Merja Ulla Margareetta Kärkkäinen

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).

Vitamin D intake is low and hypovitaminosis D common in healthy 9- to 15-year-old finnish girls

Objectives: To study the prevalence of hypovitaminosis D, the effect of vitamin D supplementation on serum 25-hydroxyvitamin D [S-25(OH)D], and the intakes of vitamin D and calcium in Finnish 9− to 15-year-old athletic and nonathletic girls.Design: 1-year follow-up study (February 1997-March 1998) with three months of vitamin D supplementation (10 μg/d) from October to January.Setting: Turku University Central Hospital, Finland.Subjects: 191 female volunteers aged 9–15 y (131 athletes and 60 controls).Methods: Vitamin D and calcium intakes were estimated by a four-day food recording and a semi-quantitative food frequency questionnaire (FFQ). S-25(OH)D was followed by radioimmunoassay (RIA).Results: At baseline the mean S-25(OH)D concentration was 33.9 nmol/l among all girls. In winter severe hypovitaminosis D (S-25(OH)D<20 nmol/l) occurred in 13.4% of the participants and in 67.7% S-25(OH)D was below 37.5 nmol/l. By the next summer the mean S-25(OH)D concentration was 62.9 nmol/l and in 1.6% of the subjects it was below 37.5 nmol/l. The prevalence of severe hypovitaminosis D was not significantly reduced by three months of vitamin D (10 μg/d) supplementation. At baseline, the mean intake of vitamin D was 2.9 μg/d by food recording and 4.3 μg/d by FFQ. The mean calcium intake was 1256 mg/d and 1580 mg/d, respectively. The intakes of vitamin D and calcium remained unchanged during the follow-up period. The athletes consumed more calcium than nonathletic controls, whereas the intake of vitamin D was quite similar among both groups. The vitamin D intake by FFQ correlated with the S-25(OH)D concentration in wintertime (r=0.28, P<0.01).Conclusion: Hypovitaminosis D is fairly common in growing Finnish girls in the wintertime, and three months of vitamin D supplementation with 10 μg/d was insufficient in preventing hypovitaminosis D. The daily dietary vitamin D intake was insufficient (<5 μg/d) in the majority of participants, while the calcium intake was usually sufficient.Sponsorship: Supported by the Yrjö Jahnsson Foundation, The Turku University Foundation, and the Medical Research Foundation of the Turku University Central Hospital.

Acute Effects of Different Phosphorus Sources on Calcium and Bone Metabolism in Young Women: A Whole-Foods Approach

The recommended dietary phosphorus intake is exceeded in the typical Western diet. However, few studies have been conducted on the bioavailability and metabolic consequences of dietary phosphorus from different food sources. In this study, acute effects of dietary phosphorus from three different food sources and a phosphate supplement on calcium and bone metabolism were investigated. Sixteen healthy women aged 20–30 years were randomized to five controlled 24-hour study sessions, each subject serving as her own control. At the control session, calcium intake was ca. 250 mg and phosphorus intake ca. 500 mg. During the other four sessions, phosphorus intake was about 1,500 mg, 1,000 mg of which was obtained from meat, cheese, whole grains, or a phosphate supplement, respectively. The foods served were exactly the same during the phosphorus sessions and the control session; only phosphorus sources varied. Markers of calcium and bone metabolism were followed. Analysis of variance with repeated measures was used to compare the study sessions. Only the phosphate supplement increased serum parathyroid hormone (S-PTH) concentration compared with the control session (P = 0.031). Relative to the control session, meat increased markers of both bone formation (P = 0.045) and bone resorption (P = 0.049). Cheese decreased S-PTH (P = 0.0001) and bone resorption (P = 0.008). These data suggest that the metabolic response was different for different foods.

