekren, Osman Ugur Sezerman, Vadim N Gladyshev, Nesrin Kartal Ozer

Biofactors . 2020 May 8. doi: 10.1002/biof.1635.

Abstract

Formation of atherosclerotic plaques, called atherogenesis, is a complex process affected by genetic and environmental factors. It was proposed that endoplasmic reticulum (ER) stress is an important factor in the pathogenesis of atherosclerosis and that vitamin E affects atherosclerotic plaque formation via its antioxidant properties. Here, we investigated ER stress-related molecular mechanisms in high-cholesterol diet (HCD, 2%)-induced atherosclerosis model and the role of vitamin E supplementation in it, beyond its antioxidant properties. The consequences of HCD and vitamin E supplementation were examined by determining protein levels of ER stress markers in aortic tissues. As vitamin E supplementation acts on several unfolded protein response (UPR) factors, it decreased ER stress induced by HCD. To elucidate the associated pathways, gene expression profiling was performed, revealing differentially expressed genes enriched in ER stress-related pathways such as the proteasome and the apoptosis pathways. We further assessed the proteasomal activity impaired by HCD in the aorta and showed that vitamin E reversed it to that of control animals. Overall, the study characterized the effects of HCD and vitamin E on ER stress-related gene expression, revealing the role of proteolytic systems during atherogenesis.

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Effect of Omega-3 and vitamin E co-supplementation on serum lipids concentrations in overweight patients with metabolic disorders: A systematic review and meta-analysis of randomized controlled trials

Asbaghi O, Choghakhori R, Abbasnezhad A

Diabetes Metab Syndr. 2019 Jul - Aug;13(4):2525-2531. doi: 10.1016/j.dsx.2019.07.001. Epub 2019 Jul 9.

Abstract

BACKGROUND:

Results of the studies assessed the effect of omega-3 and vitamin E co-supplementation on lipid profile in patients with metabolic syndrome (MS) are contradictory. Therefore, we carried out a systematic review and meta-analysis of randomized controlled trials (RCTs), to assess the effect of omega-3 and vitamin E co-supplementation on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in patients with MS.

METHODS:

A systematic search was performed to find the related articles, up to April, 2019. There was no language and time limitation. Meta-analyses were carried out using both the random and fixed effects model where appropriate, and I2 index was used to evaluate the heterogeneity.

RESULTS:

Search yielded 1236 publications. Five RCTs with 254 patients were eligible. Results of the meta-analysis indicated that omega-3 and vitamin E co-supplementation significantly reduced the serum concentrations of TG and LDL, whereas, it had no significant effect on the serum levels of TC and HDL in overweight patients with MS.

CONCLUSION:

Present systematic review and meta-analysis revealed that omega-3 and vitamin E co-supplementation have beneficial effects on lipid profile of overweight patients with MS. It significantly reduced the serum levels of TG and LDL in such patients.

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Serum vitamin E as a significant prognostic factor in patients with dyslipidemia disorders

Barzegar-Amini M, Ghazizadeh H, Seyedi SMR, Sadeghnia HR, Mohammadi A, Hassanzade-Daloee M, Barati E, Kharazmi-Khorassani S, Kharazmi-Khorassani J, Mohammadi-Bajgiran M, Tavallaie S, Ferns GA, Mouhebati M, Ebrahimi M, Tayefi M, Ghayour-Mobarhan M

Diabetes Metab Syndr. 2019 Jan - Feb;13(1):666-671. doi: 10.1016/j.dsx.2018.11.034. Epub 2018 Nov 13.

Abstract

OBJECTIVES:

Obesity and overweight are among the main causes of cardiovascular disease (CVD) mortality. Dyslipidemia, fatty liver index, is strongly related to CVD. Vitamin E as an antioxidant protects the hepatic cells against oxidative stress and prevents fatty liver disease. The aim of the current study is to evaluate the relationship between anthropometric parameters and fasted lipid profile with serum vitamin Elevels.

STUDY DESIGN:

A randomized trial was designed based on data from the Mashhad stroke and heart atherosclerotic disorders (MASHAD: 2010-2020).

METHODS:

363 CVD subjects (173 males and 190 females) was selected at random, among 9704 subjects in three regions of Mashhad, northeast of Iran to investigate the specific correlations among their serum vitamin E, lipid profile (TG, HDL-C, LDL-C and TC), and anthropometric features (height, weight, BMI, hip and waist circumferences.

RESULT:

The results indicated the significant relationships between vitamin E, and fasting serum lipid profile in subjects. Serum vitamin Ewas negatively correlated to TC, TG, and LDL-C and positively related to HDL-C. Also, statistically negative correlations were found between vitamin E and anthropometric parameters (weight, waist and hip circumference, middle Arm, and Systolic Blood Pressure). Moreover, vitamin E ratios such as vitamin E/(TC + TG) and vitamin E/TC values as standardized vitamin E, had significant negative correlation with BMI, the whole of anthropometric parameters, and dyslipidemia risk factors including TC, TG and LDL-C.

CONCLUSION:

We found that vitamin E profile was significantly lower in the dyslipidemia subjects. It is generally suggested that vitamin E monitoring might be used as a useful prognostic and therapeutic agent in dyslipidemia disorder.

