Status deficiente da vitamina D no sangue e o risco de doenças cronicas – Dr. Holick’s Responses to Participant Questions During the December 5, 2008 Live Webinar Presentation “Vitamin D & Chronic Disease Risk”

Status deficiente da vitamina D no sangue e o risco de doenças cronicas –

Dr. Holick’s Responses to Participant Questions During the December 5, 2008 Live Webinar Presentation “Vitamin D & Chronic Disease Risk”

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 Dr. Michael F. Holick

VitaminDHealth.org

vitamin-d-solution

Dr. Michael F. Holick on Vitamin D

http://vitamindhealth.org/

Articles by Category

Michael F. Holick, PhD, MD

Professor of Medicine, Physiology and Biophysics

Director of the General Clinical Research Center

Director of the Vitamin D, Skin and Bone Research Laboratory

Director, Biologic Effects of Light Research Center

Boston University Medical Center

Dr. Holick’s new book The Vitamin D Solution is now available! Click on the book cover for more information on how to order.

 

Vitamin D is not a vitamin but a hormone. It is unique in that it is made in the skin as a result of exposure to sunlight. Photosynthesis of vitamin D has been occurring on earth for more than 750 million years. Some of the earliest life forms that were exposed to sunlight for their energy requirement were also photosynthesizing vitamin D. Both children and adults have in the past depended on adequate sun exposure to satisfy their vitamin D requirement. It is well documented that at the turn of the last century upwards of 80% of children in the industrialized, polluted cities of northern Europe and northeastern United States suffered from the devastating consequences of vitamin D deficiency rickets. The skin has a large capacity to make vitamin D. Exposure of a person in a bathing suit to a minimal erythemal dose of sunlight, which is typically no more than 15-20 minutes on Cape Cod in June or July at noon time, is the equivalent to taking 20,000 IU of vitamin D orally. It is now well documented that in the absence of any sun exposure 1,000 IU of vitamin D3 a day is necessary to maintain healthy levels of 25-hydroxyvitamin D in the circulation. An analysis of the NHANES III data has demonstrated that neither children nor adults are receiving an adequate amount of vitamin D from their diet or from supplements.

Read more of this article »

 

Dr. Holick’s Responses to Participant Questions During the December 5, 2008 Live Webinar Presentation “Vitamin D & Chronic Disease Risk”

Posted by mfholick on under Cancer, Multiple Sclerosis, Osteomalacia, Osteoporosis, Rickets, Vitamin D | 57 Comments to Read

 

VITAMIN D AND DISEASE STATES

EPILEPSY

 

I have heard that vitamin D may play a role in epilepsy, possibly due to interaction with anti-epileptic drugs. Is this becoming an acknowledged effect? And how much vitamin D is necessary to combat the interaction to reduce seizures?

Response: Epileptic drugs will enhance the destruction of vitamin D making patients who are on anti-seizure medications at higher risk for developing vitamin D deficiency and osteomalacia or rickets. Measurement of 25-hydroxyvitamin D [25(OH)D] is important in patients on antiepileptic medications. Often twice as much vitamin D is required to maintain a blood level of 25(OH)D of > 30 ng/ml. Thus, 2,000-4,000 IU of vitamin D/d is usually needed. An alternative is to take 50,000 IU of vitamin D2 either once every week or once every two weeks depending on the serum 25-hydroxyvitamin D level.

 

MENTAL HEALTH

What is your position on vitamin D and depression and schizophrenia?

Response: There is evidence that vitamin D deficiency during pregnancy increases the risk of the child developing schizophrenia during their adult life. There is also evidence that vitamin D receptors exist in the brain, and that the active form of vitamin D, 1,25-dihydroxyvitamin D, Read more of this article »

 

Multiple Sclerosis and Vitamin D

Posted by admin on under Multiple Sclerosis, Vitamin D | 5 Comments to Read

It is known that if you are born above 35° latitude at approximately Atlanta, Georgia, and live at this latitude for the first ten years of your life that you have a 100% increase risk of developing multiple sclerosis. Recent studies have suggested that women and men who increase their vitamin D intake above 400 IU of vitamin D a day reduces risk of developing multiple sclerosis by approximately 40%.

 

References:

Munger KL, Zhang SM, O’Reilly E, Hernan MA, Olek MJ, Willett WC, Ascherio A. Vitamin D intake and incidence of multiple sclerosis. Neurology 2004; 62(1):60-5.

Munger KL, Levin LI, Hollis, BW, Howard NS, Ascheino A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006; 296:2832-2838.

Ponsonby A-L, McMichael A, and van der Mei I. Ultraviolet radiation and autoimmune disease: insights from epidemiological research. Toxocology 2002;181-182:71-78.

 

Infectious Diseases and Vitamin D

Posted by admin on under Infectious Disease, Vitamin D | 2 Comments to Read

It has long been recognized that patients with tuberculous do better when treated with vitamin D or exposed to sunlight. It was recently recognized that the immune cell known as the macrophage needs vitamin D in order to produce a peptide which is responsible for killing infectious agents such as tuberculous. It has been speculated that one of the reasons that influenza occurs in the winter time in tepid climates is because the sun is unable to produce vitamin D, and the resulting vitamin D insufficiency may promote and enhance the infectivity of the influenza virus.

References: Adams,J.S., Gacad,M.A., Anders,A., Endres,D.B., and Sharma,O.P. 1986. Biochemical indicators of disordered vitamin D and calcium homeostasis in sarcoidosis. Sarcoidosis 3:1-6.

Gallo, R.L., Eisenberg, D., Hewison, M., Hollis, B.W., Adams, J.S., Bloom, B.R., Modlin, R.L. 2006. Toll-like receptor Triggering of a vitamin D-mediated human antimicrobial response. Sciencexpress. 3:1770-1773. Liu, P.T., Stenger, S., Li, H., Wenzel, L., Tan, B.H., Krutzik, S., Ochoa, M.T., Schauber, J., Wu, K., Meinken, C., Kamen, D.L., Wagner, M., Bals, R., Steinmeyer, A., Zugel, U.

 

Arthritis and Vitamin D

Posted by admin on under Arthritis, Vitamin D | 9 Comments to Read

Rheumatoid Arthritis and Osteoarthritis

Recent studies have revealed that women who ingest more than 400 IU of vitamin D a day reduce their risk of developing rheumatoid arthritis by as much as 42%.

Vitamin D deficiency has been associated with an increased risk of developing osteoarthritis.

Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, and Saag KG. Vitamin D intake is inversely associated with rheumatoid arthritis. Arthritis & Rheumatism 2004; 50(1):72-77.

 

Diabetes and Vitamin D

Posted by admin on under Diabetes, Vitamin D | 6 Comments to Read

Diabetes mellitus type I

Studies in mice have suggested that pretreating mice that are prone to developing type I diabetes with the active form of vitamin D (1,25-hydroxyvitamin D [1,25(OH)2D]) reduces the development of type I diabetes by 80%. This study is supported by the observation in Finland where children in the 1960’s routinely received 2,000 IU of vitamin D a day during their first year of life. When these children were followed for the next 31 years, it was observed that these children had a reduced risk of developing type I diabetes by 78%. Children who were vitamin D deficient at the same time and also followed for 31 years had an almost 300% increased risk of developing type I diabetes.

Reference:

Hypponen E, Laara E, Jarvelin M-R, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001;358:1500-1503.

Diabetes mellitus type II

The beta islet cells that produce insulin in the pancreas have a vitamin D receptor. The active form of vitamin D stimulates the pancreas to produce insulin. It has been observed that the relative risk of developing type II diabetes is reduced by as much as 33% in men and women who increase their intake of vitamin D above 800 IU/day along with 1,000 milligrams of calcium.

Reference:

Pittas AG, Dawson-Hughes B, Li T, et al. Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care 2006:29:650-56.

 

Rickets and Vitamin D

Posted by admin on under Rickets, Vitamin D | 2 Comments to Read

Rickets occurs at approximately six months of age in children who are vitamin D deficient. They can present with growth retardation, skeletal deformities including bowing of the legs or knocked knees, prominent knob like projections along the ribs next to the sternum known as the rachitic rosary and muscle weakness. Infants with vitamin D deficiency also suffer from craniotabes which is a softening of the skull causing it to become square shaped. They can have increase in the bone formation in the front of the head which is known as frontal bossing.

References:

Holick, M.F. Resurrection of vitamin D deficiency and rickets. J Clin Invest 2006, 116(8):2062-2072..

Kreiter SR, Schwartz RP, Kirkman HN, Charlton PA, Calikoglu AS, Davenport M. Nutritional rickets in African American breast-fed infants. J Pediatr 2000;137:2-6.

Marksted, T., Halvorsen, S., Halvorsen, K.S., Aksnes, L., and Aarskog, D. 1984. Plasma concentrations of vitamin D metabolites before and during treatment of vitamin D deficiency rickets in children. Acta Padiatr Scand. 73:225-231.

 

Osteomalacia and Vitamin D

Posted by admin on under Osteomalacia, Vitamin D | Read the First Comment

Vitamin D deficiency causes a defect in the ability of the body to deposit calcium into the collagen jello-like matrix in the bone. As a result, the covering on the bone which contains pain sensing nerves is easily deformed resulting in throbbing aching bone pain. Patients with osteomalacia often complain of achiness in their muscles and bones. These non-specific aches and pains in the bones and muscles are often misdiagnoses as fibromyalgia or chronic fatigue syndrome. There have been several studies demonstrating that patients with severe bone and muscle pain and muscle weakness associated with osteomalacia have dramatic improvement in their symptoms when vitamin D deficiency is corrected. It takes months to years to develop osteomalacia and associated symptoms and it takes three to six months before significant improvement in symptoms results from correcting vitamin D deficiency.

References:

Holick, M.F. Vitamin D deficiency: What a Pain it is. Mayo Clin. Proc. 2003; 78(12): 1457-1459.

Malabanan AO, Turner AK, Holick MF. Severe generalized bone pain and osteoporosis in a premenopausal black female: effect of vitamin D replacement. J Clin Densitometr . 1998;1:201-204.

 

Osteoporosis and Vitamin D

Posted by admin on under Osteoporosis, Vitamin D | 3 Comments to Read

Vitamin D deficiency will cause removal of both the calcium and matrix from the bone, and as a result, will cause osteopenia and can precipitate and exacerbate osteoporosis. Unlike osteomalacia which causes bone pain, osteoporosis, which is porotic bone, i.e., holes in the bones and loss of bone does not cause bone pain unless there is an acute fracture. Typically this pain resolves as the fracture heals and can be easily distinguished from osteomalacia.

References:

Bischoff-Ferrari, HA, Giovannucci, E., Willett, W.C., Dietrich, T., and Dawson-Hughes, B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 2006; 84:18-28.

Boonen S, Bischoff-Ferrari A, Cooper C, Lips P, Ljunggren O, Meunier PJ, Reginster JY. Addressing the musculoskeletal components of fracture risk with calcium and vitamin D: a review of the evidence. Calcif Tissue Int 2006; 78(5):257-70.

Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992; 327(23):1637-1642.

 

Cancer and Vitamin D

Posted by admin on under Cancer, Vitamin D | 6 Comments to Read

Cancer

As early as 1941, it was observed that people living at higher latitude were at higher risk of dying of cancer. In the 1980’s and the 1990’s, several reports surfaced revealed that living at higher latitude and being at higher risk of vitamin D deficiency increased risk of developing and dying of cancers of the colon, rectum, prostate, breast, ovary. More recently, vitamin D deficiency has been associated with increased risk of developing many other cancers including cancer of the esophagus, pancreas and leukemia. Read more of this article »

 

Obesity

Posted by admin on under Obesity, Vitamin D | 14 Comments to Read

Obesity is associated with vitamin D deficiency. The reason is that the vitamin D is trapped within the fat and cannot easily exit. As a result, obese patients need at least twice as much vitamin D as a normal weighted individual in order to maintain a normal vitamin D status with a 25(OH)D between 30-60 ng/ml.Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000;72: 690-693.

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1.       Vitamina D e doenças causadas pela deficiência

https://objetodignidade.wordpress.com/2013/06/04/vitamina-d-e-doencas-causadas-pela-deficiencia/

  1. The Vitamin Which Can Cut Your Flu Risk Nearly in Half

https://objetodignidade.wordpress.com/2013/04/24/the-vitamin-which-can-cut-your-flu-risk-nearly-in-half/

 

3.       20 razões para tomar Vitamina D

https://objetodignidade.wordpress.com/2013/04/24/20-razoes-para-tomar-vitamina-d/

 

4.       Vitamin D and Health

https://objetodignidade.wordpress.com/2013/04/24/vitamin-d-and-health-2/

 

5.       Vitamina D – contra envelhecimento e contra a gripe suína

https://objetodignidade.wordpress.com/2013/04/23/vitamina-d-contra-envelhecimento-e-contra-a-gripe-suina/

 

6.       Vitamin D Deficiency – Michael F. Holick, M.D., Ph.D.

https://objetodignidade.wordpress.com/2013/04/22/vitamin-d-deficiency-michael-f-holick-m-d-ph-d/

 

7.       Como funciona e qual é a relação entre vitamina D e proteção ao câncer

https://objetodignidade.wordpress.com/2013/04/21/como-funciona-e-qual-e-a-relacao-entre-vitamina-d-e-protecao-ao-cancer/

 

8.       Fatigue and Muscle Weakness From a Vitamin D Deficiency

https://objetodignidade.wordpress.com/2013/04/16/fatigue-and-muscle-weakness-from-a-vitamin-d-deficiency/

 

9.       Serum 25-Hydroxyvitamin D Levels and Risk of Multiple Sclerosis

https://objetodignidade.wordpress.com/2013/04/15/serum-25-hydroxyvitamin-d-levels-and-risk-of-multiple-sclerosis/

 

10.   Dr. Cícero Galli Coimbra, fundador e Presidente do Instituto de Investigação e Tratamento de Autoimunidade, médico neurologista, Phd., M.D., professor na Universidade Federal de São Paulo

https://objetodignidade.wordpress.com/2013/04/21/dr-cicero-galli-coimbra-fundador-e-presidente-do-instituto-de-investigacao-e-tratamento-de-autoimunidade-medico-neurologista-phd-m-d-professor-na-universidade-federal-de-sao-paulo/

 

  1. Estudo randomizado de suplementação de vitamina D para prevenir a gripe sazonal A em crianças em idade escolar – Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren

https://objetodignidade.wordpress.com/2013/04/29/estudo-randomizado-de-suplementacao-de-vitamina-d-para-prevenir-a-gripe-sazonal-a-em-criancas-em-idade-escolar-randomized-trial-of-vitamin-d-supplementation-to-prevent-seasonal-influenza-a-in-school/

 

  1. É preciso reconhecer os sintomas da deficiência de vitamina D, o hormonio esteroide imunoregulador

https://objetodignidade.wordpress.com/2013/04/29/e-preciso-reconhecer-os-sintomas-da-deficiencia-de-vitamina-d-o-hormonio-esteroide-imunoregulador/

 

13.   A suplementação de vitamina D aumentou a resposta à terapêutica anti-tuberculose em um estudo randomizado de pacientes com tuberculose pulmonar com baciloscopia positiva.

https://objetodignidade.wordpress.com/2013/04/30/a-suplementacao-de-vitamina-d-aumentou-a-resposta-a-terapeutica-anti-tuberculose-em-um-estudo-randomizado-de-pacientes-com-tuberculose-pulmonar-com-baciloscopia-positiva/

 

14.   Estudo controlado randomizado mostra ligação entre a vitamina D e rinite alérgica

https://objetodignidade.wordpress.com/2013/05/01/estudo-controlado-randomizado-mostra-ligacao-entre-a-vitamina-d-e-rinite-alergica/

 

15.   A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis

https://objetodignidade.wordpress.com/2013/06/01/a-pilot-study-assessing-the-effect-of-prolonged-administration-of-high-daily-doses-of-vitamin-d-on-the-clinical-course-of-vitiligo-and-psoriasis/

15 . Traumatic Brain Injury and Aging: Is a Combination of Progesterone and Vitamin D Hormone a Simple Solution to a Complex Problem?

