Whole Body Health Sale

BETA CAROTENE



Table of Contents
image Inhibitory effect of conjugated dienoic derivatives of linoleic acid and beta-carotene on the in vitro growth of human cancer cells
image Vegetable and fruit consumption in relation to prostate cancer risk in Hawaii: A reevaluation of the effect of dietary beta-carotene
image Serologic precursors of cancer. Retinol, carotenoids, and tocopherol and risk of prostate cancer
image Application of molecular epidemiology to lung cancer chemoprevention.
image Antioxidant actions of beta-carotene in liposomal and microsomal membranes: role of carotenoid-membrane incorporation and alpha-tocopherol.
image Randomised trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infraction
image Validity of diagnoses of major coronary events in national registers of hospital diagnoses and deaths in Finland.
image Hypertension and borderline isolated systolic hypertension increase risks of cardiovascular disease and mortality in male physicians.
image Demonstration of organotropic effects of chemopreventive agents in multiorgan carcinogenesis models.
image Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance
image Epidemiological evidence for beta-carotene in prevention of cancer and cardiovascular disease.
image Beta-carotene, carotenoids, and disease prevention in humans.
image Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease
image Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease
image Oxidatively modified LDL and atherosclerosis: an evolving plausible scenario.
image Mortality associated with low plasma concentration of beta carotene and the effect of oral supplementation.
image Effect of vitamin E and beta carotene on the incidence of angina pectoris. A randomized, double-blind, controlled trial.
image Antioxidant defenses in metal-induced liver damage
image Natural killer cell activity in elderly men is enhanced by beta-carotene supplementation
image Prevention of cerebrovascular insults
image Antioxidant status and lipid peroxidation in patients infected with HIV
image Dietary supplementation with orange and carrot juice in cigarette smokers lowers oxidation products in copper-oxidized low-density lipoproteins
image Chemoprevention of oral leukoplakia and chronic esophagitis in an area of high incidence of oral and esophageal cancer.
image Dietary vitamin C, beta-carotene and 30-year risk of stroke: Results from the western electric study.
image Alpha-2 adrenoceptor subtype causing nitric oxide-mediated vascular relaxation in rats.
image Vitamin A and carotene values of institutionalized mentally retarded subjects with and without Down's syndrome.
image [Patients with type-II diabetes mellitus and neuropathy have nodeficiency of vitamins A, E, beta-carotene, B1, B2, B6, B12 and folic acid]
image The age-associated decline in immune function of healthy individuals is not related to changes in plasma concentrations of beta-carotene, retinol, alpha-tocopherol or zinc
image Recommended dietary allowance: support from recent research.
image Critical reappraisal of vitamins and trace minerals in nutritional support of cancer patients.
image Socioeconomic status and lung cancer incidence in men in The Netherlands: Is there a role for occupational exposure?
image [Prevention of cerebrovascular insults]
image The mechanism of apolipoprotein B-100 thiol depletion during oxidative modification of low-density lipoprotein
image The carotenoids beta-carotene, canthaxanthin and zeaxanthin inhibit macrophage-mediated LDL oxidation
image Antioxidant status of hypercholesterolemic patients treated with LDL apheresis
image Oxidized low density lipoproteins in atherogenesis: Role of dietary modification
image Effect of dietary supplementation of beta-carotene on human monocyte -macrophage-mediated oxidation of low density lipoprotein
image The role of free radicals in disease
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 Effect of vitamin E, vitamin C and beta-carotene on LDL oxidation and atherosclerosis
image Pharmacotherapy in Alzheimer's dementia: Treatment of cognitive symptoms Results of new studies
image Intake of selected micronutrients and the risk of endometrial carcinoma
image New agents for cancer chemoprevention
image Status of antioxidants in patients with diabetes mellitus with and without late complications
image Antioxidants, Helicobacter pylori and stomach cancer in Venezuela.
image Prevention of esophageal cancer: the nutrition intervention trials in Linxian, China. Linxian Nutrition Intervention Trials Study Group.
image Possible immunologic involvement of antioxidants in cancer prevention.
image Synergistic suppression of azoxymethane-induced foci of colonic aberrant crypts by the combination of beta-carotene and perilla oil in rats
image Dietary intake of specific carotenoids and vitamins A, C, and E, and prevalence of colorectal adenomas

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Inhibitory effect of conjugated dienoic derivatives of linoleic acid and beta-carotene on the in vitro growth of human cancer cells

Shultz TD; Chew BP; Seaman WR; Luedecke LO

Cancer Lett (NETHERLANDS) Apr 15 1992, 63 (2) p125-33

The effects of physiologic concentrations of conjugated linoleic acid (CLA) and beta-carotene were assessed on human (M21-HPB, malignant melanoma; HT-29, colorectal; MCF-7, breast) cancer cells. The incubation of cancer cells with CLA showed significant reductions in proliferation (18-100%) compared to control cultures. M21-HPB and MCF-7 cell mortality was dose- and time-dependent. beta-Carotene was inhibitory to breast cells only. MCF-7 cells supplemented with CLA incorporated significantly less [3H]leucine (45%), [3H]uridine (63%) and [3H]thymidine (46%) than control cultures. M21-HPB and HT-29 cells supplemented with CLA incorporated less [3H]leucine (25-30%). These in vitro results suggest that CLA and beta-carotene may be cytotoxic to human cancer cells in vivo.



Vegetable and fruit consumption in relation to prostate cancer risk in Hawaii: A reevaluation of the effect of dietary beta-carotene

AM. J. EPIDEMIOL. (USA), 1991, 133/3 (215-219)

This is a further analysis of a case-control study of 452 prostate cancer cases and 899 population controls that was conducted in 1970-1983 among the multiethnic population of Hawaii. Because a previous analysis had shown a positive association with intake of beta-carotene, a nutrient presently being tested for chemoprevention, the authors reexamined the data for consistency among the main food sources of beta-carotene. Vegetables and fruits containing other phytochemicals suspected to be cancer inhibitors were also examined. With the exception of papaya, which was positively associated with risk among men aged 70 years and older, consumption of other yellow-orange fruits and vegetables, tomatoes, dark green vegetables, and cruciferous vegetables was not associated with prostate cancer risk. These results suggest that: 1) the positive association with beta-carotene intake among older men that the authors previously reported was essentially due to the greater papaya consumption of cases compared with controls; and 2) intake of beta-carotene, lycopene, lutein, indoles, phenols, or other phytochemicals is not associated with prostate cancer risk.



