Effect of calcium and vitamin D supplementation on blood pressure: the Women's Health Initiative Randomized Trial

Experimental and epidemiological studies suggest that calcium and vitamin D supplements may lower blood pressure. We examined the effect of calcium plus vitamin D supplementation on blood pressure and the incidence of hypertension in postmenopausal women. The Women's Health Initiative Calcium/Vitamin D Trial randomly assigned 36 282 postmenopausal women to receive 1000 mg of elemental calcium plus 400 IU of vitamin D3 daily or placebo in a double-blind fashion. Change in blood pressure and the incidence of hypertension were ascertained. Over a median follow-up time of 7 years, there was no significant difference in the mean change over time in systolic blood pressure (0.22 mm Hg; 95% CI: -0.05 to 0.49 mm Hg) and diastolic blood pressure (0.11 mm Hg; 95% CI: -0.04 to 0.27 mm Hg) between the active and placebo treatment groups. This null result was robust in analyses accounting for nonadherence to study pills and in baseline subgroups of interest, including black subjects and women with hypertension or high levels of blood pressure, with low intakes of calcium and vitamin D or low serum levels of vitamin D. In 17 122 nonhypertensive participants at baseline, the hazard ratio for incident hypertension associated with calcium/vitamin D treatment was 1.01 (95% CI: 0.96 to 1.06.) In postmenopausal women, calcium plus vitamin D3 supplementation did not reduce either blood pressure or the risk of developing hypertension over 7 years of follow-up.     

Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis

OBJECTIVES: To study the efficacy of vitamin E and C supplementation on the progression of carotid atherosclerosis, hypothesizing an enhanced preventive effect in men and in smokers and synergism between vitamins. DESIGN AND SUBJECTS: Double-masked two-by-two factorial trial, randomization in four strata (by gender and smoking status) to receive twice daily either 91 mg (136 IU) of d-alpha-tocopherol, 250 mg of slow-release vitamin C, a combination of these or placebo for three years. A randomized sample of 520 smoking and nonsmoking men and postmenopausal women aged 45-69 years with serum cholesterol >/= 5.0 mmol L-1 were studied. SETTING: The population of the city of Kuopio in Eastern Finland. INTERVENTION: Twice daily either a special formulation of 91 mg of d-alpha-tocopherol, 250 mg of slow-release vitamin C, a combination of these (CellaVie(R)) or placebo for three years. MEASUREMENTS: Atherosclerotic progression, defined as the linear regression slope of ultrasonographically assessed common carotid artery mean intima-media thickness (IMT), was calculated over semi-annual assessments. RESULTS: The average increase of the mean IMT was 0.020 mm year-1 amongst men randomized to placebo and 0.018 mm year-1 in vitamin E, 0.017 mm year-1 in vitamin C and 0.011 mm year-1 in the vitamin combination group (P = 0.008 for E + C vs. placebo). The respective means in women were 0.016, 0.015, 0.017 and 0.016 mm year-1. The proportion of men with progression was reduced by 74% (95% CI 36-89%, P = 0.003) by supplementation with the formulation containing both vitamins, as compared with placebo. CONCLUSIONS: Our study shows that a combined supplementation with reasonable doses of both vitamin E and slow-release vitamin C can retard the progression of common carotid atherosclerosis in men. This may imply benefits with regard to other atherosclerosis-based events.     

The effect of micronutrient supplementation on quality-of-life and left ventricular function in elderly patients with chronic heart failure.