https://objetodignidade.wordpress.com/2013/06/02/traumatic-brain-injury-and-aging-is-a-combination-of-progesterone-and-vitamin-d-hormone-a-simple-solution-to-a-complex-problem/

16. O que você não sabe ou reconhece pode prejudicar a sua saúde

https://objetodignidade.wordpress.com/2013/05/31/o-que-voce-nao-sabe-ou-reconhece-pode-prejudicar-a-sua-saude/

17.  Câncer de mama: a vitamina D ou mastectomia

https://objetodignidade.wordpress.com/2013/05/30/cancer-de-mama-a-vitamina-d-ou-mastectomia/

18.  A vitamina D supera a vacina contra a gripe

https://objetodignidade.wordpress.com/2013/05/30/a-vitamina-d-supera-a-vacina-contra-a-gripe/

19.  Não patenteiem meus genes! Liberem os genes do câncer da mama!

https://objetodignidade.wordpress.com/2013/05/30/nao-patenteiem-meus-genes-liberem-os-genes-do-cancer-da-mama/

20.  Existe terapêutica natural e de baixo custo para doenças autoimunitárias. Depoimentos de pacientes com esclerose múltipla. Vitamina D – Dr. Cícero Galli Coimbra, PhD, MD.

https://objetodignidade.wordpress.com/2013/05/26/existe-terapeutica-natural-e-de-baixo-custo-para-doencas-autoimunitarias-depoimentos-de-pacientes-com-esclerose-multipla-vitamina-d-dr-cicero-galli-coimbra-phd-md/

21.  Vitamina D – Por uma outra terapia (p/ a esclerose múltipla) e todas as doenças autoimunes

https://www.youtube.com/watch?feature=player_detailpage&v=erAgu1XcY-U

  1. Vitamina D pode revolucionar o tratamento da esclerose múltipla*

http://biodireitomedicina.wordpress.com/category/doencas-autoimunes/

  1. POR UM NOVO PARADIGMA DE CONDUTA E TRATAMENTO http://www.institutodeautoimunidade.org.br/novo-paradigma.html

Por Dr. Cícero Galli Coimbra Médico Internista e Neurologista, Professor Associado Livre-Docente da Universidade Federal de São Paulo, Fundador e Presidente do Instituto de Investigação e Tratamento de Autoimunidade  

24.  Dr. Cícero Galli Coimbra – Doenças Autoimunes e Vitamina D

http://www.youtube.com/watch?v=4uJt1361aGw

25.  Mais de 10 anos de tratamento com a Vitamina D – Exijam que seus médicos se atualizem!

http://biodireitomedicina.wordpress.com/2012/12/23/mais-de-10-anos-de-tratamento-com-a-vitamina-d-exija-que-seus-medicos-se-atualizem/  – https://www.youtube.com/watch?v=fQN32qR_M2Y

 

26.  POR 30 ANOS, EXTENSA REVISÃO DE TODA A PESQUISA ANTERIOR CONFIRMA QUE BAIXO NÍVEL DE VITAMINA D É UMA SENTENÇA DE MORTE

http://biodireitomedicina.wordpress.com/2013/02/14/vitamina-d-reportagem-com-dr-cicero-galli-coimbra-e-daniel-cunha-na-rede-record/

27.  “As doses diárias de 10.000 unidades de colecalciferol devem ser tomadas por todas pessoas. Essa quantidade previne todas as doenças inclusive à autoimunidade. Com 10.000 unidades a pessoa sai da deficiencia de vitamina D. A dose de 1.000 unidades não tira as pessoas da deficiencia de vitamina D.’’ – Dr. Cicero Galli Coimbra, medico neurologista, Phd., professor na Universidade Federal de São Paulo, Presidente do Instituto de Investigação e Tratamento de Autoimunidade

https://objetodignidade.wordpress.com/2013/01/21/as-doses-diarias-de-10-000-unidades-de-colecalciferol-devem-ser-tomadas-por-todas-pessoas-essa-quantidade-previne-todas-as-doencas-inclusive-a-autoimunidade-com-10-000-unidades-a-pessoa-sai/

28.  Entrevistas com Dr. Cícero Galli Coimbra sobre o hormônio-vitamina D

http://www.youtube.com/playlist?list=PLeqEGmvbpULN2NfNfnLU6bYse4fp9alQS

  1. Dr. Cícero Galli Coimbra – Esclerose múltipla e o tratamento com a vitamina D – 28.01.13 – TV Mundi

https://objetodignidade.wordpress.com/2013/02/03/dr-cicero-galli-coimbra-esclerose-multipla-e-o-tratamento-com-a-vitamina-d-28-01-13-tv-mundi/

  1. Dr. Cícero Galli Coimbra – Esclerose múltipla e o tratamento com a vitamina D – 28.01.13 – TV Mundi

http://www.youtube.com/watch?v=hv6tD3B0Nlo&list=PLeqEGmvbpULNrc8biL5LF9Mp3-WbJT2Ao

http://www.youtube.com/watch?list=PLeqEGmvbpULNrc8biL5LF9Mp3-WbJT2Ao&feature=player_detailpage&v=hv6tD3B0Nlo

  1. “As doses diárias de 10.000 unidades de colecalciferol devem ser tomadas por todas pessoas. Essa quantidade previne todas as doenças inclusive à autoimunidade. Com 10.000 unidades a pessoa sai da deficiencia de vitamina D. A dose de 1.000 unidades não tira as pessoas da deficiencia de vitamina D.’’ – Dr. Cicero Galli Coimbra, medico neurologista, Phd., professor na Universidade Federal de São Paulo, Presidente do Instituto de Investigação e Tratamento de Autoimunidade

https://objetodignidade.wordpress.com/2013/01/21/as-doses-diarias-de-10-000-unidades-de-colecalciferol-devem-ser-tomadas-por-todas-pessoas-essa-quantidade-previne-todas-as-doencas-inclusive-a-autoimunidade-com-10-000-unidades-a-pessoa-sai/

32.  A responsabilidade Civil e Criminal Médica na Desinformação às pessoas – Revista VEJA, 2.304: “O que você não sabe sobre a Vitamina do Sol. Ela continua a surpreender a medicina com novos efeitos benéficos.”

https://objetodignidade.wordpress.com/2013/05/25/a-responsabilidade-civil-e-criminal-medica-na-desinformacao-as-pessoas-revista-veja-2-304-o-que-voce-nao-sabe-sobre-a-vitamina-do-sol-ela-continua-a-surpreender-a-medicina-com-novos-efe/

33.  Vitamina D: A Desinformação Médica e o Direito à Informação do Cidadão

https://objetodignidade.wordpress.com/2013/05/25/vitamina-d-a-desinformacao-medica-e-o-direito-a-informacao-do-cidadao-2/

34.  A suplementação de vitamina D aumentou a resposta à terapêutica anti-tuberculose em um estudo randomizado de pacientes com tuberculose pulmonar com baciloscopia positiva.

https://objetodignidade.wordpress.com/2013/04/30/a-suplementacao-de-vitamina-d-aumentou-a-resposta-a-terapeutica-anti-tuberculose-em-um-estudo-randomizado-de-pacientes-com-tuberculose-pulmonar-com-baciloscopia-positiva/

35.  Estudo randomizado de suplementação de vitamina D para prevenir a gripe sazonal A em crianças em idade escolar – Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren

https://objetodignidade.wordpress.com/2013/04/29/estudo-randomizado-de-suplementacao-de-vitamina-d-para-prevenir-a-gripe-sazonal-a-em-criancas-em-idade-escolar-randomized-trial-of-vitamin-d-supplementation-to-prevent-seasonal-influenza-a-in-school/

  1. É preciso reconhecer os sintomas da deficiência de vitamina D, o hormonio esteroide imunoregulador

https://objetodignidade.wordpress.com/2013/04/29/e-preciso-reconhecer-os-sintomas-da-deficiencia-de-vitamina-d-o-hormonio-esteroide-imunoregula

  1. The Vitamin Which Can Cut Your Flu Risk Nearly in Half

https://objetodignidade.wordpress.com/2013/04/24/the-vitamin-which-can-cut-your-flu-risk-nearly-in-half/

 

  1. 20 razões para tomar Vitamina D

https://objetodignidade.wordpress.com/2013/04/24/20-razoes-para-tomar-vitamina-d/

  1. Vitamin D and Health

https://objetodignidade.wordpress.com/2013/04/24/vitamin-d-and-health-2/

  1. Vitamina D – contra envelhecimento e contra a gripe suína

https://objetodignidade.wordpress.com/2013/04/23/vitamina-d-contra-envelhecimento-e-contra-a-gripe-suina/

  1. Vitamin D Deficiency – Michael F. Holick, M.D., Ph.D.

https://objetodignidade.wordpress.com/2013/04/22/vitamin-d-deficiency-michael-f-holick-m-d-ph-d/

  1. Como funciona e qual é a relação entre vitamina D e proteção ao câncer

https://objetodignidade.wordpress.com/2013/04/21/como-funciona-e-qual-e-a-relacao-entre-vitamina-d-e-protecao-ao-cancer/

  1. Fatigue and Muscle Weakness From a Vitamin D Deficiency

https://objetodignidade.wordpress.com/2013/04/16/fatigue-and-muscle-weakness-from-a-vitamin-d-deficiency/

  1. Serum 25-Hydroxyvitamin D Levels and Risk of Multiple Sclerosis

https://objetodignidade.wordpress.com/2013/04/15/serum-25-hydroxyvitamin-d-levels-and-risk-of-multiple-sclerosis/

  1. Dr. Cícero Galli Coimbra, fundador e Presidente do Instituto de Investigação e Tratamento de Autoimunidade, médico neurologista, Phd., M.D., professor na Universidade Federal de São Paulo

https://objetodignidade.wordpress.com/2013/04/21/dr-cicero-galli-coimbra-fundador-e-presidente-do-instituto-de-investigacao-e-tratamento-de-autoimunidade-medico-neurologista-phd-m-d-professor-na-universidade-federal-de-sao-paulo/

 

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Esclerose múltipla – sobre a gravidade da deficiência desse hormônio

Esclerose múltipla – sobre a gravidade da deficiência desse hormônio

CALCIFEROL

Daniel Cunha

Cicero

Vitamina D – Por uma outra terapia (p/ a esclerose múltipla)

http://www.youtube.com/watch?feature=player_detailpage&v=erAgu1XcY-U

] dc2

Mais de 10 anos com o tratamento com vitamina D p/ esclerose múltipla

http://www.youtube.com/watch?feature=player_detailpage&v=fQN32qR_M2Y

Entrevistas com Junia, Márcia e Nayra sobre a experiência da família com o tratamento da vitamina D. Nayra descobriu a EM há mais de 10 anos e é provavelmente uma das pacientes mais antigas tratando a EM com o Dr. Cícero Coimbra.

Esclerose múltipla, distúrbio metabólico – atualizado em 7/janeiro/2013

https://objetodignidade.wordpress.com/2013/01/07/esclerose-multipla-disturbio-metabolico-atualizado-em-7fevereiro2013/

“Infelizmente este conhecimento não tem sido levado aos livros textos de medicina e isso gera esse desconhecimento, não só do público em geral mas até da classe médica em relação á gravidade dessa situação sobre a deficiência desse hormonio esteroide, conhecido como vitamina D. Esta deficiencia torna as 229 funções do sistema imunológico do próprio organismo das pessoas desregulado, permitindo desenvolver qualquer doença, o que levou á pandemia do mundo atual.” – Dr. Cicero Galli Coimbra, medico neurologista, Phd., MD, neurocirurgião, neurocientista, professor na UNIFESP

 https://objetodignidade.wordpress.com/2012/12/09/por-um-novo-paradigma-de-conduta-e-tratamento-estamos-vivendo-uma-defasagem-entre-o-conhecimento-cientifico-e-a-pratica-medica-dr-cicero-galli-coimbra/

Vitamina D em medicina preventiva: estamos ignorando as provas?

“Os dados epidemiológicos indicam também um baixo status da vitamina D na tuberculose, artrite reumatóide, esclerose múltipla, doenças inflamatórias intestinais, hipertensão e certos tipos de câncer.”

https://objetodignidade.wordpress.com/2009/08/28/vitamina-d-em-medicina-preventiva-estamos-ignorando-as-provas/

Zittermann A .A Zittermann.

Department of Nutrition Science, University of Bonn, Endenicher Allee 11-13, 53115 Bonn, Germany. Departamento de Ciência da Nutrição, da Universidade de Bonn, Endenicher Allee 11-13, 53115 Bonn, Alemanha. a.zittermann@uni-bonn.de a.zittermann @ uni-bonn.de

Vitamin D is metabolised by a hepatic 25-hydroxylase into 25-hydroxyvitamin D (25(OH)D) and by a renal 1alpha-hydroxylase into the vitamin D hormone calcitriol. A vitamina D é metabolizado por uma 25-hidroxilase hepática em 25-hidroxi-vitamina D (25 (OH) D) e por um 1alpha renal-hidroxilase no hormônio calcitriol vitamina D.

Dispoível em

http://64.233.163.132/translate_c?hl=pt-BR&langpair=en%7Cpt&u=http://www.ncbi.nlm.nih.gov/pubmed/12720576&prev=/translate_s%3Fhl%3Dpt-BR%26q%3DVitamina%2BD%2Be%2Bdepress%25C3%25A3o%26sl%3Dpt%26tl%3Den&rurl=translate.google.com.br&usg=ALkJrhjspQEBlxCMyClVGNWHjrZsYK2BOA

Vitamina D é importantíssima para a saúde
Disponível em http://biodireitomedicina.wordpress.com/category/a-prevencao-de-doencas-neurodegenerativas/

Vitamina D pode revolucionar o tratamento da esclerose múltipla*
http://biodireitomedicina.wordpress.com/2010/08/03/vitamina-d-pode-revolucionar-o-tratamento-da-esclerose-multipla/
*Dr. Cícero Galli Coimbra
PHD Médico Neurologista e Professor Livre-Docente

O que é possível dizer em breves palavras, já oferece um quadro preocupante. A insuficiência de vitamina D tem desenvolvido muitas outras doenças, alem do raquitismo e da osteoporose, que já são aceitas como “comuns” e típicas da medicina das doenças crônicas.

 

Associadas á deficiencia de vitamina D estão o câncer, as diabetes, problemas cardiovasculares, transtorno bipolar, autismo, mal de Alzheimer e esquizofrenia, psoríase, depressão. O comercio industrial multimilionário da farmácia, não traz a cura, apresenta medicação cara e talvez paliativa.

 

Diz assim a medicina das doenças crônicas: “a sua doença não tem cura”… E, no entanto, todas essas doenças graves sequer teriam desenvolvido nas pessoas, se existisse o cuidado com a medicina preventiva com a suplementação da vitamina D3, o hormônio esteroide imunoregulador.

 

Os médicos vêm apresentando pesquisa que aponta o aumento de epidemias em todo planeta, por causa da falta de investimento dos governos em saúde preventiva com suplementação da vitamina D.

Vitamin D deficiency: a global perspectivehttps://objetodignidade.wordpress.com/2011/08/15/vitamin-d-deficiency-a-global-perspective/

Deficiência de vitamina D: uma epidemia global
https://objetodignidade.wordpress.com/2011/08/15/deficiencia-de-vitamina-d-uma-epidemia-global/

Symposium: Vitamin D Insufficiency: A Significant Risk Factor in Chronic Diseases and Potential Disease-Specific Biomarkers of Vitamin D Sufficiency Vitamin D Intake: A Global Perspective of Current Status
https://objetodignidade.wordpress.com/2011/08/15/symposium-vitamin-d-insufficiency-a-significant-risk-factor-in-chronic-diseases-and-potential-disease-specific-biomarkers-of-vitamin-d-sufficiency-vitamin-d-intake-a-global-perspective-of-current-s/

 

Brasil ainda investe pouco em saúde País investe apenas 8,7% do valor arrecadado com impostos em saúde. Número é inferior ao de países como Argentina, Chile e Venezuela. Um estudo realizado pela Fundação Instituto de Administração da Universidade de São Paulo (USP)
https://objetodignidade.wordpress.com/2011/08/05/brasil-ainda-investe-pouco-em-saude/

 

O aumento da Deficiência de vitamina D3 geralmente se apresentava como deformidade óssea (raquitismo) ou hipocalcemia na infância e como dor músculoesquelética e fraqueza em adultos.

