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Ou Y, Qiu Z, Geng T, Lu Q, Li R, Li L, Zhu K, Chen X, Lin X, Liu S, Pan A, Liu G. Associations of serum vitamin C concentrations with risk of all-cause and cause-specific mortality among individuals with and without type 2 diabetes. Eur J Nutr 2023; 62:2555-2565. [PMID: 37195485 DOI: 10.1007/s00394-023-03173-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 05/04/2023] [Indexed: 05/18/2023]
Abstract
PURPOSE Compared with people without diabetes, people with type 2 diabetes (T2D) are at higher risk of both subnormal vitamin C status and increased oxidative stress. We aimed to investigate the associations of serum vitamin C concentrations with all-cause and cause-specific mortality among adults with and without T2D. METHODS The current analysis included 20,045 adults (2691 people with T2D and 17,354 without T2D) from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2003-2006. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline analyses were used to examine the dose-response relationship. RESULTS After a median follow-up of 17.3 years, 5211 deaths were documented. Individuals with T2D had a lower level of serum vitamin C concentrations compared with those without T2D (the median value: 40.1 vs. 44.9 μmol/L). Furthermore, the dose-response relationship between serum vitamin C and mortality showed different patterns between participants with and without T2D. In individuals without T2D, there was a nonlinear association of serum vitamin C concentrations with all-cause, cancer, and CVD mortality, with the lowest risk around a serum vitamin C concentration of 48.0 μmol/L (all Poverall < 0.05, Pnonlinearity < 0.05). In contrast, among those with T2D in the similar concentration range, higher serum vitamin C levels (ranged from 0.46 to 116.26 μmol/L) were linearly associated with lower all-cause and cancer mortality (both Poverall < 0.05, Pnonlinearity > 0.05). Significant additive interaction was observed between diabetes status and serum vitamin C levels with regard to all-cause and cancer mortality (P < 0.001). In addition, C-reactive protein, gamma-glutamyl transpeptidase, and HbA1c explained 14.08, 8.96, and 5.60% of the association between serum vitamin C and all-cause mortality among individuals with T2D, respectively. CONCLUSIONS Higher serum vitamin C concentrations were significantly associated with lower risk of mortality in participants with T2D in a linear dose-response manner, while a nonlinear association was observed in participants without T2D, with an apparent threshold around 48.0 μmol/L. These findings suggest that the optimal vitamin C requirement may differ in individuals with and without T2D.
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Affiliation(s)
- Yunjing Ou
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zixin Qiu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tingting Geng
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qi Lu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rui Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lin Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kai Zhu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xue Chen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoyu Lin
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Sen Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - An Pan
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Gang Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Violi F, Nocella C, Loffredo L, Carnevale R, Pignatelli P. Interventional study with vitamin E in cardiovascular disease and meta-analysis. Free Radic Biol Med 2022; 178:26-41. [PMID: 34838937 DOI: 10.1016/j.freeradbiomed.2021.11.027] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 09/27/2021] [Accepted: 11/12/2021] [Indexed: 12/15/2022]
Abstract
Cardiovascular disease (CVD) is one of the major causes of morbidity and mortality and atherosclerosis is the common root to most of the CVD. Oxidative stress is one of the most important factors driving atherosclerosis and its complications. Thus, strategies for the prevention and treatment of cardiovascular events had oxidative changes as a potential target. Natural vitamin E consists of a family of eight different compounds, four tocopherols and four tocotrienols. All tocopherols and tocotrienols are potent antioxidants with lipoperoxyl radical-scavenging activities. In addition, α-tocopherol possesses also anti-inflammatory as well as anti-atherothrombotic effects by modulating platelet and clotting system. Experimental and in vitro studies described molecular and cellular signalling pathways regulated by vitamin E antithrombotic and antioxidant properties. While observational studies demonstrated an inverse association between vitamin E serum levels and CVD, interventional trials with vitamin supplements provided negative results. This review focus on the impact of vitamin E in the atherothrombotic process and describes the results of experimental and clinical studies with the caveats related to the interventional trials with vitamin E to prevent CVD.
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Affiliation(s)
- Francesco Violi
- Mediterranea Cardiocentro, Napoli, Italy; Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Italy.
| | - Cristina Nocella
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Italy
| | - Lorenzo Loffredo
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Italy
| | - Roberto Carnevale
- Mediterranea Cardiocentro, Napoli, Italy; Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100, Latina, Italy
| | - Pasquale Pignatelli
- Mediterranea Cardiocentro, Napoli, Italy; Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Italy
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Özil M, Tacal G, Baltaş N, Emirik M. Synthesis and Molecular Docking Studies of Novel Triazole Derivatives as Antioxidant Agents. LETT ORG CHEM 2020. [DOI: 10.2174/1570178616666190828200207] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
A series of 1,2,4-triazole and 1,2,4- thiadiazole derivatives were prepared starting from ethyl
4-(3-methyl-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)benzoate. Firstly, both ethyl ester groups were
simultaneously transformed into hydrazide groups, then into thiosemicarbazide groups using both microwave-
assisted and conventional methods. The latter products were interacted with NaOH and
H2SO4 to form ring assemblies containing two 1,2,4-triazole and 1,3,4-thiadiazole fragments, respectively.
Antioxidant activities of the synthesized compounds were determined with CUPRAC, ABTS,
and DPPH assays. Most of the compounds showed significant antioxidant activity and especially, compound
3 exhibited very good SC50 value for DPPH method and compound 3, 4a, 5a exhibited very high
scavenging activity to the ABTS method. In addition, the in silico analysis was carried out with the
synthesized derivatives to understand the mode of interaction with superoxide dismutase (SOD) and
human tyrosine kinase using docking protocols in order to find out the most active antioxidant drug
having high inhibitory activity in cancer.
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Affiliation(s)
- Musa Özil
- Department of Chemistry, Faculty of Art and Sciences, Recep Tayyip Erdogan University, 53100, Rize, Turkey
| | - Güven Tacal
- Department of Chemistry, Faculty of Art and Sciences, Recep Tayyip Erdogan University, 53100, Rize, Turkey
| | - Nimet Baltaş
- Department of Chemistry, Faculty of Art and Sciences, Recep Tayyip Erdogan University, 53100, Rize, Turkey
| | - Mustafa Emirik
- Department of Chemistry, Faculty of Art and Sciences, Recep Tayyip Erdogan University, 53100, Rize, Turkey
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Coto E, Fernandez N, Garcia JJ, Diez MJ, Sahagun AM, Sierra M. Assessment of the Antioxidant/Hypolipidemic Relationship of Sideritis hyssopifolia in an Experimental Animal Model. Molecules 2019; 24:molecules24112049. [PMID: 31146427 PMCID: PMC6600331 DOI: 10.3390/molecules24112049] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2019] [Revised: 05/27/2019] [Accepted: 05/28/2019] [Indexed: 01/13/2023] Open
Abstract
Many publications have described the potential cardioprotective action of different medicinal plants, relating this effect with blood lipid levels. However, these publications do not justify the right amount of plant administered, which can vary greatly. Sideritis hyssopifolia is a little woody plant endemic to western and southwestern Europe. We have quantified its antioxidant activity, which can be used as an indicator of its cardioprotective action. This study evaluates the antioxidant capacity of Sideritis hyssopifolia to design a feed whose hypolipidemic effects are proven in cholesterol-fed New Zealand rabbits. Antioxidant action was assessed in infusions, which were prepared with 1 or 3 g of plant in 200 mL of water by using an ABTS assay and expressed as Ascorbic acid Equivalent Antioxidant Capacity (AEAC). Aqueous infusions with infusion times of 10 min and prepared with 3 g plant exhibited the strongest antioxidant activity. Sideritis hyssopifolia showed an intermediate antioxidant capacity for the concentrations and times of the infusion tested. According to our results, we suggest incorporating 2.36 g of S. hyssopifolia every 150 g of rabbit feeding stuff (15.73 g/kg). This chow decreased cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides levels in cholesterol-fed rabbits, as well as the atherogenic index. This reduction was similar to that obtained with simvastatin.
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Affiliation(s)
- Esther Coto
- Pharmacology, Institute of Biomedicine (IBIOMED), University of Leon, 24071 Leon, Spain.
| | - Nelida Fernandez
- Pharmacology, Institute of Biomedicine (IBIOMED), University of Leon, 24071 Leon, Spain.
| | - Juan Jose Garcia
- Pharmacology, Institute of Biomedicine (IBIOMED), University of Leon, 24071 Leon, Spain.
| | - M Jose Diez
- Pharmacology, Institute of Biomedicine (IBIOMED), University of Leon, 24071 Leon, Spain.
| | - Ana Maria Sahagun
- Pharmacology, Institute of Biomedicine (IBIOMED), University of Leon, 24071 Leon, Spain.
| | - Matilde Sierra
- Pharmacology, Institute of Biomedicine (IBIOMED), University of Leon, 24071 Leon, Spain.
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Yuan Y, Pan S, Yang SL, Liu YL, Xu QM. Antioxidant and cardioprotective effects of Ilex cornuta on myocardial ischemia injury. Chin J Nat Med 2017; 15:94-104. [PMID: 28284430 DOI: 10.1016/s1875-5364(17)30025-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2016] [Indexed: 12/12/2022]
Abstract
Previous studies have indicated that the Ilex genus exhibits antioxidant, neuroprotective, hepatoprotective, and anti-inflammatory activities. However, the pharmacologic action and mechanisms of Ilex cornuta against cardiac diseases have not yet been explored. The present study was designed to investigate the antioxidant and cardioprotective effects of Ilex cornuta root with in vitro and in vivo models. The anti-oxidative effects of the extract of Ilex cornuta root (ICR) were measured by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging and MTT assays as well as immunoassay. Furthermore, a rat model of myocardial ischemia was established to investigate the cardioprotective effect of ICR in vivo. Eight compounds were isolated and identified from ICR and exhibited DPPH free-radical scavenging activities. They also could increase cell viability and inhibit morphological changes induced by H2O2 or Na2S2O4 in H9c2 cardiomyocytes, followed by increasing the SOD activities and decreasing the MDA and ROS levels. In addition, it could suppress the apoptosis of cardiomyocytes. In the rat model of myocardial ischemia, ICR decreased myocardial infarct size and suppressed the activities of LDH and CK. Furthermore, ICR attenuated histopathological alterations of heart tissues and the MDA levels, while increasing SOD activities in serum. In conclusion, these results suggest that ICR has cardioprotective activity and could be developed as a new food supplement for the prevention of ischemic heart disease.
