DISEASE PREVENTION
Page 8

Lynch SM; Gaziano JM; Frei B
Whitaker Cardiovascular Institute, Boston University School of Medicine, Massachusetts 02118-2394, USA.
Subcell Biochem (England) 1996, 25 p331-67

In this chapter, we have briefly reviewed the current scientific knowledge of the role of vitamin C in the prevention of atherosclerosis and its associated clinical manifestations. There is good evidence from animal studies that vitamin C can slow the progression of experimental atherosclerosis. Most of these studies, however, were done either in guinea pigs, using ascorbic acid depletion, or in cholesterol-fed rabbits, using ascorbic acid supplementation. Both animal models have limitations, as guinea pigs are not a well-established (nor well-studied) model of atherosclerosis, and rabbits develop atherosclerosis at high serum beta-VLDL cholesterol levels, and in addition can synthesize ascorbic acid. In contrast, humans develop atherosclerosis spontaneously and readily at moderately elevated serum LDL cholesterol levels and have lost the ability to synthesize ascorbic acid. Thus, the animal studies discussed, although quite promising and suggestive of an anti-atherogenic effect of ascorbic acid, need to be expanded to primates before more definitive conclusions can be drawn. Similar to the animal data, the current evidence from epidemiological studies on the role of vitamin C in the prevention of CVD is inconclusive, with some studies showing a very strong correlation between increased vitamin C intake and incidence of CVD events and other studies showing no correlation at all. Studies on CVD risk factors indicate that vitamin C may moderately decrease total serum cholesterol levels, increase HDL levels, and exert a hypotensive effect. These findings are particularly intriguing and should be pursued vigorously in basic research studies to elucidate biological mechanisms. In addition, it appears that large placebo-controlled, double-blind, randomized trials of vitamin C supplementation (without simultaneous supplementation with vitamin E) in populations with a wide range of vitamin C body levels are needed in order to confirm or refute a role for vitamin C in the prevention of CVD. Unfortunately, no such trials are currently being conducted. The possible mechanisms by which ascorbic acid may affect the development of atherosclerosis and the onset of acute coronary events include effects on arterial wall integrity related to biosynthesis of collagen and GAGs, altered cholesterol metabolile acids, and effects on triglyceride levels via modulation of lipoprotein lipase activity. A particularly intriguing possible mechanism for the anti-atherogenic effect of vitamin C is prevention of atherogenic, oxidative modification of LDL. Numerous in vitro studies have demonstrated that ascorbic acid strongly inhibits LDL oxidation by a variety of mechanisms. The potential effects of ascorbic acid on platelet function and EDRF metabolism are particularly intriguing, as they might have widespread consequences for the prevention of atherosclerotic lesion development as well as acute clinical events. Thus, both metabolic and antioxidant functions may contribute to the possible reduction of CVD risk by vitamin C. (165 Refs.)

Wang ZH; Iguchi H; Ohshio G; Imamura T; Okada N; Tanaka T; Imamura M
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Pancreas (United States) Aug 1996, 13 (2) p173-83

Recent findings have suggested that oxygen-derived free radicals play an important role in the development and progression of acute pancreatitis. Therefore, the present study was designed to investigate whether metallothionein, a free radical scavenger, can protect against acute pancreatitis. Rats were injected intraperitoneally with zinc, followed by either an infusion of cerulein at 10 micrograms/kg for 4 h or a retrograde injection with 100 microliters/100 g body weight of 5% sodium taurocholate into the pancreaticobiliary duct, in order to induce acute pancreatitis. Zn administration significantly increased the levels of both metallothionein and reduced glutathione in the pancreas; the metallothionein levels reached a peak of 83-fold of normal levels after 24 h. The indications of acute pancreatitis, as well as the mortality, were improved by Zn treatment before the onset of acute pancreatitis. Immunohistochemical studies showed that metallothionein nd with strong staining around the periphery of the vacuoles in the group treated with both Zn and cerulein. These findings suggested that Zn increased both metallothionein and glutathione levels in the pancreas and exerted a beneficial effect against ceruleinor taurocholate-induced acute pancreatitis in rats.

Kondo K; Hirano R; Matsumoto A; Igarashi O; Itakura H
Lancet (England) Nov 30 1996, 348 (9040) p1514

No abstract.

Albanes D; Heinonen OP; Taylor PR; Virtamo J; Edwards BK; Rautalahti M; Hartman AM; Palmgren J; Freedman LS; Haapakoski J; Barrett MJ; Pietinen P; Malila N; Tala E; Liippo K; Salomaa ER; Tangrea JA; Teppo L; Askin FB; Taskinen E; Erozan Y; Greenwald P; Huttunen JK
Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD 20892-7326, USA.
J Natl Cancer Inst (United States) Nov 6 1996, 88 (21) p1560-70

BACKGROUND: Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A.

PURPOSE: We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations.

METHODS: A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carot lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests.

RESULTS: No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24).

CONCLUSIONS: Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake.

IMPLICATIONS: While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation.

Omenn GS; Goodman GE; Thornquist MD; Balmes J; Cullen MR; Glass A; Keogh JP; Meyskens FL Jr; Valanis B; Williams JH Jr; Barnhart S; Cherniack MG; Brodkin CA; Hammar S
Division of Public Health Center, Seattle, WA 98104, USA.
J Natl Cancer Inst (United States) Nov 6 1996, 88 (21) p1550-9

BACKGROUND: Evidence has accumulated from observational studies that people eating more fruits and vegetables, which are rich in beta-carotene (a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver) and retinol (an alcohol chemical form of vitamin A), and people having higher serum beta-carotene concentrations had lower rates of lung cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate (vitamin A) taken daily against placebo in 18314 men and women at high risk of developing lung cancer. The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm; there were 28% more lung cancers and 17% more deaths in the active intervention group (active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate). Promptly after the January 18, 1996, announcement that the CARET active intervention had been stopped, we published preliminary findings from CARET regarding cancer, heart disease, and total mortality.

PURPOSE: We present for the first time results based on the pre-specified analytic method, details about risk factors for lung cancer, and analyses of subgroups and of factors that possibly influence response to the intervention.

METHODS: CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial, initiated with a pilot phase and then expanded 10-fold at six study centers. Cigarette smoking history and status and alcohol intake were assessed through participant self-report. Serum was collected from the participants at base line and periodically after randomization and was analyzed for beta-carotene concentration. An Endpoints Review Committee evaluated endpoint reports, including pathologic review of tissue specimens. The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence, with weighting linearly to hypothesized full effect at 24 months after randomization. Relative risks (RRs) were estimated by use of Cox regression models; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake. O'Brien-Fleming boundaries were used for stopping criteria at interim analyses. Statistical significance was set at the .05 alpha value, and all P values were derived from two-sided statistical tests.

