Calcium- and vitamin D3 - fortified milk reduces bone loss at clinically relevant skeletal sites on llder men: a 2-year randomised controlled trial

In this 2-year randomized controlled study of 167 men >50 years of age, supplementation with calcium-vitamin D3-fortified milk providing an additional 1000 mg of calcium and 800 IU of vitamin D3 per day was effective for suppressing PTH and stopping or slowing bone loss at several clinically important skeletal sites at risk for fracture.

Introduction: Low dietary calcium and inadequate vitamin D stores have long been implicated in age-related bone loss and osteoporosis. The aim of this study was to assess the effects of calcium and vitamin D3 fortified milk on BMD in community living men >50 years of age.

Materials and Methods: This was a 2-year randomized controlled study in which 167 men (mean age ± SD, 61.9 ± 7.7 years) were assigned to receive either 400 ml/day of reduced fat (1%) ultra-high temperature (UHT) milk containing 1000 mg of calcium plus 800 IU of vitamin D3 or to a control group receiving no additional milk. Primary endpoints were changes in BMD, serum 25(OH)D, and PTH.

Results: One hundred forty-nine men completed the study. Baseline characteristics between the groups were not different; mean dietary calcium and serum 25(OH)D levels were 941 ± 387 mg/day and 77 ± 23 nM, respectively. After 2 years, the mean percent change in BMD was 0.9-1.6% less in the milk supplementation compared with control group at the femoral neck, total hip, and ultradistal radius (range, p < 0.08 to p < 0.001 after adjusting for covariates). There was a greater increase in lumbar spine BMD in the milk supplementation group after 12 and 18 months (0.8-1.0%, p ≤ 0.05), but the between-group difference was not significant after 2 years (0.7%; 95% CI, −0.3, 1.7). Serum 25(OH)D increased and PTH decreased in the milk supplementation relative to control group after the first year (31% and −18%, respectively; both p < 0.001), and these differences remained after 2 years. Body weight remained unchanged in both groups at the completion of the study.

Conclusions: Supplementing the diet of men >50 years of age with reduced-fat calcium- and vitamin D3-enriched milk may represent a simple, nutritionally sound and cost-effective strategy to reduce age-related bone loss at several skeletal sites at risk for fracture in the elderly.

Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial

Objectives: To determine whether vitamin D supplementation can reduce the incidence of falls and fractures in older people in residential care who are not classically vitamin D deficient.

Design: Randomized, placebo-controlled double-blind, trial of 2 years' duration.

Setting: Multicenter study in 60 hostels (assisted living facilities) and 89 nursing homes across Australia.

Participants: Six hundred twenty-five residents (mean age 83.4) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L.

Intervention: Vitamin D supplementation (ergocalciferol, initially 10,000 IU given once weekly and then 1,000 IU daily) or placebo for 2 years. All subjects received 600 mg of elemental calcium daily as calcium carbonate.

Measurements: Falls and fractures recorded prospectively in study diaries by care staff.

Results: The vitamin D and placebo groups had similar baseline characteristics. In intention-to-treat analysis, the incident rate ratio for falling was 0.73 (95% confidence interval (CI)=0.57–0.95). The odds ratio for ever falling was 0.82 (95% CI=0.59–1.12) and for ever fracturing was 0.69 (95% CI=0.40–1.18). An a priori subgroup analysis of subjects who took at least half the prescribed capsules (n=540), demonstrated an incident rate ratio for falls of 0.63 (95% CI=0.48–0.82), an odds ratio (OR) for ever falling of 0.70 (95% CI=0.50–0.99), and an OR for ever fracturing of 0.68 (95% CI=0.38–1.22).

Conclusion: Older people in residential care can reduce their incidence of falls if they take a vitamin D supplement for 2 years even if they are not initially classically vitamin D deficient.