Dietary Intake of Vitamin D in Premenopausal, Healthy Vegans was Insufficient to Maintain Concentrations of Serum 25-hydroxyvitamin D and Intact Parathyroid Hormone Within Normal Ranges During the Winter in Finland

OBJECTIVE To study vitamin D status and bone metabolism of premenopausal vegetarians and omnivores during a 1-year period. DESIGN Longitudinal, observational study. Bone mineral density was measured, blood samples from fasting subjects were obtained, and 24-hour urinary samples were collected in February 1994, August 1994, and January 1995. Serum 25-hydroxyvitamin D [S-25(OH)D] and intact parathyroid hormone (S-iPTH) concentrations were measured and intestinal calcium absorption was estimated. Dietary intakes of vitamin D and calcium were calculated. SUBJECTS/SETTING Six vegans, 6 lactovegetarians, and 16 omnivores living in Helsinki, Finland. STATISTICAL ANALYSES PERFORMED Student-Newman-Keuls test; unbalanced, repeated-measures multiple analysis of variance; analysis of covariance; Pearson correlation test; and linear regression analysis. RESULTS Dietary intake of vitamin D was significantly lower in vegans (P < .05, yearly mean +/- standard deviation = 0.09 +/- 0.06 microgram/day) and in lactovegetarians (P < .05, 0.7 +/- 0.4 microgram/day) compared with omnivores (4.0 +/- 2.1 micrograms/day). Throughout the year S-25(OH)D (P = .01) concentrations were lower and S-iPTH (P = .01) concentrations were higher in vegans than in omnivores and lactovegetarians. Bone mineral density in the lumbar region of the spine was lower in vegans (yearly mean +/- standard deviation = 1.034 +/- 0.174 g/cm2) than in omnivores (P = .05, 1.177 +/- 0.099 g/cm2) and tended to be lower than that in lactovegetarians (P = .17, 1.138 +/- 0.06 g/cm2). Bone mineral density in the neck of the femur tended to be lower in vegans (0.843 +/- 0.116 g/cm2) than in omnivores (P = .07, 0.999 +/- 0.138 g/cm2) and lactovegetarians (P = .15, 0.961 +/- 0.059 g/cm2). No seasonal variation was found in bone mineral density in the study groups. CONCLUSIONS At northern latitudes, dietary intake of vitamin D in vegans was insufficient to maintain S-25(OH)D and S-iPTH concentrations within normal ranges in the winter, which seems to have negative effects on bone mineral density in the long run. APPLICATIONS An increase in vitamin D intake should generally be recommended for vegans at least during winter, or selections of foodstuffs fortified with vitamin D should be broadened in northern latitudes.

Vitamin D deficiency: a concern in premenopausal Bangladeshi women of two socio-economic groups in rural and urban region

Objective: The study was designed to evaluate the vitamin D status in women of different physiological status of two socio-economic groups in Bangladesh.Design: A cross-sectional study, using serum 25-hydroxyvitamin D (25-OHD), calcium, phosphorus and alkaline phosphatase activity.Setting: Two regions of Bangladesh. The Dhaka city area and west region of Nandail (Betagair Union), Mymensingh.Subjects: Representative subjects of two groups (low socio-economic group=group L, n=99; and high socio-economic group=group H, n=90) of Bangladeshi women aged 16–40 y. About 87% of the subjects were housewives and the rest, 13%, were distributed among other different professions. Each group comprised of three sub-groups (non-pregnant non-lactating=1, pregnant=2, and lactating=3).Results: The influence of socio-economic status and physiological status on serum 25-OHD concentration (P=0.038, P=0.015, respectively), serum calcium concentration (P<0.001, P<0.001, respectively) and alkaline phosphatase activity (P<0.001, P<0.001, respectively) were observed. The distribution of serum 25-OHD concentration in both groups was shifted overall toward the lower limit of the normal range. Seventeen percent of women in group L and 12% of women in group H had serum 25-OHD concentration <25 nmol/l. Hypovitaminosis D (serum 25-OHD concentration ≤ 37.5 nmol/l) was observed in 50% of subjects in group L and 38% of subjects in group H, respectively. The prevalence of hypovitaminosis was higher in lactating subjects of the groups L and H (63 and 46%, respectively) than in the other sub-groups in the same group.Conclusions: The results of the study suggested that women in Bangladesh were at risk of hypovitaminosis D and lactation was an additional risk factor in low income groups. The situation may increase the risk of bone loss.Sponsorship: The study was supported by the Academy of Finland, University of Helsinki and NorFa, Norway.

Dietary calcium intake in premenopausal Bangladeshi women: do socio-economic or physiological factors play a role?

