Life Extension Final Clerance Sale

ANTIOXIDANTS



Table of Contents
image Rationales for micronutrient supplementation in diabetes
image Contraction and relaxation of aortas from diabetic rats: effects of chronic anti-oxidant and aminoguanidine treatments.
image Antioxidant vitamins in hospitalized elderly patients: Analysed dietary intakes and biochemical status
image Antioxidant depletion, lipid peroxidation, and impairment of calcium transport induced by air-blast overpressure in rat lungs
image The use of antioxidants in healing
image Update on the biological characteristics of the antioxidant micronutrients: vitamin C, vitamin E, and the carotenoids.
image Dietary intake and plasma levels of antioxidant vitamins in health and disease: A hospital-based case-control study
image Supplementation with vitamins C and E suppresses leukocyte oxygen free radical production in patients with myocardial infarction
image Antioxidant therapy using high dose vitamin C: Reduction of postburn resuscitation fluid volume requirements
image Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise
image Modification of the daily photoreceptor membrane shedding response in vitro by antioxidants
image Tirilazad mesylate protects vitamins C and E in brain ischemia-reperfusion injury
image Biochemical basis of ozone toxicity
image Decreases in tissue levels of ubiquinol-9 and -10, ascorbate and alpha-tocopherol following spinal cord impact trauma in rats
image An in vitro model to test relative antioxidant potential: Ultraviolet-induced lipid peroxidation in liposomes
image Antioxidants, fat and skin cancer
image Photoprotective effect of superoxide scavenging antioxidants against ultraviolet radiation-induced chronic skin damage in the hairless mouse
image Impairment of enzymic and nonenzymic antioxidants in skin by UVB irradiation
image Diminished production of malondialdehyde after carotid artery surgery as a result of vitamin administration
image Spermine partially normalizes in vivo antioxidant defense potential in certain brain regions in transiently hypoperfused rat brain
image Positron-labeled antioxidant 6-deoxy-6-(18F)fluoro-L-ascorbic acid: Increased uptake in transient global ischemic rat brain
image Maternal infusion of antioxidants (Trolox and ascorbic acid) protects the fetal heart in rabbit fetal hypoxia
image Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke: Basel Prospective Study
image Antioxidant vitamins and disease - Risks of a suboptimal supply
image Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: An epidemiological update with special attention to carotene and vitamin C
image Oxidative protein damage in human diabetic eye: evidnal participation.
image Abnormalities in diabetes or experimental galactosemia. IV. Antioxidant defense system.
image Nutritional antioxidants, red cell membrane fluidity and blood viscosity in type 1 (insulin dependent) diabetes mellitus.
image [Prospective biochemical study of the antioxidant defense capacity in retinopathy of premokemiai vizsgalata retinopathia preamaturorumban.
image [Antioxidants for prophylaxis of eye diseases]
image [Erythrocyte and plasma antioxidant activity in diabetes mellitus type I]
image Oxidative protein damage in human diabetic eye: Evidence of a retinal participation
image Abnormalities of retinal metabolism in diabetes or experimental galactosemia. III. Effects of antioxidants
image Oxidative stress and diabetic vascular complications
image Pharmacological prevention of diabetic microangiopathy
image Erythrocyte and plasma antioxidant activity in type I diabetes mellitus
image Status of antioxidants in patients with diabetes mellitus with and without late complications
image Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants.
image Role of oxidant stress in the adult respiratory distress syndrome: evaluation of a novel antioxidant strategy in a porcine model of endotoxin-induced acute lung injury.
image Prevention of dopamine-induced cell death by thiol antioxidants: possible implications for treatment of Parkinson's disease.
image [The dose-dependent effects of a combination of different classes of antioxidants exemplified by dibunol and beta-carotene]
image Oxidative damage and defense.
image The effect of dietary fat, antioxidants, and pro-oxidants on blood lipids, lipoproteins, and atherosclerosis.
image Reliability of a food frequency questionnaire to assess dietary antioxidant intake.
image Dietary antioxidants and Parkinson disease. The Rotterdam Study.
image Association of serum vitamin levels, LDL susceptibility to oxidation, and autoantibodies against MDA-LDL with carotid atherosclerosis. A case-control study. The ARIC Study Investigators. Atherosclerosis Risk in Communities.
image Antioxidant flavonols and ischemic heart disease in a Welsh population of men: the Caerphilly Study.
image [Prevalence and risk factors in the population of Graz (Austrian Stroke Prevention Study)]
image Beta-2-agonists have antioxidant function in vitro. 2. The effect of beta-2-agonists on oxidant-mediated cytotoxicity and on superoxide anion generated by human polymorphonuclear leukocytes.
image Antioxidants in the prevention of atherosclerosis.
image Bronchial reactivity and dietary antioxidants.
image Antioxidant actions of beta-carotene in liposomal and microsomal membranes: role of carotenoid-membrane incorporation and alpha-tocopherol.
image [Alcohol and free radicals: from basic research to clinical prospects]
image Oxidized low-density lipoprotein and atherosclerosis.
image Serum levels of antioxidant vitamins in relation to coronary artery disease: a case control study of Koreans.
image Antioxidants in food and chronic degenerative diseases.
image Randomized trials of dietary antioxidants in cardiovascular disease prevention and treatment.
image Basic research in antioxidant inhibition of steps in atherogenesis.
image Oxidative susceptibility of low-density lipoproteins--influence of regular alcohol use.
image Do hydroxy-carotenoids prevent coronary heart disease? A comparison between Belfast and Toulouse.
image Antioxidants in cardiovascular disease: randomized trials.
image Randomized trial of antioxidants in the primary prevention of Alzheimer disease warranted?
image Lipid peroxidation and antioxidant vitamins C and E in hypertensive patients.
image Update on dietary antioxidants and cancer.
image Antioxidants in health and disease
image Multicenter ophthalmic and nutritional age-related macular degeneration study--part 2: antioxidant intervention and conclusions.
image Multicenter ophthalmic and nutritional age-related macular degeneration study--part 1: design, subjects and procedures.
image Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis?
image The role of oxidized lipoproteins in atherogenesis.
image [Bronchopulmonary dysplasia]
image Oxidative stress as a mechanism of cardiac failure in chronic volume overload in canine model.
image [The significance of oxidized low density lipoprotein in atherosclerosis]
image In vivo antioxidant treatment suppresses nuclear factor-kappa B activation and neutrophilic lung inflammation.
image Antioxidants and age-related eye disease. Current and future perspectives.
image [Free radicals in the central nervous system]
image Protection by multiple antioxidants against lipid peroxidation in rat liver homogenate.
image Inhibition of Ca2+-pump ATPase and the Na+/K+-pump ATPase by iron-generated free radicals. Protection by 6,7-dimethyl-2,4-DI-1-pyrrolidinyl-7H-pyrrolo[2,3-d] pyrimidine sulfate (U-89843D), a potent, novel, antioxidant/free radical scavenger.
image Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women
image Oxidative stress and antioxidant therapy in Parkinson's disease
image In vivo generation of hydroxyl radicals and MPTP-induced dopaminergic toxicity in the basal ganglia.
image Antioxidant mechanism and protection of nigral neurons against MPP+ toxicity by deprenyl (selegiline)
image Parkinson's disease: a chronic, low-grade antioxidant deficiency?
image Free radicals in brain metabolism and pathology.
image Free radicals and their scavengers in Parkinson's disease.
image Role of dietary lipid and antioxidants in bone metabolism
image [Preventive treatment of diabetic microangiopathy: blocking the pathogenic mechanisms]