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Affiliation(s)
- Yan Yuan
- Department of Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China
| | - Shu Pan
- Department of Pharmaceutical Chemistry, Guizhou University, Guiyang 550025, China
| | - Shi-Lin Yang
- Department of Pharmacognosy, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China
| | - Yan-Li Liu
- Department of Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China.
| | - Qiong-Ming Xu
- Department of Pharmacognosy, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China.
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6
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Benzie IFF, Strain JJ. Simultaneous automated measurement of total ‘antioxidant’ (reducing) capacity and ascorbic acid concentration. Redox Rep 2016; 3:233-8. [DOI: 10.1080/13510002.1997.11747115] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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7
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Sheikh ZA, Siddiqui ZA, Naveed S, Usmanghani K. Quantitative Determination of Catechin as Chemical Marker in Pediatric Polyherbal Syrup by HPLC/DAD. J Chromatogr Sci 2016; 54:1324-7. [PMID: 27165575 DOI: 10.1093/chromsci/bmw078] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Indexed: 11/13/2022]
Abstract
Vivabon syrup is a balanced composition of dietary ingredients of phytopharmaceutical nature for maintaining the physique, vigor, vitality and balanced growth of children. The herbal ingredients of pediatric syrup are rich in bioflavonoid, proteins, vitamins, glycosides and trace elements. Vivabon is formulated with herbal drugs such as Phoenix sylvestris, Emblica officinalis, Withania somnifera, Centella asiatica, Amomum subulatum, Zingiber officinalis, Trigonella foenum-graecum, Centaurea behen and Piper longum Catechins are flavan-3-ols that are found widely in the medicinal herbs and are utilized for anti-inflammatory, cardio protective, hepato-protective, neural protection and other biological activities. In general, the dietary intake of flavonoids has been regarded traditionally as beneficial for body growth. Standardization of Vivabon syrup dosage form using HPLC/DAD has been developed for quantitative estimation of Catechin as a chemical marker. The method was validated as per ICH guidelines. Validation studies demonstrated that the developed HPLC method is quite distinct, reproducible as well as quick and fast. The relatively high recovery and low comparable standard deviation confirm the suitability of the developed method for the determination of Catechin in syrup.
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Affiliation(s)
- Zeeshan A Sheikh
- Research and Development Department, Herbion Pakistan (Pvt.) Limited, Plot 30, Sector 28, Korangi industrial Area, Karachi 74900, Pakistan
| | - Zafar A Siddiqui
- Research and Development Department, Herbion Pakistan (Pvt.) Limited, Plot 30, Sector 28, Korangi industrial Area, Karachi 74900, Pakistan
| | - Safila Naveed
- Department of Clinical Pharmacy and Health Care, Faculty of Pharmacy, Jinnah University for Women, Karachi, Pakistan
| | - Khan Usmanghani
- Research and Development Department, Herbion Pakistan (Pvt.) Limited, Plot 30, Sector 28, Korangi industrial Area, Karachi 74900, Pakistan Department of Clinical Pharmacy and Health Care, Faculty of Pharmacy, Jinnah University for Women, Karachi, Pakistan
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8
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Baez MC. Pharmacological treatment of atherosclerosis: an unresolved issue. Acta Physiol (Oxf) 2015; 213:554-5. [PMID: 25565359 DOI: 10.1111/apha.12453] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- M. C. Baez
- Instituto de Investigación en Ciencias de la Salud Humana (IICSHUM); Universidad Nacional de La Rioja; La Rioja Argentina
- Cátedra de Física Biomédica; Facultad de Ciencias Médicas; Universidad Nacional de Córdoba; Córdoba Argentina
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Menteşe E, Yılmaz F, Baltaş N, Bekircan O, Kahveci B. Synthesis and antioxidant activities of some new triheterocyclic compounds containing benzimidazole, thiophene, and 1,2,4-triazole rings. J Enzyme Inhib Med Chem 2014; 30:435-41. [DOI: 10.3109/14756366.2014.943203] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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10
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Mechanistic insight into the radical scavenging activity of polyphenols and its application in virtual screening of phytochemical library: an in silico approach. Eur Food Res Technol 2014. [DOI: 10.1007/s00217-014-2285-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Xiao L, Tsutsui T, Miwa N. The lipophilic vitamin C derivative, 6-o-palmitoylascorbate, protects human lymphocytes, preferentially over ascorbate, against X-ray-induced DNA damage, lipid peroxidation, and protein carbonylation. Mol Cell Biochem 2014; 394:247-59. [DOI: 10.1007/s11010-014-2101-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Accepted: 05/15/2014] [Indexed: 12/20/2022]
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Antiartherosclerotic effects of plant flavonoids. BIOMED RESEARCH INTERNATIONAL 2014; 2014:480258. [PMID: 24971331 PMCID: PMC4058282 DOI: 10.1155/2014/480258] [Citation(s) in RCA: 134] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Revised: 05/11/2014] [Accepted: 05/11/2014] [Indexed: 12/13/2022]
Abstract
Atherosclerosis is the process of hardening and narrowing the arteries. Atherosclerosis is generally associated with cardiovascular diseases such as strokes, heart attacks, and peripheral vascular diseases. Since the usage of the synthetic drug, statins, leads to various side effects, the plants flavonoids with antiartherosclerotic activity gained much attention and were proven to reduce the risk of atherosclerosis in vitro and in vivo based on different animal models. The flavonoids compounds also exhibit lipid lowering effects and anti-inflammatory and antiatherogenic properties. The future development of flavonoids-based drugs is believed to provide significant effects on atherosclerosis and its related diseases. This paper discusses the antiatherosclerotic effects of selected plant flavonoids such as quercetin, kaempferol, myricetin, rutin, naringenin, catechin, fisetin, and gossypetin.
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Benzie I, Strain JJ. Effect of vitamin C supplementation on concentrations of vitamins C and E in fasting plasma. Asia Pac J Clin Nutr 2014; 8:207-10. [PMID: 24394164 DOI: 10.1046/j.1440-6047.1999.00114.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Vitamin C may 'spare' vitamin E, but this has not to date been confirmed as occurring in vivo. The aim of this study was to test the effect of dietary supplementation with vitamin C on total and lipid standardised vitamin E concentrations in fasting plasma, the hypothesis being that increased vitamin C intake leads to improved vitamin E levels. In this single-blinded study, 12 apparently healthy adults (seven men, five women) took 1 g/day vitamin C for 28 days, with a 28-day placebo-controlled run-in cycle and a 28-day placebo-controlled washout cycle. Concentrations of ascorbic acid, total vitamin E (as total tocopherols) and lipid standardised vitamin E (Vit ELS, expressed as mol vitamin E/mmol total cholesterol plus triglycerides) were measured in fasting plasma after each cycle. Results showed that vitamin C supplementation led to significant increases in ascorbic acid, total vitamin E and Vit ELS. These findings indicate that, by a combination of a vitamin E 'sparing' effect perhaps via improved redox recycling of vitamin E in vivo and a lipid lowering effect, increased intake of vitamin C could increase plasma vitamin E levels, and possibly vitamin E status. Further study of possible in vivo interrelationships between vitamins C and E, and the role of vitamin C in lipid metabolism, is needed.
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Affiliation(s)
- I Benzie
- Department of Nursing and Health Sciences, The Hong Kong Polytechnic University, Kowloon,Hong Kong SAR, China
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Shi M, He W, Liu Y, Li X, Yang S, Xu Q. Protective effect of total phenylethanoid glycosides from Monochasma savatieri Franch on myocardial ischemia injury. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2013; 20:1251-1255. [PMID: 23880328 DOI: 10.1016/j.phymed.2013.06.014] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Revised: 05/07/2013] [Accepted: 06/20/2013] [Indexed: 06/02/2023]
Abstract
The present study was designed to investigate the cardioprotective effect of total phenylethanoid glycosides from Monochasma savatieri Franch (TPG). The data showed that there were mainly four phenylethanoid glycosides isolated and identified from TPG. TPG significantly increased cells viability and inhibited morphological changes on H9c2 cardiomyocytes induced by H2O2 or Na2S2O4. In addition, TPG significantly decreased T-wave elevation and histopathological changes of heart tissues in myocardial infracted rats induced by isoproterenol. It also significantly reduced the infarct size induced by ligating the coronary artery in rats, increased the activities of antioxidative enzymes superoxide dismutase (SOD), the content of glutathione (GSH), and decreased the leakage of lactic dehydrogenase (LDH), the activities of creatine kinase (CK) and the content of maleic dialdehyde (MDA). In conclusion, these results suggested that TPG from Monochasma savatieri Franch might be developed as new natural medicine or food additives with effects of prevention of coronary artery disease due to its significant antioxidant activity.
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Affiliation(s)
- Mengfan Shi
- College of Pharmaceutical Science, Soochow University, Suzhou 215123, China
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Wang LX, Liu K, Gao DW, Hao JK. Protective effects of two Lactobacillus plantarum strains in hyperlipidemic mice. World J Gastroenterol 2013; 19:3150-3156. [PMID: 23716997 PMCID: PMC3662957 DOI: 10.3748/wjg.v19.i20.3150] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2012] [Revised: 01/17/2013] [Accepted: 03/01/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of Lactobacillus plantarum (L. plantarum) CAI6 and L. plantarum SC4 on hyperlipidemic mice.