 

Hoje os estudos são avançados e os médicos constataram muitos outros problemas de saúde, incluindo doenças cardiovasculares, diabetes, vários tipos de câncer, e autoimunes como mal de Alzheimer e esclerose múltipla, hipo e hipertireoidismo, artrite, vitiligo, associadas á alta insuficiência de vitamina D no sangue.

 

O status da vitamina D é mais confiável determinado pelo ensaio de soro de 25-hidroxivitamina D3 (25-OHD3).


O consenso entre os médicos definiu a medida da nanoterapia como ideal acima de 40 ng/ml de sangue. Abaixo de 40 já existe deficiencia mesmo que a pessoa ainda não apresente qualquer sintoma de doença. Isto significa que há meio de baixo custo para a prevenção de epidemias. A suplementação e reposição da colecalciferol, a vitamina D3 a vitamina D3, deve ser feita em altas doses. Muito alem das convencionadas 600 UI da medicina do passado, para ter uma idéia uma gota [0,05 ml] da solução de colecalciferol tem 1.000 UI [unidades internacionais].

 

O espectro dessas doenças comuns e graves, é particularmente preocupante porque os estudos observacionais têm demonstrado que a insuficiência de vitamina D3, desenvolve Raquitismo em crianças e osteomalacia em adultos são apenas manifestações clássicas de deficiência de vitamina D3 profunda. Nos últimos anos, no entanto, aparecem doenças não músculoesqueléticas condições incluindo câncer, síndrome metabólica, infecciosas e doenças autoimunes, esclerose múltipla, doenças que também foram encontrados associados aos baixos níveis de vitamina D. O Aumento da prevalência de distúrbios ligados à deficiência de VITAMINA D, É REFLETIDA NO AUMENTO DO NUMERO DE CRIANÇAS DOENTES.


EPIDEMIAS CRESCEM SE NÃO FOR DADA NUTRIÇÃO ADEQUADA E SUPLEMENTOS Á TODA POPULAÇÃO. Este é o cuidado que o governo brasileiro deve ter com todas as pessoas, indistintamente, em todas as idades.]

 

Dilma e Lula não sabem disso, e desde 2008 favorecem pesquisas com células de embriões e abortos.


“É interessante notar que as geografias de raquitismo (Hess, 1929) e MS são muito semelhantes, a geografia do raquitismo levou Sniadecki (citado por Holick, 1995) para sugerir em 1822 que o sol pode curar o raquitismo. Lamentavelmente, diz Hayes, o raquitismo continuou a aleijar crianças por um século inteiro antes de investigadores demonstrarem os benefícios da luz solar ou óleo de fígado de bacalhau (Hess & Unger, 1921; Chick et al. 1922). Hoje o óleo de fígado de bacalhau tornou-se a proteção do “inverno” para as crianças que vivem em latitudes setentrionais.”

 

  Ver Vitamin D: a natural inhibitor of multiple sclerosis, de Collen Hayes:
Disponivel em http://journals.cambridge.org/action/displayFulltext?type=1&fid=796912&jid=PNS&volumeId=59&issueId=04&aid=796900

“A evidência de que a vitamina D pode ser um inibidor natural de MS ou E.M. é irresistível. Examinando o benefício da suplementação de vitamina D para a prevenção de MS, a recusa desta verdade vai exigir um grande esforço por parte da comunidade científica, mas é claramente justificada diante dos atuais investimentos político-economicos”, diz Collen Hayes.

Ver Vitamin D: a natural inhibitor of multiple sclerosis, de Collen Hayes:
Disponivel em http://journals.cambridge.org/action/displayFulltext?type=1&fid=796912&jid=PNS&volumeId=59&issueId=04&aid=796900—-

 

As pessoas que têm doenças como Alzheimer, esclerose múltipla, lúpus, hipo e hipertireoidismo, artrite, vitiligo, diabetes, câncer e outras doenças autoimunitárias, hoje são orientadas por médicos e pesquisadores a consumir a solução oleosa [óleo de girassol ou oliva] de colecalciferol, a vitamina D3. A 25hidroxivitamin D3 é de fácil absorção pelo organismo. Passando do fígado aos rins e, depois de transformada em ativa, é absorvida por todas as células de todos os tecidos do corpo humano, como cálcio, fósforo e outras substancias, fortalecendo e recuperando inclusive o tecido neural.

 

A DEFICIENCIA ou INSUFICIENCIA DA VITAMINA D é verificada em exame de sangue, o 25[OH]D3 que o sistema de saúde publica do Brasil não oferece.


O consenso entre os médicos definiu a medida da nanoterapia como ideal acima de 40. Abaixo de 40 já existe deficiencia mesmo que a pessoa ainda não apresente qualquer sintoma de doença. Isto significa que há meio de baixo custo para a prevenção de epidemias. A suplementação e reposição da colecalciferol, a vitamina D3 a vitamina D3, deve ser feita em altas doses. Muito alem das convencionadas 600 UI da medicina do passado, para ter uma idéia uma gota [0,05 ml] da solução de colecalciferol tem 1.000 UI [unidades internacionais].

 

E há SIM UM DISTURBIO METABOLICO, pois, se as pessoas com resultado do exame de sangue abaixo de 50, já estiverem recebendo alimentação apropriada, existe indicio de dificuldade digestiva na absorção dos alimentos, depressão, estresse e tristeza que impedem a neurogenesis.

 

“Revisando-se a literatura, verificamos que a carne vermelha libera, durante a digestão, a substância hemina, que possui propriedades tóxicas, porque penetra as membranas celulares carregando ferro para o interior das células, onde este eleva a produção de radicais livres. Para evitar tal efeito, a hemina é destruída, em sua maior parte, na própria célula intestinal (e o restante, no fígado), utilizando a vitamina B2. Tornou-se claro, então, que o indivíduo absorve a hemina, não tendo então a B2 para destruí-la. Assim, solicitamos a parada completa da ingestão de carne”. Coimbra acrescenta que o tratamento tradicional contra a doença, à base de medicamentos, deve ser concomitante à dieta proposta pelos pesquisadores.
[…]
SBPC/Labjor – Brasil
SBPC/Labjor – Brasil
Disponível em http://www.comciencia.br/noticias/2003/06jun03/parkinson.htm
——

 

Vitamina D pode revolucionar o tratamento da esclerose múltipla*
http://biodireitomedicina.wordpress.com/2010/08/03/vitamina-d-pode-revolucionar-o-tratamento-da-esclerose-multipla/
*Dr. Cícero Galli Coimbra
PHD Médico Neurologista e Professor Livre-Docente

Informações médicas sobre a prevenção e tratamento de doenças neurodegenerativas e autoimunes, como Parkinson, Alzheimer, Lupus, Psoríase, Vitiligo, depressão
Dr. Cícero Galli Coimbra
PHD Médico Neurologista e Professor Livre-Docente
http://biodireitomedicina.wordpress.com/category/doencas-autoimunes/

 

“a situação fundamental é a mesma: a existência de um DISTÚRBIO METABÓLICO evidente e corrigível, capaz de explicar os eventos fisiopatológicos conhecidos, e cuja correção pode deter a progressão da doença (interrompendo a continuidade da morte neuronal crônica, recuperando células neuronais já afetadas pelo processo neurodegenerativo – mas que não atingiram ainda o ponto de irreversibilidade), promover a recuperação total em casos de início recente, ou ao menos parcial das deficiências neurológicas nos casos mais avançados (minimizando seqüelas permanentes) e impedir a morte.” [1]

 

Disponivel em
http://www.unifesp.br/dneuro/nexp/riboflavina/
—-
Dr. Cícero Galli Coimbra
PHD Médico Neurologista e Professor Livre-Docente
http://biodireitomedicina.wordpress.com/category/doencas-autoimunes/
—-

 

Vitamin D: a natural inhibitor of multiple sclerosis From Colleen E. Hayes Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock
Disponivel em 
http://journals.cambridge.org/action/displayFulltext?type=1&fid=796912&jid=PNS&volumeId=59&issueId=04&aid=796900——

 

 

Vitamin D: its role and uses in immunology
HECTOR F. DELUCA2 and MARGHERITA T. CANTORNA*
Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA; and
* Department of Nutrition, Pennsylvania State University, University Park, Pennsylvania 16802, USA
http://www.fasebj.org/cgi/content/full/15/14/2579http://www.drtheo.com/vitaminD/documents/VitaminD-itsroleandusesinimmunology.pdf
(The FASEB Journal. 2001;15:2579-2585.)
—-

 

  1. 1.      Disponivel em
    http://www.unifesp.br/dneuro/nexp/riboflavina/
    —-
    Dr. Cícero Galli Coimbra
    PHD Médico Neurologista e Professor Livre-Docente
    http://biodireitomedicina.wordpress.com/category/doencas-autoimunes/
    —-

Vitamin D: a natural inhibitor of multiple sclerosis From Colleen E. Hayes Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Disponivel em http://journals.cambridge.org/action/displayFulltext?type=1&fid=796912&jid=PNS&volumeId=59&issueId=04&aid=796900——

Vitamin D: its role and uses in immunology
HECTOR F. DELUCA2 and MARGHERITA T. CANTORNA*
Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA; and
* Department of Nutrition, Pennsylvania State University, University Park, Pennsylvania 16802, USA
http://www.fasebj.org/cgi/content/full/15/14/2579http://www.drtheo.com/vitaminD/documents/VitaminD-itsroleandusesinimmunology.pdf
(The FASEB Journal. 2001;15:2579-2585.)
—-

High prevalence of vitamin D deficiency and reduced bone mass in multiple sclerosis
http://www.huffingtonpost.com/dr-david-perlmutter-md/vitamin-d-benefits_b_818912.html
High prevalence of vitamin D deficiency and reduced bone mass in multiple sclerosis
J. Nieves, PhD,
F. Cosman, MD,
J. Herbert, MD,
V. Shen, PhD and
R. Lindsay, MD
—-

Vitamin D and the immune system: new perspectives on an old theme
Endocrinol Metab Clin North Am. 2010 June; 39(2):
365–379.
Endocrinol Metab Clin North Am. Author manuscript; available in PMC 2011 June 1.Published in final edited form as:Endocrinol Metab Clin North Am. 2010 June; 39(2): 365–379. doi: 10.1016/j.ecl.2010.02.010

Martin Hewison, PhD
Martin Hewison, Professor in Residence, Department of Orthopaedic Surgery and Molecular Biology Institute, David Geffen School of Medicine at UCLA, 615 Charles E. Young Drive South, Los Angeles, CA 90095, USA;
National Center for Biotechnology Information, U.S. National Library of Medicine 8600 Rockville Pike, Bethesda MD, 20894 USA
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879394/?tool=pubmed
—-

Lack of Vitamin D Linked to Alzheimer’s and Vascular Dementia
Friday, June 05, 2009 by: Sherry Baker, Health Sciences Editor
Sherry Baker is a widely published writer whose work has appeared in Newsweek, Health, the Atlanta Journal and Constitution, Yoga Journal, Optometry, Atlanta, Arthritis Today, Natural Healing Newsletter, OMNI, UCLA’s “Healthy Years” newsletter, Mount Sinai School of Medicine’s “Focus on Health Aging” newsletter, the Cleveland Clinic’s “Men’s Health Advisor” newsletter and many others.
Learn more:
http://www.naturalnews.com/026392_Vitamin_D_Alzheimers_disease.html#ixzz3HnBD71Qg
http://www.naturalnews.com/026392_Vitamin_D_Alzheimers_disease.html
—-

Factors in human vitamin D nutrition and in the production and cure of classical rickets Sítio canadense sobre e.m. DIRECT-MS
Fatores nutricionais e suplementares relacionados à esclerose múltipla.
http://www.direct-ms.org/
—-

“It is plausible that some 200 cases a year of MS might be prevented in Scotland alone by giving vitamin D to mothers and children,” he wrote.

disponivel emhttp://www.timesonline.co.uk/tol/life_and_style/health/article5663483.ece-VitaminD is ray of sunshine for multiple sclerosis patient
—-

Vitamin D in preventive medicine: are we ignoring the evidence? Vitamin D in preventive medicine: are we ignoring the evidence? A vitamina D em medicina preventiva: estamos ignorando as provas? Vitamina D em medicina preventiva: estamos ignorando as provas?
Dispoível em
http://64.233.163.132/translate_c?hl=pt-BR&langpair=en%7Cpt&u=http://www.ncbi.nlm.nih.gov/pubmed/12720576&prev=/translate_s%3Fhl%3Dpt-BR%26q%3DVitamina%2BD%2Be%2Bdepress%25C3%25A3o%26sl%3Dpt%26tl%3Den&rurl=translate.google.com.br&usg=ALkJrhjspQEBlxCMyClVGNWHjrZsYK2BOA


Vitamin D supplementation: Recommendations for Canadian mothers and infants. A suplementação de vitamina D: Recomendações para as mães e bebês canadenses.. 
Paediatr Child Health. . Paediatr Child Health. 2007 Sep; 12(7):583-98. 2007 Sep; 12 (7) :583-98.[Paediatr Child Health. [Paediatr Child Health. 2007] 2007]

Review Vitamin D and disease prevention with special reference to cardiovascular disease. Review vitamina D e prevenção de doenças, com especial referência à doença cardiovascular.Prog Biophys Mol Biol. Prog Biophys Mol Biol. 2006 Sep; 92(1):39-48. 2006 Sep; 92 (1) :39-48. Epub 2006 Feb 28. Epub 2006 Feb 28.[Prog Biophys Mol Biol. [Prog Biophys Mol Biol. 2006] 2006]

Vitamin D in health and disease. Vitamina D na saúde e na doença.Clin J Am Soc Nephrol. Clin J Am Soc Nephrol. 2008 Sep; 3(5):1535-41. 2008 Sep; 3 (5) :1535-41. Epub 2008 Jun 4. Epub 2008 Jun 4.[Clin J Am Soc Nephrol. [Clin J Am Soc Nephrol. 2008] 2008]

Review Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Review Luz solar e vitamina D para a saúde óssea e prevenção de doenças auto-imunes, câncer e doenças cardiovasculares.Am J Clin Nutr. Am J Clin Nutr. 2004 Dec; 80(6 Suppl):1678S-88S. 2004 Dec; 80 (6 Suppl): 1678S-88S.[Am J Clin Nutr. [Am J Clin Nutr. 2004] 2004]
—-

Cristiane Rozicki, em junho 25, 2012 às 5:20 pm disse:

Referencias Médico-Científicas Sobre Tratamento, Cura e Prevenção, doenças neurodegenerativas e autoimunes. Vitamina D.

Referencias Médico-Científicas Sobre Tratamento, Cura e Prevenção, doenças neurodegenerativas e autoimunes. Vitamina D.

