Individual participant data (IPD)-level meta-analysis of randomised controlled trials with vitamin D-fortified foods to estimate Dietary Reference Values for vitamin D.

CONTEXT AND PURPOSE: Individual participant data-level meta-regression (IPD) analysis is superior to meta-regression based on aggregate data in determining Dietary Reference Values (DRV) for vitamin D. Using data from randomized controlled trials (RCTs) with vitamin D3-fortified foods, we undertook an IPD analysis of the response of winter serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among children and adults and derived DRV for vitamin D. METHODS: IPD analysis using data from 1429 participants (ages 2-89 years) in 11 RCTs with vitamin D-fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D DRV estimates across a range of serum 25(OH)D thresholds using unadjusted and adjusted models. RESULTS: Our IPD-derived estimates of vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25 and ≥ 30 nmol/L are 6 and 12 µg/day, respectively (unadjusted model). The intake estimates to maintain 90%, 95% and 97.5% of concentrations ≥ 50 nmol/L are 33.4, 57.5 and 92.3 µg/day, respectively (unadjusted) and 17.0, 28.1 and 43.6 µg/day, respectively (adjusted for mean values for baseline serum 25(OH)D, age and BMI). CONCLUSIONS: IPD-derived vitamin D intakes required to maintain 90%, 95% and 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L are much higher than those derived from standard meta-regression based on aggregate data, due to the inability of the latter to capture between person-variability. Our IPD provides further evidence that using food-based approaches to achieve an intake of 12 µg/day could prevent vitamin D deficiency (i.e., serum 25(OH)D < 30 nmol/L) in the general population.

Protein Supplementation During a 6-Month Concurrent Training Program: Effect on Body Composition and Muscular Strength in Sedentary Individuals.

We examined the effect of a protein supplement on muscular strength and body composition during 6 months of a 5 days/week concurrent strength and endurance training program. Sedentary males (n = 26) and females (n = 25), 18-25 years, were randomly assigned to receive a protein (PRO, 42 g/serving) or carbohydrate (CON) supplement twice daily. Strength and body composition (dual-energy X-ray absorptiometry) were assessed at baseline, 3 (3M), and 6 (6M) months. Protein intake was higher in PRO (PRO: 2.2 g/kg; CON: 1.1 g/kg; p < .001). Females in both groups gained similar strength at 3M and 6M in bench press and hip sled. Males in PRO gained more bench press strength at 3M (PRO: 24.6 ± 3.2 kg; CON: 14.3 ± 3.8 kg; p = .06) and 6M (PRO: 34.4 ± 4.3 kg; CON: 18.7 ± 5.1 kg; p = .03) and hip sled strength at 3M (PRO: 67.7 ± 9.2 kg; CON: 40.8 ± 10.8 kg, p = .07) and 6M (PRO: 94.0 ± 10.6 kg; CON: 65.1 ± 12.4 kg; p = .09) compared with CON. Females in PRO experienced a greater reduction in fat mass over the course of the study (6M) than CON (PRO: -1.7 ± 0.5 kg; CON: 0.1 ± 0.5 kg; p = .06). Changes in lean mass were similar for females in PRO and CON. Loss in fat mass was similar for males in PRO and CON at 3M and 6M. Males in PRO gained more lean mass at 3M compared with CON (PRO: 3.2 ± 0.3 kg; CON: 2.2 ± 0.4 kg; p = .1) but similar gains at 6M (PRO: 2.6 ± 0.4 kg; CON: 2.2 ± 0.5 kg; p = .6). The results of this study demonstrate that PRO used during a concurrent training program may augment positive changes in body composition in young sedentary males and females, and strength gains in males.

Global Consensus Recommendations on Prevention and Management of Nutritional Rickets.

BACKGROUND: Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. EVIDENCE: A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describes the strength of the recommendation and the quality of supporting evidence. PROCESS: Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. RESULTS: This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. CONCLUSION: Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required.

Global Consensus Recommendations on Prevention and Management of Nutritional Rickets.

BACKGROUND: Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. EVIDENCE: A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describe the strength of the recommendation and the quality of supporting evidence. PROCESS: Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. RESULTS: This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. CONCLUSION: Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required.

Does vitamin D during pregnancy impact offspring growth and bone?

During pregnancy, maternal and fetal Ca demands are met through increased intestinal Ca absorption. Increased Ca absorption may be more dependent on oestrogen's up-regulation of Ca transport genes than on vitamin D status. Numerous studies, however, have found that severe vitamin D deficiency with secondary hyperparathyroidism during pregnancy leads to abnormal Ca homoeostasis in the neonate. Some, but not all, studies of maternal vitamin D supplementation during pregnancy find a greater birth weight among infants of mothers with adequate vitamin D status. Observational studies find a higher incidence of small-for-gestational age (SGA) infants among mothers who are vitamin D deficient, but this effect may be modified by genetics. In addition, the effect of vitamin D status on SGA may not be linear, with increased occurrence of SGA at high maternal 25-hydroxyvitamin D (25-OHD) concentrations. Some studies, but not all, also have found that maternal vitamin D status is associated with growth trajectory during the first year of life, although the findings are contradictory. There are recent studies that suggest maternal 25-OHD, or surrogates of vitamin D status, are associated with growth and bone mass later in childhood. These results are not consistent, and blinded randomised trials of vitamin D supplementation during pregnancy with long-term follow-up are needed to determine the benefits, and possible risks, of maternal vitamin D status on offspring growth and bone development. The possibility of adverse outcomes with higher maternal 25-OHD concentrations should be considered and investigated in all ongoing and future studies.

Fat mass gain is lower in calcium-supplemented than in unsupplemented preschool children with low dietary calcium intakes.

