Jette Jakobsen

Teenage girls and elderly women living in northern Europe have low winter vitamin D status

Objective:To determine the vitamin D status (serum 25-hydroxyvitamin D; S-25OHD) in adolescent girls and elderly community-dwelling women living in four countries of northern Europe and to explain differences in S-25OHD concentrations between and within the countries.Design:A cross-sectional observational study conducted in a standardised way during February–March. S-25OHD was analysed by high-performance liquid chromatography. Vitamin D and calcium intake was calculated using a standardised food composition database.Setting:Denmark, Finland, Ireland, and Poland.Subjects:A total of 199 girls (mean (s.d.) age 12.6 (0.5) y) and 221 women (mean (s.d.) age 71.8 (1.4) y).Results:The median (inter quartiles) concentration of S-25OHD was 29.4 (20.3, 38.3) nmol/l for the girls and 40.7 (28.0, 54.2) nmol/l for the women. S-25OHD below 25 nmol/l was found in 37% of the girls and 17% of the women, and S-25OHD below 50 nmol/l was found in 92% of the girls and 37% of the women. Positive significant determinants for S-25OHD in girls were use of vitamin D supplements, and in women sun habits, dietary vitamin D intake, use of vitamin D and calcium supplements. Body mass index and smoking were negative determinants in women. For women predictors could explain the differences between countries (Pcountry=0.09, R2=0.39), but for girls the difference remained significant even after including predictors (Pcountry=0.03, R2=0.15).Conclusion:Vitamin D status is low in northern Europe during winter. More than one-third of the adolescent girls have vitamin D status below 25 nmol/l and almost all are below 50 nmol/l. Two-thirds of the elderly community-dwelling women have vitamin D status below 50 nmol/l. Use of vitamin D supplements is a significant positive determinant for S-25OHD for both girls and women (P=0.001).Sponsorship:The European Fifth Framework Programme (Contract No. QLK1-CT-2000-00623).

A Positive Dose–Response Effect of Vitamin D Supplementation on Site-Specific Bone Mineral Augmentation in Adolescent Girls: A Double-Blinded Randomized Placebo-Controlled 1-Year Intervention†

The effect of vitamin D supplementation on bone mineral augmentation in 212 adolescent girls with adequate calcium intake was studied in a randomized placebo‐controlled setting. Bone mineral augmentation determined by DXA increased with supplementation both in the femur and the lumbar vertebrae in a dose‐responsive manner. Supplementation decreased the urinary excretion of resorption markers, but had no impact on formation markers.

Geographical differences in vitamin D status, with particular reference to European countries

Vitamin D is produced endogenously when the skin is exposed to sunlight and can be obtained exogenously from a few natural food sources, from food fortification and from supplements. Generally, vitamin D intake is low < or = 2-3 microg/d in Europe. Casual exposure to sunlight is thought to provide most of the vitamin D requirement of the human population. However, skin synthesis of vitamin D may not compensate for the low nutritional intake in Europe, even in countries with high supplies from food fortification and supplements. For assessment of vitamin D nutritional status the concentration of 25-hydroxyvitamin D (25(OH)D) in serum is considered to be an accurate integrative measure reflecting an individuals dietary intake and cutaneous production. A substantial percentage of the elderly and adolescents in Europe have a low concentration of 25(OH)D; in the elderly this percentage ranges from approximately 10 in the Nordic countries to approximately 40 in France. Low vitamin D status seems to be aggravated by disease and immobility, and by a low frequency of supplement use.

Dose-response effects of lycopene on selected drug-metabolizing and antioxidant enzymes in the rat.