Use of calcium or calcuim in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis

Background:  Whether calcium supplementation can reduce osteoporotic fractures is uncertain. We did a meta-analysis to include all the randomised trials in which calcium, or calcium in combination with vitamin D, was used to prevent fracture and osteoporotic bone loss.

Methods:  We identified 29 randomised trials (n=63 897) using electronic databases, supplemented by a hand-search of reference lists, review articles, and conference abstracts. All randomised trials that recruited people aged 50 years or older were eligible. The main outcomes were fractures of all types and percentage change of bone-mineral density from baseline. Data were pooled by use of a random-effect model.

Findings:  In trials that reported fracture as an outcome (17 trials, n=52 625), treatment was associated with a 12% risk reduction in fractures of all types (risk ratio 0·88, 95% CI 0·83–0·95; p=0·0004). In trials that reported bone-mineral density as an outcome (23 trials, n=41 419), the treatment was associated with a reduced rate of bone loss of 0·54% (0·35–0·73; p<0·0001) at the hip and 1·19% (0·76–1·61%; p<0·0001) in the spine. The fracture risk reduction was significantly greater (24%) in trials in which the compliance rate was high (p<0·0001). The treatment effect was better with calcium doses of 1200 mg or more than with doses less than 1200 mg (0·80 vs 0·94; p=0·006), and with vitamin D doses of 800 IU or more than with doses less than 800 IU (0·84 vs 0·87; p=0·03).

Interpretation:  Evidence supports the use of calcium, or calcium in combination with vitamin D supplementation, in the preventive treatment of osteoporosis in people aged 50 years or older. For best therapeutic effect, we recommend minimum doses of 1200 mg of calcium, and 800 IU of vitamin D (for combined calcium plus vitamin D supplementation).

Estimation of the dietary requirement for vitamin D in healthy adults

Background: Knowledge gaps have contributed to considerable variation among international dietary recommendations for vitamin D.

Objective: We aimed to establish the distribution of dietary vitamin D required to maintain serum 25-hydroxyvitamin D [25(OH)D] concentrations above several proposed cutoffs (ie, 25, 37.5, 50, and 80 nmol/L) during wintertime after adjustment for the effect of summer sunshine exposure and diet.

Design: A randomized, placebo-controlled, double-blind 22-wk intervention study was conducted in men and women aged 20–40 y (n = 238) by using different supplemental doses (0, 5, 10, and 15 µg/d) of vitamin D3 throughout the winter. Serum 25(OH)D concentrations were measured by using enzyme-linked immunoassay at baseline (October 2006) and endpoint (March 2007).

Results: There were clear dose-related increments (P < 0.0001) in serum 25(OH)D with increasing supplemental vitamin D3. The slope of the relation between vitamin D intake and serum 25(OH)D was 1.96 nmol·L–1·µg–1 intake. The vitamin D intake that maintained serum 25(OH)D concentrations of >25 nmol/L in 97.5% of the sample was 8.7 µg/d. This intake ranged from 7.2 µg/d in those who enjoyed sunshine exposure, 8.8 µg/d in those who sometimes had sun exposure, and 12.3 µg/d in those who avoided sunshine. Vitamin D intakes required to maintain serum 25(OH)D concentrations of >37.5, >50, and >80 nmol/L in 97.5% of the sample were 19.9, 28.0, and 41.1 µg/d, respectively.

Conclusion: The range of vitamin D intakes required to ensure maintenance of wintertime vitamin D status [as defined by incremental cutoffs of serum 25(OH)D] in the vast majority (>97.5%) of 20–40-y-old adults, considering a variety of sun exposure preferences, is between 7.2 and 41.1 µg/d.