Serologic precursors of cancer. Retinol, carotenoids, and tocopherol and risk of prostate cancer

J. NATL. CANCER INST. (USA), 1990, 82/11 (941-946)

We investigated the associations of serum retinol, the carotenoids beta-carotene and lycopene, and tocopherol (vitamin E) with the risk of prostate cancer in a nested case-control study. For the study, serum obtained in 1974 from 25,802 persons in Washington County, MD, was used. Serum levels of the nutrients in 103 men who developed prostate cancer during the subsequent 13 years were compared with levels in 103 control subjects matched for age and race. Although no significant associations were observed with beta-carotene, lycopene, or tocopherol, the data suggested an inverse relationship between serum retinol and risk of prostate cancer. We analyzed data on the distribution of serum retinol by quartiles, using the lowest quartile as the reference value. Odds ratios were 0.67, 0.39, and 0.40 for the second, third, and highest quartiles, respectively.



Application of molecular epidemiology to lung cancer chemoprevention.

Mooney LA; Perera FP

Columbia University School of Public Health, Division of Environmental Health Sciences, New York, New York 10032, USA.

J Cell Biochem Suppl (UNITED STATES) 1996, 25 p63-8

Molecular epidemiology has made great progress in detecting and documenting carcinogenic exposures and host susceptibility factors, in an effort to explain interindividual variation in disease. Interindividual differences in genetic and acquired factors including nutritional status. Eleva ted risk of lung cancer has been associated with polymorphisms of metabolic genes such as CYP1A1 and GSTM1. On the other hand, numerous studies have demonstrated that diets rich in fruits and vegetables are protective against cancer, and have correlated high levels of antioxidants in the blood with decreased risk. As a first step in identifying susceptible individuals, we have assessed the combined effect of genetic factors and nutritional status on DNA adducts in a population of healthy smokers. Plasma retinol, beta-carotene, alpha-tocopherol, and zeaxanthin were inversely correlated with DNA damage, especially in subjects lacking the "protective" GSTM1 gene. Research is ongoing using biomarkers to determine the effect of supplementation with antioxidants/vitamins on DNA damage, especially in population subsets with putative "at risk" genotypes. Information on mechanisms of interactions between exposure, micronutrients, and other susceptibility factors is important in the development of effective practical interventions. (33 Refs.)



Antioxidant actions of beta-carotene in liposomal and microsomal membranes: role of carotenoid-membrane incorporation and alpha-tocopherol.

Liebler DC; Stratton SP; Kaysen KL

College of Pharmacy, University of Arizona, Tucson, Arizona, 85721-0207, USA.

Arch Biochem Biophys (UNITED STATES) Feb 15 1997, 338 (2) p244-50

beta-Carotene and other carotenoids are widely regarded as biological antioxidants. However, recent clinical trials indicate that beta-carotene supplements are not effective in disease prevention and raise questions about the biological significance of carotenoid antioxidant actions. To further explore this evaluated the antioxidant actions of beta-carotene in liposomal and biological membrane systems. In dilinoleoylphosphatidylcholine liposomes in which 0.35 mol % beta-carotene was incorporated into the bilayer during liposome preparation, the carotenoid inhibited lipid peroxidation initiated by 10 mm azobis[amidinopropane HCl] (AAPH). In carotenoid-free liposome suspensions to which the same amount of beta-carotene was added, no antioxidant effect was observed. Supplementation of rat liver microsomes with beta-carotene in vitro yielded microsomes containing 1.7 nmol beta-carotene mg-1 and 0.16 nmol alpha-tocopherol mg-1 microsomal protein. In beta-carotene supplemented microsomes incubated with 10 mm AAPH under an air atmosphere, lipid peroxidation did not occur until alpha-tocopherol was depleted by approximately 60%. beta-Carotene exerted no apparent antioxidant effect and was not significantly depleted in the incubations. Similar results were obtained when the incubation was done at 3.8 torr O2. In liver microsomes from Mongolian gerbils fed beta-carotene-supplemented diets, beta-carotene levels were 16-37% of alpha-tocopherol levels. The kinetics of AAPH-induced lipid peroxidation were no different in beta-carotene-supplemented microsomes than in microsomes from unsupplemented animals, although the kinetics of beta-carotene and alpha-tocopherol depletion were similar. The results indicate that beta-carotene is ineffective as an antioxidant when added to preformed lipid bilayer membranes and that alpha-tocopherol is a much more effective membrane antioxidant than beta-carotene, regardless of the method of carotenoid-membrane incorporation. These results support a reevaluation of the proposed antioxidant role for beta-carotene in biological membranes.



Randomised trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infraction

Rapola JM; Virtamo J; Ripatti S; Huttunen JK; Albanes D; Taylor PR; Heinonen OP

National Public Health Institute, Helsinki, Finland.

