Effects of a multi-component exercise program and calcium–vitamin-D3-fortified milk on bone mineral density in older men : a randomised controlled trial

Summary We examined the independent and combined effects of a multi-component exercise program and calcium–vitamin-D3-fortified milk on bone mineral density (BMD) in older men. Exercise resulted in a 1.8% net gain in femoral neck BMD, but additional calcium–vitamin D3 did not enhance the response in this group of older well-nourished men.

Introduction This 12-month randomised controlled trial assessed whether calcium–vitamin-D3-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men.

Methods Men (n  = 180) aged 50–79 years were randomised into: (1) exercise + fortified milk; (2) exercise; (3) fortified milk; or (4) controls. Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise. Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D3. Femoral neck (FN), total hip, lumbar spine and trochanter BMD and body composition (DXA), muscle strength 25-hydroxyvitamin D and parathyroid hormone (PTH) were assessed.

Results There were no exercise-by-fortified milk interactions at any skeletal site. Exercise resulted in a 1.8% net gain in FN BMD relative to no-exercise (p < 0.001); lean mass (0.6 kg, p < 0.05) and muscle strength (20–52%, p < 0.001) also increased in response to exercise. For lumbar spine BMD, there was a net 1.4–1.5% increase in all treatment groups relative to controls (all p < 0.01). There were no main effects of fortified milk at any skeletal site.

Conclusion A multi-component community-based exercise program was effective for increasing FN BMD in older men, but additional calcium–vitamin D3 did not enhance the osteogenic response.

The skeletal benefits of calcium- and vitamin D3-fortified milk are sustained in older men after withdrawal of supplementation: an 18 mo follow-up study

Background: In a previous 2-y randomized controlled trial, we showed that calcium- and vitamin D₃–fortified milk stopped or slowed bone loss at several clinically relevant skeletal sites in older men.

Objective: The present study aimed to determine whether the skeletal benefits of the fortified milk were sustained after withdrawal of the supplementation.

Design: One hundred nine men >50 y old who had completed a 2-y fortified milk trial were followed for an additional 18 mo, during which no fortified milk was provided. Bone mineral density (BMD) of the total hip, femoral neck, lumbar spine, and forearm was measured by using dual-energy X-ray absorptiometry.

Results: Comparison of the mean changes from baseline between the groups (adjusted for baseline age, BMD, total calcium intake, and change in weight) showed that the net beneficial effects of fortified milk on femoral neck and ultradistal radius BMD at the end of the intervention (1.8% and 1.5%, respectively; P < 0.01 for both) were sustained at 18-mo follow-up (P < 0.05 for both). The nonsignificant between-group differences at the total hip (0.8%; P = 0.17) also persisted at follow-up (0.7%; P = 0.10), but there were no lasting benefits at the lumbar spine. The average total dietary calcium intake in the milk supplementation group at follow-up approximated recommended amounts for Australian men >50 y old (1000 mg/d) but did not differ significantly from that in the control subjects (1021 versus 890 mg/d).

Conclusion: Supplementation with calcium- and vitamin D₃–fortified milk for 2 y may provide some sustained benefits for BMD in older men after withdrawal of supplementation.

Hypoallergenic variants of the major latex allergen Hev b 6.01 retaining human T lymphocyte reactivity

Hev b 6.01 is a major allergen of natural rubber latex with sensitization of 70–86% of latex glove-allergic subjects. Recently, we mapped the immunodominant T cell sites of Hev b 6.01 to the highly IgE-reactive hevein (Hev b 6.02) domain. Hev b 6.01 contains 14 cysteine residues with multiple disulphide bridges stabilizing tertiary conformation. With the goal of a standardized specific immunotherapy we developed hypoallergenic Hev b 6.01 mutants by site-directed mutagenesis of selected cysteine residues (3, 12, 17, and 41) within the Hev b 6.02 domain. Peptides corresponding to the Hev b 6.02 domain of two of the mutants were also synthesized. These mutants and peptide variants showed markedly decreased or ablated latex-allergic patient serum IgE binding by immunoblotting and ELISA. Basophil activation testing confirmed markedly decreased activation with successive cysteine substitutions of the mutants and complete abrogation with the Hev b 6.02 (Cys 3, 12, 17, 41 Ala) peptide. Retention of T cell reactivity is crucial for effective specific immunotherapy and all mutants and peptide variants maintained their latex-specific T cell reactivity. The ablated allergenicity but retained T cell reactivity of the Hev b 6.02 (Cys 3, 12, 17, 41 Ala) peptide suggests this peptide is a suitable candidate for inclusion in a latex immunotherapy preparation.

Effect of vitamin D supplementation on vitamin D status and bone turnover markers in young adults

Objective: To assess the vitamin D status of healthy young people living in Northern Ireland and the effect of vitamin D supplementation on vitamin D status and bone turnover.

