Effect of combined supplementation with vitamin E and alpha‐lipoic acid on myocardial performance during in vivo ischaemia‐reperfusion

Reactive oxygen species (ROS) contribute significantly to myocardial ischaemia‐reperfusion (I‐R) injury. Recently the combination of the antioxidants vitamin E (VE) and alpha‐lipoic acid (α‐LA) has been reported to improve cardiac performance and reduce myocardial lipid peroxidation during in vitro I‐R. The purpose of these experiments was to investigate the effects of VE and α‐LA supplementation on cardiac performance, incidence of dysrhythmias and biochemical alterations during an in vivo myocardial I‐R insult. Female Sprague–Dawley rats (4‐months old) were assigned to one of the two dietary treatments: (1) control diet (CON) or (2) VE and α‐LA supplementation (ANTIOXID). The CON diet was prepared to meet AIN‐93M standards, which contains 75 IU VE kg^–1 diet. The ANTIOXID diet contained 10 000 IU VE kg^–1 diet and 1.65 g α‐LA kg^–1 diet. After the 14‐week feeding period, significant differences (P < 0.05) existed in mean myocardial VE levels between dietary groups. Animals in each experimental group were subjected to an in vivo I‐R protocol which included 25 min of left anterior coronary artery occlusion followed by 10 min of reperfusion. No group differences (P > 0.05) existed in cardiac performance (e.g. peak arterial pressure or ventricular work) or the incidence of ventricular dysrhythmias during the I‐R protocol. Following I‐R, two markers of lipid peroxidation were lower (P < 0.05) in the ANTIOXID animals compared with CON. These data indicate that dietary supplementation of the antioxidants, VE and α‐LA do not influence cardiac performance or the incidence of dysrhythmias but do decrease lipid peroxidation during in vivo I‐R in young adult rats.     

Cardiac hypertrophy alters myocardial response to ischaemia and reperfusion in vivo

The impact of cardiac hypertrophy on myocardial biochemical and physiological responses to ischaemia-reperfusion (I-R) was investigated in vivo. Hypertrophy was produced by aortic constriction (PH) or swimming training (TH). Open-chest rat hearts in PH, TH and a sedentary control group (SC) were subjected: (1) to ischaemia, by surgical occlusion of the main descending branch of the left coronary artery for 30 min; (2) to I-R, by releasing the occluded blood vessel for 15 min; or (3) to a sham operation. Ischaemia per se had little effect on heart oxidative and antioxidant status, or lipid peroxidation. However, I-R significantly decreased glutathione (GSH) content, increased glutathione disulfide (GSSG) content, and reduced GSH/GSSG ratio in the SC hearts. These alterations were associated with decreased activities of GSH peroxidase and GSSG reductase, and an increase in lipid peroxidation. Myocardial ATP, total adenine nucleotide content and energy charge in SC were significantly decreased after ischaemia, whereas levels of purine nucleotide derivatives, particularly adenosine, were elevated. No significant alteration of GSH status or adenine nucleotide metabolism occurred after ischaemia or I-R in hypertrophied hearts. In bodi PH and TH, glutathione content was significantly higher than in SC, whereas activities of GSH peroxidase and GSSG reductase were lower. TH rats maintained a higher heart rate (HR), peak systolic pressure, and energy charge during I-R. These data indicate that hypertrophied but well-functioned hearts may be more resistant to I-R induced disturbances of myocardial oxidative and antioxidant functions.     

