Effects of calcium supplementation on body weight and adiposity in overweight and obese adults: a randomized trial
Yanovski JA , Parikh SJ , Yanoff LB , Denkinger BI , Calis KA , Reynolds JC , Sebring NG , McHugh T . National Institutes of Health, Hatfield Clinical Research Center, Bethesda, Maryland USA.Ann Intern Med. 2009 Jun
BACKGROUND: Some data suggest that increasing calcium intake may help prevent weight gain. OBJECTIVE: To test the hypothesis that calcium supplementation can prevent weight gain in persons who are overweight or obese. DESIGN: Randomized, placebo-controlled trial. Randomization was computer-generated, and allocation was assigned by pharmacy personnel who prepared intervention and placebo capsules. Participants, providers, and those who assessed outcomes were blinded to study group assignment. SETTING: Single research center. PARTICIPANTS: 340 overweight (body mass index [BMI], 25 to <30 kg/m(2)) and obese (BMI > or =30 kg/m(2)) adults (mean age, 38.8 years [SD, 10.5]). INTERVENTION: Calcium carbonate (elemental calcium, 1500 mg/d) (n = 170) or placebo (n = 170) with meals for 2 years. MEASUREMENTS: Changes in body weight and fat mass (primary outcomes). RESULTS: Seventy-five percent of participants completed the trial (78% received calcium; 73% received placebo). There were no statistically or clinically significant differences between the calcium and placebo groups in change in body weight (difference, 0.02 kg [95% CI, -1.64 to 1.69 kg]; P = 0.98), BMI (difference, 0.32 kg/m(2) [CI, -0.41 to 1.02 kg/m(2)]; P = 0.39), or body fat mass (difference, 0.39 kg [CI, -1.04 to 1.92 kg]; P = 0.55). Parathyroid hormone concentrations decreased in the calcium group compared with the placebo group (difference, -0.71 pmol/L [CI, -1.28 to -0.13 pmol/L]). LIMITATION: The study took place at a research center, and its sample was mostly women. CONCLUSION: Dietary supplementation with elemental calcium, 1500 mg/d, for 2 years had no statistically or clinically significant effects on weight in overweight and obese adults. Calcium supplementation is unlikely to have clinically significant efficacy as a preventive measure against weight gain in such patients.
Vitamin D and periodontal disease
Amano Y , Komiyama K , Makishima M . Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, Japan. J Oral Sci. 2009 Mar
1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3); 1,25-dihydroxycholecalciferol or calcitriol] is the active form of vitamin D(3), a lipid-soluble vitamin that plays a role in calcium and bone metabolism. Recently, vitamin D(3) has been shown to function in cancer prevention, immunity and cardiovascular regulation. 1,25(OH)(2)D(3) exhibits physiological and pharmacological effects by activating the vitamin D receptor (VDR), a transcription factor of the nuclear receptor superfamily. 1,25(OH)(2)D(3) plays a role in maintaining oral health through its effects on bone and mineral metabolism and innate immunity, and several VDR gene polymorphisms have been reported to be associated with periodontal disease. VDR ligands should prove to be useful in the treatment and prevention of periodontal disease.