Design: Double-blinded randomised controlled intervention study.

Setting: University of Ulster, Coleraine, Northern Ireland.

Subjects: In total, 30 apparently healthy students (15 male and 15 female subjects), aged 18–27 years, were recruited from the university, with 27 completing the intervention.

Interventions: Subjects were randomly assigned, to receive either 15 mug (600 IU) vitamin D3 and 1500 mg calcium/day (vitamin D group), or 1500 mg calcium/day (control group) for 8 weeks between January and March. Vitamin D status, bone turnover markers, serum calcium and parathyroid hormone concentrations were measured at baseline and post intervention.

Results: At baseline, vitamin D status was low in both the vitamin D group (47.9 (s.d. 16.0)) and the control group (55.5 (s.d. 18.6) nmol/l 25(OH)D). Post intervention vitamin D status was significantly higher in the vitamin D-treated group (86.5 (s.d. 24.5)) compared to the control group (48.3 (s.d. 16.8) nmol/l) (P<0.0001). There was no significant effect of supplementation on bone turnover markers or PTH concentrations.

Conclusions: This study suggests that young adults in Northern Ireland do not consume an adequate daily dietary intake of vitamin D to maintain plasma vitamin D concentrations in the wintertime. A daily supplement of 15 mug vitamin D3 significantly increased vitamin D status in these individuals to levels of sufficiency. Achievement of an optimum vitamin D status among young adults may have future positive health implications.

Long-term effect of calcium-vitamin D3 fortified milk on blood pressure and serum lipid concenstrations in healthy older men

Background/Objectives:
Some epidemiological and clinical studies have shown that increased dairy consumption or calcium and/or vitamin D supplementation can have a beneficial effect on blood pressure, and lipid and lipoprotein concentrations. The aim of this study was to assess the long-term effects of calcium-vitamin D3 fortified milk on blood pressure and lipid-lipoprotein concentrations in community-dwelling older men.

Subjects/Methods:
This is a substudy of a 2-year randomized controlled trial in which 167 men aged >50 years were assigned to receive either 400 ml per day of reduced fat (approx1%) milk fortified with approximately 1000 mg of calcium and 800 IU of vitamin D3 or to a control group receiving no additional fortified milk. Weight, blood pressure, lipid and lipoprotein concentrations were measured every 6 months. Participants on lipid-lowering (n=32) or antihypertensive medication (n=39) were included, but those who commenced, increased or decreased their medication throughout the intervention were excluded (n=27).

Results:
In the 140 men included in this study (milk, n=73; control, n=67), there were no significant effects of the calcium-vitamin D3 fortified milk on weight, systolic or diastolic blood pressure, total cholesterol, high-density lipoprotein or low-density lipoprotein cholesterol or triglyceride concentrations at any time throughout the intervention. Similar results were observed after excluding men taking antihypertensive or lipid-lowering medication or limiting the analysis to those with baseline calcium intakes <1000 mg per day and/or with hypovitaminosis D (25(OH)D <75 nmol/l).

Conclusions:
Supplementation with reduced-fat calcium-vitamin D3 fortified milk did not have a beneficial (nor detrimental) effect on blood pressure, lipid or lipoprotein concentrations in healthy community-dwelling older men.

Intake of B vitamins in childhood and adult life in relation to psychological distress among women in a British birth cohort

Background : Lower levels of B vitamins (particularly folate, vitamin B12 and vitamin B6) may be associated with psychological distress. Little is known about the impact of childhood nutrition on psychological distress in adult life.

Objective : We investigated whether prospectively measured childhood and adult dietary intakes of thiamin, riboflavin, niacin, folate, vitamin B6 and vitamin B12 were related to the psychological distress of women in mid-age, taking into account socio-economic, behavioural and lifestyle factors.

Design : Prospective data were collected from a cohort of 636 British women followed up since their birth in 1946. Participants completed a 28-item, scaled version of the General Health Questionnaire (GHQ-28) to measure psychological distress at age 53 years. Dietary intakes in childhood (at age four) were determined by 24h recall and in adulthood (at age 36, 43 and 53 years) by a 5d food record.

Results : Low dietary vitamin B12 intake at age 53 was associated with higher psychological distress at that age. Women in the lowest third of vitamin B12 intake in adulthood had a higher GHQ-28 score compared with those in the highest third (percentage change, adjusted regression coefficient, 21 (95% CI 3, 39)). There were no other significant associations between dietary B vitamin intake in childhood or adulthood and psychological distress in the cohort.

Conclusions : Overall, there is evidence that intake of vitamin B12 at age 53 is related to adult psychological distress but there is no evidence for the effects of other adult B vitamin intakes or childhood intakes on psychological distress.