Effects of vitamin E deficiency on fatigue and muscle contractile properties

Radical-mediated oxidative damage of skeletal muscle membranes has been implicated in the fatigue process. Vitamin E (VE) is a major chain breaking antioxidant that has been shown to reduce contraction-mediated oxidative damage. We hypothesized that VE deficiency would adversely affect muscle contractile function, resulting in a more rapid development of muscular fatigue during exercise. To test this postulate, rats were fed either a VE-deficient (EDEF) diet or a control (CON) diet containing VE. Following a 12-week feeding period, animals were anesthetized and mechanically ventilated. Muscle endurance (fatigue) and contractile properties were evaluated using an in situ preparation of the tibialis anterior (TA) muscle. Contractile properties of the TA muscle were determined before and after a fatigue protocol. The muscle fatigue protocol consisted of 60 min of repetitive contractions (250 ms trains at 15 Hz; duty cycle=11%) of the TA muscle. Prior to the fatigue protocol, no significant differences existed in the force-frequency curves between EDEF and CON animals. At the completion of the fatigue protocol, muscular force production was significantly (P<0.05) lower in the EDEF group (reduced by 69%) compared to CON group (reduced by 38%). Following the fatigue protocol, a right shift existed in the force-frequency curve at low stimulation frequencies (≤40 Hz) in the EDEF animals compared to the CON animals (P<0.05). The stimulated and the contralateral TA muscle from the EDEF animals had significantly higher markers of lipid peroxidation compared to the same muscles in the CON animals (P<0.05). These data support the hypothesis that VE deficiency impairs muscular endurance and alters muscle contractile properties following a prolonged series of contractions. Electronic Publication     

Aged rat hearts are not more susceptible to ischemia-reperfusion injury in vivo: role of glutathione

The current study tested the hypothesis that ischemia-reperfusion (I-R) can cause more severe myocardial dysfunction and oxidative damage in senescent rats than young adult rats. Male Fischer 344 rats at the age of 6 (adult) and 24 (old) months were subjected to an open-chest heart surgery and randomly assigned to one of the following treatments: ischemia only (I), with the occlusion of the main descending branch of the left coronary artery (LCA) for 30 min; I-R, with the release of LCA occlusion for 20 min; or sham (S) operation. Heart mechanical performance was monitored using a fluid-filled catheter inserted in the right carotid artery and advanced to the left ventricle. Ischemia caused similar reductions of left ventricle systolic pressure (LVSP) and contractility (+/-dP/dt) in adult and aged hearts. After I-R, adult hearts regained 82% (P<0.05) of the pre-ischemic LVSP, whereas the aged hearts regained 91% (P>0.05) of LVSP. There was no significant difference in the reduction of +/-dP/dt with I-R between adult and aged hearts. Old rats had lower pre-ischemic heart rate than adult rats, however, I-R caused no reduction of heart rate, and a smaller reduction of pressure-rate double product in the aged rats (10%, P>0.05) than the adult rats (23%, P<0.01). Aged rats demonstrated greater myocardial and plasma glutathione (GSH) concentrations prior to surgery, and maintained higher GSH levels and GSH:glutathione disulfide (GSSG) ratio with I-R. Aged hearts also had higher GSH peroxidase, GSH reductase and GSH sulfur-transferase activities than adult hearts, while I-R induced lipid peroxidation was similar. It is concluded that senescent hearts with intact circulatory and neural inputs are not more susceptible to I-R injury than adult hearts during myocardial I-R, partly because they have a greater GSH antioxidant protection.     

