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International Journal for Vitamin and Nutrition Research, 1/1998


Background and Rationale Behind the SU.VI.MAX Study, a Prevention Trial Using Nutritional Doses of a Combination of Antioxidant Vitamins and Minerals to Reduce Cardiovascular Diseases and Cancers

Serge Hercberg1, Pilar Galan1, Paul Preziosi1, Anne-Marie Roussel2, Josianne Arnaud2, Marie-Jeanne Richard2, Denis Malvy3, Agnès Paul-Dauphin4, Serge Briançon4 and Alain Favier2

1 Institut Scientifique et Technique de la Nutrition et de l'Alimentation/CNAM, 2 rue Conté, F-75003 Paris;
2 Laboratoire de Biochimie, CHU de Grenoble;
3 INSERM U330, Université Victor Ségalen, Bordeaux 2;
4 Ecole de Santé Publique, Faculté de Médecine, Nancy

Summary

The "SUpplementation en VItamines et Minéraux AntioXydants" (SU.VI.MAX) study is a randomized double-blind, placebo-controlled, primary prevention trial designed to test the efficacy of daily supplementation with antioxidant vitamins (vitamin C, 120 mg; vitamin E, 30 mg; and beta-carotene, 6 mg) and minerals (selenium, 100 mg; and zinc, 20 mg), at nutritional doses (one to three times the daily recommended dietary allowances), in reducing the frequency of major health problems in industrialized countries, and especially the main causes of premature death (cancers and cardiovascular diseases). The study involves 12,735 eligible subjects (women aged 35 to 60 years; men aged 45 to 60 years) included in 1994 in France. They will be followed up for 8 years.
The objectives and the specific design of this intervention study are linked to its public health aim. The targeted population is the general population (not simply high-risk subjects) and the antioxidant agents tested are being administered at a level which is not pharmacologic and which may be attained by dietary intake of natural sources of these micronutrients and/or enriched foods. The amounts we are testing in the SU.VI.MAX study are those which, in observational studies have been associated with the lowest risk of diseases.
This report presents the rationale and discusses the justification of the design, doses and combination of antioxidant micronutrients chosen in the SU.VI.MAX study.

Keywords

Cancer, Cardiovascular Diseases, Prevention, Trial, Antioxidants, Beta-carotene, Vitamin C, Vitamin E, Selenium, Zinc

International Journal for Vitamin and Nutrition Research, Band 68, 1998, Heft 1, © Verlag Hans Huber, Bern

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Vitamin A and E Status of Some Rural Populations in the North of Cameroon

I. Gouado2, T.F. Mbiapo3, F.P. Moundipa4 and M.C. Teugwa3

1 From the laboratory of nutrition, Department of Biochemistry, Faculty of Science - University of Yaounde I
2 Department of Biochemistry, Faculty of Science, PO Box 24157, The University of Douala, Cameroon
3 Department of Biochemistry, Faculty of Science, PO Box 812, The University of Yaoundé I - Cameroon
4 Department of Biochemistry, Faculty of Science, PO Box 455, The University of Ngaoundéré - Cameroon

Summary

The vitamin A and E status was evaluated in 279 volunteer subjects, 3 to 75 years old (131 males and 148 females) from 8 villages in the north of Cameroon by fluorimetric methods.
The results obtained showed that: the mean serum vitamin A level was 16.6±0.7 mg% (ranging from 2.1 to 69.3 mg%) and vitamin E, 499.9±19.3 mg% (ranging from 222.7 to 1893.1 mg%); the percentage deficiency of vitamin A among the subjects was 71.7% and that of vitamin E was 66% (vitamin A levels <20 mg/100 ml, vitamin E levels < 500 mg/100 ml); children of ages ranging from 3 to 15 years, constituted about 50% of the subjects and were significantly deficient in vitamin A (P < 0.001). Significant correlation was observed between the serum levels of vitamin A and E (P < 0.001).
The results from this study revealed that vitamin A and E deficiencies vary from one village to another and constitute one of the major public health problems in the area.