image COSMETICS -- Marketing
image Measurement of low-molecular-weight antioxidants, uric acid, tyrosine and tryptophan in plaques and white matter from patients with multiple sclerosis.
image On the causes of multiple sclerosis
image Alpha-tocopherol and hydroperoxide content in breast adipose tissue from patients with breast tumors.
image Interaction of family history of breast cancer and dietary antioxidants with breast cancer risk (New York, United States)
image Extraocular, limb and diaphragm muscle group-specific antioxidant enzyme activity patterns in control and mdx mice.
image Free radicals, lipid peroxides and antioxidants in blood of patients ith myotonic dystrophy.
image Antioxidants and angiogenetic factor associated with age-related macular degeneration (exudative type)
image Studies on the mechanism of early onset macular degeneration in c ynomolgus monkeys. II. Suppression of metallothionein synthesis in the retina in oxidative stress
image Association of zinc and antioxidant nutrients with age-related maculopathy.
image Antioxidant enzymes of the human retina: Effect of age on enzyme activity of macula and periphery
image Antioxidant enzymes in RBCs as a biological index of age related macular degeneration
image Antioxidant defenses in metal-induced liver damage
image Antioxidant status in controlled and uncontrolled hypertension and its relationship to endothelial damage.
image The role of antioxidants in the prevention of cardiovascular diseases
image Essential antioxidants in cardiovascular diseases--lessons for Europe
image Antioxidant vitamin intake and coronary mortality in a longitudinal population study.
image Can anti-oxidants prevent ischaemic heart disease?
image Antioxidant therapy in the aging process.
image Anti-oxidants show an anti-hypertensive effect in diabetic and hypertensive subjects.
image Micronutrient profiles in HIV-1-infected heterosexual adults
image Antioxidant-micronutrients and HIV infection
image Can antioxidants prevent ischemic heart disease?
image Antioxidant therapy in the aging process.
image Acute phase response and plasma carotenoid concentrations in older women: Findings from the nun study.
image Endothelial dysfunction: Clinical implications.
image Use of antioxidant vitamins in the cardiovascular disease. A review of epidemiological study and clinical trials.
image The effect of dietary treatment on lipid peroxidation and antioxidant status in newly diagnosed noninsulin dependent diabetes.
image Smoking, plasma antioxidants and essential fatty acids before and after nutratherapy.
image Reduction of plasma peroxide levels by oral antioxidants.
image Systemic oxidative stress in asthma, COPD, and smokers
image Role of oxidants/antioxidants in smoking-induced lung diseases
image Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus
image Spice constituents scavenging free radicals and inhibiting pentosidine formation in a model system.
image Potential therapeutic approaches to the treatment or prevention of diabetic neuropathy: evidence from experimental studies.
image Prevention of postischemic cardiac injury by the orally active iron chelator 1,2-dimethyl-3-hydroxy-4-pyridone (L1) and the antioxidant (+)-cyanidanol-3
image Iron-load increases the susceptibility of rat hearts to oxygen reperfusion damage. Protection by the antioxidant (+)-cyanidanol-3 and deferoxamine
image Nutritional antioxidants and the modulation of inflammation: theory and practice.
image Antioxidant vitamins in cataract prevention.
image Free radical tissue damage: protective role of antioxidant nutrients.
image Free radical tissue damage: protective role of antioxidant nutrients.
image [Antioxidative vitamins and cataracts in the elderly]
image Prevention of cataracts by nutritional and metabolic antioxidants.
image Free radicals, exercise, and antioxidant supplementation
image Fibronectin fragment mediated cartilage chondrolysis. I. Suppression by anti-oxidants
image Overview of conditioning related life-threatening toxicities of marrow transplantation
image [Cardioprotection in chemo- and radiotherapy for malignant diseases--an echocardiographic pilot study]
image Place of antioxidants in active photoprotection
image Indicators of free radical activity in patients developing radiation pneumonitis
image The effect of antioxidants on bleomycin treatment in in vitro and in vivo genotoxicity assays
image Serum concentrations of alpha tocopherol, beta carotene, and retinol preceding the diagnosis of rheumatoid arthritis and systemic lupus erythematosus.
image Free radical tissue damages in the anterior segment of the eye in experimental autoimmune uveitis
image Intervention at diagnosis of type I diabetes using either antioxidants or photopheresis
image Free radical theory of aging: Beneficial effect of antioxidants on the life span of male NZB mice: Role of free radical reactions in the deterioration of the immune system with age and in the pathogenesis of systemic lupus erythematosus
image Reduced superoxide dismutase in lung cells of patients with asthma
image Antioxidant protection against adrenaline-induced arrhythmias in rats with chronic heart hypertrophy.
image The effects of antioxidants on reperfusion dysrhythmias
image [Essential antioxidants in cardiovascular diseases--lessons for Europe]
image Muscle ubiquinone and plasma antioxidants in effort angina
image Effect of antioxidants on postoperative hyperamylasemia in coronary bypass surgery
image Antioxidant depletion during aortic aneurysm repair
image Free radical reaction products and antioxidant capacity in arterial plasma during coronary artery bypass grafting
image Evaluation of antioxidants, protein, and lipid oxidation products in blood from sporadic amiotrophic lateral sclerosis patients.
image Antioxidants in peripheral nerve.
image Free Radicals and Neuroprotection
image Role of oxidative stress and antioxidant therapy in alcoholic and nonalcoholic liver diseases.
image Experience over 17 years with antioxidant treatment in Spielmeyer-Sjogren disease.
image Antioxidant of the coronary diet and disease
image Enhanced capacity of n-3 fatty acid-enriched macrophages to oxidize low density lipoprotein mechanisms and effects of antioxidant vitamins
image The mechanism of apolipoprotein B-100 thiol depletion during oxidative modification of low-density lipoprotein
image Polyunsaturated fatty acids, antioxidants, and cognitive function in very old men
image Animal studies on antioxidants
image Abnormal antioxidant vitamin and carotenoid status in chronic renal failure
image Antioxidants in cardiovascular disease: Randomized trials
image Dietary antioxidants and cognitive function in a population-based sample of older persons: The Rotterdam study
image Oxidized low density lipoproteins in atherogenesis: Role of dietary modification
image Antioxydant vitamins and risk of cardiovascular diseases
image The significance of oxidised low-density lipoprotein in atherosclerosis
image Prevention of atherosclerosis with dietary antioxidants: Fact or fiction?
image Randomized, controlled trial of antioxidant vitamins and cardioprotective diet on hyperlipidemia, oxidative stress, and development of experimental atherosclerosis: The diet and antioxidant trial on atherosclerosis (DATA)
image Optimal diet for reducing the risk of arteriosclerosis
image Prevention of atherosclerosis: The potential role of antioxidants
image Advanced glycation endproducts in ageing and Alzheimer's disease
image Molecular basis of Alzheimer's disease.
image New therapeutic approaches to Alzheimer's disease.
image A pilot study of blood antioxidant and free radical marker profiles in patients awaiting coronary artery bypass grafting
image Oxygen free radical-induced histamine release during intestinal ischemia and reperfusion
image Antioxidant drugs block in vitro the neurotoxicity of CSF from atients with amyotrophic lateral sclerosis
image The role of antioxidant agents on experimental ulcerative colitis
image Rutoside as mucosal protective in acetic acid-induced rat colitis
image Inhibitory effect of a traditional Chinese medicine, Juzen-taiho-to, on progressive growth of weakly malignant clone cells derived from murine fibrosarcoma.

