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Institut für Physiologische Chemie I,
Heinrich-Heine-Universität Düsseldorf, P.O. Box 10 10 07,
40001 Düsseldorf, Germany
Summary
Induction of gap junctional communication (GJC) is discussed as one possible mechanism underlying the cancer-preventive properties of carotenoids. Structurally different carotenoids have different effects on this GJC pathway. Beta-carotene, echinenone, canthaxanthin, cryptoxanthin and 4-hydroxy-b-carotene efficiently induce GJC in murine fibroblasts. Decomposition products of canthaxanthin (e.g. 4-oxo-retinoic acid) enhance both GJC and expression of connexin 43 mRNA. Thus, the biological activity of canthaxanthin is due at least in part to formation of active decomposition products such as 4-oxo-retinoic acid. A number of other small molecules such as 1,25-dihydroxycholecalciferol or thyroid hormones serve as nuclear receptor ligands. Cholecalciferol, 3,3',5-triiodo-L-thyronine and L-thyroxine induce GJC to a similar extent as carotenoids or retinoic acid. Interactions between these signalling pathways may be involved in GJC regulation.
Keywords
Carotenoids, Retinoids, Gap junctions, Intercellular communication, Connexin
International Journal for Vitamin and Nutrition Research,
Band 68, 1998, Heft 6, © Verlag Hans Huber AG, Bern
TNO Nutrition and Food Research Institute, Zeist, Netherlands
Summary
Carotenoid interactions during absorption and in postabsorptive metabolism have been observed in both human and animal studies. We reviewed the mutual interactions reported between lutein and b-carotene and report new data on the postprandial b-carotene and retinyl ester response in the triglyceride-rich plasma lipoprotein (TRL) fraction in volunteers after a single test meal with b-carotene alone, or b-carotene combined with lutein or lycopene. Results indicate an inhibitory effect of lutein on b-carotene absorption, but apparently not on b-carotene cleavage. In a comparative study with two b-carotene/lutein ratios (2:1 and 1:2, respectively), this inhibitory effect of lutein was found to be most marked when lutein was the predominant carotenoid. In studies on plasma (serum) response also an inhibitory effect of b-carotene on lutein response was observed.
Keywords
b-Carotene, Lutein, Interactions, Absorption
International Journal for Vitamin and Nutrition Research,
Band 68, 1998, Heft 6, © Verlag Hans Huber AG, Bern
1 Unilever Research Vlaardingen, P. O. Box
114, 3130 AC Vlaardingen, Netherlands
2 Division of Human Nutrition and Epidemiology, Wageningen
Agricultural University, Wageningen, Netherlands
3 Department of International Health, Rollins School of
Public Health, Emory University, Atlanta, Georgia, USA
Summary
It has been suggested that carotenoids contribute to the inverse association between vegetable consumption and risk for coronary heart disease and cancer. However, there are indications that the bioavailability of b-carotene from vegetables is less than previously thought. Therefore, it is of interest to explore whether the bioavailability of carotenoids from vegetables can be improved. We have reviewed data on the effect of vegetable processing on carotenoid bioavailability. Based on this analysis, we conclude that processing of vegetables by mechanical homogenization or heat treatment has the potential of increasing the bioavailability of carotenoids. Addition of fat during processing may also have an effect.
Keywords
Vegetables, Carotenoids, Bioavailability, Processing, Review
International Journal for Vitamin and Nutrition Research,
Band 68, 1998, Heft 6, © Verlag Hans Huber AG, Bern
Wageningen Agricultural University, Division of Human Nutrition and Epidemiology
Summary
The bioavailability of carotenoids is the fraction of ingested carotenoids utilized for normal physiological functions or storage, while bioconversion is the proportion of bioavailable carotenoid converted to retinol (vitamin A). Factors influencing carotenoid bioavailability and bioconversion have been incorporated in the mnemonic "SLAMENGHI": species of carotenoid; molecular linkage; amount of carotenoids consumed in a meal; matrix in which the carotenoid is incorporated; effectors of absorption and bioconversion; nutrient status of the host; genetic factors; host-related factors; and mathematical interactions. In this paper, an attempt is made to quantify the impact of the various SLAMENGHI factors on carotenoid bioavailability and bioconversion although many of the data available are not strictly comparable.