Effects of dietary nitrate on oxygen cost during exercise

Aim: Nitric oxide (NO), synthesized from l ‐arginine by NO synthases, plays a role in adaptation to physical exercise by modulating blood flow, muscular contraction and glucose uptake and in the control of cellular respiration. Recent studies show that NO can be formed in vivo also from the reduction of inorganic nitrate (NO₃^?) and nitrite (NO₂^?). The diet constitutes a major source of nitrate, and vegetables are particularly rich in this anion. The aim of this study was to investigate if dietary nitrate had any effect on metabolic and circulatory parameters during exercise. Method: In a randomized double‐blind placebo‐controlled crossover study, we tested the effect of dietary nitrate on physiological and metabolic parameters during exercise. Nine healthy young well‐trained men performed submaximal and maximal work tests on a cycle ergometer after two separate 3‐day periods of dietary supplementation with sodium nitrate (0.1 mmol kg^?1 day?1) or an equal amount of sodium chloride (placebo). Results: The oxygen cost at submaximal exercise was reduced after nitrate supplementation compared with placebo. On an average Vo ₂ decreased from 2.98 ± 0.57 during CON to 2.82 ± 0.58 L min^?1 during NIT (P < 0.02) over the four lowest submaximal work rates. Gross efficiency increased from 19.7 ± 1.6 during CON to 21.1 ± 1.3% during NIT (P < 0.01) over the four lowest work rates. There was no difference in heart rate, lactate [Hla], ventilation (VE), VE/Vo ₂ or respiratory exchange ratio between nitrate and placebo during any of the submaximal work rates. Conclusion: We conclude that dietary nitrate supplementation, in an amount achievable through a diet rich in vegetables, results in a lower oxygen demand during submaximal work. This highly surprising effect occurred without an accompanying increase in lactate concentration, indicating that the energy production had become more efficient. The mechanism of action needs to be clarified but a likely first step is the in vivo reduction of dietary nitrate into bioactive nitrogen oxides including nitrite and NO.     

Maternal antioxidant treatments prevent diabetes-induced alterations of mitochondrial morphology in rat embryos

Previous studies have suggested that production of reactive oxygen species by embryonic mitochondria may have a role in the induction of both high-amplitude mitochondrial swelling and embryonic dysmorphogenesis in diabetic pregnancy. The present study analyzed the relationships between a putative metabolite-induced production of free oxygen radicals, mitochondrial lipid peroxidation, and high-amplitude mitochondrial swelling in embryos during organogenesis. For studies in vitro, day 9 embryos of normal rats were cultured for 48 h with a high concentration of glucose in the absence or presence of α-cyano-4-hydroxycinnamic acid (CHC), a mitochondrial pyruvate transport inhibitor. The morphology of mitochondria in the neuroepithelium of the embryos was studied with the aid of transmission electron microscopy. For studies in vivo, normal and diabetic pregnant rats were fed a diet supplemented with the antioxidants α-tocopherol (vitamin E) or 2,6-di-tert-butyl-4-methylphenol (BHT), and the ultrastructure of mitochondria in the embryonic neuroepithelium and in the visceral yolk sac was investigated on gestational day 11. Exposure to a high concentration of glucose in vitro or to maternal diabetes in vivo induced high-amplitude swelling of mitochondria in the neuroepithelium of the embryos. The swelling of mitochondria was prevented by addition of CHC to the culture media or by maternal ingestion of antioxidant-supplemented food. In diabetic pregnancy, embryonic mitochondria during organogenesis produce free oxygen radicals that cause mitochondrial lipid peroxidation and swelling and furthermore embryonic dysmorphogenesis. Dietary supplementation with antioxidants to the mother may prevent embryonic malformations in diabetic pregnancy by inhibition of mitochondrial dysfunction. Anat. Rec. 251:303–315, 1998. © 1998 Wiley-Liss, Inc.     

脂质过氧化在老化大鼠急性胆源性肝细胞线粒体损害中的作用及维生素E的影响

目的：探讨脂质过氧化在老化大鼠胆源性肝细胞线粒体受损中及维生素Ｅ（ＶＥ）的保护作用。结果：老化大鼠非ＶＥ处理组（ＮＶＥＧ）肝细胞线粒体丙二醛（ＭＤＡ）含量明显高于非老化组，超氧化物歧化酶（ＳＯＤ）和谷胱甘肽过氧化物酶（ＧＰＤ）活性明显低于非老化组，过氧化氢酶（ＣＡＴ）无明显变化。１８和２４月龄ＶＥ处理组（ＶＥＧ）ＭＤＡ显著低于ＮＶＥＧ，ＳＯＤ和ＧＰＤ显著高于ＮＶＥＧ，并以１８月龄组为明显。急性梗阻性左肝胆管炎（ＡＯＬＨ）后ＭＤＡ水平明显高于对照组，间接致伤肝叶（ＩＡＬ）较直接致伤肝叶（ＤＡＬ）为明显；ＩＡＬ线粒体ＳＯＤ和ＣＡＴ活性均显著高于对照组，ＤＡＬ显著降低；各叶ＧＰＤ活性均显著低于对照组，ＩＡＬ和ＤＡＬ均无显著差别；以上改变以２４月龄组为明显。各月龄ＶＥＧＡＯＬＨ２４ｈ时ＩＡＬＭＤＡ含量明显低于ＮＶＥＧ；１８月龄ＶＥＧＡＯＬＨ后ＳＯＤ水平均明显高于ＮＶＥＧ；各月龄ＶＥＧ组ＡＯＰＨ后ＧＰＤ和ＣＡＴ活性与ＮＶＥＧ比较均无明显差异。结论：脂质过氧化是老化大鼠胆源性肝细胞线粒体受损的重要机制，ＶＥ具有明显的保护作用。     