bar



Antioxidant defenses in metal-induced liver damage

Seminars in Liver Disease (USA), 1996, 16/1 (39-46)

Recent investigations have begun to define more clearly the cellular and molecular roles of oxidant stress in mediating the liver injury and fibrosis of metal storage diseases. Because of a variety of perturbations in antioxidant homeostasis in iron and copper overload, restoring the antioxidant balance to normal, or even exceeding normal levels of selected antioxidants, may provide additional protection against liver injury and prevent the progression to fibrosis and cirrhosis. Inasmuch as GSH levels appear to be elevated in livers of experimentally iron-overloaded animals, attempts to increase this antioxidant should perhaps be limited to copper overload conditions in which hepatic GSH is low. Vitamin C (ascorbate) supplementation should probably be avoided in all metal overload states because of its potentiation of radical generation by transition metals. The safety of beta-carotene in alocholic liver disease has been questioned. Therefore, until more is known about its toxicity in metal overload, beta- carotene may not be an ideal antioxidant for clinical trials. Vitamin E and related compounds, therefore, appear to be the most reasonable antioxidants to test in metal overload states at this time. In the near future, the results of controlled clinical trials of the use of antioxidants in these and other liver disorders will hopefully provide clearer guidelines for their safety and possible use.



Antioxidant status in controlled and uncontrolled hypertension and its relationship to endothelial damage.

J Hum Hypertens (ENGLAND) Nov 1994, 8 (11) p843-9

Hypertension is associated with an increased risk of atherosclerosis. Free radical oxidative damage has been implicated in the atherogenic process. We measured levels of the antioxidants uric acid, thiols, vitamins C, A and E as well as the total antioxidant capacity in 21 normotensive controls, 22 patients whose hypertension was controlled on drugs and 30 patients with uncontrolled hypertension. Mean BPs in the groups were 125/76, 132/80 and 181/98 mmHg, respectively. When compared with controls, both hypertensive groups had significantly lower serum ascorbic acid (54 +/- 5 vs. 37 +/- 6 vs. 38 +/- 5 mumol/l, P < 0.05) and albumin-corrected thiol levels (9.91 +/- 0.18 vs. 8.69 +/- 0.20 vs. 8.92 +/- 0.19 mumol/g, P < 0.05). The levels of the other antioxidants did not differ significantly between the groups. Levels of von Willebrand factor, a marker of endothelial damage, were correlated with SBP but not with antioxidant status. We conclude that hypertensive subjects have lower levels of the antioxidants vitamin C and thiols and this may reflect greater oxidative consumption. The implications for atherogenesis and endothelial function and integrity in hypertension are discussed.



The role of antioxidants in the prevention of cardiovascular diseases

Bratisl Lek Listy (SLOVAKIA) May 1994, 95 (5) p199-211

The potential role of natural antioxidants (vitamin C--ascorbic acid, vitamin E--tocopherols, carotenoids and selenium) in the prevention of cardiovascular diseases is reviewed. It is probable that free oxygen radicals and oxidatively modified particles of low-density lipoproteins (LDL) participate in the development of atherosclerotic lesions. A great number of experimental, cross-sectional, retrospective and prospective epidemiological studies found a substantial increase of the risk of ischemic heart disease and stroke in individuals and populations with low intake of antioxidants from diet. Extremely high cardiovascular mortality in Slovakia and other postcommunist countries could be only partially explained by "classical" risk factors (hypertension, hypercholesterolemia and smoking). In the communist European countries there was a high consumption of spirits, cigarettes and salt, polluted environment and low consumption of the chief source of antioxidants--fruits. In these countries emphasis should be given to the prevention of antioxidant deficiencies by the increase of fruit and vegetable consumption, and to the decrease in salt, spirit, cigarettes and saturated fat consumption. (30 Refs.)



Essential antioxidants in cardiovascular diseases--lessons for Europe

Ther Umsch (SWITZERLAND) Jul 1994, 51 (7) p475-82

Complementary epidemiological studies consistently reveal a substantially increased risk of cardiovascular disease (CVD) at suboptimal plasma levels of essential antioxidants in comparison with optimum ranges of vitamin C (> 50 mumol/l), of lipid-standardized vitamin E (> 30 mumol/l or a tocopherol/cholesterol ratio > 5.2 mumol/mmol), beta-carotene (> 0.4 mumol/l). The poor level of any single essential antioxidant can increase the risk, and the combination of suboptimal levels has additive or even overmultiplicative effects on the risk for CVD. Suboptimal antioxidant levels are stronger predictors of the severalfold regional differences of CVD in Europe than classical risk factor such as hypercholesterolemia, hypertension, etc. Scotsmen and Fins tend to suboptimal levels of essential antioxidants, whereas German-speaking regions may mostly reveal a fair vitamin E status, but at least one out of four subjects can reveal suboptimal levels of vitamin C and carotene, particularly in smokers. This deficit can be avoided by 'prudent diets' rich in fruits and vegetables as practiced by Frenchmen, Italians and Spaniards. The simultaneous correction of all suboptimal antioxidant levels appears to be a promising new means for CVD prevention, particularly in the northern parts of Europe. In the USA the risk of CVD could substantially be reduced without dietary modifications by voluntary daily supplements as follows: vitamin C > 140 mg, vitamin E > 100 IU (100 mg d,l- or 74 mg d-alpha-tocopherylacetate), and in current smokers by gamma-carotene > 8.6 mg. Hence, these antioxidants may be crucial constituents of diets rich in fruits and vegetables, which are by consensus associated with a lower risk of premature death from CVD (and cancer as well).(ABSTRACT TRUNCATED AT 250 WORDS)



Antioxidant vitamin intake and coronary mortality in a longitudinal population study.

Am J Epidemiol (UNITED STATES) Jun 15 1994, 139 (12) p1180-9

Oxidation of lipoproteins is hypothesized to promote atherosclerosis and, thus, a high intake of antioxidant nutrients may protect against coronary heart disease. The relation between the intakes of dietary carotene, vitamin C, and vitamin E and the subsequent coronary mortality was studied in a cohort of 5,133 Finnish men and women aged 30-69 years and initially free from heart disease. Food consumption was estimated by the dietary history method covering the total habitual diet during the previous year. Altogether, 244 new fatal coronary heart disease cases occurred during a mean follow-up of 14 years beginning in 1966-1972. An inverse association was observed between dietary vitamin E intake and coronary mortality in both men and women with relative risks of 0.68 (p for trend = 0.01) and 0.35 (p for trend < 0.01), respectively, between the highest and lowest tertiles of the intake. Similar associations were observed for the dietary intake of vitamin C and carotenoids among women and for the intake of important food sources of these micronutrients, i.e., of vegetables and fruits, among both men and women. The associations were not attributable to confounding by major nondietary risk factors of coronary heart disease, i.e., age, smoking, serum cholesterol, hypertension, or relative weight. The results support the hypothesis that antioxidant vitamins protect against coronary heart disease, but it cannot be excluded that foods rich in these micronutrients also contain other constituents that provide the protection.



Can anti-oxidants prevent ischaemic heart disease?

J Clin Pharm Ther (ENGLAND) Apr 1993, 18 (2) p85-95

Ischaemic heart disease remains a major cause of mortality in developed countries. A number of important risk factors for the development of coronary atherosclerosis have been identified including hypertension, hypercholesterolaemia, insulin resistance and smoking. However, these factors can only partly explain variations in the incidence of ischaemic heart disease either between populations or within populations over time. In addition, population interventions based upon these factors have had little impact in the primary prevention of heart disease. Recent evidence suggests that one of the important mechanisms predisposing to the development of atherosclerosis is oxidation of the cholesterol-rich low-density lipoprotein particle. This modification accelerates its uptake into macrophages, thereby leading to the formation of the cholesterol-laden 'foam cell'. In vitro, low-density lipoprotein oxidation can be prevented by naturally occurring anti-oxidants such as vitamin C, vitamin E and beta-carotene. This article explores the evidence that these dietary anti-oxidants may influence the rate of progression of coronary atherosclerosis in vivo and discusses the need for formal clinical trials of anti-oxidant therapy. (90 Refs.)