The administration of lycopene to female rats at doses ranging from 0.001 to 0.1 g/kg b.w. per day for 2 weeks was found to alter the drug-metabolizing capacity and antioxidant status of the exposed animals. An investigation of four cytochrome P450-dependent enzymes revealed that benzyloxyresorufin O-dealkylase activity in the liver was significantly induced in a dose-dependent fashion at all lycopene doses investigated. Likewise, ethoxyresorufin O-dealkylase activity was induced, although only at the two highest lycopene concentrations tested. An investigation of selected phase 2 detoxification enzymes provided evidence that lycopene was capable of inducing hepatic quinone reductase, approximately two-fold, at doses between 0.001 and 0.05 g/kg b.w. per day, whereas no effect was observed at the remaining doses tested. Glutathione transferase, using the two substrates, 2,4-dichloronitrobenzene and 1-chloro-2, 4-dinitrobenzene, was significantly induced at the 0.1 g/kg b.w. per day dose, whereas no effect was observed at the remaining lycopene doses. Analysis of the antioxidant status of the blood compartment revealed that three out of four antioxidant enzymes were affected by lycopene treatment. The activity of superoxide dismutase was thus significantly induced at lycopene doses of 0.005 and 0.05 g/kg b.w, whereas glutathione reductase and glutathione peroxidase was only induced at the 0.005 g/kg b.w. per day dose. For all antioxidant enzymes investigated, the activities seemed to return to the control level after exerting peak induction at doses between 0.005 and 0.05 g/kg b.w. per day. The explanation for this remains unknown. The plasma concentration of lycopene at dietary levels of 0.001, 0.005, 0.05 and 0.1 g/kg b.w. per day was estimated to be 16, 32, 71 and 67 nM, which is barely within the lower range of the mean human plasma concentration of lycopene, which ranges from 70-1790 nM. Oxidative stress induced by the heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), and investigated by analyzing for malondialdehyde in plasma, was not found to be affected by prior lycopene exposure. The level of PhIP-DNA adducts in the liver or colon was likewise not affected by lycopene at any dose. Overall, the present study provides evidence that lycopene administered in the diet of young female rats exerts minor modifying effects toward antioxidant and drug-metabolizing enzymes involved in the protection against oxidative stress and cancer. The fact that these enzymatic activities are induced at all of these very low plasma levels, could be taken to suggest that modulation of antioxidant and drug-metabolizing enzymes may indeed be relevant to humans, which in general exhibit a plasma lycopene level several fold above the effective levels observed in this study.

Food Contents and Biological Activity of 25-Hydroxyvitamin D: A Vitamin D Metabolite to Be Reckoned With?

Only a limited number of foods naturally contain vitamin D such as fish, meat and offal, and eggs, and milk and dairy products. However, all these foods in addition contain the metabolite 25-hydroxyvitamin D (25OHD). From the few systematic studies which have been performed the food contents of 25OHD in animal foods are usually low but vary. Contents are typically very low in milk and fish (<0.1 µg/100 g), somewhat higher in meat and offal (0.2–0.4 µg/100 g) and up to 1 µg/100 g in egg yolk. It has been demonstrated that 25OHD is absorbed better and faster from the diet than native vitamin D and has metabolic effects of its own in regulating cell growth and calcium metabolism. Thus, the biological activity of 25OHD is greater than that of native vitamin D. However, there is as yet no consensus on the conversion factor that should be used for 25OHD to calculate vitamin D activity. Depending on the testing system used the factor varies from 1.5 to 5. If food contents and the higher potency of 25OHD are not included in dietary intake surveys, true vitamin D intake will be underestimated.

