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ABSTRACT: Data on the independent and potential combined effects of acid-base balance and vitamin D status on muscle mass and metabolism are lacking. We investigated whether alkali supplementation with potassium bicarbonate (KHCO3), with or without vitamin D3 (±VD3), alters urinary nitrogen (indicator of muscle proteolysis), muscle fiber cross-sectional area (FCSA), fiber number (FN), and anabolic (IGF-1, Akt, p70s6k) and catabolic (FOXO3a, MURF1, MAFbx) signaling pathways regulating muscle mass. Thirty-six, 20-month-old, Fischer 344/Brown-Norway rats were randomly assigned in a 2 × 2 factorial design to one of two KHCO3-supplemented diets (±VD3) or diets without KHCO3 (±VD3) for 12 weeks. Soleus, extensor digitorum longus (EDL), and plantaris muscles were harvested at 12 weeks. Independent of VD3 group, KHCO3 supplementation resulted in 35 % lower mean urinary nitrogen to creatinine ratio, 10 % higher mean type I FCSA (adjusted to muscle weight), but no statistically different mean type II FCSA (adjusted to muscle weight) or FN compared to no KHCO3. Among VD3-replete rats, phosphorylated-Akt protein expression was twofold higher in the KHCO3 compared to no KHCO3 groups, but this effect was blunted in rats on VD3-deficient diets. Neither intervention significantly affected serum or intramuscular IGF-1 expression, p70s6k or FOXO3a activation, or MURF1 and MAFbx gene expression. These findings provide support for alkali supplementation as a promising intervention to promote preservation of skeletal muscle mass, particularly in the setting of higher vitamin D status. Additional research is needed in defining the muscle biological pathways that are being targeted by alkali and vitamin D supplementation.
Endocrine 05/2013; · 1.42 Impact Factor
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Christopher T Sempos,
Ramón A Durazo-Arvizu, Bess Dawson-Hughes,
Elizabeth A Yetley,
Anne C Looker,
Rosemary L Schleicher,
Guichan Cao,
Vicki Burt,
Holly Kramer,
Regan L Bailey,
Johanna T Dwyer,
Xinli Zhang,
Jaime Gahche,
Paul R Thomas,
Paul M Coates,
Mary Frances Picciano
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ABSTRACT: Context:A reverse J-shaped association between serum 25-hydroxyvitamin D [25(OH)D] concentration and all-cause mortality was suggested in a nine-year follow-up (1991-2000) analysis of the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994).Objectives:Repeat the analyses with six years additional follow-up to evaluate if the association persists through 15-years of follow-up.Design, Setting, and Participants:15,099 participants ages 20+ years with 3,784 deaths.Main Outcome Measure:Relative risk (RR) of death from all-causes was adjusted for age, sex, race-ethnicity and season using two Poisson regression approaches - traditional categorical and cubic splines. Results were given for nine 25(OH)D (nmol/L) levels: < 20, 20-29, 30-39, 40-49, 50-59, 60-74, 75-99 (reference), 100-119, and ≥120.Results:The reverse J-shaped association became stronger with longer follow-up and was not affected by excluding deaths within the first 3-years of follow-up. Similar results were found from both statistical approaches for levels <20 through 119 nmol/L. Adjusted RR (95% CI) estimates for all levels < 60 nmol/L were significantly >1 compared to the reference group. The nadir of risk was 81 nmol/L (95% CI, 73-90 nmol/L). For 25(OH)D ≥120 nmol/L, results [RR, 95% CI] were slightly different using traditional categorical [1.5, 1.02-2.3] and cubic splines approaches [1.2, 0.9-1.4]. The association appeared in men, women, adults ages 20-64 and non-Hispanic whites but was weaker in older adults. The study was too small to evaluate the association in non-Hispanic black and Mexican-American adults.Conclusions:A reverse J-shaped association between serum 25(OH)D and all-cause mortality appears to be real. It is uncertain if the association is causal.
