Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial. Vitamin B-6 supplementation in elderly men: effects on mood, memory, performance and mental effort. Thiamine status, vitamin supplements and postoperative confusion. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. Thiamine and folate treatment of chronic epileptic patients: a controlled study with the Wechsler IQ scale. Effect of vitamin A supplementation on immune function of well-nourished children suffering from vitamin A deficiency in China. No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study. Effect of vitamin K administration on acarboxy prothrombin (PIVKA-II) levels in newborns. Vitamin A supplementation fails to reduce incidence of acute respiratory illness and diarrhea in preschool-age Indonesian children. Vitamin E status in preterm infants fed human milk or infant formula. Effect of vitamin A supplementation on childhood morbidity and mortality. Effects of a long-term vitamin D and calcium supplementation on falls and parameters of muscle function in community-dwelling older individuals. Randomised trial of vitamin A supplementation in pregnant women in rural Malawi found to be anaemic on screening by HemoCue. Zinc plus beta-carotene supplementation of pregnant women is superior to beta-carotene supplementation alone in improving vitamin A status in both mothers and infants. A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS).
Vitamin B-12 deficiency is associated with cognitive impairment in older people. However, evidence from randomized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive.
                The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged >/=70 y with mild vitamin B-12 deficiency.
                In a double-blind, placebo-controlled trial, 195 subjects were randomly assigned to receive 1000 microg vitamin B-12, 1000 microg vitamin B-12 + 400 microg folic acid, or placebo for 24 wk. Vitamin B-12 status was assessed on the basis of methylmalonic acid, total homocysteine (tHcy), and holotranscobalamin (holoTC) concentrations before and after 12 and 24 wk of treatment. Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention, construction, sensomotor speed, memory, and executive function.
                Vitamin B-12 status did not change significantly after treatment in the placebo group; however, oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency. Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36%. Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone (P = 0.0036). Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains.
                Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function. This study evaluates the effects of vitamin B-6 supplementation (20 mg pyridoxine HCL daily for 3 months) on mood and performance in 38 self-supporting healthy men, aged between 70-79 years. Effects were compared with 38 controls who received placebo and were matched for age, plasma pyridoxal-5'-phosphate (PLP) concentration and intelligence score. Before and after drug intervention vitamin B-6 status was determined, and mood and performance were measured by means of a computerized testing system. In addition, the phasic pupil response was measured in order to assess mental effort. Positive effects of vitamin B-6 supplementation were only found with respect to memory, especially concerning long-term memory. In view of the finding that mental performance improvement and delta PLP values were most strongly correlated within an intermediate range of delta PLP, it is suggested that cognitive effects are primarily associated with a certain range of vitamin B-6 status increment. The general conclusion is that vitamin B-6 supplementation improves storage of information modestly but significantly. In a prospective, randomized, controlled study an intravenous vitamin B complex and vitamin C preparation was administered pre- and post-operatively to 28 elderly patients with a fractured proximal femur and compared with 32 nonsupplemented postoperative controls. Vitamin supplementation significantly, though only transiently, improved postoperative thiamine status (P less than 0.001), but had no influence on mental state or outcome during the postsurgical period. Therefore, the use of parenteral vitamins for postoperative confusion cannot be justified on a routine basis. This study of 9605 community-dwelling residents supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in elderly in a northern European region known to be deficient in vitamin D, especially during winter periods.
                We evaluated the effect of two programs for the prevention of osteoporotic fractures leading to acute hospital admission in a population of elderly community-dwelling residents.
                This was a factorial, cluster-randomized, pragmatic, intervention study. We included 9605 community-dwelling residents aged 66+ years. We offered a prevention program of a daily supplement of 1000 mg of elemental calcium as calcium carbonate and 400 IU (10 microg) of vitamin D3 to a total of 4957 participants. Another program with evaluation and suggestions for the improvement of the domestic environment was offered to a total of 5063 participants. Both programs included revision of the resident's current pharmaceutical treatment. We achieved information on osteoporotic fractures in the study population from the Danish Hospital Registration Database. We defined osteoporotic fractures as low energy fractures of the proximal humerus, distal forearm, vertebral column, pelvis, cervical femur, and intertrochanteric femur.
                Active participation was 50.3% in the Calcium and Vitamin D Program and 46.4% in the Environmental and Health Program. We observed a 16% reduction in fracture incidence rate (relative risk [RR], 0.84; CI, 0.72-0.98; p < 0.025) among male and female residents offered the Calcium and Vitamin D Program (intention-to-prevent analysis).