Oxidative stress in leukocytes from young prematurely aging mice is reversed by supplementation with biscuits rich in antioxidants

Aging is associated with a progressive dysregulation of immune responses as a result of increased oxidative stress. Therefore, we have assessed the oxidative stress status of peritoneal leukocytes from young prematurely aging mice (PAM) as compared with non-prematurely aging mice (NPAM), as well as the effects on this oxidative stress of a dietary supplementation with biscuits rich in antioxidants (vitamin C, vitamin E, beta-carotenes, zinc and selenium). We found that, in the peritoneal leukocytes, the levels of several parameters of oxidation such as extracellular superoxide anion (O(2)(-)), Prostaglandin E(2) (PGE(2)), nitric oxide, oxidized glutathione (GSSG) and lipid peroxidation (malondialdehyde, MDA) were higher in PAM as compared with NPAM, whereas the antioxidant defences such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities, as well as reduced glutathione (GSH) levels, were decreased. Consequently, young PAM showed an oxidative stress in their leukocytes, which is characteristic of mice of an older chronological age. Antioxidant diet supplementation was able to restore redox homeostasis, increasing the antioxidant and decreasing the oxidant levels. Accordingly, supplementation with adequate levels of antioxidants, from an early age, could be useful to preserve health, especially in prematurely aging populations.     

Cardioprotective effect of Sida rhomboidea. Roxb extract against isoproterenol induced myocardial necrosis in rats

The present study investigates cardioprotective effect of Sida rhomboidea. Roxb (SR) extract on heart weight, plasma lipid profile, plasma marker enzymes, lipid peroxidation, endogenous enzymatic and non-enzymatic antioxidants and membrane bound ATPases against isoproterenol (IP) induced myocardial necrosis (MN) in rats. Rats treated with IP (85 mg/kg, s.c.) recorded significant (p<0.05) increment in heart weight, plasma lipid profile, plasma marker enzymes of cardiac damage, cardiac lipid peroxidation (LPO) and activity levels of Ca⁺² ATPase whereas there was significant (p<0.05) decrease in plasma HDL, cardiac endogenous enzymatic and non-enzymatic antioxidants, Na⁺-K⁺ ATPase and Mg⁺² ATPase. Pre-treatment with SR extract (400 mg/kg per day, p.o.) for 30 consecutive days followed by IP injections on days 29th and 30th, showed significant (p<0.05) decrease in heart weight, plasma lipid profile, plasma marker enzymes of cardiac damage, cardiac lipid peroxidation, Ca⁺² ATPase and significant increase in plasma HDL, cardiac endogenous enzymatic and non-enzymatic antioxidants, Na⁺-K⁺ ATPase and Mg⁺² ATPase compared to IP treated group. Hence, this study is the first scientific report on cardioprotective effect of SR against IP induced MN in rats.     

Spontaneous mutation frequency and pattern in Big Blue mice fed a vitamin E-supplemented diet.