The Journal of clinical endocrinology and metabolism 05/2013; · 6.50 Impact Factor
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ABSTRACT: It is sometimes assumed that dietary fat is required for vitamin D absorption, although the impact of different amounts of dietary fat on vitamin D absorption is not established. This study was conducted to determine whether the presence of a meal and the fat content of the meal influences vitamin D absorption or the 25-hydroxyvitamin D (25OHD) response to supplemental vitamin D(3) . Based on earlier studies in rats we postulated that absorption would be greatest in the low-fat meal group. Sixty two healthy older men and women were randomly assigned to one of three meal groups: no meal, high-fat meal or low-fat meal; each was given a monthly 50,000 IU vitamin D(3) supplement with the test breakfast meal (or after a fast for the no-meal group) and followed for 90 days. Plasma vitamin D(3) was measured by LC/MS before and 12 hrs after the first dose; plasma 25OHD was measured by radioimmunoassay at baseline and after 30 and 90 days. The mean 12-hr increments in vitamin D(3) , after adjusting for age and sex, were 200.9 nmol/L in the no-meal group, 207.4 nmol/L in the high-fat meal group, and 241.1 nmol/L in the low-fat meal group (P = 0.038), with the increase in the low-fat group being significantly greater than the increases in the other two groups. However, increments in 25OHD levels at 30 and 90 days didn't differ significantly in the three groups. We conclude that absorption was increased when a 50,000 IU dose of vitamin D was taken with a low-fat meal, compared with a high-fat meal and no meal, but that the greater absorption didn't result in higher plasma 25OHD levels in the low-fat meal group. © 2013 American Society for Bone and Mineral Research.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 02/2013; · 6.04 Impact Factor
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ABSTRACT: The reliability of estimating muscle fiber cross-sectional area (measure of muscle fiber size) and fiber number from only a subset of fibers in rat hindlimb muscle cross-sections has not been systematically evaluated. This study examined the variability in mean estimates of fiber cross-sectional area as a function of the number of fibers measured, and tested whether counting a subset of fibers in a cross-section could predict total fiber number in middle-aged rats.
Soleus and extensor digitorum longus (EDL) muscle cross-sections from 23-month-old, male Fisher 344 x Brown Norway rats were stained for myofibrillar ATPase activity to identify muscle fiber type (either type I [slow-twitch] or II [fast-twitch]) and laminin to facilitate fiber cross-sectional measurements. We outlined the circumference of 1000 to 1600 single muscle fibers for measurement of fiber cross-sectional area within muscle sections. Mean type I fiber cross-sectional area was based on soleus muscle sections which were predominantly composed of type I muscle fibers. Mean type II fiber cross-sectional area was based on EDL muscle sections which were predominantly composed of type II muscle fibers. A bootstrapping resampling technique demonstrated that variability in sampling distribution of mean type I and II fiber cross-sectional areas decreased and gradually stabilized as the number of fibers measured increased with large declines in variability occurring at numbers below 150 fibers. Coefficients of variation for bootstrapped mean type I fiber cross-sectional areas were lower than for type II. In the same muscle sections, total fiber number was compared to fiber numbers within 1, 2, 3, and 4 fixed field areas (10x magnification; 1000 x 1500 pixels in size/field) on the cross-section. Fiber numbers from 3 to 4 fields (approximating 15 to 20% of the cross-section) provided a reasonably predictive value of total fiber number (r=0.57-0.59, P=0.003).
These data describe a pattern of improved precision in estimating mean fiber cross-sectional area as sample size of fibers measured increases to at least 150 in this rat model. Counting 15-20% of the fibers in cross-sections provides a reasonably reliable estimate of the total fiber number.
Biological Procedures Online 01/2013; 15(1):6. · 1.29 Impact Factor
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Heike A Bischoff-Ferrari,
Walter C Willett,
Endel J Orav,
Endel J Oray,
Paul Lips,
Pierre J Meunier,
Ronan A Lyons,
Leon Flicker,
John Wark,
Rebecca D Jackson,
Jane A Cauley,
Haakon E Meyer,
Michael Pfeifer,
Kerrie M Sanders,
Hannes B Stähelin,
Robert Theiler, Bess Dawson-Hughes
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ABSTRACT: The results of meta-analyses examining the relationship between vitamin D supplementation and fracture reduction have been inconsistent.