                This study supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in community-dwelling elderly people in a northern European region known to be deficient in vitamin D, especially during winter periods. Seventy-two epileptic patients receiving phenytoin (PHT) alone or in combination with phenobarbital for more than 4 years were divided into four groups, the first taking two placebo tablets per day; the second folate (5 mg/day) and placebo; the third placebo and thiamine (50 mg/day); and the fourth both vitamins. The clinical trial lasted 6 months. At baseline assessment, 31% of the patients had subnormal blood thiamine levels and 30% had low folate. The vitamin deficiencies were independent phenomena. It was found that thiamine improved neuropsychological functions in both verbal and non-verbal IQ testing. In particular, higher scores were recorded on the block design, digit symbol, similarities and digit span subtests. Folate treatment was ineffective. These results indicate that, in epileptics chronically treated with PHT, thiamine improves neuropsychological functions, such as visuo-spatial analysis, visuo-motor speed and verbal abstracting ability. To clearly clarify the protective effect of vitamin A supplementation on immune function of well-nourished children suffering from vitamin A deficiency.
                Three hundred sixty-two children in two kindergartens in Wuhan China were enrolled. Detailed dietary assessment and anthropometry were undertaken to facilitate the exclusion of malnourished children. Seventy vitamin A-deficient children with informed consent were randomly divided into the vitamin A-deficient-supplemented group and vitamin A-deficient placebo group, 35 vitamin A-sufficient children (age- and sex-matched with the vitamin A-deficient-supplemented group children) were selected as vitamin A-sufficient placebo group. The baseline and follow-up level of selected immune parameters of the 105 children in three intervention groups were compared.
                The total proportion of severe and marginal vitamin A-deficient children was 10.9 and 21.96%, respectively. At baseline, the serum complement C3 and sIgA level of vitamin A-sufficient children was significantly higher than that of vitamin A-deficient children (P < 0.05). However, the serum lysozyme level of vitamin A-sufficient children was inversely lower. After intervention, vitamin A-deficient-supplemented children increased serum vitamin A, complement C3 and sIgA level, but their serum lysozyme level inversely decreased.
                Vitamin A deficiency was still a serious health problem in children in China cities. Vitamin A supplementation was efficacious in ameliorating serum vitamin A status and partially impaired immune function of well-nourished children suffering from vitamin A deficiency. Associations between vitamin B-12 deficiency and impaired cognitive function and depression have been reported.
                A randomized placebo controlled study including 140 individuals with an increased plasma methylmalonic acid (0.40-2.00 micromol/l) not previously treated with vitamin B-12. Cognitive function was assessed by the Cambridge Cognitive Examination (CAMCOG), Mini-Mental State Examination (MMSE), and a 12-words learning test. Symptoms of depression were evaluated by the Major Depression Inventory. The main outcome measure was change in cognitive function and depression score from baseline to follow-up 3 months later.
                At baseline 78 (56%) individuals had cognitive impairment judged from the CAMCOG score and 40 (29%) according to the MMSE; 18 (13%) individuals had symptoms of depression. No improvement was found in cognitive function comparing the treatment and placebo group (total CAMCOG score: P = 0.43), nor among individuals with only slightly impaired cognitive function (n = 44, total CAMCOG score: P = 0.42). The treatment group did not improve in depression score as compared to the placebo group (P = 0.18).
                The duration of impaired cognitive function was unknown.
