Klotho, FGF21 and FGF23: Novel Pathways to Musculoskeletal Health?

Bone mineral density, muscle mass and physical function reach their peak between the second and fourth decade of life and then decline steadily with aging. The crucial question is: what factors contribute to or modulate this decline? The aim of this mini-review is to propose a theoretical framework for the potential role of emerging biomarkers such as klotho, fibroblast growth factors (FGF)21 and FGF23 on musculoskeletal health, with a particular focus on decline in muscle mass and function, and calls for future research to examine this proposed link. The identification of new physiological mechanisms underlying these declines may open a potentially important avenue for the development of novel intervention strategies aimed at preventing or reducing their potentially detrimental consequences.

Coverage of the vitamin A supplementation programme for child survival in Nepal: success and challenges.

BACKGROUND: Nepal's national vitamin A programme, which began in 1993 and continues twice yearly, targets pre-school-aged children in all districts of the country in an effort to reduce morbidity, mortality and nutritional blindness. OBJECTIVE: To characterize the coverage of the Nepal National Vitamin A Programme (NVAP) for pre-school-aged children in Nepal and to identify risk factors for failure to receive vitamin A supplementation. METHODS: The relationship between receipt of a vitamin A capsule and demographic and health indicators was examined in a cross-sectional study of 4013 children aged 12-59 months and their families who participated in the 2011 Nepal Demographic and Health Survey (NDHS), a nationally representative survey. Coverage of the vitamin A programme was compared with coverage estimates from surveys in 2001 and 2006. RESULTS: Coverage estimates of the national vitamin A programme for children aged 12-59 months as assessed by the 2001, 2006 and 2011 NDHS were 84.3%, 96.6% and 92.1%, respectively. Children who missed a vitamin A capsule were more likely to be younger and anaemic, have less educated parents, live in rural areas, and have higher child and infant mortality in the family. CONCLUSIONS: The national vitamin A supplementation programme in Nepal has relatively high coverage of children aged 12-59 months but still misses children in families with high child mortality. Further measures might be needed to sustain a high level of programme coverage.

Diet quality and social support: factors associated with serum carotenoid concentrations among older disabled women (the Women's Health and Aging Study).

PURPOSE: This study investigated the relationship between social support (including instrumental support, emotional support, social interaction, social space, and family networks) and diet quality, as indicated by serum carotenoid levels. DESIGN AND METHODS: The sample consisted of participants in the Women's Health and Aging Study with longitudinal carotenoid data (n=325). We performed regression analyses using baseline indicators of social support and changes in social support to determine whether baseline levels and/or change in levels of social support predict changes in serum carotenoid levels. Social support changes were measured over 1 year from baseline to follow-up round 1. Carotenoid level changes were established from follow-up round 1 to round 2. To determine whether or not regression to the mean was driving these results, we performed an analysis that included baseline and change levels of social support indicators. RESULTS: At baseline, the frequency of leaving one's home was associated with a decrease in carotenoid levels. Leaving one's home more frequently predicted an increase in carotenoid levels and attending fewer activities predicted a decrease in carotenoid levels. IMPLICATIONS: In older, community-resident disabled women, baseline levels of social support did not consistently predict diet quality. However, change in social support predicted both positive and negative change in diet quality and thus provides supportive evidence that social activity and family interaction may play meaningful roles in the maintenance of diet quality among functionally compromised older women. Further research is necessary to more fully understand the impact of multiple forms of social supports on the diet quality of older adults.

Serum carotenoids and pulmonary function in older community-dwelling women.

