The effect of high-dose vitamin D supplementation on muscular function and quality of life in postmenopausal women-A randomized controlled trial.

OBJECTIVE: Observational studies have suggested positive associations between serum 25-hydroxyvitamin D (25(OH)D) levels and muscular strength, balance and quality of life. Our aim was to examine whether high-dose vitamin D supplementation would improve these measures as compared to standard-dose vitamin D, as well as the possible muscular effects of single nucleotide polymorphisms (SNPs) in genes encoding vitamin D-related enzymes. DESIGN: A 12-month randomized, double-blind, controlled trial where the participants received daily elemental calcium (1000 mg) plus vitamin D3 (800 IU). In addition, the participants were randomized to receive either capsules with vitamin D3 (20 000 IU) or matching placebos to be taken twice a week. PATIENTS: A total of 297 postmenopausal women with osteopenia or osteoporosis. MEASUREMENTS: Muscle strength (handgrip and knee extensor strength), balance (tandem test) and quality of life (EQ-5D) were measured at baseline and after 12 months. The subjects were genotyped for SNPs related to vitamin D metabolism. RESULTS: Of the 297 included women, 275 completed the study. Mean serum 25(OH)D levels dramatically increased in the high-dose group (from 64.7 to 164.1 nmol/L; P<.01), while a more moderate increased was observed in the standard-dose group (from 64.1 to 81.8 nmol/L; P<.01). There was no significant difference between the groups in change in muscular strength, balance or quality of life over the intervention period. Polymorphisms in rs3829251 (located in the 7-dehydrocholesterol reductase gene) were associated with muscle strength and treatment effects. CONCLUSION: One-year treatment with high-dose vitamin D had no effect on muscular strength, balance or quality of life in postmenopausal women with osteopenia or osteoporosis as compared to standard dose. The association between rs3829251 and muscle strength needs confirmation in other populations.

Development, validation and implementation of a quantitative food frequency questionnaire to assess habitual vitamin D intake.

BACKGROUND: A well-designed, validated quantitative food frequency questionnaire (FFQ) could offer an efficient and cost-effective method for assessing habitual vitamin D intake. The present study aimed to describe the development, validation and implementation of a vitamin D FFQ. METHODS: National food consumption survey data obtained from Irish adults (18-64 years) were used to identify foods that contribute 95% of vitamin D intake. A winter-based validation study was carried out for the resulting FFQ in 120 females, including 98 women [mean (SD) 65.0 (7.3) years] and 22 girls [12.2 (0.8) years], using a 14-day diet history (DH) as a comparator. Serum 25(OH)D concentrations were analysed. Validity coefficients were calculated using the method of triads. Cross-classification and Bland-Altman analysis were also performed. RESULTS: Median (interquartile range) vitamin D intakes (including the contribution from nutritional supplements) were 5.4 (3.7) and 3.7 (5.9) µg day(-1) from the FFQ and DH, respectively and intakes of vitamin D from food sources were 3.6 (3.1) and 2.4 (2.2) µg day(-1) . The FFQ and DH classified 86% and 87% of individuals into the same and adjacent thirds of wintertime serum 25(OH)D status, respectively. There was a strong association (r = 0.71, P < 0.0001) and no significant systematic or proportional bias observed for the difference between estimates from the FFQ and DH. The validity coefficient for the FFQ was 0.92 (95% confidence interval = 0.80-0.97). Repeatability analysis (n = 56) performed 6-12 months later showed no significant difference in estimates of vitamin D between administrations. CONCLUSIONS: The data obtained in the present study indicate high validity and good reproducibility of a short, interviewer-administered FFQ for vitamin D.

Does vitamin D supplementation of healthy Danish Caucasian girls affect bone turnover and bone mineralization?

