Terhi A. Outila

Vitamin D Deficiency and Bone Health in Healthy Adults in Finland: Could This Be a Concern in Other Parts of Europe?

A low vitamin D status could be a concern not only in children and the elderly in Europe, but also in adults. We do not know the effect of mild vitamin D deficiency on bone in this age group. The aim of this study was to detect the prevalence of low serum 25‐hydroxyvitamin D [S‐25(OH)D] and elevated serum intact parathyroid hormone (S‐iPTH) concentrations in healthy young adults in the winter in northern Europe and to characterize the determinants of these variables. In addition, we studied the association between vitamin D status and forearm bone mineral density (BMD) in this population group. Three hundred and twenty‐eight healthy adults (202 women and 126 men, 31–43 years) from southern Finland (60°N) participated in this study conducted in February through March 1998. Fasting overnight blood samples were collected in the morning. Forearm BMD was measured by dual‐energy X‐ray absorptiometry (DXA). The mean daily vitamin D intake met the recommendations in the men (5.6 ± 3.2 μg) and almost met it in the women (4.7 ± 2.5 μg). The mean S‐25(OH)D concentrations did not differ between genders (women, 47 ± 34 nM; men, 45 ± 35 nM; mean ± SD), but the women had significantly higher mean S‐iPTH levels than the men (women, 30 ± 13 ng/liter; men, 24 ± 12 ng/liter; p < 0.001). Low S‐25(OH)D concentrations (<25 nM) were found in 26.2% of the women (53 women) and 28.6% of the men (36 men), respectively. Based on nonlinear regression analysis between S‐25(OH)D and S‐iPTH concentration, the S‐iPTH concentration started to increase with S‐25(OH)D concentrations lower than ∼80 nM in the women and lower than ∼40 nM in the men. Based on this relation between S‐25(OH)D and S‐iPTH concentrations, 86% of the women and 56% of the men had an insufficient vitamin D status. In linear regression analysis, the main positive determinants of S‐25(OH)D were dietary vitamin D intake (p < 0.02), the use of supplements (p < 0.005), alcohol intake (p < 0.05), and age (p < 0.005). Smoking associated negatively with the S‐25(OH)D concentration (p < 0.03). The main determinants of S‐iPTH were S‐25(OH)D (p < 0.01), dietary calcium intake (p < 0.02), and body mass index (BMI; p < 0.01). In addition, female gender was associated with higher S‐iPTH concentration. The mean daily dietary calcium intake was 1037 ± 489 mg and 962 ± 423 mg, in the men and women, respectively. Significantly lower forearm BMD was found in the men (p = 0.01) but not in the women (p = 0.14) with higher S‐iPTH concentrations. Low vitamin D status was prevalent in these young adults in northern Europe in winter, although the vitamin D intake met the recommendation. This probably is not a local problem for northern Europe, because the natural sources of vitamin D are scarce and fortification is not very common in Europe, and with the exception of the southern part of Europe, sunshine is not very abundant in this part of the world. Thus, the results of this study indicate that more attention should be focused on vitamin D status and the sources of vitamin D in these countries.

Safety aspects and cholesterol-lowering efficacy of low fat dairy products containing plant sterols

Objective:The aim of this study was to investigate whether a plant sterol mixture would reduce serum cholesterol when added to low fat dairy products in subjects with hypercholesterolaemia, and to examine the effects of the mixture on the serum plant sterol and fat-soluble vitamin levels.Design:A parallel, double-blind study.Setting:The study was performed in three different locations in Finland.Subjects:In total, 164 mildly or moderately hypercholesterolaemic subjects participated in the study.Methods:The subjects were randomly divided into two groups: a plant sterol group and a control group. The subjects consumed the products for 6 weeks after a 3-week run-in period. The targeted plant sterol intake was 2 g/day in the sterol group.Results:During the treatment period, there was a 6.5% reduction in serum total cholesterol in the sterol group while no change was observed in the control group (P<0.0005). Serum low-density lipoprotein (LDL) cholesterol was reduced by 10.4% in the sterol group and by 0.6% in the control group (P<0.00005). There was no change during the trial in serum high-density lipoprotein (HDL) cholesterol or triacylglycerol concentrations. The HDL/LDL cholesterol ratio increased by 16.1% in the sterol group and by 4.3% in the control group (P=0.0001). Serum plant sterol levels increased significantly (P=0.0001) in the sterol group. None of the fat-soluble vitamin levels decreased significantly when changes in serum total cholesterol were taken into account. The hypocholesterolaemic effect of sterol administration was not influenced by apolipoprotein E phenotype.Conclusions:Yoghurt, low-fat hard cheese and low-fat fresh cheese enriched with a plant sterol mixture reduced serum cholesterol in hypercholesterolaemic subjects and no adverse effects were noted in the dietary control of hypercholesterolaemia.

Low calcium:phosphorus ratio in habitual diets affects serum parathyroid hormone concentration and calcium metabolism in healthy women with adequate calcium intake.