BACKGROUND AND OBJECTIVES: Deterioration in pulmonary function is associated with greater disability and mortality in older adults. Dietary antioxidants are implicated in lung health, but the relationship between major dietary antioxidants, such as serum carotenoids, and pulmonary function have not been well characterized. Serum carotenoids are considered the most reliable indicator of fruit and vegetable intake. SUBJECTS AND METHODS: We examined the relationship between serum α-carotene, ß-carotene, ß-cryptoxanthin, lutein/zeaxanthin, and lycopene with pulmonary function (forced expiratory volume in one second [FEV1] and forced vital capacity [FVC]) in a population-based sample of 631 moderately to severely disabled community-dwelling older women (Women's Health and Aging Study I) in Baltimore, Maryland, USA. RESULTS: Higher serum α-carotene and ß-carotene concentrations were positively associated with both FEV1 and FVC, respectively (all P < 0.05), in separate multivariate linear regression models adjusting for age, race, education, cognition, anemia, inflammation, and chronic diseases. Total serum carotenoids were associated with FEV1 (P = 0.08) and FVC (P = 0.06), respectively, in similar models. No association was found between ß-cryptoxanthin, lutein/zeaxanthin, and lycopene, and FEV1 or FVC. CONCLUSIONS: Higher serum α-carotene and ß-carotene concentrations, which reflect greater intake of orange and dark green leafy fruits and vegetables, were associated with better pulmonary function among older community-dwelling women.function may lead to food avoidance and to a higher incidence of digestive complaints.

Dietary intake associated with serum versus urinary carboxymethyl-lysine, a major advanced glycation end product, in adults: the Energetics Study.

BACKGROUND/OBJECTIVES: Advanced glycation end products (AGEs) are implicated in the pathogenesis of atherosclerosis, diabetes and kidney disease. The objective was to describe dietary intake, the dominant source of exposure to AGEs, with carboxymethyl-lysine (CML), a major AGE, in serum and urine, respectively. SUBJECTS/METHODS: Serum and urinary CML were measured in 261 adults, aged 21-69 years, and compared with diet as assessed by six separate 24-h dietary recalls. RESULTS: Median (25th, 75th percentile) serum and urinary CML concentrations were 686 (598, 803) µg/l and 1023 (812, 1238) µg/gm creatinine. There was no correlation between serum and urinary CML (r=-0.02, P=0.78). Serum CML was positively correlated with intake of soy, fruit juice, cold breakfast cereal, non-fat milk, whole grains, fruit, non-starchy vegetables and legumes, and negatively correlated with intake of red meat. Intake of fast food was not significantly correlated with serum CML. Urinary CML was positively correlated with intake of starchy vegetables, whole grains, sweets, nuts/seeds and chicken, and negatively correlated with intake of fast foods. Intake of AGE-rich foods such as fried chicken, French fries, bacon/sausage and crispy snacks were not significantly correlated with serum or urinary CML, except for a significant negative correlation between fried chicken and serum CML. CONCLUSIONS: These findings suggest that the high consumption of foods considered high in CML is not a major determinant of either serum or urinary CML. Further work is needed to understand the relationship of AGEs in blood and urine with the metabolism of dietary AGEs.

Relationship of household food insecurity to anaemia in children aged 6-59 months among families in rural Indonesia.

BACKGROUND: Anaemia is a significant global public health problem in developing countries with adverse health effects on young children. Household food insecurity, which reflects a household's access, availability and utilisation of food, has not been well characterised in relation to anaemia in children. OBJECTIVE: To examine the relationship of household food insecurity with anaemia (Hb <11 g/dl) in children. METHODS: In a cross-sectional study of 4940 rural households participating in the Indonesian Nutrition Surveillance System, household food insecurity was measured using a modified 9-item food security questionnaire and related to anaemia in children aged 6-59 months. RESULTS: The proportion of households with an anaemic child was 56·6%. In households with and without anaemic children, the mean (SD) food insecurity score was 1·82 (1·72) vs 1·55 (1·54) (p<0·0001), respectively. In a multivariate logistic regression model, food insecurity score was related to anaemia in children (odds ratio 0·77, 95% confidence interval 0·63-0·95, p=0·01) when the highest quintile of food insecurity score was compared with the lowest quintile, adjusting for potential confounders. CONCLUSION: A higher household food insecurity score is associated with greater prevalence of anaemia in children in rural families in Indonesia.

Magnesium and anabolic hormones in older men.