Vitamina D pode revolucionar o tratamento da esclerose múltipla*
http://biodireitomedicina.wordpress.com/category/doencas-autoimunes/

POR UM NOVO PARADIGMA DE CONDUTA E TRATAMENTO
http://www.institutodeautoimunidade.org.br/novo-paradigma.html

Por Dr. Cícero Galli Coimbra
Médico Internista e Neurologista
Professor Associado Livre-Docente da Universidade Federal de São Paulo
Presidente do Instituto de Investigação e Tratamento de Autoimunidade


O vídeo referido na reportagem dominical de 27.05.12 da Folha está no endereço:
Vitamina D – Por uma outra terapia (Vitamin D – For an alternative therapy)

http://biodireitomedicina.wordpress.com/2012/05/28/folha-de-sao-paulo-terapia-polemica-usa-vitamina-d-em-doses-altas-contra-esclerose-multipla/


Vitamina D pode revolucionar o tratamento da esclerose múltipla
http://biodireitomedicina.wordpress.com/2010/08/03/vitamina-d-pode-revolucionar-o-tratamento-da-esclerose-multipla/

Taxas baixas de vitamina D na maioria da população preocupam especialistas
http://biodireitomedicina.wordpress.com/2012/06/18/taxas-baixas-de-vitamina-d-na-maioria-da-populacao-preocupam-especialistas/

Pediatras dobram recomendação de consumo diário de vitamina D
http://biodireitomedicina.wordpress.com/2012/06/17/pediatras-dobram-recomendacao-de-consumo-diario-de-vitamina-d/

Doses diárias de Sol – nos horários certos e com os devidos cuidados
http://biodireitomedicina.wordpress.com/2012/06/12/doses-diarias-de-sol-nos-horarios-certos-e-com-os-devidos-cuidados/

“(…) cerca de 70% da população mundial apresenta taxas inadequadas de vitamina D, substância que, dentro do corpo, trabalha como um hormônio. O fenômeno da insuficiência não poupa nem países tropicais, como o Brasil, e a defasagem tende a ser maior nas grandes cidades, já que, dentro de casa, no carro ou no escritório, as pessoas acabam fugindo do sol. De acordo com o endocrinologista Geraldo Santana, do Instituto Mineiro de Endocrinologia, “a deficiência de vitamina D é um achado frequente e também preocupante devido à importante ação da substância no organismo.”
Celso Galli Coimbra
OABRS 11352
cgcoimbra@gmail.com
Em 19.06.2012
__

Vitamina D: A Desinformação Médica e o Direito à Informação do Cidadão
http://biodireitomedicina.wordpress.com/2012/06/20/vitamina-d-a-desinformacao-medica-e-o-direito-a-informacao-do-cidadao/

Vitamina D pode combater males que mais matam pessoas no mundo
http://biodireitomedicina.wordpress.com/2010/03/20/vitamina-d-pode-combater-males-que-mais-matam-pessoas-no-mundo/

Informações médicas sobre a prevenção e tratamento de doenças neurodegenerativas e autoimunes, Parkinson, Alzheimer, Lupus, Psoríase, Vitiligo, como depressão
http://biodireitomedicina.wordpress.com/2011/03/23/informacoes-medicas-sobre-a-prevencao-e-tratamento-de-doencas-neurodegenerativas-e-auto-imunes-como-parkinson-alzheimer-lupus-psoriase-vitiligo-depressao/

Vitamina D é importantíssima para a saúde
”Estudos realizados no Brasil e no exterior apontam a importância da substância na prevenção e no tratamento do câncer, diabetes e de doenças neurológicas, cardiovasculares e até degenerativas, como a esclerose múltipla.”
http://biodireitomedicina.wordpress.com/2009/09/22/vitamina-d-e-importantissima-para-a-saude/

A importância da colina para a regeneração neuronal
http://biodireitomedicina.wordpress.com/2009/09/18/a-volta-triunfal-do-ovo/
“A colina é especialmente importante na gravidez. “Vários estudos já mostraram que ela é tão ou mais importante do que o ácido fólico durante a gestação”
Antes inimigo da saúde cardiovascular, o alimento agora está liberado pelos médicos

O tratamento com vitamina D deve ser feito com indicação por médico atualizado
http://biodireitomedicina.wordpress.com/2012/06/22/o-tratamento-com-vitamina-d/

Taxas baixas de vitamina D na maioria da população preocupam especialistas
http://biodireitomedicina.wordpress.com/2012/06/18/taxas-baixas-de-vitamina-d-na-maioria-da-populacao-preocupam-especialistas/

Solução que vem do sol – com os devidos cuidados
http://biodireitomedicina.wordpress.com/2012/06/12/solucao-que-vem-do-sol-com-os-devidos-cuidados/
11 de junho de 2012
“A vitamina D, que precisa dos raios solares para ser sintetizada no corpo, é a base de uma alternativa revolucionária para tratar doenças autoimunes”

Informações médicas sobre a prevenção e tratamento de doenças neurodegenerativas e autoimunes, como Parkinson, Alzheimer, Lupus, Psoríase, Vitiligo, depressão
Entrevista em TV com o Dr. Cícero Galli Coimbra, professor neurologista da Universidade Federal de São Paulo – Unifesp.
http://biodireitomedicina.wordpress.com/2011/03/23/informacoes-medicas-sobre-a-prevencao-e-tratamento-de-doencas-neurodegenerativas-e-auto-imunes-como-parkinson-alzheimer-lupus-psoriase-vitiligo-depressao/


Vitamina D pode revolucionar o tratamento da esclerose múltipla
http://biodireitomedicina.wordpress.com/2010/08/03/vitamina-d-pode-revolucionar-o-tratamento-da-esclerose-multipla/
Sobre este assunto, assista: Vitamina D – por uma outra terapia
http://biodireitomedicina.wordpress.com/2012/04/12/vitamina-d-por-uma-outra-terapia/
http://biodireitomedicina.wordpress.com/2011/03/23/informacoes-medicas-sobre-a-prevencao-e-tratamento-de-doencas-neurodegenerativas-e-auto-imunes-como-parkinson-alzheimer-lupus-psoriase-vitiligo-depressao/
—-

Vitamina D pode combater males que mais matam pessoas no mundo
http://biodireitomedicina.wordpress.com/2010/03/20/vitamina-d-pode-combater-males-que-mais-matam-pessoas-no-mundo/

—-

“POR UM NOVO PARADIGMA DE CONDUTA E TRATAMENTO” – “Estamos vivendo uma defasagem entre o conhecimento científico e a prática médica” – Dr. Cicero Galli Coimbra, medico neurologista, Phd., professor na Universidade Federal de São Paulo,, em dezembro 9, 2012 às 7:16 pm disse:

[…] Esclerose múltipla, distúrbio metabólico. […]

·         Vitamina do Sol é sem protetor – a pele produz a Vitamina D, hormonio esteroide, na cura e na medicina preventiva

Vitamina D

o   http://biodireitomedicina.wordpress.com/category/vitamina-d/

.

Deficiência de vitamina D em grávidas

03/01/2013 — Celso Galli Coimbrahttp://biodireitomedicina.wordpress.com/2013/01/03/deficiencia-de-vitamina-d-em-gravidas/

__ Related articles

http://biodireitomedicina.wordpress.com/2012/07/23/bibiliografia-cientifica-internacional-sobre-vitamina-d-60-724-titulos-nesta-data-na-scirus/

__

POR UM NOVO PARADIGMA DE CONDUTA E TRATAMENTO

Por Dr. Cícero Galli Coimbra

Médico Internista e Neurologista

Professor Associado Livre-Docente da Universidade Federal de São Paulo

Presidente do Instituto de Investigação e Tratamento de Autoimunidade

http://www.institutodeautoimunidade.org.br/novo-paradigma.html

—-

 

A vital importância do hormônio conhecido por Vitamina D3 para a preservação ou recuperação de sua saúde de doenças autoimunes: exijam que seus médicos se atualizem

Por Celso Galli Coimbra

Celso Galli Coimbra – OABRS 11352
cgcoimbra@gmail.com
http://biodireitomedicina.wordpress.com/
https://www.facebook.com/celso.gallicoimbra
http://www.youtube.com/biodireitobioetica

http://biodireitomedicina.wordpress.com/2012/12/23/vitamina-d3-e-sua-saude/#comment-3220

 

VITAMINA D e a RESPONSABILIDADE CIVIL DO MÉDICO

 

”ATENÇÃO: o uso preventivo do Vitamina D3 é DIFERENTE do uso terapêutico deste hormônio-vitamina, que exige sempre a orientação e acompanhamento de médico com treinamento adequado para ser responsável pela avaliação caso a caso e a específica determinação de dosagem, em contrário haverá sérios danos à saúde.”

http://biodireitomedicina.wordpress.com/2012/12/23/vitamina-d3-e-sua-saude/

—-

Para estas pessoas que desenvolveram doenças autoimunes, a solução simples é o consumo de altas DOSES DE VITAMINA D QUE O MEDICO PRESCREVE SEGUNDO O CASO DE CADA PACIENTE. – Dr. Cicero Galli Coimbra, medico neurologista, Phd., professor na Universid, em fevereiro 28, 2013 às 4:21 pm disse:

[…] Esclerose múltipla, distúrbio metabólico – atualizado em 7/janeiro/2013 […]

A responsabilidade Civil e Criminal Médica na Desinformação às pessoas – Revista VEJA, 2.304: “O que você não sabe sobre a Vitamina do Sol. Ela continua a surpreender a medicina com novos efeitos benéficos.”

20/01/2013 — Celso Galli Coimbra

http://biodireitomedicina.wordpress.com/2013/01/20/a-responsabilidade-civil-e-criminal-medica-na-desinformacao-as-pessoas-revista-veja-2-304-o-que-voce-nao-sabe-sobre-a-vitamina-do-sol-ela-continua-a-surpreender-a-medicina-com-novos-efe/

Vitamina D – Entrevista com Dr. Cícero Galli Coimbra sobre esclerose múltipla e demais doenças autoimunitárias
28/01/2013 — Celso Galli Coimbra

http://biodireitomedicina.wordpress.com/2013/01/28/vitamina-d-entrevista-com-dr-cicero-galli-coimbra-sobre-esclerose-multipla-e-demais-doencas-autoimunitarias/
__

http://www.institutodeautoimunidade.org.br/novo-paradigma.html
Cícero Galli Coimbra
Médico Internista e Neurologista
Professor Associado Livre-Docente da Universidade Federal de São Paulo
Presidente do Instituto de Investigação e Tratamento de Autoimunidade

Vitamina D3 – 10.000 UI diárias é vital para à saúde
por Celso Galli Coimbra
http://www.youtube.com/playlist?list=PL301EAE2D5602A758
http://www.youtube.com/watch?v=Pn-swcSA7As&list=PL301EAE2D5602A758&index=25

Vídeos com pessoas que estão curadas e fizeram o tratamento com a Vitamina D. Mais de 10 anos que este tratamento eficiente é usado e autoimunidade tem cura sim.

Vitamina D – Por uma outra terapia (Vitamin D – For an alternative therapy)
http://www.youtube.com/watch?feature=player_detailpage&v=erAgu1XcY-U

Mais de 10 anos de tratamento com a Vitamina D – Exijam que seus médicos se atualizem!
23/12/2012 — Celso Galli Coimbra
http://biodireitomedicina.wordpress.com/2012/12/23/mais-de-10-anos-de-tratamento-com-a-vitamina-d-exija-que-seus-medicos-se-atualizem/
—-

Traíção de uma Nação: autoridades de saúde dos EUA estão protegendo a deficiência de Vitamina D para beneficiar a Indústria Farmacêutica. Betrayal of a Nation: Why U.S. health authorities are keeping you vitamin D deficient and who stands to gain
15/01/2013 — Celso Galli Coimbra
http://biodireitomedicina.wordpress.com/2013/01/15/traicao-de-uma-nacao-autoridades-de-saude-dos-eua-estao-protegendo-a-deficiencia-de-vitamina-d-para-benficiar-a-industria-farmaceutica-betrayal-of-a-nation-why-u-s-health-authorities-are-keeping-y/

Vitamina D – Por uma outra terapia (Vitamin D – For an alternative therapy)
http://www.youtube.com/watch?feature=player_detailpage&v=erAgu1XcY-U

Dr. Cícero Galli Coimbra – Doenças Autoimunes e Vitamina D
http://www.youtube.com/watch?feature=player_embedded&v=4uJt1361aGw

Vitamina D – Sem Censura – Dr. Cicero Galli Coimbra e Daniel Cunha
http://www.youtube.com/watch?feature=player_embedded&v=cIwIWim4hNM

Vitamina D – Por uma outra terapia (Vitamin D – For an alternative therapy)
http://www.youtube.com/watch?feature=player_detailpage&v=erAgu1XcY-U

Para estas pessoas que desenvolveram doenças autoimunes, a solução simples é o consumo de altas DOSES DE VITAMINA D QUE O MEDICO PRESCREVE SEGUNDO O CASO DE CADA PACIENTE. – Dr. Cicero Galli Coimbra, medico neurologista, Phd., professor na Universidade Federal de São Paulo, Presidente do Instituto de Investigação e Tratamento de Autoimunidade

“POR UM NOVO PARADIGMA DE CONDUTA E TRATAMENTO” – “Estamos vivendo uma defasagem entre o conhecimento científico e a prática médica” – Dr. Cicero Galli Coimbra, medico neurologista, Phd., professor na Universidade Federal de São Paulo, Presidente do Instituto de Investigação e Tratamento de Autoimunidade

Dr. Cícero Galli Coimbra – Doenças Autoimunes e Vitamina D
http://www.youtube.com/watch?feature=player_embedded&v=4uJt1361aGw
Vitamina D – Sem Censura – Dr. Cicero Galli Coimbra e Daniel Cunha
http://www.youtube.com/watch?feature=player_embedded&v=cIwIWim4hNM
Vitamina D – Por uma outra terapia (Vitamin D – For an alternative therapy)
http://www.youtube.com/watch?feature=player_detailpage&v=erAgu1XcY-U
Para estas pessoas que desenvolveram doenças autoimunes, a solução simples é o consumo de altas DOSES DE VITAMINA D QUE O MEDICO PRESCREVE SEGUNDO O CASO DE CADA PACIENTE. – Dr. Cicero Galli Coimbra, medico neurologista, Phd., professor na Universidade Federal de São Paulo, Presidente do Instituto de Investigação e Tratamento de Autoimunidade
———-
“por causa da deficiência de vitamina D, o hormonio esteroide do qual estamos falando, torna o sistema imunológico completamente desregulado, de tal modo que ele tem dificuldade de reagir contra infecções e permite o organismo ser atacado por qualquer outra doença.’’

“Há evidencias de que a carencia de vitamina D provoca e agrava a esclerose múltipla (Surtos da doença abalam o sistema nervoso central). Assim, também a deficiencia de Colecalciferol pode levar a problemas Cardiovasculares, AVCs, nascimento de crianças autistas, problemas na gestação, Alzheimer.”

