BACKGROUND: The impact of vitamin D supplementation on cardiovascular outcomes and mortality risk reduction remains unclear due to conflicting study findings.
METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), published between 1983 and 2022, that reported the effect of vitamin D supplementation in adults versus placebo or no treatment on all-cause mortality (ACM), cardiovascular mortality (CVM), non-cardiovascular mortality (non-CVM), and cardiovascular morbidities. Only studies with a follow-up period longer than one year were included. The primary outcomes were ACM and CVM. Secondary outcomes were non-CVM, myocardial infarction, stroke, heart failure, and major or extended adverse cardiovascular events. Subgroup analyses were performed according to low-, fair- and good-quality RCTs.
RESULTS: Eighty RCTs were assessed, including 82,210 participants receiving vitamin D supplementation and 80,921 receiving placebo or no treatment. The participants' mean (SD) age was 66.1 (11.2) years, and 68.6% were female. Vitamin D supplementation was associated with a lower risk of ACM (OR: 0.95 [95%CI 0.91-0.99] p = 0.013), was close to statistical significance for a lower risk of non-CVM (OR: 0.94 [95%CI 0.87-1.00] p = 0.055), and was not statistically associated with a lower risk of any cardiovascular morbi-mortality outcome. Meta-analysis of low-quality RCTs showed no association with cardiovascular or non-cardiovascular morbi-mortality outcomes.
CONCLUSIONS: The emerging results of our meta-analysis present evidence that vitamin D supplementation appears to decrease the risk of ACM (especially convincing in the fair- and good-quality RCTs), while not showing a decrease in the specific cardiovascular morbidity and mortality risk. Thus, we conclude that further research is warranted in this area, with well-planned and executed studies as the basis for more robust recommendations.
BACKGROUND: Vitamin D supplements may only be beneficial for the prevention of osteoporotic fractures when administered with calcium and in individuals with low blood levels of 25(OH)D, but possible hazards of calcium supplements on CVD cannot be excluded.
OBJECTIVES: We conducted a meta-analysis of all placebo-controlled randomized trials assessing the effects of calcium supplements alone or with vitamin D on CHD, stroke, and all-cause mortality.
METHODS: A meta-analysis of 11 trials included 7 comparisons of calcium alone compared with control (n = 8634) and 6 comparisons of calcium plus vitamin D compared with control (n = 46,804). Aggregated study-level data were obtained from individual trials and combined using a fixed-effects meta-analysis. The main outcomes included MI, CHD death, any CHD, stroke, and all-cause mortality.
RESULTS: Among trials of calcium alone (mean daily dose 1 g), calcium was not significantly associated with any excess risk of MI (RR, 1.15; 95% CI: 0.88, 1.51; n = 219 events), CHD death (RR, 1.24; 95% CI: 0.89, 1.73; n = 142), any CHD (RR, 1.01; 95% CI: 0.75, 1.37; n = 177), or stroke (RR, 1.15; 95% CI, 0.90, 1.46, n = 275). Among 6 trials of combined treatment, supplementation with calcium plus vitamin D was not significantly associated with any excess risk of MI (RR, 1.09; 95% CI: 0.95, 1.25; n = 854), CHD death (RR, 1.04; 95% CI: 0.85, 1.27; n = 391), any CHD (RR, 1.05; 95% CI: 0.93, 1.19; n = 1061), or stroke (RR, 1.02; 95% CI: 0.89, 1.17; n = 885). Likewise, calcium alone, or with vitamin D had no significant associations with all-cause mortality.
CONCLUSIONS: This meta-analysis demonstrated that calcium supplements were not associated with any significant hazard for CHD, stroke, or all-cause mortality and excluded excess risks above 0.3%-0.5% per year for CHD or stroke. Further trials of calcium and vitamin D are required in individuals with low blood levels of 25(OH)D for the prevention of fracture and other disease outcomes.
Revista»Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
ABSTRACT: Previous randomized controlled trials have reported inconsistent findings regarding the effects of high-dose vitamin D supplementation on a risk of falls and fractures. This meta-analysis of 15 trials shows that intermittent or single high-dose vitamin D supplementation had no preventive effect on the risk of falls and fractures and might even increase the risk of falls.