INTRODUCTION: A high peak bone mass may be essential for reducing the risk of osteoporosis later in life and a sufficient vitamin D level during puberty may be necessary for optimal bone accretion and obtaining a high peak bone mass. Dietary intake and synthesis during winter of vitamin D might be limited but the effect of vitamin D supplementation in adolescence on bone mass is not well established. OBJECTIVE: To investigate the effect of supplementation with 5 and 10 microg/day vitamin D(3) for 12 months in 11- to 12-year-old girls on bone mass and bone turnover as well as the possible influence of VDR and ER genotype on the effect of the supplementation. METHODS: The girls (n=221) were randomized to receive either 5 microg or 10 microg vitamin D(3) supplementation per day or placebo for 12 months. Whole body and lumbar spine bone mass measured by DXA and pubertal status were determined at baseline and after 12 months whereas physical activity and dietary intake of calcium and vitamin D were assessed at baseline. Serum (S) 25-hydroxyvitamin D (25OHD), S-osteocalcin, S-parathyroid hormone, S-calcium, S-inorganic phosphate, urinary (U) pyridinoline (Pyr) and deoxpyridinoline (Dpyr) were measured at baseline and after 6 and 12 months. RESULTS: The S-25OHD concentration increased (p<0.001) relative to the baseline values in the groups receiving either 5 microg/day (mean+/-SD; 11.0+/-10.3 nmol/l, baseline 41.9+/-17.6 nmol/l) or 10 microg/day (13.3+/-11.8 nmol/l, baseline 44.4+/-16.6 nmol/l) vitamin D(3) for 12 months compared to placebo (-3.1+/-9.8 nmol/l, baseline 43.4+/-17.1 nmol/l). There was no effect of vitamin D-supplementation on biomarkers for bone turnover or on whole body or spine bone mineral augmentation. However, vitamin D supplementation increased whole body bone mineral density (BMD) (p=0.007) and bone mineral content (BMC) (p=0.048) in the FF VDR genotype but not in the Ff or ff VDR genotypes. CONCLUSION: Supplementation with vitamin D (5 or 10 microg/day) over 12 months increased the S-25OHD concentration but there was no effect on indices of bone health in the entire group of girls. However, there was an effect on BMD for a subgroup with the FF VDR genotype indicating an influence of genotype.

Pakistani immigrant children and adults in Denmark have severely low vitamin D status.

OBJECTIVE: To determine vitamin D and bone status in adolescent girls, pre-menopausal women and men of Pakistani origin, to single out determinants of vitamin D status and to determine the association between vitamin D status, bone metabolism and bone status. SUBJECTS/METHODS: Cross-sectional study, Copenhagen (55 degrees N), January-November. Serum 25-hydroxyvitamin D (S-25OHD), serum intact parathyroid hormone (S-iPTH), bone turnover markers and whole body and lumbar spine bone mineral density were measured. Sun, smoking and clothing habits, age, body mass index (BMI), and vitamin D and calcium from food and from supplements were recorded. Thirty-seven girls (median age, range: 12.2 years, 10.1-14.7), 115 women (36.2 years, 18.1-52.7) and 95 men (38.3 years, 17.9-63.5) of Pakistani origin (immigrants or descendants with Pakistani parents) took part in the study. RESULTS: Median concentration of S-25OHD was 10.9, 12.0 and 20.7 nmol/l for girls, women and men, respectively. Forty-seven per cent of the girls, 37% of the women and 24% of the men had elevated S-iPTH, and there was a negative relationship between S-iPTH and S-25OHD. Use of vitamin D-containing supplements had a positive association with S-25OHD for men (P=0.04) and women (P=0.0008). Twenty-one per cent of the women and 34% of the men had osteopenia. Neither S-25OHD nor S-iPTH was associated with lumbar spine or whole body bone mineral content. CONCLUSIONS: Severely low vitamin D status and elevated S-iPTH is common among Pakistani immigrants in Denmark. The low vitamin D status is not associated with bone markers or bone mass among relatively young Pakistanis.

Vitamin D intake and status in Irish elderly women and adolescent girls.