METHODS: Male Kunming mice were fed a high-cholesterol diet for 28 d to construct hyperlipidemic models. Hyperlipidemic mice and normal mice were assigned to 3 groups which were separately treated with L. plantarum CAI6, L. plantarum SC4, and physiological saline through oral gavage for 28 d. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured by commercially available enzyme kits. FACS Calibur flow cytometry was used to examine hepatic and renal nuclear factor-erythroid 2-related factor 2 (Nrf2) expression. The morphology of livers was checked by hematoxylin and eosin staining and optical microscope observation.
RESULTS: Compared with normal mice, hyperlipidemic mice possessed significantly higher TC (3.50 ± 0.43 vs 2.89 ± 0.36, P < 0.01), TG (1.76 ± 0.07 vs 1.10 ± 0.16, P < 0.01), and LDL-C (1.72 ± 0.20 vs 0.82 ± 0.10, P< 0.01) levels, resulting in an increase of atherogenic index (AI) (2.34 ± 1.60 vs 0.93 ± 0.55, P < 0.05) and LDL-C/HDL-C ratio (1.43 ± 0.12 vs 0.51 ± 0.16, P < 0.05). After treatment with L. plantarum CAI6/L. plantarum SC4, TG (1.43 ± 0.27/1.54 ± 0.10 vs 1.76 ± 0.07, P < 0.01/P < 0.05) and LDL-C (1.42 ± 0.07/1.47 ± 0.12 vs 1.72 ± 0.20, P < 0.01/P < 0.01) in hyperlipidemic mice significantly decreased. In addition, TC, HDL-C, AI, and LDL-C/HDL-C ratio were all positively changed. Meanwhile, the treatment markedly alleviated hepatic steatosis and significantly stimulated Nrf2 expression (73.79 ± 0.80/72.96 ± 1.22 vs 54.94 ± 1.84, P < 0.01/P < 0.01) in hepatocytes of hyperlipidemic mice.
CONCLUSION: L. plantarum CAI6 and L. plantarum SC4 may protect against cardiovascular disease by lipid metabolism regulation and Nrf2-induced antioxidative defense in hyperlipidemic mice.
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Sram RJ, Binkova B, Rossner P. Vitamin C for DNA damage prevention. Mutat Res 2012; 733:39-49. [PMID: 22178550 DOI: 10.1016/j.mrfmmm.2011.12.001] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2011] [Revised: 11/25/2011] [Accepted: 12/04/2011] [Indexed: 05/27/2023]
Abstract
The ability of vitamin C to affect genetic damage was reviewed in human studies that used molecular epidemiology methods, including analysis of DNA adducts, DNA strand breakage (using the Comet assay), oxidative damage measured as levels of 8-oxo-7,8-dihydroxy-2'-deoxyguanosine (8-oxodG), cytogenetic analysis of chromosomal aberrations and micronuclei, and the induction of DNA repair proteins. The protective effect of vitamin C was observed at plasma levels>50μmol/l. Vitamin C supplementation decreased the frequency of chromosomal aberrations in groups with insufficient dietary intake who were occupationally exposed to mutagens, and also decreased the sensitivity to mutagens as assessed using the bleomycin assay. High vitamin C levels in plasma decreased the frequency of genomic translocations in groups exposed to ionizing radiation or c-PAHs in polluted air. The frequency of micronuclei was decreased by vitamin C supplementation in smokers challenged with γ-irradiation, and higher vitamin C levels in plasma counteracted the damage induced by air pollution. The prevalence of DNA adducts inversely correlated with vitamin C levels in groups environmentally exposed to high concentrations of c-PAHs. Increased vitamin C levels decreased DNA strand breakage induced by air pollution. Oxidative damage (8-oxodG levels) was decreased by vitamin C supplementation in groups with plasma levels>50μmol/l exposed to PM2.5 and c-PAHs. Modulation of DNA repair by vitamin C supplementation was observed both in poorly nourished subjects and in groups with vitamin C plasma levels>50μmol/l exposed to higher concentrations of c-PAHs. It is possible that the impact of vitamin C on DNA damage depends both on background values of vitamin C in the individual as well as on the level of exposure to xenobiotics or oxidative stress.
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Affiliation(s)
- Radim J Sram
- Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 14220 Prague 4, Czech Republic.
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17
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The basic antioxidant structure for flavonoid derivatives. J Mol Model 2012; 18:4073-80. [PMID: 22527272 DOI: 10.1007/s00894-012-1397-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2011] [Accepted: 02/29/2012] [Indexed: 12/12/2022]
Abstract
An antioxidant structure-activity study is carried out in this work with ten flavonoid compounds using quantum chemistry calculations with the functional of density theory method. According to the geometry obtained by using the B3LYP/6-31G(d) method, the HOMO, ionization potential, stabilization energies, and spin density distribution showed that the flavonol is the more antioxidant nucleus. The spin density contribution is determinant for the stability of the free radical. The number of resonance structures is related to the π-type electron system. 3-hydroxyflavone is the basic antioxidant structure for the simplified flavonoids studied here. The electron abstraction is more favored in the molecules where ether group and 3-hydroxyl are present, nonetheless 2,3-double bond and carbonyl moiety are facultative.
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Catalgol B, Ozer NK. Protective effects of vitamin E against hypercholesterolemia-induced age-related diseases. GENES AND NUTRITION 2011; 7:91-8. [PMID: 21590435 DOI: 10.1007/s12263-011-0235-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2011] [Accepted: 04/29/2011] [Indexed: 12/11/2022]
Abstract
Hypercholesterolemia is a major risk factor for age-related diseases such as atherosclerosis and Alzheimer's disease (AD). Changes in human plasma cholesterol levels results from the interaction between multiple genetic and environmental factors. The accumulation of excess cholesterol in blood vessels leads to atherosclerosis. Many studies on this field show that differential expression of oxidative stress-related proteins, lipid metabolism-related enzymes, and receptors response to atherogenic diet. Additionally, excess brain cholesterol has been associated with increased formation and deposition of amyloid-β peptide from amyloid precursor protein which may contribute to the risk and pathogenesis of AD. To consider genetically, more than 50 genes have been reported to influence the risk of late-onset AD. Some of these genes might be also important in cholesterol metabolism and transport. Epidemiological studies have shown an association between high intake and high serum concentrations of antioxidant vitamins like vitamin E and lower rates of ischemic heart diseases. It has been known that vitamin E also inhibits smooth muscle cell proliferation by non-antioxidant mechanism. On the basis of the previous results, vitamin E has been accepted as an important protective factor against hypercholesterolemia-induced age-related diseases.
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Affiliation(s)
- Betul Catalgol
- Department of Biochemistry, Faculty of Medicine, Marmara University, 34668, Haydarpasa, Istanbul, Turkey
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Cordero Z, Drogan D, Weikert C, Boeing H. Vitamin E and risk of cardiovascular diseases: a review of epidemiologic and clinical trial studies. Crit Rev Food Sci Nutr 2010; 50:420-40. [PMID: 20373188 DOI: 10.1080/10408390802304230] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Cardiovascular diseases are the leading cause of worldwide mortality. There is strong epidemiologic evidence for a beneficial effect of vitamin E on cardiovascular disease risk. However, conflicting results have been reported by intervention studies. To assess the potential benefit of vitamin E intake on the risk of cardiovascular diseases, fifty-nine published reports from observational studies, retrospective and prospective, randomised clinical trials, meta-analyses as well as pooling analyses were reviewed. The paper provides a detailed discussion about design, quality and limitations of these studies with regard to the evidence of the hypothesized relationship between vitamin E and cardiovascular diseases.
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Affiliation(s)
- Zorabel Cordero
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrucke, Nuthetal, Germany.
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Abstract
Menopause and the aging process itself cause many physiologic changes, which explain the increased prevalence of chronic diseases observed in postmenopausal women. Exercise and nutrition play important roles in the prevention and treatment of cardiovascular disease, cancer, obesity, diabetes, osteoporosis, and depression.
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Kwon HS, Kim MJ, Jeong HJ, Yang MS, Park KH, Jeong TS, Lee WS. Low-density lipoprotein (LDL)-antioxidant lignans from Myristica fragrans seeds. Bioorg Med Chem Lett 2007; 18:194-8. [PMID: 17998162 DOI: 10.1016/j.bmcl.2007.10.098] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2007] [Revised: 10/22/2007] [Accepted: 10/26/2007] [Indexed: 10/22/2022]
Abstract
Six diarylbutane lignans 1-5 and one aryltetralin lignan 6 were isolated from the methanol (95%) extracts of Myristica fragrans seeds and then 7-methyl ether diarylbutane lignan 4 has proven to be new a compound. Their compounds 1-7 were evaluated for LDL-antioxidant activity to identify the most potent LDL-antioxidant 3 with an IC50 value of 2.6 microM in TBARS assay. Due to its potency, compound 3 was tested for complementary in vitro investigations, such as lag time (140 min at 1.0 microM), relative electrophoretic mobility (REM) of ox-LDL (inhibition of 80% at 20 microM and 72% at 10 microM), and fragmentation of apoB-100 (inhibition of 93% at 20 microM) on copper-mediated LDL oxidation. In macrophage-mediated LDL oxidation, the TBARS formation was also inhibited by compound 3.