Maternal plasma ascorbic acid (vitamin C) and risk of gestational diabetes mellitus

Background : Antioxidants, particularly vitamin C (ascorbic acid), have the capacity to influence glucose tolerance. Modification of diet could reduce the likelihood of developing gestational diabetes mellitus.

Methods : In a prospective cohort study of pregnant women, we studied the association of maternal plasma ascorbic acid concentrations, measured at an average of 13 weeks' gestation, with subsequent risk of gestational diabetes. Maternal plasma ascorbic acid concentrations were determined using automated enzymatic procedures. Dietary vitamin C intake during the periconceptional period and early pregnancy was ascertained using a semiquantitative food frequency questionnaire. We fitted generalized linear models to derive estimates of relative risks and 95% confidence intervals (CIs).

Results : Approximately 4% (n = 33) of 755 women who completed pregnancy developed gestational diabetes mellitus. Plasma ascorbic acid concentrations were inversely associated with the risk of gestational diabetes (P for trend = 0.023). After adjusting for maternal age, race, prepregnancy adiposity, parity, family history of type 2 diabetes, and household income, women with plasma ascorbic acid <55.9 micromol/L (lowest quartile) experienced a 3.1-fold increased risk of gestational diabetes (95% CI = 1.0 - 9.7) compared with women whose concentrations were > or = 74.6 micromol/L (upper quartile). Women who consumed <70 mg vitamin C daily experienced a 1.8-fold increased risk of gestational diabetes compared with women who consumed higher amounts (95% CI = 0.8 - 4.4).

Conclusions : If confirmed, our results raise the possibility that current efforts to encourage populations to consume diets rich in antioxidants, including vitamin C, could reduce the occurrence of gestational diabetes mellitus.

Effects of parental perception of neighbourhood deprivation and family environment characteristics on pro-social behaviours among 4-12 year old children

Objective : To assess the effect family environment stressors (e.g. poor family functioning and parental psychological distress) and neighbourhood environment on child prosocial behaviour (CPB) and child difficulty behaviour (CDB) among 4-to-12 year old children.

Methods : Analysis of the 2006 Victorian Child Health and Wellbeing Survey (VCHWS) dataset derived from a statewide cross-sectional telephone survey, with a final total sample of 3,370 children.

Results : Only family functioning, parental psychological distress, child gender, and age were associated with CPB, explaining a total of 8% of the variance. Children from healthily functioning families and of parents without any psychological distress exhibited greater prosocial behaviours than those from poorly functioning families and of parents with mental health problems. Neighbourhood environment was not found to contribute to CPB. A total of eight variables were found to predict CDB, explaining a total of 16% of the variance. Poor family and parental psychological functioning as well as poor access to public facilities in the neighbourhood were associated with conduct problems in children.

Conclusion : Our results point to the importance of the family environment in providing a context that fosters the development of empathic, caring and responsible children; and in buffering children in exhibiting behaviour difficulties during the formative years of life. Programs aimed at promoting prosocial behaviours in children need to target stressors on the family environment.

Proceedings of the rank forum on vitamin D

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations>75 nmol/l). Any discussion of ‘optimal’ concentration of serum 25(OH)D needs to define ‘optimal’ with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations.

Is this D vitamin to worry about? Vitamin D insufficiency in an inpatient sample

Objective: The aim of the present study was to investigate the relationship between reduced serum vitamin D levels and psychiatric illness.

Method: This study was an audit of serum 25-hydroxyvitamin D (25-OHD) levels measured routinely in a sample of 53 inpatients in a private psychiatric clinic. These levels were compared with those of controls without psychiatric illness.

Results: The median levels of serum 25-OHD were 43.0 nmol L⁻¹ (range 20–102 nmol L⁻¹) in the patient population, 46.0 nmol L⁻¹ (range 20–102 nmol L⁻¹) in female patients (n =33) and 41.5 nmol L⁻¹ (range 22–97 nmol L⁻¹) in male patients (n =20). The proportion of vitamin D insufficiency (serum 25-OHD ≤50 nmol L⁻¹) in this patient population was 58%. Furthermore, 11% had moderate deficiency (serum 25-OHD ≤25 nmol L⁻¹). There was a 29% difference between mean levels in the patient population and control sample (geometric mean age- and season-adjusted levels: 46.4 nmol L⁻¹ (95% confidence interval (CI) =38.6–54.9 nmol L⁻¹) vs 65.3 nmol L⁻¹ (95%CI =63.2–67.4 nmol L⁻¹), p <0.001).

Conclusion: Low levels of serum 25-OHD were found in this patient population. These data add to the literature suggesting an association between vitamin D insufficiency and psychiatric illness, and suggest that routine monitoring of vitamin D levels may be of benefit given the high yield of clinically relevant findings.