We pooled participant-level data from 11 double-blind, randomized, controlled trials of oral vitamin D supplementation (daily, weekly, or every 4 months), with or without calcium, as compared with placebo or calcium alone in persons 65 years of age or older. Primary end points were the incidence of hip and any nonvertebral fractures according to Cox regression analyses, with adjustment for age group, sex, type of dwelling, and study. Our primary aim was to compare data from quartiles of actual intake of vitamin D (including each individual participant's adherence to the treatment and supplement use outside the study protocol) in the treatment groups of all trials with data from the control groups.
We included 31,022 persons (mean age, 76 years; 91% women) with 1111 incident hip fractures and 3770 nonvertebral fractures. Participants who were randomly assigned to receive vitamin D, as compared with those assigned to control groups, had a nonsignificant 10% reduction in the risk of hip fracture (hazard ratio, 0.90; 95% confidence interval [CI], 0.80 to 1.01) and a 7% reduction in the risk of nonvertebral fracture (hazard ratio, 0.93; 95% CI, 0.87 to 0.99). By quartiles of actual intake, reduction in the risk of fracture was shown only at the highest intake level (median, 800 IU daily; range, 792 to 2000), with a 30% reduction in the risk of hip fracture (hazard ratio, 0.70; 95% CI, 0.58 to 0.86) and a 14% reduction in the risk of any nonvertebral fracture (hazard ratio, 0.86; 95% CI, 0.76 to 0.96). Benefits at the highest level of vitamin D intake were fairly consistent across subgroups defined by age group, type of dwelling, baseline 25-hydroxyvitamin D level, and additional calcium intake.
High-dose vitamin D supplementation (≥800 IU daily) was somewhat favorable in the prevention of hip fracture and any nonvertebral fracture in persons 65 years of age or older. (Funded by the Swiss National Foundations and others.).
New England Journal of Medicine 07/2012; 367(1):40-9. · 53.30 Impact Factor
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ABSTRACT: Parathyroid hormone (PTH) increases the conversion of 25-hydroxyvitamin D [25(OH)D] to 1,25 dihydroxyvitamin D [1,25(OH)(2)D]. The purpose of this study was to assess the changes in serum concentration of vitamin D metabolites 1,25 dihydroxyvitamin D [1,25(OH)(2)D] and 25-hydroxyvitamin D [25(OH)D] during teriparatide 20 μg/day (teriparatide) therapy in the double-blind Fracture Prevention Trial of postmenopausal women with osteoporosis and in the male study of men with osteoporosis. Patients were randomized to teriparatide or placebo and received daily supplements of calcium 1000 mg and vitamin D 400-1200 IU. Serum concentrations of 1,25(OH)(2)D and 25(OH)D were measured. In women (N=336), median 1,25(OH)(2)D concentrations at 1 month increased from baseline by 27% (P<0.0001) in the teriparatide group versus -3% (P=0.87) in the placebo group (between group P<0.0001). At 12 months, the increase was 19% (P<0.0001) in the teriparatide group versus -2% (P=0.23) in the placebo group (P<0.0001). Median 25(OH)D concentrations at 12 months decreased by 19% (P<0.0001) in the teriparatide group versus 0% (P=0.13) in the placebo group (P<0.0001). In men (N=287), median 1,25(OH)(2)D concentrations at 1 month increased by 22% (P<0.0001) in the teriparatide group versus 0% (P=0.99) in the placebo group (P<0.0001). At 12 months, the increase was 14% (P<0.0001) in the teriparatide group versus 5% (P=0.004) in the placebo group (P=0.17). Median 25(OH)D concentrations at 12 months decreased by 11% (P=0.001) in the teriparatide group versus an increase of 1% (P=0.20) in the placebo group (P=0.003). Therefore, treatment with teriparatide increases 1,25(OH)(2)D concentrations and decreases 25(OH)D concentrations.