AIMS: Chronic heart failure (CHF) is a common and leading cause of death in industrialized countries. The potential benefits of micronutrient supplementation in CHF are extensive. Therefore, we examined the influence of long-term multiple micronutrient supplementation on left ventricular (LV) function, levels of pro-inflammatory cytokines, and quality-of-life (QoL) in elderly patients with CHF. METHODS AND RESULTS: Thirty CHF patients [age 75.4 (0.7), mean (SEM), LV ejection fraction (LVEF) < or =35%] were randomized to receive capsules containing a combination of high-dose micronutrients (calcium, magnesium, zinc, copper, selenium, vitamin A, thiamine, riboflavin, vitamin B(6), folate, vitamin B(12), vitamin C, vitamin E, vitamin D, and Coenzyme Q10) or placebo for 9 months in a double-blind fashion. All subjects were on stable optimal medical therapy for at least 3 months before enrolment. At randomization and at study end, tumour necrosis factor-alpha and its soluble receptors TNFR-1 and TNFR-2 were measured and six-minute walk test and QoL were assessed. Cardiac magnetic resonance scanning was performed to evaluate cardiac dimensions and LVEF. Two patients died during follow-up. The remaining patients (14 randomized to placebo and 14 to micronutrients) were well matched for LV function, symptoms, and exercise capacity. At the end of the follow-up period, LV volumes were reduced in the intervention group with no change in the placebo group [-13.1 (17.1)% vs. +3.8 (10.0)%; P<0.05]. LVEF increased by 5.3+/-1.4% in the intervention group and was unchanged in the placebo group (P<0.05). Patients taking micronutrients also had a significant improvement in QoL score between enrolment and study end [+9.5 (1.6)%; P<0.05], whereas those taking placebo had a slight deterioration [-1.1 (0.8)%; P=0.12]. Six-minute walk test and inflammatory cytokine levels remained unchanged in both groups. CONCLUSION: Long-term multiple micronutrient supplementation can improve LV volumes and LVEF and QoL scores in elderly patients with heart failure due to LV systolic dysfunction.     

Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial

BACKGROUND: A recent meta-analysis found that cholecalciferol (vitamin D) should reduce falls by more than 20%. However, little is known about whether supplemental cholecalciferol plus calcium citrate malate will lower the long-term risk of falling in men, active older individuals, and older individuals with higher 25-hydroxyvitamin D levels. METHODS: We studied the effect of 3-year supplementation with cholecalciferol-calcium on the risk of falling at least once in 199 men and 246 women 65 years or older and living at home. Individuals received 700 IU of cholecalciferol plus 500 mg of calcium citrate malate per day or placebo in a randomized double-blind manner. Subjects were classified as less physically active if physical activity was below the median level. Low 25-hydroxyvitamin D levels were classified as those below 32 ng/mL (<80 nmol/L). RESULTS: In 3 years, 55% of women and 45% of men reported at least 1 fall. Mean +/- SD baseline 25-hydroxyvitamin D levels were 26.6 +/- 12.7 ng/mL (66.4 +/- 31.7 nmol/L) in women and 33.2 +/- 14.2 ng/mL (82.9 +/- 34.9) in men. Cholecalciferol-calcium significantly reduced the odds of falling in women (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.30-0.97), but not in men (OR, 0.93; 95% CI, 0.50-1.72). Fall reduction was most pronounced in less active women (OR, 0.35; 95% CI, 0.15-0.81). Baseline 25-hydroxyvitamin D level did not modulate the treatment effect. CONCLUSIONS: Long-term dietary cholecalciferol-calcium supplementation reduces the odds of falling in ambulatory older women by 46%, and especially in less active women by 65%. Supplementation had a neutral effect in men independent of their physical activity level.     

Randomized trial testing the effect of vitamin A supplementation on pregnancy outcomes and early mother-to-child HIV-1 transmission in Durban, South Africa. South African Vitamin A Study Group.

OBJECTIVE: Poor vitamin A status has been associated with a higher risk for mother-to-child transmission of HIV-1 and there is contradictory evidence on the impact of vitamin A on perinatal outcome. We therefore assessed the effect of vitamin A supplementation to mothers on birth outcome and mother-to-child transmission of HIV-1. DESIGN AND METHODS: In Durban, South Africa 728 pregnant HIV infected women received either vitamin A (368) or placebo (360) in a randomized, double-blind trial. The vitamin A treatment consisted of a daily dose of 5000 IU retinyl palmitate and 30 mg beta-carotene during the third trimester of pregnancy and 200000 IU retinyl palmitate at delivery. HIV infection results were available on 632 children who were included in the Kaplan-Meier transmission analysis. Results are reported on mother-to-child transmission rates up to 3 months of age. RESULTS: There was no difference in the risk of HIV infection by 3 months of age between the vitamin A [20.3%; 95% confidence interval (CI), 15.7-24.9] and placebo groups (22.3%; 95% CI, 17.5-27.1), nor were there differences in foetal or infant mortality rates between the two groups. Women receiving vitamin A supplement were, however, less likely to have a preterm delivery (11.4% in the vitamin A and 17.4% in the placebo group; P = 0.03) and among the 80 preterm deliveries, those assigned to the vitamin A group were less likely to be infected (17.9%; 95% CI, 3.5-32.2) than those assigned to the placebo group (33.8%; 95% CI, 19.8-47.8). CONCLUSION: Vitamin A supplementation, a low-cost intervention, does not appear to be effective in reducing overall mother-to-child transmission of HIV; however, its potential for reducing the incidence of preterm births, and the risk of mother-to-child transmission of HIV in these infants needs further investigation.     