RESULTS: According to CARET's pre-specified analysis, there was an RR of 1.36 (95% confidence interval [CI] =the active intervention group compared with the placebo grou p, and RR = 1.59 (95% CI = 1.13-2.23; P = .01) for weighted lung cancer mortality. All subgroups, except former smokers, had a point estimate of RR of 1.10 or greater for lung cancer. There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake (RR = 1.99; 95% CI = 1.28-3.09; test for heterogeneity of RR among quartiles of alcohol intake has P = .01, unadjusted for multiple comparisons) and with large-cell histology (RR = 1.89; 95% CI = 1.09-3.26; test for heterogeneity among histologic categories has P = .35), but not with base-line serum beta-carotene concentrations.

CONCLUSIONS: CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finland.

IMPLICATIONS: Individuals at high risk of developing lung cancer, i.e., current smokers and asbestos-exposed workers, should be discouraged from taking supplemental beta-carotene (and the combination of beta-carotene with vitamin A).

Sethi S; Eastman AY; Eaton JW
Division of Experimental Pathology, Albany Medical College, NY, USA.
J Lab Clin Med (United States) Jul 1996, 128 (1) p27-38

Diets rich in marine fish oil may protect against cardie not known, fish oils have been reported to exert anti-inflammatory actions. For example, dietary fish oil supplementation was observed to profoundly decrease the numbers of monocytic cells adherent to endothelium overlying atherosclerotic lesions in pigs. We have therefore investigated the possibility that fish oil components-particularly n-3 polyunsaturated fatty acids (PUFAs)-might inhibit phagocyte-endothelium interactions. We have found that binding of a monocytic cell line (U937) to cultured endothelium (with cell adhesion molecules up-regulated by exposure to lipopolysaccharide (LPS), interleukin-1 alpha, tumor necrosis factor-alpha, or phorbol myristate acetate (PMA) is greatly decreased by pre-exposure of endothelial cells to n-3 and other PUFAs that are incidentally or purposefully oxidized; unoxidized PUFAs are completely ineffective. Decreased monocyte adherence probably derives from diminished up-regulation of endothelial cell adherence molecules VCAM-1 and ELAM-1. Oxidized n-3 PUFAs prevent LPS- or PMA-induced activation of transcription factor NF-kappa B and the consequent induction of mRNA for both cell adhesion molecules. Hydroperoxy fatty acids are the active principle in oxidized PUFAs because the activity (1) is predominantly organic soluble, (2) is obliterated by pretreatment of oxidized material with chemical reducing agents, and (3) is diminished by enzymatic reduction of organic hydroperoxides with glutathione/glutathione peroxidase. We speculate that this suppression of phagocyte-endothelium interactions by oxidized PUFAs may help explain the anti-inflammatory and possible anti-atherogenic effects of diets rich in fish oil. Perhaps more importantly, this modulation of endothelial cell adhesion molecule expression by oxidized lipids may represent a natural mechanism whereby inflammation-mediated oxidation of endothelial PUFAs may retard ingress of phagocytes and thereby prevent unrestrained phlogistic responses.

De Lorgeril M; Salen P; Martin JL; Mamelle N; Monjaud I; Touboul P; Delaye J
Centre National de la Recherche Scientifique, UMR 1216, Lyon, France.
J Am Coll Cardiol (United States) Nov 1 1996, 28 (5) p1103-8

OBJECTIVES: We sought to describe the various cardiovascular complications that occurred in the Lyon Diet Heart Study (a secondary prevention trial testing the protective effects of a Mediterranean type of diet), to analyze their relations with the associated drug treatments and to gain insights into the possible mechanisms underlying the beneficial effects of certain nutriments.

BACKGROUND: Dietary habits are implicated in coronary heart disease, and the traditional Mediterranean diet is thought to be cardioprotective. However, the exact mechanisms of this protection are unknown.

METHODS: A total of 605 patients (303 control subjects and 302 study patients) were studied over a mean period of 27 months. Major primary end points (cardiovascular death and nonfatal acute myocardial infarction), secondary end points (including unstable angina, stroke, heart failure and embolisms) and minor end points (stable angina, need for myocardial revascularization, postangioplasty restenosis and thrombophlebitis) were analyzed separately and in combination.

RESULTS: When major primary and secondary end points were combined, there were 59 events in control subjects and 14 events in the study patients, showing a risk reduction of 76% (p < 0.0001). When these end points were combined with the minor end points, there were 104 events in control subjects and 68 events in the study patients, giving a risk reduction of 37% (p < 0.005). By observational analysis, only aspirin among the medications appeared to be significantly protective (risk ratio after adjustment for prognosis factors 0.45; 95% confidence interval 0.25 to 0.80).

CONCLUSIONS: These data show a protective effect of the Mediterranean diet. However, the risk reduction varied depending on the type of end point considered. Our hypothesis is that different pathogenetic mechanisms were responsible for the development of the various complications. It is likely that certain nutriments characteristic of the Mediterranean diet (omega-3 fatty acids, oleic acid ave specific cardioprotective effects.

Wen Y; Killalea S; McGettigan P; Feely J
Department of Pharmacology and Therapeutics, Trinity Centre for Health Sciences, St. James's Hospital, Dublin, Ireland.
Ir J Med Sci (Ireland) Jul-Sep 1996, 165 (3) p210-2

Lipid peroxidation is a free radical process which is implicated in the formation of atherosclerosis. Vitamins C and E are important natural antioxidants which inhibit lipid peroxidation and a high intake of these vitamins, particularly vitamin E, is related to a reduced incidence of ischaemic heart disease. Hypertension is an independent risk factor for atherosclerosis and its relationship to antioxidant status is undetermined. In this study, we investigated free radical activity by measuring plasma malondialdehyde (MDA) using high-performance liquid chromatography (HPLC), vitamin C status measured as plasma ascorbic acid and vitamin E status measured as plasma lipid standardized alpha-tocopherol and erythrocyte alpha-tocopherol. We compared 28 patients with essential hypertension to 31 healthy subjects. Results showed that in comparison with the healthy subjects, the hypertensive patients had significantly higher plasma MDA levels (0.95 +/- 0.28 vs 0.69 +/- 0.21 mumol/l, mean +/- SD, p < 0.001) and significantly lower levels of plasma ascorbic acid (34.83 +/- 12.88 vs 51.76 +/- 13.34 mumol/L, p < 0.01). In addition, erythrocyte alpha-tocopherol concentration, which may reflect vitamin E protection in cell membranes, was significantly lower in hypertensive patients when compared with the normotensive controls (3.87 +/- 0.53 vs 4.82 +/- 1.01 mumol/l, p < 0.001), although plasma alpha-tocopherol levels were similar in the two groups (25.07 +/- 10.45 vs 23.96 +/- 6.07 mumol/l). Our results suggest that hypertensive patients may have increased lipid peroxidation and reduced protection from vitamins C and E. This may contribute to the propensity in such patients to develop atherosclerosis.