Keywords
Carotenoids, Bioavailability, Bioconversion, Absorption, Vitamin A, Retinol, Conversion factors, SLAMENGHI
International Journal for Vitamin and Nutrition Research,
Band 68, 1998, Heft 6, © Verlag Hans Huber AG, Bern
1 TNO Nutrition and Food Research
Institute, Dept. of Consumer Research & Epidemiology, Zeist,
Netherlands
2 Maastricht University, Dept. of Epidemiology,
Maastricht, Netherlands
Summary
This study presents data on dietary intake of specific carotenoids
in the Netherlands, based on a recently developed food composition
database for carotenoids. Regularly eaten vegetables, the main
dietary source of carotenoids, were sampled comprehensively and
analysed with modern analytic methods. The database was complemented
with data from recent literature and information from food
manufacturers. In addition, data on intake of vitamin A are
presented, which are based on the most recent update of the Dutch
Food Composition Table. Intake of vitamin A was calculated for adult
participants of the second Dutch National Food Consumption Survey in
1992, whereas intake of carotenoids was calculated for participants
of the Dutch Cohort Study on diet and cancer, aged 55 to 69 in 1986.
Mean intake of vitamin A amounted to 1.1 and 0.9 mg RE/day for men
and women, respectively: the contributions of meat, fats and oils,
vegetables and dairy products to total intake were 35%, 24%, 16%, and
16%, respectively. Mean intake of a-carotene, B-carotene and lutein
plus zeaxanthin was 0.7, 3.0, and 2.5 mg/day respectively for both
men and women, while mean intake of lycopene was 1.0 mg/day for men
and 1.3 mg/day for women. The most important foods contributing to
intake of B-carotene and lutein plus zeaxanthin were carrots
(B-carotene only), spinach, endive and kale.
Keywords
Vitamin A, Retionl, Carotenoids, a-Carotene, B-Carotene, Lutein , Zeaxanthin, Lycopene
International Journal for Vitamin and Nutrition Research,
Band 68, 1998, Heft 6, © Verlag Hans Huber AG, Bern
1 Department of Paediatrics, University
Hospital Nijmegen St Radboud, Nijmegen, Netherlands
2 Division of Human Nutrition and Epidemiology, Wageningen
Agricultural University, Wageningen, Netherlands
3 Tropical Diseases Research Centre, Ndola, Zambia
4 Department of Medical Microbiology, University Hospital
Nijmegen St Radboud, Nijmegen, Netherlands
Summary
Vitamin A deficiency increases the risk of illness, while infections impair vitamin A status. Malaria is highly prevalent in rural Zambia. We describe the relationship between malaria and vitamin A status. We examined dietary vitamin A intake, malaria parasitaemia and serum concentrations of retinol, C-reactive protein (CRP) and a1-acid glycoprotein (AGP) in 210 children under the age of 2. Vitamin A intake was low. Serum retinol was negatively correlated with malaria parasite count and to serum levels of CRP and AGP. Increased malaria parasite density resulted in raised CRP and AGP levels, which were negatively associated with serum retinol. We conclude that improvement of dietary vitamin A intake and prevention of infectious diseases, especially malaria, could alleviate vitamin A deficiency in this population.
Keywords
Malaria, Vitamin A, Preschool children, Zambia, Acute-phase proteins
International Journal for Vitamin and Nutrition Research,
Band 68, 1998, Heft 6, © Verlag Hans Huber AG, Bern
1 Helen Keller International, Jakarta
Pusat, Indonesia
2 Diponegoro University, Semarang, Indonesia
3 UNICEF, Jakarta, Indonesia
4 UNICEF, New York, USA
5 Nutrition Research and Development Centre, Bogor,
Indonesia
6 Directorate of Community Nutrition, Ministry of Health,
Jakarta, Indonesia
Summary
In order to work towards further reduction of vitamin A deficiency in central Java, Indonesia, a social marketing campaign promoting eggs and dark-green leafy vegetables was initiated in March 1996. The nutritional surveillance system (December 1995December 1996) found the following. The campaign's messages were well noticed. Consumption of at least one egg in the past week increased from 80% to 92% in mothers and from 78% to 92% in children 1236 months old. It increased in all socio-economic groups and was independent of ownership of chickens. Most eggs had been purchased. The quantity of vegetables prepared increased from 93 to 111 g/person daily and most was purchased. Vitamin A intake increased from 335 to 371 RE/d for mothers and from 130 to 160 RE/d for children. Serum retinol levels increased after the start of the campaign, and were related to egg consumption and vitamin A intake. Because 1. data were collected in such a way that respondents were not aware of the link between data collected and the campaign, and 2. vitamin A status increased and was related to increased consumption of eggs and vitamin A intake, we conclude that the social marketing campaign was successful.
