Saturday, 29 March 2014

Benign prostatic hyperplasia(BPH) in Vitamin D Points of View

Kyle J. Norton

Benign prostatic hyperplasia(BPH) is defined as a condition of increased in the number of cells of prostate gland, causing partial, or sometimes virtually complete obstruction of the urinary tract. According to statistic, BPH commonly starts at age of 30 and symptoms usually can not be realized until age of 50. More than half of men between age of 60-70 are experience symptoms of BPH and only 10% are required treatment.
Vitamin D is a fat-soluble secosteroids found in small amount in few foods, including salmon, mackerel, sardines and tuna. The vitamin plays an important role in modulation of cellular proliferation, apoptosis induction, tumor growth suppression and promotion in absorption of minerals, including calcium, iron, magnesium, phosphate and zinc.
Epidemiological studies, focusing the use of dietary vitamin E in reduced risk of benign prostatic hyperplasia(BPH) have produced inconsistent results(a)(b).
1. Vitamin D receptor(VDR) and BPH
The study of 222 prostate cancer patients, 209 benign prostatic hyperplasia (BPH) patients, 128 male controls who were over 60 years old and without any evidence of prostate cancer or BPH, and 198 female controls in Japanese men to exp;ore the genetic mutation of polymorphism in the VDR gene for risk of prostate cancer and BPH found the positive effect of  BsmI polymorphism in the VDR gene in protection against prostate cancer(1). Other study showed  rs731236(genetic) variant of the vitamin D receptor had a protective effect for LUTS, a common symptoms of men with BPH(2), and VDR Fok I polymorphisms(morphs of the phenotype) may be correlated with BPH complicated by histological prostatitis, the study of Graduate School, South Medical Universit showed(3). In Indian population, Taq-I(a restriction enzyme isolated from the bacterium Thermus aquaticus in 1978) and Bsm-I genetic variants of VDR gene influence susceptibility BPH(4). But in the study of polymorphims with functional significance in the Bsm, Apa 1 and Taq 1 genes were therefore compared in 28 prostate cancer (CaP), 44 benign prostate hyperplasia (BPH) and 30 control cases in Thailand, indicated no significant variation in distribution of these three groups. Of that suggested these variations in the distribution frequencies from country to country and depending to other factors such as sun exposure, dietary and other lifestyle factors(5).

2. The serum of Vitamin D
Some researchers suggested that serum of vitamin D may be an indication of early onset of benign prostatichyoerplasia BPH. According to the study by American Urological Association Education and Research, low levels of 25-OH vitamin D is associated with benign prostatic hyperplasia(6). But a study by Democritus University of Thrace showed no clear relationship between vitamin D and serum levels of PSA or-of f/t-PSA(free/total prostate specific antigen) in PD patients(7).
 
3. The effects
BPH(1). BXL-628. a vitamin D3 analog, showed to decrease prostate growth and BPH symptoms, through inhibition of cell migration and cytoskeleton(a cellular scaffolding or skeleton contained within a cell's cytoplasm) remodeling in altered bladder contractility associated with BPH-induced lower urinary tract symptoms(8). Elocalcitol, a vitamin D3 analog, reduced the static component of BPH by inhibiting the activity of intraprostatic growth factors downstream of the androgen receptor, by targeting the RhoA(regulation and timing of cell division)/ROCK(protein, RhoA, RhoC, and ROCK expression were related to poor tumor differentiation) and NF-kappaB(involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens.) pathway(9). The New York University School of Medicine study showed increase intake of vitamin D impact an adverse correlation with decreased BPH prevalence(10). Another novel nonsecosteroidal VDR agonist (CH5036249) showed an cell growth inhibitory activity of CH5036249 to be comparable to that of 1alpha,25(OH)2D3(11). Other analogs, including BXL-353, may also be potential for patients with BPH(12).

Taken altogether, serum of vitamin D may not be realizable diagnosis in determination the early onset of BPH, and vitamin D analogs are associated to reduced risk and treatment of Benign prostatic hyperplasia(BPH). As a;ways. all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying.