Endogenous oxidative DNA damage caused by normal cellular processes may play a vital role in carcinogenesis. To directly test the hypothesis that antioxidants will protect DNA from oxidative damage in vivo, Big Blue((R)) mice were fed either a control diet (66 IU vitamin E/kg diet) or a high-dose vitamin E diet containing 1000 IU vitamin E/kg diet of racemic d,l-alpha-tocopherol acetate from conception until 3 months of age. Using the standard Big Blue((R)) protocol, 15.5 million plaque forming units (pfu) were examined from five tissues (heart, liver, adipose tissue, thymus, and testis) of three control and three high-dose vitamin E supplemented male mice generating 433 mutants, which represented 373 independent mutations upon sequencing the lacI transgene. The alpha-tocopherol tissue concentration increased with high-dose vitamin E supplementation. In four of the tissues, individually or combined, mutation frequency changed little if any with vitamin E supplementation. In adipose tissue, which accumulated the highest levels of vitamin E, mutation frequency was significantly reduced with high-dose vitamin E supplementation (P = 0.047). Within the constraints of sample size, the pattern of mutation in adipose tissue was not altered significantly (P = 0.40). When data from all tissues were combined, a reduction in G:C --> T:A transversions was observed (P = 0.044). These results may have implications for cancer chemoprevention and provide insight into the efficacy of vitamin E supplementation in reducing spontaneous oxidative DNA damage in vivo. More dramatic alterations of mutation frequency and pattern may be observed with higher doses of vitamin E and substitution of the racemic supplement with d-alpha-tocopherol acetate.     

Relation of types of dietary fat to cardiovascular damage in mice

Nine edible oils or fats (hydrogenated coconut, cod liver, Wesson, linseed, olive, butter, lard, corn and cocoa-butter) were fed for 50–90 days to study the relation of saturation, chain length and essential fatty acid content to production of cardiovascular lesions. The specific oil or fat (selected for ranges in the above variables) was used as the dietary lipid in a high-fat (28%), low-protein (8%), hypolipotropic diet. Half of the animals received identical diets containing choline chloride (2 gm/100 gm of diet) as a lipotropic supplement. Atrial mural thrombosis and ventricular myocardial necrosis and calcification developed in all dietary groups. Atrial thrombosis was the most frequent lesion. The greatest incidence of atrial thrombosis occurred in mice fed the choline-deficient, butter-containing diet (92%) and the lowest incidence with the supplemented cod liver oil diet (20%). The diet containing unsupplemented hydrogenated coconut oil produced the greatest incidence of ventricular necrosis (79%) and that with choline-supplemented cocoa-butter the lowest (8%). Ventricular calcification was most extensive within the unsupplemented cod liver oil group (83%), most limited in the supplemented lard group (5%). In general, choline-supplemented diets produced a lower incidence of cardiac damage. Little correlation existed between the composition and characteristics of specific fats and their activity in producing the specific cardiac lesions observed here.     

Clerodendron glandulosum.Coleb leaf extract attenuates in vitro macrophage differentiation and expression of VCAM-1 and P-selectin in thoracic aorta of atherogenic diet fed rats

Present inventory evaluates the anti-atherogenic potential of C. glandulosum.Coleb leaf extract (CG) using in vivo and in vitro experimental models. Serum markers of low density lipoprotein (LDL-C) oxidation, cholesterol, triglycerides, lipoproteins, auto-antibody titer, ex vivo LDL-C oxidation, LDL-C aggregation, aortic lipids, histopathological evaluations and immunolocalization of macrophage surface marker (F4/80), vascular cell adhesion molecule-1 (VCAM-1) and P-selectin were performed in CON [rats treated with single dose of saline (i.p.) and fed with laboratory chow], ATH [rats treated with single dose of vitamin D3 (600,000 IU, i.p) and fed with atherogenic diet] and ATH+CG [rats treated with single dose of vitamin D3 (600,000 IU, i.p.) and fed with atherogenic diet and simultaneously treated with 200?mg/kg CG extract, p.o.] for 8 weeks. CG extract supplementation to atherogenic diet fed rats significantly prevented increment in serum cholesterol, triglycerides, and lipoproteins, markers of LDL-C oxidation, auto-antibody titer and aortic lipids. Also, LDL-C isolated from ATH+CG rats recorded mimimal aggregation and susceptibility to undergo ex vivo LDL-C oxidation. Microscopic evaluation of thoracic aorta of ATH+CG rats reveled prevention of atheromatous plaque formation, accumulation of lipid laden macrophages, calcium deposition, distortion/defragmentation of elastin, accumulation of macrophages and, down regulation of cell adhesion molecules (VCAM-1 and P-selectin) expression. Further, in vitro monocyte to macrophage differentiation was significantly attenuated in presence of CG extract (200 μg/mL). It can be concluded from the present study that, CG extract is capable of controlling induction of experimental atherosclerosis and warrants further scrutiny at the clinical level as a possible therapeutic agent.     

