Calcium nutrition and extracellular calcium sensing: relevance for the pathogenesis of osteoporosis, cancer and cardiovascular diseases.

Through a systematic search in Pubmed for literature, on links between calcium malnutrition and risk of chronic diseases, we found the highest degree of evidence for osteoporosis, colorectal and breast cancer, as well as for hypertension, as the only major cardiovascular risk factor. Low calcium intake apparently has some impact also on cardiovascular events and disease outcome. Calcium malnutrition can causally be related to low activity of the extracellular calcium-sensing receptor (CaSR).

Vitamin D insufficiency and chronic diseases: hype and reality.

In recent years an increasing number of observational studies have suggested that a low vitamin D status contributes to the development of all sorts of chronic diseases. In reality, however, studies that had been adequately controlled for confounding factors ruled out any link between vitamin D insufficiency and, for example, metabolic disorders, arterial hypertension, multiple sclerosis or cognitive dysfunction. Furthermore, a role of vitamin D insufficiency in autoimmune diseases is evident only in animal models but has not yet been established in humans.

Relative Expression of Vitamin D Hydroxylases, CYP27B1 and CYP24A1, and of Cyclooxygenase-2 and Heterogeneity of Human Colorectal Cancer in Relation to Age, Gender, Tumor Location, and Malignancy: Results from Factor and Cluster Analysis.

Previous studies on the significance of vitamin D insufficiency and chronic inflammation in colorectal cancer development clearly indicated that maintenance of cellular homeostasis in the large intestinal epithelium requires balanced interaction of 1,25-(OH)2D3 and prostaglandin cellular signaling networks. The present study addresses the question how colorectal cancer pathogenesis depends on alterations of activities of vitamin D hydroxylases, i.e.

Influence of age and gender on associations of body mass index with bone mineral density, bone turnover markers and circulating calcium-regulating and bone-active sex hormones.

Although it is well known that body mass index (BMI) and bone mineral density (BMD) are positively correlated, the mechanisms by which adiposity reduces the risk of osteoporotic fractures are not fully understood. The present study was initiated to gain deeper insight into the mechanisms underlying the osteoprotective effect of adiposity, and to assess particularly the relevance that BMI-associated changes in circulating hormone levels could have for the build-up of additional bone mineral density. Using data from a previous study on a large cohort of healthy adult Austrians, we analyzed correlations of BMI with (i) BMD at sites in the lumbar spine and hip region, (ii) bone resorption and formation markers, (iii) circulating levels of vitamin D, parathyroid hormone, testosterone and estrogen, and (iv) rates of daily vitamin D and calcium intake.

Vitamin D and calcium insufficiency-related chronic diseases: an emerging world-wide public health problem.

Vitamin D and calcium insufficiencies are risk factors for multiple chronic diseases. Data from 46 recent studies from Europe, North America, South-East Asia and the South Pacific area clearly indicate that a low vitamin D status and inadequate calcium nutrition are highly prevalent in the general population (30-80%), affecting both genders. The extent of insufficiencies is particularly high in older populations, and in some geographical areas, also in children and in young women of child-bearing age, in ethnic minorities and immigrants, as well as in people of low socio-economic status.

Mutual associations between malignancy, age, gender, and subsite incidence of colorectal cancer.

Background: A cross-sectional study was performed on a cohort of colorectal cancer (CRC) patients to reveal any influence of age, gender, and subsite on grades of malignancy.

Patients And Methods: Data from histopathological grading according to WHO criteria were pooled into groups of low-grade (well and moderately differentiated) and high-grade (poorly and undifferentiated) cancer and analyzed for associations.

Results: In general, women with CRC were significantly older than men (p<0.

Modulation of vitamin D synthesis and catabolism in colorectal mucosa: a new target for cancer prevention.

Sporadic colorectal cancer is a disease of advancing age and the percentage of the population which reaches an advanced age is strongly increasing. Multiple factors are responsible for the etiology of this cancer since the colorectal mucosa is directly influenced by nutrients reaching the colonic lumen and impacting on mucosal cells. The vitamin D system appears to be central to several preventative molecular pathways.

Calcium, vitamin D and cancer.

A low vitamin D status and inadequate calcium intake are important risk factors for various types of cancer. Ecological studies using solar UV-B exposure as an index of vitamin D3 photoproduction in the skin found a highly significant inverse association between UV-B and mortality in fifteen types of cancer. Of these, colon, rectal, breast, gastric, endometrial, renal and ovarian cancer exhibit a significant inverse relationship between incidence and oral intake of calcium.

Estimated benefit of increased vitamin D status in reducing the economic burden of disease in western Europe.

Vitamin D has important benefits in reducing the risk of many conditions and diseases. Those diseases for which the benefits are well supported and that have large economic effects include many types of cancer, cardiovascular diseases, diabetes mellitus, several bacterial and viral infections, and autoimmune diseases such as multiple sclerosis. Europeans generally have low serum 25-hydroxyvitamin D [25(OH)D] levels owing to the high latitudes, largely indoor living, low natural dietary sources of vitamin D such as cold-water ocean fish, and lack of effective vitamin D fortification of food in most countries.

Role of bile acid secretion in human colorectal cancer.

