1: J Am Geriatr Soc 2001 May;49(5):533-7
Vitamin E and lipid peroxide plasma levels predict the risk of cardiovascular events in a group of healthy very old people.
Mezzetti A, Zuliani G, Romano F, Costantini F, Pierdomenico SD, Cuccurullo F, Fellin R; The Associazione Medica Sabin.
Centro per lo Studio dell'Ipertensione Arteriosa, delle Dislipidemie e dell'Arteriosclerosi, Department of Medicine and Aging Science, University G. D'Annunzio, Chieti, Italy.
OBJECTIVES: To assess whether systemic oxidative stress can predict the risk of first myocardial infarction, ischemic stroke, and congestive heart failure. DESIGN: A longitudinal study started in 1992 and completed in 1997. SETTING: Community-based, outpatient. PARTICIPANTS: 102 apparently healthy, community-dwelling subjects age 80 and older from the Vibrata valley, Teramo, Italy. MEASUREMENTS: Plasma vitamin E, beta- carotene, vitamin C, fluorescent products of lipid peroxidation (FPLPs), and serum lipids were determined at enrollment. RESULTS: Thirty-two cardiovascular events were recorded in 47.4 months of follow-up. The subjects with vitamin E levels in the highest quartile had a risk of cardiovascular events one-sixth those with vitamin E levels in the lowest quartile (relative risk (RR) = 0.16; 95% confidence interval (CI) = 0.04-0.55). The subjects with FPLPs in the highest quartile had a risk seven times greater than those with FPLPs in the lowest quartile (RR = 7.61; 95% CI = 2.23-25.96). No association was observed for vitamin C, beta-carotene, or total cholesterol. Multivariate adjustment for known risk factors did not significantly change the results. CONCLUSIONS: Our results suggest that in apparently healthy, community-dwelling very old subjects, base-line plasma concentration of vitamin E and FPLPs predicts the risk of future cardiovascular events. We confirm previous data showing that total cholesterol is not a predictor of cardiovascular disease in people age 80 and older.
PMID: 11380744 [PubMed - indexed for MEDLINE]
1: Proc Nutr Soc 1999 Nov;58(4):1007-14 Related Articles, Books, LinkOut
Methods to detect DNA damage by free radicals: relation to exercise.
Poulsen HE, Weimann A, Loft S
Epidemiological investigations repeatedly show decreased morbidity from regular exercise compared with sedentary life. A large number of investigations have demonstrated increased oxidation of important cellular macromolecules, whereas other investigators have found no effects or even signs of lowering of oxidation of macromolecules. In particular, extreme and long-duration strenuous exercise appears to lead to deleterious oxidation of cellular macromolecules. The oxidation of DNA is important because the oxidative modifications of DNA bases, particularly the 8-hydroxylation of guanine, are mutagenic and have been implicated in a variety of diseases such as ageing and cancer. The methodologies for further investigation of the relationship between DNA oxidation and exercise are available. The preferred methods rely on HPLC or GC-mass spectrometry; whereas the theoretically-attractive liquid chromatography-tandem mass spectrometry is being developed. Caution should be taken to avoid artifacts because of the six orders of magnitude of difference between oxidized and non-oxidized DNA bases in tissues. The methods can be used to estimate tissue levels, i.e. a local concentration of oxidized DNA, or to estimate the rate of body DNA oxidation by the urinary output of repair products, the latter being a method that is independent of repair. During exercise there appears to be a shifting of dietary-dependent antioxidant, e.g. vitamin C and vitamin E, from muscle to plasma, and an increased oxidation in plasma of these antioxidants. Supplementation trials with antioxidants have not been able to increase exercise performance; however, optimum nutrition with antioxidants and possibly supplementation, could be important in the prevention of diseases in the long term. The pattern from these observations appears to be quite consistent; immediately after exercise, regardless of how intense, there do not appear to be any signs of oxidative damage to DNA. Acute or prolonged moderate exercise does not produce signs of oxidative DNA damage and might even be associated with lowering of the levels of oxidation of tissue DNA; however, after long-duration and intense exercise an increase in oxidative DNA modifications is apparent. We suggest as a hypothesis that the relationship between exercise and health is U-shaped. This hypothesis needs to be tested in detail in order to establish the maximum beneficial exercise level with regard to oxidative DNA modification, and also the level that could be deleterious and might even increase the risk for cancer and other diseases.