Schneider J; Kaffarnik H; Steinmetz A
Zentrum Innere Medizin, Klinikum der Philipps-Universitat Marburg.
Herz (Germany) Aug 1996, 21 (4) p217-26

Numerous epidemiological studies have unequivocally proven a protection from the development of coronary heart disease by moderate long-lasting alcohol consumption. During the past 20 years studies in different ethnic groups starting from an American cohort and spanning to the recently performed analysis in the MONICA-project gave evidence for a decreased morbidity and mortality from coronary heart disease at 1 to 3 drinks a day when compared to total abstainers. A part of the protection is thought to be mediated through alcohol effects on plasma lipoprotein metabolism. Substantial increases in high-density lipoprotein cholesterol and its subfractions occur and are believed to be responsible for as much as half of the alcohol-mediated benefits. In addition, moderate decreases in low-density lipoprotein cholesterol and probably also in lipoprotein(a), established cardiovascular risk factors, may contribute accordingly. Furthermore, antioxidants like flavonoids and polyphenols found in red wines by protecting low density lipoproteins from oxidative modification may explain the "French paradox", the decreased incidence of coronary heart disease in France despite a high consumption of saturated fats. Also, alcoholic vasodilation, decreases in platelet aggregability, changes in prostacyclin/thromboxane ratios and increased fibrinolytic activities are to be considered as additional benefits caused by moderate alcohol consumption. (66 Refs.)

van Poppel G
TNO Nutrition and Food Research Institute, Department of Physiology and Kinetics, Zeist, Netherlands.
Eur J Clin Nutr (England) Jul 1996, 50 Suppl 3 pS57-61

OBJECTIVE AND CONCLUSIONS: This article gives an overview of observational and experimental epidemiological studies relating beta-carotene to risk of cancer and cardiovascular disease. Observational epidemiological studies have consistently shown that a diet rich in beta-carotene are associated with a reduced risk of cancer at a number of common sites, such as lung and stomach. For other cancer sites, such as prostate and breast, the observational evidence is not very consistent or absent altogether. For cardiovascular disease, observational studies are less numerous but do point to a protective effect of high beta-carotene intake. The associations from observational epidemiology may indeed be ascribed to beta-carotene, since a number of plausible preventive mechanisms have been demonstrated for cancer as well as cardiovascular disease. However, observational epidemiology cannot resolve the question whether other constituents from fruits and vegetables or other factors may explain the findings from the case-control and cohort studies. The results of intervention studies undertaken so far are disappointing and do not indicate a preventive potential for beta-carotene. Further intervention trials with longer follow-up may be needed to elucidate whether beta-carotene is protective against certain forms of cancer and against cardiovascular disease. (33 Refs.)

Neve J
Universite Libre de Bruxelles, Institut de Pharmacie, Belgium.6277
J Cardiovasc Risk (England) Feb 1996, 3 (1) p42-7

Selenium is a powerful antioxidant regulating the activity of the glutathione peroxidase enzymes, which catalyse the detoxification of hydrogen peroxide and organic hydroperoxides. Selenium deficiency has been implicated in the aetiopathogeny of Keshan disease, an endemic cardiomyopathy observed in China, and in other cases of congestive cardiomyopathy in subjects on artificial nutrition. However, the evidence from case-control and prospective studies for an association between low selenium status and cardiovascular diseases remains controversial. Mechanisms whereby selenium protects against such diseases include increased resistance of low-density lipoproteins against oxidative modification, modulation of prostaglandin synthesis and platelet aggregation, and protection against toxic heavy metals. The therapeutic benefit of selenium administration in the prevention and treatment of cardiovascular diseases still remains insufficiently documented.

Garcia Tamayo F; Terrazas Valdes LI; Malpica Lopez N
Departamento de Biologia, Facultad de Quimica, Universidad Nacional Autonoma de Mexico, Mexico, D.F.
Arch Med Res (Mexico) Autumn 1996, 27 (3) p319-25

Experimentally induced chronic stress can produce severe retardation on the physical development of young animals. Moreover, the chronic stress and its associated secondary malnutrition cause a variable depression on immunity, whose pathogenesis has been related to the excessive production of cytokines and glucocorticoids. When stressful stimuli are excessive, animals increment their anorexia and express a progressively installed wasting syndrome, associated with hypozincemia and susceptibility to infections with high mortality rate. In this work, chronically stressed mice were studied to observe the prophylactic effect of a zinc treatment on the evolution of both their malnutrition and their immune competence. Stress was induced in newborn Balb/c mice by intraperitoneal (IP) injections with heat-killed bacteria for 4 weeks. Following this inductive period, almost all the stressed mice showed a transient wasting syndrome characterized by anorexia, deficient gain of corporal weight, diarrhea, skin infection, reduced antibody response against antigens of red blood sheep cells, and a decreased proliferative response in their Con-A stimulated splenic lymphocytes. However, when the stressed mice received an additional IP treatment with zinc acetate, their clinical condition showed a significant improvement and their immunocompetence was similar to that exhhe control groups. The results suggest that zinc supplementation can ameliorate the effects of chronic stress on the growth, corporal weight, and immunocompetence of young mice.

Traber MG; Sies H
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Annu Rev Nutr (United States) 1996, 16 p321-47

How much vitamin E is enough? An established use of supplemental vitamin E in humans is in the prevention and therapy of deficiency symptoms. The cause of vitamin E deficiency, characterized by peripheral neuropathy and ataxia, is usually malabsorption-a result of fat malabsorption or genetic abnormalities in lipoprotein metabolism. Genetic abnormalities in the hepatic alpha-tocopherol transfer protein also cause vitamin E deficiency-defects in this protein cause an impairment in plasma vitamin E transport. Impaired delivery of vitamin E to tissues, thereby, results in deficiency symptoms. Also discussed is the use of supplemental vitamin E in chronic diseases such as ischemic heart disease, atherosclerosis, diabetes, cataracts, Parkinson's disease, Alzheimer's disease, and impared immune function, as well as in subjects receiving total parenterol nutrition. In healthy individuals, a daily intake of about 15-30 mg of alpha-tocopherol is recommended to obtain "optimal plasma alpha-tocopherol concentrations" (30 microM or greater). (158 Refs.)

O'Leary VJ; Tilling L; Fleetwood G; Stone D; Darley-Usmar V
Wellcome Research Laboratories, Beckenham, Kent, UK.
Atherosclerosis (Ireland) Jan 26 1996, 119 (2) p169-79

The measurement ex vivo of the resistance of low density lipoprotein (LDL) to oxidation promoted by copper is now being used in surveys of human populations at risk of developing atherosclerosis. However, it is not known whether a relationship between LDL oxidisability measured in this way and the development of atherosclerotic lesions exists. Using Watanabe rabbits as a model of the disease, we have found that dietary supplementation with the antioxidants, probucol and alpha-tocopherol, increased the resistance of LDL isolated from small volumes of plasma to oxidation. The antioxidant effects of probucol incorporated into LDL through dietary supplementation were greater than when incorporated ex vivo. When dietary supplementation was extended to a period of three months, the well established anti-atherosclerotic effects of probucol were confirmed and a highly significant relationship between the probucol content of the LDL particle and the extent of the atherosclerotic lesion in the aorta emerged. These results suggest that the assessment of the resistance of LDL isolated from plasma to oxidation promoted ic process to antioxidant therapy.