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Affiliation(s)
- Hyun Sook Kwon
- Division of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea
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22
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Influence of feeding different vegetables on plasma levels of carotenoids, folate and vitamin C. Effect of disruption of the vegetable matrix. Br J Nutr 2007. [DOI: 10.1017/s0007114599001385] [Citation(s) in RCA: 109] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Carotenoids, folate and vitamin C may contribute to the observed beneficial effects of increased vegetable intake. Currently, knowledge on the bioavailability of these compounds from vegetables is limited. We compared the efficacy of different vegetables, at the same level of intake (i.e. 300 g/d), in increasing plasma levels of carotenoids, folate and vitamin C and we investigated if disruption of the vegetable matrix would enhance the bioavailability of these micronutrients. In an incomplete block design, sixty-nine volunteers consumed a control meal without vegetables and three out of four vegetable meals (i.e. broccoli, green peas, whole leaf spinach, chopped spinach; containing between 1·7 and 24·6 mg β-carotene, 3·8 and 26 mg lutein, 0·22 and 0·60 mg folate and 26 and 93 mg vitamin C) or a meal supplemented with synthetic β-carotene (33·3 mg). Meals were consumed for 4 d and fasting blood samples were taken at the end of each period. Consumption of the spinach-supplemented meal did not affect plasma levels of β-carotene, although the β-carotene content was 10-fold those of broccoli and green peas, which induced significant increases in plasma β-carotene levels (28 (95 % CI 6·4, 55) % and 26 (95 % CI 2·6, 54) % respectively). The β-carotene-supplemented meal increased plasma concentrations of β-carotene effectively (517 (95 % CI 409, 648) %). All vegetable meals increased the plasma concentrations of lutein and vitamin C significantly. Broccoli and green peas were, when expressed per mg carotenoid consumed, also more effective sources of lutein than spinach. A significant increase in plasma folate concentration was found only after consumption of the spinach-supplemented meal, which provided the highest level of folate. Disruption of the spinach matrix increased the plasma responses to both lutein (14 (95 % CI 3·7, 25) %) and folate (10 (95 % CI 2·2, 18) %), whereas it did not affect the response to β-carotene. We conclude that the bioavailabilities of β-carotene and lutein vary substantially among different vegetables and that the bioavailabilities of lutein and folate from spinach can be improved by disruption of the vegetable matrix.
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Xu MZ, Lee WS, Han JM, Oh HW, Park DS, Tian GR, Jeong TS, Park HY. Antioxidant and anti-inflammatory activities of N-acetyldopamine dimers from Periostracum Cicadae. Bioorg Med Chem 2006; 14:7826-34. [PMID: 16919462 DOI: 10.1016/j.bmc.2006.07.063] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2006] [Revised: 07/28/2006] [Accepted: 07/28/2006] [Indexed: 11/17/2022]
Abstract
A known N-acetyldopamine dimer, (2R,3S)-2-(3',4'-dihydroxyphenyl)-3-acetylamino-7-(N-acetyl-2''-aminoethyl)-1,4-benzodioxane (1) and a new N-acetyldopamine dimer, (2R,3S)-2-(3',4'-dihydroxyphenyl)-3-acetylamino-7-(N-acetyl-2''-aminoethylene)-1,4-benzodioxane (2) were isolated from the methanolic extracts of Periostracum Cicadae. Compounds 1 and 2 inhibited the Cu2+ -mediated, 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH)-mediated, and 3-morpholinosydnonimine (SIN)-1-mediated LDL oxidation in the thiobarbituric acid-reactive substances (TBARS) assay. The antioxidant activities of 1 and 2 were tested with respect to other parameters, such as lag time of conjugated diene formation, relative electrophoretic mobility (REM), and apoB-100 fragmentation on copper-mediated LDL-oxidation. Compounds 1 and 2 also showed 1,1-diphenyl-2-picrylhydrasyl (DPPH) radical scavenging activity. Compound 2 was more efficient than compound 1 at inhibiting the reactive oxygen species (ROS) generation, nitric oxide (NO) production, and nuclear factor-kappaB (NF-kappaB) activity as well as the expression of pro-inflammatory molecules such as inducible nitric oxide synthase (iNOS), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and cyclooxygenase (COX)-2 in LPS-induced RAW264.7 cells.
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Affiliation(s)
- Ming-Zhe Xu
- Insect Resources Research Center, KRIBB, Daejeon 305-806, Republic of Korea
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Rana VS, Rawat MSM, Pant G, Nagatsu A. Chemical Constituents and Antioxidant Activity ofMallotus roxburghianus Leaves. Chem Biodivers 2005; 2:792-8. [PMID: 17192023 DOI: 10.1002/cbdv.200590057] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Mallotus roxburghianus is used in the traditional medicine in North-Eastern India, but previously no work has been done on the identification of bioactive compounds. Two new compounds, 3-(1-C-beta-D-glucopyranosyl)-2,6-dihydroxy-5-methoxybenzoic acid (6) and 2,4,8,9,10-pentahydroxy-3,7-dimethoxyanthracene-6-O-beta-D-rhamnopyranoside (7) together with beta-sitosterol (1), stigmasterol (2), betulinic acid (3), 4-hydroxybenzoic acid (4), beta-sitosterol-beta-D-glucoside (5), and bergenin (8) were isolated and identified from the leaves of M. roxburghianus. The chloroform soluble portion of the alcoholic extract of leaf, and compounds 3, 6, 7, and 8 exhibited encouraging antioxidant activities.
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Affiliation(s)
- Virendra S Rana
- Department of Chemistry, HNB Garhwal University, Srinagar (Garhwal)-246174, Uttaranchal, India.
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25
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Lee WS, Baek YI, Kim JR, Cho KH, Sok DE, Jeong TS. Antioxidant activities of a new lignan and a neolignan from Saururus chinensis. Bioorg Med Chem Lett 2005; 14:5623-8. [PMID: 15482936 DOI: 10.1016/j.bmcl.2004.08.054] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2004] [Revised: 08/24/2004] [Accepted: 08/25/2004] [Indexed: 12/12/2022]
Abstract
A new diarylbutane lignan, 2'-hydroxy dihydroguaiaretic acid (4), and a known 8-O-4'-type neolignan, machilin D (5), were isolated from the ethyl acetate extracts of the underground parts of Saururus chinensis. Compounds 4 and 5 exhibited low-density lipoprotein (LDL)-antioxidant activity in the thiobarbituric acid-reactive substances (TBARS) assay (4: IC(50)=3.3 microM and 5: IC(50)=3.8 microM), the lag time of conjugated diene production, the relative electrophoretic mobility (REM) of ox-LDL, the apoB-100 fragmentation on copper-mediated LDL oxidation and the macrophage-mediated LDL oxidation, and radical DPPH scavenging activity.
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Affiliation(s)
- Woo Song Lee
- National Research Laboratory of Lipid Metabolism & Atherosclerosis, Korea Research Institute of Bioscience and Biotechnology, 52 Oun, Yusong, Daejeon 305-333, Republic of Korea
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26
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Ko SH, Choi SW, Ye SK, Cho BL, Kim HS, Chung MH. Comparison of the Antioxidant Activities of Nine Different Fruits in Human Plasma. J Med Food 2005; 8:41-6. [PMID: 15857208 DOI: 10.1089/jmf.2005.8.41] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Oxidative stress in humans is associated with damage to DNA, proteins, and biological membranes. Oxidative stress, which often arises as a result of an imbalance in the human antioxidant status, has been implicated in aging and a number of human diseases such as cancer, atherosclerosis, and rheumatoid arthritis. This study was performed to test the hypothesis that the consumption of fruit juices may improve antioxidant status in human plasma. Ten healthy men 25-26 years old were recruited for the study. After overnight fasting, study subjects were fed 150 mL of fruit juice, and blood was collected at 0, 30, 60, 90, and 120 minutes after consumption. After a 1-day wash-out period, subjects were fed with the next sample of fruit juice until all nine juices (pear, apple, orange, grape, peach, plum, kiwi, melon, and watermelon) had been evaluated. All juices were prepared from pure fruits ground in a home-style mixer. Dietary food records and anthropometric measurements were used to evaluate the nutritional status of subjects. The antioxidant activities of fruit juices were estimated by measuring antioxidant status in the plasma using dichlorofluorescein (DCF) fluorescence. Except for pear juice, eight kinds of juices exhibited potent antioxidant effects in human plasma. Within 30 minutes after consumption, orange, melon, grape, peach, plum, apple, and kiwi juices already effectively suppressed reactive oxygen species generation. This radical scavenging effect of fruit juices was maintained for up to 90 minutes post-consumption, but the relative DCF fluorescence had rebounded to near the initial levels at 2 hours post-consumption in most samples tested. Interestingly, however, grape juice continuously exerted persistent antioxidant activity until 2 hours after supplementation. These results suggest that the consumption of fruits or fruit juices may reduce damage from oxidative stress, and that this effect may be a consequence of the antioxidant activity of fruits in scavenging the reactive oxygen species generated in human plasma. However, long-term studies with more subjects are needed to provide additional supportive evidence and better characterize the antioxidant properties of natural fruit juices.
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Affiliation(s)
- Seong-Hee Ko
- Department of Pharmacology, Seoul National University School of Medicine, Seoul, Korea
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27
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Kiefer I, Prock P, Lawrence C, Wise J, Bieger W, Bayer P, Rathmanner T, Kunze M, Rieder A. Supplementation with Mixed Fruit and Vegetable Juice Concentrates Increased Serum Antioxidants and Folate in Healthy Adults. J Am Coll Nutr 2004; 23:205-11. [PMID: 15190044 DOI: 10.1080/07315724.2004.10719362] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
OBJECTIVE Epidemiological studies have shown that low plasma levels of antioxidant micronutrients, which are commonly found in fruit and vegetables, are associated with increased risk for diseases such as heart disease, cancer, metabolic disorders and the like. The aim of this study was to monitor the dietary habits of a group of healthy, middle-aged, men and women and to assess the effect of supplementation with a natural phytonutrient preparation from fruits and vegetables, on plasma levels of various antioxidant micronutrients and oxidative stress assessed by measuring 8-oxodGuo (8-oxo-7,8-dihydro-2'-deoxyguanosine) in urine. METHODS The study followed a double-blind randomized cross-over design involving 59 healthy men and women (40-60 years of age). The supplement or a placebo was given to two groups for a total period of 14 weeks (crossover week 7). Blood levels of beta-carotene, vitamin C, vitamin E, selenium and folate were measured at 0, 7 and 14 weeks. Fruit and vegetable consumption was monitored by means of a retrospective food frequency questionnaire at week 0, 7 and 14. Urinary 8-oxodGuo was also determined at these time points. RESULTS Significant increases in blood nutrient levels after active supplementation were observed for beta-carotene, vitamin C, vitamin E, selenium and folate. Ranges measured, after supplementation, often fell into those associated with a reduced risk for disease. Our data suggests that, although generally health conscious, participants still fell short of the recommended five portions of fruit and vegetables per day. No significant group changes were noted for 8-oxodGuo concentration in urine. CONCLUSION Supplementation with mixed fruit and vegetable juice concentrates effectively increased plasma levels of important antioxidant nutrients and folate.