(2) Bibiliografia científica internacional sobre Vitamina D – 60.724 títulos nesta data na SCIRUS
Acesse: “multiple sclerosis” (“vitamin D”)
http://www.scirus.com/srsapp/search?q=%22multiple+sclerosis%22+%28%22vitamin+D%22%29&t=all&sort=0&g=s
23/07/2012 — Celso Galli Coimbra – OABRS 11352
http://biodireitomedicina.wordpress.com/2012/07/23/bibiliografia-cientifica-internacional-sobre-vitamina-d-60-724-titulos-nesta-data-na-scirus/
__
“Infelizmente este conhecimento não tem sido levado aos livros textos de medicina e isso gera esse desconhecimento, não só do público em geral mas até da classe médica em relação á gravidade dessa situação sobre a deficiência desse hormonio esteroide. Esta deficiencia torna as 229 funções do sistema imunológico do próprio organismo das pessoas desregulado, permitindo desenvolver qualquer doença, o que levou á pandemia do mundo atual.”

http://www.institutodeautoimunidade.org.br/novo-paradigma.html
Cícero Galli Coimbra
Médico Internista e Neurologista
Professor Associado Livre-Docente da Universidade Federal de São Paulo
Presidente do Instituto de Investigação e Tratamento de Autoimunidade

Vitamina D

– –

Para estas pessoas que desenvolveram doenças autoimunes, a solução simples é o consumo de altas DOSES DE VITAMINA D QUE O MEDICO PRESCREVE SEGUNDO O CASO DE CADA PACIENTE. – Dr. Cicero Galli Coimbra, medico neurologista, Phd., professor na Universid, em fevereiro 28, 2013 às 4:21 pm disse:

[…] Esclerose múltipla, distúrbio metabólico – atualizado em 7/janeiro/2013 […]

Por 30 anos, extensa revisão de toda a pesquisa anterior confirma que baixo nível de vitamina D é uma sentença de morte
http://biodireitomedicina.wordpress.com/2013/02/13/por-30-anos-extensa-revisao-de-toda-a-pesquisa-anterior-confirma-que-baixo-nivel-de-vitamina-d-e-uma-sentenca-de-morte/
__
Hormônio-Vitamina D: quando a Medicina tem dois pesos e duas medidas e a saúde do paciente vale menos do que a saúde do médico
25/02/2013 — Celso Galli Coimbra
__
Constituição Federal, Art. 196. “A saúde é direito de todos e dever do Estado, garantido mediante políticas sociais e econômicas que visem à redução do risco de doença e de outros agravos e ao acesso universal e igualitário às ações e serviços para sua promoção, proteção e recuperação.”
http://biodireitomedicina.wordpress.com/2013/02/25/hormonio-vitamina-d-quando-a-medicina-tem-dois-pesos-e-duas-medidas-e-a-saude-do-paciente-vale-menos-do-que-a-saude-do-medico/

Informe-se:
Vitamina D3 – 10.000 UI diárias é vital para à saúde
http://www.youtube.com/watch?feature=player_embedded&list=PL301EAE2D5602A758&v=LGqg2-PiO8M
Aqui está o editorial do Multiple Sclerosis Journal :
VIt D for relative with MS
Celso Galli Coimbra
OABRS 11352
cgcoimbra@gmail.com
__
http://www.youtube.com/watch?feature=player_embedded&v=J3UvUK3_u0o
Vitamina D3 – 10.000 UI diárias é vital para preservar à saúde
https://www.youtube.com/playlist?list=PL301EAE2D5602A758
No Facebook apenas “curta” esta página e estará automaticamente inscrito:
Vitamina D é um hormônio vital para preservação da saúde
https://www.facebook.com/VitaminaD.HormonioVital
Leia também:
Por 30 anos, extensa revisão de toda a pesquisa anterior confirma que baixo nível de vitamina D é uma sentença de morte
http://biodireitomedicina.wordpress.com/2013/02/13/por-30-anos-extensa-revisao-de-toda-a-pesquisa-anterior-confirma-que-baixo-nivel-de-vitamina-d-e-uma-sentenca-de-morte/
Cientistas convocam para uma Ação de Saúde Pública tendo como modelo o uso do Hormônio-Vitamina D
http://biodireitomedicina.wordpress.com/2013/01/29/cientistas-convocam-para-uma-acao-de-saude-publica-tendo-como-modelo-o-uso-do-hormonio-vitamina-d/

__
http://www.youtube.com/watch?feature=player_embedded&v=J3UvUK3_u0o
Vitamina D3 – 10.000 UI diárias é vital para preservar à saúde
https://www.youtube.com/playlist?list=PL301EAE2D5602A758
No Facebook apenas “curta” esta página e estará automaticamente inscrito:
Vitamina D é um hormônio vital para preservação da saúde
https://www.facebook.com/VitaminaD.HormonioVital
Leia também:
Por 30 anos, extensa revisão de toda a pesquisa anterior confirma que baixo nível de vitamina D é uma sentença de morte
http://biodireitomedicina.wordpress.com/2013/02/13/por-30-anos-extensa-revisao-de-toda-a-pesquisa-anterior-confirma-que-baixo-nivel-de-vitamina-d-e-uma-sentenca-de-morte/
Cientistas convocam para uma Ação de Saúde Pública tendo como modelo o uso do Hormônio-Vitamina D
http://biodireitomedicina.wordpress.com/2013/01/29/cientistas-convocam-para-uma-acao-de-saude-publica-tendo-como-modelo-o-uso-do-hormonio-vitamina-d/

A responsabilidade Civil e Criminal Médica na Desinformação às pessoas – Revista VEJA, 2.304: “O que você não sabe sobre a Vitamina do Sol. Ela continua a surpreender a medicina com novos efeitos benéficos.”

20/01/2013 — Celso Galli Coimbra

http://biodireitomedicina.wordpress.com/2013/01/20/a-responsabilidade-civil-e-criminal-medica-na-desinformacao-as-pessoas-revista-veja-2-304-o-que-voce-nao-sabe-sobre-a-vitamina-do-sol-ela-continua-a-surpreender-a-medicina-com-novos-efe/

Para estas pessoas que desenvolveram doenças autoimunes, a solução simples é o consumo de altas DOSES DE VITAMINA D QUE O MEDICO PRESCREVE SEGUNDO O CASO DE CADA PACIENTE. – Dr. Cicero Galli Coimbra, medico neurologista, Phd., professor na Universid, em fevereiro 28, 2013 às 4:29 pm disse:

[…] Esclerose múltipla, distúrbio metabólico – atualizado em 7/janeiro/2013 […]

 

 […] Esclerose múltiplA responsabilidade Civil e Criminal Médica na Desinformação às pessoas – Revista VEJA, 2.304: “O que você não sabe sobre a Vitamina do Sol. Ela continua a surpreender a medicina com novos efeitos benéficos.”

20/01/2013 — Celso Galli Coimbra

http://biodireitomedicina.wordpress.com/2013/01/20/a-responsabilidade-civil-e-criminal-medica-na-desinformacao-as-pessoas-revista-veja-2-304-o-que-voce-nao-sabe-sobre-a-vitamina-do-sol-ela-continua-a-surpreender-a-medicina-com-novos-efe/

 

Há interesses na gestão da Medicina associados com os da Indústria Farmacêutica e não com a preservação da saúde

É impossível dimensionar a extensão CRIMINOSA dos interesses envolvidos em forçar cada vez mais o que já é comprovado pela CIÊNCIA:

SEM o hormônio conhecido por Vitamina D, em doses não inferiores a 10.000 UI diárias para pessoas AINDA saudáveis, o que a correta exposição ao SOL diariamente desenvolve pela [redundância] própria natureza através da pele HUMANA, de acordo com tipo de pele e idade, a saúde e a vida de todas as pessoas estão definitivamente comprometidas.

Os grandes beneficiários desta CONDUTA CRIMINOSA – em desinformar o que é OBRIGAÇÃO PROFISSIONAL MÉDICA informar – são os investidores da Indústria Farmacêutica e seus interesses em aumentar o universo de pessoas doentes e dependentes de inócua “medicação” de ALTO CUSTO” .

 

[…] Esclerose múltipla, distúrbio metabólico – atualizado em 7/janeiro/2013 […]

Dr. Cícero Galli Coimbra – Doenças Autoimunes e Vitamina D
http://www.youtube.com/watch?feature=player_embedded&v=4uJt1361aGw

Vitamina D – Sem Censura – Dr. Cicero Galli Coimbra e Daniel Cunha
http://www.youtube.com/watch?feature=player_embedded&v=cIwIWim4hNM

Vitamina D – Por uma outra terapia (Vitamin D – For an alternative therapy)
http://www.youtube.com/watch?feature=player_detailpage&v=erAgu1XcY-U

Para estas pessoas que desenvolveram doenças autoimunes, a solução simples é o consumo de altas DOSES DE VITAMINA D QUE O MEDICO PRESCREVE SEGUNDO O CASO DE CADA PACIENTE. – Dr. Cicero Galli Coimbra, medico neurologista, Phd., professor na Universidade Federal de São Paulo, Presidente do Instituto de Investigação e Tratamento de Autoimunidade

·       A Autoimunidade tem cura com a Vitamina D – Instituto de Investigação e Tratamento da Autoimunidade

——–

Influence of Vitamin D Status and Vitamin D3 Supplementation on Genome Wide Expression of White Blood Cells: A Randomized Double-Blind Clinical Trial

Lançamento nova publicação (26 de março de 2013)

por Michael F. Holick, Ph.D, MD

“Influência da vitamina D e suplementação de vitamina D3 sobre o genoma. Expressão clinica da variedade de células brancas do sangue: um estudo duplo-cego randomizado” foi recentemente publicado na PLoS e está disponível online.

dr_%20holick%20photoArticle

Influence of Vitamin D Status and Vitamin D3 Supplementation on Genome Wide Expression of White Blood Cells: A Randomized Double-Blind Clinical Trial

  • Arash Hossein-nezhad,

Affiliation: Department of Medicine, Section of Endocrinology, Nutrition, and Diabetes, Vitamin D, Skin and Bone Research Laboratory, Boston University Medical Center, Boston, Massachusetts, United States of America

X

  • Avrum Spira,

Affiliation: Department of Medicine, Section of Computational Biomedicine, Boston University Medical Center, Boston, Massachusetts, United States of America

X

  • Michael F. Holick mail

* E-mail: mfholick@bu.edu

Affiliation: Department of Medicine, Section of Endocrinology, Nutrition, and Diabetes, Vitamin D, Skin and Bone Research Laboratory, Boston University Medical Center, Boston, Massachusetts, United States of America

Abstract

Background

Although there have been numerous observations of vitamin D deficiency and its links to chronic diseases, no studies have reported on how vitamin D status and vitamin D3 supplementation affects broad gene expression in humans. The objective of this study was to determine the effect of vitamin D status and subsequent vitamin D supplementation on broad gene expression in healthy adults. (Trial registration: ClinicalTrials.gov NCT01696409).

Methods and Findings

A randomized, double-blind, single center pilot trial was conducted for comparing vitamin D supplementation with either 400 IUs (n = 3) or 2000 IUs (n = 5) vitamin D3 daily for 2 months on broad gene expression in the white blood cells collected from 8 healthy adults in the winter. Microarrays of the 16 buffy coats from eight subjects passed the quality control filters and normalized with the RMA method. Vitamin D3 supplementation that improved serum 25-hydroxyvitamin D concentrations was associated with at least a 1.5 fold alteration in the expression of 291 genes. There was a significant difference in the expression of 66 genes between subjects at baseline with vitamin D deficiency (25(OH)D<20 ng/ml) and subjects with a 25(OH)D>20 ng/ml. After vitamin D3 supplementation gene expression of these 66 genes was similar for both groups. Seventeen vitamin D-regulated genes with new candidate vitamin D response elements including TRIM27, CD83, COPB2, YRNA and CETN3 which have been shown to be important for transcriptional regulation, immune function, response to stress and DNA repair were identified.

Conclusion/Significance

Our data suggest that any improvement in vitamin D status will significantly affect expression of genes that have a wide variety of biologic functions of more than 160 pathways linked to cancer, autoimmune disorders and cardiovascular disease with have been associated with vitamin D deficiency. This study reveals for the first time molecular finger prints that help explain the nonskeletal health benefits of vitamin D.

Trial Registration

ClinicalTrials.gov NCT01696409

Citation: Hossein-nezhad A, Spira A, Holick MF (2013) Influence of Vitamin D Status and Vitamin D3 Supplementation on Genome Wide Expression of White Blood Cells: A Randomized Double-Blind Clinical Trial. PLoS ONE 8(3): e58725. doi:10.1371/journal.pone.0058725

Editor: Moray Campbell, Roswell Park Cancer Institute, United States of America

Received: October 3, 2012; Accepted: February 5, 2013; Published: March 20, 2013

Copyright: © 2013 Hossein-nezhad et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was supported by a pilot grant from the National Institutes of Health Clinical Translational Science Institute Grant UL-1-RR-25711. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Vitamin D deficiency defined as a serum concentration of 25-hydroxyvitamin D [25(OH)D]<20 ng/ml is the largest pandemic in the world [1],[2]. The musculoskeletal consequences of inadequate vitamin D are well-established [2],[3]. In addition to its traditional role in calcium homeostasis, a growing number of other conditions have also been linked to vitamin D insufficiency including cancers, autoimmune diseases, infectious diseases, type 2 diabetes and cardiovascular disease [1],[2],[3],[4].

Epidemiological studies have suggested that adequate levels of 25(OH)D are critical for the prevention of various solid tumors, including breast, ovarian and colon cancers [4],[5]. The risk of developing and dying of these cancers appears to be inversely correlated with sun exposure, and/or vitamin D status, suggesting that vitamin D has chemopreventive properties [4],[5]. Studies based on immunomodulatory effects of vitamin D have recommended vitamin D supplementation for prevention of autoimmune diseases and several forms of cancer [4],[6],[7].

Vitamin D requires two metabolic conversions, 25-hydroxylation in the liver and 1α-hydroxylation in the kidney, before its hormonal form, 1,25-dihydroxyvitamin D[1,25(OH)2D], can bind to the vitamin D receptor (VDR) to modulate gene transcription. The VDR is present in a wide variety of cells and tissues and 1,25(OH)2D via its receptor directly or indirectly have been reported to have effects on cell cycling and proliferation, differentiation, apoptosis and the production of cathelicidin, renin and insulin [2],[3],[4].

The wide distribution of VDR and the plethora of biologic actions reported for 1,25(OH)2D may explain how vitamin D can prevent a variety of diseases. Recent genetic association studies reported the effects of 1,25(OH)2D on gene expression and its influence on some epigenetic modifications [8],[9],[10]. It is estimated that VDR activation may regulate directly and/or indirectly the expression of a very large number of genes (0.5–5% of the total human genome i.e., 100–1250 genes) [1],[9],[10].

Our knowledge of both the molecular events controlling regulation of gene transcription by the VDR and the target genes underlying its physiological functions has benefited tremendously in the last decade by the advent of techniques for genome-wide analysis of transcriptional regulation[11]. In vitro microarray studies in cultured human cells provided insights into some target genes underlying the broad physiological actions of 1,25(OH)2D3 [11],[12]. These in vitro findings have helped provide a molecular genetic basis for the wide variety of biological and physiological responses regulated by 1,25(OH)2D3 [9],[11],[12].

Early microarray studies performed in squamous carcinoma cells derived from a tumor of the oral cavity revealed that an analog of 1,25(OH)2D3 regulated the expression of numerous genes implicated in immune function[12]. Genome-wide microarray analysis of 1,25(OH)2D3-treated human osteoblasts revealed an interplay of critical regulatory and metabolic pathways and supported the hypothesis that 1,25(OH)2D3 can modulate the coagulation process through osteoblasts, activate osteoclastogenesis through inflammation signaling and modulate the effects of monoamines by affecting their reuptake[11].

Although there have been numerous observations of vitamin D deficiency and its links to chronic diseases, a study on how a person’s vitamin D status and improvement with vitamin D supplementation affects genomic expression in vivo in humans has not been reported. The objective of this study was to determine the effect of vitamin D status and subsequent vitamin D supplementation on broad gene expression in the white blood cells collected from healthy adults before and two months after daily supplementation with either 400 or 2000 IU vitamin D3. (Trial registration: ClinicalTrials.gov NCT01696409; http://clinicaltrials.gov/ct2/show/NCT01​696409?term=Holick&rank=4).

Methods

Trial design

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This research study was a randomized, controlled, double-blind, investigator-initiated, single center pilot trial. The study protocol approved by the Boston University Medical Campus Institutional Review Board and registered in ClinicalTrials.gov with Identifier: NCT01696409. The protocol for this trial and supporting CONSORT checklist are available as supporting information; see Checklist S1 and Protocol S1. A total of 11 adult subjects were recruited for this study. However, two subjects dropped out before using supplement and the nine subjects were randomly assigned to 1 of 2 groups (Group I and Group II) using a computer-generated simple randomization scheme. Four subjects were assigned to Group I to receive 400 IU/d of vitamin D3 for 8 weeks, and five subjects were assigned to Group II to receive 2,000 IU/d of vitamin D3 for 8 weeks. After signing a consent form and receiving the supplement, one subject from group I refused further participating in the study. The eight remaining subjects included 3 subjects in group I and 5 subjects in group II who received vitamin D3 for 8 weeks and were assigned to the final analysis for studying the effect of vitamin D supplementation on broad gene expression. Based on vitamin D status at baseline, 4 subjects were vitamin D deficient and the other four subjects were insufficient or sufficient. Comparing gene expression in these two groups (deficient vs. insufficient or sufficient) led us to study the effect of vitamin D status on broad gene expression. The consent form was signed before the subjects were given the supplement so that we could evaluate the influence of vitamin D status and vitamin D3 supplementation on genome wide expression in white blood cells. None of the recruited subjects refused to give consent. To minimize sun exposure as a confounding factor, the study was conducted in the winter months. Study visits were conducted at the General Clinical Research Unit (GCRU) at Boston Medical Center. Subject demographics and total 25(OH)D levels before and after vitamin D3 supplementation are shown in Table 1.