Vitoux D; Chappuis P; Arnaud J; Bost M; Accominotti M; Roussel AM
Laboratoire central de biochimie, hopital Lariboisiere, Paris, France.
Ann Biol Clin (Paris) (France) 1996, 54 (5) p181-7

In the last five years, there has been a renewal of interest in the protective role of selenium in vascular disorders, inspired by experimental evidence that this trace element could modulate leukotriene and prostaglandin synthesis in both endothelial cells and platelets. In people living in low-selenium areas, a relationship has been established between a decrease in plasma selenium and an increase in the risk of coronary disease, atherosclerosis, platelet hyperaggregability and synthesis of proaggregant and proinflammatory compounds like thromboxane A2 and leukotrienes. Selenium, as an essential part of glutathione peroxidase, takes part in the reduction of hydrogen peroxides and lipid peroxides. The concentration of these peroxides, in turn, regulates the activities of cyclooxygenase and lipooxygenase pathways, ultimately influencing the production of eicosanoids and modulating the balance between a proaggregatory and antiaggregatory state. Recent evidence shows that selenium, via its action on glutathione peroxidase activity, may be primarily responsible for the regulation of the endogenous hydroperoxide level. In human platelets, the activity of glutathione peroxidase is particularly high and is very sensitive to the requirement of selenium. This sensitivity could explain why platelets of selenium-deficient subjects show increased aggregation, thromboxane B2 production and synthesis of the lipoxygenase-derived compounds. In these deficient subjects, selenium administration increases platelet glutathione peroxidase activity and inhibits platelet hyperaggregation and leukotriene synthesis. These results support the hypothesis that selenium supplementation has a positive effect on platelet aggregation in selenium-deficient subjects. In France, more than 10% of the population is selenium-deficient and long-term supplementation with low doses of selenium could have a beneficial effect on the prevention of both thrombosis and coronary heart disease in these subjects. (35 Refs.)

Bernarducci MP; Owens NJ
The Center for Long Term Care Research and Education, Chesapeake, Virginia 23321-5652, USA.
Pharmacotherapy (United States) Mar-Apr 1996, 16 (2) p183-200

Life expectancy has dramatically increased in industrialized countries since the 1900s due to advances in disease prevention and treatment, and improvements in nutrition and infant mortality. Thus, as a society we are living longer and experiencing more of the changes and declines associated with aging. Although the factors that cause our bodies to age are unknown, various medical interventions have been proposed and explored to prevent the process. Published research on aging conducted during the past 10 years was retrieved through MEDLINE and critically evaluated. Animal and human studies suggest potential benefits of dietary modification, exercise, antioxidants, hormones, and deprenyl. Due to the interrelationships between disease and older age and the limitations of existing research in this area, most life extension strategies are untested hypotheses. Many strategies merit scientific inquiry, but they cannot be recommended for use. More extensive research is necessary to assess their safety, effectiveness, and socioeconomic impact, and to resolve ethical controversies before they can be considered applicable in humans. (74 Refs.)

Gurney ME; Cutting FB; Zhai P; Andrus PK; Hall ED
Central Nervous System Diseases Research Unit, Upjohn Laboratories, Kalamazoo, MI 49001, USA.
Pathol Biol (Paris) (France) Jan 1996, 44 (1) p51-6

Oxidative mechanisms of damage have been implicated indirectly in the damage to brain tissue caused acutely by ischemia or chronically by neurodegenerative diseases. A direct link between pathogenesis and antioxidant enzyme systems has come from studies of a genetic form of amyotrophic lateral sclerosis (ALS). ALS causes the degeneration of motor neurons in cortex, brainstem and spinal cord with consequent progressive paralysis and death. The disease occurs in both sporadic and familial forms. Some 20% of kindreds in which ALS is inherited in an autosomal dominant fashion have mutations in the gene (SOD1) encoding Cu, Zn superoxide dismutase (SOD). Several SOD1 mutations have been shown by ourselves and others to cause motor neuron disease when expressed at high levels in transgenic mice, whereas transgenic mice expressing comparable amounts of wild-type human SOD do not show clinical disease. Thus, we have argued that motor neuron disease is caused by gain-of-function mutations in the human SOD1 gene. Our current experiments investigate the link between mutation of SOD1 and oxidative pathways of damage. (38 Refs.)

Gaziano JM; Hennekens CH
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215-1204, USA.
Pathol Biol (Paris) (France) Jan 1996, 44 (1) p42-5

Advances in diagnosis and treatment of cancer, as well as increased understanding of the mechanisms of the disease, have provided and will certainly continue to provide enormous benefit to affected individuals. At the same time, interventions that may prevent common cancers from developing in healthy people could, at least in theory, afford even greater benefits to society as a whole. The hypothesis that antioxidant vitamins might reduce cancer risk is based on a large body of both basic and human epidemiologic research. A large number of case-control and cohort studies provide remarkably consistent data suggesting that consumption of foods rich in antioxidant vitamins reduce risks of developing epithelial cancers. These data raise the question of a possible role of antioxidants, such as vitamins C and E, and beta carotene, in the primary prevention of cancer as well ar cardiovascular disease but do not provide a definitive answer. Despite the lack of clear benefit, there has been a rapid increase in the consumption of supplements of these micronutrients. Limited randomized trial data on the role of supplemental antioxidants are available. A number of randomized trials are currently underway designed to test the hypothesis that antioxidants prevent chronic diseases and to evaluate the long term safety of the widespread practice of supplementation. Well designed and well conducted large-scale randomized trials are necessary to provide a definitive positive or negative result on which public policy can be based, or a null result that is truly informative and that can then safely permit the rechanneling of already limited resources to other areas of research.

O'Keefe JH Jr; Conn RD; Lavie CJ; Bateman TM
Mid America Heart Institute, Kansas City, Missouri, USA.
Mayo Clin Proc (United States) Oct 1996, 71 (10) p957-65

The old paradigm states that the greater the stenosis, the greater the risk of cardiac events. Revascularization procedures are the only effective approach to improving prognosis associated with coronary artery disease. In contrast, on the basis of the new paradigm, the nature of the plaque determines the risk of acute cardiovascular events. Dangerous plaques have a lipid-rich core with surrounding inflammation and a thin friable overlying fibrous cap, but they usually appear innocuous on angiography. Effective risk factor modification stabilizes the dangerous plaques and is associated with prompt improvement in endothelial dysfunction and a substantial decrease in the risk of acute cardiovascular events and death.