Effects of maternal vitamin supplements on malaria in children born to HIV-infected women

Vitamin deficiencies are frequent in children suffering from malaria. The effects of maternal multivitamin supplementation on the risk of malaria in children are unknown. We examined the impact of providing multivitamins or vitamin A/beta-carotene supplements during pregnancy and lactation to HIV-infected women on their children's risk of malaria up to 2 years of age, in a randomized, placebo-controlled trial. Tanzanian women (N = 829) received one of four daily oral regimens during pregnancy and after delivery: 1) vitamins B, C, and E (multivitamins); 2) vitamin A and beta-carotene (VA/BC); 3) multivitamins including VA/BC; or 4) placebo. After 6 months of age, all children received 6-monthly oral vitamin A supplements irrespective of treatment arm. The incidence of childhood malaria was assessed through three-monthly blood smears and at monthly and interim clinic visits from birth to 24 months of age. Compared with placebo, multivitamins excluding VA/BC reduced the incidence of clinical malaria by 71% (95% CI = 11-91%; P = 0.02), whereas VA/BC alone resulted in a nonsignificant 63% reduction (95% CI = -4% to 87%; P = 0.06). Multivitamins including VA/BC significantly reduced the incidence of high parasitemia by 43% (95% CI = 2-67%; P = 0.04). The effects did not vary according to the children's HIV status. Supplementation of pregnant and lactating HIV-infected women with vitamins B, C, and E might be a useful, inexpensive intervention to decrease the burden of malaria in children born to HIV-infected women in sub-Saharan Africa.     

Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in Type 2 diabetic patients.

AIMS: Elevated levels of urinary albumin excretion rate (AER) predict high risk for progressing to end-stage renal disease. In streptozotocin-induced diabetes, supplementation with vitamin C or E reduces albuminuria and glomerular hypertrophy. We tested the hypothesis that supplementation of both vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with persistent micro/macroalbuminuria. METHODS: Thirty Type 2 diabetic patients with AER 30-300 mg/24 h were included in a double-blind randomised, cross-over trial. Patients received vitamin C (1250 mg) and vitamin E (680 IU) per day or matching placebo for 4 weeks with a 3-week wash-out period between treatment periods in random order. RESULTS: Combined treatment with vitamin C and E reduced AER by 19% (95% CI 6-34%) (p = 0.04), geometric mean 197 mg/24 h (95% CI 114-341 mg/24 h) vs. 243 mg/24 h (146-404 mg/24 h). No changes were seen in serum creatinine, haemoglobin A1C or blood pressure. Fasting plasma concentrations of vitamin C and E increased in all patients during active treatment (mean vitamin C 79.4 micromol/L (SD 27.8) vs. 41.9 micromol/L (18.4) and vitamin E 47.0 micromol/L (19.8) vs. 29.5 micromol/L (15.3), P < 0.000001). Except for two patients that started additional blood pressure lowering treatment during the run-in period, no changes in medication, food and exercise habits or in the number of smokers occurred during the study. CONCLUSION: Short-term treatment with vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with micro/macroalbuminuria. Further long-term, large-scale studies of this albuminuria reducing treatment modality are warranted.     

Impact of vitamin A on selected gastrointestinal pathogen infections and associated diarrheal episodes among children in Mexico City, Mexico