Cholic, deoxycholic and lithocholic acid promote tumor formation in the large intestine by a direct proliferative effect on rather undifferentiated mucosal epithelial cells. In addition, bile acids may play a role in colorectal cancer pathogenesis because they reduce the chemopreventive efficiency of calcium and vitamin D by interfering with calcium and vitamin D receptor-activated anti-mitogenic intracellular signalling in neoplastic colonocytes.

Clone-specific expression, transcriptional regulation, and action of interleukin-6 in human colon carcinoma cells.

Background: Many cancer cells produce interleukin-6 (IL-6), a cytokine that plays a role in growth stimulation, metastasis, and angiogenesis of secondary tumours in a variety of malignancies, including colorectal cancer. Effectiveness of IL-6 in this respect may depend on the quantity of basal and inducible IL-6 expressed as the tumour progresses through stages of malignancy. We therefore have evaluated the effect of IL-6 modulators, i.

Dysfunction of the vitamin D endocrine system as common cause for multiple malignant and other chronic diseases.

Extensive research on the CYP27B1-encoded 25-(OH)D-1alpha-hydroxylase has contributed much to our understanding about how locally produced 1,25-(OH)2D3 exerts tissue-specific control of cellular growth, differentiation and function. Because many types of epithelial, mesenchymal and immune cells express the 25-(OH)D-1alpha-hydroxylase, many organ functions are necessarily affected by changes in the activity of the enzyme. It is hypothesized that this is likely to occur under conditions of hypovitaminosis D, i.

Bone morphogenetic proteins 5 and 6 stimulate osteoclast generation.

Bone regeneration is required for fracture-healing, and different procedures have been used to promote osteogenesis. Recently, BMP-2 has been shown to induce bone formation in vivo and has been tested in clinical trials. A recent in vitro study evaluated the osteogenic activity of 14 BMPs on osteoblastic progenitor cells with an osteogenic hierarchical model in which BMP-2 and BMP-6 may play an important role in inducing osteoblast differentiation.

Differentiation-dependent expression and mitogenic action of interleukin-6 in human colon carcinoma cells: relevance for tumour progression.

Interleukin (IL)-6 mRNA expression in general is low in normal, adenomatous and cancerous human colon mucosa, except in rather undifferentiated lesions, in which IL-6 is overexpressed. Cytokeratin (CK) 8-positive carcinoma cells were identified by double immunostaining as almost exclusive source of IL-6. Likewise, in five (sub)clones of primary culture COGA-1 and COGA-13 human colon carcinoma cells, and in three established cell lines (Caco-2/AQ, Caco-2/15 and HT-29), efficient translation of IL-6 mRNA into protein was observed only in the least differentiated COGA-13 cells.

Interactions of 1 alpha,25-dihydroxyvitamin D3 with IL-12 and IL-4 on cytokine expression of human T lymphocytes.

Background: 1 alpha,25-Dihydroxyvitamin D3 (1 alpha,25[OH](2)D(3)) exerts its effects on the immune system, particularly through suppression of T helper/cytotoxic cell 1 (T(H)/T(C)1)-mediated reactions, although direct actions of 1 alpha,25(OH)(2)D(3) on human T lymphocytes have not yet been studied in detail.

Objective: We evaluated the effect of 1 alpha,25(OH)(2)D(3) on basal and cytokine-driven T-cell functions at the single-cell level.

Methods: We used 4-color flow cytometry for simultaneous detection of intracellular cytokines in CD4(+) and CD8(+) human PBMCs that had been cultured in the presence of 1 alpha,25(OH)(2)D(3) singly or in combination with either IL-12 or IL-4.

The effect of age and gender on cytokine production by human peripheral blood mononuclear cells and markers of bone metabolism.

Background: Aging has been associated with various alterations of immune functions, the musculoskeletal system and a decline of sex hormone levels. Estradiol has a central role in the regulation of bone turnover and also modulates the production of cytokines such as interleukin-1 and -6 and tumor necrosis factor-alpha. We therefore studied the effect of age and gender on cytokine production by mononuclear cells and markers of bone metabolism.

Molecular and functional characterization of the extracellular calcium-sensing receptor in human colon cancer cells.

Presence of a functional extracellular calcium-sensing receptor (CaR) is of particular relevance for the growth-inhibitory action of Ca2+ on human colon carcinoma cells. In order to detect CaR gene alterations that may have occurred during the tumorigenic process, we applied Southern blot, DNA sequence, and RT-PCR analysis to DNA from normal human colon mucosa and from cancerous lesions of different grading, as well as from primary cultured and established colonic carcinoma cell lines (e.g.

1 alpha,25(OH)2D3 inhibits not only Th1 but also Th2 differentiation in human cord blood T cells.

Human naive CD4+ T helper (Th) and CD8+ cytotoxic (Tc) T cells, which only produce IL-2, may differentiate into Th1/Tc1- or Th2/Tc2-like lymphocytes, characterized by their cytokine production profile. 1 alpha,25-dihydroxyvitamin D3 (1 alpha, 25(OH)2D3) has been reported to inhibit Th1/Tc1-related, but increase Th2/Tc2-associated cytokines in T cells from adults. In industrialized countries, vitamin D supplementation for prevention of rickets is initiated within the first days of life and continued throughout the entire first year.