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International Journal for Vitamin and Nutrition Research, 2/1999


High-dose Vitamin C: A Risk for Persons with High Iron Stores?

Helga Gerster

Vitamin Research Department, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland

Summary

The contribution of vitamin C (ascorbic acid) to the prevention of iron deficiency anemia by promoting the absorption of dietary non-heme iron ­ especially in persons with low iron stores ­ is well established. But the question has been raised whether high-dose intakes of vitamin C might unduly enhance the absorption of dietary iron in persons with high iron stores or in patients with iron overload, possibly increasing the potential risk of iron toxicity.
Extensive studies have shown that overall the uptake and storage of iron in humans is efficiently controlled by a network of regulatory mechanisms. Even high vitamin C intakes do not cause iron imbalance in healthy persons and probably in persons who are heterozygous for hemochromatosis. The uptake, renal tubular reabsorption and storage of vitamin C itself are also strictly limited after high-dose intake so that no excessive plasma and tissue concentrations of vitamin C are produced.
The effect of high-dose vitamin C on iron absorption in patients with iron overload due to homozygous hemochromatosis has not been studied. Of special importance is the early identification of hemochromatosis patients, which is assisted by the newly developed PCR test for hereditary hemochromatosis. Specific treatment consists of regular phlebotomy and possibly iron-chelating therapy. These patients should moreover avoid any possibility of facilitated absorption of iron and need to limit their intake of iron. Patients with b-thalassemia major and sickle cell anemia who suffer from iron overload due to regular blood transfusions or excessive destruction of red blood cells need specialized medical treatment with iron chelators and should also control their intake of iron. The serum of patients with pathological iron overload can contain non-transferrin-bound iron inducinglipid peroxidation with subsequent consumption of antioxidants such as vitamin E and vitamin C.
The role of iron in coronary heart disease and cancer is controversial. Early suggestions that moderately elevated iron stores are associated with an increased risk of CHD have not been confirmed by later studies. In vitro, ascorbic acid can act as a prooxidant in the presence of transition metals such as iron or copper, but in the living organism its major functions are as an antioxidant. High intakes of vitamin C have thus not been found to increase oxidative damage in humans. Accordingly, the risk of CHD or cancer is not elevated. On the contrary, most studies have shown that diets rich in vitamin C are inversely related to the incidence of these diseases.

Keywords

Vitamin C, ascorbic acid, ascorbic acid absorption, non-heme iron, non-heme iron absorption, iron control mechanism, iron deficiency anemia, iron overload, hemochromatosis, iron and coronary heart disease, iron and cancer

International Journal for Vitamin and Nutrition Research,
Band 69, 1999, Heft 2 © Verlag Hans Huber AG, Bern


Plasma Vitamin A and E in Preterm Babies Fed on Breast Milk or Formula Milk with or without Long-Chain Polyunsaturated Fatty Acids

K. Ghebremeskel1, L. Burns1, K. Costeloe2, T.J. Burden3, L. Harbige4, B. Thomas1 and E. Temple2

1 The Institute of Brain Chemistry and Human Nutrition, The University of North London, 166-222 Holloway Road, London N7 8DB
2 Academic Department of Child Health, St Bartholomew and the Royal London School of Medicine and Dentistry, Homerton Hospital, Homerton Row, London E9 6SR
3 The Rayne Institute, St Thomas Hospital, Lambeth Palace Road, London SE1 7EH
4 School of Chemical and Life Sciences, The University of Greenwich, Wellington Street, London SE18 6PF

Summary

Plasma vitamin A and E, the antioxidant nutrients copper and zinc, and magnesium were investigated in preterm babies. They were fed on their own mother's breast milk, or a formula with, or without, AA and DHA. Vitamin A (2.4 mg/d) and E (15 mg/d) supplements were also given. Vitamin A and E levels of most of the babies were sub-optimal at birth. The mean concentrations of vitamin E increased in all the groups by the expected date of delivery (EDD) (p < 0.001). Those fed on their mother's breast milk had the highest value compared with the other groups (p < 0.001). There was an increase in the mean level of vitamin A (p > 0.05) and copper (p < 0.05) and a decrease in zinc (p < 0.05) between birth and EDD. Concentrations of the two vitamins were not different (p > 0.05) between the babies fed on the formula with, and without, AA and DHA. It is concluded that the amount of AA and DHA incorporated in the formula milk did not adversely influence the plasma vitamin A and E of the babies.