Bone 03/2012; 50(6):1368-71. · 4.02 Impact Factor
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ABSTRACT: To investigate the association between vitamin D status, assessed by plasma 25-hydroxyvitamin D, and risk of incident diabetes.
Prospective observational study with a mean follow-up of 2.7 years in the Diabetes Prevention Program (DPP), a multicenter trial comparing different strategies for prevention of diabetes in patients with prediabetes. We assessed the association between plasma 25-hydroxyvitamin D, measured repeatedly during follow-up, and incident diabetes in the combined placebo (n = 1,022) and intensive lifestyle (n = 1,017) randomized arms of the DPP. Variables measured at multiple study time points (25-hydroxyvitamin D, BMI, and physical activity) entered the analyses as time-varying "lagged" covariates, as the mean of the previous and current visits at which diabetes status was assessed.
After multivariate adjustment, including for the DPP intervention, participants in the highest tertile of 25-hydroxyvitamin D (median concentration, 30.1 ng/mL) had a hazard ratio of 0.72 (95% CI 0.56-0.90) for developing diabetes compared with participants in the lowest tertile (median concentration, 12.8 ng/mL). The association was in the same direction in placebo (0.70; 0.52-0.94) versus lifestyle arm (0.80; 0.54-1.17).
Higher plasma 25-hydroxyvitamin D, assessed repeatedly, was associated with lower risk of incident diabetes in high-risk patients, after adjusting for lifestyle interventions (dietary changes, increased physical activity, and weight loss) known to decrease diabetes risk. Because of the observational nature of the study, the potential association between vitamin D and diabetes needs to be confirmed in intervention studies.
Diabetes care 03/2012; 35(3):565-73. · 8.09 Impact Factor
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Bess Dawson-Hughes
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ABSTRACT: The objective of this review is to consider the mechanisms by which vitamin D affects muscle and the evidence that vitamin D status is important for muscle performance and fall prevention in older adults. Vitamin D receptors have been identified in human skeletal-muscle cells. Activation of these receptors by 1,25-dihydroxyvitamin D is involved in the action of vitamin D on the myocyte. Several studies have examined the effect of supplemental vitamin D on muscle strength, balance and falls. Among those examining muscle strength, results have been either positive for vitamin D or null. A recent meta-analysis of seventeen such trials revealed no significant effect of vitamin D overall, but a significant improvement in strength was observed in the trials in which the mean starting level of 25-hydroxyvitamin D was 25 nmol/l or below. Evidence for an effect of vitamin D on balance, measured as sway, is less abundant but more consistently positive. Many trials have evaluated the effect of supplemental vitamin D on falls. Overall, there is about a 20% lower risk of falling with supplementation. One meta-analysis considered the vitamin D dose administered and concluded that doses up through 15 μg (600 IU) were ineffective and doses of 17·5-25 μg/d (700-1000 IU/d) significantly lowered fall risk. The minimal 25-hydroxyvitamin D level needed for benefit was 60 nmol/l.