Lancet (ENGLAND) Jun 14 1997, 349 (9067) p1715-20

BACKGROUND: Epidemiological data suggest that the intake of antioxidants such as alpha-tocopherol (vitamin E) and beta-carotene has an inverse correlation with the incidence of coronary heart disease. The results from clinical trials of antioxidant supplementation in people with known coronary heart disease are inconclusive. METHODS: We studied the frequency of major coronary events in 1862 men enrolled in the alpha-tocopherol beta-carotene Cancer Prevention Study (smokers aged between 50 and 69 years) who had a previous myocardial infarction. In this randomised, double-blind. placebo-controlled study, men had received dietary supplements of alpha-tocopherol (50 mg/day), beta-carotene (20 mg/day), both, or placebo. The median follow-up was 5.3 years. The endpoint of this substudy was the first major coronary event after randomisation. Analyses were by intention to treat. FINDINGS: 424 major coronary events (non-fatal myocardial infarction and fatal coronary heart disease) occurred during follow-up. There were no significant differences in the number of major coronary events between any supplementation group and the placebo group (alpha-tocopherol 94/466; beta-carotene 113/461; alpha-tocopherol and beta-carotene 123/497; placebo 94/438 [log-rank test, p = 0.25]). There were significantly more deaths from fatal coronary heart disease in the beta-carotene (74/461, multivariate-adjusted relative risk 1.75 [95% CI 1.16-2.64], p = 0.007) and combined alpha-tocopherol and beta-carotene groups (67/497, relative risk 1.58 [1.05-2.40], p = 0.038), but there w as no significant increase in the alpha-tocopherol supplementation group (54/466, relative risk 1.33 [0.86-2.05], p = 0.20). INTERPRETATION: The proportion of major coronary events in men with a previous myocardial infarction who smoke was not decreased with either alpha-tocopherol or beta-carotene supplements. In fact, the risk of fatal coronary heart disease increased in the groups that received either beta-carotene or the combination of alpha-tocopherol and beta-carotene; there was a non-significant trend of increased deaths in the alpha-tocopherol group. We do not recommend the use of alpha-tocopherol or beta-carotene supplements in this group of patients.



Validity of diagnoses of major coronary events in national registers of hospital diagnoses and deaths in Finland.

Rapola JM; Virtamo J; Korhonen P; Haapakoski J; Hartman AM; Edwards BK; Heinonen OP

National Public Health Institute, Helsinki, Finland.

Eur J Epidemiol (NETHERLANDS) Feb 1997, 13 (2) p133-8

We validated diagnoses of acute myocardial infarction (AMI) and death from coronary heart disease (CHD) found in the Finnish National Hospital Discharge Register and the Register of Causes of Death from a sample of the 29,133 men participating in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cases were traced to hospitals and institutes performing medico-legal death cause examinations and all relevant information was collected. The cardiac events were re-evaluated according to the diagnostic criteria of the Finnish contribution to the WHO MONICA project, i.e. the FINMONICA criteria. Altogether 408 cases of non-fatal AMI (n = 217) and death from CHD (n = 191) were reviewed. In the re-evaluation 94% of them (95% confidence interval 92-96%) were diagnosed as either definite (57%) or possible (37%) AMI. Non-fatal cases were more often classified definite AMI in the review, whereas fatal cases were more often classified possible AMI. Age or trial supplementation group did not affect classification, and no secular trend was observed. In conclusion, the diagnoses of AMI and death from CHD in the registers were highly predictive of a true major coronary event defined by strict criteria, thus their use in endpoint assessment in epidemiological studies and clinical trials is justified.



Hypertension and borderline isolated systolic hypertension increase risks of cardiovascular disease and mortality in male physicians.

O'Donnell CJ; Ridker PM; Glynn RJ; Berger K; Ajani U; Manson JE; Hennekens CH

Department of Medicine, Brigham and Women's Hospital, Boston, Mass, USA.

Circulation (UNITED STATES) Mar 4 1997, 95 (5) p1132-7

BACKGROUND: The objective of this study was to examine whether definite hypertension and borderline isolated systolic hypertension predict subsequent cardiovascular disease and mortality. METHODS AND RESULTS: This was a prospective cohort study with a mean follow-up of 11.7 years. The subjects were a group of 18,682 apparently healthy US men, aged 40 to 84 years, participating in the Physicians' Health Study, a randomized trial of low-dose aspirin and beta-carotene. The main outcome measures were total cardiovascular disease, myocardial infarction, stroke, cardiovascular death, with substantially increased risks of total cardiovascular disease (relative risk [RR] 1.92; 95% confidence interval [CI], 1.70 to 2.18), myocardial infarction (RR,1.78; 95% CI, 1.49 to 2.13), stroke (RR, 2.19; 95% CI, 1.78 to 2.69), and cardiovascular death (RR, 2.10; 95% CI, 1.68 to 2.63). Borderline isolated systolic hypertension was associated with significantly increased risks of cardiovascular disease (RR, 1.32; 95% CI, 1.09 to 1.59), stroke (RR, 1.42; 95% CI, 1.04 to 1.93), and cardiovascular death (RR, 1.56; 95% CI, 1.13 to 2.15), as well as a possible but non-significant increased risk of myocardial infarction (RR, 1.26; 95% CI, 0.95 to 1.67). Hypertension and borderline isolated systolic hypertension were associated with significantly increased risks of 41% and 22%, respectively, for all-cause mortality. CONCLUSIONS: Hypertension as well as borderline isolated systolic hypertension are associated with elevated risks of cardiovascular diseases, especially stroke and cardiovascular death. Hypertension is associated with an increased risk of myocardial infarction, and borderline isolated systolic hypertension predicts a possible but more modest increase in risk. These data add to the existing evidence that hypertension is a major cardiovascular risk factor and extend the findings to borderline isolated systolic hypertension.



Demonstration of organotropic effects of chemopreventive agents in multiorgan carcinogenesis models.

Tsuda H; Iwahori Y; Asamoto M; Baba-Toriyama H; Hori T; Kim DJ; Uehara N; Iigo M; Takasuka N; Murakoshi M; Nishino H; Kakizoe T; Araki E; Yazawa K

National Cancer Center Research Institute, National Cancer Center Hospital, Tokyo, Japan.