BACKGROUND: The overall effect of vitamin A supplementation on diarrheal disease in community trials may result from its effect on specific diarrheal pathogens. METHODS: We conducted a placebo-controlled, double-blind trial of the prophylactic effect of vitamin A on gastrointestinal pathogen infections and clinical symptoms among 188 children in Mexico City, Mexico, from January 1998 to May 1999. Children 6-15 months of age were randomly assigned to receive either a vitamin A supplement (for children <12 months of age, 20,000 international units [IU] of retinol; for children > or =12 months of age, 45,000 IU of retinol) every 2 months or a placebo and were followed for up to 15 months. Stool samples, collected semimonthly, were screened for enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC), Shiga toxin-producing E. coli (STEC), enteroinvasive E. coli (EIEC), and Giardia lamblia. RESULTS: Vitamin A supplementation reduced the prevalence of EPEC infections (rate ratio [RR], 0.52 [95% confidence interval {CI}, 0.23-0.86]) and led to shorter durations of both EPEC and ETEC infections. Supplementation also reduced the prevalence of EPEC-associated diarrhea (RR, 0.41 [95% CI, 0.16-1.00]), EPEC-associated fever (RR, 0.15 [95% CI, 0.02-0.98]), and G. lamblia-associated fever (RR, 0.27 [95% CI, 0.13-0.80]). Finally, children who received vitamin A supplementation had shorter durations of EPEC-associated diarrhea than did children who did not receive supplementation but had longer durations of G. lamblia-associated diarrhea. CONCLUSIONS: These results suggest that the effect of vitamin A supplementation on clinical outcomes may be pathogen dependent.     

HIV incidence among post-partum women in Zimbabwe: risk factors and the effect of vitamin A supplementation

OBJECTIVE: To test whether post-partum vitamin A supplementation can reduce incident HIV among post-partum women and identify risk factors for HIV incidence. DESIGN: Randomized, placebo-controlled trial METHODS: Between November 1997 and January 2001, 14,110 women were randomly administered 400,000 IU vitamin A or placebo within 96 h post-partum. HIV incidence was monitored among 9562 HIV-negative women. RESULTS: Cumulative incidence was 3.4% [95% confidence interval (CI), 3.0-3.8] and 6.5% (95% CI, 5.7-7.4) over 12 and 24 months post-partum, respectively. Vitamin A supplementation had no impact on incidence [hazard ratio (HR), 1.08; 95% CI, 0.85-1.38]. However, among 398 women for whom baseline serum retinol was measured, those with levels indicative of deficiency (< 0.7 micromol/l, 9.2% of those measured) were 10.4 (95% CI, 3.0-36.3) times more likely to seroconvert than women with higher concentrations. Furthermore, among women with low serum retinol, vitamin A supplementation tended to be protective against incidence (HR, 0.29; 95% CI, 0.03-2.60; P = 0.26), although not significantly so, perhaps due to limited statistical power. Severe anaemia (haemoglobin < 70 g/l) was associated with a 2.7-fold (95%CI, 1.2-6.1) greater incidence. Younger women were at higher risk of HIV infection: incidence declined by 5.7% (2.8-8.6) with each additional year of age. CONCLUSION: Among post-partum women, a single large-dose vitamin A supplementation had no effect on incidence, although low serum retinol was a risk factor for seroconversion. Further investigation is required to determine whether vitamin A supplementation of vitamin-A-deficient women or treatment of anaemic women can reduce HIV incidence.     

A randomized trial of beta carotene supplementation and cognitive function in men: the Physicians' Health Study II

BACKGROUND: Oxidative stress contributes to brain aging. Antioxidant treatment, especially over the long term, might confer cognitive benefits. METHODS: We added cognitive testing to the Physicians' Health Study II (PHSII), a randomized trial of beta carotene and other vitamin supplements for chronic disease prevention. The PHSII is a continuation of the Physicians' Health Study (PHS), which had randomized male participants to low-dose aspirin and beta carotene. Participants include those continuing their original beta carotene assignment from the PHS, begun in 1982, and newer recruits randomized as of 1998. The beta carotene arm (50 mg, alternate days) was terminated; follow-up is ongoing for the remaining arms. Near the close of the beta carotene arm, we interviewed 5956 participants older than 65 years to assess general cognition, verbal memory, and category fluency. The primary end point was a global score averaging all tests (using z scores); the secondary end point was a verbal memory score combining results of 4 tests. We compared mean cognition among those assigned to beta carotene vs placebo. We separately examined new recruits and continuing participants. RESULTS: Among 1904 newly recruited subjects (mean treatment duration, 1 year), cognition was similar across treatment assignments. Among 4052 continuing participants from the PHS (mean treatment duration, 18 years), the mean global score was significantly higher in the beta carotene group than in the placebo group (mean difference in z scores, 0.047 standard units; P = .03). On verbal memory, men receiving long-term beta carotene supplementation also performed significantly better than the placebo group (mean difference in z scores, 0.063; P = .007). CONCLUSION: We did not find an impact of short-term beta carotene supplementation on cognitive performance, but long-term supplementation may provide cognitive benefits.     

Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women

BACKGROUND: Ergocalciferol (vitamin D(2)) supplementation plays a role in fall prevention, but the effect in patients living in the community in sunny climates remains uncertain. We evaluated the effect of ergocalciferol and calcium citrate supplementation compared with calcium alone on the risk of falls in older women at high risk of falling. METHODS: A 1-year population-based, double-blind, randomized controlled trial of 302 community-dwelling ambulant older women aged 70 to 90 years living in Perth, Australia (latitude, 32 degrees S), with a serum 25-hydroxyvitamin D concentration of less than 24.0 ng/mL and a history of falling in the previous year. Participants were randomized to receive ergocalciferol, 1000 IU/d, or identical placebo (hereinafter, ergocalciferol and control groups, respectively). Both groups received calcium citrate, 1000 mg/d. Fall data were collected every 6 weeks. RESULTS: Ergocalciferol therapy reduced the risk of having at least 1 fall over 1 year after adjustment for baseline height, which was significantly different between the 2 groups (ergocalciferol group, 53.0%; control group, 62.9%; odds ratio [OR], 0.61; 95% confidence interval [CI], 0.37-0.99). When those who fell were grouped by the season of first fall or the number of falls they had, ergocalciferol treatment reduced the risk of having the first fall in winter and spring (ergocalciferol group, 25.2%; control group, 35.8%; OR, 0.55; 95% CI, 0.32-0.96) but not in summer and autumn, and reduced the risk of having 1 fall (ergocalciferol group, 21.2%; control group, 33.8%; OR, 0.50; 95% CI, 0.28-0.88) but not multiple falls. CONCLUSION: Patients with a history of falling and vitamin D insufficiency living in sunny climates benefit from ergocalciferol supplementation in addition to calcium, which is associated with a 19% reduction in the relative risk of falling, mostly in winter.     

The Melbourne Atherosclerosis Vitamin E Trial (MAVET): a study of high dose vitamin E in smokers.

OBJECTIVE: Our aim was to evaluate whether vitamin E (500 IU) slowed the progression of carotid atherosclerosis in a population of chronic smokers over 4 years as measured by ultrasound determination of carotid intima-media thickness (IMT) and systemic arterial compliance (SAC). METHODS: The Melbourne Atherosclerosis Vitamin E Trial (MAVET) was a randomized, double-blind, placebo-controlled trial in which 409 male and female smokers aged 55 years and over were randomized to receive 500 IU per day of natural vitamin E or placebo. The primary endpoint was progression of carotid atherosclerosis determined by intima-media thickness of the right common carotid artery. Secondary outcomes were change in systemic arterial compliance and low-density lipoprotein (LDL) oxidative susceptibility over time. RESULTS: The mean increase in intima-media thickness over time in the vitamin E group was 0.0041 mm/year faster than placebo (95% confidence interval -0.0021 to 0.0102 mm/year, P = 0.20). Similarly, a non-significant difference between vitamin E and placebo was found for rate of change in systemic arterial compliance (P = 0.11). Vitamin E supplementation did, however, significantly reduce LDL oxidative susceptibility (P < 0.001). CONCLUSION: Vitamin E supplementation is ineffective in reducing the progression of carotid atherosclerosis as measured by intima-media thickness in chronic smokers. This finding extends our knowledge of lack of effectiveness of vitamin E supplementation in populations with high oxidant stress.     