Keywords

Preterm babies, arachidonic, docosahexaenoic, vitamin A, vitamin E, copper, magnesium, zinc

International Journal for Vitamin and Nutrition Research,
Band 69, 1999, Heft 2, © Verlag Hans Huber AG, Bern


Relative Bioavailabilities of Natural and Synthetic Vitamin E Formulations Containing Mixed Tocopherols in Human Subjects

Raj K. Chopra and Hemmi N. Bhagavan

Tishcon Corp., Westbury, NY 11590 and Roche Vitamins Inc., Nutley, NJ 07110


Summary

There are several reports in the literature on the relative bioavailabilities of RRR (natural) vs. all-rac (synthetic) forms of vitamin E in humans and animal models but none on the bioavailability of a-tocopherol in mixed vitamin E formulations. In the present study we examined the bioavailability of a-tocopherol in a typical commercially available product containing mixed tocopherols. We also tested a formulation containing all-rac-a-tocopherol with mixed tocopherols for purposes of comparison along with straight RRR-and all-rac-a-tocopheryl acetate as reference products. Normal male subjects were given one of the four formulations of vitamin E (800 IU per day in softgel capsule form for 10 days): 1. All-rac-a-tocopheryl acetate, 2. RRR-a-tocopheryl acetate, 3. RRR-a-tocopherol with mixed tocopherols, and 4. all-rac-a-tocopherol with mixed tocopherols. Both serum a- and g-tocopherols were determined by HPLC at baseline, and at days 2, 4, 7 and 10. The values for a- at baseline and 10 days were 0.80, 0.80, 0.80 & 0.79 mg/dl and 1.67, 1.72, 1.76 & 1.62 mg/dl. The values for g- were 0.28, 0.29, 0.30 & 0.29 mg/dl and 0.11, 0.08, 0.10 & 0.10 mg/dl. Thus the data show that a) the bioavailability of RRR-and all-rac-a-tocopherols is not affected by other tocopherols, and b) both RRR-and all-rac-a-tocopherol (free or esterified) significantly suppress the serum gamma tocopherol to the same extent. Furthermore, since there was no difference in the serum values of a-tocopherol between RRR-and all-rac-vitamin E given the same dose as IUs, the data also support the currently accepted ratio of 1.36 for the biopotency of RRR- vs. all-rac-a-tocopheryl acetate.

Keywords

Natural vitamin E, synthetic vitamin E, formulations, mixed tocopherols, bioavailability

International Journal for Vitamin and Nutrition Research,
Band 69, 1999, Heft 2, © Verlag Hans Huber AG, Bern


Calcidiol, Calcitriol and Parathyroid Hormone Serum Concentrations in Institutionalized and Ambulatory Elderly in Switzerland

Robert Theiler1, Hannes B. Stähelin2, Alan Tyndall1, Kathrin Binder1, Gyula Somorjai1, Heike A. Bischoff2

Depts. of Rheumatology1 and Geriatrics2, University Hospital, Basel, Switzerland


Summary

The aim of the present study was to measure concentrations of vitamin D metabolites and intact parathyroid hormone (iPTH) serum concentrations and an urinary bone resorption marker in two groups of elderly subjects, who differed markedly in their sedentary status and seasonality.
Design: 193 institutionalized elderly people of a long-stay geriatric ward (106 women: mean age 82; 87 men: mean age 78) were studied during wintertime. 312 ambulatory elderly people (109 women: mean age 74; 203 men: mean age 76) were studied during summertime. Concentrations of calcidiol (25(OH)D), calcitriol (1,25(OH)2D) and serum iPTH, as well as urinary N-telopeptides (NTX) were measured.
Results: Vitamin D deficiency (defined as serum 25(OH)D < 12 ng/ml) was present in 86% of institutionalized at the expected nadir (wintertime), compared to 15% of the ambulatory elderly subjects at the expected maximum (summertime). Serum calcitriol concentrations were significantly lower in institutionalized subjects (p = .0001). However intact PTH concentrations did not differ significantly between institutionalized and ambulatory elderly. Institutionalized and female subjects showed higher urinary NTX excretion (female institutionalized: 131.9; female ambulatory: 66.8/male institutionalized: 76.3 male ambulatory: 45.8 nmol/mmol).
Conclusion: This cross-sectional study documented very low serum calcidiol and calcitriol concentrations and high urinary N-telopeptide excretion in institutionalized elderly people. There was no difference in serum iPTH concentrations between institutionalized and ambulatory elderly. This finding could not be explained by the differences in calcidiol and calcitriol concentration, nor urinary NTX excretion. These results suggest that other factors than vitamin D deficiency, such as lower mobility status and sedentary life style, might have an important role in the regulation of iPTH and mechanisms of bone loss in the elderly.