IARC Sci Publ (FRANCE) 1996, (139) p143-50

Organotropic chemopreventive effects of three (pro)vitamins and three unsaturated fatty acids were examined using mouse and rat multiorgan carcinogenesis models. For the study of (pro)vitamins, male and female B6C3F1 mice were treated with N,N-diethylnitrosamine (DEN) and N-methyl-N-nitrosourea (MNU) during the first 11 weeks, then from weeks 12 to 32 they received alpha-carotene (0.4 mg/mouse), beta-carotene (0.4 mg/mouse) or alpha-tocopherol (40 mg/mouse) three times a week by gavage; control mice received vehicle alone. In male mice, alpha-carotene significantly reduced liver weights, representing a reduced tumour mass (P < 0.001), and alpha-carotene, beta-carotene and alpha-tocopherol significantly reduced the numbers of liver tumours (adenomas a0.01) as compared with control mice, the effects being greatest with alpha-carotene. In female mice, alpha-carotene significantly decreased the number of liver tumours (P < 0.001). In the lung, alpha-carotene and alpha-tocopherol reduced the area of lesions (hyperplasias and adenomas combined) only in males (P < 0.05). For the study of unsaturated fatty acids, F344 male rats were treated with DEN, MNU, N-butyl-N-hydroxybutylnitrosamine (BBN), 1,2-dimethylhydrazine (DMH) and N,N-bis(2-hydroxy)propylnitrosamine during the first 5 weeks, then from weeks 6 to 36 they were given docosahexaenoic acid (C22:6), eicosapentaenoic acid (C20:5) or linoleic acid (C18:2) at 1.0 g/rat, three times a week by gavage; control rats were treated with oleic acid (C18:1) using the same protocol. All animals were fed a low linoleic acid and calorie-adjusted basal diet during fatty acid administration. Docosahexaenoic acid and linoleic acid reduced tumours in the large and small intestines, respectively. However, they did not influence the yield of preneoplastic liver, lung, kidney, forestomach and urinary bladder lesions. The data thus provide evidence for organotropic effects of carotenoids and unsaturated fatty acids on carcinogenesis.

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Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance

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

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.



Epidemiological evidence for beta-carotene in prevention of cancer and cardiovascular disease.

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.)



Beta-carotene, carotenoids, and disease prevention in humans.

Mayne ST

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.)



Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease

Omenn GS; Goodman GE; Thornquist MD; Balmes J; Cullen MR; Glass A; Keogh JP; Meyskens FL; Valanis B; Williams JH; Barnhart S; Hammar S

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.



Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease

Hennekens CH; Buring JE; Manson JE; Stampfer M; Rosner B; Cook NR; Belanger C; LaMotte F; Gaziano JM; Ridker PM; Willett W; Peto R

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.



Oxidatively modified LDL and atherosclerosis: an evolving plausible scenario.

Jialal I; Fuller CJ

Crit Rev Food Sci Nutr (UNITED STATES) Apr 1996, 36 (4) p341-55

Much evidence has accumulated that implicates the oxidative modification of low-density lipoprotein (LDL) in the early stages of atherogenesis. The , they have nutrients alpha-tocopherol, ascorbic acid, and betacarotene been shown to increase the resistance of LDL to oxidation when given to animals and humans. Because plasma levels of these nutrients can be increased by dietary supplementation with minimal side effects, they may show promise in the prevention of coronary artery disease. (115 Refs.)



Mortality associated with low plasma concentration of beta carotene and the effect of oral supplementation.

Greenberg ER; Baron JA; Karagas MR; Stukel TA;

JAMA (UNITED STATES) Mar 6 1996, 275 (9) p699-703

OBJECTIVE: To examine the relationship between beta carotene plasma concentration and beta carotene supplementation and risk of death from major disease causes. DESIGN: Cohort study of plasma concentrations; randomized, controlled clinical trial of supplementation. SETTING: Medical school-affiliated dermatology practices. PATIENTS: A total of 1188 men and 532 women with mean age of 63.2 years, who had enrolled in a randomized clinical trial of beta carotene supplementation to prevent nonmelanoma skin cancer. INTERVENTION: Oral beta carotene, 50 mg per day for a median of 4.3 years. MAIN OUTCOME MEASURES: All-cause mortality and mortality from cardiovascular disease and cancer. RESULTS: During a median follow-up period of 8.2 years, there were 285 deaths. Persons whose initial plasma beta carotene concentrations were in the highest quartile (>0.52 micromol/L [27.7 microg/dL]) had a lower risk of death from all causes (adjusted relative rate [RR], 0.52; 95% confidence interval [CI] 0.44 to 0.87) and from cardiovascular diseases (adjusted RR, 0.57; 95% CI, 0.34 to 0.95) compared with persons with initial concentrations in the lowest quartile (<0.21 micromol/L [11.2 microg/dL]). Patients randomly assigned to beta carotene supplementation showed no reduction in relative mortality rates from all causes (adjusted RR, 1.03; 95% CI, 0.82 to 1.30) or from cardiovascular disease (adjusted RR, 1.16; 95% CI, 0.82 to 1.64). There was no evidence of lower mortality following supplementation among patients with initial beta carotene concentrations below the median for the study group. CONCLUSIONS: These analyses provide no support for a strong effect of supplemental beta carotene in reducing mortality from cardiovascular disease or other causes. Although the possibility exists that beta carotene supplementation produces benefits that are too small or too delayed to have been detected in this study, noncausal explanations should be sought for the association between plasma concentrations of beta carotene and diminished risk of death.



Effect of vitamin E and beta carotene on the incidence of angina pectoris. A randomized, double-blind, controlled trial.