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Table 1. Subject demographics and total 25(OH)D levels before and after 400 IU/d or 2000 IU/d of vitamin D3 supplementation for 8 weeks.

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Study Subjects

Healthy, non-patient English speaking adult males and females of all ethnic groups age 18 and older were recruited for this study. Before any study procedures were initiated for any subject in this study, a written informed consent was properly executed and documented as approved by the Boston University Medical Campus Institutional Review Board. A Federal wide Assurance Number FWA00000301 has been approved for Boston University Medical Center. The informed consent form is available as supporting information; see Informed consent form. The exclusion criteria included: pregnant/lactating women; current or recent history of hepatic or renal disease; supplementation of greater than 400 IUs vitamin D2 or vitamin D3; current antiseizure medications or glucocorticoids; tanning for more than 8 hours within the past month; history of intestinal malabsorption; and unwillingness to consent to the study.

Visits

During the subjects’ first and second visits to the GCRU, demographic data, body weight, height, body mass index (BMI), past vitamin D use, urine pregnancy test (females only), diet, current medication usage and/or anticipated medication usage during the study period were collected on data collection forms. The subjects also received a bottle containing vitamin D3 capsules that contained either 400 IUs or 2000 IUs of vitamin D3 for the 8-week period. The vitamin D3 supplements were produced by Tishcon Laboratories (Westbury, NY 11590) and were found to have contained stated vitamin D content as previously described [13].

The second visit occurred 8 weeks after the first visit. Subjects returned with their vitamin D3 bottles and the investigators counted how many capsules remained and determined compliance.

Blood sample collection

Ten ml of blood was also collected at each visit and sera were collected for evaluation at Quest Diagnostics and the BUMC Corelab and utilized to determine serum levels of 25(OH)D by liquid chromatography tandem mass spectroscopy as previously described [14]. Another 10 ml of blood was collected to obtain a buffy coat including white blood cells and platelets.

The white blood cells were collected to purify total RNA, including small RNAs. Purified RNA was stored at -86 degrees Celsius and sent for analysis to the Boston University Pulmonary Center’s Microarray Resource Facility.

Microarray Data Acquisition and Preprocessing

All procedures were performed at the Boston University Microarray Resource Facility as described in the GeneChip® Whole Transcript (WT) Sense Target Labeling Assay Manual (Affymetrix, Santa Clara, CA). Total RNA was isolated using QIAGEN’s RNeasy kit as described in manual (Qiagen, Valencia, CA). For each sample, integrity was verified using RNA 6000 Nano Assay RNA chips run in Agilent 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA). RNA was reverse transcribed using Whole Transcript cDNA Synthesis kit (Affymetrix, Santa Clara, CA). The obtained antisense cRNA was purified using GeneChip Sample Cleanup Module (Affymetrix, Santa Clara, CA), and used as a template for reverse transcription (Whole Transcript cDNA Synthesis kit, Affymetrix, Santa Clara, CA) to produce single-stranded DNA in the sense orientation. During this step dUTP was incorporated. DNA was then fragmented using uracil DNA glycosylase (UDG) and apurinic/apyrimidinic endonuclease 1 (APE 1) and labeled with DNA Labeling Reagent that is covalently linked to biotin using terminal deoxynucleotidyl transferase (TdT, Whole Transcript Terminal Labeling kit, Affymetrix, Santa Clara, CA). IVT and cDNA fragmentation quality controls were carried out by running an mRNA Nano assay in the Agilent 2100 Bioanalyzer.

The labeled fragmented DNA was hybridized to the Gene Array 1.0ST for 16–18 hours in GeneChip Hybridization oven 640 at 45°C with 60 rpm rotation. The hybridized samples were washed and stained using Affymetrix fluidics station 450. The first stain used was streptavidin-R-phycoerythrin (SAPE) followed by signal amplification using a biotinilated goat anti-streptavidin antibody and another SAPE staining (Hybridization, Washing and Sataining Kit, Affymetrix, Santa Clara, CA). Microarrays were immediately scanned using Affymetrix GeneArray Scanner 3000 7G Plus (Affymetrix, Santa Clara, CA). The resulting CEL files were summarized using Affymetrix Expression Console (current version 1.1). Robust Multi-Array Average (RMA) algorithm was used to generate gene-level data.

Real time –PCR verification

The cDNA was then used to check for the gene expression of four specific genes, via qRT-PCR. This was done in duplicate, so that a total of 32 samples were tested for each gene (2×16 samples). This was accomplished by adding 2.5 uL of each of the 16 samples into a 96-well plate. 22.5 uL of the TaqMan Master Mix was then added to each sample in the plate. The TaqMan Master Mix (per sample) included 12.5 uL of 2× TaqMan, 1.25 uL of oligonucleotide ribosomal RNA (rRNA), and 8.75 uL H2O. The expression of an 18S rRNA was also tested. Since the 18S gene is expressed in all cells it was used as an endogenous control. Each 96-well plate was covered and centrifuged at 1,500 rpm and 4oC for 5 minutes. After spinning the plate was put into the Applied Biosystems StepOnePlus Real-Time PCR system to check for gene expression. The total run time for each plate in the StepOnePlus was about 40 min. The raw data was saved on a computer and later analyzed.

Searching for candidate vitamin D response elements

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To investigate the role of VDR binding in vitamin D mediated gene expression, we searched for VDR binding domain within 60 kb (especially in 5 kb) of the transcriptional start site (TSS) of vitamin D responsive genes. From the 291 genes influenced by vitamin D3 supplementation 17 genes that were most affected by vitamin D3 supplementation were selected for vitamin D response element (VDRE) analysis.

For our analysis we first evaluated known VDREs that are shown in Table S1. These motifs were entered in to the CLC workbench (version6.2) as new motifs to search for novel VDREs as shown in Table S2.

This structural study was also performed on 12 housekeeping genes. The housekeeping genes were used as negative controls for candidate VDREs. Expressions of these housekeeping genes after vitamin D3 supplementation were not changed. There were no sequences of candidate VDREs in 100 kb upstream of the TSS of these housekeeping genes. The list of these housekeeping genes and the region of the study is summarized in Table S3.

As positive controls the known target genes for 1,25(OH)2D3 and reported VDREs in them were used (Table S1). In some VDRE candidates the same sequence was found like the VDRE in the RANKL gene (Table 2). In some genes the first hexameric motif was similar to the first part in VDRE in the one target gene and the second part similar to the second part of the another genes’ VDRE. The similarity of the candidate VDREs with the known VDREs are demonstrated in Table 2. For example the candidate VDRE in coatomer protein complex, subunit beta 2 (COPB2), a gene that was stimulated at least 1.5 fold by vitamin D3 supplementation, had two hexameric binding motifs associated with the VDRE. The first binding motif (TGAACT) was similar to the VDRE in receptor activator of NFkB ligand (RANKL) and the second binding motif (AGGTGA) was similar to VDRE in cytochrome P450, family 24, subfamily A, polypeptide 1 (25-hydroxyvitamin D-24-hydroxylase, CYP24A1).

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Table 2. The motif sequences of 17 genes that were most response to vitamin D3 supplementation that is identical or similar to other known VDRE sequences.

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Sample size estimation

The sample size in this pilot study was estimated based on the pilot funding and on results from previous report of vitamin D impact on broad gene expression in vitro model [11],[12], it was estimated that vitamin D could reduce expression in some genes or increase expression in other genes between one to three fold. A two-sided risk of type 1 error, α, of 0.05; a type 2 error risk, β, of 20%; (power of 80%), changing relative expression from 1.5 to 3, standard deviation of 1(0.3 to 1) and equal group size, the sample size (N) for was calculated to N = 4 for each group.

The actual inclusion of 8 subjects in the two supplemented groups or based on their vitamin D status resulted in a power of 57%–92% for the effect of vitamin D status and vitamin D supplementation on expression of TRIM27, CD83, COPB2, YRNA and CETN3.

Data Analysis

The sample size for this study was 8 subjects. Since each subject had two samples (baseline and follow-up visits), a total of 16 samples were analyzed and linked to experimental factors of supplementation and time. All 16 arrays were normalized with the RMA method as described above. For data quality control regarding the similarity of the samples within and between the groups, the Principal Component Analysis (PCA) method was used. Microarray data normalization was conducted to correct for the mean intensity for each array. To identify the differentially expressed genes before versus after supplementation and between two kinds of supplementation (400 IUs or 2000 IUs), a 2-way ANOVA in the linear model was applied. To assess the results, the p<0.01 was used as a cutoff due a small sample size. Also all subjects were classified based on basal levels of 25(OH)D. Four subjects were vitamin D deficient with 25(OH)D of 16±3.8 ng/ml and the other four subjects were insufficient or sufficient [2] with a 25(OH)D of 27.6±5.4 ng/ml.

It is standard practice in biostatistics to use a p value threshold of 0.05 for the decision as to whether a difference is significant or not. This p value is the probability of getting a false positive result, so on average we would expect to get a false positive result about once every 20 times the test was used [15]. Thus in this study the level of statistical significance was defined as alpha <0.01 i,e. there was a 1% maximum chance of incorrectly rejecting the null hypothesis that there is no association between vitamin D supplementation and genetic expression. The FDR <0.1, (False Discovery Rate) was applied to a list of genes, not any particular gene. We conducted appropriate correction for multiple testing that included using a 1.5 fold change of gene expression combined with false discovery rate (Fdr) < 0.1 in our main analysis. Using a 1.5 fold change of gene expression combined with ANOVA in our subgroup analysis. Using P <0.01 for decreasing false positive and technique validation with the real replicate time PCR. Significant enrichment of GO biological process categories were tested for using EASE software (version 2.0) with P<0.05 [16].

Results

Demographic and other baseline characteristics

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Eight subjects who met the inclusion/exclusion criteria were enrolled. No recruited subjects refused to give consent. Sixteen microarrays (baseline and after 2 months of vitamin D3 supplementation) from eight subjects (3 women) passed the quality control filters and normalized with the RMA method. Mean of age, BMI and serum 25(OH)D levels were 26.5±4 years, 27±5.9 kg/m2 and 21.8±8.6 ng/ml respectively and all of them were white. Three participants received 400 IUs of vitamin D3 daily and five participants received 2000 IUs of vitamin D3 daily (Figure 1). After eight weeks of vitamin D3 supplementation serum 25(OH)D levels in the group that received daily 2000 IUs had a 2-fold increase (9.8±4.9 ng/ml) compared to subjects who received and had an increase of 5.6±4.9 ng/ml (Table 1).

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Figure 1. Flow Diagram of Study Subjects.

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Impact of vitamin D3 supplementation on expression of genes in human white blood cells

To explore gene-expression relationships between and within the 400 IU and 2000 IU groups principal component analysis (PCA) was performed. Total variability of individual chips after normalization is illustrated in Figure 2. There wasn’t a significant difference in order to explore gene-expression relationships between and within the 400 IU and 2000 IU groups. Regarding all participants, with false discovery rate (Fdr)<0.1, and a 1.5 fold change, 291 genes were found to have a statistically significant difference in expression from baseline to follow-up after vitamin D3 supplementation (Figure 3). The list of these 291 genes is shown in Table S4. There was at least a 1.5 fold inhibition of 82 genes (top ~30% of the heat map) whose expression was dramatically reduced and at least a 1.5 fold induction of 209 genes (bottom ~70% of the heat map) whose expression was significantly increased after supplementation with either 400 or 2000 IU of vitamin D3 for 2 months.

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Figure 2. Principal Component Analysis across 16 microarray samples.

There is no grouping of samples along the first or second principal components (representing 18.6% and 17.9% of the variance in gene expression, respectively) based on the expression of these genes. Sample types of each group before or after vitamin D3 supplementation are color-coded for the dose of vitamin D3 supplementation. Red = 2000 IUs and blue = 400 IUs (PoV = Possibility of Variance.)

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Figure 3. Heatmaps of vitamin D responsive genes whose expression levels change after 2 months vitamin D3 supplementation.

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Before supplementation (light green) four subjects were vitamin D deficient with 25(OH)D of 16.2±4.2 ng/ml (dark purple) and the other four subjects were insufficient or sufficient with a 25(OH)D of 27.5±8.4 ng/ml(light purple). After supplementation (dark green) serum levels of 25(OH)D in vitamin D insufficient/sufficient subjects increased to 35.2±8.2 ng/ml (light purple) and in the vitamin deficient subjects increased to 25.1± 4.7 ng/ml(dark purple). Two groups of gene-expression changes are seen based on stimulation (brown) or inhibition (blue) of gene expression post vitamin D3 supplementation. (Colors ranged from blue to brown; High expression = brown, average expression = white, low expression = blue). Clustering of the 291 genes affected by vitamin D3 supplementation was based on stimulation (brown) or inhibition (blue) of gene expression. The list of the 291 genes is shown in Table S1.

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For verification candidate of gene expression changes real-time PCR was performed for four genes including CD83, TNFAIP3, KLF10 and SBDS (Figure 4). The results showed gene expression changes concordant with those observed by microarray.

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Figure 4. Verification of microarray gene expression by Real-time PCR.

For verification of gene expression real-time PCR was performed for four genes including CD83, TNFAIP3, KLF10 and SBDS. Relationship between two sets of data from microarray and real-time PCR is shown by linear regression with 95% mean prediction interval. The results showed the relative expression of these genes was consistent with the expression observed from the broad gene expression by microarray.

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The effect of vitamin D status on gene expressio

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A subgroup analysis of participants was evaluated based on the baseline serum 25(OH)D levels (Figure 3 and 5) in order to determine what if any influence vitamin D status had on the basal expression of the 291 genes identified as being affected by 2 months of vitamin D3 supplementation. Four subjects were vitamin D deficient with 25(OH)D 16.2±4.2 ng/ml (range 10–19 ng/ml) and the other four subjects were insufficient or sufficient with a 25(OH)D of 27.5±8.4 ng/ml (range 22–40 ng/ml).

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Figure 5. Heatmaps of vitamin D responsive genes affected by vitamin D status.

Before supplementation (light green) four subjects were vitamin D deficient with 25(OH)D of 16.2±4.2 ng/ml (dark purple) and the other four subjects were insufficient or sufficient with a 25(OH)D of 27.5±8.4 ng/ml(light purple). After supplementation (dark green) serum levels of 25(OH)D in vitamin D insufficient/sufficient subjects increased to 35.2±8.2 ng/ml (light purple) and in the vitamin deficient subjects increased to 25(OH)D of 25.1±4.7 ng/ml(dark purple). Two groups of gene-expression changes are seen based on stimulation (brown) or inhibition (blue) of gene expression post vitamin D3 supplementation. (Colors ranged from blue to brown; High expression = brown, average expression = white, low expression = blue).Expression of 66 genes before supplementation was significantly different in the vitamin D deficient group (dark purple) compared to the vitamin D insufficient/sufficient group (light purple). Clustering of the 66 genes affected by vitamin D status and vitamin D3 supplementation was based on stimulation (brown) or inhibition (blue) of gene expression.

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This subgroup analysis of the baseline gene expression for the 291 genes (Figure 3) in the vitamin D deficient group compared to the vitamin D insufficient/sufficient group revealed that, expression of 66 genes were significantly different between the two groups (p<0.01 and fold change>1.5). (Figure 5) There was at least a 1.5 fold increase in gene expression (brown-orange) of 14 genes and at least a 1.5 fold decrease in the expression (yellow-white) of 52 genes in the vitamin D deficient adults compared to those who were vitamin D insufficient or sufficient at baseline (Figure 5). After vitamin D3 supplementation the serum 25(OH)D increased from 16.2±4.2 to 25.1±4.7 ng/ml and 27.5±8.4 to 35.2±8.2 ng/ml in the adults who were vitamin D deficient and vitamin D insufficient or sufficient respectively. After vitamin D3 supplementation gene expression in the vitamin D deficient group was similar to vitamin D insufficient/sufficient group and there was no longer a significant difference between two groups in the expression of these 66 genes.