Sida rhomboidea.Roxb extract alleviates pathophysiological changes in experimental in vivo and in vitro models of high fat diet/fatty acid induced non-alcoholic steatohepatitis

The present study was aim to evaluate protective role of Sida rhomboidea.Roxb (SR) extract against high fat diet/fatty acid induced pathophysiological alterations in experimental model of non-alcoholic steatohepatitis (NASH). Effect of SR extract on plasma levels of markers of hepatic damage, plasma and hepatic lipids, mitochondrial oxidative stress, status of enzymatic and non-enzymatic antioxidants and histopathological changes in liver tissue were evaluated in high fat diet fed C57BL/6J mice. Also, the effect of SR supplementation on lipid accumulation, lipid peroxidation, cytotoxicity and cell viability were evaluated in oleic acid treated HepG2 cells. Supplementation of NASH mice with SR extract prevented high fat diet induced elevation in plasma marker enzymes of liver damage, plasma and hepatic lipids, mitochondrial oxidative stress and compromised enzymatic and non-enzymatic antioxidant status. Further, addition of SR extract to in vitro HepG2 cells minimized oleic acid induced lipid accumulation, higher lipid peroxidation, cytotoxicity and reduced cell viability. These in vivo and in vitro studies suggest that SR extract has the potential of preventing high fat/fatty acid induced NASH mainly due to its hypolipidemic and antioxidant activities.     

Cardioprotective effect of resveratrol on atherogenic diet-fed rats

Atherogenic or high fat diets were known to induce cardiovascular diseases, and several active compounds were tested to protect/prevent the risk of cardiovascular diseases. We aimed to investigate the cardio protective effect of resveratrol against atherogenic diet fed rats. Male Wistar rats were administered atherogenic diet for 30 days and further continued for 15 days with or with resveratrol in the diet. The serum lipid profile, antioxidant enzyme activity, lipid peroxidation, lipid metabolic proteins and cardiac tissue markers were examined. The histopathology of myocardium and aorta were also examined. The abnormal serum lipid profile found in atherogenic rats was reversed by the administration of resveratrol. Similarly, the enzymatic (catalase, superoxide dismutase, glutathione-peroxidase), non-enzymatic (reduced-glutathione, Vitamin C, E) antioxidants were improved by the resveratrol fed against atherogenic diet. Interestingly, resveratrol activated the lipid metabolic proteins (SIRT1, eNOS and AMPKa), suggesting its protective effect on lipid metabolism. Further analysis on tissue damage revealed that resveratrol had significantly protected the tissue damage and maintains the morphology of cardiac tissue. Altogether, our results suggest that resveratrol played a significant role in the prevention of cardiovascular system against the high fat diet. Emphasising the anti-atherogenic property of resveratrol, we propose resveratrol as a potential compound to be consumed for the healthy life-style.     