Optimal nutritional and hormonal statuses are determinants of successful ageing. The age associated decline in anabolic hormones such as testosterone and insulin-like growth factor 1 (IGF-1) is a strong predictor of metabolic syndrome, diabetes and mortality in older men. Studies have shown that magnesium intake affects the secretion of total IGF-1 and increase testosterone bioactivity. This observation suggests that magnesium can be a modulator of the anabolic/catabolic equilibrium disrupted in the elderly people. However, the relationship between magnesium and anabolic hormones in men has not been investigated. We evaluated 399 ≥65-year-old men of CHIANTI in a study population representative of two municipalities of Tuscany (Italy) with complete data on testosterone, total IGF-1, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS) and serum magnesium levels. Linear regression models were used to test the relationship between magnesium and testosterone and IGF-1. Mean age of the population was 74.18 ± 6.43 (years ± SD, age range 65.2-92.4). After adjusting for age, magnesium was positively associated with total testosterone (ß ± SE, 34.9 ± 10.3; p = 0.001) and with total IGF-1 (ß ± SE, 15.9 ± 4.8; p = 0.001). After further adjustment for body mass index (BMI), log (IL-6), log (DHEAS), log (SHBG), log (insulin), total IGF-1, grip strength, Parkinson's disease and chronic heart failure, the relationship between magnesium and total testosterone remained strong and highly significant (ß ± SE, 48.72 ± 12.61; p = 0.001). In the multivariate analysis adjusted for age, BMI, log (IL-6), liver function, energy intake, log (insulin), log (DHEAS), selenium, magnesium levels were also still significantly associated with IGF-1 (ß ± SE, 16.43 ± 4.90; p = 0.001) and remained significant after adjusting for total testosterone (ß ± SE, 14.4 ± 4.9; p = 0.01). In a cohort of older men, magnesium levels are strongly and independently associated with the anabolic hormones testosterone and IGF-1.

Low dietary diversity is a predictor of child stunting in rural Bangladesh.

BACKGROUND/OBJECTIVES: Dietary diversity is associated with overall quality and nutrient adequacy of the diet in low-income countries. We determined the association between dietary diversity and stunting among children aged 6-59 months in rural Bangladesh. SUBJECTS/METHODS: In total, 165 111 under-fives who participated in the National Surveillance Project in 2003-2005 were included in the analysis. Dietary diversity score (DDS) was constructed through the summation of the number of days each of the nine food groups was consumed in the previous week. The association between stunting and DDS was determined adjusting for confounders using logistic regression models. All analyses were performed separately for children aged 6-11, 12-23 and 24-59 months. RESULTS: One-half of the children were stunted. In multivariate analyses, compared with low DDS, high dietary diversity was associated with a 15, 26 and 31% reduced odds of being stunted among children aged 6-11, 12-23 and 24-59 months, respectively, after adjusting for all potential confounders (odds ratio (OR)=0.85, 95% confidence interval (CI): 0.76-0.94; OR=0.74, 95% CI: 0.69-0.79; OR=0.69, 95% CI: 0.66-0.73). In all groups, children who were still breastfed were more likely to have limited diversity (OR=1.88, 95% CI: 1.32-2.67; OR=1.71, 95% CI: 1.52-1.92; OR=1.15, 95% CI: 1.11-1.19). Those having diarrhea in the past week and coming from families with low socioeconomic status were more likely to have decreased diversity (P<0.05). CONCLUSIONS: Reduced dietary diversity is a strong predictor of stunting in rural Bangladesh. The inclusion of a variety of food groups into complementary foods may be essential to improve child nutritional status.

Relationship of a dominant advanced glycation end product, serum carboxymethyl-lysine, and abnormal glucose metabolism in adults: the Baltimore Longitudinal Study of Aging.