Antioxidant therapy in the aging process.

EXS (SWITZERLAND) 1992, 62 p428-37

A total of 1,265 patients with age-related diseases such as diabetes, arthritis, vascular disease and hypertension as well as 1,100 persons in diminished health without apparent disease, were treated with the metal chelator EDTA and antioxidants such as vitamin C, E, beta-carotene, selenium, zinc and chromium. Good results were observed in the majority of patients. This is encouraging for the initiation of controlled clinical trials.



Anti-oxidants show an anti-hypertensive effect in diabetic and hypertensive subjects.

Clin Sci (Colch) (ENGLAND) Dec 1991, 81 (6) p739-42

1. In this study an acute anti-hypertensive effect of three anti-oxidant agents (vitamin C, thiopronine and glutathione) in hypertensive subjects and in both hypertensive and non-hypertensive diabetic patients is reported. 2. The anti-oxidants had no effect on blood pressure in healthy normal subjects at a dose of 6 mmol, but thiopronine and glutathione produced a significant hypotensive effect at a dose of 12 mmol. 3. These data suggest that anti-oxidants might have a dilatatory effect and that an imbalance of the nitric oxide-free radical interaction might facilitate the development of hypertension in humans.



Micronutrient profiles in HIV-1-infected heterosexual adults

Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology ( USA), 1996, 12/1 (75-83)

There is compelling evidence that micronutrients can profoundly affect immunity. We surveyed vitamin supplement use and circulating concentrations of 22 nutrients and glutathione in 64 HIV-1 seropositive men and women and 33 seronegative controls participating in a study of heterosexual HIV-1 transmission. We assayed antioxidants (vitamins A, C, and E; total carotenes), vitamins B6 and B12, folate, thiamin, niacin, biotin, riboflavin, pantothenic acid, free and total choline and carnitine, biopterin, inositol, copper, zinc, selenium, and magnesium, HIV-infected patients had lower mean circulating concentrations of magnesium (p < 0.0001), total carotenes (p = 0.009), total choline (p = 0.002), and glutathione (p = 0.045), and higher concentrations of niacin (p < 0.0001) than controls. Fifty-nine percent of HIV+ patients had low concentrations of magnesium, compared with 9% of controls (p < 0.0001). These abnormal concentrations were unrelated to stage of disease. Participants who took vitamin supplements had consistently fewer low concentrations of antioxidants, across HIV infection status and disease stage strata (p = 0.0006). Nevertheless, 29% of the HIV+ patients taking supplemental vitamins had subnormal levels of one or more antioxidants. The frequent occurrence of abnormal micronutrient nutriture, as found in these HIV+ subjects, may contribute to disease pathogenesis. The low magnesium concentrations may be particularly relevant to HIV-related symptoms of fatigue, lethargy, and impaired mentation.



Antioxidant-micronutrients and HIV infection

International Journal of STD and AIDS (United Kingdom), 1996, 7/7 (485-489)

We measured plasma levels of all the antioxidant-micronutrients in subjects with HIV infection and controls. Plasma levels of all the carotenoids, including lutein, cryptoxanthin, lycopene, alpha-carotene and beta-carotene as well as vitamins A, C and E and cholesterol were assayed in 35 subjects with HIV infection and 38 controls. We found a significant depletion of all the carotenoids (P < 0.001) and vitamin C (P < 0.01) and cholesterol (P < 0.001) but not vitamins A or E in HIV-infected subjects. Further analysis of the HIV-infected subjects revealed that plasma levels of 4 of the groups of carotenoids and cholesterol were correlated with CD4 count but that beta-carotene and vitamins A, C and E were not. These results are reviewed in the light of the published literature and we conclude that these abnormalities of antioxidant-micronutrients are likely to reflect a metabolic phenomenon associated with HIV infection. However, an additional contribution to these deficiencies from malabsorption later in HIV disease cannot be ruled out.



Can antioxidants prevent ischemic heart disease?

J Clin Pharm Ther (ENGLAND) Apr 1993

Ischemic heart disease remains a major cause of mortality in developed countries. A number of important risk factors for the development of coronary atherosclerosis have been identified including hypertension, hypercholesterolaemia, insulin resistance and smoking. However, these factors can only partly explain variations in the incidence of ischaemic heart disease either between populations or within populations over time. In addition, population interventions based upon these factors have had little impact in the primary prevention of heart disease. Recent evidence suggests that one of the important mechanisms predisposing to the development of atherosclerosis is oxidation of the cholesterol-rich low-density lipoprotein particle. This modification accelerates its uptake into macrophages, thereby leading to the formation of the cholesterol-laden 'foam cell'. In vitro, low-density lipoprotein oxidation can be prevented by naturally occurring antioxidants such as vitamin C, vitamin E and beta-carotene. This article explores the evidence that these dietary anti-oxidants may influence the rate of progression of coronary atherosclerosis in vivo and discusses the need for formal clinical trials of antioxidant therapy.



Antioxidant therapy in the aging process.

EXS (SWITZERLAND) 1992, 62

A total of 1,265 patients with age-related diseases such as diabetes, arthritis, vascular disease and hypertension as well as 1,100 persons in diminished health without apparent disease, were treated with the metal chelator EDTA and antioxidants such as vitamin C, E, beta-carotene, selenium, zinc and chromium. Good results were observed in the majority of patients. This is encouraging for the initiation of controlled clinical trials.



Acute phase response and plasma carotenoid concentrations in older women: Findings from the nun study.

Boosalis M.G.; Snowdon D.A.; Tully C.L.; Gross M.D.

Department of Clinical Sciences, University of Kentucky, Lexington, KY 40536-0003 USA

Nutrition (USA), 1996, 12/7-8 (475-478)

This cross-sectional study investigated whether the acute phase response was associated with suppressed circulating levels of antioxidants in a population of 85 Catholic sisters (nuns) ages 77-99 y. Fasting blood was drawn to determine the presence of an acute phase response, as defined by an elevation in the serum concentration of C-reactive protein. Serum concentrations of albumin, thyroxine-binding prealbumin, zinc, copper, and fibrinogen were determined as were plasma concentrations of carotenoids and alpha tocopherol. Results showed that the presence of an acute phase response was associated with (1) an expected significant decrease in the serum concentrations of albumin (p < 0.001) and thyroxine-binding prealbumin (p < 0.001); (2) an expected significant increase in copper (p < 0.001) and fibrinogen (p = 0.003); and (3) a significant decrease in the plasma concentrations of lycopene (p = 0.03), alpha carotene (p = 0.02), beta carotene (p = 0.02), and total carotenoids (p = 0.01). The acute phase response was associated with decreased plasma levels of the antioxidants lycopene, alpha carotene, and beta carotene. This decrease in circulating antioxidants may further compromise antioxidant status and increase oxidative stress and damage in elders.



Endothelial dysfunction: Clinical implications.

Drexler H.

Germany

Progress in Cardiovascular Diseases (USA), 1997, 39/4 (287-324)

The endothelium is involved in the control of vascular tone and homeostasis. Risk factors for arteriosclerosis, as well as other conditions have been shown to be associated with a dysfunctional endothelium. Clinically, endothelial function and dysfunction have been mostly evaluated by the assessment of endothelial dependent relaxation, for example in response to acetylcholine or increase inflow. The functional implications of endothelial dysfunction in cardiovascular disease are not well defined, but recent clinical trials have suggested that endothelial dysfunction may affect vascular tone and organ perfusion particularly during stress situations such as exercise. Moreover, endothelial dysfunction may represent an early event in the development of arteriosclerosis. Therefore, recent clinical studies have been performed to restore normal endothelial function in patients, using interventions such as L-arginine, lipid lowering drugs, vitamin C, other antioxidants, or exercise.