Proceedings of The Nutrition Society 02/2012; 71(1):46-9. · 2.77 Impact Factor
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Heike Annette Bischoff-Ferrari, Bess Dawson-Hughes,
Elisabeth Stöcklin,
Eduard Sidelnikov,
Walter Churchill Willett,
John Orav Edel,
Hannes Balthasar Stähelin,
Swen Wolfram,
Alexander Jetter,
Joseph Schwager,
Jana Henschkowski,
Arnold von Eckardstein,
Andreas Egli
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ABSTRACT: To test the effect of 25(OH)D3 (HyD) compared to vitamin D3 on serum 25-hydroxyvitamin D levels (25(OH)D), lower extremity function, blood pressure, and markers of innate immunity. Twenty healthy postmenopausal women with an average 25(OH)D level of 13.2 ± 3.9 ng/mL (mean ± SD) and a mean age of 61.5 ± 7.2 years were randomized to either 20 µg of HyD or 20 µg (800 IU) of vitamin D3 per day in a double-blind manner. We measured on 14 visits over 4 months, 25(OH)D serum levels, blood pressure, and seven markers of innate immunity (eotaxin, interleukin [IL]-8, IL-12, interferon gamma-induced protein 10 kDa [IP-10], monocyte chemotactic protein-1 [MCP-1], macrophage inflammatory protein beta [MIP-1β], and “Regulated upon Activation, Normal T-cell Expressed, and Secreted” [RANTES]). At baseline and at 4 months, a test battery for lower extremity function (knee extensor and flexor strength, timed up and go, repeated sit-to-stand) was assessed. All analyses were adjusted for baseline measurement, age, and body mass index. Mean 25(OH)D levels increased to 69.5 ng/mL in the HyD group. This rise was immediate and sustained. Mean 25(OH)D levels increased to 31.0 ng/mL with a slow increase in the vitamin D3 group. Women on HyD compared with vitamin D3 had a 2.8-fold increased odds of maintained or improved lower extremity function (odds ratio [OR] = 2.79; 95% confidence interval [CI], 1.18–6.58), and a 5.7-mmHg decrease in systolic blood pressure (p = 0.0002). Both types of vitamin D contributed to a decrease in five out of seven markers of innate immunity, significantly more pronounced with HyD for eotaxin, IL-12, MCP-1, and MIP-1 β. There were no cases of hypercalcemia at any time point. Twenty micrograms (20 µg) of HyD per day resulted in a safe, immediate, and sustained increase in 25(OH)D serum levels in all participants, which may explain its significant benefit on lower extremity function, systolic blood pressure, and innate immune response compared with vitamin D3. © 2012 American Society for Bone and Mineral Research
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 12/2011; 27(1):160 - 169. · 6.04 Impact Factor
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Heike Annette Bischoff-Ferrari, Bess Dawson-Hughes,
Elisabeth Stöcklin,
Eduard Sidelnikov,
Walter Churchill Willett,
Edel John Orav,
Hannes Balthasar Stähelin,
Swen Wolfram,
Alexander Jetter,
Joseph Schwager,
Jana Henschkowski,
Arnold von Eckardstein,
Andreas Egli
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ABSTRACT: AIMS: To test the effect of 25(OH)D(3) (HyD) compared to vitamin D(3) on serum 25-hydroxyvitamin D levels (25(OH)D), lower extremity function, blood pressure and markers of innate immunity. METHODS: 20 healthy postmenopausal women with an average 25(OH)D level of 13.2 ng/ml (SD = ± 3.9) and a mean age of 61.5 years (SD = ± 7.2) were randomized to either 20 µg of HyD or 20 µg (800 IU) of vitamin D(3) per day in a double-blind manner. We measured on 14 visits over 4-months, 25(OH)D serum levels, blood pressure, and 7 markers of innate immunity (eotaxin, IL-8, IL-12, IP-10, MCP-1, MIP-1β, RANTES). At baseline and at 4 months, a test battery for lower extremity function (knee extensor and flexor strength, timed up and go, repeated sit-to-stand) was assessed. All analyses adjusted for baseline measurement, age and body mass index. RESULTS: Mean 25(OH)D levels increased to 69.5 ng/ml in the HyD group. This rise was immediate and sustained. Mean 25(OH)D levels increased to 31.0 ng/ml with a slow increase in the vitamin D3 group. Women on HyD compared with vitamin D(3) had a 2.8 fold increased odds of maintained or improved lower extremity function (OR= 2.79; 95%CI: 1.18-6.58), and a 5.7 mmHg decrease in systolic blood pressure (p = 0.0002). Both types of vitamin D contributed to a decrease in 5 out of 7 markers of innate immunity, significantly more pronounced with HyD for eotaxin, IL-12, MCP-1 and MIP-1 β. There were no cases of hypercalcemia at any time point. CONCLUSIONS: 20 µg of HyD per day resulted in a safe, immediate and sustained increase in 25(OH)D serum levels in all participants, which may explain its significant benefit on lower extremity function, systolic blood pressure, and innate immune response compared with vitamin D(3) . © 2011 American Society for Bone and Mineral Research.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 10/2011; · 6.04 Impact Factor
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ABSTRACT: Fat mass is thought to be protective against osteoporosis, primarily because of its weight-bearing effect. Few studies have evaluated the association between abdominal fat mass (AFM) and bone health beyond its weight-bearing effect.