PURPOSE: Randomized controlled trials (RCTs) have reported controversial findings regarding the associations between intermittent or single high-dose vitamin D supplementation and a risk of falls and fractures in adults. This study aimed to investigate those associations using a systematic review and meta-analysis.
METHODS: We searched PubMed, EMBASE, and Cochrane Library from inception to May 25, 2022. Data were extracted for a random-effects meta-analysis to calculate a pooled relative risk (RR) with a 95% confidence interval (CI).
RESULTS: Out of 527 articles, a total of 15 RCTs were included in the final analysis. In a meta-analysis of RCTs, intermittent or single high-dose vitamin D supplementation showed no significant beneficial effect in the prevention of either falls (RR, 1.03 [95% CI, 0.98-1.09]; I2 = 56.6%; n = 11) or fractures (RR, 0.99 [95% CI, 0.87-1.14]; I2 = 48.3%; n = 11). Among the subgroup meta-analyses by various factors, intermittent or single high-dose vitamin D supplementation reduced the risk of fractures in the subgroup meta-analysis of RCTs that included fewer than 1000 participants (RR, 0.74 [95% CI 0.57-0.96]; I2 = 0.0%; n = 5). However, its beneficial effect was not observed in those including 1000 or more participants (RR, 1.06 [95% CI 0.92-1.21]; I2 = 57.5%; n = 6). In contrast, intermittent or single high-dose vitamin D3 supplementation increased the risk of falls on the borderline of statistical significance (RR, 1.06 [95% CI 0.99-1.15]; P = 0.051; I2 = 50.0%; n = 7).
CONCLUSIONS: Intermittent or single high-dose vitamin D supplementation had no preventive effect on the risk of falls and fractures and might even increase the risk of falls.
OBJECTIVES: It has been recognized that nutritional interventions play a role in improving the nutritional and functional status of older persons. This systematic review summarizes the evidence on nutritional and functional outcomes of nutritional interventions alone or in combination with physical exercise in geriatric rehabilitation patients.
DESIGN: Eight electronic databases were searched until July 1, 2019 to identify nutritional intervention studies in patients aged ≥60 years who were admitted to geriatric rehabilitation. A meta-analysis was performed to quantify intervention effects on serum albumin, muscle mass, and hand grip strength (HGS).
RESULTS: A total of 1962 studies were screened and 13 included in the systematic review. Studies were heterogeneous in interventions (4 nutritional interventions, 6 physical exercise + nutritional intervention, 1 timing of protein provision, 1 exercise + dietary advice, 1 nutrition-related nursing care) and outcomes. Among the 9 interventions that tested oral nutritional supplements (ONS) with protein, with or without exercise, 7 studies reported protein intake and 6 showed increased protein intakes, 2 of 5 studies showed increased albumin levels, and 5 of 9 reported an improvement in functional outcomes (BI, Functional Independence Measure, mobility). Meta-analyses showed no significant intervention effects on albumin [standardized mean difference (SMD) 0.45, 95% confidence interval (CI) -0.14, 1.04 (4 studies)], muscle mass [mean difference (MD) 2.14 kg, 95% CI -2.17, 6.45 (3 studies)], and HGS [SMD -0.04, 95% CI -0.55, 0.63 (3 studies)], but was based on a very limited number of studies.
CONCLUSIONS AND IMPLICATIONS: Only a limited number of studies with heterogeneous nutritional interventions and outcomes were available in the geriatric rehabilitation population. Studies that included ONS improved nutritional outcomes, especially protein intake and albumin levels. Functional outcomes improved in the majority of reporting studies. This indicates benefits of protein supplementation, with or without exercise, in this population. Future well-designed and well-powered clinical trials are needed to clarify existing controversial aspects.
BACKGROUND: Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies.
METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method.
RESULTS: We included 107 trials (193,987 postmenopausal women; mean age of 66 years; 55% Caucasian; median follow-up of 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, PTH 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone and calcitonin. Teriparatide, abaloparatide, denosumab and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and SERMs had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials.