Objective: Evaluation of data on dietary calcium intake in premenopausal women of two socio-economic groups in Bangladesh.Design: A cross sectional study. Three days dietary records were used to estimate habitual calcium intake.Setting: Two regions of Bangladesh. The Dhaka city area and the Betagair Union in the sub-district Nandail, Mymensingh.Subjects: A total of 191 subjects of two groups (low socio-economic group=group L, n=101 and high socio-economic group=group H, n=90) of Bangladeshi women aged 16–40 y. About 87% of the subjects were housewives and the rest 13% were distributed in other different professions. Each group consisted of three sub-groups (non-pregnant non-lactating=1, pregnant=2 and lactating=3).Results: The influence of socio-economic status on dietary intake of calcium (P<0.001) was observed in this study. The dietary intake of calcium was influenced by physiological status (PS) in high income group only (P<0.005). The mean dietary calcium intake was significantly higher (P<0.005) in all sub-groups of this group compared with the corresponding sub-groups in low income group. Although in group H, 47% of subjects failed to meet even the lowest level (400–500 mg/day) of WHO recommended dietary allowances (RDA) of calcium for adult women. No subject in group L was found to meet the RDA level. Moreover, 63% of the women in group L had calcium intake lower than 200 mg/day. These figure could be more critical in both groups if we consider the recent USA-RDAs of calcium for adult women (1000 mg/day). The observed sources of dietary calcium were different in the two groups.Conclusions: The results of the study suggested that low calcium intake could reduce the bone accretion rates and increase the risk of osteoporosis in the subjects of the present study. Calcium rich food may be recommended for women in both groups.Sponsorship: The study was supported by the Academy of Finland, University of Helsinki and NorFa, Norway.

Associations of vitamin D receptor, calcium-sensing receptor and parathyroid hormone gene polymorphisms with calcium homeostasis and peripheral bone density in adult Finns

Background: Thus far the search for osteoporosis candidate genes has focused less attention on the regulation of calcium homeostasis. Associations of vitamin D receptor (VDR) FokI, calcium-sensing receptor (CaSR) A986S and parathyroid hormone (PTH) BstBI polymorphisms with calcium homeostasis and peripheral bone density were investigated in adult Finns. Methods: The subgroup of the population-based FINRISK survey consists of 339 healthy adults aged 31–43 years. Lifestyle data were assessed with questionnaires and food diaries. DNA was isolated from blood, and biochemical determinants of calcium metabolism were measured from blood and 24-hour urine samples. Bone mineral density (BMD) was measured using the DXA method at the distal forearm and by quantitative ultrasound (broadband ultrasound attenuation and speed of sound) at the calcaneus. Subjects were genotyped for VDR FokI, CaSR A986S and PTH BstBI polymorphisms. Results: The CaSR 986S allele was associated with higher serum ionized calcium (p = 0.014). Forearm BMD was lowest for the PTH BstBI genotype bb in males (p = 0.023). VDR FokI and PTH BstBI polymorphisms showed a significant interaction on serum PTH (p = 0.010). The other gene–gene or diet–gene interactions studied showed no significant results. Conclusions: VDR, CaSR and PTH contribute to the genetic regulation of calcium homeostasis and peripheral bone density.

Enhancing the capacity of food consumption surveys of short duration to estimate long term consumer-only intakes by combination with a qualitative food frequency questionnaire.

In principle, a proper risk assessment for a food chemical requires that the time-frame for food chemical intake estimates matches the time-frame for the toxicological assessments upon which the safety statements (ADI, PTW I, etc.) are based. For food additives, the toxicological assessments are based on exposure over a lifetime. While food consumption data cannot be collected over the lifetimes of individuals, the information should reflect habitual intakes as closely as possible. This study investigated the possibility of combining a 3-day food diary with a food frequency questionnaire to estimate mean consumer-only food intakes comparable to estimates based on a 14-day diary. The study population consisted of 948 teenagers and analysis was based on 32 clearly defined foods. For 47% of the foods, the difference was ≤ 1g/day. When expressed as portion sizes, 56% of the foods showed differences representing <5% of an average portion and no food showed a difference >14% of an average portion. When between-method differences (portions/day) were plotted against the mean of the methods, the mean between-method difference was 0.02 (± 0.06) portions/ day with limits of agreement of -0.10 to 0.14. This preliminary investigation suggests that the combined 3-day diary and FFQ method provides comparable estimates of mean consumer only intakes to a 14-day diary. Therefore, a qualitative FFQ may be a useful adjunct to a food consumption survey of short duration if estimates of longer term food intakes are required.