BACKGROUND: Dietary calcium may play a role in the stimulation of lipolysis and the inhibition of lipogenesis, thereby reducing body fat. OBJECTIVE: The aim was to determine whether an association existed between change in percentage body fat (%BF) or fat mass and calcium intake in children aged 3-5 y. DESIGN: A secondary analysis of a 1-y randomized calcium and activity trial in 178 children was conducted. Three-day diet records and 48-h accelerometer readings were obtained at 0, 6, and 12 mo. Body composition was measured by dual-energy X-ray absorptiometry at 0 and 12 mo. RESULTS: The decrease in %BF was less in girls (-0.6 +/- 2.8%) than in boys (-1.5 +/- 2.6%; P = 0.03) and correlated with age (r = 0.19, P = 0.01) and maternal body mass index (r = 0.19, P = 0.02). Changes in fat mass were not significantly different by activity group or between children randomly assigned to receive calcium or placebo (0.5 +/- 0.9 and 0.6 +/- 0.8 kg, respectively; P = 0.32). Similar findings were observed for the change in %BF. No correlations between %BF and fat mass changes and dietary calcium (r = -0.01, P = 0.9 and r = -0.05, P = 0.5) or total (dietary + supplement) calcium intake (r = -0.02, P = 0.8 and r = -0.06, P = 0.4) were observed. Among children in the lowest tertile of dietary calcium (<821 mg/d), fat mass gain was lower in the calcium group (0.3 +/- 0.5 kg) than in the placebo group (0.8 +/- 1.1 kg) (P = 0.04) but was not correlated with mean total calcium intake (r = -0.20). CONCLUSION: These findings support a weak relation between changes in fat mass gain and calcium intake in preschool children, who typically consume below recommended amounts of dietary calcium.

Effect of protein supplementation during a 6-month strength and conditioning program on areal and volumetric bone parameters.

BACKGROUND: Skeletal loading and proper nutrition are necessary for optimal bone health. The appropriate amount of dietary protein to maximize skeletal health, however, is under constant debate. OBJECTIVE: To determine if 6 months of protein supplementation in conjunction with a strength and conditioning training program improves areal and volumetric bone mineral density (BMD). DESIGN: Fifty-two apparently healthy males and females ages 18-25 years were randomized to protein supplement (PRO, Myoplex, EAS, Inc. Golden CO) containing 280 kcal, 42 g protein, 21 g carbohydrate, and 1.5 g fat) or calorically equivalent carbohydrate control (CS). All subjects participated in a 5 sessions/week strength and conditioning program. Volumetric and areal BMD measurements were made by peripheral quantitative computed tomography (pQCT) of the tibia and whole body DXA. pSSI a measure of torsional bone strength, based on structural and material properties was obtained by pQCT. RESULTS: Measurements at the 20% tibia by pQCT revealed that overall there were significant increases in cortical vBMD (4.3 +/- 1.3 mg/cm(3)), cortical area (1.9 +/- 0.6 cm(2)), cortical thickness (0.05 +/- 0.02 mm) and pSSI (67 +/- 24 mm(3)), and a decrease in endosteal circumference (- 0.5 +/- 0.2 mm) over the intervention period (all, P < 0.05). None of the changes in DXA measures were found to differ by group or sex, there was a trend for a greater increase in whole body BMC among the carbohydrate compared to protein supplemented group and a greater increase among males (16 +/- 8 g) compared to females (-9 +/- 9 g) (P = 0.06). CONCLUSIONS: The results of this study indicate that the consumption of additional protein does not improve measurements of vBMD or bone size during a 6-month strength and conditioning program. Longer duration studies may be necessary to determine the influence of increased dietary protein on bone in young adults. Males and females may have different bone responses to increased protein intake while participating in a strength and conditioning program.

Effect of protein supplementation during a 6-mo strength and conditioning program on insulin-like growth factor I and markers of bone turnover in young adults.

BACKGROUND: Exercise is beneficial for bone when adequate nutrition is provided. The role of protein consumption in bone health, however, is controversial. OBJECTIVE: The objective was to ascertain the effect of high protein intake on insulin-like growth factor I (IGF-I) and markers of bone turnover during 6 mo of exercise training. DESIGN: Fifty-one subjects aged 18-25 y (28 men, 23 women) received a protein supplement (42 g protein, 24 g carbohydrate, 2 g fat) or a carbohydrate supplement (70 g carbohydrate) twice daily. Exercise consisted of alternating resistance training and running 5 times/wk. Plasma concentrations of IGF-I, insulin-like growth factor-binding protein 3, serum bone alkaline phosphatase, and urinary N-telopeptide collagen crosslink (NTx) concentrations were measured at 0, 3, and 6 mo after 24 h without exercise and a 12-h fast. RESULTS: Three-day diet records indicated no difference in energy intake between the groups. Average protein intakes after supplementation began in the protein and carbohydrate groups were 2.2 +/- 0.1 and 1.1 +/- 0.1 g/kg, respectively (P < 0.001). The increase in plasma IGF-I was greater in the protein group than in the carbohydrate group (time x supplement interaction, P = 0.01). There were no significant changes over time or significant differences by supplement in plasma insulin-like growth factor-binding protein 3 (44 and 40 kDa). Serum bone alkaline phosphatase increased significantly over time (P = 0.04) and tended to be higher in the protein group than in the carbohydrate group (P = 0.06). NTx concentrations changed over time (time and time squared; P < 0.01 for both) and were greater in the protein group than in the carbohydrate group (P = 0.04). Men had higher NTx concentrations than did women (74.6 +/- 3.4 and 60.0 +/- 3.8 nmol/mmol creatinine; P = 0.005). CONCLUSION: Protein supplementation during a strength and conditioning program resulted in changes in IGF-I concentrations.