Disorders of fatty acid composition and the processes of lipid peroxidation in chronic ischemic heart disease

The levels of lipid fractions, free and bound fatty acids, initial and end lipid peroxidation products in the blood plasma, red cell membrane resistance to hemolysis, and myocardial contractility before, during, and after therapy with lipostabil forte (0.6-1.8 g daily or 10 ml (0.5 g) i.v.) and bezafibrate (0.2 g 3 times daily) along with nitrates (10 to 30 tablets) have been examined by the routine methods in 159 patients with stable angina pectoris and postinfarction cardiosclerosis. A negative effect of high doses of nitrates on myocardial hemodynamics and fatty acid composition has been revealed, resulting in accumulation of bound fatty acids. Lipostabil has improved the patients' status, myocardial function, and lipid composition, reduced the levels of atherogenic lipids and lipid peroxidation products, as well as the concentration of fatty acids with an uneven number of C atoms, increased the fatty acid nonsaturation index and the level of medium-strand fatty acids. Improvement of the patient's condition in bezafibrate therapy has been less evident; the concentration of atherogenic lipids has been reduced, but the levels of bound fatty acids and of lipid peroxidation products has increased. Bezafibrate is recommended to be administered together with antioxidants.     

Improved performance in commercial broiler flocks with subclinical infectious bursal disease when fed diets containing increased concentrations of vitamin E

The economic effects of increased vitamin E supplementation in 79 commercial broiler flocks incorporating over 1.5 million birds was assessed. Approximately half of the flocks were fed on either a high (178 IU/kg) or normal (48 IU/kg) vitamin E-containing diet. In addition, in approximately half of the flocks subclinical infectious bursal disease (IBD) was present. Analysis of the performance data demonstrated that flocks with subclinical IBD were consistently worse (P< 0.001) for net income, feed conversion ratio and average weight per bird than flocks without the subclinical disease. The trial also indicated that the average net income of flocks with subclinical IBD and fed a high vitamin E-containing diet was 10% better (P < 0.05) than flocks with subclinical IBD and fed a normal vitamin E-containing diet. However, the trial also demonstrated that the difference between the average net income achieved by flocks without subclinical IBD and being fed on either a high or a normal vitamin E-containing diet was only 2% and not significantly different. It is suggested that the increased improved performance from high vitamin E-containing diets recorded in flocks with subclinical IBS is due to enhanced immunocompetence and increased resistance to disease. It is also suggested that under field conditions, high dietary inputs of vitamin E are most beneficial where there is a challenge to the host's defence system and significantly improved performance will occur more predictably under such conditions.     

Diet as a risk factor for atopy and asthma

It has been hypothesized that decreasing antioxidant (fruit and vegetables), increased n-6 polyunsaturated fatty acid (PUFA; (margarine, vegetable oil), and decreased n-3 PUFA (oily fish) intakes have contributed to the recent increases in asthma and atopic disease. Epidemiologic studies in adults and children have reported beneficial associations between dietary antioxidants and lipids and parameters of asthma and atopic disease. The associations with n-6 and n-3 PUFA appear to be very complex and might differ between asthma and atopic dermatitis. Dietary antioxidants are probably exerting antioxidant and nonantioxidant immunomodulatory effects. Dietary lipids exert numerous complex effects on proinflammatory and immunologic pathways. It has also been suggested that atopic dermatitis is associated with an enzyme defect in lipid metabolism. In spite of this, the results of interventional supplementation studies in established disease have been disappointing, and there is now increasing interest in the possibility that dietary antioxidant and lipid intakes might be important in determining expression of disease during pregnancy and early childhood and that dietary interventions should be targeted at these groups. It also seems likely that there is individual variation in the responses of individuals to lipid, and probably antioxidant, supplementation. Further research to determine whether dietary intervention can reduce the risk of asthma and atopic disease is justified.     