Rapola JM; Virtamo J; Haukka JK; Heinonen OP; Albanes D; Taylor PR; Huttunen JK

JAMA (UNITED STATES) Mar 6 1996, 275 (9) p693-8

OBJECTIVE: To examine the effect of supplementation with vitamin E (alpha tocopherol), beta carotene, or both on the incidence of angina pectoris in men without known previous coronary heart disease. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING AND PARTICIPANTS: Participants in the Alpha Tocopherol, Beta Carotene Cancer Prevention Study (N=29133) were male smokers aged 50 through 69 years who were living in southern and western Finland. Of these men, 22269 were considered free of coronary heart disease at baseline and were followed up for the incidence of angina pectoris. INTERVENTION: Participants were randomized to receive 50 mg/d of alpha tocopherol, 20 mg/d of beta carotene, both, or placebo in a 2x2 design. OUTCOME MEASURES: An incident case was defined as the first occurrence of typical angina pectoris identified in administering the annually repeated World Health Organization (Rose) Chest Pain Questionnaire. RESULTS: During a median follow-up time of 4.7 years (96427 person-years), 1983 new cases of angina pectoris were detected. Comparing alpha tocopherol-supplemented subjects with non-alpha tocopherol-supplement ed subjects showed a relative risk (RR) of angina pectoris incidence of 0.91 (95% confidence interval[CI], 0.83 to 0.99; P=.04). The RR for incidence of angina pectoris for the beta carotene- supplemented subjects compared with those not receiving beta carotene was 1.06 (95% CI, 0.97 to 1.16; P=.19). Compared with those receiving placebo, the RRs for incidence of angina pectoris were 0.97 (95% CI, 0.85 to 1.10) and 0.96 (95% CI, 0.85 to 1.09) in the alpha tocopherol and alpha tocopherol plus beta carotene groups, respectively, and 1.13 (95% CI, 1.00 to 1.27) in the beta carotene group (P=.06). Baseline dietary intakes and serum levels of alpha tocopherol and beta carotene did not predict incidence of angina pectoris. CONCLUSIONS: Supplementation with alpha tocopherol was associated with only a minor decrease in the incidence of angina pectoris. Beta carotene had no preventive effect and was associated with a slight increase of angina.



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.



Natural killer cell activity in elderly men is enhanced by beta-carotene supplementation

American Journal of Clinical Nutrition (USA), 1996, 64/5 (772-777)

Natural killer (NK) cell activity has been postulated to be an immunologic link between beta-carotene and cancer prevention. In a cross- sectional, placebo-controlled, double-blind study we examined the effect of 10-12 y of beta-carotene supplementation (50 mg on alternate days) on NK cell activity in 59 (38 middle-aged men, 51-64 y; 21 elderly men, 65-86 y) Boston area participants in the Physicians' Health Study. No significant difference was seen in NK cell activity due to beta-carotene supplementation in the middle-aged group. The elderly men had significantly lower NK cell activity than the middle-aged men; however, there was no age-associated difference in NK cell activity in men supplemented with beta-carotene. beta-carotene- supplemented elderly men had significantly greater NK cell activity than elderly men receiving placebo. The reason for this is unknown; however, it was not due to an increase in the percentage of NK cells, nor to an increase in interleukin 2 (IL-2) receptor expression, nor to IL-2 production. beta- carotene may be acting directly on one or more of the lytic stages of NK cell cytotoxicity, or on NK cell activity-enhancing cytokines other than IL-2, such as IL-12. Our results show that long-term beta-carotene supplementation enhances NK cell activity in elderly men, which may be beneficial for viral and tumoral surveillance.



Prevention of cerebrovascular insults

Schweiz Med Wochenschr (SWITZERLAND) Nov 12 1994, 124 (45) p1995-2004

Cerebrovascular infarction is the third leading cause of mortality following coronary heart disease and malignancies. WHO studies show that more than half of patients admitted for cerebrovascular infarction were not treated for hypertension. The risk factors for coronary heart disease and cerebrovascular infarction are not identical. Patients with systolic and diastolic hypertension, atrial fibrillation, stenosis of the carotid artery, and smoking, have a significantly elevated risk for cerebrovascular accidents. Hypercholesterolemia and diabetes are less important risk factors. Risk factors amendable by adequate nutritional intake are low supply of carotene and vitamin C. Homocysteineemia appears to be a risk factor that may be influenced by appropriate nutrition. Antihypertensive therapy is the most important primary and secondary preventive measure. No smoking and adequate dietary intake are also important. Primary prevention with low dose salicylic acid (ASA) is recommended in the presence of additional cardiovascular risk factors. The benefit of low dose anticoagulant therapy in atrial fibrillation without symptoms is not fully established. In subjects with atrial fibrillation with cerebrovascular events anticoagulants are superior to ASA. Surgical treatment of significant stenosis of the carotid artery is indicated. In secondary prevention of thromboembolic events, low dose ASA is recommended. A valuable alternative in case of side effects is available in ticlopidine. (58 Refs.)



Antioxidant status and lipid peroxidation in patients infected with HIV

CHEM.-BIOL. INTERACT. (Ireland), 1994, 91/2-3 (165-180)

Deficiency in antioxidant micronutrients have been observed in patients with AIDS. These observations concerning only some isolated nutrients demonstrate a defect in zinc, selenium, and glutathione. An increase in free radical production and lipid peroxidation has been also found in these patients, and takes a great importance with recent papers presenting an immunodeficiency and more important an increase in HIV-1 replication secondary to free radicals overproduction. We have assessed different studies, trying to obtain a global view of the antioxidant status of these patients. In adults we observe a progressive decrease for zinc, selenium, and vitamin E with the severity of disease, except that selenium remains normal at stage II. However, the main dramatic decrease concerns carotenoids whose level at stage II is only half the normal value. To understand if these decreases in antioxidant and increases in oxidative stress occur secondary to the aggravation of the disease or, conversely, are responsible for it, we undertook a longitudinal survey of asymptotic patients. The preliminary results of this evaluation are presented. Paradoxically, lipid peroxidation is higher at stage II than at stage IV. This may be consecutive to a more intense overproduction of oxygen free radicals by more viable polymorphonuclear (PMN) at the asymptomatic stage. The free radicals production and lipid peroxidation seem secondary to a direct induction by the virus of PMN stimulation and cytokines secretion. N-Acetyl cystein or ascorbate have been demonstrated in cell culture to be capable of blocking the expression of HIV-1 after oxidative stress and N-acetyl cysteine inhibits in vitro TNF-induced apoptosis of infected cells. In regard to all these experimental data, few serious and large trials of antioxidants have been conducted in HIV-infected patients, although some preliminary studies using zinc or selenium have been performed. In our opinion it is now time to evaluate in humans the beneficial effect of antioxidants. The more promising candidates for presenting synergistic effects when associated with N-acetyl cysteine seem to be beta-carotene, selenium and zinc.