AIM: To assess vitamin D status during summer and winter in Irish girls and elderly women, and to estimate vitamin D intake in these two age-groups. METHODS: Ambulatory free-living, elderly Irish women (aged 70-76 years; n = 43) and girls (aged 11-13 years; n = 17) were recruited. Fasting serums were collected during August/ September 2002 and February/March 2003 and analysed for 25 (OH) D by HPLC. RESULTS: Mean daily intakes of vitamin D were 4.6 microg and 2.1 microg in elderly women and girls, respectively. Serum 25 (OH) D was significantly lower (P<0.001) during winter than summer in both age-groups. Eight (20%) and one (during late summer) and sixteen (37.2%) and eight (47%) (during late winter) of the elderly women and girls, respectively, had inadequate vitamin D status (serum 25 (OH) D <40 nmol/l). CONCLUSION: Inadequate vitamin D status during winter time is quite common in elderly women and adolescent girls in Ireland.

Altered levels of biochemical indices of bone turnover and bone-related vitamins in patients with Crohn's disease and ulcerative colitis.

BACKGROUND: The pathogenesis of inflammatory bowel disease-associated osteopenia may be related to pathological rates of bone turnover; however, the literature shows mixed results. AIM: To compare bone biomarkers in inflammatory bowel disease patients (Crohn's disease: n = 68, and ulcerative colitis: n = 32, separately) with age- and sex-matched healthy controls. SUBJECTS: Patients and controls were recruited from Cork University Hospital and Cork City area, respectively. RESULTS: Relative to that in their respective controls, Crohn's disease (n = 47) and ulcerative colitis (n = 26) patients (i.e. excluding supplement users) had significantly (P < 0.05-0.001) higher serum undercarboxylated osteocalcin (by 27% and 63%, respectively) and bone-specific alkaline phosphatase (by 15% and 21%, respectively) and urinary Type I collagen cross-linked N-telopeptides concentrations (by 87% and 112%, respectively). Relative to that in their respective controls, Crohn's disease and ulcerative colitis patients had significantly (P < 0.01) lower serum total osteocalcin (by 20% and 42%, respectively) and 25-hydroxyvitamin D (by 37% and 42%, respectively), while serum parathyroid hormone levels were similar. In the combined patient group (n = 100), undercarboxylated osteocalcin was positively associated with bone markers. CONCLUSIONS: Both Crohn's disease and ulcerative colitis patients have altered bone turnover relative to that in healthy controls.

Determinants of vitamin D status in adult Crohn's disease patients, with particular emphasis on supplemental vitamin D use.

OBJECTIVE: To investigate determinants (pathophysiologic and physiologic, behavioural and lifestyle) of vitamin D status in Irish Crohn's disease (CD) patients. DESIGN: A cross-sectional observational study. SETTING: Cork City, Ireland (52 degrees N). SUBJECTS: Crohn's Disease patients (n=58; mean age 38.1 years) were recruited from Cork University Hospital. RESULTS: Fifty and nineteen percent of Irish CD patients were vitamin D deficient (defined by serum 25 hydroxyvitamin (OH) D levels <50 nmol/l) during winter and summer, respectively. Multiple regression analysis showed that summer-time serum 25 (OH) D levels were positively associated with use of vitamin D supplements (P=0.033) and negatively associated with smoking (P=0.006) and being male (P=0.063). During winter-time, use of vitamin D supplements (P=0.041) and sun habits (P=0.066) were positively associated, whereas small intestinal involvement (P=0.005) and body mass index (BMI) (P=0.083) were negatively associated with serum 25 (OH) D levels. There was no significant association between other non-pathophysiologic (age, dietary calcium or vitamin D) or pathophysiologic factors (steroid use, resection), and serum 25 (OH) D levels, at either season. Approximately 41 and 60% of the total variation in summer- and winter-time serum 25 (OH) D, respectively, was explained by this model. CONCLUSION: A high proportion of Irish CD patents had some level of vitamin D deficiency (<50 nmol/l) during late-wintertime. Use of regular low-dose supplemental vitamin D, particularly by patients with small intestinal involvement, cessation of smoking and adequate, but responsible, exposure to summer sunlight as well as maintaining BMI in the normal range could help maintain adequate vitamin D levels during wintertime.

Introduction to the ZENITH study and summary of baseline results.