Keywords

Vitamin A, Vitamin E, b-Carotene, Serum

International Journal for Vitamin and Nutrition Research, Band 68, 1998, Heft 1, © Verlag Hans Huber, Bern

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Demographic and Cardiovascular Risk Factors in Relation to Antioxidant Status: the EVA Study

Claudine Berr1, Charles Coudray2, Claire Bonithon-Kopp3, Anne-Marie Roussel2, Francine Mainard4, Annick Alperovitch1 and the EVA study Group

1 INSERM U360, Recherches Epidémiologiques en Neurologie et Psychopathologie, Hôpital La Salpêtrière, 75631 Parix
Cedex France
2 Groupe de Recherches et d'Etudes sur les Pathologies Oxidatives (GREPO), Université J. Fournier, Domaine de La Merci, 38700, La Tronche, France
3 INSERM U258, Epidémiologie Cardiovasculaire, Hôpital Broussais, 75674 Paris Cedex 14, France
4 Faculté de Pharmacie, Laboratoire de Biochimie, 1 Rue Gaston Veil, 44035 Nantes Cedex, France

Summary

The aim of the study was to examine the determinants of blood antioxidant indicators on a large sample.
Levels of plasma selenium and carotenoids, vitamin E in red blood cells, and thiobarbituric acid reactive substances (TBARS) were determined. The cross-sectional relationships between these markers and demographic and cardiovascular risk factors were examined in participants of the EVA study, a cohort of 1389 men and women, aged 59 - 71 years. Multivariable regression models including demographic (age, sex, socio-economic level), lifestyle (alcohol, tobacco), clinical and metabolic (lipids, glycemia) factors were used.
Women had higher levels of plasma carotenoids, TBARS and red blood cell vitamin E. Cholesterol levels were positively associated to lipid-soluble vitamins, selenium and TBARS. Use of lipid-lowering drugs was positively associated with selenium and vitamin E and negatively with carotenoids. Body mass index was the strongest determinant of plasma carotenoids. Education and income levels were positively associated with selenium and total carotenoids. Tobacco consumption was negatively associated with red blood cell vitamin E, whereas alcohol consumption was positively associated with TBARS.
This study emphasizes the respective place of the various determinants of antioxidant status. When considering tissue antioxidant indicators, analyses should take into account not only the metabolic parameters but also socio-economic factors and the subject's life style.

Keywords

Antioxidan, Lipid peroxidation, Vitamin, Selenium, Lifestyle, Epidemiology

International Journal for Vitamin and Nutrition Research, Band 68, 1998, Heft 1, © Verlag Hans Huber, Bern

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Elevated PTH Levels in Hypovitaminosis D are More Rapidly Suppressed by the Administration of 1,25-Dihydroxy-Vitamin D3 than by Vitamin D3

R. Theiler, H. Bischoff, A. Tyndall and H.B. Stähelin

Depts. of Rheumatology and Geriatrics, University Hospital, Basle, Switzerland

Summary

Objective: To assess markers of bone metabolism in two groups of inpatients with hypovitaminosis D and elevated PTH levels receiving two different vitamin D medications.
Methods: 26 patients with secondary hyperparathyroidism (2OHP) were treated either with 800 IU cholecalciferol and 1000 mg calcium or 0.5 mg calcitriol plus 500 mg calcium daily for 6 months. 25-OH-vitamin D3, 1,25-dihydroxyvitamin D3, intact PTH, calcium and urinary N-telopeptides of bone collagen I were mea-sured at baseline, 3 and 6 months.
Results: PTH levels decreased earlier in the calcitriol group than in the cholecalciferol group. After six month no difference could be documented. Lowering of urinary N-telopeptides excretion was observed in both groups.
Conclusion: The use of both forms of vitamin D supplementation appears to be useful for patients with hypovitaminosis D, elevated PTH levels and high telopeptide excretion.

Keywords

I, Secondary hyperparathyreoidism, Vitamin D metabolites, Elderly people, Bone resorption markers, Hypovitaminosis D

International Journal for Vitamin and Nutrition Research, Band 68, 1998, Heft 1, © Verlag Hans Huber, Bern


Modulation of Drug Metabolizing Enzymes in Guinea Pig Liver by High Intakes of Ascorbic Acid

M.W. Roomi*, Shrirang Netke and Constance Tsao

Linus Pauling Institute of Science and Medicine, 440 Page Mill Road, Palo Alto, CA 94306, USA
*Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331, USA