Dietary supplementation with orange and carrot juice in cigarette smokers lowers oxidation products in copper-oxidized low-density lipoproteins

Journal of the American Dietetic Association (USA), 1995, 95/6 (671-675)

Objective: Our objective was to evaluate the effect of daily supplementation with foods high in vitamin C and beta carotene on plasma vitamin levels and oxidation of low-density lipoprotein (LDL) in cigarette smokers. Subjects: Fifteen normolipidemic male cigarette smokers who did not usually take vitamin supplements were recruited into the study. Interventions: Throughout the study, subjects consumed a diet rich in polyunsaturated fatty acids, which provided 36% of energy as fat: 18% from meat, dairy products, vegetable oils, and fat spreads and 18% from walnuts (68 g/day). Subjects consumed a vitamin-free drink daily for 3 weeks; then for 3 weeks they consumed daily supplements of orange juice (145 mg vitamin C) and carrot juice (16 mg beta carotene). Results: Vitamin-rich food supplements raised plasma levels of ascorbic acid (1.6-fold; P<.01) and beta carotene (2.6-fold; P<.01). Malondialdehyde, one end product of oxidation, was lower in copper-oxidized LDL after vitamin supplementation (meanplus or minusstandard error=65.7plus or minus2.0 and 57.5plus or minus2.9 micromol/g LDL protein before and after supplementation, respectively; P<.01). Rate of LDL oxidation and lag time before the onset of LDL oxidation were not affected by antioxidant supplementation. Conclusions: In habitual cigarette smokers, antioxidant vitamins, which can be feasibly provided from food, partly protected LDL from oxidation despite a diet rich in polyunsaturated fatty acids.



Chemoprevention of oral leukoplakia and chronic esophagitis in an area of high incidence of oral and esophageal cancer.

Ann Epidemiol. 1993 May. 3(3). P 225-34

This intervention trial carried out in Uzbekistan (former USSR) in an area with a high incidence of oral and esophageal cancer involved random allocation of 532 men, 50 to 69 years old, with oral leukoplakia and/or chronic esophagitis to one of four arms in a double-blind, two-by-two factorial design, with active arms defined by the administration of (a) riboflavin; (b) a combination of retinol, beta-carotene, and vitamin E; or (c) both. Weekly doses were 100,000 IU of retinol, 80 mg of vitamin E, and 80 mg of riboflavin. The dose of beta-carotene was 40 mg/d. Men in the trial were followed for 20 months after randomization. The aim of the trial was to determine whether treatment with these vitamins or their combination could affect the prevalence of oral leukoplakia and/or protect against progression of oral leukoplakia and esophagitis, conditions considered to be precursors of cancer of the mouth and esophagus. A significant decrease in the prevalence odds ratio (OR) of oral leukoplakia was observed after 6 months of treatment in men receiving retinol, beta-carotene, and vitamin E (OR = 0.62; 95% confidence interval (CI): 0.39 to 0.98). After 20 months of treatment, no effect of vitamin supplementation was seen when the changes in chronic esophagitis were compared in the four different treatment groups, although the risk of progression of chronic esophagitis was lower in the subjects allocated to receive retinol, beta-carotene and vitamin E (OR = 0.65; 95% CI: 0.29 to 1.48) A secondary analysis not based on the randomized design revealed a decrease in the prevalence of oral leukoplakia in men with medium (OR = 0.45; 95% CI: 0.21 to 0.96) and high (OR = 0.59; 95% CI: 0.29 to 1.20) blood concentrations of beta-carotene after 20 months of treatment. Risk of progression of chronic esophagitis was also lower in men with a high blood concentration of beta-carotene, odds ratios being 0.30 (95% CI: 0.10 to 0.89) and 0.49 (95% CI: 0.15 to 1.58) for medium and high levels, respectively. A decrease in risk, also statistically not significant, was observed for high vitamin E levels (OR = 0.39; 95% CI: 0.14 to 1.10). These results were based on levels of vitamins in blood drawn after 20 months of treatment.



Dietary vitamin C, beta-carotene and 30-year risk of stroke: Results from the western electric study.

Daviglus M.L.; Orencia A.J.; Dyer A.R.; Liu K.; Morris D.K.; Persky V.; Chavez N.; Goldberg J.; Drum M.; Shekelle R.B.; Stamler J.

USA

Neuroepidemiology (Switzerland), 1997, 16/2 (69-77)

The relations of dietary antioxidants vitamin C and beta-carotene to 30-year risk of stroke incidence and mortality were investigated prospectively in the Chicago Western Electric Study among 1,843 middle-aged men who remained free of cardiovascular disease through their second examination. Stroke mortality was ascertained from death certificates, and nonfatal stroke from records of the Health Care Financing Administration. During 46,102 person-years of follow-up, 222 strokes occurred; 76 of them were fatal. After adjustment for age, systolic blood pressure, cigarette smoking, body mass index, serum cholesterol, total energy intake, alcohol consumption, and diabetes, relative risks (and 95% confidence intervals) for nonfatal and fatal strokes (n = 222) in highest versus lowest quartiles of dietary beta-carotene and vitamin C intake were 0.84 (0.57-1.24) and 0.71 (0.47-1.05), respectively. Generally similar results were observed for fatal strokes (n = 76). Although there was a modest decrease in risk of stroke with higher intake of beta-carotene and vitamin-C intake, these data do not provide definitive evidence that high intake of antioxidant vitamins decreases risk of stroke.



Alpha-2 adrenoceptor subtype causing nitric oxide-mediated vascular relaxation in rats.

Bockman C.S.; Gonzalez-Cabrera I.; Abel P.W.