BACKGROUND AND OBJECTIVES: Although hyperglycemia is thought to increase the generation of advanced glycation end products (AGEs), studies have not shown a consistent relationship between abnormal glucose metabolism and serum AGEs. We investigated the relationship between a dominant serum AGE, N-carboxymethyl-lysine (CML), and glucose metabolism. SUBJECTS AND METHODS: Serum CML, fasting plasma glucose, and glucose tolerance were measured in 755 adults in the Baltimore Longitudinal Study of Aging. Fasting plasma glucose was categorized as normal (< or = 99 mg/dL), impaired (100-125 mg/dL), and diabetic (> 125 mg/dL). Two-hour plasma glucose on oral glucose tolerance testing was categorized as normal (< or = 139 mg/dL), impaired (140-199 mg/dL), and diabetic (> or = 200 mg/dL). RESULTS: The proportion of adults with normal, impaired, and diabetic fasting plasma glucose was 73.8%, 22.9%, and 2.9%, respectively, and the proportion with normal, impaired, and diabetic 2-hour plasma glucose was 73.1%, 19.2%, and 7.7%, respectively. Serum CML (microg/mL) was not associated with abnormal fasting plasma glucose (Odds Ratio [O.R.] 0.60, 95% Confidence Interval [C.I.] 0.15-2.36, P = 0.47) in a multivariate, ordered logistic regression model, adjusting for age, race, gender, body mass index, and chronic diseases. Serum CML (microg/mL) was associated with abnormal 2-hour plasma glucose on glucose tolerance testing (O.R. 0.15, 95% C.I. 0.04-0.63, P = 0.009) in a multivariate, ordered logistic regression model, adjusting for the same covariates. CONCLUSIONS: Elevated CML, a dominant AGE, was not associated with elevated fasting plasma glucose and was associated with a reduced odds of abnormal glucose tolerance in older community-dwelling adults.

Relationship of 25-hydroxyvitamin D with all-cause and cardiovascular disease mortality in older community-dwelling adults.

BACKGROUND/OBJECTIVES: Vitamin D deficiency is associated with cardiovascular disease, osteoporosis, poor muscle strength, falls, fractures and mortality. Although older adults are at a higher risk of vitamin D deficiency, the relationship of serum 25-hydroxyvitamin D (25(OH)D) with all-cause and cardiovascular disease mortality has not been well characterized in the elderly. We hypothesized that low serum 25(OH)D levels predicted mortality in older adults. SUBJECTS/METHODS: Serum 25(OH)D as well as all-cause and cardiovascular disease mortality were examined in 1006 adults, aged > or =65 years, who participated in the InCHIANTI (Invecchiare in Chianti, Aging in the Chianti Area) study, a population-based, prospective cohort study of aging in Tuscany, Italy. Serum 25(OH)D levels were measured at the time of enrollment in 1998-1999, and participants were followed up for mortality. RESULTS: During 6.5 years of follow-up, 228 (22.7%) participants died, of whom 107 died due to cardiovascular diseases. Compared with participants in the highest quartile of serum 25(OH)D (>26.5 ng/ml) (to convert to nmol/l, multiply by 2.496), those in the lowest quartile (<10.5 ng/ml) had increased risk of all-cause mortality (Hazard Ratio (H.R.) 2.11, 95% Confidence Interval (95% C.I.): 1.22-3.64, P=0.007) and cardiovascular disease mortality (H.R. 2.64, 95% C.I.: 1.14-4.79, P=0.02), in multivariate Cox proportional hazards models that adjusted for age, sex, education, season, physical activity and other potential confounders. CONCLUSIONS: Older community-dwelling adults with low serum 25(OH)D levels are at higher risk of all-cause and cardiovascular disease mortality.

Circulating beta-carotene levels and type 2 diabetes-cause or effect?

AIMS/HYPOTHESIS: Circulating beta-carotene levels are inversely associated with risk of type 2 diabetes, but the causal direction of this association is not certain. In this study we used a Mendelian randomisation approach to provide evidence for or against the causal role of the antioxidant vitamin beta-carotene in type 2 diabetes. METHODS: We used a common polymorphism (rs6564851) near the BCMO1 gene, which is strongly associated with circulating beta-carotene levels (p = 2 x 10(-24)), with each G allele associated with a 0.27 standard deviation increase in levels. We used data from the InCHIANTI and Uppsala Longitudinal Study of Adult Men (ULSAM) studies to estimate the association between beta-carotene levels and type 2 diabetes. We next used a triangulation approach to estimate the expected effect of rs6564851 on type 2 diabetes risk and compared this with the observed effect using data from 4549 type 2 diabetes patients and 5579 controls from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium. RESULTS: A 0.27 standard deviation increase in beta-carotene levels was associated with an OR of 0.90 (95% CI 0.86-0.95) for type 2 diabetes in the InCHIANTI study. This association was similar to that of the ULSAM study (OR 0.90 [0.84-0.97]). In contrast, there was no association between rs6564851 and type 2 diabetes (OR 0.98 [0.93-1.04], p = 0.58); this effect size was also smaller than that expected, given the known associations between rs6564851 and beta-carotene levels, and the associations between beta-carotene levels and type 2 diabetes. CONCLUSIONS/INTERPRETATION: Our findings in this Mendelian randomisation study are in keeping with randomised controlled trials suggesting that beta-carotene is not causally protective against type 2 diabetes.