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References
(a) Dietary patterns, supplement use, and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial by Kristal AR1, Arnold KB, Schenk JM, Neuhouser ML, Goodman P, Penson DF, Thompson IM.(PubMed)
(b) Dietary patterns, supplement use, and the risk of benign prostatic hyperplasia by Poon KS1, McVary KT.(PubMed)
(c) Vitamin D and benign prostatic hyperplasia -- a review by Espinosa G1, Esposito R, Kazzazi A, Djavan B.(PubMed)
(1) Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostatic hyperplasia in a Japanese population by Habuchi T1, Suzuki T, Sasaki R, Wang L, Sato K, Satoh S, Akao T, Tsuchiya N, Shimoda N, Wada Y, Koizumi A, Chihara J, Ogawa O, Kato T.(PubMed)
(2) Systematic Review and Meta-analysis of Candidate Gene Association Studies of Lower Urinary Tract Symptoms in Men by Cartwright R1, Mangera A2, Tikkinen KA3, Rajan P4, Pesonen J5, Kirby AC6, Thiagamoorthy G7, Ambrose C8, Gonzalez-Maffe J9, Bennett PR10, Palmer T11, Walley A12, Järvelin MR13, Khullar V14, Chapple C15(PubMed)
(3) [Relationship between vitamin D receptor gene Fok I polymorphisms and benign prostatic hyperplasia complicated by histological prostatitis].[Article in Chinese] by Ruan L1, Zhong WD, Li ZM, Hua X.(PubMed)
(4) Association of genetic variants of the vitamin D receptor (VDR) gene (Fok-I, Taq-I and Bsm-I) with susceptibility of benign prostatic hyperplasia in a North Indian population by Manchanda PK1, Konwar R, Nayak VL, Singh V, Bid HK.(PubMed)
(5) Lack of association of VDR polymorphisms with Thai prostate cancer as compared with benign prostate hyperplasia and controls by Chaimuangraj S1, Thammachoti R, Ongphiphadhanakul B, Thammavit W.(PubMed)
(6) Low 25-OH vitamin D is associated with benign prostatic hyperplasia by Haghsheno MA1, Mellström D, Behre CJ, Damber JE, Johansson H, Karlsson M, Lorentzon M, Peeker R, Barret-Connor E, Waern E, Sundh V, Ohlsson C, Hammarsten J.(PubMed)
(7) Serum levels of prostate-specific antigen and vitamin D in peritoneal dialysis patients by Passadakis P1, Ersoy F, Tam P, Memmos D, Siamopoulos K, Ozener C, Akçiçek F, Camsari T, Ates K, Ataman R, Vlachojannis J, Dombros N, Utas C, Akpolat T, Bozfakioglu S, Wu GG, Karayaylali I, Arinsoy T, Stathakis C, Yavuz M, Tsakiris D, Dimitriades A, Yilmaz ME, Gültekin M, Karayalçin B, Challa A, Polat N, Oreopoulos DG.(PubMed)

(8 BXL-628, a vitamin D receptor agonist effective in benign prostatic hyperplasia treatment, prevents RhoA activation and inhibits RhoA/Rho kinase signaling in rat and human bladder by Morelli A1, Vignozzi L, Filippi S, Vannelli GB, Ambrosini S, Mancina R, Crescioli C, Donati S, Fibbi B, Colli E, Adorini L, Maggi M.(PubMed)
(9) Vitamin D receptor agonists target static, dynamic, and inflammatory components of benign prostatic hyperplasia by Adorini L1, Penna G, Fibbi B, Maggi M.(PubMed)
(10) Vitamin D and benign prostatic hyperplasia -- a review by Espinosa G1, Esposito R, Kazzazi A, Djavan B.(PubMed)
(11) A novel nonsecosteroidal VDR agonist (CH5036249) exhibits efficacy in a spontaneous benign prostatic hyperplasia beagle model by Taniguchi K1, Katagiri K, Kashiwagi H, Harada S, Sugimoto Y, Shimizu Y, Arakawa H, Ito T, Yamazaki M, Watanabe T, Kato A, Hoshino E, Takahashi T, Esaki T, Suzuki M, Takeda S, Ichikawa F, Harada A, Sekiguchi N, Ishigai M, Kawata H, Yoneya T, Onuma E, Sudoh M, Aoki Y.(PubMed)
(12) Inhibition of spontaneous and androgen-induced prostate growth by a nonhypercalcemic calcitriol analog by Crescioli C1, Ferruzzi P, Caporali A, Mancina R, Comerci A, Muratori M, Scaltriti M, Vannelli GB, Smiroldo S, Mariani R, Villari D, Bettuzzi S, Serio M, Adorini L, Maggi M.(PubMed)

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