CONCLUSIONS: This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.
Recent guidelines have advocated against the use of vitamin D supplementation as a means to prevent falls in older adults. However, meta-analyses of the available trials have reached divergent conclusions, and the key design features of these trials have not been well characterized. We conducted a systematic review of 30 randomized trials that reported the effects of vitamin D supplements on falls. Trials were identified by reviewing references of published meta-analyses and updated with a systematic PubMed search. We assessed three key design features: (1) recruitment of participants with vitamin D deficiency or insufficiency; (2) provision of daily oral vitamin D supplementation; and (3) utilization of highly sensitive at-event falls ascertainment. The trials enrolled a median of 337 (IQR: 170-1864) participants. Four (13.3%) trials restricted enrollment to those who were at least vitamin D insufficient, 18 (60.0%) included at least one arm providing daily supplementation, and 16 (53.3%) used at-event reporting. There was substantial heterogeneity between trials, and no single trial incorporated all three key design features. Rather than concluding that vitamin D is ineffective as a means to prevent falls, these findings suggest that existing trial evidence is insufficient to guide recommendations on the use of vitamin D supplements to prevent falls.
BACKGROUND: Falls in individuals aged ≥ 60 years may result in injury, hospitalisation or death. The role of anti-hypertensive medications in falls among older adults is unclear.
OBJECTIVE: The objective of this study was to assess the association of six anti-hypertensive medication classes, namely α-blockers (AB), angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), β-blockers (BB), calcium channel blockers (CCB) and diuretics, with the risk of falls, injurious falls or recurrent falls in individuals aged ≥ 60 years compared with non-users.
METHODS: We performed systematic searches in PubMed, EMBASE and CINAHL and included cohort, case-control and cross-sectional studies that investigated the associations between the use of anti-hypertensive medication classes and the risk of falls, injurious falls or recurrent falls in older adults (≥ 60 years) reported in English. We assessed study quality using the Newcastle-Ottawa Scale (NOS). Unadjusted and adjusted odds ratios (ORs) were pooled using random effects model. We performed meta-analyses for each anti-hypertensive medication class and each fall outcome. We also performed sensitivity analyses by pooling studies of high quality and subgroup analyses among studies with an average age of ≥ 80 years.
RESULTS: Seventy-eight articles (where 74, 34, 27, 18, 13 and 11 of them examined diuretics, BB, CCB, ACEi, AB and ARB, respectively) met our inclusion and exclusion criteria; we pooled estimates from 60 articles. ACEi [OR 0.85, 95% confidence interval (CI) 0.81-0.89], BB (OR 0.84, 95% CI 0.76-0.93) and CCB (OR 0.81, 95% CI 0.74-0.90) use were associated with a lower risk of injurious falls than in non-users. Results in sensitivity and subgroup analyses were largely consistent.
CONCLUSION: The use of ACEi, BB or CCB among older adults may be associated with a lower risk of injurious falls than non-use.
Background: Various interventions have been tested as primary prevention of colorectal cancers (CRC), but comprehensive evidence comparing them is absent. We examined the effects of various chemopreventive agents (CPAs) on CRC incidence and mortality. Methods: We did a network meta-analysis based on a systematic review of randomized controlled trials (RCTs) that compared at least one CPA (aspirin, antioxidants, folic acid, vitamin B6, vitamin B12, calcium, vitamin D, alone or in combination) to placebo or other CPA in persons without history of CRC. Several databases were searched from inception up to March 2017. Primary outcomes were early and long-term CRC incidence and mortality. Results: Twenty-one RCTs comprising 281,063 participants, 9 RCTS comprising 160,101 participants, and 7 RCTs comprising 24,001 participants were included in the network meta-analysis for early risk of CRC incidence, long-term risk of CRC incidence and mortality, respectively. For early CRC incidence, no CPAs were found to be effective. For long-term CRC incidence and mortality, aspirin was the only intervention that showed protective effects with potential dose-dependent effects (risk ratio [RR], 0.74 [95% CI, 0.57–0.97] for high-dose [≥325 mg/day] and RR, 0.81 [95% CI, 0.67–0.98] for very-low-dose [≤100 mg/day]). Similar trend was found for mortality (RR, 0.43 [95% CI, 0.23–0.81] for low-dose [>100–325 mg/day] and RR, 0.65 [95% CI, 0.45–0.94] for very-low-dose). However, in net clinical benefit analysis, when combining risk estimates on mortality from CRC, cardiovascular disease, and pooled risk estimates of major gastrointestinal bleeding, low-dose aspirin provided the highest net survival gain (%) of 1.736 [95% CI, 1.010–2.434]. Conclusion: Aspirin at the dose range of 75–325 mg/day is a safe and effective primary prevention for long-term CRC among people at average risk. None of the other CPAs were found to be effective. There may potentially be differential effects among various doses of aspirin that needs further investigation.