Use of antioxidant vitamins in the cardiovascular disease. A review of epidemiological study and clinical trials.

Marchioti R.

Italy

Giornale Italiano di Farmacia Clinica (Italy), 1996, 10/3 (155-162)

Persons whose diets are rich in fruits and vegetable have lower rates of several chronic diseases, mostly cardiovascular and cancer. The lower cardiovascular risk might be attributed to consumption of antioxidant substances as beta-carotene, vitamin C and vitamin E. In this article the support of epidemiological studies and randomised clinical trial to this hypothesis is reviewed and explorative meta-analyses are performed in order to give a simple overview of recurrent knowledge on this topic.



The effect of dietary treatment on lipid peroxidation and antioxidant status in newly diagnosed noninsulin dependent diabetes.

Armstrong A.M.; Chestnutt J.E.; Gormley M.J.; Young I.S.

Department of Clinical Biochemistry, Institute of Clinical Science, Royal Victoria Hospital, Belfast BT12 6BJ Ireland

Free Radical Biology and Medicine (USA), 1996, 21/5 (719-726)

Increased lipid peroxidation and reduced antioxidant status may contribute to the development of complications in diabetes. The aim of this study was to assess the effects of dietary treatment of noninsulin-dependent diabetes on these parameters. Twenty patients with newly diagnosed noninsulin-dependent diabetes were recruited along with 20 age, sex, and smoking-status-matched control subjects. Dietary intake was assessed by food frequency questionnaire and 24-h dietary recall and blood collected for biochemical analyses before and 2 months after dietary treatment was initiated. Carbohydrate, fat, and protein intake fell in patients following dietary advice. Among micronutrients, intakes of vitamins C, E, and A, carotene, selenium, copper, zinc, and iron were similar in patients and controls. Vitamin C intake in patients rose following dietary advice (44.6 plus or minus 11.7 vs. 49.5 plus or minus 5.5 mg/d, p < .05), while there was no change in intake of other micronutrients. Fasting plasma glucose in diabetic subjects fell from 13.6 plus or minus 1.1 mmol/l at recruitment to 9.7 plus or minus 1.1 mmol/l after diet (p < .01), and this was accompanied by a fall in hemoglobin Alc from 7.44 plus or minus 0.67% to 5.91 plus or minus 0.57% (p < .01). Serum malondialdehyde was higher in patients than controls at T0 (2.39 plus or minus 0.55 micromol/l vs. 1.48 plus or minus 0.33; p < .01), and fell following diet to 1.42 micromol/l (p < 0.01). Ascorbate was lower in patients than controls (12.7 plus or minus 2.9 micromol/l vs. 41.4 plus or minus 9.3; p < .01) at baseline and rose after diet to 27.8 plus or minus 6.4 (p < .01). beta-Carotene also rose after diet in patients (0.13 plus or minus 0.04 micromol/l vs. 0.17 plus or minus 0.04; p < 0.05), as did lipid corrected alpha-tocopherol (4.39 plus or minus 1.09 micromol/mmol cholesterol vs. 5.16 plus or minus 1.18; p < .05). Reduced lipid peroxidation and improved antioxidant status may be one mechanism by which dietary treatment contributes to the prevention of diabetic complications.



Smoking, plasma antioxidants and essential fatty acids before and after nutratherapy.

Karlsson J.; Lindh G.; Ronnebergh T.R.

OBLA AB, Box 242, S-185 23 Vaxholm Sweden

Canadian Journal of Cardiology (Canada), 1996, 12/7 (665-670)

OBJECTIVE: To study the effect of smoking on plasma antioxidants with and without antioxidant vitamin nutratherapy. DESIGN: Chronic smokers (n = 10, 16plus or minus4 cigarettes a day) and nonsmokers (n = 17) of both sexes were recruited from patients with arthritis-like symptoms. After baseline studies of plasma antioxidant vitamins Q (ubiquinone) and E (alpha-tocopherol) and essential fatty acids (EFA, vitamin F), three months' nutratherapy with vitamins Q (90 mg) and E (350 mg) was administered and plasma reanalyzed. RESULTS: No sex differences were seen in smoking habits or plasma nutrients. Smokers had normal Q (0.71plus or minus0.07 mg/L) but depressed E (9.4plus or minus0.6 mg/L, P < 0.01). EFA were the same in both groups. Nutratherapy increased Q by about 90% in both groups and E by 47% in smokers and 101% in nonsmokers (P < 0.01). In nonsmokers, nutratherapy protected omega-3 fatty acids (vitamin F1)-plasma docosahexaenoic acid increased by 39%. The vitamin F index (omega-6:omega-3 ratio) remained unchanged in the smokers but decreased in the nonsmokers and became related to the individual plasma vitamin Q but not to vitamin E. CONCLUSIONS: There was no difference between smokers and nonsmokers before nutratherapy. Nonsmokers may have suffered from passive smoking. After nutratherapy the quantitatively most important antioxidant, ie, vitamin E, increased more in nonsmokers than in smokers. This resulted in less vitamin F1 peroxidation. Nutratherapy cannot overcome disadvantages associated with smoking. Nonsmokers might achieve an antioxidant protection with nutratherapy, which could mean a possible reduced risk of developing cardiovascular disease.



Reduction of plasma peroxide levels by oral antioxidants.

Morcos N.C.; Tomita M.

Division of Cardiology, Department of Medicine, University of California, Irvine, CA 92717 USA

Medical Science Research (United Kingdom), 1996, 24/5 (357-359)

The role of plasma oxidants in the aetiology of cardiovascular disease has been emphasised. It is proposed that the antioxidant vitamins modulate cardiovascular disease by altering oxidative processes. We investigated whether oral intake of the antioxidant vitamins modulates their plasma levels, with resultant reductions in plasma oxidative peroxide levels. 10 normal subjects ages 18-23 with no known illness were enrolled in a double blind placebo cross-over study. Each subject while in the test group received an antioxidant tablet twice daily. Each tablet contained vitamin A, vitamin E, vitamin C and selenium prepared by low compression pressure. The placebo group received tablets of similar appearance containing mineral oil. Plasma samples were drawn at baseline prior to the initiation of the study, and after 4 weeks from the start of the study. Fasting vitamin A and vitamin E levels increased over placebo by 14% (p < 0.02) and 27% (p < 0.02) respectively. The fasting plasma oxidant peroxide levels were reduced by 10% (p < 0.001) as compared to the placebo group. Steady state oxidant levels during periods of food intake did not appear to be changed, possibly due to interference of absorbed food substances with baseline oxidant levels and the oxidant assay. These findings suggest that oral intake of antioxidant vitamins raised their plasma pool levels with a resultant reduction in fasting plasma peroxide level. This reduction is expected to modulate the oxidant-mediated mechanism of initiation of the pathological process.



Systemic oxidative stress in asthma, COPD, and smokers

American Journal of Respiratory and Critical Care Medicine (USA), 1996, 154/4 I (1055-1060)

An imbalance between oxidants and antioxidants is proposed in smokers and in patients with airways diseases. We tested this hypothesis by measuring the Trolox equivalent antioxidant capacity (TEAC) of plasma and the levels of products of lipid peroxidation as indices of overall oxidative stress. The plasma TEAC was markedly reduced (0.66 plus or minus 0.07 mmol/L; mean plus or minus SEM; n = 11), with increased levels of lipid peroxidation products, in healthy chronic smokers as compared with healthy nonsmokers (1.31 plus or minus 0.10 mmol/L, n = 14, p < 0.001), an effect that was exaggerated in those who had smoked 1 h before the study. Plasma TEAC was also low in patients presenting with acute exacerbations of chronic obstructive pulmonary disease (COPD) (0.46 plus or minus 0.10 mmol/L, n = 20, p < 0.001) or asthma (0.61 plus or minus 0.05 mmol/L, n = 9, p < 0.01) with increases in plasma lipid peroxidation products. There was a negative correlation between superoxide anion release by stimulated neutrophils and plasma antioxidant capacity (r = -0.73, p < 0.001) in patients with acute exacerbations of COPD. The profound decrease in TEAC was associated with a decreased plasma protein sulfhydryl concentrations in acute exacerbations of COPD but not in smokers or in asthmatic subjects. Therefore smoking, acute exacerbations of COPD, and asthma are associated with a marked oxidant/antioxidant imbalance in the blood, associated with evidence of increased oxidative stress. The decreased antioxidant capacity in plasma may result from different mechanisms in these conditions.