Dietary tyrosine benefits cognitive and psychomotor performance during body cooling

Supplemental tyrosine is effective at limiting cold-induced decreases in working memory, presumably by augmenting brain catecholamine levels, since tyrosine is a precursor for catecholamine synthesis. The effectiveness of tyrosine for preventing cold-induced decreases in physical performance has not been examined. This study evaluated the effect of tyrosine supplementation on cognitive, psychomotor, and physical performance following a cold water immersion protocol that lowered body core temperature. Fifteen subjects completed a control trial (CON) in warm (35 degrees C) water and two cold water trials, each spaced a week apart. Subjects ingested an energy bar during each trial; on one cold trial (TYR) the bar contained tyrosine (300 mg/kg body weight), and on the other cold trial (PLB) and on CON the bar contained no tyrosine. Following each water immersion, subjects completed a battery of performance tasks in a cold air (10 degrees C) chamber. Core temperature was lower (p=0.0001) on PLB and TYR (both 35.5+/-0.6 degrees C) than CON (37.1+/-0.3 degrees C). On PLB, performance on a Match-to-Sample task decreased 18% (p=0.02) and marksmanship performance decreased 14% (p=0.002), compared to CON, but there was no difference between TYR and CON. Step test performance decreased by 11% (p=0.0001) on both cold trials, compared to CON. These data support previous findings that dietary tyrosine supplementation is effective for mitigating cold-induced cognitive performance such as working memory, even with reduced core temperature, and extends those findings to include the psychomotor task of marksmanship.     

Novel functional foods for optimal oxidative status in healthy ageing

An antioxidant-rich diet has been shown to reduce the incidence of diet-induced metabolic diseases, such as obesity, diabetes and cardiovascular conditions, and contributes to healthy ageing. Yet, clinical trials investigating common dietary antioxidants, such as vitamins, have often failed to find a significant lowering effect on markers of oxidative stress. This review examines the latest clinical evidence on whether three novel potential antioxidant foods—fish omega-3 fatty acids, red wine and dairy products—can affect the oxidative status of healthy individuals. Clinical studies have reported heterogeneous results regarding the effect of fish oil, red wine and dairy products on oxidative stress. However, numerous studies have suggested that omega-3, red wine and dairy products may lower lipid peroxidation, a known trigger of cardiovascular disease, without affecting the oxidative status of healthy individuals. Overall, this review suggests that consumption of 1–2 g/day of omega-3, a moderate red wine intake (200–400 ml/day) or 2–3 portions/day of dairy products within a healthy diet exert beneficial effects on oxidative markers. Further investigation to ascertain these effects should focus on the antioxidant effects of long-term omega-3 supplementation, and of intake of dealcoholized red wine or higher dairy product consumption.     

Biphasic modulation of atherosclerosis induced by graded dietary copper supplementation in the cholesterol-fed rabbit

There has been considerable debate about how copper status may affect the biochemical and cellular processes associated with atherogenesis. We have investigated the effects of graded dietary copper supplementation on processes likely to contribute to atherogenesis, using the cholesterol-fed New Zealand White rabbit model. Rabbits (n = 40) were fed a 0.25-1% cholesterol diet deficient in copper. Animals received either 0, 1, 3 or 20 mg copper/day and were killed after 13 weeks. Plasma cholesterol levels were similar in each dietary group. Aortic concentrations of copper were higher in the 20 mg copper/day animals compared to those receiving 0 mg copper/day (3.70 +/- 0.78 vs. 1.33 +/- 0.46 microg/g wet tissue; P < 0.05). Aortic superoxide dismutase activity was higher in animals receiving 20 mg copper/day (323 +/- 21 IU/mg tissue) compared to the other groups (187 +/- 21; 239 +/- 53; 201 +/- 33 IU/mg tissue) (P > 0.05). En face staining of aortae with oil red O showed that both high copper supplementation (20 mg/day) (67.1 +/- 5.5%) and a deficient diet (0 mg/day) (63.1 +/- 4.8%) was associated with significantly larger lesions (P < 0.05) compared to moderately supplemented animals (1 mg/day and 3 mg/day) (51.3 +/- 6.3 and 42.8 +/- 7.9%). These data indicate that in the cholesterol-fed rabbit, there is an optimal dietary copper intake and that dietary copper deficiency or excess are associated with an increased susceptibility to aortic atherosclerosis. Many Western diets contain insufficient copper and these findings indicate that a moderate dietary copper content may confer a degree of cardiac protection to the human population.