We tested the hypothesis that higher body weight-adjusted AFM is associated with poor bone health.
A cross-sectional study was conducted in 629 Puerto Rican adults aged 47-79 y. Bone mineral density (BMD) of the femoral neck, trochanter, total femur, and lumbar spine (L2-L4) were measured by using dual-energy X-ray absorptiometry (DXA). AFM and total fat mass (TFM) were assessed by using body-composition software from whole-body DXA scans. Osteoporosis and osteopenia were defined as T-scores ≤ -2.5 and -1.0 to -2.5 SD, respectively, at the respective bone site.
After confounders were controlled for, body weight-adjusted AFM was inversely associated with BMD at all 4 bone sites in women and at the femoral neck in men. For TFM, small inverse associations were seen at the trochanter and total femur in women. In men, similar associations were seen at the 3 femur sites. In both sexes, the odds for osteoporosis or osteopenia at each of the femoral sites increased by 10-16% for every 100-g increase in body weight-adjusted AFM.
Higher AFM was associated with poor bone health in this Puerto Rican sample. Efforts to reduce abdominal obesity will not only reduce the risk of chronic disease but may also improve bone health. This trial is registered at clinicaltrials.gov as NCT01231958.
American Journal of Clinical Nutrition 08/2011; 94(4):1063-70. · 6.67 Impact Factor
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ABSTRACT: Mono- and polyunsaturated fats may have opposing effects on vitamin D absorption.
The purpose of this study was to determine whether intakes of different dietary fats are associated with the increase in serum 25-hydroxyvitamin D (25OHD) after supplementation with vitamin D(3).
This analysis was conducted in the active treatment arm of a randomized, double-blind, placebo-controlled trial of vitamin D and calcium supplementation to prevent bone loss and fracture. Subjects included 152 healthy men and women age 65 and older who were assigned to 700 IU/d vitamin D(3) and 500 mg/d calcium. Intakes of monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), and saturated fatty acids (SFA) were estimated by food frequency questionnaire.
The change in plasma 25OHD during 2 yr vitamin D and calcium supplementation was assessed.
The change in plasma 25OHD (nanograms per milliliter) during vitamin D supplementation was positively associated with MUFA, (β = 0.94; P = 0.016), negatively associated with PUFA, (β = -0.93; P = 0.038), and positively associated with the MUFA/PUFA ratio (β = 6.46; P = 0.014).
The fat composition of the diet may influence the 25OHD response to supplemental vitamin D(3). Diets rich in MUFA may improve and those rich in PUFA may reduce the effectiveness of vitamin D(3) supplements in healthy older adults. More studies are needed to confirm these findings.
The Journal of clinical endocrinology and metabolism 08/2011; 96(10):3170-4. · 6.50 Impact Factor
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ABSTRACT: A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies, but evidence from trials is lacking.
We determined whether vitamin D supplementation, with or without calcium, improved glucose homeostasis in adults at high risk of diabetes.
Ninety-two adults were randomly assigned in a 2-by-2 factorial-design, double-masked, placebo-controlled trial to receive either cholecalciferol (2000 IU once daily) or calcium carbonate (400 mg twice daily) for 16 wk. The primary outcome was the change in pancreatic β cell function as measured by the disposition index after an intravenous-glucose-tolerance test. Other outcomes were acute insulin response, insulin sensitivity, and measures of glycemia.
Participants had a mean age of 57 y, a body mass index (BMI; in kg/m(2)) of 32, and glycated hemoglobin (Hb A(1c)) of 5.9%. There was no significant vitamin D × calcium interaction on any outcomes. The disposition index increased in the vitamin D group and decreased in the no-vitamin D group (adjusted mean change ± SE: 300 ± 130 compared with -126 ± 127, respectively; P = 0.011), which was explained by an improvement in insulin secretion (62 ± 39 compared with -36 ± 37 mU · L(-1) · min, respectively; P = 0.046). Hb A(1c) increased less, but nonsignificantly, in the vitamin D group than in the no-vitamin D group (0.06 ± 0.03% compared with 0.14 ± 0.03%, respectively; P = 0.081). There was no significant difference in any outcomes with calcium compared with no calcium.