                A high proportion of individuals with an increased plasma methylmalonic acid had impaired cognitive function, and a rather high prevalence of depression was observed. However, vitamin B-12 treatment did not improve cognitive function or symptoms of depression within the 3-months study period. PIVKA-II (protein induced by vitamin K absence or antagonist-II) was measured in two groups of newborns, one group being given 5 mg vitamin K at birth and the other untreated. The untreated group had a significantly higher proportion of PIVKA-II positive babies at 3 and 5 days of age than did the treated group. When vitamin K was administered to newborn babies whose normotest levels were less than 30%, it was found that the higher the pre-treatment PIVKA-II levels the greater the response to vitamin K, as monitored by the normotest. Thus PIVKA-II levels might be more useful than a coagulation test, since the low activity of vitamin K dependent coagulation factors sometimes reflects not vitamin K deficiency but impaired production of these factors because of immaturity. The findings support the view that vitamin K given prophylactically at birth will help to prevent neonatal bleeding. Vitamin A supplementation of populations of vitamin A-deficient preschool-age children has been shown to reduce childhood mortality, but the primary preventive effects of such supplements on childhood infectious diseases have not been carefully evaluated. We conducted an individually randomized, placebo-controlled, double-masked trial among 1,407 Indonesian preschool-age children, to measure the effects of high dose vitamin A on acute respiratory and diarrheal illnesses. Signs and symptoms of morbidity were monitored using every other day home surveillance by trained interviewers. High dose vitamin A supplements increased the incidence of acute respiratory illnesses (ARI) by 8%, and acute lower respiratory illnesses (ALRI) by 39%. These detrimental effects on acute lower respiratory illnesses were most marked in children with adequate nutritional status (rate ratio 1.83, 95% confidence interval 1.257-2.669). In contrast, vitamin A tended to be protective of ALRI in chronically malnourished children (rate ratio 0.71, 95% confidence interval 0.375-1.331). There was no overall effect of high-dose vitamin A supplements on the incidence of diarrheal disease (rate ratio 1.06, 95% confidence interval 0.920-1.225). However, we found a significant interaction between supplementation and age: vitamin A increased the incidence of diarrhea in children < 30 mo of age, but tended to reduce the incidence in older children. The finding of a significant adverse effect of vitamin A supplements in adequately nourished children highlights the need to review the criteria for selecting populations of preschool-age children for vitamin A supplementation. Vitamin E status was assessed in 36 infants with birth weights less than 1500 gm who were assigned randomly to receive one of three sources of nutrition: milk obtained from mothers of preterm infants (preterm milk), mature human milk, or infant formula. Infants in each dietary group were further assigned randomly to receive iron supplementation (2 mg/kg/day) beginning at 2 weeks or to receive no iron supplementation. All infants received a standard multivitamin, providing 4.1 mg alpha-tocopherol daily. Serum vitamin E concentrations at 6 weeks were significantly related both to type of milk (P less than 0.0001) and to iron supplementation (P less than 0.05). Infants fed preterm milk had significantly higher serum vitamin E levels than did infants fed mature human milk, and both groups had significantly higher levels than did those fed formula. Ratios of serum vitamin E/total lipid were also significantly greater for infants fed human milks than for those fed formula. The addition of iron to all three diets resulted in significantly lower serum vitamin E levels at 6 weeks (P less than 0.05); however, only in the group fed formula was there evidence of vitamin E deficiency. Preterm milk with routine multivitamin supplementation uniformly resulted in vitamin E sufficiency in VLBW infants whether or not iron was administered. In a double blind design, 1520 children aged < 10 years were individually randomised in vitamin A and placebo group in slums of Chandigarh. Children > 12, 6-12 and < 6 months of age received 200,000, 100,000, 500,000 I.U. of vitamin A respectively every 4 to 6 months during 15 months trial period. The prevalence of vitamin A deficiency was significantly reduced in vitamin A compared to placebo group during the follow-up period. In vitamin A group, incidence of diarrhoea and measles was significantly reduced but incidence of acute respiratory infections was not significantly different compared to control group. Risk of death was also significantly less in vitamin A group. Therefore, promotion of vitamin A rich diet or supplementation with synthetic vitamin A at 4-6 month interval should be a priority in populations where risk of vitamin A deficiency is high. In 242 community-dwelling seniors, supplementation with either 1000 mg of calcium or 1000 mg of calcium plus vitamin D resulted in a decrease in the number of subjects with first falls of 27% at month 12 and 39% at month 20. Additionally, parameters of muscle function improved significantly.
                The efficacy of vitamin D and calcium supplementation on risk of falling in the elderly is discussed controversially. Randomized controlled trials using falls as primary outcome are needed. We investigated long-term effects of calcium and vitamin D on falls and parameters of muscle function in community-dwelling elderly women and men.
                Our study population consisted of 242 individuals recruited by advertisements and mailing lists (mean [ +/- SD] age, 77 +/- 4 years). All serum 25-hydroxyvitamin D (25[OH]D) levels were below 78 nmol/l. Individuals received in a double blinded fashion either 1000 mg of calcium or 1000 mg of calcium plus 800 IU of vitamin D per day over a treatment period of 12 months, which was followed by a treatment-free but still blinded observation period of 8 months. Falls were documented using diaries. The study took place in Bad Pyrmont, Germany (latitude 52 degrees ) and Graz, Austria (latitude 46 degrees ).