Role of oxidants/antioxidants in smoking-induced lung diseases

Free Radical Biology and Medicine (USA), 1996, 21/5 (669-681)

An imbalance between oxidants and antioxidants has been considered in the pathogenesis of smoking-induced lung diseases, such as chronic obstructive pulmonary disease (COPD), particularly emphysema. Recent evidence indicates that increased neutrophil sequestration and activation occurs in the pulmonary microvasculature in smokers and in patients with COPD, with the potential to release reactive oxygen species (ROS). ROS generated by airspace phagocytes or inhaled directly from the environment also increase the oxidant burden and may contribute to the epithelial damage. Although much research has focused on the protease/antiprotease theory of the pathogenesis of emphysema, less attention has been paid to the role of ROS in this condition. The injurious effects of the increased oxidant burden in smokers and in patients with COPD are opposed by the lung antioxidant defences. Hence, determining the mechanisms regulating the antioxidant responses is critical to our understanding of the role of oxidants in the pathogenesis of smoking- induced lung diseases and to devising future strategies for antioxidant therapy. In this article we have reviewed the evidence for the presence of an oxidant/antioxidant imbalance in smoking-induced lung disease and its relevance to therapy in these conditions.



Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus

European Journal of Clinical Investigation (United Kingdom), 1997, 27/6 (484-490)

Oxidative damage by free radicals has been implicated in the pathogenesis of vascular disease in diabetes. We compared the radical- scavenging antioxidant activity of serum from 28 patients with insulin- dependent diabetes mellitus and 24 patients with non-insulin-dependent diabetes mellitus uncomplicated by vascular disease with age-matched non- diabetic control subjects. Patients with insulin-dependent diabetes had significantly reduced total antioxidant activity (320.2plus or minus11.3 vs. 427.5plus or minus19.2similarmolL 1 P<0.001). This was attributable to lower urate (209.4plus or minus 10.4 vs. 297.1 plus or minus 16.7similarmolL 1; P<0.001) and vitamin C levels (63.6 plus or minus 6.0 vs. 87.5 plus or minus 4.9 micromol L ; P < 0.0 1). Patients with non-insulin-dependent diabetes had lower total antioxidant activity than age-matched control subjects (433.8 plus or minus 25.4 vs. 473.9 plus or minus 30.2micromol L 1 NS), reflecting lower urate (299.5 plus or minus 19.4 vs. 324.8 plus or minus21.4/micromolL -P; NS) and vitamin C levels (38.6plus or minus5.7 vs. 58.5 plus or minus 5.3micromol L -1; P<0.05). Multiple regression analysis showed that urate, vitamin C and vitamin E were the major contributors to serum total antioxidant activity. These results show that diabetic patients have significant defects of antioxidant protection, which may increase vulnerability to oxidative damage and the development of diabetic complications.



Spice constituents scavenging free radicals and inhibiting pentosidine formation in a model system.

Biosci Biotechnol Biochem (JAPAN) Feb 1997, 61 (2) p263-6

Many antioxidants have been found in spices and herbs, and some of them are well known as strong scavengers of active oxygen radicals. We have isolated active products, which markedly inhibited the formation of malondialdehyde (MDA from 2-deoxyribose and the hydroxylation of benzoate with the hydroxyl radical, from methanol extracts of allspice and clove. Pimentol from allspice, and biflorin and its isomer, abbreviated as clove3, from clove were identified as the active principles. These revealed strong activity as hydroxyl radical scavengers at a concentration of 2.0 microM. The antioxidative activities in an in vitro model system involving the rabbit erythrocyte membrane ghost were as strong as those of alpha-tocopherol at 200 microM. Such advanced glycation end products (AGE) as pentosidine are biomarkers of diabetes mellitus, and active oxygens have been suggested to be involved in the formation of AGE. The above-mentioned free radical scavengers effectively inhibited the formation of pentosidine in a model system of N alpha-t-butoxycarbonyl-fructoselysine and N alpha-t-butoxycarbonyl-arginine.



Potential therapeutic approaches to the treatment or prevention of diabetic neuropathy: evidence from experimental studies.

Diabet Med (ENGLAND) Aug-Sep 1993, 10 (7) p593-605

Recent investigations using experimental models of diabetes mellitus have emphasized the importance of impaired blood flow for the development of nerve dysfunction. Other observations suggest that this may also be the case for patients. A number of studies have revealed that several types of vasodilators can prevent or successfully treat early conduction abnormalities in diabetic rodents. These include alpha 1-adrenoreceptor antagonists, calcium channel blockers, agents that inhibit the renin-angiotensin system, and vasomodulator prostanoids. Other treatments applied to animal models, such as omega-6 essential fatty acids, aldose reductase inhibitors, aminoguanidine which prevents the formation of advanced glycation end-products, and anti-oxidants all appear to have vascular-related effects that lead to improvements in nerve conduction. These findings suggest that endothelial dysfunction and oxidative stress could be important factors in the aetiology of diabetic neuropathy. Studies have also focused on deficits in axon growth and regeneration, their relation to impaired neuronal synthesis and transport of growth-related chemicals, and neuronotrophic abnormalities. Taken together, the data give rise to the notion that an optimal therapeutic strategy could consist of improving the microenvironment of damaged nerve fibres by manipulating nerve blood flow while concurrently encouraging repair with trophic agents. (161 Refs.)



Prevention of postischemic cardiac injury by the orally active iron chelator 1,2-dimethyl-3-hydroxy-4-pyridone (L1) and the antioxidant (+)-cyanidanol-3

CIRCULATION (USA), 1989, 80/1 (158-164)

In this study, we investigated the role of oxygen-derived free radicals and iron in mediating myocardial injury during ischemia and reperfusion. Iron is of special interest because it may enhance tissue injury during ischemia and reperfusion by catalyzing the formation of highly reactive hydroxyl radicals (by modified Haber-Weiss or Fenton reactions). Rat hearts, perfused by the Langendorff method, were subjected to global ischemia (15 minutes at 37degree C) and reperfusion. The effects of two iron chelators, 1,2-dimethyl-3-hydroxy-4-pyridone (L1) and 5-hydroxy-2-hydroxymethyl-4-pyrone (kojic acid), and one antioxidant, (+)-cyanidanol-3, on contractile function, coronary flow, lactate dehydrogenase release, and lactate production were studied. The combination of these iron chelators is of special importance because L1 is known to prevent lipid peroxidation, induced by ADP/Fe3+ and NADPH in microsomes, in contrast to kojic acid. We found significant protection of contractile function (apex displacement) during reperfusion with 50 microM L1 and 20 microM (+)-cyanidanol-3 (p < 0.01, n = 6), whereas no protection was found with 50 microM kojic acid (n = 6). Measurements of lactate dehydrogenase release during reperfusion showed a protective pattern similar to that found for heart contractile function, although 50 microM kojic acid also showed a significantly lower lactate dehydrogenase release during the first 10 minutes of reperfusion. No differences in coronary resistance or lactate release were found between the various groups. Our findings indicate that iron and oxygen-derived free radicals are important in the pathogenesis of postischemic reperfusion injury probably because of the formation of hydroxyl radicals. During heart ischemia, administration of the orally active iron chelator L1 of the antioxidant (+)-cyanidanol-3 may be a promising approach in establishing postischemic cardiac protection.