Levander OA; Whanger PD
U.S. Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, MD 20705, USA.
J Nutr (United States) Sep 1996, 126 (9 Suppl) p2427S-2434S

Information is presented regarding the approaches that have been used to establish dietary recommendations for selenium and iodine. In the case of selenium, activity of the selenoenzyme glutathione peroxidase has served as a convenient biochemical endpoint for judging nutritional status. However, there are differences of opinion among various nutritionists as to whether full expression of this enzymatic activity is required for adequate nutriture, thereby resulting in differences in dietary recommendations. Endpoints for assessing selenium overexposure are much less satisfactory, but toxicological standards for selenium have nevertheless been established. Thus far, no nutritionists have attempted to shift the paradigm for determining dietary selenium recommendations away from prevention of deficiency disease to prevention of chronic degenerative disease (e.g., cancer). In the case of iodine, urinary excretion of the element is the most widely used endpoint for judging nutritional status. Numerous epidemiological surveys have been conducted to determine the level of urinary iodine excretion that is consistent with prevention of goiter, the most common endpoint of iodine deficiency. Because dietary iodine is essentially quantitatively excreted in the urine, determination of the latter in goitrous areas will allow an almost direct estimation of those intakes at risk of developing deficiency disease. Iodine toxicity is complicated by the fact that some persons are quite tolerant to the element whereas others are highly sensitive to it. There are relatively complete data sets concerning exposure vs. human health effects for both selenium and iodine so that sounder bases probably exist for their dietary recommendations than for many other trace elements.

Cheraskin E
School of Medicine, University of Alabama at Birmingham, USA.
J Am Optom Assoc (United States) Jan 1996, 67 (1) p50-7

BACKGROUND: Although numerous studies have been published about the probable causes of age-related macular degeneration, arresting or preventing the disease continues to be an elusive goal.

METHODS: The professional literature is reviewed to provide an overview of the relationship of the antioxidants to disorders such as heart disease, cancer, diabetes, arthritis, cataracts and macular degeneration.

RESULTS: Diseases associated with aging appear to have a common denominator: oxidative damage. Antioxidants have been extensively studied to determine if they can prevent or successfully treat these diseases.

CONCLUSIONS: Larger-than-recommended amounts of antioxidants need to be used earlier in life, for longer periods of time, to determine their effectiveness in arresting or preventing diseases of aging. (50 Refs.)

Richer S
Eye Clinic 112e, DVA Medical Center, North Chicago, IL 60064, USA.
J Am Optom Assoc (United States) Jan 1996, 67 (1) p30-49

BACKGROUND: The experimental design, subjects, procedures and baseline data for the prospective double blind dry ARMD-antioxidant intstudy have bee n described in Part 1.

METHODS: At eight DVA medical centers, 32 patients (group one) were assigned a placebo and 39 patients (group two) a "broad spectrum" antioxidant capsule. Data was collected in five areas: demographic; ophthalmic; dietary analysis of daily food intake; serum analysis; and adverse gastrointestinal symptoms. Data was serially acquired at baseline, 6 months, 12 months and 18 months, and was analyzed by univariate repeated factors ANOVA, p = 0.05.

RESULTS: Group two (antioxidant po BID) maintained their distance LogMAR visual acuity (p = 0.03), while there was a trend toward both stabilized near M print (p = 0.07) and 6 cycle/degree contrast sensitivity (p approximately 0.10), in left eyes. However, group two (antioxidant) also had increased cortical opacification of the right lens (p = 0.04), compared to group one (placebo). Self perceived stabilization of vision was reported by subjects in group two and supported the objective data (Pearson chi square; p = 0.05).

CONCLUSIONS: A specific 14 component antioxidant capsule taken twice daily stabilized but did not improve dry ARMD over the study period of 1.5 years. The ARMD stabilized eyes had less advanced disease functionally but not by fundus appearance. Decreased intake of cardioprotective nutrients (vitamin E, zinc, magnesium, B6 and folate) in ARMD patients remained constant over the course of the trial.

Richer S
Eye Clinic 112e, DVA Medical Center, North Chicago, IL 60064, USA.
J Am Optom Assoc (United States) Jan 1996, 67 (1) p12-29

BACKGROUND: A prospective 18 month, double-blind case-controlled study was designed to determine whether a specific over-the-counter multivitamin/mineral/antioxidant nutrient capsule taken twice daily prevents the progression of, or improves the outcome of non-exudative ARMD. Two randomly assigned experimental ARMD groups are compared to each other, to age matched ARMD-free case controls and to 1994 NHANES III nutritional data.

METHODS: Th assigned to group one (placebo) and 39 dry ARMD patients were assigned to group two (Ocuguard, a broad spectrum antioxidant capsule). A third age and sex matched ARMD-free case control group of 13 patients who met the same entrance criteria were also selected. All participants underwent thorough visual and nutritional evaluation prior to initiation of the study. Both ophthalmic tests and dietetic assessments were also performed at 6, 12 and 18 months following a 2-week initiation period.

RESULTS: In comparison to NHANES-III age stratified population data and the Recommended Daily Allowance (but not case controls), the ARMD population manifested decreased intake of nutrients vital to cardiovascular health: vitamin E, magnesium, zinc, vitamin B6 and folic acid. The two randomly assigned experimental groups were well matched, with little difference in baseline demographic, ocular, hematologic and pre-intervention symptoms. There were differences in nutritional intake between the two groups, due primarily to significantly higher percent ideal body weight in group two.

Steinmetz KA; Potter JD
World Cancer Research Fund, London, England.
J Am Diet Assoc (United States) Oct 1996, 96 (10) p1027-39

In this review of the scientific literature on the relationship between vegetable and fruit consumption and risk of cancer, results from 206 human epidemiologic studies and 22 animal studies are summarized. The evidence for a protective effect of greater vegetable and fruit consumption is consistent for cancers of the stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon. The types of vegetables or fruit that most often appear to be protective against cancer are raw vegetables, followed by allium vegetables, carrots, green vegetables, cruciferous vegetables, and tomatoes. Substances present in vegetables and fruit that may help protect against cancer, and their mechanisms, are also briefly reviewed; these include dithiolthiones, isothiocyanates, indole-3-carbinol, allium compounds, isoflavones, protease inhibitors, saponins, phytostnene, lutei n, folic acid, beta carotene, lycopene, selenium, vitamin E, flavonoids, and dietary fiber. Current US vegetable and fruit intake, which averages about 3.4 servings per day, is discussed, as are possible noncancer-related effects of increased vegetable and fruit consumption, including benefits against cardiovascular disease, diabetes, stroke, obesity, diverticulosis, and cataracts. Suggestions for dietitians to use in counseling persons toward increasing vegetable and fruit intake are presented. (262 Refs.)