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Affiliation(s)
- Ingrid Kiefer
- Institute of Social Medicine, Department of Public Health, Medical University Vienna, Vienna, Austria.
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Latha M, Pari L. Effect of an aqueous extract of Scoparia dulcis on blood glucose, plasma insulin and some polyol pathway enzymes in experimental rat diabetes. Braz J Med Biol Res 2004; 37:577-86. [PMID: 15064821 DOI: 10.1590/s0100-879x2004000400015] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
The effects of an aqueous extract of the plant Scoparia dulcis (200 mg/kg) on the polyol pathway and lipid peroxidation were examined in the liver of streptozotocin adult diabetic male albino Wistar rats. The diabetic control rats (N = 6) presented a significant increase in blood glucose, sorbitol dehydrogenase, glycosylated hemoglobin and lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS) and hydroperoxides, and a significant decrease in plasma insulin and antioxidant enzymes such as glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) compared to normal rats (N = 6). Scoparia dulcis plant extract (SPEt, 200 mg kg-1 day-1) and glibenclamide (600 microg kg-1 day-1), a reference drug, were administered by gavage for 6 weeks to diabetic rats (N = 6 for each group) and significantly reduced blood glucose, sorbitol dehydrogenase, glycosylated hemoglobin, TBARS, and hydroperoxides, and significantly increased plasma insulin, GPx, GST and GSH activities in liver. The effect of the SPEt was compared with that of glibenclamide. The effect of the extract may have been due to the decreased influx of glucose into the polyol pathway leading to increased activities of antioxidant enzymes and plasma insulin and decreased activity of sorbitol dehydrogenase. These results indicate that the SPEt was effective in attenuating hyperglycemia in rats and their susceptibility to oxygen free radicals.
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Affiliation(s)
- M Latha
- Department of Biochemistry, Faculty of Science, Annamalai University, Tamil Nadu, India
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Franke AA, Custer LJ, Arakaki C, Murphy SP. Vitamin C and flavonoid levels of fruits and vegetables consumed in Hawaii. J Food Compost Anal 2004. [DOI: 10.1016/s0889-1575(03)00066-8] [Citation(s) in RCA: 117] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Moussavi RM, Garza HM, Eisele SG, Rodriguez G, Rintala DH. Serum levels of vitamins A, C, and E in persons with chronic spinal cord injury living in the community. Arch Phys Med Rehabil 2003; 84:1061-7. [PMID: 12881835 DOI: 10.1016/s0003-9993(03)00033-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
OBJECTIVES To determine serum levels of vitamins A, C, and E among individuals with spinal cord injury (SCI) living in the community, to compare these levels with general population norms, and to assess their association with demographic and injury-related data (age at onset, time since onset, level and completeness of injury), function, nutritional behaviors, and health status. DESIGN Descriptive and correlational. SETTING General community. PARTICIPANTS A total of 110 adults (> or =18y) with traumatic SCI of at least 2 years in duration living within a 13-county area in Texas. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Demographic information, age at onset, time since onset, American Spinal Injury Association (ASIA) total motor index score, ASIA impairment score, assay of serum vitamins, FIM trade mark instrument motor items, Health-Promoting Lifestyle Profile nutrition subscale, Medical Outcomes Study 36-Item Short-Form Health Survey general health subscale, and pressure ulcer occurrence in past 12 months. RESULTS Many (16%-37%) of the participants had serum levels below the reference range for each vitamin. Being older at onset or less impaired was associated with higher serum vitamin A levels. Higher levels of serum vitamin A also were related to better function and health status and with not having a pressure ulcer within the past 12 months. Being older or older at onset was associated with higher serum levels of vitamin E. No relationships with vitamin C were found. CONCLUSIONS Vitamin levels may be related to function, general health, and pressure ulcer incidence in persons with SCI. Further study is needed to determine effective interventions to improve vitamin levels and determine the effect of such improvements on overall health and rehabilitation outcomes.
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Affiliation(s)
- Robabeh M Moussavi
- Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX 77030, USA
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Abeywardena MY, Jablonskis LT, Head RJ. Age- and hypertension-induced changes in abnormal contractions in rat aorta. J Cardiovasc Pharmacol 2002; 40:930-7. [PMID: 12451327 DOI: 10.1097/00005344-200212000-00015] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The current investigation explored the potential age-dependant modulation of abnormal spontaneous constrictions (thromboxane-like) in the spontaneously hypertensive rat (SHR) aorta, observed only after the inhibition of endogenous production of nitric oxide (NO). Aortic rings from SHR and Wistar-Kyoto (WKY) control rats of varying ages (4, 8, 12, and 18 months) were mounted in organ baths, and changes in tension were monitored. Inhibition of NO with Nomega-nitro-L-arginine (NOLA) unmasked a slow contraction, which appeared to be age dependent (p < 0.05). This contraction was found in SHRs of all age groups and in older WKY rats. Denuding the endothelium in young SHRs did not influence the constriction, confirming a nonendothelial cell origin, while in the older groups this led to a 30-40% reduction in contraction. Comparable attenuation of the constrictor response was observed after incubation of endothelium intact rings with superoxide dismutase (100 U/ml) or 3-amino-1,2,4-triazole. Of the residual activity that was unaffected by free radical scavengers or de-endothelialization, 60-70% was sensitive to cyclooxygenase inhibition by indomethacin and/or ibuprofen. The thromboxane (TxA ) receptor antagonist SQ29548 induced a complete reversal of the abnormal constriction. In contrast, thromboxane synthetase inhibition had no effect, ruling out any involvement of TxA in mediating this abnormality. Collectively, these observations support the view that as compared with the normotensive setting, contraction induced by NO inhibition in the SHR develops prematurely and deteriorates more rapidly during the aging process. In aged rats, prostaglandin endoperoxide intermediates PGG /H and endothelium-derived free radicals rather than TxA per se appear to contribute to the NOLA-dependent TxA -like vasoconstriction.
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Hayes K, Pronczuk A, Perlman D. Vitamin E in fortified cow milk uniquely enriches human plasma lipoproteins. Am J Clin Nutr 2001; 74:211-8. [PMID: 11470723 DOI: 10.1093/ajcn/74.2.211] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Milk fat may contribute to atherogenesis in humans. OBJECTIVE We sought to offset the atherogenic potential of milk fat by adding polyunsaturated fat and vitamin E to milk. DESIGN We measured plasma lipids, lipoproteins, and tocopherol and LDL oxidation in normolipemic adults. In experiment 1 (n = 48), we compared delivery of 100 mg all-rac-alpha-tocopheryl acetate/d in capsules, skim milk, and 1%-fat milks containing soybean oil, milk fat, or both (1:1). In experiment 2 (n = 24), we compared delivery of natural (RRR-alpha-tocopheryl acetate) and synthetic (all-rac-alpha-tocopheryl acetate) vitamin E in milk with delivery of all-rac-alpha-tocopheryl acetate in orange juice (200 mg/d in each group). In experiment 3 (n = 7), we compared delivery of 30 mg all-rac-alpha-tocopheryl acetate/d in milks with and without added vitamins A and D. RESULTS Enrichment of milk fat with soybean oil did not alter plasma lipoproteins. Microdispersion of vitamin E in milks increased the molar ratio of plasma tocopherol to cholesterol by >2-fold compared with the molar ratio after consuming vitamin E capsules, whereas the molar ratios were comparable after ingestion of orange juice and capsules. Synthetic and natural vitamin E performed comparably. The enhanced plasma vitamin E:cholesterol attributed to milk increased protection of LDL against oxidation. Vitamins A and D did not affect vitamin E delivery by milk. CONCLUSIONS Milk augments vitamin E transport by human lipoproteins at intakes of 100-200 but not 30 mg/d. This augmentation is independent of the presence and type of fat in milk, its vitamin A and D contents, and whether the vitamin E is natural or synthetic.
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Affiliation(s)
- K Hayes
- Foster Biomedical Research Laboratory, Brandeis University, Waltham, MA 02254, USA.
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Lancrajan I, Diehl HA, Socaciu C, Engelke M, Zorn-Kruppa M. Carotenoid incorporation into natural membranes from artificial carriers: liposomes and beta-cyclodextrins. Chem Phys Lipids 2001; 112:1-10. [PMID: 11518567 DOI: 10.1016/s0009-3084(01)00138-4] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Liposomes and beta-cyclodextrin (beta-CD) have been used as carriers for the incorporation of three dietary carotenoids (beta-carotene (BC), lutein (LUT) and canthaxanthin (CTX)) into plasma, mitochondrial, microsomal and nuclear membrane fractions from pig liver cells or the retinal epithelial cell line D407. The uptake dynamics of the carotenoids from the carriers to the organelle membranes and their incorporation yield (IY) was followed by incubations at pH 7.4 for up to 3 h. The mean IYs saturated between 0.1 and 0.9 after 10-30 min of incubation, depending on membrane characteristics (cholesterol to phospholipid ratio) and carotenoid specificity. Mitochondrial membranes (more fluid) favour the incorporation of BC (non-polar), while plasma membranes (more rigid) facilitate the incorporation of lutein, the most polar carotenoid. A high susceptibility of BC to degradation in the microsomal suspension was observed by parallel incubations with/without 2,6-di-t-buthyl-p-cresol (BHT) as antioxidant additive. The beta-CD carrier showed to be more effective for the incorporation of lutein while BC was incorporated equally into natural membranes either from liposomes or from cyclodextrins. The presence of cytosol in the incubation mixture had no significant effects on the carotenoid incorporations.