Dr. P.W. Abel, Department of Pharmacology, Crisa III, Creighton Univ. School of Medicine, 2500 California Plaza, Omaha, NE 68178 USA

Journal of Pharmacology and Experimental Therapeutics (USA), 1996, 278/3 (1235-1243)

The alpha-2 adrenoceptor subtype and its signal transduction pathway mediating vascular relaxation in rats were studied in vitro using rings of superior mesenteric arteries. Removal of endothelium or incubation with N(G)- nitro-L-arginine completely blocked relaxant responses to UK14,304, suggesting endothelium-derived nitric oxide mediates relaxation. The order of potency for full (F) or partial (P) agonists causing relaxation was guanabenz (P) > UK14,304 (F) > clonidine (P) > epinephrine (F) > norepinephrine (F). Affinities (K(B)) of alpha-2 adrenoceptor subtype-selective drugs for blocking relaxation were obtained in side-by-side experiments comparing rat mesenteric arteries with pig coronary arteries. Relaxation of pig coronary arteries is known to be mediated by the alpha-2A adrenoceptor subtype. K(B) values in nM for rauwolscine (19), WB-4101 (265), SKF-104078 (197), spiroxatrine (128), and prazosin (1531) for blocking relaxation in rat arteries were consistent with their affinities for binding at the alpha-2D adrenoceptor subtype. K(B) values for rauwolscine and WB-4101, drugs distinguishing the alpha-2D from the alpha-2A adrenoceptor subtype, were significantly higher in blocking relaxation of rat arteries compared with pig arteries, suggesting the alpha-2D adrenoceptor subtype mediates NO-induced relaxation in rat arteries. We used forskolin to oppose alpha-2 adrenoceptor- mediated inhibition of cAMP formation by directly stimulating cAMP formation in endothelium. Forskolin did not affect the relaxant response to UK14,304, suggesting that cAMP is not involved in the coupling of alpha-2 adrenoceptors to nitric oxide-induced vascular relaxation.



Vitamin A and carotene values of institutionalized mentally retarded subjects with and without Down's syndrome.

Journal of Mental Deficiency Research 1977 Mar Vol 21(1) 63-74

Assessed vitamin A and carotene values of 44 3-34 yr old Down's syndrome, 56 3-35 yr old non-Down's syndrome mentally retarded, and 40 normal 1-25 yr old Ss. Dietary and environmental uniformity was maintained by utilizing Down's and non-Down's Ss residing in the same institution. Results show that Down's Ss showed vitamin A values that were significantly higher than those of the non-Down's retarded Ss and similar to those of the normal Ss. Carotene values were similar in the Down's and non-Down's retarded groups, but were significantly higher than those of the normal Ss. This difference in carotene is seen as reflecting in part the high level of carotenoid products in the institutional diet. Carotene/vitamin A ratio values are reported, and the possibility that relatively high ratio values reflected a decreased efficiency in converting carotene to vitamin A is discussed. It is suggested that Down's Ss may suffer some impairment in the utilization of vitamin A at its site of action.



[Patients with type-II diabetes mellitus and neuropathy have nodeficiency of vitamins A, E, beta-carotene, B1, B2, B6, B12 and folic acid]

Med Klin (GERMANY) Aug 15 1993, 88 (8) p453-7

The present study was aimed to determine the vitamin status of vitamins A, E, beta-carotene, B1, B2, B6, B12 and folate in plasma using HPLC and vitamins B1, B2 and B6 in erythrocytes using the apoenzyme stimulation test with the Cobas-Bio analyzer in 29 elderly type II diabetic women with (G1: n = 17, age: 68.6 +/- 3.2 years) and without (G2: n = 12, age: 71.8 +/- 2.7 years) diabetic polyneuropathy. The basic parameters as age, hemoglobin A1c, fructosamine and duration of the disease did not differ in both groups. Furthermore, retinopathy was assessed with fundoscopy and nephropathy with creatinine clearance. The creatinine clearance (G1: 50.6 +/- 3.4 vs. G2: 63.6 +/- 3.7 ml/min, 2p < 0.025) and the percentage of retinopathy (G1: 76.5% vs. G2: 16.7%, 2p = 0.002) were different indicating that G1 had significantly more severe late complications than G2. Current plasma levels of all measured vitamins (A, E, beta-carotene, B1, B2, B6, B12 and folate) and the status of B1, B2 and B6 in erythrocytes did not vary between the two groups (2p > 0.1). In summary, we found a lack of association between the actual vitamin condition in plasma and erythrocytes and diabetic neuropathy.



The age-associated decline in immune function of healthy individuals is not related to changes in plasma concentrations of beta-carotene, retinol, alpha-tocopherol or zinc

Mechanisms of Ageing and Development (Ireland), 1997, 94/1-3 (55-69)

The decline in the lymphoproliferative response to mitogenic stimuli shows marked heterogeneity in elderly individuals. Adequate nutriture is required for optimal immune function, yet nutritional status may be compromised in the elderly. To address whether this variation in the proliferative response of elderly individuals is related to their nutritional status, we studied 61 elderly (80.5 plus or minus 5.7 year-old) and 27 young (27.3 plus or minus 3.8 year-old) individuals participating in an ongoing assessment of their immune response to influenza vaccine. Ambulatory elderly individuals were recruited from five different retirement communities and were in good health upon enrollment in the study. Thirty-three percent of young and 54% of elderly subjects reported consuming micronutrient supplements daily during the study. Plasma and peripheral blood mononuclear cells (PBMC) were isolated from fasting individuals twice, 4-6 weeks apart. At both times, proliferative responses to the mitogens phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) were significantly lower (P < 0.004) in the elderly compared to the young. However, at both times, elderly participants had plasma concentrations of beta-carotene, retinol, alpha-tocopherol and zinc that were either significantly greater than, or equal to, those of young subjects. No significant correlations between plasma concentrations of beta-carotene, retinol, alpha-tocopherol and zinc and level of proliferative responses to each stimuli were observed in elderly individuals at either time. Thus, the heterogeneity in the proliferative response to mitogenic stimuli exhibited by a healthy elderly population cannot be attributed to differences in these nutritional parameters.