Buiatti E; Munoz N
Epidemiology Unit, Centre for Cancer Study and Prevention, Florence, Italy.
IARC Sci Publ (France) 1996, (136) p35-9

JA varied and balanced diet that is rich in fresh fruit and vegetables and poor in preserved foods is thought to represent the main protection against gastric cancer. Helicobacter pylori infection also appears to have a role in the disease; its eradication therefore represents another promising potential preventive measure. The effect of diet is supposed to be mediated by micronutrients with an antioxidant role, such as ascorbic acid, beta-carotene and alpha-tocopherol, which could act on different phases of the carcinogenic process, interrupting the progression of precancerous lesions towards cancer. The two trials ongoing in Latin America and the one planned in Europe all deal with the effect of antioxidants, with or without H. pylori eradication, on the progression/ regression rate of precancerous lesions of the stomach. The trial in Venezuela has an 80% power to detect a 50% reduction in the net progression of precancerous lesions in the group (from a high-risk population) undergoing a complex antioxidant treatment for 3 years. In this population a case-control study confirmed the protective effect of fresh fruits and vegetables in relation to gastric cancer. Other trials, which aimed to evaluate the chemopreventive potential of micronutrients on other cancer sites, have reported contradictory results concerning gastric cancer risk. When interpreting these results the following should be considered; a possible interaction between H. pylori infection and the antioxidants; the baseline levels of antioxidants in these populations; and the doses and duration of treatment. (18 Refs.)

HS; Hansen JC; Dewailly E; Jul E; Pedersen M; Deguchi Y; Newman WP; Malcom GT; Tracy RE; Middaugh JP; Bjerregaard P
Center of Primary Health Care, Nuuk, Greenland.
Arctic Med Res (Finland) 1996, 55 Suppl 1 p20-4

Traditional food is culturally, economically and nutritionally important for the Greenlandic Inuit people. In the 1970s the preventive effect of marine fat on cardiovascular disease, thrombosis and atherosclerosis was described. The low incidence of ischemic heart disease among Greenlanders has been related to the high intake of marine food. Since 1990 routine autopsies have taken place in two towns in Greenland, Nuuk and Ilulissat. The autopsies represent 26% of the total number of deaths in these two towns. Samples have been collected from 104 autopsies. International cooperative studies have analysed specimens in relation to ischemic heart disease as a benefit related to diet, as well as the level of heavy metals and organochlorine in organs as a risk related to diet. High amounts of mono-unsaturated and Omega-3 poly-unsaturated fatty acid were found in adipose tissue. Liver analyses of selenium have confirmed the expected high intake among Greenlanders. Reduced atherosclerotic lesions were found in the coronary arteries. Blood pressure levels calculated from renovascholopathia of hypertension indicate prevailing levels similar to those in industrialized countries. Some factors in Greenland may be protecting the coronary arteries, thereby of setting the expected effect of hypertension. The level of methyl mercury in organs is generally high. PCB concentrations found in organs of Greenlanders are higher than among other populations.

Krinsky NI; Peacocke M; Russell RM
N Engl J Med (United States) Oct 3 1996, 335 (14) p1066-7

No abstract.

Pietrzik K
N Engl J Med (United States) Oct 3 1996, 335 (14) p1065-6

No abstract.

Bengmark S; Gianotti L
Ideon Research Center, University of Lund, Suite A 230, Beta House, S-22370 Lund, Sweden.
World J Surg (United States) May 1996, 20 (4) p474-81

Enter postoperative/posttrauma patients. Modern technologies for tube-feeding have made early EN possible. Jejunal tube-feeding has advantages over gastric tube-feeding: faster metabolic recovery, less vomiting, and less risk of regurgitation and aspiration. Immediate or early EN stimulates the splanchnic and hepatic circulations, improves mucosal blood flow, prevents intramucosal acidosis and permeability disturbances, and eliminates the need for stress ulcer prophylaxis. Saliva containing important antimicrobial substances and gastric acidity are important in sepsis prevention. Chewing, saliva, and gastric acidity support gastric nitric oxide (NO) release, important for mucosal blood flow, gastrointestinal (GI) motility, mucus formation, and bacteriostasis. An oral supply of NO-donating substances and chewing of nitrate-rich food, such as lettuce or spinach, can be useful. Oral and mucosa-protective lipids are recommended. H2 blockers and saliva-inhibiting drugs are avoided. Immediate EN should be given, starting with 25 ml/hr and increasing to 100 ml/hr over 24 to 48 hours. For the immunocompromised patient special attention should be given to the purity of water. Bottled water can contain bacteria such as Pseudomonas. Food antioxidants such as glutathione, vitamin E, and beta-carotenes are important. Ingredients for the colonic mucosa are important. Approximately 10% of caloric need is satisfied by so-called colonic food (prebiotics), fermented at the level of the colonic mucosa to produce colonic mucosa nutrients and to prevent gut origin sepsis. More than 10 g of fiber per day is recommended. The fermenting flora (probiotic flora) is deranged owing to disease or antibiotic treatment, and resupply of flora is important. A new concept of ecoimmune nutrition is presented for enteral supply of mucosa-reconditioning ingredients: new surfactants, pseudomucus, fiber, amino acids such as arginine, and mucosa-adhering Lactobacillus plantarum

McAlindon TE; Jacques P; Zhang Y; Hannan MT; Aliabadi P; Weissman B; Rush D; Levy D; Felson DT
Arthritis Center, Boston University Medical Center, Massachusetts, 02118, USA.
Arthritis Rheum (United States) Apr 1996, 39 (4) p648-56

OBJECTIVE: Cumulative damage to tissues, mediated by reactive oxygen species, has been implicated as a pathway that leads to many of the degenerative changes associated with aging. We hypothesized that increased intake of antioxidant micronutrients might be associated with decreased rates of osteoarthritis (OA) in the knees, a common age-related disorder.

METHODS: Participants in the Framingham Osteoarthritis Cohort Study underwent knee evaluations by radiography at examinations 18 (1983-1985) and 22 (1992-1993). Usual dietary intake was assessed using the Food Frequency Questionnaire, administered at examination 20 (1988-1989). Knees without OA at baseline (Kellgren and Lawrence [K & L] grade < or = 1) were classified as having incident OA if they had a K & L grade > or = 2 at followup. Knees with OA at baseline were classified as having progressive OA if their score increased by > or = 1 at followup. Knees were also classified as having cartilage loss or osteophyte growth if their maximal joint space narrowing or osteophyte growth score increased by > or = 1 (range 0-3). The association of vitamin C, beta carotene, and vitamin E intake, ranked in sex-specific tertiles, with incidence and progression of OA was compared with that of a panel of nonantioxidant vitamins, Bl, B6, niacin, and folate, using logistic regression and generalized estimation equations to adjust for correlation between fellow knees. The lowest tertile for each dietary exposure was used as the referent category. Odds ratios (OR) were adjusted for age, sex, body mass index, weight change, knee injury, physical activity, energy intake, and health status.