Keywords
Social marketing, Vitamin A intake, Eggs, Dark-green leafy vegetables, Vitamin A status, Indonesia
International Journal for Vitamin and Nutrition Research,
Band 68, 1998, Heft 6, © Verlag Hans Huber AG, Bern
1 Department of Pharmacology, Faculty of
Medicine, University of Maastricht, Maastricht, Netherlands
2 TNO Nutrition and Food Research Institute, Zeist,
Netherlands
Summary
Surprisingly, neither the precise pharmacological effect nor the toxicological profile is usually established for food components. Carotenoids are no exception in this regard. Only limited insight into the pharmacology and toxicology of carotenoids exists. It is known that the antioxidant action of carotenoids is determined by 1. electron transfer reactions and the stability of the antioxidant free radical, 2. the interplay with other antioxidants and 3. the reaction with active oxygen. Numerous metabolites of carotenoids are formed upon their action as an antioxidant. Most of these metabolites have an unknown biological activity. It is concluded that a severe lack of knowledge hampers adequate suggestions for human supplementation.
Keywords
Carotenoids, b-Carotene, Antioxidant, Free radical, Lutein, Lipid peroxidation
International Journal for Vitamin and Nutrition Research,
Band 68, 1998, Heft 6, © Verlag Hans Huber AG, Bern
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht, Netherlands
Summary
Vitamin A derived retinoids, including all-trans retinoic acid (RA), play an important role in regulating cellular growth and differentiation. Biological activities of retinoids are mediated through interactions with two classes of nuclear receptors, RA receptors (RARs) and retinoid X receptors (RXRs). In addition, cellular retinoid-binding proteins (CRBPs and CRABPs) and RA-metabolizing enzymes may explain the pleiotropic effects of retinoids. Recently, a novel cytochrome P450 enzyme (CYP26) with specific RA 4-hydroxylase activity, which is rapidly induced by RA, has been cloned from man, mouse and zebra fish, fullfilling all requirements of an enzyme which could be of crucial importance in controlling steady-state levels of active retinoids in cells and target tissues, thus protecting against excessive exposure. Besides the putative role of this newly identified CYP26 in contributing to susceptibility of cancer cells to retinoids, the possible function of this gene in early embryonic development is discussed.
Keywords
Retinoic acid receptors, Retinoids, Metabolism, Cytochrome P450, CYP26, Development, Cancer
International Journal for Vitamin and Nutrition Research,
Band 68, 1998, Heft 6, © Verlag Hans Huber AG, Bern
F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland
Summary
A still unresolved public health concern is that excessive vitamin A intake, like vitamin A deficiency, possibly causes birth defects not only in animals but also in man. Due to the low incidence of possibly vitamin A-related malformations in man, available data cannot convincingly define the upper safe limit of periconceptional vitamin A intake. Direct human intervention studies are not feasible for ethical reasons. Therefore, a novel approach in addressing this issue was chosen by combining teratogenicity data from a validated animal model with data on systemic exposure to vitamin A and its major metabolites in female volunteers. In a study in pregnant women endogenous plasma concentrations of vitamin A metabolites during early pregnancy ranged from 0.26 to 7.72 ng/ml. Since they did not cause any foetal malformations, retinoid plasma levels in this range can be considered non-teratogenic. Results of a trial in non-pregnant women document that daily oral vitamin A supplements of 4000, 10000 and 30000 IU given for 3 weeks were in the range or slightly above the range of endogenous plasma levels seen in early pregnancy. Even after a 3-week treatment with 30000 IU/day, peak plasma levels of retinoic acid and isotretinoin were within or just slightly above the range of their physiological levels. In cynomolgus monkeys (average weight: 34 kg), a NOAEL (no observed adverse effect level) of 7500 IU per kg body weight and a LOAEL (lowest observed adverse effect level) for developmental toxicity of 20000 IU/kg was found. Considering these results in the cynomolgus monkey, a dose of 30000 IU/day should also be considered as non-teratogenic in man.
Keywords
Vitamin A, Physiological retinoids, Isotretinoin, Pregnancy, Safety limits
International Journal for Vitamin and Nutrition Research,
Band 68, 1998, Heft 6, © Verlag Hans Huber AG, Bern