Activation of p38 mitogen-activated protein kinase is required for in vivo brain-derived neurotrophic factor production in the rat hippocampus.

Several lines of evidence strongly suggest that brain-derived neurotrophic factor (BDNF) is associated with the formation, storage and recall of memory in the hippocampus and that it is important to maintain a considerable level of hippocampal BDNF in order to keep normal functions. BDNF can be synthesized in an activity-dependent manner. In fact, kainic acid or AMPA enhances BDNF levels in hippocampal granule neurons. However, the mechanisms of BDNF production are largely unclear. Recently, we have found that riluzole, which blocks voltage-gated sodium channels and thereby reduces glutamate release, actually strengthens immunoreactivity of BDNF in hippocampal granule neurons of rats. Therefore, we examined the riluzole-activated signaling pathways for BDNF production. Riluzole increased levels of phospho-p38 mitogen-activated protein kinase (p38 MAPK), as well as BDNF levels. Inhibition of p38 MAPK by SB203580 reduced riluzole effects, while activation of p38 MAPK by anisomycin increased levels of BDNF, suggesting that p38 MAPK can mediate BDNF production. Riluzole-induced elevation of phospho-activating transcription factor-2, a transcription factor downstream of p38 MAPK, was also observed. A blocker of N-type voltage-gated calcium channels reduced the effects of riluzole on BDNF production and p38 MAPK activation. We also examined a possible involvement of the adenosine A1 receptor in BDNF production because riluzole can influence ecto-nucleotide levels. An A1 receptor agonist inhibited riluzole-induced elevation of BDNF levels, whereas an antagonist not only increased levels of BDNF and active p38 MAPK but also augmented riluzole effects. These results indicate that, in the rat hippocampus, there is an in vivo signaling pathway for BDNF synthesis mediated by p38 MAPK, and that N-type voltage-gated calcium channels and/or adenosine A1 receptors contribute to p38 MAPK activation.

Low serum carotenoids are associated with a decline in walking speed in older women.

BACKGROUND AND OBJECTIVES: Walking speed is an important measure of physical performance that is predictive of disability and mortality. The relationship of dietary factors to changes in physical performance has not been well characterized in older adults. The aim was to determine whether total serum carotenoid concentrations, a marker for fruit and vegetable intake, and serum selenium are related to changes in walking speed in older women. SUBJECTS AND METHODS: The relationship between total serum carotenoids and selenium measured at baseline, 12, and 24 months follow-up and walking speed assessed at baseline and every six months for 36 months was examined in 687 moderately to severely disabled women, 65 years or older, living in the community. RESULTS: Mean total serum carotenoids were associated with mean walking speed over three years of follow-up (P = 0.0003) and rate of change of walking speed (P = 0.007) in multivariate linear regression models adjusting for age, body mass index, and chronic diseases. Mean serum selenium was associated with mean walking speed over three years of follow-up (P = 0.0003) but not with the rate of change of walking speed (P = 0.26). CONCLUSIONS: These findings suggest that a higher fruit and vegetable intake, as indicated by higher total serum carotenoid concentrations, may be protective against a decline in walking speed in older women.

Low serum selenium is associated with anemia among older adults in the United States.