RESULTS: Six hundred forty participants received complete assessments. Incident and progressive OA occurred in 81 and 68 knees, respectively. We found no significant association of incident OA with any nutrient. A 3-fold reduction in risk of OA progression was found for both the middle tertile (adjusted OR = 0.3, 95% confidence interval [95% CI] 0.1-0.8) and highest tertile (adjusted OR = 0.3, 95% CI 0.1-0.6) of vitamin C intake. This related predominantly to a reduced risk of cartilage loss (adjusted OR = 0.3, 95% CI 0.1-0.8). Those with high vitamin C intake also had a reduced risk of developing knee pain (adjusted OR = 0.3, 95% CI 0.1-0.8). A reduction in risk of OA progression was seen for beta carotene (adjusted OR = 0.4, 95% CI 0.2-0.9) and vitamin E intake (adjusted OR = 0.7, 95% CI 0.3-1.6), but was less consistent. No significant associations were observed for the nonantioxidant nutrients.

CONCLUSION: High intake of antioxidant micronutrients, especially vitamin C, may reduce the risk of cartilage loss and disease progression in people with OA. We found no effecpreliminary findings warrant confirmation.

Mayne ST
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
FASEB J (United States) May 1996, 10 (7) p690-701

A growing body of literature exists regarding the effects of beta-carotene and other carotenoids on chronic diseases in humans. This article reviews and critically evaluates this literature and identifies areas for further research. This review is restricted to studies in humans, with a major emphasis on the most recent literature in the area of carotenoids and selected cancers. Effects of carotenoids on cardiovascular diseases, photosensitivity diseases, cataracts, and age-related macular degeneration are also discussed briefly. Numerous observational studies have found that people who ingest more carotenoids in their diets have a reduced risk of several chronic diseases. However, intervention trials of supplemental beta-carotene indicate that supplements are of little or no value in preventing cardiovascular disease and the major cancers occurring in well-nourished populations, and may actually increase, rather than reduce, lung cancer incidence in smokers. As a consequence of these findings, some of the ongoing trials of beta-carotene and disease prevention have been terminated or have dropped beta-carotene from their interventions. Researchers should now seek explanations for the apparently discordant findings of observational studies vs. intervention trials. The most pressing research issues include studies of interactions of carotenoids with themselves and with other phytochemicals and mechanistic studies of the actions of beta-carotene in lung carcinogenesis and cardiovascular disease. Paradoxically, the finding that lung carcinogenesis and cardiovascular disease can be enhanced by supplemental beta-carotene may ultimately lead to a clearer understanding of the role of diet in the etiology and prevention of these diseases. The conclusion that major public health on of carotenoid-rich fruits and vegetables still appears to stand; however, the pharmacological use of supplemental beta-carotene for the prevention of cardiovascular disease and lung cancer, particularly in smokers, can no longer be recommended. (70 Refs.)

Rimm EB; Ascherio A; Giovannucci E; Spiegelman D; Stampfer MJ; Willett WC
Department of Epidemiology, Harvard School of Public Health, Boston, Mass. 02115, USA.
JAMA (United States) Feb 14 1996, 275 (6) p447-51

OBJECTIVE--To examine prospectively the relationship between dietary fiber and risk of coronary heart disease.

DESIGN--Cohort study.

SETTING--In 1986, a total of 43,757 US male health professionals 40 to 75 years of age and free from diagnosed cardiovascular disease and diabetes completed a detailed 131-item dietary questionnaire used to measure usual intake of total dietary fiber and specific food sources of fiber.

MAIN OUTCOME MEASURE--Fatal and nonfatal myocardial infarction (MI).

RESULTS--During 6 years of follow-up, we documented 734 cases of MI (229 were fatal coronary heart disease). The age-adjusted relative risk (RR) for total MI was 0.59 (95% confidence interval [CI], 0.46 to 0.76) among men in the highest quintile of total dietary fiber intake (median, 28.9 g/d) compared with men in the lowest quartile (median, 12.4 g/d). The inverse association was strongest for fatal coronary disease (RR, 0.45; 95% CI, 0.28 to 0.72). After controlling for smoking, physical activity and other known nondietary cardiovascular risk factors, dietary saturated fat, vitamin E, total energy intake, and alcohol intake, the RRs were only modestly attenuated. A 10-g increase in total dietary fiber corresponded to an RR for total MI of 0.81 (95% CI, 0.70 to 0.93). Within the three main food contributors to total fiber intake (vegetable, fruisk of total MI (RR, 0.71; 95% CI, 0.55 to 0.91 for each 10-g increase in cereal fiber per day).

CONCLUSIONS--Our results suggest an inverse association between fiber intake and MI. These results support current national dietary guidelines to increase dietary fiber intake and suggest that fiber, independent of fat intake, is an important dietary component for the prevention of coronary disease.

Wiseman SA; Mathot JN; de Fouw NJ; Tijburg LB
Unilever Research Laboratory, Vlaardingen, The Netherlands.
Atherosclerosis (Ireland) Feb 1996, 120 (1-2) p15-23

Consumption of a range of dietary antioxidants may be beneficial in protecting low density lipoprotein (LDL) against oxidative modification, as studies have demonstrated that antioxidants other than vitamin E may also function against oxidation of LDL in vitro. In the present study, the effect of polyphenol antioxidants on the susceptibility of LDL to copper-mediated oxidation was investigated after feeding semi-purified diets to 3 groups of New Zealand white (NZW) rabbits. All diets comprised 40% energy as fat with 17% energy as oleic acid. Dietary fatty acid compositions were identical. Oils with different polyphenol contents were used to provide the dietary source of oleic acid-refined olive oil, extra virgin olive oil and Trisun high oleic sunflower seed oil. Polyphenolic compounds (hydroxytyrosol and p-tyrosol) could only be detected in the extra virgin olive oil. Vitamin E was equalised in all diets. LDL oxidizability in vitro was determined by continuously monitoring the copper-induced formation of conjugated dienes after 6 weeks of experimental diet feeding. The lag phase before demonstrable oxidation occurred was significantly increased in the high polyphenol, extra virgin olive oil group (P < 0.05) when compared with combined results from the low polyphenol group (refined olive oil and Trisun), even thoug vitamin E concentration in the high polyphenol group was significantly lower. The rate of conjugated diene formation was not influenced by the presence of dietary polyphenols. Results demonstrate that antioxidants, possibly phenolic compounds which are present only in extra virgin olive oil, may contribute to the endogenous antioxidant capacity of LDL, resulting in an increased resistance to oxidation as determined in vitro.

de Sanjose S; Munoz N; Sobala G; Vivas J; Peraza S; Cano E; Castro D; Sanchez V; Andrade O; Tompkins D; Schorah CJ; Axon AT; Benz M; Oliver W
Servei d'Epidemiologia i Registre del Cancer, Institut Catala d'Oncologia Hospital Duran i Reynals, Barcelona, Spain.
Eur J Cancer Prev (England) Feb 1996, 5 (1) p57-62