Vitamin C and the risk of gestational diabetes mellitus: a case-control study

OBJECTIVE: To examine whether low maternal dietary intake of vitamin C and low maternal plasma ascorbic acid (AA) concentrations are associated with an increased risk of gestational diabetes mellitus (GDM).
METHODS: Cases were 67 women with GDM meeting National Diabetes Data Group criteria. Controls were 260 women without such a diagnosis. Maternal dietary vitamin C consumption during the periconceptional period and during pregnancy was assessed using a 121-item, semiquantitative food frequency questionnaire. Maternal plasma AA concentrations were determined using automated enzymatic procedures on specimens collected during the intrapartum period.
RESULTS: Mean maternal daily consumption of vitamin C and plasma AA concentrations were 10% and 31% lower, respectively, among GDM cases as compared with controls (130.7 +/- 10.2 vs. 145 +/- 4.9 mg/d, P = .190; 36 +/- 2.0 vs. 53 +/- 1.0 micromol/L, P <.001). After controlling for maternal age, race, prepregnancy adiposity, family history of type 2 diabetes, energy intake and income, women reporting low daily vitamin C intake (< 70 mg/d), as compared with the other women, experienced a 3.7-fold increased risk of GDM (odds ratio [OR] = 3.7, 95% confidence interval [CI] 1.7-8.2). There was a linear relation in risk of GDM with decreasing concentrations of plasma AA (P for linear trend <.001). After adjusting for confounders, women in the lowest quartile (< 42.6 micromol/L), as compared with women in the highest quartile (> 63.3 micromol/L), experienced > 12-fold increased risk of GDM (OR = 12.8, 95% CI 3.5-46.2). CONCLUSION: Low maternal dietary vitamin C intake and low plasma AA concentrations are associated with an increased risk of GDM. Large, prospective, cohort studies are needed to further evaluate the potential beneficial role of vitamin C and other antioxidants in the prevention of impaired glucose tolerance in pregnancy.

Factors associated with low vitamin D status of Australian alpacas

Objective To investigate factors associated with low vitamin D status of alpacas at pasture in southern Australia.

Design A 2-year survey of alpacas from two farms in South Australia and three in Victoria. Blood samples were collected from 20 to 30 alpacas on each farm on five occasions each year. Breed, gender, age and fleece colour of animals were recorded.

Method Blood samples were assayed for plasma 2.5-hydroxycholecalciferol (25-OH D3) and plasma inorganic phosphorus (Pi). Data sets from 802 animal samples were analysed by multiple regression to determine variables associated with low vitamin D status of alpacas. The relationship between plasma 25-OH D3 and plasma Pi was also investigated.

Results Vitamin D status was significantly affected by month of sampling, with low values in late winter and high values in summer. Plasma vitamin D concentrations increased with age, were higher in alpacas with light fleeces than in those with dark fleeces and were also higher in the Suri than in the Huacaya breed. Plasma Pi concentrations were generally lower in alpacas with plasma 25-OH D3 values < 25 nmol/L.

Conclusions Young alpacas with dark fleeces are most at risk from vitamin D insufficiency in late winter in southern Australia. The present study indicates that plasma Pi values are not a reliable indicator of vitamin D status of alpacas as assessed by plasma 25-OH D3 concentrations.

Annual high-dose vitamin D3 and mental well-being: randomised controlled trial

Background Epidemiological evidence supports a relationship between vitamin D and mental well-being, although evidence from large-scale placebo-controlled intervention trials is lacking.

Aims To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms; and if there is an association between serum 25-hydroxyvitamin D levels and mental health.

Method A double-blind, randomised, placebo-controlled trial of women aged 70 or older (the Vital D Study: ISRCTN83409867 and ACTR12605000658617). Participants were randomly assigned to receive 500 000 IU vitamin D3 (cholecalciferol) orally or placebo every autumn/winter for 3–5 consecutive years. The tools utilised at various time points were the General Health Questionnaire, the 12-item Short Form Health Survey, the Patient Global Impression–Improvement scale and the WHO Well-Being Index. Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants.

Results In this non-clinical population, no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health. Serum 25-hydroxyvitamin D levels in the vitamin D group were 41% higher than the placebo group 12 months following their annual dose. Despite this difference, scores from the questionnaires did not differ. Furthermore, there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups.