                Compared to calcium mono, supplementation with calcium plus vitamin D resulted in a significant decrease in the number of subjects with first falls of 27% at month 12 (RR = 0.73; CI = 0.54-0.96) and 39% at month 20 (RR = 0.61; CI = 0.34-0.76). Concerning secondary endpoints, we observed significant improvements in quadriceps strength of 8%, a decrease in body sway of 28%, and a decrease in time needed to perform the TUG test of 11%.
                Combined calcium and vitamin D supplementation proved superior to calcium alone in reducing the number of falls and improving muscle function in community-dwelling older individuals. To assess the effects of vitamin A supplementation in women with anaemia during pregnancy.
                Single-centre randomised controlled trial.
                Rural community in southern Malawi, central Africa.
                Seven hundred women with singleton pregnancies at 12-24 weeks measured by ultrasound scan and with haemoglobin <11.0 g/dl by HemoCue screening method. Analysis was by intention to treat. All received iron and folate, and sulphadoxine/pyrimethamine for antimalarial prophylaxis.
                Women were randomised to receive oral supplementation with daily 5000 or 10,000 iu vitamin A, or placebo.
                Anaemia, as assessed by Coulter counter, severe anaemia, iron status and indices of infection.
                Vitamin A deficiency was, in this rural population, less common than predicted. Vitamin A supplementation had no significant impact on anaemia, severe anaemia, iron status and indices of infection. Vitamin A stores were less likely to be depleted at the end of pregnancy in supplemented groups.
                Vitamin A supplementation programmes to reduce anaemia should not be implemented in similar antenatal populations in rural sub-Saharan Africa unless evidence emerges of positive benefit on substantive clinical outcomes. Introducing public health interventions of unknown benefit and with unclear biological mechanisms can divert scarce resources from clinical and social interventions more likely to impact maternal mortality. Deficiencies of vitamin A, iron, and zinc are prevalent in women and infants in developing countries. Supplementation during pregnancy can benefit mother and infant.
                We examined whether supplementation during pregnancy with iron and folic acid plus beta-carotene or zinc or both improves the micronutrient status of mothers and infants postpartum.
                Pregnant women (n = 170) were supplemented daily only during pregnancy with beta-carotene (4.5 mg), zinc (30 mg), or both or placebo plus iron (30 mg) and folic acid (0.4 mg) in a randomized, double-blind, placebo-controlled trial. Micronutrient status was assessed 1 and 6 mo postpartum.
                Six months postpartum, plasma retinol concentrations were higher in the women who received zinc during pregnancy than in women who did not. Infants born to mothers supplemented with beta-carotene + zinc had higher plasma retinol concentrations, with the frequency of vitamin A deficiency reduced by >30% compared with the other 3 groups. Breast-milk beta-carotene concentrations were higher in all women supplemented with beta-carotene, but breast-milk retinol concentrations were higher only in women who received beta-carotene + zinc. Zinc concentrations did not differ among groups in mothers and infants.
                Zinc supplementation during pregnancy improved the vitamin A status of mothers and infants postpartum, which indicates a specific role of zinc in vitamin A metabolism. Addition of both beta-carotene and zinc to iron supplements during pregnancy could be effective in improving the vitamin A status of mothers and infants. To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge.
                Multicenter, randomized, controlled trial with a factorial design.
                Five hospitals in Auckland, New Zealand, and Sydney, Australia.
                Two hundred forty-three frail older people.
                Patients were randomized to receive a single dose of vitamin D (calciferol, 300,000 IU) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits.
                The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months. Physical performance and self-rated function were secondary endpoints. Assessments took place in the participants' homes at 3 and 6 months after randomization and were performed by blinded assessors.
                There was no effect of either intervention on physical health or falls, but patients in the exercise group were at increased risk of musculoskeletal injury (risk ratio = 3.6, 95% confidence interval = 1.5-8.0). Vitamin D supplementation did not improve physical performance, even in those who were vitamin D deficient (<12 ng/mL) at baseline.
                Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization. There was no effect of vitamin D on physical performance, and the exercises increased the risk of musculoskeletal injury. These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people.
In view of methodological deficiencies and limited number of individual studies, we have found no reliable evidence to support the routine use of vitamins in patients with epilepsy. Further trials are needed, especially to assess the utility of vitamin D supplementation to prevent osteomalacia and the role of vitamin E on seizures and thiamine in improving cognitive functions.