Association between apolipoprotein E4 and cognitive decline in elderly adults

OBJECTIVE: To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women. DESIGN: Prospective study. SETTING: Scotland, Ireland, and the Netherlands. PARTICIPANTS: Five thousand eight hundred four subjects aged 70 to 82 from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). MEASUREMENTS: Subjects were assessed at baseline and over a mean 3.2‐year (range 0.7–4.2) follow‐up for memory (Picture‐Word Recall), speed of information processing (Stroop and Letter‐Digit Coding), global cognitive function (Mini‐Mental State Examination), and activities of daily living. RESULTS: At baseline, subjects with apolipoprotein E₄ versus those without E₄ had poorer memory performance (mean score difference ?0.20 (95% confidence interval (CI)=?0.31 to ?0.09) for immediate recall and ?0.32 (95% CI=?0.48 to ?0.16) for delayed recall and slower information processing (difference in Stroop, 2.79 seconds, (95% CI=1.20–4.28); Letter‐Digit score, ?0.36, (95% CI=?0.77–0.05). Subjects with apolipoprotein E₄ showed a greater decline in immediate (?0.22, 95% CI=?0.33 to ?0.11) and delayed (?0.30, 95% CI=?0.46 to ?0.15) memory scores but no significant change in speed of information processing (Stroop, P=.17; Letter‐Digit, P=.06). Memory scores decreased 2.5% from baseline in those without E₄, 4.3% in E₄ heterozygotes (P=.01 for immediate and P=.03 for delayed, vs no E₄) and 8.9% to 13.8% in E₄ homozygotes (P=.04 for immediate and P=.004 for delayed, vs heterozygotes). Apolipoprotein E₄ was associated with greater decline in instrumental activities of daily living (P<.001). Cognitive decline was not associated with lipoprotein levels. CONCLUSION: Findings in PROSPER indicate that E₄ is associated with more‐rapid cognitive decline and may, therefore, predispose to dementia.     

The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals

BACKGROUND: It has been suggested that a low dietary intake of antioxidant vitamins and minerals increases the incidence rate of cardiovascular disease and cancer. To date, however, the published results of randomized, placebo-controlled trials of supplements containing antioxidant nutrients have not provided clear evidence of a beneficial effect. We tested the efficacy of nutritional doses of supplementation with a combination of antioxidant vitamins and minerals in reducing the incidence of cancer and ischemic cardiovascular disease in the general population. METHODS: The Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study is a randomized, double-blind, placebo-controlled primary prevention trial. A total of 13 017 French adults (7876 women aged 35-60 years and 5141 men aged 45-60 years) were included. All participants took a single daily capsule of a combination of 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 mug of selenium, and 20 mg of zinc, or a placebo. Median follow-up time was 7.5 years. RESULTS: No major differences were detected between the groups in total cancer incidence (267 [4.1%] for the study group vs 295 [4.5%] for the placebo group), ischemic cardiovascular disease incidence (134 [2.1%] vs 137[2.1%]), or all-cause mortality (76 [1.2%] vs 98 [1.5%]). However, a significant interaction between sex and group effects on cancer incidence was found (P = .004). Sex-stratified analysis showed a protective effect of antioxidants in men (relative risk, 0.69 [95% confidence interval [CI], 0.53-0.91]) but not in women (relative risk, 1.04 [95% CI, 0.85-1.29]). A similar trend was observed for all-cause mortality (relative risk, 0.63 [95% CI, 0.42-0.93] in men vs 1.03 [95% CI, 0.64-1.63] in women; P = .11 for interaction). CONCLUSIONS: After 7.5 years, low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women. Supplementation may be effective in men only because of their lower baseline status of certain antioxidants, especially of beta carotene.     

A randomized, placebo-controlled, double-blind, flexible-dose study of fluoxetine in the treatment of women with fibromyalgia

PURPOSE: To assess the efficacy of fluoxetine in the treatment of patients with fibromyalgia. SUBJECTS AND METHODS: Sixty outpatients (all women, aged 21-71 years) with fibromyalgia were randomly assigned to receive fluoxetine (10-80 mg/d) or placebo for 12 weeks in a double-blind, parallel-group, flexible-dose study. The primary outcome measures were the Fibromyalgia Impact Questionnaire total score (score range, 0 [no impact] to 80) and pain score (score range, 0-10). Secondary measures included the McGill Pain Questionnaire, change in the number of tender points, and total myalgic score. RESULTS: In the intent-to-treat analysis, women who received fluoxetine (mean [+/- SD] dose, 45 +/- 25 mg/d) had significant (P = 0.005) improvement in the Fibromyalgia Impact Questionnaire total score compared with those who received placebo, with a difference of -12 (95% confidence interval [CI]: -19 to -4). They also had significant (P = 0.002) improvement in the Fibromyalgia Impact Questionnaire pain score (difference, -2.2 [95% CI: -3.6 to -0.9]), as well as in the Fibromyalgia Impact Questionnaire fatigue (P = 0.05) and depression (P = 0.01) scores and the McGill Pain Questionnaire (P = 0.01), when compared with subjects who received placebo. Although counts for the number of tender points and total myalgic scores improved more in the fluoxetine group than in the placebo group, these differences were not statistically significant. CONCLUSIONS: In a 12-week, flexible-dose, placebo-controlled trial, fluoxetine was found to be effective on most outcome measures and generally well tolerated in women with fibromyalgia.     