Zinc is known to be essential for a great number of biochemical activities and physiological and cognitive functions. The objective of Zenith study was to investigate the effects of Zn, as a nutritional supplement, on psychological and behavioural factors and on surrogate markers that are indicative of trends towards better health in order to evaluate the need for dietary recommendations specific to the studied population. We report in this paper the summary of baseline results obtained before Zn supplementation.

Seasonality of vitamin D status and bone turnover in patients with Crohn's disease.

BACKGROUND: While winter-time vitamin D deficiency has been well-documented in Crohn's disease patients, less is known about vitamin D status during summertime and whether a seasonal variation exists in bone turnover. AIMS: To compare vitamin D status and bone turnover markers in Crohn's disease patients with age- and sex-matched controls during late-summer and late-winter. SUBJECTS: Crohn's disease patients (n = 44; mean age 36.9 years, currently in remission) and matched controls (n = 44) were recruited from Cork University Hospital and Cork City area, respectively. METHODS: Bloods were analysed for 25-hydroxyvitamin D, parathyroid hormone, bone-specific alkaline phosphatase, osteocalcin and urine analysed for N-telopeptides of type 1 collagen. RESULTS: Serum 25-hydroxyvitamin D concentrations were significantly (P < 0.003) lower in Crohn's disease patients than in control subjects during both seasons. In Crohn's disease patients, serum 25-hydroxyvitamin D concentrations were lower (P < 0.0001) whereas serum parathyroid hormone, osteocalcin and bone-specific alkaline phosphatase and urinary N-telopeptides of type 1 collagen levels were higher (P < 0.001) during late-winter than late-summer. CONCLUSION: There were notable seasonal variations in vitamin D status and bone turnover markers in Crohn's disease patients. The impact of winter decline in vitamin D status and increase in bone turnover on long-term risk of osteopenia/osteoporosis in Crohn's disease patients is unclear.

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 (P(country) = 0.09, R(2) = 0.39), but for girls the difference remained significant even after including predictors (P(country) = 0.03, R(2) = 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 and status in Irish postmenopausal women.

OBJECTIVE: The objective of this study was to assess vitamin D status during late-summer and late-winter/early-spring in postmenopausal Irish women, and whether it was influenced by vitamin D-containing supplement use. DESIGN: A longitudinal observational study. SETTING: Cork City, Ireland (51 degrees north). SUBJECTS: A total of 59 apparently healthy, free-living, postmenopausal women aged between 51 and 69 y were sampled during February/March 2002. Of these, 48 and 47 returned during August/September 2002 and February/March 2003, respectively. None of the women were suffering from any medical condition likely to affect vitamin D status. Fasting serums were collected and analysed for 25-hydroxyvitamin D (25 (OH) D) and parathyroid hormone (PTH) by enzyme immunoassays. RESULTS: Mean daily intake of vitamin D was 3.2 microg from food sources alone and 5.8 microg when vitamin D-containing supplements were included (P<0.01). Serum 25 (OH) D was significantly lower (P<0.001) during February/March 2002 than both August/September 2002 and February/March 2003. Serum 25 (OH) D was also significantly higher (P < or = 0.05) in women who were vitamin D-containing supplement users than nonusers during all three sampling points. Between 17 and 36% of women had inadequate vitamin D status (defined as serum 25 (OH) D <40 nmol/l) during late-winter, but only 4% had inadequate vitamin D status during late-summer. Serum 25 (OH) D was inversely related to serum PTH (r = -0.33; P = 0.028). CONCLUSION: Suboptimal vitamin D status is common in postmenopausal Irish women during winter. Vitamin D supplementation is associated with improved vitamin D status, even during summertime.

Effect of dietary supplementation with conjugated linoleic acid on markers of calcium and bone metabolism in healthy adult men.