Conclusions The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D3 is a practical intervention to prevent depressive symptoms in older community-dwelling women.

Vitamin D, obesity, and obesity-related chronic disease among ethnic minorities : a systematic review

Objective : To assess the association between 25-hydroxyvitamin D (25[OH]D) status and obesity, cardiovascular diseases (CVDs), the metabolic syndrome, and type 2 diabetes mellitus (T2DM) in ethnic minorities.

Methods : Databases searched were CINHAL with full text, Global Health, MEDLINE with full text, and PsycINFO from 1980 through 2010 (February). Studies were included if they 1) targeted immigrants from low- to high-income countries or ethnic minorities, 2) focused primarily on 25(OH)D and its relation to obesity, T2DM, and/or CVDs, and 3) were published in peer-reviewed journals. The influences of key confounders such as age, gender, and ethnicity on any observed relations were also assessed. Due to the heterogeneity of study characteristics, only a narrative synthesis was undertaken.

Results : Ethnic minorities had significantly higher rates of vitamin D insufficiency (25[OH]D <50 nmol/L; children 43.6–48.7% versus 10%; adults 30.3–53% versus 13.7–26%) than their white counterparts. None of the studies reported a prevalence of obesity stratified by ethnicity. There was evidence supporting links between vitamin D deficiency and obesity-related chronic diseases, with 14 of 14 studies reporting a statistically significant result with a measurement of obesity, four of five for T2DM, four of five for CVDs, and one of one for the metabolic syndrome. However, the strength of the association varied across ethnic groups depending on the index used to measure adiposity, T2DM, and CVDs. Because most of the included studies were cross-sectional and there were variations in outcome measurements, it was not possible to determine the relative contributions of obesity or vitamin D insufficiency to CVD risk and risk of T2DM or which is the initial driver It is possible both have a role to play.

Conclusion : Further research specific to migrant populations using randomized controlled trials are required to establish whether causal links between 25(OH)D and obesity-related chronic disease exist, and whether vitamin D supplementation could be valuable in the prevention or treatment of obesity-related diseases.

Annual high-dose oral vitamin D and falls and fractures in older women : a randomized controlled trial

Context Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor.

Objective To determine whether a single annual dose of 500 000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture.

Design, Setting, and Participants A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008.

Intervention 500 000 IU of cholecalciferol or placebo.

Main Outcome Measures Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels.

Results Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing.

Conclusion Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures.

Knowledge about folate and the contribution of nutrient supplements to the intake of folic acid and vitamin B12 in Australian adults in 1995 and 1996

The present paper reports knowledge about folate and the contribution of supplements to the intake of folic acid and vitamin B12 in Australian adults during 1995 and 1996. Data were obtained from two population survey monitor surveys conducted in a sample of 5422 adults in 1995-96. The surveys were designed to complement food intake data from the 1995 National Nutrition Survey and to provide an estimate of total folate intake prior to the implementation of voluntary fortification of foods with folic acid. The proportion with knowledge about folate increased with education level and socioeconomic status and was greater in women than men. It was also greater in those who were married, and in those residing in Western Australia and the Australian Capital Territory than in other states and territories. Five per cent of men and 10% of women had taken a supplement containing folio acid on the previous day. The equivalent figures for vitamin B12 were 7.5% for men and 12.5% for women. On average, intake of folic acid from supplements was 11 micro g per day for men and 28 micro g per day for women and intake of vitamin B12 was 2.6 micro g per day for men and 4.5 micro g per day for women. For individuals who consumed a supplement containing folic acid on the day before the survey the median folic acid contribution was 200 micro g. In 1995 and 1996 only one in two adult Australians had heard of folate and only one in ten women of child-bearing age had taken a supplement containing folic acid.