Effect of multivitamin and mineral supplementation on episodes of infection in nursing home residents: a randomized, placebo-controlled study

OBJECTIVES: To evaluate the effect of vitamin and mineral supplementation on infections in an elderly institutionalized population. DESIGN: Eighteen-month, randomized, placebo-controlled trial. SETTING: Twenty-one long-term care facilities. PARTICIPANTS: Seven hundred sixty-three subjects from 21 long-term care facilities. INTERVENTION: Participants were randomized to receive one multivitamin and mineral supplementation daily or placebo. MEASUREMENTS: The primary outcome was number of infections per subject. Secondary outcomes were antibiotic use and hospitalization rates. Infection control surveillance was conducted over 18 months using standardized criteria. RESULTS: Outcome data from 748 subjects, mean age 85, were included in the intention-to-treat analysis. Using univariate analyses, there was no difference in infectious episodes between the supplemented and placebo groups (3.5 infections per 1,000 resident-days vs 3.8 infections per 1,000 resident-days, odds ratio (OR)=0.92, 95% confidence interval (CI)=0.82-1.03, P=.12). There was a reduction in antibiotic usage in the supplementation group, but this was not significant in the multivariate model. There was no difference in the number of hospital visits. In the multivariate analysis, the effect of multivitamin use on total number of infections was not significant (OR=0.77, 95% CI=0.54-1.1). Subjects without dementia had a greater rate of infections than those with dementia (OR=1.44, 95% CI=1.19-1.76). In post hoc subgroup analysis, subjects without dementia who received supplementation had a significantly lower rate of infections than those who received placebo (relative risk=0.81, 95% CI=0.66-0.99). CONCLUSION: Overall, multivitamin and mineral supplementation does not have a significant effect on the incidence of infections in institutionalized seniors, although the subgroup of residents in long-term care without dementia may benefit from supplementation. Further research is needed to determine its effect in high-risk subgroups within the nursing home population.     

The impact of the use of statins on the prevalence of dementia and the progression of cognitive impairment

BACKGROUND: Previous evidence suggests that treatment with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors (statins) has a positive impact on dementia. We decided to investigate the association between the use of statins and the prevalence of dementia and statins' impact on the progression of cognitive impairment. METHODS: This is a case-control and a retrospective cohort study of a community-based ambulatory primary care geriatric practice. We included a convenience sample of all patients (N = 655, mean age 78.7 +/- 0.3 years, 85% Caucasian, 74% women) with hypercholesterolemia or dementia, or using statins. We compared those using statins with those who do not with respect to the clinical diagnosis of dementia and its subtypes and the progression of cognitive impairment. RESULTS: At the initial visit, 35% had dementia, and 17% were using statins. After covariate adjustments, patients on statins were less likely to have dementia (odds ratio [OR] for dementia based on composite definition = 0.23; 95% confidence interval [CI] [0.1-0.56], p =.001, OR Alzheimer's disease = 0.37; 95% CI [0.19-0.74], p =.005, OR vascular dementia = 0.25; 95% CI [0.08-0.85], p =.027). At follow-up, patients on statins showed an improvement on their Mini-Mental Status Examination score by 0.7 +/- 0.4 compared to a decline by 0.5 +/- 0.3 in controls, p =.025 (OR for no change or improvement on statins = 2.81; 95% CI [1.02-8.43], p =.045) and scored higher on the Clock Drawing Test (difference of 1.5 +/- 0.1, p =.036). CONCLUSIONS: The use of statins is associated with a lower prevalence of dementia and has a positive impact on the progression of cognitive impairment.     