BACKGROUND: older adults are known to have increased falls rates and functional decline following hospital discharge, with substantial economic healthcare costs. This systematic review aimed to synthesise the evidence for effective falls prevention interventions in older adults recently discharged from hospital.
METHODS: literature searches of six databases of quantitative studies conducted from 1990 to June 2017, reporting falls outcomes of falls prevention interventions for community-dwelling older adults discharged from hospital were included. Study quality was assessed using a standardised JBI critical appraisal tool (MAStARI) and data pooled using Rev-Man Review Manager®.
RESULTS: sixteen studies (total sample size N = 3,290, from eight countries, mean age 77) comprising 12 interventions met inclusion criteria. We found home hazard modification interventions delivered to those with a previous falls history (1 study), was effective in reducing the number of falls (RR 0.63, 95%CI 0.43, 0.93, Low GRADE evidence). Home exercise interventions (3 studies) significantly increased the proportion of fallers (OR 1.74, 95%CI 1.17, 2.60, Moderate GRADE evidence), and did not significantly reduce falls rate (RR 1.27, 95%CI 0.99, 1.62, Very Low GRADE evidence) or falls injury rate (RR 1.16, 95%CI, 0.83,1.63, Low GRADE evidence). Nutritional supplementation for malnourished older adults (1 study) significantly reduced the proportion of fallers (HR 0.41, 95% CI 0.19, 0.86, Low GRADE evidence).
CONCLUSION: the recommended falls prevention interventions for older adults recently discharged from hospital are to provide home hazard minimisation particularly if they have a recent previous falls history and consider nutritional supplementation if they are malnourished.
The impact of vitamin D supplementation on cardiovascular outcomes and mortality risk reduction remains unclear due to conflicting study findings.
METHODS:
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), published between 1983 and 2022, that reported the effect of vitamin D supplementation in adults versus placebo or no treatment on all-cause mortality (ACM), cardiovascular mortality (CVM), non-cardiovascular mortality (non-CVM), and cardiovascular morbidities. Only studies with a follow-up period longer than one year were included. The primary outcomes were ACM and CVM. Secondary outcomes were non-CVM, myocardial infarction, stroke, heart failure, and major or extended adverse cardiovascular events. Subgroup analyses were performed according to low-, fair- and good-quality RCTs.
RESULTS:
Eighty RCTs were assessed, including 82,210 participants receiving vitamin D supplementation and 80,921 receiving placebo or no treatment. The participants' mean (SD) age was 66.1 (11.2) years, and 68.6% were female. Vitamin D supplementation was associated with a lower risk of ACM (OR: 0.95 [95%CI 0.91-0.99] p = 0.013), was close to statistical significance for a lower risk of non-CVM (OR: 0.94 [95%CI 0.87-1.00] p = 0.055), and was not statistically associated with a lower risk of any cardiovascular morbi-mortality outcome. Meta-analysis of low-quality RCTs showed no association with cardiovascular or non-cardiovascular morbi-mortality outcomes.
CONCLUSIONS:
The emerging results of our meta-analysis present evidence that vitamin D supplementation appears to decrease the risk of ACM (especially convincing in the fair- and good-quality RCTs), while not showing a decrease in the specific cardiovascular morbidity and mortality risk. Thus, we conclude that further research is warranted in this area, with well-planned and executed studies as the basis for more robust recommendations.