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Affiliation(s)
- I Lancrajan
- Department of Chemistry and Biochemistry, University of Agricultural Sciences and Veterinary Medicine, Cluj, Napoca, Romania
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van den Berg R, van Vliet T, Broekmans WM, Cnubben NH, Vaes WH, Roza L, Haenen GR, Bast A, van den Berg H. A vegetable/fruit concentrate with high antioxidant capacity has no effect on biomarkers of antioxidant status in male smokers. J Nutr 2001; 131:1714-22. [PMID: 11385058 DOI: 10.1093/jn/131.6.1714] [Citation(s) in RCA: 101] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
The potential benefits of a high fruit and vegetable intake on the antioxidant status and on relevant biomarkers of oxidative damage to lipids, proteins and DNA and on (functional) markers of oxidative stress were evaluated. A randomized, free living, open placebo-controlled cross-over trial of 3 wk, with a 2-wk washout period between treatments, was performed in a group of 22 male smokers with a relatively low vegetable and fruit intake using a vegetable burger and fruit drink. The vegetable burger and fruit drink increased serum levels of vitamin C, alpha-carotene, beta-carotene, beta-cryptoxanthin and zeaxanthin and plasma total antioxidant capacity. However, no effects were demonstrated on any marker of oxidative damage to lipids (malondialdehyde F(2)-isoprostane) proteins (carbonyls) and DNA (Comet assay) and (functional) markers of oxidative stress (reduced/oxidized glutathione ratio, glutathione-S-transferase alpha, glutathione-S-transferase pi and nuclear transcription factor-kappaB). Apparently, these increased levels of antioxidants in serum were not sufficiently high to show beneficial changes with the selected biomarkers. Alternatively, oxidative stress in male smokers with a relatively low fruit and vegetable intake might have been still too low to demonstrate a beneficial effect of antioxidants.
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Affiliation(s)
- R van den Berg
- TNO Nutrition and Food Research, 3700 AJ Zeist, the Netherlands.
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35
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Roxborough HE, Burton GW, Kelly FJ. Inter- and intra-individual variation in plasma and red blood cell vitamin E after supplementation. Free Radic Res 2000; 33:437-45. [PMID: 11022852 DOI: 10.1080/10715760000300971] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
To establish the range of individual blood responses to supplemental vitamin E, 30 healthy subjects ingested 75 mg of deuterium-labelled alpha-tocopherol with a standard breakfast. Blood was collected at 6, 9, 12, 27 and 51 h post ingestion and deuterated (d6) and non-deuterated (do) alpha-tocopherol concentrations were determined in plasma and red blood cells (RBC) by GC-MS. To examine intra-individual responses, 6 of these subjects were re-examined at 6-month intervals over a 30-month period. Post ingestion, the amount of d6-alpha-tocopherol in blood increased rapidly with time with maximal concentrations seen at 12 h (plasma) and 27 h (RBC) in most subjects. At these times, d6-alpha-tocopherol concentration ranged from 0.3-12.4 micromol/l in plasma and 0.6-4.09 micromol/l packed cell in RBC. Area under the curve calculations indicated inter-individual differences of alpha-tocopherol uptake to be 40-fold for plasma (12.9-493.3 micromol h/l) and 6-fold for RBC (24.4-146.1 micromol h/l packed RBC). Intra-individual variation in alpha-tocopherol uptake was small in comparison and remained relatively constant over the 30-month period. We conclude that vitamin E uptake varies widely in the normal population, although it is comparatively stable for an individual over time. These differences likely arise from variations in the regulation of vitamin E uptake and metabolism between subjects. Factors regulating this process must be better understood before the optimal intake of vitamin E can be ascertained.
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Affiliation(s)
- H E Roxborough
- The Rayne Institute, St. Thomas' Hospital, King's College London, UK
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36
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McKay DL, Perrone G, Rasmussen H, Dallal G, Hartman W, Cao G, Prior RL, Roubenoff R, Blumberg JB. The effects of a multivitamin/mineral supplement on micronutrient status, antioxidant capacity and cytokine production in healthy older adults consuming a fortified diet. J Am Coll Nutr 2000; 19:613-21. [PMID: 11022875 DOI: 10.1080/07315724.2000.10718959] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
BACKGROUND Inadequate micronutrient intake among older adults is common despite the increased prevalence of fortified/enriched foods in the American diet. Although many older adults take multivitamin supplements in an effort to compensate, studies examining the benefits of this behavior are absent. OBJECTIVE To determine whether a daily multivitamin/mineral supplement can improve micronutrient status, plasma antioxidant capacity and cytokine production in healthy, free-living older adults already consuming a fortified diet. METHODS An eight-week double-blind, placebo-controlled clinical trial among 80 adults aged 50 to 87 years (mean = 66.5 +/- 8.6 years). RESULTS Multivitamin treatment significantly increased (p<0.01, compared to placebo) plasma concentrations of vitamins D (77 to 100 nmol/L), E (27 to 32 micromol/L), pyridoxal phosphate (55.1 to 75.2 nmol/L), folate (23 to 33 nmol/L), B12 (286 to 326 pmol/L)), C (55 to 71 micromol/L), and improved the riboflavin activity coefficient (1.23 to 1.15), but not vitamins A and thiamin. The multivitamin reduced the prevalence of suboptimal plasma levels of vitamins E (p=0.003), B12 (p=0.004), and C (p=0.08). Neither glutathione peroxidase activity nor antioxidant capacity (ORAC) were affected. No changes were observed in interleukin-2, -6 or -10 and prostaglandin E2, proxy measures of immune responses. CONCLUSIONS Supplementation with a multivitamin formulated at about 100% Daily Value can decrease the prevalence of suboptimal vitamin status in older adults and improve their micronutrient status to levels associated with reduced risk for several chronic diseases.
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Affiliation(s)
- D L McKay
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, USA
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37
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Weber C, Erl W. Modulation of vascular cell activation, function, and apoptosis: role of antioxidants and nuclear factor-kappa B. CURRENT TOPICS IN CELLULAR REGULATION 2000; 36:217-35. [PMID: 10842754 DOI: 10.1016/s0070-2137(01)80010-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The activity of NF-kappa B is critically involved in the inflammatory activation of endothelial cells and their adhesiveness and also appears to regulate apoptosis in SMC by coordinating antiapoptotic programs. The activity of NF-kappa B has been revealed within human atheromas or following angioplasty but not in undiseased arteries. Hence, the inhibition of NF-kappa B mobilization by antioxidative or anti-inflammatory agents or by adenoviral I kappa B alpha overexpression, as reviewed herein, may act in concert to suppress endothelial activation and to induce SMC apoptosis. This synergistic concept may be a vasoprotective approach to prevent atherogenesis and restenosis by attenuating inflammatory reactions and SMC proliferation in nascent and progressing atherosclerotic lesions, as well as in developing neointima formations following angioplasty.
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Affiliation(s)
- C Weber
- Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten Ludwig-Maximilians-Universität Munich, Germany
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38
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Asmis R, Jelk J. Vitamin E supplementation of human macrophages prevents neither foam cell formation nor increased susceptibility of foam cells to lysis by oxidized LDL. Arterioscler Thromb Vasc Biol 2000; 20:2078-86. [PMID: 10978252 DOI: 10.1161/01.atv.20.9.2078] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Several studies in macrophage cell lines, rodent macrophages, and animal models of atherosclerosis suggest that vitamin E may prevent the formation of foam cells. We tested this hypothesis in a recently developed, fully autologous in vitro model of human foam cell formation. During maturation, macrophages continuously increased their alpha-tocopherol/total cholesterol ratio, demonstrating that these cells accumulate alpha-tocopherol at an even higher rate than cholesterol. In the presence of unsupplemented serum, we observed no correlation between serum vitamin E levels and the increase in the cellular alpha-tocopherol/total cholesterol ratio. In contrast, under supplemented conditions, a 3.1-fold increase in the mean serum alpha-tocopherol/total cholesterol ratio resulted in a corresponding mean 3.5-fold increase in the cellular alpha-tocopherol/total cholesterol ratio. Vitamin E loading had no effect on the lipid composition of macrophages and did not affect their growth. Foam cell formation was stimulated in mature unsupplemented and vitamin E-loaded macrophages for 1 week with 50 microg autologous aggregated low density lipoprotein (LDL) in the presence of unsupplemented and vitamin E-loaded serum, respectively. We observed no effect of vitamin E supplementation on the formation of foam cells. However, foam cell formation resulted in a 36% and 44% reduction in the cellular alpha-tocopherol/total cholesterol ratio in unsupplemented and vitamin E-supplemented foam cells, respectively. The loss of vitamin E was accelerated with increasing concentrations of aggregated LDL and was accompanied by an increase in the susceptibility of these foam cells to succumb to the cell lytic effects of oxidized LDL (OxLDL). However, vitamin E supplementation did not protect macrophages or foam cells from OxLDL-mediated cell lysis, suggesting that vitamin E loss in foam cells is not the cause of their increased susceptibility to cell lysis. Our results suggest that the beneficial effects of vitamin E on cardiovascular disease observed in humans are due neither to a reduction in the propensity of macrophages to form foam cells nor to an increased resistance of these cells to cytolytic OxLDL.
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Affiliation(s)
- R Asmis
- Institute of Biochemistry, University of Basel, Basel, Switzerland.
