Hannes B. Stähelin

Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial.

Specific receptors for vitamin D have been identified in human muscle tissue. Cross‐sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls. We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls. In a double‐blind randomized controlled trial, we studied 122 elderly women (mean age, 85.3 years; range, 63–99 years) in long‐stay geriatric care. Participants received 1200 mg calcium plus 800 IU cholecalciferol (Cal+D‐group; n = 62) or 1200 mg calcium (Cal‐group; n = 60) per day over a 12‐week treatment period. The number of falls per person (0, 1, 2–5, 6–7, >7 falls) was compared between the treatment groups. In an intention to treat analysis, a Poisson regression model was used to compare falls after controlling for age, number of falls in a 6‐week pretreatment period, and baseline 25‐hydroxyvitamin D and 1,25‐dihydroxyvitamin D serum concentrations. Among fallers in the treatment period, crude excessive fall rate (treatment − pretreatment falls) was compared between treatment groups. Change in musculoskeletal function (summed score of knee flexor and extensor strength, grip strength, and the timed up&go test) was measured as a secondary outcome. Among subjects in the Cal+D‐group, there were significant increases in median serum 25‐hydroxyvitamin D (+71%) and 1,25‐dihydroxyvitamin D (+8%). Before treatment, mean observed number of falls per person per week was 0.059 in the Cal+D‐group and 0.056 in the Cal‐group. In the 12‐week treatment period, mean number of falls per person per week was 0.034 in the Cal+D‐group and 0.076 in the Cal‐group. After adjustment, Cal+D‐treatment accounted for a 49% reduction of falls (95% CI, 14–71%; p < 0.01) based on the fall categories stated above. Among fallers of the treatment period, the crude average number of excessive falls was significantly higher in the Cal‐group (p = 0.045). Musculoskeletal function improved significantly in the Cal+D‐group (p = 0.0094). A single intervention with vitamin D plus calcium over a 3‐month period reduced the risk of falling by 49% compared with calcium alone. Over this short‐term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function.

A Pooled Analysis of Vitamin D Dose Requirements for Fracture Prevention

BACKGROUND The results of meta-analyses examining the relationship between vitamin D supplementation and fracture reduction have been inconsistent. METHODS 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 participants adherence to the treatment and supplement use outside the study protocol) in the treatment groups of all trials with data from the control groups. RESULTS 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. CONCLUSIONS 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.).

Plasma levels of antioxidant vitamins in relation to ischemic heart disease and cancer

Aggressive oxygen species (such as superoxide anion, hydroxyl radical, and singlet oxygen) have been implicated in carcinogenesis and arterial injury by ischemia followed by reoxygenation, arteriosclerosis, ionizing radiation, etc (1). Health hazards by these oxygen species can to some extent be prevented by the body’s multilevel defense system against free radicals, which comprises enzymes (eg, superoxide dismutase and glutathione peroxidase), endogenous nonessential antioxidants (eg, glutathione and uric acid), and last but not least antioxidant vitamins (1). Because the dietary supply of the principal essential antioxidants, ie, a-carotene and the vitamins A, C, and E, can vary considerably the body’s defense potential may in part be inversely related to the status ofantioxidant vitamins. This concept is in agreement with data from animals and human beings. In animals deficiency of vitamin A results in metaplasia whereas experimentally induced tumors can be diminished by /3-carotene and vitamins A, C, and E (2). Chronic marginal deficiency of vitamins C or E were reported to lead to arteriosclerosis-like lesions in rodents and piglets, and, interestingly, experimental scurvy in man also caused cardiomegaly, electrocardiographic abnormalities, and acute cardiac emergency in some subjects. In animal models ofarteriosclerosis, supplements of the vitamins A, C, or E have been shown to reduce the number oflesions (1). In the human there is abundant evidence from dietary surveys that the consumption of fresh fruits and leafy green-yellow vegetables as well as the calculated consumption of the above-mentioned essential antioxidants is inversely related to the incidence of cancers (36). The measurement of plasma antioxidants in previous prospective studies regarding the overall incidence ofcancers yielded mostly inconsistent results (2). This, however, could be due to imperfections of the protocol of the blood-bank type (eg, destruction ofplasma vitamins during storage in the deep freeze, analysis of plasma of a relatively low number of cases, and analysis ofa comparably low number of matched controls). In cross-sectional comparisons the vegetarian type of diet was also associated with a lower mortality from ischemic heart disease (IHD), and the standardized mortality for heart disease in England, Wales, Scotland, Norway, and Israel was reported to be inversely correlated with the calculated ascorbic acid intake from fresh fruits and green vegetables (1). However, a calculated commodity consumption is not conclusive for the in vivo status of a vitamin since food tables have an inherent inaccuracy, losses occurring during storage, cooking procedures are hard to account for, and the calculation ofone particular constituent of fruits/ vegetables does not prove that it is the responsible ingredient. Many of these arguments thus lead to the question: Does a poor plasma status of antioxidant vitamins really occur in westernized countries and, if so, is it associated with an increased risk of cancer and IHD? There are in principle three steps to an answer: first, cross-cultural epidemiology with the measurement of the plasma levels; second, corresponding prospective studies; and third, intervention trials. The presently available evidence regarding IHD is mainly based on cross-cultural comparisons whereas the hardest data on cancer were obtained by the prospective approach.

The relation between antioxidants and memory performance in the old and very old

OBJECTIVES: Aging processes, and among them brain aging, are thought to be associated with free radical action. It is hypothesized that plasma antioxidant vitamin levels correlate with cognitive performance in healthy older subjects.