OBJECTIVE: We hypothesized that low serum selenium was associated with anemia in humans. SUBJECTS: A total of 2092 adults aged 65 and older, in the third National Nutrition Examination Survey, Phase 2 (1991-1994) (NHANES III). METHODS: Examination of the relationship between serum selenium and hematological indices in NHANES III. RESULTS: Anemia, defined by World Health Organization criteria, was present in 12.9%. Mean serum selenium among non-anemic and anemic adults was 1.60 and 1.51 micromol l(-1) (P=0.0003). The prevalence of anemia among adults in the lowest to highest quartiles of serum selenium was 18.3, 9.5, 9.7 and 6.9%, respectively (P=0.0005). The proportion of adults in the lowest quartile of selenium among those who were non-anemic or who had anemia due to nutritional causes, chronic inflammation, renal disease or unexplained anemia was 9.9, 27.5, 17.5, 24.0 and 15.4%, respectively. An increase in log(e) selenium was associated with a reduced risk of anemia (odds ratio per one standard deviation increase 0.75, 95% confidence interval 0.58-0.97, P=0.03), adjusting for age, race, education, body mass index and chronic diseases. CONCLUSION: Low serum selenium is independently associated with anemia among older men and women in the United States.

Markers of B-vitamin deficiency and frailty in older women.

OBJECTIVE: To evaluate the association between markers of vitamins B12, B6 and folate deficiency and the geriatric syndrome of frailty. DESIGN: Cross-sectional study of baseline measures from the combined Women's Health and Aging Studies. SETTING: Baltimore, Maryland. PARTICIPANTS: Seven hundred three community-dwelling women, aged 70-79. MEASUREMENTS: Frailty was defined by five-component screening criteria that include weight, grip strength, endurance, physical activity and walking speed measurements and modeled as binary and 3-level polytomous outcomes. Independent variables serum vitamin B6, vitamin B12, methylmalonic acid, total homocysteine, cystathionine and folate were modeled continuously and as abnormal versus normal. RESULTS: Serum biomarker levels varied significantly by race. All analyses were race-stratified and results are reported only for Caucasian women due to small African American sample size. In polytomous logistic regression models of 3-level frailty, Caucasian women with increasing MMA, defined either continuously or using a predefined threshold, had 40-60% greater odds of being prefrail (p-values < 0.07) and 1.66-2.33 times greater odds of being frail (p-values < 0.02) compared to nonfrails after adjustment for age, education, low serum carotenoids, alcohol intake, cardiovascular disease and renal impairment. Both binary and polytomous frailty models evaluating vitamin B12 as the main exposure estimated odds ratios that were similar in trend yet slightly less significant than the MMA results. CONCLUSIONS: These results suggest that vitamin B12 deficiency may contribute to the frailty syndrome in community-dwelling older women. Future studies are needed to explore these relationships longitudinally.

Paternal smoking and increased risk of child malnutrition among families in rural Indonesia.

OBJECTIVE: To determine whether paternal smoking is associated with an increased risk of child malnutrition among families in rural Indonesia. METHODS: The relation between paternal smoking and child malnutrition was examined in a population-based sample of 438 336 households in the Indonesia Nutrition and Health Surveillance System, 2000-2003. Main outcome measures were child underweight (weight-for-age Z score <-2) and stunting (height-for-age Z score <-2) and severe underweight and severe stunting, defined by respective Z scores <-3, for children aged 0-59 months of age. RESULTS: The prevalence of paternal smoking was 73.7%. The prevalence of underweight and stunting was 29.4% and 31.4%, and of severe underweight and severe stunting was 5.2%, and 9.1%, respectively. After adjusting for child gender, child age, maternal age, maternal education, weekly per capita household expenditure and province, paternal smoking was associated with an increased risk of underweight (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01 to 1.05, p = 0.001) and stunting (OR 1.11, 95% CI 1.09 to 1.13, p<0.001) and severe underweight (OR 1.06, 95% CI 1.01 to 1.10) p = 0.020) and severe stunting (OR 1.12, 95% CI 1.08 to 1.16, p<0.001). CONCLUSIONS: Paternal smoking is associated with an increased risk of child malnutrition in families living in rural Indonesia.

Malnutrition and morbidity among children not reached by the national vitamin A capsule programme in urban slum areas of Indonesia.