Publication Types: ? Review ? Review, tutorial
PMID: 10817169, UI: 20274870 1: Am J Clin Nutr 2000 Aug;72(2 Suppl):647S-52S
Vitamin E, vitamin C, and exercise.
Exercise increases the generation of oxygen free radicals and lipid peroxidation. Strenuous exercise in a person who is unconditioned or unaccustomed to exercise will induce oxidative damage and result in muscle injury. However, aerobic exercise training strengthens the antioxidant defense system by increasing superoxide dismutase. Vitamin C and, especially, vitamin E are shown to decrease the exercise-induced increase in the rate of lipid peroxidation. No ergogenic effects of either vitamin C or E have been shown. Vitamin E was shown to significantly increase circulating neutrophils in older, but not younger, subjects performing eccentric exercise that causes an increase in skeletal muscle damage. In addition to its effect in augmenting the neutrophil response to eccentric exercise, vitamin E causes a greater increase in circulating creatine kinase activity, perhaps indicating increased skeletal muscle repair. Increased vitamin E intake has been associated with enhanced glucose tolerance and insulin action as well as improved lipoprotein status. Future research should examine the combined effects of exercise training and vitamins E and C on these health-related outcomes.
Publication Types: ? Review ? Review, tutorial
PMID: 10919971, UI: 20380515 1: Int J Sports Med 2000 Jul;21(5):369-74
Vitamin E supplementation attenuates leakage of enzymes following 6 successive days of running training.
Itoh H, Ohkuwa T, Yamazaki Y, Shimoda T, Wakayama A, Tamura S, Yamamoto T, Sato Y, Miyamura M
[Medline record in process]
The purpose of this study was to examine whether vitamin E supplementation in humans would attenuate an increase of serum enzymes as an indirect marker of muscle damage following a sudden large increase in the running distance in a 6-day running training or not. A randomized and placebo-controlled study was carried out on fourteen male runners who were supplied vitamin E (alpha-tocopherol 1200 IU x day(-1); E) or placebo (P) 4 weeks prior to (T1) and during 6 successive days of running training (48.3 +/- 5.7 km x day(-1), means +/- SD). Resting venous blood samples were obtained before maximal treadmill running, at T1, the day immediately before (T2), the next day (T3), and three weeks (T4) after the running training. Serum levels of alpha-tocopherol, lipid peroxidation products (thiobarbituric acid; TBA), creatine kinase (CK), lactate dehydrogenase (LDH), and LDH isozyme 1-5 were quantitatively analyzed. No significant difference was found in maximal oxygen uptake (VO2max) and maximal heart rates following the exhaustive exercise between the P and E group during the experiments. Vitamin E supplementation significantly increased serum alpha-tocopherol (p<0.001) and decreased TBA levels (p < 0.001) compared with pre-supplementation levels. Although serum CK and LDH activities increased significantly at T3 in either group, significantly lower CK (p < 0.05) and LDH (p < 0.001) levels were observed in the E group compared with the P group. The ratio of LDH1 to LDH2 (LDH1/LDH2) decreased significantly at T3 in either group compared with the T1 levels, since there was no significant difference in the LDH1/LDH2 between the P and E group throughout the experiments. These results indicate that vitamin E supplementation can reduce the leakage of CK and LDH following 6 successive days of endurance running. The protective effect of vitamin E against free radicals probably inhibits free-radical-induced muscle damage caused by a sudden large increase in the running distance.