Altered calcium metabolism in patients on long-term bisphosphonate therapy for metastatic breast cancer
Simmons C , Amir E , Dranitsaris G , Clemons M , Wong B , Veith R , Cole DE . Division of Medical Oncology Sunnybrook Health Sciences Centre Odette Cancer Centre Toronto, Ontario, Canada. Anticancer Res. 2009 Jul
BACKGROUND: Bisphosphonates (BPs) are considered the standard of care in metastatic breast cancer (MBC) patients with bone metastases. Because the survival for these patients may be prolonged compared with those patients with visceral metastases, they may be prescribed BPs for several years. The effects of this long-term BP use on calcium metabolism in MBC patients have not previously been described. OBJECTIVES: The main objective of this study was to evaluate the effect of long-term BP use on calcium homeostasis in MBC patients. The secondary objective was to assess Vitamin D levels in these patients. MATERIALS AND METHODS: An exploratory analysis of serum calcium, parathyroid (PTH), and 25 hydroxycholecalsiferol (25-(OH)D) levels and their inter-relationships was undertaken in 46 MBC patients who had been on prolonged BP therapy. These results were compared to a historical control group of 420 patients without bone or mineral disease who were matched for gender, age, baseline renal function and season of seological testing. RESULTS: Patients were similar in the two groups with no significant difference in mean age, baseline creatinine or season of testing. Serum calcium was no different between the two groups. However, PTH was significantly higher in MBC patients, compared to controls (5.7 vs. 4.8 pmol/L, p=0.043). Linear regression analysis showed that PTH was significantly higher in the MBC group at lower serum calcium levels and fell sharply with increasing serum calcium levels (p=0.0001). Among the patients with MBC, 62% had suboptimal levels of vitamin D and 18% were found to have insufficient or deficient levels (25-(OH)D < 40 nM) despite taking dietary supplementation. CONCLUSION: In MBC patients with prolonged BP use, there appears to be a state of hyperparathyroidism similar to that seen with BP use in benign bone disease. Supplementation with 400 IU per day of Vitamin D per day was not sufficient to correct this metabolic abnormality.
Effectiveness and safety of vitamin D in relation to bone health
Cranney A , Horsley T , O'Donnell S , Weiler H , Puil L , Ooi D , Atkinson S , Ward L , Moher D , Hanley D , Fang M , Yazdi F , Garritty C , Sampson M , Barrowman N , Tsertsvadze A , Mamaladze V . Evid Rep Technol Assess .2007 Aug
OBJECTIVES: To review and synthesize the literature in the following areas: the association of specific circulating 25(OH)D concentrations with bone health outcomes in children, women of reproductive age, postmenopausal women and elderly men; the effect of dietary intakes (foods fortified with vitamin D and/or vitamin D supplementation) and sun exposure on serum 25(OH)D; the effect of vitamin D on bone mineral density (BMD) and fracture or fall risk; and the identification of potential harms of vitamin D above current reference intakes. DATA SOURCES: MEDLINE(R) (1966-June Week 3 2006); Embase (2002-2006 Week 25); CINAHL (1982-June Week 4, 2006); AMED (1985 to June 2006); Biological Abstracts (1990-February 2005); and the Cochrane Central Register of Controlled Trials (2nd Quarter 2006). REVIEW METHODS: Two independent reviewers completed a multi-level process of screening the literature to identify eligible studies (title and abstract, followed by full text review, and categorization of study design per key question). To minimize bias, study design was limited to randomized controlled trials (RCTs) wherever possible. Study criteria for question one were broadened to include observational studies due to a paucity of available RCTs, and question four was restricted to systematic reviews to limit scope. Data were abstracted in duplicate and study quality assessed. Differences in opinion were resolved through consensus or adjudication. If clinically relevant and statistically feasible, meta-analyses of RCTs on vitamin D supplementation and bone health outcomes were conducted, with exploration of heterogeneity. When meta-analysis was not feasible, a qualitative systematic review of eligible studies was conducted. RESULTS: 167 studies met our eligibility criteria (112 RCTs, 19 prospective cohorts, 30 case-controls and six before-after studies). The largest body of evidence on vitamin D status and bone health was in older adults with a lack of studies in premenopausal women and infants, children and adolescents. The quality of RCTs was highest in the vitamin D efficacy trials for prevention of falls and/or fractures in older adults. There was fair evidence of an association between low circulating 25(OH)D concentrations and established rickets. However, the specific 25(OH)D concentrations associated with rickets is uncertain, given the lack of studies in