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The Effects of Vitamin E from Elaeis guineensis (Oil Palm) in a Rat Model of Bone Loss Due to Metabolic Syndrome

Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S

Int J Environ Res Public Health. 2018 Aug 24;15(9). pii: E1828. doi: 10.3390/ijerph15091828.

Abstract

The beneficial effects of vitamin E in improving components of MetS or bone loss have been established. This study aimed to investigate the potential of palm vitamin E (PVE) as a single agent, targeting MetS and bone loss concurrently, using a MetS animal model. Twelve-week-old male Wistar rats were divided into five groups. The baseline group was sacrificed upon arrival. The normal group was given standard rat chow. The remaining three groups were fed with high-carbohydrate high-fat (HCHF) diet and treated with tocopherol-stripped corn oil (vehicle), 60 mg/kg or 100 mg/kg PVE. At the end of the study, the rats were evaluated for MetS parameters and bone density. After euthanasia, blood and femurs were harvested for the evaluation of lipid profile, bone histomorphometric analysis, and remodeling markers. PVE improved blood pressure, glycemic status, and lipid profile; increased osteoblast surface, osteoid surface, bone volume, and trabecular thickness, as well as decreased eroded surface and single-labeled surface. Administration of PVE also significantly reduced leptin level in the HCHF rats. PVE is a potential agent in concurrently preventing MetS and protecting bone loss. This may be, in part, achieved by reducing the leptin level and modulating the bone remodeling activity in male rats.

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Exploring the potential of tocotrienol from Bixa orellana as a single agent targeting metabolic syndrome and bone loss

Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S

Bone. 2018 Jul 7. pii: S8756-3282(18)30260-6. doi: 10.1016/j.bone.2018.07.003. [Epub ahead of print]

Abstract

Metabolic syndrome (MetS) is associated with osteoporosis due to the underlying inflammatory and hormonal changes. Annatto tocotrienolhas been shown to improve medical complications associated with MetS or bone loss in animal studies. This study aimed to investigate the effects of annatto tocotrienol as a single treatment for MetS and osteoporosis in high-carbohydrate high-fat (HCHF) diet-induced MetS animals. Three-month-old male Wistar rats were randomly divided into five groups. The baseline group was euthanized at the onset of the study. The normal group received standard rat chow and tap water. The remaining groups received HCHF diet and treated with three different regimens orally daily: (a) tocopherol-stripped corn oil (the vehicle of tocotrienol), (b) 60 mg/kg annatto tocotrienol, and (c) 100 mg/kg annatto tocotrienol. At the end of the study, measurements of MetS parameters, body compositions, and bone mineral density were performed in animals before sacrifice. Upon euthanasia, blood and femur of the rats were harvested for the evaluations of bone microstructure, biomechanical strength, remodelling activities, hormonal changes, and inflammatory response. Treatment with annatto tocotrienol improved all MetS parameters (except abdominal obesity), trabecular bone microstructure, bone strength, increased osteoclast number, normalized hormonal changes and inflammatory response in the HCHF animals. In conclusion, annatto tocotrienol is a potential agent for managing MetS and osteoporosis concurrently. The beneficial effects of annatto tocotrienol may be attributed to its ability to prevent the hormonal changes and pro-inflammatory state in animals with MetS.

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Identifying Potential Therapeutics for Osteoporosis by Exploiting the Relationship between Mevalonate Pathway and Bone Metabolism

Wan Hasan WN, Chin KY, Jolly JJ, Abd Ghafar N, Soelaiman IN.

Endocr Metab Immune Disord Drug Targets. 2018 Apr 23. doi: 10.2174/1871530318666180423122409. [Epub ahead of print]

Abstract

BACKGROUND:

Osteoporosis is a silent skeletal disease characterized by low bone mass and destruction of skeletal microarchitecture, leading to an increased fracture risk. This occurs due to an imbalance in bone remodelling, whereby the rate of bone resorption is greater than bone formation. Mevalonate pathway, previously known to involve in cholesterol synthesis, is an important regulatory pathway for bone remodelling.

OBJECTIVE:

This review aimed to provide an overview of the relationship between mevalonate pathway and bone metabolism, as well as agents which act through this pathway to achieve their therapeutic potential.

DISCUSSION:

Mevalonate pathway produces farnesyl pyrophosphate and geranylgeranyl pyrophosphate essential in protein prenylation. An increase in protein prenylation favours bone resorption over bone formation. Non-nitrogen containing bisphosphonates inhibit farnesyl diphosphate synthase which produces farnesyl pyrophosphate. They are used as the first line therapy for osteoporosis. Statins, a well-known class of cholesterol-lowering agents, inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in the mevalonate pathway. It was shown to increase bone mineral density and prevent fracture in humans. Tocotrienol is a group of vitamin E commonly found in palm oil, rice bran and annatto bean. It causes degradation of HMG-CoA reductase. Many studies demonstrated that tocotrienol prevented bone loss in animal studies but its efficacy has not been tested in humans.

CONCLUSION:

mevalonate pathway can be exploited to develop effective antiosteoporosis agents.

KEYWORDS:

bone; bone metabolism; mevalonate pathway; tocotrienol; vitamin E.

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