Keywords

Calcidiol, calcitriol, sedentary life stile, urinary N-telopeptides, secondary hyperparathyroidism

International Journal for Vitamin and Nutrition Research,
Band 69, 1999, Heft 2, © Verlag Hans Huber AG, Bern


Konjac Mannan Improves the Vitamin B-6 Status of Rats Fed a Vitamin B-6-deficient Diet

Takashi Hayakawa, Yasuhito Iida and Haruhito Tsuge

Department of Food Science, Faculty of Agriculture, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan


Summary

To investigate how dietary fiber in the diet affects vitamin B-6 nutriture of rats which have been deprived of vitamin B-6, rats were made vitamin B-6-deficient by feeding a vitamin B-6-deficient 70% casein diet. They were fed 2% cellulose powder-based vitamin B-6-deficient diets supplemented with 3% of additional dietary fiber sources (agar, konjac mannan, pectin and cellulose powder) for subsequent 18 days. Vitamin B-6 status was evaluated according to several biological criteria (weight gain, urinary excretion of xanthurenic acid after tryptophan loading, plasma pyridoxal 5'-phosphate, apparent pyridoxal 5'-phosphate-saturation of liver kynureninase, urinary excretion of 4-pyridoxic acid and fecal output of vitamin B-6). Vitamin B-6 status evaluated by these criteria was considerably improved in the konjac mannan-fed group, when compared with the respective data of the vitamin B-6 supplemented group. The relative mean effect of the konjac mannan diet was about 40% of the vitamin B-6 supplemented diet. In conclusion, konjac mannan was effective for improving the vitamin B-6 nutritional state in vitamin B-6-deprived rats.

Keywords

Dietary fiber, fecal vitamin B-6, konjac mannan, microbial production, plasma PLP, rat, vitamin B-6 deficiency, xanthurenic acid

International Journal for Vitamin and Nutrition Research,
Band 69, 1999, Heft 2, © Verlag Hans Huber AG, Bern


Studies on Wound Healing: Effects of Calcium D-Pantothenate on the Migration, Proliferation and Protein Synthesis of Human Dermal Fibroblasts in Culture

Bernd J. Weimann and Danielle Hermann

F. Hoffmann-La Roche Ltd, Vitamins and Fine Chemicals Divsions, Research and Development, 4070 Basel, Switzerland

Summary

The effect of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts from three different donors was investigated. The migration of cells into a wounded area was dose-dependently stimulated by Ca D-pantothenate. The number of cells that migrated across the edge of the wound increased from 32 ± 7 cells/ mm without Ca D-pantothenate to 76 ± 2 cells/ mm with 100 mg/ml Ca D-pantothenate. Moreover, the mean migration distance per cell increased from 0.23 ± 0.05 mm to 0.33 ± 0.02 mm. The mean migration speed was calculated to be 10.5 mm/hour without and 15 mm/hour with Ca D-pantothenate. Cell proliferation was also dose-dependently stimulated. The final cell densities were 1.2 to 1.6-fold higher in cultures containing 100 mg/ml Ca D-pantothenate. The protein synthesis was modulated, since two unidentified proteins were more strongly expressed in pantothenate supplemented cultures.
In conclusion, Ca D-pantothenate accelerates the wound healing process by increasing the number of migrating cells, their distance and hence their speed. In addition, cell division is increased and the protein synthesis changed. These results suggest that higher quantities of pantothenate are locally required to enhance wound healing.

Keywords

Calcium D-pantothenate, wound healing, human dermal fibroblasts, migration, proliferation

International Journal for Vitamin and Nutrition Research,
Band 69, 1999, Heft 2, © Verlag Hans Huber AG, Bern


Cobalt Deficiency Effects on Trace Elements, Hormones and Enzymes Involved in Energy Metabolism of Cattle

Gabriele I. Stangl, Frieder J. Schwarz and Manfred Kirchgessner

Institut für Ernährungsphysiologie, Technische Universität München, 85350 Freising-Weihenstephan, Germany