populations with dietary calcium intakes similar to North American diets and the different methods used to determine 25(OH)D concentrations. There was inconsistent evidence of an association of circulating 25(OH)D with bone mineral content in infants, and fair evidence that serum 25(OH)D is inversely associated with serum PTH. In adolescents, there was fair evidence for an association between 25(OH)D levels and changes in BMD. There were very few studies in pregnant and lactating women, and insufficient evidence for an association between serum 25(OH)D and changes in BMD during lactation, and fair evidence of an inverse correlation with PTH. In older adults, there was fair evidence that serum 25(OH)D is inversely associated with falls, fair evidence for a positive association with BMD, and inconsistent evidence for an association with fractures. The imprecision of 25(OH)D assays may have contributed to the variable thresholds of 25(OH)D below which the risk of fractures, falls or bone loss was increased. There was good evidence that intakes from vitamin D-fortified foods (11 RCTs) consistently increased serum 25(OH)D in both young and older adults. Eight randomized trials of ultraviolet (UV)-B radiation (artificial and solar exposure) were small and heterogeneous with respect to determination of the exact UV-B dose and 25(OH)D assay but there was a positive effect on serum 25(OH)D concentrations. It was not possible to determine how 25(OH)D levels varied by ethnicity, sunscreen use or latitude. Seventy-four trials examined the effect of vitamin D(3) or D(2) on 25(OH)D concentrations. Most trials used vitamin D(3), and the majority enrolled older adults. In three trials, there was a greater response of serum 25(OH)D concentrations to vitamin D(3) compared to vitamin D(2), which may have been due to more rapid clearance of vitamin D(2) in addition to other mechanisms. Meta-analysis of 16 trials of vitamin D(3) was consistent with a dose-response effect on serum 25(OH)D when comparing daily doses of <400 IU to doses >/= 400 IU. An exploratory analysis of the heterogeneity demonstrated a significant positive association comparable to an increase of 1 - 2 nmol/L in serum 25(OH)D for every 100 additional units of vitamin D although heterogeneity remained after adjusting for dose. Vitamin D(3) in combination with calcium results in small increases in BMD compared to placebo in older adults although quantitative synthesis was limited due to variable treatment durations and BMD sites. The evidence for fracture reduction with vitamin D supplementation was inconsistent across 15 trials. The combined results of trials using vitamin D(3) (700 - 800 IU daily) with calcium (500 - 1,200 mg) was consistent with a benefit on fractures although in a subgroup analysis by setting, benefit was primarily in elderly institutionalized women (fair evidence from two trials). There was inconsistent evidence across 14 RCTs of a benefit on fall risk. However, a subgroup analysis showed a benefit of vitamin D in postmenopausal women, and in trials that used vitamin D(3) plus calcium. In addition, there was a reduction in fall risk with vitamin D when six trials that adequately ascertained falls were combined. Limitations of the fall and fracture trials included poor compliance with vitamin D supplementation, incomplete assessment of vitamin D status and large losses to follow-up. We did not find any systematic reviews that addressed the question on the level of sunlight exposure that is sufficient to maintain serum 25(OH)D concentrations but minimizes risk of melanoma and non-melanoma skin cancer. There is little evidence from existing trials that vitamin D above current reference intakes is harmful. In most trials, reports of hypercalcemia and hypercalciuria were not associated with clinically relevant events. The Women's Health Initiative study did report a small increase in kidney stones in postmenopausal women aged 50 to 79 years whose daily vitamin D(3) intake was 400 IU (the reference intake for 50 to 70 years, and below the reference intake for > 70 years) combined with 1000 mg calcium. The increase in renal stones corresponded to 5.7 events per 10,000 person-years of exposure. The women in this trial had higher calcium intakes than is seen in most post-menopausal women. CONCLUSIONS: The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.
Dairy and bone health
Heaney RP . Creighton University, USA. J Am Coll Nutr. 2009 Feb
Bone health is the resultant of bone mass, bone architecture, and body mechanics. Nutrition supports all three components, with the principal nutrients concerned being calcium, protein, and vitamin D. Potassium, magnesium, zinc, and several vitamins are also involved to varying extents. Given modern food sources, it is difficult to devise a diet that is "bone healthy" without including three servings of dairy per day, not just because of dairy calcium, but dairy protein and potassium as well.