INTRODUCTION: Conjugated linoleic acid (CLA) has been shown to positively influence calcium and bone metabolism in experimental animals and cells in culture, but there are limited human data available. OBJECTIVE: To investigate the effect of CLA supplementation on biomarkers of calcium and bone metabolism in healthy adult males. DESIGN: The study consisted of a double-blind, placebo-controlled trial in which 60 healthy adult males (aged 39-64 y) were randomly assigned to receive daily either 3.0 g CLA isomer blend (50:50% cis-9,trans-11:trans-10,cis-12 isomers) or a palm/bean oil blend (placebo) for 8 weeks. Urine and blood samples were collected at weeks 0 and 8 and were analysed for biomarkers of calcium and bone metabolism. RESULTS: Supplementation with CLA or placebo for 8 weeks had no significant effects on markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) or bone resorption (serum C-telopeptide-related fraction of type 1 collagen degradation products, urinary N-telopeptide-related fraction of type 1 collagen degradation products, urinary pyridinoline and deoxypyridinoline), or on serum or urinary calcium levels. Baseline levels of these biochemical parameters were similar in both groups of subjects. While the placebo had no effect, CLA supplementation resulted in a three-fold increase (P<0.00001) in cis-9,trans-11 CLA isomer in total plasma lipids. CONCLUSION: Under the conditions tested in this double-blind, placebo-controlled trial in adult men, a CLA supplement of mixed isomers did not affect markers of calcium or bone metabolism. Further investigation of the effects of CLA on calcium and bone metabolism in other gender- and age-groups is warranted.

The effect of conjugated linoleic acid on calcium absorption and bone metabolism and composition in adult ovariectomised rats.

The effect of conjugated linoleic acid (CLA) on postmenopausal bone metabolism has not been investigated. Therefore, forty-three adult ovariectomised (OVX) rats (8-9 rats per group) were fed either a control diet containing 40 g/kg soyabean oil (SBO diet) or the SBO diet with 0 (control OVX), 2.5, 5 or 10 g/kg of CLA (replacing soybean oil) for 9 weeks. A group of sham-operated (SH) rats were fed the SBO diet. OVX rats had significantly (P<0.05) lower femoral bone mineral density and macromineral concentration, and intestinal Ca absorption compared to SH rats. CLA supplementation had no effect on these parameters. Ex vivo PGE(2) biosynthesis by bone and urinary Pyr and Dpyr (markers of bone resorption) were significantly higher (P<0.001) in control OVX rats compared with SH rats, and were significantly (P<0.001) lowered by CLA supplementation with 5 and 10, but not 2.5 g/kg diet in OVX rats. In conclusion, CLA supplementation appeared to reduce the rate of bone resorption in adult OVX rats.

Vitamin D intakes in 18-64-y-old Irish adults.

OBJECTIVE: To estimate vitamin D intakes in a representative sample of Irish adults and to assess the contribution of foods to these intake estimates. DESIGN: Vitamin D intakes in 1379, 18-64-y-old adults from the North/South Ireland Food Consumption Survey were estimated using a combination of new analytical data for vitamin D in foods, determined by HPLC, and used to revise recipe calculations, together with existing data from McCance and Widdowson's The Composition of Foods, 5th Edition plus supplements. RESULTS: The total mean daily intake (MDI) of vitamin D (1 microg=40 IU) from all sources was 4.2 microg. The MDI was significantly higher (P<0.001) when the contribution from nutritional supplements was included (4.2 microg) compared with food sources only (3.2 microg). Men had significantly higher intakes (4.4 microg) than women (4.0 microg; P<0.001), which increased significantly (P<0.001) with age in both sexes. Meat/meat products (30.1%), fish/fish products (14.3%) and eggs/egg dishes (9.1%) were the main contributors to vitamin D intake. Supplements contributed 6.8 and 12% to MDI in men and women, respectively. In all, 74% of adults had an MDI of vitamin D that was less than the median (5 microg) of the recommended daily range of 0-10 microg. CONCLUSION: The findings of this study suggest that a large number of Irish adults have low vitamin D intakes. This, along with emerging evidence of low vitamin D status in at least some population subgroups, suggests that strategies to increase vitamin D intakes, including fortification of food, should be investigated.

Selenium status of Irish adults: evidence of insufficiency.