Structural evidence for the effect of vitamin D3 supplementation on gene expression

To learn which of these genes affected by vitamin D3 supplementation contained VDR binding domains near the transcriptional start site (TSS), we performed a VDRE analysis as described in Materials and Methods.

Of the 66 genes that were influenced by at least 1.5 fold in their expression by the baseline serum 25(OH)D concentration, 17 of these genes that were significantly changed after vitamin D3 supplementation in both deficient and insufficient/sufficient groups (p<0.01) were selected for VDRE analysis.

The details of searching for candidate VDRE sequences is explained in Methods and shown in Table S1-3. We found at least one candidate VDRE in the upstream region within 30 kb of the TSS in these 17 genes (Table 1). For example, the candidate VDRE in coatomer protein complex, subunit beta 2 (COPB2), a gene that was stimulated at least 1.5 fold by vitamin D3 supplementation, had two hexameric binding motifs associated with the VDRE. The first binding motif (TGAACT) was similar to the VDRE in receptor activator of NFkB ligand (RANKL) and the second binding motif (AGGTGA) was similar to the VDRE in cytochrome P450, family 24, subfamily A, polypeptide 1 (25-hydroxyvitamin D-24-hydroxylase, CYP24A1).

The motif sequence for VDR/RXR hetrodimeric binding sites is shown in Figure 6.

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The motif sequence of candidate VDREs (6A) are compared with known VDREs (6B). All of these sequences are summarized in one motif sequence (6C). The location of other transcription factor binding sites are shown in Figure S1. These are associated with known steroidogenic factor 1 (SF-1), CTF1/nuclear factor 1 (NF1), CCAAT enhancer binding protein-β (C/EBPβ), NF-KB and RNA polymerase (TATA box) motifs. For example pseudouridylate synthase 3 (PUS3), a gene that was stimulated 1.6 fold by vitamin D3 supplementation has five VDREs (Table 2) that one of them is shown in Figure 6D located at position -1027, the TATA box located at -276 and location of other transcription factor sites near this VDRE was determined (6D).

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Figure 6. Sequence of candidate VDREs compared with known VDREs.

(A) The candidate sequences of VDREs (B), motifs created based on known VDRE sequences previously reported and (C) motifs based on the sum of these sequences and (D) the location of candidate VDREs of pseudouridylate synthase 3 (PUS3) and the location of other transcription regulation sites in this gene including TATA box, SF1and CCAAT. The major structure of candidate VDREs are based on the consensus sequence RGKTSA (R = A or G, K = G or T, and S = C or G).

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This study was also performed on 12 housekeeping genes to serve as negative controls. There were no sequences of candidate VDREs in 100 kb upstream of TSS of these housekeeping genes (Table S3). The expression of these housekeeping genes after vitamin D3 supplementation was not changed.

Biological functions for vitamin D responsive genes

An analysis of the 291 genes affected by the vitamin D3 supplementation was associated with at least a 1.5 fold induced expression of genes related to 81 pathways and at least a 1.5 fold inhibition of genes affecting 88 pathways (Table S5, S6)(p<0.05). The most relevant biological functions resulting from these changes in gene expression by vitamin D3 supplementation are listed in Table 3 and the complete list is in Tables S5 and S6. Gene ontology analysis showed that the differentially expressed genes were significantly enriched with those associated with immune functions, transcriptional regulation, cell cycle activity, DNA replication and response to stress (Figure 7).

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Figure 7. Biological functions for genes whose expression levels were altered after 2 months of vitamin D3 supplementation.

After receiving vitamin D3 supplementation we identified 291 genes whose expression was significantly decreased or increased. Some of these genes influence several pathways that are involved in response to stress and DNA repair, DNA replication, immune regulation, epigenetic modification, transcriptional regulation and other biological functions. In addition vitamin D3 supplementation influenced the expression of Y RNA and CETN3 that are involved in DNA repair in response to UVR exposure.

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Table 3. List of biological functions of the 291 genes whose expression was influenced by vitamin D3 supplementation.

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Discussion

This genome-wide expression analysis provides the first insight into the global transcriptional activity that underlies the effects of vitamin D status and vitamin D3 supplementation in cells on the human buffy coat that include immune cells. As shown in Figure 3, vitamin D supplementation caused at least a 1.5 fold change in the expression of 291 genes that are involved in apoptosis, immune function, transcriptional regulation, epigenetic modification, response to stress, cell cycle activity and differentiation (Table 3). This finding is consistent with previous in vitro studies that showed 1,25(OH)2D3 directly or indirectly controlled more than 200 genes, including genes responsible for the regulation of cellular proliferation, differentiation, angiogenesis and immunomodulatory activities on both innate and adaptive immune responses [3],[4],[6]. Our observations support previous reports that have estimated that VDR activation may regulate directly and/or indirectly the expression of a very large number of genes (0.5–5% of the total human genome i.e., 100–1250 genes) [3],[4],[8],[11],[17].

In a recent genome-wide microarray analysis of 1,25(OH)2D3-treated human osteoblasts revealed modulation of 158 genes involved in vitamin D metabolism (CYP24A1), immune function (CD14), neurotransmitter transporters (SLC1A1, SLC22A3), and coagulation [17]. A study of the human genome screened for VDREs reported 157 genes to be regulated in SCC- 25 cells, of which 126 were induced and 31 were repressed [17]. The researchers found 2,776 binding sites for the vitamin D receptor along the length of the genome. Among them included 229 genes associated with susceptibility to autoimmune disorders, and cancers including chronic lymphocytic leukemia and colorectal cancer [17]. All of these studies reporting the effect of 1,25(OH)2D3 on gene expression were in vitro studies in different cell types.

There have been two genome wide association studies that have related genomic variation on vitamin D status [18],[19]. However little is known about what effect vitamin D status has on gene expression or what happens to gene expression in response to vitamin D supplementation. We observed that 291 genes were at least a 1.5 fold stimulated or inhibited in response to vitamin D3 supplementation. We identified 66 genes, that were most significantly affected by the subjects’ vitamin D status i e those who were vitamin D deficient with 25(OH)D of 16.2±4.2 ng/ml compared to adults who had a 25(OH)D of 27.5±8.4 ng/ml at baseline. Nineteen of these 66 genes are the same reported by in vitro studies [12], [17]. Thus we have identified an additional 47 genes that were influenced by vitamin D3 status.

Of these 66 genes, 17 genes whose expression significantly changed after vitamin D3 supplementation in both deficient and insufficient/sufficient groups were found to have novel VDREs (Table 2).

After receiving 400 IUs or 2000 IUs for 8 weeks of vitamin D3 dramatic changes occurred in the expression of these 66 genes while no significant change was seen in 12 housekeeping genes. We did not see a significant dose dependent difference in the alteration in gene expression 8 weeks after the adults received daily either 400 IUs or 2000 IUs vitamin D3. This could be due to the small number of subjects studied or that any improvement in serum 25(OH)D levels can lead to significant changes in gene expression whether the person is vitamin D deficient, insufficient or sufficient. We observed the same trend in gene expression in the subjects who received 400 or 2000 IUs vitamin D3 whether the baseline 25(OH)D was 16.2±4.2 or 27.5±8.4 ng/ml. There was however a trend for a larger change in the expression of these genes for the group who received 2000 IUs vitamin D3/d compared to the group who received 400 IUs vitamin D3/d. Even the subject who had a 25(OH)D of 40 ng/ml after 2000 IUs vitamin D3 daily for two months had at least a 1-fold change in 10 genes and at least a 0.5 fold change in the expression of 33 genes from this pool of 66 genes.

Of the 66 genes, 52 increased their expression in response to vitamin D3 supplementation. The greatest increases were in genes that coded for apoptosis, T Cell intracellular antigen-1 (TIA1) (26-fold), immune function, zinc finger protein 287(ZNF287) (6.8-fold), response to cellular stress, Y-RNA(2-fold), centrin3(CETN3) (1.5-fold) and heat shock 105 kDa/110 kDa protein 1(HSPH1) (1.5-fold), tRNA processing, mitochondrial translation optimization 1 homolog (MTO1)(5-fold) and pseudouridylate synthase 3 (PUS3)(2-fold), transcriptional regulation such as ZNF 701 (2.3-fold), and genes involved in DNA repair, general transcription factor IIH, polypeptide 1 (GTF2H1) (7-fold) and chromatin modification small subunit processome component, homolog (UTP3) (4-fold).

The other 14 genes decreased their expression in response to vitamin D3 supplementation. The greatest decreases were in genes that coded for histone modification; H1 histone family, member X (H1FX) (12-fold), transcriptional regulation; early growth response 1 (EGR1)(2.8-fold). Two of the genes that had reduced expression; the cluster of differentiation 83(CD83) (2-fold) and tumor necrosis factor alpha-induced protein 3 (TNFAIP3)(1.5-fold) that are known to affect immune function also were found to have reduced expression by real-time PCR.

Our observation that vitamin D3 supplementation increased serum 25(OH)D levels resulting in the suppression of CD83 (2-fold) is consistent with the observation that 1,25(OH)2D3 inhibited CD83 expression in cultured dendritic cells[20]. This suggests that local synthesis of 1,25(OH)2D3 in immune cells including macrophages[21] regulates genes that affect immune function and improve immune health resulting in reducing risk for developing autoimmune diseases such as multiple sclerosis and type 1 diabetes[20].

The role of TNFAIP3 in antiapoptotic function [22] and the association of its’ mutations with Crohn’s disease, rheumatoid arthritis, systemic lupus erythematous, psoriasis, type 1 diabetes [23] could explain the association of vitamin D sufficiency in the prevention of chronic inflammation and autoimmune diseases. Also vitamin D’s influence on the expression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (NFKBIA)(1.5-fold) may affect immune and proinflammatory responses [24],[25].

Vitamin D3 supplementation resulted in a 1.5 fold increase in the expression of tripartite motif containing protein 27 (TRIM27) a gene that negatively regulates CD4 T cells by ubiquitinating and inhibiting the class II phosphatidylinositol 3 kinase C2β (PI3KC2β)2β [26]. TRIM27 over expression conferred resistance to oxidative stress, by decreasing the expression of thioredoxin binding protein-2 [26]. Also TRIM27 was as recently identified an important negative regulator of mast cells in vivo, and suggests that PI3KC2β is a potential new pharmacologic target to treat IgE mediated disease [25][26]. Our finding has identified a potential new pathway for vitamin D affecting the immune system, allergy risk and oxidative stress via TRIM27. Coatomer protein complex, subunit beta 2 (COPB2) was another vitamin D responsive gene in our study whose expression significantly increased (1.5-fold) after vitamin D3 supplementation. COPB2’s role in apoptosis and tumor growth suppression [27], may help explain the association of improving vitamin D status in cancer prevention [7],[17].

Higher serum concentrations of 25(OH)D at baseline and improvement in serum concentrations of 25(OH)D with either 400 IUs or 2000 IUs of vitamin D3 resulted in a 2.5 fold decrease in the expression of EGR-1, a gene that is a transcriptional regulator of not only differentiation and mitogenesis but also plays an important function in vascular health [28],[29]. An analogue of 1,25(OH)2D3, calcipotriol which a potent inhibitor of keratinocyte proliferation and used for treating the hyperproliferative skin disorder psoriasis was found to inhibit EGR-1 expression in cultured human keratinocyte[30]. It has been estimated that as a transcription factor EGR-1 affects the expression of more than 300 genes [31]. Thus by altering the expression of EGR1 with vitamin D supplementation has the potential cascading effect of altering an additional 300 genes. This could help explain the observation that vitamin D can directly or indirectly influence up to 5% of the human genome [4],[17].

These data suggest that there is a continuum in gene expression in response to increasing serum 25(OH)D levels. The definitions of vitamin D deficiency and insufficiency and sufficiency are somewhat arbitrary. As shown in Figure 3, our data suggest that any improvement in vitamin D status will improve expression of genes that have a wide variety of biologic functions that are associated with cellular proliferation, differentiation, immune function, DNA repair etc whether the 25(OH)D concentration is as low as 10 ng/ml or as high as 40 ng/ml. These genes are linked to cancer, autoimmune disorders and cardiovascular disease and have been associated with vitamin D deficiency [1],[5],[6].

These results suggest that to maximize vitamin D’s effect on gene expression may require even higher doses than 2000 IUs of vitamin D3 daily. The current observation showed the specific pattern for broad gene expression of vitamin D deficiency and significant changes with increases in serum levels of 25(OH)D. Although larger studies are required to explain the clinically relevant gene expression patterns, the present genome-wide microarray study in human buffy coat for the first time identified a wide range of critical regulatory and metabolic pathways influenced by vitamin D3 supplementation that supports the vitamin D immunomodulatory effects and potential role in response to stress and DNA repair.

The major limitation of the study is the small number of subjects studied and thus the results are reported as an exploratory study. Although gene expression was determined with a suitable false discovery rate only a few of the 291 vitamin D responsive genes were verified by real time PCR. Furthermore although our study did not identify actual VDR binding sites with a biologic function it does support vitamin D-responsive genes from in vitro studies [11],[12],[17] and suggests 17 potential novel candidate VDREs in vitamin D-regulated genes. This will need to confirm with experimental studies.

There are several strengths of the study that include accurately measuring serum 25(OH)D concentrations by the gold standard liquid chromatography tandem mass spectroscopy assay, comparing gene expression in the same individual at baseline and 2 months after vitamin D supplementation and performing this study in the winter when sunlight does not influence vitamin D status. An additional strength was provided by the real-time PCR analysis of two genes CD83 and TNFAIP3 from the 66 gene pool that were affected by vitamin D status and two genes KLF10 and SBDS from the 291 gene pool that were affected by vitamin D3 supplementation (Figure 4) that corroborated the microarray expression of these four genes (Figure 5).

In summary, this is the first report to reveal how vitamin D status and vitamin D3 supplementation affects gene expression in healthy adults. Nineteen of these vitamin D-induced genes have been previously reported to be regulated by 1,25(OH)2D3 in vitro and function on the immune system, apoptosis, transcription regulation and response to stress.

Vitamin D supplementation has proven skeletal health benefits [3],[4], particularly in individuals at risk for vitamin D deficiency. This study reveals for the first time molecular finger prints that help to explain some of the nonskeletal health benefits of vitamin D [2],[6].

Supporting Information

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The six gene upstream regions containing candidate VDRE sequences, and other transcription factors sites for steroidogenic factor 1 (SF-1), CTF1/nuclear factor 1 (NF1), CCAAT enhancer binding protein-β (C/EBPβ), NF-KB and RNA polymerase (TATA box). Arrows indicate direction of forward or revere strand. The VDREs are located at upstream region and disfigured by mines numbers relative to the ATG translation start site. The locations of other transcription factors binding sites are also shown.

Figure S1.

The six gene upstream regions containing candidate VDRE sequences, and other transcription factors sites for steroidogenic factor 1 (SF-1), CTF1/nuclear factor 1 (NF1), CCAAT enhancer binding protein-β (C/EBPβ), NF-KB and RNA polymerase (TATA box). Arrows indicate direction of forward or revere strand. The VDREs are located at upstream region and disfigured by mines numbers relative to the ATG translation start site. The locations of other transcription factors binding sites are also shown.

doi:10.1371/journal.pone.0058725.s001

(TIF)

Table S1.

The reported vitamin D response elements in known vitamin D target genes. The positions and sequences of nucleotide motifs from 5′ upstream to the transcriptional start site were identified.

doi:10.1371/journal.pone.0058725.s002

(DOCX)

Table S2.

Definition of new vitamin D response element motifs. The reported vitamin D response elements and related element collected and these definitions entered in CLC workbench (version6.2) as new motifs to search VDRE.

doi:10.1371/journal.pone.0058725.s003

(DOCX)

Table S3.

The housekeeping genes that used as negative control for VDREs searching. Expression of these housekeeping genes after vitamin D supplementation was not changed. There were no sequences of candidate VDREs in 100 kb upstream of TSS of these housekeeping genes. The list of these housekeeping genes and the region of the study is summarized in the table.

doi:10.1371/journal.pone.0058725.s004

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Table S4.

The complete list of 291 genes that affected by vitamin D3 supplementation.

doi:10.1371/journal.pone.0058725.s005

(DOCX)

Table S5.