First-line drugs for hypertension
Wright JM , Musini VM . Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia,, Canada.Cochrane Database Syst Rev. 2009 Jul
BACKGROUND: Sustained elevated blood pressure, unresponsive to lifestyle measures, leads to a critically important clinical question: What class of drug to use first-line? This review answers that question.
OBJECTIVES: Primary objective: To quantify the benefits and harms of the major first-line anti-hypertensive drug classes: thiazides, beta-blockers, calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors, alpha-blockers, and angiotensin II receptor blockers (ARB).
SEARCH STRATEGY: Electronic search of MEDLINE (Jan. 1966-June 2008), EMBASE, CINAHL, the Cochrane clinical trial register, using standard search strategy of the hypertension review group with additional terms. SELECTION CRITERIA: Randomized trials of at least one year duration comparing one of 6 major drug classes with a placebo or no treatment. More than 70% of people must have BP >140/90 mmHg at baseline.
DATA COLLECTION AND ANALYSIS: The outcomes assessed were mortality, stroke, coronary heart disease (CHD), cardiovascular events (CVS), decrease in systolic and diastolic blood pressure, and withdrawals due to adverse drug effects. Risk ratio (RR) and a fixed effects model were used to combine outcomes across trials.
MAIN RESULTS: Of 57 trials identified, 24 trials with 28 arms, including 58,040 patients met the inclusion criteria. Thiazides (19 RCTs) reduced mortality (RR 0.89, 95% CI 0.83, 0.96), stroke (RR 0.63, 95% CI 0.57, 0.71), CHD (RR 0.84, 95% CI 0.75, 0.95) and CVS (RR 0.70, 95% CI 0.66, 0.76). Low-dose thiazides (8 RCTs) reduced CHD (RR 0.72, 95% CI 0.61, 0.84), but high-dose thiazides (11 RCTs) did not (RR 1.01, 95% CI 0.85, 1.20). Beta-blockers (5 RCTs) reduced stroke (RR 0.83, 95% CI 0.72, 0.97) and CVS (RR 0.89, 95% CI 0.81, 0.98) but not CHD (RR 0.90, 95% CI 0.78, 1.03) or mortality (RR 0.96, 95% CI 0.86, 1.07). ACE inhibitors (3 RCTs) reduced mortality (RR 0.83, 95% CI 0.72-0.95), stroke (RR 0.65, 95% CI 0.52-0.82), CHD (RR 0.81, 95% CI 0.70-0.94) and CVS (RR 0.76, 95% CI 0.67-0.85). Calcium-channel blocker (1 RCT) reduced stroke (RR 0.58, 95% CI 0.41, 0.84) and CVS (RR 0.71, 95% CI 0.57, 0.87) but not CHD (RR 0.77 95% CI 0.55, 1.09) or mortality (RR 0.86 95% CI 0.68, 1.09). No RCTs were found for ARBs or alpha-blockers.
AUTHORS' CONCLUSIONS: First-line low-dose thiazides reduce all morbidity and mortality outcomes. First-line ACE inhibitors and calcium channel blockers may be similarly effective but the evidence is less robust. First-line high-dose thiazides and first-line beta-blockers are inferior to first-line low-dose thiazides.