Muscle strength in the elderly: Its relation to vitamin d metabolites

OBJECTIVE To identify a relation between loss of muscle strength and vitamin D deficiency in ambulatory elderly persons not receiving vitamin D supplementation. DESIGN Cross-sectional study. SETTING All measurements were taken at the Department of Geriatrics, University Hospital, Basel, Switzerland. SUBJECTS Three hundred nineteen patients (103 women, 216 men) selected by random sampling from participants in an ongoing interdisciplinary study on aging (mean age for women, 74.2 yrs; for men, 76.7 yrs). OUTCOME MEASURES Leg extension power (LEP) and body mass index (BMI); serum values of 25-hydroxyvitamin D [calcidiol, 25(OH)D], 1,25-hydroxyvitamin D [calcitriol, 1,25(OH)2D], and intact parathyroid hormone (iPHT). RESULTS Twelve percent of women and 18% of men had 25(OH)D values below the normal range (<12 ng/mL). Muscle strength was lower in older subjects (female: r = -.35; p = .0005/male: r = -.48; p < .0001) and was lower in women than in men (p < .0001). In men both 25(OH)D and 1,25(OH)2D was significantly correlated with LEP (r = 0.24; p = .0004/r = .14; p = .045). In women, only 1,25(OH)2D was significantly correlated with LEP (r = 0.22; p = .034). In an ANCOVA including all participants and explaining LEP by sex, age, BMI, 1,25(OH)2D, 25(OH)D, and iPTH, all factors showed significant effects except 25(OH)D and iPTH (r2 = .41). CONCLUSION Muscle strength declined with age in ambulatory elderly people and showed modest, but significant, positive correlation with 1,25(OH)2 vitamin D in both sexes and with 25(OH)D in male subjects. Therefore vitamin D deficiency appears to contribute to the age-related loss of muscle strength, which might be more pronounced in institutionalized elderly people with a high prevalence of vitamin D deficiency.

Prediction of male cancer mortality by plasma levels of interacting vitamins: 17-year follow-up of the prospective Basel study

Plasma vitamins C, E, retinol and carotene were measured in 1971–1973 in 2,974 men working in Basel Switzerland. In 1990, the vital status of all participants was assessed. A total of 290 men had died from cancer during the 17 years of follow‐up, including 87 with lung cancer, 30 with prostate cancer, 28 with stomach cancer and 22 with colon cancer. Overall mortality from cancer was associated with low mean plasma levels of carotene (adjusted for cholesterol) and of vitamin C. Lung and stomach cancers were associated with a low mean plasma carotene level. After calculation of the relative risk, using the Cox model, with exclusion of mortality during the first 2 years of follow‐up, simultaneously low levels of plasma carotene (below quartile I) and lipid‐adjusted retinol were related to a significantly increased mortality risk for all cancers and for lung cancer. Simultaneously, low levels of plasma vitamin C and lipid‐adjusted vitamin E also were associated with a significantly increased risk for lung cancer. Additionally, low vitamin E levels in smokers were related to an increased risk for prostate cancer. It is concluded that low plasma levels of the vitamins C, E, retinol and carotene are related to increased risk of subsequent overall and lung‐cancer mortality and that low levels of vitamin E in smokers are related to an increased risk of prostate‐cancer mortality.

Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily.

Objectives: To study the effect of alfacalcidol (1α(OH)D3) on fall risk in community‐dwelling elderly men and women.

Effect of High-Dosage Cholecalciferol and Extended Physiotherapy on Complications After Hip Fracture: A Randomized Controlled Trial

BACKGROUND Care of elderly patients after hip fracture is not well established. METHODS We enrolled 173 patients with acute hip fracture who were 65 years or older (79.2% women; mean age, 84 years; 77.4% living at home). Using a factorial design, we randomly allocated patients to extended physiotherapy (PT) (supervised 60 min/d during acute care plus an unsupervised home program) vs standard PT (supervised 30 min/d during acute care plus no home program; single-blinded), and to cholecalciferol therapy, 2000 vs 800 IU/d (double-blinded). Primary outcome was rate of falls; secondary outcome was rate of hospital readmissions during the 12-month follow-up. All analyses included 173 individuals and used multivariate Poisson regression analyses. RESULTS At baseline, 50.9% of participants had 25-hydroxyvitamin D levels of less than 12 ng/mL and 97.7% of less than 30 ng/mL. We documented 212 falls and 74 hospital readmissions. Because this was a factorial design trial, all analyses tested the main effect of each treatment while controlling for the other in 173 participants. Extended vs standard PT reduced the rate of falls by 25% (95% confidence interval [CI], -44% to -1%). Cholecalciferol treatment, 2000 vs 800 IU/d, did not reduce falls (28%; 95% CI, -4% to 68%), but reduced the rate of hospital readmissions by 39% (95% CI, -62% to -1%). CONCLUSIONS Extended PT was successful in reducing falls but not hospital readmissions, whereas cholecalciferol treatment, 2000 IU/d, was successful in reducing hospital readmission but not falls. Thus, the 2 strategies may be useful together because they address 2 different and important complications after hip fracture.

Oral supplementation with 25(OH)D3 versus vitamin D3: effects on 25(OH)D levels, lower extremity function, blood pressure, and markers of innate immunity.

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.

Smoking, plasma vitamins C, E, retinol, and carotene, and fatal prostate cancer: Seventeen‐year follow‐up of the prospective Basel study

Prostate cancer has one of the highest incidence rates of all cancers. Vitamin intake and tobacco use may have an impact on incidence and mortality, but epidemiologic evidence is scarce and inconsistent.