Summary

Groups of young male adult guinea pigs were fed a diet devoid in supplemental ascorbic acid (AA) or the same diet supplemented with 0.1 or 2.5% AA for four weeks. The animals were then euthanized and Phase I and Phase II drug metabolizing components in the liver were determined. Phase I components are those related to the metabolism of xenobiotics and include microsomal cytochrome P-450 and mixed function oxygenase activities. Phase II components are those related to conjugation and detoxification reactions of xenobiotics and their metabolites and include glutathione-S-transferases (GST), glutathione (GSH), UDP-glucuronyl transferase (UDP-GT) and DT-diaphorase (quinone reductase, QR). Tissue levels of AA increased progressively with increase in AA intake. The Phase I components increased in response to increased intake of AA from 0 to 0.1%, but were unaffected by further increase in AA intake to 2.5%. However, the Phase II components increased with increased intake of AA except for GST. In vitro metabolism of aflatoxin B1 (AFB1) using liver microsomes showed tendency towards increased production of aflatoxin M1 (AFM1) with increase in AA intake. The production of aflatoxin P1 (AFP1) was not affected by AA intake. AFB1-DNA production was increased when AA intake was increased to 0.1%. It was however lowered with further increase in AA intake to 2.5%.

Keywords

Ascorbic acid, Phase I and II drug metabolizing enzymes, Guinea pig, Liver

International Journal for Vitamin and Nutrition Research, Band 68, 1998, Heft 1, © Verlag Hans Huber, Bern

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Dependence of Growth, Bone Metabolism and Functions of Polymorphonuclear Leukocytes on Ascorbic Acid in Pigs

Joseph Schwager and Jürgen Schulze

Centre de Recherche en Nutrition Animale, Société Chimique Roche S.A., F-68305 Village-Neuf, France

Summary

Pigs with hereditary ascorbate deficiency (OD pigs) were depleted of, or supplemented with, ascorbic acid by respective diets. Depletion of young (i.e. 5 - 7 weeks old) animals for at least three weeks had a negative effect on growth, body temperature and levels of bone alkaline phosphatase and induced symptoms of scurvy. Doses of 5 mg ascorbic acid kg - 1 body weight day - 1 were sufficient to reverse these effects. The level of ascorbic acid sharply decreased in plasma within one week of depletion, whereas in leukocytes it declined more slowly and to a lower extent. Bone alkaline phosphatase levels substantially declined in ascorbic acid depleted animals. Supplementation with > 100 mg ascorbic acid kg - 1 body weight day - 1 did not improve growth. Dietary ascorbic acid was absorbed from the intestinal lumen into the blood within less than 1 hour and reached a peak 5 - 6 hours after the meal. The extent of this absorption depended on the systemic ascorbic acid level. Ascorbic acid influenced leukocyte function, since the production of reactive oxygen intermediates by polymorphonuclear leukocytes decreased in supplemented animals.
Thus, this animal model permits to establish the level of dietary ascorbic acid that is critical for growth of pigs as well as to study its absorption into the blood and the associated alterations in polymorphonuclear leukocytes and bone metabolism.

Keywords

Swine, Ascorbic acid, Growth, Alkaline phosphatas, Polymorphonuclear cells, Reactive oxygen intermediates

International Journal for Vitamin and Nutrition Research, Band 68, 1998, Heft 1, © Verlag Hans Huber, Bern

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A High-Affinity Folate Binding Protein in Fluid of Benign Cysts of Human Liver and Mammary Gland

Jan Holm1, Steen Ingemann Hansen2, Mimi Høier-Madsen3

1 Department of Clinical Chemistry, Horsens Hospital, Horsens, DK-8700
2 Department of Clinical Chemistry, Central Hospital, Hillerød, DK-3400
3 Laboratory for Autoimmune Serology, State Serum Institute, Copenhagen, DK-2300 S

Summary

The presence of a folate binding protein in fluid of benign cysts of human liver and mammary gland was demonstrated. Radio-ligand binding was of a high-affinity type (Kp1010M - 1). The gel filtration profile of cystic fluid contained two peaks of radiolabelled folate, a large one of 25 kDa and a small one of 100 kDa. The concentration of radioligand bound protein in samples of cystic fluid ranged from nil to 6 nM. In most cases the protein immunoreacted with antibodies against human milk folate binding protein. The data suggest that fluid of human liver and mammary gland cysts contains a folate binding protein which appears to be homologous to human milk folate binding protein.