A randomized chemoprevention trial on precancerous lesions of the stomach is being conducted in Tachira State, Venezuela. The aims of the study are to evaluate the efficacy of vitamin supplementation in preventing the progression rate of precancerous lesions. Here we report on the pilot phase of the study in which two antioxidant preparations were evaluated on their ability to raise antioxidant levels in plasma and in gastric juice. The study aimed also to determine the antibiotic sensitivity profiles of Helicobacter pylori isolates prevalent in the area. Forty-three subjects with precancerous lesions (chronic gastritis, chronic atrophic gastritis, intestinal metaplasia and dysplasia) of the stomach were randomized to one of atments. Treatment 1 (250 mg of standard vitamin C, 200 mg of vitamin E and 6 mg of beta-carotene three times a day) or treatment 2 (150 mg of standard vitamin C, 500 mg of slow release vitamin C, 75 mg of vitamin E and 15 mg of beta-carotene once a day) for 7 days. Blood levels of total vitamin C, beta-carotene and alpha-tocopherol and gastric juice levels of ascorbic acid and total vitamin C were measured before and after treatment on day 8. Both treatments increased the plasma levels of total vitamin C, beta-carotene and alpha-tocopherol/cholesterol but not those of ascorbic acid or total vitamin C in gastric juice. Treatment 1 was the best choice and resulted in a greater increase in the plasma levels of beta-carotene and alpha-tocopherol. H. pylori was cultured from 90% of the gastric biopsies; 35 isolates were identified which were highly resistant to metronidazole, a front-line antibiotic recommended against H. pylori in other settings.

Greenberg ER; Sporn MB
N Engl J Med (United States) May 2 1996, 334 (18) p1189-90, 10/L/184

No abstract.

Omenn GS; Goodman GE; Thornquist MD; Balmes J; Cullen MR; Glass A; Keogh JP; Meyskens FL; Valanis B; Williams JH; Barnhart S; Hammar S
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
N Engl J Med (United States) May 2 1996, 334 (18) p1150-5

BACKGROUND. Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders.

METHODS. We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of luew cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years.

CONCLUSIONS. After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

Hennekens CH; Buring JE; Manson JE; Stampfer M; Rosner B; Cook NR; Belanger C; LaMotte F; Gaziano JM; Ridker PM; Willett W; Peto R
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA.
N Engl J Med (United States) May 2 1996, 334 (18) p1145-9

BACKGROUND. Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease, and earlier basic research suggested plausible mechanisms. Because large randomized trials of long duration were necessary to test this hypothesis directly, we conducted a trial of beta carotene supplementation.

METHODS. In a randomized, double-blind, placebo-controlled trial of beta carotene (50 mg on alternate days), we enrolled 22,071 male physicians, 40 to 84 years of age, in the United States; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982. By December 31, 1995, the scheduled end of the study, fewer than 1 percent had been lost to follow-up, and compliance was 78 percent in the group that received beta carotene.

RESULTS. Among 11,036 physicians randomly assigned to receive beta carotene and 11,035 assigned to receive placebo, there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease, or in overall mortality. In the beta carotene group, 1273 men had any malignant neoplasm (except nonmelanoma skin cancer), as compared with 1293 in the placebo group (relative risk, 0.98; 95 percent confidence interval, 0.91 to 1.06). There were also no significant differences in the number of cases of lung cancer (82 in the beta carotene group vs. 88 in the placebo group); the number of deaths from cancer (386 vs. 380), deaths from any cause (979 vs. 968), or deaths from cardiovascular disease (338 vs. 313); the number of men with myocardial infarction (468 vs. 489); the number with stroke (367 vs. 382); or the number with any one of the previous three end points (967 vs. 972). Among current and former smokers, there were also no significant early or late differences in any of these end points.

CONCLUSIONS. In this trial among healthy men, 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms, cardiovascular disease, or death from all causes.

Dabrowski K; Ciereszko A
School of Natural Resources, The Ohio State University, Columbus 43210, USA.
Experientia (Switzerland) Feb 15 1996, 52 (2) p97-100

An animal unable to synthesize ascorbic acid uniquely mimicks human and non-human primates. Therefore, in this study we used the rainbow trout, a teleost fish, as the model animal to study the importance of dietary ascorbic acid on the fertilizing ability of sperm. A high concentration of ascorbic acid in semen plays a key role in maintaining the genetic integrity of sperm cells, by preventing oxidative damage to sperm DNA. This study will show that the concentration of ascorbic acid in seminal plasma reflects the dietary intake of vitamin C. The concentration of ascorbic acid in seminal plasma of fish declined significantly in groups fed either an ascorbate-free diet (from 4.74 +/- 0.9 to 0.16 +/- 0.08 microgram ml-1) or an ascorbate-rich diet (from 37.9 +/- 4.7 to 17.7 +/- 3.2 microgram ml-1) during the spermiation season. The relationship between ascorbate status and fertility was studied in six groups of fish fed graded levels of ascorbic acid, which spermiated over a 150-day-period. Sperm from individual males was used to fertilize several batches of eggs. When the seminal plasma ascorbate concentration decreased to 7.3 microgram ml-1 a significant decrease of fertilization rate and the hatching rate of embryos resulted. This is the first evidence that dietary ascorbate level directly affected sperm quality and influenced male fertility in a scurvy-prone vertebrate.

Kyriakis SC; Tsinas A; Lekkas S; Sarris K; Bourtzi-Hatzopoulou E
Clinic of Medicine, Faculty of Veterinary Medicine, University of Thessaloniki, Macedonia, Greece.
Vet Rec (England) May 18 1996, 138 (20) p489-92

This field trial was designed to investigate whether the incorporation of zinc bacitracin into pig feed would prevent porcine intestinal adenomatosis. Two hundred-and-eighty-eight weaned pigs on a farm with a previous history of the disease were divided into 16 pens of 18 pi bacitracin were tested: from weaning up to 100 days of age, either 300 or 200 ppm zinc bacitracin were incorporated; from 100 to 125 days of age, either 200 or 100 ppm zinc bacitracin were added; and from 125 to 156 days of age (slaughter), either 100 or 50 ppm zinc bacitracin were added. The results were compared with a positive control group which received 60, 60 and 30 ppm salinomycin during the same periods, and with a negative control group which received no antibacterial and/or performance enhancer. The mortality, diarrhoea scores, average daily weight gains, average daily feed intakes and feed conversion ratios of the pigs were assessed. At slaughter, samples of ileum were taken from eight randomly selected pigs per group for bacteriological and histopathological examinations. The three treated groups all performed better than the control group, and the group receiving the high dose regimen of zinc bacitracin performed significantly better than the groups receiving the low dose of zinc bacitracin or salinomycin.

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