OBJECTIVE: To determine whether vitamin A capsule programmes fail to reach children who are at higher risk of malnutrition and morbidity. Although it has been suggested that there are health disparities between children who are reached or not reached by these programmes, little quantitative work has been undertaken to characterize this relationship. STUDY DESIGN: As part of a national surveillance system, nutritional status and other factors were compared in 138,956 children, aged 12-59 months, who had and had not received vitamin A supplementation in urban slum areas in Indonesia. RESULTS: In total, 63.1% of children had received a vitamin A capsule within the previous 6 months. Among children who had and had not received vitamin A supplementation, respectively, the proportion with weight-for-age and height-for-age Z scores <-3 were 7.8% vs 8.6% (P<0.0001) and 9.4% vs 10.7% (P<0.0001), and with a history of diarrhoea in the previous week was 8.1% vs 10.7% (P<0.0001). In families where a child had or had not received vitamin A supplementation, the proportion with a history of infant death <12 months was 5.2% vs 7.2% (P<0.0001) and child death <5 years was 6.7% vs 9.2%, respectively (P<0.0001). Children who had not received vitamin A supplementation were also significantly more likely to be anaemic and have diarrhoea or fever on the survey day compared with children who had received supplementation. CONCLUSIONS: In the urban slums of Indonesia, children who do not receive vitamin A supplementation tend to be slightly more malnourished and ill, and are more likely to come from families with higher child mortality than children who receive vitamin A. Higher rates of child mortality in non-participating households suggest that reaching preschoolers could yield a disproportionate survival benefit. Importantly, children who are not reached by the vitamin A programme are also unlikely to be reached by vaccination and other services, emphasizing the need to identify and extend efforts to reach non-participants.

Micronutrient supplements and mortality of HIV-infected adults with pulmonary TB: a controlled clinical trial.

SETTING: Zomba and Blantyre, Malawi, Africa. OBJECTIVES: To determine whether daily micronutrient supplementation reduces the mortality of human immunodeficiency virus (HIV) infected adults with pulmonary tuberculosis (TB). DESIGN: A randomised, controlled clinical trial of micronutrient supplementation for HIV-positive and HIV-negative adults with pulmonary TB. Participants were enrolled at the commencement of chemotherapy for sputum smear-positive pulmonary TB and followed up for 24 months. RESULTS: A total of 829 HIV-positive and 573 HIV-negative adults were enrolled. During follow-up, 328 HIV-positive and 17 HIV-negative participants died. The proportion of HIV-positive participants who died in the micronutrient and placebo groups was 38.7% and 40.4%, respectively (P = 0.49). Micronutrient supplementation did not reduce mortality (hazard ratio [HR] 0.93, 95%CI 0.75-1.15) among HIV-positive adults. CONCLUSIONS: Micronutrient supplementation at the doses used in this study does not reduce mortality in HIV-positive adults with pulmonary TB in Malawi.

Physical activity in a cohort of HIV-positive and HIV-negative injection drug users.

Physical activity is beneficial for persons with HIV infection but little is known about the relationships between physical activity, HIV treatment and injection drug use (IDU). This study compared physical activity levels between HIV-negative and HIV-positive injection drug users (IDUs) and between HIV-positive participants not on any treatment and participants on highly active antiretroviral therapy (HAART). Anthropometric measurements were obtained and an interviewer-administered modified Paffenbarger physical activity questionnaire was administered to 324 participants in a sub-study of the AIDS Linked to Intravenous Experiences (ALIVE) cohort, an ongoing study of HIV-negative and HIV-positive IDUs. Generalized linear models were used to obtain univariate means and to adjust for confounding (age, gender, employment and recent IDU). Vigorous activity was lower among HAART participants than HIV-positive participants not on treatment (p=0.0025) and somewhat lower than HIV-negative participants (p=0.11). Injection drug use and viral load were not associated with vigorous activity. Energy expenditure in vigorous activity was also lower among HAART participants than both HIV-negative and HIV-positive participants not on treatment. Thus, HIV-positive participants on HAART spend less time on vigorous activity independent of recent IDU. More research is needed into the reasons and mechanism for the lack of vigorous activities, including behavioral, psychological and physiological reasons.