BACKGROUND: Sub-optimal selenium status may have a role in the aetiology of various pathologies. Selenium status depends on adequate selenium in the diet. A relatively high proportion of Irish adults (17% men; 46% women) have an inadequate dietary intake. AIM: A study was designed to examine the selenium status of healthy Irish adults. METHODS: Ninety-one healthy Irish adults, aged 18-67 years, were recruited from the Cork City area. A fasting blood sample was collected from each subject and each was assayed for serum selenium an index of serum selenium. RESULTS: Mean (+/- SD) serum selenium concentration in healthy Irish adults was 76 (+/- 21)microg/l. There was no significant difference in values between males and females or between postmenopausal and premenopausal women or between the three main age categories. CONCLUSION: Current serum selenium values of Irish adults would not appear to be sufficient to achieve optimal activity of glutathione peroxidase, which occurs at serum selenium concentration around 95microg/l. Sub-optimal selenium status may increase susceptibility to various chronic disorders.

Selenium intakes in 18-64-y-old Irish adults.

OBJECTIVE: To measure the intake of selenium (Se) and the contribution of different food groups to Se intake in adults aged 18-64 y in Ireland. The adequacy of Se intake in the population is also assessed. DESIGN: Food consumption was estimated using a 7 day food diary for a representative sample (n=1379; men=662, women=717) of 18-64-y-old Irish adults selected randomly from the electoral register. Se intake was estimated using updated tables of food composition. RESULTS: Mean daily Se intakes (+/-s.d.) from all sources (ie food plus supplements), and from food sources alone, for the group of Irish adults aged 18-64 y were 52 (+/-23) and 50 (+/-21) microg, respectively. Mean daily Se intake (from all sources) was significantly higher in men of all ages than women of all ages at levels of 60 and 44 microg, respectively (P<0.001). Meat/meat products (30%), bread and rolls (24%), fish/fish products (approximately 11%), and milk and yoghurt (9%) were the main contributors to mean daily Se intake. Adequacy of Se intake in population groups was estimated as the percentage of the population with mean daily Se intakes that were lower than the average requirement of 40 microg. Using this measure, 45.6% of women and 17.1% of men had inadequate Se intakes. CONCLUSION: A significant prevalence of inadequate Se intakes was observed in Irish adults. Therefore, it would seem prudent that the Se status of the Irish population be investigated at this time.

The effect of calcium intake on bone composition and bone resorption in the young growing rat.

A low Ca intake by both rats and man increases bone resorption, decreases bone mass and increases the risk of osteoporosis. The skeletal effect of high Ca intakes is less clear, particularly during periods of bone mineral accrual. Twenty-four female 5-week-old rats, Wistar strain, were randomized by weight into three groups of eight rats each and fed ad libitum a semi-purified diet containing 2 (Ca-restricted), 5 (normal) or 20 (Ca-supplemented) g Ca/kg for 3 weeks. When compared with the normal Ca diet, urinary Ca excretion was unaffected by the dietary restriction of Ca for 3 weeks, but was greater (P<0.001) in Ca-supplemented rats. Urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) levels were significantly greater during weeks 2 (Pyr P<0.05, Dpyr P<0.001) and 3 (Pyr P<0.01, Dpyr, P<0.001) of dietary Ca restriction, but were unaffected by Ca supplementation. Femoral dry weight and the concentration of Mg and P in femora were unaffected by dietary Ca concentration. Femoral Ca concentration was reduced (P<0.05) in the Ca-restricted group compared with the other two groups. In conclusion, these results suggest that increasing dietary Ca intake, well above the recommended level, had no effect on bone mineral composition or bone resorption (as assessed with urinary pyridinium crosslinks) in young growing female rats. In addition, these results confirm the findings of previous studies which have shown that bone Ca content in young growing rats was reduced by dietary Ca restriction and that this reduction results, at least in part, from an increased rate of bone resorption.

No effect of copper supplementation on biochemical markers of bone metabolism in healthy young adult females despite apparently improved copper status.