Determinants of vitamin D status in a general population of Danish adults

BACKGROUND AND AIMS Danish legislation regarding food fortification has been very restrictive and vitamin D deficiency is thought to be common in Denmark due to inadequate dietary intakes and the fact that in Denmark (latitude 56°N) vitamin D is only synthesized in the skin after exposure to solar radiation during summertime (April-September). The purpose of this study was to evaluate the vitamin D status of a general adult population in Denmark and, in addition, associations between vitamin D status and distinct lifestyle factors were studied. METHODS A random sample of 6784 persons from a general population aged 30-60 years participated in a health examination in 1999-2001. Serum samples from all participants were stored and levels of 25-hydroxyvitamin D (25(OH)D) were measured by HPLC in 2009. The method was compared to another HPLC method. Information on dietary intake of vitamin D and other lifestyle factors were obtained by questionnaires. A total of 6146 persons defined as ethnic Danes and with successful measurements of 25(OH)D were included in the analyses. RESULTS The overall prevalence of vitamin D deficiency (25(OH)D<25 nmol/l) and insufficiency (25(OH)D<50 nmol/l) were 13.8% and 52.2%, respectively. A marked seasonal fluctuation was seen in serum levels of 25(OH)D - median values of 25(OH)D were lowest in February and highest in August. In multiple logistic regression models (n=5506), low vitamin D status was significantly associated with obesity (BMI≥30), daily smoking and a sedentary lifestyle. However, measurements of 25(OH)D were not associated with the estimated dietary intake of vitamin D. Comparison of two HPLC methods demonstrated considerable differences in accuracy. DISCUSSION AND CONCLUSIONS Our results suggest that poor vitamin D status is common among adults in a Northern European country without food fortification with vitamin D. Methodological issues are, however, of great importance when using cut-off values to define poor vitamin D status. In addition, we demonstrated that low serum levels of 25(OH)D were associated with several lifestyle factors.

Sodium and bone health: impact of moderately high and low salt intakes on calcium metabolism in postmenopausal women.

High salt intake is a well‐recognized risk factor for osteoporosis because it induces calciuria, but the effects of salt on calcium metabolism and the potential impact on bone health in postmenopausal women have not been fully characterized. This study investigated adaptive mechanisms in response to changes in salt and calcium intake in postmenopausal women. Eleven women completed a randomized cross‐over trial consisting of four successive 5‐wk periods of controlled dietary intervention, each separated by a minimum 4‐wk washout. Moderately low and high calcium (518 versus 1284 mg) and salt (3.9 versus 11.2 g) diets, reflecting lower and upper intakes in postmenopausal women consuming a Western‐style diet, were provided. Stable isotope labeling techniques were used to measure calcium absorption and excretion, compartmental modeling was undertaken to estimate bone calcium balance, and biomarkers of bone formation and resorption were measured in blood and urine. Moderately high salt intake (11.2 g/d) elicited a significant increase in urinary calcium excretion (p = 0.0008) and significantly affected bone calcium balance with the high calcium diet (p = 0.024). Efficiency of calcium absorption was higher after a period of moderately low calcium intake (p < 0.05) but was unaffected by salt intake. Salt was responsible for a significant change in bone calcium balance, from positive to negative, when consumed as part of a high calcium diet, but with a low calcium intake, the bone calcium balance was negative on both high and low salt diets.

Increased micronuclei and bulky DNA adducts in cord blood after maternal exposures to traffic-related air pollution ☆

Exposure to traffic-related air pollution in urban environment is common and has been associated with adverse human health effects. In utero exposures that result in DNA damage may affect health later in life. Early effects of maternal and in utero exposures to traffic-related air pollution were assessed through the use of validated biomarkers in blood cells from mother-newborn pairs. A cross-sectional biomonitoring study with healthy pregnant women living in the Greater Copenhagen area, Denmark, was conducted. Bulky DNA adducts and micronuclei (MN) were measured in blood from 75 women and 69 umbilical cords, concurrently collected at the time of planned Caesarean section. Modeled residential traffic density, a proxy measure of traffic-related air pollution exposures, was validated by indoor levels of nitrogen dioxide and polycyclic aromatic hydrocarbons in 42 non-smoking homes. DNA adduct levels were similar and positively correlated in maternal and cord blood (1.40 vs. 1.37 n/10(8) nucleotides; r=0.99; p<0.01). Maternal MN frequencies were significantly associated with age (p<0.01), and higher than those of the newborns (7.0 vs. 3.2 MN per 1000 binucleated cells). Adduct levels were highest among mother-newborn pairs who lived near medium-traffic-density (>400-2500 vehicle km/24h; p<0.01) places. MN frequencies among newborns from women who lived at high-traffic-density homes (>2500 vehicle km/24h) were significantly increased (p=0.02). This trend remained after adjusting for potential confounders and effect modifiers. For the first time increased bulky DNA adducts and MN in cord blood after maternal exposures to traffic-related air pollution are found, demonstrating that these transplacental environmental exposures induce DNA damage in newborns. Given that increased DNA damage early in life indicate an increased risk for adverse health effects later in life, these findings justify intervention of pregnant women.