In adults at risk of type 2 diabetes, short-term supplementation with cholecalciferol improved β cell function and had a marginal effect on attenuating the rise in Hb A(1c). This trial was registered at clinicaltrials.gov as NCT00436475.
American Journal of Clinical Nutrition 06/2011; 94(2):486-94. · 6.67 Impact Factor
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Heike A Bischoff-Ferrari, Bess Dawson-Hughes,
John A Baron,
John A Kanis,
Endel J Orav,
Hannes B Staehelin,
Douglas P Kiel,
Peter Burckhardt,
Jana Henschkowski,
Donna Spiegelman,
Ruifeng Li,
John B Wong,
Diane Feskanich,
Walter C Willett
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ABSTRACT: Milk contains calcium, phosphorus, and protein and is fortified with vitamin D in the United States. All these ingredients may improve bone health. However, the potential benefit of milk on hip fracture prevention is not well established. The objective of this study was to assess the association of milk intake with risk of hip fracture based on a meta-analysis of cohort studies in middle-aged or older men and women. Data sources for this study were English and non-English publications via Medline (Ovid, PubMed) and EMBASE search up to June 2010, experts in the field, and reference lists. The idea was to compare prospective cohort studies on the same scale so that we could calculate the relative risk (RR) of hip fracture per glass of milk intake daily (approximately 300 mg calcium per glass of milk). Pooled analyses were based on random effects models. The data were extracted by two independent observers. The results show that in women (6 studies, 195,102 women, 3574 hip fractures), there was no overall association between total milk intake and hip fracture risk (pooled RR per glass of milk per day = 0.99; 95% confidence interval [CI] 0.96-1.02; Q-test p = .37). In men (3 studies, 75,149 men, 195 hip fractures), the pooled RR per daily glass of milk was 0.91 (95% CI 0.81-1.01). Our conclusion is that in our meta-analysis of cohort studies, there was no overall association between milk intake and hip fracture risk in women but that more data are needed in men.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 04/2011; 26(4):833-9. · 6.04 Impact Factor
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ABSTRACT: In 2006, the AHA released diet and lifestyle recommendations (AHA-DLR) for cardiovascular disease (CVD) risk reduction. The effect of adherence to these recommendations on CVD risk is unknown. Our objective was to develop a unique diet and lifestyle score based on the AHA-DLR and to evaluate this score in relation to available CVD risk factors. In a cross-sectional study of Puerto Rican adults aged 45-75 y living in the greater Boston area, information was available for the following variables: diet (semiquantitative FFQ), blood pressure, waist circumference (WC), 10-y risk of coronary heart disease (CHD) (Framingham risk score), and fasting plasma lipids, serum glucose, insulin, and C-reactive protein (CRP) concentrations. We developed a diet and lifestyle score (AHA-DLS) based on the AHA-DLR. The AHA-DLS had both internal consistency and content validity. It was associated with plasma HDL cholesterol (P = 0.001), serum insulin (P = 0.0003), and CRP concentrations (P = 0.02), WC (P < 0.0001), and 10-y risk of CHD score (P = 0.01 in women). The AHA-DLS was inversely associated with serum glucose among those with a BMI < 25 (P = 0.01). Women and men in the highest quartile of the AHA-DLS had lower serum insulin (P-trend = 0.0003) and CRP concentrations (P-trend = 0.002), WC (P-trend = 0.0003), and higher HDL cholesterol (P-trend = 0.008). The AHA-DLS is a useful tool to measure adherence to the AHA-DLR and may be used to examine associations between diet and lifestyle behaviors and CVD risk.