PMID: 10950448, UI: 20405381 1: Cardiovasc Res 2000 Aug 18;47(3):446-56
Status of myocardial antioxidants in ischemia-reperfusion injury.
Dhalla NS, Elmoselhi AB, Hata T, Makino N
BACKGROUND: Myocardial ischemia-reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. Injury of myocardium due to ischemia-reperfusion includes cardiac contractile dysfunction, arrhythmias as well as irreversible myocyte damage. These changes are considered to be the consequence of imbalance between the formation of oxidants and the availability of endogenous antioxidants in the heart. OBSERVATIONS: An increase in the formation of reactive oxygen species during ischemia-reperfusion and the adverse effects of oxyradicals on myocardium have now been well established by both direct and indirect measurements. Although several experimental studies as well as clinical trials have demonstrated the cardioprotective effects of antioxidants, some studies have failed to substantiate the results. Nonetheless, it is becoming evident that some of the endogenous antioxidants such as glutathione peroxidase, superoxide dismutase, and catalase act as a primary defense mechanism whereas the others including vitamin E may play a secondary role for attenuating the ischemia-reperfusion injury. The importance of various endogenous antioxidants in suppressing oxidative stress is evident from the depression in their activities and the inhibition of cardiac alterations which they produce during ischemia-reperfusion injury. The effects of an antioxidant thiol containing compound, N-acetylcysteine, and ischemic preconditioning were shown to be similar in preventing changes in the ischemic- reperfused hearts. CONCLUSIONS: The available evidence support the role of oxidative stress in ischemia-reperfusion injury and emphasize the importance of antioxidant mechanisms in cardioprotection.
Publication Types: ? Review ? Review, academic
PMID: 10963718, UI: 20419784 1: Cardiovasc Res 2000 Aug 18;47(3):515-28
IRFI 042, a novel dual vitamin E-like antioxidant, inhibits activation of nuclear factor-kappaB and reduces the inflammatory response in myocardial ischemia-reperfusion injury.
Altavilla D, Deodato B, Campo GM, Arlotta M, Miano M, Squadrito G, Saitta A, Cucinotta D, Ceccarelli S, Ferlito M, Tringali M, Minutoli L, Caputi AP, Squadrito F
Institute of Pharmacology, School of Medicine, University of Messina, Policlinico Universitario, Via Consolare Valeria, Policlinico Gazzi Torre Biologica 5 degrees Piano, 98125, Messina, Italy.
BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a ubiquitous rapid response transcription factor involved in inflammatory reactions which exerts its effect by expressing cytokines, chemokines, and cell adhesion molecules. Oxidative stress causes NF-kappaB activation. IRFI 042 is a novel dual vitamin E-like antioxidant and we, therefore, investigated its ability to protect the heart from oxidative stress and to halt the inflammatory response in a model of myocardial ischaemia-reperfusion injury. METHODS: Anaesthetized rats were subjected to total occlusion (45 min) of the left main coronary artery followed by 5-h reperfusion (MI/R). Sham myocardial ischaemia rats (sham-operated rats) were used as controls. Myocardial necrosis, cardiac output, cardiac and plasma vitamin E levels, myocardial malondialdehyde (MAL), cardiac SOD activity and elastase content (an index of leukocyte infiltration), hydroxyl radical (OH&z.ccirf;) formation, cardiac amount of mRNA codifying for ICAM-1 (evaluated by the means of reverse transcriptase polymerase chain reaction) and ICAM-1 immunostaining in the at-risk myocardium were investigated. NF-kappaB activation and the inhibitory protein of NF-kappaB, I-kappaBalpha, were also studied in at-risk myocardium by using electrophoretic mobility shift assay (EMSA) and Western blot analysis, respectively. RESULTS: The ischaemia-reperfusion model produced wide heart necrosis (area at risk-necrotic area=52+/-5%; necrotic area-left ventricle=28+/- 3%), increased cardiac MAL, an index of lipid peroxidation (area at risk=62.5+/-3.9 