25-hydroxyvitamin D3 affects vitamin D status similar to vitamin D3 in pigs--but the meat produced has a lower content of vitamin D.

In food databases, the specific contents of vitamin D3 and 25-hydroxyvitamin D3 in food have been implemented in the last 10 years. No consensus has yet been established on the relative activity between the components. Therefore, the objective of the present study was to assess the relative activity of 25-hydroxyvitamin D3 compared to vitamin D3. The design was a parallel study in pigs (n 24), which from an age of 12 weeks until slaughter 11 weeks later were fed approximately 55 microg vitamin D/d, as vitamin D3, in a mixture of vitamin D3 and 25-hydroxyvitamin D3, or 25-hydroxyvitamin D3. The end-points measured were plasma 25-hydroxyvitamin D3, and in the liver and loin the content of vitamin D3 and 25-hydroxyvitamin D3. Vitamin D3 and 25-hydroxyvitamin D3 in the feed did not affect 25-hydroxyvitamin D3 in the plasma, liver or loin differently, while a significant effect was shown on vitamin D3 in the liver and loin (P < 0.001). 25-Hydroxyvitamin D3 in the plasma, liver and loin significantly correlates with the sum of vitamin D3 and 25-hydroxyvitamin D3 in the feed (P < 0.05). Therefore, 25-hydroxyvitamin D3 should be regarded as having the same activity as vitamin D3 in food databases. Sole use of 25-hydroxyvitamin D3 as a vitamin D source in pig feed will produce liver and meat with a negligible content of vitamin D3, while an increased content of vitamin D3 in the feed will produce liver and meat with increased content of both vitamin D3 and 25-hydroxyvitamin D3.

High vitamin A content in some small indigenous fish species in Bangladesh: Perspectives for food-based strategies to reduce vitamin A deficiency

Recognising the importance of fish in the Bangladeshi diet, the objective of the present study was to screen commonly consumed fish species for vitamin A content to evaluate the potential of fish as a vitamin A source in food-based strategies to combat vitamin A deficiency. Samples of 26 commonly consumed fish species and one crustacean were collected in Kishoreganj and Mymensingh, Bangladesh. To obtain edible parts, the fish were cleaned by Bangladeshi women according to traditional practices. Distribution of vitamin A in parts of the fish and the effect of the cleaning practices on the vitamin A content in edible parts were assessed. The content of vitamin A compounds was analysed by high-performance liquid chromatography. The vitamin A content in small fish ranged from 2680 retinol equivalents (RE)/100 g raw edible parts in mola (Amblypharyngodon mola) to 20 RE/100 g raw edible parts in chata (Colisa lalia; an alternative scientific name is Colisa lalius). The vitamin A content in cultured species, silver carp (Hypophthalmichthys molitrix), rui (Labeo rohita), mrigal (Cirrhinus mrigala) and tilapia (Oreochromis niloticus) was low, <30 RE/100 g raw edible parts. In mola, 90% of the vitamin A was found in the eyes and viscera. The vitamin A content in the screened fish species was highly variable, by more than a factor of 100. The existence of commonly consumed fish in Bangladesh belonging to the categories of very high and high vitamin A content offers a great unexploited potential for food-based strategies to improve the vitamin A intake by promoting the production and consumption of these species.