Journal of Nutrition 03/2011; 141(3):460-9. · 3.92 Impact Factor
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Archives of internal medicine 02/2011; 171(3):265; author reply 265-6. · 11.46 Impact Factor
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ABSTRACT: Chronic mild metabolic acidosis is common among older adults, and limited evidence suggests that it may contribute to insulin resistance and type-2 diabetes. This analysis was conducted to determine whether bicarbonate supplementation, an alkalinizing treatment, improves insulin sensitivity or glucose control in non-diabetic older adults. Fasting blood glucose and insulin were measured in stored samples from subjects who had completed a 3-month clinical trial of bicarbonate supplementation to improve indicators of bone and muscle health. One hundred and fifty three ambulatory, non-diabetic adults aged 50 years and older were studied. Subjects were randomized to one of two bicarbonate groups (67.5 mmol/day of potassium bicarbonate or sodium bicarbonate) or to one of two no-bicarbonate groups (67.5 mmol/day of placebo or potassium chloride). Subjects remained on treatment throughout the 3-month study. The primary outcome measures were changes in fasting plasma glucose, serum insulin and HOMA-IR, an index of insulin resistance. Bicarbonate supplementation reduced net acid excretion (adjusted mean±SEM for the change in NAE/creatinine, mmol/mmol, was 0.23±0.22 in the no-bicarbonate group compared with -3.53±0.22 in the bicarbonate group, P<0.001) but had no effect on fasting plasma glucose, serum insulin, or HOMA-IR. In conclusion, bicarbonate supplementation does not appear to improve insulin sensitivity or glucose control in non-diabetic older adults.
Endocrine 10/2010; 38(2):221-6. · 1.42 Impact Factor
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ABSTRACT: To determine the association between 25-hydroxyvitamin D (25-OHD) concentration and risk of incident type 2 diabetes.
In a nested case-control study conducted among 608 women with newly diagnosed type 2 diabetes and 559 control subjects in the Nurses' Health Study, we measured the association between baseline plasma 25-OHD concentration and risk of incident diabetes.
After adjusting for matching factors and diabetes risk factors, including BMI, higher levels of plasma 25-OHD were associated with a lower risk for type 2 diabetes. The odds ratio for incident type 2 diabetes in the top (median 25-OHD, 33.4 ng/ml) versus the bottom (median 25-OHD, 14.4 ng/ml) quartile was 0.52 (95% CI 0.33-0.83). The associations were consistent across subgroups of baseline BMI, age, and calcium intake.
Plasma 25-OHD concentration was associated with lower risk of incident type 2 diabetes in women.
Diabetes care 09/2010; 33(9):2021-3. · 8.09 Impact Factor
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Helen L Henry,
Roger Bouillon,
Anthony W Norman,
J Christopher Gallagher,
Paul Lips,
Robert P Heaney,
Reinhold Vieth,
John M Pettifor, Bess Dawson-Hughes,
Christel J Lamberg-Allardt,
Peter R Ebeling
The Journal of steroid biochemistry and molecular biology 07/2010; 121(1-2):4-6. · 2.66 Impact Factor
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ABSTRACT: Vitamin D modulates fracture risk in two ways: by decreasing falls and increasing bone density. Two 2009 metaanalyses of double-blind
randomized controlled trials came to the conclusion that vitamin D reduces the risk of falls by 19%, the risk of hip fracture
by 18%, and the risk of any nonvertebral fracture by 20%; however, this benefit was dose-dependent. Fall prevention was only
observed in trial of at least 700 IU vitamin D per day, and fracture prevention required a received dose (treatment dose*adherence)
of more than 400 IU vitamin D per day. Antifall efficacy started with achieved 25-hydroxyvitamin D levels of at least 60 nmol/L
(24 ng/mL) and antifracture efficacy started with achieved 25-hydroxyvitamin D levels of at least 75 nmol/L (30 ng/mL) and
both end points improved further with higher achieved 25-hydroxyvitamin D levels. Based on these evidence-based data derived
from the general older population, vitamin D supplementation should be at least 700–1,000 IU/day and taken with good adherence
to cover the needs for both fall and fracture prevention. Ideally, the target range for 25-hydroxyvitamin D should be at least
75 nmol/L, which may need more than 700–1,000 IU vitamin D in individuals with severe vitamin D deficiency or those overweight.
06/2010: pages 109-113;