Effect of supplementation with antioxidants upon long-term risk of hypertension in the SU.VI.MAX study: association with plasma antioxidant levels

OBJECTIVE: To assess the effects of supplementation with a combination of antioxidant vitamins and trace elements, at nutritional doses, upon the 6.5-year risk of hypertension in the SU.VI.MAX trial. To describe the association between baseline plasma antioxidant levels and the same long-term risk using observational data from the study. SETTING: A total of 5086 adults from the SU.VI.MAX trial, a randomized primary prevention trial. RESULTS: Compared with the placebo group, no effect of supplementation upon the 6.5-year risk of hypertension could be detected (odds ratio, 1.04 and 95% confidence interval, 0.87-1.23 in men; and odds ratio, 1.10 and 95% confidence interval, 0.95-1.29 in women). Furthermore, compared with men in the first tertile, those in the second and third tertiles of serum baseline levels of beta-carotene presented a lower risk of hypertension in both the placebo and supplementation groups. Multivariate-adjusted odds ratios (95% confidence interval) were 0.70 (0.44-1.12) and 0.53 (0.33-0.86) in the placebo group, and were 0.59 (0.37-0.94) and 0.67 (0.42-1.07) in the supplementation group. In women, a decreasing trend was observed with vitamin C levels and risk of hypertension in the intervention group. No association could be shown between vitamin E and trace element plasma levels and the risk of hypertension. CONCLUSIONS: Despite an inverse association between baseline plasma levels of beta-carotene in men and the risk of developing hypertension, we could not demonstrate any beneficial effect of low-dose antioxidant supplementation upon the 6.5-year risk of hypertension in the randomized analysis.     

Effects of calcium supplementation on serum lipid concentrations in normal older women: a randomized controlled trial

PURPOSE: To determine the effect of supplementation with calcium citrate on circulating lipid concentrations in normal older women. SUBJECTS AND METHODS: As part of a study of the effects of calcium supplementation on fractures, we randomly assigned 223 postmenopausal women (mean [+/- SD] age, 72 +/- 4 years), who were not receiving therapy for hyperlipidemia or osteoporosis, to receive calcium (1 g/d, n = 111) or placebo (n = 112) for 1 year. Fasting serum lipid concentrations, including high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol, were obtained at baseline, and at 2, 6, and 12 months. RESULTS: After 12 months, HDL cholesterol levels and the HDL cholesterol to LDL cholesterol ratio had increased more in the calcium group than in the placebo group (mean between-group differences in change from baseline: for HDL cholesterol, 0.09 mmol/L (95% confidence interval [CI]: 0.02 to 0.17; P = 0.01); for HDL/LDL cholesterol ratio, 0.05 (95% CI: 0.02 to 0.08; P = 0.001). This was largely due to a 7% increase in HDL cholesterol levels in the calcium group, with a nonsignificant 6% decline in LDL cholesterol levels. There was no significant treatment effect on triglyceride level (P = 0.48). CONCLUSION: Calcium citrate supplementation causes beneficial changes in circulating lipids in postmenopausal women. This suggests that a reappraisal of the indications for calcium supplementation is necessary, and that its cost effectiveness may have been underestimated.     

The effects of vitamin C supplementation on serum concentrations of uric acid: results of a randomized controlled trial

OBJECTIVE: Reductions in serum uric acid levels are clinically relevant. Previous studies have suggested a uricosuric effect of vitamin C. Whether vitamin C reduces serum uric acid is unknown. We undertook this study to determine the effects of vitamin C supplementation on serum uric acid concentrations. METHODS: The study was a double-blinded placebo-controlled randomized trial conducted in research units affiliated with an academic institution. Study participants were 184 nonsmokers, randomized to take either placebo or vitamin C supplements (500 mg/day) for 2 months. RESULTS: At the end of the study period, serum uric acid levels were significantly reduced in the vitamin C group (mean change -0.5 mg/dl [95% confidence interval -0.6, -0.3]), but not in the placebo group (mean change 0.09 mg/dl [95% confidence interval -0.05, 0.2]) (P < 0.0001). The same pattern of results was evident in subgroups defined by age, sex, race, body mass index, chronic illness, diuretic use, and quartiles of baseline serum ascorbic acid levels. In the subgroups, from the lowest to the highest quartile of baseline serum uric acid, net mean changes (95% confidence intervals) in serum uric acid with vitamin C supplementation were -0.4 (-0.8, 0.01), -0.5 (-0.9, -0.2), -0.5 (-0.8, -0.2), and -1.0 (-1.6, -0.4) mg/dl (P = 0.06, 0.005, 0.003, and 0.002, respectively). Compared with placebo, vitamin C increased the estimated glomerular filtration rate. CONCLUSION: Supplementation with 500 mg/day of vitamin C for 2 months reduces serum uric acid, suggesting that vitamin C might be beneficial in the prevention and management of gout and other urate-related diseases.