Excessive dietary P intake alone can be deleterious to bone through increased parathyroid hormone (PTH) secretion, but adverse effects on bone increase when dietary Ca intake is low. In many countries, P intake is abundant, whereas Ca intake fails to meet recommendations; an optimal dietary Ca:P ratio is therefore difficult to achieve. Our objective was to investigate how habitual dietary Ca:P ratio affects serum PTH (S-PTH) concentration and other Ca metabolism markers in a population with generally adequate Ca intake. In this cross-sectional analysis of 147 healthy women aged 31-43 years, fasting blood samples and three separate 24-h urinary samples were collected. Participants kept a 4-d food record and were divided into quartiles according to their dietary Ca:P ratios. The 1st quartile with Ca:P molar ratio < or = 0.50 differed significantly from the 2nd (Ca:P molar ratio 0.51-0.57), 3rd (Ca:P molar ratio 0.58-0.64) and 4th (Ca:P molar ratio > or = 0.65) quartiles by interfering with Ca metabolism. In the 1st quartile, mean S-PTH concentration (P = 0.021) and mean urinary Ca (U-Ca) excretion were higher (P = 0.051) than in all other quartiles. These findings suggest that in habitual diets low Ca:P ratios may interfere with homoeostasis of Ca metabolism and increase bone resorption, as indicated by higher S-PTH and U-Ca levels. Because low habitual dietary Ca:P ratios are common in Western diets, more attention should be focused on decreasing excessively high dietary P intake and increasing Ca intake to the recommended level.

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.

Habitual high phosphorus intakes and foods with phosphate additives negatively affect serum parathyroid hormone concentration: a cross-sectional study on healthy premenopausal women.

OBJECTIVE Foods can contain natural phosphorus (NP) and phosphate-containing food additives (AP). The main objective of the present study was to investigate whether NP and AP of habitual diets differ in their effects on markers of Ca metabolism. We also investigated the impact of total habitual dietary P intake on markers of Ca metabolism. DESIGN Cross-sectional study. Fasting blood samples were collected and participants kept a 4 d food record, from which dietary intake of total P and the consumption of NP (milk and cheese, excluding processed cheese) and AP (processed cheese) sources were calculated. Participants were divided into groups according to their NP- and AP-containing food consumption and into quartiles according to their total P intake. SETTING Southern Finland. SUBJECTS One hundred and forty-seven healthy premenopausal women aged 31-43 years. RESULTS Relative to the lowest total dietary P quartile, mean serum parathyroid hormone (S-PTH) concentration was higher (P = 0.048, analysis of covariance (ANCOVA)) and the mean serum ionized Ca concentration lower (P = 0.016, ANCOVA) in the highest P intake quartile. Mean S-PTH concentrations were higher among participants who consumed processed cheese (P = 0.027, ANCOVA) and less milk and other cheese than processed cheese (P = 0.030, ANCOVA). CONCLUSIONS High total habitual dietary P intake affected S-PTH unfavourably. Furthermore, phosphate additives may have more harmful effects on bone than other P sources, as indicated by higher mean S-PTH concentration among participants who consumed AP-containing foods. Because of the high dietary P intake and current upward trend in consumption of processed foods in Western countries, these findings may have important public health implications.

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.

Vitamin D receptor gene BsmI-polymorphism in Finnish premenopausal and postmenopausal women: its association with bone mineral density, markers of bone turnover, and intestinal calcium absorption, with adjustment for lifestyle factors.

Abstract. Bone mineral density (BMD) is regulated by genetic and environmental factors. Sixty percent to 80% of bone mass is suggested to be under polygenetic control, but the role of individual genes seems to be modest. Several studies have indicated that the vitamin D receptor (VDR) gene has a role in the regulation of BMD and bone metabolism, but the results are very controversial. We studied the associations between BsmI-polymorphism of the VDR gene and BMD and bone metabolism in 24 premenopausal (aged 22–45 years) and 69 postmenopausal (aged 48–65 years) Finnish women. The BMD of the lumbar spine and femoral neck and bone turnover markers were measured, and the intestinal calcium absorption was investigated, using a method based on the absorption of non-radioactive strontium. The genotype distribution was 16%, BB; 34.5%, Bb; and 49.5%, bb, which differs from the genotype distribution found in other Caucasian populations, but is similar to earlier Finnish reports. The winter value of 25-hydroxyvitamin-D (25-OH-D) was highest for the BB genotype in both age groups (analysis of covariance [ANCOVA]; premenopausal women P = 0.5, postmenopausal women P = 0.03, and for the groups combined P = 0.02). Lumbar spine BMD and intestinal strontium absorption were highest for the BB genotype in both age groups, but these results were nonsignificant. The markers of bone metabolism did not differ significantly between the VDR genotypes. The BB genotype had the best vitamin D status, which could explain the differences in calcium absorption between the genotypes. However, the conclusions of our study are limited because of the small number of subjects.

Vitamin D receptor gene start codon polymorphism (FokI) is associated with forearm bone mineral density and calcaneal ultrasound in Finnish adolescent boys but not in girls

We examined the association between vitamin D receptor (VDR) gene FokI polymorphism and bone mineral density and quantitative ultrasound parameters in Finnish adolescents. We assessed bone mineral density at the distal sites of radius and ulna, quantitative ultrasound of the calcaneus, serum concentration of 25-hydroxyvitamin D (25-OHD), calcium intake, physical activity, and BsmI and FokI polymorphisms of the vitamin D receptor gene in 86 girls and 38 boys aged 14 to 16 years. In girls, FokI polymorphism was not significantly associated with bone mineral density or quantitative ultrasound parameters. In adolescent boys, the Ff genotype was associated with higher forearm BMD and calcaneal ultrasound values, when adjusted for body and bone size, BsmI polymorphism, calcium intake, vitamin D status, smoking, and physical activity.

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.