A 7-week reduction in salt intake does not contribute to markers of bone metabolism in young healthy subjects

Background:Sodium intake increases urinary calcium excretion and may thus lead to negative calcium balance and bone loss.Objective:We hypothesised that reducing sodium intake would reduce urinary calcium excretion and have a beneficial influence in bone metabolism.Design:A total of 29 subjects, 14 males and 15 females, were divided into two study groups. One group (low-sodium group (LS)) reduced sodium intake for 7 weeks by substituting low- salt alternatives for the most important dietary sources of sodium. The other group, serving as a control group (C), was given the same food items in the form of normally salted alternatives. Fasting serum samples as well as 24-h urine samples were obtained in the beginning and at the end of the study. Urinary sodium, urinary calcium, urinary creatinine, serum calcium, serum phosphate, serum creatinine, serum parathyroid hormone (s-PTH), serum C-terminal telopeptides of Type-I collagen and serum bone alkaline phosphatase (s-B-ALP) were analysed.Results:The LS group showed a significant decline (P=0.001) in urinary sodium/creatinine ratio without a significant effect on urinary calcium/creatinine ratio. In the LS group, s-PTH increased (P=0.03). The C group showed an increase in s-PTH (P=0.05) and in s-B-ALP, but no differences were observed between the study groups in the changes of serum markers of calcium and bone metabolism.Conclusions:We have shown that reducing the sodium intake of young, healthy people with adequate calcium intake over a 7-week period does not affect the markers of bone metabolism.Sponsorship:The study was supported by Tekes—National Technology Agency of Finland.

Serum parathyroid hormone is related to genetic variation in vitamin D binding protein with respect to total, free, and bioavailable 25-hydroxyvitamin D in middle-aged Caucasians – a cross-sectional study

BackgroundVitamin D binding protein (DBP) binds vitamin D and its plasma metabolites, including 25-hydroxyvitamin D (25(OH)D), in the circulation. Only a small fraction circulates free (free 25(OH)D). Genetic variation of the GC gene, encoding DBP, has been associated with 25(OH)D concentrations. The roles of DBP and free 25(OH)D concentrations in the biological actions of vitamin D remain unclear.MethodsWe assessed the relationship between GC gene variants rs4588, rs7041, and rs705124, and serum total 25(OH)D, free and bioavailable 25(OH)D, and serum DBP and parathyroid hormone (PTH) concentrations in 622 Caucasian females (421) and males (201) aged 37–47 years. Concentrations of 25(OH)D, DBP, and PTH were measured from fasting blood samples. Dietary intakes of vitamin D and Ca were evaluated using 1-month food use frequency data, which were collected by a validated Food Frequency Questionnaire on vitamin D and calcium intakes. The subjects filled in the questionnaire covering overall health, medications, use of vitamin D and calcium supplements, and holidays in sunny locations. Three SNPs in the GC gene were genotyped: rs4588, rs7041, and rs705124. The SNPs rs4588 and rs7041 combine to form six common diplotypes. Free and bioavailable 25(OH)D were calculated by using specific binding coefficients. Differences among the diplo- and haplotypes of the GC gene in measures of 25(OH)D, DBP, and PTH were tested by analysis of covariance (ANCOVA) using appropriate covariates.ResultsWe found significant variation among the SNPs rs4588 and rs7041 variants in DBP, total, free, and bioavailable 25(OH)D, and PTH. DBP concentration was lowest in genotype GC2/2 in both diplotypes and haplotypes (p = 0.039 and 0.039, respectively). The lowest 25(OH)D concentrations were found in diplotype variants GC1S/2, GC1S/F, and GC2/2 (p = 0.033), but free and bioavailable 25(OH)D concentrations were highest in the GC2/2 variant after corrected with a genotype-specific binding coefficient (p < 0.001 in both groups). Surprisingly, one of the lowest PTH concentrations was also present in variant GC2/2 in diplotypes (p = 0.040 of the overall ANCOVA analysis of PTH). Among SNP rs705124, there was a difference only in PTH concentrations (p = 0.013).ConclusionsOur findings indicate that genetic variation of the DBP coding gene, and free concentrations of 25(OH)D may be relevant when vitamin D status, metabolism, and action are investigated.