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39
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Feki M, Souissi M, Mokhtar E, Hsairi M, Kaabachi N, Antebi H, Alcindor LG, Mechmeche R, Mebazaa A. Vitamin E and Coronary Heart Disease in Tunisians. Clin Chem 2000. [DOI: 10.1093/clinchem/46.9.1401] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
AbstractBackground: Vitamin E (VE) is thought to be effective in preventing atherosclerosis. However, to date no consistent relationship has been identified between VE and coronary heart disease (CHD). This study was designed to assess the degree of association between VE and CHD in a sample of the Tunisian population.Methods: Sixty-two angiographically confirmed coronary atherosclerotic patients and 65 age- and sex-matched controls were included. VE was measured in plasma and in the LDL fraction by HPLC. Cholesterol, triglycerides, and phospholipids were measured by enzymatic methods.Results: A trend toward a meaningful decrease of plasma VE was observed in affected patients compared with controls (P = 0.06). VE concentrations standardized for cholesterol and lipid concentrations were significantly lower (P <0.02) in coronary patients than in controls (4.35 ± 1.03 vs 4.82 ± 1.23 mmol/mol for cholesterol-adjusted VE and 2.35 ± 0.56 vs 2.66 ± 0.65 mmol/mol for lipid-adjusted VE, respectively). In the LDL fraction, only cholesterol-standardized VE was significantly lower in cases than controls (3.84 ± 1.13 vs 4.41 ± 1.16 mmol/mol). This association between VE and CHD remained unchanged independent of age, sex, smoking habit, hypertension, and diabetes. In CHD patients, lower lipid-adjusted VE was associated with enhanced LDL susceptibility to oxidation but without alteration of the serum fatty acid profile.Conclusions: These results support the hypothesis that VE plays a role in preventing atherosclerosis.
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Affiliation(s)
| | | | - Elyes Mokhtar
- Service des Explorations Cardiologiques, Hopital La Rabta, Tunis, Tunisia
| | | | | | - Helena Antebi
- Laboratoire de Nutrition, Faculté de Medecine, rue des Saints Pères, 75270 Paris Cedex 06, France
| | - Louis Gérald Alcindor
- Laboratoire de Nutrition, Faculté de Medecine, rue des Saints Pères, 75270 Paris Cedex 06, France
| | - Rachid Mechmeche
- Service des Explorations Cardiologiques, Hopital La Rabta, Tunis, Tunisia
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40
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Tobe M, Isobe Y, Goto Y, Obara F, Tsuchiya M, Matsui J, Hirota K, Hayashi H. Synthesis and biological evaluation of CX-659S and its related compounds for their inhibitory effects on the delayed-type hypersensitivity reaction. Bioorg Med Chem 2000; 8:2037-47. [PMID: 11003148 DOI: 10.1016/s0968-0896(00)00126-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
In order to find novel nonsteroidal compounds possessing an inhibitory activity against delayed-type hypersensitivity (DTH) reactions, we conducted random screening using a picryl chloride (PC)-induced contact hypersensitivity reaction (CHR) in mice, and found compound 1 as a lead compound. Then we synthesized and evaluated an extensive series of 5-carboxamidouracil derivatives focused on both the uracil and the antioxidative moieties. Among them, we found that the hindered phenol moiety was necessary to exhibit the activities; especially, compounds 28a-28c having the partial structure of vitamin E were found to exert potent activities against the DTH reaction by both oral and topical administration. And compound 28c showed antioxidative activity against lipid peroxidation with an IC50 of 5.9 microM. Compound 28c (CX-659S) was chosen as a candidate drug for the treatment of cutaneous disorders such as atopic dermatitis and allergic contact dermatitis.
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Affiliation(s)
- M Tobe
- Pharmaceutical and Biotechnology Laboratory, Japan Energy Corporation, Saitama
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41
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Chung WY, Benzie IF. Probe-assisted flow cytometric analysis of erythrocyte membrane response to site-specific oxidant stress. CYTOMETRY 2000; 40:182-8. [PMID: 10878560 DOI: 10.1002/1097-0320(20000701)40:3<182::aid-cyto2>3.0.co;2-g] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Probe-assisted flow cytometry was used to monitor the response of membranes of living cells to oxidant stress in the presence and absence of antioxidants. Test conditions (fluorophore loading, oxidant concentration) were investigated and storage-related changes in erythrocyte response to oxidant stress explored. METHODS Erythrocytes were incubated with a lipophilic fluorescent probe and exposed to site-specific oxidant challenge, induced by cumene hydroperoxide, in the presence and absence of urate, ascorbate, or alpha tocopherol in physiological amounts. Fluorescence of labeled and treated erythrocytes was measured for 120 min using a Coulter EPICS Elite ESP flow cytometer. RESULTS Probe loading was dose and time dependent. Cumene hydroperoxide exhibited a potent and dose-dependent oxidant effect on erythrocyte membranes. Alpha tocopherol slowed, but did not prevent, membrane oxidation. Ascorbate appeared to have no effect on peroxidation initially, but then slowed and stopped propagation of membrane oxidation. The effect of urate was slight. CONCLUSIONS This technique can provide insight into oxidative processes at the cellular level. Results indicated that lipophilic alpha tocopherol was the most effective antioxidant in slowing membrane peroxidation, but ascorbate appears to stop chain propagation. This effect may be owing to vitamin C/E interaction. Further study is needed.
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Affiliation(s)
- W Y Chung
- Department of Nursing and Health Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
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42
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Meraji S, Abuja PM, Hayn M, Kostner GM, Morris R, Oraii S, Tatzber F, Wonisch W, Zechner R, Gey KF. Relationship between classic risk factors, plasma antioxidants and indicators of oxidant stress in angina pectoris (AP) in Tehran. Atherosclerosis 2000; 150:403-12. [PMID: 10856533 DOI: 10.1016/s0021-9150(99)00394-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Cardiovascular disease (CVD) in general seems to be the leading cause of death in the Eastern Mediterranean Region (EMR) including Iran. This may be due to classic risk factors such as high triglyceride (TG), high total cholesterol (TC), and low levels of high density lipoprotein cholesterol (HDL-C). The impact of antioxidants as potentially protective risk factors against early coronary heart disease (CHD) is unknown in Iran. Therefore, relationships between angina and plasma antioxidants and indicators of lipid peroxidation were investigated in a case-control study. In this study, 82 cases of previously undiagnosed angina pectoris (AP), identified by a modified WHO Rose chest pain questionnaire and verified by electrocardiography during treadmill exercise testing, were compared with 146 controls selected from the same population of over 4000 male civil servants aged 40-60 years. Subjects with AP declared significantly less physical activity and had higher serum TG [means (S.E.M.) 2.32 (0.18) versus 1.61 (0.07) mmol/l] but lower HDL-C [1.01 (0.04) versus 1.18 (0.03) mmol/l] than age-matched controls. Levels of total serum cholesterol, low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] were not significantly different between the two groups, while the ratio of LDL-C/HDL-C was significantly higher [4.51 (0.23) versus 3.54 (0. 11)] for subjects with AP than for the controls. There was no significant difference in plasma levels of alpha-tocopherol, vitamin C, alpha- and beta-carotene. However, retinol [1.90 (0.06) versus 2. 09 (0.05)] and beta-cryptoxanthin [0.398 (0.04) versus 0.467 (0.03)] were significantly lower in AP. Furthermore, angina cases exhibited a higher index of lipid peroxidation than controls (e.g. malondialdehyde, MDA; 0.376 (0.010) versus 0.337 (0.009) micromol/l). On multiple logistic regression analysis, retinol with odds ratio (OR) of 0.644 [95% confidence interval (CI; 0.425-0.978)], beta-cryptoxanthin, with an OR of 0.675 (CI; 0.487-0.940), oxidation indices, MDA with OR of 1.612 (95% CI; 1.119-2.322) and LDL-C/HDL-C ratio with OR of 2.006 (95% CI; 1.416-2.849) showed the most significant independent associations with AP in this group of Iranians. In conclusion, the state of lipid peroxidation as well as the status of special antioxidants may be co-determinants of AP in Iran, in parallel with the influence of classical risk factors for cardiovascular disease.
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Affiliation(s)
- S Meraji
- Shahid Rajaii Hospital, Cardiovascular Research Centre, Tehran University of Medical Sciences, Tehran, Iran
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Roodenburg AJ, Leenen R, van het Hof KH, Weststrate JA, Tijburg LB. Amount of fat in the diet affects bioavailability of lutein esters but not of alpha-carotene, beta-carotene, and vitamin E in humans. Am J Clin Nutr 2000; 71:1187-93. [PMID: 10799382 DOI: 10.1093/ajcn/71.5.1187] [Citation(s) in RCA: 166] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Fat-soluble vitamin E and carotenoids are regarded as being protective against chronic diseases. Little is known about the effect of dietary fat on the bioavailability of these compounds. OBJECTIVE The objective of this study was to assess the effect of the amount of dietary fat on plasma concentrations of vitamin E and carotenoids after supplementation with these compounds. DESIGN During two 7-d periods, 4 groups of 14-15 volunteers received daily, with a low-fat hot meal, 1 of 4 different supplements: vitamin E (50 mg), alpha- plus beta-carotene (8 mg), lutein esters (8 mg lutein), or placebo. The supplements were provided in a low- or high-fat spread supplied in random sequence during either of the 2 experimental periods. RESULTS As anticipated, plasma concentrations of vitamin E, alpha- and beta-carotene, and lutein were significantly higher in the supplemented groups than in the placebo group. The amount of dietary fat consumed with the hot meal (3 or 36 g) did not affect the increases in plasma concentrations of vitamin E (20% increase with the low-fat spread and 23% increase with the high-fat spread) or alpha- and beta-carotene (315% and 139% with the low-fat spread and 226% and 108% with the high-fat spread). The plasma lutein response was higher when lutein esters were consumed with the high-fat spread (207% increase) than with the low-fat spread (88% increase). CONCLUSION Optimal uptake of vitamin E and alpha- and beta-carotene requires a limited amount of fat whereas the amount of fat required for optimal intestinal uptake of lutein esters is higher. 2000;71:-93.
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Affiliation(s)
- A J Roodenburg
- Unilever Health Institute, Unilever Research Vlaardingen, Vlaardingen, Netherlands.
