Cross-sectional and longitudinal associations between the active vitamin D metabolite (1,25 dihydroxyvitamin D) and haemoglobin levels in older Australian men: the Concord Health and Ageing in Men Project

Abstract

Anaemia and low 25 hydroxyvitamin D (25D) and 1,25 dihydroxyvitamin D (1,25D) levels are common in older people and may adversely affect morbidity and mortality. While there is some evidence for an association between low serum 25D levels and anaemia, there are limited studies among community-dwelling older people. In addition, the relationship between anaemia and the active vitamin D metabolite, 1,25D, has not been investigated. The aim of this study was to examine the associations between serum 25D and 1,25D with anaemia in community-living men aged ≥70 years. Population-based, cross-sectional analysis of the baseline phase and longitudinal analysis of the Concord Health and Ageing in Men Project (CHAMP), a large epidemiological study conducted in Sydney among men aged 70 years and older, were performed; 1666 men were seen at baseline (2005-2007), 1314 men at a 2-year follow-up (2007-2009) and 917 at a 5-year follow-up (2012-2013). The main outcome measurement was haemoglobin levels as a continuous measure. Covariates included 25D and 1,25D, estimated glomerular filtration rate, demographic information, lifestyle measures, health conditions and medication information. The prevalence of anaemia (Hb < 13.0 g/dL, WHO definition) was 14.6 %. In cross-sectional analysis, serum 25D concentrations were positively associated with haemoglobin levels in unadjusted analysis (β value 0.004; 95 % confidence interval (CI) 0.0009, 0.007; p = 0.01), but the associations were no longer significant after multivariate adjustment. The association between 1,25D levels and haemoglobin levels was significant in unadjusted analysis (β value 0.003; 95 % CI 0.002, 0.004; p < 0.0001) and remained significant in adjusted analysis (β value 0.001; 95 % CI 0.004, 0.003; p = 0.01). Serum 1,25D (but not 25D) levels at baseline were significantly associated with changes in haemoglobin over 2 and 5 years in unadjusted (β value 0.002; 95 % CI 0.0009, 0.003; p < 0.0001) and in fully adjusted analyses (β value 0.001; 95 % CI 0.0004, 0.002; p = 0.001). Serum 1,25D, but not 25D, concentrations are independently associated with haemoglobin levels in older men in both cross-sectional and longitudinal analyses. This raises the question whether vitamin D metabolites may influence anaemia states, mediated through different biological pathways, or represent a time-dependent biomarker of chronic ill health.

Vitamin D and anemia

“…Past studies have demonstrated that low vitamin D status is associated with anemia risk in children, elderly adults, those with CKD, and those with heart failure [2, 3, 5, 7]. Recent studies in patients scheduled for cardiac surgery and community-dwelling elderly men have also shown vitamin D status to be inversely associated with odds of anemia and positively associated with hemoglobin concentrations, respectively [32, 33*]. New studies have also extended these findings to explore racial and ethnic differences in the association between vitamin D and anemia, and to further clarify the association with specific subtypes of anemia.…”

Association of hematology profile with serum 25-hydroxy vitamin D and Bsml polimorphism in community-dwelling older adults

“…In a cohort with 9,675 community-dwelling older adults, vitamin D deficiency was independently associated with the prevalence of anemia 7 . Nevertheless, Hirani et al 16 concluded that serum 25(OH)D was not significantly associated with hemoglobin. A recent meta-analysis of 5,183 individuals concluded that vitamin D increased the risk of anemia 30 .…”

“…In this sense, an adequate level of 25-Hydroxy Vitamin D (25(OH)D) seems to be crucial for the normal production of red blood cells, although the pathophysiological mechanisms still need to be fully elucidated 12 . Additionally, the finding that many body tissues, such as the bone marrow 13,14 , have Vitamin D Receptors (VDR), a protein responsible for gene transcription and for carrying out cell function in many tissues, reinforces the hypothesis that there is a positive relationship between vitamin D level and hemoglobin 7,15,16 , and that this phenomenon may be influenced by VDR gene polymorphisms [17][18][19] . Single-nucleotide polymorphisms are common in the human genome, and frequently, they occur in specific genes involved in the genesis of and predisposition to many human diseases.…”

“…The most common VDR gene polymorphisms occur between exons 8 and 9, such as ApaI, BsmI, and TaqI 20. Despite the great interest on the role of vitamin D on the pathogenesis of many diseases, the relationship between vitamin D insufficiency/ deficiency and blood profile, and the physiological mechanisms of its activity are still controversial and based on a limited number of studies. Until now only two studies included a population of older adults without chronic diseases 7,16 , and none of them investigated their relationship with genetic characteristics. Thus, the present study aimed to investigate the association of serum level of 25(OH)D with the VDR gene BsmI polymorphism and the blood profile of community-dwelling older adults from a metropolis in the Brazilian Northeast region.…”

Association of 25-hydroxyvitamin D and Anemia parameters in elderly with anemia of inflammation and non-inflammation

“…6,8 Previous studies showed that association between vitamin D status and anemia with inflammation was significant. 10,11 The mechanism underlying this relationship involved hepcidin, a hormone produced from hepatosit that involved in the regulation of Fe recycling in the body. Hepcidin was induced by pro-inflammatory cytokines including IL-6.…”