OBJECTIVE: To investigate the effects of increasing Cu intakes, above the usual dietary intake, on biomarkers of bone metabolism in healthy young adult females (aged 21-28 y) over a 4 week period. DESIGN: A double-blind, placebo-controlled randomised repeat crossover Cu supplementation trial. SETTING: The study was conducted at the Royal Veterinary and Agricultural University (RVAU), Copenhagen, Denmark. SUBJECTS: Sixteen healthy young adult females aged 20-28 y were recruited from among students at the RVAU. INTERVENTION: During the 4 week intervention periods in this randomised, crossover trial (3x4 weeks with a minimum 3 week wash-out period), each subject received, in addition to their usual diet, either 3 or 6 mg elemental Cu/day as CuSO4 or a matching placebo. On the last 3 days of each dietary period 24 h urines were collected. In addition, blood was collected on the last day of each dietary period. RESULTS: Serum Cu and erythrocyte superoxide dismutase (but not caeruloplasmin protein concentration or activity (putative indices of Cu status)) were significantly increased (P<0.05) after daily Cu supplementation with 3 and 6 mg/day for 4 weeks. Serum osteocalcin (biomarker of bone formation), urinary creatinine (Cr) concentration, urinary pyridinoline (Pyr)/Cr or deoxypyridinoline (Dpyr)/Cr excretion, or daily urinary Pyr or Dpyr excretion (biomarkers of bone resorption) were unaffected by Cu supplementation. CONCLUSION: Copper supplementation of the usual diet in healthy young adult females, while apparently improving Cu status, had no effect on biochemical markers of bone formation or bone resorption over 4 week periods. SPONSORSHIP: Funding from the European Commission.

The effect of high salt and high protein intake on calcium metabolism, bone composition and bone resorption in the rat.

The effects of salt (NaCl) supplementation of rat diets (50 g/kg diet), with normal (200 g/kg) or high (500 g/kg) dietary casein content, were studied in 3-week-old male rats over a 3-week period. Weight gain was reduced by dietary salt but was unaffected by dietary casein. Salt-supplemented rats exhibited a two- and three-fold increase in urinary Mg and Ca excretion respectively, irrespective of dietary casein content. Dietary casein had no effect on urinary Ca or Mg. Salt reduced femoral mass but not femoral mass expressed relative to body weight, but neither variable was affected by dietary casein. Femoral Mg and P contents and concentrations were unaffected by dietary salt or casein. While femoral Ca concentration was unaffected by dietary salt, the Ca content was reduced by salt supplementation, irrespective of dietary casein content. Neither the content nor concentration of Ca in femora was affected by dietary casein. Urinary pyridinoline and deoxypyridinoline levels were increased by salt supplementation, irrespective of dietary casein content, but were unaffected by casein. Net Ca absorption was unaffected by dietary salt or casein. In conclusion, these results show that salt supplementation over the short-term increased the rate of bone resorption in rats. This was as a consequence of Na-induced calciuria. On the other hand, a high dietary protein intake had no effect on Ca metabolism, bone composition or bone resorption, nor did it augment the Na-induced calciuria or increased rate of bone resorption.

Optimal nutrition: calcium, magnesium and phosphorus.

In the past, a major challenge for nutrition research was in defining indicators of nutritional adequacy. More recently, the research base related to the role of nutrition in chronic disease has expanded sufficiently to permit moving beyond deficiency indicators to other indicators with broader functional significance. Thus, nutrition research is faced with the new challenge of defining 'optimal nutrition'. One definition of optimal nutrition with respect to any particular nutrient could be when a functional marker reaches an 'optimal value' or plateau beyond which it is not longer affected by intake or stores of the nutrient. A functional marker of nutrient status could be defined as a physiological or biochemical factor which (1) is related to function or effect of the nutrient in target tissue(s) and (2) is affected by dietary intake or stores of the nutrient (which may include markers of disease risk). Examples of such indicators or markers are those related to risk of chronic diseases such as osteoporosis, CHD, or hypertension. The present review focuses on the concept of optimal nutrition with respect to three nutrients, Ca, Mg and P. However, for P and Mg there are as yet no functional indicators which respond to dietary intake, and in such cases nutrient requirements are established using more traditional approaches, e.g. balance data. For Ca, there has been interest in using maximal Ca retention, which is based on balance data, bone mass measurements and biomarkers of bone turnover as useful functional indicators of the adequacy of Ca intake.