Recommended dietary allowance: support from recent research.

J Nutr Sci Vitaminol (Tokyo) (JAPAN) 1992, Spec No p173-6

Increasing evidence is accumulating that a synergistic role of the so-called antioxidant vitamins (C, E, beta-carotene) may have a dominant role in the prevention of cancer, cardiovascular diseases and cataract formation. Controversy still exists regarding the optimum intake of vitamin C. This is partly due to lack of accurate and easily accessible health-relevant end-points, and lack of knowledge of the role of vitamin C in biochemical functions. Today, it is clearly recognized and broadly accepted that optimal health is a consequence of dietary optimization. Attainment of optimal health rather than prevention of deficiency symptoms is the goal. There can be little doubt that in this respect the requirements for vitamin C are greater than the amount required for the mere prevention of overt or classical scurvy. The recommendation of varying levels of requirement could overcome the controversy. The following is therefore proposed: The lowest level is that value which prevents deficiency symptoms. The second level is valid for healthy populations (< 200 mg/d). This level would take into account needs which differ according to age, sex, physical activity, physiological status (e.g. pregnancy or lactation) and environmental factors such as smoking, pollution and alcohol intake. Finally, a third level should be determined for the prevention of the above-mentioned non-communicable diseases. These diseases are an important cause of disability, resulting in costs of billions of dollars annually in medical costs. Many of the above-mentioned diseases can be prevented by supplementation with vitamin C. Medical costs could thereby also be dramatically reduced.



Critical reappraisal of vitamins and trace minerals in nutritional support of cancer patients.

Support Care Cancer. 1993 Nov. 1(6). P 295-7

The potential of a high intake of fresh fruits and vegetables in cancer prevention is well established. Epidemiological studies support carotene, vitamins A, C, E and selenium as the active compounds. Antioxidant properties and direct effects (e.g. inhibition of N-nitrosamine formation or cell-to-cell interactions) are invoked. The role of other trace elements is less clear. The modulation of immune function by vitamins and trace elements remains important and affects survival. In established cancers, the site-specific differences in the diet/cancer relation require appropriate dietary changes, e.g. low fat (20% by energy) in breast cancer, or high vegetable or fruit intake in lung cancer. Single high-dose supplements (e.g. vitamin C) have proved to have no curative or life-prolonging effect. Chemotherapy and radiation increase the requirements for antioxidant compounds. Supplementation can diminish the damage induced by peroxidation. Carefully planned and monitored trials that establish the optimal intake of micronutrients as adjuvants in cancer patients are required.



Socioeconomic status and lung cancer incidence in men in The Netherlands: Is there a role for occupational exposure?

Journal of Epidemiology and Community Health (United Kingdom), 1997, 51/1 (24-29)

Study objective - To evaluate the influence of occupational exposure to carcinogens in explaining the association between socioeconomic status and lung cancer. Design - A prospective cohort study. Data on diet, other lifestyle factors, sociodemographic characteristics and job history were collected by means of a self administered questionnaire. Follow up for incident cancer was established by record linkage with a national pathology register and with regional cancer registries. Setting - Population originating from 204 municipalities in The Netherlands. Participants - These comprised 58,279 men aged 55-69 years in September 1986. After 4.3 years of follow up there were 470 microscopically confirmed incident lung cancer cases with complete data on dietary habits and job history. Measurements and main results - Estimation of occupational exposure to asbestos, paint dust, polycyclic aromatic hydrocarbons, and welding fumes was carried out by two experts, using information on job history from the baseline questionnaire. Socioeconomic status was measured by means of highest attained level of education and two indicators based on occupation. In the initial multivariate analyses of socioeconomic status and lung cancer, adjustment was made for age, smoking habits, intake of vitamin C, betacarotene and retinol, and history of chronic obstructive pulmonary disease or asthma. Additional adjustment for occupational exposure to the four carcinogens mentioned above did not change the inverse association between the level of education and lung cancer risk (initial model: RR highest/lowest level of education = 0.53; 95% CI 0.34,0.82; additional model: RR highest/lowest level of education = 0.53; 95% CI 0.34,0.84). Nor was the association between the two occupation based indicators of socioeconomic status and lung cancer risk influenced by occupational exposure to carcinogens. The effect of occupational exposure on the association between the level of education and lung cancer risk did not differ between ex-smokers and current smokers. Conclusions - Occupational exposure to asbestos, paint dust, polycyclic aromatic hydrocarbons, and welding fumes could not explain the inverse association between socioeconomic status and lung cancer risk. More research which explicitly addresses possible explanations for the association between socioeconomic status and lung cancer risk is needed.



[Prevention of cerebrovascular insults]

Schweiz Med Wochenschr (SWITZERLAND) Nov 12 1994

Cerebrovascular infarction is the third leading cause of mortality following coronary heart disease and malignancies. WHO studies show that more than half of patients admitted for cerebrovascular infarction were not treated for hypertension. The risk factors for coronary heart disease and cerebrovascular infarction are not identical. Patients with systolic and diastolic hypertension, atrial fibrillation, stenosis of the carotid artery, and smoking, have a significantly elevated risk for cerebrovascular accidents. Hypercholesterolemia and diabetes are less important risk factors. Risk factors amendable by adequate nutritional intake are low supply of carotene and vitamin C. Homocysteineemia appears to be a risk factor that may be influenced by appropriate nutrition. Antihypertensive therapy is the most important primary and secondary preventive measure. No smoking and adequate dietary intake are also important. Primary prevention with low dose salicylic acid (ASA) is recommended in the presence of additional cardiovascular risk factors. The benefit of low dose anticoagulant therapy in atrial fibrillation without symptoms is not fully established. In subjects with atrial fibrillation with cerebrovascular events anticoagulants are superior to ASA. Surgical treatment of significant stenosis of the carotid artery is indicated. In secondary prevention of thromboembolic events, low dose ASA is recommended. A valuable alternative in case of side effects is available in ticlopidine.

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