nmol/g tissue; necrotic area=80.3+/-5.1 nmol/g tissue), induced tissue neutrophil infiltration, and caused a marked decrease in endogenous antioxidants. Furthermore, myocardial ischaemia plus reperfusion caused in the area at risk peak message for ICAM-1 at 3 h of reperfusion and increased cardiac ICAM-1 immunostaining at 5 h of reperfusion. NF-kappaB activation was also evident at 0.5 h of reperfusion and reached its maximum at 2 h of reperfusion. I-kappaBalpha was markedly decreased at 45 min of occlusion; peak reduction was observed at 1 h of reperfusion and thereafter it was gradually restored. Intraperitoneal administration of IRFI 042 (5, 10, 20 mg/kg, 5 min after reperfusion) reduced myocardial necrosis expressed as a percentage either of the area at risk (18+/-4%) or the total left ventricle (11+/-2%), and improved cardiac output. This treatment also limited membrane lipid peroxidation in the area at risk (MAL=14.3+/-2.5 nmol/g tissue) and in the necrotic area (MAL=26.5+/-3.7 nmol/g tissue), restored the endogenous antioxidants vitamin E and superoxide dismutase, and inhibited detrimental hydroxyl radical formation. Finally, IRFI 042 blocked the activation of NF-kappaB, reduced cardiac ICAM-1 expression, and blunted tissue elastase content, an index of leukocytes accumulation at the site of injury. CONCLUSIONS: Our data suggest that IRFI 042 is cardioprotective during myocardial infarction by limiting reperfusion-induced oxidative stress and by halting the inflammatory response.
PMID: 10963724, UI: 20419790 [Prevention of cardiovascular risk by vitamin E].
[Article in French]
Directeur de recherche INRA, UMI, Faculte de medecine de Montpellier, Laboratoire nutrition humaine et atherogenese, Institut de biologie, 4, boulevard Henri-IV, 34060 Montpellier.
[Medline record in process]
The antioxidant properties of vitamin E are well established. In humans, they appear very clearly from the nutritional supplementation trials. There is a strong correlation between supplied doses (>= 50 mg/j), vitamin E content of LDL and antioxidant protection of LDL. The consumption studies mostly suggest that the cardiovascular disease risk is diminished by the vitamin E supplementation, this being not true for vitamin E supplied by food strictly. In spite of the fact that there is a coherence between these results due in particular to the highly atherogenic role of oxidized low density lipoprotein, it is not allowed to claim that only the increased protection of LDL against oxidation is responsible for the diminished risk. The cell-regulating properties of vitamin E that have been more recently discovered have also to be taken into account as regards the functions of platelets, monocytes-macrophages, endothelial cells and vascular smooth muscle cells. The LDL-vitamin E capacity at decreasing the superoxide anion production (involved in turn in the oxidation process of LDL) could also play a role in preventing cardiovascular risk. The nutritional intervention studies undertaken in secondary prevention indicate a beneficial effect in terms of cardiovascular morbidity, either for low dose (50 mg), or for higher dose (>= 270 mg/d) intake, but without effect in terms of mortality. A recent study presumably supports a beneficial effect at the dose intake of 300 mg/d only in terms of cardiovascular mortality. Only one intervention has been carried out in condition of primary prevention, leading to the absence of effect at the dose employed (50 mg/d). The studies on the mechanisms of action make plausible the beneficial effects observed in analytical or experimental epidemiology. However, the experimental epidemiology does not provide indisputable evidence for the efficacy of the secondary prevention of cardiovascular risk by vitamin E supplementation. There is no intervention study using doses higher than 50 mg/d in primary prevention. There is a need for such studies in the not too distant future. A period of several years will be necessary before having new data possibly resulting in a consensus achievement.
PMID: 11022097, UI: 20477784