The pathways enriched with down regulated genes after treatment (p<0.05).

doi:10.1371/journal.pone.0058725.s006

(DOCX)

Table S6.

Pathways enriched with up regulated genes after treatment (p<0.05).

doi:10.1371/journal.pone.0058725.s007

(DOCX)

Checklist S1.

CONSORT Checklist.

doi:10.1371/journal.pone.0058725.s008

(DOCX)

Protocol S1.

Trial Protocol.

doi:10.1371/journal.pone.0058725.s009

(PDF)

Acknowledgments

We appreciate the help from Cassandre Voltaire, Timothy K.M. Calvert, Leonierose N.Dacuycuy and Chlirim Zaku master’s degree students for subject recruitment and sample preparation and Dr. Stefan Shen for his helpful advice.

Author Contributions

Conceived and designed the experiments: AH MFH AS. Performed the experiments: AH MFH AS. Analyzed the data: AH MFH AS. Contributed reagents/materials/analysis tools: AH MFH AS. Wrote the paper: AH MFH AS.

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2. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, et al. (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(7): 1911–30. doi: 10.1210/jc.2011-0385. Find this article online

3. Adams JS, Hewison M (2010) Update in Vitamin D. J Clin Endocrinol Metab. 95(2): 471–478. Find this article online

4. Holick MF (2007) Vitamin D Deficiency. N Engl J Med 357: 266–281. Find this article online

5. Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, et al. (2012) The nonskeletal effects of vitamin D: an Endocrine Society Scientific statement. Endocr Rev 33(3): 456–92. doi: 10.1210/er.2012-1000. Find this article online

6. Giovannucci E (2009) Expanding roles of vitamin D. J Clin Endocrinol Metab. 94: 418–420. Find this article online

7. Garland CF, Gorham ED, Mohr SB, Garland FC (2009) Vitamin D for cancer prevention: global perspective. Ann Epidemiol 19: 468–483. doi: 10.1016/j.annepidem.2009.03.021. Find this article online

8. Montecino M, Stein GS, Stein JL, Lian JB, Wijnen AJ, et al. (2008) Vitamin D control of gene expression: temporal and spatial parameters for organization of the regulatory machinery. Crit Rev Eukaryot Gene Expr 18(2): 163–72. doi: 10.1615/CritRevEukarGeneExpr.v18.i2.50. Find this article online

9. Zhang X, Ho SM (2011) Epigenetics meets endocrinology. J Mol Endocrinol 46(1): R11–32. doi: 10.1677/JME-10-0053. Find this article online

10. Yu S, Cantorna MT (2011) Epigenetic reduction in invariant NKT cells following in utero vitamin D deficiency in mice. J Immunol 186(3): 1384–90. doi: 10.4049/jimmunol.1002545. Find this article online

11. Tarroni P, Villa I, Mrak E, Zolezzi F, Mattioli M, et al. (2012) Microarray analysis of 1,25(OH)2D3 regulated gene expression in human primary osteoblasts. J Cell Biochem 113(2): 640–9. Find this article online

12. Wang TT, Tavera-Mendoza LE, Laperriere D, Libby E, MacLeod NB, et al. (2005) Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol 19(11): 2685–95. doi: 10.1210/me.2005-0106. Find this article online

13. Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, et al. (2007) Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. 93(3): 677–81. Find this article online

14. Holick MF, Siris ES, Binkley N, Beard MK, Khan A, et al. (2005) Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab 90(6): 3215–24. Find this article online

15. Pavlidis P (2003) Using ANOVA for gene selection from microarray studies of the nervous system. Methods 31: 282–289. doi: 10.1016/S1046-2023(03)00157-9. Find this article online

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17. Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, et al. (2010) A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res 20(10): 1352–60. doi: 10.1101/gr.107920.110. Find this article online

18. Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, et al. (2010) Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet 376(9736): 180–8. doi: 10.1016/S0140-6736(10)60588-0. Find this article online

19. Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, et al. (2010) Genome-wide association study of circulating vitamin D levels. Hum Mol Genet 19(13): 2739–45. doi: 10.1093/hmg/ddq155. Find this article online

20. Bartosik-Psujek H, Tabarkiewicz J, Pocinska K, Stelmasiak Z (2010) Rolinski (2010) Immunomodulatory effects of vitamin D on monocyte-derived dendritic cells in multiple sclerosis. Mult Scler (12): 1513–6. doi: 10.1177/1352458510379611. Find this article online

21. Rosenblatt J, Bissonnette A, Ahmad R, Wu Z, Vasir B, et al. (2010) Immunomodulatory effects of vitamin D: implications for GVHD. Bone Marrow Transplant 45(9): 1463–8. doi: 10.1038/bmt.2009.366. Find this article online

22. Vereecke L, Beyaert R, van Loo G (2009) The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology. Trends Immunol 30(8): 383–91. doi: 10.1016/j.it.2009.05.007. Find this article online

23. Maxwell JR, Gowers IR, Kuet KP, Barton A, Worthington J, et al. (2012) Expression of the autoimmunity associated TNFAIP3 is increased in rheumatoid arthritis but does not differ according to genotype at 6q23. Rheumatology (Oxford) 51(8): 1514–5. doi: 10.1093/rheumatology/kes134. Find this article online

24. Berry DM, Clark CS, Meckling-Gill KA (2002) 1alpha,25-dihydroxyvitamin D3 stimulates phosphorylation of IkappaBalpha and synergizes with TPA to induce nuclear translocation of NFkappaB during monocytic differentiation of NB4 leukemia cells. Exp Cell Res 272(2): 176–84. Find this article online

25. Kamen DL, Tangpricha V (2010) Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med (Berl) 88(5): 441–50. doi: 10.1007/s00109-010-0590-9. Find this article online

26. Srivastava S, Cai X, Li Z, Sun Y, Skolnik EY (2012) Phosphatidylinositol-3-Kinase C2β and TRIM27 function to Positively and Negatively Regulate IgE Receptor Activation of Mast Cells. Mol Cell Biol 32(15): 3132–9. Find this article online

27. Sudo H, Tsuji AB, Sugyo A, Kohda M, Sogawa C, et al. (2010) Knockdown of COPA, identified by loss-of-function screen, induces apoptosis and suppresses tumor growth in mesothelioma mouse model. Genomics 95(4): 210–6. doi: 10.1016/j.ygeno.2010.02.002. Find this article online

28. Fu M, Zhu X, Zhang J, Liang J, Lin Y, et al. (2003) Egr-1 target genes in human endothelial cells identified by microarray analysis. Gene 2 315: 33–41. doi: 10.1016/S0378-1119(03)00730-3. Find this article online

29. Wada Y, Fujimori M, Suzuki J, Tsukioka K, Ito K, et al. (2003) Egr-1 in vascular smooth muscle cell proliferation in response to allo-antigen. J Surg Res 115(2): 294–302. doi: 10.1016/S0022-4804(03)00213-0. Find this article online

30. Kristl J, Slanc P, Krasna M, Berlec A, Jeras M, et al. (2008) Calcipotriol affects keratinocyte proliferation by decreasing expression of early growth response-1 and polo-like kinase-2. Pharm Res 25(3): 521–9. doi: 10.1007/s11095-007-9388-z. Find this article online

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http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0058725

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Vitamin D linked with lower risk of deadly prostate cancer

Vitamin D linked with lower risk of deadly prostate cancer

By Karen Rowan

Published April 18, 2012

MyHealthNewsDaily

Vitamin D does not protect men from getting prostate cancer, but it may lessen their chances of dying of it.

In a new study, men with the highest levels of vitamin D in their blood were 57 percent less likely than men with the lowest levels to succumb to prostate cancer.

However, no link was found between vitamin D levels and having prostate cancer, the researchers said.

“Prostate cancer is a very heterogeneous disease,” said study researcher Irene Shui, an epidemiologist at the Harvard School of Public Health. Some tumors progress quickly, spreading to other sites in the body and causing death, while others stay within the prostate for years and never affect a man’s health or life.

It remains unclear exactly why vitamin D would lower men’s risk of dying from prostate cancer if it has no influence at all on the risk of developing the cancer, Shui said. It may be that vitamin D specifically influences the cancer cells’ abilities to progress to later stages of the disease and spread through the body, but not the actual initiation of the cancer, she said.

Still, the study was observational, and it does not show a cause-and-effect link between vitamin D and prevention of deadly prostate cancer.

The new findings were published in online April 12 in the Journal of the National Cancer Institute.

Vitamin D and prostate cancer

“There is abundant laboratory evidence that vitamin D may have anticancer properties,” Shui said. But while studies conducted on prostate cancer cells growing in lab dishes have shown that vitamin D may thwart cancer’s progression, studies in people have shown that high levels of the vitamin don’t lower a man’s risk of getting cancer of the prostate, the gland surrounding a man’s urethra.

For their study, the researchers gathered data from men who had provided blood samples between 1993 and 1995 as part an ongoing study at Harvard University. The researchers looked at 1,260 men who had developed prostate cancer by 2004, and 1,331 men who were the same age but didn’t develop the disease.

By March 2011, when the study ended, 114 of the men with prostate cancer had died. When the researchers looked at these men’s levels of vitamin D, they found that 31 of them were among the men with the lowest levels of vitamin D in the study, whereas only 19 of them were among the men with the highest levels of vitamin D in the study.

However, vitamin D levels made no difference in terms of developing any prostate cancer — 310 of the men with the cancer were in the group with the lowest vitamin D levels, and 333 of the men with cancer were among those with the highest levels.

So should men try to get more vitamin D?

While the results of this study need to be replicated in future research, Shui said, vitamin D has been shown to have numerous effects on health. “Men who are concerned that they may be deficient in vitamin D should speak with their physicians about taking supplements or eating more foods rich in vitamin D,” she said.

The vitamin is also produced naturally by the skin when exposed to the sun. Getting about 30 minutes of sun exposure between 10 a.m. and 3 p.m. twice a week usually leads to sufficient vitamin D synthesis, according to the National Institutes of Health.

The study was limited in that most of the participants were white. “As vitamin D deficiency is even more prevalent in men of African descent, and this population also has a higher prostate cancer risk, studies conducted in men of other ethnicities would be helpful to see of our results are generalizable to those populations,” Shui said.

Read more: http://www.foxnews.com/health/2012/04/18/vitamin-d-linked-with-lower-risk-deadly-prostate-cancer/#ixzz2OktTqu4s

COMUNICADO DO CONSULTÓRIO DO DR. CÍCERO GALLI COIMBRA

COMUNICADO DO CONSULTÓRIO DO DR. CÍCERO.

http://www.institutodeautoimunidade.org.br/index.html
IITA

Os problemas com o telefone devem-se em grande parte à ineficiência da operadora contratada pelo prédio onde está instalado o consultório. Conseguiram agora mudar a operadora, mas, para fazer a portabilidade e manter o número, já tão conhecido, o telefone ficará mudo no próximo dia 26/03, pelo menos no período da manhã.

Informam também que:
– o número adequado para ligar é o (11) 5908 5969, pois o outro número é utilizado o tempo todo para fazer ligações.
– os horários menos congestionados no tel 5908-5969 são os seguintes: entre 8 às 9:30; entre 11 e 12:00; e entre 17 e 18:30h.

– quem já é paciente da clínica deve preferencialmente entrar em contato pelo e-mail da secretaria.

Não divulgam esse e-mail para todos porque não há como atender a demanda (pelo menos no momento). São inúmeros os e-mails e ligações.

– está sendo organizado um curso para médicos pelo Instituto de Autoimunidade e estão sendo treinados novos assistentes para ocupar completamente o tempo das 2 outras salas.

– ficam extremamente sensibilizados com os pacientes e estão trabalhando muito para oferecer alternativas.

CONSULTORIO DR. CÍCERO GALLI COIMBRA

CONSULTORIO DR. CÍCERO GALLI COIMBRA.

CONSULTORIO DR. CÍCERO GALLI COIMBRA

Rua Doutor Diogo de Faria 775  – Sala 94  Vila Mariana – em frente ao Hospital Paulista

COMUNICADO DO CONSULTÓRIO DO DR. CÍCERO.

– o número adequado para ligar é o (11) 5908 5969, pois o outro número é utilizado o tempo todo para fazer ligações.
– os horários menos congestionados no tel 5908-5969 são os seguintes: entre 8 às 9:30; entre 11 e 12:00; e entre 17 e 18:30h.

Consultorio Faz chamadas com 11 50844642

The Effects Of Low Vitamin D On The Body

0The Effects of Low Vitamin D on the Body

 oste1

Mar 28, 2011 | By Joseph Pritchard

Joseph Pritchard graduated from Our Lady of Fatima Medical School with a medical degree. He has spent almost a decade studying humanity. Dr. Pritchard writes as a San Francisco biology expert for a prominent website and thoroughly enjoys sharing the knowledge he has accumulated.

Photo Credit x-ray of bones image by Tammy Mobley from Fotolia.com

Your body needs 13 essential vitamins. Without these vitamins, which include vitamin A, B complex, C, D, E and K, your may suffer from complications ranging from heart disease to bone deformities. Vitamin D specifically has been linked to bone disease. In children vitamin D deficiency is called rickets and in adults it is called osteomalacia. In either case, low vitamin D has numerous detrimental effects on the body.

Vitamin D

Vitamin D is a fat soluble vitamin that the body is able to store in large amounts. Most often vitamin D is stored in the liver and in the fatty tissue. The body needs vitamin D to maintain normal blood levels of phosphorus and calcium, MayoClinic.com reports. These are the two main minerals involved in the formation of bone. Vitamin D also facilitates the absorption of calcium from the diet. Vitamin D may also be useful in preventing osteoporosis, high blood pressure, autoimmune disease and cancer.

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Rickets

Infants who suffer from severe vitamin D deficiency develop a condition called rickets. Often infants who only take in breast milk, darker-skinned babies and children with parents with vitamin D deficiency are at a greater risk for rickets. Symptoms include bone pain or tenderness, teeth deformities and cavities, growth retardation, frequent bone fractures, short stature, bowlegs, spine deformities and bumps in the chest and breastbone, according to Medline Plus, a service of the National Institutes of Health. Treatment for rickets focuses on administering vitamin D in order to normalize the child’s vitamin D levels. Braces and support can help prevent skeletal deformities, but some permanent defects may require corrective surgery.

Osteomalacia

In adults, vitamin D deficiency, or osteomalacia, often causes muscle and bone weakness. Adults are done growing by the time osteomalacia begins so they rarely develop skeletal deformities or growth problems. However, osteomalacia is correlated with a decrease in skeletal structural integrity, an article in “The American Journal of Clinical Nutrition” warns. These bones are weaker than normal bones and therefore the patient may experience aches and pains especially in the joints. Osteomalacia can also cause muscles pain and weakness. The diagnosis of vitamin D deficiency is sometimes difficult, but once the diagnosis is made treatment with vitamin D supplementation usually reverses the symptoms.

Sources of Vitamin D

The main source of vitamin D for humans comes from exposure to sunlight, “The American Journal of Clinical Nutrition” explains. Your skin is able to synthesize vitamin D when exposed to adequate amounts of sunlight. Furthermore, vitamin D found in foods such as salmon, mackerel and herring. Fish oil, like cod liver oil, also contains vitamin D. In the United States, some forms of milk, juice, breads, yogurts and cheesed are fortified with vitamin D. There are also dietary supplements and pharmaceutical preparations that contain vitamin D. These man-made forms of vitamin D are usually given to patients suffering from or at risk or developing vitamin D deficiency.

 

References

  • MedlinePlus; Rickets; Neil K. Kaneshiro, MD, MHA; August 3, 2010
  • Mayo Clinic; Vitamin D; December 1, 2010
  • “The American Journal of Clinical Nutrition”; Vitamin D deficiency: a worldwide problem with health consequences; Michael F Holick and Tai C Chen; May 1, 2007

Article reviewed by Jenna Marie Last updated on: Mar 28, 2011

Read more: http://www.livestrong.com/article/408333-the-effects-of-low-vitamin-d-on-the-body/#ixzz2HmHb3700

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