Energy, protein, calcium, vitamin D and fibre intakes from meals in residential care establishments in Australia

Residents from high level (nursing homes) and low-level care facilities (hostel) being served the three common diet texture modifications (full diet, soft-minced diet and pureed diet) were assessed. Individual plate waste was estimated at three meals on one day. Fifty-six males and 156 females, mean age 82.9+/-9.5 (SD) years, of which 139 lived in nursing homes (NH) and 76 in hostels (H) were included. Mean total energy served from meals was 5.3 MJ/day, 5.1 to 5.6 MJ/day, 95% confidence intervals (CI), in NH which was less than in H, 5.9 MJ/day (CI 5.6 to 6.2 MJ/day) (P=0.007). Protein and calcium intakes were lower in NH, 44.5g (CI 41.5 to 47.5g), 359.0mg (CI 333.2 to 384.8mg), versus 50.5g (CI 46.6 to 54.3g), 480.5mg (CI 444.3 to 516.7mg) in H (P=0.017, P<0.001 respectively). There was no difference in nutrient/energy ratios, except for protein/energy, which was higher in NH 11.7 (CI 11.3 to 12.2) than in H 9.8 (CI 9.4 to 10.3) (P<0.001). Ability to self-feed had no significant effect on nutrient intakes in NH. The self fed group (N=63) had the following nutrient intakes: energy 4.0 MJ (CI 3.6 to 4.3 MJ), protein 44.6g (CI 40.3 to 48.9g), calcium 356.9mg (CI 316.3 to 397.4mg), fibre 14.9g (CI 13.2 to 16.5g). The assisted group (N=64) had the following nutrient intakes: energy 3.9MJ (CI 3.6 to 4.2MJ), protein 46.0g (CI 40.7 to 49.6), calcium 361.9mg (CI 327.8 to 396.1mg), fibre 14.9g (CI 13.2 to 16.1g). Of NH classified as eating impaired, 36% received no assistance with feeding and had lower intakes of protein 37.8g (CI 33.0 to 42.1g) compared to those receiving some assistance 46.1g (CI 41.3 to 50.9g) (P=0.026). Reduced energy intake accounted for the differences in nutrient intakes between nursing homes and hostels, except for protein. Strategies to effectively monitor nutrient intakes and to identify those with eating impairment are required in order to ensure adequate nutrition of residents in nursing homes and hostels.

Vitamin D in Australia : issues and recommendations

BACKGROUND A significant number of Australians and people from specific groups within the community are suffering from vitamin D deficiency. It is no longer acceptable to assume that all people in Australia receive adequate vitamin D from casual exposure to sunlight.

OBJECTIVE This article provides information on causes, consequences, treatment and prevention of vitamin D deficiency in Australia.

DISCUSSION People at high risk of vitamin D deficiency include the elderly, those with skin conditions where avoidance of sunlight is required, dark skinned people (particularly women during pregnancy or if veiled) and patients with malabsorption, eg. coeliac disease. For most people, deficiency can be prevented by 5–15 minutes exposure of face and upper limbs to sunlight 4–6 times per week. If this is not possible then a vitamin D supplement of at least 400 IU* per day is recommended. In cases of established vitamin D deficiency, supplementation with 3000-5000 IU per day for at least 1 month is required to replete body stores. Increased availability of larger dose preparations of cholecalciferol would be a useful therapy in the case of severe deficiencies. * 40 IU (international units) = 1 µg

Comparison of soluble manganese(IV) and acidic potassium permanganate chemiluminescence detection using flow injection and sequential injection analysis for the determination of ascorbic acid in vitamin C tablets

The limits of detection (3s) for ascorbic acid were 5×10⁻⁸ M with acidic potassium permanganate using both flow injection analysis (FIA) and sequential injection analysis (SIA) whereas the soluble manganese(IV) afforded 1×10⁻⁸ M and 5×10⁻⁹ M for FIA and SIA, respectively. Determinations of ascorbic acid in Vitamin C tablets were achieved with minimal sample pretreatment using a standard additions calibration and gave good agreement with those of iodimetric titration.