Summary

This study was conducted to investigate the physiological consequences of long-term moderate cobalt deficiency in beef cattle, which have not hitherto been studied in detail. Cobalt deficiency was induced in cattle by feeding two groups of animals either a basal corn silage-based diet that was moderately low in cobalt (83 µg Co/kg), or the same diet supplemented with cobalt to a total of 200 µg per kg, for 43 weeks. Cobalt deficiency was induced, as judged by inappetance, diminished growth gain and a markedly reduced vitamin B12 status in serum and liver. The long-term cobalt deprivation which was primarily a combination of reduced feed intake and a tissue vitamin B12 deficiency did not show evidence of a significant dysfunktion of energy metabolism. The activities of glucose-6-phosphate dehydrogenase and cytochrome oxidase in liver remained unaffected by cobalt deficiency, nor was there a significant change in serum glucose level of cattle on the cobalt-deprived diet. However, analysis of thyroid hormone status indicated a slight reduction of type I thyroxine monodeiodinase activity in liver accompanied by a significant reduction of the triiodothyronine level in serum. The diminished liver vitamin B12 level resulted in significantly reduced folate level in this tissue, reduced concentrations of heme-depending blood parameters. Moreover cobalt deficiency or rather vitamin B12 deficiency was accompanied by a dramatic accumulation of the trace elements iron and nickel in liver. These results indicate that long-term moderate cobalt deficiency may induce a number of physiological changes in cattle, but a follow-up study, which excluded different feed levels by including a pair-fed control group, will be necessary to actually obtain the single effect of cobalt deficiency in cattle.

Keywords

Cobalt Deficiency, vitamin B12, folate, heme parameters, trace elements, glucose, enzymes of energy metabolism, thyroid hormones, cattle

International Journal for Vitamin and Nutrition Research,
Band 69, 1999, Heft 2, © Verlag Hans Huber AG, Bern


The Age at which Meat is First Included in the Diet Affects the Incidence of Iron Deficiency and Ferropenic Anaemia in a Group of Pre-school Children from Madrid

A. M. Requejo1, B. Navia1, R. M. Ortega1, A. M. López-Sobaler1, E. Quintas1, M. J. Gaspar2 and O. Osorio1

1 Departamento de Nutrición, Facultad de Farmacia, Universidad Complutense, 28040 Madrid
2 Servicio de Análisis Clínicos, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain


Summary

A study was made into the effect of the age at which meat was first included in the diet on a series of haematological parameters and biochemical indicators of iron status in 94 pre-school children (aged 2­6 years) from Madrid (Spain).
Those children who first took meat during their eighth month of life or earlier (Group A) showed better iron status that did those who were introduced to meat later (Group B). Significant differences were found in hemoglobin levels (P < 0.01), mean corpuscular haemoglobin (MCH) (P < 0.05), serum ferritin (P < 0.05), transferrin levels (P < 0.05) and total iron binding capacity (TIBC) (P < 0.001). Some 13.8% of all subjects showed iron deficiency and 5.3% showed ferropenic anaemia. These latter subjects were the last to have meat included in their diets (9.3 ± 1.2 months compared to 7.4 ± 2.0 months in those without ferropenic anaemia) (P < 0.05).
It would appear that the age at which meat is included in the diet has an important effect on iron status in pre-school children. Delaying its inclusion beyond the age of eight months seems to be associated whith an impairment of later iron status.

Keywords

Pre-school children, anaemia, iron deficiency, meat, complimentary foods

International Journal for Vitamin and Nutrition Research,
Band 69, 1999, Heft 2, © Verlag Hans Huber AG, Bern


The Status of Retinoids in Women Suffering from Hyper- and Hypothyroidism: Interrelationship between Vitamin A, b-carotene and Thyroid Hormones

Umesh C. Goswami1 and Shobhita Choudhury2

1 Department of Zoology (Retinoids Research Programme) Gauhati University, Guwahati-781 014, Assam, India
2 Regional Centre for Research in Human Reproduction, Department of Obstetrics & Gynaecology, Gauhati Medical College, Guwahati-781 005, Assam, India


Summary

Retinoid status with reference to b-carotene and retinol has been studied in women suffering from hyper- and hypothyroid conditions. The interrelationship between the retinoids and triiodothyronine and thyroxine hormones has been established from the cases mentioned after estimation of the respective compounds from the blood serum. It has been found that there is an increase in b-carotene and retinol in the hypothyroid and a decrease of the same in the hyperthyroid conditions respectively.

Keywords

b-Carotene, carotenoids, retinol, thyroid hormone, thyroxine, triiodothryonine, vitamin A

International Journal for Vitamin and Nutrition Research,
Band 69, 1999, Heft 2, © Verlag Hans Huber AG, Bern


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