Keywords

Folate binding, Protein, Benign cysts, Liver, Breast

International Journal for Vitamin and Nutrition Research, Band 68, 1998, Heft 1, © Verlag Hans Huber, Bern

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Variation of the Total Amount of Fluoride in Blood of Young Women During the Menstrual Cycle

Takahide Kimura1, Fumiko Hayakawa2, Gaku Yamamoto3, Kasusada Yoshitake3 and Takashi Ando1

1 Department of Chemistry, Shiga University of Medical Science, Seta, Otsu, Shiga 520-21 Japan
2 Department of Life Style Studies, School of Human Cultures, The University of Shiga Prefectue, Hassaka-cho, Hikone,
Shiga 522 Japan
3 Department of Oral Maxillofacial Surgery, Shiga University of Medical Science, Seta, Otsu, Shiga 520-21 Japan

Summary

We have previously reported the distribution and the forms of fluorides in the blood of men. This study is concerned with the distribution of fluorides in the blood of young women and sex-related differences in the fluoride metabolism related to the calcium metabolism keeping the postmenopausal osteoporosis in mind.
The present study shows that women, aged 18 to 20 years, retain more fluorides in blood compared with men and that the nonionic fluoride level in blood varies during a menstrual cycle, whereas the ionic fluoride level is constant. Since fluoride has strong affinity for calcium, behavior of fluoride may reflect that of calcium balance during the menstrual cycle. However, fluoride which binds to calcium is believed to be ionic. Therefore, there must be a transformation between ionic fluoride and nonionic fluoride in order to keep the homeostasis.

Keywords

Ionic fluoride, Nonionic fluoride, Calcium, Blood, Serum, Menstrual cycle

International Journal for Vitamin and Nutrition Research, Band 68, 1998, Heft 1, © Verlag Hans Huber, Bern


Porcine Somatotropin, Dietary Protein and Energy Effects on Arginase and Transaminase Activities in Pigs

R. W. Rosebrough1, T. J. Caperna1, R. G. Campbell2 and N. C. Steele1

1 Growth Biology Laboratory, Livestock and Poultry Sciences Institute, United States Department of Agriculture-Agricultural Research Service, Beltsville Agricultural Research Center, Beltsville, MD 20705, USA
2 Bunge Meats, Ltd. Corowa, N.S.W. 2646, Australia

Summary

Two experiments were conducted with cross-bred barrows to determine the effect of somatotropin administration on liver enzyme activities. In the first experiment, pigs growing from 26 to 55 kg body weight were given two doses of pituitary porcine somatotropin (pST; 0 and 100 mg per kg body weight) and three levels of dietary energy (60, 80 and 100% of free choice intake). In the second experiment, pigs growing from 30 to 60 kg body weight were given two doses of recombinant porcine somatotropin (rpST; 0 and 100 mg per kg body weight) and five levels of dietary crude protein (110, 150, 190, 230 and 270 g crude protein/kg diet). Liver arginase (ARG, EC 3.5.3.1) and aspartate aminotransferase (AAT, EC 2.6.1.1) activities were then determined in organ samples taken at slaughter time. Dietary energy did not change liver ARG. Activities of both ARG and AAT increased as dietary crude protein increased. Both pST and rpST decreased ARG, AAT and serum utrea nitrogen. There was a lack of interaction between rpST therapy and dietary protein on either ARG or AAT activities, suggesting that set nutritional states are not required for expression of pST effects.

Keywords

Pigs, Diet Protein, Enzymes

International Journal for Vitamin and Nutrition Research, Band 68, 1998, Heft 1, © Verlag Hans Huber, Bern


Effects of Soy Protein on the Morphology of Ileum and the Ultrastructure of Liver Cells in Adult Mice

Motoi Tamura and Hiramitsu Suzuki

National Food Research Institute, 2-1-2, Kannondai, Tsukuba, Ibaraki 305, Japan

Summary

The influences of soy protein on the morphology of ileum and on the ultrastructure of liver were studied. Adult male mice of the Crj: CD-1 (ICR) strain were fed a semisynthetic diet containing casein or soy protein for three weeks. Villus heights in ileum from the mice fed soy protein diet were significantly greater than those fed casein diet. There were evident ultrastructural differences in the liver cells between the mice fed the two diets. Many lipid droplets from the mice fed the casein diet were larger than those fed the soy protein diet. The maximum diameter of lipid droplet per liver cell in the soy protein diet group was smaller than that in the casein diet group (p < 0.01). These results suggest that soy protein and casein affect the ultrastructure of liver and the morphology of ileum in different ways.

Keywords

Mouse, Soy protein, Casein, Liver cells, Ileum, Ultrastructure, Morphology

International Journal for Vitamin and Nutrition Research, Band 68, 1998, Heft 1, © Verlag Hans Huber, Bern


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