Vitamin D and cardiovascular disease
Nemerovski CW , Dorsch MP , Simpson RU , Bone HG , Aaronson KD , Bleske BE . Department of Pharmacy Services, University of Michigan Health System, USA. Pharmacotherapy. 2009 Jun
The hormonal derivative of vitamin D, 1,25-dihydroxyvitamin D (1,25[OH](2)D) or calcitriol, has been implicated in many physiologic processes beyond calcium and phosphorus homeostasis, and likely plays a role in several chronic disease states, in particular, cardiovascular disease. Experimental data suggest that 1,25(OH)(2)D affects cardiac muscle directly, controls parathyroid hormone secretion, regulates the renin-angiotensin-aldosterone system, and modulates the immune system. Because of these biologic effects, vitamin D deficiency has been associated with hypertension, several types of vascular diseases, and heart failure. We conducted a MEDLINE search of the English-language literature (1950-2008) to identify studies that examined these relationships; additional citations were obtained from the articles retrieved from the literature search. Treatment with vitamin D lowered blood pressure in patients with hypertension and modified the cytokine profile in patients with heart failure. Measurement of serum 25-hydroxyvitamin D concentration usually provides the best assessment of an individual's vitamin D status. Serum levels below 20 ng/ml represent vitamin D deficiency, and levels above 30 ng/ml are considered optimal. Although the observational data linking vitamin D status to cardiovascular disease appear robust, vitamin D supplementation is not recommended as routine treatment for heart disease until definitive prospective, randomized trials can be carried out to assess its effects. However, such supplementation is often appropriate for other reasons and may be beneficial to cardiovascular health in certain patients.
Dietary calcium and magnesium intakes and the risk of type 2 diabetes: the Shanghai Women's Health Study.
Villegas R , Gao YT , Dai Q , Yang G , Cai H , Li H , Zheng W , Shu XO . Vanderbilt Epidemiology Center, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville,Am J Clin Nutr. 2009 Apr
BACKGROUND: Diet plays a key role in the development of type 2 diabetes (T2D), but little is known about the contributions of specific nutrients in populations in which dietary patterns differ from Western populations. OBJECTIVE: We examined associations between calcium and magnesium intakes and the risk of T2D in a Chinese population. DESIGN: We used data from a population-based, prospective study of 64,191 women who were free of T2D or other chronic diseases at study recruitment and were living in urban Shanghai, China. Dietary intake, physical activity, and anthropometric measurements were assessed through in-person interviews. A Cox regression model was used to evaluate the association of the exposures under study with the risk of T2D. RESULTS: An inverse association between calcium and magnesium intakes and T2D risk was observed. The relative risks for the lowest to the highest quintiles of calcium intake were 1.00, 0.82, 0.73, 0.67, and 0.74 (P for trend < 0.001), and for magnesium they were 1.00, 0.84, 0.84, 0.79, and 0.86 (P for trend < 0.001). Milk intake was also inversely associated with the risk of T2D. CONCLUSION: Our data suggest that calcium and magnesium intakes may protect against the development of T2D in this population.
Epidemiology of vitamin D insufficiency and cancer mortality
Pilz S , Tomaschitz A , Obermayer-Pietsch B , Dobnig H , Pieber TR . Department of Internal Medicine, Division of Endocrinology and Nuclear Medicine, Medical University of Graz, Graz, Austria. Anticancer Res. 2009 Sep
There is growing evidence that vitamin D exerts anticarcinogenic effects. Ultraviolet-B (UV-B) radiation, which is required for vitamin D production in the skin, was found to be inversely associated with cancer incidence and mortality. Recent studies have largely but not consistently shown that low 25-hydroxyvitamin D (25(OH)D) levels, which are considered to be the best indicator of vitamin D status, are a significant risk factor for cancer mortality. Circulating 25(OH)D levels were also associated with improved survival in colorectal and lung cancer patients and vitamin D insufficiency was observed in various other diseases such as autoimmune, infectious, musculoskeletal, neurological and cardiovascular diseases. In conclusion, we still need further studies to evaluate the association of vitamin D insufficiency and cancer incidence and mortality, but the multiple health benefits of vitamin D and the easy, safe and inexpensive way by which vitamin D can be supplemented should already guide current public health strategies to achieve 25(OH)D levels of at least 75 nmol/l (30 ng/ml) in the general population.