Iron-load increases the susceptibility of rat hearts to oxygen reperfusion damage. Protection by the antioxidant (+)-cyanidanol-3 and deferoxamine

CIRCULATION (USA), 1988, 78/2 (442-449)

To investigate whether iron is involved in the reperfusion syndrome by aggravating free radical injury, the hearts from iron-loaded and control rats were perfused under normoxic, anoxic, and reperfusion conditions. Normoxic perfusion revealed no change in coronary flow, contractility, or lactate dehydrogenase (LDH) release between these two groups. Under anoxic and reperfusion conditions, however, we found a significant increase of ventricle fibrillation (56% vs. 0%, p<0.01, n=9), a significantly lower recovery of contractility (21plus or minus7.4% vs 81plus or minus6.6%, mean plus or minus SEM; p<0.001), and a significant increase of LDH release (667plus or minus142 vs. 268plus or minus37 mU LDH/min/g wet wt, mean plus or minus SEM; p<0.05). Administration of either 20 microM of the antioxidant (+)-cyanidanol-3 or 50 microM of the iron-chelator deferoxamine totally prevented the generation of ventricle fibrillation and normalized contractility to control levels in the iron-loaded group. Moreover, 20 microM (+)-cyanidanol-3 significantly lowered LDH release in this period (312plus or minus67 mU), whereas deferoxamine had no protective effect on this LDH release (1,494plus or minus288 mU). Normal hearts appeared to be protected by 20 microM (+)-cyanidanol-3 as well. In this group (n=6), a significantly higher recovery of contractility (97.1plus or minus3.2% vs 81plus or minus6.6%, p<0.05) and a significantly lower release of LDH (110plus or minus27 vs. 268plus or minus37 mU, p<0.05) was found compared with the control group (n=9). No difference in superoxide dismutase or glutathione peroxidase activity was found between the groups. It is concluded that 1) iron-loaded rat hearts are more susceptible to anoxia and oxygen reperfusion damage; 2) iron load itself, under normoxic conditions, does not seem to be harmful; and 3) the antioxidant (+)-cyanidanol-3 is able to protect normal as well as iron-loaded hearts against anoxic and reperfusion damage. We suggest that iron plays an important role in the occurrence of tissue damage and ventricle fibrillation during anoxia and reperfusion, probably through the formation of hydroxyl radicals and/or perferryl oxide.



Nutritional antioxidants and the modulation of inflammation: theory and practice.

New Horiz (UNITED STATES) May 1994

Highly potent substances are produced by the immune system. These substances include cytokines and oxidant molecules, such as hydrogen peroxide, free radicals, and hypochlorous acid. The purpose of immune cell products is to destroy invading organisms and damaged tissue, bringing about recovery. However, oxidants and cytokines can damage healthy tissue. Excessive or inappropriate production of these substances is associated with mortality and morbidity after infection and trauma, and in inflammatory diseases. Oxidants enhance interleukin-1, interleukin-8, and tumor necrosis factor production in response to inflammatory stimuli by activating the nuclear transcription factor, NF kappa B. Sophisticated antioxidant defenses directly and indirectly protect the host against the damaging influence of cytokines and oxidants. Indirect protection is afforded by antioxidants, which reduce activation of NF kappa B, thereby preventing up-regulation of cytokine production by oxidants. Cytokines increase both oxidant production and antioxidant defenses, thus minimizing damage to the host. While antioxidant defenses interact when a component is compromised, the nature and extent of the defenses are influenced by dietary intake of sulfur amino acids, for glutathione synthesis, and vitamins E and C. In animal studies, in vivo and in vitro responses to inflammatory stimuli are influenced by dietary intake of copper, zinc, selenium, N-acetylcysteine, cysteine, methionine, taurine, and vitamin E. Information from animal studies has yet to be fully translated into a clinical context. However, N-acetylcysteine, vitamin E, and a cocktail of antioxidant nutrients have reduced inflammatory symptoms in inflammatory joint disease, acute and chronic pancreatitis, and adult respiratory distress syndrome. Impaired antioxidant defenses may contribute to disease progression after infection with human immunodeficiency virus. Powerful arguments have been advanced for treatment with antioxidants to slow progression of acquired immunodeficiency syndrome. (76 Refs.)



Antioxidant vitamins in cataract prevention.

Z Ernahrungswiss (GERMANY, WEST) Mar 1989, 28 (1) p56-75

The ocular lens, which is continually exposed to light and ambient oxygen, is at high risk of photooxidative damage resulting in cataract. Oxygen free radicals appear to impair not only lens crystallins which will aggregate and precipitate forming opacities but also proteolytic enzymes whose function it would be to eliminate the damaged proteins. Apart from an enzymatic defense system consisting of superoxide dismutase, catalase and glutathione peroxidase against excited oxygen species the lens contains the antioxidant vitamins C, E and presumably beta-carotene as another line of defense. In vitro and in vivo studies in different animal species have demonstrated a significant protective effect of vitamins C and E against light-induced cataract. Sugar and steroid cataracts were prevented as well. Epidemiological evidence in humans suggests that persons with comparatively higher intakes or blood concentrations of antioxidant vitamins are at a reduced risk of cataract development. These positive findings established by several research groups justify extensive intervention trials with antioxidant vitamins in humans using presenile cataract development as a model.



Free radical tissue damage: protective role of antioxidant nutrients.

FASEB J (UNITED STATES) Dec 1987, 1 (6) p441-5

Highly reactive molecules called free radicals can cause tissue damage by reacting with polyunsaturated fatty acids in cellular membranes, nucleotides in DNA, and critical sulfhydryl bonds in proteins. Free radicals can originate endogenously from normal metabolic reactions or exogenously as components of tobacco smoke and air pollutants and indirectly through the metabolism of certain solvents, drugs, and pesticides as well as through exposure to radiation. There is some evidence that free radical damage contributes to the etiology of many chronic health problems such as emphysema, cardiovascular and inflammatory diseases, cataracts, and cancer. Defenses against free radical damage include tocopherol (vitamin E), ascorbic acid (vitamin C), beta-carotene, glutathione, uric acid, bilirubin, and several metalloenzymes including glutathione peroxidase (selenium), catalase (iron), and superoxide dismutase (copper, zinc, manganese) and proteins such as ceruloplasmin (copper). The extent of tissue damage is the result of the balance between the free radicals generated and the antioxidant protective defense system. Several dietary micronutrients contribute greatly to the protective system. Based on the growing interest in free radical biology and the lack of effective therapies for many of the chronic diseases, the usefulness of essential, safe nutrients in protecting against the adverse effects of oxidative injury warrants further study.



Free radical tissue damage: protective role of antioxidant nutrients.