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Abstract
When life first evolved on Earth, there was little oxygen in the atmosphere. Evolution of antioxidant defences must have been closely associated with the evolution of photosynthesis and of O2-dependent electron transport mechanisms. Studies with mice lacking antioxidant defences confirm the important roles of MnSOD and transferrin in maintaining health, but show that glutathione peroxidase (GPX) and CuZnSOD are not essential for everyday life (at least in mice). Superoxide can be cytotoxic by several mechanisms: one is the formation of hydroxyl radicals. There is good evidence that OH* formation occurs in vivo. Other important antioxidants may include thioredoxin, and selenoproteins other than GPX. Nitric oxide may be an important antioxidant in the vascular system. Diet-derived antioxidants are important in maintaining human health, but recent studies employing "biomarkers" of oxidative DNA damage are questioning the "antioxidant" roles of beta-carotene and ascorbate. An important area of future research will be elucidation of the reasons why levels of steady-state oxidative damage to DNA and lipids vary so much between individuals, and their predictive value for the later development of human disease.
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Affiliation(s)
- B Halliwell
- Department of Biochemistry, National University of Singapore, Singapore
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45
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van het Hof KH, Brouwer IA, West CE, Haddeman E, Steegers-Theunissen RP, van Dusseldorp M, Weststrate JA, Eskes TK, Hautvast JG. Bioavailability of lutein from vegetables is 5 times higher than that of beta-carotene. Am J Clin Nutr 1999; 70:261-8. [PMID: 10426704 DOI: 10.1093/ajcn.70.2.261] [Citation(s) in RCA: 179] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND To gain more insight into the relation between vegetable consumption and the risk of chronic diseases, it is important to determine the bioavailability of carotenoids from vegetables and the effect of vegetable consumption on selected biomarkers of chronic diseases. OBJECTIVE To assess the bioavailability of beta-carotene and lutein from vegetables and the effect of increased vegetable consumption on the ex vivo oxidizability of LDL. DESIGN Over 4 wk, 22 healthy adult subjects consumed a high-vegetable diet (490 g/d), 22 consumed a low-vegetable diet (130 g/d), and 10 consumed a low-vegetable diet supplemented with pure beta-carotene (6 mg/d) and lutein (9 mg/d). RESULTS Plasma concentrations of vitamin C and carotenoids (ie, alpha-carotene, beta-carotene, lutein, zeaxanthin, and beta-cryptoxanthin) were significantly higher after the high-vegetable diet than after the low-vegetable diet. In addition to an increase in plasma beta-carotene and lutein, the pure carotenoid-supplemented diet induced a significant decrease in plasma lycopene concentration of -0.11 micromol/L (95% CI: -0.21, -0.0061). The responses of plasma beta-carotene and lutein to the high-vegetable diet were 14% and 67%, respectively, of those to the pure carotenoid- supplemented diet. Conversion of beta-carotene to retinol may have attenuated its plasma response compared with that of lutein. There was no significant effect on the resistance of LDL to oxidation ex vivo. CONCLUSIONS Increased vegetable consumption enhances plasma vitamin C and carotenoid concentrations, but not resistance of LDL to oxidation. The relative bioavailability of lutein from vegetables is higher than that of beta-carotene.
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Woodside JV, Young IS, Yarnell JW, Roxborough HE, McMaster D, McCrum EE, Gey KF, Evans A. Antioxidants, but not B-group vitamins increase the resistance of low-density lipoprotein to oxidation: a randomized, factorial design, placebo-controlled trial. Atherosclerosis 1999; 144:419-27. [PMID: 10407503 DOI: 10.1016/s0021-9150(98)00334-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
We have conducted an intervention trial to assess the effects of antioxidants and B-group vitamins on the susceptibility of low-density lipoprotein (LDL) to oxidation. A total of 509 men aged 30-49 from a local workforce were screened for total plasma homocysteine. The 132 selected (homocysteine concentration > or = 8.34 mumol/l) men were randomly assigned, using a factorial design, to one of four groups receiving supplementation with B group vitamins alone (1 mg folic acid, 7.2 mg pyridoxine, 0.02 mg cyanocobalamin), antioxidant vitamins (150 mg ascorbic acid, 67 mg alpha-tocopherol, 9 mg beta-carotene), B vitamins with antioxidant vitamins, or placebo. Intervention was double-blind. A total of 101 men completed the 8-week study. The lag time of LDL isolated ex vivo to oxidation (induced by 2 mumol/l cupric chloride) was increased in the two groups receiving antioxidants whether with (6.88 +/- 1.65 min) or without (8.51 +/- 1.77 min) B-vitamins, compared with placebo (-2.03 +/- 1.50) or B-vitamins alone (-3.34 +/- 1.08) (Mean +/- S.E., P < 0.001). Antibodies to malondialdehyde (MDA) modified LDL were also measured, but there were no significant changes in titers of these antibodies in any group of subjects whether receiving antioxidants or not. Contrast analysis showed that there was no interaction between antioxidants and B-group vitamins. This study indicates that while B-group vitamins lower plasma homocysteine they do not have an antioxidant effect. Thus B-group vitamins and antioxidants appear to have separate, independent effects in reducing cardiovascular risk.
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Affiliation(s)
- J V Woodside
- School of Clinical Medicine, Queen's University of Belfast, Northern Ireland, UK
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47
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Abstract
Most species of plants and animals synthesize ascorbic acid, but human subjects cannot, making vitamin C an essential component of our diet. Relationships between vitamin C intake and status, and between status and health are not yet clear. There is evidence, however, that higher intake of vitamin C is associated with lower risk of disease, supporting the concept that optimal intake is needed for optimal vitamin C status, and that both factors are required for optimal health. Vitamin C has low toxicity in healthy subjects, but a clear definition of optimal status and the dietary intake required to meet and maintain this status is needed before a change in the current recommended intake can be considered. Available evidence suggests that intake of 200 mg vitamin C/d saturates tissues and maintains fasting plasma levels above the proposed threshold (50 mumol/l) for minimum risk of CHD. However, the issue of whether or not these levels produce 'optimal vitamin C status' awaits the clear and accepted definition of the term. This definition in turn awaits the development of reliable functional markers capable of assessing the effects of varying levels of vitamin C nutriture. In the present paper the relationship between intake and body stores of vitamin C and the role of vitamin C in human health are reviewed briefly. The requirements of a reliable functional marker of human vitamin C status are defined, three classes of functional markers (molecular, biochemical and physiological) are described, and possible candidate markers are examined.
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Affiliation(s)
- I F Benzie
- Department of Nursing & Health Sciences, Hong Kong Polytechnic University, Kowloon, SAR, China.
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48
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Abstract
Interest in the role of vitamin E in disease prevention has encouraged the search for reliable indices of vitamin E status. Most studies in human subjects make use of static markers, usually alpha-tocopherol concentrations in plasma or serum. Plasma or serum alpha-tocopherol concentrations of < 11.6, 11.6-16.2, and > 16.2 mumol/l are normally regarded as indicating deficient, low and acceptable vitamin E status respectively, although more recently it has been suggested that the optimal plasma alpha-tocopherol concentration for protection against cardiovascular disease and cancer is > 30 mumol/l at common plasma lipid concentrations in combination with plasma vitamin C concentrations of > 50 mumol/l and > 0.4 mumol beta-carotene/l. Assessment of vitamin E status has also been based on alpha-tocopherol concentrations in erythrocytes, lymphocytes, platelets, lipoproteins, adipose tissue, buccal mucosal cells and LDL, and on alpha-tocopherol: gamma-tocopherol in serum or plasma. Erythrocyte susceptibility to haemolysis or lipid oxidation, breath hydrocarbon exhalation, oxidative resistance of LDL, and alpha-tocopheryl quinone concentrations in cerebrospinal fluid have been used as functional markers of vitamin E status. However, many of these tests tend to be non-specific and poorly standardized. The recognition that vitamin E has important roles in platelet, vascular and immune function in addition to its antioxidant properties may lead to the identification of more specific biomarkers of vitamin E status.
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Affiliation(s)
- P A Morrissey
- Department of Nutrition, University College, Cork, Republic of Ireland.
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Munday JS, James KA, Fray LM, Kirkwood SW, Thompson KG. Daily supplementation with aged garlic extract, but not raw garlic, protects low density lipoprotein against in vitro oxidation. Atherosclerosis 1999; 143:399-404. [PMID: 10217370 DOI: 10.1016/s0021-9150(98)00293-7] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
The oxidation of low density lipoprotein (LDL) is believed to be an important process in the development and progression of atherosclerosis. In this study, human subjects were supplemented daily with one of: 6 g raw garlic; 2.4 g aged garlic extract (AGE); or 0.8 g DL-alpha-tocopherol acetate for 7 days to determine the effect on the susceptibility of LDL particles to Cu2+-mediated oxidation. LDL isolated from subjects given either alpha-tocopherol or AGE, but not raw garlic, was significantly more resistant to oxidation than LDL isolated from subjects receiving no supplements. These results suggest that if antioxidants are proven to be antiatherogenic, AGE may be useful in preventing atherosclerotic disease.
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Affiliation(s)
- J S Munday
- Institute of Veterinary and Animal Biomedical Science, Massey University, Palmerston North, New Zealand.
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50
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Halliwell B. Establishing the significance and optimal intake of dietary antioxidants: the biomarker concept. Nutr Rev 1999; 57:104-13. [PMID: 10228347 DOI: 10.1111/j.1753-4887.1999.tb06933.x] [Citation(s) in RCA: 176] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Diets rich in fruits and vegetables are associated with decreased risk of cardiovascular disease and cancer. Biomarkers of oxidative DNA damage and lipid peroxidation can be used to establish the role of antioxidants in this protection and the optimal intake of those antioxidants. This concept is based on the presumptions that oxidative DNA damage is a significant contributor to the age-related development of some cancers and that lipid peroxidation plays a key role in the development of cardiovascular disease. Mass spectrometric measurements of various families of isoprostanes (F2-, F3-, and F4-isoprostanes) and of multiple DNA base oxidation products are probably the most promising biomarkers for use in human nutritional intervention studies. Biomarker studies should precede, as well as accompany, major intervention trials that measure disease incidence. The use of biomarkers provides a logical scientific basis for major intervention trials of antioxidants; such trials will, in turn, eventually validate or disprove the biomarker concept.
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Affiliation(s)
- B Halliwell
- Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore
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