Am J Clin Nutr (UNITED STATES) Jun 1996, 63 (6) p985S-990S

Increased production of reactive oxygen species is a feature of most, if not all, human disease, including cardiovascular disease and cancer. Dietary antioxidants may be especially important in protecting against human diseases associated with free radical damage to cellular DNA, lipids, and proteins. Ascorbic acid is an effective water-soluble antioxidant, and epidemiologic studies suggest that increased ascorbate nutriture is associated with reduced risk of some degenerative diseases, especially cancer and eye cataracts. Population studies have also shown that high vitamin E intakes are associated with decreased risk of coronary heart disease, possibly as a result of inhibition of atherogenic forms of oxidized low-density lipoprotein. Recent data suggest that beta-carotene provides protection against lipid peroxidation in humans, as well as provitamin A activity. Yet, present data are not sufficient to quantitate micronutrient requirements needed to protect against oxidative damage. The antioxidant roles of many food constituents, such as polyphenols, have not been clarified. Most antioxidants can act as prooxidants under certain conditions, and more research is needed to determine the occurrence and importance of this in vivo. The few controlled intervention trials carried out so far have shown mixed results as to the potential of antioxidant supplements for reducing the incidence of chronic diseases. Definitive recommendations on antioxidant intakes for disease prevention must await evidence from controlled studies and intervention trials, some currently in progress. Overall, the present data suggest that protection against oxidative damage and related disease is best served by the variety of antioxidant substances found in fruit and vegetables. (43 Refs.)



[Antioxidative vitamins and cataracts in the elderly]

Z Ernahrungswiss (GERMANY) Sep 1995, 34 (3) p167-76

Senile cataract indicates the opacity of ocular lenses occurring in old and especially in very old people. Lens proteins are extremely long-living and often show oxidative damages. Aging and smoking appear to be the greatest risk factors for the development of lens opacities. The sufficient antioxidant protection of young lenses decreases with the aging process. Consequently, the importance of other protective factors increases. Nutritional factors, particularly vitamins with antioxidant properties, may influence the development of senile cataracts in the ocular lens. Meanwhile an association between the supply with vitamin C, E and beta-carotene and the risk of cataract development was demonstrated in animal studies and also in an increasing number of epidemiological studies. These epidemiological studies mainly support the hypothesis that higher vitamin intakes reduce the risk of developing cataracts in old age. The antioxidant properties of the named nutrients give a plausible explanation for the mechanism of cataractogenesis. On the basis of the present data definitive recommendation, necessary for cataract prevention can not yet be established. Some results seem to support higher recommendations. At the moment several large human intervention trials are carried out. Form these studies a further confirmation of the antioxidant hypothesis and of a dose-response-relationship are expected.



Prevention of cataracts by nutritional and metabolic antioxidants.

Crit Rev Food Sci Nutr (UNITED STATES) 1995, 35 (1-2) p111-29

Among aging disabilities, the one associated with the progressive decline of vision is functionally most disadvantageous. Cataracts are one of the more common causes of such visual disability. Several predisposing factors have been identified in the genesis of this disease. While it is perhaps a multifactorial process, significant developments have taken place in recent years suggesting that oxygen radicals are involved in the development of this aging manifestation. Antioxidant enzymes, such as catalase and superoxide dismutase, have been demonstrated to protect the lens cell membrane from oxidative stress as reflected by the prevention of the Na(+)-K(+)-ATPase-dependent pump deterioration due to oxyradical-dependent oxidation of its proteins and lipids. From the nutritional point of view, antioxidants such as ascorbate and vitamin E also offer significant protection to the lens against damage due to oxidative stress. Evidence regarding the protective effect of these nutrients has been based on lens organ culture studies in the presence of active oxygen, generated photochemically as well as enzymatically. The experiment involving photochemical environs simulate the status of the eye during the photopic vision. In vivo, the effectiveness of ascorbate against cataracts has been tested in rat pups developing cataracts under the oxidative influence of sodium selenite. Certain antioxidants produced metabolically also may be useful in protecting against cataracts. Pyruvate produced in glucose metabolism seems to be an important antioxidant. The efficacy of this compound has been tested within in vitro organ culture as well as in vivo, the latter experiments being done with selenite-treated rats. There is a hope that these and other nutritional and metabolic antioxidants may one day be useful in delaying or even preventing cataract formation in human beings.



Free radicals, exercise, and antioxidant supplementation

Int J Sport Nutr (UNITED STATES) Sep 1994, 4 (3) p205-20

Comment in Int J Sport Nutr 1994 Sep;4(3):203-4

Free radicals have been implicated in the development of diverse diseases such as cancer, diabetes, and cataracts, and recent epidemiological data suggest an inverse relationship between antioxidant intake and cardiovascular disease risk. Data also suggest that antioxidants may delay aging. Research has indicated that free radical production and subsequent lipid peroxidation are normal sequelae to the rise in oxygen consumption with exercise. Consequently, antioxidant supplementation may detoxify the peroxides produced during exercise and diminish muscle damage and soreness. Vitamin E, beta carotene, and vitamin C have shown promise as protective antioxidants. Other ingestible products with antioxidant properties include selenium and coenzyme Q10. The role (if any) that free radicals play in the development of exercise-induced tissue damage, or the protective role that antioxidants may play, remains to be elucidated. Current methods used to assess exercise-induced lipid peroxidation are not extremely specific or sensitive; research that utilizes more sophisticated methodologies should help to answer many questions regarding dietary antioxidants.



Fibronectin fragment mediated cartilage chondrolysis. I. Suppression by anti-oxidants

Biochimica et Biophysica Acta - Molecular Basis of Disease (Netherlands), 1996, 1317/2 (134-142)

Fibronectin fragments damage cartilage in vitro by greatly enhancing metalloproteinases and suppressing proteoglycan (PG) synthesis which results in severe cartilage PG depletion. Since reactive oxygen species (ROS) have been implicated in catabolic cytokine action and preliminary data suggested that catabolic cytokines such as TNF-alpha, IL-1alpha, IL-1beta and IL-6 are responsible for fibronectin fragment mediated damage, selected anti-oxidants (Aos) were tested as inhibitors of cytokine, ROS and fibronectin fragment activity. Damage was measured by depletion of cartilage PG during tissue culture. The AO, N-acetylcysteine (NAC), decreased the extent of cartilage PG depletion caused by TNF-alpha and IL-1alpha and by the ROS, hydrogen peroxide and superoxide anion, confirming that the cytokines operate through ROS and that ROS can initiate cartilage PG depletion. NAC at 0.1 and 1 mM, totally suppressed PG depletion caused by a highly potent amino-terminal 29-kDa fibronectin fragment (Fn-f) for 14 days in culture. NAC at 10 mM totally blocked Fn-f mediated PG depletion for 21 days and increased the cartilage PG content by 30% above normal levels, Glutathione (10 microM) and DMSO (1%) were also totally effective while catalase and superoxide decreased Fn-f mediated damage only during the first week and superoxide dismutase alone caused damage after 1 wk. The AOs caused protection by reducing the major catabolic activities of the Fn-f: enhanced release of stromelysin-1 (MMP-3) and suppression of PG and protein synthesis. NAC also decreased normal rates of PG degradation and increased the half-lives of labeled PG in both control and Fn-f treated cartilage. We conclude that the Fn-f mediates cartilage chondrolysis through ROS, consistent with the involvement of catabolic cytokines in the Fn-f mechanism, and that AOs greatly reduce Fn-fmediated cartilage chondrolysis. In an accompanying manuscript we also report that AOs promote reparative responses in Fn-f and cytokine treated cartilage.



Overview of conditioning related life-threatening toxicities of marrow transplantation

Seminars in Respiratory and Critical Care Medicine (USA), 1996, 17/5 (365-372)

Chemotherapeutic agents used for blood and marrow transplantation are administered at doses up to 10 times greater than what would be used in conventional treatment of malignancies. This aggressive use of chemotherapy, with or without concomitant radiation, is associated with multiple organ toxicities. Common, and frequently life-threatening toxicities include cardiac toxicity, veno-occlusive disease of the liver, idiopathic pneumonia, neurotoxicity, renal failure, and oral mucositis. Often these toxicities are difficult to distinguish from other treatment-related complications, such as infection. The precise mechanisms of these injuries are poorly understood, but may relate to depletion of antioxidants. Although preventative strategies do not appear to be particularly effective, prompt recognition of the problems may be life-saving.

image